Datasets:

CognitiveLab

/

Aarogya_wiki_medical_terms

like 0

Follow

CL 5

Aarogya, Please give me a short description about Infection prevention and control

Infection prevention and control

Infection prevention and control is the discipline concerned with preventing healthcare-associated infections; a practical rather than academic sub-discipline of epidemiology. In Northern Europe, infection prevention and control is expanded from healthcare into a component in public health, known as "infection protection" (smittevern, smittskydd, Infektionsschutz in the local languages). It is an essential part of the infrastructure of health care. Infection control and hospital epidemiology are akin to public health practice, practiced within the confines of a particular health-care delivery system rather than directed at society as a whole.Infection control addresses factors related to the spread of infections within the healthcare setting, whether among patients, from patients to staff, from staff to patients, or among staff. This includes preventive measures such as hand washing, cleaning, disinfecting, sterilizing, and vaccinating. Other aspects include surveillance, monitoring, and investigating and managing suspected outbreaks of infection within a healthcare setting.A subsidiary aspect of infection control involves preventing the spread of antimicrobial-resistant organisms such as MRSA. This in turn connects to the discipline of antimicrobial stewardship—limiting the use of antimicrobials to necessary cases, as increased usage inevitably results in the selection and dissemination of resistant organisms. Antimicrobial medications (aka antimicrobials or anti-infective agents) include antibiotics, antibacterials, antifungals, antivirals and antiprotozoals.The World Health Organization (WHO) has set up an Infection Prevention and Control (IPC) unit in its Service Delivery and Safety department that publishes related guidelines. Infection prevention and control Aseptic technique is a key component of all invasive medical procedures. Similar control measures are also recommended in any healthcare setting to prevent the spread of infection generally. Hand hygiene Hand hygiene is one of the basic, yet most important steps in IPC (Infection Prevention and Control). Hand hygiene reduces the chances of HAI (Healthcare Associated Infections) drastically at a floor-low cost. Hand hygiene consists of either hand wash(water based) or hand rubs(alcohol based). Hand wash is a solid 7-steps according to the WHO standards, wherein hand rubs are 5-steps.The American Nurses Association (ANA) and American Association of Nurse Anesthesiology (AANA) have set specific checkpoints for nurses to clean their hands; the checkpoints for nurses include, before patient contact, before putting on protective equipment, before doing procedures, after contact with patient’s skin and surroundings, after contamination of foreign substances, after contact with bodily fluids and wounds, after taking off protective equipment, and after using the restroom. To ensure all before and after checkpoints for hand washing are done, precautions such as hand sanitizer dispensers filled with sodium hypochlorite, alcohol, or hydrogen peroxide, which are three approved disinfectants that kill bacteria, are placed in certain points, and nurses carrying mini hand sanitizer dispensers help increase sanitation in the work field. In cases where equipment is being placed in a container or bin and picked back up, nurses and doctors are required to wash their hands or use alcohol sanitizer before going back to the container to use the same equipment.Independent studies by Ignaz Semmelweis in 1846 in Vienna and Oliver Wendell Holmes, Sr. in 1843 in Boston established a link between the hands of health care workers and the spread of hospital-acquired disease. The U.S. Centers for Disease Control and Prevention (CDC) state that "It is well documented that the most important measure for preventing the spread of pathogens is effective handwashing". In the developed world, hand washing is mandatory in most health care settings and required by many different regulators.In the United States, OSHA standards require that employers must provide readily accessible hand washing facilities, and must ensure that employees wash hands and any other skin with soap and water or flush mucous membranes with water as soon as feasible after contact with blood or other potentially infectious materials (OPIM).In the UK healthcare professionals have adopted the Ayliffe Technique, based on the 6 step method developed by Graham Ayliffe, JR Babb and AH Quoraishi. Drying is an essential part of the hand hygiene process. In November 2008, a non-peer-reviewed study was presented to the European Tissue Symposium by the University of Westminster, London, comparing the bacteria levels present after the use of paper towels, warm air hand dryers, and modern jet-air hand dryers. Of those three methods, only paper towels reduced the total number of bacteria on hands, with "through-air dried" towels the most effective.The presenters also carried out tests to establish whether there was the potential for cross-contamination of other washroom users and the washroom environment as a result of each type of drying method. They found that: the jet air dryer, which blows air out of the unit at claimed speeds of 400 mph, was capable of blowing micro-organisms from the hands and the unit and potentially contaminating other washroom users and the washroom environment up to 2 metres away use of a warm air hand dryer spread micro-organisms up to 0.25 metres from the dryer paper towels showed no significant spread of micro-organisms.In 2005, in a study conducted by TUV Produkt und Umwelt, different hand drying methods were evaluated. The following changes in the bacterial count after drying the hands were observed: Cleaning, Disinfection, Sterilization The field of infection prevention describes a hierarchy of removal of microorganisms from surfaces including medical equipment and instruments. Cleaning is the lowest level, accomplishing substantial removal. Disinfection involves the removal of all pathogens other than bacterial spores. Sterilization is defined as the removal or destruction of ALL microorganisms including bacterial spores. Cleaning Cleaning is the first and simplest step in preventing the spread of infection via surfaces and fomites. Cleaning reduces microbial burden by chemical deadsorption of organisms (loosening bioburden/organisms from surfaces via cleaning chemicals), simple mechanical removal (rinsing, wiping), as well as disinfection (killing of organisms by cleaning chemicals).In order to reduce their chances to contract an infection, individuals are recommended to maintain a good hygiene by washing their hands after every contact with questionable areas or bodily fluids and by disposing of garbage at regular intervals to prevent germs from growing. Disinfection Disinfection uses liquid chemicals on surfaces and at room temperature to kill disease causing microorganisms. Ultraviolet light has also been used to disinfect the rooms of patients infected with Clostridium difficile after discharge. Disinfection is less effective than sterilization because it does not kill bacterial endospores.Along with ensuring proper hand washing techniques are followed, another major component to decrease the spread of disease is sanitation of all medical equipment. The ANA and AANA set guidelines for sterilization and disinfection based on the Spaulding Disinfection and Sterilization Classification Scheme (SDSCS). The SDSCS classifies sterilization techniques into three categories: critical, semi-critical, and non-critical. For critical situations, or situations involving contact with sterile tissue or the vascular system, sterilize devices with sterilants that destroy all bacteria, rinse with sterile water, and use chemical germicides. In semi-critical situations, or situations with contact of mucous membranes or non-intact skin, high-level disinfectants are required. Cleaning and disinfecting devices with high-level disinfectants, rinsing with sterile water, and drying all equipment surfaces to prevent microorganism growth are methods nurses and doctors must follow. For non-critical situations, or situations involving electronic devices, stethoscopes, blood pressure cuffs, beds, monitors and other general hospital equipment, intermediate level disinfection is required. "Clean all equipment between patients with alcohol, use protective covering for non-critical surfaces that are difficult to clean, and hydrogen peroxide gas. . .for reusable items that are difficult to clean." Sterilization Sterilization is a process intended to kill all microorganisms and is the highest level of microbial kill that is possible.Sterilization, if performed properly, is an effective way of preventing Infections from spreading. It should be used for the cleaning of medical instruments and any type of medical item that comes into contact with the blood stream and sterile tissues.There are four main ways in which such items are usually sterilized: autoclave (by using high-pressure steam), dry heat (in an oven), by using chemical sterilants such as glutaraldehydes or formaldehyde solutions or by exposure to ionizing radiation. The first two are the most widely used methods of sterilization mainly because of their accessibility and availability. Steam sterilization is one of the most effective types of sterilizations, if done correctly which is often hard to achieve. Instruments that are used in health care facilities are usually sterilized with this method. The general rule in this case is that in order to perform an effective sterilization, the steam must get into contact with all the surfaces that are meant to be disinfected. On the other hand, dry heat sterilization, which is performed with the help of an oven, is also an accessible type of sterilization, although it can only be used to disinfect instruments that are made of metal or glass. The very high temperatures needed to perform sterilization in this way are able to melt the instruments that are not made of glass or metal.Effectiveness of the sterilizer, for example a steam autoclave is determined in three ways. First, mechanical indicators and gauges on the machine itself indicate proper operation of the machine. Second heat sensitive indicators or tape on the sterilizing bags change color which indicate proper levels of heat or steam. And, third (most importantly) is biological testing in which a microorganism that is highly heat and chemical resistant (often the bacterial endospore) is selected as the standard challenge. If the process kills this microorganism, the sterilizer is considered to be effective.Steam sterilization is done at a temperature of 121 C (250 F) with a pressure of 209 kPa (~2atm). In these conditions, rubber items must be sterilized for 20 minutes, and wrapped items 134 C with pressure of 310 kPa for 7 minutes. The time is counted once the temperature that is needed has been reached. Steam sterilization requires four conditions in order to be efficient: adequate contact, sufficiently high temperature, correct time and sufficient moisture. Sterilization using steam can also be done at a temperature of 132 C (270 F), at a double pressure.Dry heat sterilization is performed at 170 C (340 F) for one hour or two hours at a temperature of 160 C (320 F). Dry heat sterilization can also be performed at 121 C, for at least 16 hours.Chemical sterilization, also referred to as cold sterilization, can be used to sterilize instruments that cannot normally be disinfected through the other two processes described above. The items sterilized with cold sterilization are usually those that can be damaged by regular sterilization. A variety of chemicals can be used including aldehydes, hydrogen peroxide, and peroxyacetic acid. Commonly, glutaraldehydes and formaldehyde are used in this process, but in different ways. When using the first type of disinfectant, the instruments are soaked in a 2–4% solution for at least 10 hours while a solution of 8% formaldehyde will sterilize the items in 24 hours or more. Chemical sterilization is generally more expensive than steam sterilization and therefore it is used for instruments that cannot be disinfected otherwise. After the instruments have been soaked in the chemical solutions, they must be rinsed with sterile water which will remove the residues from the disinfectants. This is the reason why needles and syringes are not sterilized in this way, as the residues left by the chemical solution that has been used to disinfect them cannot be washed off with water and they may interfere with the administered treatment. Although formaldehyde is less expensive than glutaraldehydes, it is also more irritating to the eyes, skin and respiratory tract and is classified as a potential carcinogen, so it is used much less commonly. Ionizing radiation is typically used only for sterilizing items for which none of the above methods are practical, because of the risks involved in the process Personal protective equipment Personal protective equipment (PPE) is specialized clothing or equipment worn by a worker for protection against a hazard. The hazard in a health care setting is exposure to blood, saliva, or other bodily fluids or aerosols that may carry infectious materials such as Hepatitis C, HIV, or other blood borne or bodily fluid pathogen. PPE prevents contact with a potentially infectious material by creating a physical barrier between the potential infectious material and the healthcare worker.The United States Occupational Safety and Health Administration (OSHA) requires the use of personal protective equipment (PPE) by workers to guard against blood borne pathogens if there is a reasonably anticipated exposure to blood or other potentially infectious materials.Components of PPE include gloves, gowns, bonnets, shoe covers, face shields, CPR masks, goggles, surgical masks, and respirators. How many components are used and how the components are used is often determined by regulations or the infection control protocol of the facility in question, which in turn are derived from knowledge of the mechanism of transmission of the pathogen(s) of concern. Many or most of these items are disposable to avoid carrying infectious materials from one patient to another patient and to avoid difficult or costly disinfection. In the US, OSHA requires the immediate removal and disinfection or disposal of a workers PPE prior to leaving the work area where exposure to infectious material took place. For health care professionals who may come into contact with highly infectious bodily fluids, using personal protective coverings on exposed body parts improves protection. Breathable personal protective equipment improves user-satisfaction and may offer a similar level of protection. In addition, adding tabs and other modifications to the protective equipment may reduce the risk of contamination during donning and doffing (putting on and taking off the equipment). Implementing an evidence-based donning and doffing protocol such as a one-step glove and gown removal technique, giving oral instructions while donning and doffing, double gloving, and the use of glove disinfection may also improve protection for health care professionals.Guidelines set by the ANA and ANAA for proper use of disposable gloves include, removing and replacing gloves frequently and when they are contaminated, damaged, or in between treatment of multiple patients. When removing gloves, “grasp outer edge of glove near wrist, peel away from hand turning inside out, hold removed glove in opposite gloved hand, slide ungloved finger under wrist of gloved hand so finger is inside gloved area, peel off the glove from inside creating a ‘bag’ for both gloves, dispose of gloves in proper waste receptacle”.The inappropriate use of PPE equipment such as gloves, has been linked to an increase in rates of the transmission of infection, and the use of such must be compatible with the other particular hand hygiene agents used. Research studies in the form of randomized controlled trials and simulation studies are needed to determine the most effective types of PPE for preventing the transmission of infectious diseases to healthcare workers. There is low quality evidence that supports making improvements or modifications to personal protective equipment in order to help decrease contamination. Examples of modifications include adding tabs to masks or gloves to ease removal and designing protective gowns so that gloves are removed at the same time. In addition, there is weak evidence that the following PPE approaches or techniques may lead to reduced contamination and improved compliance with PPE protocols: Wearing double gloves, following specific doffing (removal) procedures such as those from the CDC, and providing people with spoken instructions while removing PPE. Antimicrobial surfaces Microorganisms are known to survive on non-antimicrobial inanimate touch surfaces (e.g., bedrails, over-the-bed trays, call buttons, bathroom hardware, etc.) for extended periods of time. This can be especially troublesome in hospital environments where patients with immunodeficiencies are at enhanced risk for contracting nosocomial infections. Products made with antimicrobial copper alloy (brasses, bronzes, cupronickel, copper-nickel-zinc, and others) surfaces destroy a wide range of microorganisms in a short period of time. The United States Environmental Protection Agency has approved the registration of 355 different antimicrobial copper alloys and one synthetic copper-infused hard surface that kill E. coli O157:H7, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus, Enterobacter aerogenes, and Pseudomonas aeruginosa in less than 2 hours of contact. Other investigations have demonstrated the efficacy of antimicrobial copper alloys to destroy Clostridium difficile, influenza A virus, adenovirus, and fungi. As a public hygienic measure in addition to regular cleaning, antimicrobial copper alloys are being installed in healthcare facilities in the UK, Ireland, Japan, Korea, France, Denmark, and Brazil. The synthetic hard surface is being installed in the United States as well as in Israel. Vaccination of health care workers Health care workers may be exposed to certain infections in the course of their work. Vaccines are available to provide some protection to workers in a healthcare setting. Depending on regulation, recommendation, the specific work function, or personal preference, healthcare workers or first responders may receive vaccinations for hepatitis B; influenza; measles, mumps and rubella; Tetanus, diphtheria, pertussis; N. meningitidis; and varicella. Surveillance for infections Surveillance is the act of infection investigation using the CDC definitions. Determining the presence of a hospital acquired infection requires an infection control practitioner (ICP) to review a patients chart and see if the patient had the signs and symptom of an infection. Surveillance definitions exist for infections of the bloodstream, urinary tract, pneumonia, surgical sites and gastroenteritis. Surveillance traditionally involved significant manual data assessment and entry in order to assess preventative actions such as isolation of patients with an infectious disease. Increasingly, computerized software solutions are becoming available that assess incoming risk messages from microbiology and other online sources. By reducing the need for data entry, software can reduce the data workload of ICPs, freeing them to concentrate on clinical surveillance. As of 1998, approximately one third of healthcare acquired infections were preventable. Surveillance and preventative activities are increasingly a priority for hospital staff. The Study on the Efficacy of Nosocomial Infection Control (SENIC) project by the U.S. CDC found in the 1970s that hospitals reduced their nosocomial infection rates by approximately 32 per cent by focusing on surveillance activities and prevention efforts. Isolation and quarantine In healthcare facilities, medical isolation refers to various physical measures taken to interrupt nosocomial spread of contagious diseases. Various forms of isolation exist, and are applied depending on the type of infection and agent involved, and its route of transmission, to address the likelihood of spread via airborne particles or droplets, by direct skin contact, or via contact with body fluids.In cases where infection is merely suspected, individuals may be quarantined until the incubation period has passed and the disease manifests itself or the person remains healthy. Groups may undergo quarantine, or in the case of communities, a cordon sanitaire may be imposed to prevent infection from spreading beyond the community, or in the case of protective sequestration, into a community. Public health authorities may implement other forms of social distancing, such as school closings, when needing to control an epidemic. Barriers and facilitators of implementing infection prevention and control guidelines Barriers to the ability of healthcare workers to follow PPE and infection control guidelines include communication of the guidelines, workplace support (manager support), the culture of use at the workplace, adequate training, the amount of physical space in the facility, access to PPE, and healthcare worker motivation to provide good patient care.Facilitators include the importance of including all the staff in a facility (healthcare workers and support staff) should be done when guidelines are implemented. Outbreak investigation When an unusual cluster of illness is noted, infection control teams undertake an investigation to determine whether there is a true disease outbreak, a pseudo-outbreak (a result of contamination within the diagnostic testing process), or just random fluctuation in the frequency of illness. If a true outbreak is discovered, infection control practitioners try to determine what permitted the outbreak to occur, and to rearrange the conditions to prevent ongoing propagation of the infection. Often, breaches in good practice are responsible, although sometimes other factors (such as construction) may be the source of the problem.Outbreaks investigations have more than a single purpose. These investigations are carried out in order to prevent additional cases in the current outbreak, prevent future outbreaks, learn about a new disease or learn something new about an old disease. Reassuring the public, minimizing the economic and social disruption as well as teaching epidemiology are some other obvious objectives of outbreak investigations.According to the WHO, outbreak investigations are meant to detect what is causing the outbreak, how the pathogenic agent is transmitted, where it all started from, what is the carrier, what is the population at risk of getting infected and what are the risk factors. Training in infection control and health care epidemiology Practitioners can come from several different educational streams. Many begin as nurses, some as medical technologists (particularly in clinical microbiology), and some as physicians (typically infectious disease specialists). Specialized training in infection control and health care epidemiology are offered by the professional organizations described below. Physicians who desire to become infection control practitioners often are trained in the context of an infectious disease fellowship. Training that is conducted "face to face", via a computer, or via video conferencing may help improve compliance and reduce errors when compared with "folder based" training (providing health care professionals with written information or instructions).In the United States, Certification Board of Infection Control and Epidemiology is a private company that certifies infection control practitioners based on their educational background and professional experience, in conjunction with testing their knowledge base with standardized exams. The credential awarded is CIC, Certification in Infection Control and Epidemiology. It is recommended that one has 2 years of Infection Control experience before applying for the exam. Certification must be renewed every five years.A course in hospital epidemiology (infection control in the hospital setting) is offered jointly each year by the Centers for Disease Control and Prevention (CDC) and the Society for Healthcare Epidemiology of America. Standardization Australia In 2002, the Royal Australian College of General Practitioners published a revised standard for office-based infection control which covers the sections of managing immunisation, sterilisation and disease surveillance. However, the document on the personal hygiene of health workers is only limited to hand hygiene, waste and linen management, which may not be sufficient since some of the pathogens are air-borne and could be spread through air flow.Since 1 November 2019, the Australian Commission on Safety and Quality in Health Care has managed the Hand Hygiene initiative in Australia, an initiative focused on improving hand hygiene practices to reduce the incidence of healthcare-associated infections. United States Currently, the federal regulation that describes infection control standards, as related to occupational exposure to potentially infectious blood and other materials, is found at 29 CFR Part 1910.1030 Bloodborne pathogens. See also Pandemic prevention – Organization and management of preventive measures against pandemics Wong, P., & Lim, W. Y. (2020). Aligning difficult airway guidelines with the anesthetic COVID-19 guidelines to develop a COVID-19 difficult airway strategy: A narrative review. Journal of Anesthesia, 34(6), 924-943. https://doi.org/10.1007/s00540-020-02819-2 Footnotes External links Association for Professionals in Infection Control and Epidemiology is primarily composed of infection prevention and control professionals with nursing or medical technology backgrounds The Society for Healthcare Epidemiology of America is more heavily weighted towards practitioners who are physicians or doctoral-level epidemiologists. Regional Infection Control Networks The Certification Board of Infection Control and Epidemiology, Inc. Association for Professionals in Infection Control and Epidemiology

Please give me a short description about Intermittent claudication , Aarogya

Intermittent claudication

Intermittent claudication, also known as vascular claudication, is a symptom that describes muscle pain on mild exertion (ache, cramp, numbness or sense of fatigue), classically in the calf muscle, which occurs during exercise, such as walking, and is relieved by a short period of rest. It is classically associated with early-stage peripheral artery disease, and can progress to critical limb ischemia unless treated or risk factors are modified and maintained. Claudication derives from the Latin verb claudicare, "to limp". Signs and symptoms One of the hallmarks of arterial claudication is that it occurs intermittently. It disappears after a very brief rest and the patient can start walking again until the pain recurs. The following signs are general signs of atherosclerosis of the lower extremity arteries: cyanosis atrophic changes like loss of hair, shiny skin decreased temperature decreased pulse redness when limb is returned to a "dependent" position (part of Buergers test)The six "P"s of ischemia Pain Pallor (increased) Pulse (decreased) Perishing cold Paraesthesia Paralysis Causes Most commonly, intermittent (or vascular or arterial) claudication is due to peripheral arterial disease which implies significant atherosclerotic blockages resulting in arterial insufficiency. Other uncommon causes are coarctation of the aorta, Trousseau disease and Beurgers disease (Thromboangiitis obliterans), in which vasculitis occurs. Raynauds phenomenon functional vasospasm. It is distinct from neurogenic claudication, which is associated with lumbar spinal stenosis. It is strongly associated with smoking, hypertension, and diabetes. Diagnosis Intermittent claudication is a symptom and is by definition diagnosed by a patient reporting a history of leg pain with walking relieved by rest. However, as other conditions such as sciatica can mimic intermittent claudication, testing is often performed to confirm the diagnosis of peripheral artery disease.Magnetic resonance angiography and duplex ultrasonography appear to be slightly more cost-effective in diagnosing peripheral artery disease among people with intermittent claudication than projectional angiography. Treatment Exercise can improve symptoms, as can revascularization. Both together may be better than one intervention of its own. In people with stable leg pain, exercise, such as strength training, polestriding and upper or lower limb exercises, compared to usual care or placebo improves maximum walking time, pain-free walking distance and maximum walking distance. Alternative exercise modes, such as cycling, strength training and upper-arm ergometry compared to supervised walking programmes showed no difference in maximum walking distance or pain-free walking distance for people with intermittent claudication.Pharmacological options exist, as well. Medicines that control lipid profile, diabetes, and hypertension may increase blood flow to the affected muscles and allow for increased activity levels. Angiotensin converting enzyme inhibitors, adrenergic agents such as alpha-1 blockers and beta-blockers and alpha-2 agonists, antiplatelet agents (aspirin and clopidogrel), naftidrofuryl, pentoxifylline, and cilostazol (selective PDE3 inhibitor) are used for the treatment of intermittent claudication. However, medications will not remove the blockages from the body. Instead, they simply improve blood flow to the affected area.Catheter-based intervention is also an option. Atherectomy, stenting, and angioplasty to remove or push aside the arterial blockages are the most common procedures for catheter-based intervention. These procedures can be performed by interventional radiologists, interventional cardiologists, vascular surgeons, and thoracic surgeons, among others.Surgery is the last resort; vascular surgeons can perform either endarterectomies on arterial blockages or perform an arterial bypass. However, open surgery poses a host of risks not present with catheter-based interventions. Epidemiology Atherosclerosis affects up to 10% of the Western population older than 65 years and for intermittent claudication this number is around 5%. Intermittent claudication most commonly manifests in men older than 50 years.One in five of the middle-aged (65–75 years) population of the United Kingdom have evidence of peripheral arterial disease on clinical examination, although only a quarter of them have symptoms. The most common symptom is muscle pain in the lower limbs on exercise—intermittent claudication. See also Peripheral artery disease References Further reading Burns P, Gough S, Bradbury AW (March 2003). "Management of peripheral arterial disease in primary care". BMJ. 326 (7389): 584–8. doi:10.1136/bmj.326.7389.584. PMC 1125476. PMID 12637405. Shammas NW (2007). "Epidemiology, classification, and modifiable risk factors of peripheral arterial disease". Vasc Health Risk Manag. 3 (2): 229–34. doi:10.2147/vhrm.2007.3.2.229. PMC 1994028. PMID 17580733. External links Cochrane Peripheral Vascular Diseases Review Group

Hi Aarogya, could you help me understand about Intermittent explosive disorder

Intermittent explosive disorder

Intermittent explosive disorder (sometimes abbreviated as IED) is a behavioral disorder characterized by explosive outbursts of anger and/or violence, often to the point of rage, that are disproportionate to the situation at hand (e.g., impulsive shouting, screaming or excessive reprimanding triggered by relatively inconsequential events). Impulsive aggression is not premeditated, and is defined by a disproportionate reaction to any provocation, real or perceived. Some individuals have reported affective changes prior to an outburst, such as tension, mood changes, energy changes, etc.The disorder is currently categorized in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) under the "Disruptive, Impulse-Control, and Conduct Disorders" category. The disorder itself is not easily characterized and often exhibits comorbidity with other mood disorders, particularly bipolar disorder. Individuals diagnosed with IED report their outbursts as being brief (lasting less than an hour), with a variety of bodily symptoms (sweating, stuttering, chest tightness, twitching, palpitations) reported by a third of one sample. Aggressive acts are frequently reported to be accompanied by a sensation of relief and in some cases pleasure, but often followed by later remorse. Pathophysiology Impulsive behavior, and especially impulsive violence predisposition, have been correlated to a low brain serotonin turnover rate, indicated by a low concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). This substrate appears to act on the suprachiasmatic nucleus in the hypothalamus, which is the target for serotonergic output from the dorsal and median raphe nuclei playing a role in maintaining the circadian rhythm and regulation of blood sugar. A tendency towards low 5-HIAA may be hereditary. A putative hereditary component to low CSF 5-HIAA and concordantly possibly to impulsive violence has been proposed. Other traits that correlate with IED are low vagal tone and increased insulin secretion. A suggested explanation for IED is a polymorphism of the gene for tryptophan hydroxylase, which produces a serotonin precursor; this genotype is found more commonly in individuals with impulsive behavior.IED may also be associated with damage or lesions in the prefrontal cortex, with damage to these areas, including the amygdala and hippocampus, increasing the incidences of impulsive and aggressive behavior and the inability to predict the outcomes of an individuals own actions. Lesions in these areas are also associated with improper blood sugar control, leading to decreased brain function in these areas, which are associated with planning and decision making. A national sample in the United States estimated that 16 million Americans may fit the criteria for IED. Diagnosis DSM-5 diagnosis The current DSM-5 criteria for Intermittent Explosive Disorder include: Recurrent outbursts that demonstrate an inability to control impulses, including either of the following: Verbal aggression (tantrums, verbal arguments, or fights) or physical aggression that occurs twice in a week-long period for at least three months and does not lead to the destruction of property or physical injury (Criterion A1) Three outbursts that involve injury or destruction within a year-long period (Criterion A2) Aggressive behavior is grossly disproportionate to the magnitude of the psychosocial stressors (Criterion B) The outbursts are not premeditated and serve no premeditated purpose (Criterion C) The outbursts cause distress or impairment of functioning or lead to financial or legal consequences (Criterion D) The individual must be at least six years old (Criterion E) The recurrent outbursts cannot be explained by another mental disorder and are not the result of another medical disorder or substance use (Criterion F)It is important to note that DSM-5 now includes two separate criteria for types of aggressive outbursts (A1 and A2) which have empirical support: Criterion A1: Episodes of verbal and/or non-damaging, nondestructive, or non-injurious physical assault that occur, on average, twice weekly for three months. These could include temper tantrums, tirades, verbal arguments/fights, or assault without damage. This criterion includes high frequency/low-intensity outbursts. Criterion A2: More severe destructive/assaultive episodes which are more infrequent and occur, on average, three times within a twelve-month period. These could be destroying an object without regard to value, assaulting an animal or individual. This criterion includes high-intensity/low-frequency outbursts. DSM-IV diagnosis The past DSM-IV criteria for IED were similar to the current criteria, however, verbal aggression was not considered as part of the diagnostic criteria. The DSM-IV diagnosis was characterized by the occurrence of discrete episodes of failure to resist aggressive impulses that result in violent assault or destruction of property. Additionally, the degree of aggressiveness expressed during an episode should be grossly disproportionate to provocation or precipitating psychosocial stressor, and, as previously stated, diagnosis is made when certain other mental disorders have been ruled out, e.g., a head injury, Alzheimers disease, etc., or due to substance use or medication. Diagnosis is made using a psychiatric interview to affective and behavioral symptoms to the criteria listed in the DSM-IV.The DSM-IV-TR was very specific in its definition of Intermittent Explosive Disorder which was defined, essentially, by the exclusion of other conditions. The diagnosis required: several episodes of impulsive behavior that result in serious damage to either persons or property, wherein the degree of the aggressiveness is grossly disproportionate to the circumstances or provocation, and the episodic violence cannot be better accounted for by another mental or physical medical condition. Differential diagnosis Many psychiatric disorders and some substance use disorders are associated with increased aggression and are frequently comorbid with IED, often making differential diagnosis difficult. Individuals with IED are, on average, four times more likely to develop depression or anxiety disorders, and three times more likely to develop substance use disorders. Bipolar disorder has been linked to increased agitation and aggressive behavior in some individuals, but for these individuals, aggressiveness is limited to manic and/or depressive episodes, whereas individuals with IED experience aggressive behavior even during periods with a neutral or positive mood.In one clinical study, the two disorders co-occurred 60% of the time. Patients report manic-like symptoms occurring just before outbursts and continuing throughout. According to a study, the average onset age of IED was around five years earlier than the onset age of bipolar disorder, indicating a possible correlation between the two.Similarly, alcohol and other substance use disorders may exhibit increased aggressiveness, but unless this aggression is experienced outside of periods of acute intoxication and withdrawal, no diagnosis of IED is given. For chronic disorders, such as PTSD, it is important to assess whether the level of aggression met IED criteria before the development of another disorder. In antisocial personality disorder, interpersonal aggression is usually instrumental in nature (i.e., motivated by tangible rewards), whereas IED is more of an impulsive, unpremeditated reaction to situational stress. Treatment Although there is no cure, treatment is attempted through cognitive behavioral therapy and psychotropic medication regimens, though the pharmaceutical options have shown limited success. Therapy aids in helping the patient recognize the impulses in hopes of achieving a level of awareness and control of the outbursts, along with treating the emotional stress that accompanies these episodes. Multiple drug regimens are frequently indicated for IED patients. Cognitive Relaxation and Coping Skills Therapy (CRCST) has shown preliminary success in both group and individual settings compared to waitlist control groups. This therapy consists of 12 sessions, the first three focusing on relaxation training, then cognitive restructuring, then exposure therapy. The final sessions focus on resisting aggressive impulses and other preventative measures.In France, antipsychotics such as cyamemazine, levomepromazine and loxapine are sometimes used.Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs, including fluoxetine, fluvoxamine, and sertraline) appear to alleviate some pathopsychological symptoms. GABAergic mood stabilizers and anticonvulsive drugs such as gabapentin, lithium, carbamazepine, and divalproex seem to aid in controlling the incidence of outbursts. Anxiolytics help alleviate tension and may help reduce explosive outbursts by increasing the provocative stimulus tolerance threshold, and are especially indicated in patients with comorbid obsessive-compulsive or other anxiety disorders. However, certain anxiolytics are known to increase anger and irritability in some individuals, especially benzodiazepines. Epidemiology Two epidemiological studies of community samples approximated the lifetime prevalence of IED to be 4–6%, depending on the criteria set used. A Ukrainian study found comparable rates of lifetime IED (4.2%), suggesting that a lifetime prevalence of IED of 4–6% is not limited to American samples. One-month and one-year point prevalences of IED in these studies were reported as 2.0% and 2.7%, respectively. Extrapolating to the national level, 16.2 million Americans would have IED during their lifetimes and as many as 10.5 million in any year and 6 million in any month. Among a clinical population, a 2005 study found the lifetime prevalence of IED to be 6.3%.Prevalence appears to be higher in men than in women.Of US subjects with IED, 67.8% had engaged in direct interpersonal aggression, 20.9% in threatened interpersonal aggression, and 11.4% in aggression against objects. Subjects reported engaging in 27.8 high-severity aggressive acts during their worst year, with 2–3 outbursts requiring medical attention. Across the lifespan, the mean value of property damage due to aggressive outbursts was $1603.A study in the March 2016 Journal of Clinical Psychiatry suggests a relationship between infection with the parasite Toxoplasma gondii and psychiatric aggression such as IED. History In the first edition of the American Psychiatric Associations Diagnostic and Statistical Manual (DSM-I), a disorder of impulsive aggression was referred to as a passive-aggressive personality type (aggressive type). This construct was characterized by a "persistent reaction to frustration are "generally excitable, aggressive, and over-responsive to environmental pressures" with "gross outbursts of rage or of verbal or physical aggressiveness different from their usual behavior".In the third edition (DSM-III), this was for the first time codified as intermittent explosive disorder and assigned clinical disorder status under Axis I. However, some researchers saw the criteria as poorly operationalized. About 80% of individuals who would now be diagnosed with the disorder would have been excluded.In the DSM-IV, the criteria were improved but still lacked objective criteria for the intensity, frequency, and nature of aggressive acts to meet criteria for IED. This led some researchers to adopt alternate criteria set with which to conduct research, known as the IED-IR (Integrated Research). The severity and frequency of aggressive behavior required for the diagnosis were clearly operationalized, the aggressive acts were required to be impulsive in nature, subjective distress was required to precede the explosive outbursts, and the criteria allowed for comorbid diagnoses with borderline personality disorder and antisocial personality disorder. These research criteria became the basis for the DSM-5 diagnosis. In the current version of the DSM (DSM-5), the disorder appears under the "Disruptive, Impulse-Control, and Conduct Disorders" category. In the DSM-IV, physical aggression was required to meet the criteria for the disorder, but these criteria were modified in the DSM-5 to include verbal aggression and non-destructive/noninjurious physical aggression. The listing was also updated to specify frequency criteria. Further, aggressive outbursts are now required to be impulsive in nature and must cause marked distress, impairment, or negative consequences for the individual. Individuals must be at least six years old to receive the diagnosis. The text also clarified the disorders relationship to other disorders such as ADHD and disruptive mood dysregulation disorder. See also Episodic dyscontrol syndrome Passive–aggressive personality disorder References == External links ==

Hello Aarogya, what is Interstitial cystitis

Interstitial cystitis

Interstitial cystitis (IC), a type of bladder pain syndrome (BPS), is chronic pain in the bladder and pelvic floor of unknown cause. It is the urologic chronic pelvic pain syndrome of women. Symptoms include feeling the need to urinate right away, needing to urinate often, and pain with sex. IC/BPS is associated with depression and lower quality of life. Many of those affected also have irritable bowel syndrome and fibromyalgia.The cause of interstitial cystitis is unknown. While it can, it does not typically run in a family. The diagnosis is usually based on the symptoms after ruling out other conditions. Typically the urine culture is negative. Ulceration or inflammation may be seen on cystoscopy. Other conditions which can produce similar symptoms include overactive bladder, urinary tract infection (UTI), sexually transmitted infections, prostatitis, endometriosis in females, and bladder cancer.There is no cure for interstitial cystitis and management of this condition can be challenging. Treatments that may improve symptoms include lifestyle changes, medications, or procedures. Lifestyle changes may include stopping smoking and reducing stress. Medications may include ibuprofen, pentosan polysulfate, or amitriptyline. Procedures may include bladder distention, nerve stimulation, or surgery. Pelvic floor exercises and long term antibiotics are not recommended.In the United States and Europe, it is estimated that around 0.5% of people are affected. Women are affected about five times as often as men. Onset is typically in middle age. The term "interstitial cystitis" first came into use in 1887. Signs and symptoms The most common symptoms of IC/BPS are suprapubic pain, urinary frequency, painful sexual intercourse, and waking up from sleep to urinate.In general, symptoms may include painful urination described as a burning sensation in the urethra during urination, pelvic pain that is worsened with the consumption of certain foods or drinks, urinary urgency, and pressure in the bladder or pelvis. Other frequently described symptoms are urinary hesitancy (needing to wait for the urinary stream to begin, often caused by pelvic floor dysfunction and tension), and discomfort and difficulty driving, working, exercising, or traveling. Pelvic pain experienced by those with IC typically worsens with filling of the urinary bladder and may improve with urination.During cystoscopy, 5–10% of people with IC are found to have Hunners ulcers. A person with IC may have discomfort only in the urethra, while another might struggle with pain in the entire pelvis. Interstitial cystitis symptoms usually fall into one of two patterns: significant suprapubic pain with little frequency or a lesser amount of suprapubic pain but with increased urinary frequency. Association with other conditions Some people with IC/BPS have been diagnosed with other conditions such as irritable bowel syndrome (IBS), fibromyalgia, chronic fatigue syndrome, allergies, Sjögren syndrome, which raises the possibility that interstitial cystitis may be caused by mechanisms that cause these other conditions. There is also some evidence of an association between urologic pain syndromes, such as IC/BPS and CP/CPPS, with non-celiac gluten sensitivity in some people.In addition, men with IC/PBS are frequently diagnosed as having chronic nonbacterial prostatitis, and there is an extensive overlap of symptoms and treatment between the two conditions, leading researchers to posit that the conditions may share the same cause and pathology. Causes The cause of IC/BPS is not known. However, several explanations have been proposed and include the following: autoimmune theory, nerve theory, mast cell theory, leaky lining theory, infection theory, and a theory of production of a toxic substance in the urine. Other suggested etiological causes are neurologic, allergic, genetic, and stress-psychological. In addition, recent research shows that those with IC may have a substance in the urine that inhibits the growth of cells in the bladder epithelium. An infection may then predispose those people to develop IC. Evidence from clinical and laboratory studies confirms that mast cells play a central role in IC/BPS possibly due to their ability to release histamine and cause pain, swelling, scarring, and interfere with healing. Research has shown a proliferation of nerve fibers is present in the bladders of people with IC which is absent in the bladders of people who have not been diagnosed with IC.Regardless of the origin, most people with IC/BPS struggle with a damaged urothelium, or bladder lining. When the surface glycosaminoglycan (GAG) layer is damaged (via a urinary tract infection (UTI), excessive consumption of coffee or sodas, traumatic injury, etc.), urinary chemicals can "leak" into surrounding tissues, causing pain, inflammation, and urinary symptoms. Oral medications like pentosan polysulfate and medications placed directly into the bladder via a catheter sometimes work to repair and rebuild this damaged/wounded lining, allowing for a reduction in symptoms. Most literature supports the belief that ICs symptoms are associated with a defect in the bladder epithelium lining, allowing irritating substances in the urine to penetrate into the bladder—a breakdown of the bladder lining (also known as the adherence theory). Deficiency in this glycosaminoglycan layer on the surface of the bladder results in increased permeability of the underlying submucosal tissues.GP51 has been identified as a possible urinary biomarker for IC with significant variations in GP51 levels in those with IC when compared to individuals without interstitial cystitis.Numerous studies have noted the link between IC, anxiety, stress, hyper-responsiveness, and panic. Another proposed cause for interstitial cystitis is that the bodys immune system attacks the bladder. Biopsies on the bladder walls of people with IC usually contain mast cells. Mast cells containing histamine packets gather when an allergic reaction is occurring. The body identifies the bladder wall as a foreign agent, and the histamine packets burst open and attack. The body attacks itself, which is the basis of autoimmune disorders. Additionally, IC may be triggered by an unknown toxin or stimulus which causes nerves in the bladder wall to fire uncontrollably. When they fire, they release substances called neuropeptides that induce a cascade of reactions that cause pain in the bladder wall. Genes Some genetic subtypes, in some people, have been linked to the disorder. An antiproliferative factor is secreted by the bladders of people with IC/BPS which inhibits bladder cell proliferation, thus possibly causing the missing bladder lining. PAND, at gene map locus 13q22–q32, is associated with a constellation of disorders (a "pleiotropic syndrome") including IC/BPS and other bladder and kidney problems, thyroid diseases, serious headaches/migraines, panic disorder, and mitral valve prolapse. Diagnosis A diagnosis of IC/BPS is one of exclusion, as well as a review of clinical symptoms. The American Urological Association Guidelines recommend starting with a careful history of the person, physical examination and laboratory tests to assess and document symptoms of interstitial cytitis, as well as other potential disorders. The KCl test, also known as the potassium sensitivity test, is no longer recommended. The test uses a mild potassium solution to evaluate the integrity of the bladder wall. Though the latter is not specific for IC/BPS, it has been determined to be helpful in predicting the use of compounds, such as pentosan polysulphate, which are designed to help repair the GAG layer.For complicated cases, the use of hydrodistention with cystoscopy may be helpful. Researchers, however, determined that this visual examination of the bladder wall after stretching the bladder was not specific for IC/BPS and that the test, itself, can contribute to the development of small glomerulations (petechial hemorrhages) often found in IC/BPS. Thus, a diagnosis of IC/BPS is one of exclusion, as well as a review of clinical symptoms. In 2006, the ESSIC society proposed more rigorous and demanding diagnostic methods with specific classification criteria so that it cannot be confused with other, similar conditions. Specifically, they require that a person must have pain associated with the bladder, accompanied by one other urinary symptom. Thus, a person with just frequency or urgency would be excluded from a diagnosis. Secondly, they strongly encourage the exclusion of confusable diseases through an extensive and expensive series of tests including (A) a medical history and physical exam, (B) a dipstick urinalysis, various urine cultures, and a serum PSA in men over 40, (C) flowmetry and post-void residual urine volume by ultrasound scanning and (D) cystoscopy. A diagnosis of IC/BPS would be confirmed with a hydrodistention during cystoscopy with biopsy.They also propose a ranking system based upon the physical findings in the bladder. People would receive a numeric and letter based score based upon the severity of their disease as found during the hydrodistention. A score of 1–3 would relate to the severity of the disease and a rating of A–C represents biopsy findings. Thus, a person with 1A would have very mild symptoms and disease while a person with 3C would have the worst possible symptoms. Widely recognized scoring systems such as the OLeary Sant symptom and problem score have emerged to evaluate the severity of IC symptoms such as pain and urinary symptoms. Differential diagnosis The symptoms of IC/BPS are often misdiagnosed as a urinary tract infection. However, IC/BPS has not been shown to be caused by a bacterial infection and antibiotics are an ineffective treatment. IC/BPS is commonly misdiagnosed as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men, and endometriosis and uterine fibroids (in women). Treatment In 2011, the American Urological Association released consensus-based guideline for the diagnosis and treatment of interstitial cystitis.They include treatments ranging from conservative to more invasive: First-line treatments — education, self care (diet modification), stress management Second-line treatments — physical therapy, oral medications (amitriptyline, cimetidine or hydroxyzine, pentosan polysulfate), bladder instillations (DMSO, heparin, or lidocaine) Third-line treatments — treatment of Hunners lesions (laser, fulguration or triamcinolone injection), hydrodistention (low pressure, short duration) Fourth-line treatments — neuromodulation (sacral or pudendal nerve) Fifth-line treatments — cyclosporine A, botulinum toxin (BTX-A) Sixth-line treatments — surgical intervention (urinary diversion, augmentation, cystectomy)The American Urological Association guidelines also listed several discontinued treatments, including long-term oral antibiotics, intravesical bacillus Calmette Guerin, intravesical resiniferatoxin), high-pressure and long-duration hydrodistention, and systemic glucocorticoids. Bladder distension Bladder distension while under general anesthesia, also known as hydrodistention (a procedure which stretches the bladder capacity), has shown some success in reducing urinary frequency and giving short-term pain relief to those with IC. However, it is unknown exactly how this procedure causes pain relief. Recent studies show pressure on pelvic trigger points can relieve symptoms. The relief achieved by bladder distensions is only temporary (weeks or months), so is not viable as a long-term treatment for IC/BPS. The proportion of people with IC/BPS who experience relief from hydrodistention is currently unknown and evidence for this modality is limited by a lack of properly controlled studies. Bladder rupture and sepsis may be associated with prolonged, high-pressure hydrodistention. Bladder instillations Bladder instillation of medication is one of the main forms of treatment of interstitial cystitis, but evidence for its effectiveness is currently limited. Advantages of this treatment approach include direct contact of the medication with the bladder and low systemic side effects due to poor absorption of the medication. Single medications or a mixture of medications are commonly used in bladder instillation preparations. Dimethyl sulfoxide (DMSO) is the only approved bladder instillation for IC/BPS yet it is much less frequently used in urology clinics.A 50% solution of DMSO had the potential to create irreversible muscle contraction. However, a lesser solution of 25% was found to be reversible. Long-term use of DMSO is questionable, as its mechanism of action is not fully understood though DMSO is thought to inhibit mast cells and may have anti-inflammatory, muscle-relaxing, and analgesic effects. Other agents used for bladder instillations to treat interstitial cystitis include: heparin, lidocaine, chondroitin sulfate, hyaluronic acid, pentosan polysulfate, oxybutynin, and botulinum toxin A. Preliminary evidence suggests these agents are efficacious in reducing symptoms of interstitial cystitis, but further study with larger, randomized, controlled clinical trials is needed. Diet Diet modification is often recommended as a first-line method of self-treatment for interstitial cystitis, though rigorous controlled studies examining the impact diet has on interstitial cystitis signs and symptoms are currently lacking. An increase in fiber intake may alleviate symptoms. Individuals with interstitial cystitis often experience an increase in symptoms when they consume certain foods and beverages. Avoidance of these potential trigger foods and beverages such as caffeine-containing beverages including coffee, tea, and soda, alcoholic beverages, chocolate, citrus fruits, hot peppers, and artificial sweeteners may be helpful in alleviating symptoms. Diet triggers vary between individuals with IC; the best way for a person to discover his or her own triggers is to use an elimination diet. Sensitivity to trigger foods may be reduced if calcium glycerophosphate and/or sodium bicarbonate is consumed. The foundation of therapy is a modification of diet to help people avoid those foods which can further irritate the damaged bladder wall.The mechanism by which dietary modification benefits people with IC is unclear. Integration of neural signals from pelvic organs may mediate the effects of diet on symptoms of IC. Medications The antihistamine hydroxyzine failed to demonstrate superiority over placebo in treatment of people with IC in a randomized, controlled, clinical trial.Amitriptyline has been shown to be effective in reducing symptoms such as chronic pelvic pain and nocturia in many people with IC/BPS with a median dose of 75 mg daily. In one study, the antidepressant duloxetine was found to be ineffective as a treatment, although a patent exists for use of duloxetine in the context of IC, and is known to relieve neuropathic pain. The calcineurin inhibitor cyclosporine A has been studied as a treatment for interstitial cystitis due to its immunosuppressive properties. A prospective randomized study found cyclosporine A to be more effective at treating IC symptoms than pentosan polysulfate, but also had more adverse effects.Oral pentosan polysulfate is believed to repair the protective glycosaminoglycan coating of the bladder, but studies have encountered mixed results when attempting to determine if the effect is statistically significant compared to placebo. Pelvic floor treatments Urologic pelvic pain syndromes, such as IC/BPS and CP/CPPS, are characterized by pelvic muscle tenderness, and symptoms may be reduced with pelvic myofascial physical therapy.This may leave the pelvic area in a sensitized condition, resulting in a loop of muscle tension and heightened neurological feedback (neural wind-up), a form of myofascial pain syndrome. Current protocols, such as the Wise–Anderson Protocol, largely focus on stretches to release overtensed muscles in the pelvic or anal area (commonly referred to as trigger points), physical therapy to the area, and progressive relaxation therapy to reduce causative stress.Pelvic floor dysfunction is a fairly new area of specialty for physical therapists worldwide. The goal of therapy is to relax and lengthen the pelvic floor muscles, rather than to tighten and/or strengthen them as is the goal of therapy for people with urinary incontinence. Thus, traditional exercises such as Kegel exercises, which are used to strengthen pelvic muscles, can provoke pain and additional muscle tension. A specially trained physical therapist can provide direct, hands on evaluation of the muscles, both externally and internally.A therapeutic wand can also be used to perform pelvic floor muscle myofascial release to provide relief. Surgery Surgery is rarely used for IC/BPS. Surgical intervention is very unpredictable, and is considered a treatment of last resort for severe refractory cases of interstitial cystitis. Some people who opt for surgical intervention continue to experience pain after surgery. Typical surgical interventions for refractory cases of IC/BPS include: bladder augmentation, urinary diversion, transurethral fulguration and resection of ulcers, and bladder removal (cystectomy).Neuromodulation can be successful in treating IC/BPS symptoms, including pain. One electronic pain-killing option is TENS. Percutaneous tibial nerve stimulation stimulators have also been used, with varying degrees of success. Percutaneous sacral nerve root stimulation was able to produce statistically significant improvements in several parameters, including pain. Alternative medicine There is little evidence looking at the effects of alternative medicine though their use is common. There is tentative evidence that acupuncture may help pain associated with IC/BPS as part of other treatments. Despite a scarcity of controlled studies on alternative medicine and IC/BPS, "rather good results have been obtained" when acupuncture is combined with other treatments.Biofeedback, a relaxation technique aimed at helping people control functions of the autonomic nervous system, has shown some benefit in controlling pain associated with IC/BPS as part of a multimodal approach that may also include medication or hydrodistention of the bladder. Prognosis IC/BPS has a profound impact on quality of life. A 2007 Finnish epidemiologic study showed that two-thirds of women at moderate to high risk of having interstitial cystitis reported impairment in their quality of life and 35% of people with IC reported an impact on their sexual life. A 2012 survey showed that among a group of adult women with symptoms of interstitial cystitis, 11% reported suicidal thoughts in the past two weeks. Other research has shown that the impact of IC/BPS on quality of life is severe and may be comparable to the quality of life experienced in end-stage kidney disease or rheumatoid arthritis.International recognition of interstitial cystitis has grown and international urology conferences to address the heterogeneity in diagnostic criteria have recently been held. IC/PBS is now recognized with an official disability code in the United States of America. Epidemiology IC/BPS affects men and women of all cultures, socioeconomic backgrounds, and ages. Although the disease was previously believed to be a condition of menopausal women, growing numbers of men and women are being diagnosed in their twenties and younger. IC/BPS is not a rare condition. Early research suggested that the number of IC/BPS cases ranged from 1 in 100,000 to 5.1 in 1,000 of the general population. In recent years, the scientific community has achieved a much deeper understanding of the epidemiology of interstitial cystitis. Recent studies have revealed that between 2.7 and 6.53 million women in the USA have symptoms of IC and up to 12% of women may have early symptoms of IC/BPS. Further study has estimated that the condition is far more prevalent in men than previously thought ranging from 1.8 to 4.2 million men having symptoms of interstitial cystitis.The condition is officially recognized as a disability in the United States. History Philadelphia surgeon Joseph Parrish published the earliest record of interstitial cystitis in 1836 describing three cases of severe lower urinary tract symptoms without the presence of a bladder stone. The term "interstitial cystitis" was coined by Dr. Alexander Skene in 1887 to describe the disease. In 2002, the United States amended the Social Security Act to include interstitial cystitis as a disability. The first guideline for diagnosis and treatment of interstitial cystitis is released by a Japanese research team in 2009. The American Urological Association released the first American clinical practice guideline for diagnosing and treating IC/BPS in 2011. Names Originally called interstitial cystitis, this disorder was renamed to interstitial cystitis/bladder pain syndrome (IC/BPS) in the 2002–2010 timeframe. In 2007, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) began using the umbrella term urologic chronic pelvic pain syndrome (UCPPS) to refer to pelvic pain syndromes associated with the bladder (e.g., interstitial cystitis/bladder pain syndrome) and with the prostate gland or pelvis (e.g., chronic prostatitis/chronic pelvic pain syndrome).In 2008, terms currently in use in addition to IC/BPS include painful bladder syndrome, bladder pain syndrome and hypersensitive bladder syndrome, alone and in a variety of combinations. These different terms are being used in different parts of the world. The term "interstitial cystitis" is the primary term used in ICD-10 and MeSH. Grover et al. said, "The International Continence Society named the disease interstitial cystitis/painful bladder syndrome (IC/PBS) in 2002 [Abrams et al. 2002], while the Multinational Interstitial Cystitis Association have labeled it as painful bladder syndrome/interstitial cystitis (PBS/IC) [Hanno et al. 2005]. Recently, the European Society for the study of Interstitial Cystitis (ESSIC) proposed the moniker, bladder pain syndrome (BPS) [van de Merwe et al. 2008]." See also Chronic prostatitis/chronic pelvic pain syndrome—women have vestigial prostate glands that may cause IC/BPS-like symptoms. Men with IC/BPS may have prostatitis, and vice versa. Overactive bladder Trigger point—a key to myofascial pain syndrome. References External links Interstitial cystitis at Curlie Parsons, J. Kellogg; Parsons, C. Lowell (2004). "The Historical Origins of Interstitial Cystitis". The Journal of Urology. 171 (1): 20–2. doi:10.1097/01.ju.0000099890.35040.8d. PMID 14665834. The National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC) Homma, Yukio; Ueda, Tomohiro; Tomoe, Hikaru; Lin, Alex TL; Kuo, Hann-Chorng; Lee, Ming-Huei; Lee, Jeong Gu; Kim, Duk Yoon; Lee, Kyu-Sung (2009). "Clinical guidelines for interstitial cystitis and hypersensitive bladder syndrome". International Journal of Urology. 16 (7): 597–615. doi:10.1111/j.1442-2042.2009.02326.x. PMID 19548999. S2CID 20796904. European Urology

Hello Aarogya, what is Iron poisoning

Iron poisoning

Iron poisoning typically occurs from ingestion of excess iron that results in acute toxicity. Mild symptoms which occur within hours include vomiting, diarrhea, abdominal pain, and drowsiness. In more severe cases, symptoms can include tachypnea, low blood pressure, seizures, or coma. If left untreated, iron poisoning can lead to multi-organ failure resulting in permanent organ damage or death.Iron is available over the counter as a single entity supplement in an iron salt form or in combination with vitamin supplements and is commonly used in the treatment of anemias. Overdoses on iron can be categorized as unintentional ingestion which is predominantly associated with children or intentional ingestion involving suicide attempts in adults. Unintentional ingestion of iron containing drug products are a major cause of mortality in children under the age of 6 years old in the United States. As a response, in 1997 the US Food and Drug Administration (FDA) implemented a regulation requiring warning labels and unit dose packaging for products containing more than 30 mg of elemental iron per dose.The diagnosis of iron poisoning is based on clinical presentation including laboratory tests for serum iron concentrations and metabolic acidosis along with physical examination. Treatment for iron poisoning involves providing fluid replacement, gastrointestinal decontamination, administering deferoxamine intravenously, liver transplants, and monitoring the patients condition. The degree of intervention required depends on whether the patient is at risk for serious toxicity. Signs and symptoms Manifestation of iron poisoning may vary depending on the amount of iron ingested by the individual and is further classified by five stages based on timing of signs and symptoms. In mild to moderate cases, individuals may be asymptomatic or only experience mild gastrointestinal symptoms that resolve within six hours. In serious cases, individuals may present with systemic signs and symptoms and require treatment. Clinical presentation of iron poisoning in the absence of treatment progresses in five stages: the gastrointestinal phase, latent phase, metabolic acidosis and shock phase, hepatotoxicity phase, and bowel obstruction due to scarring. The first indication of iron poisoning occurs within the first six hours post-ingestion and involves gastrointestinal symptoms including abdominal pain accompanied by nausea and vomiting with or without blood. Due to the disintegration of iron tablets, the stool may appear as black or dark green or gray. After the first stage, gastrointestinal symptoms appear to resolve in the latent phase and individuals may show signs of improvement. Following this stage, the iron begins to affect the cells of the bodys organs which manifests as numerous systemic signs and symptoms developing after 6 to 72 hours, in the metabolic acidosis phase. Individuals may present with signs of cardiogenic shock indicated by low blood pressure, rapid heart rate and severe shortness of breath. Hypovolemic shock occurs due to loss of blood from the gastrointestinal bleeding caused by the iron. During this phase, metabolic acidosis may also develop damaging internal organs such as the brain and liver. In the fourth stage taking place 12 to 96 hours after ingestion, liver toxicity and failure occurs as the cells begin to die. In the last stage of iron poisoning following 2 to 8 weeks after ingestion, scarring of the gastrointestinal mucosal lining resulting in bowel obstruction. Cause Pathophysiology Iron is essential for the production of hemoglobin in red blood cells which is responsible for transporting oxygen throughout the body. In normal physiologic conditions, nonionic forms of iron (Fe°) are converted into ferrous iron (Fe2+) by gastric acid in the stomach. Ferrous iron is then absorbed in the small intestine where it is oxidized into its ferric iron (Fe3+) form before being released into the bloodstream. Free iron in the blood is toxic to the body as it disrupts normal cell function, damaging organs such as the liver, stomach, and cardiovascular system. The human body has protective mechanisms in place to prevent excess free ferric iron from circulating the body. When being transported throughout the body, iron is bound to an iron transporting protein called transferrin to prevent iron from being absorbed into different cells. Any excess iron is stored as ferritin in the liver. In the event of iron overdose, iron stores become oversaturated and the bodys protective mechanisms fail resulting in excess free circulating iron. Toxic Dose Iron poisoning can occur when doses of 20 to 60 mg/kg or more of elemental iron is ingested with most cases reporting primarily gastrointestinal symptoms. Systemic signs and symptoms shown in serious toxicity occur at higher doses exceeding 60 mg/kg. Ingesting above 120 mg/kg may be fatal. The therapeutic dose for iron deficiency anemia is 3–6 mg/kg/day. Individuals who have ingested less than 20 mg/kg of elemental iron typically do not exhibit symptoms. It is unlikely to get iron poisoning from diet alone with iron supplements being the cause of overdose. The amount of elemental iron in an iron supplement can be calculate based on the percentage it constitutes for per tablet. For example, a 300 mg tablet of ferrous fumarate will contain 100 mg of elemental iron or 33%. Ferrous sulfate contains 20% elemental iron per mg of mineral salt Ferrous gluconate contains 12% elemental iron per mg of mineral salt Ferrous fumarate contains 33% elemental iron per mg of mineral salt Diagnosis Iron toxicity is primarily a clinical diagnosis that involves getting a detailed patient history and physical examination of the individuals signs and symptoms. Information such as how much iron was ingested and the timing should be gathered to assess the level of toxicity. Signs for severe iron poisoning should be evaluated such as any confusion or extreme lethargy, increased heart rates, low blood pressure for adults. In children, signs of shock can be noted with behavioral changes such as decreased responsiveness, crying, and inability to focus. Persistent vomiting is often associated with iron poisoning and also used to determine severity of iron poisoning. Laboratory tests such as measuring the peak serum iron level after 4 to 6 hours of ingestion can be useful in determining the severity of iron toxicity. In general, levels below 350mcg/dL are associated with more mild iron poisoning while upper levels above 500mcg/dL are associated with more severe iron poisoning. Measuring electrolyte levels, kidney function, serum glucose, liver function tests (enzymes and bilirubin), complete blood count, clotting time via prothrombin and partial thromboplastin time, anion gap for metabolic acidosis, should be conducted for clinical monitoring and confirmation of iron poisoning.The deferoxamine challenge test is a diagnostic test for confirming iron poisoning, however it is no longer recommended for diagnostic purposes due to concerns regarding the accuracy. Deferoxamine can be administered intramuscularly as a single dose where it then binds to free iron in the blood and is excreted into the urine turning it to a "brick orange" or pink/red/orange color. Radiographs are no longer used for diagnosis due to the lack of connection between severity of iron toxicity and the presence of radiopaque iron tablets in the stomach on X-rays. This method also requires that the ingested tablet to be radiopaque which most iron preparations are not. Treatment Management of acute iron poisoning involves providing a patient with respiratory support and intravenous deferoxamine. Patients exhibiting severe symptoms in the gastrointestinal phase should receive volume resuscitation to prevent hypovolemic shock from the loss of blood volume. Normal saline is administered intravenously to maintain adequate volume of fluid in the body. Deferoxamine is a drug that is used in cases of serious iron poisoning. It is a chelating agent and binds to free iron in the body in order to be eliminated by the kidneys into urine. Dosing of deferoxamine should be determined through consultation with a toxicologist but is typically continuously infused at 15 mg/kg to 35 mg/kg per hour and not exceeding the maximum daily dose of 6 grams for adults. In pediatric patients, doses should not exceed 15 mg/kg per hour. recommended duration of treatment is until symptoms have resolved which is usually 24 hours. In non-fatal cases of iron poisoning where there is liver failure, liver transplantation may be necessary.Treatment of iron poisoning should be based on clinical presentation, peak serum iron levels and other laboratory results. As a general guideline, patients who have ingested lower doses of elemental iron, have a peak serum iron level less than 500mcg/dL and are asymptomatic or only exhibit mild gastrointestinal symptoms typically do not require treatment and should be monitored for 6 hours after ingestion. In cases where high doses of elemental iron have been ingested and the patient is exhibiting signs and symptoms of severe systemic iron poisoning, supportive care measures like volume resuscitation and deferoxamine should be initiated immediately. A quick response to iron poisoning can significantly improve clinical outcomes. See also Overnutrition Iron overload References External links Iron poisoning in General Practice Notebook Iron Poisoning at WebMD Iron Poisoning Merck Manual

Hello Aarogya , Do you know what is Iron supplement,

Iron supplement

Iron supplements, also known as iron salts and iron pills, are a number of iron formulations used to treat and prevent iron deficiency including iron deficiency anemia. For prevention they are only recommended in those with poor absorption, heavy menstrual periods, pregnancy, hemodialysis, or a diet low in iron. Prevention may also be used in low birth weight babies. They are taken by mouth, injection into a vein, or injection into a muscle. While benefits may be seen in days, up to two months may be required until iron levels return to normal.Common side effects include constipation, abdominal pain, dark stools, and diarrhea. Other side effects, which may occur with excessive use, include iron overload and iron toxicity. Ferrous salts used as supplements by mouth include ferrous fumarate, ferrous gluconate, ferrous succinate, and ferrous sulfate. Injectable forms include iron dextran and iron sucrose. They work by providing the iron needed for making red blood cells.Iron pills have been used medically since at least 1681, with an easy-to-use formulation being created in 1832. Ferrous salt is on the World Health Organizations List of Essential Medicines. Ferrous salts are available as a generic medication and over the counter. Slow release formulations, while available, are not recommended. In 2017, ferrous sulfate was the 92nd most commonly prescribed medication in the United States, with more than eight million prescriptions. Medical uses Iron supplements are used to treat iron deficiency and iron-deficiency anemia; parenteral irons can also be used to treat functional iron deficiency, where requirements for iron are greater than the bodys ability to supply iron such as in inflammatory states. The main criterion is that other causes of anemia have also been investigated, such as vitamin B12 or folate deficiency, drug induced or due to other poisons such as lead, as often the anemia has more than one underlying cause. Iron deficiency anemia is classically a microcytic, hypochromic anemia. Generally, in the UK oral preparations are trialled before using parenteral delivery, unless there is the requirement for a rapid response, previous intolerance to oral iron or likely failure to respond. Intravenous iron may decrease the need for blood transfusions however it increases the risk of infections when compared to oral iron. A 2015 Cochrane Collaboration review found that daily oral supplementation of iron during pregnancy reduces the risk of maternal anemia and that effects on infant and on other maternal outcomes are not clear. Another review found tentative evidence that intermittent iron supplements by mouth for mothers and babies is similar to daily supplementation with fewer side effects. Supplements by mouth should be taken on an empty stomach, optionally with a small amount of food to reduce discomfort. Athletes Athletes may be at elevated risk of iron deficiency and so benefit from supplementation, but the circumstances vary between individuals and dosage should be based on tested ferritin levels, since in some cases supplementation may be harmful. Frequent blood donors Frequent blood donors may be advised to take iron supplements. Canadian Blood Services recommends discussing "taking iron supplements with your doctor or pharmacist" as "the amount of iron in most multivitamins may not meet your needs and iron supplements may be necessary". The American Red Cross recommends "taking a multivitamin with 18 mg of iron or an iron supplement with 18-38 mg of elemental iron for 60 days after each blood donation, for 120 days after each power red donation or after frequent platelet donations". A 2014 Cochrane Review found that blood donors were less likely to be deferred for low hemoglobin levels if they were taking oral iron supplements, although 29% of those who took them experienced side effects in contrast to the 17% that took a placebo. It is unknown what the long-term effects of iron supplementation for blood donors may be. Side effects Side effects of therapy with oral iron are most often diarrhea or constipation and epigastric abdominal discomfort. Taken after a meal, side effects decrease, but there is an increased risk of interaction with other substances. Side effects are dose-dependent, and the dose may be adjusted. The patient may notice that their stools become black. This is completely harmless, but patients must be warned about this to avoid unnecessary concern. When iron supplements are given in a liquid form, teeth may reversibly discolor (this can be avoided through the use of a straw). Intramuscular injection can be painful, and brown discoloration may be noticed. Treatments with iron(II) sulfate have higher incidence of adverse events than iron(III)-hydroxide polymaltose complex (IPC) or iron bis-glycinate chelate.Iron overdose has been one of the leading causes of death caused by toxicological agents in children younger than 6 years.Iron poisoning may result in mortality or short-term and long-term morbidity. Infection risk Because one of the functions of elevated ferritin (an acute phase reaction protein) in acute infections is thought to be to sequester iron from bacteria, it is generally thought that iron supplementation (which circumvents this mechanism) should be avoided in patients who have active bacterial infections. Replacement of iron stores is seldom such an emergency situation that it cannot wait for any such acute infection to be treated. Some studies have found that iron supplementation can lead to an increase in infectious disease morbidity in areas where bacterial infections are common. For example, children receiving iron-enriched foods have demonstrated an increased rate in diarrhea overall and enteropathogen shedding. Iron deficiency protects against infection by creating an unfavorable environment for bacterial growth. Nevertheless, while iron deficiency might lessen infections by certain pathogenic diseases, it also leads to a reduction in resistance to other strains of viral or bacterial infections, such as Salmonella typhimurium or Entamoeba histolytica. Overall, it is sometimes difficult to decide whether iron supplementation will be beneficial or harmful to an individual in an environment that is prone to many infectious diseases; however this is a different question than the question of supplementation in individuals who are already ill with a bacterial infection.Children living in areas prone for malarial infections are also at risk of developing anemia. It was thought that iron supplementation given to such children could increase the risk of malarial infection in them. A Cochrane systematic review published in 2016 found high quality evidence that iron supplementation does not increase the risk of clinical malaria in children. Contraindications Contraindications often depend on the substance in question. Documented hypersensitivity to any ingredients and anemias without proper work-up (i.e., documentation of iron deficiency) is true of all preparations. Some can be used in iron deficiency, others require iron deficiency anaemia to be present. Some are also contraindicated in rheumatoid arthritis. Hemochromatosis Individuals may be genetically predisposed to excessive iron absorption, as is the case with those with HFE hereditary hemochromatosis. Within the general population, 1 out of 400 people has the homozygous form of this genetic trait, and 1 out of every 10 people has its heterozygous form. Neither individuals with the homozygous or heterozygous form should take iron supplements. Interactions Non-heme iron forms an insoluble complex with several other drugs, resulting in decreased absorption of both iron and the other drug. Examples include tetracycline, penicillamine, methyldopa, levodopa, bisphosphonates and quinolones. The same can occur with elements in food, such as calcium, which impacts both heme and non-heme iron absorption. Absorption of iron is better at a low pH (i.e. an acidic environment), and absorption is decreased if there is a simultaneous intake of antacids. Many other substances decrease the rate of non-heme iron absorption. One example is tannins from foods such as tea and phytic acid. Because iron from plant sources is less easily absorbed than the heme-bound iron of animal sources, vegetarians and vegans should have a somewhat higher total daily iron intake than those who eat meat, fish or poultry.Taken after a meal, there are fewer side effects but there is also less absorption because of interaction and pH alteration. Generally, an interval of 2–3 hours between the iron intake and that of other drugs seems advisable, but is less convenient for patients and can impact on compliance. History The first pills were commonly known as Blauds pills, which were named after P. Blaud of Beaucaire, the French physician who introduced and started the use of these medications as a treatment for patients with anemia. Administration By mouth Iron can be supplemented by mouth using various forms, such as iron(II) sulfate. This is the most common and well studied soluble iron salt sold under brand names such as Feratab, Fer-Iron, and Slow-FE. It is in complex with gluconate, dextran, carbonyl iron, and other salts. Ascorbic acid, vitamin C, increases the absorption of non-heme sources of iron.Heme iron polypeptide (HIP) (e.g. Proferrin ES and Proferrin Forte) can be used when regular iron supplements such as ferrous sulfate or ferrous fumarate are not tolerated or absorbed. A clinical study demonstrated that HIP increased serum iron levels 23 times greater than ferrous fumarate on a milligram-per-milligram basis.Another alternative is ferrous glycine sulfate or ferroglycine sulfate, has less gastrointestinal side-effects than standard preparations such as iron fumarate. It is unusual among oral preparations of iron supplements in that the iron in this preparation has very high oral bioavailability, especially in the liquid formulation. This option should be evaluated before resorting to parenteral therapy. It is especially useful in iron deficiency anemia associated with autoimmune gastritis and Helicobacter pylori gastritis, where it generally has satisfactory effect.Since iron stores in the body are generally depleted, and there is a limit to what the body can process (about 2–6 mg/kg of body mass per day; i.e. for a 100 kg/220 lb man this is equal to a maximum dose of 200–600 mg/per day) without iron poisoning, this is a chronic therapy which may take 3–6 months.Due to the frequent intolerance of oral iron and the slow improvement, parenteral iron is recommended in many indications. By injection Iron therapy (intravenously or intramuscular) is given when therapy by mouth has failed (not tolerated), oral absorption is seriously compromised (by illnesses, or when the person cannot swallow), benefit from oral therapy cannot be expected, or fast improvement is required (for example, prior to elective surgery). Parenteral therapy is more expensive than oral iron preparations and is not suitable during the first trimester of pregnancy.There are cases where parenteral iron is preferable over oral iron. These are cases where oral iron is not tolerated, where the haemoglobin needs to be increased quickly (e.g. post partum, post operatively, post transfusion), where there is an underlying inflammatory condition (e.g. inflammatory bowel disease) or renal patients, the benefits of parenteral iron far outweigh the risks. In many cases, use of intravenous iron such as ferric carboxymaltose has lower risks of adverse events than a blood transfusion and as long as the person is stable is a better alternative. Ultimately this always remains a clinical decision based on local guidelines, although National Guidelines are increasingly stipulating IV iron in certain groups of patients.Soluble iron salts have a significant risk of adverse effects and can cause toxicity due to damage to cellular macromolecules. Delivering iron parenterally has utilised various different molecules to limit this. This has included dextrans, sucrose, carboxymaltose and more recently Isomaltoside 1000.One formulation of parenteral iron is iron dextran which covers the old high molecular weight (trade name DexFerrum) and the much safer low molecular iron dextrans (tradenames including Cosmofer and Infed).Iron sucrose has an occurrence of allergic reactions of less than 1 in 1000. A common side effect is taste changes, especially a metallic taste, occurring in between 1 in 10 and 1 in 100 treated patients. It has a maximum dose of 200 mg on each occasion according to the SPC, but it has been given in doses of 500 mg. Doses can be given up to 3 times a week.Iron carboxymaltose is marketed as Ferinject, Injectafer, and Iroprem in various countries. The most common side effects are headaches which occur in 3.3%, and hypophosphatemia, which occurs in more than 35%.Iron Isomaltoside 1000 (Trade name Monofer) is a newer formulation of parenteral iron that has a matrix structure that results in very low levels of free iron and labile iron. It can be given at high doses – 20 mg/kg in a single visit – no upper dose limit. This formulation has the benefit of giving a full iron correction in a single visit. Follow-up Follow-up is needed to ensure compliance and to detect adequate response to therapy. The interval of follow up can widely depend on both the method of administration, and the underlying pathology. For parenteral irons it is recommended that there be a period of 4 weeks before repeating blood test to allow the body to utilise the iron. For oral iron, this can take considerably longer, so waiting three months may be appropriate. See also Geritol Human iron metabolism Lucky iron fish == References ==

Hey Aarogya!, what is Juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a common form of genetic generalized epilepsy (previously known as idiopathic generalized epilepsy), representing 5-10% of all epilepsy cases. This disorder typically first presents between the ages of 12 and 18 with myoclonic seizure manifesting as sudden brief involuntary single or multiple episodes of muscle(s) contractions caused by an abnormal excessive or synchronous neuronal activity in the brain. These events typically occur after awakening from sleep, during the evening or upon sleep deprivation. JME is also characterized by generalized tonic-clonic seizures and a minority also have absence seizures. The genetics of JME are complex and rapidly evolving as over 20 chromosomal loci and multiple genes have been identified thus far. Given the genetic and clinical heterogeneity of JME some authors have suggested that it should be thought of as a spectrum disorder. Epidemiology The prevalence of JME is approximately 0.1-0.2 per 100,000 and constitutes approximately 5-10% of all epilepsies. Some studies suggest that JME is slightly more common in females than males. The onset of symptoms ranges between the ages of 8 and 36 years and has a peak between the ages of 12 and 18 years. Approximately 15% of children with childhood absence epilepsy and juvenile absence epilepsy subsequently develop JME. In most cases, myoclonic jerks precede the first generalized tonic-clonic seizure by a mean of 3.3 years. A long-term population-based study suggested that at 25 years from seizure onset all seizure types in JME resolved in 17% and in 13% only myoclonus remained despite discontinuing medication. Thus, disabling seizures resolve in around one-third of patients. Signs and symptoms There are three principle seizures types which may occur in JME: myoclonus, generalized tonic-clonic seizures and absence seizures. Approximately one-third of patients have all three seizure types. The majority of patients (58.2%) have frequent myoclonic jerks and uncommon generalized tonic-clonic seizures. Absence seizures are believed to be the least common with studies estimating a prevalence of 10% to as high as 38%. Myoclonic status epilepticus may occur as a complication but it is uncommon. Patient’s typically initially present to medical providers following their first generalized tonic-clonic seizure. It is often subsequently reported that the patient was having myoclonus for several years prior. The first generalized tonic-clonic seizure usually occurs in the context of a particular provoking factor such as sleep deprivation, stress or alcohol consumption. There are other potential provoking factors such as praxis induction which refers to the precipitation of seizures or epileptiform discharges in the context of a complex cognitive tasks. Patients with JME tend to perform worse on neuropsychological assessments in multiple cognitive domains and are also more likely to have psychiatric comorbidities such as depression and anxiety when compared to control populations. The majority of patients with JME report satisfaction with their health, work, friendships and social life. Cause JME is believed to be most often caused by a heterogeneous and complex interaction of multiple genes rather than an unidentified single genetic cause. Thus far seven genes and over 20 chromosomal loci have been implicated in the pathogenesis of JME. A minority of cases are caused by single genes and are inherited in an autosomal dominant fashion. The majority of the genes which have been associated with JME encode for ion channel subunits. More recently, variants in intestinal cell kinase which is encoded by a gene on chromosome 6p12 was found to be associated with JME. This gene is involved in mitosis, cell-cycle exit and radial neuroblast migration as well as apoptosis. Another gene that is associated with JME called EFHC1 has similar functions. These findings may explain subtle structural and functional brain abnormalities that are seen in patients with JME.JME is distinct from other forms of genetic generalized epilepsies due to the prominence of myoclonus. There is evidence that patients with JME have hyperexcitable motor cortexes that is most pronounced in the morning and after sleep deprivation. In addition, there is evidence that patients with JME have hyperexcitable and hyperconnected cortical networks that are involved in ictogenesis. Genetics CACNB4 CACNB4 is a gene that encodes the calcium channel β subunit protein. β subunits are important regulators of calcium channel current amplitude, voltage dependence, and also regulate channel trafficking. In mice, a naturally occurring null mutation leads to the "lethargic" phenotype. This is characterized by ataxia and lethargic behavior at early stages of development followed within days by the onset of both focal motor seizures as well as episodes of behavioral immobility which correlates with patterns of cortical spike and wave discharges at the EEG A premature-termination mutation R482X was identified in a patient with JME while an additional missense mutation C104F was identified in a German family with generalized epilepsy and praxis – induced seizures.The R482X mutation results in increased current amplitudes and an accelerated fast time constant of inactivation. Whether these modest functional differences may be in charge of JME remains to be established. Calcium channel β4 subunit (CACNB4) is not strictly considered a putative JME gene because its mutation did not segregate in affected family members, and it was found in only one member of a JME family from Germany, and it has not been replicated. GABRA1 GABRA1 is a gene that encodes for an α subunit of the GABA A receptor protein, which encodes one of the major inhibitory neurotransmitter receptors. There is one known mutation in this gene that is associated with JME, A322D, which is located in the third segment of the protein. This missense mutation results in channels with reduced peak GABA-evoked currents. Furthermore, the presence of such mutation alters the composition and reduces the expression of wild-type GABAA receptors. GABRD GABRD encodes the δ subunit of the GABA receptor, which is an important constituent of the GABAA receptor mediating tonic inhibition in neurons (extrasynaptic GABA receptors, i.e. receptors that are localized outside of the synapse). Among the mutations that have been reported in this in this gene, one (R220H) has been identified in a small family with JME. This mutation affects GABAergic transmission by altering the surface expression of the receptor as well as reducing the channel – opening duration. Myoclonin1/EFHC1 The final known associated gene is EFHC1. Myoclonin1/EFHC1 encodes for a protein that has been known to play a wide range of wild-type cell division, neuroblast migration and synapse/dendrite formation. EFHC1 is expressed in many tissues, including the brain, where it is localized to the soma and dendrites of neurons, particularly the hippocampal CA1 region, pyramidal neurons in the cerebral cortex, and Purkinje cells in the cerebellum.There are four JME-causing mutations discovered (D210N, R221H, F229L and D253Y). The mutations do not seem to alter the ability of the protein to colocalize with centrosomes and mitotic spindles but induce mitotic spindle defects. Moreover, the mutations impact radial and tangential migration during brain development. As such a theory has been put forward that JME may be the result of a brain developmental disorder. Other loci Three SNP alleles in BRD2, Cx-36 and ME2 and microdeletions in 15q13.3, 15q11.2 and 16p.13.11 also contribute risk to JME. Diagnosis Diagnosis is typically made based on patient history. The physical examination is usually normal. The primary diagnosis for JME is a good knowledge of patient history and the neurologists familiarity with the myoclonic jerks, which are the hallmark of the syndrome. Additionally, an electroencephalogram (EEG), will indicate a characteristic pattern of waves and spikes associated with the syndrome such as generalized 4–6 Hz polyspike and slow wave discharges. These discharges may be evoked by photic stimulation (blinking lights) and/or hyperventilation. Both a magnetic resonance imaging scan (MRI) and computed tomography scan (CT scan) generally appear normal in JME patients. However a number of quantitative MRI studies have reported focal or regional abnormalities of the subcortical and cortical grey matter, particularly the thalamus and frontal cortex, in JME patients. Positron emission tomography reports in some patients may indicate local deviations in many transmitter systems. Management The most effective anti-epileptic medication for JME is valproic acid (Depakote).Due to valproic acids high incidence of fetal malformations, women of child-bearing age are started on alternative medications such as Lamotrigine, levetiracetam. Carbamazepine may aggravate genetic generalized epilepsies and as such its use should be avoided in JME. Treatment is lifelong. However, recent follow-up researches on a subgroup of patients showed them becoming seizure-free and off anti-epileptic drugs in due course of time. This makes this dogma questionable. Patients should be warned to avoid sleep deprivation. History The first citation of JME was made in 1857 when Théodore Herpin described a 13-year-old boy with myoclonic jerks, which progressed to tonic-clonic seizures three months later. In 1957, Janz and Christian published a journal article describing several patients with JME. The name Juvenile Myoclonic Epilepsy was proposed in 1975 and adopted by the International League Against Epilepsy. Culture Stand-up comedian Maisie Adam has JME and her award-winning show "Vague" (2018) discussed it.The 2018 documentary film Separating The Strains dealt with the use of CBD oil to treat symptoms of JME. Currently, no scientific evidence exist to support the use of CBD oil to treat symptoms of JME. See also Progressive myoclonus epilepsies Spinal muscular atrophy with progressive myoclonic epilepsy == References ==

Hello Aarogya, what is Kaposis sarcoma

Kaposis sarcoma

Kaposis sarcoma (KS) is a type of cancer that can form masses in the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limited area, or may be widespread. Depending on the sub-type of disease and level of immune suppression, KS may worsen either gradually or quickly. KS is caused by a combination of immune suppression (such as due to HIV/AIDS) and infection by Human herpesvirus 8 (HHV8 – also called KS-associated herpesvirus (KSHV)).Four sub-types are described: classic, endemic, immunosuppression therapy-related (also called iatrogenic), and epidemic (also called AIDS-related). Classic KS tends to affect older men in regions where KSHV is highly prevalent (Mediterranean, Eastern Europe, Middle East), is usually slow-growing, and most often affects only the legs. Endemic KS is most common in Sub-Saharan Africa and is more aggressive in children, while older adults present similarly to classic KS. Immunosuppression therapy-related KS generally occurs in people following organ transplantation and mostly affects the skin. Epidemic KS occurs in people with AIDS and many parts of the body can be affected. KS is diagnosed by tissue biopsy, while the extent of disease may be determined by medical imaging.Treatment is based on the sub-type, whether the condition is localized or widespread, and the persons immune function. Localized skin lesions may be treated by surgery, injections of chemotherapy into the lesion, or radiation therapy. Widespread disease may be treated with chemotherapy or biologic therapy. In those with HIV/AIDS, highly active antiretroviral therapy (HAART) prevents and often treats KS. In certain cases the addition of chemotherapy may be required. With widespread disease, death may occur.The condition is relatively common in people with HIV/AIDS and following organ transplant. Over 35% of people with AIDS may be affected. KS was first described by Moritz Kaposi in 1872. It became more widely known as one of the AIDS-defining illnesses in the 1980s. KSHV was discovered as a causative agent in 1994. Signs and symptoms KS lesions are nodules or blotches that may be red, purple, brown, or black, and are usually papular.They are typically found on the skin, but spread elsewhere is common, especially the mouth, gastrointestinal tract and respiratory tract. Growth can range from very slow to explosively fast, and is associated with significant mortality and morbidity.The lesions are painless, but become cosmetically disfiguring or interruptive to organs. Skin Commonly affected areas include the lower limbs, back, face, mouth, and genitalia. The lesions are usually as described above, but may occasionally be plaque-like (often on the soles of the feet) or even involved in skin breakdown with resulting fungating lesions. Associated swelling may be from either local inflammation or lymphoedema (obstruction of local lymphatic vessels by the lesion). Skin lesions may be quite disfiguring for the patient, and a cause of much psychosocial pathology. Mouth The mouth is involved in about 30% of cases, and is the initial site in 15% of AIDS-related KS. In the mouth, the hard palate is most frequently affected, followed by the gums. Lesions in the mouth may be easily damaged by chewing and bleed or develop secondary infection, and even interfere with eating or speaking. Gastrointestinal tract Involvement can be common in those with transplant-related or AIDS-related KS, and it may occur in the absence of skin involvement. The gastrointestinal lesions may be silent or cause weight loss, pain, nausea/vomiting, diarrhea, bleeding (either vomiting blood or passing it with bowel movements), malabsorption, or intestinal obstruction. Respiratory tract Involvement of the airway can present with shortness of breath, fever, cough, coughing up blood or chest pain, or as an incidental finding on chest x-ray. The diagnosis is usually confirmed by bronchoscopy, when the lesions are directly seen and often biopsied. Kaposis sarcoma of the lung has a poor prognosis. Cause Kaposis sarcoma-associated herpesvirus (KSHV), also called HHV-8, is present in almost 100% of Kaposi sarcoma lesions, whether HIV-related, classic, endemic, or iatrogenic. KSHV encodes oncogenes, microRNAs and circular RNAs that promote cancer cell proliferation and escape from the immune system. Transmission In Europe and North America, KSHV is transmitted through saliva. Thus, kissing is a risk factor for transmission. Higher rates of transmission among gay and bisexual men have been attributed to "deep kissing" sexual partners with KSHV. Another alternative theory suggests that use of saliva as a sexual lubricant might be a major mode for transmission. Prudent advice is to use commercial lubricants when needed and avoid deep kissing with partners with KSHV infection or whose status is unknown.KSHV is also transmissible via organ transplantation and blood transfusion. Testing for the virus before these procedures is likely to effectively limit iatrogenic transmission. Pathology Despite its name, in general it is not considered a true sarcoma, which is a tumor arising from mesenchymal tissue. The histogenesis of KS remains controversial. KS may arise as a cancer of lymphatic endothelium and forms vascular channels that fill with blood cells, giving the tumor its characteristic bruise-like appearance. KSHV proteins are uniformly detected in KS cancer cells.KS lesions contain tumor cells with a characteristic abnormal elongated shape, called spindle cells. The most typical feature of Kaposi sarcoma is the presence of spindle cells forming slits containing red blood cells. Mitotic activity is only moderate and pleomorphism is usually absent. The tumor is highly vascular, containing abnormally dense and irregular blood vessels, which leak red blood cells into the surrounding tissue and give the tumor its dark color. Inflammation around the tumor may produce swelling and pain. Variously sized PAS positive hyaline bodies are often seen in the cytoplasm or sometimes extracellularly.The spindle cells of Kaposi sarcoma differentiate toward endothelial cells, probably of lymph vessel rather than blood vessel origin. The consistent immunoreactivity for podoplanin supports the lymphatic nature of the lesion. Diagnosis Although KS may be suspected from the appearance of lesions and the patients risk factors, a definite diagnosis can be made only by biopsy and microscopic examination. Detection of the KSHV protein LANA in tumor cells confirms the diagnosis.In differential diagnosis, arteriovenous malformations, pyogenic granuloma and other vascular proliferations can be microscopically confused with KS. Differential diagnosis of Kaposis sarcoma Source: Naevus Histiocytoma Cryptococcosis Histoplasmosis Leishmaniasis Pneumocystis lesions Dermatophytosis Angioma Bacillary angiomatosis Pyogenic granuloma Melanoma Classification HHV-8 is responsible for all varieties of KS. Since Moritz Kaposi first described the cancer, the disease has been reported in five separate clinical settings, with different presentations, epidemiology, and prognoses.: 599  All of the forms are infected with KSHV and are different manifestations of the same disease but have differences in clinical aggressiveness, prognosis, and treatment. Classic Kaposi sarcoma most commonly appears early on the toes and soles as reddish, violaceous, or bluish-black macules and patches that spread and coalesce to form nodules or plaques.: 599  A small percentage of these patients may have visceral lesions. In most cases the treatment involves surgical removal of the lesion. The condition tends to be indolent and chronic, affecting elderly men from the Mediterranean region, Arab countries, or of Eastern European descent. Israeli Jews have a higher rate of KSHV/HHV-8 infection than European peoples. Endemic KS, which has two types. Although this may be present worldwide, it has been originally described later in young African peoples, mainly those from sub-Saharan Africa. This variant is not related to HIV infection and is a more aggressive disease that infiltrates the skin extensively.African lymphadenopathic Kaposi sarcoma is aggressive, occurring in children under 10 years of age, presenting with lymph node involvement, with or without skin lesions.: 599  African cutaneous Kaposi sarcoma presents with nodular, infiltrative, vascular masses on the extremities, mostly in men between the ages of 20 and 50, and is endemic in tropical Africa.: 599  Immunosuppression-associated Kaposi sarcoma had been described, but only rarely until the advent of calcineurin inhibitors (such as ciclosporines, which are inhibitors of T-cell function) for transplant patients in the 1980s, when its incidence grew rapidly. The tumor arises either when an HHV 8-infected organ is transplanted into someone who has not been exposed to the virus or when the transplant recipient already harbors pre-existing HHV 8 infection. Unlike classic Kaposi sarcoma, the site of presentation is more variable.: 600  AIDS-associated Kaposi sarcoma typically presents with cutaneous lesions that begin as one or several red to purple-red macules, rapidly progressing to papules, nodules, and plaques, with a predilection for the head, back, neck, trunk, and mucous membranes. In more advanced cases, lesions can be found in the stomach and intestines, the lymph nodes, and the lungs.: 599  Compared to other forms of KS, KS-AIDS stimulated more interest in KS research, as it was one of the first illnesses associated with AIDS and first described in 1981. This form of KS is over 300 times more common in AIDS patients than in renal transplant recipients. In this case, HHV 8 is sexually transmitted among people also at risk for sexually transmitted HIV infection. Prevention Blood tests to detect antibodies against KSHV have been developed and can be used to determine whether a person is at risk for transmitting the infection to their sexual partner, or whether an organ is infected before transplantation. However, these tests are not available except as research tools, and, thus, there is little screening for persons at risk for becoming infected with KSHV, such as people following a transplant. Treatment Kaposi sarcoma is not curable, but it can often be treatable for many years. In KS associated with immunodeficiency or immunosuppression, treating the cause of the immune system dysfunction can slow or stop the progression of KS. In 40% or more of patients with AIDS-associated Kaposi sarcoma, the Kaposi lesions will shrink upon first starting highly active antiretroviral therapy (HAART). Therefore, HAART is considered the cornerstone of therapy in AIDS-associated Kaposi sarcoma. However, in a certain percentage of such people, Kaposi sarcoma may recur after many years on HAART, especially if HIV is not completely suppressed. People with a few local lesions can often be treated with local measures such as radiation therapy or cryosurgery. Weak evidence suggests that antiretroviral therapy in combination with chemotherapy is more effective than either of those two therapies individually. Limited basic and clinical evidence suggest that topical beta-blockers, such as timolol, may induce regression of localized lesions in classic as well as HIV-associated Kaposi sarcoma. In general, surgery is not recommended, as Kaposi sarcoma can appear in wound edges. In general, more widespread disease, or disease affecting internal organs, is treated with systemic therapy with interferon alpha, liposomal anthracyclines (such as liposomal doxorubicin or daunorubicin), thalidomide, or paclitaxel.Alitretinoin, applied to the lesion, may be used when the lesion is not getting better with standard treatment of HIV/AIDS and chemotherapy or radiation therapy cannot be used. Epidemiology With the decrease in the death rate among people with HIV/AIDS receiving new treatments in the 1990s, the rates and severity of epidemic KS also decreased. However, the number of people living with HIV/AIDS is increasing in the United States, and it is possible that the number of people with AIDS-associated Kaposi sarcoma will again rise as these people live longer with HIV infection. Society Because of their highly visible nature, external lesions are sometimes the presenting symptom of AIDS. Kaposi sarcoma entered the awareness of the general public with the release of the film Philadelphia, in which the main character was fired after his employers found out he was HIV-positive due to visible lesions. By the time KS lesions appear, likely, the immune system has already been severely weakened. It has been reported that only 6% of men who have sex with men are aware that KS is caused by a virus different from HIV. Thus, there is little community effort to prevent KSHV infection. Likewise, no systematic screening of organ donations is in place. In people with AIDS, Kaposi sarcoma is considered an opportunistic infection, a disease that can gain a foothold in the body because the immune system has been weakened. With the rise of HIV/AIDS in Africa, where KSHV is widespread, KS has become the most frequently reported cancer in some countries. References External links Kaposi sarcoma photo library at Dermnet

Hey Aarogya , Do you know what is Keloid,

Keloid

Keloid, also known as keloid disorder and keloidal scar, is the formation of a type of scar which, depending on its maturity, is composed mainly of either type III (early) or type I (late) collagen. It is a result of an overgrowth of granulation tissue (collagen type 3) at the site of a healed skin injury which is then slowly replaced by collagen type 1. Keloids are firm, rubbery lesions or shiny, fibrous nodules, and can vary from pink to the color of the persons skin or red to dark brown in color. A keloid scar is benign and not contagious, but sometimes accompanied by severe itchiness, pain, and changes in texture. In severe cases, it can affect movement of skin. Worldwide, men and women of African, Asian, Hispanic and European descent can develop these raised scars. In the United States keloid scars are seen 15 times more frequently in people of sub-Saharan African descent than in people of European descent. There is a higher tendency to develop a keloid among those with a family history of keloids and people between the ages of 10 and 30 years. Keloids should not be confused with hypertrophic scars, which are raised scars that do not grow beyond the boundaries of the original wound. Signs and symptoms Keloids expand in claw-like growths over normal skin. They have the capability to hurt with a needle-like pain or to itch, the degree of sensation varying from person to person.Keloids form within scar tissue. Collagen, used in wound repair, tends to overgrow in this area, sometimes producing a lump many times larger than that of the original scar. They can also range in color from pink to red. Although they usually occur at the site of an injury, keloids can also arise spontaneously. They can occur at the site of a piercing and even from something as simple as a pimple or scratch. They can occur as a result of severe acne or chickenpox scarring, infection at a wound site, repeated trauma to an area, excessive skin tension during wound closure or a foreign body in a wound. Keloids can sometimes be sensitive to chlorine. If a keloid appears when someone is still growing, the keloid can continue to grow as well. Location Keloids can develop in any place where skin trauma has occurred. They can be the result of pimples, insect bites, scratching, burns, or other skin injury. Keloid scars can develop after surgery. They are more common in some sites, such as the central chest (from a sternotomy), the back and shoulders (usually resulting from acne), and the ear lobes (from ear piercings). They can also occur on body piercings.The most common spots are earlobes, arms, pelvic region, and over the collar bone. Cause Most skin injury types can contribute to scarring. This includes burns, acne scars, chickenpox scars, ear piercing, scratches, surgical incisions, and vaccination sites. According to the (US) National Center for Biotechnology Information, keloid scarring is common in young people between the ages of 10 and 20. Studies have shown that those with darker complexions are at a higher risk of keloid scarring as a result of skin trauma. They occur in 15–20% of individuals with sub-Saharan African, Asian or Latino ancestry, significantly less in those of a Caucasian background. Although it was previously believed that people with albinism did not get keloids, a recent report described the incidence of keloids in Africans with albinism. Keloids tend to have a genetic component, which means one is more likely to have keloids if one or both of their parents has them. However, no single gene has yet been identified which is a causing factor in keloid scarring but several susceptibility loci have been discovered, most notably in Chromosome 15. Genetics People who have ancestry from Sub-Saharan Africa, Asia, or Latin America are more likely to develop a keloid. Among ethnic Chinese in Asia, the keloid is the most common skin condition. In the United States, keloids are more common in African Americans and Hispanic Americans than European Americans. Those who have a family history of keloids are also susceptible since about 1/3 of people who get keloids have a first-degree blood relative (mother, father, sister, brother, or child) who also gets keloids. This family trait is most common in people of African and/or Asian descent. Development of keloids among twins also lends credibility to existence of a genetic susceptibility to develop keloids. Marneros et al. (1) reported four sets of identical twins with keloids; Ramakrishnan et al. also described a pair of twins who developed keloids at the same time after vaccination. Case series have reported clinically severe forms of keloids in individuals with a positive family history and black African ethnic origin. Pathology Histologically, keloids are fibrotic tumors characterized by a collection of atypical fibroblasts with excessive deposition of extracellular matrix components, especially collagen, fibronectin, elastin, and proteoglycans. Generally, they contain relatively acellular centers and thick, abundant collagen bundles that form nodules in the deep dermal portion of the lesion. Keloids present a therapeutic challenge that must be addressed, as these lesions can cause significant pain, pruritus (itching), and physical disfigurement. They may not improve in appearance over time and can limit mobility if located over a joint.Keloids affect both sexes equally, although the incidence in young female patients has been reported to be higher than in young males, probably reflecting the greater frequency of earlobe piercing among women. The frequency of occurrence is 15 times higher in highly pigmented people. People of African descent have increased risk of keloid occurrences. Treatments Prevention of keloid scars in patients with a known predisposition to them includes preventing unnecessary trauma or surgery (such as ear piercing and elective mole removal) whenever possible. Any skin problems in predisposed individuals (e.g., acne, infections) should be treated as early as possible to minimize areas of inflammation. Treatments (both preventive and therapeutic) available are pressure therapy, silicone gel sheeting, intra-lesional triamcinolone acetonide (TAC), cryosurgery (freezing), radiation, laser therapy (PDL), IFN, 5-FU and surgical excision as well as a multitude of extracts and topical agents. Appropriate treatment of a keloid scar is age-dependent: radiotherapy, anti-metabolites and corticosteroids would not be recommended to be used in children, in order to avoid harmful side effects, like growth abnormalities.In adults, corticosteroids combined with 5-FU and PDL in a triple therapy, enhance results and diminish side effects.Cryotherapy (or cryosurgery) refers to the application of extreme cold to treat keloids. This treatment method is easy to perform, effective and safe and has the least chance of recurrence.Surgical excision is currently still the most common treatment for a significant amount of keloid lesions. However, when used as the solitary form of treatment there is a large recurrence rate of between 70 and 100%. It has also been known to cause a larger lesion formation on recurrence. While not always successful alone, surgical excision when combined with other therapies dramatically decreases the recurrence rate. Examples of these therapies include but are not limited to radiation therapy, pressure therapy and laser ablation. Pressure therapy following surgical excision has shown promising results, especially in keloids of the ear and earlobe. The mechanism of how exactly pressure therapy works is unknown at present, but many patients with keloid scars and lesions have benefited from it.Intralesional injection with a corticosteroid such as Kenalog (triamcinolone acetonide) does appear to aid in the reduction of fibroblast activity, inflammation and pruritus.Tea tree oil, salt or other topical oil has no effect on keloid lesions.A 2022 systematic review included multiple studies on laser therapy for treating keloid scars. There was not enough evidence for the review authors to determine if laser therapy was more effective than other treatments. They were also unable to conclude if laser therapy leads to more harm than benefits compared with no treatment or different kinds of treatment. Epidemiology Persons of any age can develop a keloid. Children under 10 are less likely to develop keloids, even from ear piercing. Keloids may also develop from Pseudofolliculitis barbae; continued shaving when one has razor bumps will cause irritation to the bumps, infection, and over time keloids will form. Persons with razor bumps are advised to stop shaving in order for the skin to repair itself before undertaking any form of hair removal. The tendency to form keloids is speculated to be hereditary. Keloids can tend to appear to grow over time without even piercing the skin, almost acting out a slow tumorous growth; the reason for this tendency is unknown. Extensive burns, either thermal or radiological, can lead to unusually large keloids; these are especially common in firebombing casualties, and were a signature effect of the atomic bombings of Hiroshima and Nagasaki. True incidence and prevalence of keloid in United States is not known. Indeed, there has never been a population study to assess the epidemiology of this disorder. In his 2001 publication, Marneros stated that “reported incidence of keloids in the general population ranges from a high of 16% among the adults in the Democratic Republic of the Congo to a low of 0.09% in England,” quoting from Blooms 1956 publication on heredity of keloids. Clinical observations show that the disorder is more common among sub-Saharan Africans, African Americans and Asians, with unreliable and very wide estimated prevalence rates ranging from 4.5 to 16%. History Keloids were described by Egyptian surgeons around 1700 BC, recorded in the Smith papyrus, regarding surgical techniques. Baron Jean-Louis Alibert (1768–1837) identified the keloid as an entity in 1806. He called them cancroïde, later changing the name to chéloïde to avoid confusion with cancer. The word is derived from the Ancient Greek χηλή, chele, meaning "crab pincers", and the suffix -oid, meaning "like". The famous American Civil War-era photograph "Whipped Peter" depicts an escaped former slave with extensive keloid scarring as a result of numerous brutal beatings from his former overseer. Intralesional corticosteroid injections was introduced as a treatment in mid-1960s as a method to attenuate scaring.Pressure therapy has been use for prophylaxis and treatment of keloids since the 1970s.Topical silicone gel sheeting was introduced as a treatment in the early 1980s. References Further reading Roßmann, Nico (2005). Beitrag zur Pathogenese des Keloids und seine Beeinflussbarkeit durch Steroidinjektionen [Contribution to the pathogenesis of the keloid and its influence by steroid injections] (PhD Thesis) (in German). OCLC 179740918. Ogawa, Rei; Mitsuhashi, Kiyoshi; Hyakusoku, Hiko; Miyashita, Tuguhiro (2003). "Postoperative Electron-Beam Irradiation Therapy for Keloids and Hypertrophic Scars: Retrospective Study of 147 Cases Followed for More Than 18 Months". Plastic and Reconstructive Surgery. 111 (2): 547–53, discussion 554–5. doi:10.1097/01.PRS.0000040466.55214.35. PMID 12560675. S2CID 8411788. Okada, Emi; Maruyama, Yu (2007). "Are Keloids and Hypertrophic Scars Caused by Fungal Infection?". Plastic and Reconstructive Surgery. 120 (3): 814–5. doi:10.1097/01.prs.0000278813.23244.3f. PMID 17700144. == External links ==

Hello Aarogya, explain a situation where Keratoconus occurs

Keratoconus

Keratoconus (KC) is a disorder of the eye that results in progressive thinning of the cornea. This may result in blurry vision, double vision, nearsightedness, irregular astigmatism, and light sensitivity leading to poor quality-of-life. Usually both eyes are affected. In more severe cases a scarring or a circle may be seen within the cornea.While the cause is unknown, it is believed to occur due to a combination of genetic, environmental, and hormonal factors. Patients with a parent, sibling, or child who has keratoconus have 15 to 67 times higher risk in developing corneal ectasia compared to patients with no affected relatives. Proposed environmental factors include rubbing the eyes and allergies. The underlying mechanism involves changes of the cornea to a cone shape. Diagnosis is most often by topography. Topography measures the curvature of the cornea and creates a colored "map" of the cornea. Keratoconus causes very distinctive changes in the appearance of these maps, which allows doctors to make the diagnosis. Initially the condition can typically be corrected with glasses or soft contact lenses. As the disease progresses, special contact lenses (such as scleral contact lenses) may be required. In most people the disease stabilizes after a few years without severe vision problems. In 2016, the FDA approved corneal collagen cross-linking to halt the progression of keratoconus. In some cases, when the cornea becomes dangerously thin or when sufficient vision can no longer be achieved by contact lenses due to steepening of the cornea, scarring or lens intolerance, corneal cross-linking is not an option and a corneal transplant may be required. Keratoconus affects about 1 in 2,000 people. However, some estimates suggest that the incidence may be as high as 1 in 400 individuals. It occurs most commonly in late childhood to early adulthood. While it occurs in all populations it may be more frequent in certain ethnic groups such as those of Asian descent. The word is from the Greek kéras meaning cornea and the Latin cōnus meaning cone. Signs and symptoms People with early keratoconus often notice a minor blurring or distortion of their vision, as well as an increased sensitivity to light, and visit their clinician seeking corrective lenses for reading or driving. At early stages, the symptoms of keratoconus may be no different from those of any other refractive defect of the eye. As the disease progresses, vision deteriorates, sometimes rapidly due to irregular astigmatism. Visual acuity becomes impaired at all distances, and night vision is often poor. Some individuals have vision in one eye that is markedly worse than the other eye. The disease is often bilateral, though asymmetrical. Some develop photophobia (sensitivity to bright light), eye strain from squinting in order to read, or itching in the eye, but there is normally little or no sensation of pain. It may cause luminous objects to appear as cylindrical pipes with the same intensity at all points. The classic symptom of keratoconus is the perception of multiple "ghost" images, known as monocular polyopia. This effect is most clearly seen with a high contrast field, such as a point of light on a dark background. Instead of seeing just one point, a person with keratoconus sees many images of the point, spread out in a chaotic pattern. This pattern does not typically change from day to day, but over time, it often takes on new forms. People also commonly notice streaking and flaring distortion around light sources. Some even notice the images moving relative to one another in time with their heartbeat. The predominant optical aberration of the eye in keratoconus is coma. The visual distortion experienced by the person comes from two sources, one being the irregular deformation of the surface of the cornea, and the other being scarring that occurs on its exposed highpoints. These factors act to form regions on the cornea that map an image to different locations on the retina. The effect can worsen in low light conditions, as the dark-adapted pupil dilates to expose more of the irregular surface of the cornea. Genetics Six genes have been found to be associated with the condition. These genes include BANP-ZNF469, COL4A4, FOXO1, FNDC3B, IMMP2L and RXRA-COL5A1. Others likely also exist.Patients with a parent, sibling, or child who has keratoconus have 15 to 67 times higher risk in developing corneal ectasia compared to patients with no affected relatives. Pathophysiology Despite considerable research, the cause of keratoconus remains unclear. Several sources suggest that keratoconus likely arises from a number of different factors: genetic, environmental or cellular, any of which may form the trigger for the onset of the disease. Once initiated, the disease normally develops by progressive dissolution of Bowmans layer, which lies between the corneal epithelium and stroma. As the two come into contact, cellular and structural changes in the cornea adversely affect its integrity and lead to the bulging and scarring characteristic of the disorder. Within any individual keratoconic cornea, regions of degenerative thinning coexisting with regions undergoing wound healing may be found. Scarring appears to be an aspect of the corneal degradation; however, a recent, large, multicenter study suggests abrasion by contact lenses may increase the likelihood of this finding by a factor over two.A number of studies have indicated keratoconic corneas show signs of increased activity by proteases, a class of enzymes that break some of the collagen cross-linkages in the stroma, with a simultaneous reduced expression of protease inhibitors. Other studies have suggested that reduced activity by the enzyme aldehyde dehydrogenase may be responsible for a build-up of free radicals and oxidising species in the cornea. Whatever the pathogenetical process, the damage caused by activity within the cornea likely results in a reduction in its thickness and biomechanical strength. At an ultrastructural level the weakening of the corneal tissue is associated with a disruption of the regular arrangement of the collagen layers and collagen fibril orientation. While keratoconus is considered a noninflammatory disorder, one study shows wearing rigid contact lenses by people leads to overexpression of proinflammatory cytokines, such as IL-6, TNF-alpha, ICAM-1, and VCAM-1 in the tear fluid.A genetic predisposition to keratoconus has been observed, with the disease running in certain families, and incidences reported of concordance in identical twins. The frequency of occurrence in close family members is not clearly defined, though it is known to be considerably higher than that in the general population, and studies have obtained estimates ranging between 6% and 19%. Two studies involving isolated, largely homogenetic communities have contrarily mapped putative gene locations to chromosomes 16q and 20q. Most genetic studies agree on an autosomal dominant model of inheritance. A rare, autosomal dominant form of severe keratoconus with anterior polar cataract is caused by a mutation in the seed region of mir-184, a microRNA that is highly expressed in the cornea and anterior lens. Keratoconus is diagnosed more often in people with Downs syndrome, though the reasons for this link have not yet been determined.Keratoconus has been associated with atopic diseases, which include asthma, allergies, and eczema, and it is not uncommon for several or all of these diseases to affect one person. Keratoconus is also associated with Alport syndrome, Down syndrome and Marfan syndrome. A number of studies suggest vigorous eye rubbing contributes to the progression of keratoconus, and people should be discouraged from the practice. Keratoconus differs from ectasia, which is caused by LASIK eye surgery. Post-LASIK Ectasia has been associated with the excessive removal of the eyes stromal bed tissue during surgery. Diagnosis Prior to any physical examination, the diagnosis of keratoconus frequently begins with an ophthalmologists or optometrists assessment of the persons medical history, particularly the chief complaint and other visual symptoms, the presence of any history of ocular disease or injury that might affect vision, and the presence of any family history of ocular disease. An eye chart, such as a standard Snellen chart of progressively smaller letters, is then used to determine the persons visual acuity. The eye examination may proceed to measurement of the localized curvature of the cornea with a manual keratometer, with detection of irregular astigmatism suggesting a possibility of keratoconus. Severe cases can exceed the instruments measuring ability. A further indication can be provided by retinoscopy, in which a light beam is focused on the persons retina and the reflection, or reflex, observed as the examiner tilts the light source back and forth. Keratoconus is amongst the ophthalmic conditions that exhibit a scissor reflex action of two bands moving toward and away from each other like the blades of a pair of scissors.If keratoconus is suspected, the ophthalmologist or optometrist will search for other characteristic findings of the disease by means of slit lamp examination of the cornea. An advanced case is usually readily apparent to the examiner, and can provide for an unambiguous diagnosis prior to more specialized testing. Under close examination, a ring of yellow-brown to olive-green pigmentation known as a Fleischer ring can be observed in around half of keratoconic eyes. The Fleischer ring, caused by deposition of the iron oxide hemosiderin within the corneal epithelium, is subtle and may not be readily detectable in all cases, but becomes more evident when viewed under a cobalt blue filter. Similarly, around 50% of subjects exhibit Vogts striae, fine stress lines within the cornea caused by stretching and thinning. The striae temporarily disappear while slight pressure is applied to the eyeball. A highly pronounced cone can create a V-shaped indentation in the lower eyelid when the persons gaze is directed downwards, known as Munsons sign. Other clinical signs of keratoconus will normally have presented themselves long before Munsons sign becomes apparent, and so this finding, though a classic sign of the disease, tends not to be of primary diagnostic importance. A handheld keratoscope, sometimes known as "Placidos disk", can provide a simple noninvasive visualization of the surface of the cornea by projecting a series of concentric rings of light onto the cornea. A more definitive diagnosis can be obtained using corneal topography, in which an automated instrument projects the illuminated pattern onto the cornea and determines its topography from analysis of the digital image. The topographical map indicates any distortions or scarring in the cornea, with keratoconus revealed by a characteristic steepening of curvature that is usually below the centerline of the eye. The technique can record a snapshot of the degree and extent of the deformation as a benchmark for assessing its rate of progression. It is of particular value in detecting the disorder in its early stages when other signs have not yet presented. Stages Once keratoconus has been diagnosed, its degree may be classified by several metrics: The steepness of greatest curvature from mild (< 45 D), advanced (up to 52 D) or severe (> 52 D); The morphology of the cone: nipple (small: 5 mm and near-central), oval (larger, below-center and often sagging), or globus (more than 75% of cornea affected); The corneal thickness from mild (> 506 μm) to advanced (< 446 μm).Increasing use of corneal topography has led to a decline in use of these terms. Treatment Lenses In early stages of keratoconus, glasses or soft contact lenses can suffice to correct for the mild astigmatism. As the condition progresses, these may no longer provide the person with a satisfactory degree of visual acuity, and most practitioners will move to manage the condition with rigid contact lenses, known as rigid, gas-permeable, (RGP) lenses. RGP lenses provide a good level of visual correction, but do not arrest progression of the condition.In people with keratoconus, rigid contact lenses improve vision by means of tear fluid filling the gap between the irregular corneal surface and the smooth regular inner surface of the lens, thereby creating the effect of a smoother cornea. Many specialized types of contact lenses have been developed for keratoconus, and affected people may seek out both doctors specialized in conditions of the cornea, and contact lens fitters who have experience managing people with keratoconus. The irregular cone presents a challenge and the fitter will endeavor to produce a lens with the optimal contact, stability and steepness. Some trial-and-error fitting may prove necessary. Hybrid lenses Traditionally, contact lenses for keratoconus have been the hard or RGP variety, although manufacturers have also produced specialized soft or hydrophilic lenses and, most recently, silicone hydrogel lenses. A soft lens has a tendency to conform to the conical shape of the cornea, thus diminishing its effect. To counter this, hybrid lenses have been developed that are hard in the centre and encompassed by a soft skirt. However, soft or earlier generation hybrid lenses did not prove effective for every person. Early generation lenses have been discontinued. The fourth generation of hybrid lens technology has improved, giving more people an option that combines the comfort of a soft lens with the visual acuity of an RGP lens. Scleral lenses Scleral lenses are sometimes prescribed for cases of advanced or very irregular keratoconus; these lenses cover a greater proportion of the surface of the eye and hence can offer improved stability. Easier handling can find favor with people with reduced dexterity, such as the elderly. Piggybacking Some people find good vision correction and comfort with a "piggyback" lens combination, in which RGP lenses are worn over soft lenses, both providing a degree of vision correction. One form of piggyback lens makes use of a soft lens with a countersunk central area to accept the rigid lens. Fitting a piggyback lens combination requires experience on the part of the lens fitter, and tolerance on the part of the person with keratoconus. Surgery Corneal transplant Between 11% and 27% of cases of keratoconus will progress to a point where vision correction is no longer possible, thinning of the cornea becomes excessive, or scarring as a result of contact lens wear causes problems of its own, and a corneal transplantation or penetrating keratoplasty becomes required. Keratoconus is the most common grounds for conducting a penetrating keratoplasty, generally accounting for around a quarter of such procedures. The corneal transplant surgeon trephines a lenticule of corneal tissue and then grafts the donor cornea to the existing eye tissue, usually using a combination of running and individual sutures. The cornea does not have a direct blood supply, so the donor tissue is not required to be blood type matched. Eye banks check the donor corneas for any disease or cellular irregularities. The acute recovery period can take four to six weeks, and full postoperative vision stabilization often takes a year or more, but most transplants are very stable in the long term. The National Keratoconus Foundation reports that penetrating keratoplasty has the most successful outcome of all transplant procedures, and when performed for keratoconus in an otherwise healthy eye, its success rate can be 95% or greater. The sutures used usually dissolve over a period of three to five years, but individual sutures can be removed during the healing process if they are causing irritation to the person. In the US, corneal transplants (also known as corneal grafts) for keratoconus are usually performed under sedation as outpatient surgery. In other countries, such as Australia and the UK, the operation is commonly performed with the person undergoing a general anaesthetic. All cases require a careful follow-up with an eye doctor (ophthalmologist or optometrist) for a number of years. Frequently, vision is greatly improved after the surgery, but even if the actual visual acuity does not improve, because the cornea is a more normal shape after the healing is completed, people can more easily be fitted with corrective lenses. Complications of corneal transplants are mostly related to vascularization of the corneal tissue and rejection of the donor cornea. Vision loss is very rare, though difficult-to-correct vision is possible. When rejection is severe, repeat transplants are often attempted, and are frequently successful. Keratoconus will not normally reoccur in the transplanted cornea; incidences of this have been observed, but are usually attributed to incomplete excision of the original cornea or inadequate screening of the donor tissue. The long-term outlook for corneal transplants performed for keratoconus is usually favorable once the initial healing period is completed and a few years have elapsed without problems. One way of reducing the risk of rejection is to use a technique called deep anterior lamellar keratoplasty (DALK). In a DALK graft, only the outermost epithelium and the main bulk of the cornea, the stroma, are replaced; the persons rearmost endothelium layer and the Descemets membrane are left, giving some additional structural integrity to the postgraft cornea. Furthermore, it is possible to transplant freeze-dried donor tissue. The freeze-drying process ensures this tissue is dead, so there is no chance of rejection. Research from two trials in Iran provide low to moderate evidence that graft rejection is more likely to occur in penetrating keratoplasty than in DALK, though the likelihood for graft failure were similar with both procedures. Epikeratophakia Rarely, a nonpenetrating keratoplasty known as an epikeratophakia (or epikeratoplasty) may be performed in cases of keratoconus. The corneal epithelium is removed and a lenticule of donor cornea is grafted on top of it. The procedure requires a greater level of skill on the part of the surgeon, and is less frequently performed than a penetrating keratoplasty, as the outcome is generally less favorable. However, it may be seen as an option in a number of cases, particularly for young people. Corneal ring implants A possible surgical alternative to corneal transplant is the insertion of intrastromal corneal ring segments. A small incision is made in the periphery of the cornea and two thin arcs of polymethyl methacrylate are slid between the layers of the stroma on either side of the pupil before the incision is closed by a suture. The segments push out against the curvature of the cornea, flattening the peak of the cone and returning it to a more natural shape. The procedure offers the benefit of being reversible and even potentially exchangeable as it involves no removal of eye tissue.Corneal intrastromal implantation surgery involving the implantation of a full ring is also available as a treatment option for keratoconus. Evidence supports that the full-ring implant improves vision outcomes for at least a year. Cross-linking Corneal collagen cross-linking is a developing treatment that aims to strengthen the cornea, however, according to a 2015 Cochrane review, there is insufficient evidence to determine if it is useful in keratoconus. In 2016, however, the FDA approved cross-linking surgery as a treatment for keratoconus and recommended that a registry system should be set-up to evaluate the long-term treatment effect. The Save Sight Keratoconus Registry is an international database of keratoconus patients that is tracking outcomes of cross-linking in patients with keratoconus. Radial keratotomy Radial keratotomy is a refractive surgery procedure where the surgeon makes a spoke-like pattern of incisions into the cornea to modify its shape. This early surgical option for myopia has been largely superseded by LASIK and other similar procedures. LASIK is absolutely contraindicated in keratoconus and other corneal thinning conditions as removal of corneal stromal tissue will further damage an already thin and weak cornea. For similar reasons, radial keratotomy has also generally not been used for people with keratoconus. Prognosis Patients with keratoconus typically present initially with mild astigmatism and myopia, commonly at the onset of puberty, and are diagnosed by the late teenage years or early 20s. The disease can, however, present or progress at any age; in rare cases, keratoconus can present in children or not until later adulthood. A diagnosis of the disease at an early age may indicate a greater risk of severity in later life. Patients vision will seem to fluctuate over a period of months, driving them to change lens prescriptions frequently, but as the condition worsens, contact lenses are required in the majority of cases. The course of the disorder can be quite variable, with some patients remaining stable for years or indefinitely, while others progress rapidly or experience occasional exacerbations over a long and otherwise steady course. Most commonly, keratoconus progresses for a period of 10 to 20 years before the course of the disease generally ceases in the third and fourth decades of life. Corneal hydrops In advanced cases, bulging of the cornea can result in a localized rupture of Descemets membrane, an inner layer of the cornea. Aqueous humor from the eyes anterior chamber seeps into the cornea before Descemets membrane reseals. The patient experiences pain and a sudden severe clouding of vision, with the cornea taking on a translucent milky-white appearance known as a corneal hydrops.Although disconcerting to the patient, the effect is normally temporary and after a period of six to eight weeks, the cornea usually returns to its former transparency. The recovery can be aided nonsurgically by bandaging with an osmotic saline solution. Although a hydrops usually causes increased scarring of the cornea, occasionally it will benefit a patient by creating a flatter cone, aiding the fitting of contact lenses. Corneal transplantation is not usually indicated during corneal hydrops. Epidemiology The National Eye Institute reports keratoconus is the most common corneal dystrophy in the United States, affecting about one in 2,000 Americans, but some reports place the figure as high as one in 500. The inconsistency may be due to variations in diagnostic criteria, with some cases of severe astigmatism interpreted as those of keratoconus, and vice versa. A long-term study found a mean incidence rate of 2.0 new cases per 100,000 population per year. Some studies have suggested a higher prevalence amongst females, or that people of South Asian ethnicity are 4.4 times as likely to develop keratoconus as Caucasians, and are also more likely to be affected with the condition earlier.Keratoconus is normally bilateral (affecting both eyes) although the distortion is usually asymmetric and is rarely completely identical in both corneas. Unilateral cases tend to be uncommon, and may in fact be very rare if a very mild condition in the better eye is simply below the limit of clinical detection. It is common for keratoconus to be diagnosed first in one eye and not until later in the other. As the condition then progresses in both eyes, the vision in the earlier-diagnosed eye will often remain poorer than that in its fellow. History The German oculist Burchard Mauchart provided an early description in a 1748 doctoral dissertation of a case of keratoconus, which he called staphyloma diaphanum. However, it was not until 1854 that British physician John Nottingham (1801–1856) clearly described keratoconus and distinguished it from other ectasias of the cornea. Nottingham reported the cases of "conical cornea" that had come to his attention, and described several classic features of the disease, including polyopia, weakness of the cornea, and difficulty matching corrective lenses to the patients vision. In 1859, British surgeon William Bowman used an ophthalmoscope (recently invented by Hermann von Helmholtz) to diagnose keratoconus, and described how to angle the instruments mirror so as to best see the conical shape of the cornea. Bowman also attempted to restore vision by pulling on the iris with a fine hook inserted through the cornea and stretching the pupil into a vertical slit, like that of a cat. He reported that he had had a measure of success with the technique, restoring vision to an 18-year-old woman who had previously been unable to count fingers at a distance of 8 inches (20 cm). By 1869, when the pioneering Swiss ophthalmologist Johann Horner wrote a thesis entitled On the treatment of keratoconus, the disorder had acquired its current name. The treatment at that time, endorsed by the leading German ophthalmologist Albrecht von Graefe, was an attempt to physically reshape the cornea by chemical cauterization with a silver nitrate solution and application of a miosis-causing agent with a pressure dressing. In 1888, the treatment of keratoconus became one of the first practical applications of the then newly invented contact lens, when the French physician Eugène Kalt manufactured a glass scleral shell that improved vision by compressing the cornea into a more regular shape. Since the start of the 20th century, research on keratoconus has both improved understanding of the disease and greatly expanded the range of treatment options. The first successful corneal transplantation to treat keratoconus was done in 1936 by Ramón Castroviejo. Society and culture According to the findings of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK), people who have keratoconus could be expected to pay more than $25,000 over their lifetime post-diagnosis, with a standard deviation of $19,396. There is limited evidence on the costs of corneal cross-linking, a cost-effectiveness study estimated the costs of the total treatment for one person as £928 ($1,392 U.S.) in the UK National Health Service, but this may be as high as $6,500 per eye in other countries. A 2013 cost-benefit analysis by the Lewin Group for Eye Bank Association of America, estimated an average cost of $16,500 for each corneal transplant. Related disorders Several other corneal ectatic disorders also cause thinning of the cornea: Keratoglobus is a very rare condition that causes corneal thinning primarily at the margins, resulting in a spherical, slightly enlarged eye. It may be genetically related to keratoconus. Pellucid marginal degeneration causes thinning of a narrow (1–2 mm) band of the cornea, usually along the inferior corneal margin. It causes irregular astigmatism that, in the early stages of the disease can be corrected by spectacles. Differential diagnosis may be made by slit-lamp examination. Posterior keratoconus, a distinct disorder despite its similar name, is a rare abnormality, usually congenital, which causes a nonprogressive thinning of the inner surface of the cornea, while the curvature of the anterior surface remains normal. Usually only a single eye is affected. Post-LASIK ectasia is a complication of LASIK eye surgery. References External links Keratoconus at Curlie

Please give me a short description about Keratosis follicularis , Aarogya

Keratosis follicularis

Keratosis follicularis may refer to: Dariers disease Focal palmoplantar keratoderma with oral mucosal hyperkeratosisSee also: Isolated dyskeratosis follicularis Keratosis follicularis spinulosa decalvans

Aarogya , Do you know what is Labor induction,

Labor induction

Labor induction is the process or treatment that stimulates childbirth and delivery. Inducing (starting) labor can be accomplished with pharmaceutical or non-pharmaceutical methods. In Western countries, it is estimated that one-quarter of pregnant women have their labor medically induced with drug treatment. Inductions are most often performed either with prostaglandin drug treatment alone, or with a combination of prostaglandin and intravenous oxytocin treatment. Medical uses Commonly accepted medical reasons for induction include: Postterm pregnancy, i.e. if the pregnancy has gone past the end of the 42nd week. Intrauterine fetal growth restriction (IUGR). There are health risks to the woman in continuing the pregnancy (e.g. she has pre-eclampsia). Premature rupture of the membranes (PROM); this is when the membranes have ruptured, but labor does not start within a specific amount of time. Premature termination of the pregnancy (abortion). Fetal death in utero and previous history of stillbirth. Twin pregnancy continuing beyond 38 weeks. Previous health conditions that puts risk on the woman and/or her child such as diabetes, high blood pressure High BMIInduction of labor in those who are either at or after term improves outcomes for newborns and decreases the number of C-sections performed. Methods of induction Methods of inducing labor include both pharmacological medication and mechanical or physical approaches.Mechanical and physical approaches can include artificial rupture of membranes or membrane sweeping. Membrane sweeping may lead to more women spontaneously going into labor (and fewer women having labor induction) but it may make little difference to the risk of maternal or neonatal death, or to the number of women having c-sections or spontaneous vaginal births.The use of intrauterine catheters are also indicated. These work by compressing the cervix mechanically to generate release on prostaglandins in local tissues. There is no direct effect on the uterus.Results from a 2021 systematic review found no differences in cesarean delivery nor neonatal outcomes in women with low-risk pregnancies between inpatient nor outpatient cervical ripening. Medication Intravaginal, endocervical or extra-amniotic administration of prostaglandin, such as dinoprostone or misoprostol. Prostaglandin E2 is the most studied compound and with most evidence behind it. A range of different dosage forms are available with a variety of routes possible. The use of misoprostol has been extensively studied but normally in small, poorly defined studies. Only a very few countries have approved misoprostol for use in induction of labor. Intravenous (IV) administration of synthetic oxytocin preparations is used to artificially induce labor if it is deemed medically necessary. A high dose of oxytocin does not seem to have greater benefits than a standard dose. There are risks associated with IV oxytocin induced labor. Risks include the women having induced contractions that are too vigorous, too close together (frequent), or that last too long, which may lead to added stress on the baby (changes in babys heart rate) and may require the mother to have an emergency caesarean section. There is no high quality evidence to indicate if IV oxytocin should be stopped once a woman reaches active labor in order to reduce the incidence of women requiring caesarean sections. Use of mifepristone has been described but is rarely used in practice. Relaxin has been investigated, but is not currently commonly used. mnemonic; ARNOP: Antiprogesterone, relaxin, nitric oxide donors, oxytocin, prostaglandins Non-pharmaceutical Membrane sweep, also known as membrane stripping, Hamilton maneuver, or "stretch and sweep". The procedure is carried out by a midwife or doctor as part of an internal vaginal examination. The midwife or doctor puts a couple of lubricated, gloved fingers into the womens vagina and inserts their index finger into the opening of the cervix or neck of the womb. They then use a circular movement to try to separate the membranes of the amniotic sac, containing the baby, from the cervix. This action, which releases hormones called prostaglandins, may prepare the cervix for birth and may initiate labour. Artificial rupture of the membranes (AROM or ARM) ("breaking the waters") Extra-amniotic saline infusion (EASI), in which a Foley catheter is inserted into the cervix and the distal portion expanded to dilate it and to release prostaglandins. Cook Medical Double Balloon known as the Cervical Ripening Balloon with Stylet for assisted placement is FDA approved. The Double balloon provides one balloon to be inflated with saline on one side of the Uterine side of the cervix and the second balloon to be inflated with saline on the vaginal side of the cervix. When to induce The American Congress of Obstetricians and Gynecologists has recommended against elective induction before 39 weeks if there is no medical indication and the cervix is unfavorable. One recent study indicates that labor induction at term (41 weeks) or post-term reduces the rate of caesarean section by 12 per cent, and also reduces fetal death. Some observational/retrospective studies have shown that non-indicated, elective inductions before the 41st week of gestation are associated with an increased risk of requiring a caesarean section. Randomized clinical trials have not addressed this question. However, researchers have found that multiparous women who undergo labor induction without medical indicators are not predisposed to caesarean sections. Doctors and pregnant women should have a discussion of risks and benefits when considering an induction of labor in the absence of an accepted medical indication. There is insufficient evidence to determine if inducing a womens labor at home is a safe and effective approach for both the women and the baby.Studies have shown a slight increase in risk of infant mortality for births in the 41st and particularly 42nd week of gestation, as well as a higher risk of injury to the mother and child. Due to the increasing risks of advanced gestation, induction appears to reduce the risk for caesarean delivery after 41 weeks gestation and possibly earlier. Inducing labour after 41 weeks of completed gestion is likely to reduce the risk of perinatal death and stillbirth compared with waiting for labour to start spontaneously.Inducing labor before 39 weeks in the absence of a medical indication (such as hypertension, IUGR, or pre-eclampsia) increases the risk of complications of prematurity including difficulties with respiration, infection, feeding, jaundice, neonatal intensive care unit admissions, and perinatal death.Inducing labour after 34 weeks and before 37 weeks in women with hypertensive disorders (pre-eclampsia, eclampsia, pregnancy-induced hypertension) may lead to better outcomes for the woman but does not improve or worsen outcomes for the baby. More research is needed to produce more certain results. If waters break (membranes rupture) between 24 and 37 weeks gestation, waiting for the labour to start naturally with careful monitoring of the woman and baby is more likely to lead to healthier outcomes. For women over 37 weeks pregnant whose babies are suspected of not coping well in the womb, it is not yet clear from research whether it is best to have an induction or caesarean immediately, or to wait until labour happens by itself. Similarly, there is not yet enough research to show whether it is best to deliver babies prematurely if they are not coping in the womb or whether to wait so that they are less premature when they are born.Clinicians assess the odds of having a vaginal delivery after labor induction by a "Bishop score". However, recent research has questioned the relationship between the Bishop score and a successful induction, finding that a poor Bishop score actually may improve the chance for a vaginal delivery after induction. A Bishop Score is done to assess the progression of the cervix prior to an induction. In order to do this, the cervix must be checked to see how much it has effaced, thinned out, and how far dilated it is. The score goes by a points system depending on five factors. Each factor is scored on a scale of either 0–2 or 0–3, any total score less than 5 holds a higher risk of delivering by caesarean section.Sometimes when a womans waters break after 37 weeks she is induced instead of waiting for labour to start naturally. This may decrease the risks of infection for the woman and baby but more research is needed to find out whether inducing is good for women and babies longer term.Women who have had a caesarean section for a previous pregnancy are at risk of having a uterine rupture, when their caesarean scar re-opens. Uterine rupture is very serious for the woman and the baby, and induction of labour increases this risk further. There is not yet enough research to determine which method of induction is safest for a woman who has had a caesarean section before. There is also no research to say whether it is better for these women and their babies to have an elective caesarean section instead of being induced. Criticisms of induction Induced labor may be more painful for the woman as one of the side effects of intravenous oxytocin is increased contraction pains, mainly due to the rigid onset. This may lead to the increased use of analgesics and other pain-relieving pharmaceuticals. These interventions may also lead to an increased likelihood of caesarean section delivery for the baby. However, studies into this matter show differing results. One study indicated that while overall caesarean section rates from 1990 to 1997 remained at or below 20 per cent, elective induction was associated with a doubling of the rate of Caesarean section. Another study showed that elective induction in women who were not post-term increased a womans chance of a C-section by two to three times. A more recent study indicated that induction may increase the risk of caesarean section if performed before the 40th week of gestation, but it has no effect or actually lowers the risk if performed after the 40th week.A 2014 systematic review and meta analysis on the subject of induction and its effect on cesarean section indicate that after 41 weeks of gestation there is a reduction of cesarean deliveries when the labour is induced.The Institute for Safe Medication Practices labeled pitocin a "high-alert medication" because of the high likelihood of "significant patient harm when it is used in error." See also Tocolytic, labor suppressant References External links Harman, Kim (1999). "Current Trends in Cervical Ripening and Labor Induction". American Family Physician. 60 (2): 477–84. PMID 10465223. Inducing Labor – WebMD.com Induction of labour. Clinical guideline, UK National Institute for Health and Clinical Excellence, June 2001. Josie L. Tenore: Methods for cervical ripening and induction of labor Archived 2008-05-16 at the Wayback Machine. American Family Physician, 15 May 2003. "Catecholamines – blood ." National Library of Medicine . N.p., n.d. Web. 28 Mar. 2011. <https://www.nlm.nih.gov/medlineplus>.

Hi Aarogya, explain a situation where Childbirth occurs

Childbirth

Childbirth, also known as labour and delivery, is the ending of pregnancy where one or more babies exits the internal environment of the mother via vaginal delivery or Caesarean section. In 2019, there were about 140.11 million births globally. In the developed world most deliveries occur in hospitals, while in the developing world most were at home births.The most common childbirth method is vaginal delivery. It involves four stages of labour: the shortening and opening of the cervix during the first stage, descent and birth of the baby during the second, the delivery of the placenta during the third, and the recovery of the mother and infant during the fourth stage, which is referred to as the postpartum. The first stage is characterized by abdominal cramping or back pain that typically lasts half a minute and occurs every 10 to 30 minutes. Contractions gradually becomes stronger and closer together. Since the pain of childbirth correlates with contractions, the pain becomes more frequent and strong as the labor progresses. The second stage ends when the infant is fully expelled. The third stage is the delivery of the placenta. The fourth stage of labour involves the recovery of the mother, delayed clamping of the umbilical cord, and monitoring of the neonate. As of 2014, all major health organizations advise that immediately following a live birth, regardless of the delivery method, that the infant be placed on the mothers chest (termed skin-to-skin contact), and to delay neonate procedures for at least one to two hours or until the baby has had its first breastfeeding.A vaginal delivery is recommended over a cesarean section due to increased risk for complications of a cesarean section and natural benefits of a vaginal delivery in both mother and baby. Various methods may help with pain, such as relaxation techniques, opioids, and spinal blocks. It is best practice to limit the amount of interventions that occur during labour and delivery such as an elective cesarean section, however in some cases a scheduled cesarean section must be planned for a successful delivery and recovery of the mother. An emergency cesarean section may be recommended if unexpected complications occur or little to no progression through the birthing canal is observed in a vaginal delivery. Each year, complications from pregnancy and childbirth result in about 500,000 birthing deaths, seven million women have serious long-term problems, and 50 million women giving birth have negative health outcomes following delivery, most of which occur in the developing world. Complications in the mother include obstructed labour, postpartum bleeding, eclampsia, and postpartum infection. Complications in the baby include lack of oxygen at birth, birth trauma, and prematurity. Signs and symptoms The most prominent sign of labour is strong repetitive uterine contractions. Pain in contractions has been described as feeling similar to very strong menstrual cramps. Women giving birth are often encouraged to refrain from screaming. However, moaning and grunting may be encouraged to help lessen pain. Crowning may be experienced as an intense stretching and burning. Back labour is a term for specific pain occurring in the lower back, just above the tailbone, during childbirth.Another prominent sign of labour is the rupture of membranes, commonly known as "water breaking". This is the leaking of fluid from the amniotic sac that surrounds a fetus in the uterus and helps provide cushion and thermoregulation. However, it is common for water to break long before contractions begin and in which case it is not a sign of immediate labor and hospitalization is generally required for monitoring the fetus and prevention of preterm birth. Psychological During the later stages of gestation there is an increase in abundance of oxytocin, a hormone that is known to evoke feelings of contentment, reductions in anxiety, and feelings of calmness and security around the mate. Oxytocin is further released during labour when the fetus stimulates the cervix and vagina, and it is believed that it plays a major role in the bonding of a mother to her infant and in the establishment of maternal behavior. The act of nursing a child also causes a release of oxytocin to help the baby get milk more easily from the nipple. Vaginal birth Station refers to the relationship of the fetal presenting part to the level of the ischial spines. When the presenting part is at the ischial spines the station is 0 (synonymous with engagement). If the presenting fetal part is above the spines, the distance is measured and described as minus stations, which range from −1 to −4 cm. If the presenting part is below the ischial spines, the distance is stated as plus stations ( +1 to +4 cm). At +3 and +4 the presenting part is at the perineum and can be seen.The fetal head may temporarily change shape (becoming more elongated or cone shaped) as it moves through the birth canal. This change in the shape of the fetal head is called molding and is much more prominent in women having their first vaginal delivery.Cervical ripening is the physical and chemical changes in the cervix to prepare it for the stretching that will take place as the fetus moves out of the uterus and into the birth canal. A scoring system called a Bishop score can be used to judge the degree of cervical ripening in order to predict the timing of labour and delivery of the infant or for women at risk for preterm labour. It is also used to judge when a woman will respond to induction of labour for a postdate pregnancy or other medical reasons. There are several methods of inducing cervical ripening which will allow the uterine contractions to effectively dilate the cervix.Vaginal delivery involves four stages of labour: the shortening and opening of the cervix during the first stage, descent and birth of the baby during the second, the delivery of the placenta during the third, and the 4th stage of recovery which lasts until two hours after the delivery. The first stage is characterized by abdominal cramping or back pain that typically lasts around half a minute and occurs every 10 to 30 minutes. The contractions (and pain) gradually becomes stronger and closer together. The second stage ends when the infant is fully expelled. In the third stage, the delivery of the placenta. The fourth stage of labour involves recovery, the uterus beginning to contract to pre-pregnancy state, delayed clamping of the umbilical cord, and monitoring of the neonatal tone and vitals. As of 2014, all major health organizations advise that immediately following a live birth, regardless of the delivery method, that the infant be placed on the mothers chest, termed skin-to-skin contact, and delaying routine procedures for at least one to two hours or until the baby has had its first breastfeeding. Onset of labour Definitions of the onset of labour include: Regular uterine contractions at least every six minutes with evidence of change in cervical dilation or cervical effacement between consecutive digital examinations. Regular contractions occurring less than 10 minutes apart and progressive cervical dilation or cervical effacement. At least three painful regular uterine contractions during a 10-minute period, each lasting more than 45 seconds.Many women are known to experience what has been termed the "nesting instinct". Women report a spurt of energy shortly before going into labour. Common signs that labour is about to begin may include what is known as lightening, which is the process of the baby moving down from the rib cage with the head of the baby engaging deep in the pelvis. The pregnant woman may then find breathing easier, since her lungs have more room for expansion, but pressure on her bladder may cause more frequent need to void (urinate). Lightening may occur a few weeks or a few hours before labour begins, or even not until labour has begun. Some women also experience an increase in vaginal discharge several days before labour begins when the "mucus plug", a thick plug of mucus that blocks the opening to the uterus, is pushed out into the vagina. The mucus plug may become dislodged days before labour begins or not until the start of labour.While inside the uterus the baby is enclosed in a fluid-filled membrane called the amniotic sac. Shortly before, at the beginning of, or during labour the sac ruptures. Once the sac ruptures, termed "the water breaks", the baby is at risk for infection and the mothers medical team will assess the need to induce labour if it has not started within the time they believe to be safe for the infant.The first stage of labour is divided into latent and active phases, where the latent phase is sometimes included in the definition of labour, and sometimes not. First stage: latent phase The latent phase is generally defined as beginning at the point at which the woman perceives regular uterine contractions. In contrast, Braxton Hicks contractions, which are contractions that may start around 26 weeks gestation and are sometimes called "false labour", are infrequent, irregular, and involve only mild cramping.Cervical effacement, which is the thinning and stretching of the cervix, and cervical dilation occur during the closing weeks of pregnancy. Effacement is usually complete or near-complete and dilation is about 5 cm by the end of the latent phase. The degree of cervical effacement and dilation may be felt during a vaginal examination. First stage: active phase The active stage of labour (or "active phase of first stage" if the previous phase is termed "latent phase of first stage") has geographically differing definitions. The World Health Organization describes the active first stage as "a period of time characterized by regular painful uterine contractions, a substantial degree of cervical effacement and more rapid cervical dilatation from 5 cm until full dilatation for first and subsequent labours. In the US, the definition of active labour was changed from 3 to 4 cm, to 5 cm of cervical dilation for multiparous women, mothers who had given birth previously, and at 6 cm for nulliparous women, those who had not given birth before. This was done in an effort to increase the rates of vaginal delivery.Health care providers may assess a labouring mothers progress in labour by performing a cervical exam to evaluate the cervical dilation, effacement, and station. These factors form the Bishop score. The Bishop score can also be used as a means to predict the success of an induction of labour. During effacement, the cervix becomes incorporated into the lower segment of the uterus. During a contraction, uterine muscles contract causing shortening of the upper segment and drawing upwards of the lower segment, in a gradual expulsive motion. The presenting fetal part then is permitted to descend. Full dilation is reached when the cervix has widened enough to allow passage of the babys head, around 10 cm dilation for a term baby. A standard duration of the latent first stage has not been established and can vary widely from one woman to another. However, the duration of active first stage (from 5 cm until full cervical dilatation) usually does not extend beyond 12 hours in the first labour("primiparae"), and usually does not extend beyond 10 hours in subsequent labours ("multiparae").Dystocia of labour, also called "dysfunctional labour" or "failure to progress", is difficult labour or abnormally slow progress of labour, involving progressive cervical dilatation or lack of descent of the fetus. Friedmans Curve, developed in 1955, was for many years used to determine labour dystocia. However, more recent medical research suggests that the Friedman curve may not be currently applicable. Second stage: fetal expulsion The expulsion stage begins when the cervix is fully dilated, and ends when the baby is born. As pressure on the cervix increases, a sensation of pelvic pressure is experienced, and, with it, an urge to begin pushing. At the beginning of the normal second stage, the head is fully engaged in the pelvis; the widest diameter of the head has passed below the level of the pelvic inlet. The fetal head then continues descent into the pelvis, below the pubic arch and out through the vaginal introitus (opening). This is assisted by the additional maternal efforts of "bearing down" or pushing, similar to defecation. The appearance of the fetal head at the vaginal orifice is termed the "crowning". At this point, the mother will feel an intense burning or stinging sensation. When the amniotic sac has not ruptured during labour or pushing, the infant can be born with the membranes intact. This is referred to as "delivery en caul". Complete expulsion of the baby signals the successful completion of the second stage of labour. Some babies, especially preterm infants, are born covered with a waxy or cheese-like white substance called vernix. It is thought to have some protective roles during fetal development and for a few hours after birth. The second stage varies from one woman to another. In first labours, birth is usually completed within three hours whereas in subsequent labours, birth is usually completed within two hours. Second-stage labours longer than three hours are associated with declining rates of spontaneous vaginal delivery and increasing rates of infection, perineal tears, and obstetric haemorrhage, as well as the need for intensive care of the neonate. Third stage: placenta delivery The period from just after the fetus is expelled until just after the placenta is expelled is called the third stage of labour or the involution stage. Placental expulsion begins as a physiological separation from the wall of the uterus. The average time from delivery of the baby until complete expulsion of the placenta is estimated to be 10–12 minutes dependent on whether active or expectant management is employed. In as many as 3% of all vaginal deliveries, the duration of the third stage is longer than 30 minutes and raises concern for retained placenta.Placental expulsion can be managed actively or it can be managed expectantly, allowing the placenta to be expelled without medical assistance. Active management is the administration of a uterotonic drug within one minute of fetal delivery, controlled traction of the umbilical cord and fundal massage after delivery of the placenta, followed by performance of uterine massage every 15 minutes for two hours. In a joint statement, World Health Organization, the International Federation of Gynaecology and Obstetrics and the International Confederation of Midwives recommend active management of the third stage of labour in all vaginal deliveries to help to prevent postpartum haemorrhage.Delaying the clamping of the umbilical cord for at least one minute or until it ceases to pulsate, which may take several minutes, improves outcomes as long as there is the ability to treat jaundice if it occurs. For many years it was believed that late cord cutting led to a mothers risk of experiencing significant bleeding after giving birth, called postpartum bleeding. However a recent review found that delayed cord cutting in healthy full-term infants resulted in early haemoglobin concentration and higher birthweight and increased iron reserves up to six months after birth with no change in the rate of postpartum bleeding. Fourth stage The "fourth stage of labour" is the period beginning immediately after the birth of a child and extending for about six weeks. The terms postpartum and postnatal are often used for this period. The womans body, including hormone levels and uterus size, return to a non-pregnant state and the newborn adjusts to life outside the mothers body. The World Health Organization (WHO) describes the postnatal period as the most critical and yet the most neglected phase in the lives of mothers and babies; most deaths occur during the postnatal period.Following the birth, if the mother had an episiotomy or a tearing of the perineum, it is stitched. This is also an optimal time for uptake of long-acting reversible contraception (LARC), such as the contraceptive implant or intrauterine device (IUD), both of which can be inserted immediately after delivery while the woman is still in the delivery room. The mother has regular assessments for uterine contraction and fundal height, vaginal bleeding, heart rate and blood pressure, and temperature, for the first 24 hours after birth. Some women may experience an uncontrolled episode of shivering or postpartum chills following the birth. The first passing of urine should be documented within six hours. Afterpains (pains similar to menstrual cramps), contractions of the uterus to prevent excessive blood flow, continue for several days. Vaginal discharge, termed "lochia", can be expected to continue for several weeks; initially bright red, it gradually becomes pink, changing to brown, and finally to yellow or white.At one time babies born in hospitals were removed from their mothers shortly after birth and brought to the mother only at feeding times. Mothers were told that their newborn would be safer in the nursery and that the separation would offer the mother more time to rest. As attitudes began to change, some hospitals offered a "rooming in" option wherein after a period of routine hospital procedures and observation, the infant could be allowed to share the mothers room. As of 2020, rooming in has increasingly become standard practice in maternity wards. Cardinal Movements of birth Humans are bipedal with an erect stance. The erect posture causes the weight of the abdominal contents to thrust on the pelvic floor, a complex structure which must not only support this weight but allow, in women, three channels to pass through it: the urethra, the vagina and the rectum. The infants head and shoulders must go through a specific sequence of maneuvers in order to pass through the ring of the mothers pelvis. Range of motion and ambulation are typically unaffected during labour and it is encouraged that the mother move to help facilitate progression of labour. The vagina is called a birth canal when the baby enters this passage. Six phases of a typical vertex or cephalic (head-first presentation) delivery: Engagement of the fetal head in the transverse position. The babys head is facing across the pelvis at one or other of the mothers hips. Descent and flexion of the fetal head. The babies head moves down the birthing canal and tucks its chin on its chest so that the back or crown of its head leads the way through the birth canal. Internal rotation. The fetal head rotates 90 degrees to the occipito-anterior position so that the babys face is towards the mothers rectum. Delivery by extension. The back of the neck presses against the pubic bone and its chin leaves its chest, extending the neck – as if to look up, and the rest of its head passes out of the birth canal. Restitution. The fetal head turns through 45 degrees to restore its normal relationship with the shoulders, which are still at an angle. External rotation. The shoulders repeat the corkscrew movements of the head, which can be seen in the final movements of the fetal head.Failure to complete the cardinal movements of birth in the correct order may result in complications of labour and birth injuries. Early skin-to-skin contact Skin-to-skin contact (SSC), sometimes also called kangaroo care, is a technique of newborn care where babies are kept chest-to-chest and skin-to-skin with a parent, typically their mother, though more recently (2022) their father as well. This means without the shirt or undergarments on the chest of both the baby and parent. A 2011 medical review found that early skin-to-skin contact resulted in a decrease in infant crying, improved cardio-respiratory stability and blood glucose levels, and improved breastfeeding duration. A 2016 Cochrane review also found that SSC at birth promotes the likelihood and effectiveness of breastfeeding.As of 2014, early postpartum SSC is endorsed by all major organizations that are responsible for the well-being of infants, including the American Academy of Pediatrics. The World Health Organization (WHO) states that "the process of childbirth is not finished until the baby has safely transferred from placental to mammary nutrition." It is advised that the newborn be placed skin-to-skin with the mother following vaginal birth, or as soon as the mother is alert and responsive after a Caesarean section, postponing any routine procedures for at least one to two hours. The babys father or other support person may also choose to hold the baby SSC until the mother recovers from the anesthetic.The WHO suggests that any initial observations of the infant can be done while the infant remains close to the mother, saying that even a brief separation before the baby has had its first feed can disturb the bonding process. They further advise frequent skin-to-skin contact as much as possible during the first days after delivery, especially if it was interrupted for some reason after the delivery.La Leche League advises a women to have a delivery team which includes a support person who will advocate to assure that: The mother and her baby are not separated unnecessarily The baby will receive only her milk The baby will receive no supplementation without a medical reason All testing, bathing or other procedures are done in the parents roomIt has long been known that a mothers level of the hormone oxytocin, sometimes called "the love hormone", elevates in a mother when she interacts with her infant. In 2019, a large review of the effects of oxytocin found that the oxytocin level in fathers that engage in SSC is increased as well. Two studies found that "when the infant is clothed only in a diaper and placed in between the mother or fathers breasts, chest-to-chest [elevated paternal oxytocin levels were] shown to reduce stress and anxiety in parents after interaction." Discharge For births that occur in hospitals the WHO recommends a hospital stay of at least 24 hours following an uncomplicated vaginal delivery and 96 hours for a Cesarean section. Looking at length of stay (in 2016) for an uncomplicated delivery around the world shows an average of less that 1 day in Egypt to 6 days in (pre-war) Ukraine. Averages for Australia are 2.8 days and 1.5 days in the UK. While this number is low, two-thirds of women in the UK have midwife-assisted births and in some cases the mother may choose a hospital setting for birth to be closer to the wide range of assistance available for an emergency situation. However, women with midwife care may leave the hospital shortly after birth and her midwife will continue her care at her home. In the U.S. the average length of stay has gradually dropped from 4.1 days in 1970 to a current stay of 2 days. The CDC attributed the drop to the rise in health care costs, saying people could not afford to stay in the hospital any longer. To keep it from dropping any lower, in 1996 congress passed the Newborns and Mothers Health Protection Act that requires insurers to cover at least 48 hours for uncomplicated delivery. Labour induction and Caesarean section In many cases and with increasing frequency, childbirth is achieved through labour induction or caesarean section. Labour induction is the process or treatment that stimulates childbirth and delivery. Inducing labour can be accomplished with pharmaceutical or non-pharmaceutical methods. Inductions are most often performed either with prostaglandin drug treatment alone, or with a combination of prostaglandin and intravenous oxytocin treatment. Caesarean section is the removal of the neonate through a surgical incision in the abdomen, rather than through vaginal birth. Childbirth by C-sections increased 50% in the US from 1996 to 2006. In 2012, about 23 million deliveries occurred by Caesarean section. Induced births and elective cesarean before 39 weeks can be harmful to the neonate as well as harmful or without benefit to the mother. Therefore, many guidelines recommend against non-medically required induced births and elective cesarean before 39 weeks. The 2012 rate of labour induction in the United States was 23.3 per cent, and had more than doubled from 1990 to 2010. The American Congress of Obstetricians and Gynecologists (ACOG) guidelines recommend a full evaluation of the maternal-fetal status, the status of the cervix, and at least a 39 completed weeks (full term) of gestation for optimal health of the newborn when considering elective induction of labour. Per these guidelines, indications for induction may include: Abruptio placentae Chorioamnionitis Fetal compromise such as isoimmunisation leading to haemolytic disease of the newborn or oligohydramnios Fetal demise Gestational hypertension Maternal conditions such as gestational diabetes or chronic kidney disease Preeclampsia or eclampsia Premature rupture of membranes Post-term pregnancyInduction is also considered for logistical reasons, such as the distance from hospital or psychosocial conditions, but in these instances gestational age confirmation must be done, and the maturity of the fetal lung must be confirmed by testing. The ACOG also note that contraindications for induced labour are the same as for spontaneous vaginal delivery, including vasa previa, complete placenta praevia, umbilical cord prolapse or active genital herpes simplex infection.A Caesarean section, also called a C section, can be the safest option for delivery in some pregnancies. During a C section, the patient is usually numbed with an epidural or a spinal block, but general anesthesia can be used as well. A cut is made in the patient’s abdomen and then in the uterus to remove the baby. A C section may be the best option when the small size or shape of the mothers pelvis makes delivery of the baby impossible, or the lie or presentation of the baby as it prepares to enter the birth canal is dangerous. Other medical reasons for C section are placenta previa (the placenta blocks the baby’s path to the birth canal), uterine rupture, or fetal distress, like due to endangerment of the baby’s oxygen supply. Before the 1970s, once a patient delivered one baby via C section, it was recommended that all of her future babies be delivered by C section, but that recommendation has changed. Unless there is some other indication, mothers can attempt a trial of labor and most are able to have a vaginal birth after C section (VBAC).Like any procedure, a C section is not without risks. Having a C section puts the mother at greater risk for uterine rupture and abnormal attachment of the placenta to the uterus in future pregnancies (placenta accreta spectrum). The rate of deliveries occurring via C section instead of vaginal deliveries has been increasing since the 1970s. The WHO recommends a C section rate of between 10 to 15 percent because C sections rates higher than 10 percent are not associated with a decrease in morbidity and mortality. Management Obstetric care frequently subjects women to institutional routines, which may have adverse effects on the progress of labour. Supportive care during labour may involve emotional support, comfort measures, and information and advocacy which may promote the physical process of labour as well as womens feelings of control and competence, thus reducing the need for obstetric intervention. The continuous support may be provided either by hospital staff such as nurses or midwives, doulas, or by companions of the womans choice from her social network.There is increasing evidence to show that the participation of the childs father in the birth leads to a better birth and also post-birth outcomes, providing the father does not exhibit excessive anxiety.Continuous labour support may help women to give birth spontaneously, that is, without caesarean or vacuum or forceps, with slightly shorter labours, and to have more positive feelings regarding their experience of giving birth. Continuous labour support may also reduce womens use of pain medication during labour and reduce the risk of babies having low five-minute Agpar scores. Preparation Eating or drinking during labour is an area of ongoing debate. While some have argued that eating in labour has no harmful effects on outcomes, others continue to have concern regarding the increased possibility of an aspiration event (choking on recently eaten foods) in the event of an emergency delivery due to the increased relaxation of the oesophagus in pregnancy, upward pressure of the uterus on the stomach, and the possibility of general anaesthetic in the event of an emergency cesarean. A 2013 Cochrane review found that with good obstetrical anaesthesia there is no change in harms from allowing eating and drinking during labour in those who are unlikely to need surgery. They additionally acknowledge that not eating does not mean there is an empty stomach or that its contents are not as acidic. They therefore conclude that "women should be free to eat and drink in labour, or not, as they wish."At one time shaving of the area around the vagina, was common practice due to the belief that hair removal reduced the risk of infection, made an episiotomy (a surgical cut to enlarge the vaginal entrance) easier, and helped with instrumental deliveries. It is currently less common, though it is still a routine procedure in some countries even though a systematic review found no evidence to recommend shaving. Side effects appear later, including irritation, redness, and multiple superficial scratches from the razor. Another effort to prevent infection has been the use of the antiseptic chlorhexidine or providone-iodine solution in the vagina. Evidence of benefit with chlorhexidine is lacking. A decreased risk is found with providone-iodine when a cesarean section is to be performed. Forceps or vacuum assisted delivery An assisted delivery is used in about 1 in 8 births, and may be needed if either mother or infant appears to be at risk during a vaginal delivery. The methods used are termed obstetrical forceps extraction and vacuum extraction, also called ventouse extraction. Done properly, they are both safe with some preference for forceps rather than vacuum, and both are seen as preferable to an unexpected C-section. While considered safe, some risks for the mother include vaginal tearing, including a higher chance of having a more major vaginal tear that involves the muscle or wall of the anus or rectum. For women undergoing operative vaginal delivery with vacuum extraction or forceps, there is strong evidence that prophylactic antibiotics help to reduce the risk of infection. There is a higher risk of blood clots forming in the legs or pelvis – anti-clot stockings or medication may be ordered to avoid clots. Urinary incontinence is not unusual after childbirth but it is more common after an instrument delivery. Certain exercises and physiotherapy will help the condition to improve. Pain control Non pharmaceutical Some women prefer to avoid analgesic medication during childbirth. Psychological preparation may be beneficial. Relaxation techniques, immersion in water, massage, and acupuncture may provide pain relief. Acupuncture and relaxation were found to decrease the number of caesarean sections required. Immersion in water has been found to relieve pain during the first stage of labour and to reduce the need for anaesthesia and shorten the duration of labour, however the safety and efficacy of immersion during birth, water birth, has not been established or associated with maternal or fetal benefit.Most women like to have someone to support them during labour and birth; such as a midwife, nurse, or doula; or a lay person such as the father of the baby, a family member, or a close friend. Studies have found that continuous support during labour and delivery reduce the need for medication and a caesarean or operative vaginal delivery, and result in an improved Apgar score for the infant. Pharmaceutical Different measures for pain control have varying degrees of success and side effects to the woman and her baby. In some countries of Europe, doctors commonly prescribe inhaled nitrous oxide gas for pain control, especially as 53% nitrous oxide, 47% oxygen, known as Entonox; in the UK, midwives may use this gas without a doctors prescription. Opioids such as fentanyl may be used, but if given too close to birth there is a risk of respiratory depression in the infant.Popular medical pain control in hospitals include the regional anaesthetics epidurals (EDA), and spinal anaesthesia. Epidural analgesia is a generally safe and effective method of relieving pain in labour, but has been associated with longer labour, more operative intervention (particularly instrument delivery), and increases in cost. However, a more recent (2017) Cochrane review suggests that the new epidural techniques have no effect on labour time and the use of instruments or the need for C-section deliveries. Generally, pain and stress hormones rise throughout labour for women without epidurals, while pain, fear, and stress hormones decrease upon administration of epidural analgesia, but rise again later. Medicine administered via epidural can cross the placenta and enter the bloodstream of the fetus. Epidural analgesia has no statistically significant impact on the risk of caesarean section, and does not appear to have an immediate effect on neonatal status as determined by Apgar scores. Augmentation Augmentation is the process of stimulating the uterus to increase the intensity and duration of contractions after labour has begun. Several methods of augmentation are commonly been used to treat slow progress of labour (dystocia) when uterine contractions are assessed to be too weak. Oxytocin is the most common method used to increase the rate of vaginal delivery. The World Health Organization recommends its use either alone or with amniotomy (rupture of the amniotic membrane) but advises that it must be used only after it has been correctly confirmed that labour is not proceeding properly if harm is to be avoided. The WHO does not recommend the use of antispasmodic agents for prevention of delay in labour. Episiotomy For years an episiotomy was thought to help prevent more extensive vaginal tears and heal better than a natural tear. Perineal tears can occur at the vaginal opening as the babys head passes through, especially if the baby descends quickly. Tears can involve the perineal skin or extend to the muscles and the anal sphincter and anus. Once common, they are now recognised as generally not needed. When needed, the midwife or obstetrician makes a surgical cut in the perineum to prevent severe tears that can be difficult to repair. A 2017 Cochrane review compared episiotomy as needed (restrictive) with routine episiotomy to determine the possible benefits and harms for mother and baby. The review found that restrictive episiotomy policies appeared to give a number of benefits compared with using routine episiotomy. Women experienced less severe perineal trauma, less posterior perineal trauma, less suturing and fewer healing complications at seven days with no difference in occurrence of pain, urinary incontinence, painful sex or severe vaginal/perineal trauma after birth. Multiple births In cases of a head first-presenting first twin, twins can often be delivered vaginally. In some cases twin delivery is done in a larger delivery room or in an operating theatre, in the event of complication e.g. Both twins born vaginally – this can occur both presented head first or where one comes head first and the other is breech and/or helped by a forceps/ventouse delivery One twin born vaginally and the other by caesarean section. If the twins are joined at any part of the body – called conjoined twins, delivery is mostly by caesarean section. Fetal monitoring For external monitoring of the fetus during childbirth, a simple pinard stethoscope or doppler fetal monitor ("doptone") can be used. A method of external (noninvasive) fetal monitoring (EFM) during childbirth is cardiotocography (CTG), using a cardiotocograph that consists of two sensors: The heart (cardio) sensor is an ultrasonic sensor, similar to a Doppler fetal monitor, that continuously emits ultrasound and detects motion of the fetal heart by the characteristic of the reflected sound. The pressure-sensitive contraction transducer, called a tocodynamometer (toco) has a flat area that is fixated to the skin by a band around the belly. The pressure required to flatten a section of the wall correlates with the internal pressure, thereby providing an estimate of contraction. Monitoring with a cardiotocograph can either be intermittent or continuous. The World Health Organization (WHO) advises that for healthy women undergoing spontaneous labour continuous cardiotocography is not recommended for assessment of fetal well-being. The WHO states: "In countries and settings where continuous CTG is used defensively to protect against litigation, all stakeholders should be made aware that this practice is not evidence-based and does not improve birth outcomes."A mothers water has to break before internal (invasive) monitoring can be used. More invasive monitoring can involve a fetal scalp electrode to give an additional measure of fetal heart activity, and/or intrauterine pressure catheter (IUPC). It can also involve fetal scalp pH testing. Complications Per figures retrieved in 2015, since 1990 there has been a 44 per cent decline in the maternal death rate. However, according to 2015 figures 830 women die every day from causes related to pregnancy or childbirth and for every woman who dies, 20 or 30 encounter injuries, infections or disabilities. Most of these deaths and injuries are preventable.In 2008, noting that each year more than 100,000 women die of complications of pregnancy and childbirth and at least seven million experience serious health problems while 50 million more have adverse health consequences after childbirth, the World Health Organization (WHO) has urged midwife training to strengthen maternal and newborn health services. To support the upgrading of midwifery skills the WHO established a midwife training program, Action for Safe Motherhood.The rising maternal death rate in the US is of concern. In 1990 the US ranked 12th of the 14 developed countries that were analysed. However, since that time the rates of every country have steadily continued to improve while the US rate has spiked dramatically. While every other developed nation of the 14 analysed in 1990 shows a 2017 death rate of less than 10 deaths per every 100,000 live births, the US rate has risen to 26.4. By comparison, the United Kingdom ranks second highest at 9.2 and Finland is the safest at 3.8. Furthermore, for every one of the 700 to 900 US woman who die each year during pregnancy or childbirth, 70 experience significant complications such as haemorrhage and organ failure, totalling more than one per cent of all births.Compared to other developed nations, the United States also has high infant mortality rates. The Trust for Americas Health reports that as of 2011, about one-third of American births have some complications; many are directly related to the mothers health including increasing rates of obesity, type 2 diabetes, and physical inactivity. The U.S. Centers for Disease Control and Prevention (CDC) has led an initiative to improve womans health previous to conception in an effort to improve both neonatal and maternal death rates. Labour and delivery complications Obstructed labour The second stage of labour may be delayed or lengthy due to poor or uncoordinated uterine action, an abnormal uterine position such as breech or shoulder dystocia, and cephalopelvic disproportion (a small pelvis or large infant). Prolonged labour may result in maternal exhaustion, fetal distress, and other complications including obstetric fistula. Eclampsia Eclampsia is the onset of seizures (convulsions) in a woman with pre-eclampsia. Pre-eclampsia is a disorder of pregnancy in which there is high blood pressure and either large amounts of protein in the urine or other organ dysfunction. Pre-eclampsia is routinely screened for during prenatal care. Onset may be before, during, or rarely, after delivery. Around one per cent of women with eclampsia die. Maternal complications A puerperal disorder or postpartum disorder is a complication which presents primarily during the puerperium, or postpartum period. The postpartum period can be divided into three distinct stages; the initial or acute phase, six to 12 hours after childbirth; subacute postpartum period, which lasts two to six weeks, and the delayed postpartum period, which can last up to six months. In the subacute postpartum period, 87% to 94% of women report at least one health problem. Long-term health problems (persisting after the delayed postpartum period) are reported by 31 per cent of women. Postpartum bleeding According to the WHO, hemorrhage is the leading cause of maternal death worldwide accounting for approximately 27.1% of maternal deaths. Within maternal deaths due to hemorrhage, two-thirds are caused by postpartum hemorrhage. The causes of postpartum hemorrhage can be separated into four main categories: Tone, Trauma, Tissue, and Thrombin. Tone represents uterine atony, the failure of the uterus to contract adequately following delivery. Trauma includes lacerations or uterine rupture. Tissue includes conditions that can lead to a retained placenta. Thrombin, which is a molecule used in the human body’s blood clotting system, represents all coagulopathies. Postpartum infections Postpartum infections, also historically known as childbed fever and medically as puerperal fever, are any bacterial infections of the reproductive tract following childbirth or miscarriage. Signs and symptoms usually include a fever greater than 38.0 °C (100.4 °F), chills, lower abdominal pain, and possibly bad-smelling vaginal discharge. The infection usually occurs after the first 24 hours and within the first ten days following delivery. Infection remains a major cause of maternal deaths and morbidity in the developing world. The work of Ignaz Semmelweis was seminal in the pathophysiology and treatment of childbed fever and his work saved many lives. Psychological complications Childbirth can be an intense event and strong emotions, both positive and negative, can be brought to the surface. Abnormal and persistent fear of childbirth is known as tokophobia. The prevalence of fear of childbirth around the world ranges between 4–25%, with 3–7% of pregnant women having clinical fear of childbirth.Most new mothers may experience mild feelings of unhappiness and worry after giving birth. Babies require a lot of care, so it is normal for mothers to be worried about, or tired from, providing that care. The feelings, often termed the "baby blues", affect up to 80 per cent of mothers. They are somewhat mild, last a week or two, and usually go away on their own.Postpartum depression is different from the "baby blues". With postpartum depression, feelings of sadness and anxiety can be extreme and might interfere with a womans ability to care for herself or her family. Because of the severity of the symptoms, postpartum depression usually requires treatment. The condition, which occurs in nearly 15 percent of births, may begin shortly before or any time after childbirth, but commonly begins between a week and a month after delivery.Childbirth-related posttraumatic stress disorder is a psychological disorder that can develop in women who have recently given birth. Causes include issues such as an emergency C-section, preterm labour, inadequate care during labour, lack of social support following childbirth, and others. Examples of symptoms include intrusive symptoms, flashbacks and nightmares, as well as symptoms of avoidance (including amnesia for the whole or parts of the event), problems in developing a mother-child attachment, and others similar to those commonly experienced in posttraumatic stress disorder (PTSD). Many women who are experiencing symptoms of PTSD after childbirth are misdiagnosed with postpartum depression or adjustment disorders. These diagnoses can lead to inadequate treatment.Postpartum psychosis is a rare psychiatric emergency in which symptoms of high mood and racing thoughts (mania), depression, severe confusion, loss of inhibition, paranoia, hallucinations and delusions set in, beginning suddenly in the first two weeks after childbirth. The symptoms vary and can change quickly. It usually requires hospitalisation. The most severe symptoms last from two to 12 weeks, and recovery takes six months to a year. Fetal complications Five causes make up about 80 per cent of newborn deaths globally: prematurity, low-birth-weight, infections, lack of oxygen at birth, and trauma during birth. Stillbirth Stillbirth is typically defined as fetal death at or after 20 to 28 weeks of pregnancy. It results in a baby born without signs of life.Worldwide prevention of most stillbirths is possible with improved health systems. About half of stillbirths occur during childbirth, and stillbirth is more common in the developing than developed world. Otherwise depending on how far along the pregnancy is, medications may be used to start labour or a type of surgery known as dilation and evacuation may be carried out. Following a stillbirth, women are at higher risk of another one; however, most subsequent pregnancies do not have similar problems.Worldwide in 2019 there were about 2 million stillbirths that occurred after 28 weeks of pregnancy, this equates to 1 in 72 total births or one every 16 seconds. Still births are more common in South Asia and Sub-Saharan Africa. Stillbirth rates have declined, though more slowly since the 2000s. Preterm birth Preterm birth is the birth of an infant at fewer than 37 weeks gestational age. Globally, about 15 million infants were born before 37 weeks of gestation. Premature birth is the leading cause of death in children under five years of age though many that survive experience disabilities including learning defects and visual and hearing problems. Causes for early birth may be unknown or may be related to certain chronic conditions such as diabetes, infections, and other known causes. The World Health Organization has developed guidelines with recommendations to improve the chances of survival and health outcomes for preterm infants.If a pregnant woman enters preterm labor, delivery can be delayed by giving medications called tocolytics. Tocolytics delay labor by inhibiting contractions of the uterine muscles that progress labor. The most widely used tocolytics include beta agonists, calcium channel blockers, and magnesium sulfate. The goal of administering tocolytics is not to delay delivery to the point that the child can be delivered at term, but instead to postponing delivery long enough for the administration of glucocorticoids which can help the fetal lungs to mature enough to reduce morbidity and mortality from infant respiratory distress syndrome. Post-term birth The term postterm pregnancy is used to discribe a condition in which a woman has not yet delivered her baby after 42 weeks of gestation, two weeks beyond the usual 40-week duration of pregnancy. Postmature births carry risks for both the mother and the baby, including meconium aspiration syndrome, fetal malnutrition, and stillbirths. The placenta, which supplies the baby with oxygen and nutrients, begins to age and will eventually fail after the 42nd week of gestation. Induced labor is indicated for postterm pregnancy. Neonatal infection Newborns are prone to infection in the first month of life. The organism S. agalactiae (Group B Streptococcus) or (GBS) is most often the cause of these occasionally fatal infections. The baby contracts the infection from the mother during labour. In 2014 it was estimated that about one in 2000 newborn babies have GBS bacterial infections within the first week of life, usually evident as respiratory disease, general sepsis, or meningitis.Untreated sexually transmitted infections (STIs) are associated with congenital and infections in newborn babies, particularly in the areas where rates of infection remain high. The majority of STIs have no symptoms or only mild symptoms that may not be recognised. Mortality rates resulting from some infections may be high, for example the overall perinatal mortality rate associated with untreated syphilis is 30 per cent. Perinatal asphyxia Perinatal asphyxia is the medical condition resulting from deprivation of oxygen to a newborn infant that lasts long enough during the birth process to cause physical harm. Hypoxic damage can also occur to most of the infants organs (heart, lungs, liver, gut, kidneys), but brain damage is of most concern and perhaps the least likely to quickly or completely heal. Oxygen deprivation can lead to permanent disabilities in the child, such as cerebral palsy. Mechanical fetal injury Risk factors for fetal birth injury include fetal macrosomia (big baby), maternal obesity, the need for instrumental delivery, and an inexperienced attendant. Specific situations that can contribute to birth injury include breech presentation and shoulder dystocia. Most fetal birth injuries resolve without long term harm, but brachial plexus injury may lead to Erbs palsy or Klumpkes paralysis. History Role of males Historically, women have been attended and supported by other women during labour and birth. Midwife training in European cities began in the 1400s, but rural women were usually assisted by female family or friends. However, it was not simply a ladies social bonding event as some historians have portrayed – fear and pain often filled the atmosphere, as death during childbirth was a common occurrence. In the United States before the 1950s, a father would not be in the birthing room. It did not matter if it was a home birth; the father would be waiting downstairs or in another room in the home. If it was in a hospital, then the father would wait in the waiting room. Fathers were only permitted in the room if the life of the mother or baby was severely at-risk. In 1522, a German physician was sentenced to death for sneaking into a delivery room dressed as a woman.The majority of guidebooks related to pregnancy and childbirth were written by men who had never been involved in the birthing process. A Greek physician, Soranus of Ephesus, wrote a book about obstetrics and gynaecology in the second century, which was referenced for the next thousand years. The book contained endless home remedies for pregnancy and childbirth, many of which would be considered heinous by modern women and medical professionals.Both preterm and full term infants benefit from skin to skin contact, sometimes called Kangaroo care, immediately following birth and for the first few weeks of life. Some fathers have begun to hold their newborns skin to skin; the new baby is familiar with the fathers voice and it is believed that contact with the father helps the infant to stabilise and promotes father to infant bonding. Looking at recent studies, a 2019 review found that the level of oxytocin was found to increase not only in mothers who had experienced early skin to skin attachment with their infants but in the fathers as well, suggesting a neurobiological connection. If the infants mother had a caesarean birth, the father can hold their baby in skin-to-skin contact while the mother recovers from the anaesthetic. Hospitals Historically, most women gave birth at home without emergency medical care available. In the early days of hospitalisation of childbirth, a 17th-century maternity ward in Paris was incredibly congested, with up to five pregnant women sharing one bed. At this hospital, one in five women died during the birthing process. At the onset of the Industrial Revolution, giving birth at home became more difficult due to congested living spaces and dirty living conditions. That drove urban and lower-class women to newly available hospitals, while wealthy and middle-class women continued to labour at home. Consequently, wealthier women experienced lower maternal mortality rates than those of a lower social class. Throughout the 1900s, there was an increasing availability of hospitals, and more women began going into the hospital for labour and delivery. In the United States, 5% of women gave birth in hospitals in 1900. By 1930, 50% of all women and 75% of urban-dwelling women delivered in hospitals. By 1960, this number increased to 96%. By the 1970s, home birth rates fell to approximately 1%. In the United States, the middle classes were especially receptive to the medicalisation of childbirth, which promised a safer and less painful labour.Accompanied by the shift from home to hospital was the shift from midwife to physician. Male physicians began to replace female midwives in Europe and the United States in the 1700s. The rise in status and popularity of this new position was accompanied by a drop in status for midwives. By the 1800s, affluent families were primarily calling male doctors to assist with their deliveries, and female midwives were seen as a resource for women who could not afford better care. That completely removed women from assisting in labour, as only men were eligible to become doctors at the time. Additionally, it privatised the birthing process as family members and friends were often banned from the delivery room.There was opposition to the change from both progressive feminists and religious conservatives. The feminists were concerned about job security for a role that had traditionally been held by women. The conservatives argued that it was immoral for a woman to be exposed in such a way in front of a man. For that reason, many male obstetricians performed deliveries in dark rooms or with their patient fully covered with a drape. Baby Friendly Hospitals In 1991 the WHO launched a global program, the Baby Friendly Hospital Initiative (BFHI), that encourages birthing centers and hospitals to institute procedures that encourage mother/baby bonding and breastfeeding. The Johns Hopkins Hospital describes the process of receiving the Baby Friendly designation: It involves changing long-standing policies, protocols and behaviors. The Baby-Friendly Hospital Initiative includes a very rigorous credentialing process that includes a two-day site visit, where assessors evaluate policies, community partnerships and education plans, as well as interview patients, physicians and staff members. Every major health organization, such as the CDC, supports the BFHI. As of 2019, 28% of hospitals in the US have been accredited by the WHO. Medication The use of pain medication in labour has been a controversial issue for hundreds of years. A Scottish woman was burned at the stake in 1591 for requesting pain relief in the delivery of twins. Medication became more acceptable in 1852, when Queen Victoria used chloroform as pain relief during labour. The use of morphine and scopolamine, also known as "twilight sleep", was first used in Germany and popularised by German physicians Bernard Kronig and Karl Gauss. This concoction offered minor pain relief but mostly allowed women to completely forget the entire delivery process. Under twilight sleep, mothers were often blindfolded and restrained as they experienced the immense pain of childbirth. The cocktail came with severe side effects, such as decreased uterine contractions and altered mental state. Additionally, babies delivered with the use of childbirth drugs often experienced temporarily-ceased breathing. The feminist movement in the United States openly and actively supported the use of twilight sleep, which was introduced to the country in 1914. Some physicians, many of whom had been using painkillers for the past fifty years, including opium, cocaine, and quinine, embraced the new drug. Others were rightfully hesitant. Caesarean sections There are many conflicting stories of the first successful cesarean section (or C-section) in which both mother and baby survived. It is, however, known that the procedure had been attempted for hundreds of years before it became accepted in the beginning of the twentieth century. While forceps have gone through periods of high popularity, today they are only used in approximately 10 percent of deliveries. The c-section has become the more popular solution for difficult deliveries. In 2005, one-third of babies were born via C-section. Historically, surgical delivery was a last-resort method of extracting a baby from its deceased or dying mother but today caesarean delivery on maternal request is a medically unnecessary caesarean section, where the infant is born by a caesarean section requested by the parent even though there is not a medical indication to have the surgery. Natural childbirth The reemergence of "natural childbirth" began in Europe and was adopted by some in the US as early as the late 1940s. Early supporters believed that the drugs used during deliveries interfered with "happy childbirth" and could negatively impact the newborns "emotional wellbeing". By the 1970s, the call for natural childbirth was spread nationwide, in conjunction with the second-wave of the feminist movement. While it is still most common for American women to deliver in the hospital, supporters of natural birth still widely exist, especially in the UK where midwife-assisted home births have gained popularity. Epidemiology The United Nations Population Fund estimated that 303,000 women died of pregnancy or childbirth related causes in 2015. These causes range from severe bleeding to obstructed labour, for which there are highly effective interventions. As women have gained access to family planning and skilled birth attendants with backup emergency obstetric care, the global maternal mortality ratio has fallen from 385 maternal deaths per 100,000 live births in 1990 to 216 deaths per 100,000 live births in 2015, and it was reported in 2017 that many countries had halved their maternal death rates in the last 10 years.Outcomes for mothers in childbirth were especially poor before antibiotics were discovered in the 1930s, because of high rates of puerperal fever. Until germ theory was accepted in the mid-1800s, it was assumed that puerperal fever was caused by a variety of sources, including the leakage of breast milk into the body and anxiety. Later, it was discovered that puerperal fever was transmitted by the dirty hands and tools of doctors.Home births facilitated by trained midwives produced the best outcomes from 1880 to 1930 in the US and Europe, whereas physician-facilitated hospital births produced the worst. The change in trend of maternal mortality can be attributed with the widespread use of antibiotics along with the progression of medical technology, more extensive physician training, and less medical interference with normal deliveries.Since the US began recording childbirth statistics in 1915, the US has had historically poor maternal mortality rates in comparison to other developed countries. Britain started recording maternal mortality data from 1880 onward. Society and culture Distress levels vary widely during pregnancy as well as during labour and delivery. They appear to be influenced by fear and anxiety levels, experience with prior childbirth, cultural ideas of childbirth pain, mobility during labour, and the support received during labour. Personal expectations, the amount of support from caregivers, quality of the caregiver-patient relationship, and involvement in decision-making are more important in mothers overall satisfaction with the birthing experience than are other factors such as age, socioeconomic status, ethnicity, preparation, physical environment, pain, immobility, or medical interventions. Costs According to a 2013 analysis performed commissioned by the New York Times and performed by Truven Healthcare Analytics, the cost of childbirth varies dramatically by country. In the United States the average amount actually paid by insurance companies or other payers in 2012 averaged $9,775 for an uncomplicated conventional delivery and $15,041 for a caesarean birth. The aggregate charges of healthcare facilities for four million annual births in the United States was estimated at over $50 billion. The summed cost of prenatal care, childbirth, and newborn care came to $30,000 for a vaginal delivery and $50,000 for a caesarian section.In the United States, childbirth hospital stays have some of the lowest ICU utilisations. Vaginal delivery with and without complicating diagnoses and caesarean section with and without comorbidities or major comorbidities account for four of the 15 types of hospital stays with low rates of ICU utilisation (where less than 20% of visits were admitted to the ICU). During stays with ICU services, approximately 20% of costs were attributable to the ICU.A 2013 study found varying costs by facility for childbirth expenses in California, varying from $3,296 to $37,227 for a vaginal birth and from $8,312 to $70,908 for a caesarean birth.Beginning in 2014, the National Institute for Health and Care Excellence began recommending that many women give birth at home under the care of a midwife rather than an obstetrician, citing lower expenses and better healthcare outcomes. The median cost associated with home birth was estimated to be about $1,500 vs. about $2,500 in hospital. Location Childbirth routinely occurs in hospitals in many developed countries. Before the 20th century and in some countries to the present day, such as the Netherlands, it has more typically occurred at home.In rural and remote communities of many countries, hospitalised childbirth may not be readily available or the best option. Maternal evacuation is the predominant risk management method for assisting mothers in these communities. Maternal evacuation is the process of relocating pregnant women in remote communities to deliver their babies in a nearby urban hospital setting. This practice is common in Indigenous Inuit and Northern Manitoban communities in Canada as well as Australian aboriginal communities. There has been research considering the negative effects of maternal evacuation due to a lack of social support provided to these women. These negative effects include an increase in maternal newborn complications and postpartum depression, and decreased breastfeeding rates.The exact location in which childbirth takes place is an important factor in determining nationality, in particular for birth aboard aircraft and ships. Facilities Facilities for childbirth include: A labour ward, also called a delivery ward or labour and delivery, is generally a department of a hospital that focuses on providing health care to women and their children during childbirth. It is generally closely linked to the hospitals neonatal intensive care unit and/or obstetric surgery unit if present. A maternity ward or maternity unit may include facilities both for childbirth and for postpartum rest and observation of mothers in normal as well as complicated cases. A maternity hospital is a hospital that specialises in caring for women while they are pregnant and during childbirth and provide care for newborn babies, A birthing center generally presents a simulated home-like environment. Birthing centers may be located on hospital grounds or "free standing" (that is, not affiliated with a hospital). A home birth is usually accomplished with the assist of a midwife. Some women choose to give birth at home without any professionals present, termed an unassisted childbirth. Associated occupations Different categories of birth attendants may provide support and care during pregnancy and childbirth, although there are important differences across categories based on professional training and skills, practice regulations, and the nature of care delivered. Many of these occupations are highly professionalised, but other roles exist on a less formal basis. "Childbirth educators" are instructors who aim to teach pregnant women and their partners about the nature of pregnancy, labour signs and stages, techniques for giving birth, breastfeeding and newborn baby care. Training for this role can be found in hospital settings or through independent certifying organisations. Each organisation teaches its own curriculum and each emphasises different techniques. The Lamaze technique is one well-known example. Doulas are assistants who support mothers during pregnancy, labour, birth, and postpartum. They are not medical attendants; rather, they provide emotional support and non-medical pain relief for women during labour. Like childbirth educators and other unlicensed assistive personnel, certification to become a doula is not compulsory, thus, anyone can call themself a doula or a childbirth educator.Confinement nannies are individuals who are employed to provide assistance and stay with the mothers at their home after childbirth. They are usually experienced mothers who took courses on how to take care of mothers and newborn babies.Midwives are autonomous practitioners who provide basic and emergency health care before, during and after pregnancy and childbirth, generally to women with low-risk pregnancies. Midwives are trained to assist during labour and birth, either through direct-entry or nurse-midwifery education programs. Jurisdictions where midwifery is a regulated profession will typically have a registering and disciplinary body for quality control, such as the American Midwifery Certification Board in the United States, the College of Midwives of British Columbia in Canada or the Nursing and Midwifery Council in the United Kingdom.In the past, midwifery played a crucial role in childbirth throughout most indigenous societies. Although western civilisations attempted to assimilate their birthing technologies into certain indigenous societies, like Turtle Island, and get rid of the midwifery, the National Aboriginal Council of Midwives brought back the cultural ideas and midwifery that were once associated with indigenous birthing.In jurisdictions where midwifery is not a regulated profession, traditional birth attendants, also known as traditional or lay midwives, may assist women during childbirth, although they do not typically receive formal health care education and training. Medical doctors who practise in the field of childbirth include categorically specialised obstetricians, family practitioners and general practitioners whose training, skills and practices include obstetrics, and in some contexts general surgeons. These physicians and surgeons variously provide care across the whole spectrum of normal and abnormal births and pathological labour conditions. Categorically specialised obstetricians are qualified surgeons, so they can undertake surgical procedures relating to childbirth. Some family practitioners or general practitioners also perform obstetrical surgery. Obstetrical procedures include cesarean sections, episiotomies, and assisted delivery. Categorical specialists in obstetrics are commonly trained in both obstetrics and gynaecology (OB/GYN), and may provide other medical and surgical gynaecological care, and may incorporate more general, well-woman, primary care elements in their practices. Maternal–fetal medicine specialists are obstetrician/gynecologists subspecialised in managing and treating high-risk pregnancy and delivery. Anaesthetists or anesthesiologists are medical doctors who specialise in pain relief and the use of drugs to facilitate surgery and other painful procedures. They may contribute to the care of a woman in labour by performing an epidural or by providing anaesthesia (often spinal anaesthesia) for Cesarean section or forceps delivery. They are experts in pain management during childbirth. Obstetric nurses assist midwives, doctors, women, and babies before, during, and after the birth process, in the hospital system. They hold various nursing certifications and typically undergo additional obstetric training in addition to standard nursing training. Paramedics are healthcare providers that are able to provide emergency care to both the mother and infant during and after delivery using a wide range of medications and tools on an ambulance. They are capable of delivering babies but can do very little for infants that become "stuck" and are unable to be delivered vaginally. Lactation consultants assist the mother and newborn to breastfeed successfully. A health visitor comes to see the mother and baby at home, usually within 24 hours of discharge, and checks the infants adaptation to extrauterine life and the mothers postpartum physiological changes. Non-western communities Cultural values, assumptions, and practices of pregnancy and childbirth vary across cultures. For example, some Maya women who work in agricultural fields of some rural communities will usually continue to work in a similar function to how they normally would throughout pregnancy, in some cases working until labour begins.Comfort and proximity to extended family and social support systems may be a childbirth priority of many communities in developing countries, such as the Chillihuani in Peru and the Mayan town of San Pedro La Laguna. Home births can help women in these cultures feel more comfortable as they are in their own home with their family around them helping out in different ways. Traditionally, it has been rare in these cultures for the mother to lie down during childbirth, opting instead for standing, kneeling, or walking around prior to and during birthing.Some communities rely heavily on religion for their birthing practices. It is believed that if certain acts are carried out, then it will allow the child for a healthier and happier future. One example of this is the belief in the Chillihuani that if a knife or scissors are used for cutting the umbilical cord, it will cause for the child to go through clothes very quickly. In order to prevent this, a jagged ceramic tile is used to cut the umbilical cord. In Mayan societies, ceremonial gifts are presented to the mother throughout pregnancy and childbirth in order to help her into the beginning of her childs life.Ceremonies and customs can vary greatly between countries. See; Collecting stem cells It is currently possible to collect two types of stem cells during childbirth: amniotic stem cells and umbilical cord blood stem cells. They are being studied as possible treatments of a number of conditions. Placentophagy Some animal mothers are known to eat their afterbirth, called placentophagy. In some cultures the placenta may be consumed as a nutritional boost, but it may also be seen as a special part of birth and eaten by the newborns family ceremonially. In the developed world the placenta may be eaten believing that it reduces postpartum bleeding, increases milk supply, provides micronutrients such as iron, and improves mood and boosts energy. The CDC advises against this practice, saying it has not been shown to promote health but has been shown to possibly transmit disease organisms that were passed from the placenta into the mothers breastmilk and then infecting the baby. See also References External links Spontaneous Vaginal Delivery, Video by Merck Manual Professional Edition Maternal Morbidity/Mortality in the Media

Aarogya, give me a short description about Lambert–Eaton myasthenic syndrome

Lambert–Eaton myasthenic syndrome

Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder characterized by muscle weakness of the limbs. Around 60% of those with LEMS have an underlying malignancy, most commonly small-cell lung cancer; it is therefore regarded as a paraneoplastic syndrome (a condition that arises as a result of cancer elsewhere in the body). It is the result of antibodies against presynaptic voltage-gated calcium channels, and likely other nerve terminal proteins, in the neuromuscular junction (the connection between nerves and the muscle that they supply). The diagnosis is usually confirmed with electromyography and blood tests; these also distinguish it from myasthenia gravis, a related autoimmune neuromuscular disease.If the disease is associated with cancer, direct treatment of the cancer often relieves the symptoms of LEMS. Other treatments often used are steroids, azathioprine, which suppress the immune system, intravenous immunoglobulin, which outcompetes autoreactive antibody for Fc receptors, and pyridostigmine and 3,4-diaminopyridine, which enhance the neuromuscular transmission. Occasionally, plasma exchange is required to remove the antibodies.The condition affects about 3.4 per million people. LEMS usually occurs in people over 40 years of age, but may occur at any age. Signs and symptoms The weakness from LEMS typically involves the muscles of the proximal arms and legs (the muscles closer to the trunk). In contrast to myasthenia gravis, the weakness affects the legs more than the arms. This leads to difficulties climbing stairs and rising from a sitting position. Weakness is often relieved temporarily after exertion or physical exercise. High temperatures can worsen the symptoms. Weakness of the bulbar muscles (muscles of the mouth and throat) is occasionally encountered. Weakness of the eye muscles is uncommon. Some may have double vision, drooping of the eyelids and difficulty swallowing, but generally only together with leg weakness; this too distinguishes LEMS from myasthenia gravis, in which eye signs are much more common. In the advanced stages of the disease, weakness of the respiratory muscles may occur. Some may also experience problems with coordination (ataxia).Three-quarters of people with LEMS also have disruption of the autonomic nervous system. This may be experienced as a dry mouth, constipation, blurred vision, impaired sweating, and orthostatic hypotension (falls in blood pressure on standing, potentially leading to blackouts). Some report a metallic taste in the mouth.On neurological examination, the weakness demonstrated with normal testing of power is often less severe than would be expected on the basis of the symptoms. Strength improves further with repeated testing, e.g. improvement of power on repeated hand grip (a phenomenon known as "Lamberts sign"). At rest, reflexes are typically reduced; with muscle use, reflex strength increases. This is a characteristic feature of LEMS. The pupillary light reflex may be sluggish.In LEMS associated with lung cancer, most have no suggestive symptoms of cancer at the time, such as cough, coughing blood, and unintentional weight loss. LEMS associated with lung cancer may be more severe. Causes LEMS is often associated with lung cancer (50–70%), specifically small-cell carcinoma, making LEMS a paraneoplastic syndrome. Of the people with small-cell lung cancer, 1–3% have LEMS. In most of these cases, LEMS is the first symptom of the lung cancer, and it is otherwise asymptomatic.LEMS may also be associated with endocrine diseases, such as hypothyroidism (an underactive thyroid gland) or diabetes mellitus type 1. Myasthenia gravis, too, may happen in the presence of tumors (thymoma, a tumor of the thymus in the chest); people with MG without a tumor and people with LEMS without a tumor have similar genetic variations that seem to predispose them to these diseases. HLA-DR3-B8 (an HLA subtype), in particular, seems to predispose to LEMS. Mechanism In normal neuromuscular function, a nerve impulse is carried down the axon (the long projection of a nerve cell) from the spinal cord. At the nerve ending in the neuromuscular junction, where the impulse is transferred to the muscle cell, the nerve impulse leads to the opening of voltage-gated calcium channels (VGCC), the influx of calcium ions into the nerve terminal, and the calcium-dependent triggering of synaptic vesicle fusion with plasma membrane. These synaptic vesicles contain acetylcholine, which is released into the synaptic cleft and stimulates the acetylcholine receptors on the muscle. The muscle then contracts.In LEMS, antibodies against VGCC, particularly the P/Q-type VGCC, decrease the amount of calcium that can enter the nerve ending, hence less acetylcholine can be released from the neuromuscular junction. Apart from skeletal muscle, the autonomic nervous system also requires acetylcholine neurotransmission; this explains the occurrence of autonomic symptoms in LEMS. P/Q voltage-gated calcium channels are also found in the cerebellum, explaining why some experience problems with coordination. The antibodies bind particularly to the part of the receptor known as the "domain III S5–S6 linker peptide". Antibodies may also bind other VGCCs. Some have antibodies that bind synaptotagmin, the protein sensor for calcium-regulated vesicle fusion. Many people with LEMS, both with and without VGCC antibodies, have detectable antibodies against the M1 subtype of the acetylcholine receptor; their presence may participate in a lack of compensation for the weak calcium influx.Apart from the decreased calcium influx, a disruption of active zone vesicle release sites also occurs, which may also be antibody-dependent, since people with LEMS have antibodies to components of these active zones (including voltage-dependent calcium channels). Together, these abnormalities lead to the decrease in muscle contractility. Repeated stimuli over a period of about 10 seconds eventually lead to sufficient delivery of calcium, and an increase in muscle contraction to normal levels, which can be demonstrated using an electrodiagnostic medicine study called needle electromyography by increasing amplitude of repeated compound muscle action potentials.The antibodies found in LEMS associated with lung cancer also bind to calcium channels in the cancer cells, and it is presumed that the antibodies originally develop as a reaction to these cells. It has been suggested that the immune reaction to the cancer cells suppresses their growth and improves the prognosis from the cancer. Diagnosis The diagnosis is usually made with nerve conduction study (NCS) and electromyography (EMG), which is one of the standard tests in the investigation of otherwise unexplained muscle weakness. EMG involves the insertion of small needles into the muscles. NCS involves administering small electrical impulses to the nerves, on the surface of the skin, and measuring the electrical response of the muscle in question. NCS investigation in LEMS primarily involves evaluation of compound motor action potentials (CMAPs) of effected muscles and sometimes EMG single-fiber examination can be used.CMAPs show small amplitudes but normal latency and conduction velocities. If repeated impulses are administered (2 per second or 2 Hz), it is normal for CMAP amplitudes to become smaller as the acetylcholine in the motor end plate is depleted. In LEMS, this decrease is larger than observed normally. Eventually, stored acetylcholine is made available, and the amplitudes increase again. In LEMS, this remains insufficient to reach a level sufficient for transmission of an impulse from nerve to muscle; all can be attributed to insufficient calcium in the nerve terminal. A similar pattern is witnessed in myasthenia gravis. In LEMS, in response to exercising the muscle, the CMAP amplitude increases greatly (over 200%, often much more). This also occurs on the administration of a rapid burst of electrical stimuli (20 impulses per second for 10 seconds). This is attributed to the influx of calcium in response to these stimuli. On single-fiber examination, features may include increased jitter (seen in other diseases of neuromuscular transmission) and blocking.Blood tests may be performed to exclude other causes of muscle disease (elevated creatine kinase may indicate a myositis, and abnormal thyroid function tests may indicate thyrotoxic myopathy). Antibodies against voltage-gated calcium channels can be identified in 85% of people with EMG-confirmed LEMS. Once LEMS is diagnosed, investigations such as a CT scan of the chest are usually performed to identify any possible underlying lung tumors. Around 50–60% of these are discovered immediately after the diagnosis of LEMS. The remainder is diagnosed later, but usually within two years and typically within four years. As a result, scans are typically repeated every six months for the first two years after diagnosis. While CT of the lungs is usually adequate, a positron emission tomography scan of the body may also be performed to search for an occult tumour, particularly of the lung. Treatment If LEMS is caused by an underlying cancer, treatment of the cancer usually leads to resolution of the symptoms. Treatment usually consists of chemotherapy, with radiation therapy in those with limited disease. Immunosuppression Some evidence supports the use of intravenous immunoglobulin (IVIG). Immune suppression tends to be less effective than in other autoimmune diseases. Prednisolone (a glucocorticoid or steroid) suppresses the immune response, and the steroid-sparing agent azathioprine may replace it once therapeutic effect has been achieved. IVIG may be used with a degree of effectiveness. Plasma exchange (or plasmapheresis), the removal of plasma proteins such as antibodies and replacement with normal plasma, may provide improvement in acute severe weakness. Again, plasma exchange is less effective than in other related conditions such as myasthenia gravis, and additional immunosuppressive medication is often needed. Other Three other treatment modalities also aim at improving LEMS symptoms, namely pyridostigmine, 3,4-diaminopyridine (amifampridine), and guanidine. They work to improve neuromuscular transmission. Tentative evidence supports 3,4-diaminopyridine] at least for a few weeks. The 3,4-diaminopyridine base or the water-soluble 3,4-diaminopyridine phosphate may be used. Both 3,4-diaminopyridine formulations delay the repolarization of nerve terminals after a discharge, thereby allowing more calcium to accumulate in the nerve terminal.Pyridostigmine decreases the degradation of acetylcholine after release into the synaptic cleft, and thereby improves muscle contraction. An older agent, guanidine, causes many side effects and is not recommended. 4-Aminopyridine (dalfampridine), an agent related to 3,4-aminopyridine, causes more side effects than 3,4-DAP and is also not recommended. History Anderson and colleagues from St Thomas Hospital, London, were the first to mention a case with possible clinical findings of LEMS in 1953, but Edward H. Lambert, Lee Eaton, and E.D. Rooke at the Mayo Clinic were the first physicians to substantially describe the clinical and electrophysiological findings of the disease in 1956. In 1972, the clustering of LEMS with other autoimmune diseases led to the hypothesis that it was caused by autoimmunity. Studies in the 1980s confirmed the autoimmune nature, and research in the 1990s demonstrated the link with antibodies against P/Q-type voltage-gated calcium channels. References == External links ==

Give me a short description about Larva migrans , Aarogya

Larva migrans

Larva migrans can refer to: Cutaneous larva migrans, a skin disease in humans, caused by the larvae of various nematode parasites Visceral larva migrans, a condition in children caused by the migratory larvae of nematodes Ocular larva migrans, an ocular form of the larva migrans syndrome that occurs when larvae invade the eye Larva migrans profundus, also known as Gnathostomiasis

Hi Aarogya, explain a situation where Lead poisoning occurs

Lead poisoning

Lead poisoning, also known as plumbism and saturnism, is a type of metal poisoning caused by lead in the body. The brain is the most sensitive. Symptoms may include abdominal pain, constipation, headaches, irritability, memory problems, infertility, and tingling in the hands and feet. It causes almost 10% of intellectual disability of otherwise unknown cause and can result in behavioral problems. Some of the effects are permanent. In severe cases, anemia, seizures, coma, or death may occur.Exposure to lead can occur by contaminated air, water, dust, food, or consumer products. Children are at greater risk as they are more likely to put objects in their mouth such as those that contain lead paint and absorb a greater proportion of the lead that they eat. Exposure at work is a common cause of lead poisoning in adults with certain occupations at particular risk. Diagnosis is typically by measurement of the blood lead level. The Centers for Disease Control and Prevention (US) has set the upper limit for blood lead for adults at 10 µg/dl (10 µg/100 g) and for children at 3.5 µg/dl, previously before October 2021 5 µg/dl Elevated lead may also be detected by changes in red blood cells or dense lines in the bones of children as seen on X-ray.Lead poisoning is preventable. This includes individual efforts such as removing lead-containing items from the home, workplace efforts such as improved ventilation and monitoring, state laws that ban the use of and national policies such as laws that ban lead in products such as paint, gasoline, ammunition, wheel weights, and fishing weights reduce allowable levels in water or soil, and provide for cleanup of contaminated soil. Workers education could be helpful as well. The major treatments are removal of the source of lead and the use of medications that bind lead so it can be eliminated from the body, known as chelation therapy. Chelation therapy in children is recommended when blood levels are greater than 40–45 µg/dl. Medications used include dimercaprol, edetate calcium disodium, and succimer.In 2016, lead is believed to have resulted in 540,000 deaths worldwide. It occurs most commonly in the developing world. There also are numerous cases in the developed world, with there being thousands of American communities with higher lead burdens than seen during the peak of the Flint water crisis. Those who are poor are at greater risk. Lead is believed to result in 0.6% of the worlds disease burden. According to a study, half of the US population has been exposed to substantially detrimental lead levels in early childhood – mainly from car exhaust whose lead pollution peaked in the 1970s and caused widespread loss in cognitive ability.People have been mining and using lead for thousands of years. Descriptions of lead poisoning date to at least 2000 BC, while efforts to limit leads use date back to at least the 16th century. Concerns for low levels of exposure began in the 1970s with there being no safe threshold for lead exposure. Classification Classically, "lead poisoning" or "lead intoxication" has been defined as exposure to high levels of lead typically associated with severe health effects. Poisoning is a pattern of symptoms that occur with toxic effects from mid to high levels of exposure; toxicity is a wider spectrum of effects, including subclinical ones (those that do not cause symptoms). However, professionals often use "lead poisoning" and "lead toxicity" interchangeably, and official sources do not always restrict the use of "lead poisoning" to refer only to symptomatic effects of lead.The amount of lead in the blood and tissues, as well as the time course of exposure, determine toxicity. Lead poisoning may be acute (from intense exposure of short duration) or chronic (from repeat low-level exposure over a prolonged period), but the latter is much more common. Diagnosis and treatment of lead exposure are based on blood lead level (the amount of lead in the blood), measured in micrograms of lead per deciliter of blood (μg/dL). Urine lead levels may be used as well, though less commonly. In cases of chronic exposure, lead often sequesters in the highest concentrations first in the bones, then in the kidneys. If a provider is performing a provocative excretion test, or "chelation challenge", a measurement obtained from urine rather than blood is likely to provide a more accurate representation of total lead burden to a skilled interpreter.The US Centers for Disease Control and Prevention and the World Health Organization state that a blood lead level of 10 μg/dL or above is a cause for concern; however, lead may impair development and have harmful health effects even at lower levels, and there is no known safe exposure level. Authorities such as the American Academy of Pediatrics define lead poisoning as blood lead levels higher than 10 μg/dL.Lead forms a variety of compounds and exists in the environment in various forms. Features of poisoning differ depending on whether the agent is an organic compound (one that contains carbon), or an inorganic one. Organic lead poisoning is now very rare, because countries across the world have phased out the use of organic lead compounds as gasoline additives, but such compounds are still used in industrial settings. Organic lead compounds, which cross the skin and respiratory tract easily, affect the central nervous system predominantly. Signs and symptoms Lead poisoning can cause a variety of symptoms and signs which vary depending on the individual and the duration of lead exposure. Symptoms are nonspecific and may be subtle, and someone with elevated lead levels may have no symptoms. Symptoms usually develop over weeks to months as lead builds up in the body during a chronic exposure, but acute symptoms from brief, intense exposures also occur. Symptoms from exposure to organic lead, which is probably more toxic than inorganic lead due to its lipid solubility, occur rapidly. Poisoning by organic lead compounds has symptoms predominantly in the central nervous system, such as insomnia, delirium, cognitive deficits, tremor, hallucinations, and convulsions.Symptoms may be different in adults and children; the main symptoms in adults are headache, abdominal pain, memory loss, kidney failure, male reproductive problems, and weakness, pain, or tingling in the extremities.Early symptoms of lead poisoning in adults are commonly nonspecific and include depression, loss of appetite, intermittent abdominal pain, nausea, diarrhea, constipation, and muscle pain. Other early signs in adults include malaise, fatigue, decreased libido, and problems with sleep. An unusual taste in the mouth and personality changes are also early signs.In adults, symptoms can occur at levels above 40 μg/dL, but are more likely to occur only above 50–60 μg/dL. Symptoms begin to appear in children generally at around 60 μg/dL. However, the lead levels at which symptoms appear vary widely depending on unknown characteristics of each individual. At blood lead levels between 25 and 60 μg/dL, neuropsychiatric effects such as delayed reaction times, irritability, and difficulty concentrating, as well as slowed motor nerve conduction and headache can occur. Anemia may appear at blood lead levels higher than 50 μg/dL. In adults, abdominal colic, involving paroxysms of pain, may appear at blood lead levels greater than 80 μg/dL. Signs that occur in adults at blood lead levels exceeding 100 μg/dL include wrist drop and foot drop, and signs of encephalopathy (a condition characterized by brain swelling), such as those that accompany increased pressure within the skull, delirium, coma, seizures, and headache. In children, signs of encephalopathy such as bizarre behavior, discoordination, and apathy occur at lead levels exceeding 70 μg/dL. For both adults and children, it is rare to be asymptomatic if blood lead levels exceed 100 μg/dL. Acute poisoning In acute poisoning, typical neurological signs are pain, muscle weakness, numbness and tingling, and, rarely, symptoms associated with inflammation of the brain. Abdominal pain, nausea, vomiting, diarrhea, and constipation are other acute symptoms. Leads effects on the mouth include astringency and a metallic taste. Gastrointestinal problems, such as constipation, diarrhea, poor appetite, or weight loss, are common in acute poisoning. Absorption of large amounts of lead over a short time can cause shock (insufficient fluid in the circulatory system) due to loss of water from the gastrointestinal tract. Hemolysis (the rupture of red blood cells) due to acute poisoning can cause anemia and hemoglobin in the urine. Damage to kidneys can cause changes in urination such as acquired fanconi syndrome and decreased urine output. People who survive acute poisoning often go on to display symptoms of chronic poisoning. Chronic poisoning Chronic poisoning usually presents with symptoms affecting multiple systems, but is associated with three main types of symptoms: gastrointestinal, neuromuscular, and neurological. Central nervous system and neuromuscular symptoms usually result from intense exposure, while gastrointestinal symptoms usually result from exposure over longer periods. Signs of chronic exposure include loss of short-term memory or concentration, depression, nausea, abdominal pain, loss of coordination, and numbness and tingling in the extremities. Fatigue, problems with sleep, headaches, stupor, slurred speech, and anemia are also found in chronic lead poisoning. A "lead hue" of the skin with pallor and/or lividity is another feature. A blue line along the gum with bluish black edging to the teeth, known as a Burton line, is another indication of chronic lead poisoning. Children with chronic poisoning may refuse to play or may have hyperkinetic or aggressive behavior disorders. Visual disturbance may present with gradually progressing blurred vision as a result of central scotoma, caused by toxic optic neuritis. Effects on children A pregnant woman who has elevated blood lead levels is at greater risk of a premature birth or with a low birth weight. Children are more at risk for lead poisoning because their smaller bodies are in a continuous state of growth and development. Young children are much more vulnerable to lead poisoning, as they absorb 4 to 5 times more lead than an adult from a given source. Furthermore, children, especially as they are learning to crawl and walk, are constantly on the floor and therefore more prone to ingesting and inhaling dust that is contaminated with lead.The classic signs and symptoms in children are loss of appetite, abdominal pain, vomiting, weight loss, constipation, anemia, kidney failure, irritability, lethargy, learning disabilities, and behavioral problems. Slow development of normal childhood behaviors, such as talking and use of words, and permanent intellectual disability are both commonly seen. Although less common, it is possible for fingernails to develop leukonychia striata if exposed to abnormally high lead concentrations.On July 30, 2020, a report by UNICEF and Pure Earth revealed that lead poisoning is affecting children on a "massive and previously unknown scale". According to the report, one in three children, up to 800 million globally, have blood lead levels at, or above, 5 micrograms per decilitre (µg/dL), the amount at which action is required. By organ system Lead affects every one of the bodys organ systems, especially the nervous system, but also the bones and teeth, the kidneys, and the cardiovascular, immune, and reproductive systems. Hearing loss and tooth decay have been linked to lead exposure, as have cataracts. Intrauterine and neonatal lead exposure promote tooth decay. Aside from the developmental effects unique to young children, the health effects experienced by adults are similar to those in children, although the thresholds are generally higher. Kidneys Kidney damage occurs with exposure to high levels of lead, and evidence suggests that lower levels can damage kidneys as well. The toxic effect of lead causes nephropathy and may cause Fanconi syndrome, in which the proximal tubular function of the kidney is impaired. Long-term exposure at levels lower than those that cause lead nephropathy have also been reported as nephrotoxic in patients from developed countries that had chronic kidney disease or were at risk because of hypertension or diabetes mellitus. Lead poisoning inhibits excretion of the waste product urate and causes a predisposition for gout, in which urate builds up. This condition is known as saturnine gout. Cardiovascular system Evidence suggests lead exposure is associated with high blood pressure, and studies have also found connections between lead exposure and coronary heart disease, heart rate variability, and death from stroke, but this evidence is more limited. People who have been exposed to higher concentrations of lead may be at a higher risk for cardiac autonomic dysfunction on days when ozone and fine particles are higher. Reproductive system Lead affects both the male and female reproductive systems. In men, when blood lead levels exceed 40 μg/dL, sperm count is reduced and changes occur in volume of sperm, their motility, and their morphology. A pregnant womans elevated blood lead level can lead to miscarriage, prematurity, low birth weight, and problems with development during childhood. Lead is able to pass through the placenta and into breast milk, and blood lead levels in mothers and infants are usually similar. A fetus may be poisoned in utero if lead from the mothers bones is subsequently mobilized by the changes in metabolism due to pregnancy; increased calcium intake in pregnancy may help mitigate this phenomenon. Nervous system Lead affects the peripheral nervous system (especially motor nerves) and the central nervous system. Peripheral nervous system effects are more prominent in adults and central nervous system effects are more prominent in children. Lead causes the axons of nerve cells to degenerate and lose their myelin coats.Lead exposure in young children has been linked to learning disabilities, and children with blood lead concentrations greater than 10 μg/dL are in danger of developmental disabilities. Increased blood lead level in children has been correlated with decreases in intelligence, nonverbal reasoning, short-term memory, attention, reading and arithmetic ability, fine motor skills, emotional regulation, and social engagement.The effect of lead on childrens cognitive abilities takes place at very low levels. There is apparently no lower threshold to the dose-response relationship (unlike other heavy metals such as mercury). Reduced academic performance has been associated with lead exposure even at blood lead levels lower than 5 μg/dL. Blood lead levels below 10 μg/dL have been reported to be associated with lower IQ and behavior problems such as aggression, in proportion with blood lead levels. Between the blood lead levels of 5 and 35 μg/dL, an IQ decrease of 2–4 points for each μg/dL increase is reported in children. However, studies that show associations between low-level lead exposure and health effects in children may be affected by confounding and overestimate the effects of low-level lead exposure.High blood lead levels in adults are also associated with decreases in cognitive performance and with psychiatric symptoms such as depression and anxiety. It was found in a large group of current and former inorganic lead workers in Korea that blood lead levels in the range of 20–50 μg/dL were correlated with neuro-cognitive defects. Increases in blood lead levels from about 50 to about 100 μg/dL in adults have been found to be associated with persistent, and possibly permanent, impairment of central nervous system function.Lead exposure in children is also correlated with neuropsychiatric disorders such as attention deficit hyperactivity disorder and anti-social behaviour. Elevated lead levels in children are correlated with higher scores on aggression and delinquency measures. A correlation has also been found between prenatal and early childhood lead exposure and violent crime in adulthood. Countries with the highest air lead levels have also been found to have the highest murder rates, after adjusting for confounding factors. A May 2000 study by economic consultant Rick Nevin theorizes that lead exposure explains 65% to 90% of the variation in violent crime rates in the US. A 2007 paper by the same author claims to show a strong association between preschool blood lead and subsequent crime rate trends over several decades across nine countries. Lead exposure in childhood appears to increase school suspensions and juvenile detention among boys. It is believed that the U.S. ban on lead paint in buildings in the late 1970s, as well as the phaseout of leaded gasoline in the 1970s and 1980s, partially helped contribute to the decline of violent crime in the United States since the early 1990s. Exposure routes Lead is a common environmental pollutant. Causes of environmental contamination include industrial use of lead, such as found in facilities that process lead-acid batteries or produce lead wire or pipes, and metal recycling and foundries. Storage batteries and ammunition are made with the largest amounts of lead consumed in the economy each year, in the US as of 2013. Children living near facilities that process lead, such as lead smelters, have been found to have unusually high blood lead levels. In August 2009, parents rioted in China after lead poisoning was found in nearly 2000 children living near zinc and manganese smelters. Lead exposure can occur from contact with lead in air, household dust, soil, water, and commercial products. Leaded gasoline has also been linked to increases in lead pollution. Some research has suggested a link between leaded gasoline and crime rates. Man made lead pollution has been elevated in the air for the past 2000 years. Lead pollution in the air is entirely due to human activity (mining and smelting, as well as in gasoline). Occupational exposure In adults, occupational exposure is the main cause of lead poisoning. People can be exposed when working in facilities that produce a variety of lead-containing products; these include radiation shields, ammunition, certain surgical equipment, developing dental X-ray films prior to digital X-rays (each film packet had a lead liner to prevent the radiation from going through), fetal monitors, plumbing, circuit boards, jet engines, and ceramic glazes. In addition, lead miners and smelters, plumbers and fitters, auto mechanics, glass manufacturers, construction workers, battery manufacturers and recyclers, firing range workers, and plastic manufacturers are at risk for lead exposure. Other occupations that present lead exposure risks include welding, manufacture of rubber, printing, zinc and copper smelting, processing of ore, combustion of solid waste, and production of paints and pigments. Lead exposure can also occur with intense use of gun ranges, regardless of whether these ranges are indoor or out. Parents who are exposed to lead in the workplace can bring lead dust home on clothes or skin and expose their children. Occupational exposure to lead increases the risk of cardiovascular disease, in particular: stroke, and high blood pressure. Food Lead may be found in food when food is grown in soil that is high in lead, airborne lead contaminates the crops, animals eat lead in their diet, or lead enters the food either from what it was stored or cooked in. Ingestion of lead paint and batteries is also a route of exposure for livestock, which can subsequently affect humans. Milk produced by contaminated cattle can be diluted to a lower lead concentration and sold for consumption.In Bangladesh, lead compounds have been added to turmeric to make it more yellow. This is believed to have started in the 1980s and continues as of 2019. It is believed to be one of the main sources of high lead levels in the country. In Hong Kong the maximum allowed lead parts per million is 6 in solid foods and 1 in liquid foods. Paint Some lead compounds are colorful and are used widely in paints, and lead paint is a major route of lead exposure in children. A study conducted in 1998–2000 found that 38 million housing units in the US had lead-based paint, down from a 1990 estimate of 64 million. Deteriorating lead paint can produce dangerous lead levels in household dust and soil. Deteriorating lead paint and lead-containing household dust are the main causes of chronic lead poisoning. The lead breaks down into the dust and since children are more prone to crawling on the floor, it is easily ingested. Many young children display pica, eating things that are not food. Even a small amount of a lead-containing product such as a paint chip or a sip of glaze can contain tens or hundreds of milligrams of lead. Eating chips of lead paint presents a particular hazard to children, generally producing more severe poisoning than occurs from dust. Because removing lead paint from dwellings, e.g. by sanding or torching, creates lead-containing dust and fumes, it is generally safer to seal the lead paint under new paint (excepting moveable windows and doors, which create paint dust when operated). Alternatively, special precautions must be taken if the lead paint is to be removed.In oil painting, it was once common for colours such as yellow or white to be made with lead carbonate. Lead white oil colour was the main white of oil painters until superseded by compounds containing zinc or titanium in the mid-20th century. It is speculated that the painter Caravaggio and possibly Francisco Goya and Vincent Van Gogh had lead poisoning due to overexposure or carelessness when handling this colour. Soil Residual lead in soil contributes to lead exposure in urban areas. It has been thought that the more polluted an area is with various contaminants, the more likely it is to contain lead. However, this is not always the case, as there are several other reasons for lead contamination in soil.Lead content in soil may be caused by broken-down lead paint, residues from lead-containing gasoline, used engine oil, tire weights, or pesticides used in the past, contaminated landfills, or from nearby industries such as foundries or smelters. For example, in the Montevideo neighborhood of La Teja, former industrial sites became important sources of exposure in local communities in the early 2000s. Although leaded soil is less of a problem in countries that no longer have leaded gasoline, it remains prevalent, raising concerns about the safety of urban agriculture; eating food grown in contaminated soil can present a lead hazard. Interfacial solar evaporation has been recently studied as a technique for remediating lead-contaminated sites, which involves the evaporation of heavy metal ions from moist soil. Water Lead from the atmosphere or soil can end up in groundwater and surface water. It is also potentially in drinking water, e.g. from plumbing and fixtures that are either made of lead or have lead solder. Since acidic water breaks down lead in plumbing more readily, chemicals can be added to municipal water to increase the pH and thus reduce the corrosivity of the public water supply. Chloramines, which were adopted as a substitute for chlorine disinfectants due to fewer health concerns, increase corrositivity. In the US, 14–20% of total lead exposure is attributed to drinking water. In 2004, a team of seven reporters from The Washington Post discovered high levels of lead in the drinking water in Washington, DC, and won an award for investigative reporting for a series of articles about this contamination. In the water crisis in Flint, Michigan, a switch to a more corrosive municipal water source caused elevated lead levels in domestic tap water.Like Flint MI and Washington DC, a similar situation affects the State of Wisconsin, where estimates call for replacement of up to 176,000 underground pipes made of lead known as lead service lines. The city of Madison, Wisconsin addressed the issue and replaced all of their lead service lines, but there are still others that have yet to follow suit. While there are chemical methods that could help reduce the amount of lead in the water distributed, a permanent fix would be to replace the pipes completely. While the state may replace the pipes below ground, it will be up to the homeowners to replace the pipes on their property, at an average cost of $3,000. Experts say that if the city were to replace their pipes and the citizens were to keep the old pipes located within their homes, there would be a potential for more lead to dissolve into their drinking water.Collected rainwater from roof runoff used as potable water may contain lead, if there are lead contaminants on the roof or in the storage tank. The Australian Drinking Water Guidelines allow a maximum of 0.01 mg/L (10 ppb) lead in water.Lead wheel weights have been found to accumulate on roads and interstates and erode in traffic entering the water runoff through drains. Leaded fishing weights accumulate in rivers, streams, ponds, and lakes. Gasoline Lead was first added to gasoline in 1923, as it helped keep car engines healthy. Automotive exhaust represented a major way for lead to be inhaled, invade the bloodstream and pass into the brain.The use of lead in gasoline peaked in the 1970s. By the next decade most high incomes countries prohibited the use of leaded petrol. As late as 2002, almost all low- and middle-income countries including some OECD members still used it. The UN Environment Programme (UNEP) thus launched a campaign in 2002 to eliminate its use, leading to Algeria being the last country to stop its use in July 2021. Lead-containing products Lead can be found in products such as kohl, an ancient cosmetic from the Middle East, South Asia, and parts of Africa that has many other names; and from some toys. In 2007, millions of toys made in China were recalled from multiple countries owing to safety hazards including lead paint. Vinyl mini-blinds, found especially in older housing, may contain lead. Lead is commonly incorporated into herbal remedies such as Indian Ayurvedic preparations and remedies of Chinese origin. There are also risks of elevated blood lead levels caused by folk remedies like azarcon and greta, which each contain about 95% lead.Ingestion of metallic lead, such as small lead fishing lures, increases blood lead levels and can be fatal. Ingestion of lead-contaminated food is also a threat. Ceramic glaze often contains lead, and dishes that have been improperly fired can leach the metal into food, potentially causing severe poisoning. In some places, the solder in cans used for food contains lead. When manufacturing medical instruments and hardware, solder containing lead may be present. People who eat animals hunted with lead bullets may be at risk for lead exposure. Bullets lodged in the body rarely cause significant levels of lead, but bullets lodged in the joints are the exception, as they deteriorate and release lead into the body over time.In May 2015, Indian food safety regulators in the state of Uttar Pradesh found that samples of Maggi 2 Minute Noodles contained lead up to 17 times beyond permissible limits. On 3 June 2015, New Delhi Government banned the sale of Maggi noodles in New Delhi stores for 15 days because it was found to contain lead beyond the permissible limit. The Gujarat FDA on 4 June 2015 banned the noodles for 30 days after 27 out of 39 samples were detected with objectionable levels of metallic lead, among other things. Some of Indias biggest retailers like Future Group, Big Bazaar, Easyday and Nilgiris have imposed a nationwide ban on Maggi noodles. Many other states too have banned Maggi noodles. Bullets Contact with ammunition is a source of lead exposure. As of 2013, lead-based ammunition production is the second largest annual use of lead in the US, accounting for over 84,800 metric tons consumed in 2013, second only to the manufacture of storage batteries. The Environmental Protection Agency (EPA) cannot regulate cartridges and shells, as a matter of law. Lead birdshot is banned in some areas, but this is primarily for the benefit of the birds and their predators, rather than humans. Contamination from heavily used gun ranges is of concern to those who live near by. Non-lead alternatives include copper, zinc, steel, tungsten-nickel-iron, bismuth-tin, and polymer blends such as tungsten-polymer and copper-polymer. Because game animals can be shot using lead bullets, the potential for lead ingestion from game meat consumption has been studied clinically and epidemiologically. In a recent study conducted by the CDC, a cohort from North Dakota was enrolled and asked to self-report historical consumption of game meat, and participation in other activities that could cause lead exposure. The study found that participants age, sex, housing age, current hobbies with potential for lead exposure, and game consumption were all associated with blood lead level (PbB). According to a study published in 2008, 1.1% of the 736 persons consuming wild game meat tested had PbB ≥5 μg/dl In November 2015 The US HHS/CDC/NIOSH designated 5 µg/dL (five micrograms per deciliter) of whole blood, in a venous blood sample, as the reference blood lead level for adults. An elevated BLL is defined as a BLL ≥5 µg/dL. This case definition is used by the ABLES program, the Council of State and Territorial Epidemiologists (CSTE), and CDCs National Notifiable Diseases Surveillance System (NNDSS). Previously (i.e. from 2009 until November 2015), the case definition for an elevated BLL was a BLL ≥10 µg/dL. To virtually eliminate the potential for lead contamination, some researchers have suggested the use of lead-free copper non-fragmenting bullets.Bismuth is an element used as a lead-replacement for shotgun pellets used in waterfowl hunting although shotshells made from bismuth are nearly ten times the cost of lead. Opium Lead contaminated opium has been the source of poisoning in Iran and other Middle Eastern countries. This has also appeared in the illicit narcotic supply in North America, resulting in confirmed lead poisoning. Pathophysiology Exposure occurs through inhalation, ingestion or occasionally skin contact. Lead may be taken in through direct contact with mouth, nose, and eyes (mucous membranes), and through breaks in the skin. Tetraethyllead, which was a gasoline additive and is still used in aviation gasoline, passes through the skin; and other forms of lead, including inorganic lead are also absorbed through skin. The main sources of absorption of inorganic lead are from ingestion and inhalation. In adults, about 35–40% of inhaled lead dust is deposited in the lungs, and about 95% of that goes into the bloodstream. Of ingested inorganic lead, about 15% is absorbed, but this percentage is higher in children, pregnant women, and people with deficiencies of calcium, zinc, or iron. Infants may absorb about 50% of ingested lead, but little is known about absorption rates in children.The main body tissues that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Lead in the bones, teeth, hair, and nails is bound tightly and not available to other tissues, and is generally thought not to be harmful. In adults, 94% of absorbed lead is deposited in the bones and teeth, but children only store 70% in this manner, a fact which may partially account for the more serious health effects on children. The half-life of lead in bone has been estimated as years to decades, and bone can introduce lead into the bloodstream long after the initial exposure is gone. The half-life of lead in the blood in men is about 40 days, but it may be longer in children and pregnant women, whose bones are undergoing remodeling, which allows the lead to be continuously re-introduced into the bloodstream. Also, if lead exposure takes place over years, clearance is much slower, partly due to the re-release of lead from bone. Many other tissues store lead, but those with the highest concentrations (other than blood, bone, and teeth) are the brain, spleen, kidneys, liver, and lungs. Lead is removed from the body very slowly, mainly through urine. Smaller amounts of lead are also eliminated through the feces, and very small amounts in hair, nails, and sweat.Lead has no known physiologically relevant role in the body, and its harmful effects are myriad. Lead and other heavy metals create reactive radicals which damage cell structures including DNA and cell membranes. Lead also interferes with DNA transcription, enzymes that help in the synthesis of vitamin D, and enzymes that maintain the integrity of the cell membrane. Anemia may result when the cell membranes of red blood cells become more fragile as the result of damage to their membranes. Lead interferes with metabolism of bones and teeth and alters the permeability of blood vessels and collagen synthesis. Lead may also be harmful to the developing immune system, causing production of excessive inflammatory proteins; this mechanism may mean that lead exposure is a risk factor for asthma in children. Lead exposure has also been associated with a decrease in activity of immune cells such as polymorphonuclear leukocytes. Lead also interferes with the normal metabolism of calcium in cells and causes it to build up within them. Enzymes The primary cause of leads toxicity is its interference with a variety of enzymes because it binds to sulfhydryl groups found on many enzymes. Part of leads toxicity results from its ability to mimic other metals that take part in biological processes, which act as cofactors in many enzymatic reactions, displacing them at the enzymes on which they act. Lead is able to bind to and interact with many of the same enzymes as these metals but, due to its differing chemistry, does not properly function as a cofactor, thus interfering with the enzymes ability to catalyze its normal reaction or reactions. Among the essential metals with which lead interacts are calcium, iron, and zinc.The lead ion has a lone pair in its electronic structure, which can result in a distortion in the coordination of ligands, and in 2007 was hypothesized to be important in lead poisonings effects on enzymes (see Lone pair § Unusual lone pairs).One of the main causes for the pathology of lead is that it interferes with the activity of an essential enzyme called delta-aminolevulinic acid dehydratase, or ALAD (see image of the enzyme structure), which is important in the biosynthesis of heme, the cofactor found in hemoglobin. Lead also inhibits the enzyme ferrochelatase, another enzyme involved in the formation of heme. Ferrochelatase catalyzes the joining of protoporphyrin and Fe2+ to form heme. Leads interference with heme synthesis results in production of zinc protoporphyrin and the development of anemia. Another effect of leads interference with heme synthesis is the buildup of heme precursors, such as aminolevulinic acid, which may be directly or indirectly harmful to neurons. Elevation of aminolevulinic acid results in lead poisoning having symptoms similar to acute porphyria. Neurons The brain is the organ most sensitive to lead exposure. Lead is able to pass through the endothelial cells at the blood brain barrier because it can substitute for calcium ions and be taken up by calcium-ATPase pumps. Lead poisoning interferes with the normal development of a childs brain and nervous system; therefore children are at greater risk of lead neurotoxicity than adults are. In a childs developing brain, lead interferes with synapse formation in the cerebral cortex, neurochemical development (including that of neurotransmitters), and organization of ion channels. It causes loss of neurons myelin sheaths, reduces numbers of neurons, interferes with neurotransmission, and decreases neuronal growth.Lead-ions (Pb2+), like magnesium-ions (Mg2+), block NMDA receptors. Therefore, an increase in Pb2+ concentration will effectively inhibit ongoing long-term potentiation (LTP), and lead to an abnormal increase in long-term depression (LTD) on neurons in the affected parts of the nervous system. These abnormalities lead to the indirect downregulation of NMDA-receptors, effectively initiating a positive feedback-loop for LTD. The targeting of NMDA receptors is thought to be one of the main causes for leads toxicity to neurons. Diagnosis Diagnosis includes determining the clinical signs and the medical history, with inquiry into possible routes of exposure. Clinical toxicologists, medical specialists in the area of poisoning, may be involved in diagnosis and treatment. The main tool in diagnosing and assessing the severity of lead poisoning is laboratory analysis of the blood lead level (BLL). Blood film examination may reveal basophilic stippling of red blood cells (dots in red blood cells visible through a microscope), as well as the changes normally associated with iron-deficiency anemia (microcytosis and hypochromasia). This may be known as sideroblastic anemia. However, basophilic stippling is also seen in unrelated conditions, such as megaloblastic anemia caused by vitamin B12 (colbalamin) and folate deficiencies. Contrary to other sideroblastic anemia, there are no ring sideroblasts in a bone marrow smear.Exposure to lead also can be evaluated by measuring erythrocyte protoporphyrin (EP) in blood samples. EP is a part of red blood cells known to increase when the amount of lead in the blood is high, with a delay of a few weeks. Thus EP levels in conjunction with blood lead levels can suggest the time period of exposure; if blood lead levels are high but EP is still normal, this finding suggests exposure was recent. However, the EP level alone is not sensitive enough to identify elevated blood lead levels below about 35 μg/dL. Due to this higher threshold for detection and the fact that EP levels also increase in iron deficiency, use of this method for detecting lead exposure has decreased.Blood lead levels are an indicator mainly of recent or current lead exposure, not of total body burden. Lead in bones can be measured noninvasively by X-ray fluorescence; this may be the best measure of cumulative exposure and total body burden. However this method is not widely available and is mainly used for research rather than routine diagnosis. Another radiographic sign of elevated lead levels is the presence of radiodense lines called lead lines at the metaphysis in the long bones of growing children, especially around the knees. These lead lines, caused by increased calcification due to disrupted metabolism in the growing bones, become wider as the duration of lead exposure increases. X-rays may also reveal lead-containing foreign materials such as paint chips in the gastrointestinal tract.Fecal lead content that is measured over the course of a few days may also be an accurate way to estimate the overall amount of childhood lead intake. This form of measurement may serve as a useful way to see the extent of oral lead exposure from all the diet and environmental sources of lead.Lead poisoning shares symptoms with other conditions and may be easily missed. Conditions that present similarly and must be ruled out in diagnosing lead poisoning include carpal tunnel syndrome, Guillain–Barré syndrome, renal colic, appendicitis, encephalitis in adults, and viral gastroenteritis in children. Other differential diagnoses in children include constipation, abdominal colic, iron deficiency, subdural hematoma, neoplasms of the central nervous system, emotional and behavior disorders, and intellectual disability. Reference levels The current reference range for acceptable blood lead concentrations in healthy persons without excessive exposure to environmental sources of lead is less than 3.5 µg/dL for children. It was less than 25 µg/dL for adults. Previous to 2012 the value for children was 10 (µg/dl). Lead-exposed workers in the U.S. are required to be removed from work when their level is greater than 50 µg/dL if they do construction and otherwise greater than 60 µg/dL.In 2015, US HHS/CDC/NIOSH designated 5 µg/dL (five micrograms per deciliter) of whole blood, in a venous blood sample, as the reference blood lead level for adults. An elevated BLL is defined as a BLL ≥5 µg/dL. This case definition is used by the ABLES program, the Council of State and Territorial Epidemiologists (CSTE), and CDCs National Notifiable Diseases Surveillance System (NNDSS). Previously (i.e. from 2009 until November 2015), the case definition for an elevated BLL was a BLL ≥10 µg/dL. The U.S. national BLL geometric mean among adults was 1.2 μg/dL in 2009–2010.Blood lead concentrations in poisoning victims have ranged from 30 to 80 µg/dL in children exposed to lead paint in older houses, 77–104 µg/dL in persons working with pottery glazes, 90–137 µg/dL in individuals consuming contaminated herbal medicines, 109–139 µg/dL in indoor shooting range instructors and as high as 330 µg/dL in those drinking fruit juices from glazed earthenware containers. Prevention In most cases, lead poisoning is preventable by avoiding exposure to lead. Prevention strategies can be divided into individual (measures taken by a family), preventive medicine (identifying and intervening with high-risk individuals), and public health (reducing risk on a population level).Recommended steps by individuals to reduce the blood lead levels of children include increasing their frequency of hand washing and their intake of calcium and iron, discouraging them from putting their hands to their mouths, vacuuming frequently, and eliminating the presence of lead-containing objects such as blinds and jewellery in the house. In houses with lead pipes or plumbing solder, these can be replaced. Less permanent but cheaper methods include running water in the morning to flush out the most contaminated water, or adjusting the waters chemistry to prevent corrosion of pipes. Lead testing kits are commercially available for detecting the presence of lead in the household. Testing kit accuracy depends on the user testing all layers of paint and the quality of the kit; the US Environmental Protection Agency (EPA) only approves kits with an accuracy rating of at least 95%. Professional lead testing companies caution that DIY test kits can create health risks for users that do not understand their limitations and liability issues for employers with regard to worker protection. As hot water is more likely than cold water to contain higher amounts of lead, use only cold water from the tap for drinking, cooking, and making baby formula. Since most of the lead in household water usually comes from plumbing in the house and not from the local water supply, using cold water can avoid lead exposure. Measures such as dust control and household education do not appear to be effective in changing childrens blood levels.Prevention measures also exist on national and municipal levels. Recommendations by health professionals for lowering childhood exposures include banning the use of lead where it is not essential and strengthening regulations that limit the amount of lead in soil, water, air, household dust, and products. Regulations exist to limit the amount of lead in paint; for example, a 1978 law in the US restricted the lead in paint for residences, furniture, and toys to 0.06% or less. In October 2008, the US EPA reduced the allowable lead level by a factor of ten to 0.15 micrograms per cubic meter of air, giving states five years to comply with the standards. The European Unions Restriction of Hazardous Substances Directive limits amounts of lead and other toxic substances in electronics and electrical equipment. In some places, remediation programs exist to reduce the presence of lead when it is found to be high, for example in drinking water. As a more radical solution, entire towns located near former lead mines have been "closed" by the government, and the population resettled elsewhere, as was the case with Picher, Oklahoma, in 2009. Removing lead from airplane fuel would also be useful. Screening Screening may be an important method of prevention for those at high risk, such as those who live near lead-related industries. The USPSTF has stated that general screening of those without symptoms include children and pregnant women is of unclear benefit as of 2019. The ACOG and APP, however, recommends asking about risk factors and testing those who have them. Education The education of workers on lead, its danger and how its workplace exposure can be decreased, especially when initial blood lead level and urine lead level are high, could help reduce the risk of lead poisoning in the workplace. Treatment The mainstays of treatment are removal from the source of lead and, for people who have significantly high blood lead levels or who have symptoms of poisoning, chelation therapy. Treatment of iron, calcium, and zinc deficiencies, which are associated with increased lead absorption, is another part of treatment for lead poisoning. When lead-containing materials are present in the gastrointestinal tract (as evidenced by abdominal X-rays), whole bowel irrigation, cathartics, endoscopy, or even surgical removal may be used to eliminate it from the gut and prevent further exposure. Lead-containing bullets and shrapnel may also present a threat of further exposure and may need to be surgically removed if they are in or near fluid-filled or synovial spaces. If lead encephalopathy is present, anticonvulsants may be given to control seizures, and treatments to control swelling of the brain include corticosteroids and mannitol. Treatment of organic lead poisoning involves removing the lead compound from the skin, preventing further exposure, treating seizures, and possibly chelation therapy for people with high blood lead concentrations. A chelating agent is a molecule with at least two negatively charged groups that allow it to form complexes with metal ions with multiple positive charges, such as lead. The chelate that is thus formed is nontoxic and can be excreted in the urine, initially at up to 50 times the normal rate. The chelating agents used for treatment of lead poisoning are edetate disodium calcium (CaNa2EDTA), dimercaprol (BAL), which are injected, and succimer and d-penicillamine, which are administered orally.Chelation therapy is used in cases of acute lead poisoning, severe poisoning, and encephalopathy, and is considered for people with blood lead levels above 25 µg/dL. While the use of chelation for people with symptoms of lead poisoning is widely supported, use in asymptomatic people with high blood lead levels is more controversial. Chelation therapy is of limited value for cases of chronic exposure to low levels of lead. Chelation therapy is usually stopped when symptoms resolve or when blood lead levels return to premorbid levels. When lead exposure has taken place over a long period, blood lead levels may rise after chelation is stopped because lead is leached into blood from stores in the bone; thus repeated treatments are often necessary.People receiving dimercaprol need to be assessed for peanut allergies since the commercial formulation contains peanut oil. Calcium EDTA is also effective if administered four hours after the administration of dimercaprol. Administering dimercaprol, DMSA (Succimer), or DMPS prior to calcium EDTA is necessary to prevent the redistribution of lead into the central nervous system. Dimercaprol used alone may also redistribute lead to the brain and testes. An adverse side effect of calcium EDTA is renal toxicity. Succimer (DMSA) is the preferred agent in mild to moderate lead poisoning cases. This may be the case in instances where children have a blood lead level >25μg/dL. The most reported adverse side effect for succimer is gastrointestinal disturbances. It is also important to note that chelation therapy only lowers blood lead levels and may not prevent the lead-induced cognitive problems associated with lower lead levels in tissue. This may be because of the inability of these agents to remove sufficient amounts of lead from tissue or inability to reverse preexisting damage. Chelating agents can have adverse effects; for example, chelation therapy can lower the bodys levels of necessary nutrients like zinc. Chelating agents taken orally can increase the bodys absorption of lead through the intestine.Chelation challenge, also known as provocation testing, is used to indicate an elevated and mobilizable body burden of heavy metals including lead. This testing involves collecting urine before and after administering a one-off dose of chelating agent to mobilize heavy metals into the urine. Then urine is analyzed by a laboratory for levels of heavy metals; from this analysis overall body burden is inferred. Chelation challenge mainly measures the burden of lead in soft tissues, though whether it accurately reflects long-term exposure or the amount of lead stored in bone remains controversial. Although the technique has been used to determine whether chelation therapy is indicated and to diagnose heavy metal exposure, some evidence does not support these uses as blood levels after chelation are not comparable to the reference range typically used to diagnose heavy metal poisoning. The single chelation dose could also redistribute the heavy metals to more sensitive areas such as central nervous system tissue. Epidemiology Since lead has been used widely for centuries, the effects of exposure are worldwide. Environmental lead is ubiquitous, and everyone has some measurable blood lead level. Atmospheric lead pollution increased dramatically beginning in the 1950s as a result of the widespread use of leaded gasoline. Lead is one of the largest environmental medicine problems in terms of numbers of people exposed and the public health toll it takes. Lead exposure accounts for about 0.2% of all deaths and 0.6% of disability adjusted life years globally.Although regulation reducing lead in products has greatly reduced exposure in the developed world since the 1970s, lead is still allowed in products in many developing countries. Despite phase out in many parts of the Global North, Global South exposure has increased by nearly three times. In all countries that have banned leaded gasoline, average blood lead levels have fallen sharply. However, some developing countries still allow leaded gasoline, which is the primary source of lead exposure in most developing countries. Beyond exposure from gasoline, the frequent use of pesticides in developing countries adds a risk of lead exposure and subsequent poisoning. Poor children in developing countries are at especially high risk for lead poisoning. Of North American children, 7% have blood lead levels above 10 μg/dL, whereas among Central and South American children, the percentage is 33–34%. About one fifth of the worlds disease burden from lead poisoning occurs in the Western Pacific, and another fifth is in Southeast Asia.In developed countries, people with low levels of education living in poorer areas are most at risk for elevated lead. In the US, the groups most at risk for lead exposure are the impoverished, city-dwellers, and immigrants. African-American children and those living in old housing have also been found to be at elevated risk for high blood lead levels in the US. Low-income people often live in old housing with lead paint, which may begin to peel, exposing residents to high levels of lead-containing dust. Risk factors for elevated lead exposure include alcohol consumption and smoking (possibly because of contamination of tobacco leaves with lead-containing pesticides). Adults with certain risk factors might be more susceptible to toxicity; these include calcium and iron deficiencies, old age, disease of organs targeted by lead (e.g. the brain, the kidneys), and possibly genetic susceptibility. Differences in vulnerability to lead-induced neurological damage between males and females have also been found, but some studies have found males to be at greater risk, while others have found females to be.In adults, blood lead levels steadily increase with increasing age. In adults of all ages, men have higher blood lead levels than women do. Children are more sensitive to elevated blood lead levels than adults are. Children may also have a higher intake of lead than adults; they breathe faster and may be more likely to have contact with and ingest soil. Children of ages one to three tend to have the highest blood lead levels, possibly because at that age they begin to walk and explore their environment, and they use their mouths in their exploration. Blood levels usually peak at about 18–24 months old. In many countries including the US, household paint and dust are the major route of exposure in children. Notable cases Cases of mass lead poisoning can occur. 15,000 people are being relocated from Jiyuan in central Henan province to other locations after 1000 children living around Chinas largest smelter plant (owned and operated by Yuguang Gold and Lead) were found to have excess lead in their blood. The total cost of this project is estimated to around 1 billion yuan ($150 million). 70% of the cost will be paid by local government and the smelter company, while the rest will be paid by the residents themselves. The government has suspended production at 32 of 35 lead plants. The affected area includes people from 10 different villages.The Zamfara State lead poisoning epidemic occurred in Nigeria in 2010. As of 5 October 2010 at least 400 children have died from the effects of lead poisoning. Prognosis Reversibility Outcome is related to the extent and duration of lead exposure. Effects of lead on the physiology of the kidneys and blood are generally reversible; its effects on the central nervous system are not. While peripheral effects in adults often go away when lead exposure ceases, evidence suggests that most of leads effects on a childs central nervous system are irreversible. Children with lead poisoning may thus have adverse health, cognitive, and behavioral effects that follow them into adulthood. Encephalopathy Lead encephalopathy is a medical emergency and causes permanent brain damage in 70–80% of children affected by it, even those that receive the best treatment. The mortality rate for people who develop cerebral involvement is about 25%, and of those who survive who had lead encephalopathy symptoms by the time chelation therapy was begun, about 40% have permanent neurological problems such as cerebral palsy. Long-term Exposure to lead may also decrease lifespan and have health effects in the long term. Death rates from a variety of causes have been found to be higher in people with elevated blood lead levels; these include cancer, stroke, and heart disease, and general death rates from all causes. Lead is considered a possible human carcinogen based on evidence from animal studies. Evidence also suggests that age-related mental decline and psychiatric symptoms are correlated with lead exposure. Cumulative exposure over a prolonged period may have a more important effect on some aspects of health than recent exposure. Some health effects, such as high blood pressure, are only significant risks when lead exposure is prolonged (over about one year). Furthermore, the neurological effects of lead exposure have been shown to be exacerbated and long lasting in low income children in comparison to those of higher economic standing. This does not imply that being wealthy can prevent lead from causing long-term mental health issues. Violence Lead poisoning in children has been linked to changes in brain function that can result in low IQ, and increased impulsivity and aggression. These traits of childhood lead exposure are associated with crimes of passion, such as aggravated assault in young adults. An increase in lead exposure in children was linked to an increase in aggravated assault rates 22 years later. For instance, the peak in leaded gasoline use in the late 1970s corresponds to a peak in aggravated assault rates in the late 1990s in urban areas across the United States. History Lead poisoning was among the first known and most widely studied work regarding environmental hazards. One of the first metals to be smelted and used, lead is thought to have been discovered and first mined in Anatolia around 6500 BC. Its density, workability, and corrosion resistance were among the metals attractions.In the 2nd century BC the Greek botanist Nicander described the colic and paralysis seen in lead-poisoned people. Dioscorides, a Greek physician who lived in the 1st century AD, wrote that lead makes the mind "give way".Lead was used extensively in Roman aqueducts from about 500 BC to 300 AD. Julius Caesars engineer, Vitruvius, reported, "water is much more wholesome from earthenware pipes than from lead pipes. For it seems to be made injurious by lead, because white lead is produced by it, and this is said to be harmful to the human body." Gout, prevalent in affluent Rome, is thought to be the result of lead, or leaded eating and drinking vessels. Sugar of lead (lead(II) acetate) was used to sweeten wine, and the gout that resulted from this was known as "saturnine" gout. It is even hypothesized that lead poisoning may have contributed to the decline of the Roman Empire, a hypothesis thoroughly disputed: The great disadvantage of lead has always been that it is poisonous. This was fully recognised by the ancients, and Vitruvius specifically warns against its use. Because it was nevertheless used in profusion for carrying drinking water, the conclusion has often been drawn that the Romans must therefore have suffered from lead poisoning; sometimes conclusions are carried even further and it is inferred that this caused infertility and other unwelcome conditions, and that lead plumbing was largely responsible for the decline and fall of Rome. Two things make this otherwise attractive hypothesis impossible. First, the calcium carbonate deposit that formed so thickly inside the aqueduct channels also formed inside the pipes, effectively insulating the water from the lead, so that the two never touched. Second, because the Romans had so few taps and the water was constantly running, it was never inside the pipes for more than a few minutes, and certainly not long enough to become contaminated. However, recent research supports the idea that the lead found in the water came from the supply pipes, rather than another source of contamination. It was not unknown for locals to punch holes in the pipes to draw water off, increasing the number of people exposed to the lead. Thirty years ago, Jerome Nriagu argued in a milestone paper that Roman civilization collapsed as a result of lead poisoning. Clair Patterson, the scientist who convinced governments to ban lead from gasoline, enthusiastically endorsed this idea, which nevertheless triggered a volley of publications aimed at refuting it. Although today lead is no longer seen as the prime culprit of Romes demise, its status in the system of water distribution by lead pipes (fistulæ) still stands as a major public health issue. By measuring Pb isotope compositions of sediments from the Tiber River and the Trajanic Harbor, the present work shows that "tap water" from ancient Rome had 100 times more lead than local spring waters. Romans also consumed lead through the consumption of defrutum, carenum, and sapa, musts made by boiling down fruit in lead cookware. Defrutum and its relatives were used in ancient Roman cuisine and cosmetics, including as a food preservative. The use of leaden cookware, though popular, was not the general standard and copper cookware was used far more generally. There is also no indication how often sapa was added or in what quantity. The consumption of sapa as having a role in the fall of the Roman Empire was used in a theory proposed by geochemist Jerome Nriagu to state that "lead poisoning contributed to the decline of the Roman Empire". In 1984, John Scarborough, a pharmacologist and classicist, criticized the conclusions drawn by Nriagus book as "so full of false evidence, miscitations, typographical errors, and a blatant flippancy regarding primary sources that the reader cannot trust the basic arguments."After antiquity, mention of lead poisoning was absent from medical literature until the end of the Middle Ages. In 1656 the German physician Samuel Stockhausen recognized dust and fumes containing lead compounds as the cause of disease, called since ancient Roman times morbi metallici, that were known to afflict miners, smelter workers, potters, and others whose work exposed them to the metal.The painter Caravaggio might have died of lead poisoning. Bones with high lead levels were recently found in a grave thought likely to be his. Paints used at the time contained high amounts of lead salts. Caravaggio is known to have exhibited violent behavior, a symptom commonly associated with lead poisoning. In 17th-century Germany, the physician Eberhard Gockel discovered lead-contaminated wine to be the cause of an epidemic of colic. He had noticed that monks who did not drink wine were healthy, while wine drinkers developed colic, and traced the cause to sugar of lead, made by simmering litharge with vinegar. As a result, Eberhard Ludwig, Duke of Württemberg issued an edict in 1696 banning the adulteration of wines with litharge.In the 18th century lead poisoning was fairly frequent on account of the widespread drinking of rum, which was made in stills with a lead component (the "worm"). It was a significant cause of mortality amongst slaves and sailors in the colonial West Indies. Lead poisoning from rum was also noted in Boston. Benjamin Franklin suspected lead to be a risk in 1786. Also in the 18th century, "Devonshire colic" was the name given to the symptoms experienced by people of Devon who drank cider made in presses that were lined with lead. Lead was added to cheap wine illegally in the 18th and early 19th centuries as a sweetener. The composer Beethoven, a heavy wine drinker, had elevated lead levels (as later detected in his hair) possibly due to this; the cause of his death is controversial, but lead poisoning is a contender as a factor.With the Industrial Revolution in the 19th century, lead poisoning became common in the work setting. The introduction of lead paint for residential use in the 19th century increased childhood exposure to lead; for millennia before this, most lead exposure had been occupational. William James Furnival (1853-1928), research ceramist of City & Guilds London Institute, appeared before Parliament in 1901 and presented a decades evidence to convince the nations leaders to remove lead completely from the British ceramic industry. His 852-page treatise, Leadless Decorative Tiles, Faience, and Mosaic of 1904 published that campaign and provided recipes to promote lead-free ceramics. At the request of the Illinois state government, Alice Hamilton (1869-1970) documented lead toxicity in Illinois industry and in 1911 presented results to the 23rd Annual Meeting of the American Economic Association. Dr. Hamilton was a founder of the field of occupational safety and health and published the first edition of her manual, Industrial Toxicology in 1934, yet in print in revised forms. An important step in the understanding of childhood lead poisoning occurred when toxicity in children from lead paint was recognized in Australia in 1897. France, Belgium, and Austria banned white lead interior paints in 1909; the League of Nations followed suit in 1922. However, in the United States, laws banning lead house paint were not passed until 1971,and it was phased out and not fully banned until 1978.The 20th century saw an increase in worldwide lead exposure levels due to the increased widespread use of the metal. Beginning in the 1920s, lead was added to gasoline to improve its combustion; lead from this exhaust persists today in soil and dust in buildings. Midcentury ceramicist Carol Janeway provides a case history of lead poisoning in an artist using lead glazes in decorating tiles in the 1940s; her monograph suggests that other artists potential for lead poisoning be investigated, for example Vally Wieselthier and Dora Carrington. Blood lead levels worldwide have been declining sharply since the 1980s, when leaded gasoline began to be phased out. In those countries that have banned lead in solder for food and drink cans and have banned leaded gasoline additives, blood lead levels have fallen sharply since the mid-1980s.The levels found today in most people are orders of magnitude greater than those of pre-industrial society. Due to reductions of lead in products and the workplace, acute lead poisoning is rare in most countries today, but low-level lead exposure is still common. |bot=InternetArchiveBot |fix-attempted=yes }}</ref> It was not until the second half of the 20th century that subclinical lead exposure became understood to be a problem. During the end of the 20th century, the blood lead levels deemed acceptable steadily declined. Blood lead levels once considered safe are now considered hazardous, with no known safe threshold.In the late 1950s through the 1970s Herbert Needleman and Clair Cameron Patterson did research trying to prove leads toxicity to humans. In the 1980s Needleman was falsely accused of scientific misconduct by the lead industry associates.In 2002 Tommy Thompson, secretary of Health and Human Services appointed at least two persons with conflicts of interest to the CDCs Lead Advisory Committee. In 2014 a case by the state of California against a number of companies decided against Sherwin-Williams, NL Industries and ConAgra and ordered them to pay $1.15 billion. The disposition of The People v. ConAgra Grocery Products Company et al. in the California 6th Appellate District Court on 14 November 2017 is that:... the judgment is reversed, and the matter is remanded to the trial court with directions to (1) recalculate the amount of the abatement fund to limit it to the amount necessary to cover the cost of remediating pre-1951 homes, and (2) hold an evidentiary hearing regarding the appointment of a suitable receiver. The Plaintiff shall recover its costs on appeal. On 6 December 2017, the petitions for rehearing from NL Industries, Inc., ConAgra Grocery Products Company and The Sherwin-Williams Company were denied.Studies have found a weak link between lead from leaded gasoline and crime rates.As of 2022 in the United States lead paint in rental housing remains a hazard to children. Both landlords and insurance companies have adopted strategies which limit the chance of recovery for damages due to lead poisoning: insurance companies by excluding coverage for lead poisoning from policies and landlords by crafting barriers to collection of any money damages compensating plaintiffs for damage. Other species Humans are not alone in suffering from leads effects; plants and animals are also affected by lead toxicity to varying degrees depending on species. Animals experience many of the same effects of lead exposure as humans do, such as abdominal pain, peripheral neuropathy, and behavioral changes such as increased aggression. Much of what is known about human lead toxicity and its effects is derived from animal studies. Animals are used to test the effects of treatments, such as chelating agents, and to provide information on the pathophysiology of lead, such as how it is absorbed and distributed in the body.Farm animals such as cows and horses as well as pet animals are also susceptible to the effects of lead toxicity. Sources of lead exposure in pets can be the same as those that present health threats to humans sharing the environment, such as paint and blinds, and there is sometimes lead in toys made for pets. Lead poisoning in a pet dog may indicate that children in the same household are at increased risk for elevated lead levels. Wildlife Lead, one of the leading causes of toxicity in waterfowl, has been known to cause die-offs of wild bird populations. When hunters use lead shot, waterfowl such as ducks can ingest the spent pellets later and be poisoned; predators that eat these birds are also at risk. Lead shot-related waterfowl poisonings were first documented in the US in the 1880s. By 1919, the spent lead pellets from waterfowl hunting was positively identified as the source of waterfowl deaths. Lead shot has been banned for hunting waterfowl in several countries, including the US in 1991 and Canada in 1997. Other threats to wildlife include lead paint, sediment from lead mines and smelters, and lead weights from fishing lines. Lead in some fishing gear has been banned in several countries.The critically endangered California condor has also been affected by lead poisoning. As scavengers, condors eat carcasses of game that have been shot but not retrieved, and with them the fragments from lead bullets; this increases their lead levels. Among condors around the Grand Canyon, lead poisoning due to eating lead shot is the most frequently diagnosed cause of death. In an effort to protect this species, in areas designated as the California condors range the use of projectiles containing lead has been banned to hunt deer, feral pigs, elk, pronghorn antelope, coyotes, ground squirrels, and other non-game wildlife. Also, conservation programs exist which routinely capture condors, check their blood lead levels, and treat cases of poisoning. Notes References Further reading == External links ==

Aarogya, explain a scenario commonly referred as Leishmaniasis

Leishmaniasis

Leishmaniasis is a wide array of clinical manifestations caused by parasites of the trypanosome genus Leishmania. It is generally spread through the bite of phlebotomine sandflies, Phlebotomus and Lutzomyia, and occurs most frequently in the tropics and sub-tropics of Africa, Asia, the Americas, and southern Europe. The disease can present in three main ways: cutaneous, mucocutaneous, or visceral. The cutaneous form presents with skin ulcers, while the mucocutaneous form presents with ulcers of the skin, mouth, and nose. The visceral form starts with skin ulcers and later presents with fever, low red blood cell count, and enlarged spleen and liver.Infections in humans are caused by more than 20 species of Leishmania. Risk factors include poverty, malnutrition, deforestation, and urbanization. All three types can be diagnosed by seeing the parasites under microscopy. Additionally, visceral disease can be diagnosed by blood tests.Leishmaniasis can be partly prevented by sleeping under nets treated with insecticide. Other measures include spraying insecticides to kill sandflies and treating people with the disease early to prevent further spread. The treatment needed is determined by where the disease is acquired, the species of Leishmania, and the type of infection. Some possible medications used for visceral disease include liposomal amphotericin B, a combination of pentavalent antimonials and paromomycin, and miltefosine. For cutaneous disease, paromomycin, fluconazole, or pentamidine may be effective.About 4 to 12 million people are currently infected in some 98 countries. About 2 million new cases and between 20 and 50 thousand deaths occur each year. About 200 million people in Asia, Africa, South and Central America, and southern Europe live in areas where the disease is common. The World Health Organization has obtained discounts on some medications to treat the disease. It is classified as a neglected tropical disease. The disease may occur in a number of other animals, including dogs and rodents. Signs and symptoms The symptoms of leishmaniasis are skin sores which erupt weeks to months after the person is bitten by infected sand flies. Leishmaniasis may be divided into the following types: Cutaneous leishmaniasis is the most common form, which causes an open sore at the bite sites, which heals in a few months to a year and half, leaving an unpleasant-looking scar. Diffuse cutaneous leishmaniasis produces widespread skin lesions which resemble leprosy, and may not heal on its own. Mucocutaneous leishmaniasis causes both skin and mucosal ulcers with damage primarily of the nose and mouth. Visceral leishmaniasis or kala-azar (black fever) is the most serious form, and is generally fatal if untreated. Other consequences, which can occur a few months to years after infection, include fever, damage to the spleen and liver, and anemia.Leishmaniasis is considered one of the classic causes of a markedly enlarged (and therefore palpable) spleen; the organ, which is not normally felt during examination of the abdomen, may even become larger than the liver in severe cases. Cause Leishmaniasis is transmitted by the bite of infected female phlebotomine sandflies which can transmit the protozoa Leishmania. (1) The sandflies inject the infective stage, metacyclic promastigotes, during blood meals. (2) Metacyclic promastigotes in the puncture wound are phagocytized by macrophages, and (3) transform into amastigotes. (4) Amastigotes multiply in infected cells and affect different tissues, depending in part on the host, and in part on which Leishmania species is involved. These differing tissue specificities cause the differing clinical manifestations of the various forms of leishmaniasis. (5,6) Sandflies become infected during blood meals on infected hosts when they ingest macrophages infected with amastigotes. (7) In the sandflys midgut, the parasites differentiate into promastigotes, (8) which multiply, differentiate into metacyclic promastigotes, and migrate to the proboscis. The genomes of three Leishmania species (L. major, L. infantum, and L. braziliensis) have been sequenced, and this has provided much information about the biology of the parasite. For example, in Leishmania, protein-coding genes are understood to be organized as large polycistronic units in a head-to-head or tail-to-tail manner; RNA polymerase II transcribes long polycistronic messages in the absence of defined RNA pol II promoters, and Leishmania has unique features with respect to the regulation of gene expression in response to changes in the environment. The new knowledge from these studies may help identify new targets for urgently needed drugs and aid the development of vaccines. Vector Although most of the literature mentions only one genus transmitting Leishmania to humans (Lutzomyia) in the New World, a 2003 study by Galati suggested a new classification for New World sand flies, elevating several subgenera to the genus level. Elsewhere in the world, the genus Phlebotomus is considered the vector of leishmaniasis. Possible non-human reservoirs Some cases of infection of non-human animals of human-infecting species of Leishmania have been observed. In one study, L. major was identified in twelve out of ninety-one wild western lowland gorilla fecal samples and in a study of fifty-two captive non-human primates under zoo captivity in a leishmaniasis endemic area, eight (all three chimpanzees, three golden lion tamarins, a tufted capuchin, and an Angolan talapoin), were found to be infected with L. infantum and capable of infecting Lutzomyia longipalpis sand flies, although "parasite loads in infected sand flies observed in this study were considered low". Organisms Visceral disease is usually caused by Leishmania donovani, L. infantum, or L. chagasi, but occasionally these species may cause other forms of disease. The cutaneous form of the disease is caused by more than 15 species of Leishmania. Risk factors Risk factors include malnutrition, deforestation, lack of sanitation, suppressed immune system and urbanization. Diagnosis Leishmaniasis is diagnosed in the hematology laboratory by direct visualization of the amastigotes (Leishman–Donovan bodies). Buffy-coat preparations of peripheral blood or aspirates from marrow, spleen, lymph nodes, or skin lesions should be spread on a slide to make a thin smear and stained with Leishman stain or Giemsa stain (pH 7.2) for 20 minutes. Amastigotes are seen within blood and spleen monocytes or, less commonly, in circulating neutrophils and in aspirated tissue macrophages. They are small, round bodies 2–4 μm in diameter with indistinct cytoplasm, a nucleus, and a small, rod-shaped kinetoplast. Occasionally, amastigotes may be seen lying free between cells. However, the retrieval of tissue samples is often painful for the patient and identification of the infected cells can be difficult. So, other indirect immunological methods of diagnosis are developed, including enzyme-linked immunosorbent assay, antigen-coated dipsticks, and direct agglutination test. Although these tests are readily available, they are not the standard diagnostic tests due to their insufficient sensitivity and specificity. Several different polymerase chain reaction (PCR) tests are available for the detection of Leishmania DNA. With this assay, a specific and sensitive diagnostic procedure is finally possible. The most sensitive PCR tests use minicircle kinetoplast DNA found in the parasite. Kinetoplast DNA contains sequences for mitochondrial proteins in its maxicircles(~25-50 per parasite), and guide RNA in its minicircles(~10000 per parasite) of the kinetoplast. With this specific method, one can still detect Leishmania even with a very low parasite load. When needing to diagnose a specific species of Leishmania, as opposed to only detection, other PCR methods have been superior.Most forms of the disease are transmitted only from nonhuman animals, but some can be spread between humans. Infections in humans are caused by about 21 of 30 species that infect mammals; the different species look the same, but they can be differentiated by isoenzyme analysis, DNA sequence analysis, or monoclonal antibodies. Prevention Using insect repellent to exposed skin and under the ends of sleeves and pant legs. Follow the instructions on the label of the repellent. The most effective repellents generally are those that contain the chemical DEET (N,N-diethylmetatoluamide) Leishmaniasis can be partly prevented by using nets treated with insecticide or insect repellent while sleeping. To provide good protection against sandflies, fine mesh sizes of 0.6 mm or less are required, but a mosquito net with 1.2mm mesh will provide a limited reduction in the number of sandfly bites. Finer mesh sizes have the downside of higher cost and reduced air circulation which can cause overheating. Many Phlebotomine sandfly attacks occur at sunset rather than at night, so it may also be useful to put nets over doors and windows or to use insect repellents. Use of insecticide-impregnated dog collars and treatment or culling of infected dogs. Spraying houses and animal shelters with insecticides. Treatment The treatment is determined by where the disease is acquired, the species of Leishmania, and the type of infection. For visceral leishmaniasis in India, South America, and the Mediterranean, liposomal amphotericin B is the recommended treatment and is often used as a single dose. Rates of cure with a single dose of amphotericin have been reported as 95%. In India, almost all infections are resistant to pentavalent antimonials. In Africa, a combination of pentavalent antimonials and paromomycin is recommended. These, however, can have significant side effects. Miltefosine, an oral medication, is effective against both visceral and cutaneous leishmaniasis. Side effects are generally mild, though it can cause birth defects if taken within 3 months of getting pregnant. It does not appear to work for L. major or L. braziliensis.The evidence around the treatment of cutaneous leishmaniasis is poor. A number of topical treatments may be used for cutaneous leishmaniasis. Which treatments are effective depends on the strain, with topical paromomycin effective for L. major, L. tropica, L. mexicana, L. panamensis, and L. braziliensis. Pentamidine is effective for L. guyanensis. Oral fluconazole or itraconazole appears effective in L. major and L. tropica. There is limited evidence to support the use of heat therapy in cutaneous leishmaniasis as of 2015.There are no studies determining the effect of oral nutritional supplements on visceral leishmaniasis being treated with anti-leishmanial drug therapy. Epidemiology Out of 200 countries and territories reporting to WHO, 97 countries and territories are endemic for leishmaniasis. The settings in which leishmaniasis is found range from rainforests in Central and South America to deserts in western Asia and the Middle East. It affects as many as 12 million people worldwide, with 1.5–2.0 million new cases each year. The visceral form of leishmaniasis has an estimated incidence of 500,000 new cases. In 2014, more than 90% of new cases reported to WHO occurred in six countries: Brazil, Ethiopia, India, Somalia, South Sudan and Sudan. As of 2010, it caused about 52,000 deaths, down from 87,000 in 1990. Different types of the disease occur in different regions of the world. Cutaneous disease is most common in Afghanistan, Algeria, Brazil, Colombia, and Iran, while mucocutaneous disease is most common in Bolivia, Brazil, and Peru, and visceral disease is most common in Bangladesh, Brazil, Ethiopia, India, and Sudan.Leishmaniasis is found through much of the Americas from northern Argentina to South Texas, though not in Uruguay or Chile, and has recently been shown to be spreading to North Texas and Oklahoma, and further expansion to the north may be facilitated by climate change as more habitat becomes suitable for vector and reservoir species for leishmaniasis. Leishmaniasis is also known as papalomoyo, papa lo moyo, úlcera de los chicleros, and chiclera in Latin America. During 2004, an estimated 3,400 troops from the Colombian army, operating in the jungles near the south of the country (in particular around the Meta and Guaviare departments), were infected with leishmaniasis. Allegedly, a contributing factor was that many of the affected soldiers did not use the officially provided insect repellent because of its disturbing odor. Nearly 13,000 cases of the disease were recorded in all of Colombia throughout 2004, and about 360 new instances of the disease among soldiers had been reported in February 2005.The disease is found across much of Asia, and in the Middle East. Within Afghanistan, leishmaniasis occurs commonly in Kabul, partly due to bad sanitation and waste left uncollected in streets, allowing parasite-spreading sand flies an environment they find favorable. In Kabul, the number of people infected was estimated to be at least 200,000, and in three other towns (Herat, Kandahar, and Mazar-i-Sharif) about 70,000 more occurred, according to WHO figures from 2002. Kabul is estimated as the largest center of cutaneous leishmaniasis in the world, with around 67,500 cases as of 2004. Africa, in particular the East and North, is also home to cases of leishmaniasis. Leishmaniasis is considered endemic also in some parts of southern parts of western Europe and spreading towards north in recent years. For example, an outbreak of cutaneous and visceral leishmaniasis was reported from Madrid, Spain, between 2010 and 2012.Leishmaniasis is mostly a disease of the developing world, and is rarely known in the developed world outside a small number of cases, mostly in instances where troops are stationed away from their home countries. Leishmaniasis has been reported by U.S. troops stationed in Saudi Arabia and Iraq since the Gulf War of 1990, including visceral leishmaniasis. In September 2005, the disease was contracted by at least four Dutch marines who were stationed in Mazar-i-Sharif, Afghanistan, and subsequently repatriated for treatment. History Descriptions of conspicuous lesions similar to cutaneous leishmaniasis appear on tablets from King Ashurbanipal from the seventh century BCE, some of which may have derived from even earlier texts from 1500 to 2500 BCE. Persian physicians, including Avicenna in the 10th century CE, gave detailed descriptions of what was called balkh sore. In 1756, Alexander Russell, after examining a Turkish patient, gave one of the most detailed clinical descriptions of the disease. Physicians in the Indian subcontinent would describe it as kala-azar (pronounced kālā āzār, the Urdu, Hindi, and Hindustani phrase for "black fever", kālā meaning black and āzār meaning fever or disease). In the Americas, evidence of the cutaneous form of the disease in Ecuador and Peru appears in pre-Inca pottery depicting skin lesions and deformed faces dating back to the first century CE. Some 15th- and 16th-century texts from the Inca period and from Spanish colonials mention "valley sickness", "Andean sickness", or "white leprosy", which are likely to be the cutaneous form.It remains unclear who first discovered the organism. David Douglas Cunningham, Surgeon Major of the British Indian army, may have seen it in 1885 without being able to relate it to the disease. Peter Borovsky, a Russian military surgeon working in Tashkent, conducted research into the etiology of "oriental sore", locally known as sart sore, and in 1898 published the first accurate description of the causative agent, correctly described the parasites relation to host tissues and correctly referred it to the protozoa. However, because his results were published in Russian in a journal with low circulation, his results were not internationally acknowledged during his lifetime. In 1901, William Boog Leishman identified certain organisms in smears taken from the spleen of a patient who had died from "dum-dum fever" (Dum Dum is an area close to Calcutta) and proposed them to be trypanosomes, found for the first time in India. A few months later, Captain Charles Donovan (1863–1951) confirmed the finding of what became known as Leishman-Donovan bodies in smears taken from people in Madras in southern India. But it was Ronald Ross who proposed that Leishman-Donovan bodies were the intracellular stages of a new parasite, which he named Leishmania donovani. The link with the disease kala-azar was first suggested by Charles Donovan, and was conclusively demonstrated by Charles Bentleys discovery of L. donovani in patients with kala-azar. Transmission by the sandfly was hypothesized by Lionel Napier and Ernest Struthers at the School of Tropical Medicine at Calcutta and later proven by his colleagues. The disease became a major problem for Allied troops fighting in Sicily during the Second World War; research by Leonard Goodwin then showed pentostam was an effective treatment. Society and culture The Institute for OneWorld Health has reintroduced the drug paromomycin for treatment of leishmaniasis, results with which led to its approval as an orphan drug. The Drugs for Neglected Diseases Initiative is also actively facilitating the search for novel therapeutics. A treatment with paromomycin will cost about US$10. The drug had originally been identified in the 1960s, but had been abandoned because it would not be profitable, as the disease mostly affects poor people. The Indian government approved paromomycin for sale in August 2006.By 2012 the World Health Organization had successfully negotiated with the manufacturers to achieve a reduced cost for liposomal amphotericin B, to US$18 a vial, but a number of vials are needed for treatment and it must be kept at a stable, cool temperature. Research As of 2017, no leishmaniasis vaccine for humans was available. Research to produce a human vaccine is ongoing.Currently some effective leishmaniasis vaccines for dogs exist. There is also consideration that public health practices can control or eliminate leishmaniasis without a vaccine. See also Canine vector-borne disease Tropical disease References External links Leishmaniasis at Curlie Doctors Without Borders Leishmaniasis Information Page CDC Leishmaniasis Page

Hey Aarogya, could you help me understand about Lentigo

Lentigo

A lentigo () (plural lentigines, ) is a small pigmented spot on the skin with a clearly defined edge, surrounded by normal-appearing skin. It is a harmless (benign) hyperplasia of melanocytes which is linear in its spread. This means the hyperplasia of melanocytes is restricted to the cell layer directly above the basement membrane of the epidermis where melanocytes normally reside. This is in contrast to the "nests" of multi-layer melanocytes found in moles (melanocytic nevi). Because of this characteristic feature, the adjective "lentiginous" is used to describe other skin lesions that similarly proliferate linearly within the basal cell layer. Diagnosis Conditions characterized by lentigines include: Lentigo simplex Solar lentigo (Liver spots) PUVA lentigines Ink spot lentigo LEOPARD syndrome Mucosal lentigines Multiple lentigines syndrome Moynahan syndrome Generalized lentiginosis Centrofacial lentiginosis Carney complex Inherited patterned lentiginosis in black persons Partial unilateral lentiginosis Peutz–Jeghers syndrome Lentigo maligna Lentigo maligna melanoma Acral lentiginous melanoma Differential diagnosis Lentigines are distinguished from freckles (ephelis) based on the proliferation of melanocytes. Freckles have a relatively normal number of melanocytes but an increased amount of melanin. A lentigo has an increased number of melanocytes. Freckles will increase in number and darkness with sunlight exposure, whereas lentigines will stay stable in their color regardless of sunlight exposure. Treatment Lentigines by themselves are benign, however one might desire the removal or treatment of some of them for cosmetic purposes. In this case they can be removed surgically, or lightened with the use of topical depigmentation agents. Some common depigmentation agents such as azelaic acid and kojic acid seem to be inefficient in this case, however other agents might work well (4% hydroquinone, 5% topical cysteamine, 10% topical ascorbic acid). See also Freckle List of skin diseases Mole Skin disease Skin lesion References == External links ==

Hey Aarogya , Do you know what is Leprosy,

Leprosy

Leprosy, also known as Hansens disease (HD), is a long-term infection by the bacteria Mycobacterium leprae or Mycobacterium lepromatosis. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damage may result in a lack of ability to feel pain, which can lead to the loss of parts of a persons extremities from repeated injuries or infection through unnoticed wounds. An infected person may also experience muscle weakness and poor eyesight. Leprosy symptoms may begin within one year, but, for some people, symptoms may take 20 years or more to occur.Leprosy is spread between people, although extensive contact is necessary. Leprosy has a low pathogenicity, and 95% of people who contract M. leprae do not develop the disease. Spread is thought to occur through a cough or contact with fluid from the nose of a person infected by leprosy. Genetic factors and immune function play a role in how easily a person catches the disease. Leprosy does not spread during pregnancy to the unborn child or through sexual contact. Leprosy occurs more commonly among people living in poverty. There are two main types of the disease – paucibacillary and multibacillary, which differ in the number of bacteria present. A person with paucibacillary disease has five or fewer poorly-pigmented, numb skin patches, while a person with multibacillary disease has more than five skin patches. The diagnosis is confirmed by finding acid-fast bacilli in a biopsy of the skin.Leprosy is curable with multidrug therapy. Treatment of paucibacillary leprosy is with the medications dapsone, rifampicin, and clofazimine for six months. Treatment for multibacillary leprosy uses the same medications for 12 months. A number of other antibiotics may also be used. These treatments are provided free of charge by the World Health Organization.Leprosy is not highly contagious. People with leprosy can live with their families and go to school and work. In the 1980s, there were 5.2 million cases globally but went down to less than 0.2 million by 2020. Most new cases occur in 14 countries, with India accounting for more than half. In the 20 years from 1994 to 2014, 16 million people worldwide were cured of leprosy. About 200 cases per year are reported in the United States. Separating people affected by leprosy by placing them in leper colonies still occurs in some areas of India, China, areas in the African continent, and Thailand.Leprosy has affected humanity for thousands of years. The disease takes its name from the Greek word λέπρᾱ (léprā), from λεπῐ́ς (lepís; scale), while the term "Hansens disease" is named after the Norwegian physician Gerhard Armauer Hansen. Leprosy has historically been associated with social stigma, which continues to be a barrier to self-reporting and early treatment. Some consider the word leper offensive, preferring the phrase "person affected with leprosy". Leprosy is classified as a neglected tropical disease. World Leprosy Day was started in 1954 to draw awareness to those affected by leprosy. Signs and symptoms Common symptoms present in the different types of leprosy include a runny nose; dry scalp; eye problems; skin lesions; muscle weakness; reddish skin; smooth, shiny, diffuse thickening of facial skin, ear, and hand; loss of sensation in fingers and toes; thickening of peripheral nerves; a flat nose from destruction of nasal cartilage; and changes in phonation and other aspects of speech production. In addition, atrophy of the testes and impotence may occur.Leprosy can affect people in different ways. The average incubation period is five years. People may begin to notice symptoms within the first year or up to 20 years after infection. The first noticeable sign of leprosy is often the development of pale or pink coloured patches of skin that may be insensitive to temperature or pain. Patches of discolored skin are sometimes accompanied or preceded by nerve problems including numbness or tenderness in the hands or feet. Secondary infections (additional bacterial or viral infections) can result in tissue loss, causing fingers and toes to become shortened and deformed, as cartilage is absorbed into the body. A persons immune response differs depending on the form of leprosy.Approximately 30% of people affected with leprosy experience nerve damage. The nerve damage sustained is reversible when treated early, but becomes permanent when appropriate treatment is delayed by several months. Damage to nerves may cause loss of muscle function, leading to paralysis. It may also lead to sensation abnormalities or numbness, which may lead to additional infections, ulcerations, and joint deformities. Cause M. leprae and M. lepromatosis M. leprae and M. lepromatosis are the mycobacteria that cause leprosy. M. lepromatosis is a relatively newly identified mycobacterium isolated from a fatal case of diffuse lepromatous leprosy in 2008. M. lepromatosis is indistinguishable clinically from M. leprae.M. leprae is an intracellular, acid-fast bacterium that is aerobic and rod-shaped. M. leprae is surrounded by the waxy cell envelope coating characteristic of the genus Mycobacterium.Genetically, M. leprae and M. lepromatosis lack the genes that are necessary for independent growth. M. leprae and M. lepromatosis are obligate intracellular pathogens, and can not be grown (cultured) in the laboratory. The inability to culture M. leprae and M. lepromatosis has resulted in a difficulty definitively identifying the bacterial organism under a strict interpretation of Kochs postulates.While the causative organisms have to date been impossible to culture in vitro, it has been possible to grow them in animals such as mice and armadillos.Naturally occurring infection has been reported in nonhuman primates (including the African chimpanzee, the sooty mangabey, and the cynomolgus macaque), armadillos, and red squirrels. Multilocus sequence typing of the armadillo M. leprae strains suggests that they were of human origin for at most a few hundred years. Thus, it is suspected that armadillos first acquired the organism incidentally from early American explorers. This incidental transmission was sustained in the armadillo population, and it may be transmitted back to humans, making leprosy a zoonotic disease (spread between humans and animals).Red squirrels (Sciurus vulgaris), a threatened species in Great Britain, were found to carry leprosy in November 2016. It has been suggested that the trade in red squirrel fur, highly prized in the medieval period and intensively traded, may have been responsible for the leprosy epidemic in medieval Europe. A pre-Norman-era skull excavated in Hoxne, Suffolk, in 2017 was found to carry DNA from a strain of Mycobacterium leprae, which closely matched the strain carried by modern red squirrels on Brownsea Island, UK. Risk factors The greatest risk factor for developing leprosy is contact with another person infected by leprosy. People who are exposed to a person who has leprosy are 5–8 times more likely to develop leprosy than members of the general population. Leprosy also occurs more commonly among those living in poverty. Not all people who are infected with M. leprae develop symptoms.Conditions that reduce immune function, such as malnutrition, other illnesses, or genetic mutations, may increase the risk of developing leprosy. Infection with HIV does not appear to increase the risk of developing leprosy. Certain genetic factors in the person exposed have been associated with developing lepromatous or tuberculoid leprosy. Transmission Transmission of leprosy occurs during close contact with those who are infected. Transmission of leprosy is through the upper respiratory tract. Older research suggested the skin as the main route of transmission, but recent research has increasingly favored the respiratory route.Leprosy is not sexually transmitted and is not spread through pregnancy to the unborn child. The majority (95%) of people who are exposed to M. leprae do not develop leprosy; casual contact such as shaking hands and sitting next to someone with leprosy does not lead to transmission. People are considered non-infectious 72 hours after starting appropriate multi-drug therapy.Two exit routes of M. leprae from the human body often described are the skin and the nasal mucosa, although their relative importance is not clear. Lepromatous cases show large numbers of organisms deep in the dermis, but whether they reach the skin surface in sufficient numbers is doubtful.Leprosy may also be transmitted to humans by armadillos, although the mechanism is not fully understood. Genetics Not all people who are infected or exposed to M. leprae develop leprosy, and genetic factors are suspected to play a role in susceptibility to an infection. Cases of leprosy often cluster in families and several genetic variants have been identified. In many people who are exposed, the immune system is able to eliminate the leprosy bacteria during the early infection stage before severe symptoms develop. A genetic defect in cell-mediated immunity may cause a person to be susceptible to develop leprosy symptoms after exposure to the bacteria. The region of DNA responsible for this variability is also involved in Parkinsons disease, giving rise to current speculation that the two disorders may be linked at the biochemical level. Mechanism Most leprosy complications are the result of nerve damage. The nerve damage occurs from direct invasion by the M. leprae bacteria and a persons immune response resulting in inflammation. The molecular mechanism underlying how M. leprae produces the symptoms of leprosy is not clear, but M. leprae has been shown to bind to Schwann cells, which may lead to nerve injury including demyelination and a loss of nerve function (specifically a loss of axonal conductance). Numerous molecular mechanisms have been associated with this nerve damage including the presence of a laminin-binding protein and the glycoconjugate (PGL-1) on the surface of M. leprae that can bind to laminin on peripheral nerves.As part of the human immune response, white blood cell-derived macrophages may engulf M. leprae by phagocytosis.In the initial stages, small sensory and autonomic nerve fibers in the skin of a person with leprosy are damaged. This damage usually results in hair loss to the area, a loss of the ability to sweat, and numbness (decreased ability to detect sensations such as temperature and touch). Further peripheral nerve damage may result in skin dryness, more numbness, and muscle weaknesses or paralysis in the area affected. The skin can crack and if the skin injuries are not carefully cared for, there is a risk for a secondary infection that can lead to more severe damage. Diagnosis In countries where people are frequently infected, a person is considered to have leprosy if they have one of the following two signs: Skin lesion consistent with leprosy and with definite sensory loss. Positive skin smears.Skin lesions can be single or many, and usually hypopigmented, although occasionally reddish or copper-colored. The lesions may be flat (macules), raised (papules), or solid elevated areas (nodular). Experiencing sensory loss at the skin lesion is a feature that can help determine if the lesion is caused by leprosy or by another disorder such as tinea versicolor. Thickened nerves are associated with leprosy and can be accompanied by loss of sensation or muscle weakness, but muscle weakness without the characteristic skin lesion and sensory loss is not considered a reliable sign of leprosy.In some cases, acid-fast leprosy bacilli in skin smears are considered diagnostic; however, the diagnosis is typically made without laboratory tests, based on symptoms. If a person has a new leprosy diagnosis and already has a visible disability caused by leprosy, the diagnosis is considered late.In countries or areas where leprosy is uncommon, such as the United States, diagnosis of leprosy is often delayed because healthcare providers are unaware of leprosy and its symptoms. Early diagnosis and treatment prevent nerve involvement, the hallmark of leprosy, and the disability it causes.There is no recommended test to diagnose latent leprosy in people without symptoms. Few people with latent leprosy test positive for anti PGL-1. The presence of M. leprae bacterial DNA can be identified using a polymerase chain reaction (PCR)-based technique. This molecular test alone is not sufficient to diagnose a person, but this approach may be used to identify someone who is at high risk of developing or transmitting leprosy such as those with few lesions or an atypical clinical presentation. Classification Several different approaches for classifying leprosy exist. There are similarities between the classification approaches. The World Health Organization system distinguishes "paucibacillary" and "multibacillary" based upon the proliferation of bacteria. ("pauci-" refers to a low quantity.) The Ridley-Jopling scale provides five gradations. The ICD-10, though developed by the WHO, uses Ridley-Jopling and not the WHO system. It also adds an indeterminate ("I") entry. In MeSH, three groupings are used. Leprosy may also occur with only neural involvement, without skin lesions. Prevention Early detection of the disease is important, since physical and neurological damage may be irreversible even if cured. Medications can decrease the risk of those living with people who have leprosy from acquiring the disease and likely those with whom people with leprosy come into contact outside the home. The WHO recommends that preventive medicine be given to people who are in close contact with someone who has leprosy. The suggested preventive treatment is a single dose of rifampicin (SDR) in adults and children over 2 years old who do not already have leprosy or tuberculosis. Preventive treatment is associated with a 57% reduction in infections within 2 years and a 30% reduction in infections within 6 years.The Bacillus Calmette–Guérin (BCG) vaccine offers a variable amount of protection against leprosy in addition to its closely related target of tuberculosis. It appears to be 26% to 41% effective (based on controlled trials) and about 60% effective based on observational studies with two doses possibly working better than one. The WHO concluded in 2018 that the BCG vaccine at birth reduces leprosy risk and is recommended in countries with high incidence of TB and people who have leprosy. People living in the same home as a person with leprosy are suggested to take a BCG booster which may improve their immunity by 56%. Development of a more effective vaccine is ongoing.A novel vaccine called LepVax entered clinical trials in 2017 with the first encouraging results reported on 24 participants published in 2020. If successful, this would be the first leprosy-specific vaccine available. Treatment Anti-leprosy medication A number of leprostatic agents are available for treatment. A three-drug regimen of rifampicin, dapsone and clofazimine is recommended for all people with leprosy, for six months for paucibacillary leprosy and 12 months for multibacillary leprosy.Multidrug therapy (MDT) remains highly effective, and people are no longer infectious after the first monthly dose. It is safe and easy to use under field conditions because of its presentation in calendar blister packs. Post-treatment relapse rates remain low. Resistance has been reported in several countries, although the number of cases is small. People with rifampicin-resistant leprosy may be treated with second line drugs such as fluoroquinolones, minocycline, or clarithromycin, but the treatment duration is 24 months because of their lower bactericidal activity. Evidence on the potential benefits and harms of alternative regimens for drug-resistant leprosy is not yet available. Skin changes For people with nerve damage, protective footwear may help prevent ulcers and secondary infection. Canvas shoes may be better than PVC boots. There may be no difference between double rocker shoes and below-knee plaster.Topical ketanserin seems to have a better effect on ulcer healing than clioquinol cream or zinc paste, but the evidence for this is weak. Phenytoin applied to the skin improves skin changes to a greater degree when compared to saline dressings. Outcomes Although leprosy has been curable since the mid-20th century, left untreated it can cause permanent physical impairments and damage to a persons nerves, skin, eyes, and limbs. Despite leprosy not being very infectious and having a low pathogenicity, there is still significant stigma and prejudice associated with the disease. Because of this stigma, leprosy can affect a persons participation in social activities and may also affect the lives of their family and friends. People with leprosy are also at a higher risk for problems with their mental well-being. The social stigma may contribute to problems obtaining employment, financial difficulties, and social isolation. Efforts to reduce discrimination and reduce the stigma surrounding leprosy may help improve outcomes for people with leprosy. Epidemiology In 2018, there were 208,619 new cases of leprosy recorded, a slight decrease from 2017. In 2015, 94% of the new leprosy cases were confined to 14 countries. India reported the greatest number of new cases (60% of reported cases), followed by Brazil (13%) and Indonesia (8%). Although the number of cases worldwide continues to fall, there are parts of the world where leprosy is more common, including Brazil, South Asia (India, Nepal, Bhutan), some parts of Africa (Tanzania, Madagascar, Mozambique), and the western Pacific. About 150 to 250 cases are diagnosed in the United States each year.In the 1960s, there were tens of millions of leprosy cases recorded when the bacteria started to develop resistance to dapsone, the most common treatment option at the time. International (e.g., the WHOs "Global Strategy for Reducing Disease Burden Due to Leprosy") and national (e.g., the International Federation of Anti-Leprosy Associations) initiatives have reduced the total number and the number of new cases of the disease. Disease burden The number of new leprosy cases is difficult to measure and monitor because of leprosys long incubation period, delays in diagnosis after onset of the disease, and lack of medical care in affected areas. The registered prevalence of the disease is used to determine disease burden. Registered prevalence is a useful proxy indicator of the disease burden, as it reflects the number of active leprosy cases diagnosed with the disease and receiving treatment with MDT at a given point in time. The prevalence rate is defined as the number of cases registered for MDT treatment among the population in which the cases have occurred, again at a given point in time. History Historical distribution Using comparative genomics, in 2005, geneticists traced the origins and worldwide distribution of leprosy from East Africa or the Near East along human migration routes. They found four strains of M. leprae with specific regional locations. Strain 1 occurs predominantly in Asia, the Pacific region, and East Africa; strain 4, in West Africa and the Caribbean; strain 3 in Europe, North Africa, and the Americas; and strain 2 only in Ethiopia, Malawi, Nepal, north India, and New Caledonia. This confirms the spread of the disease along the migration, colonisation, and slave trade routes taken from East Africa to India, West Africa to the New World, and from Africa into Europe and vice versa.Skeletal remains discovered in 2009 represent the oldest documented evidence for leprosy, dating to the 2nd millennium BC. Located at Balathal, Rajasthan, in northwest India, the discoverers suggest that, if the disease did migrate from Africa to India during the 3rd millennium BC "at a time when there was substantial interaction among the Indus Civilization, Mesopotamia, and Egypt, there needs to be additional skeletal and molecular evidence of leprosy in India and Africa to confirm the African origin of the disease." A proven human case was verified by DNA taken from the shrouded remains of a man discovered in a tomb next to the Old City of Jerusalem, Israel, dated by radiocarbon methods to the first half of the 1st century.The oldest strains of leprosy known from Europe are from Great Chesterford in southeast England and dating back to AD 415–545. These findings suggest a different path for the spread of leprosy, meaning it may have originated in Western Eurasia. This study also indicates that there were more strains in Europe at the time than previously determined. Discovery and scientific progress Literary attestation of leprosy is unclear because of the ambiguity of many early sources, including the Indian Atharvaveda and Kausika Sutra, the Egyptian Ebers papyrus, and the Hebrew Bibles various sections regarding signs of impurity (tzaraath). Clearly leprotic symptoms are attested in the Indian doctor Sushrutas Compendium, originally dating to c. 600 BC but only surviving in emended texts no earlier than the 5th century. They were separately described by Hippocrates in 460 BC. However, Hansens disease probably did not exist in Greece or the Middle East before the Common Era. In 1846, Francis Adams produced The Seven Books of Paulus Aegineta which included a commentary on all medical and surgical knowledge and descriptions and remedies to do with leprosy from the Romans, Greeks, and Arabs.Leprosy did not exist in the Americas before colonization by modern Europeans nor did it exist in Polynesia until the middle of the 19th century. The causative agent of leprosy, M. leprae, was discovered by G. H. Armauer Hansen in Norway in 1873, making it the first bacterium to be identified as causing disease in humans. Treatment The first effective treatment (promin) became available in the 1940s. In the 1950s, dapsone was introduced. The search for further effective antileprosy drugs led to the use of clofazimine and rifampicin in the 1960s and 1970s. Later, Indian scientist Shantaram Yawalkar and his colleagues formulated a combined therapy using rifampicin and dapsone, intended to mitigate bacterial resistance. Multi-drug therapy (MDT) combining all three drugs was first recommended by the WHO in 1981. These three antileprosy drugs are still used in the standard MDT regimens.Leprosy was once believed to be highly contagious and was treated with mercury, as was syphilis, which was first described in 1530. Many early cases thought to be leprosy could actually have been syphilis.Resistance has developed to initial treatment. Until the introduction of MDT in the early 1980s, leprosy could not be diagnosed and treated successfully within the community.Japan still has sanatoriums (although Japans sanatoriums no longer have active leprosy cases, nor are survivors held in them by law).The importance of the nasal mucosa in the transmission of M leprae was recognized as early as 1898 by Schäffer, in particular, that of the ulcerated mucosa. The mechanism of plantar ulceration in leprosy and its treatment was first described by Dr Ernest W Price. Etymology The word "leprosy" comes from the Greek word "λέπος (lépos) – skin" and "λεπερός (leperós) – scaly man". Society and culture India British India enacted the Leprosy Act of 1898 which institutionalized those affected and segregated them by sex to prevent reproduction. The act was difficult to enforce but was repealed in 1983 only after multidrug therapy had become widely available. In 1983, the National Leprosy Elimination Programme, previously the National Leprosy Control Programme, changed its methods from surveillance to the treatment of people with leprosy. India still accounts for over half of the global disease burden. According to WHO, new cases in India during 2019 diminished to 114,451 patients (57% of the worlds total new cases). Until 2019, one could justify a petition for divorce with the spouses diagnosis of leprosy. Treatment cost Between 1995 and 1999, the WHO, with the aid of the Nippon Foundation, supplied all endemic countries with free multidrug therapy in blister packs, channeled through ministries of health. This free provision was extended in 2000 and again in 2005, 2010 and 2015 with donations by the multidrug therapy manufacturer Novartis through the WHO. In the latest agreement signed between the company and the WHO in October 2015, the provision of free multidrug therapy by the WHO to all endemic countries will run until the end of 2025. At the national level, nongovernment organizations affiliated with the national program will continue to be provided with an appropriate free supply of multidrug therapy by the WHO. Historical texts Written accounts of leprosy date back thousands of years. Various skin diseases translated as leprosy appear in the ancient Indian text, the Atharava Veda, by 600 BC. Another Indian text, the Manusmriti (200 BC), prohibited contact with those infected with the disease and made marriage to a person infected with leprosy punishable.The Hebraic root tsara or tsaraath (צָרַע, – tsaw-rah – to be struck with leprosy, to be leprous) and the Greek (λεπρός–lepros), are of broader classification than the more narrow use of the term related to Hansens Disease. Any progressive skin disease (a whitening or splotchy bleaching of the skin, raised manifestations of scales, scabs, infections, rashes, etc....), as well as generalized molds and surface discoloration of any clothing, leather, or discoloration on walls or surfaces throughout homes all, came under the "law of leprosy" (Leviticus 14:54–57). Ancient sources such as the Talmud (Sifra 63) make clear that tzaraath refers to various types of lesions or stains associated with ritual impurity and occurring on cloth, leather, or houses, as well as skin. Traditional Judaism and Jewish rabbinical authorities, both historical and modern, emphasize that the tsaraath of Leviticus is a spiritual ailment with no direct relationship to Hansens disease or physical contagions. The relation of tsaraath to "leprosy" comes from translations of Hebrew Biblical texts into Greek and ensuing misconceptions.All three Synoptic Gospels of the New Testament describe instances of Jesus healing people with leprosy (Matthew 8:1–4, Mark 1:40–45, and Luke 5:12–16). The Bibles description of leprosy is congruous (if lacking detail) with the symptoms of modern leprosy, but the relationship between this disease, tzaraath, and Hansens disease has been disputed. The biblical perception that people with leprosy were unclean can be found in a passage from Leviticus 13: 44–46. While this text defines the leper as impure, it did not explicitly make a moral judgement on those with leprosy. Some Early Christians believed that those affected by leprosy were being punished by God for sinful behavior. Moral associations have persisted throughout history. Pope Gregory the Great (540–604) and Isidor of Seville (560–636) considered people with the disease to be heretics. Middle Ages It is likely that a rise in leprosy in Western Europe occurred in the Middle Ages based on the increased number of hospitals created to treat people with leprosy in the 12th and 13th centuries. France alone had nearly 2,000 leprosariums during this period.The social perception of leprosy in medieval communities was generally one of fear, and people infected with the disease were thought to be unclean, untrustworthy, and morally corrupt. Segregation from mainstream society was common, and people with leprosy were often required to wear clothing that identified them as such or carry a bell announcing their presence. The third Lateran Council of 1179 and a 1346 edict by King Edward expelled lepers from city limits. Because of the moral stigma of the disease, methods of treatment were both physical and spiritual, and leprosariums were established under the purview of the Roman Catholic Church. 19th century Norway Norway was the location of a progressive stance on leprosy tracking and treatment and played an influential role in European understanding of the disease. In 1832, Dr. JJ Hjort conducted the first leprosy survey, thus establishing a basis for epidemiological surveys. Subsequent surveys resulted in the establishment of a national leprosy registry to study the causes of leprosy and for tracking the rate of infection. Early leprosy research throughout Europe was conducted by Norwegian scientists Daniel Cornelius Danielssen and Carl Wilhelm Boeck. Their work resulted in the establishment of the National Leprosy Research and Treatment Center. Danielssen and Boeck believed the cause of leprosy transmission was hereditary. This stance was influential in advocating for the isolation of those infected by sex to prevent reproduction. Colonialism and imperialism Though leprosy in Europe was again on the decline by the 1860s, Western countries embraced isolation treatment out of fear of the spread of disease from developing countries, minimal understanding of bacteriology, lack of diagnostic ability or knowledge of how contagious the disease was, and missionary activity. Growing imperialism and pressures of the industrial revolution resulted in a Western presence in countries where leprosy was endemic, namely the British presence in India. Isolation treatment methods were observed by Surgeon-Mayor Henry Vandyke Carter of the British Colony in India while visiting Norway, and these methods were applied in India with the financial and logistical assistance of religious missionaries. Colonial and religious influence and associated stigma continued to be a major factor in the treatment and public perception of leprosy in endemic developing countries until the mid-twentieth century. 20th century United States The National Leprosarium at Carville, Louisiana, known in 1955 as the Louisiana Leper Home, was the only leprosy hospital on the mainland United States. Leprosy patients from all over the United States were sent to Carville in order to be kept in isolation away from the public, as not much about leprosy transmission was known at the time and stigma against those with leprosy was high (see Leprosy stigma). The Carville leprosarium was known for its innovations in reconstructive surgery for those with leprosy. In 1941, 22 patients at Carville underwent trials for a new drug called promin. The results were described as miraculous, and soon after the success of promin came dapsone, a medicine even more effective in the fight against leprosy. Stigma Despite now effective treatment and education efforts, leprosy stigma continues to be problematic in developing countries where the disease is common. Leprosy is most common amongst impoverished populations where social stigma is likely to be compounded by poverty. Fears of ostracism, loss of employment, or expulsion from family and society may contribute to a delayed diagnosis and treatment.Folk beliefs, lack of education, and religious connotations of the disease continue to influence social perceptions of those affected in many parts of the world. In Brazil, for example, folklore holds that leprosy is a disease transmitted by dogs, or that it is associated with sexual promiscuity, or that it is a punishment for sins or moral transgressions (distinct from other diseases and misfortunes, which are in general thought of as being according to the will of God). Socioeconomic factors also have a direct impact. Lower-class domestic workers who are often employed by those in a higher socioeconomic class may find their employment in jeopardy as physical manifestations of the disease become apparent. Skin discoloration and darker pigmentation resulting from the disease also have social repercussions.In extreme cases in northern India, leprosy is equated with an "untouchable" status that "often persists long after individuals with leprosy have been cured of the disease, creating lifelong prospects of divorce, eviction, loss of employment, and ostracism from family and social networks." Public policy A goal of the World Health Organization is to "eliminate leprosy" and in 2016 the organization launched "Global Leprosy Strategy 2016–2020: Accelerating towards a leprosy-free world". Elimination of leprosy is defined as "reducing the proportion of leprosy patients in the community to very low levels, specifically to below one case per 10 000 population". Diagnosis and treatment with multidrug therapy are effective, and a 45% decline in disease burden has occurred since multidrug therapy has become more widely available. The organization emphasizes the importance of fully integrating leprosy treatment into public health services, effective diagnosis and treatment, and access to information. The approach includes supporting an increase in health care professionals who understand the disease, and a coordinated and renewed political commitment that includes coordination between countries and improvements in the methodology for collecting and analysing data.Interventions in the "Global Leprosy Strategy 2016–2020: Accelerating towards a leprosy-free world": Early detection of cases focusing on children to reduce transmission and disabilities Enhanced healthcare services and improved access for people who may be marginalized For countries where leprosy is endemic, further interventions include an improved screening of close contacts, improved treatment regimens, and interventions to reduce stigma and discrimination against people who have leprosy. Community-based interventions In some instances in India, community-based rehabilitation is embraced by local governments and NGOs alike. Often, the identity cultivated by a community environment is preferable to reintegration, and models of self-management and collective agency independent of NGOs and government support have been desirable and successful. Notable cases Josephine Cafrine of Seychelles had leprosy from the age of 12 and kept a personal journal that documented her struggles and suffering. It was published as an autobiography in 1923. Saint Damien De Veuster, a Roman Catholic priest from Belgium, himself eventually contracting leprosy, ministered to lepers who had been placed under a government-sanctioned medical quarantine on the island of Molokaʻi in the Kingdom of Hawaiʻi. Baldwin IV of Jerusalem was a Christian king of Latin Jerusalem who had leprosy. Josefina Guerrero was a Filipino spy during World War II, who used the Japanese fear of her leprosy to listen to their battle plans and deliver the information to the American forces under Douglas MacArthur. King Henry IV of England (reigned 1399 to 1413) possibly had leprosy. Vietnamese poet Hàn Mặc Tử Ōtani Yoshitsugu, a Japanese daimyō Leprosy in the media English author Graham Greenes novel A Burnt-Out Case is set in a leper colony in Belgian Congo. The story is also predominantly about a disillusioned architect working with a doctor on devising new cure and amenities for mutilated victims of lepers; the title, too, refers to the condition of mutilation and disfigurement in the disease. Forugh Farrokhzad made a 22-minute documentary about a leprosy colony in Iran in 1962 titled The House Is Black. The film humanizes the people affected and opens by saying that "there is no shortage of ugliness in the world, but by closing our eyes on ugliness, we will intensify it." Molokai is a novel by Alan Brennert about a leper colony in Hawaii. This novel follows the story of a seven year old girl taken from her family and put on the small Hawaiian island of Molokais leper settlement. Even though this is a fiction novel it is based upon some very true and revealing incidents which occurred at this Leprosy settlement. The lead character in The Chronicles of Thomas Covenant by Stephen R. Donaldson suffers from leprosy. His condition seems to be cured by the magic of the fantasy land he finds himself in, but he resists believing in its reality, for example, by continuing to perform a regular visual surveillance of extremities as a safety check. Donaldson gained experience with the disease as a young man in India, where his father worked in a missionary for people with leprosy. Infection of animals Wild nine-banded armadillos (Dasypus novemcinctus) in south central United States often carry Mycobacterium leprae. This is believed to be because armadillos have a low body temperature. Leprosy lesions appear mainly in cooler body regions such as the skin and mucous membranes of the upper respiratory tract. Because of armadillos armor, skin lesions are hard to see. Abrasions around the eyes, nose and feet are the most common signs. Infected armadillos make up a large reservoir of M. leprae and may be a source of infection for some humans in the United States or other locations in the armadillos home range. In armadillo leprosy, lesions do not persist at the site of entry in animals, M. leprae multiply in macrophages at the site of inoculation and lymph nodes.A recent outbreak in chimpanzees in West Africa is showing that the bacteria can infect another species and also possibly have additional rodent hosts.Recent studies have demonstrated that the disease is endemic in the UK red Eurasian squirrel population, with Mycobacterium leprae and Mycobacterium lepromatosis appearing in different populations. The Mycobacteria leprae strain discovered on Brownsea Island is equated to one thought to have died out in the human population in mediaeval times. Despite this, and speculation regarding past transmission through trade in squirrel furs, there does not seem to be a high risk of squirrel to human transmission from the wild population: although leprosy continues to be diagnosed in immigrants to the UK, the last known human case of leprosy arising in the UK was recorded over 200 years ago. See also Leper Colony Alice Ball Maurice Born Kate Marsden References Further reading Pam Fessler (2020). Carvilles Cure: Leprosy, Stigma, and the Fight for Justice. Liveright. ISBN 978-1631495038. External links Leprosy at Curlie Links and resources to information about leprosy selected by the World Health Organization

Hey Aarogya, explain a situation where Liver abscess occurs

Liver abscess

A liver abscess is a mass filled with pus inside the liver. Common causes are abdominal conditions such as appendicitis or diverticulitis due to haematogenous spread through the portal vein. It can also develop as a complication of a liver injury. Causes Risk factors for developing liver abscess can be due to infection, post-procedural infection and metastasis such as primary liver tumours, liver metastasis, biliary procedures, biliary injuries, biliary tract disease, appendicitis, and diverticulitis.Major bacterial causes of liver abscess include the following: Streptococcus species (including Enterococcus) Escherichia species Staphylococcus species Klebsiella species (Higher rates in the Far East) Anaerobes (including Bacteroides species) Pseudomonas species Proteus species Entamoeba HistolyticaHowever, as noted above, many cases are polymicrobial. Diagnosis Types There are several major forms of liver abscess, classified by cause: Pyogenic liver abscess, which is most often polymicrobial, accounts for 80% of hepatic abscess cases in the United States. Amoebic liver abscess due to Entamoeba histolytica accounts for 10% of cases. The incidence is much higher in developing countries. Fungal abscess, most often due to Candida species, accounts for less than 10% of cases. Iatrogenic abscess, caused by medical interventions Management Antibiotics: IV metronidazole and third generation cephalosporin/quinolones, β-lactam antibiotics, and aminoglycosides are effective. Prognosis The prognosis has improved for liver abscesses. The mortality rate in-hospital is about 2.5-19%. The elderly, ICU admissions, shock, cancer, fungal infections, cirrhosis, chronic kidney disease, acute respiratory failure, severe disease, or disease of biliary origin have a worse prognosis. References External links Liver Abscess CT Images CTCases Liver Abscess CT Scan.

Give me a short description about Liver fluke , Aarogya

Liver fluke

Liver fluke is a collective name of a polyphyletic group of parasitic trematodes under the phylum Platyhelminthes. They are principally parasites of the liver of various mammals, including humans. Capable of moving along the blood circulation, they can occur also in bile ducts, gallbladder, and liver parenchyma. In these organs, they produce pathological lesions leading to parasitic diseases. They have complex life cycles requiring two or three different hosts, with free-living larval stages in water. Biology The body of liver flukes is leaf-like and flattened. The body is covered with a tegument. They are hermaphrodites having complete sets of both male and female reproductive systems. They have simple digestive systems and primarily feed on blood. The anterior end is the oral sucker opening into the mouth. Inside, mouth lead to a small pharynx which is followed by an extended intestine that runs through the entire length of the body. The intestine is heavily branched and anus is absent. Instead, the intestine runs along an excretory canal that opens at the posterior end. Adult flukes produce eggs that are passed out through the excretory pore. The eggs infect different species of snails (as intermediate hosts) in which they grow into larvae. The larvae are released into the environment from where the definitive hosts (humans and other mammals) get the infection. In some species, another intermediate host is required, generally a cyprinid fish. In this case, the definitive hosts are infected from eating infected fish. Hence, they are food-borne parasites. Pathogenicity Liver fluke infections cause serious medical and veterinary diseases. Fasciolosis of sheep, goats and cattle, is the major cause of economic losses in dairy and meat industry. Fasciolosis of humans produces clinical symptoms such as fever, nausea, swollen liver, extreme abdominal pain, jaundice and anemia.Clonorchiasis and opisthorchiasis (due to Opisthorchis viverrini) are particularly dangerous. They can survive for several decades in humans causing chronic inflammation of the bile ducts, epithelial hyperplasia, periductal fibrosis and bile duct dilatation. In many infections these symptoms cause further complications such as stone formation, recurrent pyogenic cholangitis and cancer (cholangiocarcinoma). Opisthorchiasis is particularly the leading cause of cholangiocarcinoma in Thailand and Laos. Both clonorchiasis and opisthorchiasis are classified as Group 1 human biological agents (carcinogens) by International Agency of Research on Cancer (IARC). Species Species of liver fluke include: Clonorchis sinensis (the Chinese liver fluke, or the Oriental liver fluke) Dicrocoelium dendriticum (the lancet liver fluke) Dicrocoelium hospes Fasciola hepatica (the sheep liver fluke) Fascioloides magna (the giant liver fluke) Fasciola gigantica Fasciola jacksoni Metorchis conjunctus Metorchis albidus Protofasciola robusta Parafasciolopsis fasciomorphae Opisthorchis viverrini (Southeast Asian liver fluke) Opisthorchis felineus (Cat liver fluke) Opisthorchis guayaquilensis See also The Integrated Opisthorchiasis Control Program == References ==

Aarogya , Do you know what is Lymphogranuloma venereum,

Lymphogranuloma venereum

Lymphogranuloma venereum (LGV; also known as climatic bubo, Durand–Nicolas–Favre disease, poradenitis inguinale, lymphogranuloma inguinale, and strumous bubo) is a sexually transmitted disease caused by the invasive serovars L1, L2, L2a, L2b, or L3 of Chlamydia trachomatis.LGV is primarily an infection of lymphatics and lymph nodes. Chlamydia trachomatis is the bacterium responsible for LGV. It gains entrance through breaks in the skin, or it can cross the epithelial cell layer of mucous membranes. The organism travels from the site of inoculation down the lymphatic channels to multiply within mononuclear phagocytes of the lymph nodes it passes. In developed nations, it was considered rare before 2003. However, a recent outbreak in the Netherlands among gay men has led to an increase of LGV in Europe and the United States.LGV was first described by Wallace in 1833 and again by Durand, Nicolas, and Favre in 1913. Since the 2004 Dutch outbreak many additional cases have been reported, leading to greater surveillance. Soon after the initial Dutch report, national and international health authorities launched warning initiatives and multiple LGV cases were identified in several more European countries (Belgium, France, the UK, Germany, Sweden, Italy and Switzerland) and the US and Canada. All cases reported in Amsterdam and France and a considerable percentage of LGV infections in the UK and Germany were caused by a newly discovered Chlamydia variant, L2b, a.k.a. the Amsterdam variant. The L2b variant could be traced back and was isolated from anal swabs of men who have sex with men (MSM) who visited the STI city clinic of San Francisco in 1981. This finding suggests that the recent LGV outbreak among MSM in industrialised countries is a slowly evolving epidemic. The L2b serovar has also been identified in Australia. Signs and symptoms The clinical manifestation of LGV depends on the site of entry of the infectious organism (the sex contact site) and the stage of disease progression. Inoculation at the mucous lining of external sex organs (penis and vagina) can lead to the inguinal syndrome named after the formation of buboes or abscesses in the groin (inguinal) region where draining lymph nodes are located. These signs usually appear from 3 days to a month after exposure. The rectal syndrome (lymphogranuloma venereum proctitis, or LGVP) arises if the infection takes place via the rectal mucosa (through anal sex) and is mainly characterized by proctocolitis or proctitis symptoms. The pharyngeal syndrome is rare. It starts after infection of pharyngeal tissue, and buboes in the neck region can occur. Primary stage LGV may begin as a self-limited painless genital ulcer that occurs at the contact site 3–12 days after infection. Women rarely notice a primary infection because the initial ulceration where the organism penetrates the mucosal layer is often located out of sight, in the vaginal wall. In men fewer than one-third of those infected notice the first signs of LGV. This primary stage heals in a few days. Erythema nodosum occurs in 10% of cases. Secondary stage The secondary stage most often occurs 10–30 days later, but can present up to six months later. The infection spreads to the lymph nodes through lymphatic drainage pathways. The most frequent presenting clinical manifestation of LGV among males whose primary exposure was genital is unilateral (in two-thirds of cases) lymphadenitis and lymphangitis, often with tender inguinal and/or femoral lymphadenopathy because of the drainage pathway for their likely infected areas. Lymphangitis of the dorsal penis may also occur and resembles a string or cord. If the route was anal sex, the infected person may experience lymphadenitis and lymphangitis noted above. They may instead develop proctitis, inflammation limited to the rectum (the distal 10–12 cm) that may be associated with anorectal pain, tenesmus, and rectal discharge, or proctocolitis, inflammation of the colonic mucosa extending to 12 cm above the anus and associated with symptoms of proctitis plus diarrhea or abdominal cramps.In addition, symptoms may include inflammatory involvement of the perirectal or perianal lymphatic tissues. In females, cervicitis, perimetritis, or salpingitis may occur as well as lymphangitis and lymphadenitis in deeper nodes. Because of lymphatic drainage pathways, some patients develop an abdominal mass which seldom suppurates, and 20–30% develop inguinal lymphadenopathy. Systemic signs which can appear include fever, decreased appetite, and malaise. Diagnosis is more difficult in women and men who have sex with men (MSM) who may not have the inguinal symptoms.Over the course of the disease, lymph nodes enlarge, as may occur in any infection of the same areas as well. Enlarged nodes are called buboes. Buboes are commonly painful. Nodes commonly become inflamed, thinning and fixation of the overlying skin. These changes may progress to necrosis, fluctuant and suppurative lymph nodes, abscesses, fistulas, strictures, and sinus tracts. During the infection and when it subsides and healing takes place, fibrosis may occur. This can result in varying degrees of lymphatic obstruction, chronic edema, and strictures. These late stages characterised by fibrosis and edema are also known as the third stage of LGV, and are mainly permanent. Diagnosis The diagnosis usually is made serologically (through complement fixation) and by exclusion of other causes of inguinal lymphadenopathy or genital ulcers. Serologic testing has a sensitivity of 80% after two weeks. Serologic testing may not be specific for serotype (has some cross reactivity with other chlamydia species) and can suggest LGV from other forms because of their difference in dilution, 1:64 more likely to be LGV and lower than 1:16 is likely to be other chlamydia forms (emedicine).For identification of serotypes, culture is often used. Culture is difficult. Requiring a special medium, cycloheximide-treated McCoy or HeLa cells, and yields are still only 30-50%. DFA, or direct fluorescent antibody test, PCR of likely infected areas and pus, are also sometimes used. DFA test for the L-type serovar of C. trachomatis is the most sensitive and specific test, but is not readily available.If polymerase chain reaction (PCR) tests on infected material are positive, subsequent restriction endonuclease pattern analysis of the amplified outer membrane protein A gene can be done to determine the genotype.Recently a fast realtime PCR (TaqMan analysis) has been developed to diagnose LGV. With this method an accurate diagnosis is feasible within a day. It has been noted that one type of testing may not be thorough enough. Treatment Treatment involves antibiotics and may involve drainage of the buboes or abscesses by needle aspiration or incision. Further supportive measure may need to be taken: dilatation of the rectal stricture, repair of rectovaginal fistulae, or colostomy for rectal obstruction.Common antibiotic treatments include tetracycline (doxycycline) (all tetracyclines, including doxycycline, are contraindicated during pregnancy and in children due to effects on bone development and tooth discoloration), and erythromycin. Azithromycin is also a drug of choice in LGV. Further recommendations As with all STIs, sex partners of patients who have LGV should be examined and tested for urethral or cervical chlamydial infection. After a positive culture for chlamydia, clinical suspicion should be confirmed with testing to distinguish serotype. Antibiotic treatment should be started if they had sexual contact with the patient during the 30 days preceding onset of symptoms in the patient. Patients with a sexually transmitted disease should be tested for other STDs due to high rates of comorbid infections. Antibiotics are not without risks and prophylactic broad antibiotic coverage is not recommended. Prognosis Prognosis is highly variable. Spontaneous remission is common. Complete cure can be obtained with proper antibiotic treatments to kill the causative bacteria, such as tetracycline, doxycycline, or erythromycin. Prognosis is more favorable with early treatment. Bacterial superinfections may complicate course. Death can occur from bowel obstruction or perforation, and follicular conjunctivitis due to autoinoculation of infectious discharge can occur. Long-term complications Genital elephantiasis or esthiomene, which is the dramatic end-result of lymphatic obstruction, which may occur because of the strictures themselves, or fistulas. This is usually seen in females, may ulcerate and often occurs 1–20 years after primary infection. Fistulas of, but not limited to, the penis, urethra, vagina, uterus, or rectum. Also, surrounding edema often occurs. Rectal or other strictures and scarring. Systemic spread may occur, possible results are arthritis, pneumonitis, hepatitis, or perihepatitis. Notes References External links Sexually transmitted infections (BMJ publishing)

Hey Aarogya!, what is Lysosomal acid lipase deficiency

Lysosomal acid lipase deficiency

Lysosomal acid lipase deficiency (LAL deficiency or LAL-D) is an autosomal recessive inborn error of metabolism that results in the body not producing enough active lysosomal acid lipase (LAL) enzyme. This enzyme plays an important role in breaking down fatty material (cholesteryl esters and triglycerides) in the body. Infants, children and adults that have LAL deficiency experience a range of serious health problems. The lack of the LAL enzyme can lead to a build-up of fatty material in a number of body organs including the liver, spleen, gut, in the wall of blood vessels and other important organs. Very low levels of the LAL enzyme lead to LAL deficiency. LAL deficiency typically affects infants in the first year of life. The accumulation of fat in the walls of the gut in early onset disease leads to serious digestive problems including malabsorption, a condition in which the gut fails to absorb nutrients and calories from food. Because of these digestive complications, affected infants usually fail to grow and gain weight at the expected rate for their age (failure to thrive). As the disease progresses, it can cause life-threatening liver dysfunction or liver failure.Until 2015, there was no treatment, and very few infants with LAL-D survived beyond the first year of life. In 2015, an enzyme replacement therapy, sebelipase alfa, was approved in the US and EU. The therapy was additionally approved in Japan in 2016. Symptoms and signs Infants may present with feeding difficulties with frequent vomiting, diarrhea, swelling of the abdomen, and failure to gain weight or sometimes weight loss.As the disease progresses in infants, increasing fat accumulation in the liver leads to other complications including yellowing of the skin and whites of the eyes (jaundice), and a persistent low-grade fever. An ultrasound examination shows accumulation of chalky material (calcification) in the adrenal gland in about half of infants with LAL-D. Complications of LAL-D progress over time, eventually leading to life-threatening problems such as extremely low levels of circulating red blood cells (severe anemia), liver dysfunction or failure, and physical wasting (cachexia).People who are older children or adults generally present with a wide range of signs and symptoms that overlap with other disorders. They may have diarrhoea, stomach pain, vomiting, or poor growth, a sign of malabsorption. They may have signs of bile duct problems, like itchiness, jaundice, pale stool, or dark urine. Their feces may be excessively greasy. They often have an enlarged liver, liver disease, and may have yellowish deposits of fat underneath the skin, usually around their eyelids. The disease is often undiagnosed in adults. The person may have a history of premature cardiac disease or premature stroke. Cause Lysosomal acid lipase deficiency is a genetic disease that is autosomal recessive. It is an inborn error of metabolism that causes a lysosomal storage disease. The condition is caused by a mutation of the LIPA gene, which is responsible for the gene coding of the lysosomal lipase protein (also called lysosomal acid lipase or LAL), which results in a loss of the proteins normal function. When LAL functions normally, it breaks down cholesteryl esters and triglycerides in low density lipoprotein particles into free cholesterol and free fatty acids that the body can reuse; when LAL doesnt function, cholesteryl esters and triglycerides build up in the liver, spleen and other organs. The accumulation of fat in the walls of the gut and other organs in leads to serious digestive problems including malabsorption, a condition in which the gut fails to absorb nutrients and calories from food, persistent and often forceful vomiting, frequent diarrhea, foul-smelling and fatty stools (steatorrhea), and failure to grow.Lysosomal acid lipase deficiencies occur when a person has defects (mutations) in both copies of the LIPA gene. Each parent of a person with LAL deficiency carries one copy of the defective LIPA gene. With every pregnancy, parents with a son or daughter affected by LAL deficiency have a 1 in 4 (25%) chance of having another affected child. A person born with defects in both LIPA genes is not able to produce adequate amounts of the LAL enzyme. Diagnosis Blood tests may show anaemia and their lipid profiles are generally similar to people with more common familial hypercholesterolemia, including elevated total cholesterol, elevated low-density lipoprotein cholesterol, decreased high-density lipoprotein cholesterol and elevated serum transaminases.Liver biopsy findings will generally show a bright yellow-orange color, enlarged, lipid-laden hepatocytes and Kupffer cells, microvesicular and macrovesicular steatosis, fibrosis, and cirrhosis. The only definitive tests are genetic, which may be conducted in any number of ways. Screening Because LAL deficiency is inherited, each sibling of an affected individual has a 25% chance of having pathological mutations in LAL genes from both their mother and their father, a 50% chance of having a pathological mutation in only one gene, and a 25% chance of having no pathological mutations. Genetic testing for family members and genetic prenatal diagnosis of pregnancies for women who are at increased risk are possible if family members carrying pathological mutations have been identified. Management LAL deficiency can be treated with sebelipase alfa is a recombinant form of LAL that was approved in 2015 in the US and EU. The disease of LAL affects < 0.2 in 10,000 people in the EU. According to an estimate by a Barclays analyst, the drug will be priced at about US$375,000 per year.It is administered once a week via intraveneous infusion in people with rapidly progressing disease in the first six months of life. In people with less aggressive disease, it is given every other week.Before the drug was approved, treatment of infants was mainly focused on reducing specific complications and was provided in specialized centers. Specific interventions for infants included changing from breast or normal bottle formula to a specialized low fat formula, intravenous feeding, antibiotics for infections, and steroid replacement therapy because of concerns about adrenal function.Statins were used in people with LAL-D prior to the approval of sebelipase alfa; they helped control cholesterol but did not appear to slow liver damage; liver transplantation was necessary in most patients. Prognosis Infants with LAL deficiencies typically show signs of disease in the first weeks of life and if untreated, die within 6–12 months due to multi-organ failure. Older children or adults with LAL-D may remain undiagnosed or be misdiagnosed until they die early from a heart attack or stroke or die suddenly of liver failure. The first enzyme replacement therapy was approved in 2015. In those clinical trials nine infants were followed for one year; 6 of them lived beyond one year. Older children and adults were followed for 36 weeks. Epidemiology Depending on ethnicity and geography, prevalence has been estimated to be between 1 in 40,000 and 1 in 300,000; based on these estimates the disease may be underdiagnosed. Jewish infants of Iraqi or Iranian origin appear to be most at risk based on a study of a community in Los Angeles in which there was a prevalence of 1 in 4200. History In 1956, Moshe Wolman, along with two other doctors, published the first case study of a LAL deficiency in a child born to closely related Persian Jews; 12 years later a case study on an older boy was published, which turned out to be the first case study of LAL-D.LAL-D was historically referred to as two separate disorders: Wolman disease, presenting in infant patients Cholesteryl Ester Storage Disease, presenting in pediatric and adult patientsAround 2010 both presentations have come to be known as LAL-D, as both are due to a deficiency of the LAL enzyme.In 2015 an enzyme replacement therapy, sebelipase alfa, was approved in the US and EU for the treatment of human LAL enzyme deficiency. Before the approval of that drug, as of 2009 the two oldest survivors of LAL-D in the world were then aged 4 and 11; both of them had been treated with hematopoietic stem cell treatment. Research directions Some children with LAL-D have had an experimental therapy called hematopoietic stem cell transplantation (HSCT), also known as bone marrow transplant, to try to prevent the disease from getting worse. Data are sparse but there is a known high risk of serious complications including death, graft-versus-host disease. References External links National Organization for Rare Disorders (NORD) Article - LYSOSOMAL ACID LIPASE/NIH.gov Article - LYSOSOMAL ACID LIPASE DEFICIENCY/NIH.gov Lipid Storage Diseases Fact Sheet at ninds.nih.gov

Would you describe Maceration, to me Aarogya

Maceration

Maceration may refer to: Maceration (food), in food preparation Maceration (wine), a step in wine-making Carbonic maceration, a wine-making technique Maceration (sewage), in sewage treatment Maceration (bone), a method of preparing bones Acid maceration, the use of an acid to extract micro-fossils from rock Maceration, in chemistry, the preparation of an extract by solvent extraction Maceration, in biology, the mechanical breakdown of ingested food into chyme Skin maceration, in dermatology, the softening and whitening of skin that is kept constantly wet Maceration, in poultry farming, a method of chick culling

Please give me a short description about Malaria , Aarogya

Malaria

Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin ten to fifteen days after being bitten by an infected mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria.Malaria is caused by single-celled microorganisms of the Plasmodium group. It is spread exclusively through bites of infected Anopheles mosquitoes. The mosquito bite introduces the parasites from the mosquitos saliva into a persons blood. The parasites travel to the liver where they mature and reproduce. Five species of Plasmodium can infect and be spread by humans. Most deaths are caused by P. falciparum, whereas P. vivax, P. ovale, and P. malariae generally cause a milder form of malaria. The species P. knowlesi rarely causes disease in humans. Malaria is typically diagnosed by the microscopic examination of blood using blood films, or with antigen-based rapid diagnostic tests. Methods that use the polymerase chain reaction to detect the parasites DNA have been developed, but are not widely used in areas where malaria is common due to their cost and complexity.The risk of disease can be reduced by preventing mosquito bites through the use of mosquito nets and insect repellents or with mosquito-control measures such as spraying insecticides and draining standing water. Several medications are available to prevent malaria for travellers in areas where the disease is common. Occasional doses of the combination medication sulfadoxine/pyrimethamine are recommended in infants and after the first trimester of pregnancy in areas with high rates of malaria. As of 2020, there is one vaccine which has been shown to reduce the risk of malaria by about 40% in children in Africa. A pre-print study of another vaccine has shown 77% vaccine efficacy, but this study has not yet passed peer review. Efforts to develop more effective vaccines are ongoing. The recommended treatment for malaria is a combination of antimalarial medications that includes artemisinin. The second medication may be either mefloquine, lumefantrine, or sulfadoxine/pyrimethamine. Quinine, along with doxycycline, may be used if artemisinin is not available. It is recommended that in areas where the disease is common, malaria is confirmed if possible before treatment is started due to concerns of increasing drug resistance. Resistance among the parasites has developed to several antimalarial medications; for example, chloroquine-resistant P. falciparum has spread to most malarial areas, and resistance to artemisinin has become a problem in some parts of Southeast Asia.The disease is widespread in the tropical and subtropical regions that exist in a broad band around the equator. This includes much of sub-Saharan Africa, Asia, and Latin America. In 2020 there were 241 million cases of malaria worldwide resulting in an estimated 627,000 deaths. Approximately 95% of the cases and deaths occurred in sub-Saharan Africa. Rates of disease have decreased from 2010 to 2014 but increased from 2015 to 2020. Malaria is commonly associated with poverty and has a significant negative effect on economic development. In Africa, it is estimated to result in losses of US$12 billion a year due to increased healthcare costs, lost ability to work, and adverse effects on tourism. Signs and symptoms Adults with malaria tend to experience chills and fever – classically in periodic intense bouts lasting around six hours, followed by a period of sweating and fever relief – as well as headache, fatigue, abdominal discomfort, and muscle pain. Children tend to have more general symptoms: fever, cough, vomiting, and diarrhea.Initial manifestations of the disease—common to all malaria species—are similar to flu-like symptoms, and can resemble other conditions such as sepsis, gastroenteritis, and viral diseases. The presentation may include headache, fever, shivering, joint pain, vomiting, hemolytic anemia, jaundice, hemoglobin in the urine, retinal damage, and convulsions.The classic symptom of malaria is paroxysm—a cyclical occurrence of sudden coldness followed by shivering and then fever and sweating, occurring every two days (tertian fever) in P. vivax and P. ovale infections, and every three days (quartan fever) for P. malariae. P. falciparum infection can cause recurrent fever every 36–48 hours, or a less pronounced and almost continuous fever.Symptoms typically begin 10–15 days after the initial mosquito bite, but can occur as late as several months after infection with some P. vivax strains. Travellers taking preventative malaria medications may develop symptoms once they stop taking the drugs.Severe malaria is usually caused by P. falciparum (often referred to as falciparum malaria). Symptoms of falciparum malaria arise 9–30 days after infection. Individuals with cerebral malaria frequently exhibit neurological symptoms, including abnormal posturing, nystagmus, conjugate gaze palsy (failure of the eyes to turn together in the same direction), opisthotonus, seizures, or coma. Complications Malaria has several serious complications. Among these is the development of respiratory distress, which occurs in up to 25% of adults and 40% of children with severe P. falciparum malaria. Possible causes include respiratory compensation of metabolic acidosis, noncardiogenic pulmonary oedema, concomitant pneumonia, and severe anaemia. Although rare in young children with severe malaria, acute respiratory distress syndrome occurs in 5–25% of adults and up to 29% of pregnant women. Coinfection of HIV with malaria increases mortality. Kidney failure is a feature of blackwater fever, where haemoglobin from lysed red blood cells leaks into the urine.Infection with P. falciparum may result in cerebral malaria, a form of severe malaria that involves encephalopathy. It is associated with retinal whitening, which may be a useful clinical sign in distinguishing malaria from other causes of fever. An enlarged spleen, enlarged liver or both of these, severe headache, low blood sugar, and haemoglobin in the urine with kidney failure may occur. Complications may include spontaneous bleeding, coagulopathy, and shock.Malaria in pregnant women is an important cause of stillbirths, infant mortality, miscarriage and low birth weight, particularly in P. falciparum infection, but also with P. vivax. Cause Malaria is caused by infection with parasites in the genus Plasmodium. In humans, malaria is caused by six Plasmodium species: P. falciparum, P. malariae, P. ovale curtisi, P. ovale wallikeri, P. vivax and P. knowlesi. Among those infected, P. falciparum is the most common species identified (~75%) followed by P. vivax (~20%). Although P. falciparum traditionally accounts for the majority of deaths, recent evidence suggests that P. vivax malaria is associated with potentially life-threatening conditions about as often as with a diagnosis of P. falciparum infection. P. vivax proportionally is more common outside Africa. There have been documented human infections with several species of Plasmodium from higher apes; however, except for P. knowlesi—a zoonotic species that causes malaria in macaques—these are mostly of limited public health importance. Parasites are typically introduced by the bite of an infected Anopheles mosquito. What these inoculated parasites, called "sporozoites", do in the skin and lymphatics, exactly, has yet to be accurately determined. However, a percentage of sporozoites follow the bloodstream to the liver, where they invade hepatocytes. They grow and divide in the liver for 2–10 days, with each infected hepatocyte eventually harboring up to 40,000 parasites. The infected hepatocytes break down, releasing this invasive form of Plasmodium cells, called "merozoites" into the bloodstream. In the blood, the merozoites rapidly invade individual red blood cells, replicating over 24–72 hours to form 16–32 new merozoites. The infected red blood cell lyses, and the new merozoites infect new red blood cells, resulting in a cycle that continuously amplifies the number of parasites in an infected person. However, most of the P. vivax replicating merozoite biomass is now (since 2021) known to be hidden in the spleen and bone marrow (perhaps elsewhere too), thereby supporting the astute, long-standing (since 2011) but previously ignored theory that non-circulating merozoites are the source many P. vivax malarial recurrences (see “Recurrent malaria” section below). Over rounds of this red blood cell infection cycle in the bloodstream and elsewhere, a small portion of parasites do not replicate, but instead develop into early sexual stage parasites called male and female "gametocytes". These gametocytes develop in the bone marrow for 11 days, then return to the blood circulation to await uptake by the bite of another mosquito. Once inside a mosquito, the gametocytes undergo sexual reproduction, and eventually form daughter sporozoites that migrate to the mosquitos salivary glands to be injected into a new host when the mosquito bites.The liver infection causes no symptoms; all symptoms of malaria result from the infection of red blood cells. Symptoms develop once there are more than around 100,000 parasites per milliliter of blood. Many of the symptoms associated with severe malaria are caused by the tendency of P. falciparum to bind to blood vessel walls, resulting in damage to the affected vessels and surrounding tissue. Parasites sequestered in the blood vessels of the lung contribute to respiratory failure. In the brain, they contribute to coma. In the placenta they contribute to low birthweight and preterm labor, and increase the risk of abortion and stillbirth. The destruction of red blood cells during infection often results in anemia, exacerbated by reduced production of new red blood cells during infection.Only female mosquitoes feed on blood; male mosquitoes feed on plant nectar and do not transmit the disease. Females of the mosquito genus Anopheles prefer to feed at night. They usually start searching for a meal at dusk, and continue through the night until they succeed. Malaria parasites can also be transmitted by blood transfusions, although this is rare. Recurrent malaria Symptoms of malaria can recur after varying symptom-free periods. Depending upon the cause, recurrence can be classified as recrudescence, relapse, or reinfection. Recrudescence is when symptoms return after a symptom-free period and the origin is parasites that survived in the blood as a result of inadequate or ineffective treatment. Relapse is when symptoms reappear after the parasites have been eliminated from the blood and the recurrence source is activated parasites which had persisted as dormant hypnozoites in liver cells. Relapse commonly occurs after 8–24 weeks and is often seen in P. vivax and P. ovale infections. However, relapse-like P. vivax recurrences are probably being over-attributed to hypnozoite activation. Some of them might have an extra-vascular or sequestered merozoite origin, making those recurrences recrudescences, not relapses. Newly recognised, non-hypnozoite, possible contributing sources to recurrent peripheral P. vivax parasitemia are erythrocytic forms in the bone marrow and spleen. P. vivax malaria cases in temperate areas often involve overwintering by hypnozoites, with relapses beginning the year after the mosquito bite. Reinfection means that the parasites responsible for the past infection were eliminated from the body but a new parasite(s) was introduced. Reinfection cannot readily be distinguished from relapse and recrudescence, although recurrence of infection within two weeks of treatment for the initial malarial manifestations is typically attributed to treatment failure. But doing this is not necessarily correct. People may develop some immunity when exposed to frequent infections. Pathophysiology Malaria infection develops via two phases: one that involves the liver (exoerythrocytic phase), and one that involves red blood cells, or erythrocytes (erythrocytic phase). When an infected mosquito pierces a persons skin to take a blood meal, sporozoites in the mosquitos saliva enter the bloodstream and migrate to the liver where they infect hepatocytes, multiplying asexually and asymptomatically for a period of 8–30 days.After a potential dormant period in the liver, these organisms differentiate to yield thousands of merozoites, which, following rupture of their host cells, escape into the blood and infect red blood cells to begin the erythrocytic stage of the life cycle. The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their host cells to invade fresh red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells.Some P. vivax sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead, produce hypnozoites that remain dormant for periods ranging from several months (7–10 months is typical) to several years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in P. vivax infections, although their existence in P. ovale is uncertain.The parasite is relatively protected from attack by the bodys immune system because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen. The blockage of the microvasculature causes symptoms such as those in placental malaria. Sequestered red blood cells can breach the blood–brain barrier and cause cerebral malaria. Genetic resistance According to a 2005 review, due to the high levels of mortality and morbidity caused by malaria—especially the P. falciparum species—it has placed the greatest selective pressure on the human genome in recent history. Several genetic factors provide some resistance to it including sickle cell trait, thalassaemia traits, glucose-6-phosphate dehydrogenase deficiency, and the absence of Duffy antigens on red blood cells.The impact of sickle cell trait on malaria immunity illustrates some evolutionary trade-offs that have occurred because of endemic malaria. Sickle cell trait causes a change in the haemoglobin molecule in the blood. Normally, red blood cells have a very flexible, biconcave shape that allows them to move through narrow capillaries; however, when the modified haemoglobin S molecules are exposed to low amounts of oxygen, or crowd together due to dehydration, they can stick together forming strands that cause the cell to distort into a curved sickle shape. In these strands, the molecule is not as effective in taking or releasing oxygen, and the cell is not flexible enough to circulate freely. In the early stages of malaria, the parasite can cause infected red cells to sickle, and so they are removed from circulation sooner. This reduces the frequency with which malaria parasites complete their life cycle in the cell. Individuals who are homozygous (with two copies of the abnormal haemoglobin beta allele) have sickle-cell anaemia, while those who are heterozygous (with one abnormal allele and one normal allele) experience resistance to malaria without severe anaemia. Although the shorter life expectancy for those with the homozygous condition would tend to disfavour the traits survival, the trait is preserved in malaria-prone regions because of the benefits provided by the heterozygous form. Liver dysfunction Liver dysfunction as a result of malaria is uncommon and usually only occurs in those with another liver condition such as viral hepatitis or chronic liver disease. The syndrome is sometimes called malarial hepatitis. While it has been considered a rare occurrence, malarial hepatopathy has seen an increase, particularly in Southeast Asia and India. Liver compromise in people with malaria correlates with a greater likelihood of complications and death. Diagnosis Due to the non-specific nature of malaria symptoms, diagnosis is typically suspected based on symptoms and travel history, then confirmed with a parasitological test. In areas where malaria is common, the World Health Organization (WHO) recommends clinicians suspect malaria in any person who reports having fevers, or who has a current temperature above 37.5 °C without any other obvious cause. Malaria should similarly be suspected in children with signs of anemia: pale palms or a laboratory test showing hemoglobin levels below 8 grams per deciliter of blood. In areas with little to no malaria, the WHO recommends only testing people with possible exposure to malaria (typically travel to a malaria-endemic area) and unexplained fever.Malaria is usually confirmed by the microscopic examination of blood films or by antigen-based rapid diagnostic tests (RDT). Microscopy – i.e. examining Giemsa-stained blood with a light microscope – is the gold standard for malaria diagnosis. Microscopists typically examine both a "thick film" of blood, allowing them to scan many blood cells in a short time, and a "thin film" of blood, allowing them to clearly see individual parasites and identify the infecting Plasmodium species. Under typical field laboratory conditions, a microscopist can detect parasites when there are at least 100 parasites per microliter of blood, which is around the lower range of symptomatic infection. Microscopic diagnosis is relatively resource intensive, requiring trained personnel, specific equipment, electricity, and a consistent supply of microscopy slides and stains.In places where microscopy is unavailable, malaria is diagnosed with RDTs, rapid antigen tests that detect parasite proteins in a fingerstick blood sample. A variety of RDTs are commercially available, targeting the parasite proteins histidine rich protein 2 (HRP2, detects P. falciparum only), lactate dehydrogenase, or aldolase. The HRP2 test is widely used in Africa, where P. falciparum predominates. However, since HRP2 persists in the blood for up to five weeks after an infection is treated, an HRP2 test sometimes cannot distinguish whether someone currently has malaria or previously had it. Additionally, some P. falciparum parasites in the Amazon region lack the HRP2 gene, complicating detection. RDTs are fast and easily deployed to places without full diagnostic laboratories. However they give considerably less information than microscopy, and sometimes vary in quality from producer to producer and lot to lot.Serological tests to detect antibodies against Plasmodium from the blood have been developed, but are not used for malaria diagnosis due to their relatively poor sensitivity and specificity. Highly sensitive nucleic acid amplification tests have been developed, but are not used clinically due to their relatively high cost, and poor specificity for active infections. Classification Malaria is classified into either "severe" or "uncomplicated" by the World Health Organization (WHO). It is deemed severe when any of the following criteria are present, otherwise it is considered uncomplicated. Decreased consciousness Significant weakness such that the person is unable to walk Inability to feed Two or more convulsions Low blood pressure (less than 70 mmHg in adults and 50 mmHg in children) Breathing problems Circulatory shock Kidney failure or haemoglobin in the urine Bleeding problems, or hemoglobin less than 50 g/L (5 g/dL) Pulmonary oedema Blood glucose less than 2.2 mmol/L (40 mg/dL) Acidosis or lactate levels of greater than 5 mmol/L A parasite level in the blood of greater than 100,000 per microlitre (μL) in low-intensity transmission areas, or 250,000 per μL in high-intensity transmission areasCerebral malaria is defined as a severe P. falciparum-malaria presenting with neurological symptoms, including coma (with a Glasgow coma scale less than 11, or a Blantyre coma scale less than 3), or with a coma that lasts longer than 30 minutes after a seizure. Prevention Methods used to prevent malaria include medications, mosquito elimination and the prevention of bites. As of 2020, there is one vaccine for malaria (known as RTS,S) which is licensed for use. The presence of malaria in an area requires a combination of high human population density, high anopheles mosquito population density and high rates of transmission from humans to mosquitoes and from mosquitoes to humans. If any of these is lowered sufficiently, the parasite eventually disappears from that area, as happened in North America, Europe, and parts of the Middle East. However, unless the parasite is eliminated from the whole world, it could re-establish if conditions revert to a combination that favors the parasites reproduction. Furthermore, the cost per person of eliminating anopheles mosquitoes rises with decreasing population density, making it economically unfeasible in some areas.Prevention of malaria may be more cost-effective than treatment of the disease in the long run, but the initial costs required are out of reach of many of the worlds poorest people. There is a wide difference in the costs of control (i.e. maintenance of low endemicity) and elimination programs between countries. For example, in China—whose government in 2010 announced a strategy to pursue malaria elimination in the Chinese provinces—the required investment is a small proportion of public expenditure on health. In contrast, a similar programme in Tanzania would cost an estimated one-fifth of the public health budget. In 2021, the World Health Organization confirms that China has eliminated malaria. In areas where malaria is common, children under five years old often have anaemia, which is sometimes due to malaria. Giving children with anaemia in these areas preventive antimalarial medication improves red blood cell levels slightly but does not affect the risk of death or need for hospitalisation. Mosquito control Vector control refers to methods used to decrease malaria by reducing the levels of transmission by mosquitoes. For individual protection, the most effective insect repellents are based on DEET or picaridin. However, there is insufficient evidence that mosquito repellents can prevent malaria infection. Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are effective, have been commonly used to prevent malaria, and their use has contributed significantly to the decrease in malaria in the 21st century. ITNs and IRS may not be sufficient to eliminate the disease, as these interventions depend on how many people use nets, how many gaps in insecticide there are (low coverage areas), if people are not protected when outside of the home, and an increase in mosquitoes that are resistant to insecticides. Modifications to peoples houses to prevent mosquito exposure may be an important long term prevention measure. Insecticide-treated nets Mosquito nets help keep mosquitoes away from people and reduce infection rates and transmission of malaria. Nets are not a perfect barrier and are often treated with an insecticide designed to kill the mosquito before it has time to find a way past the net. Insecticide-treated nets (ITNs) are estimated to be twice as effective as untreated nets and offer greater than 70% protection compared with no net. Between 2000 and 2008, the use of ITNs saved the lives of an estimated 250,000 infants in Sub-Saharan Africa. About 13% of households in Sub-Saharan countries owned ITNs in 2007 and 31% of African households were estimated to own at least one ITN in 2008. In 2000, 1.7 million (1.8%) African children living in areas of the world where malaria is common were protected by an ITN. That number increased to 20.3 million (18.5%) African children using ITNs in 2007, leaving 89.6 million children unprotected and to 68% African children using mosquito nets in 2015. Most nets are impregnated with pyrethroids, a class of insecticides with low toxicity. They are most effective when used from dusk to dawn. It is recommended to hang a large "bed net" above the center of a bed and either tuck the edges under the mattress or make sure it is large enough such that it touches the ground. ITNs are beneficial towards pregnancy outcomes in malaria-endemic regions in Africa but more data is needed in Asia and Latin America.In areas of high malaria resistance, piperonyl butoxide (PBO) combined with pyrethroids in mosquito netting is effective in reducing malaria infection rates. Questions remain concerning the durability of PBO on nets as the impact on mosquito mortality was not sustained after twenty washes in experimental trials. Indoor residual spraying Indoor residual spraying is the spraying of insecticides on the walls inside a home. After feeding, many mosquitoes rest on a nearby surface while digesting the bloodmeal, so if the walls of houses have been coated with insecticides, the resting mosquitoes can be killed before they can bite another person and transfer the malaria parasite. As of 2006, the World Health Organization recommends 12 insecticides in IRS operations, including DDT and the pyrethroids cyfluthrin and deltamethrin. This public health use of small amounts of DDT is permitted under the Stockholm Convention, which prohibits its agricultural use. One problem with all forms of IRS is insecticide resistance. Mosquitoes affected by IRS tend to rest and live indoors, and due to the irritation caused by spraying, their descendants tend to rest and live outdoors, meaning that they are less affected by the IRS. Communities using insecticide treated nets, in addition to indoor residual spraying with non-pyrethroid-like insecticides found associated reductions in malaria. Additionally, the use of pyrethroid-like insecticides in addition to indoor residual spraying did not result in a detectable additional benefit in communities using insecticide treated nets. Housing modifications Housing is a risk factor for malaria and modifying the house as a prevention measure may be a sustainable strategy that does not rely on the effectiveness of insecticides such as pyrethroids. The physical environment inside and outside the home that may improve the density of mosquitoes are considerations. Examples of potential modifications include how close the home is to mosquito breeding sites, drainage and water supply near the home, availability of mosquito resting sites (vegetation around the home), the proximity to live stock and domestic animals, and physical improvements or modifications to the design of the home to prevent mosquitoes from entering. Other mosquito control methods People have tried a number of other methods to reduce mosquito bites and slow the spread of malaria. Efforts to decrease mosquito larvae by decreasing the availability of open water where they develop, or by adding substances to decrease their development, are effective in some locations. Electronic mosquito repellent devices, which make very high-frequency sounds that are supposed to keep female mosquitoes away, have no supporting evidence of effectiveness. There is a low certainty evidence that fogging may have an effect on malaria transmission. Larviciding by hand delivery of chemical or microbial insecticides into water bodies containing low larval distribution may reduce malarial transmission. There is insufficient evidence to determine whether larvivorous fish can decrease mosquito density and transmission in the area. Medications There are a number of medications that can help prevent or interrupt malaria in travellers to places where infection is common. Many of these medications are also used in treatment. In places where Plasmodium is resistant to one or more medications, three medications—mefloquine, doxycycline, or the combination of atovaquone/proguanil (Malarone)—are frequently used for prevention. Doxycycline and the atovaquone/proguanil are better tolerated while mefloquine is taken once a week. Areas of the world with chloroquine-sensitive malaria are uncommon. Antimalarial mass drug administration to an entire population at the same time may reduce the risk of contracting malaria in the population, however the effectiveness of mass drug administration may vary depending on the prevalence of malaria in the area. Other factors such as drug administration plus other protective measures such as mosiquito control, the proportion of people treated in the area, and the risk of reinfection with malaria may play a role in the effectiveness of mass drug treatment approaches.The protective effect does not begin immediately, and people visiting areas where malaria exists usually start taking the drugs one to two weeks before they arrive, and continue taking them for four weeks after leaving (except for atovaquone/proguanil, which only needs to be started two days before and continued for seven days afterward). The use of preventive drugs is often not practical for those who live in areas where malaria exists, and their use is usually given only to pregnant women and short-term visitors. This is due to the cost of the drugs, side effects from long-term use, and the difficulty in obtaining antimalarial drugs outside of wealthy nations. During pregnancy, medication to prevent malaria has been found to improve the weight of the baby at birth and decrease the risk of anaemia in the mother. The use of preventive drugs where malaria-bearing mosquitoes are present may encourage the development of partial resistance.Giving antimalarial drugs to infants through intermittent preventive therapy can reduce the risk of having malaria infection, hospital admission, and anaemia.Mefloquine is more effective than sulfadoxine-pyrimethamine in preventing malaria for HIV-negative pregnant women. Cotrimoxazole is effective in preventing malaria infection and reduce the risk of getting anaemia in HIV-positive women. Giving sulfadoxine-pyrimethamine for three or more doses as intermittent preventive therapy is superior than two doses for HIV-positive women living in malaria-endemic areas.Prompt treatment of confirmed cases with artemisinin-based combination therapies (ACTs) may also reduce transmission. Others Community participation and health education strategies promoting awareness of malaria and the importance of control measures have been successfully used to reduce the incidence of malaria in some areas of the developing world. Recognising the disease in the early stages can prevent it from becoming fatal. Education can also inform people to cover over areas of stagnant, still water, such as water tanks that are ideal breeding grounds for the parasite and mosquito, thus cutting down the risk of the transmission between people. This is generally used in urban areas where there are large centers of population in a confined space and transmission would be most likely in these areas. Intermittent preventive therapy is another intervention that has been used successfully to control malaria in pregnant women and infants, and in preschool children where transmission is seasonal. Treatment Malaria is treated with antimalarial medications; the ones used depends on the type and severity of the disease. While medications against fever are commonly used, their effects on outcomes are not clear. Providing free antimalarial drugs to households may reduce childhood deaths when used appropriately. Programmes which presumptively treat all causes of fever with antimalarial drugs may lead to overuse of antimalarials and undertreat other causes of fever. Nevertheless, the use of malaria rapid-diagnostic kits can help to reduce over-usage of antimalarials. Uncomplicated malaria Simple or uncomplicated malaria may be treated with oral medications. Artemisinin drugs are effective and safe in treating uncomplicated malaria. Artemisinin in combination with other antimalarials (known as artemisinin-combination therapy, or ACT) is about 90% effective when used to treat uncomplicated malaria. The most effective treatment for P. falciparum infection is the use of ACT, which decreases resistance to any single drug component. Artemether-lumefantrine (six-dose regimen) is more effective than the artemether-lumefantrine (four-dose regimen) or other regimens not containing artemisinin derivatives in treating falciparum malaria. Another recommended combination is dihydroartemisinin and piperaquine. Artemisinin-naphthoquine combination therapy showed promising results in treating falciparum malaria. However, more research is needed to establish its efficacy as a reliable treatment. Artesunate plus mefloquine performs better than mefloquine alone in treating uncomplicated falciparum malaria in low transmission settings. Atovaquone-proguanil is effective against uncomplicated falciparum with a possible failure rate of 5% to 10%; the addition of artesunate may reduce failure rate. Azithromycin monotherapy or combination therapy has not shown effectiveness in treating plasmodium or vivax malaria. Amodiaquine plus sulfadoxine-pyrimethamine may achieve less treatment failures when compared to sulfadoxine-pyrimethamine alone in uncomplicated falciparum malaria. There is insufficient data on chlorproguanil-dapsone in treating uncomplicated falciparum malaria. The addition of primaquine with artemisinin-based combination therapy for falciparum malaria reduces its transmission at day 3-4 and day 8 of infection. Sulfadoxine-pyrimethamine plus artesunate is better than sulfadoxine-pyrimethamine plus amodiaquine in controlling treatment failure at day 28. However, the latter is better than the former in reducing gametocytes in blood at day 7.Infection with P. vivax, P. ovale or P. malariae usually does not require hospitalisation. Treatment of P. vivax requires both treatment of blood stages (with chloroquine or artemisinin-based combination therapy) and clearance of liver forms with an 8-aminoquinoline agent such as primaquine or tafenoquine.To treat malaria during pregnancy, the WHO recommends the use of quinine plus clindamycin early in the pregnancy (1st trimester), and ACT in later stages (2nd and 3rd trimesters). There is limited safety data on the antimalarial drugs in pregnancy. Severe and complicated malaria Cases of severe and complicated malaria are almost always caused by infection with P. falciparum. The other species usually cause only febrile disease. Severe and complicated malaria cases are medical emergencies since mortality rates are high (10% to 50%).Recommended treatment for severe malaria is the intravenous use of antimalarial drugs. For severe malaria, parenteral artesunate was superior to quinine in both children and adults. In another systematic review, artemisinin derivatives (artemether and arteether) were as efficacious as quinine in the treatment of cerebral malaria in children. Treatment of severe malaria involves supportive measures that are best done in a critical care unit. This includes the management of high fevers and the seizures that may result from it. It also includes monitoring for poor breathing effort, low blood sugar, and low blood potassium. Artemisinin derivatives have the same or better efficacy than quinolones in preventing deaths in severe or complicated malaria. Quinine loading dose helps to shorten the duration of fever and increases parasite clearance from the body. There is no difference in effectiveness when using intrarectal quinine compared to intravenous or intramuscular quinine in treating uncomplicated/complicated falciparum malaria. There is insufficient evidence for intramuscular arteether to treat severe malaria. The provision of rectal artesunate before transfer to hospital may reduce the rate of death for children with severe malaria.Cerebral malaria is the form of severe and complicated malaria with the worst neurological symptoms. There is insufficient data on whether osmotic agents such as mannitol or urea are effective in treating cerebral malaria. Routine phenobarbitone in cerebral malaria is associated with fewer convulsions but possibly more deaths. There is no evidence that steroids would bring treatment benefits for cerebral malaria.Managing Cerebral Malaria Cerebral malaria usually makes a patient comatose, if the cause of the coma is in doubt, test for other locally prevalent causes of encephalopathy (bacterial, viral or fungal infection) should be carried out. In areas where there is a high prevalence of malaria infection (e.g. tropical region) treatment can start without testing first. To manage the cerebral malaria when confirmed the following can be done: Patients in coma should be given meticulous nursing care ( monitor vital signs, turn patient every 2 hours, avoid lying the patient in a wet bed etc.) A sterile urethral catheter should be inserted to help with urinating To aspirate stomach content, a sterile nasogastric tube should be inserted. In the occasion of convulsions, a slow intravenous injection of benzodiazepine is administered.There is insufficient evidence to show that blood transfusion is useful in either reducing deaths for children with severe anaemia or in improving their haematocrit in one month. There is insufficient evidence that iron chelating agents such as deferoxamine and deferiprone improve outcomes of those with malaria falciparum infection. Resistance Drug resistance poses a growing problem in 21st-century malaria treatment. In the 2000s (decade), malaria with partial resistance to artemisins emerged in Southeast Asia. Resistance is now common against all classes of antimalarial drugs apart from artemisinins. Treatment of resistant strains became increasingly dependent on this class of drugs. The cost of artemisinins limits their use in the developing world. Malaria strains found on the Cambodia–Thailand border are resistant to combination therapies that include artemisinins, and may, therefore, be untreatable. Exposure of the parasite population to artemisinin monotherapies in subtherapeutic doses for over 30 years and the availability of substandard artemisinins likely drove the selection of the resistant phenotype. Resistance to artemisinin has been detected in Cambodia, Myanmar, Thailand, and Vietnam, and there has been emerging resistance in Laos. Resistance to the combination of artemisinin and piperaquine was first detected in 2013 in Cambodia, and by 2019 had spread across Cambodia and into Laos, Thailand and Vietnam (with up to 80 percent of malaria parasites resistant in some regions).There is insufficient evidence in unit packaged antimalarial drugs in preventing treatment failures of malaria infection. However, if supported by training of healthcare providers and patient information, there is improvement in compliance of those receiving treatment. Prognosis When properly treated, people with malaria can usually expect a complete recovery. However, severe malaria can progress extremely rapidly and cause death within hours or days. In the most severe cases of the disease, fatality rates can reach 20%, even with intensive care and treatment. Over the longer term, developmental impairments have been documented in children who have had episodes of severe malaria. Chronic infection without severe disease can occur in an immune-deficiency syndrome associated with a decreased responsiveness to Salmonella bacteria and the Epstein–Barr virus.During childhood, malaria causes anaemia during a period of rapid brain development, and also direct brain damage resulting from cerebral malaria. Some survivors of cerebral malaria have an increased risk of neurological and cognitive deficits, behavioural disorders, and epilepsy. Malaria prophylaxis was shown to improve cognitive function and school performance in clinical trials when compared to placebo groups. Epidemiology The WHO estimates that in 2019 there were 229 million new cases of malaria resulting in 409,000 deaths. Children under 5 years old are the most affected, accounting for 67% of malaria deaths worldwide in 2019. About 125 million pregnant women are at risk of infection each year; in Sub-Saharan Africa, maternal malaria is associated with up to 200,000 estimated infant deaths yearly. There are about 10,000 malaria cases per year in Western Europe, and 1300–1500 in the United States. The United States eradicated malaria as a major public health concern in 1951, though small outbreaks persist. About 900 people died from the disease in Europe between 1993 and 2003. Both the global incidence of disease and resulting mortality have declined in recent years. According to the WHO and UNICEF, deaths attributable to malaria in 2015 were reduced by 60% from a 2000 estimate of 985,000, largely due to the widespread use of insecticide-treated nets and artemisinin-based combination therapies. In 2012, there were 207 million cases of malaria. That year, the disease is estimated to have killed between 473,000 and 789,000 people, many of whom were children in Africa. Efforts at decreasing the disease in Africa since 2000 have been partially effective, with rates of the disease dropping by an estimated forty percent on the continent.Malaria is presently endemic in a broad band around the equator, in areas of the Americas, many parts of Asia, and much of Africa; in Sub-Saharan Africa, 85–90% of malaria fatalities occur. An estimate for 2009 reported that countries with the highest death rate per 100,000 of population were Ivory Coast (86.15), Angola (56.93) and Burkina Faso (50.66). A 2010 estimate indicated the deadliest countries per population were Burkina Faso, Mozambique and Mali. The Malaria Atlas Project aims to map global levels of malaria, providing a way to determine the global spatial limits of the disease and to assess disease burden. This effort led to the publication of a map of P. falciparum endemicity in 2010 and an update in 2019. As of 2010, about 100 countries have endemic malaria. Every year, 125 million international travellers visit these countries, and more than 30,000 contract the disease.The geographic distribution of malaria within large regions is complex, and malaria-afflicted and malaria-free areas are often found close to each other. Malaria is prevalent in tropical and subtropical regions because of rainfall, consistent high temperatures and high humidity, along with stagnant waters where mosquito larvae readily mature, providing them with the environment they need for continuous breeding. In drier areas, outbreaks of malaria have been predicted with reasonable accuracy by mapping rainfall. Malaria is more common in rural areas than in cities. For example, several cities in the Greater Mekong Subregion of Southeast Asia are essentially malaria-free, but the disease is prevalent in many rural regions, including along international borders and forest fringes. In contrast, malaria in Africa is present in both rural and urban areas, though the risk is lower in the larger cities.Since 1900 there has been substantial change in temperature and rainfall over Africa. However, factors that contribute to how rainfall results in water for mosquito breeding are complex, incorporating the extent to which it is absorbed into soil and vegetation for example, or rates of runoff and evaporation. Recent research has provided a more in-depth picture of conditions across Africa, combining a malaria climatic suitability model with a continental-scale model representing real-world hydrological processes. History Although the parasite responsible for P. falciparum malaria has been in existence for 50,000–100,000 years, the population size of the parasite did not increase until about 10,000 years ago, concurrently with advances in agriculture and the development of human settlements. Close relatives of the human malaria parasites remain common in chimpanzees. Some evidence suggests that the P. falciparum malaria may have originated in gorillas.References to the unique periodic fevers of malaria are found throughout history. Hippocrates described periodic fevers, labelling them tertian, quartan, subtertian and quotidian. The Roman Columella associated the disease with insects from swamps. Malaria may have contributed to the decline of the Roman Empire, and was so pervasive in Rome that it was known as the "Roman fever". Several regions in ancient Rome were considered at-risk for the disease because of the favourable conditions present for malaria vectors. This included areas such as southern Italy, the island of Sardinia, the Pontine Marshes, the lower regions of coastal Etruria and the city of Rome along the Tiber. The presence of stagnant water in these places was preferred by mosquitoes for breeding grounds. Irrigated gardens, swamp-like grounds, run-off from agriculture, and drainage problems from road construction led to the increase of standing water. The term malaria originates from Mediaeval Italian: mala aria—"bad air"; the disease was formerly called ague or marsh fever due to its association with swamps and marshland. The term appeared in English at least as early as 1768. Malaria was once common in most of Europe and North America, where it is no longer endemic, though imported cases do occur.Malaria is not referenced in the medical books of the Mayans or Aztecs. European settlers and the West Africans they enslaved likely brought malaria to the Americas starting in the 16th century.Scientific studies on malaria made their first significant advance in 1880, when Charles Louis Alphonse Laveran—a French army doctor working in the military hospital of Constantine in Algeria—observed parasites inside the red blood cells of infected people for the first time. He, therefore, proposed that malaria is caused by this organism, the first time a protist was identified as causing disease. For this and later discoveries, he was awarded the 1907 Nobel Prize for Physiology or Medicine. A year later, Carlos Finlay, a Cuban doctor treating people with yellow fever in Havana, provided strong evidence that mosquitoes were transmitting disease to and from humans. This work followed earlier suggestions by Josiah C. Nott, and work by Sir Patrick Manson, the "father of tropical medicine", on the transmission of filariasis. In April 1894, a Scottish physician, Sir Ronald Ross, visited Sir Patrick Manson at his house on Queen Anne Street, London. This visit was the start of four years of collaboration and fervent research that culminated in 1897 when Ross, who was working in the Presidency General Hospital in Calcutta, proved the complete life-cycle of the malaria parasite in mosquitoes. He thus proved that the mosquito was the vector for malaria in humans by showing that certain mosquito species transmit malaria to birds. He isolated malaria parasites from the salivary glands of mosquitoes that had fed on infected birds. For this work, Ross received the 1902 Nobel Prize in Medicine. After resigning from the Indian Medical Service, Ross worked at the newly established Liverpool School of Tropical Medicine and directed malaria-control efforts in Egypt, Panama, Greece and Mauritius. The findings of Finlay and Ross were later confirmed by a medical board headed by Walter Reed in 1900. Its recommendations were implemented by William C. Gorgas in the health measures undertaken during construction of the Panama Canal. This public-health work saved the lives of thousands of workers and helped develop the methods used in future public-health campaigns against the disease.In 1896, Amico Bignami discussed the role of mosquitoes in malaria. In 1898, Bignami, Giovanni Battista Grassi and Giuseppe Bastianelli succeeded in showing experimentally the transmission of malaria in humans, using infected mosquitoes to contract malaria themselves which they presented in November 1898 to the Accademia dei Lincei. The first effective treatment for malaria came from the bark of cinchona tree, which contains quinine. This tree grows on the slopes of the Andes, mainly in Peru. The indigenous peoples of Peru made a tincture of cinchona to control fever. Its effectiveness against malaria was found and the Jesuits introduced the treatment to Europe around 1640; by 1677, it was included in the London Pharmacopoeia as an antimalarial treatment. It was not until 1820 that the active ingredient, quinine, was extracted from the bark, isolated and named by the French chemists Pierre Joseph Pelletier and Joseph Bienaimé Caventou.Quinine was the predominant malarial medication until the 1920s when other medications began to appear. In the 1940s, chloroquine replaced quinine as the treatment of both uncomplicated and severe malaria until resistance supervened, first in Southeast Asia and South America in the 1950s and then globally in the 1980s.The medicinal value of Artemisia annua has been used by Chinese herbalists in traditional Chinese medicines for 2,000 years. In 1596, Li Shizhen recommended tea made from qinghao specifically to treat malaria symptoms in his "Compendium of Materia Medica". Artemisinins, discovered by Chinese scientist Tu Youyou and colleagues in the 1970s from the plant Artemisia annua, became the recommended treatment for P. falciparum malaria, administered in severe cases in combination with other antimalarials. Tu says she was influenced by a traditional Chinese herbal medicine source, The Handbook of Prescriptions for Emergency Treatments, written in 340 by Ge Hong. For her work on malaria, Tu Youyou received the 2015 Nobel Prize in Physiology or Medicine.Plasmodium vivax was used between 1917 and the 1940s for malariotherapy—deliberate injection of malaria parasites to induce a fever to combat certain diseases such as tertiary syphilis. In 1927, the inventor of this technique, Julius Wagner-Jauregg, received the Nobel Prize in Physiology or Medicine for his discoveries. The technique was dangerous, killing about 15% of patients, so it is no longer in use. The first pesticide used for indoor residual spraying was DDT. Although it was initially used exclusively to combat malaria, its use quickly spread to agriculture. In time, pest control, rather than disease control, came to dominate DDT use, and this large-scale agricultural use led to the evolution of pesticide-resistant mosquitoes in many regions. The DDT resistance shown by Anopheles mosquitoes can be compared to antibiotic resistance shown by bacteria. During the 1960s, awareness of the negative consequences of its indiscriminate use increased, ultimately leading to bans on agricultural applications of DDT in many countries in the 1970s. Before DDT, malaria was successfully eliminated or controlled in tropical areas like Brazil and Egypt by removing or poisoning the breeding grounds of the mosquitoes or the aquatic habitats of the larval stages, for example by applying the highly toxic arsenic compound Paris Green to places with standing water.Malaria vaccines have been an elusive goal of research. The first promising studies demonstrating the potential for a malaria vaccine were performed in 1967 by immunising mice with live, radiation-attenuated sporozoites, which provided significant protection to the mice upon subsequent injection with normal, viable sporozoites. Since the 1970s, there has been a considerable effort to develop similar vaccination strategies for humans. The first vaccine, called RTS,S, was approved by European regulators in 2015. Names Various types of malaria have been called by the names below: Eradication efforts Malaria has been successfully eliminated or significantly reduced in certain areas, but not globally. Malaria was once common in the United States, but the US eliminated malaria from most parts of the country in the early 20th century using vector control programs, which combined the monitoring and treatment of infected humans, draining of wetland breeding grounds for agriculture and other changes in water management practices, and advances in sanitation, including greater use of glass windows and screens in dwellings. The use of the pesticide DDT and other means eliminated malaria from the remaining pockets in southern states of the US the 1950s, as part of the National Malaria Eradication Program. Most of Europe, North America, Australia, North Africa and the Caribbean, and parts of South America, Asia and Southern Africa have also eliminated malaria. The WHO defines "elimination" (or "malaria-free") as having no domestic transmission (indigenous cases) for the past three years. They also define "pre-elimination" and "elimination" stages when a country has fewer than 5 or 1, respectively, cases per 1000 people at risk per year. In 1955 the WHO launched the Global Malaria Eradication Program (GMEP), which supported substantial reductions in malaria cases in some countries, including India. However, due to vector and parasite resistance and other factors, the feasibility of eradicating malaria with the strategy used at the time and resources available led to waning support for the program. WHO suspended the program in 1969. Target 6C of the Millennium Development Goals included reversal of the global increase in malaria incidence by 2015, with specific targets for children under 5 years old. Since 2000, support for malaria eradication increased, although some actors in the global health community (including voices within the WHO) view malaria eradication as a premature goal and suggest that the establishment of strict deadlines for malaria eradication may be counterproductive as they are likely to be missed.In 2006, the organization Malaria No More set a public goal of eliminating malaria from Africa by 2015, and the organization claimed they planned to dissolve if that goal was accomplished. In 2007, World Malaria Day was established by the 60th session of the World Health Assembly. As of 2018, they are still functioning. As of 2012, The Global Fund to Fight AIDS, Tuberculosis, and Malaria has distributed 230 million insecticide-treated nets intended to stop mosquito-borne transmission of malaria. The U.S.-based Clinton Foundation has worked to manage demand and stabilize prices in the artemisinin market. Other efforts, such as the Malaria Atlas Project, focus on analysing climate and weather information required to accurately predict malaria spread based on the availability of habitat of malaria-carrying parasites. The Malaria Policy Advisory Committee (MPAC) of the World Health Organization (WHO) was formed in 2012, "to provide strategic advice and technical input to WHO on all aspects of malaria control and elimination". In November 2013, WHO and the malaria vaccine funders group set a goal to develop vaccines designed to interrupt malaria transmission with malaria eradications long-term goal.In 2015 the WHO targeted a 90% reduction in malaria deaths by 2030, and Bill Gates said in 2016 that he thought global eradication would be possible by 2040. According to the WHOs World Malaria Report 2015, the global mortality rate for malaria fell by 60% between 2000 and 2015. The WHO targeted a further 90% reduction between 2015 and 2030, with a 40% reduction and eradication in 10 countries by 2020. However, the 2020 goal was missed with a slight increase in cases compared to 2015.Before 2016, the Global Fund against HIV/AIDS, Tuberculosis and Malaria had provided 659 million ITN (insecticide treated bed nets), organise support and education to prevents malaria. The challenges are high due to the lack of funds, the fragile health structure and the remote indigenous population that could be hard to reach and educate. Most of indigenous population rely on self-diagnosis, self-treatment, healer, and traditional medicine. The WHO applied for fund to the Gates Foundation which favour the action of malaria eradication in 2007. Six countries, the United Arab Emirates, Morocco, Armenia, Turkmenistan, Kyrgyzstan, and Sri Lanka managed to have no endemic cases of malaria for three consecutive years and certified malaria-free by the WHO despite the stagnation of the funding in 2010. The funding is essential to finance the cost of medication and hospitalisation cannot be supported by the poor countries where the disease is widely spread. The goal of eradication has not been met nevertheless the decrease rate of the disease is considerable. While 31 out of 92 endemic countries were estimated to be on track with the WHO goals for 2020, 15 countries reported an increase of 40% or more between 2015 and 2020. Between 2000 and 30 June 2021, twelve countries were certified by the WHO as being malaria-free. Argentina and Algeria were declared free of malaria in 2019. El Salvador and China were declared malaria-free in the first half of 2021.Regional disparities were evident: Southeast Asia was on track to meet WHOs 2020 goals, while Africa, Americas, Eastern Mediterranean and West Pacific regions were off-track. The six Greater Mekong Subregion countries aim for elimination of P. falciparum transmitted malaria by 2025 and elimination of all malaria by 2030, having achieved a 97% and 90% reduction of cases respectively since 2000. Ahead of World Malaria Day, 25 April 2021, WHO named 25 countries in which it is working to eliminate malaria by 2025 as part of its E-2025 initiative.A major challenge to malaria elimination is the persistence of malaria in border regions, making international cooperation crucial.One of the targets of Goal 3 of the UNs Sustainable Development Goals is to end the malaria epidemic in all countries by 2030. In 2018, WHO announced that Paraguay was free of malaria, after a national malaria eradication effort that began in 1950.As of 2019, the eradication process is ongoing, but it will be difficult to achieve a world free of malaria with the current approaches and tools. Only one malaria vaccine is licensed for use, and it shows relatively low effectiveness, while several other vaccine candidates in clinical trials aim to provide protection for children in endemic areas and reduce the speed of malaria transmission. Approaches may require investing more in research and greater primary health care. Continuing surveillance will also be important to prevent the return of malaria in countries where the disease has been eliminated. Society and culture Economic impact Malaria is not just a disease commonly associated with poverty: some evidence suggests that it is also a cause of poverty and a major hindrance to economic development. Although tropical regions are most affected, malarias furthest influence reaches into some temperate zones that have extreme seasonal changes. The disease has been associated with major negative economic effects on regions where it is widespread. During the late 19th and early 20th centuries, it was a major factor in the slow economic development of the American southern states.A comparison of average per capita GDP in 1995, adjusted for parity of purchasing power, between countries with malaria and countries without malaria gives a fivefold difference (US$1,526 versus US$8,268). In the period 1965 to 1990, countries where malaria was common had an average per capita GDP that increased only 0.4% per year, compared to 2.4% per year in other countries.Poverty can increase the risk of malaria since those in poverty do not have the financial capacities to prevent or treat the disease. In its entirety, the economic impact of malaria has been estimated to cost Africa US$12 billion every year. The economic impact includes costs of health care, working days lost due to sickness, days lost in education, decreased productivity due to brain damage from cerebral malaria, and loss of investment and tourism. The disease has a heavy burden in some countries, where it may be responsible for 30–50% of hospital admissions, up to 50% of outpatient visits, and up to 40% of public health spending. Cerebral malaria is one of the leading causes of neurological disabilities in African children. Studies comparing cognitive functions before and after treatment for severe malarial illness continued to show significantly impaired school performance and cognitive abilities even after recovery. Consequently, severe and cerebral malaria have far-reaching socioeconomic consequences that extend beyond the immediate effects of the disease. Counterfeit and substandard drugs Sophisticated counterfeits have been found in several Asian countries such as Cambodia, China, Indonesia, Laos, Thailand, and Vietnam, and are a major cause of avoidable death in those countries. The WHO said that studies indicate that up to 40% of artesunate-based malaria medications are counterfeit, especially in the Greater Mekong region. They have established a rapid alert system to rapidly report information about counterfeit drugs to relevant authorities in participating countries. There is no reliable way for doctors or lay people to detect counterfeit drugs without help from a laboratory. Companies are attempting to combat the persistence of counterfeit drugs by using new technology to provide security from source to distribution.Another clinical and public health concern is the proliferation of substandard antimalarial medicines resulting from inappropriate concentration of ingredients, contamination with other drugs or toxic impurities, poor quality ingredients, poor stability and inadequate packaging. A 2012 study demonstrated that roughly one-third of antimalarial medications in Southeast Asia and Sub-Saharan Africa failed chemical analysis, packaging analysis, or were falsified. War Throughout history, the contraction of malaria has played a prominent role in the fates of government rulers, nation-states, military personnel, and military actions. In 1910, Nobel Prize in Medicine-winner Ronald Ross (himself a malaria survivor), published a book titled The Prevention of Malaria that included a chapter titled "The Prevention of Malaria in War". The chapters author, Colonel C. H. Melville, Professor of Hygiene at Royal Army Medical College in London, addressed the prominent role that malaria has historically played during wars: "The history of malaria in war might almost be taken to be the history of war itself, certainly the history of war in the Christian era. ... It is probably the case that many of the so-called camp fevers, and probably also a considerable proportion of the camp dysentery, of the wars of the sixteenth, seventeenth and eighteenth centuries were malarial in origin." In British-occupied India the cocktail gin and tonic may have come about as a way of taking quinine, known for its antimalarial properties.Malaria was the most significant health hazard encountered by U.S. troops in the South Pacific during World War II, where about 500,000 men were infected. According to Joseph Patrick Byrne, "Sixty thousand American soldiers died of malaria during the African and South Pacific campaigns."Significant financial investments have been made to procure existing and create new antimalarial agents. During World War I and World War II, inconsistent supplies of the natural antimalaria drugs cinchona bark and quinine prompted substantial funding into research and development of other drugs and vaccines. American military organisations conducting such research initiatives include the Navy Medical Research Center, Walter Reed Army Institute of Research, and the U.S. Army Medical Research Institute of Infectious Diseases of the US Armed Forces.Additionally, initiatives have been founded such as Malaria Control in War Areas (MCWA), established in 1942, and its successor, the Communicable Disease Center (now known as the Centers for Disease Control and Prevention, or CDC) established in 1946. According to the CDC, MCWA "was established to control malaria around military training bases in the southern United States and its territories, where malaria was still problematic". Research The Malaria Eradication Research Agenda (malERA) initiative was a consultative process to identify which areas of research and development (R&D) must be addressed for worldwide eradication of malaria. Vaccine A vaccine against malaria called RTS,S/AS01 (RTS,S) was approved by European regulators in 2015. As of 2019 it is undergoing pilot trials in 3 sub-Saharan African countries – Ghana, Kenya and Malawi – as part of the WHOs Malaria Vaccine Implementation Programme (MVIP).Immunity (or, more accurately, tolerance) to P. falciparum malaria does occur naturally, but only in response to years of repeated infection. An individual can be protected from a P. falciparum infection if they receive about a thousand bites from mosquitoes that carry a version of the parasite rendered non-infective by a dose of X-ray irradiation. The highly polymorphic nature of many P. falciparum proteins results in significant challenges to vaccine design. Vaccine candidates that target antigens on gametes, zygotes, or ookinetes in the mosquito midgut aim to block the transmission of malaria. These transmission-blocking vaccines induce antibodies in the human blood; when a mosquito takes a blood meal from a protected individual, these antibodies prevent the parasite from completing its development in the mosquito. Other vaccine candidates, targeting the blood-stage of the parasites life cycle, have been inadequate on their own. For example, SPf66 was tested extensively in areas where the disease was common in the 1990s, but trials showed it to be insufficiently effective.In 2021, researchers from the University of Oxford reported findings from a Phase IIb trial of a candidate malaria vaccine, R21/Matrix-M, which demonstrated efficacy of 77% over 12-months of follow-up. This vaccine is the first to meet the World Health Organizations Malaria Vaccine Technology Roadmap goal of a vaccine with at least 75% efficacy. Medications Malaria parasites contain apicoplasts, organelles related to the plastids found in plants, complete with their own genomes. These apicoplasts are thought to have originated through the endosymbiosis of algae and play a crucial role in various aspects of parasite metabolism, such as fatty acid biosynthesis. Over 400 proteins have been found to be produced by apicoplasts and these are now being investigated as possible targets for novel antimalarial drugs.With the onset of drug-resistant Plasmodium parasites, new strategies are being developed to combat the widespread disease. One such approach lies in the introduction of synthetic pyridoxal-amino acid adducts, which are taken up by the parasite and ultimately interfere with its ability to create several essential B vitamins. Antimalarial drugs using synthetic metal-based complexes are attracting research interest. (+)-SJ733: Part of a wider class of experimental drugs called spiroindolone. It inhibits the ATP4 protein of infected red blood cells that cause the cells to shrink and become rigid like the aging cells. This triggers the immune system to eliminate the infected cells from the system as demonstrated in a mouse model. As of 2014, a Phase 1 clinical trial to assess the safety profile in human is planned by the Howard Hughes Medical Institute. NITD246 and NITD609: Also belonged to the class of spiroindolone and target the ATP4 protein.On the basis of molecular docking outcomes, compounds 3j, 4b, 4h, 4m were exhibited selectivity towards PfLDH. The post docking analysis displayed stable dynamic behavior of all the selected compounds compared to Chloroquine. The end state thermodynamics analysis stated 3j compound as a selective and potent PfLDH inhibitor. New targets Targeting Plasmodium liver-stage parasites selectively is emerging as an alternative strategy in the face of resistance to the latest frontline combination therapies against blood stages of the parasite.In a research conducted in 2019, using experimental analysis with knockout (KO) mutants of Plasmodium berguei the authors were able to identify genes that are potentially essential in the liver stage. Moreover, they generated a computational model to analyse pre–erytrocytic development and liver–stage metabolism. Combining both methods they identified seven metabolic subsystems that become essential compared to the blood stage. Some of these metabolic pathways are fatty acid synthesis and elongation, tricarboxylic acid, amino acid and heme metabolism among others.Specifically, they studied 3 subsystems: fatty acid synthesis and elongation, and amino sugar biosynthesis. For the first two pathways they demonstrated a clear dependence of the liver stage on its own fatty acid metabolism.They proved for the first time the critical role of amino sugar biosynthesis in the liver stage of P. berghei. The uptake of N–acetyl–glucosamine appears to be limited in the liver stage, being its synthesis needed for the parasite development.These findings and the computational model provide a basis for the design of antimalarial therapies targeting metabolic proteins. Other A non-chemical vector control strategy involves genetic manipulation of malaria mosquitoes. Advances in genetic engineering technologies make it possible to introduce foreign DNA into the mosquito genome and either decrease the lifespan of the mosquito, or make it more resistant to the malaria parasite. Sterile insect technique is a genetic control method whereby large numbers of sterile male mosquitoes are reared and released. Mating with wild females reduces the wild population in the subsequent generation; repeated releases eventually eliminate the target population.Genomics is central to malaria research. With the sequencing of P. falciparum, one of its vectors Anopheles gambiae, and the human genome, the genetics of all three organisms in the malaria life cycle can be studied. Another new application of genetic technology is the ability to produce genetically modified mosquitoes that do not transmit malaria, potentially allowing biological control of malaria transmission.In one study, a genetically modified strain of Anopheles stephensi was created that no longer supported malaria transmission, and this resistance was passed down to mosquito offspring.Gene drive is a technique for changing wild populations, for instance to combat or eliminate insects so they cannot transmit diseases (in particular mosquitoes in the cases of malaria, zika, dengue and yellow fever).In December 2020, a review article found that malaria-endemic regions had lower reported COVID-19 case fatality rates on average than regions where malaria was not known to be endemic. Other animals While there are no animal reservoirs for the strains of malaria that cause human infections, nearly 200 parasitic Plasmodium species have been identified that infect birds, reptiles, and other mammals, and about 30 species naturally infect non-human primates. Some malaria parasites that affect non-human primates (NHP) serve as model organisms for human malarial parasites, such as P. coatneyi (a model for P. falciparum) and P. cynomolgi (P. vivax). Diagnostic techniques used to detect parasites in NHP are similar to those employed for humans. Malaria parasites that infect rodents are widely used as models in research, such as P. berghei. Avian malaria primarily affects species of the order Passeriformes, and poses a substantial threat to birds of Hawaii, the Galapagos, and other archipelagoes. The parasite P. relictum is known to play a role in limiting the distribution and abundance of endemic Hawaiian birds. Global warming is expected to increase the prevalence and global distribution of avian malaria, as elevated temperatures provide optimal conditions for parasite reproduction. References Citations Sources Further reading External links WHO site on malaria CDC site on malaria PAHO site on malaria

Hello Aarogya , Do you know what is Malaria prophylaxis,

Malaria prophylaxis

Malaria prophylaxis is the preventive treatment of malaria. Several malaria vaccines are under development. For pregnant women who are living in malaria endemic areas, routine malaria chemoprevention is recommended. It improves anemia and parasite level in the blood for the pregnant women and the birthweight in their infants. Strategies Risk management Bite prevention—clothes that cover as much skin as possible, insect repellent, insecticide-impregnated bed nets and indoor residual spraying Chemoprophylaxis Rapid diagnosis and treatmentRecent improvements in malaria prevention strategies have further enhanced its effectiveness in combating areas highly infected with the malaria parasite. Additional bite prevention measures include mosquito and insect repellents that can be directly applied to skin. This form of mosquito repellent is slowly replacing indoor residual spraying, which is considered to have high levels of toxicity by WHO (World Health Organization). Further additions to preventive care are sanctions on blood transfusions. Once the malaria parasite enters the erythrocytic stage, it can adversely affect blood cells, making it possible to contract the parasite through infected blood. Chloroquine may be used where the parasite is still sensitive, however many malaria parasite strains are now resistant. Mefloquine (Lariam), or doxycycline (available generically), or the combination of atovaquone and proguanil hydrochloride (Malarone) are frequently recommended. Medications In choosing the agent, it is important to weigh the risk of infection against the risks and side effects associated with the medications. Disruptive prophylaxis An experimental approach involves preventing the parasite from binding with red blood cells by blocking calcium signalling between the parasite and the host cell. Erythrocyte-binding-like proteins (EBLs) and reticulocyte-binding protein homologues (RHs) are both used by specialized P. falciparum organelles known as rhoptries and micronemes to bind with the host cell. Disrupting the binding process can stop the parasite.Monoclonal antibodies were used to interrupt calcium signalling between PfRH1 (an RH protein), EBL protein EBA175 and the host cell. This disruption completely stopped the binding process. Suppressive prophylaxis Chloroquine, proguanil, mefloquine, and doxycycline are suppressive prophylactics. This means that they are only effective at killing the malaria parasite once it has entered the erythrocytic stage (blood stage) of its life cycle, and therefore have no effect until the liver stage is complete. That is why these prophylactics must continue to be taken for four weeks after leaving the area of risk. Mefloquine, doxycycline, and atovaquone-proguanil appear to be equally effective at reducing the risk of malaria for short-term travelers and are similar with regard to their risk of serious side effects. Mefloquine is sometimes preferred due to its once a week dose, however mefloquine is not always as well tolerated when compared with atovaquone-proguanil. There is low-quality evidence suggesting that mefloquine and doxycycline are similar with regards to the number of people who discontinue treatments due to minor side effects. People who take mefloquine may be more likely to experience minor side effects such as sleep disturbances, depressed mood, and an increase in abnormal dreams. There is very low quality evidence indicating that doxycycline use may be associated with an increased risk of indigestion, photosensitivity, vomiting, and yeast infections, when compared with mefloquine and atovaquone-proguanil. Causal prophylaxis Causal prophylactics target not only the blood stages of malaria, but the initial liver stage as well. This means that the user can stop taking the drug seven days after leaving the area of risk. Malarone and primaquine are the only causal prophylactics in current use. Regimens Specific regimens are recommended by the WHO, UK HPA and CDC for prevention of P. falciparum infection. HPA and WHO advice are broadly in line with each other (although there are some differences). CDC guidance frequently contradicts HPA and WHO guidance. These regimens include: doxycycline 100 mg once daily (started one day before travel, and continued for four weeks after returning); mefloquine 250 mg once weekly (started two-and-a-half weeks before travel, and continued for four weeks after returning); atovaquone/proguanil (Malarone) 1 tablet daily (started one day before travel, and continued for 1 week after returning). Can also be used for therapy in some cases.In areas where chloroquine remains effective: chloroquine 300 mg once weekly, and proguanil 200 mg once daily (started one week before travel, and continued for four weeks after returning); hydroxychloroquine 400 mg once weekly (started one to two weeks before travel and continued for four weeks after returning)What regimen is appropriate depends on the person who is to take the medication as well as the country or region travelled to. This information is available from the UK HPA, WHO or CDC (links are given below). Doses depend also on what is available (e.g., in the US, mefloquine tablets contain 228 mg base, but 250 mg base in the UK). The data is constantly changing and no general advice is possible. Doses given are appropriate for adults and children aged 12 and over. Other chemoprophylactic regimens that have been used on occasion: Dapsone 100 mg and pyrimethamine 12.5 mg once weekly (available as a combination tablet called Maloprim or Deltaprim): this combination is not routinely recommended because of the risk of agranulocytosis; Primaquine 30 mg once daily (started the day before travel, and continuing for seven days after returning): this regimen is not routinely recommended because of the need for G-6-PD testing prior to starting primaquine (see the article on primaquine for more information). Quinine sulfate 300 to 325 mg once daily: this regimen is effective but not routinely used because of the unpleasant side effects of quinine.Prophylaxis against Plasmodium vivax requires a different approach given the long liver stage of this parasite. This is a highly specialist area. Vaccines In November 2012, findings from a Phase III trials of an experimental malaria vaccine known as RTS,S reported that it provided modest protection against both clinical and severe malaria in young infants. The efficacy was about 30% in infants 6 to 12 weeks of age and about 50% in infants 5 to 17 months of age in the first year of the trial.The RTS,S vaccine was engineered using a fusion hepatitis B surface protein containing epitopes of the outer protein of Plasmodium falciparum malaria sporozite, which is produced in yeast cells. It also contains a chemical adjuvant to boost the immune system response. The vaccine is being developed by PATH and GlaxoSmithKline (GSK), which has spent about $300 million on the project, plus about $200 million more from the Bill and Melinda Gates Foundation. Risk factors Most adults from endemic areas have a degree of long-term infection, which tends to recur, and also possess partial immunity (resistance); the resistance reduces with time, and such adults may become susceptible to severe malaria if they have spent a significant amount of time in non-endemic areas. They are strongly recommended to take full precautions if they return to an endemic area. History Malaria is one of the oldest known pathogens, and began having a major impact on human survival about 10,000 years ago with the birth of agriculture. The development of virulence in the parasite has been demonstrated using genomic mapping of samples from this period, confirming the emergence of genes conferring a reduced risk of developing the malaria infection. References to the disease can be found in manuscripts from ancient Egypt, India and China, illustrating its wide geographical distribution. The first treatment identified is thought to be Quinine, one of four alkaloids from the bark of the Cinchona tree. Originally it was used by the tribes of Ecuador and Peru for treating fevers. Its role in treating malaria was recognised and recorded first by an Augustine monk from Lima, Peru in 1633. Seven years later the drug had reached Europe and was being used widely with the name the Jesuits bark. From this point onwards the use of Quinine and the public interest in malaria increased, although the compound was not isolated and identified as the active ingredient until 1820. By the mid-1880s the Dutch had grown vast plantations of cinchona trees and monopolised the world market. Quinine remained the only available treatment for malaria until the early 1920s. During the First World War German scientists developed the first synthetic antimalarial compound—Atabrin and this was followed by Resochin and Sontochin derived from 4-aminoquinoline compounds. American troops, on capturing Tunisia during the Second World War, acquired, then altered the drugs to produce Chloroquine. The development of new antimalarial drugs spurred the World Health Organization in 1955 to attempt a global malaria eradication program. This was successful in much of Brazil, the US and Egypt but ultimately failed elsewhere. Efforts to control malaria are still continuing, with the development of drug-resistant parasites presenting increasingly difficult problems. The CDC publishes recommendations for travels advising about the risk of contracting malaria in various countries.Some of the factors in deciding whether to use chemotherapy as malaria pre-exposure prophylaxis include the specific itinerary, length of trip, cost of drug, previous adverse reactions to antimalarials, drug allergies, and current medical history. See also Malaria prevention Mosquito control == References ==

Hey Aarogya!, what is Pattern hair loss

Pattern hair loss

Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front hairline, loss of hair on the crown (vertex) of the scalp, or a combination of both. Female-pattern hair loss (FPHL) typically presents as a diffuse thinning of the hair across the entire scalp.Male pattern hair loss seems to be due to a combination of oxidative stress, the microbiome of the scalp, genetics, and circulating androgens; particularly dihydrotestosterone (DHT). Men with early onset androgenic alopecia (before the age of 35) have been deemed as the male phenotypic equivalent for polycystic ovary syndrome (PCOS). As an early clinical expression of insulin resistance and metabolic syndrome, AGA is related to being an increased risk factor for cardiovascular diseases, glucose metabolism disorders, type 2 diabetes, and enlargement of the prostate.The cause in female pattern hair loss remains unclear, androgenetic alopecia for women is associated with an increased risk of polycystic ovary syndrome (PCOS).Management may include simply accepting the condition or shaving ones head to improve the aesthetic aspect of the condition. Otherwise, common medical treatments include minoxidil, finasteride, dutasteride, or hair transplant surgery. Use of finasteride and dutasteride in women is not well-studied and may result in birth defects if taken during pregnancy.Pattern hair loss by the age of 50 affects about half of males and a quarter of females. It is the most common cause of hair loss. Both males aged 40–91 and younger male patients of early onset AGA (before the age of 35), had a higher likelihood of metabolic syndrome (MetS) and insulin resistance. With younger males, studies found metabolic syndrome to be at approximately a 4x increased frequency which is clinically deemed as significant. Abdominal obesity, hypertension and lowered high density lipoprotein were also significantly higher for younger groups. Signs and symptoms Pattern hair loss is classified as a form of non-scarring hair loss. Male-pattern hair loss begins above the temples and at the vertex (calvaria) of the scalp. As it progresses, a rim of hair at the sides and rear of the head remains. This has been referred to as a Hippocratic wreath, and rarely progresses to complete baldness.Female-pattern hair loss more often causes diffuse thinning without hairline recession; similar to its male counterpart, female androgenic alopecia rarely leads to total hair loss. The Ludwig scale grades severity of female-pattern hair loss. These include Grades 1, 2, 3 of balding in women based on their scalp showing in the front due to thinning of hair.In most cases, receding hairline is the first starting point; the hairline starts moving backwards from the front of the head and the sides. Causes Hormones and genes KRT37 is the only keratin that is regulated by androgens. This sensitivity to androgens was acquired by Homo sapiens and is not shared with their great ape cousins. Although Winter et al. found that KRT37 is expressed in all the hair follices of chimpanzees, it was not detected in the head hair of modern humans. As androgens are known to grow hair on the body, but decrease it on the scalp, this lack of scalp KRT37 may help explain the paradoxical nature of Androgenic alopecia as well as the fact that head hair anagen cycles are extremely long. The initial programming of pilosebaceous units of hair follicles begins in utero. The physiology is primarily androgenic, with dihydrotestosterone (DHT) being the major contributor at the dermal papillae. Men with premature androgenic alopecia tend to have lower than normal values of sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH), testosterone, and epitestosterone when compared to men without pattern hair loss. Although hair follicles were previously thought to be permanently gone in areas of complete hair loss, they are more likely dormant, as recent studies have shown the scalp contains the stem cell progenitor cells from which the follicles arose.Transgenic studies have shown that growth and dormancy of hair follicles are related to the activity of insulin-like growth factor (IGF) at the dermal papillae, which is affected by DHT. Androgens are important in male sexual development around birth and at puberty. They regulate sebaceous glands, apocrine hair growth, and libido. With increasing age, androgens stimulate hair growth on the face, but can suppress it at the temples and scalp vertex, a condition that has been referred to as the androgen paradox.Men with androgenic alopecia typically have higher 5α-reductase, higher total testosterone, higher unbound/free testosterone, and higher free androgens, including DHT. 5-alpha-reductase converts free testosterone into DHT, and is highest in the scalp and prostate gland. DHT is most commonly formed at the tissue level by 5α-reduction of testosterone. The genetic corollary that codes for this enzyme has been discovered. Prolactin has also been suggested to have different effects on the hair follicle across gender.Also, crosstalk occurs between androgens and the Wnt-beta-catenin signaling pathway that leads to hair loss. At the level of the somatic stem cell, androgens promote differentiation of facial hair dermal papillae, but inhibit it at the scalp. Other research suggests the enzyme prostaglandin D2 synthase and its product prostaglandin D2 (PGD2) in hair follicles as contributive.These observations have led to study at the level of the mesenchymal dermal papillae. Types 1 and 2 5α reductase enzymes are present at pilosebaceous units in papillae of individual hair follicles. They catalyze formation of the androgens testosterone and DHT, which in turn regulate hair growth. Androgens have different effects at different follicles: they stimulate IGF-1 at facial hair, leading to growth, but can also stimulate TGF β1, TGF β2, dickkopf1, and IL-6 at the scalp, leading to catagenic miniaturization. Hair follicles in anaphase express four different caspases. Significant levels of inflammatory infiltrate have been found in transitional hair follicles. Interleukin 1 is suspected to be a cytokine mediator that promotes hair loss.The fact that hair loss is cumulative with age while androgen levels fall as well as the fact that finasteride does not reverse advanced stages of androgenetic alopecia remains a mystery, but possible explanations are higher conversion of testosterone to DHT locally with age as higher levels of 5-alpha reductase are noted in balding scalp, and higher levels of DNA damage in the dermal papilla as well as senescence of the dermal papilla due to androgen receptor activation and environmental stress. The mechanism by which the androgen receptor triggers dermal papilla permanent senescence is not known, but may involve IL6, TGFB-1 and oxidative stress. Senescence of the dermal papilla is measured by lack of mobility, different size and shape, lower replication and altered output of molecules and different expression of markers. The dermal papilla is the primary location of androgen action and its migration towards the hair bulge and subsequent signaling and size increase are required to maintain the hair follicle so senescence via the androgen receptor explains much of the physiology. Inheritance Male pattern baldness is an X-linked recessive condition, because of its "particularly strong signals on the X chromosome". Metabolic syndrome Multiple cross-sectional studies have found associations between early androgenic alopecia, insulin resistance, and metabolic syndrome, with low HDL being the component of metabolic syndrome with highest association. Linolenic and linoleic acids, two major dietary sources of HDL, are 5 alpha reductase inhibitors. Premature androgenic alopecia and insulin resistance may be a clinical constellation that represents the male homologue, or phenotype, of polycystic ovary syndrome. Others have found a higher rate of hyperinsulinemia in family members of women with polycystic ovarian syndrome. With early-onset AGA having an increased risk of metabolic syndrome, poorer metabolic profiles are noticed in those with AGA, including metrics for body mass index, waist circumference, fasting glucose, blood lipids, and blood pressure.In support of the association, finasteride improves glucose metabolism and decreases glycosylated hemoglobin HbA1c, a surrogate marker for diabetes mellitus. The low SHBG seen with premature androgenic alopecia is also associated with, and likely contributory to, insulin resistance, and for which it still is used as an assay for pediatric diabetes mellitus.Obesity leads to upregulation of insulin production and decrease in SHBG. Further reinforcing the relationship, SHBG is downregulated by insulin in vitro, although SHBG levels do not appear to affect insulin production. In vivo, insulin stimulates both testosterone production and SHBG inhibition in normal and obese men. The relationship between SHBG and insulin resistance has been known for some time; decades prior, ratios of SHBG and adiponectin were used before glucose to predict insulin resistance. Patients with Laron syndrome, with resultant deficient IGF, demonstrate varying degrees of alopecia and structural defects in hair follicles when examined microscopically.Because of its association with metabolic syndrome and altered glucose metabolism, both men and women with early androgenic hair loss should be screened for impaired glucose tolerance and diabetes mellitus II. Measurement of subcutaneous and visceral adipose stores by MRI, demonstrated inverse association between visceral adipose tissue and testosterone/DHT, while subcutaneous adipose correlated negatively with SHBG and positively with estrogen. SHBG association with fasting blood glucose is most dependent on intrahepatic fat, which can be measured by MRI in and out of phase imaging sequences. Serum indices of hepatic function and surrogate markers for diabetes, previously used, show less correlation with SHBG by comparison.Female patients with mineralocorticoid resistance present with androgenic alopecia.IGF levels have been found lower in those with metabolic syndrome. Circulating serum levels of IGF-1 are increased with vertex balding, although this study did not look at mRNA expression at the follicle itself. Locally, IGF is mitogenic at the dermal papillae and promotes elongation of hair follicles. The major site of production of IGF is the liver, although local mRNA expression at hair follicles correlates with increase in hair growth. IGF release is stimulated by growth hormone (GH). Methods of increasing IGF include exercise, hypoglycemia, low fatty acids, deep sleep (stage IV REM), estrogens, and consumption of amino acids such as arginine and leucine. Obesity and hyperglycemia inhibit its release. IGF also circulates in the blood bound to a large protein whose production is also dependent on GH. GH release is dependent on normal thyroid hormone. During the sixth decade of life, GH decreases in production. Because growth hormone is pulsatile and peaks during sleep, serum IGF is used as an index of overall growth hormone secretion. The surge of androgens at puberty drives an accompanying surge in growth hormone. Age A number of hormonal changes occur with aging: Decrease in testosterone Decrease in serum DHT and 5-alpha reductase Decrease 3AAG, a peripheral marker of DHT metabolism Increase in SHBG Decrease in androgen receptors, 5-alpha reductase type I and II activity, and aromatase in the scalpThis decrease in androgens and androgen receptors, and the increase in SHBG are opposite the increase in androgenic alopecia with aging. This is not intuitive, as testosterone and its peripheral metabolite, DHT, accelerate hair loss, and SHBG is thought to be protective. The ratio of T/SHBG, DHT/SHBG decreases by as much as 80% by age 80, in numeric parallel to hair loss, and approximates the pharmacology of antiandrogens such as finasteride.Free testosterone decreases in men by age 80 to levels double that of a woman at age 20. About 30% of normal male testosterone level, the approximate level in females, is not enough to induce alopecia; 60%, closer to the amount found in elderly men, is sufficient. The testicular secretion of testosterone perhaps "sets the stage" for androgenic alopecia as a multifactorial diathesis stress model, related to hormonal predisposition, environment, and age. Supplementing eunuchs with testosterone during their second decade, for example, causes slow progression of androgenic alopecia over many years, while testosterone late in life causes rapid hair loss within a month.An example of premature age effect is Werners syndrome, a condition of accelerated aging from low-fidelity copying of mRNA. Affected children display premature androgenic alopecia.Permanent hair-loss is a result of reduction of the number of living hair matrixes. Long-term of insufficiency of nutrition is an important cause for the death of hair matrixes. Misrepair-accumulation aging theory suggests that dermal fibrosis is associated with the progressive hair-loss and hair-whitening in old people. With age, the dermal layer of the skin has progressive deposition of collagen fibers, and this is a result of accumulation of Misrepairs of derma. Fibrosis makes the derma stiff and makes the tissue have increased resistance to the walls of blood vessels. The tissue resistance to arteries will lead to the reduction of blood supply to the local tissue including the papillas. Dermal fibrosis is progressive; thus the insufficiency of nutrition to papillas is permanent. Senile hair-loss and hair-whitening are partially a consequence of the fibrosis of the skin. Diagnosis The diagnosis of androgenic alopecia can be usually established based on clinical presentation in men. In women, the diagnosis usually requires more complex diagnostic evaluation. Further evaluation of the differential requires exclusion of other causes of hair loss, and assessing for the typical progressive hair loss pattern of androgenic alopecia. Trichoscopy can be used for further evaluation. Biopsy may be needed to exclude other causes of hair loss, and histology would demonstrate perifollicular fibrosis. The Hamilton–Norwood scale has been developed to grade androgenic alopecia in males by severity. Treatment Androgen-dependent Finasteride is a medication of the 5α-reductase inhibitors (5-ARIs) class. By inhibiting type II 5-AR, finasteride prevents the conversion of testosterone to dihydrotestosterone in various tissues including the scalp. Increased hair on the scalp can be seen within three months of starting finasteride treatment and longer-term studies have demonstrated increased hair on the scalp at 24 and 48 months with continued use. Treatment with finasteride more effectively treats male-pattern hair loss at the crown than male-pattern hair loss at the front of the head and temples.Dutasteride is a medication in the same class as finasteride but inhibits both type I and type II 5-alpha reductase. Dutasteride is approved for the treatment of male-pattern hair loss in Korea and Japan, but not in the United States. However, it is commonly used off-label to treat male-pattern hair loss. Androgen-independent Minoxidil dilates small blood vessels; it is not clear how this causes hair to grow. Other treatments include tretinoin combined with minoxidil, ketoconazole shampoo, dermarolling (Collagen induction therapy), spironolactone, alfatradiol, topilutamide (fluridil), topical melatonin, and intradermal and intramuscular botulinum toxin injections to the scalp. Female pattern There is evidence supporting the use of minoxidil as a safe and effective treatment for female pattern hair loss, and there is no significant difference in efficiency between 2% and 5% formulations. Finasteride was shown to be no more effective than placebo based on low-quality studies. The effectiveness of laser-based therapies is unclear. Bicalutamide, an antiandrogen, is another option for the treatment of female pattern hair loss. Procedures More advanced cases may be resistant or unresponsive to medical therapy and require hair transplantation. Naturally occurring units of one to four hairs, called follicular units, are excised and moved to areas of hair restoration. These follicular units are surgically implanted in the scalp in close proximity and in large numbers. The grafts are obtained from either follicular unit transplantation (FUT) or follicular unit extraction (FUE). In the former, a strip of skin with follicular units is extracted and dissected into individual follicular unit grafts, and in the latter individual hairs are extracted manually or robotically. The surgeon then implants the grafts into small incisions, called recipient sites. Cosmetic scalp tattoos can also mimic the appearance of a short, buzzed haircut. Alternative therapies Many people use unproven treatments. Regarding female pattern alopecia, there is no evidence for vitamins, minerals, or other dietary supplements. As of 2008, there is little evidence to support the use of lasers to treat male-pattern hair loss. The same applies to special lights. Dietary supplements are not typically recommended. A 2015 review found a growing number of papers in which plant extracts were studied but only one randomized controlled clinical trial, namely a study in 10 people of saw palmetto extract. Prognosis Androgenic alopecia is typically experienced as a "moderately stressful condition that diminishes body image satisfaction". However, although most men regard baldness as an unwanted and distressing experience, they usually are able to cope and retain integrity of personality.Although baldness is not as common in women as in men, the psychological effects of hair loss tend to be much greater. Typically, the frontal hairline is preserved, but the density of hair is decreased on all areas of the scalp. Previously, it was believed to be caused by testosterone just as in male baldness, but most women who lose hair have normal testosterone levels. Epidemiology Female androgenic alopecia has become a growing problem that, according to the American Academy of Dermatology, affects around 30 million women in the United States. Although hair loss in females normally occurs after the age of 50 or even later when it does not follow events like pregnancy, chronic illness, crash diets, and stress among others, it is now occurring at earlier ages with reported cases in women as young as 15 or 16.For male androgenic alopecia, by the age of 50 30-50% of men have it, hereditarily there is an 80% predisposition. Notably, the link between androgenetic alopecia and metabolic syndrome is strongest in non-obese men. Society and culture Studies have been inconsistent across cultures regarding how balding men rate on the attraction scale. While a 2001 South Korean study showed that most people rated balding men as less attractive, a 2002 survey of Welsh women found that they rated bald and gray-haired men quite desirable. One of the proposed social theories for male pattern hair loss is that men who embraced complete baldness by shaving their heads subsequently signaled dominance, high social status, and/or longevity.Biologists have hypothesized the larger sunlight-exposed area would allow more vitamin D to be synthesized, which might have been a "finely tuned mechanism to prevent prostate cancer" as the malignancy itself is also associated with higher levels of DHT. Myths Many myths exist regarding the possible causes of baldness and its relationship with ones virility, intelligence, ethnicity, job, social class, wealth, and many other characteristics. Weight training and other types of physical activity cause baldness Because it increases testosterone levels, many Internet forums have put forward the idea that weight training and other forms of exercise increase hair loss in predisposed individuals. Although scientific studies do support a correlation between exercise and testosterone, no direct study has found a link between exercise and baldness. However, a few have found a relationship between a sedentary life and baldness, suggesting exercise is causally relevant. The type or quantity of exercise may influence hair loss. Testosterone levels are not a good marker of baldness, and many studies actually show paradoxical low testosterone in balding persons, although research on the implications is limited. Baldness can be caused by emotional stress, sleep deprivation, etc. Emotional stress has been shown to accelerate baldness in genetically susceptible individuals. Stress due to sleep deprivation in military recruits lowered testosterone levels, but is not noted to have affected SHBG. Thus, stress due to sleep deprivation in fit males is unlikely to elevate DHT, which is one cause of male pattern baldness. Whether sleep deprivation can cause hair loss by some other mechanism is not clear. Bald men are more virile or sexually active than others Levels of free testosterone are strongly linked to libido and DHT levels, but unless free testosterone is virtually nonexistent, levels have not been shown to affect virility. Men with androgenic alopecia are more likely to have a higher baseline of free androgens. However, sexual activity is multifactoral, and androgenic profile is not the only determining factor in baldness. Additionally, because hair loss is progressive and free testosterone declines with age, a males hairline may be more indicative of his past than his present disposition. Frequent ejaculation causes baldness Many misconceptions exist about what can help prevent hair loss, one of these being that lack of sexual activity will automatically prevent hair loss. While a proven direct correlation exists between increased frequency of ejaculation and increased levels of DHT, as shown in a recent study by Harvard Medical School, the study suggests that ejaculation frequency may be a sign, rather than a cause, of higher DHT levels. Another study shows that although sexual arousal and masturbation-induced orgasm increase testosterone concentration around orgasm, they reduce testosterone concentration on average, and because about 5% of testosterone is converted to DHT, ejaculation does not elevate DHT levels.The only published study to test correlation between ejaculation frequency and baldness was probably large enough to detect an association (1,390 subjects) and found no correlation, although persons with only vertex androgenetic alopecia had fewer female sexual partners than those of other androgenetic alopecia categories (such as frontal or both frontal and vertex). One study may not be enough, especially in baldness, where there is a complex with age. Other animals Animal models of androgenic alopecia occur naturally and have been developed in transgenic mice; chimpanzees (Pan troglodytes); bald uakaris (Cacajao rubicundus); and stump-tailed macaques (Macaca speciosa and M. arctoides). Of these, macaques have demonstrated the greatest incidence and most prominent degrees of hair loss.Baldness is not a trait unique to human beings. One possible case study is about a maneless male lion in the Tsavo area. The Tsavo lion prides are unique in that they frequently have only a single male lion with usually seven or eight adult females, as opposed to four females in other lion prides. Male lions may have heightened levels of testosterone, which could explain their reputation for aggression and dominance, indicating that lack of mane may at one time have had an alpha correlation.Although primates do not go bald, their hairlines do undergo recession. In infancy the hairline starts at the top of the supraorbital ridge, but slowly recedes after puberty to create the appearance of a small forehead. References External links NLM- Genetics Home Reference Scow DT, Nolte RS, Shaughnessy AF (April 1999). "Medical treatments for balding in men". American Family Physician. 59 (8): 2189–94, 2196. PMID 10221304.

Hey Aarogya, could you help me understand about Malignant hyperthermia

Malignant hyperthermia

Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, high fever, and a fast heart rate. Complications can include muscle breakdown and high blood potassium. Most people who are susceptible are generally otherwise unaffected when not exposed.The cause of MH is the use of certain volatile anesthetic agents or succinylcholine in those who are susceptible. Susceptibility can occur due to at least six genetic mutations, with the most common one being of the RYR1 gene. These genetic variations are often inherited from a persons parents in an autosomal dominant manner. The condition may also occur as a new mutation or be associated with a number of inherited muscle diseases, such as central core disease.In susceptible individuals, the medications induce the release of stored calcium ions within muscle cells. The resulting increase in calcium concentrations within the cells cause the muscle fibers to contract. This generates excessive heat and results in metabolic acidosis. Diagnosis is based on symptoms in the appropriate situation. Family members may be tested to see if they are susceptible by muscle biopsy or genetic testing.Treatment is with dantrolene and rapid cooling along with other supportive measures. The avoidance of potential triggers is recommended in susceptible people. The condition affects one in 5,000 to 50,000 cases where people are given anesthetic gases. Males are more often affected than females. The risk of death with proper treatment is about 5% while without it is around 75%. While cases that appear similar to MH have been documented since the early 20th century, the condition was only formally recognized in 1960. Signs and symptoms The typical signs of malignant hyperthermia are due to a hypercatabolic state, which presents as a very high temperature, an increased heart rate and abnormally rapid breathing, increased carbon dioxide production, increased oxygen consumption, mixed acidosis, rigid muscles, and rhabdomyolysis. These signs can develop any time during the administration of the anesthetic triggering agents. Rarely, signs may develop up to 40 minutes after the end of anaesthesia. Causes Malignant hyperthermia is a disorder that can be considered a gene–environment interaction. In most people with malignant hyperthermia susceptibility, they have few or no symptoms unless they are exposed to a triggering agent. The most common triggering agents are volatile anesthetic gases, such as halothane, sevoflurane, desflurane, isoflurane, enflurane or the depolarizing muscle relaxants suxamethonium and decamethonium used primarily in general anesthesia. In rare cases, the biological stresses of physical exercise or heat may be the trigger. In fact, malignant hyperthermia susceptibility (MHS), predisposed by mutations in the skeletal muscle calcium release channel (RYR1), is one of the most severe heat-related illnesses. The MHS-associated heat susceptibilities predominantly affect children and metabolically active young adults, often leading to life- threatening hypermetabolic responses to heat.Other anesthetic drugs do not trigger malignant hyperthermia. Some examples of drugs that dont cause MH include local anesthetics (lidocaine, bupivacaine, mepivacaine), opiates (morphine, fentanyl), ketamine, barbiturates, nitrous oxide, propofol, etomidate, and benzodiazepines. The nondepolarizing muscle relaxants pancuronium, cisatracurium, atracurium, mivacurium, vecuronium and rocuronium also do not cause MH.There is mounting evidence that some individuals with malignant hyperthermia susceptibility may develop MH with exercise and/or on exposure to hot environments. Genetics Malignant hyperthermias inheritance is autosomal dominant with variable penetrance. The defect is typically located on the long arm of chromosome 19 (19q13.2) involving the ryanodine receptor. More than 25 different mutations in this gene are linked with malignant hyperthermia. These mutations tend to cluster in one of three domains within the protein, designated MH1-3. MH1 and MH2 are located in the N-terminus of the protein, which interacts with L-type calcium channels and Ca2+. MH3 is located in the transmembrane forming C-terminus. This region is important for allowing Ca2+ passage through the protein following opening.Chromosome 7q and chromosome 17 have also been implicated. It has also been postulated that MH and central core disease may be allelic and thus can be co-inherited. Pathophysiology Disease mechanism In a large proportion (50–70%) of cases, the propensity for malignant hyperthermia is due to a mutation of the ryanodine receptor (type 1), located on the sarcoplasmic reticulum (SR), the organelle within skeletal muscle cells that stores calcium. RYR1 opens in response to conformational changes in the L-type calcium channels following membrane depolarisation, thereby resulting in a drastic increase in intracellular calcium levels and muscle contraction. RYR1 has two sites believed to be important for reacting to changing Ca2+ concentrations: the A-site and the I-site. The A-site is a high affinity Ca2+ binding site that mediates RYR1 opening. The I-site is a lower affinity site that mediates the proteins closing. Caffeine, halothane, and other triggering agents act by drastically increasing the affinity of the A-site for Ca2+ and concomitantly decreasing the affinity of the I-site in mutant proteins. Mg2+ also affect RYR1 activity, causing the protein to close by acting at either the A- or I-sites. In MH mutant proteins, the affinity for Mg2+ at either one of these sites is greatly reduced. The result of these alterations is greatly increased Ca2+ release due to a lowered activation and heightened deactivation threshold. The process of sequestering this excess Ca2+ consumes large amounts of adenosine triphosphate (ATP), the main cellular energy carrier, and generates the excessive heat (hyperthermia) that is the hallmark of the disease. The muscle cell is damaged by the depletion of ATP and possibly the high temperatures, and cellular constituents "leak" into the circulation, including potassium, myoglobin, creatine, phosphate and creatine kinase.The other known causative gene for MH is CACNA1S, which encodes an L-type voltage-gated calcium channel α-subunit. There are two known mutations in this protein, both affecting the same residue, R1086. This residue is located in the large intracellular loop connecting domains 3 and 4, a domain possibly involved in negatively regulating RYR1 activity. When these mutant channels are expressed in human embryonic kidney (HEK 293) cells, the resulting channels are five times more sensitive to activation by caffeine (and presumably halothane) and activate at 5–10mV more hyperpolarized. Furthermore, cells expressing these channels have an increased basal cytosolic Ca2+ concentration. As these channels interact with and activate RYR1, these alterations result in a drastic increase of intracellular Ca2+, and, thereby, muscle excitability.Other mutations causing MH have been identified, although in most cases the relevant gene remains to be identified. Animal model Research into malignant hyperthermia was limited until the discovery of "porcine stress syndrome" (PSS) in Danish Landrace and other pig breeds selected for muscling, a condition in which stressed pigs develop "pale, soft, exudative" flesh (a manifestation of the effects of malignant hyperthermia) rendering their meat less marketable at slaughter. This "awake triggering" was not observed in humans, and initially cast doubts on the value of the animal model, but subsequently, susceptible humans were discovered to "awake trigger" (develop malignant hyperthermia) in stressful situations. This supported the use of the pig model for research. Pig farmers use halothane cones in swine yards to expose piglets to halothane. Those that die were MH-susceptible, thus saving the farmer the expense of raising a pig whose meat he would not be able to market. This also reduced the use of breeding stock carrying the genes for PSS. The condition in swine is also due to a defect in ryanodine receptors.Gillard et al. discovered the causative mutation in humans only after similar mutations had first been described in pigs.Horses also develop malignant hyperthermia. A causative mutated allele, ryanodine receptor 1 gene (RyR1) at nucleotide C7360G, generating a R2454G amino acid substitution. has been identified in the American Quarter Horse and breeds with Quarter Horse ancestry, inherited as an autosomal dominant. It can be caused by overwork, anesthesia, or stress. In dogs, its inheritance is autosomal recessive.An MH mouse has been constructed, bearing the R163C mutation prevalent in humans. These mice display signs similar to human MH patients, including sensitivity to halothane (increased respiration, body temperature, and death). Blockade of RYR1 by dantrolene prevents adverse reaction to halothane in these mice, as with humans. Muscle from these mice also shows increased K+-induced depolarization and an increased caffeine sensitivity. Diagnosis During an attack The earliest signs may include: masseter muscle contracture following administration of succinylcholine, a rise in end-tidal carbon dioxide concentration (despite increased minute ventilation), unexplained tachycardia, and muscle rigidity. Despite the name, elevation of body temperature is often a late sign, but may appear early in severe cases. Respiratory acidosis is universally present and many patients have developed metabolic acidosis at the time of diagnosis. A fast rate of breathing (in a spontaneously breathing patient), cyanosis, hypertension, abnormal heart rhythms, and high blood potassium may also be seen. Core body temperatures should be measured in any patient undergoing general anesthesia longer than 30 minutes. Malignant hyperthermia is diagnosed on clinical grounds, but various laboratory investigations may prove confirmatory. These include a raised creatine kinase level, elevated potassium, increased phosphate (leading to decreased calcium) and—if determined—raised myoglobin; this is the result of damage to muscle cells. Severe rhabdomyolysis may lead to acute kidney failure, so kidney function is generally measured on a frequent basis. Patients may also experience premature ventricular contractions due to the increased levels of potassium released from the muscles during episodes. Susceptibility testing Muscle testing The main candidates for testing are those with a close relative who has had an episode of MH or have been shown to be susceptible. The standard procedure is the "caffeine-halothane contracture test", CHCT. A muscle biopsy is carried out at an approved research center, under local anesthesia. The fresh biopsy is bathed in solutions containing caffeine or halothane and observed for contraction; under good conditions, the sensitivity is 97% and the specificity 78%. Negative biopsies are not definitive, so any patient who is suspected of MH by their medical history or that of blood relatives is generally treated with non-triggering anesthetics, even if the biopsy was negative. Some researchers advocate the use of the "calcium-induced calcium release" test in addition to the CHCT to make the test more specific.Less invasive diagnostic techniques have been proposed. Intramuscular injection of halothane 6 vol% has been shown to result in higher than normal increases in local pCO2 among patients with known malignant hyperthermia susceptibility. The sensitivity was 100% and specificity was 75%. For patients at similar risk to those in this study, this leads to a positive predictive value of 80% and negative predictive value of 100%. This method may provide a suitable alternative to more invasive techniques. A 2002 study examined another possible metabolic test. In this test, intramuscular injection of caffeine was followed by local measurement of the pCO2; those with known MH susceptibility had a significantly higher pCO2 (63 versus 44 mmHg). The authors propose larger studies to assess the tests suitability for determining MH risk. Genetic testing Genetic testing is being performed in a limited fashion to determine susceptibility to MH. In people with a family history of MH, analysis for RYR1 mutations may be useful. Criteria A 1994 consensus conference led to the formulation of a set of diagnostic criteria. The higher the score (above 6), the more likely a reaction constituted MH: Respiratory acidosis (end-tidal CO2 above 55 mmHg/7.32 kPa or arterial pCO2 above 60 mmHg/7.98 kPa) Heart involvement (unexplained sinus tachycardia, ventricular tachycardia or ventricular fibrillation) Metabolic acidosis (base excess lower than -8, pH <7.25) Muscle rigidity (generalized rigidity including severe masseter muscle rigidity) Muscle breakdown (CK >20,000/L units, cola colored urine or excess myoglobin in urine or serum, potassium above 6 mmol/L) Temperature increase (rapidly increasing temperature, T >38.8 °C) Other (rapid reversal of MH signs with dantrolene, elevated resting serum CK levels) Family history (autosomal dominant pattern) Prevention In the past, the prophylactic use of dantrolene was recommended for MH-susceptible patients undergoing general anesthesia. However, multiple retrospective studies have demonstrated the safety of trigger-free general anesthesia in these patients in the absence of prophylactic dantrolene administration. The largest of these studies looked at the charts of 2214 patients who underwent general or regional anesthesia for an elective muscle biopsy. About half (1082) of the patients were muscle biopsy positive for MH. Only five of these patients exhibited signs consistent with MH, four of which were treated successfully with parenteral dantrolene, and the remaining one recovered with only symptomatic therapy. After weighing its questionable benefits against its possible adverse effects (including nausea, vomiting, muscle weakness and prolonged duration of action of nondepolarizing neuromuscular blocking agents), experts no longer recommend the use of prophylactic dantrolene prior to trigger-free general anesthesia in MH-susceptible patients. Anesthesia machine preparation Anesthesia for people with known MH susceptible requires avoidance of triggering agent concentrations above 5 parts per million (all volatile anesthetic agents and succinylcholine). Most other drugs are safe (including nitrous oxide), as are regional anesthetic techniques. Where general anesthesia is planned, it can be provided safely by either flushing the machine or using charcoal filters.To flush the machine, first remove or disable the vaporizers and then flush the machine with 10 L/min or greater fresh gas flow rate for at least 20 minutes. While flushing the machine the ventilator should be set to periodically ventilate a new breathing circuit. The soda lime should also be replaced. After machine preparation, anesthesia should be induced and maintained with non-triggering agents. The time required to flush a machine varies for different machines and volatile anesthetics. This prevention technique was optimized to prepare older generation anesthesia machines. Modern anesthetic machines have more rubber and plastic components which provide a reservoir for volatile anesthetics, and should be flushed for 60 minutes.Charcoal filters can be used to prepare an anesthesia machine in less than 60 seconds for people at risk of malignant hyperthermia. These filters prevent residual anesthetic from triggering malignant hyperthermia for up to 12 hours, even at low fresh gas flows. Prior to placing the charcoal filters, the machine should be flushed with fresh gas flows greater than 10 L/min for 90 seconds. Treatment The current treatment of choice is the intravenous administration of dantrolene, the only known antidote, discontinuation of triggering agents, and supportive therapy directed at correcting hyperthermia, acidosis, and organ dysfunction. Treatment must be instituted rapidly on clinical suspicion of the onset of malignant hyperthermia. Dantrolene Dantrolene is a muscle relaxant that appears to work directly on the ryanodine receptor to prevent the release of calcium. After the widespread introduction of treatment with dantrolene, the mortality of malignant hyperthermia fell from 80% in the 1960s to less than 5%. Dantrolene remains the only drug known to be effective in the treatment of MH. The recommended dose of dantrolene is 2.5 mg/kg, repeated as necessary. It is recommended that each hospital keeps a minimum stock of 36 dantrolene vials (720 mg), sufficient for four doses in a 70-kg person. Training Fast recognition and treatment of MH utilizes skills and procedures that are utilized with a low-frequency and high-risk. Conducting MH crisis training for perioperative teams can identify system failures as well as improve response to these events. Simulation techniques to include the use of cognitive aids have also been shown to improve communication in clinical treatment of MH. Prognosis Prognosis is poor if this condition is not aggressively treated. In the 1970s, mortality was greater than 80%; however, with the current management mortality is now less than 5%. Epidemiology It occurs in between 1:5,000 and 1:100,000 in procedures involving general anaesthesia. This disorder occurs worldwide and affects all racial groups. In the Manawatu region of New Zealand, up to 1 in 200 people are at high risk of the condition. History The syndrome was first recognized in Royal Melbourne Hospital, Australia in an affected family by Denborough et al. in 1962. Denborough did much of his subsequent work on the condition at the Royal Canberra Hospital. Similar reactions were found in pigs. The efficacy of dantrolene as a treatment was discovered by South African anesthesiologist Gaisford Harrison and reported in a 1975 article published in the British Journal of Anaesthesia. After further animal studies corroborated the possible benefit from dantrolene, a 1982 study confirmed its usefulness in humans.In 1981, the Malignant Hyperthermia Association of the United States (MHAUS) hotline was established to provide telephone support to clinical teams treating patients with suspected malignant hyperthermia. The hotline became active in 1982 and since that time MHAUS has provided continuous access to board-certified anesthesiologists to assist teams in treatment. Other animals Other animals, including certain pig breeds, dogs, and horses, are susceptible to malignant hyperthermia.In dogs its inheritance is autosomal dominant. The syndrome has been reported in Pointers, Greyhounds, Labrador Retrievers, Saint Bernards, Springer Spaniels, Bichon Frises, Golden Retrievers, and Border Collies.In pigs its inheritance is autosomal recessive.In horses its inheritance is autosomal dominant, and most associated with the American Quarter Horse although it can occur in other breeds. Research Azumolene is a 30-fold more water-soluble analog of dantrolene that also works to decrease the release of intracellular calcium by its action on the ryanodine receptor. In MH-susceptible swine, azumolene was as potent as dantrolene. It has yet to be studied in vivo in humans, but may present a suitable alternative to dantrolene in the treatment of MH. References External links GeneReview/NIH/UW entry on Malignant Hyperthermia Susceptibility

Hello Aarogya, could you help me understand about Breast pain

Breast pain

Breast pain is the symptom of discomfort in the breast. Pain that involves both breasts and which occurs repeatedly before the menstrual period is generally not serious. Pain that involves only one part of a breast is more concerning. It is particularly concerning if a hard mass or nipple discharge is also present.Causes may be related to the menstrual cycle, birth control pills, hormone therapy, or psychiatric medication. Pain may also occur in those with large breasts, during menopause, and in early pregnancy. In about 2% of cases breast pain is related to breast cancer. Diagnosis involves examination, with medical imaging if only a specific part of the breast hurts.In more than 75% of people the pain resolves without any specific treatment. Otherwise treatments may include paracetamol or NSAIDs. A well fitting bra may also help. In those with severe pain tamoxifen or danazol may be used. About 70% of women have breast pain at some point in time. Breast pain is one of the most common breast symptoms, along with breast masses and nipple discharge. Causes Cyclical breast pain is often associated with fibrocystic breast changes or duct ectasia and thought to be caused by changes of prolactin response to thyrotropin. Some degree of cyclical breast tenderness is normal in the menstrual cycle, and is usually associated with menstruation and/or premenstrual syndrome (PMS).Noncyclical breast pain has various causes and is harder to diagnose and frequently the root cause is outside the breast. Some degree of non-cyclical breast tenderness can normally be present due to hormonal changes in puberty (both in girls and boys), in menopause and during pregnancy. After pregnancy, breast pain can be caused by breastfeeding. Other causes of non-cyclical breast pain include alcoholism with liver damage (likely due to abnormal steroid metabolism), mastitis and medications such as digitalis, methyldopa (an antihypertensive), spironolactone, certain diuretics, oxymetholone (an anabolic steroid), and chlorpromazine (a typical antipsychotic). Also, shingles can cause a painful blistering rash on the skin of the breasts. Breast cancer Some women who have pain in one or both breasts may fear breast cancer. However, breast pain is not a common symptom of cancer. The great majority of breast cancer cases do not present with symptoms of pain, though breast pain in older women is more likely to be associated with cancer. Diagnosis Diagnosis involves breast examination, with medical imaging if only a specific part of the breast hurts. Medical imaging by ultrasound is recommended for all ages, well in those over 30 it is recommended together with mammography.Ruling out the other possible causes of the pain is one way to differentiate the source of the pain. Breast pain can be due to: Medications can be associated with breast pain and include: Diagnostic testing can be useful. Typical tests used are mammogram, excisional biopsy for solid lumps, fine-needle aspiration and biopsy, pregnancy test, ultrasonography, and magnetic resonance imaging (MRI). Treatment In more than 75% of people the pain resolves without any specific treatment. Otherwise treatments may include paracetamol or NSAIDs. A well fitting bra may also help. In those with severe pain tamoxifen or danazol may be used.Bromocriptine may be used as well.Spironolactone, low dose oral contraceptives, and low-dose estrogen have helped to relieve pain. Topical anti-inflammatory medications can be used for localized pain. Vitamin E is not effective in relieving pain nor is evening primrose oil. Vitamin B6 and vitamin A have not been consistently found to be beneficial. Flaxseed has shown some activity in the treatment of cyclic mastalgia.Pain may be relieved by the use of nonsteroidal anti-inflammatory drugs or, for more severe localized pain, by local anaesthetic. Pain may be relieved by reassurance that it does not signal a serious underlying problem, and an active life style can also effect an improvement.Information regarding how the pain is real but not necessarily caused by disease can help to understand the problem. Counseling can also be to describe changes that vary during the monthly cycle. Women on hormone replacement therapy may benefit from a dose adjustment. Another non-pharmacological measure to help relieve symptoms of pain may be to use good bra support. Breasts change during adolescence and menopause and refitting may be beneficial. Applying heat and/or ice can bring relief. Dietary changes may also help with the pain. Methylxanthines can be eliminated from the diet to see if a sensitivity is present. Some clinicians recommending a reduction in salt, though no evidence supports this practice. See also Galactagogue Mammoplasia Pain management References == External links ==

Hey Aarogya!, what is Megaloblastic anemia

Megaloblastic anemia

Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis. Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias. The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically vitamin B12 deficiency or folate deficiency. Loss of micronutrients may also be a cause. Megaloblastic anemia not due to hypovitaminosis may be caused by antimetabolites that poison DNA production directly, such as some chemotherapeutic or antimicrobial agents (for example azathioprine or trimethoprim). The pathological state of megaloblastosis is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow and also by hypersegmented neutrophils (defined as the presence of neutrophils with six or more lobes or the presence of more than 3% of neutrophils with at least five lobes). These hypersegmented neutrophils can be detected in the peripheral blood (using a diagnostic smear of a blood sample). Causes Vitamin B12 deficiency: Achlorhydria-induced malabsorption Deficient intake Deficient intrinsic factor, a molecule produced by cells in the stomach that is required for B12 absorption (pernicious anemia or gastrectomy) Coeliac disease Biological competition for vitamin B12 by diverticulosis, fistula, intestinal anastomosis, or infection by the marine parasite Diphyllobothrium latum (fish tapeworm) Selective vitamin B12 malabsorption (congenital—juvenile megaloblastic anemia 1—and drug-induced) Chronic pancreatitis Ileal resection and bypass Nitrous oxide anesthesia (usually requires repeated instances). Folate deficiency: Alcoholism Deficient intake Increased needs: pregnancy, infant, rapid cellular proliferation, and cirrhosis Malabsorption (congenital and drug-induced) Intestinal and jejunal resection (indirect) Deficient thiamine and factors (e.g., enzymes) responsible for abnormal folate metabolism. Combined Deficiency: vitamin B12 & folate. Inherited Pyrimidine Synthesis Disorders: Orotic aciduria Inherited DNA Synthesis Disorders Toxins and Drugs: Folic acid antagonists (methotrexate) Purine synthesis antagonists (6-mercaptopurine, azathioprine) Pyrimidine antagonists (cytarabine) Phenytoin Nitrous Oxide Erythroleukemia Inborn genetic mutations of the Methionine synthase gene Di Guglielmos syndrome Congenital dyserythropoietic anemia Copper deficiency resulting from an excess of zinc from unusually high oral consumption of zinc-containing denture-fixation creams has been found to be a cause. Pathophysiology There is a defect in DNA synthesis in the rapidly dividing cells and to a lesser extent, RNA and protein synthesis are also impaired. Therefore, unbalanced cell proliferation and impaired cell division occur as a result of arrested nuclear maturation so the cells show nuclear-cytoplasmic asynchrony. In the bone marrow, most megaloblasts are destroyed prior to entering the peripheral blood (intramedullary hemolysis). Some can escape the bone marrow (macrocytes) to peripheral blood but they are destroyed by the reticulo-endothelial system (extramedullary hemolysis). Diagnosis The gold standard for the diagnosis of Vitamin B12 deficiency is a low blood level of Vitamin B12. A low level of blood Vitamin B12 is a finding that normally can and should be treated by injections, supplementation, or dietary or lifestyle advice, but it is not a diagnosis. Hypovitaminosis B12 can result from a number of mechanisms, including those listed above. For determination of cause, further patient history, testing, and empirical therapy may be clinically indicated. A measurement of methylmalonic acid (methylmalonate) can provide an indirect method for partially differentiating Vitamin B12 and folate deficiencies. The level of methylmalonic acid is not elevated in folic acid deficiency. Direct measurement of blood cobalamin remains the gold standard because the test for elevated methylmalonic acid is not specific enough. Vitamin B12 is one necessary prosthetic group to the enzyme methylmalonyl-coenzyme A mutase. Vitamin B12 deficiency is but one among the conditions that can lead to dysfunction of this enzyme and a buildup of its substrate, methylmalonic acid, the elevated level of which can be detected in the urine and blood. Due to the lack of available radioactive Vitamin B12, the Schilling test is now largely a historical artifact. The Schilling test was performed in the past to help determine the nature of the vitamin B12 deficiency. An advantage of the Schilling test was that it often included Vitamin B12 with intrinsic factor. Blood findings The blood film can point towards vitamin deficiency: Decreased red blood cell (RBC) count and hemoglobin levels Increased mean corpuscular volume (MCV, >100 fL) and mean corpuscular hemoglobin (MCH) Normal mean corpuscular hemoglobin concentration (MCHC, 32–36 g/dL) Decreased reticulocyte count due to destruction of fragile and abnormal megaloblastic erythroid precursor. The platelet count may be reduced. Neutrophil granulocytes may show multisegmented nuclei ("senile neutrophil"). This is thought to be due to decreased production and a compensatory prolonged lifespan for circulating neutrophils, which increase numbers of nuclear segments with age. Anisocytosis (increased variation in RBC size) and poikilocytosis (abnormally shaped RBCs). Macrocytes (larger than normal RBCs) are present. Ovalocytes (oval-shaped RBCs) are present. Howell-Jolly bodies (chromosomal remnant) also present.Blood chemistries will also show: An increased lactic acid dehydrogenase (LDH) level. The isozyme is LDH-2 which is typical of the serum and hematopoietic cells. Increased homocysteine and methylmalonic acid in Vitamin B12 deficiency Increased homocysteine in folate deficiencyNormal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty.Bone marrow (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic hyperplasia. See also List of circulatory system conditions List of hematologic conditions References External links GeneReview/NCBI/NIH/UW entry on Thiamine-Responsive Megaloblastic Anemia Syndrome Rare Anemias Foundation

Hey Aarogya!, what is Mercury poisoning

Mercury poisoning

Mercury poisoning is a type of metal poisoning due to exposure to mercury. Symptoms depend upon the type, dose, method, and duration of exposure. They may include muscle weakness, poor coordination, numbness in the hands and feet, skin rashes, anxiety, memory problems, trouble speaking, trouble hearing, or trouble seeing. High-level exposure to methylmercury is known as Minamata disease. Methylmercury exposure in children may result in acrodynia (pink disease) in which the skin becomes pink and peels. Long-term complications may include kidney problems and decreased intelligence. The effects of long-term low-dose exposure to methylmercury are unclear.Forms of mercury exposure include metal, vapor, salt, and organic compound. Most exposure is from eating fish, amalgam-based dental fillings, or exposure at a workplace. In fish, those higher up in the food chain generally have higher levels of mercury, a process known as biomagnification. Less commonly, poisoning may occur as a method of attempted suicide. Human activities that release mercury into the environment include the burning of coal and mining of gold. Tests of the blood, urine, and hair for mercury are available but do not relate well to the amount in the body.Prevention includes eating a diet low in mercury, removing mercury from medical and other devices, proper disposal of mercury, and not mining further mercury. In those with acute poisoning from inorganic mercury salts, chelation with either dimercaptosuccinic acid (DMSA) or dimercaptopropane sulfonate (DMPS) appears to improve outcomes if given within a few hours of exposure. Chelation for those with long-term exposure is of unclear benefit. In certain communities that survive on fishing, rates of mercury poisoning among children have been as high as 1.7 per 100. Signs and symptoms Common symptoms of mercury poisoning include peripheral neuropathy, presenting as paresthesia or itching, burning, pain, or even a sensation that resembles small insects crawling on or under the skin (formication); skin discoloration (pink cheeks, fingertips and toes); swelling; and desquamation (shedding or peeling of skin).Mercury irreversibly inhibits selenium-dependent enzymes (see below) and may also inactivate S-adenosyl-methionine, which is necessary for catecholamine catabolism by catechol-O-methyl transferase. Due to the bodys inability to degrade catecholamines (e.g. adrenaline), a person with mercury poisoning may experience profuse sweating, tachycardia (persistently faster-than-normal heart beat), increased salivation, and hypertension (high blood pressure).Affected children may show red cheeks, nose and lips, loss of hair, teeth, and nails, transient rashes, hypotonia (muscle weakness), and increased sensitivity to light. Other symptoms may include kidney dysfunction (e.g. Fanconi syndrome) or neuropsychiatric symptoms such as emotional lability, memory impairment, or insomnia.Thus, the clinical presentation may resemble pheochromocytoma or Kawasaki disease. Desquamation (skin peeling) can occur with severe mercury poisoning acquired by handling elemental mercury. Causes Consumption of fish containing mercury is by far the most significant source of ingestion-related mercury exposure in humans, although plants and livestock also contain mercury due to bioconcentration of organic mercury from seawater, freshwater, marine and lacustrine sediments, soils, and atmosphere, and due to biomagnification by ingesting other mercury-containing organisms. Exposure to mercury can occur from breathing contaminated air, from eating foods that have acquired mercury residues during processing, from exposure to mercury vapor in mercury amalgam dental restorations, and from improper use or disposal of mercury and mercury-containing objects, for example, after spills of elemental mercury or improper disposal of fluorescent lamps.All of these, except elemental liquid mercury, produce toxicity or death with less than a gram. Mercurys zero oxidation state (Hg0) exists as vapor or as liquid metal, its mercurous state (Hg+) exists as inorganic salts, and its mercuric state (Hg2+) may form either inorganic salts or organomercury compounds.Consumption of whale and dolphin meat, as is the practice in Japan, is a source of high levels of mercury poisoning. Tetsuya Endo, a professor at the Health Sciences University of Hokkaido, has tested whale meat purchased in the whaling town of Taiji and found mercury levels more than 20 times the acceptable Japanese standard.Human-generated sources, such as coal-burning power plants emit about half of atmospheric mercury, with natural sources such as volcanoes responsible for the remainder. A 2021 publication investigating the mercury distribution in European soils found that high mercury concentrations are found close to abandoned mines Almadén (Castilla-La Mancha, Spain), Mt. Amiata (Italy), Idrija (Slovenia) and Rudnany (Slovakia)] and coal-fired power plants. An estimated two-thirds of human-generated mercury comes from stationary combustion, mostly of coal. Other important human-generated sources include gold production, nonferrous metal production, cement production, waste disposal, human crematoria, caustic soda production, pig iron and steel production, mercury production (mostly for batteries), and biomass burning.Small independent gold-mining operation workers are at higher risk of mercury poisoning because of crude processing methods. Such is the danger for the galamsey in Ghana and similar workers known as orpailleurs in neighboring francophone countries. While no official government estimates of the labor force have been made, observers believe 20,000–50,000 work as galamseys in Ghana, a figure including many women, who work as porters. Similar problems have been reported amongst the gold miners of Indonesia.Some mercury compounds, especially organomercury compounds, can also be readily absorbed through direct skin contact. Mercury and its compounds are commonly used in chemical laboratories, hospitals, dental clinics, and facilities involved in the production of items such as fluorescent light bulbs, batteries, and explosives.Many traditional medicines, including ones used in Ayurvedic medicine and Traditional Chinese medicine, contain mercury and other heavy metals. Sources Compounds of mercury tend to be much more toxic than either the elemental form or the salts. These compounds have been implicated in causing brain and liver damage. The most dangerous mercury compound, dimethylmercury, is so toxic that even a few microliters spilled on the skin, or even on a latex glove, can cause death. Methylmercury and related organomercury compounds Methylmercury is the major source of organic mercury for all individuals. Due to bioaccumulation it works its way up through the food web and thus biomagnifies, resulting in high concentrations among populations of some species. Top predatory fish, such as tuna or swordfish, are usually of greater concern than smaller species. The US FDA and the EPA advise women of child-bearing age, nursing mothers, and young children to completely avoid swordfish, shark, king mackerel and tilefish from the Gulf of Mexico, and to limit consumption of albacore ("white") tuna to no more than 170 g (6 oz) per week, and of all other fish and shellfish to no more than 340 g (12 oz) per week. A 2006 review of the risks and benefits of fish consumption found, for adults, the benefits of one to two servings of fish per week outweigh the risks, even (except for a few fish species) for women of childbearing age, and that avoidance of fish consumption could result in significant excess coronary heart disease deaths and suboptimal neural development in children.Because the process of mercury-dependent sequestration of selenium is slow, the period between exposure to methylmercury and the appearance of symptoms in adult poisoning cases tends to be extended. The longest recorded latent period is five months after a single exposure, in the Dartmouth case (see History); other latent periods in the range of weeks to months have also been reported. When the first symptom appears, typically paresthesia (a tingling or numbness in the skin), it is followed rapidly by more severe effects, sometimes ending in coma and death. The toxic damage appears to be determined by the peak value of mercury, not the length of the exposure.Methylmercury exposure during rodent gestation, a developmental period that approximately models human neural development during the first two trimesters of gestation, has long-lasting behavioral consequences that appear in adulthood and, in some cases, may not appear until aging. Prefrontal cortex or dopamine neurotransmission could be especially sensitive to even subtle gestational methylmercury exposure and suggests that public health assessments of methylmercury based on intellectual performance may underestimate the impact of methylmercury in public health. Ethylmercury is a breakdown product of the antibacteriological agent ethylmercurithiosalicylate, which has been used as a topical antiseptic and a vaccine preservative (further discussed under Thiomersal below). Its characteristics have not been studied as extensively as those of methylmercury. It is cleared from the blood much more rapidly, with a half-life of seven to ten days, and it is metabolized much more quickly than methylmercury. It is presumed not to have methylmercurys ability to cross the blood–brain barrier via a transporter, but instead relies on simple diffusion to enter the brain. Other exposure sources of organic mercury include phenylmercuric acetate and phenylmercuric nitrate. These compounds were used in indoor latex paints for their antimildew properties, but were removed in 1990 because of cases of toxicity. Inorganic mercury compounds Mercury occurs as salts such as mercuric chloride (HgCl2) and mercurous chloride (Hg2Cl2), the latter also known as calomel. Because they are more soluble in water, mercuric salts are usually more acutely toxic than mercurous salts. Their higher solubility lets them be more readily absorbed from the gastrointestinal tract. Mercury salts affect primarily the gastrointestinal tract and the kidneys, and can cause severe kidney damage; however, as they cannot cross the blood–brain barrier easily, these salts inflict little neurological damage without continuous or heavy exposure. Mercuric cyanide (Hg(CN)2) is a particularly toxic mercury compound that has been used in murders, as it contains not only mercury but also cyanide, leading to simultaneous cyanide poisoning. The drug n-acetyl penicillamine has been used to treat mercury poisoning with limited success. Elemental mercury Quicksilver (liquid metallic mercury) is poorly absorbed by ingestion and skin contact. Its vapor is the most hazardous form. Animal data indicate less than 0.01% of ingested mercury is absorbed through the intact gastrointestinal tract, though it may not be true for individuals with ileus. Cases of systemic toxicity from accidental swallowing are rare, and attempted suicide via intravenous injection does not appear to result in systemic toxicity, though it still causes damage by physically blocking blood vessels both at the site of injection and the lungs. Though not studied quantitatively, the physical properties of liquid elemental mercury limit its absorption through intact skin and in light of its very low absorption rate from the gastrointestinal tract, skin absorption would not be high. Some mercury vapor is absorbed dermally, but uptake by this route is only about 1% of that by inhalation.In humans, approximately 80% of inhaled mercury vapor is absorbed via the respiratory tract, where it enters the circulatory system and is distributed throughout the body. Chronic exposure by inhalation, even at low concentrations in the range 0.7–42 μg/m3, has been shown in case–control studies to cause effects such as tremors, impaired cognitive skills, and sleep disturbance in workers.Acute inhalation of high concentrations causes a wide variety of cognitive, personality, sensory, and motor disturbances. The most prominent symptoms include tremors (initially affecting the hands and sometimes spreading to other parts of the body), emotional lability (characterized by irritability, excessive shyness, confidence loss, and nervousness), insomnia, memory loss, neuromuscular changes (weakness, muscle atrophy, muscle twitching), headaches, polyneuropathy (paresthesia, stocking-glove sensory loss, hyperactive tendon reflexes, slowed sensory and motor nerve conduction velocities), and performance deficits in tests of cognitive function. Mechanism The toxicity of mercury sources can be expected to depend on its nature, i.e., salts vs. organomercury compounds vs. elemental mercury. The primary mechanism of mercury toxicity involves its irreversible inhibition of selenoenzymes, such as thioredoxin reductase (IC50 = 9 nM). Although it has many functions, thioredoxin reductase restores vitamins C and E, as well as a number of other important antioxidant molecules, back into their reduced forms, enabling them to counteract oxidative damage. Since the rate of oxygen consumption is particularly high in brain tissues, production of reactive oxygen species (ROS) is accentuated in these vital cells, making them particularly vulnerable to oxidative damage and especially dependent upon the antioxidant protection provided by selenoenzymes. High mercury exposures deplete the amount of cellular selenium available for the biosynthesis of thioredoxin reductase and other selenoenzymes that prevent and reverse oxidative damage, which, if the depletion is severe and long lasting, results in brain cell dysfunctions that can ultimately cause death. Mercury in its various forms is particularly harmful to fetuses as an environmental toxin in pregnancy, as well as to infants. Women who have been exposed to mercury in substantial excess of dietary selenium intakes during pregnancy are at risk of giving birth to children with serious birth defects. Mercury exposures in excess of dietary selenium intakes in young children can have severe neurological consequences, preventing nerve sheaths from forming properly. Exposure to methylmercury causes increased levels of antibodies sent to myelin basic protein (MBP), which is involved in the myelination of neurons, and glial fibrillary acidic protein (GFAP), which is essential to many functions in the central nervous system (CNS). This causes an autoimmmune response against MBP and GFAP and results in the degradation of neural myelin and general decline in function of the CNS. Diagnosis Diagnosis of elemental or inorganic mercury poisoning involves determining the history of exposure, physical findings, and an elevated body burden of mercury. Although whole-blood mercury concentrations are typically less than 6 μg/L, diets rich in fish can result in blood mercury concentrations higher than 200 μg/L; it is not that useful to measure these levels for suspected cases of elemental or inorganic poisoning because of mercurys short half-life in the blood. If the exposure is chronic, urine levels can be obtained; 24-hour collections are more reliable than spot collections. It is difficult or impossible to interpret urine samples of people undergoing chelation therapy, as the therapy itself increases mercury levels in the samples.Diagnosis of organic mercury poisoning differs in that whole-blood or hair analysis is more reliable than urinary mercury levels. Prevention Mercury poisoning can be prevented or minimized by eliminating or reducing exposure to mercury and mercury compounds. To that end, many governments and private groups have made efforts to heavily regulate the use of mercury, or to issue advisories about the use of mercury. Most countries have signed the Minamata Convention on Mercury. The export from the European Union of mercury and some mercury compounds has been prohibited since 15 March 2010. The European Union has banned most uses of mercury. Mercury is allowed for fluorescent light bulbs because of pressure from countries such as Germany, the Netherlands and Hungary, which are connected to the main producers of fluorescent light bulbs: General Electric, Philips and Osram. The United States Environmental Protection Agency (EPA) issued recommendations in 2004 regarding exposure to mercury in fish and shellfish. The EPA also developed the "Fish Kids" awareness campaign for children and young adults on account of the greater impact of mercury exposure to that population. Cleaning spilled mercury Mercury thermometers and mercury light bulbs are not as common as they used to be, and the amount of mercury they contain is unlikely to be a health concern if handled carefully. However, broken items still require careful cleanup, as mercury can be hard to collect and it is easy to accidentally create a much larger exposure problem. If available, powdered sulfur may be applied to the spill, in order to create a solid compound that is more easily removed from surfaces than liquid mercury. Treatment Identifying and removing the source of the mercury is crucial. Decontamination requires removal of clothes, washing skin with soap and water, and flushing the eyes with saline solution as needed. Chelation therapy Chelation therapy for acute inorganic mercury poisoning, a formerly common method, was done with DMSA, 2,3-dimercapto-1-propanesulfonic acid (DMPS), D-penicillamine (DPCN), or dimercaprol (BAL). Only DMSA is FDA-approved for use in children for treating mercury poisoning. However, several studies found no clear clinical benefit from DMSA treatment for poisoning due to mercury vapor. No chelator for methylmercury or ethylmercury is approved by the FDA; DMSA is the most frequently used for severe methylmercury poisoning, as it is given orally, has fewer side-effects, and has been found to be superior to BAL, DPCN, and DMPS. α-Lipoic acid (ALA) has been shown to be protective against acute mercury poisoning in several mammalian species when it is given soon after exposure; correct dosage is required, as inappropriate dosages increase toxicity. Although it has been hypothesized that frequent low dosages of ALA may have potential as a mercury chelator, studies in rats have been contradictory. Glutathione and N-acetylcysteine (NAC) are recommended by some physicians, but have been shown to increase mercury concentrations in the kidneys and the brain.Chelation therapy can be hazardous if administered incorrectly. In August 2005, an incorrect form of EDTA (edetate disodium) used for chelation therapy resulted in hypocalcemia, causing cardiac arrest that killed a five-year-old autistic boy. Other Experimental animal and epidemiological study findings have confirmed the interaction between selenium and methylmercury. Instead of causing a decline in neurodevelopmental outcomes, epidemiological studies have found that improved nutrient (i.e., omega-3 fatty acids, selenium, iodine, vitamin D) intakes as a result of ocean fish consumption during pregnancy improves maternal and fetal outcomes. For example, increased ocean fish consumption during pregnancy was associated with 4-6 point increases in child IQs. Prognosis Some of the toxic effects of mercury are partially or wholly reversible provided specific therapy is able to restore selenium availability to normal before tissue damage from oxidation becomes too extensive. Autopsy findings point to a half-life of inorganic mercury in human brains of 27.4 years. Heavy or prolonged exposure can do irreversible damage, in particular in fetuses, infants, and young children. Youngs syndrome is believed to be a long-term consequence of early childhood mercury poisoning.Mercuric chloride may cause cancer as it has caused increases in several types of tumors in rats and mice, while methyl mercury has caused kidney tumors in male rats. The EPA has classified mercuric chloride and methyl mercury as possible human carcinogens (ATSDR, EPA) Detection in biological fluids Mercury may be measured in blood or urine to confirm a diagnosis of poisoning in hospitalized people or to assist in the forensic investigation in a case of fatal over dosage. Some analytical techniques are capable of distinguishing organic from inorganic forms of the metal. The concentrations in both fluids tend to reach high levels early after exposure to inorganic forms, while lower but very persistent levels are observed following exposure to elemental or organic mercury. Chelation therapy can cause a transient elevation of urine mercury levels. History Neolithic artists using cinnabar show signs of mercury poisoning. Several Chinese emperors and other Chinese nobles are known or suspected to have died or been sickened by mercury poisoning after alchemists administered them "elixirs" to promote health, longevity, or immortality that contained either elemental mercury or (more commonly) cinnabar. Among the most prominent examples: The first emperor of unified China, Qin Shi Huang, it is reported, died in 210 BC of ingesting mercury pills that were intended to give him eternal life. Emperor Xuānzong of Tang, one of the emperors of the late Tang dynasty of China, was prescribed "cinnabar that had been treated and subdued by fire" to achieve immortality. Concerns that the prescription was having ill effects on the emperors health and sanity were waved off by the imperial alchemists, who cited medical texts listing a number of the emperors conditions (including itching, formication, swelling, and muscle weakness), today recognized as signs and symptoms of mercury poisoning, as evidence that the elixir was effectively treating the emperors latent ailments. Xuānzong became irritable and paranoid, and he seems to have ultimately died in 859 from the poisoning. The phrase mad as a hatter is likely a reference to mercury poisoning among milliners (so-called "mad hatter disease"), as mercury-based compounds were once used in the manufacture of felt hats in the 18th and 19th century. (The Mad Hatter character of Alice in Wonderland was, it is presumed, inspired by an eccentric furniture dealer named Theophilus Carter. Carter was not a victim of mad hatter disease although Lewis Carroll would have been familiar with the phenomenon of dementia that occurred among hatters.) In 1810, two British ships, HMS Triumph and HMS Phipps, salvaged a large load of elemental mercury from a wrecked Spanish vessel near Cadiz, Spain. The bladders containing the mercury soon ruptured. The element spread about the ships in liquid and vapor forms. The sailors presented with neurologic compromises: tremor, paralysis, and excessive salivation as well as tooth loss, skin problems, and pulmonary complaints. In 1823 William Burnet, MD published a report on the effects of mercurial vapor. Triumphs surgeon, Henry Plowman, had concluded that the ailments had arisen from inhaling the mercurialized atmosphere. His treatment was to order the lower deck gun ports to be opened, when it was safe to do so; sleeping on the orlop was forbidden; and no men slept in the lower deck if they were at all symptomatic. Windsails were set to channel fresh air into the lower decks day and night. Historically, gold-mercury amalgam was widely used in gilding, applied to the object and then heated to vaporize the mercury and deposit the gold, leading to numerous casualties among the workers. It is estimated that during the construction of Saint Isaacs Cathedral alone, 60 men died from the gilding of the main dome. For years, including the early part of his presidency, Abraham Lincoln took a common medicine of his time called "blue mass", which contained significant amounts of mercury. On September 5, 1920, silent movie actress Olive Thomas ingested mercury capsules dissolved in an alcoholic solution at the Hotel Ritz in Paris. There is still controversy over whether it was suicide, or whether she consumed the external preparation by mistake. Her husband, Jack Pickford (the brother of Mary Pickford), had syphilis, and the mercury was used as a treatment of the venereal disease at the time. She died a few days later at the American Hospital in Neuilly. An early scientific study of mercury poisoning was in 1923–1926 by the German inorganic chemist, Alfred Stock, who himself became poisoned, together with his colleagues, by breathing mercury vapor that was being released by his laboratory equipment—diffusion pumps, float valves, and manometers—all of which contained mercury, and also from mercury that had been accidentally spilt and remained in cracks in the linoleum floor covering. He published a number of papers on mercury poisoning, founded a committee in Berlin to study cases of possible mercury poisoning, and introduced the term micromercurialism. The term Hunter-Russell syndrome derives from a study of mercury poisoning among workers in a seed-packaging factory in Norwich, England in the late 1930s who breathed methylmercury that was being used as a seed disinfectant and pesticide. Outbreaks of methylmercury poisoning occurred in several places in Japan during the 1950s due to industrial discharges of mercury into rivers and coastal waters. The best-known instances were in Minamata and Niigata. In Minamata alone, more than 600 people died due to what became known as Minamata disease. More than 21,000 people filed claims with the Japanese government, of which almost 3000 became certified as having the disease. In 22 documented cases, pregnant women who consumed contaminated fish showed mild or no symptoms but gave birth to infants with severe developmental disabilities. Mercury poisoning of generations of Grassy Narrows and Whitedog native people in Ontario, Canada who were exposed to high levels of mercury by consuming mercury-contaminated fish when Dryden Chemical Company discharged over 9,000 kilograms (20,000 lb) of mercury directly into the Wabigoon–English River system and continued with mercury air pollution until 1975. Widespread mercury poisoning occurred in rural Iraq in 1971–1972, when grain treated with a methylmercury-based fungicide that was intended for planting only was used by the rural population to make bread, causing at least 6530 cases of mercury poisoning and at least 459 deaths (see Basra poison grain disaster). On August 14, 1996, Karen Wetterhahn, a chemistry professor working at Dartmouth College, spilled a small amount of dimethylmercury on her latex glove. She began experiencing the symptoms of mercury poisoning five months later and, despite aggressive chelation therapy, died a few months later from a mercury induced neurodegenerative disease In April 2000, Alan Chmurny attempted to kill a former employee, Marta Bradley, by pouring mercury into the ventilation system of her car. On March 19, 2008, Tony Winnett, 55, inhaled mercury vapors while trying to extract gold from computer parts (by using liquid mercury to separate gold from the rest of the alloy), and died ten days later. His Oklahoma residence became so contaminated that it had to be gutted. In December 2008, actor Jeremy Piven was diagnosed with mercury poisoning possibly resulting from eating sushi twice a day for twenty years or from taking herbal remedies. In India, a study by Centre for Science and Environment and Indian Institute of Toxicology Research has found that in the countrys energy capital Singrauli, mercury is slowly entering peoples homes, food, water and even blood. The Minamata Convention on Mercury in 2016 announced that the signing of the "international treaty designed to protect human health and the environment from anthropogenic releases and emission of mercury and mercury compounds" on April 22, 2016—Earth Day. It was the sixtieth anniversary of the discovery of the disease. Infantile acrodynia Infantile acrodynia (also known as "calomel disease", "erythredemic polyneuropathy", and "pink disease") is a type of mercury poisoning in children characterized by pain and pink discoloration of the hands and feet. The word is derived from the Greek, where άκρο means end or extremity, and οδυνη means pain. Acrodynia resulted primarily from calomel in teething powders and decreased greatly after calomel was excluded from most teething powders in 1954.Acrodynia is difficult to diagnose; "it is most often postulated that the etiology of this syndrome is an idiosyncratic hypersensitivity reaction to mercury because of the lack of correlation with mercury levels, many of the symptoms resemble recognized mercury poisoning." Medicine Mercury was once prescribed as a purgative. Many mercury-containing compounds were once used in medicines. These include calomel (mercurous chloride), and mercuric chloride. Thiomersal In 1999, the Centers for Disease Control (CDC) and the American Academy of Pediatrics (AAP) asked vaccine makers to remove the organomercury compound thiomersal (spelled "thimerosal" in the US) from vaccines as quickly as possible, and thiomersal has been phased out of US and European vaccines, except for some preparations of influenza vaccine. The CDC and the AAP followed the precautionary principle, which assumes that there is no harm in exercising caution even if it later turns out to be unwarranted, but their 1999 action sparked confusion and controversy that thiomersal was a cause of autism.Since 2000, the thiomersal in child vaccines has been alleged to contribute to autism, and thousands of parents in the United States have pursued legal compensation from a federal fund. A 2004 Institute of Medicine (IOM) committee favored rejecting any causal relationship between thiomersal-containing vaccines and autism. Autism incidence rates increased steadily even after thiomersal was removed from childhood vaccines. Currently there is no accepted scientific evidence that exposure to thiomersal is a factor in causing autism. Dental amalgam toxicity Dental amalgam is a possible cause of low-level mercury poisoning due to its use in dental fillings. Discussion on the topic includes debates on whether amalgam should be used, with critics arguing that its toxic effects make it unsafe. Cosmetics Some skin whitening products contain the toxic mercury(II) chloride as the active ingredient. When applied, the chemical readily absorbs through the skin into the bloodstream. The use of mercury in cosmetics is illegal in the United States. However, cosmetics containing mercury are often illegally imported. Following a certified case of mercury poisoning resulting from the use of an imported skin whitening product, the United States Food and Drug Administration warned against the use of such products. Symptoms of mercury poisoning have resulted from the use of various mercury-containing cosmetic products. The use of skin whitening products is especially popular amongst Asian women. In Hong Kong in 2002, two products were discovered to contain between 9,000 and 60,000 times the recommended dose. Fluorescent lamps Fluorescent lamps contain mercury, which is released when bulbs break. Mercury in bulbs is typically present as either elemental mercury liquid, vapor, or both, since the liquid evaporates at ambient temperature. When broken indoors, bulbs may emit sufficient mercury vapor to present health concerns, and the U.S. Environmental Protection Agency recommends evacuating and airing out a room for at least 15 minutes after breaking a fluorescent light bulb. Breakage of multiple bulbs presents a greater concern. A 1987 report described a 23-month-old toddler who had anorexia, weight loss, irritability, profuse sweating, and peeling and redness of fingers and toes. This case of acrodynia was traced to exposure of mercury from a carton of 8-foot fluorescent light bulbs that had broken in a potting shed adjacent to the main nursery. The glass was cleaned up and discarded, but the child often used the area to play in. Assassination attempts Mercury has, allegedly, been used at various times to assassinate people. In 2008, Russian lawyer Karinna Moskalenko claimed to have been poisoned by mercury left in her car, while in 2010 journalists Viktor Kalashnikov and Marina Kalashnikova accused Russias FSB of trying to poison them. See also References External links Hazardous Substances: Mercury at Curlie Toxic Substances: Mercury at Curlie

Give me a short description about Mesothelioma , Aarogya

Mesothelioma

Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall. Less commonly the lining of the abdomen and rarely the sac surrounding the heart, or the sac surrounding the testis may be affected. Signs and symptoms of mesothelioma may include shortness of breath due to fluid around the lung, a swollen abdomen, chest wall pain, cough, feeling tired, and weight loss. These symptoms typically come on slowly.More than 80% of mesothelioma cases are caused by exposure to asbestos. The greater the exposure the greater the risk. As of 2013, about 125 million people worldwide have been exposed to asbestos at work. High rates of disease occur in people who mine asbestos, produce products from asbestos, work with asbestos products, live with asbestos workers, or work in buildings containing asbestos. Asbestos exposure and the onset of cancer are generally separated by about 40 years. Washing the clothing of someone who worked with asbestos also increases the risk. Other risk factors include genetics and infection with the simian virus 40. The diagnosis may be suspected based on chest X-ray and CT scan findings, and is confirmed by either examining fluid produced by the cancer or by a tissue biopsy of the cancer.Prevention focuses on reducing exposure to asbestos. Treatment often includes surgery, radiation therapy, and chemotherapy. A procedure known as pleurodesis, which involves using substances such as talc to scar together the pleura, may be used to prevent more fluid from building up around the lungs. Chemotherapy often includes the medications cisplatin and pemetrexed. The percentage of people that survive five years following diagnosis is on average 8% in the United States.In 2015, about 60,800 people had mesothelioma, and 32,000 died from the disease. Rates of mesothelioma vary in different areas of the world. Rates are higher in Australia, the United Kingdom, and lower in Japan. It occurs in about 3,000 people per year in the United States. It occurs more often in males than females. Rates of disease have increased since the 1950s. Diagnosis typically occurs after the age of 65 and most deaths occur around 70 years old. The disease was rare before the commercial use of asbestos. Signs and symptoms Lungs Symptoms or signs of mesothelioma may not appear until 20 to 50 years (or more) after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space (pleural effusion) are often symptoms of pleural mesothelioma.Mesothelioma that affects the pleura can cause these signs and symptoms: Chest wall pain Pleural effusion, or fluid surrounding the lung Shortness of breath – which could be due to a collapsed lung Fatigue or anemia Wheezing, hoarseness, or a cough Blood in the sputum (fluid) coughed up (hemoptysis)In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread to other parts of the body. Abdomen The most common symptoms of peritoneal mesothelioma are abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other features may include weight loss, fever, night sweats, poor appetite, vomiting, constipation, and umbilical hernia. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face. These symptoms may be caused by mesothelioma or by other, less serious conditions.Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include: Abdominal pain Ascites, or an abnormal buildup of fluid in the abdomen A mass in the abdomen Problems with bowel function Weight loss Heart Pericardial mesothelioma is not well characterized, but observed cases have included cardiac symptoms, specifically constrictive pericarditis, heart failure, pulmonary embolism, and cardiac tamponade. They have also included nonspecific symptoms, including substernal chest pain, orthopnea (shortness of breath when lying flat), and cough. These symptoms are caused by the tumor encasing or infiltrating the heart. End stage In severe cases of the disease, the following signs and symptoms may be present: Blood clots in the veins, which may cause thrombophlebitis Disseminated intravascular coagulation, a disorder causing severe bleeding in many body organs Jaundice, or yellowing of the eyes and skin Low blood sugar Pleural effusion Pulmonary embolism, or blood clots in the arteries of the lungs Severe ascitesIf a mesothelioma forms metastases, these most commonly involve the liver, adrenal gland, kidney, or other lung. Causes Working with asbestos is the most common risk factor for mesothelioma. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. Tentative evidence also raises concern about carbon nanotubes. Asbestos The incidence of mesothelioma has been found to be higher in populations living near naturally occurring asbestos. People can be exposed to naturally occurring asbestos in areas where mining or road construction is occurring, or when the asbestos-containing rock is naturally weathered. Another common route of exposure is through asbestos-containing soil, which is used to whitewash, plaster, and roof houses in Greece. In central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villages—Tuzköy, Karain, and Sarıhıdır. Initially, this was attributed to erionite. Environmental exposure to asbestos has caused mesothelioma in places other than Turkey, including Corsica, Greece, Cyprus, China, and California. In the northern Greek mountain town of Metsovo, this exposure had resulted in mesothelioma incidence around 300 times more than expected in asbestos-free populations, and was associated with very frequent pleural calcification known as Metsovo lung.The documented presence of asbestos fibers in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibers.Exposure to talc is also a risk factor for mesothelioma; exposure can affect those who live near talc mines, work in talc mines, or work in talc mills.In the United States, asbestos is considered the major cause of malignant mesothelioma and has been considered "indisputably" associated with the development of mesothelioma. Indeed, the relationship between asbestos and mesothelioma is so strong that many consider mesothelioma a "signal" or "sentinel" tumor. A history of asbestos exposure exists in most cases. Pericardial mesothelioma may not be associated with asbestos exposure.Asbestos was known in antiquity, but it was not mined and widely used commercially until the late 19th century. The dangers were not unknown in antiquity. Pliny the Elder, a Roman author and naturalist, observed that quarry slaves from asbestos mines tended to die young. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not publicly known. However, an increased risk of developing mesothelioma was later found among naval personnel (e.g., Navy, Marine Corps, and Coast Guard), shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the official position of the U.S. Occupational Safety and Health Administration (OSHA) and the U.S. EPA is that protections and "permissible exposure limits" required by U.S. regulations, while adequate to prevent most asbestos-related non-malignant disease, are not adequate to prevent or protect against asbestos-related cancers such as mesothelioma. Likewise, the British Governments Health and Safety Executive (HSE) states formally that any threshold for exposure to asbestos must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE assumes that no such "safe" threshold exists. Others have noted as well that there is no evidence of a threshold level below which there is no risk of mesothelioma. There appears to be a linear, dose–response relationship, with increasing dose producing increasing risk of disease. Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos. The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer. Again, there is no known safe level of exposure to asbestos as it relates to increased risk of mesothelioma. The time from first exposure to onset of the disease, is between 25 and 70 years. It is virtually never less than fifteen years and peaks at 30–40 years. The duration of exposure to asbestos causing mesothelioma can be short. For example, cases of mesothelioma have been documented with only 1–3 months of exposure. Occupational Exposure to asbestos fibers has been recognized as an occupational health hazard since the early 20th century. Numerous epidemiological studies have associated occupational exposure to asbestos with the development of pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumors, and diffuse malignant mesothelioma of the pleura and peritoneum. Asbestos has been widely used in many industrial products, including cement, brake linings, gaskets, roof shingles, flooring products, textiles, and insulation.Commercial asbestos mining at Wittenoom, Western Australia, took place from 1937 to 1966. The first case of mesothelioma in the town occurred in 1960. The second case was in 1969, and new cases began to appear more frequently thereafter. The lag time between initial exposure to asbestos and the development of mesothelioma varied from 12 years 9 months up to 58 years. A cohort study of miners employed at the mine reported that 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.Occupational exposure to asbestos in the United States mainly occurs when people are maintaining buildings that already have asbestos. Approximately 1.3 million US workers are exposed to asbestos annually; in 2002, an estimated 44,000 miners were potentially exposed to asbestos. Paraoccupational secondary exposure Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases. This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers via washing a workers clothes or coming into contact with asbestos-contaminated work clothing. To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace. Asbestos in buildings Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or DIY activities may expose themselves to asbestos dust. In the UK, use of chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos were banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.Therefore, it is a legal requirement that all who may come across asbestos in their day-to-day work have been provided with the relevant asbestos training. Genetic disposition In a recent research carried on white American population in 2012, it was found that people with a germline mutation in their BAP1 gene are at higher risk of developing mesothelioma and uveal melanoma. Erionite Erionite is a zeolite mineral with similar properties to asbestos and is known to cause mesothelioma. Detailed epidemiological investigation has shown that erionite causes mesothelioma mostly in families with a genetic predisposition. Erionite is found in deposits in the Western United States, where it is used in gravel for road surfacing, and in Turkey, where it is used to construct homes. In Turkey, the United States, and Mexico, erionite has been associated with mesothelioma and has thus been designated a "known human carcinogen" by the US National Toxicology Program. Other In rare cases, mesothelioma has also been associated with irradiation of the chest or abdomen, intrapleural thorium dioxide (thorotrast) as a contrast medium, and inhalation of other fibrous silicates, such as erionite or talc. Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma. This has been confirmed in animal studies, but studies in humans are inconclusive. Pathophysiology Systemic The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Deposition of asbestos fibers in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fiber can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibers from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibers may be deposited in the gut after ingestion of sputum contaminated with asbestos fibers.Pleural contamination with asbestos or other mineral fibers has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers). However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System.Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibers. It has been suggested that in humans, transport of fibers to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localized lesions of accumulated asbestos fibers in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumor.Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibers remain unclear despite the demonstration of its oncogenic capabilities (see next-but-one paragraph). However, complete in vitro transformation of normal human mesothelial cells to a malignant phenotype following exposure to asbestos fibers has not yet been achieved. In general, asbestos fibers are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages. Intracellular Analysis of the interactions between asbestos fibers and DNA has shown that phagocytosed fibers are able to make contact with chromosomes, often adhering to the chromatin fibers or becoming entangled within the chromosome. This contact between the asbestos fiber and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes: Neurofibromatosis type 2 at 22q12 P16INK4A P14ARFAsbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms: Inactivation of tumor suppressor genes Activation of oncogenes In tumor cells, these genes are often mutated, or expressed at high levels. Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region Activation of DNA repair enzymes, which may be prone to error Activation of telomerase Prevention of apoptosisSeveral genes are commonly mutated in mesothelioma, and may be prognostic factors. These include epidermal growth factor receptor (EGFR) and C-Met, receptor tyrosine kinases which are overexpressed in many mesotheliomas. Some association has been found with EGFR and epithelioid histology but no clear association has been found between EGFR overexpression and overall survival. Expression of AXL receptor tyrosine kinase is a negative prognostic factor. Expression of PDGFRB is a positive prognostic factor. In general, mesothelioma is characterized by loss of function in tumor suppressor genes, rather than by an overexpression or gain of function in oncogenes.As an environmentally triggered malignancy, mesothelioma tumors have been found to be polyclonal in origin, by performing an X-inactivation based assay on epitheloid and biphasic tumors obtained from female patients. These results suggest that an environmental factor, most likely asbestos exposure, may damage and transform a group of cells in the tissue, resulting in a population of tumor cells that are, albeit only slightly, genetically different. Immune system Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic (chromosome-breaking) and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres. Diagnosis Diagnosis of mesothelioma can be suspected with imaging but is confirmed with biopsy. It must be clinically and histologically differentiated from other pleural and pulmonary malignancies, including reactive pleural disease, primary lung carcinoma, pleural metastases of other cancers, and other primary pleural cancers. Primary pericardial mesothelioma is often diagnosed after it has metastasized to lymph nodes or the lungs. Imaging Diagnosing mesothelioma is often difficult because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patients medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytopathology if this fluid is aspirated with a syringe. For pleural fluid, this is done by thoracentesis or tube thoracostomy (chest tube); for ascites, with paracentesis or ascitic drain; and for pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g., tuberculosis, heart failure). However, with primary pericardial mesothelioma, pericardial fluid may not contain malignant cells and a tissue biopsy is more useful in diagnosis. Using conventional cytology diagnosis of malignant mesothelioma is difficult, but immunohistochemistry has greatly enhanced the accuracy of cytology. Biopsy Generally, a biopsy is needed to confirm a diagnosis of malignant mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. Alternatively, the cardiothoracic surgeon might directly open the chest (thoracotomy). If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, an open surgical procedure may be necessary. Immunochemistry Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics, such as breast or lung cancer that has metastasized to the pleura. There are numerous tests and panels available, but no single test is perfect for distinguishing mesothelioma from carcinoma or even benign versus malignant. The positive markers indicate that mesothelioma is present; if other markers are positive it may indicate another type of cancer, such as breast or lung adenocarcinoma. Calretinin is a particularly important marker in distinguishing mesothelioma from metastatic breast or lung cancer. Subtypes There are three main histological subtypes of malignant mesothelioma: epithelioid, sarcomatous, and biphasic. Epithelioid and biphasic mesothelioma make up approximately 75-95% of mesotheliomas and have been well characterized histologically, whereas sarcomatous mesothelioma has not been studied extensively. Most mesotheliomas express high levels of cytokeratin 5 regardless of subtype.Epithelioid mesothelioma is characterized by high levels of calretinin.Sarcomatous mesothelioma does not express high levels of calretinin.Other morphological subtypes have been described: Desmoplastic Clear cell Deciduoid Adenomatoid Glandular Mucohyaline Cartilaginous and osseous metaplasia Lymphohistiocytic Differential diagnosis Metastatic adenocarcinoma Pleural sarcoma Synovial sarcoma Thymoma Metastatic clear cell renal cell carcinoma Metastatic osteosarcoma Staging Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group. TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged Ia–IV (one-A to four) based on the TNM status. Prevention Mesothelioma can be prevented in most cases by preventing exposure to asbestos. The US National Institute for Occupational Safety and Health maintains a recommended exposure limit of 0.1 asbestos fiber per cubic centimeter. Screening There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening. Doctors have begun testing the Mesomark assay, which measures levels of soluble mesothelin-related proteins (SMRPs) released by mesothelioma cells. Treatment Mesothelioma is generally resistant to radiation and chemotherapy treatment. Long-term survival and cures are exceedingly rare. Treatment of malignant mesothelioma at earlier stages has a better prognosis. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease. The histological subtype and the patients age and health status also help predict prognosis. The epithelioid histology responds better to treatment and has a survival advantage over sarcomatoid histology.The effectiveness of radiotherapy compared to chemotherapy or surgery for malignant pleural mesothelioma is not known. Surgery Surgery, by itself, has proved disappointing. In one large series, the median survival with surgery (including extrapleural pneumonectomy) was only 11.7 months. However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008), or with one of the latter. A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed. In localized pericardial mesothelioma, pericardectomy can be curative; when the tumor has metastasized, pericardectomy is a palliative care option. It is often not possible to remove the entire tumor. Radiation For patients with localized disease, and who can tolerate a radical surgery, radiation can be given post-operatively as a consolidative treatment. The entire hemithorax is treated with radiation therapy, often given simultaneously with chemotherapy. Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations. It can also induce severe side-effects, including fatal pneumonitis. As part of a curative approach to mesothelioma, radiotherapy is commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy, when given alone with curative intent, has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be beyond human tolerance. Radiotherapy is of some use in pericardial mesothelioma. Chemotherapy Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery. This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in the combination with pemetrexed and who also received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration (FDA) approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give. Cisplatin and pemetrexed together give patients a median survival of 12.1 months.Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin. Cisplatin in combination with premetrexed disodium, folic acid, and vitamin B12 may also improve survival for people who are responding to chemotherapy.In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.In pericardial mesothelioma, chemotherapy – typically adriamycin or cisplatin – is primarily used to shrink the tumor and is not curative. Immunotherapy Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.In October 2020, the FDA approved the combination of nivolumab (Opdivo) with ipilimumab (Yervoy) for the first-line treatment of adults with malignant pleural mesothelioma (MPM) that cannot be removed by surgery. Nivolumab and ipilimumab are both monoclonal antibodies that, when combined, decrease tumor growth by enhancing T-cell function. The combination therapy was evaluated through a randomized, open-label trial in which participants who received nivolumab in combination with ipilimumab survived a median of 18.1 months while participants who underwent chemotherapy survived a median of 14.1 months. Hyperthermic intrathoracic chemotherapy Hyperthermic intrathoracic chemotherapy is used in conjunction with surgery, including in patients with malignant pleural mesothelioma. The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48 °C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained. High concentrations of selected drugs are then administered into the pleural cavity. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells. Multimodality therapy Multimodal therapy, which includes a combined approach of surgery, radiation or photodynamic therapy, and chemotherapy, is not suggested for routine practice for treating malignant pleural mesothelioma. The effectiveness and safety of multimodal therapy is not clear (not enough research has been performed) and one clinical trial has suggested a possible increased risk of adverse effects.Large series of examining multimodality treatment have only demonstrated modest improvement in survival (median survival 14.5 months and only 29.6% surviving 2 years). Reducing the bulk of the tumor with cytoreductive surgery is key to extending survival. Two surgeries have been developed: extrapleural pneumonectomy and pleurectomy/decortication. The indications for performing these operations are unique. The choice of operation namely depends on the size of the patients tumor. This is an important consideration because tumor volume has been identified as a prognostic factor in mesothelioma. Pleurectomy/decortication spares the underlying lung and is performed in patients with early stage disease when the intention is to remove all gross visible tumor (macroscopic complete resection), not simply palliation. Extrapleural pneumonectomy is a more extensive operation that involves resection of the parietal and visceral pleurae, underlying lung, ipsilateral (same side) diaphragm, and ipsilateral pericardium. This operation is indicated for a subset of patients with more advanced tumors, who can tolerate a pneumonectomy. Prognosis Mesothelioma usually has a poor prognosis. Typical survival despite surgery is between 12 and 21 months depending on the stage of disease at diagnosis with about 7.5% of people surviving for 5 years.Women, young people, people with low-stage cancers, and people with epithelioid cancers have better prognoses. Negative prognostic factors include sarcomatoid or biphasic histology, high platelet counts (above 400,000), age over 50 years, white blood cell counts above 15.5, low glucose levels in the pleural fluid, low albumin levels, and high fibrinogen levels. Several markers are under investigation as prognostic factors, including nuclear grade, and serum c-reactive protein. Long-term survival is rare.Pericardial mesothelioma has a 10-month median survival time.In peritoneal mesothelioma, high expression of WT-1 protein indicates a worse prognosis. Epidemiology Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate varies from one country to another, from a low rate of less than 1 per 1,000,000 in Tunisia and Morocco, to the highest rate in Britain, Australia and Belgium: 30 per 1,000,000 per year. For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades. Worldwide incidence is estimated at 1-6 per 1,000,000. Incidence of mesothelioma lags behind that of asbestosis due to the longer time it takes to develop; due to the cessation of asbestos use in developed countries, mesothelioma incidence is expected to decrease. Incidence is expected to continue increasing in developing countries due to continuing use of asbestos. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal. Less than 5% of mesotheliomas are pericardial. The prevalence of pericardial mesothelioma is less than 0.002%; it is more common in men than women. It typically occurs in a persons 50s-70s.Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States. Between 1973 and 1984, the incidence of pleural mesothelioma among Caucasian males increased 300%. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. More than 80% of mesotheliomas are caused by asbestos exposure.The incidence of peritoneal mesothelioma is 0.5–3.0 per million per year in men, and 0.2–2.0 per million per year in women. UK Mesothelioma accounts for less than 1% of all cancers diagnosed in the UK, (around 2,600 people were diagnosed with the disease in 2011), and it is the seventeenth most common cause of cancer death (around 2,400 people died in 2012). History The connection between asbestos exposure and mesothelioma was discovered in the 1970s. In the United States, asbestos manufacture stopped in 2002. Asbestos exposure thus shifted from workers in asbestos textile mills, friction product manufacturing, cement pipe fabrication, and insulation manufacture and installation to maintenance workers in asbestos-containing buildings. Society and culture Notable cases Mesothelioma, though rare, has had a number of notable patients: Malcolm McLaren, musician and manager of the punk rock band the Sex Pistols, was diagnosed with peritoneal mesothelioma in October 2009 and died on 8 April 2010 in Switzerland. Steve McQueen, American actor, was diagnosed with peritoneal mesothelioma on December 22, 1979. He was not offered surgery or chemotherapy because doctors felt the cancer was too advanced. McQueen subsequently sought alternative treatments at clinics in Mexico. He died of a heart attack on November 7, 1980, in Juárez, Mexico, following cancer surgery. He may have been exposed to asbestos while serving with the U.S. Marines as a young adult—asbestos was then commonly used to insulate ships piping—or from its use as an insulating material in automobile racing suits (McQueen was an avid racing driver and fan). Mickie Most, record producer, died of peritoneal mesothelioma in May 2003; however, it has been questioned whether this was due to asbestos exposure. Warren Zevon, American musician, was diagnosed with pleural mesothelioma in 2002, and died on September 7, 2003. It is believed that this was caused through childhood exposure to asbestos insulation in the attic of his fathers shop. David Martin, Australian sailor and politician, died on 10 August 1990 of pleural mesothelioma. It is believed that this was caused by his exposure to asbestos on military ships during his career in the Royal Australian Navy. Paul Kraus, diagnosed in 1997, is considered the longest currently living (as of 2017) mesothelioma survivor in the world. F. W. De Klerk, South African retired politician, was diagnosed with mesothelioma on March 19, 2021, and died in November 2021. Paul Gleason, American actor, died on May 27, 2006, just a few months after diagnosis.Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay Gould, a well-regarded paleontologist, was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould wrote "The Median Isnt the Message", in which he argued that statistics such as median survival are useful abstractions, not destiny. Gould lived for another 20 years, eventually succumbing to cancer not linked to his mesothelioma. Legal issues Some people who were exposed to asbestos have collected damages for an asbestos-related disease, including mesothelioma. Compensation via asbestos funds or class action lawsuits is an important issue in law practices regarding mesothelioma.The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars. The amounts and method of allocating compensation have been the source of many court cases, reaching up to the United States Supreme Court, and government attempts at resolution of existing and future cases. However, to date, the US Congress has not stepped in and there are no federal laws governing asbestos compensation. In 2013, the "Furthering Asbestos Claim Transparency (FACT) Act of 2013" passed the US House of representatives and was sent to the US Senate, where it was referred to the Senate Judiciary Committee. As the Senate did not vote on it before the end of the 113th Congress, it died in committee. It was revived in the 114th Congress, where it has not yet been brought before the House for a vote. History The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. In 1960, an article published by Wagner et al. was seminal in establishing mesothelioma as a disease arising from exposure to asbestos. The article referred to over 30 case studies of people who had had mesothelioma in South Africa. Some exposures were transient and some were mine workers. Before the use of advanced microscopy techniques, malignant mesothelioma was often diagnosed as a variant form of lung cancer. In 1962, McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker. The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950.In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965, an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.Despite proof that the dust associated with asbestos mining and milling causes asbestos-related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974, the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australias Bulletin magazine. In 1978, the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.By 1979, the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.In Leeds, England the Armley asbestos disaster involved several court cases against Turner & Newall where local residents who contracted mesothelioma demanded compensation because of the asbestos pollution from the companys factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997. Research The WT-1 protein is overexpressed in mesothelioma and is being researched as a potential target for drugs.There are two high-confidence miRNAs that can potentially serve as biomarkers of asbestos exposure and malignant mesothelioma. Validation studies are needed to assess their relevance. References This article includes information from a public domain U.S. National Cancer Institute fact sheet. External links Mesothelioma at Curlie

Hey Aarogya, explain a scenario commonly referred as Methanol toxicity

Methanol toxicity

Methanol toxicity (also methanol poisoning) is poisoning from methanol, characteristically via ingestion. Symptoms may include a decreased level of consciousness, poor or no coordination, hypothermia, vomiting, abdominal pain, and a specific smell on the breath. Decreased vision may start as early as twelve hours after exposure. Long-term outcomes may include blindness and kidney failure. Toxicity and death may occur after drinking in large quantities.Methanol poisoning most commonly occurs following the drinking of windshield washer fluid. This may be accidental or as part of an attempted suicide. Toxicity may also rarely occur through extensive skin exposure or breathing in fumes. When methanol is broken down by the body it results in formaldehyde, formic acid, and formate which cause much of the toxicity. The diagnosis may be suspected when there is acidosis or an increased osmol gap and confirmed by directly measuring blood levels. Other conditions that can produce similar symptoms include infections, exposure to other toxic alcohols, serotonin syndrome, and diabetic ketoacidosis.Early treatment increases the chance of a good outcome. Treatment consists of stabilizing the person, followed by the use of an antidote. The preferred antidote is fomepizole, with ethanol used if this is not available. Hemodialysis may also be used in those where there is organ damage or a high degree of acidosis. Other treatments may include sodium bicarbonate, folate, and thiamine.Outbreaks of methanol ingestion have occurred due to contamination of drinking alcohol. This is more common in the developing world. In 2013 more than 1700 cases occurred in the United States. Those affected are usually adult and male. Toxicity to methanol has been described as early as 1856. Signs and symptoms The initial symptoms of methanol intoxication include central nervous system depression, headache, dizziness, nausea, lack of coordination, and confusion. Sufficiently large doses cause unconsciousness and death. The initial symptoms of methanol exposure are usually less severe than the symptoms from the ingestion of a similar quantity of ethanol. Once the initial symptoms have passed, a second set of symptoms arises, from 10 to as many as 30 hours after the initial exposure, that may include blurring or complete loss of vision, acidosis, and putaminal hemorrhages, an uncommon but serious complication. These symptoms result from the accumulation of toxic levels of formate in the blood, and may progress to death by respiratory failure. Physical examination may show tachypnea, and eye examination may show dilated pupils with hyperemia of the optic disc and retinal edema. Cause Methanol has a moderate to high toxicity in humans. As little as 10 mL of pure methanol when drunk is metabolized into formic acid, which can cause permanent blindness by destruction of the optic nerve. 15 mL is potentially fatal, although the median lethal dose is typically 100 mL (3.4 fl oz) (i.e. 1–2 mL/kg body weight of pure methanol). Reference dose for methanol is 0.5 mg/kg/day.Ethanol is sometimes denatured (adulterated), and made poisonous, by the addition of methanol. The result is known as methylated spirit, "meths" (British use) or "metho" (Australian slang). This is not to be confused with "meth", a common abbreviation for methamphetamine and for methadone in Britain and the United States. Mechanism Methanol is toxic by two mechanisms. First, methanol (whether it enters the body by ingestion, inhalation, or absorption through the skin) can be fatal due to its CNS depressant properties in the same manner as ethanol poisoning. Second, in a process of toxication, it is metabolized to formic acid (which is present as the formate ion) via formaldehyde in a process initiated by the enzyme alcohol dehydrogenase in the liver. Methanol is converted to formaldehyde via alcohol dehydrogenase and formaldehyde is converted to formic acid (formate) via aldehyde dehydrogenase. The conversion to formate via ALDH proceeds completely, with no detectable formaldehyde remaining. Formate is toxic because it inhibits mitochondrial cytochrome c oxidase, causing hypoxia at the cellular level, and metabolic acidosis, among a variety of other metabolic disturbances. Treatment Methanol poisoning can be treated with fomepizole, or if unavailable, ethanol may be used. Both drugs act to reduce the action of alcohol dehydrogenase on methanol by means of competitive inhibition. Ethanol, the active ingredient in alcoholic beverages, acts as a competitive inhibitor by more effectively binding and saturating the alcohol dehydrogenase enzyme in the liver, thus blocking the binding of methanol. Methanol is excreted by the kidneys without being converted into the very toxic metabolites formaldehyde and formic acid. Alcohol dehydrogenase instead enzymatically converts ethanol to acetaldehyde, a much less toxic organic molecule. Additional treatment may include sodium bicarbonate for metabolic acidosis, and hemodialysis or hemodiafiltration to remove methanol and formate from the blood. Folinic acid or folic acid is also administered to enhance the metabolism of formate. History There are cases of methanol resistance, such as that of Mike Malloy, whom someone tried and failed to poison by methanol in the early 1930s.In December 2016, 78 people died in Irkutsk, Russia from methanol poisoning after ingesting a counterfeit body lotion that was primarily methanol rather than ethanol as labeled. The body lotion, prior to the event, had been used as a cheap substitute for vodka by the impoverished people in the region despite warnings on the lotions bottles that it was not safe for drinking and long-standing problems with alcohol poisoning across the country.During the COVID-19 pandemic, Iranian media reported that nearly 300 people had died and over a thousand became ill due to methanol poisoning in the belief that drinking the alcohol could help with the disease. In the United States, the Food and Drug Administration discovered that a number of brands of hand sanitizer manufactured in Mexico during the pandemic contained methanol, and urged the public to avoid using the affected products. See also Ethylene glycol poisoning References == External links ==

Hey Aarogya , Do you know what is Mevalonate kinase deficiency,

Mevalonate kinase deficiency

Mevalonate kinase deficiency (MKD) is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids. It is a very rare genetic disease. It is characterized by an elevated level of immunoglobulin D in the blood. Mevalonate kinase (MVK) is an enzyme involved in biosynthesis of cholesterols and isoprenoids and is necessary for the conversion of mevalonate to mevalonate-5-phosphate in the presence of Mg2+. MKD is due to a mutation in the gene that encodes mevalonate kinase which results in a reduced or deficient activity of this enzyme. Because of this deficiency, mevalonic acid can build up in the body, with high levels found in the urine. The severity of MKD depends on the level of this deficiency with hyperimmunoglobulinemia D syndrome (first described as HIDS in 1984) being less severe, but more common, and mevalonic aciduria (MVA); a more severe, but rarer form. Genetics Mevalonate kinase deficiency is inherited in an autosomal recessive manner, meaning that a child must inherit a defective copy of the gene from both parents to be affected. It is an example of a loss-of-function mutation. The gene which codes for mevalonate kinase consists of 10 exons at locus 12q14. About 63 pathological sequence variations in the gene have been characterized. The most common of these are V377I, I268T, H20P/N and P167L, present in 70% of affected individuals. Immunoglobulin D Immunoglobulin D (IgD) is a protein produced by a certain type of white blood cells. There are five classes of Immunoglobulin: IgG, IgA, IgM, IgE and IgD. They each play an important role in the immune system. The function of IgD is still unclear, although one of its many effects is to active the immune system. Biochemistry There is an increased secretion of the fever promoting cytokine interleukin 1 beta (IL-1β) in MKD, most likely mediated by defective protein prenylation. Prenylation refers to addition of hydrophobic isoprenoids to proteins, such as farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP). When isoprenoids such as these are coupled to a target protein, this affects the proteins cellular location and function. In a human monocytic MKD model it was found that the deficiency of GGPP leads to overproduction of IL-1β and defective prenylation of RhoA. This causes an increased level of Rac1 and PKB which in turn affects GTPases and B7-glycoproteins. It was earlier found that Rac1/PI3K/PKB pathway had been linked to the pathogenesis of MKD. The inactivation of RhoA acts an inducer of IL-1β mRNA transcription independent of NLRP3- or caspase-1 activity. Due to defective RhoA there is a formation of defective mitochondria (elongated and instable) in the cell. Normally, defective mitochondria are cleared in the cell by the mechanism of autophagy. But, in MKD the clearance of defective mitochondria from the cytosol is disrupted. As a result, mitochondrial DNA starts accumulating in the cytosol, binding and activating NLRP3, which is responsible for the production of IL-1β. The activation can be direct or indirect. It can also be activated by reactive oxygen species (ROS). It is known that monocytes and macrophages in affected individuals also produce higher levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) other than IL-Iβ During febrile (fever) attacks, C-reactive protein (CRP) also increases. CRP is released by liver which causes inflammation. Hyper-IgD syndrome Hyperimmunoglobulinemia D with recurrent fever is a periodic fever syndrome originally described in 1984 by the internist Jos van der Meer, then at Leiden University Medical Centre. No more than 300 cases have been described worldwide. It is now recognised as an allelic variant of MKD. Signs and symptoms HIDS is one of a number of periodic fever syndromes. It is characterised by attacks of fever, arthralgia, skin lesions including cyclical mouth ulcers, and diarrhea. Laboratory features include an acute phase response (elevated CRP and ESR) and markedly elevated IgD (and often IgA), although cases with normal IgD have been described.It has mainly been described in the Netherlands and France, although the international registry includes a number of cases from other countries.The differential diagnosis includes fever of unknown origin, familial Mediterranean fever (FMF) and familial Hibernian fever (or TNFα reception associated periodic syndrome/TRAPS). Cause Virtually all people with the syndrome have mutations in the gene for mevalonate kinase, which is part of the HMG-CoA reductase pathway, an important cellular metabolic pathway. Indeed, similar fever attacks (but normal IgD) have been described in patients with mevalonic aciduria – an inborn error of metabolism now seen as a severe form of HIDS. Pathophysiology It is not known how mevalonate kinase mutations cause the febrile episodes, although it is presumed that other products of the cholesterol biosynthesis pathway, the prenylation chains (geranylgeraniol and farnesol) might play a role. Diagnosis Mevalonate kinase deficiency causes an accumulation of mevalonic acid in the urine, resulting from insufficient activity of the enzyme mevalonate kinase (ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36). The disorder was first described in 1985.Classified as an inborn error of metabolism, mevalonate kinase deficiency usually results in developmental delay, hypotonia, anemia, hepatosplenomegaly, various dysmorphic features, mental retardation, an overall failure to thrive and several other features. Treatment There is no treatment for MKD. But, the inflammation and the other effects can be reduced to a certain extent. IL-1 targeting drugs can be used to reduce the effects of the disorder. Anakinra is antagonist to IL-1 receptors. Anakinra binds the IL-1 receptor, preventing the actions of both IL-1α and IL-1β, and it has been proved to reduce the clinical and biochemical inflammation in MKD. It can effectively decreases the frequency as well as the severity of inflammatory attacks when used on a daily basis. Disadvantages with the usage of this drug are occurrence of painful injection site reaction and as the drug is discontinued in the near future the febrile attacks start. (Examined in a 12-year-old patient). Canakinumab is a long acting monoclonal antibody which is directed against IL-1β has shown to be effective in reducing both frequency and severity in patients with mild and severe MKD in case reports and observational case series. It reduces the physiological effects but the biochemical parameter still remain elevated (Galeotti et al. demonstrated that it is more effective than anakinra –considered 6 patients with MKD). Anti-TNF therapy might be effective in MKD, but the effect is mostly partial and therapy failure and clinical deterioration have been described frequently in patients on infliximab or etanercept. A beneficial effect of human monoclonal anti-TNFα antibody adalimumab was seen in a small number of MKD patients. Most MKD patients are benefited by anti-IL-1 therapy. However, anti-IL-1-resistant disease may also occur. Example. tocilizumab (a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor). This drug is used when the patients are unresponsive towards Anakinra. (Shendi et al. treated a young woman in whom anakinra was ineffective with tocilizumab). It was found that it was effective in reducing the biochemical and clinical inflammation [30].Stoffels et al. observed reduction of frequency and severity of the inflammatory attacks, although after several months of treatment one of these two patients persistently showed mild inflammatory symptoms in the absence of biochemical inflammatory markers. A beneficial effect of hematopoietic stem cell transplantation can be used in severe mevalonate kinase deficiency conditions (Improvement of cerebral myelinisation on MRI after allogenic stem cell transplantation was observed in one girl). But, liver transplantation did not influence febrile attacks in this patient. Treatment for HIDS Canakinumab has been approved for treatment of HIDS and has shown to be effective. The immunosuppressant drugs etanercept and anakinra have also shown to be effective. Statin drugs might decrease the level of mevalonate and are presently being investigated. A recent single case report highlighted bisphosphonates as a potential therapeutic option. Epidemiology Globally, less than 1 in 100,000 people have HIDS, and of these, ~200 individuals have MKD. This categorises the condition as a rare genetic disease. Additional images References External links Mevalonic aciduria at NIHs Office of Rare Diseases

Hey Aarogya , Do you know what is Microscopic polyangiitis,

Microscopic polyangiitis

Microscopic polyangiitis is an ill-defined autoimmune disease characterized by a systemic, pauci-immune, necrotizing, small-vessel vasculitis without clinical or pathological evidence of necrotizing granulomatous inflammation. Signs and symptoms Clinical features may include constitutional symptoms like fever, loss of appetite, weight loss, fatigue, and kidney failure. A majority of patients may have blood in the urine and protein in the urine. Rapidly progressive glomerulonephritis may occur. Because many different organ systems may be involved, a wide range of symptoms are possible in MPA. Purpura and livedo racemosa may be present. Cause While the mechanism of disease has yet to be fully elucidated, the leading hypothesis is that the process is begun with an autoimmune process of unknown cause that triggers production of p-ANCA. These antibodies will circulate at low levels until a pro-inflammatory trigger—such as infection, malignancy, or drug therapy. The trigger upregulates production of p-ANCA. Then, the large number of antibodies make it more likely that they will bind a neutrophil. Once bound, the neutrophil degranulates. The degranulation releases toxins that cause endothelial injury. Most recently, two different groups of investigators have demonstrated that anti-MPO antibodies alone can cause necrotizing and crescentic glomerulonephritis. Diagnosis Laboratory tests may reveal an increased sedimentation rate, elevated CRP, anemia and elevated creatinine due to kidney impairment. An important diagnostic test is the presence of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) with myeloperoxidase specificity (a constituent of neutrophil granules), and protein and red blood cells in the urine. In patients with neuropathy, electromyography may reveal a sensorimotor peripheral neuropathy. Differential diagnosis The signs and symptoms of microscopic polyangiitis may resemble those of granulomatosis with polyangiitis (GPA) (another form of small-vessel vasculitis) but typically lacks the significant upper respiratory tract involvement (e.g., sinusitis) frequently seen in people affected by GPA. Treatment The customary treatment involves long term dosage of prednisone, alternated or combined with cytotoxic drugs, such as cyclophosphamide or azathioprine. Plasmapheresis may also be indicated in the acute setting to remove ANCA antibodies.Rituximab has been investigated, and in April 2011 approved by the FDA when used in combination with glucocorticoids in adult patients. See also ANCA-associated vasculitides Polyarteritis nodosa List of cutaneous conditions Granulomatosis with polyangitis References == External links ==

Hey Aarogya, explain a situation where Microsporidiosis occurs

Microsporidiosis

Microsporidiosis is an opportunistic intestinal infection that causes diarrhea and wasting in immunocompromised individuals (HIV, for example). It results from different species of microsporidia, a group of microbial (unicellular) fungi.In HIV infected individuals, microsporidiosis generally occurs when CD4+ T cell counts fall below 150. Microsporidia have emerged with significant mortality risk in immunocompromised individuals. These are small, single-celled, obligately intracellular parasites linked to water sources as well as wild, and domestic animals. They were once considered protozoans or protists, but are now known to be fungi, or a sister group to fungi. The most common causes of microsporidiosis is Enterocytozoon bieneusi and Encephalitozoon intestinalis. Cause At least 15 microsporidian species have been recognized as human pathogens, spread across nine genera: Anncaliia A. algerae, A. connori, A. vesicularum Encephalitozoon E. cuniculi, E. hellem, E. intestinalis Enterocytozoon E. bieneusi Microsporidium M. ceylonensis, M. africanum Nosema N. ocularum Pleistophora sp. Trachipleistophora T. hominis, T. anthropophthera Vittaforma V. corneae. Tubulinosema T. acridophagusThe primary causes are Enterocytozoon bieneusi and Encephalitozoon intestinalis. Life cycle (Coded to image at right). The infective form of microsporidia is the resistant spore and it can survive for an extended period of time in the environment. The spore extrudes its polar tubule and infects the host cell. The spore injects the infective sporoplasm into the eukaryotic host cell through the polar tubule. Inside the cell, the sporoplasm undergoes extensive multiplication either by merogony (binary fission) or schizogony (multiple fission). This development can occur either in direct contact with the host cell cytoplasm (E. bieneusi) or inside a vacuole called a parasitophorous vacuole (E. intestinalis). Either free in the cytoplasm or inside a parasitophorous vacuole, microsporidia develop by sporogony to mature spores. During sporogony, a thick wall is formed around the spore, which provides resistance to adverse environmental conditions. When the spores increase in number and completely fill the host cell cytoplasm, the cell membrane is disrupted and releases the spores to the surroundings. These free mature spores can infect new cells thus continuing the cycle. Diagnosis The best option for diagnosis is using PCR.Diagnosis with Microsporidia can be done through gram-positive, acid-fast spores in stool and biopsy material with morphologic demonstration of the organism. Initial detection through light microscopic examination of tissue sections, stools, duodenal aspirates, nasal discharges, bronchoalveolar lavage fluids, and conjunctival smears. Definitive diagnosis can also be achieved through fluorescein-tagged antibody immunofluorescence or electron microscopy, and species identification can be done through PCR. Classification Although it is classified as a protozoal disease in ICD-10, their phylogenetic placement has been resolved to be within the Fungi, and some sources classify microsporidiosis as a mycosis, however, they are highly divergent and rapidly evolving. Treatment Fumagillin has been used in the treatment. Another agent used is albendazole.Because of its severe mortality risk in immunocompromised individuals, two main agents are used: Albendazole, which inhibits tubulin, and Fumagillin, which inhibits methionine aminopeptidase type two. References External links CDCs microsporidiosis info page.

Aarogya, explain a scenario commonly referred as Miscarriage

Miscarriage

Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Some use the cutoff of 20 weeks of gestation, after which fetal death is known as a stillbirth. The most common symptom of a miscarriage is vaginal bleeding with or without pain. Sadness, anxiety, and guilt may occur afterwards. Tissue and clot-like material may leave the uterus and pass through and out of the vagina. Recurrent miscarriage may also be considered a form of infertility.Risk factors for miscarriage include being an older parent, previous miscarriage, exposure to tobacco smoke, obesity, diabetes, thyroid problems, and drug or alcohol use. About 80% of miscarriages occur in the first 12 weeks of pregnancy (the first trimester). The underlying cause in about half of cases involves chromosomal abnormalities. Diagnosis of a miscarriage may involve checking to see if the cervix is open or closed, testing blood levels of human chorionic gonadotropin (hCG), and an ultrasound. Other conditions that can produce similar symptoms include an ectopic pregnancy and implantation bleeding.Prevention is occasionally possible with good prenatal care. Avoiding drugs, alcohol, infectious diseases, and radiation may decrease the risk of miscarriage. No specific treatment is usually needed during the first 7 to 14 days. Most miscarriages will complete without additional interventions. Occasionally the medication misoprostol or a procedure such as vacuum aspiration is used to remove the remaining tissue. Women who have a blood type of rhesus negative (Rh negative) may require Rho(D) immune globulin. Pain medication may be beneficial. Emotional support may help with processing the loss.Miscarriage is the most common complication of early pregnancy. Among women who know they are pregnant, the miscarriage rate is roughly 10% to 20%, while rates among all fertilisation is around 30% to 50%. In those under the age of 35 the risk is about 10% while it is about 45% in those over the age of 40. Risk begins to increase around the age of 30. About 5% of women have two miscarriages in a row. Some recommend not using the term "abortion" in discussions with those experiencing a miscarriage in an effort to decrease distress. In Britain, the term "miscarriage" has replaced any use of the term "spontaneous abortion" in relation to pregnancy loss and in response to complaints of insensitivity towards women who had suffered such loss. An additional benefit of this change is reducing confusion among medical laymen, who may not realize that the term "spontaneous abortion" refers to a naturally-occurring medical phenomenon, and not the intentional termination of pregnancy. Signs and symptoms Signs of a miscarriage include vaginal spotting, abdominal pain, cramping, and fluid, blood clots, and tissue passing from the vagina. Bleeding can be a symptom of miscarriage, but many women also have bleeding in early pregnancy and do not miscarry. Bleeding during the first half of pregnancy may be referred to as a threatened miscarriage. Of those who seek treatment for bleeding during pregnancy, about half will miscarry. Miscarriage may be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing. Risk factors Miscarriage may occur for many reasons, not all of which can be identified. Risk factors are those things that increase the likelihood of having a miscarriage but do not necessarily cause a miscarriage. Up to 70 conditions, infections, medical procedures, lifestyle factors, occupational exposures, chemical exposure, and shift work are associated with increased risk for miscarriage. Some of these risks include endocrine, genetic, uterine, or hormonal abnormalities, reproductive tract infections, and tissue rejection caused by an autoimmune disorder. Trimesters First trimester Most clinically apparent miscarriages (two-thirds to three-quarters in various studies) occur during the first trimester. About 30% to 40% of all fertilized eggs miscarry, often before the pregnancy is known. The embryo typically dies before the pregnancy is expelled; bleeding into the decidua basalis and tissue necrosis causes uterine contractions to expel the pregnancy. Early miscarriages can be due to a developmental abnormality of the placenta or other embryonic tissues. In some instances an embryo does not form but other tissues do. This has been called a "blighted ovum".Successful implantation of the zygote into the uterus is most likely eight to ten days after fertilization. If the zygote has not implanted by day ten, implantation becomes increasingly unlikely in subsequent days.A chemical pregnancy is a pregnancy that was detected by testing but ends in miscarriage before or around the time of the next expected period.Chromosomal abnormalities are found in more than half of embryos miscarried in the first 13 weeks. Half of embryonic miscarriages (25% of all miscarriages) have an aneuploidy (abnormal number of chromosomes). Common chromosome abnormalities found in miscarriages include an autosomal trisomy (22–32%), monosomy X (5–20%), triploidy (6–8%), tetraploidy (2–4%), or other structural chromosomal abnormalities (2%). Genetic problems are more likely to occur with older parents; this may account for the higher rates observed in older women.Luteal phase progesterone deficiency may or may not be a contributing factor to miscarriage. Second and third trimesters Second trimester losses may be due to maternal factors such as uterine malformation, growths in the uterus (fibroids), or cervical problems. These conditions also may contribute to premature birth. Unlike first-trimester miscarriages, second-trimester miscarriages are less likely to be caused by a genetic abnormality; chromosomal aberrations are found in a third of cases. Infection during the third trimester can cause a miscarriage. Age The age of the pregnant woman is a significant risk factor. Miscarriage rates increase steadily with age, with more substantial increases after age 35. In those under the age of 35 the risk is about 10% while it is about 45% in those over the age of 40. Risk begins to increase around the age of 30. Paternal age is associated with increased risk. Obesity, eating disorders and caffeine Not only is obesity associated with miscarriage; it can result in sub-fertility and other adverse pregnancy outcomes. Recurrent miscarriage is also related to obesity. Women with bulimia nervosa and anorexia nervosa may have a greater risk for miscarriage. Nutrient deficiencies have not been found to impact miscarriage rates but hyperemesis gravidarum sometimes precedes a miscarriage.Caffeine consumption also has been correlated to miscarriage rates, at least at higher levels of intake. However, such higher rates are statistically significant only in certain circumstances. Vitamin supplementation has generally not shown to be effective in preventing miscarriage. Chinese traditional medicine has not been found to prevent miscarriage. Endocrine disorders Disorders of the thyroid may affect pregnancy outcomes. Related to this, iodine deficiency is strongly associated with an increased risk of miscarriage. The risk of miscarriage is increased in those with poorly controlled insulin-dependent diabetes mellitus. Women with well-controlled diabetes have the same risk of miscarriage as those without diabetes. Food poisoning Ingesting food that has been contaminated with listeriosis, toxoplasmosis, and salmonella is associated with an increased risk of miscarriage. Amniocentesis and chorionic villus sampling Amniocentesis and chorionic villus sampling (CVS) are procedures conducted to assess the fetus. A sample of amniotic fluid is obtained by the insertion of a needle through the abdomen and into the uterus. Chorionic villus sampling is a similar procedure with a sample of tissue removed rather than fluid. These procedures are not associated with pregnancy loss during the second trimester but they are associated with miscarriages and birth defects in the first trimester. Miscarriage caused by invasive prenatal diagnosis (chorionic villus sampling (CVS) and amniocentesis) is rare (about 1%). Surgery The effects of surgery on pregnancy are not well-known including the effects of bariatric surgery. Abdominal and pelvic surgery are not risk factors for miscarriage. Ovarian tumours and cysts that are removed have not been found to increase the risk of miscarriage. The exception to this is the removal of the corpus luteum from the ovary. This can cause fluctuations in the hormones necessary to maintain the pregnancy. Medications There is no significant association between antidepressant medication exposure and spontaneous abortion. The risk of miscarriage is not likely decreased by discontinuing SSRIs prior to pregnancy. Some available data suggest that there is a small increased risk of miscarriage for women taking any antidepressant, though this risk becomes less statistically significant when excluding studies of poor quality.Medicines that increase the risk of miscarriage include: retinoids nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen misoprostol methotrexate statins Immunizations Immunizations have not been found to cause miscarriage. Live vaccinations, like the MMR vaccine, can theoretically cause damage to the fetus as the live virus can cross the placenta and potentially increase the risk for miscarriage. Therefore, the Center for Disease Control (CDC) recommends against pregnant women receiving live vaccinations. However, there is no clear evidence that has shown live vaccinations to increase the risk for miscarriage or fetal abnormalities.Some live vaccinations include: MMR, varicella, certain types of the influenza vaccine, and rotavirus. Treatments for cancer Ionizing radiation levels given to a woman during cancer treatment cause miscarriage. Exposure can also impact fertility. The use of chemotherapeutic drugs used to treat childhood cancer increases the risk of future miscarriage. Pre-existing diseases Several pre-existing diseases in pregnancy can potentially increase the risk of miscarriage, including diabetes, polycystic ovary syndrome (PCOS), hypothyroidism, certain infectious diseases, and autoimmune diseases. PCOS may increase the risk of miscarriage. Two studies suggested treatment with the drug metformin significantly lowers the rate of miscarriage in women with PCOS, but the quality of these studies has been questioned. Metformin treatment in pregnancy has not been shown to be safe. In 2007 the Royal College of Obstetricians and Gynaecologists also recommended against use of the drug to prevent miscarriage. Thrombophilias or defects in coagulation and bleeding were once thought to be a risk in miscarriage but have been subsequently questioned. Severe cases of hypothyroidism increase the risk of miscarriage. The effect of milder cases of hypothyroidism on miscarriage rates has not been established. A condition called luteal phase defect (LPD) is a failure of the uterine lining to be fully prepared for pregnancy. This can keep a fertilized egg from implanting or result in miscarriage.Mycoplasma genitalium infection is associated with increased risk of preterm birth and miscarriage.Infections can increase the risk of a miscarriage: rubella (German measles), cytomegalovirus, bacterial vaginosis, HIV, chlamydia, gonorrhoea, syphilis, and malaria. Immune status Autoimmunity is a possible cause of recurrent or late-term miscarriages. In the case of an autoimmune-induced miscarriage, the womans body attacks the growing fetus or prevents normal pregnancy progression. Autoimmune disease may cause abnormalities in embryos, which in turn may lead to miscarriage. As an example, Celiac disease increases the risk of miscarriage by an odds ratio of approximately 1.4. A disruption in normal immune function can lead to the formation of antiphospholipid antibody syndrome. This will affect the ability to continue the pregnancy, and if a woman has repeated miscarriages, she can be tested for it. Approximately 15% of recurrent miscarriages are related to immunologic factors. The presence of anti-thyroid autoantibodies is associated with an increased risk with an odds ratio of 3.73 and 95% confidence interval 1.8–7.6. Having lupus also increases the risk for miscarriage. Immunohistochemical studies on decidual basalis and chorionic villi found that the imbalance of the immunological environment could be associated with recurrent pregnancy loss. Anatomical defects and trauma Fifteen per cent of women who have experienced three or more recurring miscarriages have some anatomical defect that prevents the pregnancy from being carried for the entire term. The structure of the uterus affects the ability to carry a child to term. Anatomical differences are common and can be congenital. In some women, cervical incompetence or cervical insufficiency occurs with the inability of the cervix to stay closed during the entire pregnancy. It does not cause first trimester miscarriages. In the second trimester, it is associated with an increased risk of miscarriage. It is identified after a premature birth has occurred at about 16–18 weeks into the pregnancy. During the second trimester, major trauma can result in a miscarriage. Smoking Tobacco (cigarette) smokers have an increased risk of miscarriage. There is an increased risk regardless of which parent smokes, though the risk is higher when the gestational mother smokes. Morning sickness Nausea and vomiting of pregnancy (NVP, or morning sickness) is associated with a decreased risk. Several possible causes have been suggested for morning sickness but there is still no agreement. NVP may represent a defense mechanism which discourages the mothers ingestion of foods that are harmful to the fetus; according to this model, a lower frequency of miscarriage would be an expected consequence of the different food choices made by women experiencing NVP. Chemicals and occupational exposure Chemical and occupational exposures may have some effect in pregnancy outcomes. A cause and effect relationship almost can never be established. Those chemicals that are implicated in increasing the risk for miscarriage are DDT, lead, formaldehyde, arsenic, benzene and ethylene oxide. Video display terminals and ultrasound have not been found to have an effect on the rates of miscarriage. In dental offices where nitrous oxide is used with the absence of anesthetic gas scavenging equipment, there is a greater risk of miscarriage. For women who work with cytotoxic antineoplastic chemotherapeutic agents there is a small increased risk of miscarriage. No increased risk for cosmetologists has been found. Other Alcohol increases the risk of miscarriage. Cocaine use increases the rate of miscarriage. Some infections have been associated with miscarriage. These include Ureaplasma urealyticum, Mycoplasma hominis, group B streptococci, HIV-1, and syphilis. Infections of Chlamydia trachomatis, Camphylobacter fetus, and Toxoplasma gondii have not been found to be linked to miscarriage. Subclinical infections of the lining of the womb, commonly known as chronic endometritis are also associated with poor pregnancy outcomes, compared to women with treated chronic endometritis or no chronic endometritis. Diagnosis In the case of blood loss, pain, or both, transvaginal ultrasound is performed. If a viable intrauterine pregnancy is not found with ultrasound, blood tests (serial βHCG tests) can be performed to rule out ectopic pregnancy, which is a life-threatening situation.If hypotension, tachycardia, and anemia are discovered, exclusion of an ectopic pregnancy is important.A miscarriage may be confirmed by an obstetric ultrasound and by the examination of the passed tissue. When looking for microscopic pathologic symptoms, one looks for the products of conception. Microscopically, these include villi, trophoblast, fetal parts, and background gestational changes in the endometrium. When chromosomal abnormalities are found in more than one miscarriage, genetic testing of both parents may be done. Ultrasound criteria A review article in The New England Journal of Medicine based on a consensus meeting of the Society of Radiologists in Ultrasound in America (SRU) has suggested that miscarriage should be diagnosed only if any of the following criteria are met upon ultrasonography visualization: Classification A threatened miscarriage is any bleeding during the first half of pregnancy. At investigation it may be found that the fetus remains viable and the pregnancy continues without further problems.An anembryonic pregnancy (also called an "empty sac" or "blighted ovum") is a condition where the gestational sac develops normally, while the embryonic part of the pregnancy is either absent or stops growing very early. This accounts for approximately half of miscarriages. All other miscarriages are classified as embryonic miscarriages, meaning that there is an embryo present in the gestational sac. Half of embryonic miscarriages have aneuploidy (an abnormal number of chromosomes).An inevitable miscarriage occurs when the cervix has already dilated, but the fetus has yet to be expelled. This usually will progress to a complete miscarriage. The fetus may or may not have cardiac activity. A complete miscarriage is when all products of conception have been expelled; these may include the trophoblast, chorionic villi, gestational sac, yolk sac, and fetal pole (embryo); or later in pregnancy the fetus, umbilical cord, placenta, amniotic fluid, and amniotic membrane. The presence of a pregnancy test that is still positive, as well as an empty uterus upon transvaginal ultrasonography, does, however, fulfil the definition of pregnancy of unknown location. Therefore, there may be a need for follow-up pregnancy tests to ensure that there is no remaining pregnancy, including ectopic pregnancy. An incomplete miscarriage occurs when some products of conception have been passed, but some remains inside the uterus. However, an increased distance between the uterine walls on transvaginal ultrasonography may also simply be an increased endometrial thickness and/or a polyp. The use of a Doppler ultrasound may be better in confirming the presence of significant retained products of conception in the uterine cavity. In cases of uncertainty, ectopic pregnancy must be excluded using techniques like serial beta-hCG measurements. A missed miscarriage is when the embryo or fetus has died, but a miscarriage has not yet occurred. It is also referred to as delayed miscarriage, silent miscarriage, or missed abortion.A septic miscarriage occurs when the tissue from a missed or incomplete miscarriage becomes infected, which carries the risk of spreading infection (septicaemia) and can be fatal.Recurrent miscarriage ("recurrent pregnancy loss" (RPL) or "habitual abortion") is the occurrence of multiple consecutive miscarriages; the exact number used to diagnose recurrent miscarriage varies. If the proportion of pregnancies ending in miscarriage is 15% and assuming that miscarriages are independent events, then the probability of two consecutive miscarriages is 2.25% and the probability of three consecutive miscarriages is 0.34%. The occurrence of recurrent pregnancy loss is 1%. A large majority (85%) of those who have had two miscarriages will conceive and carry normally afterward.The physical symptoms of a miscarriage vary according to the length of pregnancy, though most miscarriages cause pain or cramping. The size of blood clots and pregnancy tissue that are passed become larger with longer gestations. After 13 weeks gestation, there is a higher risk of placenta retention. Prevention Prevention of a miscarriage can sometimes be accomplished by decreasing risk factors. This may include good prenatal care, avoiding drugs and alcohol, preventing infectious diseases, and avoiding x-rays. Identifying the cause of the miscarriage may help prevent future pregnancy loss, especially in cases of recurrent miscarriage. Often there is little a person can do to prevent a miscarriage. Vitamin supplementation before or during pregnancy has not been found to affect the risk of miscarriage. Progesterone has been shown to prevent miscarriage in women with 1) vaginal bleeding early in their current pregnancy and 2) a previous history of miscarriage. Non-modifiable risk factors Preventing a miscarriage in subsequent pregnancies may be enhanced with assessments of: Modifiable risk factors Maintaining a healthy weight and good prenatal care can reduce the risk of miscarriage. Some risk factors can be minimized by avoiding the following: Smoking Cocaine use Alcohol Poor nutrition Occupational exposure to agents that can cause miscarriage Medications associated with miscarriage Drug abuse Management Women who miscarry early in their pregnancy usually do not require any subsequent medical treatment but they can benefit from support and counseling. Most early miscarriages will complete on their own; in other cases, medication treatment or aspiration of the products of conception can be used to remove remaining tissue. While bed rest has been advocated to prevent miscarriage, this has not been found to be of benefit. Those who are experiencing or who have experienced a miscarriage benefit from the use of careful medical language. Significant distress can often be managed by the ability of the clinician to clearly explain terms without suggesting that the woman or couple are somehow to blame.Evidence to support Rho(D) immune globulin after a spontaneous miscarriage is unclear. In the UK, Rho(D) immune globulin is recommended in Rh-negative women after 12 weeks gestational age and before 12 weeks gestational age in those who need surgery or medication to complete the miscarriage. Methods No treatment is necessary for a diagnosis of complete miscarriage (so long as ectopic pregnancy is ruled out). In cases of an incomplete miscarriage, empty sac, or missed abortion there are three treatment options: watchful waiting, medical management, and surgical treatment. With no treatment (watchful waiting), most miscarriages (65–80%) will pass naturally within two to six weeks. This treatment avoids the possible side effects and complications of medications and surgery, but increases the risk of mild bleeding, need for unplanned surgical treatment, and incomplete miscarriage. Medical treatment usually consists of using misoprostol (a prostaglandin) alone or in combination with mifepristone pre-treatment. These medications help the uterus to contract and expel the remaining tissue out of the body. This works within a few days in 95% of cases. Vacuum aspiration or sharp curettage can be used, with vacuum aspiration being lower-risk and more common. Delayed and incomplete miscarriage In delayed or incomplete miscarriage, treatment depends on the amount of tissue remaining in the uterus. Treatment can include surgical removal of the tissue with vacuum aspiration or misoprostol. Studies looking at the methods of anaesthesia for surgical management of incomplete miscarriage have not shown that any adaptation from normal practice is beneficial. Induced miscarriage An induced abortion may be performed by a qualified healthcare provider for women who cannot continue the pregnancy. Self-induced abortion performed by a woman or non-medical personnel can be dangerous and is still a cause of maternal mortality in some countries. In some locales it is illegal or carries heavy social stigma. However, in the United States, many choose to self-induce or self-manage their abortion and have done so safely. Sex Some organizations recommend delaying sex after a miscarriage until the bleeding has stopped to decrease the risk of infection. However, there is not sufficient evidence for the routine use of antibiotic to try to avoid infection in incomplete abortion. Others recommend delaying attempts at pregnancy until one period has occurred to make it easier to determine the dates of a subsequent pregnancy. There is no evidence that getting pregnant in that first cycle affects outcomes and an early subsequent pregnancy may actually improve outcomes. Support Organizations exist that provide information and counselling to help those who have had a miscarriage. Family and friends often conduct a memorial or burial service. Hospitals also can provide support and help memorialize the event. Depending on locale others desire to have a private ceremony. Providing appropriate support with frequent discussions and sympathetic counselling are part of evaluation and treatment. Those who experience unexplained miscarriage can be treated with emotional support. Miscarriage leave Miscarriage leave is leave of absence in relation to miscarriage. The following countries offer paid or unpaid leave to women who have had a miscarriage. The Philippines – 60 days fully paid leave for miscarriages (before 20 weeks of gestation) or emergency termination of the pregnancy (on the 20th week or after) The husband of the mother gets seven days fully paid leave up to the 4th pregnancy. India – six weeks leave New Zealand – three days bereavement leave for both parents Mauritius – two weeks leave Indonesia – six weeks leave Taiwan – five days, one week or four weeks, depending on how advanced the pregnancy was Outcomes Psychological and emotional effects Every womans personal experience of miscarriage is different, and women who have more than one miscarriage may react differently to each event.In Western cultures since the 1980s, medical providers assume that experiencing a miscarriage "is a major loss for all pregnant women". A miscarriage can result in anxiety, depression or stress for those involved. It can have an effect on the whole family. Many of those experiencing a miscarriage go through a grieving process. "Prenatal attachment" often exists that can be seen as parental sensitivity, love and preoccupation directed toward the unborn child. Serious emotional impact is usually experienced immediately after the miscarriage. Some may go through the same loss when an ectopic pregnancy is terminated. In some, the realization of the loss can take weeks. Providing family support to those experiencing the loss can be challenging because some find comfort in talking about the miscarriage while others may find the event painful to discuss. The father can have the same sense of loss. Expressing feelings of grief and loss can sometimes be harder for men. Some women are able to begin planning their next pregnancy after a few weeks of having the miscarriage. For others, planning another pregnancy can be difficult. Some facilities acknowledge the loss. Parents can name and hold their infant. They may be given mementos such as photos and footprints. Some conduct a funeral or memorial service. They may express the loss by planting a tree.Some health organizations recommend that sexual activity be delayed after the miscarriage. The menstrual cycle should resume after about three to four months. Women report that they were dissatisfied with the care they received from physicians and nurses. Subsequent pregnancies Some parents want to try to have a baby very soon after the miscarriage. The decision of trying to become pregnant again can be difficult. Reasons exist that may prompt parents to consider another pregnancy. For older mothers, there may be some sense of urgency. Other parents are optimistic that future pregnancies are likely to be successful. Many are hesitant and want to know about the risk of having another or more miscarriages. Some clinicians recommend that the women have one menstrual cycle before attempting another pregnancy. This is because the date of conception may be hard to determine. Also, the first menstrual cycle after a miscarriage can be much longer or shorter than expected. Parents may be advised to wait even longer if they have experienced late miscarriage or molar pregnancy, or are undergoing tests. Some parents wait for six months based upon recommendations from their health care provider.The risks of having another miscarriage vary according to the cause. The risk of having another miscarriage after a molar pregnancy is very low. The risk of another miscarriage is highest after the third miscarriage. Pre-conception care is available in some locales. Later cardiovascular disease There is a significant association between miscarriage and later development of coronary artery disease, but not of cerebrovascular disease. Epidemiology Among women who know they are pregnant, the miscarriage rate is roughly 10% to 20%, while rates among all fertilized zygotes are around 30% to 50%. A 2012 review found the risk of miscarriage between 5 and 20 weeks from 11% to 22%. Up to the 13th week of pregnancy, the risk of miscarriage each week was around 2%, dropping to 1% in week 14 and reducing slowly between 14 and 20 weeks.The precise rate is not known because a large number of miscarriages occur before pregnancies become established and before the woman is aware she is pregnant. Additionally, those with bleeding in early pregnancy may seek medical care more often than those not experiencing bleeding. Although some studies attempt to account for this by recruiting women who are planning pregnancies and testing for very early pregnancy, they still are not representative of the wider population.The prevalence of miscarriage increases with the age of both parents. In a Danish register-based study where the prevalence of miscarriage was 11%, the prevalence rose from 9% at 22 years of age to 84% by 48 years of age. Another, later study in 2013 found that when either parent was over the age of 40, the rate of known miscarriages doubled.In 2010, 50,000 inpatient admissions for miscarriage occurred in the UK. Terminology Most affected women and family members refer to miscarriage as the loss of a baby, rather than an embryo or fetus, and healthcare providers are expected to respect and use the language that the person chooses. Clinical terms can suggest blame, increase distress, and even cause anger. Terms that are known to cause distress in those experiencing miscarriage include: abortion (including spontaneous abortion) rather than miscarriage, habitual aborter rather than a woman experiencing recurrent pregnancy loss, products of conception rather than baby, blighted ovum rather than early pregnancy loss or delayed miscarriage, cervical incompetence rather than cervical weakness, and evacuation of retained products of conception (ERPC) rather than surgical management of miscarriage.Pregnancy loss is a broad term that is used for miscarriage, ectopic and molar pregnancies. The term fetal death applies variably in different countries and contexts, sometimes incorporating weight, and gestational age from 16 weeks in Norway, 20 weeks in the US and Australia, 24 weeks in the UK to 26 weeks in Italy and Spain. A fetus that died before birth after this gestational age may be referred to as a stillbirth. Under UK law, all stillbirths should be registered, although this does not apply to miscarriages. History The medical terminology applied to experiences during early pregnancy has changed over time. Before the 1980s, health professionals used the phrase spontaneous abortion for a miscarriage and induced abortion for a termination of the pregnancy. In the late 1980s and 1990s, doctors became more conscious of their language in relation to early pregnancy loss. Some medical authors advocated change to use of miscarriage instead of spontaneous abortion because they argued this would be more respectful and help ease a distressing experience. The change was being recommended by some in the profession in Britain in the late 1990s. In 2005 the European Society for Human Reproduction and Embryology (ESHRE) published a paper aiming to facilitate a revision of nomenclature used to describe early pregnancy events. Society and culture Societys reactions to miscarriage have changed over time. In the early 20th century, the focus was on the mothers physical health and the difficulties and disabilities that miscarriage could produce. Other reactions, such as the expense of medical treatments and relief at ending an unwanted pregnancy, were also heard. In the 1940s and 1950s, people were more likely to express relief, not because the miscarriage ended an unwanted or mistimed pregnancy, but because people believed that miscarriages were primarily caused by birth defects, and miscarrying meant that the family would not raise a child with disabilities. The dominant attitude in the mid-century was that a miscarriage, although temporarily distressing, was a blessing in disguise for the family, and that another pregnancy and a healthier baby would soon follow, especially if women trusted physicians and reduced their anxieties. Media articles were illustrated with pictures of babies, and magazine articles about miscarriage ended by introducing the healthy baby—usually a boy—that had shortly followed it.Beginning in the 1980s, miscarriage in the US was primarily framed in terms of the individual womans personal emotional reaction, and especially her grief over a tragic outcome. The subject was portrayed in the media with images of an empty crib or an isolated, grieving woman, and stories about miscarriage were published in general-interest media outlets, not just womens magazines or health magazines. Family members were encouraged to grieve, to memorialize their losses through funerals and other rituals, and to think of themselves as being parents. This shift to recognizing these emotional responses was partly due to medical and political successes, which created an expectation that pregnancies are typically planned and safe, and to womens demands that their emotional reactions no longer be dismissed by the medical establishments. It also reinforces the anti-abortion movement’s belief that human life begins at conception or early in pregnancy, and that motherhood is a desirable life goal. The modern one-size-fits-all model of grief does not fit every womans experience, and an expectation to perform grief creates unnecessary burdens for some women. The reframing of miscarriage as a private emotional experience brought less awareness of miscarriage and a sense of silence around the subject, especially compared to the public discussion of miscarriage during campaigns for access to birth control during the early 20th century, or the public campaigns to prevent miscarriages, stillbirths, and infant deaths by reducing industrial pollution during the 1970s.In places where induced abortion is illegal or carries social stigma, suspicion may surround miscarriage, complicating an already sensitive issue. In the 1960s, the use of the word miscarriage in Britain (instead of spontaneous abortion) occurred after changes in legislation. Developments in ultrasound technology (in the early 1980s) allowed them to identify earlier miscarriages.According to French statutes, an infant born before the age of viability, determined to be 28 weeks, is not registered as a child. If birth occurs after this, the infant is granted a certificate that allows women who have given birth to a stillborn child, to have a symbolic record of that child. This certificate can include a registered and given name to allow a funeral and acknowledgement of the event. Other animals Miscarriage occurs in all animals that experience pregnancy, though in such contexts it is more commonly referred to as a spontaneous abortion (the two terms are synonymous). There are a variety of known risk factors in non-human animals. For example, in sheep, miscarriage may be caused by crowding through doors, or being chased by dogs. In cows, spontaneous abortion may be caused by contagious disease, such as brucellosis or Campylobacter, but often can be controlled by vaccination. In many species of sharks and rays, stress induced miscarriage occurs frequently on capture.Other diseases are also known to make animals susceptible to miscarriage. Spontaneous abortion occurs in pregnant prairie voles when their mate is removed and they are exposed to a new male, an example of the Bruce effect, although this effect is seen less in wild populations than in the laboratory. Female mice who had spontaneous abortions showed a sharp rise in the amount of time spent with unfamiliar males preceding the abortion than those who did not. See also Pregnancy and Infant Loss Remembrance Day Citations General and cited references Hoffman, Barbara; J. Whitridge Williams (2012). Williams Gynecology (2nd ed.). New York: McGraw-Hill Medical. ISBN 978-0071716727. == External links ==

Hi Aarogya , Do you know what is Hurler syndrome,

Hurler syndrome

Hurler syndrome, also known as mucopolysaccharidosis Type IH (MPS-IH), Hurlers disease, and formerly gargoylism, is a genetic disorder that results in the buildup of large sugar molecules called glycosaminoglycans (GAGs) in lysosomes. The inability to break down these molecules results in a wide variety of symptoms caused by damage to several different organ systems, including but not limited to the nervous system, skeletal system, eyes, and heart. The underlying mechanism is a deficiency of alpha-L iduronidase, an enzyme responsible for breaking down GAGs.: 544  Without this enzyme, a buildup of dermatan sulfate and heparan sulfate occurs in the body. Symptoms appear during childhood, and early death usually occurs. Other, less severe forms of MPS Type I include Hurler-Scheie Syndrome (MPS-IHS) and Scheie Syndrome (MPS-IS). Hurler syndrome is classified as a lysosomal storage disease. It is clinically related to Hunter syndrome (MPS II); however, Hunter syndrome is X-linked, while Hurler syndrome is autosomal recessive. Signs and symptoms Children with Hurler syndrome may appear normal at birth and develop symptoms over the first years of life. Symptoms vary between patients.One of the first abnormalities that may be detected is coarsening of the facial features; these symptoms can begin at 3–6 months of age. The head can be large with prominent frontal bones. The skull can be elongated. The nose can have a flattened nasal bridge with continuous nasal discharge. The eye sockets may be widely spaced, and the eyes may protrude from the skull. The lips can be large, and affected children may hold their jaws open constantly. Skeletal abnormalities occur by about age 6 months, but may not be clinically obvious until 10–14 months. Patients may experience debilitating spine and hip deformities, carpal tunnel syndrome, and joint stiffness. Patients may be normal height in infancy, but stop growing by the age of 2 years. They may not reach a height of greater than 4 feet.Other early symptoms may include inguinal and umbilical hernias. These may be present at birth, or they may develop within the first months of life. Clouding of the cornea and retinal degeneration may occur within the first year of life, leading to blindness. Enlarged liver and spleen are common. There is no organ dysfunction, but GAG deposition in these organs may lead to a massive increase in size. Patients may also have diarrhea. Aortic valve disease may occur.Airway obstruction is frequent, usually secondary to abnormal cervical vertebrae. Upper and lower respiratory tract infections can be frequent.Developmental delay may become apparent by age 1–2 years, with a maximum functional age of 2–4 years. Progressive deterioration follows. Most children develop limited language capabilities. Death usually occurs by age 10. Genetics Children with Hurler Syndrome carry two defective copies of the IDUA gene, which has been mapped to the 4p16.3 site on chromosome 4. This is the gene which encodes for the protein iduronidase. As of 2018, more than 201 different mutations in the IDUA gene have been shown to cause MPS I.Because Hurler syndrome is an autosomal recessive disorder, affected persons have two nonworking copies of the gene. A person born with one normal copy and one defective copy is called a carrier. They will produce less α-L-iduronidase than an individual with two normal copies of the gene. The reduced production of the enzyme in carriers, however, remains sufficient for normal function; the person should not show any symptoms of the disease. Mechanisms The IDUA gene is responsible for encoding an enzyme called alpha-L-iduronidase. Through hydrolysis, alpha-L-iduronidase is responsible for breaking down a molecule called unsulfated alpha-L-iduronic acid. This is a uronic acid found in the GAGs dermatan sulfate and heparan sulfate. The alpha-L-iduronidase enzyme is located in lysosomes. Without sufficient enzymatic function, these GAGs cannot be digested properly. Diagnosis Diagnosis often can be made through clinical examination and urine tests (excess mucopolysaccharides are excreted in the urine). Enzyme assays (testing a variety of cells or body fluids in culture for enzyme deficiency) are also used to provide definitive diagnosis of one of the mucopolysaccharidoses. Prenatal diagnosis using amniocentesis and chorionic villus sampling can verify if a fetus either carries a copy of the defective gene or is affected with the disorder. Genetic counseling can help parents who have a family history of the mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders. Classification All members of the mucopolysaccharidosis family are also lysosomal storage diseases. Mucopolysaccharidosis type I (MPS I) is divided into three subtypes based on severity of symptoms. All three types result the absence or decreased functioning of the same enzyme. MPS-IH (Hurler syndrome) is the most severe of the MPS I subtypes. The other two types are MPS-IS (Scheie syndrome) and MPS-IHS (Hurler-Scheie syndrome).Because of the substantial overlap between Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome, some sources consider these terms to be outdated. Instead, MPS I may be divided into "severe" and "attenuated" forms. Treatment There is currently no cure for Hurler Syndrome. Enzyme replacement therapy with iduronidase (Aldurazyme) may improve pulmonary function and mobility. It can reduce the amount of carbohydrates being improperly stored in organs. Surgical correction of hand and foot deformities may be necessary. Corneal surgery may help alleviate vision problems.Bone marrow transplantation (BMT) and umbilical cord blood transplantation (UCBT) can be used as treatments for MPS I. BMT from siblings with identical HLA genes and from relatives with similar HLA genes can significantly improve survival, cognitive function, and physical symptoms. Patients can develop graft versus host disease; this is more likely in non-sibling donors. In a 1998 study, children with HLA-identical sibling donors had a 5-year survival of 75%; children with non-sibling donors had a 5-year survival of 53%.Children often lack access to a suitable bone marrow donor. In these cases, UCBT from unrelated donors can increase survival, decrease physical signs of the disease, and improve cognition. Complications from this treatment may include graft versus host disease. Prognosis A British study from 2008 found a median estimated life expectancy of 8.7 years for patients with Hurler syndrome. In comparison, the median life expectancy for all forms of MPS type I was 11.6 years. Patients who received successful bone marrow transplants had a 2-year survival rate of 68% and a 10-year survival rate of 64%. Patients who did not receive bone marrow transplants had a significantly reduced lifespan, with a median age of 6.8 years. Epidemiology Hurler syndrome has an overall frequency of one per 100,000. Combined, all of the mucopolysaccharidoses have a frequency of approximately one in every 25,000 births in the United States. Research Gene therapy A great deal of interest exists in treating MPS I with gene therapy. In animal models, delivery of the iduronidase gene has been accomplished with retrovirus, adenovirus, adeno-associated virus, and plasmid vectors. Mice and dogs with MPS I have been successfully treated with gene therapy. Most vectors can correct the disease in the liver and spleen, and can correct brain effects with a high dosage. Gene therapy has improved survival, neurological, and physical symptoms; however, some animals have developed unexplained liver tumors. If safety issues can be resolved, gene therapy may provide an alternative human treatment for MPS disorders in the future.Sangamo Therapeutics, headquartered in Richmond, California, is currently conducting a clinical trial involving gene editing using Zinc Finger Nuclease (ZFN) for the treatment of MPS I. History In 1919, Gertrud Hurler, a German pediatrician, described a syndrome involving corneal clouding, skeletal abnormalities, and mental retardation. A similar disease of "gargoylism" had been described in 1917 by Charles A. Hunter. Hurler did not mention Hunters paper. Because of the communications interruptions caused by World War I, it is likely that she was unaware of his study. Hurler syndrome now refers to MPS IH, while Hunter syndrome refers to MPS II. In 1962, a milder form of MPS I was identified by Scheie, leading to the designation of Scheie syndrome. See also Hunter syndrome (MPS II) Sanfilippo syndrome (MPS III) Morquio syndrome (MPS IV) Maroteaux-Lamy syndrome (MPS VI) References External links GeneReview/NIH/UW entry on Mucopolysaccharidosis Type I

Hey Aarogya , Do you know what is Hunter syndrome,

Hunter syndrome

Hunter syndrome, or mucopolysaccharidosis type II (MPS II), is a rare genetic disorder in which large sugar molecules called glycosaminoglycans (or GAGs or mucopolysaccharides) build up in body tissues. It is a form of lysosomal storage disease. Hunter syndrome is caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (I2S). The lack of this enzyme causes heparan sulfate and dermatan sulfate to accumulate in all body tissues. Hunter syndrome is the only MPS syndrome to exhibit X-linked recessive inheritance.The symptoms of Hunter syndrome are comparable to those of MPS I. It causes abnormalities in many organs, including the skeleton, heart, and respiratory system. In severe cases, this leads to death during the teenaged years. Unlike MPS I, corneal clouding is not associated with this disease. Signs and symptoms Hunter syndrome may present with a wide variety of phenotypes. It has traditionally been categorized as either "mild" or "severe" depending on the presence of central nervous system symptoms, but this is an oversimplification. Patients with "attenuated" or "mild" forms of the disease may still have significant health issues. For severely affected patients, the clinical course is relatively predictable; patients will normally die at an early age. For those with milder forms of the disease, a wider variety of outcomes exist. Many live into their 20s and 30s, but some may have near-normal life expectancies. Cardiac and respiratory abnormalities are the usual cause of death for patients with milder forms of the disease.The symptoms of Hunter syndrome (MPS II) are generally not apparent at birth. Often, the first symptoms may include abdominal hernias, ear infections, runny noses, and colds. As the buildup of GAGs continues throughout the cells of the body, signs of MPS II become more visible. Physical appearances of many children with the syndrome include a distinctive coarseness in their facial features, including a prominent forehead, a nose with a flattened bridge, and an enlarged tongue. They may also have a large head, as well as an enlarged abdomen. For severe cases of MPS II, a diagnosis is often made between the ages of 18 and 36 months. In milder cases, patients present similarly to children with Hurler–Scheie syndrome, and a diagnosis is usually made between the ages of 4 and 8 years.The continued storage of GAGs leads to abnormalities in multiple organ systems. After 18 months, children with severe MPS II may experience developmental decline and progressive loss of skills. The thickening of the heart valves and walls of the heart can result in progressive decline in cardiac function. The walls of the airway may become thickened, as well, leading to obstructive airway disease. As the liver and spleen grow larger with time, the abdomen may become distended, making hernias more noticeable. All major joints may be affected by MPS II, leading to joint stiffness and limited motion. Progressive involvement of the finger and thumb joints results in decreased ability to pick up small objects. The effects on other joints, such as hips and knees, can make walking normally increasingly difficult. If carpal tunnel syndrome develops, a further decrease in hand function can occur. The bones themselves may be affected, resulting in short stature. In addition, pebbly, ivory-colored skin lesions may be found on the upper arms, legs, and upper back of some people with it. These skin lesions are considered pathognomic for the disease. Finally, the storage of GAGs in the brain can lead to delayed development with subsequent intellectual disability and progressive loss of function.The age at onset of symptoms and the presence or absence of behavioral disturbances are predictive factors of ultimate disease severity in very young patients. Behavioral disturbances can often mimic combinations of symptoms of attention deficit hyperactivity disorder, autism, obsessive compulsive disorder, and/or sensory processing disorder, although the existence and level of symptoms differ in each affected child. They often also include a lack of an appropriate sense of danger, and aggression. The behavioral symptoms of MPS II generally precede neurodegeneration and often increase in severity until the mental handicaps become more pronounced. By the time of death, most children with severe MPS II have severe mental disabilities and are completely dependent on their caretakers. Genetics Since Hunter syndrome is an X-linked recessive disorder, it preferentially affects male patients. The IDS gene is located on the X chromosome. The IDS gene encodes for an enzyme called iduronate-2-sulfatase (I2S). A lack of this enzyme leads to a buildup of GAGs, which cause the symptoms of MPS II. Females generally have two X chromosomes, whereas males generally have one X chromosome that they inherit from their mother and one Y chromosome that they inherit from their father.If a female inherits one copy of the mutant allele for MPS II, she will usually have a normal copy of the IDS gene which can compensate for the mutant allele. This is known as being a genetic carrier. A male who inherits a defective X chromosome, though, usually does not have another X chromosome to compensate for the mutant gene. Thus, a female would need to inherit two mutant genes to develop MPS II, while a male patient only needs to inherit one mutant gene. A female carrier can be affected due to X-inactivation, which is a random process. Pathophysiology The human body depends on a vast array of biochemical reactions to support critical functions. One of these functions is the breakdown of large biomolecules. The failure of this process is the underlying problem in Hunter syndrome and related storage disorders.The biochemistry of Hunter syndrome is related to a problem in a part of the connective tissue known as the extracellular matrix, which is made up of a variety of sugars and proteins. It helps to form the architectural framework of the body. The matrix surrounds the cells of the body in an organized meshwork and functions as the glue that holds the cells of the body together. One of the parts of the extracellular matrix is a molecule called a proteoglycan. Like many components of the body, proteoglycans need to be broken down and replaced. When the body breaks down proteoglycans, one of the resulting products is mucopolysaccharides (GAGs).In MPS II, the problem concerns the breakdown of two GAGs: dermatan sulfate and heparan sulfate. The first step in the breakdown of dermatan sulfate and heparan sulfate requires the lysosomal enzyme iduronate-2-sulfatase, or I2S. In people with MPS II, this enzyme is either partially or completely inactive. As a result, GAGs build up in cells throughout the body, particularly in tissues that contain large amounts of dermatan sulfate and heparan sulfate. The rate of GAGs buildup is not the same for all people with MPS II, resulting in a wide spectrum of medical problems. Diagnosis The first laboratory screening test for an MPS disorder is a urine test for GAGs. Abnormal values indicate that an MPS disorder is likely. The urine test can occasionally be normal even if the child actually has an MPS disorder. A definitive diagnosis of MPS II is made by measuring I2S activity in serum, white blood cells, or fibroblasts from skin biopsy. In some people with MPS II, analysis of the I2S gene can determine clinical severity.Prenatal diagnosis is routinely available by measuring I2S enzymatic activity in amniotic fluid or in chorionic villus tissue. If a specific mutation is known to run in the family, prenatal molecular genetic testing can be performed. DNA sequencing can reveal if someone is a carrier for the disease. Treatment Because of the wide variety of phenotypes, the treatment for this disorder is specifically determined for each patient. Until recently, no effective therapy for MPS II was available, so palliative care was used. Recent advances, though, have led to medications that can improve survival and well-being in people with MPS II. Enzyme replacement therapy Idursulfase, a purified form of the missing lysosomal enzyme, underwent clinical trial in 2006 and was subsequently approved by the United States Food and Drug Administration as an enzyme replacement treatment for MPS II. Idursulfase beta, another enzyme replacement treatment, was approved in Korea by the Ministry of Food and Drug Safety. Recent advances in enzyme replacement therapy (ERT) with idursulfase have been proven to improve many signs and symptoms of MPS II, especially if started early in the disease. After administration, it can be transported into cells to break down GAGs, but as the medication cannot cross the blood–brain barrier, it is not expected to lead to cognitive improvement in patients with severe central nervous system symptoms. Even with ERT, treatment of various organ problems from a wide variety of medical specialists is necessary. Bone-marrow and stem-cell transplantation Bone-marrow transplantation and hematopoietic stem-cell transplantation (HSCT) have been used as treatments in some studies. While transplantation has provided benefits for many organ systems, it has not been shown to improve the neurological symptoms of the disease. Although HSCT has shown promise in the treatment of other MPS disorders, its results have been unsatisfactory so far in the treatment of MPS II. ERT has been shown to lead to better outcomes in MPS II patients. Gene editing therapy In February 2019, medical scientists working with Sangamo Therapeutics, headquartered in Richmond, California, announced the first "in body" human gene editing therapy to permanently alter DNA - in a patient with MPS II. Clinical trials by Sangamo involving gene editing using zinc finger nuclease are ongoing as of February 2019. Prognosis Earlier onset of symptoms is linked to a worse prognosis. For children who exhibit symptoms between the ages of 2 and 4, death usually occurs by the age of 15 to 20 years. The cause of death is usually due to neurological complications, obstructive airway disease, and cardiac failure. If patients have minimal neurologic involvement, they may survive into their 50s or beyond. Epidemiology An estimated 2,000 people have MPS II worldwide, 500 of whom live in the United States.A study in the United Kingdom indicated an incidence among males around one in 130,000 male live births. History The syndrome is named after physician Charles A. Hunter (1873–1955), who first described it in 1917. Research Beginning in 2010, a phase I/II clinical trial evaluated intrathecal injections of a more concentrated dose of idursulfase than the intravenous formulation used in enzyme replacement therapy infusions, in hopes of preventing the cognitive decline associated with the severe form of the condition. Results were reported in October 2013. A phase II/III clinical trial began in 2014.In 2017, a 44-year-old patient with MPS II was treated with gene therapy in an attempt to prevent further damage by the disease. This is the first case of gene therapy being used in vivo in humans. The study was extended to six patients in 2018. Society On 24 July 2004, Andrew Wragg, 38, of Worthing, West Sussex, England, suffocated his 10-year-old son Jacob with a pillow, because of the boys disabilities related to MPS II. A military security specialist, Wragg also claimed that he was under stress after returning from the war in Iraq. He denied murdering Jacob, but pleaded guilty to manslaughter by reason of diminished capacity. Mrs Justice Anne Rafferty called the case "exceptional", gave Wragg a two-year prison sentence for manslaughter, then suspended his sentence for two years. Rafferty said "nothing [was] to be gained" from sending Wragg to prison for the crime. See also Hurler syndrome (MPS I) Sanfilippo syndrome (MPS III) Morquio syndrome (MPS IV) Prenatal testing Genetic counseling References External links Media related to Hunter syndrome at Wikimedia Commons GeneReview/NIH/UW entry on Mucopolysaccharidosis Type II

Aarogya, could you share information about a health condition involving Maroteaux–Lamy syndrome

Maroteaux–Lamy syndrome

Maroteaux–Lamy syndrome, or Mucopolysaccharidosis Type VI (MPS-VI), is an inherited disease caused by a deficiency in the enzyme arylsulfatase B (ARSB). ASRB is responsible for the breakdown of large sugar molecules called glycosaminoglycans (GAGs, also known as mucopolysaccharides). In particular, ARSB breaks down dermatan sulfate and chondroitin sulfate. Because people with MPS-VI lack the ability to break down these GAGs, these chemicals build up in the lysosomes of cells. MPS-VI is therefore a type of lysosomal storage disease. Signs and symptoms Unlike other MPS diseases, children with Maroteaux–Lamy syndrome usually have normal intelligence. They share many of the physical symptoms found in Hurler syndrome. Maroteaux–Lamy syndrome has a variable spectrum of severe symptoms. Neurological complications include clouded corneas, deafness, thickening of the dura (the membrane that surrounds and protects the brain and spinal cord), and pain caused by compressed or traumatized nerves and nerve roots.Signs are revealed early in the affected childs life, with one of the first symptoms often being a significantly prolonged age of learning how to walk. Growth begins normally, but children usually stop growing by age 8. By age 10, children often develop a shortened trunk, crouched stance, and restricted joint movement. In more severe cases, children also develop a protruding abdomen and forward-curving spine. Skeletal changes, particularly in the pelvis, are progressive and limit movement. Many children also have umbilical hernia or inguinal hernias. Nearly all children have some form of heart disease, usually involving the heart valves. Genetics This disorder is inherited in an autosomal recessive pattern. People with two working copies of the gene are unaffected. People with one working copy are genetic carriers of Maroteaux-Lamy Syndrome. They have no symptoms but may pass down the defective gene to their children. People with two defective copies will have MPS-VI. Diagnosis A urinalysis will show elevated levels of dermatan sulfate in the urine. A blood sample may be taken to assess the level of ASRB activity. Dermal fibroblast cells may also be examined for ASRB activity. Molecular genetic testing can give information about the specific mutation causing MPS-VI, but it is only available at specialized laboratories. Treatment The treatment of Maroteaux–Lamy syndrome is symptomatic and individually tailored. A variety of specialists may be needed. In 2005, the FDA approved the orphan drug galsulfase (Naglazyme) for the treatment of Maroteaux–Lamy syndrome. Galsulfase is an enzyme replacement therapy (ERT) in which the missing ASRB enzyme is replaced with a recombinant version.In addition to ERT, various procedures can alleviate the symptoms of MPS-VI. Surgery may be necessary to treat abnormalities such as carpal tunnel syndrome, skeletal malformations, spinal cord compression, hip degeneration, and hernias. Some patients may need heart valve replacement. It may be necessary to remove the tonsils and/or adenoids. Severe tracheomalacia may require surgery. Physical therapy and exercise may improve joint stiffness.Hydrocephalus may be treated by the insertion of a shunt to drain excess cerebrospinal fluid. A corneal transplantation can be performed for individuals with severe corneal clouding. A myringotomy, in which a small incision is made in the eardrum, may be helpful for patients with fluid accumulation in the ears. Hearing aids may be useful, and speech therapy may help children with hearing loss communicate more effectively.Certain medications can be used to treat heart abnormalities, asthma-like episodes, and chronic infections associated with MPS-VI. Anti-inflammatory medications may be of benefit. Respiratory insufficiency may require treatment with supplemental oxygen. Aggressive management of airway secretions is necessary as well. Sleep apnea may be treated with a CPAP or BPAP device. Prognosis The life expectancy of individuals with MPS VI varies depending on the severity of symptoms. Without treatment, some individuals may survive through late childhood or early adolescence. People with milder forms of the disorder usually live into adulthood, although they may have reduced life expectancy. Heart disease and airway obstruction are major causes of death in people with Maroteaux–Lamy syndrome. Epidemiology Males and females are affected equally. Studies have shown a birth prevalence between 1 in 43,261 and 1 in 1,505,160 live births. These numbers are likely an underestimate of the true number of cases, because newborn screening for MPS-VI is not widely available. Although studies have not revealed an ethnic predisposition, certain groups with a high degree of consanguinity have a higher prevalence of MPS-VI. For example, one study of a population of Turkish immigrants in Germany revealed that this group had a rate of 1 in 43,261; this was approximately ten times higher than the rate of MPS-VI in non-Turkish Germans. In different populations worldwide, MPS-VI made up between 2 and 18.5% of all MPS disorders. History It is named after Pierre Maroteaux (1926–2019) and his mentor Maurice Emil Joseph Lamy (1895–1975), both French physicians. Society and culture Keenan Cahill is a YouTuber with Maroteaux–Lamy syndrome.Isabel Bueso, a Guatemalan woman with Maroteaux–Lamy syndrome who has been receiving treatment at UCSF Benioff Childrens Hospital, was at risk of deportation from the United States after the Trump Administration ended the deferred action program in August 2019. In December 2019, she was granted another deferral of two years. See also Hurler syndrome (MPS I) Hunter syndrome (MPS II) Sanfilippo syndrome (MPS III) Morquio syndrome (MPS IV) References == External links ==

Do you know what is Sly syndrome, Aarogya

Sly syndrome

Sly syndrome, also called mucopolysaccharidosis type VII (MPS-VII), is an autosomal recessive lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase. This enzyme is responsible for breaking down large sugar molecules called glycosaminoglycans (AKA GAGs, or mucopolysaccharides). The inability to break down GAGs leads to a buildup in many tissues and organs of the body. The severity of the disease can vary widely. Signs and symptoms The most severe cases of Sly syndrome can result in hydrops fetalis, which results in fetal death or death soon after birth. Some people with Sly syndrome may begin to have symptoms in early childhood. Symptoms can include an enlarged head, fluid buildup in the brain, coarse facial features, enlarged tongue, enlarged liver, enlarged spleen, problems with the heart valves, and abdominal hernias. People with Sly syndrome may also suffer from sleep apnea, frequent lung infections, and problems with vision secondary to cloudy corneas. Sly syndrome causes various musculoskeletal abnormalities that worsen with age. These can include short stature, joint deformities, dysostosis multiplex, spinal stenosis, and carpal tunnel syndrome.While some individuals have developmental delay, others may have normal intelligence. However, the accumulation of GAGs in the brain usually leads to the slowing of development from ages 1–3, and then a loss of previously learned skills until death. Genetics The defective gene responsible for Sly syndrome is located on chromosome 7. Diagnosis Most people with Sly disease will have elevated levels of GAGs seen in the urine. A confirmatory test is necessary for diagnosis. Skin cells and red blood cells of affected people will have low levels of β-glucuronidase activity. Sly syndrome can also be diagnosed through prenatal testing. Treatment Vestronidase alfa-vjbk (trade name Mepsevii), an enzyme replacement therapy which is a recombinant form of human β-glucuronidase, is approved by U.S. Food and Drug Administration for the treatment of Sly syndrome. Hematopoietic stem cell transplant (HSCT) has been used to treat other types of MPS diseases, but this is not yet available for MPS-VII. Animal experiments suggest that HSCT may be an effective treatment for MPS-VII in humans. Prognosis The life expectancy of individuals with MPS VII varies depending on the symptoms. Some individuals are stillborn, while some may survive into adulthood. Epidemiology MPS-VII is one of the rarest forms of MPS. It occurs in less than 1 in 250,000 births. As a family, MPS diseases occur in 1 in 25,000 births, and the larger family of lysosomal storage diseases occur in 1 out of 7,000 to 8,000 births. History Sly syndrome was originally discovered in 1972. It was named after its discoverer William S. Sly, an American biochemist who has spent nearly his entire academic career at Saint Louis University. References == External links ==

Aarogya, give me a short description about Mucormycosis

Mucormycosis

Mucormycosis, also known as black fungus, is a serious fungal infection that comes under fulminant fungal sinusitis, usually in people who are immunocompromised. It is curable only when diagnosed early. Symptoms depend on where in the body the infection occurs. It most commonly infects the nose, sinuses, eye, and brain resulting in a runny nose, one-sided facial swelling and pain, headache, fever, blurred vision, bulging or displacement of the eye (proptosis), and tissue death. Other forms of disease may infect the lungs, stomach and intestines, and skin.It is spread by spores of molds of the order Mucorales, most often through inhalation, contaminated food, or contamination of open wounds. These fungi are common in soils, decomposing organic matter (such as rotting fruit and vegetables), and animal manure, but usually do not affect people. It is not transmitted between people. Risk factors include diabetes with persistently high blood sugar levels or diabetic ketoacidosis, low white cells, cancer, organ transplant, iron overload, kidney problems, long-term steroids or use of immunosuppressants, and to a lesser extent in HIV/AIDS.Diagnosis is by biopsy and culture, with medical imaging to help determine the extent of disease. It may appear similar to aspergillosis. Treatment is generally with amphotericin B and surgical debridement. Preventive measures include wearing a face mask in dusty areas, avoiding contact with water-damaged buildings, and protecting the skin from exposure to soil such as when gardening or certain outdoor work. It tends to progress rapidly and is fatal in about half of sinus cases and almost all cases of the widespread type.Mucormycosis is usually rare, affecting fewer than 2 people per million people each year in San Francisco, but is now ~80 times more common in India. People of any age may be affected, including premature infants. The first known case of mucormycosis was possibly the one described by Friedrich Küchenmeister in 1855. The disease has been reported in natural disasters; 2004 Indian Ocean tsunami and the 2011 Missouri tornado. During the COVID-19 pandemic, an association between mucormycosis and COVID-19 has been reported. This association is thought to relate to reduced immune function during the course of the illness and may also be related to glucocorticoid therapy for COVID-19. A rise in cases was particularly noted in India. Classification Generally, mucormycosis is classified into five main types according to the part of the body affected. A sixth type has been described as mucormycosis of the kidney, or miscellaneous, i.e., mucormycosis at other sites, although less commonly affected. Sinuses and brain (rhinocerebral); most common in people with poorly controlled diabetes and in people who have had a kidney transplant. Lungs (pulmonary); the most common type of mucormycosis in people with cancer and in people who have had an organ transplant or a stem cell transplant. Stomach and intestine (gastrointestinal); more common among young, premature, and low birth weight infants, who have had antibiotics, surgery, or medications that lower the bodys ability to fight infection. Skin (cutaneous); after a burn, or other skin injury, in people with leukaemia, poorly controlled diabetes, graft-versus-host disease, HIV and intravenous drug use. Widespread (disseminated); when the infection spreads to other organs via the blood. Signs and symptoms Signs and symptoms of mucormycosis depend on the location in the body of the infection. Infection usually begins in the mouth or nose and enters the central nervous system via the eyes.If the fungal infection begins in the nose or sinus and extends to brain, symptoms and signs may include one-sided eye pain or headache, and may be accompanied by pain in the face, numbness, fever, loss of smell, a blocked nose or runny nose. The person may appear to have sinusitis. The face may look swollen on one side, with rapidly progressing "black lesions" across the nose or upper inside of mouth. One eye may look swollen and bulging, and vision may be blurred.Fever, cough, chest pain, and difficulty breathing, or coughing up blood, can occur when the lungs are involved. A stomach ache, nausea, vomiting and bleeding can occur when the gastrointestinal tract is involved. Affected skin may appear as a dusky reddish tender patch with a darkening centre due to tissue death. There may be an ulcer, and it can be very painful.Invasion of the blood vessels can result in thrombosis and subsequent death of surrounding tissue due to a loss of blood supply. Widespread (disseminated) mucormycosis typically occurs in people who are already sick from other medical conditions, so it can be difficult to know which symptoms are related to mucormycosis. People with disseminated infection in the brain can develop changes in mental status or lapse into a coma. Cause Mucormycosis is a fungal infection caused by fungi in the order Mucorales. In most cases it is due to an invasion of the genera Rhizopus and Mucor, common bread molds. Most fatal infections are caused by Rhizopus oryzae. It is less likely due to Lichtheimia, and rarely due to Apophysomyces. Others include Cunninghamella, Mortierella, and Saksenaea.The fungal spores are in the environment, can be found on, for instance, moldy bread and fruit, and are breathed in frequently, but cause disease only in some people. In addition to being breathed in to be deposited in the nose, sinuses and lungs, the spores can also enter the skin via blood or directly through a cut or open wound, or grow in the intestine if eaten. Once deposited, the fungus grows branch-like filaments which invade blood vessels, causing clots to form and surrounding tissues to die. Other reported causes include contaminated wound dressings. Mucormycosis has been reported following the use of elastoplast and the use of tongue depressors for holding in place intravenous catheters. Outbreaks have also been linked to hospital bed sheets, negative-pressure rooms, water leaks, poor ventilation, contaminated medical equipment, and building works. Risk factors Predisposing factors for mucormycosis include conditions where people are less able to fight infection, have a low neutrophil count or metabolic acidosis. Risk factors include poorly controlled diabetes mellitus (particularly DKA), organ transplant, iron overload, such cancers as lymphomas, kidney failure, long term corticosteroid and immunosuppressive therapy, liver disease and severe malnutrition. Other risk factors include tuberculosis (TB), deferoxamine and to a lesser extent HIV/AIDS. Cases of mucormycosis in fit and healthy people are rare.Corticosteroids are commonly used in the treatment of COVID-19 and reduce damage caused by the bodys own immune response to the virus. They are immunosuppressant and increase blood sugar levels in both diabetic and non-diabetic patients. It is thought that both these effects may contribute to cases of mucormycosis. Mechanism Most people are frequently exposed to Mucorales without developing the disease. Mucormycosis is generally spread by breathing in, eating food contaminated by, or getting spores of molds of the Mucorales type in an open wound. It is not transmitted between people.The precise mechanism by which diabetics become susceptible is unclear. In vivo, a high sugar alone does not permit the growth of the fungus, but acidosis alone does. People with high sugars frequently have higher iron levels, also known to be a risk factor for developing mucormycosis. In people on deferoxamine, the iron removed is captured by siderophores on Rhizopus species, which uses the iron to grow. Diagnosis There is no blood test that can confirm the diagnosis. Diagnosis requires identifying the mold in the affected tissue by biopsy and confirming it with a fungal culture. Because the causative fungi occur all around, a culture alone is not decisive. Tests may also include culture and direct detection of the fungus in lung fluid, blood, serum, plasma and urine. Blood tests include a complete blood count to look specifically for neutropenia. Other blood tests include iron levels, blood glucose, bicarbonate, and electrolytes. Endoscopic examination of the nasal passages may be needed. Imaging Imaging is often performed, such as CT scan of lungs and sinuses. Signs on chest CT scans, such as nodules, cavities, halo signs, pleural effusion and wedge-shaped shadows, showing invasion of blood vessels, may suggest a fungal infection, but do not confirm mucormycosis. A reverse halo sign in a person with a blood cancer and low neutrophil count, is highly suggestive of mucormycosis. CT scan images of mucormycosis can be useful to distinguish mucormycosis of the orbit and cellulitis of the orbit, but images may appear identical to those of aspergillosis. MRI may also be useful. Currently (when?), MRI with gadolinium contrast is the investigation of choice in rhinoorbito cerebral mucormycosis. Culture and biopsy To confirm the diagnosis, biopsy samples can be cultured. Culture from biopsy samples does not always give a result as the organism is very fragile. To precisely identify the species requires an expert. The appearance of the fungus under the microscope will determine the genus and species. The appearances can vary but generally show wide, ribbon-like filaments that generally do not have septa and that—unlike in aspergillosis—branch at right angles, resembling antlers of a moose, which may be seen to be invading blood vessels. Other Matrix-assisted laser desorption/ionization may be used to identify the species. A blood sample from an artery may be useful to assess for metabolic acidosis. Differential diagnosis Other filamentous fungi may however look similar. It may be difficult to differentiate from aspergillosis. Other possible diagnoses include anthrax, cellulitis, bowel obstruction, ecthyma gangrenosum, lung cancer, clot in lungs, sinusitis, tuberculosis and fusariosis. Prevention Preventive measures include wearing a face mask in dusty areas, washing hands, avoiding direct contact with water-damaged buildings, and protecting skin, feet, and hands where there is exposure to soil or manure, such as gardening or certain outdoor work. In high risk groups, such as organ transplant patients, antifungal drugs may be given as a preventative. Treatment Treatment involves a combination of antifungal drugs, surgically removing infecting tissue and correcting underlying medical problems, such as diabetic ketoacidosis. Medication Once mucormycosis is suspected, amphotericin B at an initial dose of 1 mg is initially given slowly over 10–15 minutes into a vein, then given as a once daily dose according to body weight for the next 14 days. It may need to be continued for longer. Isavuconazole and Posaconazole are alternatives. Surgery Surgery can be very drastic, and, in some cases of disease involving the nasal cavity and the brain, removal of infected brain tissue may be required. Removal of the palate, nasal cavity, or eye structures can be very disfiguring. Sometimes more than one operation is required. Other considerations The disease must be monitored carefully for any signs of reemergence. Treatment also requires correcting sugar levels and improving neutrophil counts. Hyperbaric oxygen may be considered as an adjunctive therapy, because higher oxygen pressure increases the ability of neutrophils to kill the fungus. The efficacy of this therapy is uncertain. Prognosis It tends to progress rapidly and is fatal in about half of sinus cases, two thirds of lung cases, and almost all cases of the widespread type. Skin involvement carries the lowest mortality rate of around 15%. Possible complications of mucormycosis include the partial loss of neurological function, blindness, and clotting of blood vessels in the brain or lung.As treatment usually requires extensive and often disfiguring facial surgery, the effect on life after surviving, particularly sinus and brain involvement, is significant. Epidemiology The true incidence and prevalence of mucormycosis may be higher than appears. Mucormycosis is rare, affecting fewer than 1.7 people per million population each year in San Francisco. It is around 80 times more prevalent in India, where it is estimated that there are around 0.14 cases per 1000 population, and where its incidence has been rising. Causative fungi are highly dependent on location. Apophysomyces variabilis has its highest prevalence in Asia and Lichtheimia spp. in Europe. It is the third most common serious fungal infection to infect people, after aspergillosis and candidiasis.Diabetes is the main underlying disease in low and middle-income countries, whereas, blood cancers and organ transplantation are the more common underlying problems in developed countries. As new immunomodulating drugs and diagnostic tests are developed, the statistics for mucormycosis have been changing. In addition, the figures change as new genera and species are identified, and new risk factors reported such as tuberculosis and kidney problems. COVID-19–associated mucormycosis During the COVID-19 pandemic in India, the Indian government reported that more than 11,700 people were receiving care for mucormycosis as of 25 May 2021. Many Indian media outlets called it "black fungus" because of the black discoloration of dead and dying tissue the fungus causes. Even before the COVID-19 pandemic, rates of mucormycosis in India were estimated to be about 70 times higher than in the rest of the world. Due to its rapidly growing number of cases some Indian state governments have declared it an epidemic. One treatment was a daily injection for eight weeks of anti-fungal intravenous injection of amphotericin B which was in short supply. The injection could be standard amphotericin B deoxycholate or the liposomal form. The liposomal form cost more but it was considered "safer, more effective and [with] lesser side effects".§ The major obstacle of using antifungal drugs in black fungus is the lack of clinical trials. Recurrence of mucormycosis during COVID-19 second wave in India Pre-COVID mucormycosis was a very rare infection, even in India. It is so rare that an ENT (ear, nose, throat) doctor would not witness often a case during their university time. So, the documentation available on the treatment of mucormycosis is limited. In fact, there used to be a couple of mucormycosis expert ENT surgeons for millions of people pre-pandemic. The sudden rise in mucormycosis cases has left a majority of the ENT doctors with no option but to accept mucormycosis cases, as the expert doctors were very much occupied and the patient would die if left untreated. The majority of the ENT doctors had to manage with minimal or no experience on mucormycosis, this has led to the recurrence of mucormycosis in the patients they treated. When a highly experienced doctor in mucormycosis treats a patient even he cannot guarantee that the individual is completely cured and will not have a relapse of mucormycosis; an inexperienced ENT surgeon will definitely have a high number of patients with recurrence due to which there were many recurrent cases of mucormycosis although it did not get the limelight of media or the Indian Government. History The first case of mucormycosis was possibly one described by Friedrich Küchenmeister in 1855. Fürbringer first described the disease in the lungs in 1876. In 1884, Lichtheim established the development of the disease in rabbits and described two species; Mucor corymbifera and Mucor rhizopodiformis, later known as Lichtheimia and Rhizopus, respectively. In 1943, its association with poorly controlled diabetes was reported in three cases with severe sinus, brain and eye involvement.In 1953, Saksenaea vasiformis, found to cause several cases, was isolated from Indian forest soil, and in 1979, P. C. Misra examined soil from an Indian mango orchard, from where they isolated Apophysomyces, later found to be a major cause of mucormycosis. Several species of mucorales have since been described. When cases were reported in the United States in the mid-1950s, the author thought it to be a new disease resulting from the use of antibiotics, ACTH and steroids. Until the latter half of the 20th century, the only available treatment was potassium iodide. In a review of cases involving the lungs diagnosed following flexible bronchoscopy between 1970 and 2000, survival was found to be better in those who received combined surgery and medical treatment, mostly with amphotericin B. Naming Arnold Paltauf coined the term "Mycosis Mucorina" in 1885, after describing a case with systemic symptoms involving the sinus, brain and gastrointestinal tract, following which the term "mucormycosis" became popular. "Mucormycosis" is often used interchangeably with "zygomycosis", a term made obsolete following changes in classification of the kingdom Fungi. The former phylum Zygomycota included Mucorales, Entomophthorales, and others. Mucormycosis describes infections caused by fungi of the order Mucorales. COVID-19–associated mucormycosis COVID-19 associated mucormycosis cases were reported during first and second(delta) wave, with maximum number of cases in delta wave. There were no cases reported during the Omicron wave. A number of cases of mucormycosis, aspergillosis, and candidiasis, linked to immunosuppressive treatment for COVID-19 were reported during the COVID-19 pandemic in India in 2020 and 2021. One review in early 2021 relating to the association of mucormycosis and COVID-19 reported eight cases of mucormycosis; three from the U.S., two from India, and one case each from Brazil, Italy, and the UK. The most common underlying medical condition was diabetes. Most had been in hospital with severe breathing problems due to COVID-19, had recovered, and developed mucormycosis 10–14 days following treatment for COVID-19. Five had abnormal kidney function tests, three involved the sinus, eye and brain, three the lungs, one the gastrointestinal tract, and in one the disease was widespread. In two of the seven deaths, the diagnosis of mucormycosis was made at postmortem. That three had no traditional risk factors led the authors to question the use of steroids and immunosuppressive drugs. Although, there were cases without diabetes or use of immunosuppressive drugs. There were cases reported even in children. In May 2021, the BBC reported increased cases in India. In a review of COVID-19-related eye problems, mucormycosis affecting the eyes was reported to occur up to several weeks following recovery from COVID-19. It was observed that people with COVID-19 were recovering from mucormycosis a bit easily when compared to non-COVID-19 patients. This is because unlike non-COVID-19 patients with severe diabetes, cancer or HIV, the recovery time required for the main cause of immune suppression is temporary.Other countries affected included Pakistan, Nepal, Bangladesh, Russia, Uruguay, Paraguay, Chile, Egypt, Iran, Brazil, Iraq, Mexico, Honduras, Argentina Oman, and Afghanistan. One explanation for why the association has surfaced remarkably in India is high rates of COVID-19 infection and high rates of diabetes. In May 2021, the Indian Council of Medical Research issued guidelines for recognising and treating COVID-19–associated mucormycosis. In India, as of 28 June 2021, over 40,845 people have been confirmed to have mucormycosis, and 3,129 have died. From these cases, 85.5% (34,940) had a history of being infected with SARS-CoV-2 and 52.69% (21,523) were on steroids, also 64.11% (26,187) had diabetes. Society and culture The disease has been reported in natural disasters and catastrophes; 2004 Indian Ocean tsunami and the 2011 Missouri tornado. The first international congress on mucormycosis was held in Chicago in 2010, set up by the Hank Schueuler 41 & 9 Foundation, which was established in 2008 for the research of children with leukaemia and fungal infections. A cluster of infections occurred in the wake of the 2011 Joplin tornado. By July 19, 2011, a total of 18 suspected cases of mucormycosis of the skin had been identified, of which 13 were confirmed. A confirmed case was defined as 1) necrotizing soft-tissue infection requiring antifungal treatment or surgical debridement in a person injured in the tornado, 2) with illness onset on or after May 22 and 3) positive fungal culture or histopathology and genetic sequencing consistent with a mucormycete. No additional cases related to that outbreak were reported after June 17. Ten people required admission to an intensive-care unit, and five died.In 2014, details of a lethal mucormycosis outbreak that occurred in 2008 emerged after television and newspaper reports responded to an article in a pediatric medical journal. Contaminated hospital linen was found to be spreading the infection. A 2018 study found many freshly laundered hospital linens delivered to U.S. transplant hospitals were contaminated with Mucorales. Another study attributed an outbreak of hospital-acquired mucormycosis to a laundry facility supplying linens contaminated with Mucorales. The outbreak stopped when major changes were made at the laundry facility. The authors raised concerns on the regulation of healthcare linens. Other animals Mucormycosis in other animals is similar, in terms of frequency and types, to that in people. Cases have been described in cats, dogs, cows, horses, dolphins, bison, and seals. References Further reading == External links ==

Hello Aarogya, what is Multifocal motor neuropathy

Multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is a progressively worsening condition where muscles in the extremities gradually weaken. The disorder, a pure motor neuropathy syndrome, is sometimes mistaken for amyotrophic lateral sclerosis (ALS) because of the similarity in the clinical picture, especially if muscle fasciculations are present. MMN is thought to be autoimmune. It was first described in the mid-1980s.Unlike ALS, which affects both upper and lower motor neuron pathways, MMN involves only the lower motor neuron pathway, specifically, the peripheral nerves emanating from the lower motor neurons. Definitive diagnosis is often difficult, and many MMN patients labor for months or years under an ALS diagnosis before finally getting a determination of MMN. MMN usually involves very little pain; however, muscle cramps, spasms and twitches can cause pain for some people. MMN is not fatal, and does not diminish life expectancy. Many patients, once undergoing treatment, only experience mild symptoms over prolonged periods, though the condition remains slowly progressive. MMN can however, lead to significant disability, with loss of function in hands affecting ability to work and perform everyday tasks, and "foot drop" leading to inability to stand and walk; some patients end up using aids like canes, splints and walkers. Symptoms Usually beginning in one or both hands, MMN is characterized by weakness, muscle atrophy, cramping, and often profuse fasciculations (muscle twitching). The symptoms are progressive over long periods, often in a stepwise fashion, but unlike ALS are often treatable.Sensory nerves are usually unaffected.Wrist drop and foot drop (leading to trips and falls) are common symptoms. Other effects can include gradual loss of finger extension, leading to a clawlike appearance. Cold & hot temperatures exacerbate MMN symptoms to such an extent, unlike other neuropathies, that this temperature response is being investigated as a diagnostic tool. Cause MMN is thought to be caused by alterations in the immune system, such that certain proteins (antibodies) that would normally protect one from viruses and bacteria begin to attack constituents of peripheral nerves. Antibodies may be directed against "GM-1", a ganglioside found at the Nodes of Ranvier. These antibodies have been detected in at least one-third of MMN patients. More recent studies also suggest that newer tests for antibodies directed against GM-1, as well as a number of related gangliosides, are positive in over 80% of MMN patients. There are increasing reasons to believe these antibodies are the cause of MMN. Diagnosis The diagnosis of MMN depends on demonstrating that a patient has a purely motor disorder affecting individual nerves, that there are no upper motor neuron (UMN) signs, that there are no sensory deficits, and that there is evidence of conduction block. These criteria are designed to differentiate the disorder from ALS (purely motor but with UMN signs), the Lewis-Sumner Syndrome variant of Chronic inflammatory demyelinating polyneuropathy (CIDP) (similar to MMN but usually with significant sensory loss), and "vasculitis" (a type of multiple mononeuropathy syndrome caused by inflammatory damage to the blood vessels in nerves that also causes sensory and motor symptoms).A neurologist is usually needed to determine the diagnosis, which is based on the history and physical examination along with the electrodiagnostic study, which includes nerve conduction studies (NCS) and needle electromyography (EMG). The NCS usually demonstrate conduction block. This can be done by showing that the nerve signal cannot conduct past a "lesion" at some point along the nerve. For example, if the nerve is blocked in the forearm, an electrical impulse can easily get from the wrist to the hand if the stimulus is placed at the wrist. However, the signal will be blocked from reaching the hand if the stimulus is applied at the elbow. In MMN, sensory conduction along the same path should be normal. The EMG portion of the test looks for signals in the way muscles fire. In MMN it will most likely reveal abnormalities suggesting that some percentage of the motor axons has been damaged. Laboratory testing for GM1 antibodies is frequently done, and can be very helpful if they are abnormal. However, since only a third of patients with MMN have these antibodies, a negative test does not rule out the disorder. Spinal fluid examination is not usually helpful. Treatment Multifocal motor neuropathy is normally treated by receiving intravenous immunoglobulin (IVIG), which can in many cases be highly effective, or immunosuppressive therapy with cyclophosphamide or rituximab. Steroid treatment (prednisone) and plasmapheresis are no longer considered to be useful treatments(not usually some pt highly recommended); prednisone can exacerbate symptoms. IVIg is the primary treatment, with about 80% of patients responding, usually requiring regular infusions at intervals of 1 week to several months. Other treatments are considered in case of lack of response to IVIg, or sometimes because of the high cost of immunoglobulin. Subcutaneous immunoglobulin is under study as a less invasive, more-convenient alternative to IV delivery. References External links Overview of MMN at National Institute of Neurological Disorders and Stroke

Aarogya what is Necrobiosis lipoidica

Necrobiosis lipoidica

Necrobiosis lipoidica is a necrotising skin condition that usually occurs in patients with diabetes mellitus but can also be associated with rheumatoid arthritis. In the former case it may be called necrobiosis lipoidica diabeticorum (NLD). NLD occurs in approximately 0.3% of the diabetic population, with the majority of those affected are women (approximately 3:1 females to males affected). The severity or control of diabetes in an individual does not affect who will or will not get NLD. Better maintenance of diabetes after being diagnosed with NLD will not change how quickly the NLD will resolve. Signs and symptoms NL/NLD most frequently appears on the patients shins, often on both legs, although it may also occur on forearms, hands, trunk, and, rarely, nipple, penis, and surgical sites. The lesions are often asymptomatic but may become tender and ulcerate when injured. The first symptom of NL is often a "bruised" appearance (erythema) that is not necessarily associated with a known injury. The extent to which NL is inherited is unknown. NLD appears as a hardened, raised area of the skin. The center of the affected area usually has a yellowish tint while the area surrounding it is a dark pink. It is possible for the affected area to spread or turn into an open sore. When this happens the patient is at greater risk of developing ulcers. If an injury to the skin occurs on the affected area, it may not heal properly or it will leave a dark scar. Pathophysiology Although the exact cause of this condition is not known, it is an inflammatory disorder characterised by collagen degeneration, combined with a granulomatous response. It always involves the dermis diffusely, and sometimes also involves the deeper fat layer. Commonly, dermal blood vessels are thickened (microangiopathy).It can be precipitated by local trauma, though it often occurs without any injury. Diagnosis NL is diagnosed by a skin biopsy, demonstrating superficial and deep perivascular and interstitial mixed inflammatory cell infiltrate (including lymphocytes, plasma cells, mononucleated and multinucleated histiocytes, and eosinophils) in the dermis and subcutis, as well as necrotising vasculitis with adjacent necrobiosis and necrosis of adnexal structures. Areas of necrobiosis are often more extensive and less well defined than in granuloma annulare. Presence of lipid in necrobiotic areas may be demonstrated by Sudan stains. Cholesterol clefts, fibrin, and mucin may also be present in areas of necrobiosis. Depending on the severity of the necrobiosis, certain cell types may be more predominant. When a lesion is in its early stages, neutrophils may be present, whereas in later stages of development lymphocytes and histiocytes may be more predominant. Treatment There is no clearly defined cure for necrobiosis. NLD may be treated with PUVA therapy, Photodynamic therapy and improved therapeutic control.Although there are some techniques that can be used to diminish the signs of necrobiosis such as low dose aspirin orally, a steroid cream or injection into the affected area, this process may be effective for only a small percentage of those treated. See also Diabetic dermadromes List of cutaneous conditions References External links Information and image at NIH

Aarogya, share information about a health condition involving Neonatal withdrawal

Neonatal withdrawal

Neonatal withdrawal or neonatal abstinence syndrome (NAS) or neonatal opioid withdrawal syndrome (NOWS) is a withdrawal syndrome of infants after birth caused by in utero exposure to drugs of dependence, most commonly opioids. Common signs and symptoms include tremors, irritability, vomiting, diarrhea, and fever. NAS is primarily diagnosed with a detailed medication history and scoring systems. First-line treatment should begin with non-medication interventions to support neonate growth, though medication interventions may be used in certain situations.In 2017, approximately 7.3 per 1,000 hospitalized infants in the United States were diagnosed with NOWS. Not all opioid-exposed infants will show clinical signs of withdrawal after birth. Clinical signs range from mild to severe, depending on the quantity and type of substance exposure.The most common form on neonatal withdrawal occurs after in utero exposure, however, iatrogenic withdrawal can also occur after medications are used to treat critically ill infants after they are born. Signs and symptoms Drug and alcohol use during pregnancy can lead to many health problems in the fetus and infants, including neonatal abstinence syndrome (NAS). The onset of clinical presentation typically appears within 48 to 72 hours of birth but may take up to 8 days. The signs and symptoms of NAS may be different depending on which substance the mother used.Common signs and symptoms in infants with NAS may include: Signs due to hyperactivity of the central nervous system: Tremors (trembling) Irritability (excessive mood crying) Sleep problems High-pitched crying Muscle tightness Hyperactive reflexes Seizures (2% to 11%), notably this clinical sign is controversial given it does not occur in other populations experiencing opioid withdrawal. Signs due to hyperactivity of stomach and intestines: Poor feeding and sucking reflex Vomiting Diarrhea Signs due to hyperactivity of autonomous nervous system: Fever Sweating Yawning, stuffy nose, and sneezing Fast breathing Causes The drugs involved can include opioids, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitor (SNRIs), tricyclic antidepressants (TCAs), ethanol, and benzodiazepines. Opioids may be more likely to cause NAS than other substances due to an increase in its usage. Exposure to heroin and methadone claimed to be correlated with a 60 to 80% occurrence of neonatal withdrawal, whereas buprenorphine has been associated with a lower risk. Neonatal abstinence syndrome does not happen in prenatal cocaine exposure. Prematurity and exposure to other drugs may instead be the cause of symptoms.The main mechanistic pathway of prescribed and illicit substance-induced NAS is the hyperactivity of the central and autonomic nervous system and gastrointestinal tract There are several potential mechanisms and pathways that have been proposed, which includes the interaction between the neurotransmitters and lack of adequate expression of opioid receptors. However, the main pathophysiology of this syndrome remains unknown. Most of the opioid induced NAS are due to opioid exposure during pregnancy for pain relief, misuse, or abuse of prescribed opioids or other medication-assisted treatment of opioid use disorder. Diagnosis The presence of withdrawal in the neonate can be confirmed by taking a detailed medical history from the mother. The medical history should include physical and mental health problems, prescription and non-prescription medication use, nutritional supplement use, history of alcohol and substance use, childhood adversities, cultural and social beliefs, past traumatic experiences, and infectious diseases such as HIV. Since the medical history of the birth giver may not be available immediately after delivery, some testing needs to be done in the infant to confirm possible exposure. Infants urine, meconium, umbilical cord tissue or hair can be used for testing. The timing of urine sample collection is critical because some drugs may become undetectable after they are metabolized and eliminated from the body. Also, urine test results can only confirm if the fetus was exposed to drugs a few days before birth. Meconium testing can be used to confirm drug exposure in earlier stage of pregnancy, but the collecting process is more difficult. Umbilical cord tissue testing is a relatively new testing method and its accuracy is still controversial. The mothers blood and urine sample should also be collected for drug screening. Chest X-rays can confirm or infirm the presence of heart defects. Assessment Depending on what hospital setting the infant is in, different scoring systems are used for assessing the severity and the need for medication treatment in neonatal withdrawal syndrome. One challenge with existing clinical predication tools is that they were designed to assess opiate withdrawal only. The Finnegan Neonatal Abstinence Scoring System (FNASS), or its modified version is the most widely used prediction tool currently in the United States. The FNASS tool focuses on 21 signs of neonatal opioid withdrawal, and a score from 0 to 5 is assigned based on the severity of the symptom. The measurement needs to be repeated every two to four hours. The cutoff for initiation, escalation or de-escalation of medication treatment may be varied. A 2019 review shows that "most institutions using the FNASS have protocols that call for starting or increasing pharmacologic treatment after an infant has received three FNASS scores ≥8 or two scores ≥12." However, there are limitations to the FNASS tool. The repeated measurements may delay treatment and result in increased treatment need. In order to assess some of the signs in the measurement process, infants will be stimulated as opposed to minimizing stimulation recommended in non-medication treatment. A study also indicates that the FNASS tool "has not been validated to show utility in improving outcomes for infants with NAS". Prevention Neonatal withdrawal is prevented by the mother abstaining from illicit or prescribed substances. In some cases, a prescribed medication may need to be discontinued during the pregnancy to prevent addiction by the infant. Early prenatal care can identify addictive behaviors in the mother and family system. Referrals to treatment centers is appropriate. Some prescribed medicines should not be stopped without medical supervision, or harm may result. Suddenly stopping a medication can result in a premature birth, fetal complications, and miscarriage. It is recommended that pregnant individuals discuss medication, alcohol, and tobacco use with their health-care provider and to seek assistance to abstain when appropriate. She may need medical attention if she is using drugs non-medically, using drugs not prescribed to them, or using alcohol or tobacco.There are several strategies to prevent the incidence of NAS, those include: Primary Preventions Follow guidance of 2016 CDC Guideline for Prescribing Opioids for Chronic Pain, which addresses the effectiveness of opioid dosing and treatment, the benefits and risks, and strategies to avoid opioid misuse Utilize prescription drug monitoring programs (PDMPs) to avoid overuse of opioids Provision of treatment for opioid use disorder among pregnant women Non-medicine strategies via minimizing environmental stimuliHowever, there are some barriers to prevention which includes lack of consensus to screening tools to identify substance use while pregnant, stigma, provider bias, and legal consequences. Treatment Treatment depends on the drug involved, the infants overall health, abstinence scores (FNASS scoring system), and whether the infant was born full-term or premature. It is recommended to observe and provide supportive measure to infants who are at risk of neonatal abstinence syndrome in the hospital. Infants with severe symptoms may require both supportive measures and medicines. Treatment for NAS may require the infant to stay in the hospital for weeks or months after birth. The goal of treatment is to minimize negative outcomes and promote normal development. Infants may be prescribed a drug similar to the one the mother used during pregnancy, and slowly decrease the dose over time. This helps wean the infant off the drug and relieves some withdrawal symptoms. Non-medication treatment First-line treatment should begin with non-medication interventions to support maturation of the neonate. It is not clear if one type of non-medication therapy is better than another. Common non-medication approaches include physical environment adjustments, swaddling, and breastfeeding. Adjusting physical environments Infants with NAS symptoms may have hypersensitivity to light and sounds. Techniques such as darkening the room and eliminating surrounding sounds work to lessen the neonates visual and auditory stimuli. Swaddling Swaddling (wrapping an infant firmly in a blanket) can help improve sleep, develop nerves and muscles, decrease stress, and improve motor skills. Breastfeeding Infants with NAS may have problems with feeding or slow growth, which require higher-calorie feedings that provide greater nutrition. It is beneficial to give smaller portions more often throughout the day. Breastfeeding promotes infant attachment and bonding, and is associated with a decreased need for medication, may lessen the severity of NAS, and lead to shorter hospital stays.Most pregnant people who are taking buprenorphine or methadone can safely breastfeed their infant. Both buprenorphine and methadone remain in the human milk at low concentrations, which will reduce signs and symptoms of NAS and likely decrease the treatment time. However, there are exclusions in which it is not safe to breastfeed, such as an HIV-positive mother and a mother with history of street drug use or multiple illicit drug use. Medication treatment Although non-medication intervention remains first-line treatment, pharmacological intervention, when appropriate and indicated, can improve signs of neonatal withdrawal.Common medication approaches: Opioids Opioids have shown to improve symptoms to a clinically safe level but may not affect length of hospital stay. Its common to slowly taper down to wean the infant off. Sedatives Sedatives such as phenobarbital or diazepam are less effective at symptom control compared to opioids but can reduce length of hospital stay. Clonidine When compared to opioids, clonidine was just as effective at improving clinical symptoms.Additional medication is used to relieve fever, seizures, and weight loss or dehydration. A 2021 systematic review found low-certainty evidence that phenobarbital lengthened hospital stays but resulted in a return to birth-weight more rapidly. Low-certainty evidence also showed phenobarbital reduced treatment failure rates compared to diazepam and chlorpromazine. There was also low-certainty evidence of increased hospitalization days with clonidine and opioid compared to phenobarbital and opioid. Outcomes A 2018 meta-analysis reported that newborns diagnosed with NAS are likely to recover with non-medication intervention when roomed with family during their hospital stay compared to newborns diagnosed with NAS that are treated in newborn intensive care unit.Data is limited and more research needs to be conducted to properly evaluate long-term outcomes in children with a prior diagnosis of NAS. However, long-term monitoring into adolescence may be necessary as a 2019 meta-analysis gave evidence of some longterm cognitive and physical side effects associated with prenatal opioid exposure. Epidemiology United States A 2012 study analyzed information on 7.4 million discharges from 4,121 hospitals in 44 states, to measure trends and costs associated with NAS over the past decade. The study indicated that between 2000 and 2009, the number of pregnant people using opiates increased from 1.19 to 5.63 per 1,000 hospital births per year.In 2017 the Centers for Disease Control (CDC) reported an increase of diagnosis of NAS to 7 cases every 1,000 births with indiscrimination to state or demographic group. Additionally, the CDC reported in 2019 that 7% of pregnant individuals self-reported use of opioids at some point in their pregnancy.A 2018 review of NAS reports that the epidemiology of NAS continues to change and evolve. Though opioids are still the most common drug reported in diagnosis of NAS, there are instances where opioids are not the only class of drug the infant is exposed to during pregnancy. Diagnosis of NAS continues and is substantially greater in rural areas compared to urban areas. As the epidemiology continues to change and evolve calls for the need for more research and standardization of treatment. Other A 2020 literature review published by the Saskatchewan Prevention Institute reports that NAS has significantly increased in England, Western Australia, and Canada within the last decade, noting that current statistics may be underestimated as reluctance to report can be attributed to stigma associated with diagnosis or differing protocols amongst institutions. From 2016 to 2017 Canada overall reported 1,850 diagnosis of NAS. See also Prenatal cocaine exposure Neonatal opioid withdrawal References == External links ==

Aarogya, elaborate on Cystinosis

Cystinosis

Cystinosis is a lysosomal storage disease characterized by the abnormal accumulation of cystine, the oxidized dimer of the amino acid cysteine. It is a genetic disorder that follows an autosomal recessive inheritance pattern. It is a rare autosomal recessive disorder resulting from accumulation of free cystine in lysosomes, eventually leading to intracellular crystal formation throughout the body. Cystinosis is the most common cause of Fanconi syndrome in the pediatric age group. Fanconi syndrome occurs when the function of cells in renal tubules is impaired, leading to abnormal amounts of carbohydrates and amino acids in the urine, excessive urination, and low blood levels of potassium and phosphates. Cystinosis was the first documented genetic disease belonging to the group of lysosomal storage disease disorders. Cystinosis is caused by mutations in the CTNS gene that codes for cystinosin, the lysosomal membrane-specific transporter for cystine. Intracellular metabolism of cystine, as it happens with all amino acids, requires its transport across the cell membrane. After degradation of endocytosed protein to cystine within lysosomes, it is normally transported to the cytosol. But if there is a defect in the carrier protein, cystine is accumulated in lysosomes. As cystine is highly insoluble, when its concentration in tissue lysosomes increases, its solubility is immediately exceeded and crystalline precipitates are formed in almost all organs and tissues.However, the progression of the disease is not related to the presence of crystals in target tissues. Although tissue damage might depend on cystine accumulation, the mechanisms of tissue damage are not fully understood. Increased intracellular cystine profoundly disturbs cellular oxidative metabolism and glutathione status, leading to altered mitochondrial energy metabolism, autophagy, and apoptosis.Cystinosis is usually treated with cysteamine, which is prescribed to decrease intralysosomal cystine accumulation. However, the discovery of new pathogenic mechanisms and the development of an animal model of the disease may open possibilities for the development of new treatment modalities to improve long-term prognosis. Symptoms There are three distinct types of cystinosis each with slightly different symptoms: nephropathic cystinosis, intermediate cystinosis, and non-nephropathic or ocular cystinosis. Infants affected by nephropathic cystinosis initially exhibit poor growth and particular kidney problems (sometimes called renal Fanconi syndrome). The kidney problems lead to the loss of important minerals, salts, fluids, and other nutrients. The loss of nutrients not only impairs growth, but may result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. The nutrient imbalances in the body lead to increased urination, thirst, dehydration, and abnormally acidic blood (acidosis). By about age two, cystine crystals may also be present in the cornea. The buildup of these crystals in the eye causes an increased sensitivity to light (photophobia). Without treatment, children with cystinosis are likely to experience complete kidney failure by about age ten. With treatment this may be delayed into the patients teens or 20s. Other signs and symptoms that may occur in patients include muscle deterioration, blindness, inability to swallow, impaired sweating, decreased hair and skin pigmentation, diabetes, and thyroid and nervous system problems. The signs and symptoms of intermediate cystinosis are the same as nephropathic cystinosis, but they occur at a later age. Intermediate cystinosis typically begins to affect individuals around age twelve to fifteen. Malfunctioning kidneys and corneal crystals are the main initial features of this disorder. If intermediate cystinosis is left untreated, complete kidney failure will occur, but usually not until the late teens to mid twenties. People with non-nephropathic or ocular cystinosis do not usually experience growth impairment or kidney malfunction. The only symptom is photophobia due to cystine crystals in the cornea. Crystal morphology and identification Cystine crystals are hexagonal in shape and are colorless. They are not found often in alkaline urine due to their high solubility. The colorless crystals can be difficult to distinguish from uric acid crystals which are also hexagonal. Under polarized examination, the crystals are birefringent with a polarization color interference. Genetics Cystinosis occurs due to a mutation in the gene CTNS, located on chromosome 17, which codes for cystinosin, the lysosomal cystine transporter. Symptoms are first seen at about 3 to 18 months of age with profound polyuria (excessive urination), followed by poor growth, photophobia, and ultimately kidney failure by age 6 years in the nephropathic form. All forms of cystinosis (nephropathic, juvenile and ocular) are autosomal recessive, which means that the trait is located on an autosomal chromosome, and only an individual who inherits two copies of the gene – one from both parents – will have the disorder. There is a 25% risk of having a child with the disorder, when both parents are carriers of an autosomal recessive trait. Cystinosis affects approximately 1 in 100,000 to 200,000 newborns. and there are only around 2,000 known individuals with cystinosis in the world. The incidence is higher in the province of Brittany, France, where the disorder affects 1 in 26,000 individuals. Diagnosis Cystinosis is a rare genetic disorder that causes an accumulation of the amino acid cystine within cells, forming crystals that can build up and damage the cells. These crystals negatively affect many systems in the body, especially the kidneys and eyes.The accumulation is caused by abnormal transport of cystine from lysosomes, resulting in a massive intra-lysosomal cystine accumulation in tissues. Via an as yet unknown mechanism, lysosomal cystine appears to amplify and alter apoptosis in such a way that cells die inappropriately, leading to loss of renal epithelial cells. This results in renal Fanconi syndrome, and similar loss in other tissues can account for the short stature, retinopathy, and other features of the disease. Definitive diagnosis and treatment monitoring are most often performed through measurement of white blood cell cystine level using tandem mass spectrometry. Types Online Mendelian Inheritance in Man (OMIM): 219800 – Infantile nephropathic Online Mendelian Inheritance in Man (OMIM): 219900 – Adolescent nephropathic Online Mendelian Inheritance in Man (OMIM): 219750 – Adult nonnephropathic Treatment Cystinosis is normally treated with cysteamine, which is available in capsules and in eye drops. People with cystinosis are also often given sodium citrate to treat the blood acidosis, as well as potassium and phosphorus supplements as well as others. If the kidneys become significantly impaired or fail, then treatment must be begun to ensure continued survival, up to and including renal transplantation. See also Hartnup disease Cystinuria CTNS References External links Cystinosis at NLM Genetics Home Reference GeneReviews/NCBI/NIH/UW entry on Cystinosis

Could you describe Neurocysticercosis, to me Aarogya

Neurocysticercosis

Neurocysticercosis is a specific form of the infectious parasitic disease cysticercosis that is caused by the infection with Taenia solium, a tapeworm found in pigs. Neurocysticercosis occurs when cysts formed by the infection take hold within the brain, causing neurologic syndromes such as epileptic seizures. It is a common cause of seizures worldwide. It has been called a "hidden epidemic" and "arguably the most common parasitic disease of the human nervous system". Common symptoms of neurocysticercosis include seizures, headaches, blindness, meningitis and dementia. Pathophysiology Neurocysticercosis most commonly involves the cerebral cortex followed by the cerebellum. The pituitary gland is very rarely involved in neurocysticercosis. The cysts may rarely coalesce and form a tree-like pattern which is known as racemose neurocysticercosis, which when involving the pituitary gland may result in multiple pituitary hormone deficiency. Diagnosis Neurocysticerosis is diagnosed by computed tomography (CT) scan. Diagnosis may be confirmed by detection of antibodies against cysticerci in CSF or serum through ELISA or immunoblotting techniques. Treatment Treatment of neurocysticerosis includes epileptic therapy and a long-course medication of praziquantel (PZQ) and/or albendazole. Steroid therapy may be necessary to minimize the inflammatory reaction to dying cysticerci. Surgical removal of brain cysts may be necessary, e.g. in cases of large parenchymal cysts, intraventricular cysts or hydrocephalus.Albendazole has been shown to reduce seizure recurrence in those with a single non-viable intraparenchymal cyst. For seizures further randomized controlled trials are needed to evaluate the efficacy of antiepileptic drugs (AED) for seizure prevention in patients with symptoms other than seizures and the duration of AED treatment in these cases. Epidemiology The epidemiology of Taenia solium cysticercosis is associated with poor sanitation and is highly prevalent in Sub-Saharan Africa, Latin America and Asia. Cysticercosis in the United States, which commonly presents in the form of neurocysticercosis, has been classified as a "neglected tropical disease", which commonly affects the poor and homeless, particularly those without access or in the habit of inadequate hand-washing and in the habit of eating with their hands. == References ==

Hi Aarogya , Do you know what is Neurogenic bladder dysfunction,

Neurogenic bladder dysfunction

Neurogenic bladder dysfunction, or neurogenic bladder, refers to urinary bladder problems due to disease or injury of the central nervous system or peripheral nerves involved in the control of urination. There are multiple types of neurogenic bladder depending on the underlying cause and the symptoms. Symptoms include overactive bladder, urinary urgency, frequency, incontinence or difficulty passing urine. A range of diseases or conditions can cause neurogenic bladder including spinal cord injury, multiple sclerosis, stroke, brain injury, spina bifida, peripheral nerve damage, Parkinsons disease, or other neurodegenerative diseases. Neurogenic bladder can be diagnosed through a history and physical as well as imaging and more specialized testing. Treatment depends on underlying disease as well as symptoms and can be managed with behavioral changes, medications, surgeries, or other procedures. The symptoms of neurogenic bladder, especially incontinence, can have a significant impact on quality of life. Classification There are different types of neurogenic bladder depending on the underlying cause. Many of these types may have similar symptoms. Uninhibited Uninhibited bladder is usually due to damage to the brain from a stroke or brain tumor. This can cause reduced sensation of bladder fullness, low capacity bladder and urinary incontinence. Unlike other forms of neurogenic bladder, it does not lead to high bladder pressures that can cause kidney damage. Spastic In spastic neurogenic bladder (also known as upper motor neuron or hyper-reflexive bladder), the muscle of the bladder (detrusor) and urethral sphincter do not work together and are usually tightly contracted at the same time. This phenomenon is also called detrusor external sphincter dyssynergia (DESD). This leads to urinary retention with high pressures in the bladder that can damage the kidneys. The bladder volume is usually smaller than normal due to increased muscle tone in the bladder. Spastic neurogenic bladder is usually caused by damage to the spinal cord above the level of the 10th thoracic vertebrae (T10). Flaccid In flaccid bladder (also known as lower motor neuron or hypotonic bladder), the muscles of the bladder lose ability to contract normally. This can cause the inability to void urine even if the bladder is full and cause a large bladder capacity. The internal urinary sphincter can contract normally, however urinary incontinence is common. This type of neurogenic bladder is caused by damage to the peripheral nerves that travel from the spinal cord to the bladder. Mixed Mixed type of neurogenic bladder can cause a combination of the above presentations. In mixed type A, the bladder muscle is flaccid but the sphincter is overactive. This creates a large, low pressure bladder and inability to void, but does not carry as much risk for kidney damage as a spastic bladder. Mixed type B is characterized by a flaccid external sphincter and a spastic bladder causing problems with incontinence. Signs and symptoms Neurogenic bladder can cause a range of urinary symptoms including urinary urgency, urinary incontinence or difficulty urinating (urinary retention). The first sign of bladder dysfunction may be recurrent urinary tract infections (UTIs). Complications Neurogenic bladder can cause hydronephrosis (swelling of a kidney due to a build-up of urine), recurrent urinary tract infections, and recurrent kidney stones which may compromise kidney function. This is especially significant in spastic neurogenic bladder that leads to high bladder pressures. Kidney failure was previously a leading cause of mortality in patients with spinal cord injury but is now dramatically less common due to improvements in bladder management. Causes Urine storage and elimination (urination) requires coordination between the bladder emptying muscle (detrusor) and the external sphincter of the bladder. This coordination can be disrupted by damage or diseases of the central nervous system, peripheral nerves or autonomic nervous system. This includes any condition that impairs bladder signaling at any point along the path from the urination center in the brain, spinal cord, peripheral nerves and the bladder. Central nervous system Damage to the brain or spinal cord is the most common cause of neurogenic bladder. Damage to the brain can be caused by stroke, brain tumors, multiple sclerosis, Parkinsons disease or other neurodegenerative conditions. Bladder involvement is more likely if the damage is in the area of the pons. Damage to the spinal cord can be caused by traumatic injury, demyelinating disease, syringomyelia, cauda equina syndrome, or spina bifida. Spinal cord compression from herniated disks, tumor, or spinal stenosis can also result in neurogenic bladder. Peripheral nervous system Damage to the nerves that travel from the spinal cord to the bladder (peripheral nerves) can cause neurogenic bladder, usually the flaccid type. Nerve damage can be caused by diabetes, alcoholism, and vitamin B12 deficiency. Peripheral nerves can also be damaged as a complication of major surgery of the pelvis, such as for removal of tumors. Diagnosis The diagnosis of neurogenic bladder is made based on a complete history and physical examination and may require imaging and specialized studies. History should include information on the onset, duration, triggers, severity, other medical conditions and medications (including anticholinergics, calcium channel blockers, diuretics, sedatives, alpha-adrenergic agonist, alpha 1 antagonists). Urinary symptoms may include frequency, urgency, incontinence or recurrent urinary tract infections (UTIs). Questionnaires can be helpful in quantifying symptom burden. In children it is important to obtain a prenatal and developmental history.Ultrasound imaging can give information on the shape of the bladder, post-void residual volume, and evidence of kidney damage such as kidney size, thickness or ureteral dilation. Trabeculated bladder on ultrasound indicates high risk of developing urinary tract abnormalities such as hydronephrosis and stones. A voiding cystourethrography study uses contrast dye to obtain images of the bladder both when it is full and after urination which can show changes in bladder shape consistent with neurogenic bladder.Urodynamic studies are an important component of the evaluation for neurogenic bladder. Urodynamics refers to the measurement of the pressure-volume relationship in the bladder. The bladder usually stores urine at low pressure and urination can be completed without a dramatic pressure rise. Damage to the kidneys is probable if the pressure rises above 40 cm of water during filling. Bladder pressure can be measured by cystometry, during which the bladder is artificially filled with a catheter and bladder pressures and detrusor activity are monitored. Patterns of involuntary detrusor activity as well as bladder flexibility, or compliance, can be evaluated. The most valuable test to test for detrusor sphincter dyssynergia (DESD) is to perform cystometry simultaneously with external sphincter electromyography (EMG). Uroflowmetry is a less-invasive study that can measure urine flow rate and use it to estimate detrusor strength and sphincter resistance. Urethral pressure monitoring is another less-invasive approach to assessing detrusor sphincter dyssynergia. These studies can be repeated at regular intervals, especially if symptoms worsen or to measure response to therapies.Evaluation of kidney function through blood tests such as serum creatinine should be obtained.Imaging of the pelvis with CT scan or magnetic resonance imaging may be necessary, especially if there is concern for an obstruction such as a tumor. The inside of the bladder can be visualized by cystoscopy. Treatment Treatment depends on the type of neurogenic bladder and other medical problems. Treatment strategies include catheterization, medications, surgeries or other procedures. The goals of treatment is to keep bladder pressures in a safe range and eliminate residual urine in the bladder after urination (post-void residual volumes). Catherization Emptying the bladder with the use of a catheter is the most common strategy for managing urinary retention from neurogenic bladder. For most patients, this can be accomplished with intermittent catherization which involves no surgery or permanently attached appliances. Intermittent catheterization involves using straight catheters (which are usually disposable or single-use products) several times a day to empty the bladder. This can be done independently or with assistance. For people who are unable to use disposable straight catheters, a Foley catheter allows continuous drainage of urine into a sterile drainage bag that is worn by the patient, but such catheters are associated with higher rates of complications. Medications Oxybutynin is a common anti-cholinergic medication used to reduce bladder contractions by blocking M3 muscarinic receptors in the detrusor. Its use is limited by side effects such as dry mouth, constipation and decreased sweating. Tolterodine is a longer acting anticholinergic that may have fewer side effects.For urinary retention, cholinergics (muscarinic agonists) like bethanechol can improve the squeezing ability of the bladder. Alpha blockers can also reduce outlet resistance and allow complete emptying if there is adequate bladder muscle function. Botulinum Toxin Botulinum toxin (Botox) can be used through two different approaches. For spastic neurogenic bladder, the bladder muscle (detrusor) can be injected which will cause it to be flaccid for 6–9 months. This prevents high bladder pressures and intermittent catherization must be used during this time.Botox can also be injected into the external sphincter to paralyze a spastic sphincter in patients with detrusor sphincter dyssynergia. Neuromodulation There are various strategies to alter the interaction between the nerves and muscles of the bladder, including nonsurgical therapies (transurethral electrical bladder stimulation), minimally invasive procedures (sacral neuromodulation pacemaker), and operative (reconfiguration of sacral nerve root anatomy). Surgery Surgical interventions may be pursued if medical approaches have been maximized. Surgical options depend on the type of dysfunction observed on urodynamic testing, and may include: Urinary Diversion: Creation of a stoma (from the intestines, called "conduit") that bypasses the urethra to empty the bladder directly through a skin opening. Several techniques may be used. One technique is the Mitrofanoff stoma, where the appendix or a portion of the ileum (‘Yang-Monti’ conduit) are used to create the diversion. The ileum and ascending colon can also be used to create a pouch accessible for catheterization (Indiana pouch). Urethral stents or urethral sphincterotomy are other surgical approaches that can reduce bladder pressures but require use of an external urinary collection device. Urethral slings may be used in both adults and children Artificial Urinary Sphincters have shown good term outcomes in adults and pediatric patients. One study on 97 patients followed for a mean duration of 4 years found that 92% percent were continent at day and night during follow up. However, patients in this study who had intermediate-type bladders underwent adjuvant cystoplasty. Bladder Neck Closure is a major surgical procedure which can be a last resort treatment for incontinence, a Mitrofanoff stoma is necessary to empty the bladder. Epidemiology The overall prevalence of neurogenic bladder is limited due to the broad range of conditions that can lead to urinary dysfunction. Neurogenic bladder is common with spinal cord injury and multiple sclerosis. Rates of some type of urinary dysfunction surpass 80% one year after spinal cord injury. Among patients with multiple sclerosis, 20–25% will develop neurogenic bladder although the type and severity bladder dysfunction is variable. See also Bladder sphincter dyssynergia Multiple sclerosis Pseudodyssynergia Spinal cord injury Urinary retention References == External links ==

Hi Aarogya , Do you know what is Neurosyphilis,

Neurosyphilis

Neurosyphilis refers to infection of the central nervous system in a patient with syphilis. In the era of modern antibiotics the majority of neurosyphilis cases have been reported in HIV-infected patients. Meningitis is the most common neurological presentation in early syphilis. Tertiary syphilis symptoms are exclusively neurosyphilis, though neurosyphilis may occur at any stage of infection. To diagnose neurosyphilis, patients undergo a lumbar puncture to obtain cerebrospinal fluid (CSF) for analysis. The CSF is tested for antibodies for specific Treponema pallidum antigens. The preferred test is the VDRL test, which is sometimes supplemented by fluorescent treponemal antibody absorption test (FTA-ABS).Historically, the disease was studied under the Tuskegee study, a notable example of unethical human experimentation. The study was done on approximately 400 African-American men with untreated syphilis who were followed from 1932 to 1972 and compared to approximately 200 men without syphilis. The study began without informed consent of the subjects and was continued by the United States Public Health Service until 1972. The researchers failed to notify and withheld treatment for patients despite knowing penicillin was found as an effective cure for neurosyphilis. After four years of follow up, neurosyphilis was identified in 26.1% of patients vs. 2.5% of controls. After 20 years of followup, 14% showed signs of neurosyphilis and 40% had died from other causes. Signs and symptoms The signs and symptoms of neurosyphilis vary with the disease stage of syphilis. The stages of syphilis are categorized as primary, secondary, latent, and tertiary. It is important to note that neurosyphilis may occur at any stage of infection.Meningitis is the most common neurological presentation in early syphilis. It typically occurs in the secondary stage, arising within one year of initial infection. The symptoms are similar to other forms of meningitis. The most common associated with neurosyphilitic meningitis is cranial nerve palsy, especially of the facial nerve.Nearly any part of the eye may be involved. The most common form of ocular syphilis is uveitis. Other forms include episcleritis, vitritis, retinitis, papillitis, retinal detachment, and interstitial keratitis.Meningovascular syphilis usually occurs in late syphilis but may affect those with early disease. It is due to inflammation of the vasculature supplying the central nervous system, that results in ischemia. It typically occurs about 6–7 years after initial infection and it may affect those with early disease. It may present as stroke or spinal cord infarct. Signs and symptoms vary with vascular territory involved. The middle cerebral artery is most often affected.Parenchymal syphilis occurs years to decades after initial infection. It presents with the constellation of symptoms known as tabes dorsalis, because of a degenerative process of the posterior columns of the spinal cord. The constellation includes Argyll Robertson pupil, ataxic wide-based gait, paresthesias, bowel or bladder incontinence, loss of position and vibratory sense, loss of deep pain and temperature sensation, acute episodic gastrointestinal pain, Charcot joints, and general paresis.Gummatous disease may also present with destructive inflammation and space-occupying lesions. It is caused by granulomatous destruction of visceral organs. They most often involve the frontal and parietal lobes of the brain.Movement disorders can be found in a small percentage of individuals with neurosyphilis. The abnormal movements already reported were tremor, chorea, parkinsonism, ataxia, myoclonus, dystonia, athetosis, and ballism. Neuropsychiatric Although neurosyphilis is a neurological disease, neuropsychiatric symptoms might appear due to overall damage to the brain. These symptoms can make the diagnosis more difficult and can include symptoms of dementia, mania, psychosis, depression, and delirium:These symptoms are not always present, and when they are, they usually appear in more advanced stages of the disease. Complications The Jarisch-Herxheimer reaction is an immune-mediated response to syphilis therapy occurring within 2–24 hours. The exact mechanisms of reaction are unclear, however most likely caused by proinflammatory treponemal lipoproteins that are released from dead and dying organisms following antibiotic treatment. It is typically characterized by fever, headache, myalgia and possibly intensification of skin rash. It most often occurs in early-stage syphilis (up to 50%–75% of patients with primary and secondary syphilis). It is usually self-limiting and managed with antipyretics and nonsteroidal anti-inflammatory medications. Risk factors There are several risk factors: high-risk sexual behavior from unprotected sex and multiple sexual partners. The HIV infection antiretroviral therapy (ART) suppresses HIV transmission, but not syphilis transmission. It may also be associated with recreational drug use. Pathophysiology The pathogenesis is not fully known, in part due to fact that the organism is not easily cultured. Within days to weeks after initial infection, Treponema pallidum disseminates via blood and lymphatics. The organism may accumulate in perivascular spaces of nearly any organ, including the central nervous system (CNS). It is unclear why some patients develop CNS infection and others do not. Rarely, organisms may invade any structures of the eye (such as cornea, anterior chamber, vitreous and choroid, and optic nerve) and cause local inflammation and edema. In primary or secondary syphilis, invasion of the meninges may result in lymphocytic and plasma cell infiltration of perivascular spaces (Virchow-Robin spaces). The extension of cellular immune response to the brainstem and spinal cord causes inflammation and necrosis of small meningeal vessels.In tertiary syphilis, reactivation of chronic latent infection may result in meningovascular syphilis, arising from endarteritis obliterans of small, medium, or large arteries supplying the CNS. The parenchymal syphilis, presents as tabes dorsalis and general paresis. Tabes dorsalis thought to be due to irreversible degeneration of nerve fibers in posterior columns of the spinal cord involving the lumbosacral and lower thoracic levels. The general paresis is caused by meningeal vascular inflammation and ependymal granulomatous infiltration may lead to neuronal loss, along with astrocytic and microglial proliferation and damage may preferentially occur in the cerebral cortex, striatum, hypothalamus, and meninges.Concurrent infection of T. pallidum with human immunodeficiency virus (HIV) has been found to affect the course of syphilis. Syphilis can lie dormant for 10 to 20 years before progressing to neurosyphilis, but HIV may accelerate the rate of the progress. Also, infection with HIV has been found to cause penicillin therapy to fail more often. Therefore, neurosyphilis has once again been prevalent in societies with high HIV rates and limited access to penicillin. Diagnosis To diagnose neurosyphilis, cerebrospinal fluid (CSF) analysis is required. Lumbar puncture ("spinal tap") is used to acquire CSF. The Venereal Disease Research Laboratory test of the CSF is the preferred test for making a diagnosis of neurosyphilis. A positive test confirms neurosyphilis but a negative result does not rule out neurosyphilis. Due to the low sensitivity of the CSF VDRL, fluorescent treponemal antibody absorption test (FTA-ABS) can be used to supplement VDRL. Reported sensitivity is variable. False-negative antibody test result occurring when antibody concentration is so high that agglutination reaction cannot occur, which is typically seen during secondary stage and can be overcome by diluting test sample 1:10. CSF white blood cell count is often elevated in the early stages of neurosyphilis, ranging from about 50 to 100 white blood cells/mcL with a lymphocyte predominance. Cell counts are typically lower in late syphilis. Regardless of syphilis disease stage, the absence of CSF white blood cells rules out neurosyphilis. Treatment Penicillin is used to treat neurosyphilis. Two examples of penicillin therapies include: Aqueous penicillin G 3–4 million units every four hours for 10 to 14 days. One daily intramuscular injection and oral probenecid four times daily, both for 10 to 14 days.Follow-up blood tests are generally performed at 3, 6, 12, 24, and 36 months to make sure the infection is gone. Lumbar punctures for CSF fluid analysis are generally performed every 6 months until cell counts normalize. All patients with syphilis should be tested for HIV infection. All cases of syphilis should be reported to public health authorities and public health departments can aid in partner notification, testing, and determining need for treatment.The treatment success is measured with a 4-fold drop in the nontreponemal antibody test. In early-stage syphilis drop should occur in 6–12 months. in late syphilis drop can take 12–24 months. Titers may decline more slowly in persons who have previously had syphilis.In people who cannot take penicillin it is uncertain if other antibiotic therapy is effective for treating neurosyphilis. == References ==

Aarogya, could you share information about a health condition involving Neurotrophic keratitis

Neurotrophic keratitis

Neurotrophic keratitis (NK) is a degenerative disease of the cornea caused by damage of the trigeminal nerve, which results in impairment of corneal sensitivity, spontaneous corneal epithelium breakdown, poor corneal healing and development of corneal ulceration, melting and perforation. This is because, in addition to the primary sensory role, the nerve also plays a role maintaining the integrity of the cornea by supplying it with trophic factors and regulating tissue metabolism.Neurotrophic keratitis is classified as a rare disease, with an estimated prevalence of less than 5 in 10,000 people in Europe. It has been recorded that on average, 6% of herpetic keratitis cases may evolve to this disease, with a peak of 12.8% of cases of keratitis due to varicella zoster virus.The diagnosis, and particularly the treatment of neurotrophic keratitis are the most complex and challenging aspects of this disease, as a satisfactory therapeutic approach is not yet available. Causes The cornea lacks blood vessels and is among the most densely innervated structures of the human body. Corneal nerves are responsible for maintaining the anatomical and functional integrity of the cornea, conveying tactile, temperature and pain sensations, playing a role in the blink reflex, in wound healing and in the production and secretion of tears.Most corneal nerve fibres are sensory in origin and are derived from the ophthalmic branch of the trigeminal nerve. Congenital or acquired ocular and systemic diseases can determine a lesion at different levels of the trigeminal nerve, which can lead to a reduction (hypoesthesia) or loss (anesthesia) of sensitivity of the cornea. The most common causes of loss of corneal sensitivity are viral infections (herpes simplex and herpes zoster ophthalmicus), chemical burns, physical injuries, corneal surgery, neurosurgery, chronic use of topical medications, or chronic use of contact lenses.Possible causes also include systemic diseases such as diabetes mellitus, multiple sclerosis or leprosy. Other, albeit less frequent, potential causes of the disease are: intracranial space-occupying lesions such as neuroma, meningioma and aneurysms, which may compress the trigeminal nerve and reduce corneal sensitivity.Conversely, congenital conditions that may lead to this disorder are very rare. Diagnosis NK is diagnosed on the basis of the patients medical history and a careful examination of the eye and surrounding area.With regard to the patients medical history, special attention should be paid to any herpes virus infections and possible surgeries on the cornea, trauma, abuse of anaesthetics or chronic topical treatments, chemical burns or, use of contact lenses. It is also necessary to investigate the possible presence of diabetes or other systemic diseases such as multiple sclerosis. The clinical examination is usually performed through a series of assessments and tools: General examination of cranial nerves, to determine the presence of nerve damage. Eye examinations:Complete eye examination: examination of the eyelids, blink rate, presence of inflammatory reactions and secretions, corneal epithelial alterations. Corneal sensitivity test: performed by placing a cotton wad or cotton thread in contact with the corneal surface: this only allows to determine whether corneal sensitivity is normal, reduced or absent; or using an esthesiometer that allows to assess corneal sensitivity. Tear film function test, such as Schirmers test, and tear film break-up time. Fluorescein eye stain test, which shows any damage to the corneal and conjunctival epithelium Classification According to Mackies classification, neurotrophic keratitis can be divided into three stages based on severity: Stage I: characterized by alterations of the corneal epithelium, which is dry and opaque, with superficial punctate keratopathy and corneal oedema. Long-lasting neurotrophic keratitis may also cause hyperplasia of the epithelium, stromal scarring and neovascularization of the cornea. Stage II: characterized by development of epithelial defects, often in the area near the centre of the cornea. Stage III: characterized by ulcers of the cornea accompanied by stromal oedema and/or melting that may result in corneal perforation. Treatment Early diagnosis, targeted treatment according to the severity of the disease, and regular monitoring of patients with neurotrophic keratitis are critical to prevent damage progression and the occurrence of corneal ulcers, especially considering that the deterioration of the condition is often poorly symptomatic.The purpose of treatment is to prevent the progression of corneal damage and promote healing of the corneal epithelium. The treatment should always be personalized according to the severity of the disease. Conservative treatment is typically the best option.In stage I, the least serious, treatment consists of the administration of preservative-free artificial tears several times a day in order to lubricate and protect the ocular surface, improving the quality of the epithelium and preventing the possible loss of transparency of the cornea.In stage II, treatment should be aimed at preventing the development of corneal ulcers and promoting the healing of epithelial lesions. In addition to artificial tears, topical antibiotics may also be prescribed to prevent possible infections. Patients should be monitored very carefully since, being the disease poorly symptomatic, the corneal damage may progress without the patient noticing any worsening of the symptoms. Corneal contact lenses can also be used in this stage of the disease, for their protective action to improve corneal healing.In the most severe forms (stage III), it is necessary to stop the progression towards corneal perforation: in these cases, a possible surgical treatment option is tarsorrhaphy, i.e. the temporary or permanent closure of the eyelids by means of sutures or botulinum toxin injection. This protects the cornea, although the aesthetic result of these procedures may be difficult to accept for patients. Similarly, a procedure that entails the creation of a conjunctival flap has been shown to be effective in the treatment of chronic corneal ulcers with or without corneal perforation.In addition, another viable therapeutic option is amniotic membrane graft, which has recently been shown to play a role in stimulating corneal epithelium healing and in reducing vascularisation and inflammation of the ocular surface. Other approaches used in severe forms include the administration of autologous serum eye drops.Research studies have focused on developing novel treatments for neurotrophic keratitis, and several polypeptides, growth factors and neuromediators have been proposed. Studies were conducted on topical treatment with Substance P and IGF-1 (insulin-like growth factor-1), demonstrating an effect on epithelial healing. Nerve Growth Factor (NGF) play a role in the epithelial proliferation and differentiation and in the survival of corneal sensory nerves. Topical treatment with murine NGF showed to promote recovery of epithelial integrity and corneal sensitivity in NK patients. Recently, a recombinant human nerve growth factor eye drop formulation has been developed for clinical use.Cenegermin, a recombinant form of human NGF, has recently been approved in Europe in an eye drop formulation for neurotrophic keratitis. Cenegermin as an eye drop formulation for treatment of NK is approved by FDA in August 2018 See also Keratitis Cornea Rare disease References == External links ==

Aarogya, can you share information about a health condition involving Nightmare

Nightmare

A nightmare, also known as a bad dream, is an unpleasant dream that can cause a strong emotional response from the mind, typically fear but also despair, anxiety or great sadness. However, psychological nomenclature differentiates between nightmares and bad dreams; specifically, people remain asleep during bad dreams, whereas nightmares can awaken individuals. The dream may contain situations of discomfort, psychological or physical terror, or panic. After a nightmare, a person will often awaken in a state of distress and may be unable to return to sleep for a short period of time. Recurrent nightmares may require medical help, as they can interfere with sleeping patterns and cause insomnia. Nightmares can have physical causes such as sleeping in an uncomfortable position or having a fever, or psychological causes such as stress or anxiety. Eating before going to sleep, which triggers an increase in the bodys metabolism and brain activity, can be a potential stimulus for nightmares.The prevalence of nightmares in children (5–12 years old) is between 20 and 30%, and for adults is between 8 and 30%. In common language, the meaning of nightmare has extended as a metaphor to many bad things, such as a bad situation or a scary monster or person. Etymology The word nightmare is derived from the Old English mare, a mythological demon or goblin who torments others with frightening dreams. The term has no connection with the Modern English word for a female horse. The word nightmare is cognate with the Dutch term nachtmerrie and German Nachtmahr (dated). The sorcerous demons of Iranian mythology known as Divs are likewise associated with the ability to afflict their victims with nightmares. Signs and symptoms Those with nightmares experience abnormal sleep architecture. The impact of having a nightmare during the night has been found to be very similar to that of insomnia. This is thought to be caused by frequent nocturnal awakenings and fear of falling asleep. Nightmare disorder symptoms include repeated awakenings from the major sleep period or naps with detailed recall of extended and extremely frightening dreams, usually involving threats to survival, security, or self-esteem. The awakenings generally occur during the second half of the sleep period. Classification According to the International Classification of Sleep Disorders-Third Edition (ICSD-3), the nightmare disorder, together with REM sleep behaviour disorder (RBD) and recurrent isolated sleep paralysis, form the REM-related parasomnias subcategory of the Parasomnias cluster. Nightmares may be idiopathic without any signs of psychopathology or associated with disorders like stress, anxiety, substance abuse, psychiatric illness or PTSD (>80% of PTSD patients report nightmares). As regarding the dream content of the dreams they are usually imprinting negative emotions like sadness, fear or rage. According to the clinical studies the content can include being chased, injury or death of others, falling, natural disasters or accidents. Typical dreams or recurrent dreams may also have some of these topics. Cause Scientific research shows that nightmares may have many causes. In a study focusing on children, researchers were able to conclude that nightmares directly correlate with the stress in childrens lives. Children who experienced the death of a family member or a close friend or know someone with a chronic illness have more frequent nightmares than those who are only faced with stress from school or stress from social aspects of daily life. A study researching the causes of nightmares focuses on patients who have sleep apnea. The study was conducted to determine whether or not nightmares may be caused by sleep apnea, or being unable to breathe. In the nineteenth century, authors believed that nightmares were caused by not having enough oxygen, therefore it was believed that those with sleep apnea had more frequent nightmares than those without it. The results actually showed that healthy people have more nightmares than sleep apnea patients. Another study supports the hypothesis. In this study, 48 patients (aged 20–85 yrs) with obstructive airways disease (OAD), including 21 with and 27 without asthma, were compared with 149 sex- and age-matched controls without respiratory disease. OAD subjects with asthma reported approximately 3 times as many nightmares as controls or OAD subjects without asthma. The evolutionary purpose of nightmares then could be a mechanism to awaken a person who is in danger. Lucid-dreaming advocate Stephen LaBerge has outlined a possible reason for how dreams are formulated and why nightmares occur. To LaBerge, a dream starts with an individual thought or scene, such as walking down a dimly lit street. Since dreams are not predetermined, the brain responds to the situation by either thinking a good thought or a bad thought, and the dream framework follows from there. If bad thoughts in a dream are more prominent than good thoughts, the dream may proceed to be a nightmare.There is a view, possibly featured in the story A Christmas Carol, that eating cheese before sleep can cause nightmares, but there is little scientific evidence for this.Severe nightmares are also likely to occur when person has a fever, these nightmares are often referred to as fever dreams. Treatment Sigmund Freud and Carl Jung seemed to have shared a belief that people frequently distressed by nightmares could be re-experiencing some stressful event from the past. Both perspectives on dreams suggest that therapy can provide relief from the dilemma of the nightmarish experience. Halliday (1987) grouped treatment techniques into four classes. Direct nightmare interventions that combine compatible techniques from one or more of these classes may enhance overall treatment effectiveness: Analytic and cathartic techniques Storyline alteration procedures Face-and-conquer approaches Desensitization and related behavioral techniques Post-traumatic stress disorder Recurring post-traumatic stress disorder (PTSD) nightmares in which traumas are re-experienced respond well to a technique called imagery rehearsal. This involves dreamers coming up with alternative, mastery outcomes to the nightmares, mentally rehearsing those outcomes while awake, and then reminding themselves at bedtime that they wish these alternate outcomes should the nightmares reoccur. Research has found that this technique not only reduces the occurrence of nightmares and insomnia, but also improves other daytime PTSD symptoms. The most common variations of imagery rehearsal therapy (IRT) "relate to the number of sessions, duration of treatment, and the degree to which exposure therapy is included in the protocol". Medication Prazosin (alpha-1 blocker) appears useful in decreasing the number of nightmares and the distress caused by them in people with PTSD. Risperidone (atypical antipsychotic) at a dosage of 2 mg per day, has been shown in case series to remission of nightmares on the first night. Trazodone (antidepressant) has been shown in a case report to treat nightmares associated with a depressed patient.Trials have included hydrocortisone, gabapentin, paroxetine, tetrahydrocannabinol, eszopiclone, xyrem, and carvedilol. See also Bogeyman False awakening Hag § In folklore Horror and terror Mare (folklore) Night terror Nightmare disorder Nocnitsa Sleep disorder Sleep paralysis Succubus Incubus A Nightmare on Elm Street, 1984 film References Further reading Anch, A. M.; Browman, C. P.; Mitler, M. M.; Walsh, J. K. (1988). Sleep: A Scientific Perspective. New Jersey: Prentice-Hall. ISBN 9780138129187. Harris, J. C. (2004). "The Nightmare". Archives of General Psychiatry. 61 (5): 439–40. doi:10.1001/archpsyc.61.5.439. PMID 15123487. Husser, J.-M.; Mouton, A., eds. (2010). Le Cauchemar dans les sociétés antiques. Actes des journées détude de lUMR 7044 (15–16 Novembre 2007, Strasbourg) (in French). Paris: De Boccard. Jones, Ernest (1951). On the Nightmare. ISBN 978-0-87140-912-6. Forbes, D.; et al. (2001). "Brief Report: Treatment of Combat-Related Nightmares Using Imagery Rehearsal: A Pilot Study". Journal of Traumatic Stress. 14 (2): 433–442. doi:10.1023/A:1011133422340. PMID 11469167. S2CID 44630028. Siegel, A. (2003). "A mini-course for clinicians and trauma workers on posttraumatic nightmares". Burns, Sarah (2004). Painting the Dark Side : Art and the Gothic Imagination in Nineteenth-Century America. Ahmanson-Murphy Fine Are Imprint. University of California Press. ISBN 978-0-520-23821-3. Davenport-Hines, Richard (1999). Gothic: Four Hundred Years of Excess, Horror, Evil and Ruin. North Point Press. pp. 160–61. ISBN 9780865475441. Hill, Anne (2009). What To Do When Dreams Go Bad: A Practical Guide to Nightmares. Serpentine Media. ISBN 978-1-887590-04-4. Simons, Ronald C.; Hughes, Charles C., eds. (1985). Culture-Bound Syndromes. Springer. Sagan, Carl (1997). The Demon-Haunted World: Science as a Candle in the Dark. Coalson, Bob (1995). "Nightmare help: Treatment of trauma survivors with PTSD". Psychotherapy: Theory, Research, Practice, Training. 32 (3): 381–388. doi:10.1037/0033-3204.32.3.381. "Nightmares? Bad Dreams, or Recurring Dreams? Lucky You!". Archived from the original on 19 March 2012. Retrieved 8 December 2015. Halliday, G. (1987). "Direct psychological therapies for nightmares: A review". Clinical Psychology Review. 7 (5): 501–523. doi:10.1016/0272-7358(87)90041-9. Doctor, Ronald M.; Shiromoto, Frank N., eds. (2010). "Imagery Rehearsal Therapy (IRT)". The Encyclopedia of Trauma and Traumatic Stress Disorders. New York: Facts on File. p. 148. ISBN 9780816067640. Mayer, Mercer (1976). Theres a Nightmare in My Closet. [New York]: Puffin Pied Piper. Moore, Bret A.; Kraków, Barry (2010). "Imagery rehearsal therapy: An emerging treatment for posttraumatic nightmares in veterans". Psychological Trauma: Theory, Research, Practice, and Policy. 2 (3): 232–238. doi:10.1037/a0019895. External links Night-Mares: Demons that Cause Nightmares

Aarogya, Please give me a short description about Nocturnal enuresis

Nocturnal enuresis

Nocturnal enuresis, also informally called bedwetting, is involuntary urination while asleep after the age at which bladder control usually begins. Bedwetting in children and adults can result in emotional stress. Complications can include urinary tract infections.Most bedwetting is a developmental delay—not an emotional problem or physical illness. Only a small percentage (5 to 10%) of bedwetting cases have a specific medical cause. Bedwetting is commonly associated with a family history of the condition. Nocturnal enuresis is considered primary when a child has not yet had a prolonged period of being dry. Secondary nocturnal enuresis is when a child or adult begins wetting again after having stayed dry. Treatments range from behavioral therapy, such as bedwetting alarms, to medication, such as hormone replacement, and even surgery such as urethral dilatation. Since most bedwetting is simply a developmental delay, most treatment plans aim to protect or improve self-esteem. Treatment guidelines recommend that the physician counsel the parents, warning about psychological consequences caused by pressure, shaming, or punishment for a condition children cannot control.Bedwetting is the most common childhood complaint. Impact A review of medical literature shows doctors consistently stressing that a bedwetting child is not at fault for the situation. Many medical studies state that the psychological impacts of bedwetting are more important than the physical considerations. "It is often the childs and family members reaction to bedwetting that determines whether it is a problem or not." Self-esteem Whether bedwetting causes low self-esteem remains a subject of debate, but several studies have found that self-esteem improved with management of the condition.Children questioned in one study ranked bedwetting as the third most stressful life event, after "parental war of words", divorce and parental fighting. Adolescents in the same study ranked bedwetting as tied for second with parental fighting.Bedwetters face problems ranging from being teased by siblings, being punished by parents, the embarrassment of still having to wear diapers, and being afraid that friends will find out. Psychologists report that the amount of psychological harm depends on whether the bedwetting harms self-esteem or development of social skills. Key factors are: How much the bedwetting limits social activities like sleep-overs and campouts The degree of the social ostracism by peers (Perceived) Anger, punishment, refusal and rejection by caregivers along with subsequent guilt The number of failed treatment attempts How long the child has been wetting Behavioral impact Studies indicate that children with behavioral problems are more likely to wet their beds. For children who have developmental problems, the behavioral problems and the bedwetting are frequently part of/caused by the developmental issues. For bedwetting children without other developmental issues, these behavioral issues can result from self-esteem issues and stress caused by the wetting.As mentioned below, current studies show that it is very rare for a child to intentionally wet the bed as a method of acting out. Punishment for bedwetting Medical literature states, and studies show, that punishing or shaming a child for bedwetting will frequently make the situation worse. It is best described as a downward cycle, where a child punished for bedwetting feels shame and a loss of self-confidence. This can cause increased bedwetting incidents, leading to more punishment and shaming.In the United States, about 25% of enuretic children are punished for wetting the bed. In Hong Kong, 57% of enuretic children are punished for wetting. Parents with only a grade-school level education punish bedwetting children at twice the rate of high-school- and college-educated parents. Families Parents and family members are frequently stressed by a childs bedwetting. Soiled linens and clothing cause additional laundry. Wetting episodes can cause lost sleep if the child wakes and/or cries, waking the parents. A European study estimated that a family with a child who wets nightly will pay about $1,000 a year for additional laundry, extra sheets, diapers, and mattress replacement.Despite these stressful effects, doctors emphasize that parents should react patiently and supportively. Sociopathy Bedwetting does not indicate a greater possibility of being a sociopath, as long as caregivers do not cause trauma by shaming or punishing a bedwetting child. Bedwetting was part of the Macdonald triad, a set of three behavioral characteristics described by John Macdonald in 1963. The other two characteristics were firestarting and animal abuse. Macdonald suggested that there was an association between a person displaying all three characteristics, then later displaying sociopathic criminal behavior.Up to 60% of multiple-murderers, according to some estimates, wet their beds post-adolescence.Enuresis is an "unconscious, involuntary [..] act".Bedwetting can be connected to past emotions and identity. Children under substantial stress, particularly in their home environment, frequently engage in bedwetting, in order to alleviate the stress produced by their surroundings. Trauma can also trigger a return to bedwetting (secondary enuresis) in both children and adults. It is not bedwetting that increases the chance of criminal behavior, but the associated trauma. For example, parental cruelty can result in "homicidal proneness". Causes The aetiology of NE is not fully understood, although there are three common causes: excessive urine volume, poor sleep arousal, and bladder contractions. Differentiation of cause is mainly based on patient history and fluid charts completed by the parent or carer to inform management options.Bedwetting has a strong genetic component. Children whose parents were not enuretic have only a 15% incidence of bedwetting. When one or both parents were bedwetters, the rates jump to 44% and 77% respectively.These first two factors (aetiology and genetic component) are the most common in bedwetting, but current medical technology offers no easy testing for either cause. There is no test to prove that bedwetting is only a developmental delay, and genetic testing offers little or no benefit. As a result, other conditions should be ruled out. The following causes are less common, but are easier to prove and more clearly treated:In some bed-wetting children there is no increase in ADH (antidiuretic hormone) production, while other children may produce an increased amount of ADH but their response is insufficient. Individuals with reported bedwetting issues are 2.7 times more likely to be diagnosed with Attention deficit hyperactivity disorder. Caffeine increases urine production. Chronic constipation can cause bed wetting. When the bowels are full, it can put pressure on the bladder. Often such children defecate normally, yet they retain a significant mass of material in the bowel which causes bed wetting. Infections and disease are more strongly connected with secondary nocturnal enuresis and with daytime wetting. Less than 5% of all bedwetting cases are caused by infection or disease, the most common of which is a urinary tract infection. Patients with more severe neurological-developmental issues have a higher rate of bedwetting problems. One study of seven-year-olds showed that "handicapped and intellectually disabled children" had a bedwetting rate almost three times higher than "non-handicapped children" (26.6% vs. 9.5%, respectively). Psychological issues (e.g., death in the family, sexual abuse, extreme bullying) are established as a cause of secondary nocturnal enuresis (a return to bedwetting), but are very rarely a cause of PNE-type bedwetting. Bedwetting can also be a symptom of a pediatric neuropsychological disorder called PANDAS. Sleep apnea stemming from an upper airway obstruction has been associated with bedwetting. Snoring and enlarged tonsils or adenoids are a sign of potential sleep apnea problems. Sleepwalking can lead to bedwetting. During sleepwalking, the sleepwalker may think he/she is in another room. When the sleepwalker urinates during a sleepwalking episode, he/she usually thinks they are in the bathroom, and therefore urinate where they think the toilet should be. Cases of this have included opening a closet and urinating in it; urinating on the sofa and simply urinating in the middle of the room. Stress is a cause of people who return to wetting the bed. Researchers find that moving to a new town, parent conflict or divorce, arrival of a new baby, or loss of a loved one or pet can cause insecurity, contributing to returning bedwetting. Type 1 diabetes mellitus can first present as nocturnal enuresis. It is classically associated with polyuria, polydipsia, and polyphagia; weight loss, lethargy, and diaper candidiasis may also be present in those with new-onset disease. Unconfirmed Food allergies may be part of the cause for some patients. This link is not well established, requiring further research. Improper toilet training is another disputed cause of bedwetting. This theory was more widely supported in the last century and is still cited by some authors today. Some say bedwetting can be caused by improper toilet training, either by starting the training when the child is too young or by being too forceful. Recent research has shown more mixed results and a connection to toilet training has not been proven or disproven. According to the American Academy of Pediatrics, more child abuse occurs during potty training than in any other developmental stage. Dandelions are reputed to be a potent diuretic, and anecdotal reports and folk wisdom say children who handle them can end up wetting the bed. English folk names for the plant are "peebeds" and "pissabeds". In French the dandelion is called pissenlit, which means "piss in bed"; likewise "piscialletto", an Italian folkname, and "meacamas" in Spanish. Mechanism Two physical functions prevent bedwetting. The first is a hormone that reduces urine production at night. The second is the ability to wake up when the bladder is full. Children usually achieve nighttime dryness by developing one or both of these abilities. There appear to be some hereditary factors in how and when these develop.The first ability is a hormone cycle that reduces the bodys urine production. At about sunset each day, the body releases a minute burst of antidiuretic hormone (also known as arginine vasopressin or AVP). This hormone burst reduces the kidneys urine output well into the night so that the bladder does not get full until morning. This hormone cycle is not present at birth. Many children develop it between the ages of two and six years old, others between six and the end of puberty, and some not at all.The second ability that helps people stay dry is waking when the bladder is full. This ability develops in the same age range as the vasopressin hormone, but is separate from that hormone cycle. The typical development process begins with one- and two-year-old children developing larger bladders and beginning to sense bladder fullness. Two- and three-year-old children begin to stay dry during the day. Four- and five-year-olds develop an adult pattern of urinary control and begin to stay dry at night. Diagnosis Thorough history regarding frequency of bedwetting, any period of dryness in between, associated daytime symptoms, constipation, and encopresis should be sought. Voiding diary People are asked to observe, record and measure when and how much their child voids and drinks, as well as associated symptoms. A voiding diary in the form of a frequency volume chart records voided volume along with the time of each micturition for at least 24 hours. The frequency volume chart is enough for patients with complaints of nocturia and frequency only. If other symptoms are also present then a detailed bladder diary must be maintained. In a bladder diary, times of micturition and voided volume, incontinence episodes, pad usage, and other information such as fluid intake, the degree of urgency, and the degree of incontinence are recorded. Physical examination Each child should be examined physically at least once at the beginning of treatment. A full pediatric and neurological exam is recommended. Measurement of blood pressure is important to rule out any renal pathology. External genitalia and lumbosacral spine should be examined thoroughly. A spinal defect, such as a dimple, hair tuft, or skin discoloration, might be visible in approximately 50% of patients with an intraspinal lesion. Thorough neurologic examination of the lower extremities, including gait, muscle power, tone, sensation, reflexes, and plantar responses should be done during first visit. Classification Nocturnal urinary continence is dependent on 3 factors: 1) nocturnal urine production, 2) nocturnal bladder function and 3) sleep and arousal mechanisms. Any child will experience nocturnal enuresis if more urine is produced than can be contained in the bladder or if the detrusor is hyperactive, provided that he or she is not awakened by the imminent bladder contraction. Primary nocturnal enuresis Primary nocturnal enuresis is the most common form of bedwetting. Bedwetting becomes a disorder when it persists after the age at which bladder control usually occurs (4–7 years), and is either resulting in an average of at least two wet nights a week with no long periods of dryness or not able to sleep dry without being taken to the toilet by another person. New studies show that anti-psychotic drugs can have a side effect of causing enuresis.It has been shown that diet impacts enuresis in children. Constipation from a poor diet can result in impacted stool in the colon putting undue pressure on the bladder creating loss of bladder control (overflow incontinence).Some researchers, however, recommend a different starting age range. This guidance says that bedwetting can be considered a clinical problem if the child regularly wets the bed after turning 7 years old. Secondary nocturnal enuresis Secondary enuresis occurs after a patient goes through an extended period of dryness at night (six months or more) and then reverts to night-time wetting. Secondary enuresis can be caused by emotional stress or a medical condition, such as a bladder infection. Psychological definition Psychologists are usually allowed to diagnose and write a prescription for diapers if nocturnal enuresis causes the patient significant distress. Psychiatists may instead use a definition from the DSM-IV, defining nocturnal enuresis as repeated urination into bed or clothes, occurring twice per week or more for at least three consecutive months in a child of at least 5 years of age and not due to either a drug side effect or a medical condition. Management There are a number of management options for bedwetting. The following options apply when the bedwetting is not caused by a specifically identifiable medical condition such as a bladder abnormality or diabetes. Treatment is recommended when there is a specific medical condition such as bladder abnormalities, infection, or diabetes. It is also considered when bedwetting may harm the childs self-esteem or relationships with family/friends. Only a small percentage of bedwetting is caused by a specific medical condition, so most treatment is prompted by concern for the childs emotional welfare. Behavioral treatment of bedwetting overall tends to show increased self-esteem for children.Parents become concerned much earlier than doctors. A study in 1980 asked parents and physicians the age that children should stay dry at night. The average parent response was 2.75 years old, while the average physician response was 5.13 years old.Punishment is not effective and can interfere with treatment. Treatment approaches Simple behavioral methods are recommended as initial treatment. Other treatment methods include the following: Motivational therapy in nocturnal enuresis mainly involves parent and child education. Guilt should be allayed by providing facts. Fluids should be restricted 2 hours prior to bed. The child should be encouraged to empty the bladder completely prior to going to bed. Positive reinforcement can be initiated by setting up a diary or chart to monitor progress and establishing a system to reward the child for each night that they are dry. The child should participate in morning cleanup as a natural, nonpunitive consequence of wetting. This method is particularly helpful in younger children (<8 years) and will achieve dryness in 15-20% of the patients. Waiting: Almost all children will outgrow bedwetting. For this reason, urologists and pediatricians frequently recommend delaying treatment until the child is at least six or seven years old. Physicians may begin treatment earlier if they perceive the condition is damaging the childs self-esteem and/or relationships with family/friends. Bedwetting alarms: Physicians also frequently suggest bedwetting alarms which sound a loud tone when they sense moisture. This can help condition the child to wake at the sensation of a full bladder. These alarms are considered more effective than no treatment and may have a lower risk of adverse events than some medical therapies but it is still uncertain if alarms are more effective than other treatments. There may be a 29% to 69% relapse rate, so the treatment may need to be repeated. DDAVP (desmopressin) tablets are a synthetic replacement for antidiuretic hormone, the hormone that reduces urine production during sleep. Desmopressin is usually used in the form of desmopressin acetate, DDAVP. Patients taking DDAVP are 4.5 times more likely to stay dry than those taking a placebo. The drug replaces the hormone for that night with no cumulative effect. US drug regulators have banned using desmopressin nasal sprays for treating bedwetting since the oral form is considered safer. DDAVP is most efficient in children with nocturnal polyuria (nocturnal urine production greater than 130% of expected bladder capacity for age) and normal bladder reservoir function (maximum voided volume greater than 70% of expected bladder capacity for age). Other children who are likely candidates for desmopressin treatment are those in whom alarm therapy has failed or those considered unlikely to comply with alarm therapy. It can be very useful for summer camp and sleepovers to prevent enuresis. Tricyclic antidepressants: Tricyclic antidepressant prescription drugs with anti-muscarinic properties have been proven successful in treating bedwetting, but also have an increased risk of side effects, including death from overdose. These drugs include amitriptyline, imipramine and nortriptyline. Studies find that patients using these drugs are 4.2 times as likely to stay dry as those taking a placebo. The relapse rates after stopping the medicines are close to 50%. Condition management Diapers: Wearing a diaper can reduce embarrassment for bedwetters and make cleanup easier for caregivers. These products are known as training pants or diapers when used for younger children, and as absorbent underwear or incontinence briefs when marketed for older children and adults. Some diapers are marketed especially for people with bedwetting. A major benefit is the reduced stress on both the bedwetter and caregivers. Wearing diapers can be especially beneficial for bedwetting children wishing to attend sleepovers or campouts, reducing emotional problems caused by social isolation and/or embarrassment in front of peers. According to one study of an adult with severe disabilities, extended diaper usage may interfere with learning to stay dry. Waterproof mattress pads are used in some cases to ease clean-up of bedwetting incidents, however they only protect the mattress, and the sheets, bedding or sleeping partner may be soiled. Unproven Acupuncture: While acupuncture is safe in most adolescents, studies done to assess its effectiveness for nocturnal enuresis are of low quality. Dry bed training: Dry bed training is frequently waking the child at night. Studies show this training is ineffective by itself and does not increase the success rate when used in conjunction with a bedwetting alarm. Star chart: A star chart allows a child and parents to track dry nights, as a record and/or as part of a reward program. This can be done either alone or with other treatments. There is no research to show effectiveness, either in reducing bedwetting or in helping self-esteem. Some psychologists, however, recommend star charts as a way to celebrate successes and help a childs self-esteem. Epidemiology Doctors frequently consider bedwetting as a self-limiting problem, since most children will outgrow it. Children 5 to 9 years old have a spontaneous cure rate of 14% per year. Adolescents 10 to 18 years old have a spontaneous cure rate of 16% per year.As can be seen from the numbers above, a portion of bedwetting children will not outgrow the problem. Adult rates of bedwetting show little change due to spontaneous cure. Persons who are still enuretic at age 18 are likely to deal with bedwetting throughout their lives.Studies of bedwetting in adults have found varying rates. The most quoted study in this area was done in the Netherlands. It found a 0.5% rate for 20- to 79-year-olds. A Hong Kong study, however, found a much higher rate. The Hong Kong researchers found a bedwetting rate of 2.3% in 16- to 40-year-olds. History In the first century B.C., at lines 1026-29 of the fourth book of his On the Nature of Things, Lucretius gave a high-style description of bed-wetting: "Innocent children often, when they are bound up by sleep, believe they are raising up their clothing by a latrine or shallow pot; they pour out the urine from their whole body, and the Babylonian bedding with its magnificent splendor is soaked."An early psychological perspective on bedwetting was given in 1025 by Avicenna in The Canon of Medicine: "Urinating in bed is frequently predisposed by deep sleep: when urine begins to flow, its inner nature and hidden will (resembling the will to breathe) drives urine out before the child awakes. When children become stronger and more robust, their sleep is lighter and they stop urinating."Psychological theory through the 1960s placed much greater focus on the possibility that a bedwetting child might be acting out, purposefully striking back against parents by soiling linens and bedding. However, more recent research and medical literature states that this is very rare. See also Enuresis Nocturnal emission References == External links ==

What does Onchocerciasis mean Aarogya

Onchocerciasis

Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm Onchocerca volvulus. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindness due to infection, after trachoma.The parasite worm is spread by the bites of a black fly of the Simulium type. Usually, many bites are required before infection occurs. These flies live near rivers, hence the common name of the disease. Once inside a person, the worms create larvae that make their way out to the skin, where they can infect the next black fly that bites the person. There are a number of ways to make the diagnosis, including: placing a biopsy of the skin in normal saline and watching for the larva to come out; looking in the eye for larvae; and looking within the bumps under the skin for adult worms.A vaccine against the disease does not exist. Prevention is by avoiding being bitten by flies. This may include the use of insect repellent and proper clothing. Other efforts include those to decrease the fly population by spraying insecticides. Efforts to eradicate the disease by treating entire groups of people twice a year are ongoing in a number of areas of the world. Treatment of those infected is with the medication ivermectin every six to twelve months. This treatment kills the larvae but not the adult worms. The antibiotic doxycycline weakens the worms by killing an associated bacterium called Wolbachia, and is recommended by some as well. The lumps under the skin may also be removed by surgery.About 15.5 million people are infected with river blindness. Approximately 0.8 million have some amount of loss of vision from the infection. Most infections occur in sub-Saharan Africa, although cases have also been reported in Yemen and isolated areas of Central and South America. In 1915, the physician Rodolfo Robles first linked the worm to eye disease. It is listed by the World Health Organization (WHO) as a neglected tropical disease. In 2013 Colombia became first country to eradicate this disease. Signs and symptoms Adult worms remain in subcutaneous nodules, limiting access to the hosts immune system. Microfilariae, in contrast, are able to induce intense inflammatory responses, especially upon their death. Wolbachia species have been found to be endosymbionts of O. volvulus adults and microfilariae, and are thought to be the driving force behind most of O. volvulus morbidity. Dying microfilariae have been recently discovered to release Wolbachia surface protein that activates TLR2 and TLR4, triggering innate immune responses and producing the inflammation and its associated morbidity. The severity of illness is directly proportional to the number of infected microfilariae and the power of the resultant inflammatory response.Skin involvement typically consists of intense itching, swelling, and inflammation. A grading system has been developed to categorize the degree of skin involvement: Acute papular onchodermatitis – scattered pruritic papules Chronic papular onchodermatitis – larger papules, resulting in hyperpigmentation Lichenified onchodermatitis – hyperpigmented papules and plaques, with edema, lymphadenopathy, pruritus and common secondary bacterial infections Skin atrophy – loss of elasticity, the skin resembles tissue paper, lizard skin appearance Depigmentation – leopard skin appearance, usually on anterior lower leg Glaucoma effect – eyes malfunction, begin to see shadows or nothingOcular involvement provides the common name associated with onchocerciasis, river blindness, and may involve any part of the eye from conjunctiva and cornea to uvea and posterior segment, including the retina and optic nerve. The microfilariae migrate to the surface of the cornea. Punctate keratitis occurs in the infected area. This clears up as the inflammation subsides. However, if the infection is chronic, sclerosing keratitis can occur, making the affected area become opaque. Over time, the entire cornea may become opaque, thus leading to blindness. Some evidence suggests the effect on the cornea is caused by an immune response to bacteria present in the worms.The infected persons skin is itchy, with severe rashes permanently damaging patches of skin. Mazzotti reaction The Mazzotti reaction, first described in 1948, is a symptom complex seen in patients after undergoing treatment of onchocerciasis with the medication diethylcarbamazine (DEC). Mazzotti reactions can be life-threatening, and are characterized by fever, urticaria, swollen and tender lymph nodes, tachycardia, hypotension, arthralgias, oedema, and abdominal pain that occur within seven days of treatment of microfilariasis. The phenomenon is so common when DEC is used that this drug is the basis of a skin patch test used to confirm that diagnosis. The drug patch is placed on the skin, and if the patient is infected with O. volvulus microfilaria, localized pruritus and urticaria are seen at the application site. Nodding disease This is an unusual form of epidemic epilepsy associated with onchocerciasis although definitive link has not been established. This syndrome was first described in Tanzania by Louise Jilek-Aall, a Norwegian psychiatric doctor in Tanzanian practice, during the 1960s. It occurs most commonly in Uganda and South Sudan. It manifests itself in previously healthy 5–15-year-old children, is often triggered by eating or low temperatures and is accompanied by cognitive impairment. Seizures occur frequently and may be difficult to control. The electroencephalogram is abnormal but cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) are normal or show non-specific changes. If there are abnormalities on the MRI they are usually present in the hippocampus. Polymerase chain reaction testing of the CSF does not show the presence of the parasite. Cause The cause is Onchocerca volvulus. Life cycle The life of the parasite can be traced through the black fly and the human hosts in the following steps: A Simulium female black fly takes a blood meal on an infected human host, and ingests microfilaria. The microfilaria enter the gut and thoracic flight muscles of the black fly, progressing into the first larval stage (J1.). The larvae mature into the second larval stage (J2.), and move to the proboscis and into the saliva in its third larval stage (J3.). Maturation takes about seven days. The black fly takes another blood meal, passing the larvae into the next human hosts blood. The larvae migrate to the subcutaneous tissue and undergo two more molts. They form nodules as they mature into adult worms over six to 12 months. After maturing, adult male worms mate with female worms in the subcutaneous tissue to produce between 700 and 1,500 microfilaria per day. The microfilaria migrate to the skin during the day, and the black flies only feed in the day, so the parasite is in a prime position for the female fly to ingest it. Black flies take blood meals to ingest these microfilaria to restart the cycle. Diagnosis Diagnosis can be made by skin biopsy (with or without PCR) or antibody testing. Classification Onchocerciasis causes different kinds of skin changes, which vary in different geographic regions; it may be divided into the following phases or types:: 440–441  Erisipela de la costa An acute phase, it is characterized by swelling of the face, with erythema and itching.: 440  This skin change, erisípela de la costa, of acute onchocerciasis is most commonly seen among victims in Central and South America.Mal morando This cutaneous condition is characterized by inflammation accompanied by hyperpigmentation.: 440  Sowda A cutaneous condition, it is a localized type of onchocerciasis.: 440 Additionally, the various skin changes associated with onchocerciasis may be described as follows:: 440  Leopard skin The spotted depigmentation of the skin that may occur with onchocerciasis: 440  Elephant skin The thickening of human skin that may be associated with onchocerciasis: 440  Lizard skin The thickened, wrinkled skin changes that may result with onchocerciasis: 441 Prevention Various control programs aim to stop onchocerciasis from being a public health problem. The first was the Onchocerciasis Control Programme (OCP), which was launched in 1974, and at its peak, covered 30 million people in 11 countries. Through the use of larvicide spraying of fast-flowing rivers to control black fly populations, and from 1988 onwards, the use of ivermectin to treat infected people, the OCP eliminated onchocerciasis as a public health problem. The OCP, a joint effort of the World Health Organization, the World Bank, the United Nations Development Programme, and the UN Food and Agriculture Organization, was considered to be a success, and came to an end in 2002. Continued monitoring ensures onchocerciasis cannot reinvade the area of the OCP. Elimination In 1995, the African Programme for Onchocerciasis Control (APOC) began covering another 19 countries, mainly relying upon the use of the drug ivermectin. Its goal was to set up community-directed treatment with ivermectin for those at risk of infection. In these ways, transmission has declined. APOC closed in 2015 and aspects of its work taken over by the WHO Expanded Special Programme for the Elimination of Neglected Tropical Diseases (ESPEN). As in the Americas, the objective of ESPEN working with Government Health Ministries and partner NGDOs, is the elimination of transmission of onchocerciasis. This requires consistent annual treatment of 80% of the population in endemic areas for at least 10–12 years – the life span of the adult worm. No African country has so far verified elimination of onchocerciasis, but treatment has stopped in some areas (e.g. Nigeria), following epidemiological and entomological assessments that indicated that no ongoing transmission could be detected. In 2015, WHO facilitated the launch of an elimination program in Yemen which was subsequently put on hold due to conflict.In 1992, the Onchocerciasis Elimination Programme for the Americas, which also relies on ivermectin, was launched. On July 29, 2013, the Pan American Health Organization (PAHO) announced that after 16 years of efforts, Colombia had become the first country in the world to eliminate onchocerciasis. In September 2015, the Onchocerciasis Elimination Program for the Americas announced that onchocerciasis only remained in a remote region on the border of Brazil and Venezuela. The area is home to the Yanomami indigenous people. The first countries to receive verification of elimination were Colombia in 2013, Ecuador in 2014, Mexico in 2015 and Guatemala in 2016. The key factor in elimination is mass administration of the antiparasitic drug ivermectin. The initial projection was that the disease would be eliminated from remaining foci in the Americas by 2012.No vaccine to prevent onchocerciasis infection in humans is available. A vaccine to prevent onchocerciasis infection for cattle is in phase three trials. Cattle injected with a modified and weakened form of O. ochengi larvae have developed very high levels of protection against infection. The findings suggest that it could be possible to develop a vaccine that protects people against river blindness using a similar approach. Unfortunately, a vaccine to protect humans is still many years off. Treatment In mass drug administration (MDA) programmes, the treatment for onchocerciasis is ivermectin (trade name: Mectizan); infected people can be treated with two doses of ivermectin, six months apart, repeated every three years. The drug paralyses and kills the microfilariae causing fever, itching, and possibly oedema, arthritis and lymphadenopathy. Intense skin itching is eventually relieved, and the progression towards blindness is halted. In addition, while the drug does not kill the adult worms, it does prevent them for a limited time from producing additional offspring. The drug therefore prevents both morbidity and transmission for up to several months.Ivermectin treatment is particularly effective because it only needs to be taken once or twice a year, needs no refrigeration, and has a wide margin of safety, with the result that it has been widely given by minimally trained community health workers. Antibiotics For the treatment of individuals, doxycycline is used to kill the Wolbachia bacteria that live in adult worms. This adjunct therapy has been shown to significantly lower microfilarial loads in the host, and may kill the adult worms, due to the symbiotic relationship between Wolbachia and the worm. In four separate trials over ten years with various dosing regimens of doxycycline for individualized treatment, doxycycline was found to be effective in sterilizing the female worms and reducing their numbers over a period of four to six weeks. Research on other antibiotics, such as rifampicin, has shown it to be effective in animal models at reducing Wolbachia both as an alternative and as an adjunct to doxycycline. However, doxycycline treatment requires daily dosing for at least four to six weeks, making it more difficult to administer in the affected areas. Ivermectin Ivermectin kills the parasite by interfering with the nervous system and muscle function, in particular, by enhancing inhibitory neurotransmission. The drug binds to and activates glutamate-gated chloride channels. These channels, present in neurons and myocytes, are not invertebrate-specific, but are protected in vertebrates from the action of ivermectin by the blood–brain barrier. Ivermectin is thought to irreversibly activate these channel receptors in the worm, eventually causing an inhibitory postsynaptic potential. The chance of a future action potential occurring in synapses between neurons decreases and the nematodes experience flaccid paralysis followed by death.Ivermectin is directly effective against the larval stage microfilariae of O. volvulus; they are paralyzed and can be killed by eosinophils and macrophages. It does not kill adult females (macrofilariae), but does cause them to cease releasing microfilariae, perhaps by paralyzing the reproductive tract. Ivermectin is very effective in reducing microfilarial load and reducing number of punctate opacities in individuals with onchocerciasis. Moxidectin Moxidectin was approved for onchocerciasis in 2018 for people over the age of 11 in the United States. The safety of multiple doses is unclear. Epidemiology About 21 million people were infected with this parasite in 2017; about 1.2 million of those had vision loss. As of 2017, about 99% of onchocerciasis cases occurred in Africa. Onchocerciasis is currently relatively common in 31 African countries, Yemen, and isolated regions of South America. Over 85 million people live in endemic areas, and half of these reside in Nigeria. Another 120 million people are at risk for contracting the disease. Due to the vectors breeding habitat, the disease is more severe along the major rivers in the northern and central areas of the continent, and severity declines in villages farther from rivers. Onchocerciasis was eliminated in the northern focus in Chiapas, Mexico, and the focus in Oaxaca, Mexico, where Onchocerca volvulus existed, was determined, after several years of treatment with ivermectin, as free of the transmission of the parasite.According to a 2002 WHO report, onchocerciasis has not caused a single death, but its global burden is 987,000 disability adjusted life years (DALYs). The severe pruritus alone accounts for 60% of the DALYs. Infection reduces the hosts immunity and resistance to other diseases, which results in an estimated reduction in life expectancy of 13 years. History Onchocerca originated in Africa and was exported to the Americas by the slave trade, as part of the Columbian exchange that introduced other old world diseases such as yellow fever into the New World. Findings of a phylogenetic study in the mid-90s are consistent with an introduction to the New World in this manner. DNA sequences of savannah and rainforest strains in Africa differ, while American strains are identical to savannah strains in western Africa. The microfilarial parasite that causes the disease was first identified in 1874 by an Irish naval surgeon, John ONeill, who was seeking to identify the cause of a common skin disease along the west coast of Africa, known as "craw-craw". Rudolf Leuckart, a German zoologist, later examined specimens of the same filarial worm sent from Africa by a German missionary doctor in 1890 and named the organism Filaria volvulus.Rodolfo Robles and Rafael Pacheco in Guatemala first mentioned the ocular form of the disease in the Americas about 1915. They described a tropical worm infection with adult Onchocerca that included inflammation of the skin, especially the face (erisipela de la costa), and eyes. The disease, commonly called the "filarial blinding disease", and later referred to as "Robles disease", was common among coffee plantation workers. Manifestations included subcutaneous nodules, anterior eye lesions, and dermatitis. Robles sent specimens to Émile Brumpt, a French parasitologist, who named it O. caecutiens in 1919, indicating the parasite caused blindness (Latin "caecus" meaning blind). The disease was also reported as being common in Mexico. By the early 1920s, it was generally agreed that the filaria in Africa and Central America were morphologically indistinguishable and the same as that described by ONeill 50 years earlier.Robles hypothesized that the vector of the disease was the day-biting black fly, Simulium. Scottish physician Donald Blacklock of the Liverpool School of Tropical Medicine confirmed this mode of transmission in studies in Sierra Leone. Blacklocks experiments included the re-infection of Simulium flies exposed to portions of the skin of infected subjects on which nodules were present, which led to elucidation of the life cycle of the Onchocerca parasite. Blacklock and others could find no evidence of eye disease in Africa. Jean Hissette, a Belgian ophthalmologist, discovered in 1930 that the organism was the cause of a "river blindness" in the Belgian Congo. Some of the patients reported seeing tangled threads or worms in their vision, which were microfilariae moving freely in the aqueous humor of the anterior chamber of the eye. Blacklock and Strong had thought the African worm did not affect the eyes, but Hissette reported that 50% of patients with onchocerciasis near the Sankuru river in the Belgian Congo had eye disease and 20% were blind. Hisette Isolated the microfilariae from an enucleated eye and described the typical chorioretinal scarring, later called the "Hissette-Ridley fundus" after another ophthalmologist, Harold Ridley, who also made extensive observations on onchocerciasis patients in north west Ghana, publishing his findings in 1945. Ridley first postulated that the disease was brought by the slave trade. The international scientific community was initially skeptical of Hisettes findings, but they were confirmed by the Harvard African Expedition of 1934, led by Richard P. Strong, an American physician of tropical medicine. Society and culture Since 1987, ivermectin has been provided free of charge for use in humans by Merck through the Mectizan donation program (MDP). The MDP works together with ministries of health and nongovernmental development organisations, such as the World Health Organization, to provide free ivermectin to those who need it in endemic areas.In 2015 William C. Campbell and Satoshi Ōmura were co-awarded half of that years Nobel Prize in Physiology or Medicine for the discovery of the avermectin family of compounds, the forerunner of ivermectin. The latter has come to decrease the occurrence of lymphatic filariasis and onchocerciasis.Ugandas government, working with the Carter Center river blindness program since 1996, switched strategies for distribution of Mectizan. The male-dominated volunteer distribution system had failed to take advantage of traditional kinship structures and roles. The program switched in 2014 from village health teams to community distributors, primarily selecting women with the goal of assuring that everyone in the circle of their family and friends received river blindness information and Mectizan. Research Animal models for the disease are somewhat limited, as the parasite only lives in primates, but there are close parallels. Litomosoides sigmodontis , which will naturally infect cotton rats, has been found to fully develop in BALB/c mice. Onchocerca ochengi, the closest relative of O. volvulus, lives in intradermal cavities in cattle, and is also spread by black flies. Both systems are useful, but not exact, animal models.A study of 2501 people in Ghana showed the prevalence rate doubled between 2000 and 2005 despite treatment, suggesting the parasite is developing resistance to the drug. A clinical trial of another antiparasitic agent, moxidectin (manufactured by Wyeth), began on July 1, 2009 (NCT00790998).A Cochrane review compared outcomes of people treated with ivermectin alone versus doxycycline plus ivermectin. While there were no differences in most vision-related outcomes between the two treatments, there was low quality evidence suggesting treatment with doxycycline plus ivermectine showed improvement in iridocyclitis and punctate keratitis, over those treated with ivermectine alone. See also Carter Center River Blindness Program List of parasites (human) Neglected tropical diseases Rodolfo Robles United Front Against Riverblindness Harold Ridley (ophthalmologist) References External links CDC Parasites of public health concern

Aarogya, explain a scenario commonly referred as Onychomycosis

Onychomycosis

Onychomycosis, also known as tinea unguium, is a fungal infection of the nail. Symptoms may include white or yellow nail discoloration, thickening of the nail, and separation of the nail from the nail bed. Toenails or fingernails may be affected, but it is more common for toenails. Complications may include cellulitis of the lower leg. A number of different types of fungus can cause onychomycosis, including dermatophytes and Fusarium. Risk factors include athletes foot, other nail diseases, exposure to someone with the condition, peripheral vascular disease, and poor immune function. The diagnosis is generally suspected based on the appearance and confirmed by laboratory testing.Onychomycosis does not necessarily require treatment. The antifungal medication terbinafine taken by mouth appears to be the most effective but is associated with liver problems. Trimming the affected nails when on treatment also appears useful.There is a ciclopirox-containing nail polish, but there is no evidence that it works. The condition returns in up to half of cases following treatment. Not using old shoes after treatment may decrease the risk of recurrence.Onychomycosis occurs in about 10 percent of the adult population, with older people more frequently affected. Males are affected more often than females. Onychomycosis represents about half of nail disease. It was first determined to be the result of a fungal infection in 1853 by Georg Meissner. Etymology The term is from Ancient Greek ὄνυξ onyx "nail", μύκης mykēs "fungus", and the suffix -ωσις ōsis "functional disease". Signs and symptoms The most common symptom of a fungal nail infection is the nail becoming thickened and discoloured: white, black, yellow or green. As the infection progresses the nail can become brittle, with pieces breaking off or coming away from the toe or finger completely. If left untreated, the skin underneath and around the nail can become inflamed and painful. There may also be white or yellow patches on the nailbed or scaly skin next to the nail, and a foul smell. There is usually no pain or other bodily symptoms, unless the disease is severe. People with onychomycosis may experience significant psychosocial problems due to the appearance of the nail, particularly when fingers – which are always visible – rather than toenails are affected.Dermatophytids are fungus-free skin lesions that sometimes form as a result of a fungus infection in another part of the body. This could take the form of a rash or itch in an area of the body that is not infected with the fungus. Dermatophytids can be thought of as an allergic reaction to the fungus. Causes The causative pathogens of onychomycosis are all in the fungus kingdom and include dermatophytes, Candida (yeasts), and nondermatophytic molds. Dermatophytes are the fungi most commonly responsible for onychomycosis in the temperate western countries; while Candida and nondermatophytic molds are more frequently involved in the tropics and subtropics with a hot and humid climate. Dermatophytes When onychomycosis is due to a dermatophyte infection, it is termed tinea unguium. Trichophyton rubrum is the most common dermatophyte involved in onychomycosis. Other dermatophytes that may be involved are T. interdigitale, Epidermophyton floccosum, T. violaceum, Microsporum gypseum, T. tonsurans, and T. soudanense. A common outdated name that may still be reported by medical laboratories is Trichophyton mentagrophytes for T. interdigitale. The name T. mentagrophytes is now restricted to the agent of favus skin infection of the mouse; though this fungus may be transmitted from mice and their danders to humans, it generally infects skin and not nails. Other Other causative pathogens include Candida and nondermatophytic molds, in particular members of the mold genus Scytalidium (name recently changed to Neoscytalidium), Scopulariopsis, and Aspergillus. Candida species mainly cause fingernail onychomycosis in people whose hands are often submerged in water. Scytalidium mainly affects people in the tropics, though it persists if they later move to areas of temperate climate. Other molds more commonly affect people older than 60 years, and their presence in the nail reflects a slight weakening in the nails ability to defend itself against fungal invasion. Nail injury and nail psoriasis can cause damaged toenails to become thick, discolored & brittle. Risk factors Advancing age (usually over the age of 60) is the most common risk factor for onychomycosis due to diminished blood circulation, longer exposure to fungi, nails which grow more slowly and thicken, and reduced immune function increasing susceptibility to infection. Nail fungus tends to affect men more often than women and is associated with a family history of this infection. Other risk factors include perspiring heavily, being in a humid or moist environment, psoriasis, wearing socks and shoes that hinder ventilation and do not absorb perspiration, going barefoot in damp public places such as swimming pools, gyms and shower rooms, having athletes foot (tinea pedis), minor skin or nail injury, damaged nail, or other infection, and having diabetes, circulation problems, which may also lead to lower peripheral temperatures on hands and feet, or a weakened immune system. Diagnosis The diagnosis is generally suspected based on the appearance and confirmed by laboratory testing. The four main tests are a potassium hydroxide smear, culture, histology examination, and polymerase chain reaction. The sample examined is generally nail scrapings or clippings. These being from as far up the nail as possible.Nail plate biopsy with periodic acid-Schiff stain appear more useful than culture or direct KOH examination. To reliably identify nondermatophyte molds, several samples may be necessary. Classification There are five classic types of onychomycosis: Distal subungual onychomycosis is the most common form of tinea unguium and is usually caused by Trichophyton rubrum, which invades the nail bed and the underside of the nail plate. White superficial onychomycosis (WSO) is caused by fungal invasion of the superficial layers of the nail plate to form "white islands" on the plate. It accounts for around 10 percent of onychomycosis cases. In some cases, WSO is a misdiagnosis of "keratins granulations" which are not a fungus, but a reaction to nail polish that can cause the nails to have a chalky white appearance. A laboratory test should be performed to confirm. Proximal subungual onychomycosis is fungal penetration of the newly formed nail plate through the proximal nail fold. It is the least common form of tinea unguium in healthy people, but is found more commonly when the patient is immunocompromised. Endonyx onychomycosis is characterized by leukonychia along with a lack of onycholysis or subungual hyperkeratosis. Candidal onychomycosis is Candida species invasion of the fingernails, usually occurring in persons who frequently immerse their hands in water. This normally requires the prior damage of the nail by infection or trauma. Differential diagnosis In many cases of suspected nail fungus there is actually no fungal infection, but only nail deformity.To avoid misdiagnosis as nail psoriasis, lichen planus, contact dermatitis, nail bed tumors such as melanoma, trauma, or yellow nail syndrome, laboratory confirmation may be necessary.Other conditions that may appear similar to onychomycosis include: psoriasis, normal aging, yellow nail syndrome, and chronic paronychia. Treatment Medications Most treatments are with antifungal medications, either topically or by mouth. Avoiding use of antifungal therapy by mouth (e.g., terbinafine) in persons without a confirmed infection is recommended, because of the possible side effects of that treatment.Medications that may be taken by mouth include terbinafine (76% effective), itraconazole (60% effective), and fluconazole (48% effective). They share characteristics that enhance their effectiveness: prompt penetration of the nail and nail bed, and persistence in the nail for months after discontinuation of therapy. Ketoconazole by mouth is not recommended due to side effects. Oral terbinafine is better tolerated than itraconazole. For superficial white onychomycosis, systemic rather than topical antifungal therapy is advised.Topical agents include ciclopirox nail paint, amorolfine, and efinaconazole. Some topical treatments need to be applied daily for prolonged periods (at least one year). Topical amorolfine is applied weekly.Efinaconazole, a topical azole antifungal, led to cure rates two or three times better than the next-best topical treatment, ciclopirox. In trials, about 17% of people were cured using efinaconazole, as opposed to 4% of people using placebo.Topical ciclopirox results in a cure in 6% to 9% of cases. Ciclopirox when used with terbinafine appears to be better than either agent alone. Although eficonazole, P-3051 (ciclopirox 8% hydrolacquer), and tavaborole are effective at treating fungal infection of toenails, complete cure rates are low. Other Chemical (keratolytic) or surgical debridement of the affected nail appears to improve outcomes.As of 2014 evidence for laser treatment is unclear as the evidence is of low quality and varies by type of laser.Tea tree oil is not recommended as a treatment, since it is not effective and can irritate the surrounding skin. Cost United States According to a 2015 study, the cost in the United States of testing with the periodic acid–Schiff stain (PAS) was about $148. Even if the cheaper KOH test is used first and the PAS test is used only if the KOH test is negative, there is a good chance that the PAS will be done (because of either a true or a false negative with the KOH test). But the terbinafine treatment costs only $10 (plus an additional $43 for liver function tests). In conclusion the authors say that terbinafine has a relatively benign adverse effect profile, with liver damage very rare, so it makes more sense cost-wise for the dermatologist to prescribe the treatment without doing the PAS test. (Another option would be to prescribe the treatment only if the potassium hydroxide test is positive, but it gives a false negative in about 20% of cases of fungal infection.) On the other hand, as of 2015 the price of topical (non-oral) treatment with efinaconazole was $2307 per nail, so testing is recommended before prescribing it.The cost of efinaconazole treatment can be reduced to $65 per 1-month dose using drug coupons, bringing the treatment cost to $715 per nail. Canada In 2019, a study by the Canadian Agency for Drugs and Technologies in Health found the cost for a 48-week efinaconazole course to be $178 for a big toe, and $89 for an other toe. Prognosis Recurrence may occur following treatment, with a 20-25% relapse rate within 2 years of successful treatment. Nail fungus can be painful and cause permanent damage to nails. It may lead to other serious infections if the immune system is suppressed due to medication, diabetes or other conditions. The risk is most serious for people with diabetes and with immune systems weakened by leukemia or AIDS, or medication after organ transplant. Diabetics have vascular and nerve impairment, and are at risk of cellulitis, a potentially serious bacterial infection; any relatively minor injury to feet, including a nail fungal infection, can lead to more serious complications. Infection of the bone is another rare complication. Epidemiology A 2003 survey of diseases of the foot in 16 European countries found onychomycosis to be the most frequent fungal foot infection and estimated its prevalence at 27%. Prevalence was observed to increase with age. In Canada, the prevalence was estimated to be 6.48%. Onychomycosis affects approximately one-third of diabetics and is 56% more frequent in people with psoriasis. Research Research suggests that fungi are sensitive to heat, typically 40–60 °C (104–140 °F). The basis of laser treatment is to try to heat the nail bed to these temperatures in order to disrupt fungal growth. As of 2013 research into laser treatment seemed promising. There is also ongoing development in photodynamic therapy, which uses laser or LED light to activate photosensitisers that eradicate fungi. == References ==

Hey Aarogya!, what is Neonatal conjunctivitis

Neonatal conjunctivitis

Neonatal conjunctivitis is a form of conjunctivitis (inflammation of the outer eye) which affects newborn babies following birth. It is typically due to neonatal bacterial infection, although can also be non-infectious (e.g. chemical exposure). Infectious neonatal conjunctivitis is typically contracted during vaginal delivery from exposure to bacteria from the birth canal, most commonly Neisseria gonorrhoeae or Chlamydia trachomatis.Antibiotic ointment is typically applied to the newborns eyes within 1 hour of birth as prevention for gonococcal ophthalmia. This practice is recommended for all newborns and most hospitals in the United States are required by state law to apply eye drops or ointment soon after birth to prevent the disease.If left untreated, neonatal conjunctivitis can cause blindness. Signs and symptoms Neonatal conjunctivitis by definition presents during the first month of life. Signs and symptoms include: Pain and tenderness in the eyeball Conjunctival discharge: purulent, mucoid or mucopurulent (depending on the cause) Conjunctival hyperaemia and chemosis, usually also with swelling of the eyelids Corneal involvement (rare) may occur in herpes simplex ophthalmia neonatorum Time of onset Chemical causes: Right after delivery Neisseria gonorrhoeae: Delivery of the baby until 5 days after birth (early onset) Chlamydia trachomatis: 5 days after birth to 2 weeks (late onset – C. trachomatis has a longer incubation period) Complications Untreated cases may develop corneal ulceration, which may perforate, resulting in corneal opacification and staphyloma formation. Cause Non-infectious Chemical irritants such as silver nitrate can cause chemical conjunctivitis, usually lasting 2–4 days. Thus, prophylaxis with a 1% silver nitrate solution is no longer in common use. In most countries, neomycin and chloramphenicol eye drops are used, instead. However, newborns can develop neonatal conjunctivitis due to reactions with chemicals in these common eye drops. Additionally, a blocked tear duct may be another noninfectious cause of neonatal conjunctivitis. Infectious The two most common infectious causes of neonatal conjunctivitis are N. gonorrheae and Chlamydia, typically acquired from the birth canal during delivery. However, other different bacteria and viruses can be the cause, including herpes simplex virus (HSV 2), Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae.Ophthalmia neonatorum due to gonococci (N. gonorrhoeae) typically manifests in the first 5 days after birth and is associated with marked bilateral purulent discharge and local inflammation. In contrast, conjunctivitis secondary to infection with C. trachomatis produces conjunctivitis 3 days to 2 weeks after delivery. The discharge is usually more watery in nature (mucopurulent) and less inflamed. Babies infected with chlamydia may develop pneumonitis (chest infection) at a later stage (range 2–19 weeks after delivery). Infants with chlamydia pneumonitis should be treated with oral erythromycin for 10–14 days.Diagnosis is performed after taking swab from the infected conjunctivae. Prevention Antibiotic ointment is typically applied to the newborns eyes within 1 hour of birth as prevention against gonococcal ophthalmia. This may be erythromycin, tetracycline, or rarely silver nitrate or Argyrol (mild silver protein). Treatment Prophylaxis needs antenatal, natal, and postnatal care. Antenatal measures include thorough care of mother and treatment of genital infections when suspected. Natal measures are of utmost importance, as most infection occurs during childbirth. Deliveries should be conducted under hygienic conditions taking all aseptic measures. The newborn babys closed lids should be thoroughly cleansed and dried. If the cause is determined to be due to a blocked tear duct, gentle palpation between the eye and the nasal cavity may be used to clear the tear duct. If the tear duct is not cleared by the time the newborn is 1 year old, surgery may be required. Postnatal measures include: Use of 1% tetracycline ointment, 0.5% erythromycin ointment, or 1% silver nitrate solution (Credés method) into the eyes of babies immediately after birth Single injection of ceftriaxone IM or IV should be given to infants born to mothers with untreated gonococcal infection. Curative treatment as a rule, conjunctival cytology samples and culture sensitivity swabs should be taken before starting treatment. Chemical ophthalmia neonatorum is a self-limiting condition and does not require any treatment. Gonococcal ophthalmia neonatorum needs prompt treatment to prevent complications. Topical therapy should include: Saline lavage hourly until the discharge is eliminated Bacitracin eye ointment four times per day (because of resistant strains, topical penicillin therapy is not reliable, but in cases with proven penicillin susceptibility, penicillin drops 5000 to 10000 units per ml should be instilled every minute for half an hour, every five minutes for next half an hour, and then half-hourly until the infection is controlled.) If the cornea is involved, then atropine sulfate ointment should be applied. The advice of both the pediatrician and ophthalmologist should be sought for proper management.Systemic therapy: Newborns with gonococcal ophthalmia neonatorum should be treated for 7 days with ceftriaxone, cefotaxime, ciprofloxacin, or crystalline benzyl penicillin. Other bacterial ophthalmia neonatorum should be treated by broad-spectrum antibiotics drops and ointment for 2 weeks. Neonatal inclusion conjunctivitis caused by C. trachomatis should be treated with oral erythromycin. Topical therapy is not effective and also does not treat the infection of the nasopharynx. Herpes simplex conjunctivitis should be treated with intravenous acyclovir for a minimum of 14 days to prevent systemic infection. Epidemiology The incidence of neonatal conjunctivitis varies widely depending on the geographical location. The incidence in England was 257 (95% confidence interval: 245 to 269) per 100,000 in 2011. See also List of systemic diseases with ocular manifestations References == External links ==

Hey Aarogya, could you help me understand about Osteogenesis imperfecta

Osteogenesis imperfecta

Osteogenesis imperfecta (IPA: ; OI), colloquially known as brittle bone disease, is a group of genetic disorders that all result in bones that break easily.: 85  The range of symptoms—on the skeleton as well as on the bodys other organs—may be mild to severe.: 1512  Symptoms found in various types of OI include whites of the eye (sclerae) that are blue instead, short stature, loose joints, hearing loss, breathing problems and problems with the teeth (dentinogenesis imperfecta). Potentially life-threatening complications, all of which become more common in more severe OI, include: tearing (dissection) of the major arteries, such as the aorta;: 333  pulmonary valve insufficiency secondary to distortion of the ribcage;: 335–341  and basilar invagination.: 106–107 The underlying mechanism is usually a problem with connective tissue due to a lack of, or poorly formed, type I collagen.: 1513  In more than 90% of cases, OI occurs due to mutations in the COL1A1 or COL1A2 genes. These mutations may be inherited from a persons parents in an autosomal dominant manner but may also occur spontaneously (de novo). There are four clinically defined types: type I, the least severe; type IV, moderately severe; type III, severe and progressively deforming; and type II, perinatally lethal. As of September 2021, 19 different genes are known to cause the 21 documented genetically defined types of OI, many of which are extremely rare and have only been documented in a few individuals. Diagnosis is often based on symptoms and may be confirmed by collagen biopsy or DNA sequencing.Although there is no cure, most cases of OI do not have a major effect on life expectancy,: 461  death during childhood from it is rare, and many adults with OI can achieve a significant degree of autonomy despite disability. Maintaining a healthy lifestyle by exercising, eating a balanced diet sufficient in vitamin D and calcium, and avoiding smoking can help prevent fractures. Genetic counseling may be sought by those with OI to prevent their children from inheriting the disorder from them.: 101  Treatment may include acute care of broken bones, pain medication, physical therapy, mobility aids such as leg braces and wheelchairs, vitamin D supplementation, and, especially in childhood, rodding surgery. Rodding is an implantation of metal intramedullary rods along the long bones (such as the femur) in an attempt to strengthen them. Medical research also supports the use of medications of the bisphosphonate class, such as pamidronate, to increase bone density. Bisphosphonates are especially effective in children, however it is unclear if they either increase quality of life or decrease the rate of fracture incidence.OI affects only about one in 15,000 to 20,000 people, making it a rare genetic disease. Outcomes depend on the genetic cause of the disorder (its type). Type I (the least severe) is the most common, with other types comprising a minority of cases. Moderate-to-severe OI primarily affects mobility; if rodding surgery is performed during childhood, some of those with more severe types of OI may gain the ability to walk. The condition has been described since ancient history. The Latinate term osteogenesis imperfecta was coined by Dutch anatomist Willem Vrolik in 1849; translated literally, it means "imperfect bone formation".: 683 Signs and symptoms Orthopedic The main symptom of osteogenesis imperfecta is fragile, low mineral density bones; all types of OI have some bone involvement. In moderate and especially severe OI, the long bones may be bowed, sometimes extremely so. The weakness of the bones causes them to fracture easily; a study in Pakistan found an average of 5.8 fractures per year in untreated children. Fractures typically occur much less after puberty, but begin to increase again in women after menopause and in men between the ages of 60 and 80.: 486 Joint hypermobility is also a common sign of OI, thought to be because the affected genes are the same as those that cause some types of Ehlers–Danlos syndrome.: 1513 Otologic By the age of 50, about 50% of adults with OI experience significant hearing loss, much earlier as compared to the general population. Hearing loss in OI may or may not be associated with visible deformities of the ossicles and inner ear. Hearing loss frequently begins during the second, third, and fourth decades of life, and may be conductive, sensorineural, or a combination of both ("mixed"). If hearing loss does not occur by age 50, it is significantly less likely to occur in the years afterwards. Mixed hearing loss is most common among those with OI of all age groups, while conductive hearing loss is most likely to affect older people, with sensorineural hearing loss most likely to affect children.Although relatively rare, OI-related hearing loss can also begin in childhood; in a study of forty-five children aged four to sixteen, two were found to be affected, aged 11 and 15. In a different 2008 study, the hearing of 41 people with OI was checked. The results showed that 88% of those over 20 years of age had some form of hearing loss, while only 38% of those under 20 did.Hearing loss is most common in type I OI; it is less common in types III and IV.: 294–296  Other parts of the inner ear may also be affected by OI. causing balance issues; however, only small studies have found links between vertigo and OI.: 308  OI may worsen the outcome of medical treatments which correct hearing loss.Besides OIs association with sensorineural hearing loss, OI is associated with a number of neurological abnormalities, usually involving the central nervous system, due to deformities in the skeletal structures surrounding it. Neurological complications, especially basilar invagination, may adversely affect life expectancy. In OI, this is most often due to upwards migration of the dens,: 106–107  a feature of the C2 vertebra. Neurosurgery may be needed to correct severe abnormalities when they risk the patients life or cause either great suffering or intolerable neurological deficits.: 106–107 Systemic As its biological causes have been more precisely determined, it has become more widely recognized that while the primary disease process of OI happens in the bones, the most common types of OI—those caused by type I collagen gene mutations—affect virtually all of the human bodys organs in some way.Type I collagen is present throughout the circulatory and respiratory systems: from the ventricles of the heart itself, to the heart valves, to the vasculature,: 329  it is an integral part of the connective tissue of the lungs.: 336  As such, cardiovascular complications, among them aortic insufficiency, aortic aneurysm, and arterial dissections, are sometimes comorbid with OI,: 333  but not as frequently as they are comorbid with Marfan syndrome.: 332 Respiratory illnesses are a major cause of death in OI.: 335  The most obvious source of respiratory problems in OI is pulmonary insufficiency caused by problems in the architecture of the thoracic wall.: 341  However, respiratory tract infections, such as pneumonia, are also more fatal among those with OI than the general population. Those with more severe ribcage deformities were found to have worse lung restriction in a small-scale 2012 study involving 22 Italian patients with OI types III and IV, plus 26 non-affected controls.OI—especially its severe form type III—also has effects on the gastrointestinal system. It was found to be associated with recurrent abdominal pain and chronic constipation in two studies on patients affected by OI. Chronic constipation is especially common,: 377  and is thought to be aggravated by an asymmetric pelvis (acetabular protrusion).: 377  Especially in childhood, OI-associated constipation may cause a feeling of fullness and associated food refusal, leading to malnutrition.: 377 Classification There are two typing systems for OI in modern use. The first, created by David Sillence in 1979, classifies patients into four types, or syndromes, according to their clinical presentation, without taking into account the genetic cause of their disease.: 114–115  The second system expands on the Sillence model, but assigns new numbered types genetically as they are found. Therefore, people with OI can be described as having both a clinical type and a genetic type, which may or may not be equivalent.Type I is the most common, and 90% of cases result from mutations to either COL1A1 or COL1A2. Symptoms vary a lot between types, as well as vary from person to person, even in the same family.As of 2021, 21 types of OI have been defined: Sillence types Sillences four types have both a clinical and a genetic meaning; the descriptions below are clinical and can be applied to several genetic types of OI. When used to refer to a genetic as well as a clinical type, it indicates that the clinical symptoms are indeed caused by mutations in the COL1A1 or COL1A2 genes which are inherited in an autosomal dominant fashion. Type I Collagen is of normal quality but is produced in insufficient quantities.: 1516  Bones fracture more easily than in the general public, but not as easily as more severe types of OI; there might be scoliosis, albeit mild compared to OI types III and IV, with a lower Cobb angle; the joints may be loose; blue sclerae may be apparent; hearing loss is likely to occur;: Table 1  and there might be a slight decrease in height. Because cases exist missing one or more of these symptoms, OI type I in some cases goes undetected into adulthood.: 1513–1514 Some further split type I into types I–A and I–B, defined as being distinguished by the absence (I–A) or presence (I–B) of dentinogenesis imperfecta (opalescent teeth).: 217  People with type I generally have a normal lifespan. Type II Collagen is fatally defective at its C-terminus.: 1512  Most cases result in death shortly after birth, or within the first year of life, due to respiratory failure. Another common cause of death is intracranial bleeds from skull fractures present at, or sustained during or shortly after, birth.: 1511  In many cases, the newborn already has multiple broken bones at the time of birth. Type II infants also exhibit severe respiratory problems, and have severely deformed bones. Sixty percent of infants die less than 24 hours after being born, and survival after the first year is extremely unlikely and normally requires mechanical ventilation. In the rare cases of infants who survive their first year of life, severe developmental and motor delays are seen; neither of two infants studied in 2019, both aged around two years, had achieved head control, and both required a ventilator to breathe.Type II is also known as the "lethal perinatal" form of OI, and is not compatible with survival into adulthood. Due to similarly severely deformed bones, sometimes infants with severe type III are wrongly initially classified as type II; once long-term survival is shown, they are considered as having type III instead.: 1511 Type III Collagen quantity is sufficient, but is not of a high enough quality.: 1512  Clinical differentiation between types III and IV is not always simple, and is further confounded by the fact that an untreated adult with type IV may have worse symptoms than a treated adult with type III;: 1511  features only found in type III are its progressively deforming nature: 1511–1512  and the presence of a face with a "triangular" appearance. Another differentiating factor between type III and IV is blue sclerae; in type III, infants commonly have blue sclerae that gradually turn white with age, but blue sclerae are not commonly seen in type IV,: 294–296  although they are seen in 10% of cases.OI type III causes osteopenic bones that fracture very easily, sometimes even in utero, often leading to hundreds of fractures during a lifetime; early scoliosis that progresses until puberty; dwarfism (a final adult height frequently less than 4 feet or 120 centimetres); loose joints; and possible respiratory problems due to low rib cage volume causing low lung volumes.: 1512 Due to the severity of the issues with the bones, neurological and seizure disorders are more likely to develop in type III.: 1512  Basilar invagination, which puts pressure on the brainstem, may cause or contribute to early death; surgical treatment of it is more complex in OI cases.: 1512 : 106–107 Type IV Collagen quantity is sufficient, but is not of a high enough quality.: 1512  Type IV is for cases of variable severity, which do not fit into either types III or I. While one of Sillences required characteristics for type IV was having normal sclerae,: 294–296 : 114  modern classification allows even those with blue sclerae to fit the criteria for type IV if they meet the other clinical requirements of the type.In type IV, bone deformity can be mild to severe, bones fracture easily (especially before puberty), dwarfism is common, vertebral collapse and scoliosis are evident, and hearing loss is possible, although uncommon. Type IV OI is mostly defined in contrast to type III and type I, being the clinical classification for patients somewhere in the middle ground between the two.: 1511  As such, type IV OI is often termed "variable" OI,: 111  with the severity of even those in the same family (so, with the same genetic mutation) differing.Prepubertal bone fracture rates are another way of clinically assessing type IV OI—those with it tend to have fracture rates of ≈1 per year, compared to ≈3 per year for severe OI (type III).As in type I, some further split type IV into types IV–A and IV–B, defined again by the absence (IV–A) or presence (IV–B) of dentinogenesis imperfecta.: 217 Genetically defined types (types V–XXI) As of 2020, fifteen types of OI are defined genetically: Type V – Having the same clinical features as type IV, it can be clinically distinguished by observing a "mesh-like" appearance to a bone biopsy under a microscope. Type V can be further distinguished from other types of OI by the "V triad": an opaque band (visible on X-ray) adjacent to the growth plates; hypertrophic calluses (abnormally large masses of bony repair tissue) which form at fracture sites during the healing process; and calcification of the interosseous membrane of the forearm, which may make it difficult to turn the wrist.: 429  Other features of this condition may include pulled elbow, and, as in other types of OI, long bone bowing and hearing loss. Cases of this type are caused by mutations in the IFITM5 gene on chromosome 11p15.5. The separation of type V from type IV OI, its clinical type, was initially suggested even before its genetic cause was known, by Glorieux et al. in 2000. Type V is relatively common compared to other genetically defined types of OI—4% of OI patients at the genetics department of the Brazilian Hospital de Clínicas de Porto Alegre were found to have it. Type VI – With the same clinical features as type III, it is distinguished by bones which have an appearance similar to that seen in osteomalacia.: 168  Type VI is caused by a loss-of-function mutation in the SERPINF1 gene on chromosome 17p13.3.: 170  Type VII – OI caused by a mutation in the gene CRTAP on chromosome 3p22.3; clinically similar to OI types II and III, depending on affected individual. Type VII was the first recessive OI type confirmed, initially found among First Nations people in Quebec. Type VIII – OI caused by a mutation in the gene LEPRE1 on chromosome 1p34.2; clinically similar to OI types II and III, depending on affected individual. Type IX – OI caused by homozygous or compound heterozygous mutation in the PPIB gene on chromosome 15q22.31. Type X – OI caused by homozygous mutation in the SERPINH1 gene on chromosome 11q13. Type XI – OI caused by mutations in FKBP10 on chromosome 17q21. The mutations cause a decrease in secretion of trimeric procollagen molecules. Other mutations in this gene can cause autosomal recessive Bruck syndrome, which is similar to OI. Type XII – OI caused by a frameshift mutation in SP7 on chromosome 12q13.13. This mutation causes bone deformities, fractures, and delayed tooth eruption. Type XIII – OI caused by a mutation in the bone morphogenetic protein 1 (BMP1) gene on chromosome 8p21.3. This mutation causes recurrent fractures, high bone mass, and hypermobile joints. Type XIV – OI caused by mutations in the TMEM38B gene on chromosome 9q31.2. This mutation causes recurrent fractures and osteopenia, although the disease trajectory is highly variable. Type XV – OI caused by homozygous or compound heterozygous mutations in the WNT1 gene on chromosome 12q13.12. It is autosomal recessive. Type XVI – OI caused by mutations in the CREB3L1 gene on chromosome 11p11.2. The homozygous mutation causes prenatal onset of recurrent fractures of the ribs and long bones, demineralization, decreased ossification of the skull, and blue sclerae; it is clinically type II or type III. Family members who are heterozygous for OI XVI may have recurrent fractures, osteopenia and blue sclerae. Type XVII – OI caused by homozygous mutation in the SPARC gene on chromosome 5q33, causing a defect in the protein osteonectin, which leads to severe disease characterized by generalized platyspondyly, dependence on a wheelchair, and recurrent fractures. Type XVIII – OI caused by homozygous mutation in the FAM46A gene on chromosome 6q14.1. Characterized by congenital bowing of the long bones, Wormian bones, blue sclerae, vertebral collapse, and multiple fractures in the first years of life. Type XIX – OI caused by hemizygous mutation in the MBTPS2 gene on chromosome Xp22.12. Thus far, OI type XIX is the only known type of OI with an X-linked recessive pattern of inheritance, making it the only type that is more common in males than females. OI type XIX disrupts regulated intramembrane proteolysis, which is critical for healthy bone formation. Type XX – OI caused by homozygous mutation in the MESD gene on chromosome 15q25.1. Initial studies of type XX indicate that it may cause global developmental delay, a first among OI types. OI type XX disrupts the Wnt signaling pathway, which is thought to have a role in bone development. Type XXI – OI caused by homozygous mutation in the KDELR2 gene on chromosome 7p22.1. Causes disease clinically similar to types II and III, thought to be related to inability of chaperone protein HP47 to unbind from collagen type I, as to do so it needs to bind to the missing ER lumen protein retaining receptor 2 protein encoded by KDELR2.Given the rapid rate of type discovery, it is extremely likely that there are other genes associated with OI that have yet to be reported.: 491–492 Genetics Osteogenesis imperfecta is a group of genetic disorders, all of which cause bone fragility. OI has high genetic heterogeneity, that is, many different genetic mutations lead to the same or similar sets of observable symptoms (phenotypes).The main causes for developing the disorder are a result of mutations in the COL1A1 and/or COL1A2 genes which are jointly responsible for the production of collagen type I. Approximately 90% of people with OI are heterozygous for mutations in either the COL1A1 or COL1A2 genes. There are several biological factors that are results of the dominant form of OI. These factors include: intracellular stress; abnormal tissue mineralization; abnormal cell to cell interactions; abnormal cell-matrix interactions; a compromised cell matrix structure; and, abnormal interaction between non-collagenous proteins and collagen.Previous research lead to the belief that OI was an autosomal dominant disorder with few other variations in genomes. However, with the lowering of the cost of DNA sequencing in the wake of 2003s Human Genome Project, autosomal recessive forms of the disorder have been identified. Recessive forms of OI relate heavily to defects in the collagen chaperones responsible for production of procollagen and the assembly of the related proteins. Examples of collagen chaperones that are defective in patients with recessive forms of OI include chaperone HSP47 (Cole-Carpenter syndrome) and FKBP65. Mutations in these chaperones result in an improper folding pattern in the collagen 1 proteins which causes the recessive form of the disorder. There are three significant types of OI that are a result of mutations in the collagen prolyl 3-hydroxylation complex (components CRTAP, P3H1, and CyPB). These components are responsible for the modification of collagen α1(l)Pro986. Mutations in other genes such as SP7, SERPINF1, TMEM38B and BMP1 can also lead to irregularly formed proteins and enzymes that result in other recessive types of osteogenesis imperfecta.Defects in the proteins pigment epithelium-derived factor (PEDF) and bone-restricted interferon-induced transmembrane protein (BRIL) are the causes of type V and VI osteogenesis imperfecta. Defects in these proteins lead to defective bone mineralization which causes the characteristic brittle bones of osteogenesis imperfecta. A single point mutation in the 5′ untranslated region (5′ UTR) of the IFITM5 gene, which encodes BRIL, is linked directly to OI type V.In the rare case of type XIX, first discovered in 2016, OI is inherited as an X-linked genetic disorder, with its detrimental effects resulting ultimately from a mutation in the gene MBTPS2. Genetic research is ongoing, and it is uncertain when all the genetic causes of OI will be identified, as the number of genes that need to be tested to rule out the disorder continue to increase.: 491–492 In a study of 37 families, a 1.3% chance was found that OI recurs in multiple siblings born to two unaffected parents—this is a much higher rate than would be expected if all such recurrences were de novo. The cause is genetic mosaicism; that is, some of, or most of, the germ cells of one parent have a dominant form of OI, but not enough of their somatic cells do to cause symptoms or obvious disability in the parent—the parents different cells have two (or more) sets of slightly different DNA.: 1513  It has been clinically observed that ≈5–10% of cases of OI types II and III are attributable to genetic mosaicism.: 532 Pathophysiology People with OI are either born with defective connective tissue, born without the ability to make it in sufficient quantities, or, in the rarest genetic types, born with deficiencies in other aspects of bone formation such as chaperone proteins, the Wnt signaling pathway, the BRIL protein, et cetera. In type I the collagens structure itself is normal, it is just its quantity that is low.: 1516  Types II, III and IV are usually, but not always, related to a deficiency of type I collagen. One possible deficiency arises from an amino acid substitution of glycine to a bulkier amino acid, such as alanine, in the collagen proteins triple helix structure. The larger amino acid side-chains lead to steric effects that creates a bulge in the collagen complex, which in turn influences both the molecular nanomechanics and the interaction between molecules, which are both compromised. Depending on both the location of the substitution and the amino acid being used instead, different effects are seen which account for the type diversity in OI despite the same two collagen genes being responsible for most cases. Replacements of glycine with serine or cysteine are seen less often in fatal type II OI, while replacements with valine, aspartic acid, glutamic acid, or arginine are seen more often.At a larger scale, the relationship between the collagen fibrils and hydroxyapatite crystals to form bone is altered, causing brittleness. Bone fractures occur because the stress state within collagen fibrils is altered at the locations of mutations, where locally larger shear forces lead to rapid failure of fibrils even at moderate loads because the homogeneous stress state normally found in healthy collagen fibrils is lost. OI is therefore a multi-scale phenomenon, where defects at the smallest levels of tissues (genetic, nano, micro) domino to affect the macro level of tissues. Diagnosis Diagnosis is typically based on medical imaging, including plain X-rays, and symptoms. In severe OI, signs on medical imaging include abnormalities in all extremities and in the spine. As X-rays are often insensitive to the comparatively smaller bone density loss associated with type I OI, DEXA scans may be needed.: 1514 An OI diagnosis can be confirmed through DNA or collagen protein analysis, but in many cases, the occurrence of bone fractures with little trauma and the presence of other clinical features such as blue sclerae are sufficient for a diagnosis. A skin biopsy can be performed to determine the structure and quantity of type I collagen. While DNA testing can confirm the diagnosis, it cannot absolutely exclude it because not all mutations causing OI are yet known and/or tested for.: 491–492  OI type II is often diagnosed by ultrasound during pregnancy, where already multiple fractures and other characteristic features may be visible. Relative to control, OI cortical bone shows increased porosity, canal diameter, and connectivity in micro-computed tomography. OI can also be detected before birth by using an in vitro genetic testing technique such as amniocentresis. Genetic testing In order to determine whether osteogenesis imperfecta is present, genetic sequencing of the most common problematic genes, COL1A1, COL1A2, and IFITM5, may be done; if no mutation is found yet OI is still suspected, the other 10+ genes known to cause OI may be tested. Duplication and deletion testing is also suggested to parents who suspect their child has OI. The presence of frameshift mutations caused by duplications and deletions is generally the cause of increased severity of disease. Differential diagnosis An important differential diagnosis of OI is child abuse, as both may present to a clinician with multiple fractures in various stages of healing.: 1514  Differentiating them can be difficult, especially when no other characteristic features of OI are present.: 391  This can become an issue in court; in the United States, several child abuse cases were resolved with a finding that osteogenesis imperfecta was the true cause of a childs fractures, leading to lawsuits seeking redress such as Alice Velasquez, et al. v. United States.: 391 Other differential diagnoses include rickets and osteomalacia, both caused by malnutrition, as well as rare skeletal syndromes such as Bruck syndrome, hypophosphatasia, geroderma osteodysplasticum, and Ehlers–Danlos syndrome.: 1513 : 253–256  Various forms of osteoporosis, such as iatrogenic osteoporosis, idiopathic juvenile osteoporosis, disuse osteoporosis and exercise-related osteoporosis should also be considered as explanations when OI is suspected.: 255–256 Treatment There is no cure for osteogenesis imperfecta. Maintaining a healthy lifestyle by exercising and avoiding smoking can help prevent fractures. Treatment may include care of broken bones, pain medication, physical therapy, mobility aids such as braces or wheelchairs, and surgery.Judging the success or failure of treatment can be difficult in OI patients, as decreased bone fracture rates may just be coincidental. While these rates are often used in medical studies to judge treatment efficacy, a Norwegian study of fifteen people with OI emphasized that they feel doctors should consider the whole patient and not just fracture rates. Acute bone fracture care Bone fractures are treated in individuals with osteogenesis imperfecta in much the same way as they are treated in the general population—OI bone heals at the same rate as non-OI bone.: 431  A greater emphasis is placed on using lightweight materials to immobilize the fracture, as in moderate or severe types of OI, using heavy casts, such as hip spica casts, can cause fractures at the bones at the boundaries of the cast, as well as generalized osteopenia.: 431  The lightweight cast or splint is then replaced with a removable orthosis after a few weeks and once evidence of union is seen on X-ray.: 431  In order to prevent a nonunion or malunion, all fractures should be immobilized, even if the fracture seems trivial (microfracture),: 439  as people with OI are at greater risk of nonunion.: 438 Bone infections secondary to fractures are treated as and when they occur with the appropriate antibiotics and antiseptics, as in the general population.: 424 Medications Bisphosphonates In 1998, an initial observational trial demonstrated the effectiveness of intravenous pamidronate, a bisphosphonate which had previously been used in adults to treat osteoporosis. In severe OI, this trial showed that pamidronate reduced bone pain, prevented new vertebral fractures, reshaped previously fractured vertebral bodies, and reduced the number of long-bone fractures.Although oral bisphosphonates are more convenient and cheaper, they are not absorbed as well, and intravenous bisphosphonates are generally more effective, although this is under study. Some studies have found oral and intravenous bisphosphonates, such as oral alendronate and intravenous pamidronate, equivalent. In a 2013 double-blind trial of children with mild OI, oral risedronate increased bone mineral densities, and reduced nonvertebral fractures. However, it did not decrease new vertebral fractures. A Cochrane review in 2016 concluded that though bisphosphonates seem to improve bone mineral density, it is uncertain whether this leads either to a reduction in bone fractures or improvement in the quality of life of individuals with osteogenesis imperfecta. Even in trials with as many as 125 children, no causal link has been found between bisphosphonates and decreased fracture rates; placebo controlled trials were also unable to prove that they brought about increased strength, motor control or lower pain levels.Bisphosphonates are not as effective at increasing the bone mineral density of adults. Nutritional supplements OI is a genetic disorder and is not caused by insufficient intake of any vitamin or mineral; supplementation cannot cure OI. With that said, people with OI tend to be severely deficient in vitamin D at much higher rates than the general population, and the cause of this is not well understood. The severity of the deficiency and the likelihood of its occurrence is thought to be related to severity of OI. Vitamin D supplementation may be recommended, at least until levels of 25(OH)D3 in blood return to normal. Below normal levels of vitamin D are also concerning as they may decrease the benefit of bisphosphanates. Surgery A surgery of any type inherently carries more risks when done on a patient who has (especially moderate to severe) OI. Skeletal deformities and dentinogenesis imperfecta may hinder access to the airway.: 333  Use of, and weaning off of, mechanical ventilation is also more challenging to carry out on patients with OI.: 333  During the procedure itself or the healing process, defective OI collagen may lead to bleeding diatheses.: 333 The safety of anesthesia is also of more concern among patients with OI,: 333  with anesthetic complications 5.6x more likely to occur when the patient has OI type III. A unique concern of anesthesia in OI is perioperative fracture—fractures sustained due to patient transfer and airway access techniques that, while routine when a patients bones are strong, may cause injury with brittle OI bones. As an example, due to a 1972 report of a humerus fracture from a sphygmomanometer cuff sustained in an OI patient during surgery, blood pressure monitoring protocols are often modified for patients with OI, with neonatal size cuffs and machine settings being used even in adults;: ¶11.72  further, the least deformed of the patients limbs is preferred to receive the cuff.: ¶14.23 Rodding Metal rods can be surgically inserted in the long bones to improve strength, a procedure developed by Harold A. Sofield when he was Chief of Staff at Chicagos Shriners Hospitals for Children, a hospital that offers orthopedic care and surgery to children regardless of their familys ability to pay. Large numbers of children with OI came to Shriners, and Sofield experimented with various methods to strengthen their bones. In 1959, with Edward A. Millar [sic], Sofield wrote a seminal article describing a three-part surgery that seemed radical at the time: precisely breaking the bones ("fragmentation"), putting the resulting bone fragments in a straight line ("realignment"), then placing metal rods into the intramedullary canals of the long bones to stabilize and strengthen them ("rod fixation"). His treatment proved useful for increasing the mobility of people with OI, and it has been adopted throughout the world—it became standard surgical treatment for severe OI by 1979, in which year David Sillence found that ≈2⁄3 of the patients he surveyed with OI type III had undergone at least one rodding surgery.: 108 Rodding surgery is often done with the hope that it will offer a path to ambulation, walking, to patients with moderate or severe OI. A 2020 review in The Journal of Bone and Joint Surgery (JB&JS) found it remains broadly popular: ≈2⁄3 of people with OI types III and IV (severe OI) have undergone some form of rodding surgery in their lives, at a mean age of 4+1⁄10 and 7+1⁄2 years respectively;: Table I  one possible explanation for a tendency towards earlier intervention in type III is that one half of affected children could not walk at all without the surgery, as their limbs were more bowed, so surgery was sought sooner.In those with type III OI who had undergone rodding surgery, 79.5% had the femurs and tibias of both legs rodded.: Table I  The most common form of rods used are intramedullary (IM) rods, some of which, such as the Fassier–Duval IM rod, are telescoping, meaning that they are designed to grow as the child grows, in an attempt to avoid the necessity of revision surgeries. Telescoping IM rods are widely used, and the common Fassier–Duval IM rod is designed to be used to rod the femur, tibia, and humerus.: 1  The surgery involves breaking the long bones in between one and three (or more): Figure 4  places, then fixing the rod alongside the bone to keep it straight.: 11 While telescoping IM rods are intended to grow along with both the femur and tibia in developing children; surgeons have a preference to use non-telescoping IM rods, such as Rush rods, in the tibia, which grows less comparatively—the JB&JS review found that while 69.7% of femurs were treated with telescoping IM rods, only 36.9% of tibiae were.: Table IV While the review in the JB&JS was able to correlate receiving rodding surgery with greater mobility across all types of OI, in patients with type IV, the surgery did not decrease the incidence of broken bones as compared to non-rodded patients—while type IV patients with rodded tibiae experienced 0.93 tibia fractures per year, patients with natural tibiae experienced only 0.81. However, in patients with type III, rodding surgery decreased the average number of tibia fractures per year from 0.84 to 0.57.: Table V Spinal Spinal fusion can be performed either as a preventative measure or to correct existing scoliosis, although the inherent fragility of OI bone makes this operation more complex in OI patients than it does with patients who have adolescent idiopathic scoliosis, but normal bone density. Despite the risks, however, three Nemours–duPont orthopedic surgeons who specialize in surgical intervention for osteogenesis imperfecta recommend operating if the curve is greater than 50° after a child is past peak height velocity, as the spines curve can continue to worsen even into adulthood.: 104 Due to the risk involved, the same surgeons recommend that surgery for basilar impressions and basilar invaginations should only be carried out if the pressure being exerted on the spinal cord and brain stem is causing actual neurological symptoms.: 106–107  Once basilar invagination has become symptomatic, only surgery can halt or reverse the progression of neurological deficits.: 345 Physical therapy Physical therapy is generally recommended, however individualized protocols are required due to the variability of OI.: 378  Physical therapy is used to strengthen muscles, improve motility, improve flexibility, and help with weight maintenance, although it must be done in a gentle manner to minimize the risk of bone fracture.: 378  In people with OI, exercise often involves water aerobics, light resistance exercises, and walking, if the patient is able.: 378  However, even in patients with mild OI, contact sports, as well as activities likely to put unnecessary stress on the joints, such as jumping, are contraindicated due to the risks they pose.: 378 Individuals with more limited mobility are encouraged to change positions regularly throughout the day; people who sit in a wheelchair most or all of the day are recommended to get out of it every two hours, as a form of exercise, to decrease stiffness, and to prevent pressure ulcers.: 378 Individuals with moderate to severe OI, who require assistive mobility devices and adapted vehicles, face significant barriers to access wheelchair-accessible pools or gyms—they either may not have any in their area, nor the means to get there.: 378  Obesity may be more likely to present among those with severe OI, (especially after the age of 20,) and can, in some, cause further declines in mobility.: 371, 373 Tilt table whole body vibration may also be done to increase the mobility of long-term immobilized (bedridden) patients with OI; in at least two cases it helped bedridden children to be able to sit upright. Teeth More than 1 in 2 people with OI also have dentinogenesis imperfecta (DI)—a congenital abnormality in the formation of dentin, one of the four major components of the human tooth. Dental treatment may pose as a challenge as a result of the various deformities, skeletal and dental, due to OI. Children with OI should go for a dental check-up as soon as their teeth erupt; this may minimize tooth structure loss as a result of abnormal dentine, and they should be monitored regularly to preserve their teeth and oral health.Many people with OI are treated with bisphosphonates, and there are several possible related complications with dental procedures, for example, medication-related osteonecrosis of the jaw (MRONJ). However, no report of bisphosphonate-related MRONJ in either a child or adult with OI was found in a 2016 Cochrane review of the safety and efficacy of bisphosphonates for OI. In development Monoclonal antibodies Monoclonal antibodies have long been considered for OI, but as of 2021, such therapy has not been approved for OI, neither in the European Union nor in the United States. Thus, it is unclear whether they are safe or effective. Among the monoclonal antibodies that have been studied are romosozumab (targets sclerostin, by Amgen), fresolimumab (TGF-β, Sanofi), blosozumab (sclerostin, Lilly), and setrusumab (sclerostin, begun by Novartis).Setrusumab, formerly known as BPS-804, is a monoclonal antibody that targets sclerostin, and has been studied in OI specifically more than any of the others. In the body, sclerostin binds to the LRP5 and LRP6 receptors, resulting in inhibition of the Wnt signaling pathway. This decreases bone formation, and is not a problem when a person has healthy bones. It is thought, though, that decreasing the concentration of sclerostin in the body may lead to the formation of more bone, and that is the premise as to why monoclonal antibodies that reduce the concentrations of naturally occurring sclerostin may help strengthen OI bone. While setrusumab was first developed at the pharmaceutical company Novartis, Novartis sold its rights to patent the drug to Mereo Biopharma in 2015, who has continued its development in conjunction with Ultragenyx. In 2019, Mereo announced that it had concluded collecting data for its phase II-B trial of setrusumab; the study was completed on 12 November 2020. Despite the trial data failing to show improvements in bone density on QCT scans, its primary goal, there were improvements on DXA scans. In a September 2020 press release, Mereo said it was seeking to do a phase III trial in 2021, and had received a Rare Pediatric Disease (RPD) designation from the US Food and Drug Administration (FDA).Romosozumab, which also is a monoclonal antibody targeting sclerostin, is an approved drug in the US and EU for the treatment of osteoporosis. The pharmaceutical industry analyst Evercore has remarked that "it could wipe out setrusumabs economics", as romosozumab is priced more cheaply than a drug for a rare disease would be, claiming that it will be "vital" to Ultragenyxs profit margins to prove its setrusumab is more efficacious than romosozumab for OI. A clinical trial evaluating romosozumabs efficacy in OI began in September 2020 and as of September 2021 is ongoing. Ultragenyx predicts that its phase 2/3 trials for setrusumab will be completed in 2026. Prevention As a genetic disorder, the mainstay of twenty-first century prevention of osteogenesis imperfecta is based on preventing affected individuals from being born in the first place. Genetic counseling can help patients and their families determine what types of screening, if any, are right for their situation. Patients can consider preimplantation genetic diagnosis after in vitro fertilization to select fertilized embryos which are not affected.: 247–248  Common mutations which cause OI may be caught by exome sequencing and whole genome sequencing. If a pregnancy is already in progress, the procedure of amniocentesis may be undergone to see if the fetus is affected.: 247  If affected, it is up to the family to consider whether or not they want to terminate the pregnancy and try again—raising questions of medical ethics and a womans right to choose.Without intervention, patients with the most common mutations causing osteogenesis imperfecta have a 50% chance per gestation of passing on the disorder, as these mutations are inherited in an autosomal dominant pattern of Mendelian inheritance.: 247  Those with the rare autosomal recessive forms of OI have a 25% chance of passing on the disorder. Genetic testing of the affected members of the family can be used to determine which inheritance pattern applies.: 101 As OI type I may be difficult to detect in a newborn child, the cord blood of the child can be tested to determine if it has been passed on if the family has already rejected the more invasive genetic screening methods.: 247  In more severe cases, the diagnosis may be able to be done via ultrasound, especially if OI is already a possibility.: 248  An ethical concern with prenatal screening for OI often arises when parents inquire as to how severely affected their child will be—such questions are as yet difficult to answer conclusively.: 382 If a non-affected person has already had a child with OI, there is a greater likelihood (although still quite remote), that their future children will have OI due to genetic mosaicism.: 100, 1513 The disability rights critique of prenatal screening for OI, held by some bioethicists and some affected individuals, negatively compares it to eugenics, with even those not opposed to abortion opposing selective abortions on the ethical ground that their existence betrays the belief that the lives of those with OI are "less worth living [and] less valuable".: 388 Prognosis The prognosis of osteogenesis imperfecta depends entirely on its type (see § Classification). Life expectancy In the mild form of the disorder, type I, the life expectancy of patients is near that of the general population.: 461  In type II, however, patients only very rarely live past the age of two, and typically die in their first weeks of life.: 1511  Assessment of the life expectancy of patients with types III and IV is more complicated, as lifestyle choices can cause fatally traumatic injuries that would not have otherwise occurred, or not been fatal in the general population. Life expectancy in type IV OI is thought to be close to normal, but in type III it is lower than in the general population.A 2016 study of data in Denmarks National Patient Register found that across all types of OI, all-cause mortality was three times higher, leading to a loss of around seven years in females and nine years in males. A 1996 study published in the British Medical Journal found that mortality in type III OI is significantly higher, with many patients dying in their 20s, 30s, and 40s; patients who survive to the age of 10 were further found to have longer life expectancy than newborns. Mobility People with mild (type I) OI as adults need few pieces of adaptive equipment, although in infancy they reach motor milestones at a significant delay compared to the general population.: 477 With adaptive equipment such as crutches, motorized wheelchairs, splints, reach extenders, and/or modifications to the home, many individuals with moderate to severe OI can achieve or maintain a significant degree of independence.: 488  With treatment and physical therapy, the maximum levels of mobility are expected to be unassisted community walking for type I, household or exercise walking for type III, and household or community walking for type IV; due to the variability of OI between individuals, mobility achieved varies and may be below this expected maximum.: 476 Epidemiology In the United States, the incidence of osteogenesis imperfecta is estimated to be one per 20,000 live births. An estimated 20,000 to 50,000 people are affected by OI in the United States.The most common types are I, II, III, and IV, while the rest are very rare. Type I is the most common and has been reported to be around three times more common than type II. The prevalence of types III and IV is less certain. In a 1989 study in Denmark, type I was found to comprise 71% of cases and type II 12% of cases, with other types comprising the other 17%. In a 2015 study in Sweden, type I was nearly six times more common than type III and nearly four times more common than type IV.Most people with OI receive it from a parent, but in many cases, it is a brand new (de novo or "sporadic") mutation in a family. Among a study of patients with survivable types of OI, OI type III is most often de novo (85%), followed by type IV (50%) and type I (34%).: Table 1 Some populations can have a higher incidence of OI than would be otherwise expected if they have a larger than average number of carriers of the recessive forms of the disease.: 20–21 History The condition, or types of it, has had various other names over the years and in different nations; "osteogenesis imperfecta" has, however, been the most widely accepted name for the condition since the late 20th century. Among some of the most common alternatives are "fragilitas ossium"; "Ekman–Lobstein syndrome", and "Vrolik syndrome", both eponyms; and, the colloquialism, "brittle bone disease". Earliest recorded cases OI has been identified in an ancient Egyptian infant mummified in around 1000 BC, originally dismissed by archaeologists as containing the remains of a monkey.: 161  The Norse king Ivar the Boneless, who lived c. 800 CE, is speculated to have had OI as well.Nicolas de Malebranche is oft credited as being the first person to describe the physical characteristics of OI in his 1688 book The Search after Truth, in which he describes a man who has had his "bones broken in the places a murderers would be" all his life. His confident description of the pathology of the disorder, however, which creates what he termed «enfants monstrueux» ("monstrous children"), is scientifically void—he wrote that it was due to the mothers antepartum viewership of a public execution by breaking wheel.: 683 : 165–168 The earliest modern scientific studies of OI began in 1788 by Olof Jakob Ekman, who described the condition, which he termed "osteomalacia congenital", in his doctoral thesis and mentioned cases of it going back to 1678, all in the same family, through three generations. Ekmans description of the condition mentioned dwarfism, bone fragility, and bowing of the long bones.: 763  In 1831, Edmund Axmann gave a detailed description of it in himself and his two brothers, being the first to mention blue sclerae as a characteristic sign of OI.: 683  Jean Lobstein first described the mild form of the condition, today known as type I, in 1833, calling it "osteopsathyrosis idiopathica".: 347 It was not until 1912 that hearing loss was positively recognized as a symptom of OI, first mentioned in a brief paper by the English physician Charles Allen Adair-Dighton.: 168–169 Of the term Willem Vrolik, a Dutch anatomist who was also curator of the "Museum Vrolikianum", which made him privy to many specimens of bodies having birth defects, coined the term "osteogenesis imperfecta": 683  in his bilingual Latin and Dutch language book on teratology, Illustrations of Human and Mammalian Embryogenesis, first published in 1849.Included is a description of the remains of an infant who had what is now known as perinatally fatal OI type II: 347 : 5  (as verified in a 1998 re-examination of the remains by Baljet et al.). The remains were first given to Vroliks father, who could not make sense of them. Vrolik described poorly mineralized bones, bowed long bones, and fractures in various states of healing. Vrolik correctly determined that what he termed OI in the infant was not caused by secondary rickets, but a congenital abnomality causing primary osteopenia; he theorized this was due to a lack of "intrinsic generative energy". Of its classification Classification of OI has also evolved as scientific understanding of it has improved. Before the advent of modern genetic testing, OI was classified in two broad groups: osteogenesis imperfecta congenita, and osteogenesis imperfecta tarda, a division first proposed by the German physician E. Looser in 1906. Congenita was used to describe the modern clinical types II, III, and some cases of IV, where upon birth the condition was obvious, either due to bowing of the limbs or due to fractures sustained in utero. Tarda was used to classify the modern OI type I and some cases of type IV, where the inherent fragility of the bones did not become clear until long after birth. The idea that these "late" and "prenatal" forms were manifestations of the same disorder was first proposed in 1897 by Martin Benno Schmidt; by the 1950s this fact was well accepted.: 346 The modern system of four types (I, II, III, IV), meanwhile, were introduced in a paper by David Sillence, Alison Senn, and David Danks in the Journal of Medical Genetics in 1979, and have since become standard terms among doctors, patients, and researchers. The modern genetic types, (those with numbers greater than IV,) have come into use as more and more recessively inherited forms of OI have been discovered since the discovery of the first one by Roy Morello et al. in 2006. In 2010, the International Nomenclature Group for Constitutional Disorders of the Skeleton (INCDS) "freed" the Sillence types from molecular reference, acquiescing to their new clinical-first role in the wake of what was to them a "surprising" increase in the number of genetic causes of OI.Writing for the Annual Review of Genetics in 2012, Drs. Peter Byers and Shawna M. Pyott lamented how the expansion of the number of types to include genetic types has created a system that "grew like Topsy".: 492  They suggest that it may indeed be impossible to create a system which is useful for clinicians and which accurately describes the genetic cause of a persons OI, with attempts always prioritizing one use at the expense of the other.: 492 Society and culture Much medical research has been done into the causes of osteogenesis imperfecta, benefiting not only those with OI but medicine more broadly; in the ten years between 2006 and 2016, the many discoveries of non-collagen related recessive gene mutations, which still led in those who have them to the clinical signs of OI, led to numerous breakthroughs in medical understanding of the process of healthy bone development. Other animals In dogs, OI is an autosomal recessive condition, meaning that dogs with two copies of the allele will be affected. Many breed organizations and veterinarians offer OI tests to tell if a dog is a carrier of OI. Dogs who are heterozygous for OI should only be bred to non-carriers. Homozygous carriers should never be bred, unless it is to a non-carrier.Naturally occurring mutations causing OI have been found in Golden Retrievers, Dachshunds, and Beagles. OI has also been identified in zebrafish and mice.Although dogs, mice, fish, and humans are not genetically identical, some of these animal models have been officially recognized to represent the varying types of OI in humans. For example, homozygous oim/oim mice experience spontaneous bone fractures, small body size, and kyphosis, making them a model of OI type III. Meanwhile, heterozygous oim/+ mice appear normal but have bones which are quite a bit weaker than wild mice, making them a model for OI type I. As in human OI, the location on the gene which is mutated affects the severity of resulting disease—the G859C Col1a1 mouse is a model for OI type II as affected mice all die in the perinatal period.Animal testing on identified animal models may lead to human therapies for OI. Explanatory notes References External links "Osteogenesis Imperfecta Overview". NIH Osteoporosis and Related Bone Diseases — National Resource Center. National Institutes of Health, U.S. Department of Health and Human Services.

Would you describe Osteopetrosis, to me Aarogya

Osteopetrosis

Osteopetrosis, literally "stone bone", also known as marble bone disease or Albers-Schönberg disease, is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis, in which the bones become less dense and more brittle, or osteomalacia, in which the bones soften. Osteopetrosis can cause bones to dissolve and break.It is one of the hereditary causes of osteosclerosis. It is considered to be the prototype of osteosclerosing dysplasias. The cause of the disease is understood to be malfunctioning osteoclasts and their inability to resorb bone. Although human osteopetrosis is a heterogeneous disorder encompassing different molecular lesions and a range of clinical features, all forms share a single pathogenic nexus in the osteoclast. The exact molecular defects or location of the mutations taking place are unknown. Osteopetrosis was first described in 1903, by German radiologist Albers-Schönberg. Signs and symptoms Despite this excess bone formation, people with osteopetrosis tend to have bones that are more brittle than normal. Mild osteopetrosis may cause no symptoms, and present no problems. However, serious forms can result in the following: Stunted growth, deformity, and increased likelihood of fractures Patients experience anemia, recurrent infections, and hepatosplenomegaly due to bone expansion leading to bone marrow narrowing and extramedullary hematopoiesis It can also result in blindness, facial paralysis, and deafness, due to the increased pressure put on the nerves by the extra bone Abnormal cortical bone morphology Abnormal form of the vertebral bodies Abnormality of temperature regulation Abnormality of the ribs Abnormality of vertebral epiphysis morphology Bone pain Cranial nerve paralysis Craniosynostosis Hearing impairment Hypocalcemia Malignant infantile osteopetrosis Autosomal recessive osteopetrosis (ARO), also known as malignant infantile osteopetrosis or infantile malignant osteopetrosis (IMO), is a rare type of skeletal dysplasia characterized by a distinct radiographic pattern of overall increased density of the bones with fundamental involvement of the medullary portion. Infantile osteopetrosis typically manifests in infancy. Diagnosis is principally based on clinical and radiographic evaluation, confirmed by gene analysis where applicable. As a result of medullary canal obliteration and bony expansion, grave pancytopenia, cranial nerve compression, and pathologic fractures may ensue. The prognosis is poor if untreated. The classic radiographic features include endobone or "bone-within-bone" appearance in the spine, pelvis and proximal femora, upper limbs, and short tubular bones of the hand. Additionally, there is the Erlenmeyer flask deformity type 2 which is characterized by the absence of normal diaphysial metaphysical modeling of the distal femora with abnormal radiographic appearance of trabecular bone and alternating radiolucent metaphyseal bands.The precise and early diagnosis of infantile osteopetrosis is important for management of complications, genetic counselling, and timely institution of appropriate treatment, namely hematopoietic stem cell transplantation (HSCT), which offers a satisfactory treatment modality for a considerable percentage of infantile osteopetrosis. Amelioration of radiographic bone lesions after HSCT in infantile osteopetrosis has been proposed as an important indicator of success of the therapy. A few publications with limited study participants have demonstrated the resolution of skeletal radiographic pathology following HSCT. Adult osteopetrosis Autosomal dominant osteopetrosis (ADO) is also known as Albers-Schonberg disease. Most do not know they have this disorder because most individuals do not show any symptoms. However, the ones that do show symptoms will typically have a curvature of the spine (scoliosis), and multiple bone fractures. There are two types of adult osteopetrosis based on the basis of radiographic, biochemical, and clinical features. Many patients will have bone pains. The defects are very common and include neuropathies due to cranial nerve entrapment, osteoarthritis, and carpal tunnel syndrome. About 40% of patients will experience recurrent fractures of their bones. 10% of patients will have osteomyelitis of the mandible. Causes The various types of osteopetrosis are caused by genetic changes (mutations) in one of at least ten genes. There is nothing a parent can do before, during or after a pregnancy to cause osteopetrosis in a child.The genes associated with osteopetrosis are involved in the development and/or function of osteoclasts, cells that break down bone tissue when old bone is being replaced by new bone (bone remodeling). This process is necessary to keep bones strong and healthy. Mutations in these genes can lead to abnormal osteoclasts, or having too few osteoclasts. If this happens, old bone cannot be broken down as new bone is formed, so bones become too dense and prone to breaking. Mutations in the CLCN7 gene cause most cases of autosomal dominant osteopetrosis, 10-15% of cases of autosomal recessive osteopetrosis (the most severe form), and all known cases of intermediate autosomal osteopetrosis. Mutations in the TCIRG1 gene cause about 50% of cases of autosomal recessive osteopetrosis. Mutations in the IKBKG gene cause X-linked osteopetrosis. Mutations in other genes are less common causes of osteopetrosis. In about 30% percent of affected people, the cause is unknown.Normally, bone growth is a balance between osteoblasts (cells that create bone tissue) and osteoclasts (cells that destroy bone tissue). Those with osteopetrosis have a deficiency of osteoclasts, meaning too little bone is being resorbed, resulting in too much bone being created. Gene variation Mechanisms Normal bone growth is achieved by a balance between bone formation by osteoblasts and bone resorption (breakdown of bone matrix) by osteoclasts. In osteopetrosis, the number of osteoclasts may be reduced, normal, or increased. Most importantly, osteoclast dysfunction mediates the pathogenesis of this disease.Osteopetrosis is caused by underlying mutations that interfere with the acidification of the osteoclast resorption pit, for example due to a deficiency of the carbonic anhydrase enzyme encoded by the CA2 gene. Carbonic anhydrase is required by osteoclasts for proton production. Without this enzyme hydrogen ion pumping is inhibited and bone resorption by osteoclasts is defective, as an acidic environment is needed to dissociate calcium hydroxyapatite from the bone matrix. As bone resorption fails while bone formation continues, excessive bone is formed.Mutations in at least nine genes cause the various types of osteopetrosis. Mutations in the CLCN7 gene are responsible for about 75 percent of cases of autosomal dominant osteopetrosis, 10 to 15 percent of cases of autosomal recessive osteopetrosis, and all known cases of intermediate autosomal osteopetrosis. TCIRG1 gene mutations cause about 50 percent of cases of autosomal recessive osteopetrosis. Mutations in other genes are less common causes of autosomal dominant and autosomal recessive forms of the disorder. The X-linked type of osteopetrosis, OL-EDA-ID, results from mutations in the IKBKG gene. In about 30 percent of all cases of osteopetrosis, the cause of the condition is unknown.The genes associated with osteopetrosis are involved in the formation, development, and function of specialized cells called osteoclasts. These cells break down bone tissue during bone remodeling, a normal process in which old bone is removed and new bone is created to replace it. Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy. Mutations in any of the genes associated with osteopetrosis lead to abnormal or missing osteoclasts. Without functional osteoclasts, old bone is not broken down as new bone is formed. As a result, bones throughout the skeleton become unusually dense. The bones are also structurally abnormal, making them prone to fracture. These problems with bone remodeling underlie all of the major features of osteopetrosis. Diagnosis The differential diagnosis of osteopetrosis includes other disorders that produce osteosclerosis. They constitute a wide array of disorders with clinically and radiologically diverse manifestations. Among the differential diagnosis are hereditary ostoesclerosing dysplasias such as; neuropathic infantile osteopetrosis, infantile osteopetrosis with renal tubular acidosis, infantile osteopetrosis with immunodeficiency, infantile osteopetrosis with leukocyte adhesion deficiency syndrome (LAD-III), pyknodysostosis (osteopetrosis acro-osteolytica), osteopoikilosis (Buschke–Ollendorff syndrome), osteopathia striata with cranial sclerosis, mixed sclerosing skeletal dysplasias, progressive diaphyseal dysplasia (Camurati–Engelmann disease), SOST-related sclerosing skeletal dysplasias. Besides, the differential diagnosis includes acquired conditions that induce osteosclerosis such as osteosclerotic metastasis notably carcinomas of the prostate gland and breast, Pagets disease of bone, myelofibrosis (primary disorder or secondary to intoxication or malignancy), Erdheim-Chester disease, osteosclerosing types of osteomyelitis, sickle cell disease, hypervitaminosis D, and hypoparathyroidism. Treatment It was the first genetic disease treated with hematopoietic stem cell transplantation (osteoclasts are derived from hematopoietic precursors). There is no cure, although curative therapy with bone marrow transplantion is being investigated in clinical trials. It is believed the healthy marrow will provide cells from which osteoclasts will develop. If complications occur in children, patients can be treated with vitamin D. Gamma interferon has also been shown to be effective, and it can be associated to vitamin D. Erythropoetin has been used to treat any associated anemia. Corticosteroids may alleviate both the anemia and stimulate bone resorption. Fractures and osteomyelitis can be treated as usual. Treatment for osteopetrosis depends on the specific symptoms present and the severity in each person. Therefore, treatment options must be evaluated on an individual basis. Nutritional support is important to improve growth and it also enhances responsiveness to other treatment options. A calcium-deficient diet has been beneficial for some affected people.Treatment is necessary for the infantile form: Vitamin D (calcitriol) appears to stimulate dormant osteoclasts, which stimulates bone resorption Gamma interferon can have long-term benefits. It improves white blood cell function (leading to fewer infections), decreases bone volume, and increases bone marrow volume. Erythropoietin can be used for anemia, and corticosteroids can be used for anemia and to stimulate bone resorption.Bone marrow transplantation (BMT) improves some cases of severe, infantile osteopetrosis associated with bone marrow failure, and offers the best chance of longer-term survival for individuals with this type.In pediatric (childhood) osteopetrosis, surgery is sometimes needed because of fractures. Adult osteopetrosis typically does not require treatment, but complications of the condition may require intervention. Surgery may be needed for aesthetic or functional reasons (such as multiple fractures, deformity, and loss of function), or for severe degenerative joint disease. Prognosis The long-term-outlook for people with osteopetrosis depends on the subtype and the severity of the condition in each person. The severe infantile forms of osteopetrosis are associated with shortened life expectancy, with most untreated children not surviving past their first decade. Bone marrow transplantation seems to have cured some infants with early-onset disease. However, the long-term prognosis after transplantation is unknown. For those with onset in childhood or adolescence, the effect of the condition depends on the specific symptoms (including how fragile the bones are and how much pain is present). Life expectancy in the adult-onset forms is normal. Prevalence Approximately eight to 40 children are born in the United States each year with the malignant infantile type of osteopetrosis. One in every 100,000 to 500,000 individuals is born with this form of osteopetrosis. Higher rates have been found in Denmark and Costa Rica. Males and females are affected in equal numbers.The adult type of osteopetrosis affects about 1,250 individuals in the United States. One in every 200,000 individuals is affected by the adult type of osteopetrosis. Higher rates have been found in Brazil. Males and females are affected in equal numbers.Osteopetrosis affects one newborn out of every 20,000 to 250,000 worldwide, but the odds are much higher in the Russian region of Chuvashia (1 of every 3,500–4,000 newborns) due to genetic traits of the Chuvash people. Recent research Recent research demonstrated that the systematic administration of RANKL for one month to Rankl(-/-) mice, which closely resemble the human disease, significantly improved the bone phenotype and has beneficial effects on bone marrow, spleen and thymus; major adverse effects arise only when mice are clearly overtreated. Overall, it provided evidence that the pharmacological administration of RANKL represents the appropriate treatment option for RANKL-deficient ARO patients, to be validated in a pilot clinical trial.Interferon gamma-1b is FDA-approved to delay the time to disease progression in patients with severe, malignant osteopetrosis. Notable cases Laurel Burch Lil Bub References Bibliography == External links ==

Hey Aarogya!, what is Otitis externa

Otitis externa

Otitis externa, also called swimmers ear, is inflammation of the ear canal. It often presents with ear pain, swelling of the ear canal, and occasionally decreased hearing. Typically there is pain with movement of the outer ear. A high fever is typically not present except in severe cases.Otitis externa may be acute (lasting less than six weeks) or chronic (lasting more than three months). Acute cases are typically due to bacterial infection, and chronic cases are often due to allergies and autoimmune disorders. the most common cause of Otitis externa is bacterial. Risk factors for acute cases include swimming, minor trauma from cleaning, using hearing aids and ear plugs, and other skin problems, such as psoriasis and dermatitis. People with diabetes are at risk of a severe form of malignant otitis externa. Diagnosis is based on the signs and symptoms. Culturing the ear canal may be useful in chronic or severe cases.Acetic acid ear drops may be used as a preventive measure. Treatment of acute cases is typically with antibiotic drops, such as ofloxacin or acetic acid. Steroid drops may be used in addition to antibiotics. Pain medications such as ibuprofen may be used for the pain. Antibiotics by mouth are not recommended unless the person has poor immune function or there is infection of the skin around the ear. Typically, improvement occurs within a day of the start of treatment. Treatment of chronic cases depends on the cause.Otitis externa affects 1–3% of people a year; more than 95% of cases are acute. About 10% of people are affected at some point in their lives. It occurs most commonly among children between the ages of seven and twelve and among the elderly. It occurs with near equal frequency in males and females. Those who live in warm and wet climates are more often affected. Signs and symptoms Tenderness of pinna is the predominant complaint and the only symptom directly related to the severity of acute external otitis. Unlike other forms of ear infections, we observe tenderness in outer ear i.e., the pain of acute external otitis is worsened when the outer ear is touched or pulled gently. Pushing the tragus, the tablike portion of the auricle that projects out just in front of the ear canal opening, also typically causes pain in this condition as to be diagnostic of external otitis on physical examination. People may also experience ear discharge and itchiness. When enough swelling and discharge in the ear canal is present to block the opening, external otitis may cause temporary conductive hearing loss.Because the symptoms of external otitis lead many people to attempt to clean out the ear canal (or scratch it) with slim implements, self-cleaning attempts generally lead to additional traumas of the injured skin, so rapid worsening of the condition often occurs. Causes The two factors that are required for external otitis to develop are (1) the presence of germs that can infect the skin and (2) impairments in the integrity of the skin of the ear canal that allow an infection to occur. If the skin is healthy and uninjured, only exposure to a high concentration of pathogens, such as submersion in a pond contaminated by sewage, is likely to set off an episode. However, if there are chronic skin conditions that affect the ear canal skin, such as atopic dermatitis, seborrheic dermatitis, psoriasis or abnormalities of keratin production, or if there has been a break in the skin from trauma, even the normal bacteria found in the ear canal may cause infection and full-blown symptoms of external otitis.Fungal ear canal infections, also known as otomycosis, range from inconsequential to extremely severe. Fungi can be saprophytic, in which there are no symptoms and the fungus simply co-exists in the ear canal in a harmless parasitic relationship with the host, in which case the only physical finding is the presence of a fungus. If the fungus begins active reproduction, the ear canal can fill with dense fungal debris, causing pressure and ever-increasing pain that is unrelenting until the fungus is removed from the canal and anti-fungal medication is used. Most antibacterial ear drops also contain a steroid to hasten resolution of canal edema and pain. Unfortunately, such drops make the fungal infection worse. Prolonged use of them promotes the growth of fungus in the ear canal. Antibacterial ear drops should be used for a maximum of one week, but 5 days is usually enough. Otomycosis responds more than 95% of the time to a three-day course of the same over-the-counter anti-fungal solutions used for athletes foot. Swimming Swimming in polluted water is a common way to contract swimmers ear, but it is also possible to contract swimmers ear from water trapped in the ear canal after a shower, especially in a humid climate. Prolonged swimming can saturate the skin of the canal, compromising its barrier function and making it more susceptible to further damage if the ear is instrumented with cotton swabs after swimming. Constriction of the ear canal from bone growth (Surfers ear) can trap debris leading to infection. Saturation divers have reported otitis externa during occupational exposure. Objects in ear Even without exposure to water, the use of objects such as cotton swabs or other small objects to clear the ear canal is enough to cause breaks in the skin, and allow the condition to develop. Once the skin of the ear canal is inflamed, external otitis can be drastically enhanced by either scratching the ear canal with an object or by allowing water to remain in the ear canal for any prolonged length of time. Infections The majority of cases are due to Pseudomonas aeruginosa and Staphylococcus aureus, followed by a great number of other gram-positive and gram-negative species. Candida albicans and Aspergillus species are the most common fungal pathogens responsible for the condition. Diagnosis When the ear is inspected, the canal appears red and swollen in well-developed cases. The ear canal may also appear eczema-like, with scaly shedding of skin. Touching or moving the outer ear increases the pain, and this maneuver on physical exam is important in establishing the clinical diagnosis. It may be difficult to see the eardrum with an otoscope at the initial examination because of narrowing of the ear canal from inflammation and the presence of drainage and debris. Sometimes the diagnosis of external otitis is presumptive and return visits are required to fully examine the ear. The culture of the drainage may identify the bacteria or fungus causing infection, but is not part of the routine diagnostic evaluation. In severe cases of external otitis, there may be swelling of the lymph node(s) directly beneath the ear.The diagnosis may be missed in most early cases because the examination of the ear, with the exception of pain with manipulation, is nearly normal. In some early cases, the most striking visual finding is the lack of earwax. As a moderate or severe case of external otitis resolves, weeks may be required before the ear canal again shows a normal amount of it. Classification In contrast to the chronic otitis externa, acute otitis externa (AOE) is predominantly a bacterial infection, occurs suddenly, rapidly worsens, and becomes painful. The ear canal has an abundant nerve supply, so the pain is often severe enough to interfere with sleep. Wax in the ear can combine with the swelling of the canal skin and the associated pus to block the canal and dampen hearing, creating a temporary conductive hearing loss. In more severe or untreated cases, the infection can spread to the soft tissues of the face that surround the adjacent parotid gland and the jaw joint, making chewing painful. In its mildest forms, otitis externa is so common that some ear nose and throat physicians have suggested that most people will have at least a brief episode at some point in life. The skin of the bony ear canal is unique, in that it is not movable but is closely attached to the bone, and it is almost paper-thin. For these reasons, it is easily abraded or torn by even minimal physical force. Inflammation of the ear canal skin typically begins with a physical insult, most often from injury caused by attempts at self-cleaning or scratching with cotton swabs, pen caps, fingernails, hair pins, keys, or other small implements. Another causative factor for acute infection is prolonged water exposure in the forms of swimming or exposure to extreme humidity, which can compromise the protective barrier function of the canal skin, allowing bacteria to flourish, hence the name "swimmers ear". Prevention The strategies for preventing acute external otitis are similar to those for treatment. Avoid inserting anything into the ear canal: use of cotton buds or swabs is the most common event leading to acute otitis externa. Most normal ear canals have a self-cleaning and self-drying mechanism, the latter by simple evaporation. After prolonged swimming, a person prone to external otitis can dry the ears using a small battery-powered ear dryer, available at many retailers, especially shops catering to watersports enthusiasts. Alternatively, drops containing dilute acetic acid (vinegar diluted 3:1) or Burows solution may be used. It is especially important not to instrument ears when the skin is saturated with water, as it is very susceptible to injury, which can lead to external otitis. Avoid swimming in polluted water. Avoid washing hair or swimming if very mild symptoms of acute external otitis begin Although the use of earplugs, when swimming and shampooing hair, may help prevent external otitis, there are important details in the use of plugs. Hard and poorly fitting earplugs can scratch the ear canal skin and set off an episode. When earplugs are used during an acute episode, either disposable plugs are recommended, or used plugs must be cleaned and dried properly to avoid contaminating the healing ear canal with infected discharge.According to one source, the use of in-ear headphones during otherwise "dry" exercise in the summer has been associated with the development of swimmers ear since the plugs can create a warm and moist environment inside the ears. The source claims that on-ear or over-ear headphones can be a better alternative for preventing swimmers ear. Treatment Medications Effective solutions for the ear canal include acidifying and drying agents, used either singly or in combination. When the ear canal skin is inflamed from the acute otitis externa, the use of dilute acetic acid may be painful. Burows solution is a very effective remedy against both bacterial and fungal external otitis. This is a buffered mixture of aluminium sulfate and acetic acid, and is available without prescription in the United States.Ear drops are the mainstay of treatment for external otitis. Some contain antibiotics, either antibacterial or antifungal, and others are simply designed to mildly acidify the ear canal environment to discourage bacterial growth. Some prescription drops also contain anti-inflammatory steroids, which help to resolve swelling and itching. Although there is evidence that steroids are effective at reducing the length of treatment time required, fungal otitis externa (also called otomycosis) may be caused or aggravated by overly prolonged use of steroid-containing drops.Antibiotics by mouth should not be used to treat uncomplicated acute otitis externa. Antibiotics by mouth are not a sufficient response to bacteria which cause this condition and have significant side effects including increased risk of opportunistic infection. In contrast, topical products can treat this condition. Oral anti-pseudomonal antibiotics can be used in case of severe soft tissue swelling extending into the face and neck and may hasten recovery.Although the acute external otitis generally resolves in a few days with topical washes and antibiotics, complete return of hearing and cerumen gland function may take a few more days. Once healed completely, the ear canal is again self-cleaning. Until it recovers fully, it may be more prone to repeat infection from further physical or chemical insult.Effective medications include ear drops containing antibiotics to fight infection, and corticosteroids to reduce itching and inflammation. In painful cases, a topical solution of antibiotics such as aminoglycoside, polymyxin or fluoroquinolone is usually prescribed. Antifungal solutions are used in the case of fungal infections. External otitis is almost always predominantly bacterial or predominantly fungal so that only one type of medication is necessary and indicated. Cleaning Removal of debris (wax, shed skin, and pus) from the ear canal promotes direct contact of the prescribed medication with the infected skin and shortens recovery time. When canal swelling has progressed to the point where the ear canal is blocked, ear drops may not penetrate far enough into the ear canal to be effective. The physician may need to carefully insert a wick of cotton or other commercially available, pre-fashioned, absorbent material called an ear wick and then saturate that with the medication. The wick is kept saturated with medication until the canal opens enough that the drops will penetrate the canal without it. Removal of the wick does not require a health professional. Antibiotic ear drops should be dosed in a quantity that allows coating of most of the ear canal and used for no more than 4 to 7 days. The ear should be left open. It is imperative that visualization of an intact tympanic membrane (eardrum) is noted. Use of certain medications with a ruptured tympanic membrane can cause tinnitus, vertigo, dizziness and hearing loss in some cases. Prognosis Otitis externa responds well to treatment, but complications may occur if it is not treated. Individuals with underlying diabetes, disorders of the immune system, or history of radiation therapy to the base of the skull are more likely to develop complications, including malignant otitis externa. In these individuals, rapid examination by an otolaryngologist (ear, nose, and throat physician) is very important. Chronic otitis externa Spread of infection to other areas of the body Necrotizing external otitis Otitis externa haemorhagica Necrotizing external otitis Necrotizing external otitis (malignant otitis externa) is an uncommon form of external otitis that occurs mainly in elderly diabetics, being somewhat more likely and more severe when the diabetes is poorly controlled. Even less commonly, it can develop due to a severely compromised immune system. Beginning as infection of the external ear canal, there is an extension of the infection into the bony ear canal and the soft tissues deep to the bony canal. Unrecognized and untreated, it may result in death. The hallmark of malignant otitis externa (MOE) is unrelenting pain that interferes with sleep and persists even after swelling of the external ear canal may have resolved with topical antibiotic treatment. It can also cause skull base osteomyelitis (SBO), manifested by multiple cranial nerve palsies, described below under the "Treatment" heading. Natural history MOE follows a much more chronic and indolent course than ordinary acute otitis externa. There may be granulation involving the floor of the external ear canal, most often at the bony-cartilaginous junction. Paradoxically, the physical findings of MOE, at least in its early stages, are often much less dramatic than those of ordinary acute otitis externa. In later stages, there can be soft tissue swelling around the ear, even in the absence of significant canal swelling. While fever and leukocytosis might be expected in response to bacterial infection invading the skull region, MOE does not cause fever or elevation of white blood count. Treatment of MOE Unlike ordinary otitis externa, MOE requires oral or intravenous antibiotics for cure. Pseudomonas is the most common offending pathogen. Diabetes control is also an essential part of treatment. When MOE goes unrecognized and untreated, the infection continues to smolder and over weeks or months can spread deeper into the head and involve the bones of the skull base, constituting skull base osteomyelitis (SBO). Multiple cranial nerve palsies can result, including the facial nerve (causing facial palsy), the recurrent laryngeal nerve (causing vocal cord paralysis), and the cochlear nerve (causing deafness). The infecting organism is almost always pseudomonas aeruginosa, but it can instead be fungal (aspergillus or mucor). MOE and SBO are not amenable to surgery, but exploratory surgery may facilitate the culture of unusual organism(s) that are not responding to empirically used anti-pseudomonal antibiotics (ciprofloxacin being the drug of choice). The usual surgical finding is diffuse cellulitis without localized abscess formation. SBO can extend into the petrous apex of the temporal bone or more inferiorly into the opposite side of the skull base.The use of hyperbaric oxygen therapy as an adjunct to antibiotic therapy remains controversial. Complications As the skull base is progressively involved, the adjacent exiting cranial nerves and their branches, especially the facial nerve and the vagus nerve, may be affected, resulting in facial paralysis and hoarseness, respectively. If both of the recurrent laryngeal nerves are paralyzed, shortness of breath may develop and necessitate tracheotomy. Profound deafness can occur, usually later in the disease course due to relative resistance of the inner ear structures. Gallium scans are sometimes used to document the extent of the infection but are not essential to disease management. Skull base osteomyelitis is a chronic disease that can require months of IV antibiotic treatment, tends to recur, and has a significant mortality rate. Epidemiology The incidence of otitis externa is high. In the Netherlands, it has been estimated at 12–14 per 1000 population per year, and has been shown to affect more than 1% of a sample of the population in the United Kingdom over a 12-month period. History During the Tektite Project in 1969 there was a great deal of otitis externa. The Diving Medical Officer devised a prophylaxis that came to be known as, "Tektite Solution", equal parts of 15% tannic acid, 15% acetic acid and 50% isopropyl alcohol or ethanol. During Tektite ethanol was used because it was available in the lab for pickling specimens. Other animals References == External links ==

Aarogya, What does Ovarian hyperstimulation syndrome mean

Ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a medical condition that can occur in some women who take fertility medication to stimulate egg growth, and in other women in very rare cases. Most cases are mild, but rarely the condition is severe and can lead to serious illness or death. Signs and symptoms Symptoms are set into 3 categories: mild, moderate, and severe. Mild symptoms include abdominal bloating and feeling of fullness, nausea, diarrhea, and slight weight gain. Moderate symptoms include excessive weight gain (weight gain of greater than 2 pounds per day), increased abdominal girth, vomiting, diarrhea, darker urine, decreased urine output, excessive thirst, and skin and/or hair feeling dry (in addition to mild symptoms). Severe symptoms are fullness/bloating above the waist, shortness of breath, pleural effusion, urination significantly darker or has ceased, calf and chest pains, marked abdominal bloating or distention, and lower abdominal pains (in addition to mild and moderate symptoms). Complications OHSS may be complicated by ovarian torsion, ovarian rupture, venous thromboembolism, acute respiratory distress syndrome, electrolytes imbalance, thrombophlebitis and chronic kidney disease. Symptoms generally resolve in 1 to 2 weeks, but will be more severe and persist longer if pregnancy occurs. This is due to human chorionic gonadotropin (hCG) from the pregnancy acting on the corpus luteum in the ovaries in sustaining the pregnancy before the placenta has fully developed. Typically, even in severe OHSS with a developing pregnancy, the duration does not exceed the first trimester. Cause Sporadic OHSS is very rare, and may have a genetic component. Clomifene citrate therapy can occasionally lead to OHSS, but the vast majority of cases develop after use of gonadotropin therapy (with administration of FSH), such as Pergonal, and administration of hCG to induce final oocyte maturation and/or trigger oocyte release, often in conjunction with IVF. The frequency varies and depends on a womans risk factors, management, and methods of surveillance. About 5% of treated women may encounter moderate to severe OHSS. Risk factors include polycystic ovary syndrome, young age, low BMI, high antral follicle count, the development of many ovarian follicles under stimulation, extreme elevated serum estradiol concentrations, the use of hCG for final oocyte maturation and/or release, the continued use of hCG for luteal support, and the occurrence of a pregnancy (resulting in hCG production). Mortality is low, but several fatal cases have been reported. Medications Ovarian hyperstimulation syndrome is particularly associated with injection of a hormone called human chorionic gonadotropin (hCG) which is used for inducing final oocyte maturation and/or triggering oocyte release. The risk is further increased by multiple doses of hCG after ovulation and if the procedure results in pregnancy.Using a GnRH agonist instead of hCG for inducing final oocyte maturation and/or release results in an elimination of the risk of ovarian hyperstimulation syndrome, but a slight decrease of the delivery rate of approximately 6%. Pathophysiology OHSS has been characterized by the presence of multiple luteinized cysts within the ovaries leading to ovarian enlargement and secondary complications, but that definition includes almost all women undergoing ovarian stimulation. The central feature of clinically significant OHSS is the development of vascular hyperpermeability and the resulting shift of fluids into the third space.As hCG causes the ovary to undergo extensive luteinization, large amounts of estrogens, progesterone, and local cytokines are released. It is almost certain that vascular endothelial growth factor (VEGF) is a key substance that induces vascular hyperpermeability, making local capillaries "leaky", leading to a shift of fluids from the intravascular system to the abdominal and pleural cavity. Supraphysiologic production of VEGF from many follicles under the prolonged effect of hCG appears to be the specific key process underlying OHSS. Thus, while the woman accumulates fluid in the third space, primarily in the form of ascites, she actually becomes hypovolemic and is at risk for respiratory, circulatory (such as arterial thromboembolism since blood is now thicker), and renal problems. Women who are pregnant sustain the ovarian luteinization process through the production of hCG.Avoiding OHSS typically requires interrupting the pathological sequence, such as avoiding the use of hCG. One alternative is to use a GnRH agonist instead of hCG. While this has been repeatedly shown to "virtually eliminate" OHSS risk, there is some controversy regarding the effect on pregnancy rates if a fresh non-donor embryo transfer is attempted, almost certainly due to a luteal phase defect. There is no dispute that the GnRH agonist trigger is effective for oocyte donors and for embryo banking (cryopreservation) cycles. Classification OHSS is divided into the categories mild, moderate, severe, and critical. In mild forms of OHSS the ovaries are enlarged (5–12 cm) and there may be additional accumulation of ascites with mild abdominal distension, abdominal pain, nausea, and diarrhea. In severe forms of OHSS there may be hemoconcentration, thrombosis, distension, oliguria (decreased urine production), pleural effusion, and respiratory distress. Early OHSS develops before pregnancy testing and late OHSS is seen in early pregnancy. Criteria for severe OHSS include enlarged ovary, ascites, hematocrit > 45%, WBC > 15,000, oliguria, creatinine 1.0-1.5 mg/dl, creatinine clearance > 50 ml/min, liver dysfunction, and anasarca. Critical OHSS includes enlarged ovary, tense ascites with hydrothorax and pericardial effusion, hematocrit > 55%, WBC > 25,000, oligoanuria, creatinine > 1.6 mg/dl, creatinine clearance < 50 ml/min, kidney failure, thromboembolic phenomena, and ARDS. Prevention Physicians can reduce the risk of OHSS by monitoring of FSH therapy to use this medication judiciously, and by withholding hCG medication. Cabergoline confers a significant reduction in the risk of OHSS in high risk women according to a Cochrane review of randomized studies, but the included trials did not report the live birth rates or multiple pregnancy rates. Cabergoline, as well as other dopamine agonists, might reduce the severity of OHSS by interfering with the VEGF system. A systematic review and meta-analysis concluded that prophylactic treatment with cabergoline reduces the incidence, but not the severity of OHSS, without compromising pregnancy outcomes.The risk of OHSS is smaller when using GnRH antagonist protocol instead of GnRH agonist protocol for suppression of ovulation during ovarian hyperstimulation. The underlying mechanism is that, with the GnRH antagonist protocol, initial follicular recruitment and selection is undertaken by endogenous endocrine factors prior to starting the exogenous hyperstimulation, resulting in a smaller number of growing follicles when compared with the standard long GnRH agonist protocol.A Cochrane review found administration of hydroxyethyl starch decreases the incidence of severe OHSS. There was insufficient evidence to support routine cryopreservation and insufficient evidence for the relative merits of intravenous albumin versus cryopreservation. Also, coasting, which is ovarian hyperstimulation without induction of final maturation, does not significantly decrease the risk of OHSS.Volume expanders such as albumin and hydroxyethyl starch solutions act providing volume to the circulatory system Treatment Treatment of OHSS depends on the severity of the hyperstimulation. Mild OHSS can be treated conservatively with monitoring of abdominal girth, weight, and discomfort on an outpatient basis until either conception or menstruation occurs. Conception can cause mild OHSS to worsen in severity.Moderate OHSS is treated with bed rest, fluids, and close monitoring of labs such as electrolytes and blood counts. Ultrasound may be used to monitor the size of ovarian follicles. Depending on the situation, a physician may closely monitor a womens fluid intake and output on an outpatient basis, looking for increased discrepancy in fluid balance (over 1 liter discrepancy is cause for concern). Resolution of the syndrome is measured by decreasing size of the follicular cysts on 2 consecutive ultrasounds.Aspiration of accumulated fluid (ascites) from the abdominal/pleural cavity may be necessary, as well as opioids for the pain. If the OHSS develops within an IVF protocol, it can be prudent to postpone transfer of the pre-embryos since establishment of pregnancy can lengthen the recovery time or contribute to a more severe course. Over time, if carefully monitored, the condition will naturally reverse to normal – so treatment is typically supportive, although a woman may need to be treated or hospitalized for pain, paracentesis, and/or intravenous hydration. References Further reading Delvigne A, Rozenberg S (2002). "Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review". Hum Reprod Update. 8 (6): 559–77. doi:10.1093/humupd/8.6.559. PMID 12498425. Delvigne A, Rozenberg S (2003). "Review of clinical course and treatment of ovarian hyperstimulation syndrome (OHSS)". Hum Reprod Update. 9 (1): 77–96. doi:10.1093/humupd/dmg005. PMID 12638783. == External links ==

Hello Aarogya , Do you know what is Overactive bladder,

Overactive bladder

Overactive bladder (OAB) is a condition where there is a frequent feeling of needing to urinate to a degree that it negatively affects a persons life. The frequent need to urinate may occur during the day, at night, or both. If there is loss of bladder control then it is known as urge incontinence. More than 40% of people with overactive bladder have incontinence. Conversely, about 40% to 70% of urinary incontinence is due to overactive bladder. Overactive bladder is not life-threatening, but most people with the condition have problems for years.The cause of overactive bladder is unknown. Risk factors include obesity, caffeine, and constipation. Poorly controlled diabetes, poor functional mobility, and chronic pelvic pain may worsen the symptoms. People often have the symptoms for a long time before seeking treatment and the condition is sometimes identified by caregivers. Diagnosis is based on a persons signs and symptoms and requires other problems such as urinary tract infections or neurological conditions to be excluded. The amount of urine passed during each urination is relatively small. Pain while urinating suggests that there is a problem other than overactive bladder.Specific treatment is not always required. If treatment is desired pelvic floor exercises, bladder training, and other behavioral methods are initially recommended. Weight loss in those who are overweight, decreasing caffeine consumption, and drinking moderate fluids, can also have benefits. Medications, typically of the anti-muscarinic type, are only recommended if other measures are not effective. They are no more effective than behavioral methods; however, they are associated with side effects, particularly in older people. Some non-invasive electrical stimulation methods appear effective while they are in use. Injections of botulinum toxin into the bladder is another option. Urinary catheters or surgery are generally not recommended. A diary to track problems can help determine whether treatments are working.Overactive bladder is estimated to occur in 7-27% of men and 9-43% of women. It becomes more common with age. Some studies suggest that the condition is more common in women, especially when associated with loss of bladder control. Economic costs of overactive bladder were estimated in the United States at US$12.6 billion and 4.2 billion Euro in 2000. Signs and symptoms Overactive bladder is characterized by a group of four symptoms: urgency, urinary frequency, nocturia, and urge incontinence. Urge incontinence is not present in the "dry" classification.Urgency is considered the hallmark symptom of OAB, but there are no clear criteria for what constitutes urgency and studies often use other criteria. Urgency is currently defined by the International Continence Society (ICS), as of 2002, as "Sudden, compelling desire to pass urine that is difficult to defer." The previous definition was "Strong desire to void accompanied by fear of leakage or pain." The definition does not address the immediacy of the urge to void and has been criticized as subjective.Urinary frequency is considered abnormal if the person urinates more than eight times in a day. This frequency is usually monitored by having the person keep a voiding diary where they record urination episodes. The number of episodes varies depending on sleep, fluid intake, medications, and up to seven is considered normal if consistent with the other factors.Nocturia is a symptom where the person complains of interrupted sleep because of an urge to void and, like the urinary frequency component, is affected by similar lifestyle and medical factors. Individual waking events are not considered abnormal, one study in Finland established two or more voids per night as affecting quality of life.Urge incontinence is a form of urinary incontinence characterized by the involuntary loss of urine occurring for no apparent reason while feeling urinary urgency as discussed above. Like frequency, the person can track incontinence in a diary to assist with diagnosis and management of symptoms. Urge incontinence can also be measured with pad tests, and these are often used for research purposes. Some people with urge incontinence also have stress incontinence and this can complicate clinical studies.It is important that the clinician and the person with overactive bladder both reach a consensus on the term, urgency. Some common phrases used to describe OAB include, When Ive got to go, Ive got to go, or When I have to go, I have to rush, because I think I will wet myself. Hence the term, fear of leakage, is an important concept to people. Causes The cause of OAB is unclear, and indeed there may be multiple causes. It is often associated with overactivity of the detrusor urinae muscle, a pattern of bladder muscle contraction observed during urodynamics. It is also possible that the increased contractile nature originates from within the urothelium and lamina propria, and abnormal contractions in this tissue could stimulate dysfunction in the detrusor or whole bladder. Catheter-related irritation If bladder spasms occur or there is no urine in the drainage bag when a catheter is in place, the catheter may be blocked by blood, thick sediment, or a kink in the catheter or drainage tubing. Sometimes spasms are caused by the catheter irritating the bladder, prostate or penis. Such spasms can be controlled with medication such as butylscopolamine, although most people eventually adjust to the irritation and the spasms go away. Diagnosis Diagnosis of OAB is made primarily on the persons signs and symptoms and by ruling out other possible causes such as an infection. Urodynamics, a bladder scope, and ultrasound are generally not needed. Additionally, urine culture may be done to rule out infection. The frequency/volume chart may be maintained and cystourethroscopy may be done to exclude tumor and kidney stones. If there is an underlying metabolic or pathologic condition that explains the symptoms, the symptoms may be considered part of that disease and not OAB.Psychometrically robust self-completion questionnaires are generally recognized as a valid way of measuring a persons signs and symptoms, but there does not exist a single ideal questionnaire. These surveys can be divided into two groups: general surveys of lower urinary tract symptoms and surveys specific to overactive bladder. General questionnaires include: American Urological Association Symptom Index (AUASI), Urogenital Distress Inventory (UDI), Incontinence Impact Questionnaire (IIQ), and Bristol Female Lower Urinary Tract Symptoms (BFLUTS). Overactive bladder questionnaires include: Overactive Bladder Questionnaire (OAB-q), Urgency Questionnaire (UQ), Primary OAB Symptom Questionnaire (POSQ), and the International Consultation on Incontinence Questionnaire (ICIQ). OAB causes similar symptoms to some other conditions such as urinary tract infection (UTI), bladder cancer, and benign prostatic hyperplasia (BPH). Urinary tract infections often involve pain and hematuria (blood in the urine) which are typically absent in OAB. Bladder cancer usually includes hematuria and can include pain, both not associated with OAB, and the common symptoms of OAB (urgency, frequency, and nocturia) may be absent. BPH frequently includes symptoms at the time of voiding as well as sometimes including pain or hematuria, and all of these are not usually present in OAB. Diabetes insipidus, which causes high frequency and volume, though not necessarily urgency. Classification There is some controversy about the classification and diagnosis of OAB. Some sources classify overactive bladder into two different variants: "wet" (i.e., an urgent need to urinate with involuntary leakage) or "dry" (i.e., an urgent need to urinate but no involuntary leakage). Wet variants are more common than dry variants. The distinction is not absolute; one study suggested that many classified as "dry" were actually "wet" and that people with no history of any leakage may have had other syndromes.OAB is distinct from stress urinary incontinence, but when they occur together, the condition is usually known as mixed incontinence. Management A recent (2019) systematic review of studies related to urinary incontinence in women found that behavioral therapy, alone or combined with other treatments, is generally more effective than any other single treatment alone. Behavioral therapy as a treatment has been used to improve or cure urgency urinary incontinence, including improving patient satisfaction. Lifestyle Treatment for OAB includes nonpharmacologic methods such as lifestyle modification (fluid restriction, avoidance of caffeine), bladder retraining, and pelvic floor muscle (PFM) exercise. Timed voiding is a form of bladder training that uses biofeedback to reduce the frequency of accidents resulting from poor bladder control. This method is aimed at improving the persons control over the time, place and frequency of urination. Timed voiding programs involve establishing a schedule for urination. To do this, a person fills in a chart of voiding and leaking. From the patterns that appear in the chart, the person can plan to empty his or her bladder before he or she would otherwise leak. Some individuals find it helpful to use a vibrating reminder watch to help them remember to use the bathroom. Vibrating watches can be set to go off at certain intervals or at specific times throughout the day, depending on the watch. Through this bladder training exercise, the person can alter their bladders schedule for storing and emptying urine. Medications A number of antimuscarinic drugs (e.g., darifenacin, hyoscyamine, oxybutynin, tolterodine, solifenacin, trospium, fesoterodine) are frequently used to treat overactive bladder. Long term use, however, has been linked to dementia. β3 adrenergic receptor agonists (e.g., mirabegron, vibegron), may be used, as well. However, both antimuscarinic drugs and β3 adrenergic receptor agonists constitute a second-line treatment due to the risk of side effects.Few people get complete relief with medications and all medications are no more than moderately effective.A typical person with overactive bladder may urinate 12 times per day. Medication may reduce this number by 2-3 and reduce urinary incontinence events by 1-2 per day. Procedures Various devices (Urgent PC Neuromodulation System) may also be used. Botulinum toxin A (Botox) is approved by the Food and Drug Administration in adults with neurological conditions, including multiple sclerosis and spinal cord injury. Botulinum Toxin A injections into the bladder wall can suppress involuntary bladder contractions by blocking nerve signals and may be effective for up to 9 months. The growing knowledge of pathophysiology of overactive bladder fuelled a huge amount of basic and clinical research in this field of pharmacotherapy. A surgical intervention involves the enlargement of the bladder using bowel tissues, although generally used as a last resort. This procedure can greatly enlarge urine volume in the bladder.OAB may be treated with electrical stimulation, which aims to reduce the contractions of the muscle that tenses around the bladder and causes urine to pass out of it. There are invasive and non-invasive electrical stimulation options. Non-invasive options include the introduction of a probe into the vagina or anus, or the insertion of an electrical probe into a nerve near the ankle with a fine needle. These non-invasive options appear to reduce symptoms while they are in use, and are better than no treatment, or treatment with drugs, or pelvic floor muscle treatment, but the quality of evidence is low. It is unknown which electrical stimulation option works best. Also, it is unknown whether the benefits last after treatment stops. Prognosis Many people with OAB symptoms had those symptoms subside within a year, with estimates as high as 39%, but most have symptoms for several years. Epidemiology Earlier reports estimated that about one in six adults in the United States and Europe had OAB. The number of people affected with OAB increases with age, thus it is expected that OAB will become more common in the future as the average age of people living in the developed world is increasing. However, a recent Finnish population-based survey suggested that the number of people affected had been largely overestimated due to methodological shortcomings regarding age distribution and low participation (in earlier reports). It is suspected, then, that OAB affects approximately half the number of individuals as earlier reported.The American Urological Association reports studies showing rates as low as 7% to as high as 27% in men and rates as low as 9% to 43% in women. Urge incontinence was reported as higher in women. Older people are more likely to be affected, and the number of symptoms increases with age. See also National Association For Continence Underactive bladder References External links Sacco E, Bientinesi R, Marangi F, DAddessi A, Racioppi M, Gulino G, Pinto F, Totaro A, Bassi P (2011). "[Overactive bladder syndrome: the social and economic perspective]". Urologia (in Italian). 78 (4): 241–56. doi:10.5301/RU.2011.8886. PMID 22237808. S2CID 36693916. "Overactive Bladder". MedlinePlus. U.S. National Library of Medicine.

Would you describe Ovulation induction, to me Aarogya

Ovulation induction

Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles to reverse anovulation or oligoovulation. Scope The term ovulation induction can potentially also be used for: Final maturation induction, in the sense of triggering oocyte release from relatively mature ovarian follicles during late follicular phase. In any case, ovarian stimulation (in the sense of stimulating the development of oocytes) is often used in conjunction with triggering oocyte release, such as for proper timing of artificial insemination. Controlled ovarian hyperstimulation (stimulating the development of multiple follicles of the ovaries in one single cycle), has also appeared in the scope of ovulation induction. Controlled ovarian hyperstimulation is generally part of in vitro fertilization, and the aim is generally to develop multiple follicles (optimally between 11 and 14 antral follicles measuring 2–8 mm in diameter), followed by transvaginal oocyte retrieval, co-incubation, followed by embryo transfer of a maximum of two embryos at a time. Also, where anovulation or oligovulation is secondary to another disease, the treatment for the underlying disease can be regarded as ovulation induction, by indirectly resulting in ovulation.However, this article focuses on medical ovarian stimulation, during early to mid-follicular phase, without subsequent in vitro fertilization, with the aim of developing one or two ovulatory follicles (the maximum number before recommending sexual abstinence). Indications Ovulation induction helps reversing anovulation or oligoovulation, that is, helping women who do not ovulate on their own regularly, such as those with polycystic ovary syndrome (PCOS). Regimen alternatives The main alternatives for ovulation induction medications are: Antiestrogen, causing an inhibition of the negative feedback of estrogen on the pituitary gland, resulting in an increase in secretion of follicle-stimulating hormone. Medications in use for this effect are mainly clomifene citrate and tamoxifen (both being selective estrogen-receptor modulators), as well as letrozole (an aromatase inhibitor. Follicle-stimulating hormone, directly stimulating the ovaries. In women with anovulation, it may be an alternative after 7 to 12 attempted cycles of antiestrogens (as evidenced by clomifene citrate), since the latter ones are less expensive and more easy to control. Antiestrogens Clomifene citrate Clomifene citrate (or clomid) is the medication which is most commonly used to treat anovulation. It is a selective estrogen-receptor modulator, affecting the hypothalamic–pituitary–gonadal axis to respond as if there was an estrogen deficit in the body, in effect increasing the production of follicle-stimulating hormone. It is relatively easy and convenient to use. Clomifene appears to inhibit estrogen receptors in hypothalamus, thereby inhibiting negative feedback of estrogen on production of follicle-stimulating hormone. It may also result in direct stimulation of the hypothalamic-pituitary axis. It also has an effect on cervical mucus quality and uterine mucosa, which might affect sperm penetration and survival, hence its early administration during the menstrual cycle. Clomifene citrate is a very efficient ovulation inductor, and has a success rate of 67%. Nevertheless, it only has a 37% success rate in inducing pregnancy. This difference may be due to the anti-estrogenic effect which clomifene citrate has on the endometrium, cervical mucus, uterine blood flow, as well as the resulting decrease in the motility of the fallopian tubes and the maturation of the oocytes. Letrozole Letrozole has been used for ovarian stimulation by fertility doctors since 2001 because it has fewer side-effects than clomiphene and less chance of multiple gestation. A study of 150 babies following treatment with letrozole or letrozole and follicle-stimulating hormone presented at the American Society of Reproductive Medicine 2005 Conference found no difference in overall abnormalities but did find a significantly higher rate of locomotor and cardiac abnormalities among the group having taken letrozole compared to natural conception. A larger, follow-up study with 911 babies compared those born following treatment with letrozole to those born following treatment with clomiphene. That study also found no significant difference in the rate of overall abnormalities, but found that congenital cardiac anomalies was significantly higher in the clomiphene group compared to the letrozole group. Dosage is generally 2.5 to 7.5 mg daily over 5 days. A higher dose of up to 12.5 mg per day results in increased follicular growth and a higher number of predicted ovulations, without a detrimental effect on endometrial thickness, and is considered in those who do not respond adequately to a lower dose. Tamoxifen Tamoxifen affects estrogen receptors in a similar fashion as clomifene citrate. It is often used in the prevention and treatment of breast cancer. It can therefore also be used to treat patients that have a reaction to clomifene citrate. Follicle-stimulating hormone Preparations of follicle-stimulating hormone mainly include those derived from the urine of menopausal women, as well as recombinant preparations. The recombinant preparations are more pure and more easily administered, but they are more expensive. The urinary preparations are equally effective and less expensive, but are not as convenient to administer as they are available in vials versus injection pens. Gonadotropin-releasing hormone pump The gonadotropin-releasing hormone pump is used to release doses in a pulsatile fashion. This hormone is synthesised by the hypothalamus and induces the secretion of follicle-stimulating hormone by the pituitary gland. Gonadotropin-releasing hormone must be delivered in a pulsatile fashion to imitate the random secretion of the hypothalamus in order to stimulate the pituitary into secreting luteinizing hormone and follicle-stimulating hormone. The gonadotropin-releasing hormone pump is the size of a cigarette box and has a small catheter. Unlike other treatments, using the gonadotropin-releasing hormone pump usually does not result in multiple pregnancies. Filicori from the University of Bologna suggests that this might be because gonadotrophins are absent when the treatment is initiated, and therefore the hormones released by the pituitary (luteinizing hormone and follicle-stimulating hormone) can still take part in the retro-control of gonadotrophin secretion, mimicking the natural cycle. This treatment can also be used for underweight and/or anorexic patients; it has also been used in certain cases of hyperprolactimenia. National and regional usage In the Nordic countries, letrozole is practically the standard initial regimen used for ovulation induction, since no formulation of clomifene is registered for use there.India banned the usage of letrozole in 2011, citing potential risks to infants. In 2012, an Indian parliamentary committee said that the drug controller office colluded with letrozoles makers to approve the drug for infertility in India. Technique Although there are many possible additional diagnostic and interventional techniques, protocols for ovulation induction generally consist of: Determining the first day of the last menstruation, which is termed day 1. In case of amenorrhea, a period can be induced by intake of an oral progestin for 10 days. Daily administration of the ovulation induction regimen, starting on day 3, 4, or 5, and it is usually taken for 5 days. Sexual intercourse or artificial insemination by the time of ovulation. Ultrasonography During ovulation induction, it is recommended to start at a low dose and monitor the ovarian response with transvaginal ultrasound, including discernment of the number of developing follicles. Initial exam is most commonly started 4–6 days after last pill. Serial transvaginal ultrasound can reveal the size and number of developing follicles. It can also provide presumptive evidence of ovulation such as sudden collapse of the preovulatory follicle, and an increase in fluid volume in the rectouterine pouch. After ovulation, it may reveal signs of luteinization such as loss of clearly defined follicular margins and appearance of internal echoes. Supernumerary follicles A cycle with supernumerary follicles is usually defined as one where there are more than two follicles >16 mm in diameter. It is generally recommended to have such cycles cancelled because of the risk of multiple pregnancy (see also the "Risks and side effects" section below). In cancelled cycles, the woman or couple should be warned of the risks in case of supernumerary follicles, and should avoid sexual intercourse or use contraception until the next menstruation. Induction of final maturation (such as done with hCG) may need to be withheld because of increased risk of ovarian hyperstimulation syndrome. The starting dose of the inducing drug should be reduced in the next cycle.Alternatives to cancelling a cycle are mainly: Aspiration of supernumerary follicles until one or two remain. Converting the protocol to IVF treatment with embryo transfer of up to two embryos only. Selective fetal reduction. This alternative confers a high risk of complications. Proceeding with any multiple pregnancy without fetal reduction, with the ensuing risk of complications. This alternative is not recommended. Lab tests The following laboratory tests may be used to monitor induced cycles: Serum estradiol levels, starting 4–6 days after last pill Adequacy of luteinizing hormone surge LH surge by urine tests 3 to 4 days after last clomifene pill Post-coital test 1–3 days before ovulation to check whether there are at least 5 progressive sperm per HPF Mid-luteal progesterone, with at least 10 ng/ml 7–9 days after ovulation being regarded as adequate. Final maturation induction Final maturation induction and release, such as by human chorionic gonadotropin (HCG or hCG) or recombinant luteinizing hormone, results in a predictable time of ovulation, with the interval from drug administration to ovulation depending on the type of drug. This avails for sexual intercourse or intrauterine insemination to conveniently be scheduled at ovulation, the most likely time to achieve pregnancy.As evidenced by clomifene-induced cycles, however, triggering oocyte release has been shown to decrease pregnancy chances compared to frequent monitoring with LH surge tests. Therefore, in such cases, triggering oocyte release is best reserved for women who require intrauterine insemination and in whom luteinizing hormone monitoring proves difficult or unreliable. It may also be used when luteinizing hormone monitoring has no shown an luteinizing hormone surge by cycle day 18 (where cycle day 1 is the first day of the preceding menstruation) and there is an ovarian follicle of over 20 mm in size. Repeat cycles Ovulation induction can be repeated every menstrual cycle. For clomifene, the dosage may be increased by 50-mg increments in subsequent cycles until ovulation is achieved. However, at a dosage of 200 mg, further increments are unlikely to increase pregnancy chances.It is not recommended by the manufacturer of clomifene to use it for more than 6 consecutive cycles. In women with anovulation, 7 - 12 attempted cycles of pituitary feedback regimens (as evidenced by clomifene citrate) are recommended before switching to gonadotrophins, since the latter ones are more expensive and less easy to control.It is no longer recommended to perform an ultrasound examination to exclude any significant residual ovarian enlargement before each new treatment cycle. Risks and side effects Ultrasound and regular hormone checks mitigate risks throughout the process. However, there are still some risks with the procedure. Ovarian hyperstimulation syndrome occurs in 5-10% of cases. Symptoms depend on whether the case is mild, moderate, or severe, and can range from bloating and nausea, through to shortness of breathe, pleural effusion, and excessive weight gain (more than 2 pounds per day). Multiple pregnancy There is also the risk that more than one egg is produced, leading to twins or triplets. Women with polycystic ovary syndrome may be particularly at risk. Multiple pregnancy occurs in approximately 15-20% of cases following cycles induced with gonadotrophins such as human menopausal gonadotropin and follicle-stimulating hormone. The risks associated with multiple pregnancy are much higher than singleton pregnancy; incidence of perinatal death is seven times higher in triplet births and five times higher in twin births than the risks associated with a singleton pregnancy. It is therefore important to adapt the treatment to each individual patient. If more than one or two ovulatory follicles are detected on ultrasonography, sexual abstinence is recommended. Alternatives In vitro fertilization, including controlled ovarian hyperstimulation. In vitro maturation is letting ovarian follicles mature in vitro, and this technique can potentially be an alternative both to anovulation reversal and oocyte release triggering. Rather, oocytes can mature outside the body, such as prior to IVF. Hence, no (or at least a lower dose of) gonadotropins have to be injected in the body. However, there still isnt enough evidence to prove the effectiveness and security of the technique. == References ==

Aarogya, elaborate on Paracentesis

Paracentesis

Paracentesis (from Greek κεντάω, "to pierce") is a form of body fluid sampling procedure, generally referring to peritoneocentesis (also called laparocentesis or abdominal paracentesis) in which the peritoneal cavity is punctured by a needle to sample peritoneal fluid.The procedure is used to remove fluid from the peritoneal cavity, particularly if this cannot be achieved with medication. The most common indication is ascites that has developed in people with cirrhosis. Indications It is used for a number of reasons: to relieve abdominal pressure from ascites to diagnose spontaneous bacterial peritonitis and other infections (e.g. abdominal TB) to diagnose metastatic cancer to diagnose blood in peritoneal space in trauma For ascites The procedure is often performed in a doctors office or an outpatient clinic. In an experts hands, it is usually very safe, although there is a small risk of infection, excessive bleeding or perforating a loop of bowel. These last two risks can be minimized greatly with the use of ultrasound guidance.The patient is requested to urinate before the procedure; alternately, a Foley catheter is used to empty the bladder. The patient is positioned in the bed with the head elevated at 45–60 degrees to allow fluid to accumulate in lower abdomen. After cleaning the side of the abdomen with an antiseptic solution, the physician numbs a small area of skin and inserts a large-bore needle with a plastic sheath 2 to 5 cm (1 to 2 in) in length to reach the peritoneal (ascitic) fluid. The needle is removed, leaving the plastic sheath to allow drainage of the fluid. The fluid is drained by gravity, a syringe, or by connection to a vacuum bottle. Several litres of fluid may be drained during the procedure; however, if more than two litres are to be drained, it will usually be done over the course of several treatments. After the desired level of drainage is complete, the plastic sheath is removed and the puncture site bandaged. The plastic sheath can be left in place with a flow control valve and protective dressing if further treatments are expected to be necessary.If fluid drainage in cirrhotic ascites is more than 5 litres, patients may receive intravenous serum albumin (25% albumin, 8g/L) to prevent hypotension (low blood pressure). There has been debate as to whether albumin administration confers benefit, but a recent 2016 meta-analysis concluded that it can reduce mortality after large-volume paracentesis significantly. However, for every end-point investigated, while albumin was favorable as compared to other agents (e.g., plasma expanders, vasoconstrictors), these were not statistically significant and the meta-analysis was limited by the quality of the studies — two of which that were in fact unsuitable — included in it.The procedure generally is not painful and does not require sedation. The patient is usually discharged within several hours following post-procedure observation provided that blood pressure is otherwise normal and the patient experiences no dizziness. Fluid analysis The serum-ascites albumin gradient can help determine the cause of the ascites.The ascitic white blood cell count can help determine if the ascites is infected. A count of 250 neutrophils per ml or higher is considered diagnostic for spontaneous bacterial peritonitis. Cultures of the fluid can be taken, but the yield is approximately 40% (72-90% if blood culture bottles are used). Contraindications Mild hematologic abnormalities do not increase the risk of bleeding. The risk of bleeding may be increased if: prothrombin time > 21 seconds international normalized ratio > 1.6 platelet count < 50,000 per cubic millimeter.Absolute contraindication is the acute abdomen that requires surgery. Relative contraindications are: Pregnancy Distended urinary bladder Abdominal wall cellulitis Distended bowel Intra-abdominal adhesions. See also Anterior chamber paracentesis References External links WebMD: Patient guide

Give me a short description about Paroxysmal nocturnal hemoglobinuria , Aarogya

Paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the bodys innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. Other key features of the disease, such as the high incidence of venous blood clot formation, are incompletely understood.PNH is the only hemolytic anemia caused by an acquired (rather than inherited) intrinsic defect in the cell membrane (deficiency of glycophosphatidylinositol or GPI) leading to the absence of protective exterior surface proteins that normally attach via a GPI anchor. It may develop on its own ("primary PNH") or in the context of other bone marrow disorders such as aplastic anemia ("secondary PNH"). Only a minority of affected people have the telltale red urine in the morning that originally gave the condition its name.Allogeneic bone marrow transplantation is the only cure, but has significant rates of additional medical problems and death. The monoclonal antibody eculizumab reduces the need for blood transfusions and improves quality of life for those affected by PNH. Eculizumab dramatically alters the natural course of PNH, reducing symptoms and disease complications as well as improving survival to the extent that it may be equivalent to that of the general population. Eculizumab costs at least US$440,000 for a single year of treatment and has been reported as one of the worlds most expensive drugs. Signs and symptoms The classic sign of PNH is red discoloration of the urine due to the presence of hemoglobin and hemosiderin from the breakdown of red blood cells. As the urine is more concentrated in the morning, this is when the color is most pronounced. This phenomenon mainly occurs in those who have the primary form of PNH, who will notice this at some point in their disease course. The remainder mainly experience the symptoms of anemia, such as tiredness, shortness of breath, and palpitations.A small proportion of patients report attacks of abdominal pain, difficulty swallowing and pain during swallowing, as well as erectile dysfunction in men; this occurs mainly when the breakdown of red blood cells is rapid, and is attributable to spasm of smooth muscle due to depletion of nitric oxide by red cell breakdown products.Forty percent of people with PNH develop thrombosis (a blood clot) at some point in their illness. This is the main cause of severe complications and death in PNH. These may develop in common sites (deep vein thrombosis of the leg and resultant pulmonary embolism when these clots break off and enter the lungs), but in PNH blood clots may also form in more unusual sites: the hepatic vein (causing Budd-Chiari syndrome), the portal vein of the liver (causing portal vein thrombosis), the superior or inferior mesenteric vein (causing mesenteric ischemia) and veins of the skin. Cerebral venous thrombosis, an uncommon form of stroke, is more common in those with PNH. Pathophysiology All cells have proteins attached to their membranes, often serving as a mode of communication or signaling between the cell and the surrounding environment. These signaling proteins are physically attached to the cell membrane in various ways, commonly anchored by glycolipids such as glycosyl phosphatidylinositols (GPI). PNH occurs as a result of a defect in the assembling of these glycolipid-protein structures on the surface of blood cells.The most common defective enzyme in PNH is phosphatidylinositol glycan A (PIGA), one of several enzymes needed to make GPI. The gene that codes for PIGA is located on the X chromosome, which means that only one active copy of the gene for PIGA is present in each cell (initially, females have two copies, but one is silenced through X-inactivation). A mutation in the PIGA gene can lead to the absence of GPI anchors expressed on the cell membrane. When this mutation occurs in a hematopoietic stem cell in the bone marrow, all of the cells it produces will also have the defect.Several of the proteins that anchor to GPI on the cell membrane are used to protect the cell from destruction by the complement system, and, without these anchors, the cells are more easily targeted by the complement proteins. Although red blood cells, white blood cells, and platelets are targeted by complement, red blood cells are particularly vulnerable to lysis. The complement system is part of the innate immune system and has a variety of functions, from destroying invading microorganisms by opsonization to direct destabilization by the membrane attack complex. The main proteins that protect blood cells from destruction are decay-accelerating factor (DAF/CD55), which disrupts formation of C3-convertase, and protectin (CD59/MIRL/MAC-IP), which binds the membrane attack complex and prevents C9 from binding to the cell.The symptoms of esophageal spasm, erectile dysfunction, and abdominal pain are attributed to the fact that hemoglobin released during hemolysis binds with circulating nitric oxide, a substance that is needed to relax smooth muscle. This theory is supported by the fact that these symptoms improve on administration of nitrates or sildenafil (Viagra), which improves the effect of nitric oxide on muscle cells. There is a suspicion that chronic hemolysis causing chronically depleted nitric oxide may lead to the development of pulmonary hypertension (increased pressure in the blood vessels supplying the lung), which in turn puts strain on the heart and causes heart failure.Historically, the role of sleep and night in this disease (the "nocturnal" component of the name) has been attributed to acidification of the blood at night due to relative hypoventilation and accumulation of carbon dioxide in the blood during sleep. This hypothesis has been questioned by researchers who note that not all those with PNH have increased hemolysis during sleep, so it is uncertain how important a role sleep actually plays in this disease. Diagnosis Blood tests in PNH show changes consistent with intravascular hemolytic anemia: low hemoglobin, raised lactate dehydrogenase, raised bilirubin (a breakdown product of hemoglobin), and decreased levels of haptoglobin; there can be raised reticulocytes (immature red cells released by the bone marrow to replace the destroyed cells) if there is no iron deficiency present. The direct antiglobulin test (DAT, or direct Coombs test) is negative, as the hemolysis of PNH is not caused by antibodies. If the PNH occurs in the setting of known (or suspected) aplastic anemia, abnormal white blood cell counts and decreased platelet counts may be seen at this. In this case, anemia may be caused by insufficient red blood cell production in addition to the hemolysis.Historically, the sucrose lysis test, in which a patients red blood cells are placed in low-ionic-strength solution and observed for hemolysis, was used for screening. If this was positive, the Hams acid hemolysis test (after Dr Thomas Ham, who described the test in 1937) was performed for confirmation. The Ham test involves placing red blood cells in mild acid; a positive result (increased RBC fragility) indicates PNH or Congenital dyserythropoietic anemia. This is now an obsolete test for diagnosing PNH due to its low sensitivity and specificity.Today, the gold standard is flow cytometry for CD55 and CD59 on white and red blood cells. Based on the levels of these cell proteins, erythrocytes may be classified as type I, II, or III PNH cells. Type I cells have normal levels of CD55 and CD59; type II have reduced levels; and type III have absent levels. The fluorescein-labeled proaerolysin (FLAER) test is being used more frequently to diagnose PNH. FLAER binds selectively to the glycophosphatidylinositol anchor and is more accurate in demonstrating a deficit than simply for CD59 or CD55. Classification PNH is classified by the context under which it is diagnosed: Classic PNH. Evidence of PNH in the absence of another bone marrow disorder. PNH in the setting of another specified bone marrow disorder such as aplastic anemia and myelodysplastic syndrome (MDS). Subclinical PNH. PNH abnormalities on flow cytometry without signs of hemolysis. Screening There are several groups where screening for PNH should be undertaken. These include patients with unexplained thrombosis who are young, have thrombosis in an unusual site (e.g. intra-abdominal veins, cerebral veins, dermal veins), have any evidence of hemolysis (e.g. a raised LDH), or have a low red blood cell, white blood cell, or platelet count. Those who have a diagnosis of aplastic anemia should be screened annually. Treatment Acute attacks There is disagreement as to whether steroids (such as prednisolone) can decrease the severity of hemolytic crises. Transfusion therapy may be needed; in addition to correcting significant anemia, this suppresses the production of PNH cells by the bone marrow, and indirectly the severity of the hemolysis. Iron deficiency develops with time, due to losses in urine, and may have to be treated if present. Iron therapy can result in more hemolysis as more PNH cells are produced. Long-term PNH is a chronic condition. In patients with only a small clone and few problems, monitoring of the flow cytometry every six months gives information on the severity and risk of potential complications. Given the high risk of thrombosis in PNH, preventive treatment with warfarin decreases the risk of thrombosis in those with a large clone (50% of white blood cells type III).Episodes of thrombosis are treated as they would in other patients, but, given that PNH is a persisting underlying cause, it is likely that treatment with warfarin or similar drugs needs to be continued long-term after an episode of thrombosis. Eculizumab In 2007, the drug eculizumab was approved for the treatment of PNH. Prior to eculizumab, the median life expectancy of an individual with PNH was approximately 10 years. Since that time, short and mid-term studies of patients on eculizumab demonstrate that the drug returns the patient to a normal life expectancy, improves quality of life, and decreases the need for blood transfusions.Eculizumab is controversial due to its high cost, as it is among the most expensive pharmaceuticals in the world, with a price of US$440,000 per person per year. Eculizumab is a humanized monoclonal antibody that acts as a terminal complement inhibitor. The drug interferes with the formation of the membrane attack complex in erythrocytes by binding to C5, compensating for the loss of protective function that results from CD59 deficiency. This alleviates the primary source of intravascular hemolysis, but it does not reduce the opsonization of erythrocytes caused by CD55 deficiency, so patients who receive this medication often still experience mild to moderate hemolysis. The U.S. Food and Drug Administration (FDA) has issued a black-box warning as those who take the medication have a 1,000 to 2,000-fold greater risk of invasive meningococcal disease. People on eculizumab are strongly advised to receive meningococcal vaccination at least two weeks prior to starting therapy and to consider preventative antibiotics for the duration of treatment. Pegcetacoplan Pegcetacoplan was approved for medical use in the United States in May 2021. Epidemiology PNH is rare, with an annual rate of 1-2 cases per million. The prognosis without disease-modifying treatment is 10–20 years. Many cases develop in people who have previously been diagnosed with aplastic anemia or myelodysplastic syndrome. The fact that PNH develops in MDS also explains why there appears to be a higher rate of leukemia in PNH, as MDS can sometimes transform into leukemia.25% of female cases of PNH are discovered during pregnancy. This group has a high rate of thrombosis, and the risk of death of both mother and child are significantly increased (20% and 8% respectively). History The first description of paroxysmal hemoglobinuria was by the German physician Paul Strübing (Greifswald, 1852–1915) during a lecture in 1881, later published in 1882. Later comprehensive descriptions were made by Ettore Marchiafava and Alessio Nazari in 1911, with further elaborations by Marchiafava in 1928 and Ferdinando Micheli in 1931.The Dutch physician Enneking coined the term "paroxysmal nocturnal hemoglobinuria" (or haemoglobinuria paroxysmalis nocturna in Latin) in 1928, which has since become the default description. References == External links ==

Hello Aarogya, could you help me understand about Patent ductus arteriosus

Patent ductus arteriosus

Patent ductus arteriosus (PDA) is a medical condition in which the ductus arteriosus fails to close after birth: this allows a portion of oxygenated blood from the left heart to flow back to the lungs by flowing from the aorta, which has a higher pressure, to the pulmonary artery. Symptoms are uncommon at birth and shortly thereafter, but later in the first year of life there is often the onset of an increased work of breathing and failure to gain weight at a normal rate. With time, an uncorrected PDA usually leads to pulmonary hypertension followed by right-sided heart failure. The ductus arteriosus is a fetal blood vessel that normally closes soon after birth. In a PDA, the vessel does not close, but remains patent (open), resulting in an abnormal transmission of blood from the aorta to the pulmonary artery. PDA is common in newborns with persistent respiratory problems such as hypoxia, and has a high occurrence in premature newborns. Premature newborns are more likely to be hypoxic and have PDA due to underdevelopment of the heart and lungs. If transposition of the great vessels is present in addition to a PDA, the PDA is not surgically closed since it is the only way that oxygenated blood can mix with deoxygenated blood. In these cases, prostaglandins are used to keep the PDA open, and NSAIDs are not administered until surgical correction of the two defects is completed. Signs and symptoms Common symptoms include: dyspnea (shortness of breath)Signs include: tachycardia (a heart rate exceeding the normal resting rate) continuous "machine-like" (also described as "rolling-thunder" and "to-and-fro") heart murmur (usually from aorta to pulmonary artery, with higher flow during systole and lower flow during diastole) cardiomegaly (enlarged heart, reflecting ventricular dilation and volume overload) left subclavicular thrill bounding pulse widened pulse pressure increased cardiac output increased systolic pressure poor growth differential cyanosis, i.e. cyanosis of the lower extremities but not of the upper body.People with patent ductus arteriosus typically present in good health, with normal respirations and heart rate. If the PDA is moderate or large, widened pulse pressure and bounding peripheral pulses are frequently present, reflecting increased left ventricular stroke volume and diastolic run-off of blood into the (initially lower-resistance) pulmonary vascular bed. Eisenmenger physiology is pulmonary hypertension due to a left-to-right shunt. Prominent suprasternal and carotid pulsations may be noted secondary to increased left ventricular stroke volume. Risk factors Known risk factors include: Preterm birth Congenital rubella syndrome Chromosomal abnormalities (e.g., Down syndrome) Genetic conditions such as Loeys–Dietz syndrome (would also present with other heart defects), Wiedemann–Steiner syndrome, and CHARGE syndrome. Fetal Alcohol Spectrum Disorder Diagnosis PDA is usually diagnosed using noninvasive techniques. Echocardiography (in which sound waves are used to capture the motion of the heart) and associated Doppler studies are the primary methods of detecting PDA. Electrocardiography (ECG), in which electrodes are used to record the electrical activity of the heart, is not particularly helpful as no specific rhythms or ECG patterns can be used to detect PDA.A chest X-ray may be taken, which reveals overall heart size (as a reflection of the combined mass of the cardiac chambers) and the appearance of blood flow to the lungs. A small PDA most often accompanies a normal-sized heart and normal blood flow to the lungs. A large PDA generally accompanies an enlarged cardiac silhouette and increased blood flow to the lungs. Prevention Some evidence suggests that intravenous NSAIDs, such as indomethacin, administration on the first day of life to all preterm infants reduces the risk of developing a PDA and the complications associated with PDA. Intravenous Indomethacin treatment in premature infants also may reduce the need for surgical intervention. Administering ibuprofen probably helps to prevent PDA and reduce the need for surgery but it also likely increases the risk of kidney complications. Treatment Symptomatic PDA can be treated with both surgical and non-surgical methods. Conservative Neonates without adverse symptoms may simply be monitored as outpatients. Surgery Surgically, the DA may be closed by ligation (though support in premature infants is mixed). This can either be performed manually and be tied shut, or with intravascular coils or plugs that leads to formation of a thrombus in the DA.Devices developed by Franz Freudenthal block the blood vessel with woven structures of nitinol wire.Newer procedures performed effectively in older, bigger children include catheter PDA occlusion and video-assisted thoracoscopic PDA clipping. Prostaglandin inhibitors Because prostaglandin E2 is responsible for keeping the DA open, NSAIDs (which can inhibit prostaglandin synthesis) such as indomethacin or a special form of ibuprofen have been used to initiate PDA closure. Findings from a 2015 systematic review concluded that, for closure of a PDA in preterm and/or low birth weight infants, ibuprofen is as effective as indomethacin. It also causes fewer side effects (such as transient acute kidney injury) and reduces the risk of necrotising enterocolitis. A review and meta-analysis showed that paracetamol may be effective for closure of a PDA in preterm infants. A 2018 network meta-analysis that compared indomethacin, paracetamol and ibuprofen at different doses and administration schemes among them found that a high dose of oral ibuprofen may offer the highest likelihood of closure in preterm infants. However, a 2020 systematic review found that early (≤7 days of life) or very early (≤72 hours of life) pharmacological treatment of symptomatic PDA does not reduce death or other poor clinical outcomes in preterm infants but instead increases their exposure to NSAIDS. Vasodilator therapy is suitable for people with Eisenmenger physiology. To assess improvement in people with Eisenmenger physiology, close monitory of toe oxygen saturation is required, for there exists a chance of reversal after a successful right-to-left shuntWhile indometacin can be used to close a PDA, some neonates require their PDA be kept open. Keeping a ductus arteriosus patent is indicated in neonates born with concurrent heart malformations, such as transposition of the great vessels. Drugs such as alprostadil, a PGE-1 analog, can be used to keep a PDA open until the primary defect is corrected surgically. Prognosis If left untreated, the disease may progress from left-to-right shunt (acyanotic heart) to right-to-left shunt (cyanotic heart), called Eisenmengers syndrome. Pulmonary hypertension is a potential long-term outcome, which may require a heart and/or lung transplant. Another complication of PDA is intraventricular hemorrhage. History Robert Edward Gross, MD performed the first successful ligation of a patent ductus arteriosus on a seven-year-old girl at Childrens Hospital Boston in 1938. Adult Since PDA is usually identified in infants, it is less common in adults, but it can have serious consequences, and is usually corrected surgically upon diagnosis. See also George Alexander Gibson References External links Patent Ductus Arteriosus Causes from US Department of Health and Human Services Patent Ductus Arteriosus from Merck Patent ductus arteriosus information for parents.

Hello Aarogya, explain a situation where Head lice infestation occurs

Head lice infestation

Head lice infestation, also known as pediculosis capitis, is the infection of the head hair and scalp by the head louse (Pediculus humanus capitis). Itching from lice bites is common. During a persons first infection, the itch may not develop for up to six weeks. If a person is infected again, symptoms may begin much more quickly. The itch may cause problems with sleeping. Generally, however, it is not a serious condition. While head lice appear to spread some other diseases in Africa, they do not appear to do so in Europe or North America.Head lice are spread by direct contact with the hair of someone who is infected. The cause of head lice infestations in children is not related to cleanliness. Other animals, such as cats and dogs, do not play a role in transmission. Head lice feed only on human blood and are only able to survive on human head hair. When adults, they are about 2 to 3 mm long. When not attached to a human, they are unable to live beyond three days. Humans can also become infected with two other lice – the body louse and the crab louse. To make the diagnosis, live lice must be found. Using a comb can help with detection. Empty eggshells (known as nits) are not sufficient for the diagnosis.Possible treatments include: combing the hair frequently with a fine tooth comb or shaving the head completely. A number of topical medications are also effective, including malathion, ivermectin, and dimethicone. Dimethicone, which is a silicone oil, is often preferred due to the low risk of side effects. Pyrethroids such as permethrin have been commonly used; however, they have become less effective due to increasing pesticide resistance. There is little evidence for alternative medicines.Head-lice infestations are common, especially in children. In Europe, they infect between 1 and 20% of different groups of people. In the United States, between 6 and 12 million children are infected a year. They occur more often in girls than boys. It has been suggested that historically, head lice infection were beneficial, as they protected against the more dangerous body louse. Infestations may cause stigmatization of the infected individual. Epidemiology Reliable data describing the usual incidence of infestation in the general public, in the average school community, or during specific times of the year are lacking. The number of cases of human louse infestations (or pediculosis) has increased worldwide since the mid-1960s, reaching hundreds of millions annually. It is estimated between 1 and 20% of specific groups in Europe are infected.Despite improvements in medical treatment and prevention of human diseases during the 20th century, head louse infestation remains stubbornly prevalent. In 1997, 80% of American elementary schools reported at least one outbreak of lice. Lice infestation during that same period was more prevalent than chickenpox.About 6–12 million children between the ages of 3 and 11 are treated annually for head lice in the United States alone. High levels of louse infestations have also been reported from all over the world, including Israel, Denmark, Sweden, U.K., France, and Australia.The United Kingdoms National Health Service report that lice have no preference for any type of hair be it clean, dirty, or short. The number of children per family, the sharing of beds and closets, hair washing habits, local customs and social contacts, healthcare in a particular area (e.g. school), and socioeconomic status were found to be factors in head louse infestation in Iran. Other studies found no relationship between frequency of brushing or shampooing. The California Department of Public Health indicates that chronic head lice infestation may be a sign of socioeconomic or family problems. Children between 4 and 13 years of age are the most frequently infested group. In the U.S., African-American children have lower rates of infestation.Head lice (Pediculus humanus capitis) infestation is most frequent on children aged 3–10 and their families. Females get head lice twice as often as males, and infestation in persons of Afro-Caribbean or other black descent could be rare due to difference in hair shape or width. But these children may have nits that hatch and the live lice could be transferred by head contact to other children. Signs and symptoms Head lice are generally uncomfortable, but typically do not constitute a serious condition. The most common symptom is itching of the head, which normally worsens 3 to 4 weeks after the initial infestation. The bite reaction is very mild, and it can be rarely seen between the hairs. Bites can be seen, especially in the neck of long-haired individuals when the hair is pushed aside. Swelling of the local lymph nodes and fever are rare. Itching may cause skin breakdown and uncommonly result in a bacterial infection. Many individuals do not experience symptoms. Itching may take 2–6 weeks to develop upon first infestation, and sooner in subsequent infestations.In Ethiopia, head lice appear to be able to spread louse-born epidemic typhus and Bartonella quintana. In Europe, the head lice do not appear to carry these infections. Transmission Head lice spreads through direct contact of the head of an infested person with the head of a non-infested person. The presence of live lice indicates an active infestation while the presence of nits indicates a past or currently inactive infection with the potential to become active. Head lice do not leap or spring as a means to transfer to their hosts; instead, they move by crawling. Transmission by indirect contact (e.g. sharing bedding, clothing, headwear, the same comb) is much less common. The cause of head lice infestations is not related to cleanliness. Neither hair length nor how often the hair is brushed affects the risk of infection. Pets are not vectors for head lice.Other lice that infest humans are the body louse and the crab louse (aka pubic lice). The claws of these three species are adapted to attach to specific hair diameters. Pubic lice are most often spread by sexual contact with an infested person. Body lice can be found on clothing and they are not known to burrow into the skin. Diagnosis The condition is diagnosed by finding live lice and unhatched eggs in the hair. Finding empty eggs is not enough. Dandruff, lint, sand, hair casts, and dried hairspray, can be mistaken for eggs and nits. This is made easier by using a magnifying glass or running a comb through the childs wet hair, the latter of which is the most assured method of diagnosis and can be used to monitor treatment. In questionable cases, a child can be referred to a health professional. However, head lice infestation is commonly overdiagnosed, with extinct infestations being mistaken for active ones. Infestations are only considered extinct if nits are more than 0.25 inches away from the scalp and nymphs and adult lice are absent. As a result, lice-killing treatments are more often used on non-infested than infested children. The use of a louse comb is the most effective way to detect living lice. With both methods, special attention should be paid to the area near the ears and the nape of the neck. The use of a magnifying glass to examine the material collected between the teeth of the comb could prevent misdiagnosis.The presence of nits alone, however, is not an accurate indicator of an active head louse infestation. Generally, white nits are empty egg casings, while brown nits may still contain viable louse larva. One way of determining the nit is to squeeze it between two fingernails; it gives a characteristic snapping pop sound as the egg bursts. Children with nits on their hair have a 35–40% chance of also being infested with living lice and eggs. If lice are detected, the entire family needs to be checked (especially children up to the age of 13 years) with a louse comb, and only those who are infested with living lice should be treated. As long as no living lice are detected, the child should be considered negative for head louse infestation. Accordingly, a child should be treated with a pediculicide only when living lice are detected on their hair (not because he/she has louse eggs/nits on the hair and not because the scalp is itchy). Prevention Examination of the childs head at regular intervals using a louse comb allows the diagnosis of louse infestation at an early stage. Early diagnosis makes treatment easier and reduces the possibility of infesting others. In times and areas when louse infestations are common, weekly examinations of children, especially those 4–15 years old, carried out by their parents, will aid control. Additional examinations are necessary if the child came in contact with infested individuals, if the child frequently scratches his/her head, or if nits suddenly appear on the childs hair. Clothes, towels, bedding, combs, and brushes, which came in contact with the infested individual, can be disinfected either by leaving them outside for at least two days or by washing them at 60 °C (140 °F) for 30 minutes. This is because adult lice can survive only one to two days without a blood meal and are highly dependent on human body warmth. Treatment There are a number of treatments effective for head lice. These methods include combs, shaving, medical creams, and hot air. Medical creams usually require two treatments a week apart. Head lice are not justification to keep children home from school as the risk of spread is low. Mechanical measures Wet combing (mechanical removal of lice through combing wet hair) can be used as treatment measure for those who are too young for pediculicide treatment, which is intended for 6 years of age or older. Wet combing a few times a day for a few weeks may also get rid of the infestation in half of people. This requires the use of a special lice comb with extra fine teeth. This is the recommended method for infants and women who are pregnant. Shaving the head can also effectively treat lice. Another treatment is the use of heated air applied by a hair dryer. This can be of special use in the early stages of an infestation, since it has very high mortality for eggs. Medications There are many medications which can kill lice. Dimethicone is between 70 and 97% effective with a low rate of side effects, and thus is seen as the preferred treatment. It works by physical means and there is no evidence of pesticide resistance. Ivermectin is around 80% effective, but can cause local skin irritation. Malathion has an effectiveness around 90%, but theres the possibility of toxicity. Pyrethroids such as permethrin, while commonly used, have lower rates of effectiveness due to the resistance among lice. Effectiveness varies from 10 to 80%, depending on the population studied. Medications within a lotion appear to work better than those within a shampoo. Benzyl alcohol appears effective but it is unclear if it is better than standard treatments. Abametapir was approved for medical use in the United States in July 2020.Resistance to several commonly used treatments is increasing worldwide, with patterns of resistance varying by region. Head lice have demonstrated resistance to permethrin, malathion, phenothrin, and carbaryl in several countries around the world. A previous method used to delay resistance included utilizing a rotating list of recommended insecticides by health authorities. The mosaic model is the current recommendation, in which it is advised to use one product for a treatment course, followed by a different insecticide from another substance class if the first treatment fails. Home Remedies Tea tree oil has been promoted as a treatment for head lice; however, there is no clear evidence of its effectiveness. A 2012 review of head lice treatment recommended against the use of tea tree oil for children because it could cause skin irritation or allergic reactions, because of contraindications, and because of a lack of knowledge about the oils safety and effectiveness. Other home remedies, such as putting vinegar, isopropyl alcohol, olive oil, mayonnaise, or melted butter under a shower cap, have been disproven. The CDC states that swimming has no effect on drowning lice, and can decrease the effectiveness of some treatments. Environment After treatment, people are often instructed to wash all bedding and vacuum all areas the head may have been, such as car seats, coat hoods, and sofas, but this is not always necessary, since adult lice will die within 2 days without a blood meal, and newly hatched lice die within minutes of hatching. Combs and brushes may be deloused in boiling water for 5–10 minutes. Items may also be frozen for 24 hours well below the freezing point of water to ensure that ice crystals form within the cells of the lice. Outbreak Management In addition to environmental management, an outbreak of head lice infestation requires synchronous treatment of all who are infested and evaluation of those who have been exposed or are suspected to have head lice. Synchronous ovoidal dimethicone treatment has been shown to successfully manage and terminate outbreaks, and a single treatment is likely sufficient. Other treatment methods can be repeated 8–10 days following initial treatment, and may sometimes require a third treatment. Outbreak status and treatment effectiveness can be monitored using the wet combing method. Stigma Head lice infestations are notably common, as is the stigma associated with those who experience infestations. Such stigma is even evidenced in the English language as the term "lousy," an adjective that describes something as very poor, bad or disgusting. Misperceptions of those infected with head lice include that it is associated with low socioeconomic status, poor hygiene, unhealthiness, immigration status, and homelessness. Though these negative beliefs are unfounded, they can lead to consequences for both the caregivers and the affected individual, such as social exclusion and isolation from peers, victim-blaming, caregiver strain, inappropriate or unsafe treatment practices, and missed work or school. Public Health Implications Over-treatment or mismanagement of head lice, which can be driven by stigma, has important implications at the level of the individual and community. Though evidence-based guidelines from the CDC, American Academy of Pediatrics (AAP) and National Association of School Nurses (NASN) all recommend discontinuing "no-nit" policies in schools (meaning that a child does not need to be free of nits before returning to school), 80 percent of schools in the United States still maintain stringent policies that prevent children with infestations from attending. Thus, to foster a return to school in a timely fashion, these policies can encourage unsafe or harsh treatment practices, including chemicals like bleach or kerosene. Similarly, over-treatment of head-lice using pesticide-based pediculicides has been linked to increased resistance and declining efficacy of these treatments. Society and culture To a Louse (on a ladys bonnet). Perhaps the most widely known cultural reference to pediculosis capitis, occurring in a noted poem by Robert Burns. Other animals Lice infestation in general is known as pediculosis, and occurs in many mammalian and bird species. Lice infesting other host species are not the same organism as that which causes head lice infestations in humans, nor do the three louse species which infest humans infest any other host species. References External links CDC: Head lice

Hey Aarogya, explain a situation where Pediculosis corporis occurs

Pediculosis corporis

Pediculosis corporis is a cutaneous condition caused by body lice (specifically Pediculus humanus humanus) that lay their eggs in the seams of clothing.: 447 Signs and symptoms Body lice are a nuisance in themselves and cause intense itching. They are also vectors (transmitters) of other diseases and can spread epidemic typhus, trench fever, and louse-borne relapsing fever. Risk factors Body lice are spread through prolonged direct physical contact with a person who has them or through contact with articles such as clothing, beds, bed linens, or towels that have been in contact with an infested person. In the United States, body lice infestations are rare, typically found mainly in homeless transient populations who do not have access to bathing and regular changes of clean clothes. Infestation is unlikely to persist on anyone who bathes regularly and who has at least weekly access to freshly laundered clothing and bedding.Although louse-borne (epidemic) typhus is no longer widespread, outbreaks of this disease still occur during times of war, civil unrest, natural or man-made disasters, and in prisons where people live together in unsanitary conditions. Louse-borne typhus still exists in places where climate, chronic poverty, and social customs or war and social upheaval prevent regular changes and laundering of clothing. Pathophysiology Body lice frequently lay their eggs on or near the seams of clothing. They must feed on blood and usually only move to the skin to feed. They exist worldwide and infest people of all races and can therefore spread rapidly under crowded living conditions where hygiene is poor (homeless, refugees, victims of war or natural disasters). Treatment A body lice infestation is treated by improving the personal hygiene of the infested person, including assuring a regular (at least weekly) change of clean clothes. Clothing, bedding, and towels used by the infested person should be laundered using hot water (at least 130 °F or 54 °C) and machine dried using the hot cycle.Sometimes the infested person also is treated with a pediculicide (a medicine that can kill lice); however, a pediculicide generally is not necessary if hygiene is maintained and items are laundered appropriately at least once a week. A pediculicide should be applied exactly as directed on the bottle or by a physician.Delousing can also be practically achieved by boiling all clothes and bedding, or washing them at a high temperature. A temperature of 130 °F or 54 °C for 5 minutes will kill most of the adults and prevent eggs from hatching. Leaving the clothes unwashed, but unworn for a full week, also results in the death of lice and eggs.Where this is not practical or possible, powder dusting with 10% DDT, 1% malathion or 1% permethrin is also effective. Oral ivermectin at a dose of 12 mg on days 0, 7 and 14 has been used in a small trial of 33 people in Marseilles, but did not result in complete eradication, although there was a significant fall in the number of parasites and proportion of people infected. At the moment, ivermectin cannot be routinely recommended for the treatment of body lice. Medication, insecticide or burning of clothing and bedding is usually not necessary, as the problem normally goes away with daily bathing, and weekly (or more frequent) laundering and drying of clothing, bedding, towels, etc. in a hot clothes drier. See also List of cutaneous conditions Pediculosis Skin lesion Vagabonds leukomelanoderma == References ==

Aarogya, explain a scenario commonly referred as Pediculosis pubis

Pediculosis pubis

Pediculosis pubis (also known as "crabs" and "pubic lice") is an infestation by the pubic louse, Pthirus pubis, a wingless insect which feeds on blood and lays its eggs (nits) on mainly pubic hair. Less commonly, hair near the anus, armpit, beard, eyebrows, moustache, and eyelashes may be involved. It is usually acquired during sex, but can be spread via bedding, clothing and towels, and is more common in crowded conditions where there is close contact between people.The main symptom is an intense itch in the groin, particularly at night. There may be some grey-blue discolouration at the feeding site, and eggs and lice may be visible. Scratch marks, crusting and scarring may be seen, and there may be signs of secondary bacterial infection.Diagnosis is by visualising the nits or live lice, either directly or with a magnifying glass. Investigations for other sexually transmitted infections (STIs) are usually performed.First line treatment usually contains permethrin and is available over the counter. Two rounds of treatment at least a week apart are usually required to kill newly hatched nymphs. Washing bedding and clothing in hot water kills the lice, and transmission can be prevented by avoiding sexual contact until no signs of infestation exist. Eggs may be removed by combing pubic hair with a comb dipped in vinegar. Sexual partners should be evaluated and treated.Infestation with pubic lice is found in all parts of the world and occurs in all ethnic groups and all levels of society. Worldwide, the condition affects about 2% of the population. Definition Pediculosis pubis is an infestation by the pubic louse, Pthirus pubis, a wingless insect which feeds on blood and lays its eggs (nits) on mainly pubic hair. Less commonly, hair near the anus, armpit, beard, eyebrows, moustache, and eyelashes may be involved. Although the presence of pubic lice are associated with the presence of other sexually transmitted diseases, pubic lice do not spread infectious diseases. Signs and symptoms The onset of symptoms is typically three weeks after the first infestation of lice and is mainly an intense itch in the pubic area and groin, particularly at night, resulting from an allergic reaction to the saliva of feeding lice. In some infestations, a characteristic grey-blue or slate coloration macule appears (maculae caeruleae) at the feeding site, which may last for days. Nits or live lice may be seen crawling on the skin. Louse droppings may be noticed as a black powder in the underwear.Scratch marks, crusting, scarring, rust-colored faecal material, blood stained underwear and secondary bacterial infection may sometimes be seen. Large lymph nodes in the groin and armpits may be felt. Some people with pubic lice infestation may not have any symptoms. Causes Spread Pubic lice are usually transmitted from one person to another during vaginal, oral or anal sex, whether a condom is used or not. One sexual encounter with an infected person carries a high risk of catching pubic lice. In some circumstances transmission can occur through kissing and hugging, and less likely via bedding, clothing and towels. The lice spread more easily in crowded conditions where the distance between people is close, allowing the lice to crawl from one person to another.Infestation on the eyebrows or eyelashes of a child may indicate sexual exposure or abuse. Characteristics and life cycle Pubic lice (Pthirus pubis) have three stages: the egg (also called a nit), the nymph, and the adult. They can be hard to see and are found firmly attached to the hair shaft. They are oval and usually yellow to white. Pubic lice nits take about 6–10 days to hatch. The nymph is an immature louse that hatches from the nit (egg). A nymph looks like an adult pubic louse but it is smaller. Pubic lice nymphs take about 2–3 weeks after hatching to mature into adults capable of reproducing. To live, a nymph must feed on blood. The adult pubic louse resembles a miniature crab when viewed through a strong magnifying glass. Pubic lice have six legs; their two front legs are very large and look like the pincher claws of a crab—thus the nickname "crabs". Pubic lice are tan to grayish-white in color. Females lay nits and are usually larger than males. To live, lice must feed on blood. If the louse falls off a person, it dies within 1–2 days. Eggs (nits) are laid on a hair shaft. Females will lay approximately 30 eggs during their 3–4 week life span. Eggs hatch after about a week and become nymphs, which look like smaller versions of the adults. The nymphs undergo three molts before becoming adults. Adults are 1.5–2.0 mm long and flattened. They are much broader in comparison to head and body lice. Adults are found only on the human host and require human blood to survive. Pubic lice are transmitted from person to person most-commonly via sexual contact, although fomites (bedding, clothing) may play a minor role in their transmission. Diagnosis Diagnosis is made by carefully looking at the pubic hair for nits, young lice and adult lice. Lice and nits can be removed either with forceps or by cutting the infested hair with scissors (with the exception of an infestation of the eye area). A magnifying glass, dermatoscope or a stereo-microscope can be used for identification. Testing for other sexually transmitted infections is recommended in those who are infested with pubic lice. Treatment Pubic lice can be treated at home. Available treatments may vary from country to country and include mainly permethrin-containing creams and lotions applied to cool dry skin.Treatment with medication is combined with combing pubic hair with a fine-toothed comb after applying vinegar directly to skin or dipping the comb in vinegar, to remove nits. It is recommended to wash bedding, clothing and towels in hot water or preferably in a washing machine at 50°C or higher. When this is not possible, the clothing can be stored in a sealed plastic bag for at least three days. Re-infestation can be prevented by wearing clean underwear at the start of treatment and after completing treatment. Shaving the affected hair is not essential. First line At first, treatment is usually with topical permethrin 1% cream, which can be bought over the counter without a prescription. It is applied to the areas affected by pubic lice and washed off after 10 minutes. Brands of permethrin include Lyclear, available in the UK as a creme rinse or dermal cream at 5% strengths. In the US, permethrin may be familiar as NIX, Actin and ElimiteAn alternative is the combination of pyrethrins and piperonyl butoxide, in a topical application, which include the brands Licide, and A-200, Pronto and RID shampoos. These medications are safe and effective when used exactly according to the instructions in the package or on the label. To kill newly hatched lice, both treatments can be repeated within the following seven to ten days.European guidelines state alternatives to permethrin as including either the application of 0.2% phenothrin (washed off after two hours), or 0.5% malathion lotions (washed off after 12 hours). The CDC states alternatives as topical 0.5% malathion or oral ivermectin. Other treatments Lindane is still used in a shampoo form in some non-European countries. Its licence was withdrawn by the European Medicines Agency in 2008. It may be considered as a last resort in some people who show resistance to other treatments, but is not recommended to be used for a second round of treatment. Lindane is not recommended in pregnant and breastfeeding women, children under the age of two years, and people who have extensive dermatitis. The FDA warns against use in people with a history of uncontrolled seizure disorders and cautious use in infants, children, the elderly, and individuals with other skin conditions (e.g., atopic dermatitis, psoriasis) and in those who weigh less than 110 lbs (50 kg). Carbaryl has been used since 1976 but found to have the potential to cause cancer in rodents and not to be as effective as previously thought. It is either not used at all or its use is restricted.Sexual partners should be evaluated and treated, and sexual contact should be avoided until all partners are better. Because of the strong association between the presence of pubic lice and sexually transmitted infections (STIs), affected people require investigation for other STIs. Eyes Infestation of the eyes is treated differently than other parts of the body. Lice can be removed with forceps or by removing or trimming the lashes. Eyelashes may be treated with a gentle petroleum jelly for occlusion. Complications Complications are usually as a result of persistent scratching and include thickening of the skin, darkened skin, and secondary bacterial infection including impetigo, conjunctivitis and blepharitis. Epidemiology Infestation with pubic lice is found in all parts of the world, occurs in all ethnic groups and all levels of society.Current worldwide prevalence has been very approximately estimated at two percent of the human population. Accurate numbers are difficult to acquire, because pubic lice infestations are not considered a reportable condition by many governments. Many cases are self-treated or treated discreetly by personal physicians, which further adds to the difficulty of producing accurate statistics.It has been reported that the trend of pubic hair removal has led to the destruction of the natural habitat of the crab louse populations in some parts of the world, thereby reducing the incidence of the disease. Etymology and history Infestation with pubic lice is also called phthiriasis or phthiriasis pubis, while infestation of eyelashes with pubic lice is called phthiriasis palpebrarum or pediculosis ciliarum. Linnaeus was first to describe and name the pubic louse in 1758, when he called it Pediculus pubis. The disease is spelled with phth, but the scientific name of the louse Pthirus pubis is spelled with pth (an etymologically incorrect spelling that was nonetheless officially adopted in 1958). Other animals Humans are the only known hosts of this parasite, although a closely related species, Pthirus gorillae, infects gorilla populations. References External links Crab louse on the UF / Institute of Food and Agriculture

Hello Aarogya, could you help me understand about Pellagra

Pellagra

Pellagra is a disease caused by a lack of the vitamin niacin (vitamin B3). Symptoms include inflamed skin, diarrhea, dementia, and sores in the mouth. Areas of the skin exposed to either sunlight or friction are typically affected first. Over time affected skin may become darker, stiffen, peel, or bleed.There are two main types of pellagra, primary and secondary. Primary pellagra is due to a diet that does not contain enough niacin and tryptophan. Secondary pellagra is due to a poor ability to use the niacin within the diet. This can occur as a result of alcoholism, long-term diarrhea, carcinoid syndrome, Hartnup disease, and a number of medications such as isoniazid. Diagnosis is typically based on symptoms and may be assisted by urine testing.Treatment is with either niacin or nicotinamide supplementation. Improvements typically begin within a couple of days. General improvements in diet are also frequently recommended. Decreasing sun exposure via sunscreen and proper clothing is important while the skin heals. Without treatment death may occur. The disease occurs most commonly in the developing world, often as a disease of poverty associated with malnutrition, specifically sub-Saharan Africa. Signs and symptoms The classic symptoms of pellagra are diarrhea, dermatitis, dementia, and death ("the four Ds"). A more comprehensive list of symptoms includes: Sensitivity to sunlight Dermatitis (characteristic "broad collar" rash known as casal collar) Hair loss Swelling Smooth, beefy red glossitis (tongue inflammation) Trouble sleeping Weakness Mental confusion or aggression Ataxia (lack of coordination), paralysis of extremities, peripheral neuritis (nerve damage) Diarrhea Dilated cardiomyopathy (enlarged, weakened heart) Eventually dementiaJ. Frostigs and Tom Spies—according to Cleary and Cleary—described more specific psychological symptoms of pellagra as: Psychosensory disturbances (impressions as being painful, annoying bright lights, odors intolerance causing nausea and vomiting, dizziness after sudden movements), Psychomotor disturbances (restlessness, tense and a desire to quarrel, increased preparedness for motor action), as well as Emotional disturbancesIndependently of clinical symptoms, blood level of tryptophan or urinary metabolites such as 2-pyridone/N-methylniacinamide ratio <2 or NAD/NADP ratio in red blood cells can diagnose pellagra. The diagnosis is confirmed by rapid improvements in symptoms after doses of niacin (250–500 mg/day) or niacin enriched food. Pathophysiology Pellagra can develop according to several mechanisms, classically as a result of niacin (vitamin B3) deficiency, which results in decreased nicotinamide adenine dinucleotide (NAD). Since NAD and its phosphorylated NADP form are cofactors required in many body processes, the pathological impact of pellagra is broad and results in death if not treated. The first mechanism is simple dietary lack of niacin. Second, it may result from deficiency of tryptophan, an essential amino acid found in meat, poultry, fish, eggs, and peanuts that the body uses to make niacin. Third, it may be caused by excess leucine, as it inhibits quinolinate phosphoribosyl transferase (QPRT) and inhibits the formation of niacin or nicotinic acid to nicotinamide mononucleotide (NMN) causing pellagra like symptoms to occur.Some conditions can prevent the absorption of dietary niacin or tryptophan and lead to pellagra. Inflammation of the jejunum or ileum can prevent nutrient absorption, leading to pellagra, and this can in turn be caused by Crohns disease. Gastroenterostomy can also cause pellagra. Chronic alcoholism can also cause poor absorption which combines with a diet already low in niacin and tryptophan to produce pellagra. Hartnup disease is a genetic disorder that reduces tryptophan absorption, leading to pellagra. Alterations in protein metabolism may also produce pellagra-like symptoms. An example is carcinoid syndrome, a disease in which neuroendocrine tumors along the GI tract use tryptophan as the source for serotonin production, which limits the available tryptophan for niacin synthesis. In normal patients, only one percent of dietary tryptophan is converted to serotonin; however, in patients with carcinoid syndrome, this value may increase to 70%. Carcinoid syndrome thus may produce niacin deficiency and clinical manifestations of pellagra. Anti-tuberculosis medication tends to bind to vitamin B6 and reduce niacin synthesis, since B6 (pyridoxine) is a required cofactor in the tryptophan-to-niacin reaction. Several therapeutic drugs can provoke pellagra. These include the antibiotics isoniazid, which decreases available B6 by binding to it and making it inactive, so it cannot be used in niacin synthesis, and chloramphenicol; the anti-cancer agent fluorouracil; and the immunosuppressant mercaptopurine. Treatment If untreated, pellagra can kill within four or five years. Treatment is with nicotinamide, which has the same vitamin function as niacin and a similar chemical structure, but has lower toxicity. The frequency and amount of nicotinamide administered depends on the degree to which the condition has progressed. Epidemiology Pellagra can be common in people who obtain most of their food energy from corn, notably rural South America, where maize is a staple food. If maize is not nixtamalized, it is a poor source of tryptophan, as well as niacin. Nixtamalization corrects the niacin deficiency, and is a common practice in Native American cultures that grow corn, but most especially in Mexico and the countries of Central America. Following the corn cycle, the symptoms usually appear during spring, increase in the summer due to greater sun exposure, and return the following spring. Indeed, pellagra was once endemic in the poorer states of the U.S. South, such as Mississippi and Alabama, where its cyclical appearance in the spring after meat-heavy winter diets led to it being known as "spring sickness" (particularly when it appeared among more vulnerable children), as well as among the residents of jails and orphanages as studied by Dr. Joseph Goldberger.Pellagra is common in Africa, Indonesia, and China. In affluent societies, a majority of patients with clinical pellagra are poor, homeless, alcohol-dependent, or psychiatric patients who refuse food. Pellagra was common among prisoners of Soviet labor camps (the Gulags). In addition, pellagra, as a micronutrient deficiency disease, frequently affects populations of refugees and other displaced people due to their unique, long-term residential circumstances and dependence on food aid. Refugees typically rely on limited sources of niacin provided to them, often peanuts (which, in Africa, may be supplied in place of local groundnut staples, such as the Bambara or Hausa groundnut); the instability in the nutritional content and distribution of food aid can be the cause of pellagra in displaced populations. In the 2000s, there were outbreaks in countries such as Angola, Zimbabwe and Nepal. In Angola specifically, recent reports show a similar incidence of pellagra since 2002, with clinical pellagra in 0.3% of women and 0.2% of children and niacin deficiency in 29.4% of women and 6% of children related to high untreated corn consumption.In other countries such as the Netherlands and Denmark, even with sufficient intake of niacin, cases have been reported. In this case, deficiency might happen not just because of poverty or malnutrition but secondary to alcoholism, drug interaction (psychotropic, cytostatic, tuberculostatic or analgesics), HIV, vitamin B2 and B6 deficiency, or malabsorption syndromes such as Hartnup disease and carcinoid tumors. History Native American cultivators who first domesticated corn (maize) prepared it by nixtamalization, in which the grain is treated with a solution of alkali such as lime. Nixtamalization makes the niacin nutritionally available and prevents pellagra. When maize was cultivated worldwide, and eaten as a staple without nixtamalization, pellagra became common. Pellagra was first described for its dermatological effect in Spain in 1735 by Gaspar Casal. He explained that the disease causes dermatitis in exposed skin areas such as hands, feet and neck and that the origin of the disease is poor diet and atmospheric influences. His work published in 1762 by his friend Juan Sevillano was titled Historia Natural y Medicina del Principado de Asturias or Natural and Medical History of the Principality of Asturias (1762). This led to the disease being known as "Asturian leprosy", and it is recognized as the first modern pathological description of a syndrome. It was an endemic disease in northern Italy, where it was named, from Lombard, as "pell agra" (agra = holly-like or serum-like; pell = skin) by Francesco Frapolli of Milan. With pellagra affecting over 100,000 people in Italy by the 1880s, debates raged as to how to classify the disease (as a form of scurvy, elephantiasis or as something new), and over its causation. In the 19th century, Roussel started a campaign in France to restrict consumption of maize and eradicated the disease in France, but it remained endemic in many rural areas of Europe. Because pellagra outbreaks occurred in regions where maize was a dominant food crop, the most convincing hypothesis during the late 19thcentury, as espoused by Cesare Lombroso, was that the maize either carried a toxic substance or was a carrier of disease. Louis Sambon, an Anglo-Italian doctor working at the London School of Tropical Medicine, was convinced that pellagra was carried by an insect, along the lines of malaria. Later, the lack of pellagra outbreaks in Mesoamerica, where maize is a major food crop, led researchers to investigate processing techniques in that region. Pellagra was studied mostly in Europe until the late 19th century when it became epidemic especially in the southern United States. In the early 1900s, pellagra reached epidemic proportions in the American South. Between 1906 and 1940 more than 3 million Americans were affected by pellagra with more than 100,000 deaths, yet the epidemic resolved itself right after dietary niacin fortification. Pellagra deaths in South Carolina numbered 1,306 during the first ten months of 1915; 100,000 Southerners were affected in 1916. At this time, the scientific community held that pellagra was probably caused by a germ or some unknown toxin in corn. The Spartanburg Pellagra Hospital in Spartanburg, South Carolina, was the nations first facility dedicated to discovering the cause of pellagra. It was established in 1914 with a special Congressional appropriation to the U.S. Public Health Service (PHS) and set up primarily for research. In 1915, Dr. Joseph Goldberger, assigned to study pellagra by the Surgeon General of the United States, showed it was linked to diet by observing the outbreaks of pellagra in orphanages and mental hospitals. Goldberger noted that children between the ages of 6 and 12 (but not older or younger children at the orphanages) and patients at the mental hospitals (but not doctors or nurses) were the ones who seemed most susceptible to pellagra. Goldberger theorized that a lack of meat, milk, eggs, and legumes made those particular populations susceptible to pellagra. By modifying the diet served in these institutions with "a marked increase in the fresh animal and the leguminous protein foods," Goldberger was able to show that pellagra could be prevented. By 1926, Goldberger established that a diet that included these foods, or a small amount of brewers yeast, prevented pellagra. Goldberger experimented on 11 prisoners (one was dismissed because of prostatitis). Before the experiment, the prisoners were eating the prison fare fed to all inmates at Rankin Prison Farm in Mississippi. Goldberger started feeding them a restricted diet of grits, syrup, mush, biscuits, cabbage, sweet potatoes, rice, collards, and coffee with sugar (no milk). Healthy white male volunteers were selected as the typical skin lesions were easier to see in Caucasians and this population was felt to be those least susceptible to the disease, and thus provide the strongest evidence that the disease was caused by a nutritional deficiency. Subjects experienced mild, but typical cognitive and gastrointestinal symptoms, and within five months of this cereal-based diet, 6 of the 11 subjects broke out in the skin lesions that are necessary for a definitive diagnosis of pellagra. The lesions appeared first on the scrotum. Goldberger was not given the opportunity to experimentally reverse the effects of diet-induced pellagra as the prisoners were released shortly after the diagnoses of pellagra were confirmed. In the 1920s, he connected pellagra to the corn-based diets of rural areas rather than infection as contemporary medical opinion would suggest. Goldberger believed that the root cause of pellagra amongst Southern farmers was limited diet resulting from poverty, and that social and land reform would cure epidemic pellagra. His reform efforts were not realized, but crop diversification in the Southern United States, and the accompanying improvement in diet, dramatically reduced the risk of pellagra. Goldberger is remembered as the "unsung hero of American clinical epidemiology". Though he identified that a missing nutritional element was responsible for pellagra, he did not discover the specific vitamin responsible. In 1937, Conrad Elvehjem, a biochemistry professor at the University of Wisconsin-Madison, showed that the vitamin niacin cured pellagra (manifested as black tongue) in dogs. Later studies by Dr. Tom Spies, Marion Blankenhorn, and Clark Cooper established that niacin also cured pellagra in humans, for which Time Magazine dubbed them its 1938 Men of the Year in comprehensive science.Research conducted between 1900 and 1950 found the number of cases of women with pellagra was consistently double the number of cases of affected men. This is thought to be due to the inhibitory effect of estrogen on the conversion of the amino acid tryptophan to niacin. Some researchers of the time gave a few explanations regarding the difference.Gillman and Gillman related skeletal tissue and pellagra in their research in South Africans. They provide some of the best evidence for skeletal manifestations of pellagra and the reaction of bone in malnutrition. They claimed radiological studies of adult pellagrins demonstrated marked osteoporosis. A negative mineral balance in pellagrins was noted, which indicated active mobilization and excretion of endogenous mineral substances, and undoubtedly impacted the turnover of bone. Extensive dental caries were present in over half of pellagra patients. In most cases, caries were associated with "severe gingival retraction, sepsis, exposure of cementum, and loosening of teeth". Etymology The word pellagra comes from the Lombard words "pell" (skin) and "agra" (fem. sour). United States Pellagra was first reported in 1902 in the United States, and has "caused more deaths than any other nutrition-related disease in American history", reaching epidemic proportions in the American South during the early 1900s. Poverty and consumption of corn were the most frequently observed risk factors, but the exact cause was not known, until groundbreaking work by Joseph Goldberger. A 2017 National Bureau of Economic Research paper explored the role of cotton production in the emergence of disease; one prominent theory is that "widespread cotton production had displaced local production of niacin-rich foods and driven poor Southern farmers and mill workers to consume milled Midwestern corn, which was relatively cheap but also devoid of the niacin necessary to prevent pellagra." The study provided evidence in favor of the theory: there were lower pellagra rates in areas where farmers had been forced to abandon cotton production (a highly profitable crop) in favor of food crops (less profitable crops) due to boll weevil infestation of cotton crops (which occurred randomly).The whole dried corn kernel contains a nutritious germ and a thin seed coat that provides some fiber. There are two important considerations for using ground whole-grain corn. The germ contains oil that is exposed by grinding, thus whole-grain cornmeal and grits turn rancid quickly at room temperature and should be refrigerated. Whole-grain cornmeal and grits require extended cooking times as seen in the following cooking directions for whole-grain grits:"Place the grits in a pan and cover them with water. Allow the grits to settle a full minute, tilt the pan, and skim off and discard the chaff and hulls with a fine tea strainer. Cook the grits for 50 minutes if the grits were soaked overnight or else 90 minutes if not." Most of the niacin in mature cereal grains is present as niacytin, which is niacin bound up in a complex with hemicellulose which is nutritionally unavailable. In mature corn this may be up to 90% of the total niacin content. The preparation method of nixtamalization using the whole dried corn kernel made this niacin nutritionally available and reduced the chance of developing pellagra. Niacytin is concentrated in the aleurone and germ layers which are removed by milling. The milling and degerming of corn in the preparation of cornmeal became feasible with the development of the Beall degerminator, which was originally patented in 1901 and was used to separate the grit from the germ in corn processing. However, this process of degermination reduces the niacin content of the cornmeal. Casimir Funk, who helped elucidate the role of thiamin in the etiology of beriberi, was an early investigator of the problem of pellagra. Funk suggested that a change in the method of milling corn was responsible for the outbreak of pellagra, but no attention was paid to his article on this subject.Pellagra developed especially among the vulnerable populations in institutions such as orphanages and prisons, because of the monotonous and restricted diet. Soon pellagra began to occur in epidemic proportions in states south of the Potomac and Ohio rivers. The pellagra epidemic lasted for nearly four decades beginning in 1906. It was estimated that there were 3 million cases, and 100,000 deaths due to pellagra during the epidemic. Popular culture George Sessions Perrys 1941 novel Hold Autumn in Your Hand – and Jean Renoirs 1945 film adaptation of it, The Southerner – incorporates pellagra ("spring sickness") as a major plot element in the story of an impoverished Texas farm family. See also Central chromatolysis Harriette Chick Zeism References Further reading External links "Pellagra" . Encyclopædia Britannica. Vol. 21 (11th ed.). 1911. p. 69. Pellagra – Food and Agriculture Organization (FAO)

Aarogya what is Pemphigus vulgaris

Pemphigus vulgaris

Pemphigus vulgaris is a rare chronic blistering skin disease and the most common form of pemphigus. Pemphigus was derived from the Greek word pemphix, meaning blister. It is classified as a type II hypersensitivity reaction in which antibodies are formed against desmosomes, components of the skin that function to keep certain layers of skin bound to each other. As desmosomes are attacked, the layers of skin separate and the clinical picture resembles a blister. These blisters are due to acantholysis, or breaking apart of intercellular connections through an autoantibody-mediated response. Over time the condition inevitably progresses without treatment: lesions increase in size and distribution throughout the body, behaving physiologically like a severe burn. Before the advent of modern treatments, mortality for the disease was close to 90%. Today, the mortality rate with treatment is between 5-15% due to the introduction of corticosteroids as primary treatment. Nevertheless, in 1998, pemphigus vulgaris was the fourth most common cause of death due to a skin disorder. The disease mainly affects middle-aged and older adults between 50–60 years old. There has historically been a higher incidence in women. Signs and symptoms Pemphigus vulgaris most commonly presents with oral blisters (buccal and palatine mucosa, especially), but also includes cutaneous blisters. Other mucosal surfaces, the conjunctiva, nose, esophagus, penis, vulva, vagina, cervix, and anus, may also be affected. Flaccid blisters over the skin are frequently seen with sparing of the skin covering the palms and soles.Blisters commonly erode and leave ulcerated lesions and erosions. A positive Nikolsky sign (induction of blistering in normal skin or at the edge of a blister) is indicative of the disease.Severe pain with chewing can lead to weight loss and malnutrition. Pathophysiology Pemphigus is an autoimmune disease caused by antibodies directed against both desmoglein 1 and desmoglein 3 present in desmosomes. Loss of desmosomes results in loss of cohesion between keratinocytes in the epidermis, and a disruption of the barrier function served by intact skin. The process is classified as a type II hypersensitivity reaction (in which antibodies bind to antigens on the bodys own tissues). On histology, the basal keratinocytes are usually still attached to the basement membrane leading to a characteristic appearance called "tombstoning". Transudative fluid accumulates in between the keratinocytes and the basal layer (suprabasal split), forming a blister and resulting in what is known as a positive Nikolskys sign. This is a contrasting feature from bullous pemphigoid, which is thought to be due to anti-hemidesmosome antibodies, and where the detachment occurs between the epidermis and dermis (subepidermal bullae). Clinically, pemphigus vulgaris is characterized by extensive flaccid blisters and mucocutaneous erosions. The severity of the disease, as well as the mucosal lesions, is believed to be directly proportional to the levels of desmoglein 3. Milder forms of pemphigus (like foliacious and erythematoses) are more anti-desmoglein 1 heavy. The disease arises most often in middle-aged or older people, usually starting with a blister that ruptures easily. It can also start with blisters in the mouth. The lesions can become quite extensive. Diagnosis Because it is a rare disease, diagnosis is often complicated and takes a long time. Early in the disease patients may have erosions in the mouth or blisters on the skin. These blisters can be itchy or painful. Theoretically, the blisters should demonstrate a positive Nikolskys sign, in which the skin sloughs off from slight rubbing, but this is not always reliable. The gold standard for diagnosis is a punch biopsy from the area around the lesion that is examined by direct immunofluorescent staining, in which cells are acantholytic, that is, lacking the normal intercellular connections that hold them together. These can also be seen on a Tzanck smear. These cells are basically rounded, nucleated keratinocytes formed due to antibody mediated damage to cell adhesion protein desmoglein. Pemphigus vulgaris is easily confused with impetigo and candidiasis. IgG4 is considered pathogenic. The diagnosis can be confirmed by testing for the infections that cause these other conditions, and by a lack of response to antibiotic treatment. Treatment Corticosteroids and other immunosuppressive medications have historically been employed to reduce pemphigus symptoms, yet steroids are associated with serious and long-lasting side effects and their use should be limited as much as possible. Intravenous immunoglobulin, mycophenolate mofetil, methotrexate, azathioprine, and cyclophosphamide have also been used with varying degrees of success. An established alternative to steroids are monoclonal antibodies such as rituximab, which are increasingly being used as first-line treatment. In summer 2018, the FDA granted full approval to rituximab for this application, following successful fast track evaluation. In numerous case series, many patients achieve remission after one cycle of rituximab. Treatment is more successful if initiated early on in the course of disease, perhaps even at diagnosis. Rituximab treatment combined with monthly IV immunoglobulin infusions has resulted in long-term remission with no recurrence of disease in 10 years after treatment was halted. This was a small trial study of 11 patients with 10 patients followed to completion. Rituximab demonstrated superior efficacy compared to mycophenolate mofetil in a Phase III clinical trial, results of which were published in 2021. Epidemiology Pemphigus vulgaris is a relatively rare disease that only affects about 1 to 5 people in 1 million in the United Kingdom, with an incidence of 1-10 cases per 1 million people across the world. There is an estimated prevalence of 30,000-40,000 cases in the United States. Cases of P. vulgaris usually dont develop until after the age of 50 or so. The disease is not contagious which means it cannot be spread from person to person. There is currently no way of knowing who will be affected with P. vulgaris in their life as it is usually not a genetic disorder and is usually triggered later in life by environmental factors. Men and women are both equally affected and the disease has been found to affect people of many different cultures and racial backgrounds, especially Ashkenazi Jews, people of Mediterranean, North Indian and Persian descent. There has been no found difference in the rate of disease when looking at socioeconomic factors as well.If left untreated, 8 of 10 people with the disease die within a year with a cause of death being infection or loss of fluids, which is very common for raw, open sores that are characteristic of P. vulgaris. With treatment, only about 1 in 10 people with the disease die, either from the condition, or side effects of the medicine.An effect of the disease being so rare is that there is not enough evidence to prove that the treatments currently being used are actually as effective as they could be. Doctors are trying to find effective steroid-sparing agents to use in the treatment, to decrease the side effects of long term steroid treatment. The small amount of case numbers make it hard to test statistical significance between the affected and the control groups when testing if these types of systematic treatments are effective. Research Research into using genetically modified T-cells to treat pemphigus vulgaris in mice was reported in 2016. Rituximab indiscriminately attacks all B cells, which reduces the bodys ability to control infections. In the experimental treatment, human T cells are genetically engineered to recognize only those B cells that produce antibodies to desmoglein. In PV, autoreactive B cells produce antibodies against Dsg3, disrupting its adhesive function and causing skin blistering. By expressing Dsg3 on their surfaces, the CAAR-T cells lure those B cells in and kill them. The Dsg 3 CAAR-T cells eliminated Dsg3-specific B cells in lab dishes and in mice, the researchers reported at the time. Penns Aimee Payne, M.D., Ph.D., and Michael Milone, M.D., Ph.D., a co-inventor of Novartis’ CAR-T cancer therapy Kymriah, pioneered the CAAR-T idea and have founded biotech Cabaletta Bio, hoping to bring their therapies through clinical studies to the market. The MuSK-CAAR-T is the second candidate in its pipeline; the company has already received FDA clearance to test its lead project, DSG3-CAAR-T, in patients with mucosal pemphigus vulgaris (PV), and a phase 1 trial is expected to start in 2020. See also List of conditions caused by problems with junctional proteins List of cutaneous conditions List of immunofluorescence findings for autoimmune bullous conditions References External links Pemphigus vulgaris - DermNet New Zealand

Hey Aarogya , Do you know what is Periodic paralysis,

Periodic paralysis

Periodic paralysis is a group of rare genetic diseases that lead to weakness or paralysis from common triggers such as cold, heat, high carbohydrate meals, not eating, stress or excitement and physical activity of any kind. The underlying mechanism of these diseases are malfunctions in the ion channels in skeletal muscle cell membranes that allow electrically charged ions to leak in or out of the muscle cell, causing the cell to depolarize and become unable to move.The symptoms of periodic paralysis can also be caused by hyperthyroidism, and are then labeled thyrotoxic periodic paralysis; however, if this is the underlying condition there are likely to be other characteristic manifestations, enabling a correct diagnosis. Types Periodic paralysis is an autosomal dominant myopathy with considerable variation in penetrance, leading to a spectrum of familial phenotypes (only one parent needs to carry the gene mutation to affect the children, but not all family members who share the gene are affected to the same degree). Specific diseases include: Hypokalemic periodic paralysis (Online Mendelian Inheritance in Man (OMIM): 170400), where potassium leaks into the muscle cells from the bloodstream. Hyperkalemic periodic paralysis (Online Mendelian Inheritance in Man (OMIM): 170500), where potassium leaks out of the cells into the bloodstream. Paramyotonia congenita (Online Mendelian Inheritance in Man (OMIM): 168300), a form which often accompanies hyperkalemic periodic paralysis, but may present alone. The primary symptom of paramyotonia congenita is muscle contracture which develops during exercise or activity. Paramyotonia congenita attacks may also be triggered by a low level of potassium in the bloodstream. This means people with both hyperkalemic periodic paralysis and paramyotonia congenita can have attacks with fluctuations of potassium up or down. Andersen-Tawil syndrome (Online Mendelian Inheritance in Man (OMIM): 170390), a form of periodic paralysis that includes significant heart rhythm problems, fainting and risk of sudden death. Potassium levels may be low, high, or normal during attacks of ATS. Patients with ATS may also have skeletal abnormalities like scoliosis (curvature of the spine), webbing between the second and third toes or fingers (syndactyly), crooked fingers (clinodactyly), a small jaw (micrognathia) and low-set ears. Patients need to have another form of periodic paralysis to have the Andersen-Tawil. If a patient has hypo or hyper periodic paralysis they have a 50% chance of getting Andersen-Tawil. They just have to have the gene that causes it. This is a rare occurrence of having this. Only around 100 people in the world are recorded to have it. Cause One of the most common descriptions of periodic paralysis are episodic attacks of muscle weakness, which are commonly associated with serum potassium levels. Physical activity and diet content (carbohydrates) have been identified as PP triggers. Unlike non-dystrophic myotonias, the periodic paralysis phenotype is triggered after resting following exercise. Voltage-gated sodium channel (Nav1.4) mutations are among the key causes behind periodic paralysis.Hyper-kalemic PP (hyperPP) is identified with high extracellular potassium levels which are typically greater than 5 mM during attacks; however, HyperPP attacks can also take place without rise in potassium concentrations. HyperPP has a prevalence rate of 1/100,000. Patients become symptomatic around the age of 10. The weakness attacks in hyperPP are relatively short lasting, and range from minutes to hours. The attacks can happen upwards of ten times per month.Hypo-kalemic PP (hypoPP) is associated with low potassium levels. The onset of hypoPP occurs between the ages of 15 and 35. The prevalence of hypoPP is estimated to 1/100,000. HypoPP can be triggered by many external factors such as stress, high-sugar diet, and rest after exercise. During hypoPP attacks, the serum potassium concentrations can drop to less than 3 mM. Furthermore, hypoPP attacks are considerably longer lasting than hyperPP. As exercise is a trigger for periodic paralysis attacks, recently there is more research going into the physiological changes that accompany exercise including changes in blood pH. Diagnosis This disease is unusually difficult to diagnose. Patients often report years of wrong diagnosis and treatments that made them worse instead of better. Part of this may be that migraines are present in up to 50% of patients and can cause a confusing array of symptoms including headaches, speech difficulties and visual, auditory or sensory auras. DNA testing is available for only a half dozen common gene mutations, while dozens of known mutations are possible but are not routinely tested. Electromyography (EMG) findings are not specific but the McManis Protocol, also called the Compound Muscle Amplitude Potential test (CMAP) can be used by a skilled neurologist capable of utilizing the EMG, which can give assistance in diagnosing several of these PP disorders. The old glucose/insulin provocative testing can cause life-threatening symptoms and should not be used.Also of note is that potassium levels do not have to range outside of normal limits to cause serious, even life-threatening paralysis. These diseases are not the same as having a very low level of potassium (hypokalemia) or high potassium (hyperkalemia) and must not be treated as such. The total body store of potassium is usually normal; it is just in the wrong place. Treatment Treatment of the periodic paralyses may include carbonic anhydrase inhibitors (such as acetazolamide, methazolamide or dichlorphenamide), taking supplemental oral potassium chloride and a potassium-sparing diuretic (for hypos) or avoiding potassium (for hypers), thiazide diuretics to increase the amount of potassium excreted by the kidneys (for hypers), and significant lifestyle changes including tightly controlled levels of exercise or activity. However, treatment should be tailored to the particular type of periodic paralysis.Treatment of periodic paralysis in Andersen-Tawil syndrome is similar to that for other types. However, pacemaker insertion or an implantable cardioverter-defibrillator may be required to control cardiac symptoms. Prognosis While the disability can range from minor, occasional weakness to permanent muscle damage, inability to hold a normal job and use of a powerchair, most people function fairly well with drugs and lifestyle changes. References Song, YW; Kim, SJ; Heo, TH; Kim, MH; Kim, JB (Dec 2012). "Normokalemic periodic paralysis is not a distinct disease". Muscle & Nerve. 46 (6): 908–913. doi:10.1002/mus.23441. PMID 22926674. S2CID 43821573. External links NIH information page on periodic paralysis

Hello Aarogya, explain a situation where Periodontal disease occurs

Periodontal disease

Periodontal disease, also known as gum disease, is a set of inflammatory conditions affecting the tissues surrounding the teeth. In its early stage, called gingivitis, the gums become swollen and red and may bleed. It is considered the main cause of tooth loss for adults worldwide. In its more serious form, called periodontitis, the gums can pull away from the tooth, bone can be lost, and the teeth may loosen or fall out. Bad breath may also occur.Periodontal disease is generally due to bacteria in the mouth infecting the tissue around the teeth. Factors that increase the risk of disease include smoking, diabetes, HIV/AIDS, family history, and certain medications. Diagnosis is by inspecting the gum tissue around the teeth both visually and with a probe and X-rays looking for bone loss around the teeth.Treatment involves good oral hygiene and regular professional teeth cleaning. Recommended oral hygiene include daily brushing and flossing. In certain cases antibiotics or dental surgery may be recommended. Clinical trials show that smoking cessation and dietary improvements improve disease outcomes. Globally 538 million people were estimated to be affected in 2015 and has been known to affect 10-15% of the population generally. In the United States nearly half of those over the age of 30 are affected to some degree, and about 70% of those over 65 have the condition. Males are affected more often than females. Signs and symptoms In the early stages, periodontitis has very few symptoms, and in many individuals the disease has progressed significantly before they seek treatment. Symptoms may include: Redness or bleeding of gums while brushing teeth, using dental floss or biting into hard food (e.g., apples) (though this may also occur in gingivitis, where there is no attachment loss gum disease ) Gum swelling that recurs Spitting out blood after brushing teeth Halitosis, or bad breath, and a persistent metallic taste in the mouth Gingival recession, resulting in apparent lengthening of teeth (this may also be caused by heavy-handed brushing or with a stiff toothbrush) Deep pockets between the teeth and the gums (pockets are sites where the attachment has been gradually destroyed by collagen-destroying enzymes, known as collagenases) Loose teeth, in the later stages (though this may occur for other reasons, as well)Gingival inflammation and bone destruction are largely painless. Hence, people may wrongly assume painless bleeding after teeth cleaning is insignificant, although this may be a symptom of progressing periodontitis in that person. Associated conditions Periodontitis has been linked to increased inflammation in the body, such as indicated by raised levels of C-reactive protein and interleukin-6. It is associated with an increased risk of stroke, myocardial infarction, atherosclerosis and hypertension. It also linked in those over 60 years of age to impairments in delayed memory and calculation abilities. Individuals with impaired fasting glucose and diabetes mellitus have higher degrees of periodontal inflammation, and often have difficulties with balancing their blood glucose level owing to the constant systemic inflammatory state, caused by the periodontal inflammation. Although no causal association was proven, there is an association between chronic periodontitis and erectile dysfunction, inflammatory bowel disease, heart disease, and pancreatic cancer. Diabetes and Periodontal Disease A positive correlation between raised levels of glucose within the blood and the onset or progression of periodontal disease has been shown in the current literature. Data has also shown that there is a significant increase in the incidence or progression of periodontitis in patients with uncontrolled diabetes compared to those who do not have diabetes or have well-controlled diabetes. In uncontrolled diabetes, the formation of reactive oxygen species can damage cells such as those in the connective tissue of the periodontal ligament, resulting in cell necrosis or apoptosis. Furthermore, individuals with uncontrolled diabetes mellitus who have frequent exposure to periodontal pathogens have a greater immune response to these bacteria. This can subsequently cause and/or accelerate periodontal tissue destruction leading to periodontal disease.Oral Cancer and Periodontal Disease Current literature suggests a link between periodontal disease and oral cancer. Studies have confirmed an increase in systemic inflammation markers such as C-Reactive Protein and Interleukin-6 to be found in patients with advanced periodontal disease. The link between systemic inflammation and oral cancer has also been well established. Both periodontal disease and cancer risk are associated with genetic susceptibility and it is possible that there is a positive association by a shared genetic susceptibility in the two diseases. Due to the low incidence rate of oral cancer, studies have not been able to conduct quality studies to prove the association between the two, however future larger studies may aid in the identification of individuals at a higher risk.Systemic implications Periodontal disease (PD) can be described as an inflammatory condition affecting the supporting structures of the teeth. Studies have shown that PD is associated with higher levels of systemic inflammatory markers such as Interleukin-6 (IL-6), C-Reactive Protein (CRP) and Tumor Necrosis Factor (TNF). To compare, elevated levels of these inflammatory markers are also associated with cardiovascular disease and cerebrovascular events such as ischemic strokes.The presence of a wide spectrum inflammatory oral diseases can increase the risk of an episode of stroke in an acute or chronic phase. Inflammatory markers, CRP, IL-6 are known risk factors of stroke. Both inflammatory markers are also biomarkers of PD and found to be an increased level after daily activities, such as mastication or toothbrushing, are performed. Bacteria from the periodontal pockets will enter the bloodstream during these activities and the current literature suggests that this may be a possible triggering of the aggravation of the stroke process.Other mechanisms have been suggested, PD is a known chronic infection. It can aid in the promotion of atherosclerosis by the deposition of cholesterol, cholesterol esters and calcium within the subendothelial layer of vessel walls. Atherosclerotic plaque that is unstable may rupture and release debris and thrombi that may travel to different parts of the circulatory system causing embolization and therefore, an ischemic stroke. Therefore, PD has been suggested as an independent risk factor for stroke. A variety of cardiovascular diseases can also be associated with periodontal disease. Patients with higher levels of inflammatory markers such as TNF, IL-1, IL-6 and IL-8 can lead to progression of atherosclerosis and the development and perpetuation of atrial fibrillation, as it is associated with platelet and coagulation cascade activations, leading to thrombosis and thrombotic complications. Experimental animal studies have shown a link between periodontal disease, oxidative stress and cardiac stress. Oxidative stress favours the development and progression of heart failure as it causes cellular dysfunction, oxidation of proteins and lipids, and damage to the deoxyribonucleic acid (DNA), stimulating fibroblast proliferation and metalloproteinases activation favouring cardiac remodelling. Clinical Significance Inadequate Nutrition and Periodontal Disease Periodontal disease is multifactorial, and nutrition can significantly affect its prognosis. Studies have shown that a healthy and well-balanced diet is crucial to maintaining periodontal health. Nutritional deficiencies can lead to oral manifestations such as those in scurvy and rickets disease. Different vitamins will play a different role in periodontal health: Vitamin C: Deficiencies may lead to gingival inflammation and bleeding, subsequently advancing periodontal disease Vitamin D: Deficiencies may lead to delayed post-surgical healing Vitamin E: Deficiencies may lead to impaired gingival wound healing Vitamin K: Deficiencies may lead to gingival bleedingNutritional supplements of vitamins have also been shown to positively affect healing after periodontal surgery and many of these vitamins can be found in a variety of food that we eat within a regular healthy diet. Therefore, vitamin intakes (particularly vitamin C) and dietary supplements not only play a role in improving periodontal health, but also influence the rate of bone formation and periodontal regeneration. However, studies supporting the correlation between nutrition and periodontal health are limited, and more long-term research is required to confirm this. Causes Periodontitis is an inflammation of the periodontium, i.e., the tissues that support the teeth. The periodontium consists of four tissues: gingiva, or gum tissue, cementum, or outer layer of the roots of teeth, alveolar bone, or the bony sockets into which the teeth are anchored, and periodontal ligaments (PDLs), which are the connective tissue fibers that run between the cementum and the alveolar bone. The primary cause of gingivitis is poor or ineffective oral hygiene, which leads to the accumulation of a mycotic and bacterial matrix at the gum line, called dental plaque. Other contributors are poor nutrition and underlying medical issues such as diabetes. Diabetics must be meticulous with their homecare to control periodontal disease. New finger prick tests have been approved by the Food and Drug Administration in the US, and are being used in dental offices to identify and screen people for possible contributory causes of gum disease, such as diabetes. In some people, gingivitis progresses to periodontitis – with the destruction of the gingival fibers, the gum tissues separate from the tooth and deepened sulcus, called a periodontal pocket. Subgingival microorganisms (those that exist under the gum line) colonize the periodontal pockets and cause further inflammation in the gum tissues and progressive bone loss. Examples of secondary causes are those things that, by definition, cause microbic plaque accumulation, such as restoration overhangs and root proximity. Smoking is another factor that increases the occurrence of periodontitis, directly or indirectly, and may interfere with or adversely affect its treatment. It is arguably the most important environmental risk factor for periodontitis. Research has shown that smokers have more bone loss, attachment loss and tooth loss compared to non-smokers. This is likely due to several effects of smoking on the immune response including decreased wound healing, suppression of antibody production, and the reduction of phagocytosis by neutrophilsEhlers–Danlos syndrome and Papillon–Lefèvre syndrome (also known as palmoplantar keratoderma) are also risk factors for periodontitis. If left undisturbed, microbial plaque calcifies to form calculus, which is commonly called tartar. Calculus above and below the gum line must be removed completely by the dental hygienist or dentist to treat gingivitis and periodontitis. Although the primary cause of both gingivitis and periodontitis is the microbial plaque that adheres to the tooth surfaces, there are many other modifying factors. A very strong risk factor is ones genetic susceptibility. Several conditions and diseases, including Down syndrome, diabetes, and other diseases that affect ones resistance to infection, also increase susceptibility to periodontitis. Periodontitis may be associated with higher stress. Periodontitis occurs more often in people from the lower end of the socioeconomic scale than people from the upper end of the socioeconomic scale.Genetics appear to play a role in determining the risk for periodontitis. It is believed genetics could explain why some people with good plaque control have advanced periodontitis, whilst some others with poor oral hygiene are free from the disease. Genetic factors which could modify the risk of a person developing periodontitis include: Defects of phagocytosis: person may have hypo-responsive phagocytes. Hyper-production of interleukins, prostaglandins and cytokines, resulting in an exaggerated immune response. Interleukin 1 (IL-1) gene polymorphism: people with this polymorphism produce more IL-1, and subsequently are more at risk of developing chronic periodontitis.Diabetes appears to exacerbate the onset, progression, and severity of periodontitis. Although the majority of research has focused on type 2 diabetes, type 1 diabetes appears to have an identical effect on the risk for periodontitis. The extent of the increased risk of periodontitis is dependent on the level of glycaemic control. Therefore, in well managed diabetes there seems to be a small effect of diabetes on the risk for periodontitis. However, the risk increases exponentially as glycaemic control worsens. Overall, the increased risk of periodontitis in diabetics is estimated to be between two and three times higher. So far, the mechanisms underlying the link are not fully understood, but it is known to involve aspects of inflammation, immune functioning, neutrophil activity, and cytokine biology. Mechanism As dental plaque or biofilm accumulates on the teeth near and below the gums there is some dysbiosis of the normal oral microbiome. As of 2017 it was not certain what species were most responsible for causing harm, but gram-negative anaerobic bacteria, spirochetes, and viruses have been suggested; in individual people it is sometimes clear that one or more species is driving the disease. Research in 2004 indicated three gram negative anaerobic species: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides forsythus and Eikenella corrodens.Plaque may be soft and uncalcified, hard and calcified, or both; for plaques that are on teeth the calcium comes from saliva; for plaques below the gumline, it comes from blood via oozing of inflamed gums.The damage to teeth and gums comes from the immune system as it attempts to destroy the microbes that are disrupting the normal symbiosis between the oral tissues and the oral microbe community. As in other tissues, Langerhans cells in the epithelium take up antigens from the microbes, and present them to the immune system, leading to movement of white blood cells into the affected tissues. This process in turn activates osteoclasts which begin to destroy bone, and it activates matrix metalloproteinases that destroy ligaments. So, in summary, it is bacteria which initiates the disease, but key destructive events are brought about by the exaggerated response from the hosts immune system. Classification There were several attempts to introduce an agreed-upon classification system for periodontal diseases: in 1989, 1993, 1999, and 2017. 1999 classification The 1999 classification system for periodontal diseases and conditions listed seven major categories of periodontal diseases, of which 2–6 are termed destructive periodontal disease, because the damage is essentially irreversible. The seven categories are as follows: Gingivitis Chronic periodontitis Aggressive periodontitis Periodontitis as a manifestation of systemic disease Necrotizing ulcerative gingivitis/periodontitis Abscesses of the periodontium Combined periodontic-endodontic lesionsMoreover, terminology expressing both the extent and severity of periodontal diseases are appended to the terms above to denote the specific diagnosis of a particular person or group of people. Severity The "severity" of disease refers to the amount of periodontal ligament fibers that have been lost, termed "clinical attachment loss". According to the 1999 classification, the severity of chronic periodontitis is graded as follows: Slight: 1–2 mm (0.039–0.079 in) of attachment loss Moderate: 3–4 mm (0.12–0.16 in) of attachment loss Severe: ≥ 5 mm (0.20 in) of attachment loss Extent The "extent" of disease refers to the proportion of the dentition affected by the disease in terms of percentage of sites. Sites are defined as the positions at which probing measurements are taken around each tooth and, generally, six probing sites around each tooth are recorded, as follows: Mesiobuccal Mid-buccal Distobuccal Mesiolingual Mid-lingual DistolingualIf up to 30% of sites in the mouth are affected, the manifestation is classified as "localized"; for more than 30%, the term "generalized" is used. 2017 classification The 2017 classification of periodontal diseases is as follows:Periodontal health, gingival disease and conditions Periodontal health and gingival health Clinical gingival health on an intact periodontium Clinical gingival health on an intact periodontium Stable periodontitis Non periodontitis person Gingivitis - Dental biofilm induced Associated with the dental biofilm alone Mediated by systemic and local risk factors Drug induced gingival enlargement. Gingival diseases - Non dental biofilm induced Genetic/developmental disorders Specific infections Inflammatory and immune conditions Reactive processes Neoplasms Endocrine, nutritional and metabolic Traumatic lesions Gingival pigmentation.Periodontitis Necrotizing periodontal diseases Necrotizing Gingivitis Necrotizing Periodontitis Necrotizing Stomatitis Periodontitis as a manifestation of systemic disease PeriodontitisOther conditions affecting the periodontium (Periodontal Manifestations of Systemic Diseases and Developmental and Acquired Conditions) Systemic disease of conditions affecting the periodontal support tissues Other Periodontal Conditions Periodontal abscesses Endodontic- periodontal lesions Mucogingival deformities and conditions Gingival Phenotype Gingival/Soft Tissue Recession Lack of Gingiva Decreased Vestibular Depth Aberrant Frenum/muscle position Gingival Excess Abnormal Color Condition of the exposed root surface Traumatic occlusal forces Primary Occlusal Trauma Secondary Occlusal Trauma Tooth and prosthesis related factors Localized tooth-related factors Localized dental prostheses-related factorsPeri-implant diseases and conditions Peri-implant health Peri-implant mucositis Peri-implantitis Peri-implant soft and hard tissue deficiencies Staging The goals of staging periodontitis is to classify the severity of damage and assess specific factors that may affect management.According to the 2017 classification, periodontitis is divided into four stages; after considering a few factors such as: Amount and percentage bone loss radiographically Clinical attachment loss, probing depth Presence of furcation Vertical bony defects History of tooth loss related to periodontitis Tooth hypermobility due to secondary occlusal trauma Grading According to the 2017 classification, the grading system for periodontitis consists of three grades: Grade A: Slow progression of disease; no evidence of bone loss over last five years Grade B: Moderate progression; < 2mm of bone loss over last five years Grade C: Rapid progression or future progression at high risk; ≥ 2mm bone loss over five yearsRisk factors affecting which grade a person is classified into include: Smoking Diabetes Prevention Daily oral hygiene measures to prevent periodontal disease include: Brushing properly on a regular basis (at least twice daily), with the person attempting to direct the toothbrush bristles underneath the gumline, helps disrupt the bacterial-mycotic growth and formation of subgingival plaque. Flossing daily and using interdental brushes (if the space between teeth is large enough), as well as cleaning behind the last tooth, the third molar, in each quarter Using an antiseptic mouthwash: Chlorhexidine gluconate-based mouthwash in combination with careful oral hygiene may cure gingivitis, although they cannot reverse any attachment loss due to periodontitis. Regular dental check-ups and professional teeth cleaning as required: Dental check-ups serve to monitor the persons oral hygiene methods and levels of attachment around teeth, identify any early signs of periodontitis, and monitor response to treatment.Clinical trials show that smoking cessation abd dietary improvements improve disease outcomes.Typically, dental hygienists (or dentists) use special instruments to clean (debride) teeth below the gumline and disrupt any plaque growing below the gumline. This is a standard treatment to prevent any further progress of established periodontitis. Studies show that after such a professional cleaning (periodontal debridement), microbial plaque tends to grow back to precleaning levels after about three to four months. Nonetheless, the continued stabilization of a persons periodontal state depends largely, if not primarily, on the persons oral hygiene at home, as well as on the go. Without daily oral hygiene, periodontal disease will not be overcome, especially if the person has a history of extensive periodontal disease. Management The cornerstone of successful periodontal treatment starts with establishing excellent oral hygiene. This includes twice-daily brushing with daily flossing. Also, the use of an interdental brush is helpful if space between the teeth allows. For smaller spaces, products such as narrow picks with soft rubber bristles provide excellent manual cleaning. Persons with dexterity problems, such as with arthritis, may find oral hygiene to be difficult and may require more frequent professional care and/or the use of a powered toothbrush. Persons with periodontitis must realize it is a chronic inflammatory disease and a lifelong regimen of excellent hygiene and professional maintenance care with a dentist/hygienist or periodontist is required to maintain affected teeth. Initial therapy Removal of microbial plaque and calculus is necessary to establish periodontal health. The first step in the treatment of periodontitis involves nonsurgical cleaning below the gum line with a procedure called "root surface instrumentation" or "RSI", this causes a mechanical disturbance to the bacterial biofilm below the gumline. This procedure involves the use of specialized curettes to mechanically remove plaque and calculus from below the gumline, and may require multiple visits and local anesthesia to adequately complete. In addition to initial RSI, it may also be necessary to adjust the occlusion (bite) to prevent excessive force on teeth that have reduced bone support. Also, it may be necessary to complete any other dental needs, such as replacement of rough, plaque-retentive restorations, closure of open contacts between teeth, and any other requirements diagnosed at the initial evaluation. It is important to note that RSI is different to scaling and root planing: RSI only removes the calculus, while scaling and root planing removes the calculus as well as underlying softened dentine, which leaves behind a smooth and glassy surface, which is not a requisite for periodontal healing. Therefore, RSI is now advocated over root planing. Reevaluation Nonsurgical scaling and root planing are usually successful if the periodontal pockets are shallower than 4–5 mm (0.16–0.20 in). The dentist or hygienist must perform a re-evaluation four to six weeks after the initial scaling and root planing, to determine if the persons oral hygiene has improved and inflammation has regressed. Probing should be avoided then, and an analysis by gingival index should determine the presence or absence of inflammation. The monthly reevaluation of periodontal therapy should involve periodontal charting as a better indication of the success of treatment, and to see if other courses of treatment can be identified. Pocket depths of greater than 5–6 mm (0.20–0.24 in) which remain after initial therapy, with bleeding upon probing, indicate continued active disease and will very likely lead to further bone loss over time. This is especially true in molar tooth sites where furcations (areas between the roots) have been exposed. Surgery If nonsurgical therapy is found to have been unsuccessful in managing signs of disease activity, periodontal surgery may be needed to stop progressive bone loss and regenerate lost bone where possible. Many surgical approaches are used in the treatment of advanced periodontitis, including open flap debridement and osseous surgery, as well as guided tissue regeneration and bone grafting. The goal of periodontal surgery is access for definitive calculus removal and surgical management of bony irregularities which have resulted from the disease process to reduce pockets as much as possible. Long-term studies have shown, in moderate to advanced periodontitis, surgically treated cases often have less further breakdown over time and, when coupled with a regular post-treatment maintenance regimen, are successful in nearly halting tooth loss in nearly 85% of diagnosed people. Local drug delivery Local drug deliveries in periodontology has gained acceptance and popularity compared to systemic drugs due to decreased risk in development of resistant flora and other side effects. A meta analysis of local tetracycline found improvement. Local application of statin may be useful. Systemic drug delivery Systemic drug delivery in conjunction with non-surgical therapy may be used as a means to reduce the percentage of the bacterial plaque load in the mouth. Many different antibiotics and also combinations of them have been tested; however, there is yet very low-certainty evidence of any significant difference in the short and long term compared to non-surgical therapy alone. It may be beneficial to limit the use of systemic drugs, since bacteria can develop antimicrobial resistance and some specific antibiotics might induce temporary mild adverse effects, such as nausea, diarrhoea and gastrointestinal disturbances. Adjunctive systemic antimicrobial treatment There is currently low-quality evidence suggesting if adjunctive systemic antimicrobials are beneficial for the non-surgical treatment of periodontitis. It is not sure whether some antibiotics are better than others when used alongside scaling and root planing). Maintenance Once successful periodontal treatment has been completed, with or without surgery, an ongoing regimen of "periodontal maintenance" is required. This involves regular checkups and detailed cleanings every three months to prevent repopulation of periodontitis-causing microorganisms, and to closely monitor affected teeth so early treatment can be rendered if the disease recurs. Usually, periodontal disease exists due to poor plaque control resulting from inappropriate brushing. Therefore, if the brushing techniques are not modified, a periodontal recurrence is probable. Other Most alternative "at-home" gum disease treatments involve injecting antimicrobial solutions, such as hydrogen peroxide, into periodontal pockets via slender applicators or oral irrigators. This process disrupts anaerobic micro-organism colonies and is effective at reducing infections and inflammation when used daily. A number of other products, functionally equivalent to hydrogen peroxide, are commercially available, but at substantially higher cost. However, such treatments do not address calculus formations, and so are short-lived, as anaerobic microbial colonies quickly regenerate in and around calculus. Doxycycline may be given alongside the primary therapy of scaling (see § initial therapy). Doxycycline has been shown to improve indicators of disease progression (namely probing depth and attachment level). Its mechanism of action involves inhibition of matrix metalloproteinases (such as collagenase), which degrade the teeths supporting tissues (periodontium) under inflammatory conditions. To avoid killing beneficial oral microbes, only small doses of doxycycline (20 mg) are used.Phage therapy may be a new therapeutic alternative. Prognosis Dentists and dental hygienists measure periodontal disease using a device called a periodontal probe. This thin "measuring stick" is gently placed into the space between the gums and the teeth, and slipped below the gumline. If the probe can slip more than 3 mm (0.12 in) below the gumline, the person is said to have a gingival pocket if no migration of the epithelial attachment has occurred or a periodontal pocket if apical migration has occurred. This is somewhat of a misnomer, as any depth is, in essence, a pocket, which in turn is defined by its depth, i.e., a 2-mm pocket or a 6-mm pocket. However, pockets are generally accepted as self-cleansable (at home, by the person, with a toothbrush) if they are 3 mm or less in depth. This is important because if a pocket is deeper than 3 mm around the tooth, at-home care will not be sufficient to cleanse the pocket, and professional care should be sought. When the pocket depths reach 6 to 7 mm (0.24 to 0.28 in) in depth, the hand instruments and ultrasonic scalers used by the dental professionals may not reach deeply enough into the pocket to clean out the microbial plaque that causes gingival inflammation. In such a situation, the bone or the gums around that tooth should be surgically altered or it will always have inflammation which will likely result in more bone loss around that tooth. An additional way to stop the inflammation would be for the person to receive subgingival antibiotics (such as minocycline) or undergo some form of gingival surgery to access the depths of the pockets and perhaps even change the pocket depths so they become 3 mm or less in depth and can once again be properly cleaned by the person at home with his or her toothbrush. If people have 7-mm or deeper pockets around their teeth, then they would likely risk eventual tooth loss over the years. If this periodontal condition is not identified and people remain unaware of the progressive nature of the disease, then years later, they may be surprised that some teeth will gradually become loose and may need to be extracted, sometimes due to a severe infection or even pain. According to the Sri Lankan tea laborer study, in the absence of any oral hygiene activity, approximately 10% will experience severe periodontal disease with rapid loss of attachment (>2 mm/year). About 80% will experience moderate loss (1–2 mm/year) and the remaining 10% will not experience any loss. Epidemiology Periodontitis is very common, and is widely regarded as the second most common dental disease worldwide, after dental decay, and in the United States has a prevalence of 30–50% of the population, but only about 10% have severe forms. Chronic periodontitis affects about 750 million people or about 10.8% of the world population as of 2010.Like other conditions intimately related to access to hygiene and basic medical monitoring and care, periodontitis tends to be more common in economically disadvantaged populations or regions. Its occurrence decreases with a higher standard of living. In Israeli population, individuals of Yemenite, North-African, South Asian, or Mediterranean origin have higher prevalence of periodontal disease than individuals from European descent. Periodontitis is frequently reported to be socially patterned, i.e. people from the lower end of the socioeconomic scale are affected more often than people from the upper end of the socioeconomic scale. History An ancient hominid from 3 million years ago had gum disease. Records from China and the Middle East, along with archaeological studies, show that mankind has had Periodontal disease for at least many thousands of years. In Europe and the Middle East archaeological research looking at ancient plaque DNA, shows that in the ancient hunter-gatherer lifestyle there was less gum disease, but that it became more common when more cereals were eaten. The Otzi Iceman was shown to have had severe gum disease. Furthermore, research has shown that in the Roman era in the UK, there was less periodontal disease than in modern times. The researchers suggest that smoking may be a key to this. Society and culture Etymology The word "periodontitis" (Greek: περιοδοντίτις) comes from the Greek peri, "around", odous (GEN odontos), "tooth", and the suffix -itis, in medical terminology "inflammation". The word pyorrhea (alternative spelling: pyorrhoea) comes from the Greek pyorrhoia (πυόρροια), "discharge of matter", itself from pyon, "discharge from a sore", rhoē, "flow", and the suffix -ia. In English this term can describe, as in Greek, any discharge of pus; i.e. it is not restricted to these diseases of the teeth. Economics It is estimated that lost productivity due to severe periodontitis costs the global economy about US$54 billion each year. Other animals Periodontal disease is the most common disease found in dogs and affects more than 80% of dogs aged three years or older. Its prevalence in dogs increases with age, but decreases with increasing body weight; i.e., toy and miniature breeds are more severely affected. Recent research undertaken at the Waltham Centre for Pet Nutrition has established that the bacteria associated with gum disease in dogs are not the same as in humans. Systemic disease may develop because the gums are very vascular (have a good blood supply). The blood stream carries these anaerobic micro-organisms, and they are filtered out by the kidneys and liver, where they may colonize and create microabscesses. The microorganisms traveling through the blood may also attach to the heart valves, causing vegetative infective endocarditis (infected heart valves). Additional diseases that may result from periodontitis include chronic bronchitis and pulmonary fibrosis. Footnotes External links Canadian Academy of Periodontology — What is periodontitis? Periodontal disease and braces. Orthodontics Australia.

Aarogya, elaborate on Pernicious anemia

Pernicious anemia

Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic factor needed for the absorption of vitamin B12. Anemia is defined as a condition in which the blood has a lower than normal amount of red blood cells or hemoglobin. The disease may come on slowly and insidiously.The most common initial symptoms are tiredness, and weakness. Other signs and symptoms of anemia include breathlessness, dizziness, a sore red tongue, lightheadedness, headaches, poor ability to exercise, cold hands and feet, low blood pressure, pale or yellow skin, chest pain, and an irregular heartbeat. The digestive tract may also be disturbed giving symptoms that can include nausea and vomiting, heartburn, upset stomach and loss of appetite. Pernicious anemia can cause osteoporosis and may lead to bone fractures. Symptoms of severe vitamin B12 deficiency can include tingling or numbness in the hands and feet, memory problems, blurred vision, unsteady walking, poor balance, muscle weakness, impaired sense of taste and smell, poor reflexes, clumsiness, depression, and confusion. Without treatment, some of these problems may become permanent.Pernicious anemia occurs due to an autoimmune response that produces antibodies that attack the parietal cells in the stomach lining and prevents them from creating intrinsic factor. Malabsorption may also result from the surgical removal of all or part of the stomach or small intestine; from an inherited disorder or from certain drugs or illnesses that damage the stomach lining. Other causes of low vitamin B12 include not enough dietary intake (which can be a risk in a vegan diet), celiac disease, or tapeworm infection. When suspected, diagnosis is made by blood tests initially a complete blood count, and occasionally, bone marrow tests. Blood tests may show fewer but larger red blood cells, low numbers of young red blood cells, low levels of vitamin B12, and antibodies to intrinsic factor.Pernicious anemia can be treated with intramuscular injections or pills of vitamin B12. Nasal sprays and gels are also available for those who have trouble swallowing pills. Treatment may need to be lifelong.Pernicious anemia due to autoimmune problems occurs in about one per 1000 people in the USA. Among those over the age of 60, about 2% have the condition. It more commonly affects people of northern European descent. Women are more commonly affected than men. With proper treatment, most people live normal lives. Due to a higher risk of stomach cancer, those with pernicious anemia should be checked regularly for this. The first clear description was by Thomas Addison in 1849. The term "pernicious" means "deadly", and this term came into use because before the availability of treatment the disease was often fatal. Signs and symptoms Pernicious anemia often presents slowly, and can cause harm insidiously and unnoticeably. Untreated, it can lead to neurological complications, and in serious cases, death. It can take several years for pernicious anemia to appear, and the disease often goes unrecognized, as the body becomes used to feeling unwell. The onset may be vague and slow, as the same symptoms are often also present with anemia; in 81.1% of cases of cobalamin deficiency, pernicious anemia is not observed. Pernicious anemia may be present without a person experiencing symptoms at first, over time, feeling tired and weak, lightheadedness, dizziness, headaches, rapid or irregular heartbeat, breathlessness, glossitis (a sore red tongue), poor ability to exercise, low blood pressure, cold hands and feet, pale or yellow skin, easy bruising and bleeding, low-grade fevers, shakiness, cold sensitivity, chest pain, upset stomach, nausea, loss of appetite, heartburn, weight loss, diarrhea, constipation, severe joint pain, feeling abnormal sensations including tingling or numbness to the fingers and toes (pins and needles), and tinnitus, may occur. Anemia may present with a number of further common symptoms, including hair thinning and loss, early greying of the hair, mouth ulcers, bleeding gums, angular cheilitis, a look of exhaustion with pale and dehydrated or cracked lips and dark circles around the eyes, as well as brittle nails.In more severe or prolonged cases of pernicious anemia, nerve cell damage may occur, which can lead to more severe symptoms, including sense loss, difficulty in proprioception, neuropathic pain, unsteady walking (ataxia), poor balance, loss of sensation in the feet, muscle weakness, blurred vision (either due to retinopathy or optic neuropathy), impaired urination, fertility problems, decreased sense of taste and smell, decreased level of consciousness, changes in reflexes, memory loss, mood swings, depression, irritability, slurred speech, cognitive impairment, confusion, anxiety, clumsiness, psychosis, and, in more severe cases, dementia. Anemia may also lead to cardiac murmurs and/or altered blood pressure (low or high). The deficiency may also present with thyroid disorders. In severe cases, the anemia may cause congestive heart failure. A complication of severe chronic PA is subacute combined degeneration of spinal cord, which leads to distal sensory loss (posterior column), absent ankle reflex, increased knee reflex response, and extensor plantar response. Other than anemia, hematological symptoms may include cytopenias, intramedullary hemolysis, and pseudothrombotic microangiopathy. Vitamin B12 deficiency, which is reversible, is occasionally confused with acute myeloid leukemia, which is an irreversible autoimmune condition presenting with some of the same hematological symptoms, including hypercellular bone marrow with blastic differentiation and hypersegmented neutrophils. Pernicious anemia can contribute to a delay in physical growth in children, and may also be a cause for delay in puberty for adolescents. Causes Vitamin B12 cannot be produced by the human body, and must be obtained from the diet. When foods containing B12 are eaten, the vitamin is usually bound to protein and is released by proteases released by the pancreas into the small bowel. Following its release, most B12 is absorbed by the body in the small bowel (ileum) after binding to a protein known as intrinsic factor. Intrinsic factor is produced by parietal cells of the gastric mucosa (stomach lining) and the intrinsic factor-B12-complex is absorbed by enterocytes in the ileums cubam receptors. PA is characterised by B12 deficiency caused by the absence of intrinsic factor. Other disorders that can disrupt the absorption of vitamin B12 in the small intestine include celiac disease, surgical removal of crohns disease, and HIV. PA may be considered as an end stage of autoimmune atrophic gastritis, a disease characterised by stomach atrophy and the presence of antibodies to parietal cells and intrinsic factor. Autoimmune atrophic gastritis, is localised to the body of the stomach, where parietal cells are located. Antibodies to intrinsic factor and parietal cells cause the destruction of the oxyntic gastric mucosa, in which the parietal cells are located, leading to the subsequent loss of intrinsic factor synthesis. Without intrinsic factor, the ileum can no longer absorb the B12. Atrophic gastritis is often a precursor to gastric cancer.Although the exact role of Helicobacter pylori infection in PA remains controversial, evidence indicates H. pylori is involved in the pathogenesis of the disease. A long-standing H. pylori infection may cause gastric autoimmunity by a mechanism known as molecular mimicry. Antibodies produced by the immune system can be cross-reactive and may bind to both H. pylori antigens and those found in the gastric mucosa. The antibodies are produced by activated B cells that recognise both pathogen and self-derived peptides. The autoantigens believed to cause the autoreactivity are the alpha and beta subunits of the sodium-potassium pump. In a study, B12 deficiency caused by Helicobacter pylori was positively correlated with CagA positivity and gastric inflammatory activity, rather than gastric atrophy. Less commonly, H. pylori and Zollinger-Ellison syndrome may cause a form of nonautoimmune gastritis that can lead to pernicious anemia.Impaired B12 absorption can also occur following gastric removal (gastrectomy) or gastric bypass surgery. In these surgeries, either the parts of the stomach that produce gastric secretions are removed or they are bypassed. This means intrinsic factor, as well as other factors required for B12 absorption, are not available. However, B12 deficiency after gastric surgery does not usually become a clinical issue. This is probably because the body stores many years worth of B12 in the liver and gastric surgery patients are adequately supplemented with the vitamin.Although no specific PA susceptibility genes have been identified, a genetic factor likely is involved in the disease. Pernicious anemia is often found in conjunction with other autoimmune disorders, suggesting common autoimmune susceptibility genes may be a causative factor. In spite of that, previous family studies and case reports focusing on PA have suggested that there is a tendency of genetic heritance of PA in particular, and close relatives of the PA patients seem to have higher incidence of PA and associated PA conditions. Moreover, it was further indicated that the formation of antibodies to gastric cells was autosomal dominant gene determined, and the presence of antibodies to the gastric cells might not be necessarily related to the occurrence of atrophic gastritis related to PA. Pathophysiology Although the healthy body stores three to five years worth of B12 in the liver, the usually undetected autoimmune activity in ones gut over a prolonged period of time leads to B12 depletion and the resulting anemia; pernicious anemia refers to one of the hematologic manifestations of chronic auto-immune gastritis, in which the immune system targets the parietal cells of the stomach or intrinsic factor itself, leading to decreased absorption of vitamin B12. B12 is required by enzymes for two reactions: the conversion of methylmalonyl-CoA to succinyl-CoA, and the conversion of homocysteine to methionine. In the latter reaction, the methyl group of levomefolic acid is transferred to homocysteine to produce tetrahydrofolate and methionine. This reaction is catalyzed by the enzyme methionine synthase with B12 as an essential cofactor. During B12 deficiency, this reaction cannot proceed, which leads to the accumulation of levomefolic acid. This accumulation depletes the other types of folate required for purine and thymidylate synthesis, which are required for the synthesis of DNA. Inhibition of DNA replication in maturing red blood cells results in the formation of large, fragile megaloblastic erythrocytes. The neurological aspects of the disease are thought to arise from the accumulation of methylmalonyl- CoA due to the requirement of B12 as a cofactor to the enzyme methylmalonyl-CoA mutase. Diagnosis Pernicious anemia is thought mainly to be an autoimmune disorder that attacks the gastric parietal cells that produce intrinsic factor resulting in impaired absorption of B12. However, pernicious anemia may also have a genetic component, potentially running in families. Pernicious anemia may be suspected when a blood smear shows large, brittle, immature, erythrocytes, known as megaloblasts. To make a diagnosis a full blood count, and blood smear, with the following tests included is needed: A complete blood count and blood smear evaluates the mean corpuscular volume (MCV) and the mean corpuscular hemoglobin concentration (MCHC) to demonstrate megaloblastic anemia. PA is identified with a high MCV (macrocytic anemia) and a normal MCHC (normochromic anemia). Ovalocytes are also typically seen on the blood smear, and a pathognomonic feature of megaloblastic anemias (which include PA and others) is hypersegmented neutrophils. Vitamin B12 serum levels are used to detect its deficiency, but do not distinguish its causes. Vitamin B12 levels can be falsely high or low and data for sensitivity and specificity vary widely. Normal serum levels may be found in cases of deficiency where myeloproliferative disorders, liver disease, transcobalamin II deficiency, or small intestinal bacterial overgrowth are present. Intrinsic factor and parietal cell antibodies – the blood is checked for antibodies against IF and parietal cells in the stomach. The presence of antibodies to gastric parietal cells and IF is common in PA. Parietal cell antibodies are found in other autoimmune disorders and also in up to 10% of healthy individuals. However, around 85% of PA patients have parietal cell antibodies, which means they are a sensitive marker for the disease. Intrinsic factor antibodies are much less sensitive than parietal cell antibodies, but they are much more specific. They are found in about half of PA patients and are very rarely found in other disorders. These antibody tests can distinguish between PA and food-B12 malabsorption. Methylmalonic acid and/or homocysteine – vitamin B12 plays an important role in metabolic processes and cellular functions. Therefore, its deficiency leads to the accumulation of some metabolic products. Methylmalonic acid and/or homocysteine is one of the metabolic products that can be measured in the blood. as the increase in the levels of both helps differentiate between vitamin B12 deficiency and folic acid deficiency, because homocysteine alone increases in the latter.Elevated gastrin levels can be found in around 80–90% of PA cases, but they may also be found in other forms of gastritis. Decreased pepsinogen I levels or a decreased pepsinogen I to pepsinogen II ratio may also be found, although these findings are less specific to PA and can be found in food-B12 malabsorption and other forms of gastritis.The diagnosis of atrophic gastritis type A should be confirmed by gastroscopy and stepwise biopsy. About 90% of individuals with PA have antibodies for parietal cells; however, only 50% of all individuals in the general population with these antibodies have pernicious anemia.Forms of vitamin B12 deficiency other than PA must be considered in the differential diagnosis of megaloblastic anemia. For example, a B12-deficient state which causes megaloblastic anemia and which may be mistaken for classical PA may be caused by infection with the tapeworm Diphyllobothrium latum, possibly due to the parasites competition with host for vitamin B12.The classic test for PA, the Schilling test, is no longer widely used, as more efficient methods are available. This historic test consisted, in its first step, of taking an oral dose of radiolabelled vitamin B12, followed by quantitation of the vitamin in the patients urine over a 24-hour period via measurement of the radioactivity. A second step of the test repeats the regimen and procedure of the first step, with the addition of oral intrinsic factor. A patient with PA presents lower than normal amounts of intrinsic factor; hence, addition of intrinsic factor in the second step results in an increase in vitamin B12 absorption (over the baseline established in the first). The Schilling test distinguished PA from other forms of B12 deficiency, specifically, from Imerslund–Gräsbeck syndrome, a B12-deficiency caused by mutations in CUBN that codes for cubilin the cobalamin receptor. Treatment Pernicious anemia may not be diagnosed at first. More in-depth diagnosis may be required. Pernicious anemia caused by a loss of intrinsic factor cannot be prevented. If there are other, reversible causes of low vitamin B12 levels, the cause must be treated. Pernicious anemia is usually easily treated by providing the necessary level of vitamin B12 supplementation. Severe cases can be treated with intramuscular injections of vitamin B12. Less severe cases may be treated with high doses of oral supplemenation of vitamin B12. A nasal spray, gel, and sublingual preparation are also available for people who may have difficulty in swallowing. Folate supplementation may affect the course and treatment of pernicious anemia, therefore vitamin B12 replacement is often recommended initially. In some severe cases of anemia, a blood transfusion may be needed to resolves haematological effects. Often treatment will be needed for life. Prognosis A person with well-treated PA can live a healthy life. Failure to diagnose and treat in time, however, may result in permanent neurological damage, excessive fatigue, depression, memory loss, and other complications. In severe cases, the neurological complications of pernicious anemia can lead to death – hence the name, "pernicious", meaning deadly.There is an increased risk of gastric cancer in those with pernicious anemia linked to the common feature of atrophic gastritis. Epidemiology PA is estimated to affect 0.1% of the general population and 1.9% of those over 60, accounting for 20–50% of B12 deficiency in adults. A review of literature shows that the prevalence of PA is higher in Northern Europe, especially in Scandinavian countries, and among people of African descent, and that increased awareness of the disease and better diagnostic tools might play a role in apparently higher rates of incidence. History A case of anemia with a first recognition of associated atrophic gastritis a feature of pernicious anemia, was first described in 1824 by James Combe. This was fully investigated in 1849, by British physician Thomas Addison, from which it acquired the common name of Addisons anemia. In 1871, the first accurate description of the disease in Europe was by Michael Anton Biermer, a German physician who referred to the insidious course of the condition, and because it was untreatable and fatal at the time, he first referred to it as "pernicious" anemia. In 1900 Russell coined the term subacute combined degeneration of spinal cord.In 1907, Richard Clarke Cabot reported on a series of 1200 patients with PA; their average survival was between one and three years. Pernicious anemia was a fatal disease before about the year 1920, until the importance of the liver in hematopoiesis was recognized, the treatment of pernicious anemia was unsuccessful and arbitrary. It may have motivated George Whipple, who had a keen interest in liver diseases, to investigate the livers role in hematopoiesis. Whipple began evaluating the effects of treatments for anemia caused by chronic blood loss. Whipple, Huber, and Robchett have studied the effects on hemoglobin and blood regeneration of a variety of treatments – among which only raw liver has shown real promise. Serendipity is said to have played a role in this discovery. Whipple observed that blood regeneration was poor in dogs fed cooked liver after chronic blood loss, had it not been that a lazy laboratory technician had given the dogs raw liver, the much more dramatic response might not have been discovered at that point in history. Around 1926, George Minot and William P. Murphy, who learned of Whipples discovery, sought raw liver as a treatment for pernicious anemia. They later suggested a high-protein diet with high amounts of raw liver. This caused a rapid improvement in symptoms and a simultaneous rise in red blood cell counts. Fruit and iron were also part of the diet, and it appears that at this point, Minot and Murphy were not quite sure that the liver was a very important factor. It was thought that iron in liver tissue, not liver juice-soluble factor, cured hemorrhagic anemia in dogs. Thus, the discovery of liver juice as a treatment for pernicious anemia had been by coincidence. However, Minot, Murphy, and Whipple received the joint Nobel Prize for discovering a cure for a previously fatal disease of unknown cause in 1934, becoming the first Americans to be awarded the Nobel Prize in Physiology and Medicine.It is not easy to eat uncooked liver, and extracts were developed as a concentrate of liver juice for intramuscular injection. In 1928, chemist Edwin Cohn prepared an extract that was 50 to 100 times stronger than obtained from raw liver. This became part of the standard management of pernicious anemia until the 1950s. The active ingredient in the liver remained unknown until 1948. The anti-pernicious anemia factor was only isolated from the liver by Smith, Rex and others. The substance was cobalamin, which the discoverers called "vitamin B12". They showed that giving a few micrograms could prevent relapse in the disease. Dorothy Hodgkin and co-workers went on to use X-ray crystallography to elucidate the structure of cobalamin for which she, too, was awarded a Nobel Prize.Understanding of the pathogenesis of pernicious anaemia increased over subsequent decades. It had long been known that the disease was associated with defects in the gastrointestinal tract: patients had chronic gastritis and lack of acid secretion (achlorhydria). It is known that transport of physiological amounts of vitamin B12 depends on the combined actions of gastric, ileal and pancreatic components. The gastric moiety was discovered and named intrinsic factor by William Castle in 1930. A further important advance was made in the early 1960s by Doniach with the recognition that pernicious anemia is an autoimmune disease. Pernicious anemia is eventually treated with either injections or large oral doses of B12, typically between 1 and 4 mg daily. A medical author takes the view that Mary Todd Lincoln, the wife of American President Abraham Lincoln, had pernicious anemia for decades and died from it in 1882. Research Permeation enhancers Treatment using oral drugs is an easier option in management but the bioavailabity of B12 is low. This is due to low absorption in the intestine, and breakdown by enzyme activity. Research continues to focus on the use of permeation enhancers or permeation absorbers in combination with the treatment. One of the better performing enhancers studied is salcoprozate sodium (SNAC). SNAC is able to form a noncovalent complex with cobalamin while preserving its chemical integrity and protect B12 from gastric acidity. This complex is much more lipophilic than the water-soluble vitamin B12, so is able to pass through cellular membranes with greater ease. Molecular dynamics are used in experiments to gain an understanding of the molecular interactions involved in the different molecules used and the degree of ease achieved in absorption across the gastric epithelium. References External links Pernicious anemia at Curlie

Hi Aarogya, could you help me understand about Peroxisomal disorder

Peroxisomal disorder

Peroxisomal disorders represent a class of medical conditions caused by defects in peroxisome functions. This may be due to defects in single enzymes important for peroxisome function or in peroxins, proteins encoded by PEX genes that are critical for normal peroxisome assembly and biogenesis. Peroxisome biogenesis disorders Peroxisome biogenesis disorders (PBDs) include the Zellweger syndrome spectrum (PBD-ZSD) and rhizomelic chondrodysplasia punctata type 1 (RCDP1). PBD-ZSD represents a continuum of disorders including infantile Refsum disease, neonatal adrenoleukodystrophy, and Zellweger syndrome. Collectively, PBDs are autosomal recessive developmental brain disorders that also result in skeletal and craniofacial dysmorphism, liver dysfunction, progressive sensorineural hearing loss, and retinopathy.PBD-ZSD is most commonly caused by mutations in the PEX1, PEX6, PEX10, PEX12, and PEX26 genes. This results in the over-accumulation of very long chain fatty acids and branched chain fatty acids, such as phytanic acid. In addition, PBD-ZSD patients show deficient levels of plasmalogens, ether-phospholipids necessary for normal brain and lung function.RCDP1 is caused by mutations in the PEX7 gene, which encodes the PTS2 receptor. RCDP1 patients can develop large tissue stores of branched chain fatty acids, such as phytanic acid, and show reduced levels of plasmalogens. Enzyme and transporter defects Peroxisomal disorders also include: References External links Peroxisomal+disorders at the US National Library of Medicine Medical Subject Headings (MeSH)

Hey Aarogya!, what is PID

PID

PID or Pid may refer to: Medicine Pelvic inflammatory disease or pelvic inflammatory disorder, an infection of the upper part of the female reproductive system Primary immune deficiency, disorders in which part of the bodys immune system is missing or does not function properly Prolapsed intervertebral disc, commonly called a herniated disc Science, technology and engineering BBC Programme Identifier, a unique identifier for a BBC television or radio programme brand, a season or series, or an individual episode OBD-II PIDs (on-board diagnostics parameter IDs), requests for data through an OBD connector in automotive repair Packet Identifier, a field in a MPEG transport stream packet Passive infrared detector, a passive infrared sensor Persistent identifier, a long-lasting reference to a document, file, web page, or other object Phosphotyrosine-interacting domain, also known as phosphotyrosine-binding domain, a protein domain which bind to phosphotyrosine Photoionization detector, measures volatile organic compounds and other gases Physical Interface Device, a class of a USB device PID controller (proportional-integral-derivative controller), a control concept used in automation Piping and instrumentation diagram (P&ID), a diagram in the process industry which shows the piping of the process flow etc. Principal ideal domain, an algebraic structure Process identifier, a number used by many operating systems to identify a process Organisations Police Intelligence Department, a staff department of the Singapore Police Force Political Intelligence Department (disambiguation), multiple organisations Politieke Inlichtingen Dienst (Political Intelligence Department), was the main security agency for the Dutch East Indies Prague Integrated Transport (Pražská integrovaná doprava – PID in Czech), an integrated public transport system in Prague Other uses Pathways into Darkness, a 1993 video game by Bungie "Paul is dead", a 1960s urban legend that Paul McCartney was dead Pid (video game), a 2012 video game by Might and Delight Project Initiation Documentation, in project management Party identification, the political party with which an individual identifies Everett Pid Purdy (1904–1951), American athlete who played in both Major League Baseball and the National Football League See also PIDS (disambiguation)

Hello Aarogya, explain a situation where Pinworm infection occurs

Pinworm infection

Pinworm infection (threadworm infection in the UK), also known as enterobiasis, is a human parasitic disease caused by the pinworm. The most common symptom is itching in the anal area. This can make sleeping difficult. The period of time from swallowing eggs to the appearance of new eggs around the anus is 4 to 8 weeks. Some people who are infected do not have symptoms.The disease is spread between people by pinworm eggs. The eggs initially occur around the anus and can survive for up to three weeks in the environment. They may be swallowed following contamination of the hands, food, or other articles. Those at risk are those who go to school, live in a health care institution or prison, or take care of people who are infected. Other animals do not spread the disease. Diagnosis is by seeing the worms which are about one centimetre long or the eggs under a microscope.Treatment is typically with two doses of the medications mebendazole, pyrantel pamoate, or albendazole two weeks apart. Everyone who lives with or takes care of an infected person should be treated at the same time. Washing personal items in hot water after each dose of medication is recommended. Good handwashing, daily bathing in the morning, and daily changing of underwear can help prevent reinfection.Pinworm infections commonly occur in all parts of the world. They are the most common type of worm infection in Western Europe and the United States. School-aged children are the most commonly infected. In the United States about 20% of children will develop pinworm at some point. Infection rates among high-risk groups may be as high as 50%. It is not considered a serious disease. Pinworms are believed to have affected humans throughout history. Signs and symptoms One-third of individuals with pinworm infection are totally asymptomatic. The main symptoms are itching in and around the anus and perineum. The itching occurs mainly during the night, and is caused by the female pinworms migrating to lay eggs around the anus. Both the migrating females and the clumps of eggs are irritating, as well as the sticky substance that is produced by the worms when the eggs are laid. The intensity of the itching varies, and it can be described as tickling, crawling sensations, or even acute pain. The itching leads to continuously scratching the area around the anus, which can further result in tearing of the skin and complications such as secondary bacterial infections, including bacterial skin inflammation, and hair follicle inflammation. General symptoms are trouble sleeping, and restlessness. A considerable proportion of children experience loss of appetite, weight loss, irritability, emotional instability, and bed wetting.Pinworms cannot damage the skin, and they do not normally migrate through tissues. However, they may move onto the vulva and into the vagina, from there moving to the external orifice of the uterus, and onwards to the uterine cavity, fallopian tubes, ovaries, and peritoneal cavity. This can cause inflammation of the vulva and vagina. This causes vaginal discharge and itchiness of the vulva. The pinworms can also enter the urethra, and presumably, they carry intestinal bacteria with them. According to Gutierrez (2000), a statistically significant correlation between pinworm infection and urinary tract infections has been shown; however, Burkhart & Burkhart (2005) maintain that the incidence of pinworms as a cause of urinary tract infections remains unknown. One report indicated that 36% of young girls with a urinary tract infection also had pinworms. Painful urination has been associated with pinworm infection.The relationship between pinworm infestation and appendicitis has been researched, but there is a lack of clear consensus on the matter: While Gutiérrez maintains that there exists a consensus that pinworms do not produce the inflammatory reaction, Cook (1994) states that it is controversial whether pinworms are causatively related to acute appendicitis, and Burkhart & Burkhart (2004) state that pinworm infection causes symptoms of appendicitis to surface. Cause The cause of a pinworm infection is the worm Enterobius vermicularis. The entire lifecycle – from egg to adult – takes place in the human gastrointestinal tract of a single human host. This process is two to eight weeks. Spread Pinworm infection spreads through human-to-human transmission, by swallowing infectious pinworm eggs. The eggs are hardy and can remain infectious in a moist environment for up to three weeks, though in a warm dry environment they usually last only 1–2 days. They do not tolerate heat well, but can survive in low temperatures: at −8 degrees Celsius (18 °F), two-thirds of the eggs are still viable after 18 hours.After the eggs have been initially deposited near the anus, they are readily transmitted to other surfaces through contamination. The surface of the eggs is sticky when laid, and the eggs are readily transmitted from their initial deposit near the anus to fingernails, hands, night-clothing and bed linen. From here, eggs are further transmitted to food, water, furniture, toys, bathroom fixtures and other objects. Household pets often carry the eggs in their fur, while not actually being infected. Dust containing eggs can become airborne and widely dispersed when dislodged from surfaces, for instance when shaking out bed clothes and linen. Consequently, the eggs can enter the mouth and nose through inhalation, and be swallowed later. Although pinworms do not strictly multiply inside the body of their human host, some of the pinworm larvae may hatch on the anal mucosa, and migrate up the bowel and back into the gastrointestinal tract of the original host. This process is called retroinfection. According to Burkhart (2005), when this retroinfection occurs, it leads to a heavy parasitic load and ensures that the pinworm infestation continues. This statement is contradictory to a statement by Caldwell, who contends that retroinfection is rare and not clinically significant. Despite the limited, 13-week lifespan of individual pinworms, autoinfection (infection from the original host to itself), either through the anus-to-mouth route or through retroinfection, causes the pinworms to inhabit the same host indefinitely. Life cycle The life cycle begins with eggs being ingested. The eggs hatch in the duodenum (first part of the small intestine). The emerging pinworm larvae grow rapidly to a size of 140 to 150 micrometres, and migrate through the small intestine towards the colon. During this migration they moult twice and become adults. Females survive for 5 to 13 weeks, and males about 7 weeks. The male and female pinworms mate in the ileum (last part of the small intestine), whereafter the male pinworms usually die, and are passed out with stool. The gravid female pinworms settle in the ileum, caecum (beginning of the large intestine), appendix and ascending colon, where they attach themselves to the mucosa and ingest colonic contents. Almost the entire body of a gravid female becomes filled with eggs. The estimations of the number of eggs in a gravid female pinworm ranges from about 11,000 to 16,000. The egg-laying process begins approximately five weeks after initial ingestion of pinworm eggs by the human host. The gravid female pinworms migrate through the colon towards the rectum at a rate of 12 to 14 centimetres per hour. They emerge from the anus, and while moving on the skin near the anus, the female pinworms deposit eggs either through (1) contracting and expelling the eggs, (2) dying and then disintegrating, or (3) bodily rupture due to the host scratching the worm. After depositing the eggs, the female becomes opaque and dies. The reason the female emerges from the anus is to obtain the oxygen necessary for the maturation of the eggs. Diagnosis Diagnosis relies on finding the eggs or the adult pinworms. Individual eggs are invisible to the naked eye, but they can be seen using a low-power microscope. On the other hand, the light-yellowish thread-like adult pinworms are clearly visually detectable, usually during the night when they move near the anus, or on toilet paper. Shining a flashlight on the infected individuals anus about one hour after they fall asleep is one form of detection and may show worms crawling out of the anus. Another form of detection is the use of transparent adhesive tape (e.g. Scotch Tape) applied on the anal area which will pick up deposited eggs, and diagnosis can be made by examining the tape with a microscope. This test is most successful if done every morning for several days, because the females do not lay eggs every day, and the number of eggs varies. A third method of diagnosis is examining a sample from under their fingernails under a microscope as itching around the anal area is common and therefore they may have collected some eggs under their nails as a result.Pinworms do not lay eggs in the feces, but sometimes eggs are deposited in the intestine. As such, routine examination of fecal material gives a positive diagnosis in only 5 to 15% of infected subjects, and is therefore of little practical diagnostic use. In a heavy infection, female pinworms may adhere to stools that pass out through the anus, and they may thus be detected on the surface on the stool. Adult pinworms are occasionally seen during colonoscopy. On a microscopic level, pinworms have an identifying feature of alae (i.e., protruding ridges) running the length of the worm. Prevention Pinworm infection cannot be totally prevented under most circumstances. This is due to the prevalence of the parasite and the ease of transmission through soiled night clothes, airborne eggs, contaminated furniture, toys and other objects. Infection may occur in the highest strata of society, where hygiene and nutritional status are typically high. The stigma associated with pinworm infection is hence considered a possible over-emphasis. Counselling is sometimes needed for upset parents who have discovered their children are infected, as they may not realize how prevalent the infection is.Preventive action revolves around personal hygiene and the cleanliness of the living quarters. The rate of reinfection can be reduced through hygienic measures, and this is recommended especially in recurring cases.The main measures are keeping fingernails short, and washing and scrubbing hands and fingers carefully, especially after defecation and before meals. Showering every morning is also highly recommended to wash off any eggs that may be still laying on the skin. Under ideal conditions, bed covers, sleeping garments, and hand towels should be changed daily and clothes and linens should be washed in hot water and then be placed in a hot dryer in order to kill off any eggs. Children can wear gloves while asleep, and the bedroom floor should be kept clean. Regular disinfection of kitchen and bathroom surfaces will help to prevent spread as well. Food should be covered to limit contamination with dust-borne parasite eggs. It is not recommended to shake clothes and bed linen as the eggs may detach and spread or to share clothes and towels. Nail biting and sucking on fingers is also discouraged. Treatment Medication is the primary treatment for pinworm infection. However, reinfection is frequent regardless of the medication used. Total elimination of the parasite in a household may require repeated doses of medication for up to a year or more. Because the drugs kill the adult pinworms, but not the eggs, the first retreatment is recommended in two weeks. Also, if one household member spreads the eggs to another, it will be a matter of two or three weeks before those eggs become adult worms and thus amenable to treatment. Asymptomatic infections, often in small children, can serve as reservoirs of infection, and therefore the entire household should be treated regardless of whether or not symptoms are present.The benzimidazole compounds albendazole (brand names e.g., Albenza, Eskazole, Zentel and Andazol) and mebendazole (brand names e.g., Ovex, Vermox, Antiox and Pripsen) are the most effective. They work by inhibiting the microtubule function in the pinworm adults, causing glycogen depletion, thereby effectively starving the parasite. A single 100 milligram dose of mebendazole with one repetition after two weeks, is considered the safest, and is usually effective with cure rate of 96%. Mebendazole has no serious side effects, although abdominal pain and diarrhea have been reported. Pyrantel pamoate (also called pyrantel embonate, brand names e.g., Reeses Pinworm Medicine, Pin-X, Combantrin, Anthel, Helmintox, and Helmex) kills adult pinworms through neuromuscular blockade, and is considered as effective as the benzimidazole compounds and is used as a second-line medication. Pyrantel pamoate is available over the counter and does not require a prescription. Pinworms located in the genitourinary system (in this case, female genital area) may require other drug treatments. Treatment in Pregnancy and Breastfeeding The available data on mebendazole, albendazole, and pyrantel pamoate use in pregnancy is limited and they are all assigned to pregnancy category level C. Treatment of a pinworm infection during pregnancy is only recommended for patients with significant symptoms that may be causing adverse effects to the pregnant person such as loss of sleep and weight loss. Pyrantel pamoate is the treatment of choice in pregnancy but should be used only after consultation with a health care practitioner rather than self-treatment. Treatment should be avoided in the first trimester, and if possible done in the third trimester. If the pregnant individual is asymptomatic, then they should be treated after the baby is delivered.Mebendazole has less than 10% of the oral dose absorbed into systemic circulation with a clinically insignificant amount of drug excreted in breastmilk, and therefore treatment should not be withheld during breastfeeding. There is limited data on the use of pyrantel pamoate and albendazole in breastfeeding but WHO also classifies them as compatible with breastfeeding. This is due to the drugs acting mainly in the intestinal system of the mother with only a very small amount of drug being absorbed into the systemic circulation. Epidemiology Pinworm infection occurs worldwide, and is the most common helminth (i.e., parasitic worm) infection in the United States and Western Europe. In the United States, a study by the Center of Disease Control reported an overall incidence rate of 11.4% among people of all ages. Pinworms are particularly common in children with approximately 30% of children being infected and most commonly seen in children between 7 and 11 years old. The prevalence rates in children having been reported as high as 61% in India, 50% in England, 39% in Thailand, 37% in Sweden, and 29% in Denmark. Finger sucking has been shown to increase both incidence and relapse rates, and nail biting has been similarly associated. Because it spreads from host to host through contamination, enterobiasis is common among people living in close contact, and tends to occur in all people within a household. The prevalence of pinworms is not associated with gender, nor with any particular social class, race, or culture. Pinworms are an exception to the tenet that intestinal parasites are uncommon in affluent communities. History The earliest known instance of pinworms is evidenced by pinworm eggs found in coprolite, carbon dated to 7837 BC at western Utah. Pinworm infection is not classified as a neglected tropical disease unlike many other parasitic worm infections.Garlic has been used as a treatment in the ancient cultures of China, India, Egypt, and Greece. Hippocrates (459–370 BC) mentioned garlic as a remedy against intestinal parasites. German botanist Lonicerus (1564) recommended garlic against parasitic worms. Notes References External links Brown MD (March 2006). "Images in clinical medicine. Enterobius vermicularis". The New England Journal of Medicine. 354 (13): e12. doi:10.1056/NEJMicm040931. PMID 16571876.

Hey Aarogya, could you help me understand about Pleurodesis

Pleurodesis

Pleurodesis is a medical procedure in which part of the pleural space is artificially obliterated. It involves the adhesion of the visceral and the costal pleura. The mediastinal pleura is spared. Uses Pleurodesis is performed to prevent recurrence of spontaneous pneumothorax or pleural effusion, and can be done chemically or mechanically. It is generally avoided in patients with cystic fibrosis if possible, because lung transplantation becomes more difficult following this procedure. Previous pneumothorax with or without pleurodesis is not a contraindication to subsequent lung transplantation. Chemical Chemicals such as bleomycin, tetracycline (e.g., minocycline), povidone-iodine, or a slurry of talc can be introduced into the pleural space through a chest drain. The instilled chemicals cause irritation between the parietal and the visceral layers of the pleura which closes off the space between them and prevents further fluid from accumulating. Pharmacy-prepared chemicals for pleurodesis should be clearly labeled "NOT FOR IV ADMINISTRATION" to avoid potentially fatal wrong-site medication errors.Sterile talc powder, administered intrapleurally via a chest tube, is indicated as a sclerosing agent to decrease the recurrence of malignant pleural effusions in symptomatic patients. It is usually performed at the time of a diagnostic thoracoscopy.Povidone iodine is equally effective and safe as talc, and may be preferred because of easy availability and low cost.Chemical pleurodesis is a painful procedure, and so patients are often premedicated with a sedative and analgesics. A local anesthetic may be instilled into the pleural space, or an epidural catheter may be placed for anesthesia. Surgical Surgical pleurodesis, also known as mechanical or abrasive pleurodesis, may be performed via thoracotomy or thoracoscopy. This involves mechanically irritating the parietal pleura, often with a scratchpad (a small foam pad with coated abrasive) normally used for cleaning electrocautery blade tips. Moreover, surgical removal of parietal pleura is an effective way of achieving stable pleurodesis.Alternatively, tunneled pleural catheters (TPCs) may be placed in an outpatient setting and often result in auto-pleurodesis, whereby portable vacuum bottles are used to evacuate the pleural fluid. Routine evacuation keeps the pleura together, resulting in physical agitation by the catheter, which slowly causes the pleura to scar together. This method, though the minimally invasive and minimal cost solution, takes an average of about 30 days to achieve pleurodesis and is therefore the slowest means of achieving pleurodesis among other modalities. References External links Media related to Pleurodesis at Wikimedia Commons

Aarogya, What does Polycystic ovary syndrome mean

Polycystic ovary syndrome

Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and not the underlying cause of the disorder.Women with PCOS may experience irregular menstrual periods, heavy periods, excess hair, acne, pelvic pain, difficulty getting pregnant, and patches of thick, darker, velvety skin. The primary characteristics of this syndrome include: hyperandrogenism, anovulation, insulin resistance, and neuroendocrine disruption.A review of the international evidence found that the prevalence of PCOS could be as high as 26% among some populations, though ranges between 4% and 18% are reported for general populations. Despite its high prevalence, the exact cause of PCOS remains uncertain and there is no known cure. Definition Two definitions are commonly used: NIHIn 1990 a consensus workshop sponsored by the NIH/NICHD suggested that a person has PCOS if they have all of the following:oligoovulation signs of androgen excess (clinical or biochemical) exclusion of other disorders that can result in menstrual irregularity and hyperandrogenismRotterdamIn 2003 a consensus workshop sponsored by ESHRE/ASRM in Rotterdam indicated PCOS to be present if any 2 out of 3 criteria are met, in the absence of other entities that might cause these findings: oligoovulation and/or anovulation excess androgen activity polycystic ovaries (by gynecologic ultrasound)The Rotterdam definition is wider, including many more women, the most notable ones being women without androgen excess. Critics say that findings obtained from the study of women with androgen excess cannot necessarily be extrapolated to women without androgen excess. Androgen Excess PCOS SocietyIn 2006, the Androgen Excess PCOS Society suggested a tightening of the diagnostic criteria to all of the following:excess androgen activity oligoovulation/anovulation and/or polycystic ovaries exclusion of other entities that would cause excess androgen activity Signs and symptoms Signs and symptoms of PCOS include irregular or no menstrual periods, heavy periods, excess body and facial hair, acne, pelvic pain, difficulty getting pregnant, and patches of thick, darker, velvety skin. This metabolic, endocrine and reproductive disorder is not universally defined, but the most common symptoms are irregular or absent periods, ovarian cysts, enlarged ovaries, excess androgen, weight gain and hirsutism. Associated conditions include type 2 diabetes, obesity, obstructive sleep apnea, heart disease, mood disorders, and endometrial cancer. This disease is related to the number of follicles per ovary each month growing from the average range of 6 to 8 to double, triple or more. it is important to distinguish between PCOS (the syndrome) and a woman with PCO (polycystic ovaries): to have PCOS, a woman must have at least two of these three symptoms (PCO, anovulation/oligoovulation and hyperandrogenism). This means that a woman can have PCOS (displaying anovulation and hyperandrogenism) without having PCO. Conversely, having PCO does not indicate that a person necessarily has PCOS. Common signs and symptoms of PCOS include the following: Menstrual disorders: PCOS mostly produces oligomenorrhea (fewer than nine menstrual periods in a year) or amenorrhea (no menstrual periods for three or more consecutive months), but other types of menstrual disorders may also occur. Infertility: This generally results directly from chronic anovulation (lack of ovulation). High levels of masculinizing hormones: Known as hyperandrogenism, the most common signs are acne and hirsutism (male pattern of hair growth, such as on the chin or chest), but it may produce hypermenorrhea (heavy and prolonged menstrual periods), androgenic alopecia (increased hair thinning or diffuse hair loss), or other symptoms. Approximately three-quarters of women with PCOS (by the diagnostic criteria of NIH/NICHD 1990) have evidence of hyperandrogenemia. Metabolic syndrome: This appears as a tendency towards central obesity and other symptoms associated with insulin resistance, including low energy levels and food cravings. Serum insulin, insulin resistance, and homocysteine levels are higher in women with PCOS. Polycystic Ovaries: Ovaries might get enlarged and comprise follicles surrounding the eggs. As result, ovaries might fail to function regularly.Women with PCOS tend to have central obesity, but studies are conflicting as to whether visceral and subcutaneous abdominal fat is increased, unchanged, or decreased in women with PCOS relative to reproductively normal women with the same body mass index. In any case, androgens, such as testosterone, androstanolone (dihydrotestosterone), and nandrolone decanoate have been found to increase visceral fat deposition in both female animals and women.Although 80% of PCOS presents in women with obesity, 20% of women diagnosed with the disease are non-obese or "lean" women. However, obese women that have PCOS have a higher risk of adverse outcomes, such as hypertension, insulin resistance, metabolic syndrome, and endometrial hyperplasia.Even though most women with PCOS are overweight or obese, it is important to acknowledge that non-overweight women can also be diagnosed with PCOS. Up to 30% of women diagnosed with PCOS maintain a normal weight before and after diagnosis. "Lean" women still face the various symptoms of PCOS with the added challenges of having their symptoms properly addressed and recognized. Lean women often go undiagnosed for years, and usually are diagnosed after struggles to conceive. Lean women are likely to have a missed diagnosis of diabetes and cardiovascular disease. These women also have an increased risk of developing insulin resistance, despite not being overweight. Lean women are often taken less seriously with their diagnosis of PCOS, and also face challenges finding appropriate treatment options. This is because most treatment options are limited to approaches of losing weight and healthy dieting.Testosterone levels are usually elevated in women with PCOS. In a 2020 systematic review and meta-analysis of sexual dysfunction related to PCOS which included 5,366 women with PCOS from 21 studies, testosterone levels were analyzed and were found to be 2.34 nmol/L (67 ng/dL) in women with PCOS and 1.57 nmol/L (45 ng/dL) in women without PCOS. In a 1995 study of 1,741 women with PCOS, mean testosterone levels were 2.6 (1.1–4.8) nmol/L (75 (32–140) ng/dL). In a 1998 study which reviewed many studies and subjected them to meta-analysis, testosterone levels in women with PCOS were 62 to 71 ng/dL (2.2–2.5 nmol/L) and testosterone levels in women without PCOS were about 32 ng/dL (1.1 nmol/L). In a 2010 study of 596 women with PCOS which used liquid chromatography–mass spectrometry (LC–MS) to quantify testosterone, median levels of testosterone were 41 and 47 ng/dL (with 25th–75th percentiles of 34–65 ng/dL and 27–58 ng/dL and ranges of 12–184 ng/dL and 1–205 ng/dL) via two different labs. If testosterone levels are above 140 to 200 ng/dL (per different sources), other possible causes of hyperandrogenism such as congenital adrenal hyperplasia or an androgen-secreting tumor may be present and should be excluded. Associated conditions Many individuals arent under the impression that the first warning sign is usually a change in appearance. But there are also manifestations of mental health problems, such as anxiety, depression, and eating disorders.A diagnosis of PCOS suggests an increased risk of the following: Endometrial hyperplasia and endometrial cancer (cancer of the uterine lining) are possible, due to overaccumulation of uterine lining, and also lack of progesterone, resulting in prolonged stimulation of uterine cells by estrogen. It is not clear whether this risk is directly due to the syndrome or from the associated obesity, hyperinsulinemia, and hyperandrogenism. Insulin resistance/Type II diabetes. A review published in 2010 concluded that women with PCOS have an elevated prevalence of insulin resistance and type II diabetes, even when controlling for body mass index (BMI). PCOS also makes a woman at higher risk for diabetes. High blood pressure, in particular if obese or during pregnancy Depression and anxiety Dyslipidemia – disorders of lipid metabolism — cholesterol and triglycerides. Women with PCOS show a decreased removal of atherosclerosis-inducing remnants, seemingly independent of insulin resistance/Type II diabetes. Cardiovascular disease, with a meta-analysis estimating a 2-fold risk of arterial disease for women with PCOS relative to women without PCOS, independent of BMI. Strokes Weight gain Miscarriage Sleep apnea, particularly if obesity is present Non-alcoholic fatty liver disease, particularly if obesity is present Acanthosis nigricans (patches of darkened skin under the arms, in the groin area, on the back of the neck) Autoimmune thyroiditis Some studies report a higher incidence of PCOS among transgender men (prior to taking testosterone), though not all have not found the same association. People with PCOS in general are also reportedly more likely to see themselves as "sexually undifferentiated" or "androgynous" and "less likely to identify with a female gender scheme."The risk of ovarian cancer and breast cancer is not significantly increased overall. Cause PCOS is caused by a combination of genetic and environmental factors. Risk factors include obesity, a lack of physical exercise, and a family history of someone with the condition. Transgender men may also experience a higher than expected rate of PCOS. Diagnosis is based on two of the following three findings: anovulation, high androgen levels, and ovarian cysts. Cysts may be detectable by ultrasound. Other conditions that produce similar symptoms include adrenal hyperplasia, hypothyroidism, and high blood levels of prolactin.PCOS is a heterogeneous disorder of uncertain cause. There is some evidence that it is a genetic disease. Such evidence includes the familial clustering of cases, greater concordance in monozygotic compared with dizygotic twins and heritability of endocrine and metabolic features of PCOS. There is some evidence that exposure to higher than typical levels of androgens and the anti-Müllerian hormone (AMH) in utero increases the risk of developing PCOS in later life. Genetics The genetic component appears to be inherited in an autosomal dominant fashion with high genetic penetrance but variable expressivity in females; this means that each child has a 50% chance of inheriting the predisposing genetic variant(s) from a parent, and, if a daughter receives the variant(s), the daughter will have the disease to some extent. The genetic variant(s) can be inherited from either the father or the mother, and can be passed along to both sons (who may be asymptomatic carriers or may have symptoms such as early baldness and/or excessive hair) and daughters, who will show signs of PCOS. The phenotype appears to manifest itself at least partially via heightened androgen levels secreted by ovarian follicle theca cells from women with the allele. The exact gene affected has not yet been identified. In rare instances, single-gene mutations can give rise to the phenotype of the syndrome. Current understanding of the pathogenesis of the syndrome suggests, however, that it is a complex multigenic disorder.Due to the scarcity of large-scale screening studies, the prevalence of endometrial abnormalities in PCOS remains unknown, though women with the condition may be at increased risk for endometrial hyperplasia and carcinoma as well as menstrual dysfunction and infertility. The severity of PCOS symptoms appears to be largely determined by factors such as obesity. PCOS has some aspects of a metabolic disorder, since its symptoms are partly reversible. Even though considered as a gynecological problem, PCOS consists of 28 clinical symptoms.Even though the name suggests that the ovaries are central to disease pathology, cysts are a symptom instead of the cause of the disease. Some symptoms of PCOS will persist even if both ovaries are removed; the disease can appear even if cysts are absent. Since its first description by Stein and Leventhal in 1935, the criteria of diagnosis, symptoms, and causative factors are subject to debate. Gynecologists often see it as a gynecological problem, with the ovaries being the primary organ affected. However, recent insights show a multisystem disorder, with the primary problem lying in hormonal regulation in the hypothalamus, with the involvement of many organs. The term PCOS is used due to the fact that there is a wide spectrum of symptoms possible. It is common to have polycystic ovaries without having PCOS; approximately 20% of European women have polcystic ovaries, but most of those women do not have PCOS. Environment PCOS may be related to or worsened by exposures during the prenatal period, epigenetic factors, environmental impacts (especially industrial endocrine disruptors, such as bisphenol A and certain drugs) and the increasing rates of obesity.Endocrine disruptors are defined as chemicals that can interfere with the endocrine system by mimicking hormones such as estrogen. However, additional research is needed to assess the role that endocrine disruptors may play in disrupting reproductive health in women and possibly triggering or exacerbating PCOS and its related symptoms. Pathogenesis Polycystic ovaries develop when the ovaries are stimulated to produce excessive amounts of androgenic hormones, in particular testosterone, by either one or a combination of the following (almost certainly combined with genetic susceptibility): the release of excessive luteinizing hormone (LH) by the anterior pituitary gland through high levels of insulin in the blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulusA majority of women with PCOS have insulin resistance and/or are obese, which is a strong risk factor for insulin resistance, although insulin resistance is a common finding among women with PCOS in normal-weight women as well. Elevated insulin levels contribute to or cause the abnormalities seen in the hypothalamic-pituitary-ovarian axis that lead to PCOS. Hyperinsulinemia increases GnRH pulse frequency, which in turn results in an increase in the LH/FSH ratio increased ovarian androgen production; decreased follicular maturation; and decreased SHBG binding. Furthermore, excessive insulin increases the activity of 17α-hydroxylase, which catalyzes the conversion of progesterone to androstenedione, which is in turn converted to testosterone. The combined effects of hyperinsulinemia contribute to an increased risk of PCOS.Adipose (fat) tissue possesses aromatase, an enzyme that converts androstenedione to estrone and testosterone to estradiol. The excess of adipose tissue in obese women creates the paradox of having both excess androgens (which are responsible for hirsutism and virilization) and excess estrogens (which inhibit FSH via negative feedback).The syndrome acquired its most widely used name due to the common sign on ultrasound examination of multiple (poly) ovarian cysts. These "cysts" are in fact immature ovarian follicles. The follicles have developed from primordial follicles, but this development has stopped ("arrested") at an early stage, due to the disturbed ovarian function. The follicles may be oriented along the ovarian periphery, appearing as a string of pearls on ultrasound examination.PCOS may be associated with chronic inflammation, with several investigators correlating inflammatory mediators with anovulation and other PCOS symptoms. Similarly, there seems to be a relation between PCOS and an increased level of oxidative stress. Diagnosis Not every person with PCOS has polycystic ovaries (PCO), nor does everyone with ovarian cysts have PCOS; although a pelvic ultrasound is a major diagnostic tool, it is not the only one. The diagnosis is fairly straightforward using the Rotterdam criteria, even when the syndrome is associated with a wide range of symptoms. Differential diagnosis Other causes of irregular or absent menstruation and hirsutism, such as hypothyroidism, congenital adrenal hyperplasia (21-hydroxylase deficiency), Cushings syndrome, hyperprolactinemia, androgen-secreting neoplasms, and other pituitary or adrenal disorders, should be investigated. Assessment and testing Standard assessment History-taking, specifically for menstrual pattern, obesity, hirsutism and acne. A clinical prediction rule found that these four questions can diagnose PCOS with a sensitivity of 77.1% (95% confidence interval [CI] 62.7%–88.0%) and a specificity of 93.8% (95% CI 82.8%–98.7%). Gynecologic ultrasonography, specifically looking for small ovarian follicles. These are believed to be the result of disturbed ovarian function with failed ovulation, reflected by the infrequent or absent menstruation that is typical of the condition. In a normal menstrual cycle, one egg is released from a dominant follicle – in essence, a cyst that bursts to release the egg. After ovulation, the follicle remnant is transformed into a progesterone-producing corpus luteum, which shrinks and disappears after approximately 12–14 days. In PCOS, there is a so-called "follicular arrest"; i.e., several follicles develop to a size of 5–7 mm, but not further. No single follicle reaches the preovulatory size (16 mm or more). According to the Rotterdam criteria, which are widely used for diagnosis of PCOS, 12 or more small follicles should be seen in a suspect ovary on ultrasound examination. More recent research suggests that there should be at least 25 follicles in an ovary to designate it as having polycystic ovarian morphology (PCOM) in women aged 18–35 years. The follicles may be oriented in the periphery, giving the appearance of a string of pearls. If a high-resolution transvaginal ultrasonography machine is not available, an ovarian volume of at least 10 ml is regarded as an acceptable definition of having polycystic ovarian morphology. rather than follicle count. Laparoscopic examination may reveal a thickened, smooth, pearl-white outer surface of the ovary. (This would usually be an incidental finding if laparoscopy were performed for some other reason, as it would not be routine to examine the ovaries in this way to confirm a diagnosis of PCOS.) Serum (blood) levels of androgens, including androstenedione and testosterone may be elevated. Dehydroepiandrosterone sulfate (DHEA-S) levels above 700–800 µg/dL are highly suggestive of adrenal dysfunction because DHEA-S is made exclusively by the adrenal glands. The free testosterone level is thought to be the best measure, with approximately 60 per cent of PCOS patients demonstrating supranormal levels.Some other blood tests are suggestive but not diagnostic. The ratio of LH (Luteinizing hormone) to FSH (Follicle-stimulating hormone), when measured in international units, is elevated in women with PCOS. Common cut-offs to designate abnormally high LH/FSH ratios are 2:1 or 3:1 as tested on Day 3 of the menstrual cycle. The pattern is not very sensitive; a ratio of 2:1 or higher was present in less than 50% of women with PCOS in one study. There are often low levels of sex hormone-binding globulin, in particular among obese or overweight women.Anti-Müllerian hormone (AMH) is increased in PCOS, and may become part of its diagnostic criteria. Glucose tolerance testing 2-hour oral glucose tolerance test (GTT) in women with risk factors (obesity, family history, history of gestational diabetes) may indicate impaired glucose tolerance (insulin resistance) in 15–33% of women with PCOS. Frank diabetes can be seen in 65–68% of women with this condition. Insulin resistance can be observed in both normal weight and overweight people, although it is more common in the latter (and in those matching the stricter NIH criteria for diagnosis); 50–80% of people with PCOS may have insulin resistance at some level. Fasting insulin level or GTT with insulin levels (also called IGTT). Elevated insulin levels have been helpful to predict response to medication and may indicate women needing higher doses of metformin or the use of a second medication to significantly lower insulin levels. Elevated blood sugar and insulin values do not predict who responds to an insulin-lowering medication, low-glycemic diet, and exercise. Many women with normal levels may benefit from combination therapy. A hypoglycemic response in which the two-hour insulin level is higher and the blood sugar lower than fasting is consistent with insulin resistance. A mathematical derivation known as the HOMAI, calculated from the fasting values in glucose and insulin concentrations, allows a direct and moderately accurate measure of insulin sensitivity (glucose-level x insulin-level/22.5). Management The primary treatments for PCOS include lifestyle changes and use of medications.Goals of treatment may be considered under four categories: Lowering of insulin resistance Restoration of fertility Treatment of hirsutism or acne Restoration of regular menstruation, and prevention of endometrial hyperplasia and endometrial cancerIn each of these areas, there is considerable debate as to the optimal treatment. One of the major factors undelying the debate is the lack of large-scale clinical trials comparing different treatments. Smaller trials tend to be less reliable and hence may produce conflicting results. General interventions that help to reduce weight or insulin resistance can be beneficial for all these aims, because they address what is believed to be the underlying cause. As PCOS appears to cause significant emotional distress, appropriate support may be useful. Diet Where PCOS is associated with overweight or obesity, successful weight loss is the most effective method of restoring normal ovulation/menstruation. The American Association of Clinical Endocrinologists guidelines recommend a goal of achieving 5 to 15% weight loss or more, which improves insulin resistance and all hormonal disorders. Still, many women find it very difficult to achieve and sustain significant weight loss. Insulin resistance itself can cause increased food cravings and lower energy levels, which can make it difficult to lose weight on a regular weight-loss diet. A scientific review in 2013 found similar improvements in weight, body composition and pregnancy rate, menstrual regularity, ovulation, hyperandrogenism, insulin resistance, lipids, and quality of life to occur with weight loss, independent of diet composition. Still, a low GI diet, in which a significant portion of total carbohydrates is obtained from fruit, vegetables, and whole-grain sources, has resulted in greater menstrual regularity than a macronutrient-matched healthy diet.Vitamin D deficiency may play some role in the development of the metabolic syndrome, and treatment of any such deficiency is indicated. However, a systematic review of 2015 found no evidence that vitamin D supplementation reduced or mitigated metabolic and hormonal dysregulations in PCOS. As of 2012, interventions using dietary supplements to correct metabolic deficiencies in people with PCOS had been tested in small, uncontrolled and nonrandomized clinical trials; the resulting data are insufficient to recommend their use. Medications Medications for PCOS include oral contraceptives and metformin. The oral contraceptives increase sex hormone binding globulin production, which increases binding of free testosterone. This reduces the symptoms of hirsutism caused by high testosterone and regulates return to normal menstrual periods. Metformin is a medication commonly used in type 2 diabetes mellitus to reduce insulin resistance, and is used off label (in the UK, US, AU and EU) to treat insulin resistance seen in PCOS. In many cases, metformin also supports ovarian function and return to normal ovulation. Spironolactone can be used for its antiandrogenic effects, and the topical cream eflornithine can be used to reduce facial hair. A newer insulin resistance medication class, the thiazolidinediones (glitazones), have shown equivalent efficacy to metformin, but metformin has a more favorable side effect profile. The United Kingdoms National Institute for Health and Clinical Excellence recommended in 2004 that women with PCOS and a body mass index above 25 be given metformin when other therapy has failed to produce results. Metformin may not be effective in every type of PCOS, and therefore there is some disagreement about whether it should be used as a general first line therapy. In addition to this, metformin is associated with several unpleasant side effects: including abdominal pain, metallic taste in the mouth, diarrhoea and vomiting. The use of statins in the management of underlying metabolic syndrome remains unclear.It can be difficult to become pregnant with PCOS because it causes irregular ovulation. Medications to induce fertility when trying to conceive include the ovulation inducer clomiphene or pulsatile leuprorelin. Evidence from randomised controlled trials suggests that in terms of live birth, metformin may be better than placebo, and metform plus clomiphene may be better than clomiphene alone, but that in both cases women may be more likely to experience gastrointestinal side effects with metformin.Metformin is thought to be safe to use during pregnancy (pregnancy category B in the US). A review in 2014 concluded that the use of metformin does not increase the risk of major birth defects in women treated with metformin during the first trimester. Liraglutide may reduce weight and waist circumference in people with PCOS more than other medications. Infertility Not all women with PCOS have difficulty becoming pregnant. But some women with PCOS may have difficulty getting pregnant since their body does not produce the hormones necessary for regular ovulation. PCOS might also increase the risk of miscarriage or premature delivery. However, it is possible to have a normal pregnancy. Including medical care and a healthy lifestyle to follow. For those that do, anovulation or infrequent ovulation is a common cause and PCOS is the main cause of anovulatory infertility. Other factors include changed levels of gonadotropins, hyperandrogenemia, and hyperinsulinemia. Like women without PCOS, women with PCOS that are ovulating may be infertile due to other causes, such as tubal blockages due to a history of sexually transmitted diseases.For overweight anovulatory women with PCOS, weight loss and diet adjustments, especially to reduce the intake of simple carbohydrates, are associated with resumption of natural ovulation. Digital health interventions have been shown to be particularly effective in providing combined therapy to manage PCOS through both lifestyle changes and medication.For those women that after weight loss still are anovulatory or for anovulatory lean women, then the medications letrozole and clomiphene citrate are the principal treatments used to promote ovulation. Previously, the anti-diabetes medication metformin was recommended treatment for anovulation, but it appears less effective than letrozole or clomiphene.For women not responsive to letrozole or clomiphene and diet and lifestyle modification, there are options available including assisted reproductive technology procedures such as controlled ovarian hyperstimulation with follicle-stimulating hormone (FSH) injections followed by in vitro fertilisation (IVF).Though surgery is not commonly performed, the polycystic ovaries can be treated with a laparoscopic procedure called "ovarian drilling" (puncture of 4–10 small follicles with electrocautery, laser, or biopsy needles), which often results in either resumption of spontaneous ovulations or ovulations after adjuvant treatment with clomiphene or FSH. (Ovarian wedge resection is no longer used as much due to complications such as adhesions and the presence of frequently effective medications.) There are, however, concerns about the long-term effects of ovarian drilling on ovarian function. Mental Health Although women with PCOS are far more likely to have depression than women without, the evidence for anti-depressant use in women with PCOS remains inconclusive. However, the pathophysiology of depression and mental stress during PCOS is linked to various changes including psychological changes such as high activity of pro-inflammatory markers and immune system during stress.PCOS is associated with other mental health related conditions besides depression such as Anxiety, Bipolar disorder, and Obsessive–compulsive disorder. Hirsutism and acne When appropriate (e.g., in women of child-bearing age who require contraception), a standard contraceptive pill is frequently effective in reducing hirsutism. Progestogens such as norgestrel and levonorgestrel should be avoided due to their androgenic effects. Metformin combined with an oral contraceptive may be more effective than either metformin or the oral contraceptive on its own.Other medications with anti-androgen effects include flutamide, and spironolactone, which can give some improvement in hirsutism. Metformin can reduce hirsutism, perhaps by reducing insulin resistance, and is often used if there are other features such as insulin resistance, diabetes, or obesity that should also benefit from metformin. Eflornithine (Vaniqa) is a medication that is applied to the skin in cream form, and acts directly on the hair follicles to inhibit hair growth. It is usually applied to the face. 5-alpha reductase inhibitors (such as finasteride and dutasteride) may also be used; they work by blocking the conversion of testosterone to dihydrotestosterone (the latter of which responsible for most hair growth alterations and androgenic acne). Although these agents have shown significant efficacy in clinical trials (for oral contraceptives, in 60–100% of individuals), the reduction in hair growth may not be enough to eliminate the social embarrassment of hirsutism, or the inconvenience of plucking or shaving. Individuals vary in their response to different therapies. It is usually worth trying other medications if one does not work, but medications do not work well for all individuals. Menstrual irregularity If fertility is not the primary aim, then menstruation can usually be regulated with a contraceptive pill. The purpose of regulating menstruation, in essence, is for the womans convenience, and perhaps her sense of well-being; there is no medical requirement for regular periods, as long as they occur sufficiently often.If a regular menstrual cycle is not desired, then therapy for an irregular cycle is not necessarily required. Most experts say that, if a menstrual bleed occurs at least every three months, then the endometrium (womb lining) is being shed sufficiently often to prevent an increased risk of endometrial abnormalities or cancer. If menstruation occurs less often or not at all, some form of progestogen replacement is recommended. Alternative medicine A 2017 review concluded that while both myo-inositol and D-chiro-inositols may regulate menstrual cycles and improve ovulation, there is a lack of evidence regarding effects on the probability of pregnancy. A 2012 and 2017 review have found myo-inositol supplementation appears to be effective in improving several of the hormonal disturbances of PCOS. Myo-inositol reduces the amount of gonadotropins and the length of controlled ovarian hyperstimulation in women undergoing in vitro fertilization. A 2011 review found not enough evidence to conclude any beneficial effect from D-chiro-inositol. There is insufficient evidence to support the use of acupuncture, current studies are inconclusive and theres a need for additional randomized controlled trials. Treatment PCOS has no cure, as of 2020. Treatment may involve lifestyle changes such as weight loss and exercise. Birth control pills may help with improving the regularity of periods, excess hair growth, and acne. Metformin and anti-androgens may also help. Other typical acne treatments and hair removal techniques may be used. Efforts to improve fertility include weight loss, clomiphene, or metformin. In vitro fertilization is used by some in whom other measures are not effective. Epidemiology PCOS is the most common endocrine disorder among women between the ages of 18 and 44. It affects approximately 2% to 20% of this age group depending on how it is defined. When someone is infertile due to lack of ovulation, PCOS is the most common cause and could guide to patients diagnosis. The earliest known description of what is now recognized as PCOS dates from 1721 in Italy. The prevalence of PCOS depends on the choice of diagnostic criteria. The World Health Organization estimates that it affects 116 million women worldwide as of 2010 (3.4% of women). Another estimate indicates that 7% of women of reproductive age are affected. Another study using the Rotterdam criteria found that about 18% of women had PCOS, and that 70% of them were previously undiagnosed. Prevalence also varies across countries due to lack of large-scale scientific studies; India, for example, has a purported rate of 1 in 5 women having PCOS.There are few studies that have investigated the racial differences in cardiometabolic factors in women with PCOS. There is also limited data on the racial differences in the risk of metabolic syndrome and cardiovascular disease in adolescents and young adults with PCOS. The first study to comprehensively examine racial differences discovered notable racial differences in risk factors for cardiovascular disease. African American women were found to be significantly more obese, with a significantly higher prevalence of metabolic syndrome compared to white adult women with PCOS. It is important for the further research of racial differences among women with PCOS, to ensure that every woman that is affected by PCOS has the available resources for management. Ultrasonographic findings of polycystic ovaries are found in 8–25% of women non-affected by the syndrome. 14% women on oral contraceptives are found to have polycystic ovaries. Ovarian cysts are also a common side effect of levonorgestrel-releasing intrauterine devices (IUDs).There are few studies that have investigated the racial differences in cardiometabolic factors in women with PCOS. History The condition was first described in 1935 by American gynecologists Irving F. Stein, Sr. and Michael L. Leventhal, from whom its original name of Stein–Leventhal syndrome is taken. Stein and Leventhal first described PCOS as an endocrine disorder in the United States, and since then, it has become recognized as one of the most common causes of oligo ovulatory infertility among women.The earliest published description of a person with what is now recognized as PCOS was in 1721 in Italy. Cyst-related changes to the ovaries were described in 1844. Etymology Other names for this syndrome include polycystic ovarian syndrome, polycystic ovary disease, functional ovarian hyperandrogenism, ovarian hyperthecosis, sclerocystic ovary syndrome, and Stein–Leventhal syndrome. The eponymous last option is the original name; it is now used, if at all, only for the subset of women with all the symptoms of amenorrhea with infertility, hirsutism, and enlarged polycystic ovaries.Most common names for this disease derive from a typical finding on medical images, called a polycystic ovary. A polycystic ovary has an abnormally large number of developing eggs visible near its surface, looking like many small cysts. Society and culture In 2005, 4 million cases of PCOS were reported in the US, costing $4.36 billion in healthcare costs. In 2016 out of the National Institute Healths research budget of $32.3 billion for that year, 0.1% was spent on PCOS research. Among those aged between 14 and 44, PCOS is conservatively estimated to cost $4.37 billion per year.As opposed to women in the general population, women with PCOS experience higher rates of depression and anxiety. International guidelines and Indian guidelines suggest psychosocial factors should be considered in women with PCOS, as well as screenings for depression and anxiety. Globally, this aspect has been increasingly focused on because it reflects the true impact of PCOS on the lives of patients. Research shows that PCOS adversely impacts a patients quality of life. Public figures A number of celebrities and public figures have spoken about their experiences with PCOS, including: Victoria Beckham Harnaam Kaur Chrisette Michele Keke Palmer Frankie Bridge Daisy Ridley Romee Strijd Jaime King Sasha Pieterse Lea Michele See also Androgen-dependent syndromes PCOS Challenge (reality television series) References Further reading == External links ==

Hi Aarogya, could you help me understand about Porphyria

Porphyria

Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are rapid in onset and short in duration. Symptoms of an attack include abdominal pain, chest pain, vomiting, confusion, constipation, fever, high blood pressure, and high heart rate. The attacks usually last for days to weeks. Complications may include paralysis, low blood sodium levels, and seizures. Attacks may be triggered by alcohol, smoking, hormonal changes, fasting, stress, or certain medications. If the skin is affected, blisters or itching may occur with sunlight exposure.Most types of porphyria are inherited from one or both of a persons parents and are due to a mutation in one of the genes that make heme. They may be inherited in an autosomal dominant, autosomal recessive, or X-linked dominant manner. One type, porphyria cutanea tarda, may also be due to hemochromatosis (increased iron in the liver), hepatitis C, alcohol, or HIV/AIDS. The underlying mechanism results in a decrease in the amount of heme produced and a build-up of substances involved in making heme. Porphyrias may also be classified by whether the liver or bone marrow is affected. Diagnosis is typically made by blood, urine, and stool tests. Genetic testing may be done to determine the specific mutation.Treatment depends on the type of porphyria and the persons symptoms. Treatment of porphyria of the skin generally involves the avoidance of sunlight, while treatment for acute porphyria may involve giving intravenous heme or a glucose solution. Rarely, a liver transplant may be carried out.The precise prevalence of porphyria is unclear, but it is estimated to affect between 1 and 100 per 50,000 people. Rates are different around the world. Porphyria cutanea tarda is believed to be the most common type. The disease was described as early as 370 BC by Hippocrates. The underlying mechanism was first described by German physiologist and chemist Felix Hoppe-Seyler in 1871. The name porphyria is from the Greek πορφύρα, porphyra, meaning "purple", a reference to the color of the urine that may be present during an attack. Signs and symptoms Acute porphyrias Acute intermittent porphyria (AIP), variegate porphyria (VP), aminolevulinic acid dehydratase deficiency porphyria (ALAD) and hereditary coproporphyria (HCP). These diseases primarily affect the nervous system, resulting in episodic crises known as acute attacks. The major symptom of an acute attack is abdominal pain, often accompanied by vomiting, hypertension (elevated blood pressure), and tachycardia (an abnormally rapid heart rate).The most severe episodes may involve neurological complications: typically motor neuropathy (severe dysfunction of the peripheral nerves that innervate muscle), which leads to muscle weakness and potentially to quadriplegia (paralysis of all four limbs) and central nervous system symptoms such as seizures and coma. Occasionally, there may be short-lived psychiatric symptoms such as anxiety, confusion, hallucinations, and, very rarely, overt psychosis. All these symptoms resolve once the acute attack passes.Given the many presentations and the relatively low occurrence of porphyria, patients may initially be suspected to have other, unrelated conditions. For instance, the polyneuropathy of acute porphyria may be mistaken for Guillain–Barré syndrome, and porphyria testing is commonly recommended in those situations. Elevation of aminolevulinic acid from lead-induced disruption of heme synthesis results in lead poisoning having symptoms similar to acute porphyria. Chronic porphyrias The non-acute porphyrias are X-linked dominant protoporphyria (XLDPP), congenital erythropoietic porphyria (CEP), porphyria cutanea tarda (PCT), and erythropoietic protoporphyria (EPP). None of these are associated with acute attacks; their primary manifestation is with skin disease. For this reason, these four porphyrias—along with two acute porphyrias, VP and HCP, that may also involve skin manifestations—are sometimes called cutaneous porphyrias. Skin disease is encountered where excess porphyrins accumulate in the skin. Porphyrins are photoactive molecules, and exposure to light results in promotion of electrons to higher energy levels. When these return to the resting energy level or ground state, energy is released. This accounts for the property of fluorescence typical of the porphyrins. This causes local skin damage. Two distinct patterns of skin disease are seen in porphyria: Immediate photosensitivity. This is typical of XLDPP and EPP. Following a variable period of sun exposure—typically about 30 minutes—patients complain of severe pain, burning, and discomfort in exposed areas. Typically, the effects are not visible, though occasionally there may be some redness and swelling of the skin. Vesiculo-erosive skin disease. This—a reference to the characteristic blistering (vesicles) and open sores (erosions) noted in patients—is the pattern seen in CEP, PCT, VP, and HCP. The changes are noted only in sun-exposed areas such as the face and back of the hands. Milder skin disease, such as that seen in VP and HCP, consists of increased skin fragility in exposed areas with a tendency to form blisters and erosions, particularly after minor knocks or scrapes. These heal slowly, often leaving small scars that may be lighter or darker than normal skin. More severe skin disease is sometimes seen in PCT, with prominent lesions, darkening of exposed skin such as the face, and hypertrichosis: abnormal hair growth on the face, particularly the cheeks. The most severe disease is seen in CEP and a rare variant of PCT known as hepatoerythropoietic porphyria (HEP); symptoms include severe shortening of digits, loss of skin appendages such as hair and nails, and severe scarring of the skin with progressive disappearance of ears, lips, and nose. Patients may also show deformed, discolored teeth or gum and eye abnormalities. Cause The porphyrias are generally considered genetic in nature. Genetics Subtypes of porphyrias depend on which enzyme is deficient. X-linked dominant protoporphyria is a rare form of erythropoietic protoporphyria caused by a gain-of-function mutation in ALAS2 characterized by severe photosensitivity.In the autosomal recessive types, if a person inherits a single gene they may become a carrier. Generally they do not have symptoms, but may pass the gene onto offspring. Triggers Acute porphyria can be triggered by a number of drugs, most of which are believed to trigger it by interacting with enzymes in the liver which are made with heme. Such drugs include: Sulfonamides, including sulfadiazine, sulfasalazine and trimethoprim/sulfamethoxazole. Sulfonylureas like glibenclamide, gliclazide and glimepiride, although glipizide is thought to be safe. Barbiturates including thiopental, phenobarbital, primidone, etc. Systemic treatment with antifungals including fluconazole, griseofulvin, ketoconazole and voriconazole. (Topical use of these agents is thought to be safe due to minimal systemic absorption.) Certain antibiotics like rifapentine, rifampicin, rifabutine, isoniazid, nitrofurantoin and, possibly, metronidazole. Ergot derivatives including dihydroergotamine, ergometrine, ergotamine, methysergide, etc. Certain antiretroviral medications (e.g. indinavir, nevirapine, ritonavir, saquinavir, etc.) Progestogens Some anticonvulsants including: carbamazepine, ethosuximide, phenytoin, topiramate, valproate. Some painkillers like dextropropoxyphene, ketorolac, metamizole, pentazocine Some cancer treatments like bexarotene, busulfan, chlorambucil, estramustine, etoposide, flutamide, idarubicin, ifosfamide, irinotecan, ixabepilone, letrozole, lomustine, megestrol, mitomycin, mitoxantrone, paclitaxel, procarbazine, tamoxifen, topotecan Some antidepressants like imipramine, phenelzine, trazodone Some antipsychotics like risperidone, ziprasidone Some retinoids used for skin conditions like acitretin and isotretinoin Miscellaneous others including: cocaine, methyldopa, fenfluramine, disulfiram, orphenadrine, pentoxifylline, and sodium aurothiomalate. Pathogenesis In humans, porphyrins are the main precursors of heme, an essential constituent of hemoglobin, myoglobin, catalase, peroxidase, and P450 liver cytochromes.The body requires porphyrins to produce heme, which is used to carry oxygen in the blood among other things, but in the porphyrias there is a deficiency (inherited or acquired) of the enzymes that transform the various porphyrins into others, leading to abnormally high levels of one or more of these substances. Porphyrias are classified in two ways, by symptoms and by pathophysiology. Physiologically, porphyrias are classified as liver or erythropoietic based on the sites of accumulation of heme precursors, either in the liver or in the bone marrow and red blood cells.Deficiency in the enzymes of the porphyrin pathway leads to insufficient production of heme. Heme function plays a central role in cellular metabolism. This is not the main problem in the porphyrias; most heme synthesis enzymes—even dysfunctional enzymes—have enough residual activity to assist in heme biosynthesis. The principal problem in these deficiencies is the accumulation of porphyrins, the heme precursors, which are toxic to tissue in high concentrations. The chemical properties of these intermediates determine the location of accumulation, whether they induce photosensitivity, and whether the intermediate is excreted (in the urine or feces).There are eight enzymes in the heme biosynthetic pathway, four of which—the first one and the last three—are in the mitochondria, while the other four are in the cytosol. Defects in any of these can lead to some form of porphyria. The hepatic porphyrias are characterized by acute neurological attacks (seizures, psychosis, extreme back and abdominal pain, and an acute polyneuropathy), while the erythropoietic forms present with skin problems, usually a light-sensitive blistering rash and increased hair growth.Variegate porphyria (also porphyria variegata or mixed porphyria), which results from a partial deficiency in PROTO oxidase, manifests itself with skin lesions similar to those of porphyria cutanea tarda combined with acute neurologic attacks. Hereditary coproporphyria, which is characterized by a deficiency in coproporphyrinogen oxidase, coded for by the CPOX gene, may also present with both acute neurologic attacks and cutaneous lesions. All other porphyrias are either skin- or nerve-predominant. Diagnosis Porphyrin studies Porphyria is diagnosed through biochemical analysis of blood, urine, and stool. In general, urine estimation of porphobilinogen (PBG) is the first step if acute porphyria is suspected. As a result of feedback, the decreased production of heme leads to increased production of precursors, PBG being one of the first substances in the porphyrin synthesis pathway. In nearly all cases of acute porphyria syndromes, urinary PBG is markedly elevated except for the very rare ALA dehydratase deficiency or in patients with symptoms due to hereditary tyrosinemia type I. In cases of mercury- or arsenic poisoning-induced porphyria, other changes in porphyrin profiles appear, most notably elevations of uroporphyrins I & III, coproporphyrins I & III, and pre-coproporphyrin.Repeat testing during an attack and subsequent attacks may be necessary in order to detect a porphyria, as levels may be normal or near-normal between attacks. The urine screening test has been known to fail in the initial stages of a severe, life-threatening attack of acute intermittent porphyria.Up to 90% of the genetic carriers of the more common, dominantly inherited acute hepatic porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria) have been noted in DNA tests to be latent for classic symptoms and may require DNA or enzyme testing. The exception to this may be latent post-puberty genetic carriers of hereditary coproporphyria.As most porphyrias are rare conditions, general hospital labs typically do not have the expertise, technology, or staff time to perform porphyria testing. In general, testing involves sending samples of blood, stool, and urine to a reference laboratory. All samples to detect porphyrins must be handled properly. Samples should be taken during an acute attack; otherwise a false negative result may occur. Samples must be protected from light and either refrigerated or preserved.If all the porphyrin studies are negative, one must consider pseudoporphyria. A careful medication review often will find the cause of pseudoporphyria. Additional tests Further diagnostic tests of affected organs may be required, such as nerve conduction studies for neuropathy or an ultrasound of the liver. Basic biochemical tests may assist in identifying liver disease, hepatocellular carcinoma, and other organ problems. Management Acute porphyria Carbohydrate administration Often, empirical treatment is required if the diagnostic suspicion of a porphyria is high since acute attacks can be fatal. A high-carbohydrate diet is typically recommended; in severe attacks, a dextrose 10% infusion is commenced, which may aid in recovery by suppressing heme synthesis, which in turn reduces the rate of porphyrin accumulation. However, this can worsen cases of low blood sodium levels (hyponatraemia) and should be done with extreme caution as it can prove fatal. Heme analogs Hematin (trade name Panhematin) and heme arginate (trade name NormoSang) are the drugs of choice in acute porphyria, in the United States and the United Kingdom, respectively. These drugs need to be given very early in an attack to be effective; effectiveness varies amongst individuals. They are not curative drugs but can shorten attacks and reduce the intensity of an attack. Side effects are rare but can be serious. These heme-like substances theoretically inhibit ALA synthase and hence the accumulation of toxic precursors. In the United Kingdom, supplies of NormoSang are kept at two national centers; emergency supply is available from St Thomass Hospital, London. In the United States, Lundbeck manufactures and supplies Panhematin for infusion.Heme arginate (NormoSang) is used during crises but also in preventive treatment to avoid crises, one treatment every 10 days.Any sign of low blood sodium (hyponatremia) or weakness should be treated with the addition of hematin, heme arginate, or even tin mesoporphyrin, as these are signs of impending syndrome of inappropriate antidiuretic hormone (SIADH) or peripheral nervous system involvement that may be localized or severe, progressing to bulbar paresis and respiratory paralysis. Cimetidine Cimetidine has also been reported to be effective for acute porphyric crisis and possibly effective for long-term prophylaxis. Symptom control Pain is severe, frequently out of proportion to physical signs, and often requires the use of opiates to reduce it to tolerable levels. Pain should be treated as early as medically possible. Nausea can be severe; it may respond to phenothiazine drugs but is sometimes intractable. Hot baths and showers may lessen nausea temporarily, though caution should be used to avoid burns or falls. Early identification It is recommended that patients with a history of acute porphyria, and even genetic carriers, wear an alert bracelet or other identification at all times. This is in case they develop severe symptoms, or in case of accidents where there is a potential for drug exposure, and as a result they are unable to explain their condition to healthcare professionals. Some drugs are absolutely contraindicated for patients with any form of porphyria. Neurologic and psychiatric disorders Patients who experience frequent attacks can develop chronic neuropathic pain in extremities as well as chronic pain in the abdomen. Intestinal pseudo-obstruction, ileus, intussusception, hypoganglionosis, and encopresis in children have been associated with porphyrias. This is thought to be due to axonal nerve deterioration in affected areas of the nervous system and vagal nerve dysfunction. Pain treatment with long-acting opioids, such as morphine, is often indicated, and, in cases where seizure or neuropathy is present, gabapentin is known to improve outcome.Seizures often accompany this disease. Most seizure medications exacerbate this condition. Treatment can be problematic: barbiturates especially must be avoided. Some benzodiazepines are safe and, when used in conjunction with newer anti-seizure medications such as gabapentin, offer a possible regimen for seizure control. Gabapentin has the additional feature of aiding in the treatment of some kinds of neuropathic pain. Magnesium sulfate and bromides have also been used in porphyria seizures; however, development of status epilepticus in porphyria may not respond to magnesium alone. The addition of hematin or heme arginate has been used during status epilepticus.Depression often accompanies the disease and is best dealt with by treating the offending symptoms and if needed the judicious use of antidepressants. Some psychotropic drugs are porphyrinogenic, limiting the therapeutic scope. Other psychiatric symptoms such as anxiety, restlessness, insomnia, depression, mania, hallucinations, delusions, confusion, catatonia, and psychosis may occur. Underlying liver disease Some liver diseases may cause porphyria even in the absence of genetic predisposition. These include hemochromatosis and hepatitis C. Treatment of iron overload may be required.Patients with the acute porphyrias (AIP, HCP, VP) are at increased risk over their life for hepatocellular carcinoma (primary liver cancer) and may require monitoring. Other typical risk factors for liver cancer need not be present. Hormone treatment Hormonal fluctuations that contribute to cyclical attacks in women have been treated with oral contraceptives and luteinizing hormones to shut down menstrual cycles. However, oral contraceptives have also triggered photosensitivity and withdrawal of oral contraceptives has triggered attacks. Androgens and fertility hormones have also triggered attacks. In 2019, givosiran was approved in the United States for the treatment of acute hepatic porphyria. Erythropoietic porphyria These are associated with accumulation of porphyrins in erythrocytes and are rare. The pain, burning, swelling, and itching that occur in erythropoietic porphyrias generally require avoidance of bright sunlight. Most kinds of sunscreen are not effective, but SPF-rated long-sleeve shirts, hats, bandanas, and gloves can help. Chloroquine may be used to increase porphyrin secretion in some EPs. Blood transfusion is occasionally used to suppress innate heme production.The rarest is congenital erythropoietic porphyria (CEP), otherwise known as Gunthers disease. The signs may present from birth and include severe photosensitivity, brown teeth that fluoresce in ultraviolet light due to deposition of Type 1 porphyrins, and later hypertrichosis. Hemolytic anemia usually develops. Pharmaceutical-grade beta carotene may be used in its treatment. A bone marrow transplant has also been successful in curing CEP in a few cases, although long-term results are not yet available.In December 2014, afamelanotide received authorization from the European Commission as a treatment for the prevention of phototoxicity in adult patients with EPP. Epidemiology Rates of all types of porphyria taken together have been estimated to be approximately one in 25,000 in the United States. The worldwide prevalence has been estimated to be between one in 500 and one in 50,000 people.Porphyrias have been detected in all races and in multiple ethnic groups on every continent. There are high incidence reports of AIP in areas of India and Scandinavia. More than 200 genetic variants of AIP are known, some of which are specific to families, although some strains have proven to be repeated mutations. History The underlying mechanism was first described by Felix Hoppe-Seyler in 1871, and acute porphyrias were described by the Dutch physician Barend Stokvis in 1889.The links between porphyrias and mental illness have been noted for decades. In the early 1950s, patients with porphyrias (occasionally referred to as "porphyric hemophilia") and severe symptoms of depression or catatonia were treated with electroshock therapy. Vampires and werewolves Porphyria has been suggested as an explanation for the origin of vampire and werewolf legends, based upon certain perceived similarities between the condition and the folklore. In January 1964, L. Illiss 1963 paper, "On Porphyria and the Aetiology of Werewolves," was published in Proceedings of the Royal Society of Medicine. Later, Nancy Garden argued for a connection between porphyria and the vampire belief in her 1973 book, Vampires. In 1985, biochemist David Dolphins paper for the American Association for the Advancement of Science, "Porphyria, Vampires, and Werewolves: The Aetiology of European Metamorphosis Legends," gained widespread media coverage, popularizing the idea.The theory has been rejected by a few folklorists and researchers as not accurately describing the characteristics of the original werewolf and vampire legends or the disease, and as potentially stigmatizing people with porphyria.A 1995 article from the Postgraduate Medical Journal (via NIH) explains: As it was believed that the folkloric vampire could move about freely in daylight hours, as opposed to the 20th century variant, congenital erythropoietic porphyria cannot readily explain the folkloric vampire but may be an explanation of the vampire as we know it in the 20th century. In addition, the folkloric vampire, when unearthed, was always described as looking quite healthy ("as they were in life"), while due to disfiguring aspects of the disease, sufferers would not have passed the exhumation test. Individuals with congenital erythropoietic porphyria do not crave blood. The enzyme (hematin) necessary to alleviate symptoms is not absorbed intact on oral ingestion, and drinking blood would have no beneficial effect on the sufferer. Finally, and most important, the fact that vampire reports were literally rampant in the 18th century, and that congenital erythropoietic porphyria is an extremely rare manifestation of a rare disease, makes it an unlikely explanation of the folkloric vampire. Notable cases King George III. The mental illness exhibited by George III in the regency crisis of 1788 has inspired several attempts at retrospective diagnosis. The first, written in 1855, thirty-five years after his death, concluded that he had acute mania. M. Guttmacher, in 1941, suggested manic-depressive psychosis as a more likely diagnosis. The first suggestion that a physical illness was the cause of King Georges mental derangement came in 1966, in a paper called "The Insanity of King George III: A Classic Case of Porphyria", with a follow-up in 1968, "Porphyria in the Royal Houses of Stuart, Hanover and Prussia". The papers, by a mother/son psychiatrist team, were written as though the case for porphyria had been proven, but the response demonstrated that many experts, including those more intimately familiar with the manifestations of porphyria, were unconvinced. Many psychiatrists disagreed with the diagnosis, suggesting bipolar disorder as far more probable. The theory is treated in Purple Secret, which documents the ultimately unsuccessful search for genetic evidence of porphyria in the remains of royals suspected to have had it. In 2005, it was suggested that arsenic (which is known to be porphyrogenic) given to George III with antimony may have caused his porphyria. This study found high levels of arsenic in King Georges hair. In 2010, one analysis of historical records argued that the porphyria claim was based on spurious and selective interpretation of contemporary medical and historical sources. The mental illness of George III is the basis of the plot in The Madness of King George, a 1994 British film based upon the 1991 Alan Bennett play, The Madness of George III. The closing credits of the film include the comment that the Kings symptoms suggest that he had porphyria and notes that the disease is "periodic, unpredictable, and hereditary". The traditional argument that George III did NOT have porphyria, but rather bipolar disorder, is thoroughly defended by Andrew Roberts in his new biography, "The Last King of America." Descendants of George III. Among other descendants of George III theorized by the authors of Purple Secret to have had porphyria (based on analysis of their extensive and detailed medical correspondence) were his great-great-granddaughter Princess Charlotte of Prussia (Emperor William IIs eldest sister) and her daughter Princess Feodora of Saxe-Meiningen. They uncovered better evidence that George IIIs great-great-great-grandson Prince William of Gloucester was reliably diagnosed with variegate porphyria. Mary, Queen of Scots. It is believed that Mary, Queen of Scots, King George IIIs ancestor, also had acute intermittent porphyria, although this is subject to much debate. It is assumed she inherited the disorder, if indeed she had it, from her father, James V of Scotland. Both father and daughter endured well-documented attacks that could fall within the constellation of symptoms of porphyria. Maria I of Portugal. Maria I—known as "Maria the Pious" or "Maria the Mad" because of both her religious fervor and her acute mental illness, which made her incapable of handling state affairs after 1792 – is also thought to have had porphyria. Francis Willis, the same physician who treated George III, was even summoned by the Portuguese court but returned to England after the court limited the treatments he could oversee. Contemporary sources, such as Secretary of State for Foreign Affairs Luís Pinto de Sousa Coutinho, noted that the queen had ever-worsening stomach pains and abdominal spasms: hallmarks of porphyria. Vlad III Dracula, “The Impaler.” Vlad III was also said to have had acute porphyria, which may have started the notion that vampires were allergic to sunlight. Vincent van Gogh. Other commentators have suggested that Vincent van Gogh may have had acute intermittent porphyria. King Nebuchadnezzar of Babylon. The description of this king in Daniel 4 suggests to some that he had porphyria. Physician Archie Cochrane. He was born with porphyria, which caused health problems throughout his life. Paula Frías Allende. The daughter of the Chilean novelist Isabel Allende. She fell into a porphyria-induced coma in 1991, which inspired Isabel to write the memoir Paula, dedicated to her. Uses in Literature Stated or implied references to porphyria are included in some literature, particularly gothic literature. These include the following: The condition is the name of the title character in the gothic poem "Porphyrias Lover," by Robert Browning. The condition is heavily implied to be the cause of the symptoms suffered by the narrator in the gothic short story "Lusus Naturae," by Margaret Atwood. Some of the narrators symptoms resemble those of porphyria, and one passage of the story states that the name of the narrators disease "had some Ps and Rs in it." References External links Porphyria at Curlie The Drug Database for Acute Porphyria - comprehensive database on drug porphyrinogenicity Orphanets disease page on Porphyria

Aarogya, can you share information about a health condition involving Postherpetic neuralgia

Postherpetic neuralgia

Postherpetic neuralgia (PHN) is neuropathic pain that occurs due to damage to a peripheral nerve caused by the reactivation of the varicella zoster virus (herpes zoster, also known as shingles). Typically, the nerve pain (neuralgia) is confined to an area of skin innervated by a single sensory nerve, which is known as a dermatome. PHN is defined as dermatomal nerve pain that persists for more than 90 days after an outbreak of herpes zoster affecting the same dermatome. Several types of pain may occur with PHN including continuous burning pain, episodes of severe shooting or electric-like pain, and a heightened sensitivity to gentle touch which would not otherwise cause pain (mechanical allodynia) or to painful stimuli (hyperalgesia). Abnormal sensations and itching may also occur.The nerve pain of PHN is thought to result from damage in a peripheral nerve that was affected by the reactivation of the varicella zoster virus or troubles after chemotherapy. PHN typically begins when the herpes zoster vesicles have crusted over and begun to heal, but can begin in the absence of herpes zoster—a condition called zoster sine herpete.There is no treatment that modifies the disease course of PHN; therefore, controlling the affected persons symptoms is the main goal of treatment. Medications applied to the skin such as capsaicin or topical anesthetics (e.g., lidocaine) are used for mild pain and can be used in combination with oral medications for moderate to severe pain. Oral anticonvulsant medications such as gabapentin and pregabalin are also approved for treatment of PHN. Tricyclic antidepressants reduce PHN pain, but their use is limited by side effects. Opioid medications are not generally recommended for treatment except in specific circumstances. Such cases should involve a pain specialist in patient care due to mixed evidence of efficacy and concerns about potential for abuse and addiction.PHN is the most common long-term complication of herpes zoster. The incidence and prevalence of PHN are uncertain due to varying definitions. Approximately 20% of people affected by herpes zoster report pain in the affected area three months after the initial episode of herpes zoster, and 15% of people similarly report this pain two years after the herpes zoster rash. Since herpes zoster occurs due to reactivation of the varicella zoster virus, which is more likely to occur with a weakened immune system, both herpes zoster and PHN occur more often in the elderly and in people with diabetes mellitus. Risk factors for PHN include older age, a severe herpes-zoster rash, and pain during the herpes zoster episode. PHN is often very painful and can be quite debilitating. Affected individuals often experience a decrease in their quality of life. Signs and symptoms Symptoms: With resolution of the herpes zoster eruption, pain that continues for three months or more is defined as postherpetic neuralgia. Pain is variable, from discomfort to very severe, and may be described as burning, stabbing, or gnawing.Signs: Area of previous herpes zoster may show evidence of cutaneous scarring. Sensation may be altered over the areas involved, in the form of either hypersensitivity or decreased sensation. In rare cases, the patient might also experience muscle weakness, tremor, or paralysis if the nerves involved also control muscle movement. Pathophysiology Postherpetic neuralgia is thought to be due to nerve damage caused by herpes zoster. The damage causes nerves in the affected dermatomic area of the skin to send abnormal electrical signals to the brain. These signals may convey excruciating pain, and may persist or recur for months, years, or for life.A key factor in the neural plasticity underlying neuropathic pain is altered gene expression in sensory dorsal root ganglia neurons. Injury to sensory nerves induces neurochemical, physiological, and anatomical modifications to afferent and central neurons, such as afferent terminal sprouting and inhibitory interneuron loss. Following nerve damage, NaCl channel accumulation causes hyperexcitability, and downregulation of the TTX-resistant Nav1.8 (sensory neuron specific, SNS1) channel and upregulation of TTX-sensitive Nav1.3 (brain type III) and TRPV1 channels. These changes contribute to increased NMDA glutamate receptor-dependent excitability of spinal dorsal horn neurons and are restricted to the ipsilateral (injured) side. A combination of these factors could contribute to the neuropathic pain state of postherpetic neuralgia. Diagnosis Lab Studies: No laboratory work is usually necessary. Results of cerebrospinal fluid evaluation are abnormal in 61%. Pleocytosis is observed in 46%, elevated protein in 26%, and VZV DNA in 22%. These findings are not predictive of the clinical course of postherpetic neuralgia. Viral culture or immunofluorescence staining may be used to differentiate herpes simplex from herpes zoster in cases that are difficult to distinguish clinically. Antibodies to herpes zoster can be measured. A 4-fold increase has been used to support the diagnosis of subclinical herpes zoster (zoster sine herpete). However, a rising titer secondary to viral exposure rather than reactivation cannot be ruled out.Imaging studies: Magnetic resonance imaging lesions attributable to herpes zoster were seen in the brain stem and cervical cord in 56% (9/16) of patients. At three months after onset of herpes zoster, 56% (5/9) of patients with an abnormal magnetic resonance image had developed postherpetic neuralgia. Of the seven patients who had no herpes-zoster-related lesions on the magnetic resonance image, none had residual pain. Prevention Primary prevention In 1995, the Food and Drug Administration (FDA) approved the Varicella vaccine to prevent chickenpox. Its effect on postherpetic neuralgia is still unknown. The vaccine—made from a weakened form of the varicella-zoster virus—may keep chickenpox from occurring in nonimmune children and adults, or at least lessen the risk of the varicella zoster virus lying dormant in the body and reactivating later as shingles. If shingles could be prevented, postherpetic neuralgia could be completely avoided.In May 2006 the Advisory Committee on Immunization Practices approved a new vaccine by Merck (Zostavax) against shingles. This vaccine is a more potent version of the chickenpox vaccine, and evidence shows that it reduces the incidence of postherpetic neuralgia. The CDC recommends use of this vaccine in all persons over 60 years old.The most effective means of preventing PHN from a herpes zoster infection is prior vaccination with the varicella vaccine. Vaccination decreases the overall incidence of virus reactivation but also decreases the severity of disease development and incidence of PHN if reactivation does occur. Secondary prevention A 2013 Cochrane meta-analysis of 6 randomized controlled trials (RCTs) investigating oral antiviral medications given within 72 hours after the onset of herpes zoster rash in immunocompetent people for preventing postherpetic neuralgia (PHN) found no significant difference between placebo and acyclovir. Additionally, there was no significant difference in preventing the incidence of PHN found in the one RCT included in the meta-analysis that compared placebo to oral famciclovir treatment within 72 hours of HZ rash onset. Studies using valacyclovir treatment were not included in the meta-analysis. PHN was defined as pain at the site of the dermatomic rash at 120 days after the onset of rash, and incidence was evaluated at 1, 4, and 6 months after rash onset. Patients who are prescribed oral antiviral agents after the onset of rash should be informed that their chances of developing PHN are no different than those not taking oral antiviral agents. Treatment The pain from postherpetic neuralgia can be very severe and requires immediate treatment. There is no treatment which modifies the course of the disease and management primarily aims to control symptoms. Medications Topical medications Medications applied to the skin can be used alone if the pain from PHN is mild or in combination with oral medications if the pain is moderate to severe. Topical medications for PHN include low-dose (0.075%) and high-dose (8%) capsaicin and anesthetics such as lidocaine patches. Lidocaine patches (5% concentration) are approved in the United States and Europe to treat PHN though evidence supporting their use is limited. A meta-analysis of multiple small placebo-controlled randomized controlled trials found that for every two people treated with topical lidocaine, one person experienced at least a 50% reduction in their PHN-associated pain (number needed to treat (NNT)=2).Low-dose capsaicin may be useful for reducing PHN-associated pain but is limited by side effects (redness and a burning or stinging sensation with application) and the need to apply it four times daily. Approximately three people must be treated with low-dose capsaicin cream for one person to experience significant pain relief (number needed to treat =3.3). A single topical application of a high-dose capsaicin patch over the affected area after numbing the area with a topical anesthetic has also been found to relieve PHN-associated pain. For every eleven people treated with a high-dose capsaicin patch for up to 12 weeks, one person experienced a significant improvement in their pain. (number needed to treat=11). Due to the need for topical anesthesia before application of the high-dose capsaicin patch, referral to a pain specialist is generally recommended if this approach is being considered. Oral medications Multiple oral medications have demonstrated efficacy in relieving postherpetic neuralgia pain. Tricyclic antidepressants (TCAs), such as nortriptyline or desipramine, are effective in reducing postherpetic neuralgia pain but are limited by their numerous side effects. For every three people treated with a tricyclic antidepressant, one person is expected to have a clinically significant reduction in their pain (NNT=3). Additionally, of every sixteen people treated with a TCA, one person is expected to stop the medication due to a bothersome side effect, such as dry mouth, constipation, or urinary retention (number needed to harm=16). The anticonvulsant medications pregabalin and gabapentin also effectively relieve postherpetic neuralgia pain. Treatment with pregabalin leads to a reduction in pain intensity of 50% or more in one person out of every 4–5 people treated (NNT=4–5). Similarly, treatment with gabapentin also leads to a 50% reduction in pain intensity in one person out of every 7-8 people treated (NNT=7.5).Opioids such as tramadol, methadone, oxycodone, and morphine have not been well-studied for postherpetic neuralgia treatment. Acetaminophen and nonsteroidal anti-inflammatory drugs are thought to be ineffective and have not undergone rigorous study for PHN. Prognosis The natural history of postherpetic neuralgia involves slow resolution of the pain syndrome. A subgroup of affected individuals may develop severe, long-lasting pain that does not respond to medical therapy. Epidemiology In the United States each year approximately 1,000,000 individuals develop herpes zoster. Of those individuals, approximately 10–18% develop postherpetic neuralgia.Fewer than 10 percent of people younger than 60 develop postherpetic neuralgia after a bout of herpes zoster, while about 40 percent of people older than 60 do. References Further reading Hempenstall K, Nurmikko TJ, Johnson RW, AHern RP, Rice AS (July 2005). "Analgesic therapy in postherpetic neuralgia: a quantitative systematic review". PLOS Medicine. 2 (7): e164. doi:10.1371/journal.pmed.0020164. PMC 1181872. PMID 16013891. == External links ==

Aarogya, explain a scenario commonly referred as Post-traumatic stress disorder

Post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats on a persons life. Symptoms may include disturbing thoughts, feelings, or dreams related to the events, mental or physical distress to trauma-related cues, attempts to avoid trauma-related cues, alterations in the way a person thinks and feels, and an increase in the fight-or-flight response. These symptoms last for more than a month after the event. Young children are less likely to show distress but instead may express their memories through play. A person with PTSD is at a higher risk of suicide and intentional self-harm.Most people who experience traumatic events do not develop PTSD. People who experience interpersonal violence such as rape, other sexual assaults, being kidnapped, stalking, physical abuse by an intimate partner, and incest or other forms of childhood sexual abuse are more likely to develop PTSD than those who experience non-assault based trauma, such as accidents and natural disasters. Those who experience prolonged trauma, such as slavery, concentration camps, or chronic domestic abuse, may develop complex post-traumatic stress disorder (C-PTSD). C-PTSD is similar to PTSD but has a distinct effect on a persons emotional regulation and core identity.Prevention may be possible when counselling is targeted at those with early symptoms but is not effective when provided to all trauma-exposed individuals whether or not symptoms are present. The main treatments for people with PTSD are counselling (psychotherapy) and medication. Antidepressants of the SSRI or SNRI type are the first-line medications used for PTSD and are moderately beneficial for about half of people. Benefits from medication are less than those seen with counselling. It is not known whether using medications and counselling together has greater benefit than either method separately. Medications, other than some SSRIs or SNRIs, do not have enough evidence to support their use and, in the case of benzodiazepines, may worsen outcomes.In the United States, about 3.5% of adults have PTSD in a given year, and 9% of people develop it at some point in their life. In much of the rest of the world, rates during a given year are between 0.5% and 1%. Higher rates may occur in regions of armed conflict. It is more common in women than men.Symptoms of trauma-related mental disorders have been documented since at least the time of the ancient Greeks. A few instances of evidence of post-traumatic illness have been argued to exist from the seventeenth and eighteenth centuries, such as the diary of Samuel Pepys, who described intrusive and distressing symptoms following the 1666 Fire of London. During the world wars, the condition was known under various terms, including shell shock, war nerves, neurasthenia and combat neurosis. The term "post-traumatic stress disorder" came into use in the 1970s in large part due to the diagnoses of U.S. military veterans of the Vietnam War. It was officially recognized by the American Psychiatric Association in 1980 in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III). Symptoms Symptoms of PTSD generally begin within the first three months after the inciting traumatic event, but may not begin until years later. In the typical case, the individual with PTSD persistently avoids either trauma-related thoughts and emotions or discussion of the traumatic event and may even have amnesia of the event. However, the event is commonly relived by the individual through intrusive, recurrent recollections, dissociative episodes of reliving the trauma ("flashbacks"), and nightmares (50 to 70%). While it is common to have symptoms after any traumatic event, these must persist to a sufficient degree (i.e., causing dysfunction in life or clinical levels of distress) for longer than one month after the trauma to be classified as PTSD (clinically significant dysfunction or distress for less than one month after the trauma may be acute stress disorder). Some following a traumatic event experience post-traumatic growth. Associated medical conditions Trauma survivors often develop depression, anxiety disorders, and mood disorders in addition to PTSD.Substance use disorder, such as alcohol use disorder, commonly co-occur with PTSD. Recovery from post-traumatic stress disorder or other anxiety disorders may be hindered, or the condition worsened, when substance use disorders are comorbid with PTSD. Resolving these problems can bring about improvement in an individuals mental health status and anxiety levels.In children and adolescents, there is a strong association between emotional regulation difficulties (e.g. mood swings, anger outbursts, temper tantrums) and post-traumatic stress symptoms, independent of age, gender, or type of trauma.Moral injury the feeling of moral distress such as a shame or guilt following a moral transgression is associated with PTSD but is distinguished from it. Moral injury is associated with shame and guilt while PTSD is associated with anxiety and fear.: 2,8,11 Risk factors Persons considered at risk include combat military personnel, survivors of natural disasters, concentration camp survivors, and survivors of violent crime. Persons employed in occupations that expose them to violence (such as soldiers) or disasters (such as emergency service workers) are also at risk. Other occupations that are at higher risk include police officers, firefighters, ambulance personnel, health care professionals, train drivers, divers, journalists, and sailors, in addition to people who work at banks, post offices or in stores. Trauma PTSD has been associated with a wide range of traumatic events. The risk of developing PTSD after a traumatic event varies by trauma type and is highest following exposure to sexual violence (11.4%), particularly rape (19.0%). Men are more likely to experience a traumatic event (of any type), but women are more likely to experience the kind of high-impact traumatic event that can lead to PTSD, such as interpersonal violence and sexual assault.Motor vehicle collision survivors, both children and adults, are at an increased risk of PTSD. Globally, about 2.6% of adults are diagnosed with PTSD following a non-life-threatening traffic accident, and a similar proportion of children develop PTSD. Risk of PTSD almost doubles to 4.6% for life-threatening auto accidents. Females were more likely to be diagnosed with PTSD following a road traffic accident, whether the accident occurred during childhood or adulthood.Post-traumatic stress reactions have been studied in children and adolescents. The rate of PTSD might be lower in children than adults, but in the absence of therapy, symptoms may continue for decades. One estimate suggests that the proportion of children and adolescents having PTSD in a non-wartorn population in a developed country may be 1% compared to 1.5% to 3% of adults. On average, 16% of children exposed to a traumatic event develop PTSD, varying according to type of exposure and gender. Similar to the adult population, risk factors for PTSD in children include: female gender, exposure to disasters (natural or manmade), negative coping behaviours, and/or lacking proper social support systems.Predictor models have consistently found that childhood trauma, chronic adversity, neurobiological differences, and familial stressors are associated with risk for PTSD after a traumatic event in adulthood. It has been difficult to find consistently aspects of the events that predict, but peritraumatic dissociation has been a fairly consistent predictive indicator of the development of PTSD. Proximity to, duration of, and severity of the trauma make an impact. It has been speculated that interpersonal traumas cause more problems than impersonal ones, but this is controversial. The risk of developing PTSD is increased in individuals who are exposed to physical abuse, physical assault, or kidnapping. Women who experience physical violence are more likely to develop PTSD than men. Intimate partner violence An individual that has been exposed to domestic violence is predisposed to the development of PTSD. There is a strong association between the development of PTSD in mothers that experienced domestic violence during the perinatal period of their pregnancy.Those who have experienced sexual assault or rape may develop symptoms of PTSD. PTSD symptoms include re-experiencing the assault, avoiding things associated with the assault, numbness, and increased anxiety and an increased startle response. The likelihood of sustained symptoms of PTSD is higher if the rapist confined or restrained the person, if the person being raped believed the rapist would kill them, the person who was raped was very young or very old, and if the rapist was someone they knew. The likelihood of sustained severe symptoms is also higher if people around the survivor ignore (or are ignorant of) the rape or blame the rape survivor. War-related trauma Military service is a risk factor for developing PTSD. Around 78% of people exposed to combat do not develop PTSD; in about 25% of military personnel who develop PTSD, its appearance is delayed.Refugees are also at an increased risk for PTSD due to their exposure to war, hardships, and traumatic events. The rates for PTSD within refugee populations range from 4% to 86%. While the stresses of war affect everyone involved, displaced persons have been shown to be more so than others.Challenges related to the overall psychosocial well-being of refugees are complex and individually nuanced. Refugees have reduced levels of well-being and a high rates of mental distress due to past and ongoing trauma. Groups that are particularly affected and whose needs often remain unmet are women, older people and unaccompanied minors. Post-traumatic stress and depression in refugee populations also tend to affect their educational success. Unexpected death of a loved one Sudden, unexpected death of a loved one is the most common traumatic event type reported in cross-national studies. However, the majority of people who experience this type of event will not develop PTSD. An analysis from the WHO World Mental Health Surveys found a 5.2% risk of developing PTSD after learning of the unexpected death of a loved one. Because of the high prevalence of this type of traumatic event, unexpected death of a loved one accounts for approximately 20% of PTSD cases worldwide. Life-threatening illness Medical conditions associated with an increased risk of PTSD include cancer, heart attack, and stroke. 22% of cancer survivors present with lifelong PTSD like symptoms. Intensive-care unit (ICU) hospitalization is also a risk factor for PTSD. Some women experience PTSD from their experiences related to breast cancer and mastectomy. Loved ones of those who experience life-threatening illnesses are also at risk for developing PTSD, such as parents of child with chronic illnesses. Pregnancy-related trauma Women who experience miscarriage are at risk of PTSD. Those who experience subsequent miscarriages have an increased risk of PTSD compared to those experiencing only one. PTSD can also occur after childbirth and the risk increases if a woman has experienced trauma prior to the pregnancy. Prevalence of PTSD following normal childbirth (that is, excluding stillbirth or major complications) is estimated to be between 2.8 and 5.6% at six weeks postpartum, with rates dropping to 1.5% at six months postpartum. Symptoms of PTSD are common following childbirth, with prevalence of 24–30.1% at six weeks, dropping to 13.6% at six months. Emergency childbirth is also associated with PTSD. Genetics There is evidence that susceptibility to PTSD is hereditary. Approximately 30% of the variance in PTSD is caused from genetics alone. For twin pairs exposed to combat in Vietnam, having a monozygotic (identical) twin with PTSD was associated with an increased risk of the co-twins having PTSD compared to twins that were dizygotic (non-identical twins). Women with a smaller hippocampus might be more likely to develop PTSD following a traumatic event based on preliminary findings. Research has also found that PTSD shares many genetic influences common to other psychiatric disorders. Panic and generalized anxiety disorders and PTSD share 60% of the same genetic variance. Alcohol, nicotine, and drug dependence share greater than 40% genetic similarities.Several biological indicators have been identified that are related to later PTSD development. Heightened startle responses and, with only preliminary results, a smaller hippocampal volume have been identified as possible biomarkers for heightened risk of developing PTSD. Additionally, one study found that soldiers whose leukocytes had greater numbers of glucocorticoid receptors were more prone to developing PTSD after experiencing trauma. Pathophysiology Neuroendocrinology PTSD symptoms may result when a traumatic event causes an over-reactive adrenaline response, which creates deep neurological patterns in the brain. These patterns can persist long after the event that triggered the fear, making an individual hyper-responsive to future fearful situations. During traumatic experiences, the high levels of stress hormones secreted suppress hypothalamic activity that may be a major factor toward the development of PTSD.PTSD causes biochemical changes in the brain and body, that differ from other psychiatric disorders such as major depression. Individuals diagnosed with PTSD respond more strongly to a dexamethasone suppression test than individuals diagnosed with clinical depression.Most people with PTSD show a low secretion of cortisol and high secretion of catecholamines in urine, with a norepinephrine/cortisol ratio consequently higher than comparable non-diagnosed individuals. This is in contrast to the normative fight-or-flight response, in which both catecholamine and cortisol levels are elevated after exposure to a stressor.Brain catecholamine levels are high, and corticotropin-releasing factor (CRF) concentrations are high. Together, these findings suggest abnormality in the hypothalamic-pituitary-adrenal (HPA) axis. The maintenance of fear has been shown to include the HPA axis, the locus coeruleus-noradrenergic systems, and the connections between the limbic system and frontal cortex. The HPA axis that coordinates the hormonal response to stress, which activates the LC-noradrenergic system, is implicated in the over-consolidation of memories that occurs in the aftermath of trauma. This over-consolidation increases the likelihood of ones developing PTSD. The amygdala is responsible for threat detection and the conditioned and unconditioned fear responses that are carried out as a response to a threat.The HPA axis is responsible for coordinating the hormonal response to stress. Given the strong cortisol suppression to dexamethasone in PTSD, HPA axis abnormalities are likely predicated on strong negative feedback inhibition of cortisol, itself likely due to an increased sensitivity of glucocorticoid receptors. PTSD has been hypothesized to be a maladaptive learning pathway to fear response through a hypersensitive, hyperreactive, and hyperresponsive HPA axis.Low cortisol levels may predispose individuals to PTSD: Following war trauma, Swedish soldiers serving in Bosnia and Herzegovina with low pre-service salivary cortisol levels had a higher risk of reacting with PTSD symptoms, following war trauma, than soldiers with normal pre-service levels. Because cortisol is normally important in restoring homeostasis after the stress response, it is thought that trauma survivors with low cortisol experience a poorly contained—that is, longer and more distressing—response, setting the stage for PTSD. It is thought that the locus coeruleus-noradrenergic system mediates the over-consolidation of fear memory. High levels of cortisol reduce noradrenergic activity, and because people with PTSD tend to have reduced levels of cortisol, it has been proposed that individuals with PTSD cannot regulate the increased noradrenergic response to traumatic stress. Intrusive memories and conditioned fear responses are thought to be a result of the response to associated triggers. Neuropeptide Y (NPY) has been reported to reduce the release of norepinephrine and has been demonstrated to have anxiolytic properties in animal models. Studies have shown people with PTSD demonstrate reduced levels of NPY, possibly indicating their increased anxiety levels.Other studies indicate that people with PTSD have chronically low levels of serotonin, which contributes to the commonly associated behavioral symptoms such as anxiety, ruminations, irritability, aggression, suicidality, and impulsivity. Serotonin also contributes to the stabilization of glucocorticoid production. Dopamine levels in a person with PTSD can contribute to symptoms: low levels can contribute to anhedonia, apathy, impaired attention, and motor deficits; high levels can contribute to psychosis, agitation, and restlessness.Several studies described elevated concentrations of the thyroid hormone triiodothyronine in PTSD. This kind of type 2 allostatic adaptation may contribute to increased sensitivity to catecholamines and other stress mediators. Hyperresponsiveness in the norepinephrine system can also be caused by continued exposure to high stress. Overactivation of norepinephrine receptors in the prefrontal cortex can be connected to the flashbacks and nightmares frequently experienced by those with PTSD. A decrease in other norepinephrine functions (awareness of the current environment) prevents the memory mechanisms in the brain from processing the experience, and emotions the person is experiencing during a flashback are not associated with the current environment.There is considerable controversy within the medical community regarding the neurobiology of PTSD. A 2012 review showed no clear relationship between cortisol levels and PTSD. The majority of reports indicate people with PTSD have elevated levels of corticotropin-releasing hormone, lower basal cortisol levels, and enhanced negative feedback suppression of the HPA axis by dexamethasone. Neuroanatomy A meta-analysis of structural MRI studies found an association with reduced total brain volume, intracranial volume, and volumes of the hippocampus, insula cortex, and anterior cingulate. Much of this research stems from PTSD in those exposed to the Vietnam War.People with PTSD have decreased brain activity in the dorsal and rostral anterior cingulate cortices and the ventromedial prefrontal cortex, areas linked to the experience and regulation of emotion.The amygdala is strongly involved in forming emotional memories, especially fear-related memories. During high stress, the hippocampus, which is associated with placing memories in the correct context of space and time and memory recall, is suppressed. According to one theory this suppression may be the cause of the flashbacks that can affect people with PTSD. When someone with PTSD undergoes stimuli similar to the traumatic event, the body perceives the event as occurring again because the memory was never properly recorded in the persons memory.The amygdalocentric model of PTSD proposes that the amygdala is very much aroused and insufficiently controlled by the medial prefrontal cortex and the hippocampus, in particular during extinction. This is consistent with an interpretation of PTSD as a syndrome of deficient extinction ability.The basolateral nucleus (BLA) of the amygdala is responsible for the comparison and development of associations between unconditioned and conditioned responses to stimuli, which results in the fear conditioning present in PTSD. The BLA activates the central nucleus (CeA) of the amygdala, which elaborates the fear response, (including behavioral response to threat and elevated startle response). Descending inhibitory inputs from the medial prefrontal cortex (mPFC) regulate the transmission from the BLA to the CeA, which is hypothesized to play a role in the extinction of conditioned fear responses. While as a whole, amygdala hyperactivity is reported by meta analysis of functional neuroimaging in PTSD, there is a large degree of heterogeniety, more so than in social anxiety disorder or phobic disorder. Comparing dorsal (roughly the CeA) and ventral(roughly the BLA) clusters, hyperactivity is more robust in the ventral cluster, while hypoactivity is evident in the dorsal cluster. The distinction may explain the blunted emotions in PTSD (via desensitization in the CeA) as well as the fear related component.In a 2007 study Vietnam War combat veterans with PTSD showed a 20% reduction in the volume of their hippocampus compared with veterans who did not have such symptoms. This finding was not replicated in chronic PTSD patients traumatized at an air show plane crash in 1988 (Ramstein, Germany).Evidence suggests that endogenous cannabinoid levels are reduced in PTSD, particularly anandamide, and that cannabinoid receptors (CB1) are increased in order to compensate. There appears to be a link between increased CB1 receptor availability in the amygdala and abnormal threat processing and hyperarousal, but not dysphoria, in trauma survivors. A 2020 study found no evidence for conclusions from prior research that suggested low IQ is a risk factor for developing PTSD. Diagnosis PTSD can be difficult to diagnose, because of: the subjective nature of most of the diagnostic criteria (although this is true for many mental disorders); the potential for over-reporting, e.g., while seeking disability benefits, or when PTSD could be a mitigating factor at criminal sentencing the potential for under-reporting, e.g., stigma, pride, fear that a PTSD diagnosis might preclude certain employment opportunities; symptom overlap with other mental disorders such as obsessive compulsive disorder and generalized anxiety disorder; association with other mental disorders such as major depressive disorder and generalized anxiety disorder; substance use disorders, which often produce some of the same signs and symptoms as PTSD; and substance use disorders can increase vulnerability to PTSD or exacerbate PTSD symptoms or both; and PTSD increases the risk for developing substance use disorders. the differential expression of symptoms culturally (specifically with respect to avoidance and numbing symptoms, distressing dreams, and somatic symptoms) Screening There are a number of PTSD screening instruments for adults, such as the PTSD Checklist for DSM-5 (PCL-5) and the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5).There are also several screening and assessment instruments for use with children and adolescents. These include the Child PTSD Symptom Scale (CPSS), Child Trauma Screening Questionnaire, and UCLA Post-traumatic Stress Disorder Reaction Index for DSM-IV.In addition, there are also screening and assessment instruments for caregivers of very young children (six years of age and younger). These include the Young Child PTSD Screen, the Young Child PTSD Checklist, and the Diagnostic Infant and Preschool Assessment. Assessment Evidence-based assessment principles, including a multimethod assessment approach, form the foundation of PTSD assessment. Diagnostic and statistical manual PTSD was classified as an anxiety disorder in the DSM-IV, but has since been reclassified as a "trauma- and stressor-related disorder" in the DSM-5. The DSM-5 diagnostic criteria for PTSD include four symptom clusters: re-experiencing, avoidance, negative alterations in cognition/mood, and alterations in arousal and reactivity. International classification of diseases The International Classification of Diseases and Related Health Problems 10 (ICD-10) classifies PTSD under "Reaction to severe stress, and adjustment disorders." The ICD-10 criteria for PTSD include re-experiencing, avoidance, and either increased reactivity or inability to recall certain details related to the event.The ICD-11 diagnostic description for PTSD contains three components or symptom groups (1) re-experiencing, (2) avoidance, and (3) heightened sense of threat. ICD-11 no longer includes verbal thoughts about the traumatic event as a symptom. There is a predicted lower rate of diagnosed PTSD using ICD-11 compared to ICD10 or DSM-5. ICD-11 also proposes identifying a distinct group with complex post-traumatic stress disorder (CPTSD), who have more often experienced several or sustained traumas and have greater functional impairment than those with PTSD. Differential diagnosis A diagnosis of PTSD requires that the person has been exposed to an extreme stressor. Any stressor can result in a diagnosis of adjustment disorder and it is an appropriate diagnosis for a stressor and a symptom pattern that does not meet the criteria for PTSD. The symptom pattern for acute stress disorder must occur and be resolved within four weeks of the trauma. If it lasts longer, and the symptom pattern fits that characteristic of PTSD, the diagnosis may be changed.Obsessive compulsive disorder may be diagnosed for intrusive thoughts that are recurring but not related to a specific traumatic event.In extreme cases of prolonged, repeated traumatization where there is no viable chance of escape, survivors may develop complex post-traumatic stress disorder. This occurs as a result of layers of trauma rather than a single traumatic event, and includes additional symptomatology, such as the loss of a coherent sense of self. Prevention Modest benefits have been seen from early access to cognitive behavioral therapy. Critical incident stress management has been suggested as a means of preventing PTSD, but subsequent studies suggest the likelihood of its producing negative outcomes. A 2019 Cochrane review did not find any evidence to support the use of an intervention offered to everyone", and that "multiple session interventions may result in worse outcome than no intervention for some individuals." The World Health Organization recommends against the use of benzodiazepines and antidepressants in for acute stress (symptoms lasting less than one month). Some evidence supports the use of hydrocortisone for prevention in adults, although there is limited or no evidence supporting propranolol, escitalopram, temazepam, or gabapentin. Psychological debriefing Trauma-exposed individuals often receive treatment called psychological debriefing in an effort to prevent PTSD, which consists of interviews that are meant to allow individuals to directly confront the event and share their feelings with the counselor and to help structure their memories of the event. However, several meta-analyses find that psychological debriefing is unhelpful and is potentially harmful. This is true for both single-session debriefing and multiple session interventions. As of 2017 the American Psychological Association assessed psychological debriefing as No Research Support/Treatment is Potentially Harmful. Risk-targeted interventions Risk-targeted interventions are those that attempt to mitigate specific formative information or events. It can target modeling normal behaviors, instruction on a task, or giving information on the event. Management Reviews of studies have found that combination therapy (psychological and pharmacotherapy) is no more effective than psychological therapy alone. Counselling The approaches with the strongest evidence include behavioral and cognitive-behavioral therapies such as prolonged exposure therapy, cognitive processing therapy, and eye movement desensitization and reprocessing (EMDR). There is some evidence for brief eclectic psychotherapy (BEP), narrative exposure therapy (NET), and written exposure therapy.A 2019 Cochrane review evaluated couples and family therapies compared to no care and individual and group therapies for the treatment of PTSD. There were too few studies on couples therapies to determine if substantive benefits were derived but preliminary RCTs suggested that couples therapies may be beneficial for reducing PTSD symptoms.A meta-analytic comparison of EMDR and cognitive behavioral therapy (CBT) found both protocols indistinguishable in terms of effectiveness in treating PTSD; however, "the contribution of the eye movement component in EMDR to treatment outcome" is unclear. A meta-analysis in children and adolescents also found that EMDR was as efficacious as CBT.Children with PTSD are far more likely to pursue treatment at school (because of its proximity and ease) than at a free clinic. Cognitive behavioral therapy CBT seeks to change the way a person feels and acts by changing the patterns of thinking or behavior, or both, responsible for negative emotions. Results from a 2018 systematic review found high strength of evidence that supports CBT-exposure therapy efficacious for a reduction in PTSD and depression symptoms, as well as the loss of PTSD diagnosis. CBT has been proven to be an effective treatment for PTSD and is currently considered the standard of care for PTSD by the United States Department of Defense. In CBT, individuals learn to identify thoughts that make them feel afraid or upset and replace them with less distressing thoughts. The goal is to understand how certain thoughts about events cause PTSD-related stress. The provision of CBT in an Internet-based format has also been studied in a 2018 Cochrane review. This review did find similar beneficial effects for Internet-based settings as in face-to-face but the quality of the evidence was low due to the small number of trials reviewed.Exposure therapy is a type of cognitive behavioral therapy that involves assisting trauma survivors to re-experience distressing trauma-related memories and reminders in order to facilitate habituation and successful emotional processing of the trauma memory. Most exposure therapy programs include both imaginal confrontation with the traumatic memories and real-life exposure to trauma reminders; this therapy modality is well supported by clinical evidence. The success of exposure-based therapies has raised the question of whether exposure is a necessary ingredient in the treatment of PTSD. Some organizations have endorsed the need for exposure. The U.S. Department of Veterans Affairs has been actively training mental health treatment staff in prolonged exposure therapy and Cognitive Processing Therapy in an effort to better treat U.S. veterans with PTSD. Recent research on contextually based third-generation behavior therapies suggests that they may produce results comparable to some of the better validated therapies. Many of these therapy methods have a significant element of exposure and have demonstrated success in treating the primary problems of PTSD and co-occurring depressive symptoms. Eye movement desensitization and reprocessing Eye movement desensitization and reprocessing (EMDR) is a form of psychotherapy developed and studied by Francine Shapiro. She had noticed that, when she was thinking about disturbing memories herself, her eyes were moving rapidly. When she brought her eye movements under control while thinking, the thoughts were less distressing.In 2002, Shapiro and Maxfield published a theory of why this might work, called adaptive information processing. This theory proposes that eye movement can be used to facilitate emotional processing of memories, changing the persons memory to attend to more adaptive information. The therapist initiates voluntary rapid eye movements while the person focuses on memories, feelings or thoughts about a particular trauma. The therapists uses hand movements to get the person to move their eyes backward and forward, but hand-tapping or tones can also be used. EMDR closely resembles cognitive behavior therapy as it combines exposure (re-visiting the traumatic event), working on cognitive processes and relaxation/self-monitoring. However, exposure by way of being asked to think about the experience rather than talk about it has been highlighted as one of the more important distinguishing elements of EMDR.There have been several small controlled trials of four to eight weeks of EMDR in adults as well as children and adolescents. There is moderate strength of evidence to support the efficacy of EMDR "for reduction in PTSD symptoms, loss of diagnosis, and reduction in depressive symptoms" according to a 2018 systematic review update. EMDR reduced PTSD symptoms enough in the short term that one in two adults no longer met the criteria for PTSD, but the number of people involved in these trials was small and thus results should be interpreted with caution pending further research. There was not enough evidence to know whether or not EMDR could eliminate PTSD in adults. In children and adolescents, a recent meta-analysis of randomized controlled trials using MetaNSUE to avoid biases related to missing information found that EMDR was at least as efficacious as CBT, and superior to waitlist or placebo. There was some evidence that EMDR might prevent depression. There were no studies comparing EMDR to other psychological treatments or to medication. Adverse effects were largely unstudied. The benefits were greater for women with a history of sexual assault compared with people who had experienced other types of traumatizing events (such as accidents, physical assaults and war). There is a small amount of evidence that EMDR may improve re-experiencing symptoms in children and adolescents, but EMDR has not been shown to improve other PTSD symptoms, anxiety, or depression.The eye movement component of the therapy may not be critical for benefit. As there has been no major, high quality randomized trial of EMDR with eye movements versus EMDR without eye movements, the controversy over effectiveness is likely to continue. Authors of a meta-analysis published in 2013 stated, "We found that people treated with eye movement therapy had greater improvement in their symptoms of post-traumatic stress disorder than people given therapy without eye movements.... Secondly we found that in laboratory studies the evidence concludes that thinking of upsetting memories and simultaneously doing a task that facilitates eye movements reduces the vividness and distress associated with the upsetting memories." Interpersonal psychotherapy Other approaches, in particular involving social supports, may also be important. An open trial of interpersonal psychotherapy reported high rates of remission from PTSD symptoms without using exposure. A current, NIMH-funded trial in New York City is now (and into 2013) comparing interpersonal psychotherapy, prolonged exposure therapy, and relaxation therapy. Medication While many medications do not have enough evidence to support their use, four (sertraline, fluoxetine, paroxetine, and venlafaxine) have been shown to have a small to modest benefit over placebo. With many medications, residual PTSD symptoms following treatment is the rule rather than the exception. Antidepressants Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) may have some benefit for PTSD symptoms. Tricyclic antidepressants are equally effective but are less well tolerated. Evidence provides support for a small or modest improvement with sertraline, fluoxetine, paroxetine, and venlafaxine. Thus, these four medications are considered to be first-line medications for PTSD. Benzodiazepines Benzodiazepines are not recommended for the treatment of PTSD due to a lack of evidence of benefit and risk of worsening PTSD symptoms. Some authors believe that the use of benzodiazepines is contraindicated for acute stress, as this group of drugs can cause dissociation. Nevertheless, some use benzodiazepines with caution for short-term anxiety and insomnia. While benzodiazepines can alleviate acute anxiety, there is no consistent evidence that they can stop the development of PTSD and may actually increase the risk of developing PTSD 2–5 times. Additionally, benzodiazepines may reduce the effectiveness of psychotherapeutic interventions, and there is some evidence that benzodiazepines may actually contribute to the development and chronification of PTSD. For those who already have PTSD, benzodiazepines may worsen and prolong the course of illness, by worsening psychotherapy outcomes, and causing or exacerbating aggression, depression (including suicidality), and substance use. Drawbacks include the risk of developing a benzodiazepine dependence, tolerance (i.e., short-term benefits wearing off with time), and withdrawal syndrome; additionally, individuals with PTSD (even those without a history of alcohol or drug misuse) are at an increased risk of abusing benzodiazepines. Due to a number of other treatments with greater efficacy for PTSD and less risks (e.g., prolonged exposure, cognitive processing therapy, eye movement desensitization and reprocessing, cognitive restructuring therapy, trauma-focused cognitive behavioral therapy, brief eclectic psychotherapy, narrative therapy, stress inoculation training, serotonergic antidepressants, adrenergic inhibitors, antipsychotics, and even anticonvulsants), benzodiazepines should be considered relatively contraindicated until all other treatment options are exhausted. For those who argue that benzodiazepines should be used sooner in the most severe cases, the adverse risk of disinhibition (associated with suicidality, aggression and crimes) and clinical risks of delaying or inhibiting definitive efficacious treatments, make other alternative treatments preferable (e.g., inpatient, residential, partial hospitalization, intensive outpatient, dialectic behavior therapy; and other fast-acting sedating medications such as trazodone, mirtazapine, amitripytline, doxepin, prazosin, propranolol, guanfacine, clonidine, quetiapine, olanzapine, valproate, gabapentin). Prazosin Prazosin, an alpha-1 adrenergic antagonist, has been used in veterans with PTSD to reduce nightmares. Studies show variability in the symptom improvement, appropriate dosages, and efficacy in this population. Glucocorticoids Glucocorticoids may be useful for short-term therapy to protect against neurodegeneration caused by the extended stress response that characterizes PTSD, but long-term use may actually promote neurodegeneration. Cannabinoids Cannabis is not recommended as a treatment for PTSD because scientific evidence does not currently exist demonstrating treatment efficacy for cannabinoids. However, use of cannabis or derived products is widespread among U.S. veterans with PTSD.The cannabinoid nabilone is sometimes used for nightmares in PTSD. Although some short-term benefit was shown, adverse effects are common and it has not been adequately studied to determine efficacy. An increasing number of states permit and have legalized the use of medical cannabis for the treatment of PTSD. Other Exercise, sport and physical activity Physical activity can influence peoples psychological and physical health. The U.S. National Center for PTSD recommends moderate exercise as a way to distract from disturbing emotions, build self-esteem and increase feelings of being in control again. They recommend a discussion with a doctor before starting an exercise program. Play therapy for children Play is thought to help children link their inner thoughts with their outer world, connecting real experiences with abstract thought. Repetitive play can also be one way a child relives traumatic events, and that can be a symptom of trauma in a child or young person. Although it is commonly used, there have not been enough studies comparing outcomes in groups of children receiving and not receiving play therapy, so the effects of play therapy are not yet understood. Military programs Many veterans of the wars in Iraq and Afghanistan have faced significant physical, emotional, and relational disruptions. In response, the United States Marine Corps has instituted programs to assist them in re-adjusting to civilian life, especially in their relationships with spouses and loved ones, to help them communicate better and understand what the other has gone through. Walter Reed Army Institute of Research (WRAIR) developed the Battlemind program to assist service members avoid or ameliorate PTSD and related problems. Wounded Warrior Project partnered with the US Department of Veterans Affairs to create Warrior Care Network, a national health system of PTSD treatment centers. Nightmares In 2020, the United States Food and Drug Administration granted marketing approval for an Apple Watch app call NightWare. The app aims to improve sleep for people suffering from PTSD-related nightmares, by vibrating when it detects a nightmare in progress based on monitoring heart rate and body movement. Epidemiology There is debate over the rates of PTSD found in populations, but, despite changes in diagnosis and the criteria used to define PTSD between 1997 and 2013, epidemiological rates have not changed significantly. Most of the current reliable data regarding the epidemiology of PTSD is based on DSM-IV criteria, as the DSM-5 was not introduced until 2013. The United Nations World Health Organization publishes estimates of PTSD impact for each of its member states; the latest data available are for 2004. Considering only the 25 most populated countries ranked by overall age-standardized Disability-Adjusted Life Year (DALY) rate, the top half of the ranked list is dominated by Asian/Pacific countries, the US, and Egypt. Ranking the countries by the male-only or female-only rates produces much the same result, but with less meaningfulness, as the score range in the single-sex rankings is much-reduced (4 for women, 3 for men, as compared with 14 for the overall score range), suggesting that the differences between female and male rates, within each country, is what drives the distinctions between the countries.As of 2017, the cross-national lifetime prevalence of PTSD was 3.9%, based on a survey were 5.6% had been exposed to trauma. The primary factor impacting treatment-seeking behavior, which can help to mitigate PTSD development after trauma was income, while being younger, female, and having less social status (less education, lower individual income, and being unemployed) were all factors associated with less treatment-seeking behaviour. United States The National Comorbidity Survey Replication has estimated that the lifetime prevalence of PTSD among adult Americans is 6.8%, with women (9.7%) more than twice as likely as men (3.6%) to have PTSD at some point in their lives. More than 60% of men and more than 60% of women experience at least one traumatic event in their life. The most frequently reported traumatic events by men are rape, combat, and childhood neglect or physical abuse. Women most frequently report instances of rape, sexual molestation, physical attack, being threatened with a weapon and childhood physical abuse. 88% of men and 79% of women with lifetime PTSD have at least one comorbid psychiatric disorder. Major depressive disorder, 48% of men and 49% of women, and lifetime alcohol use disorder or dependence, 51.9% of men and 27.9% of women, are the most common comorbid disorders. Military combat The United States Department of Veterans Affairs estimates that 830,000 Vietnam War veterans had symptoms of PTSD. The National Vietnam Veterans Readjustment Study (NVVRS) found 15% of male and 9% of female Vietnam veterans had PTSD at the time of the study. Life-time prevalence of PTSD was 31% for males and 27% for females. In a reanalysis of the NVVRS data, along with analysis of the data from the Matsunaga Vietnam Veterans Project, Schnurr, Lunney, Sengupta, and Waelde found that, contrary to the initial analysis of the NVVRS data, a large majority of Vietnam veterans had PTSD symptoms (but not the disorder itself). Four out of five reported recent symptoms when interviewed 20–25 years after Vietnam.A 2011 study from Georgia State University and San Diego State University found that rates of PTSD diagnosis increased significantly when troops were stationed in combat zones, had tours of longer than a year, experienced combat, or were injured. Military personnel serving in combat zones were 12.1 percentage points more likely to receive a PTSD diagnosis than their active-duty counterparts in non-combat zones. Those serving more than 12 months in a combat zone were 14.3 percentage points more likely to be diagnosed with PTSD than those having served less than one year. Experiencing an enemy firefight was associated with an 18.3 percentage point increase in the probability of PTSD, while being wounded or injured in combat was associated with a 23.9 percentage point increase in the likelihood of a PTSD diagnosis. For the 2.16 million U.S. troops deployed in combat zones between 2001 and 2010, the total estimated two-year costs of treatment for combat-related PTSD are between $1.54 billion and $2.69 billion.As of 2013, rates of PTSD have been estimated at up to 20% for veterans returning from Iraq and Afghanistan. As of 2013 13% of veterans returning from Iraq were unemployed. Man-made disasters The September 11 attacks took the lives of nearly 3,000 people, leaving 6,000 injured. First responders (police, firefighters, and emergency medical technicians), sanitation workers, and volunteers were all involved in the recovery efforts. The prevalence of probable PTSD in these highly exposed populations was estimated across several studies using in-person, telephone, and online interviews and questionnaires. Overall prevalence of PTSD was highest immediately following the attacks and decreased over time. However, disparities were found among the different types of recovery workers. The rate of probable PTSD for first responders was lowest directly after the attacks and increased from ranges of 4.8-7.8% to 7.4-16.5% between the 5-6 year follow-up and a later assessment. When comparing traditional responders to non-traditional responders (volunteers), the probable PTSD prevalence 2.5 years after the initial visit was greater in volunteers with estimates of 11.7% and 17.2% respectively. Volunteer participation in tasks atypical to the defined occupational role was a significant risk factor for PTSD. Other risk factors included exposure intensity, earlier start date, duration of time spent on site, and constant, negative reminders of the trauma. Additional research has been performed to understand the social consequences of the September 11 attacks. Alcohol consumption was assessed in a cohort of World Trade Center workers using the cut-annoyed-guilty-eye (CAGE) questionnaire for alcohol use disorder. Almost 50% of World Trade Center workers who self-identified as alcohol users reported drinking more during the rescue efforts. Nearly a quarter of these individuals reported drinking more following the recovery. If determined to have probable PTSD status, the risk of developing an alcohol problem was double compared to those without psychological morbidity. Social disability was also studied in this cohort as a social consequence of the September 11 attacks. Defined by the disruption of family, work, and social life, the risk of developing social disability increased 17-fold when categorized as having probable PTSD. Anthropology Cultural and medical anthropologists have questioned the validity of applying the diagnostic criteria of PTSD cross-culturally. Trauma (and resulting PTSD) is often experienced through the outermost limits of suffering, pain and fear. The images and experiences relived through PTSD often defy easy description through language. Therefore, the translation of these experiences from one language to another is problematic, and the primarily Euro-American research on trauma is necessarily limited. The Sapir-Whorf hypothesis suggests that people perceive the world differently according to the language they speak: language and the world it exists within reflect back on the perceptions of the speaker. For example, ethnopsychology studies in Nepal have found that cultural idioms and concepts often don’t translate to western terminologies: piDaa is a term that may align to trauma/suffering, but also people who suffer from this are considered paagal (mad) and are subject to negative social stigma, indicating the need for culturally appropriate and carefully tailored support interventions. In summary, different cultures remember past experiences within different linguistic and cultural paradigms. As such, cultural and medical anthropologists have questioned the validity of applying the diagnostic criteria of PTSD cross-culturally, as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), and constructed through the Euro-American paradigm of psychology.There remains a dearth of studies into the conceptual frameworks that surround trauma in non-Western cultures. There is little evidence to suggest therapeutic benefit in synthesizing local idioms of distress into a culturally constructed disorder of the post-Vietnam era, a practice anthropologist believe contributes to category fallacy. For many cultures there is no single linguistic corollary to PTSD, psychological trauma being a multi-faceted concept with corresponding variances of expression. Designating the effects of trauma as an affliction of the spirit is common in many non-Western cultures where idioms such as “soul loss” and “weak heart” indicate a preference to confer suffering to a spirit-body or heart-body diametric. These idioms reflect the emphasis that collectivist cultures place on healing trauma through familial, cultural and religious activities while avoiding the stigma that accompanies a mind-body approach. Prescribing PTSD diagnostics within these communities is ineffective and often detrimental. For trauma that extends beyond the individual such as the effects of war, anthropologists believe applying the term “social suffering” or “cultural bereavement” to be more beneficial.Every facet of society is affected by conflict; the prolonged exposure to mass violence can lead to a ‘continuous suffering’ among civilians, soldiers, and bordering countries. Entered into the DSM in 1980, clinicians and psychiatrists based the diagnostic criteria for PTSD around American veterans of the Vietnam war. Though the DSM (in its fifth edition at the time of writing) gets reviewed and updated regularly, it is unable to fully encompass the disorder due to its Americanization (or Westernization). That is, what may be considered characteristics of PTSD in western society, may not directly translate across to other cultures around the world. Displaced people of the African country Burundi experienced symptoms of depression and anxiety, though little symptoms of PTSD were noted. In a similar review, Sudanese refugees relocated in Uganda were ‘concerned with material [effects]’ (lack of food, shelter, and healthcare), rather than psychological distress. In this case, many refugees didn’t present symptoms at all, with a minor few developing anxiety and depression. War-related stresses and traumas will be ingrained in the individual, however they will be affected differently from culture to culture, and the “clear-cut” rubric for diagnosing PTSD doesn’t allow for culturally contextual reactions to take place. Veterans United States The United States provides a range of benefits for veterans that the VA has determined have PTSD, which developed during, or as a result of, their military service. These benefits may include tax-free cash payments, free or low-cost mental health treatment and other healthcare, vocational rehabilitation services, employment assistance, and independent living support. Iraq Young Iraqis have high rates of post-traumatic stress disorder due to the 2003 invasion of Iraq. United Kingdom In the UK, there are various charities and service organisations dedicated to aiding veterans in readjusting to civilian life. The Royal British Legion and the more recently established Help for Heroes are two of Britains more high-profile veterans organisations which have actively advocated for veterans over the years. There has been some controversy that the NHS has not done enough in tackling mental health issues and is instead "dumping" veterans on charities such as Combat Stress. Canada Veterans Affairs Canada offers a new program that includes rehabilitation, financial benefits, job placement, health benefits program, disability awards, peer support and family support. History The 1952 edition of the DSM-I includes a diagnosis of "gross stress reaction", which has similarities to the modern definition and understanding of PTSD. Gross stress reaction is defined as a normal personality using established patterns of reaction to deal with overwhelming fear as a response to conditions of great stress. The diagnosis includes language which relates the condition to combat as well as to "civilian catastrophe".A USAF study carried out in 1979 focused on individuals (civilian and military) who had worked to recover or identify the remains of those who died in Jonestown. The bodies had been dead for several days, and a third of them had been children. The study used the term "dysphoria" to describe PTSD-like symptoms.Early in 1978, the diagnosis term "post-traumatic stress disorder" was first recommended in a working group finding presented to the Committee of Reactive Disorders. The condition was described in the DSM-III (1980) as posttraumatic stress disorder. In the DSM-IV, the spelling "posttraumatic stress disorder" is used, while in the ICD-10, the spelling is "post-traumatic stress disorder".The addition of the term to the DSM-III was greatly influenced by the experiences and conditions of U.S. military veterans of the Vietnam War. Owing to its association with the war in Vietnam, PTSD has become synonymous with many historical war-time diagnoses such as railway spine, stress syndrome, nostalgia, soldiers heart, shell shock, battle fatigue, combat stress reaction, or traumatic war neurosis. Some of these terms date back to the 19th century, which is indicative of the universal nature of the condition. In a similar vein, psychiatrist Jonathan Shay has proposed that Lady Percys soliloquy in the William Shakespeare play Henry IV, Part 1 (act 2, scene 3, lines 40–62), written around 1597, represents an unusually accurate description of the symptom constellation of PTSD. The correlations between combat and PTSD are undeniable; according to Stéphane Audoin-Rouzeau and Annette Becker, "One-tenth of mobilized American men were hospitalized for mental disturbances between 1942 and 1945, and, after thirty-five days of uninterrupted combat, 98% of them manifested psychiatric disturbances in varying degrees." In fact, much of the available published research regarding PTSD is based on studies done on veterans of the war in Vietnam. A study based on personal letters from soldiers of the 18th-century Prussian Army concludes that combatants may have had PTSD. Aspects of PTSD in soldiers of ancient Assyria have been identified using written sources from 1300 to 600 BCE. These Assyrian soldiers would undergo a three-year rotation of combat before being allowed to return home, and were reported to have faced immense challenges in reconciling their past actions in war with their civilian lives. Connections between the actions of Viking berserkers and the hyperarousal of post-traumatic stress disorder have also been drawn.The researchers from the Grady Trauma Project highlight the tendency people have to focus on the combat side of PTSD: "less public awareness has focused on civilian PTSD, which results from trauma exposure that is not combat related... " and "much of the research on civilian PTSD has focused on the sequelae of a single, disastrous event, such as the Oklahoma City bombing, September 11th attacks, and Hurricane Katrina". Disparity in the focus of PTSD research affects the already popular perception of the exclusive interconnectedness of combat and PTSD. This is misleading when it comes to understanding the implications and extent of PTSD as a neurological disorder. Dating back to the definition of Gross stress reaction in the DSM-I, civilian experience of catastrophic or high stress events is included as a cause of PTSD in medical literature. The 2014 National Comorbidity Survey reports that "the traumas most commonly associated with PTSD are combat exposure and witnessing among men and rape and sexual molestation among women." Because of the initial overt focus on PTSD as a combat related disorder when it was first fleshed out in the years following the war in Vietnam, in 1975 Ann Wolbert Burgess and Lynda Lytle Holmstrom defined rape trauma syndrome (RTS) in order to draw attention to the striking similarities between the experiences of soldiers returning from war and of rape victims. This paved the way for a more comprehensive understanding of causes of PTSD. After PTSD became an official psychiatric diagnosis with the publication of DSM-III (1980), the number of personal injurylawsuits (tort claims) asserting the plaintiff had PTSD increased rapidly. However, triers of fact (judges and juries) often regarded the PTSD diagnostic criteria as imprecise, a view shared by legal scholars, trauma specialists, forensic psychologists, and forensic psychiatrists. Professional discussions and debates in academic journals, at conferences, and between thought leaders, led to a more clearly-defined set of diagnostic criteria in DSM-IV, particularly the definition of a "traumatic event".The DSM-IV classified PTSD under anxiety disorders, but the DSM-5 created a new category called "trauma and stressor-related disorders", in which PTSD is now classified. Terminology The Diagnostic and Statistical Manual of Mental Disorders does not hyphenate "post" and "traumatic", thus, the DSM-5 lists the disorder as posttraumatic stress disorder. However, many scientific journal articles and other scholarly publications do hyphenate the name of the disorder, viz., "post-traumatic stress disorder". Dictionaries also differ with regard to the preferred spelling of the disorder with the Collins English Dictionary – Complete and Unabridged using the hyphenated spelling, and the American Heritage Dictionary of the English Language, Fifth Edition and the Random House Kernerman Websters College Dictionary giving the non-hyphenated spelling.Some authors have used the terms "post-traumatic stress syndrome" or "post-traumatic stress symptoms" ("PTSS"), or simply "post-traumatic stress" ("PTS") in the case of the U.S. Department of Defense, to avoid stigma associated with the word "disorder". The comedian George Carlin criticized the euphemism treadmill which led to progressive change of the way PTSD was referred to over the course of the 20th century, from "shell shock" in the First World War to the "battle fatigue" in the Second World War, to "operational exhaustion" in the Korean War, to the current "post-traumatic stress disorder", coined during the Vietnam War, which "added a hyphen" and which, he commented, "completely burie[s] [the pain] under jargon". He also stated that the name given to the condition has had a direct effect on the way veteran soldiers with PTSD were treated and perceived by civilian populations over time. Research Most knowledge regarding PTSD comes from studies in high-income countries.To recapitulate some of the neurological and neurobehavioral symptoms experienced by the veteran population of recent conflicts in Iraq and Afghanistan, researchers at the Roskamp Institute and the James A Haley Veterans Hospital (Tampa) have developed an animal model to study the consequences of mild traumatic brain injury (mTBI) and PTSD. In the laboratory, the researchers exposed mice to a repeated session of unpredictable stressor (i.e. predator odor while restrained), and physical trauma in the form of inescapable foot-shock, and this was also combined with a mTBI. In this study, PTSD animals demonstrated recall of traumatic memories, anxiety, and an impaired social behavior, while animals subject to both mTBI and PTSD had a pattern of disinhibitory-like behavior. mTBI abrogated both contextual fear and impairments in social behavior seen in PTSD animals. In comparison with other animal studies, examination of neuroendocrine and neuroimmune responses in plasma revealed a trend toward increase in corticosterone in PTSD and combination groups. Stellate ganglion block is an experimental procedure for the treatment of PTSD.Researchers are investigating a number of experimental FAAH and MAGL-inhibiting drugs of hopes of finding a better treatment for anxiety and stress-related illnesses. In 2016, the FAAH-inhibitor drug BIA 10-2474 was withdrawn from human trials in France due to adverse effects.Preliminary evidence suggests that MDMA-assisted psychotherapy might be an effective treatment for PTSD. However, it is important to note that the results in clinical trials of MDMA-assisted psychotherapy might be substantially influenced by expectancy effects given the unblinding of participants. Furthermore, there is a conspicuous lack of trials comparing MDMA-assisted psychotherapy to existent first-line treatments for PTSD, such as trauma-focused psychological treatments, which seems to achieve similar or even better outcomes than MDMA-assisted psychotherapy. Psychotherapy Trauma-focused psychotherapies for PTSD (also known as "exposure-based" or "exposure" psychotherapies), such as prolonged exposure therapy (PE), eye movement desensitization and reprocessing (EMDR), and cognitive-reprocessing therapy (CPT) have the most evidence for efficacy and are recommended as first-line treatment for PTSD by almost all clinical practice guidelines. Exposure-based psychotherapies demonstrate efficacy for PTSD caused by different trauma "types", such as combat, sexual-assault, or natural disasters. At the same time, many trauma-focused psychotherapies evince high drop-out rates.Most systematic reviews and clinical guidelines indicate that psychotherapies for PTSD, most of which are trauma-focused therapies, are more effective than pharmacotherapy (medication), although there are reviews that suggest exposure-based psychotherapies for PTSD and pharmacotherapy are equally effective. Interpersonal psychotherapy shows preliminary evidence of probable efficacy, but more research is needed to reach definitive conclusions. Notes References This article incorporates text from a free content work. Licensed under CC BY-SA 3.0 IGO Text taken from A Lifeline to learning: leveraging mobile technology to support education for refugees, UNESCO, UNESCO. UNESCO. To learn how to add open license text to Wikipedia articles, please see this how-to page. For information on reusing text from Wikipedia, please see the terms of use. External links Post-traumatic stress disorder at Curlie Post traumatic stress disorder information from The National Child Traumatic Stress Network Information resources from The University of Queensland School of Medicine APA practice parameters for assessment and treatment for PTSD (Updated 2017) Resources for professionals from the VA National PTSD Center Psychiatry portal

Hey Aarogya!, what is Precocious puberty

Precocious puberty

In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. In a minority of children with precocious puberty, the early development is triggered by a disease such as a tumor or injury of the brain. Even when there is no disease, unusually early puberty can have adverse effects on social behavior and psychological development, can reduce adult height potential, and may shift some lifelong health risks. Central precocious puberty can be treated by suppressing the pituitary hormones that induce sex steroid production. The opposite condition is delayed puberty.The term is used with several slightly different meanings that are usually apparent from the context. In its broadest sense, and often simplified as early puberty, "precocious puberty" sometimes refers to any physical sex hormone effect, due to any cause, occurring earlier than the usual age, especially when it is being considered as a medical problem. Stricter definitions of "precocity" may refer only to central puberty starting before a statistically specified age based on percentile in the population (e.g., 2.5 standard deviations below the population mean), on expert recommendations of ages at which there is more than a negligible chance of discovering an abnormal cause, or based on opinion as to the age at which early puberty may have adverse effects. A common definition for medical purposes is onset before 8 years in girls or 9 years in boys. Causes Early pubic hair, breast, or genital development may result from natural early maturation or from several other conditions. Central If the cause can be traced to the hypothalamus or pituitary, the cause is considered central. Other names for this type are complete or true precocious puberty.Causes of central precocious puberty can include: hypothalamic hamartoma produces pulsatile gonadotropin-releasing hormone (GnRH) Langerhans cell histiocytosis McCune–Albright syndromeCentral precocious puberty can also be caused by brain tumors, infection (most commonly tuberculous meningitis, especially in developing countries), trauma, hydrocephalus, and Angelman syndrome. Precocious puberty is associated with advancement in bone age, which leads to early fusion of epiphyses, thus resulting in reduced final height and short stature.Adrenocortical oncocytomas are rare with mostly benign and nonfunctioning tumors. There have been only three cases of functioning adrenocortical oncocytoma that have been reported up until 2013. Children with adrenocortical oncocytomas will present with "premature pubarche, clitoromegaly, and increased serum dehydroepiandrosterone sulfate and testosterone" which are some of the presentations associated with precocious puberty.Precocious puberty in girls begins before the age of 8. The youngest mother on record is Lina Medina, who gave birth at the age of either 5 years, 7 months and 17 days or 6 years 5 months as mentioned in another report."Central precocious puberty (CPP) was reported in some patients with suprasellar arachnoid cysts (SAC), and SCFE (slipped capital femoral epiphysis) occurs in patients with CPP because of rapid growth and changes of growth hormone secretion."If no cause can be identified, it is considered idiopathic or constitutional. Peripheral Secondary sexual development induced by sex steroids from other abnormal sources is referred to as peripheral precocious puberty or precocious pseudopuberty. It typically presents as a severe form of disease with children. Symptoms are usually as a sequelae from adrenal hyperplasia (because of 21-hydroxylase deficiency or 11-beta hydroxylase deficiency, the former being more common), which includes but is not limited to hypertension, hypotension, electrolyte abnormalities, ambiguous genitalia in females, signs of virilization in females. Blood tests will typically reveal high level of androgens with low levels of cortisol. Causes can include: Endogenous sources Gonadal tumors (such as arrhenoblastoma) Adrenal tumors Germ cell tumor Congenital adrenal hyperplasia McCune–Albright syndrome Silver–Russell syndrome Familial male-limited precocious puberty (testotoxicosis) Exogenous hormones Environmental exogenous hormones As treatment for another condition Isosexual and heterosexual Generally, patients with precocious puberty develop phenotypically appropriate secondary sexual characteristics. This is called isosexual precocity.In some cases, a patient may develop characteristics of the opposite sex. For example, a male may develop breasts and other feminine characteristics, while a female may develop a deepened voice and facial hair. This is called heterosexual or contrasexual precocity. It is very rare in comparison to isosexual precocity and is usually the result of unusual circumstances. As an example, children with a very rare genetic condition called aromatase excess syndrome – in which exceptionally high circulating levels of estrogen are present – usually develop precocious puberty. Males and females are hyper-feminized by the syndrome. The "opposite" case would be the hyper-masculinisation of both male and female patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, in which there is an excess of androgens. Thus, in the aromatase excess syndrome the precocious puberty is isosexual in females and heterosexual in males, whilst in the CAH its isosexual in males and heterosexual in females. Research Although the causes of early puberty are still somewhat unclear, girls who have a high-fat diet and are not physically active or are obese are more likely to physically mature earlier. "Obese girls, defined as at least 10 kilograms (22 pounds) overweight, had an 80 percent chance of developing breasts before their ninth birthday and starting menstruation before age 12 – the western average for menstruation is about 12.7 years." In addition to diet and exercise habits, exposure to chemicals that mimic estrogen (known as xenoestrogens) is another possible cause of early puberty in girls. Bisphenol A, a xenoestrogen found in hard plastics, has been shown to affect sexual development. "Factors other than obesity, however, perhaps genetic and/or environmental ones, are needed to explain the higher prevalence of early puberty in black versus white girls." While more girls are increasingly entering puberty at younger ages, new research indicates that some boys are actually starting later (delayed puberty). "Increasing rates of obese and overweight children in the United States may be contributing to a later onset of puberty in boys, say researchers at the University of Michigan Health System."High levels of beta-hCG in serum and cerebrospinal fluid observed in a 9-year-old boy suggest a pineal gland tumor. The tumor is called a chorionic gonadotropin secreting pineal tumor. Radiotherapy and chemotherapy reduced tumor and beta-hCG levels normalized.In a study using neonatal melatonin on rats, results suggest that elevated melatonin could be responsible for some cases of early puberty.Familial cases of idiopathic central precocious puberty (ICPP) have been reported, leading researchers to believe there are specific genetic modulators of ICPP. Mutations in genes such as LIN28, and LEP and LEPR, which encode leptin and the leptin receptor, have been associated with precocious puberty. The association between LIN28 and puberty timing was validated experimentally in vivo, when it was found that mice with ectopic over-expression of LIN28 show an extended period of pre-pubertal growth and a significant delay in puberty onset.Mutations in the kisspeptin (KISS1) and its receptor, KISS1R (also known as GPR54), involved in GnRH secretion and puberty onset, are also thought to be the cause for ICPP However, this is still a controversial area of research, and some investigators found no association of mutations in the LIN28 and KISS1/KISS1R genes to be the common cause underlying ICPP.The gene MKRN3, which is a maternally imprinted gene, was first cloned by Jong et al. in 1999. MKRN3 was originally named Zinc finger protein 127. It is located on human chromosome 15 on the long arm in the Prader-Willi syndrome critical region2, and has since been identified as a cause of premature sexual development or CPP. The identification of mutations in MKRN3 leading to sporadic cases of CPP has been a significant contribution to better understanding the mechanism of puberty. MKRN3 appears to act as a "brake" on the central hypothalamic-pituitary access. Thus, loss of function mutations of the protein allow early activation of the GnRH pathway and cause phenotypic CPP. Patients with a MKRN3 mutation all display the classic signs of CCP including early breast and testes development, increased bone aging and elevated hormone levels of GnRH and LH. Diagnosis Studies indicate that breast development in girls and the appearance of pubic hair in both girls and boys are starting earlier than in previous generations. As a result, "early puberty" in children as young as 9 and 10 is no longer considered abnormal, particularly with girls. Although it is not considered as abnormal, it may be upsetting to parents and can be harmful to children who mature physically at a time when they are immature mentally.No age reliably separates normal from abnormal processes in children, but the following age thresholds for evaluation are thought to minimize the risk of missing a significant medical problem: Breast development in boys before appearance of pubic hair or testicular enlargement Pubic hair or genital enlargement (gonadarche) in boys with onset before 9 years Pubic hair (pubarche) before 8 or breast development (thelarche) in girls with onset before 7 years Menstruation (menarche) in girls before 10 yearsMedical evaluation is sometimes necessary to recognize the few children with serious conditions from the majority who have entered puberty early but are still medically normal. Early sexual development warrants evaluation because it may: induce early bone maturation and reduce eventual adult height indicate the presence of a tumour or other serious problem cause the child, particularly a girl, to become an object of adult sexual interest. Treatment One possible treatment is with anastrozole. GnRH agonists, including histrelin, triptorelin, or leuprorelin, are other possible treatments. Non-continuous use of GnRH agonists stimulates the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH). Prognosis Early puberty is posited to put girls at higher risk of sexual abuse; however, a causal relationship is, as yet, inconclusive. Early puberty also puts girls at a higher risk for teasing or bullying, mental health disorders and short stature as adults. Girls as young as 8 are increasingly starting to menstruate, develop breasts and grow pubic and underarm hair; these "biological milestones" typically occurred only at 13 or older in the past. African-American girls are especially prone to early puberty.Though boys face fewer problems from early puberty than girls do, early puberty is not always positive for boys. Early sexual maturation in boys can be accompanied by increased aggressiveness due to the surge of pubertal hormones. Because they appear older than their peers, pubescent boys may face increased social pressure to conform to adult norms; society may view them as more emotionally advanced, although their cognitive and social development may lag behind their physical development. Studies have shown that early-maturing boys are more likely to be sexually active and are more likely to participate in risky behaviors. History Pubertas praecox is the Latin term used by physicians from the 1790s onward. Various hypotheses and inferences on pubertal (menstrual, procreative) timing are attested since ancient times, which, well into early modernity were explained on the basis of temperamental, humoral and Jungian "complexional" causes, or general or local "plethora" (blood excess). Endocrinological (hormonal) theories and discoveries are a twentieth-century development. See also List of youngest birth mothers List of youngest birth fathers Premature menopause Premature ovarian failure References == External links ==

Aarogya, could you share information about a health condition involving Abortion

Abortion

Abortion is the termination of a pregnancy by removal or expulsion of an embryo or fetus. An abortion that occurs without intervention is known as a miscarriage or "spontaneous abortion"; these occur in approximately 30% to 40% of pregnancies. When deliberate steps are taken to end a pregnancy, it is called an induced abortion, or less frequently "induced miscarriage". The unmodified word abortion generally refers to an induced abortion. The reasons why women have abortions are diverse and vary across the world. Reasons include maternal health, an inability to afford a child, domestic violence, lack of support, feeling they are too young, wishing to complete education or advance a career, and not being able or willing to raise a child conceived as a result of rape or incest.When properly done, induced abortion is one of the safest procedures in medicine.: 1  In the United States, the risk of maternal mortality is 14 times lower after induced abortion than after childbirth. Unsafe abortions—those performed by people lacking the necessary skills, or in inadequately resourced settings—are a major cause of maternal death, especially in the developing world, though self-managed medication abortions are highly effective and safe. Public health data shows that making safe abortion legal and accessible reduces maternal deaths.Modern methods use medication or surgery for abortions. The drug mifepristone in combination with prostaglandin appears to be as safe and effective as surgery during the first and second trimester of pregnancy. The most common surgical technique involves dilating the cervix and using a suction device. Birth control, such as the pill or intrauterine devices, can be used immediately following abortion. When performed legally and safely on a woman who desires it, induced abortions do not increase the risk of long-term mental or physical problems. In contrast, unsafe abortions performed by unskilled individuals, with hazardous equipment, or in unsanitary facilities cause 47,000 deaths and 5 million hospital admissions each year. The World Health Organization states that "access to legal, safe and comprehensive abortion care, including post-abortion care, is essential for the attainment of the highest possible level of sexual and reproductive health".Around 73 million abortions are performed each year in the world, with about 45% done unsafely. Abortion rates changed little between 2003 and 2008, before which they decreased for at least two decades as access to family planning and birth control increased. As of 2018, 37% of the worlds women had access to legal abortions without limits as to reason. Countries that permit abortions have different limits on how late in pregnancy abortion is allowed. Abortion rates are similar between countries that ban abortion and countries that allow it.Historically, abortions have been attempted using herbal medicines, sharp tools, forceful massage, or through other traditional methods. Abortion laws and cultural or religious views of abortions are different around the world. In some areas, abortion is legal only in specific cases such as rape, fetal defects, poverty, risk to a womans health, or incest. There is debate over the moral, ethical, and legal issues of abortion. Those who oppose abortion often argue that an embryo or fetus is a person with a right to life, and thus equate abortion with murder. Those who support the legality of abortion often argue that it is part of a womans right to make decisions about her own body. Others favor legal and accessible abortion as a public health measure. Types Induced Approximately 205 million pregnancies occur each year worldwide. Over a third are unintended and about a fifth end in induced abortion. Most abortions result from unintended pregnancies. In the United Kingdom, 1 to 2% of abortions are done due to genetic problems in the fetus. A pregnancy can be intentionally aborted in several ways. The manner selected often depends upon the gestational age of the embryo or fetus, which increases in size as the pregnancy progresses. Specific procedures may also be selected due to legality, regional availability, and doctor or a womans personal preference. Reasons for procuring induced abortions are typically characterized as either therapeutic or elective. An abortion is medically referred to as a therapeutic abortion when it is performed to save the life of the pregnant woman; to prevent harm to the womans physical or mental health; to terminate a pregnancy where indications are that the child will have a significantly increased chance of mortality or morbidity; or to selectively reduce the number of fetuses to lessen health risks associated with multiple pregnancy. An abortion is referred to as an elective or voluntary abortion when it is performed at the request of the woman for non-medical reasons. Confusion sometimes arises over the term "elective" because "elective surgery" generally refers to all scheduled surgery, whether medically necessary or not. Spontaneous Miscarriage, also known as spontaneous abortion, is the unintentional expulsion of an embryo or fetus before the 24th week of gestation. A pregnancy that ends before 37 weeks of gestation resulting in a live-born infant is a "premature birth" or a "preterm birth". When a fetus dies in utero after viability, or during delivery, it is usually termed "stillborn". Premature births and stillbirths are generally not considered to be miscarriages, although usage of these terms can sometimes overlap.Studies of pregnant women in the US and China have shown that between 40% and 60% of embryos do not progress to birth. The vast majority of miscarriages occur before the woman is aware that she is pregnant, and many pregnancies spontaneously abort before medical practitioners can detect an embryo. Between 15% and 30% of known pregnancies end in clinically apparent miscarriage, depending upon the age and health of the pregnant woman. 80% of these spontaneous abortions happen in the first trimester.The most common cause of spontaneous abortion during the first trimester is chromosomal abnormalities of the embryo or fetus, accounting for at least 50% of sampled early pregnancy losses. Other causes include vascular disease (such as lupus), diabetes, other hormonal problems, infection, and abnormalities of the uterus. Advancing maternal age and a womans history of previous spontaneous abortions are the two leading factors associated with a greater risk of spontaneous abortion. A spontaneous abortion can also be caused by accidental trauma; intentional trauma or stress to cause miscarriage is considered induced abortion or feticide. Methods Medical Medical abortions are those induced by abortifacient pharmaceuticals. Medical abortion became an alternative method of abortion with the availability of prostaglandin analogs in the 1970s and the antiprogestogen mifepristone (also known as RU-486) in the 1980s.The most common early first-trimester medical abortion regimens use mifepristone in combination with misoprostol (or sometimes another prostaglandin analog, gemeprost) up to 10 weeks (70 days) gestational age, methotrexate in combination with a prostaglandin analog up to 7 weeks gestation, or a prostaglandin analog alone. Mifepristone–misoprostol combination regimens work faster and are more effective at later gestational ages than methotrexate–misoprostol combination regimens, and combination regimens are more effective than misoprostol alone. This regimen is effective in the second trimester. Medical abortion regimens involving mifepristone followed by misoprostol in the cheek between 24 and 48 hours later are effective when performed before 70 days gestation.In very early abortions, up to 7 weeks gestation, medical abortion using a mifepristone–misoprostol combination regimen is considered to be more effective than surgical abortion (vacuum aspiration), especially when clinical practice does not include detailed inspection of aspirated tissue. Early medical abortion regimens using mifepristone, followed 24–48 hours later by buccal or vaginal misoprostol are 98% effective up to 9 weeks gestational age; from 9 to 10 weeks efficacy decreases modestly to 94%. If medical abortion fails, surgical abortion must be used to complete the procedure.Early medical abortions account for the majority of abortions before 9 weeks gestation in Britain, France, Switzerland, United States, and the Nordic countries.Medical abortion regimens using mifepristone in combination with a prostaglandin analog are the most common methods used for second-trimester abortions in Canada, most of Europe, China and India, in contrast to the United States where 96% of second-trimester abortions are performed surgically by dilation and evacuation.A 2020 Cochrane Systematic Review concluded that providing women with medications to take home to complete the second stage of the procedure for an early medical abortion results in an effective abortion. Further research is required to determine if self-administered medical abortion is as safe as provider-administered medical abortion, where a health care professional is present to help manage the medical abortion. Safely permitting women to self-administer abortion medication has the potential to improve access to abortion. Other research gaps that were identified include how to best support women who choose to take the medication home for a self-administered abortion. Surgical Up to 15 weeks gestation, suction-aspiration or vacuum aspiration are the most common surgical methods of induced abortion. Manual vacuum aspiration (MVA) consists of removing the fetus or embryo, placenta, and membranes by suction using a manual syringe, while electric vacuum aspiration (EVA) uses an electric pump. These techniques can both be used very early in pregnancy. MVA can be used up to 14 weeks but is more often used earlier in the U.S. EVA can be used later.MVA, also known as "mini-suction" and "menstrual extraction" or EVA can be used in very early pregnancy when cervical dilation may not be required. Dilation and curettage (D&C) refers to opening the cervix (dilation) and removing tissue (curettage) via suction or sharp instruments. D&C is a standard gynecological procedure performed for a variety of reasons, including examination of the uterine lining for possible malignancy, investigation of abnormal bleeding, and abortion. The World Health Organization recommends sharp curettage only when suction aspiration is unavailable.Dilation and evacuation (D&E), used after 12 to 16 weeks, consists of opening the cervix and emptying the uterus using surgical instruments and suction. D&E is performed vaginally and does not require an incision. Intact dilation and extraction (D&X) refers to a variant of D&E sometimes used after 18 to 20 weeks when removal of an intact fetus improves surgical safety or for other reasons.Abortion may also be performed surgically by hysterotomy or gravid hysterectomy. Hysterotomy abortion is a procedure similar to a caesarean section and is performed under general anesthesia. It requires a smaller incision than a caesarean section and can be used during later stages of pregnancy. Gravid hysterectomy refers to removal of the whole uterus while still containing the pregnancy. Hysterotomy and hysterectomy are associated with much higher rates of maternal morbidity and mortality than D&E or induction abortion.First-trimester procedures can generally be performed using local anesthesia, while second-trimester methods may require deep sedation or general anesthesia. Labor induction abortion In places lacking the necessary medical skill for dilation and extraction, or where preferred by practitioners, an abortion can be induced by first inducing labor and then inducing fetal demise if necessary. This is sometimes called "induced miscarriage". This procedure may be performed from 13 weeks gestation to the third trimester. Although it is very uncommon in the United States, more than 80% of induced abortions throughout the second trimester are labor-induced abortions in Sweden and other nearby countries.Only limited data are available comparing this method with dilation and extraction. Unlike D&E, labor-induced abortions after 18 weeks may be complicated by the occurrence of brief fetal survival, which may be legally characterized as live birth. For this reason, labor-induced abortion is legally risky in the United States. Other methods Historically, a number of herbs reputed to possess abortifacient properties have been used in folk medicine. Among these are: tansy, pennyroyal, black cohosh, and the now-extinct silphium.: 44–47, 62–63, 154–55, 230–31 In 1978, one woman in Colorado died and another developed organ damage when they attempted to terminate their pregnancies by taking pennyroyal oil. Because the indiscriminant use of herbs as abortifacients can cause serious—even lethal—side effects, such as multiple organ failure, such use is not recommended by physicians. Abortion is sometimes attempted by causing trauma to the abdomen. The degree of force, if severe, can cause serious internal injuries without necessarily succeeding in inducing miscarriage. In Southeast Asia, there is an ancient tradition of attempting abortion through forceful abdominal massage. One of the bas reliefs decorating the temple of Angkor Wat in Cambodia depicts a demon performing such an abortion upon a woman who has been sent to the underworld.Reported methods of unsafe, self-induced abortion include misuse of misoprostol and insertion of non-surgical implements such as knitting needles and clothes hangers into the uterus. These and other methods to terminate pregnancy may be called "induced miscarriage". Such methods are rarely used in countries where surgical abortion is legal and available. Safety The health risks of abortion depend principally upon whether the procedure is performed safely or unsafely. The World Health Organization (WHO) defines unsafe abortions as those performed by unskilled individuals, with hazardous equipment, or in unsanitary facilities. Legal abortions performed in the developed world are among the safest procedures in medicine. In the United States as of 2012, abortion was estimated to be about 14 times safer for women than childbirth. CDC estimated in 2019 that US pregnancy-related mortality was 17.2 maternal deaths per 100,000 live births, while the US abortion mortality rate is 0.7 maternal deaths per 100,000 procedures. In the UK, guidelines of the Royal College of Obstetricians and Gynaecologists state that "Women should be advised that abortion is generally safer than continuing a pregnancy to term." Worldwide, on average, abortion is safer than carrying a pregnancy to term. A 2007 study reported that "26% of all pregnancies worldwide are terminated by induced abortion," whereas "deaths from improperly performed [abortion] procedures constitute 13% of maternal mortality globally." In Indonesia in 2000 it was estimated that 2 million pregnancies ended in abortion, 4.5 million pregnancies were carried to term, and 14-16 percent of maternal deaths resulted from abortion.In the US from 2000 to 2009, abortion had a mortality rate lower than plastic surgery, lower or similar to running a marathon, and about equivalent to traveling 760 miles (1,220 km) in a passenger car. Five years after seeking abortion services, women who gave birth after being denied an abortion reported worse health than women who had either first or second trimester abortions. The risk of abortion-related mortality increases with gestational age, but remains lower than that of childbirth. Outpatient abortion is as safe from 64 to 70 days gestation as it before 63 days.There is little difference in terms of safety and efficacy between medical abortion using a combined regimen of mifepristone and misoprostol and surgical abortion (vacuum aspiration) in early first trimester abortions up to 10 weeks gestation. Medical abortion using the prostaglandin analog misoprostol alone is less effective and more painful than medical abortion using a combined regimen of mifepristone and misoprostol or surgical abortion.Vacuum aspiration in the first trimester is the safest method of surgical abortion, and can be performed in a primary care office, abortion clinic, or hospital. Complications, which are rare, can include uterine perforation, pelvic infection, and retained products of conception requiring a second procedure to evacuate. Infections account for one-third of abortion-related deaths in the United States. The rate of complications of vacuum aspiration abortion in the first trimester is similar regardless of whether the procedure is performed in a hospital, surgical center, or office. Preventive antibiotics (such as doxycycline or metronidazole) are typically given before abortion procedures, as they are believed to substantially reduce the risk of postoperative uterine infection; however, antibiotics are not routinely given with abortion pills. The rate of failed procedures does not appear to vary significantly depending on whether the abortion is performed by a doctor or a mid-level practitioner.Complications after second-trimester abortion are similar to those after first-trimester abortion, and depend somewhat on the method chosen. The risk of death from abortion approaches roughly half the risk of death from childbirth the farther along a woman is in pregnancy; from one in a million before 9 weeks gestation to nearly one in ten thousand at 21 weeks or more (as measured from the last menstrual period). It appears that having had a prior surgical uterine evacuation (whether because of induced abortion or treatment of miscarriage) correlates with a small increase in the risk of preterm birth in future pregnancies. The studies supporting this did not control for factors not related to abortion or miscarriage, and hence the causes of this correlation have not been determined, although multiple possibilities have been suggested.Some purported risks of abortion are promoted primarily by anti-abortion groups, but lack scientific support. For example, the question of a link between induced abortion and breast cancer has been investigated extensively. Major medical and scientific bodies (including the WHO, National Cancer Institute, American Cancer Society, Royal College of OBGYN and American Congress of OBGYN) have concluded that abortion does not cause breast cancer.In the past even illegality has not automatically meant that the abortions were unsafe. Referring to the U.S., historian Linda Gordon states: "In fact, illegal abortions in this country have an impressive safety record.": 25  According to Rickie Solinger, A related myth, promulgated by a broad spectrum of people concerned about abortion and public policy, is that before legalization abortionists were dirty and dangerous back-alley butchers.... [T]he historical evidence does not support such claims.: 4  Authors Jerome Bates and Edward Zawadzki describe the case of an illegal abortionist in the eastern U.S. in the early 20th century who was proud of having successfully completed 13,844 abortions without any fatality.: 59  In 1870s New York City the famous abortionist/midwife Madame Restell (Anna Trow Lohman) appears to have lost very few women among her more than 100,000 patients—a lower mortality rate than the childbirth mortality rate at the time. In 1936, the prominent professor of obstetrics and gynecology Frederick J. Taussig wrote that a cause of increasing mortality during the years of illegality in the U.S. was that With each decade of the past fifty years the actual and proportionate frequency of this accident [perforation of the uterus] has increased, due, first, to the increase in the number of instrumentally induced abortions; second, to the proportionate increase in abortions handled by doctors as against those handled by midwives; and, third, to the prevailing tendency to use instruments instead of the finger in emptying the uterus.: 223 Mental health Current evidence finds no relationship between most induced abortions and mental health problems other than those expected for any unwanted pregnancy. A report by the American Psychological Association concluded that a womans first abortion is not a threat to mental health when carried out in the first trimester, with such women no more likely to have mental-health problems than those carrying an unwanted pregnancy to term; the mental-health outcome of a womans second or greater abortion is less certain. Some older reviews concluded that abortion was associated with an increased risk of psychological problems; however, they did not use an appropriate control group.Although some studies show negative mental-health outcomes in women who choose abortions after the first trimester because of fetal abnormalities, more rigorous research would be needed to show this conclusively. Some proposed negative psychological effects of abortion have been referred to by anti-abortion advocates as a separate condition called "post-abortion syndrome", but this is not recognized by medical or psychological professionals in the United States.A 2020 long term-study among US women found that about 99% of women felt that they made the right decision five years after they had an abortion. Relief was the primary emotion with few women feeling sadness or guilt. Social stigma was a main factor predicting negative emotions and regret years later. Unsafe abortion Women seeking an abortion may use unsafe methods, especially when it is legally restricted. They may attempt self-induced abortion or seek the help of a person without proper medical training or facilities. This can lead to severe complications, such as incomplete abortion, sepsis, hemorrhage, and damage to internal organs.Unsafe abortions are a major cause of injury and death among women worldwide. Although data are imprecise, it is estimated that approximately 20 million unsafe abortions are performed annually, with 97% taking place in developing countries. Unsafe abortions are believed to result in millions of injuries. Estimates of deaths vary according to methodology, and have ranged from 37,000 to 70,000 in the past decade; deaths from unsafe abortion account for around 13% of all maternal deaths. The World Health Organization believes that mortality has fallen since the 1990s. To reduce the number of unsafe abortions, public health organizations have generally advocated emphasizing the legalization of abortion, training of medical personnel, and ensuring access to reproductive-health services.A major factor in whether abortions are performed safely or not is the legal standing of abortion. Countries with restrictive abortion laws have higher rates of unsafe abortion and similar overall abortion rates compared to those where abortion is legal and available. For example, the 1996 legalization of abortion in South Africa had an immediate positive impact on the frequency of abortion-related complications, with abortion-related deaths dropping by more than 90%. Similar reductions in maternal mortality have been observed after other countries have liberalized their abortion laws, such as Romania and Nepal. A 2011 study concluded that in the United States, some state-level anti-abortion laws are correlated with lower rates of abortion in that state. The analysis, however, did not take into account travel to other states without such laws to obtain an abortion. In addition, a lack of access to effective contraception contributes to unsafe abortion. It has been estimated that the incidence of unsafe abortion could be reduced by up to 75% (from 20 million to 5 million annually) if modern family planning and maternal health services were readily available globally. Rates of such abortions may be difficult to measure because they can be reported variously as miscarriage, "induced miscarriage", "menstrual regulation", "mini-abortion", and "regulation of a delayed/suspended menstruation".Forty percent of the worlds women are able to access therapeutic and elective abortions within gestational limits, while an additional 35 percent have access to legal abortion if they meet certain physical, mental, or socioeconomic criteria. While maternal mortality seldom results from safe abortions, unsafe abortions result in 70,000 deaths and 5 million disabilities per year. Complications of unsafe abortion account for approximately an eighth of maternal mortalities worldwide, though this varies by region. Secondary infertility caused by an unsafe abortion affects an estimated 24 million women. The rate of unsafe abortions has increased from 44% to 49% between 1995 and 2008. Health education, access to family planning, and improvements in health care during and after abortion have been proposed to address this phenomenon. Incidence There are two commonly used methods of measuring the incidence of abortion: Abortion rate – number of abortions annually per 1,000 women between 15 and 44 years of age; some sources use a range of 15–49. Abortion percentage – number of abortions out of 100 known pregnancies; pregnancies include live births, abortions, and miscarriages.In many places, where abortion is illegal or carries a heavy social stigma, medical reporting of abortion is not reliable. For this reason, estimates of the incidence of abortion must be made without determining certainty related to standard error. The number of abortions performed worldwide seems to have remained stable in recent years, with 41.6 million having been performed in 2003 and 43.8 million having been performed in 2008. The abortion rate worldwide was 28 per 1000 women per year, though it was 24 per 1000 women per year for developed countries and 29 per 1000 women per year for developing countries. The same 2012 study indicated that in 2008, the estimated abortion percentage of known pregnancies was at 21% worldwide, with 26% in developed countries and 20% in developing countries.On average, the incidence of abortion is similar in countries with restrictive abortion laws and those with more liberal access to abortion. Restrictive abortion laws are associated with increases in the percentage of abortions performed unsafely. The unsafe abortion rate in developing countries is partly attributable to lack of access to modern contraceptives; according to the Guttmacher Institute, providing access to contraceptives would result in about 14.5 million fewer unsafe abortions and 38,000 fewer deaths from unsafe abortion annually worldwide.The rate of legal, induced abortion varies extensively worldwide. According to the report of employees of Guttmacher Institute it ranged from 7 per 1000 women per year (Germany and Switzerland) to 30 per 1000 women per year (Estonia) in countries with complete statistics in 2008. The proportion of pregnancies that ended in induced abortion ranged from about 10% (Israel, the Netherlands and Switzerland) to 30% (Estonia) in the same group, though it might be as high as 36% in Hungary and Romania, whose statistics were deemed incomplete.An American study in 2002 concluded that about half of women having abortions were using a form of contraception at the time of becoming pregnant. Inconsistent use was reported by half of those using condoms and three-quarters of those using the birth control pill; 42% of those using condoms reported failure through slipping or breakage. The Guttmacher Institute estimated that "most abortions in the United States are obtained by minority women" because minority women "have much higher rates of unintended pregnancy". In a 2022 analysis by the Kaiser Family Foundation, while people of color comprise 44% of the population in Mississippi, 59% of the population in Texas, 42% of the population in Louisiana (by the state Health Department), and 35% of the population in Alabama, they comprise 80%, 74%, 72%, and 70% of those receiving abortions.The abortion rate may also be expressed as the average number of abortions a woman has during her reproductive years; this is referred to as total abortion rate (TAR). Gestational age and method Abortion rates also vary depending on the stage of pregnancy and the method practiced. In 2003, the Centers for Disease Control and Prevention (CDC) reported that 26% of reported legal induced abortions in the United States were known to have been obtained at less than 6 weeks gestation, 18% at 7 weeks, 15% at 8 weeks, 18% at 9 through 10 weeks, 10% at 11 through 12 weeks, 6% at 13 through 15 weeks, 4% at 16 through 20 weeks and 1% at more than 21 weeks. 91% of these were classified as having been done by "curettage" (suction-aspiration, dilation and curettage, dilation and evacuation), 8% by "medical" means (mifepristone), >1% by "intrauterine instillation" (saline or prostaglandin), and 1% by "other" (including hysterotomy and hysterectomy). According to the CDC, due to data collection difficulties the data must be viewed as tentative and some fetal deaths reported beyond 20 weeks may be natural deaths erroneously classified as abortions if the removal of the dead fetus is accomplished by the same procedure as an induced abortion.The Guttmacher Institute estimated there were 2,200 intact dilation and extraction procedures in the US during 2000; this accounts for <0.2% of the total number of abortions performed that year. Similarly, in England and Wales in 2006, 89% of terminations occurred at or under 12 weeks, 9% between 13 and 19 weeks, and 2% at or over 20 weeks. 64% of those reported were by vacuum aspiration, 6% by D&E, and 30% were medical. There are more second trimester abortions in developing countries such as China, India and Vietnam than in developed countries. Motivation Personal The reasons why women have abortions are diverse and vary across the world. Some of the reasons may include an inability to afford a child, domestic violence, lack of support, feeling they are too young, and the wish to complete education or advance a career. Additional reasons include not being able or willing to raise a child conceived as a result of rape or incest. Societal Some abortions are undergone as the result of societal pressures. These might include the preference for children of a specific sex or race, disapproval of single or early motherhood, stigmatization of people with disabilities, insufficient economic support for families, lack of access to or rejection of contraceptive methods, or efforts toward population control (such as Chinas one-child policy). These factors can sometimes result in compulsory abortion or sex-selective abortion. Maternal and fetal health An additional factor is maternal health which was listed as the main reason by about a third of women in 3 of 27 countries and about 7% of women in a further 7 of these 27 countries.In the U.S., the Supreme Court decisions in Roe v. Wade and Doe v. Bolton: "ruled that the states interest in the life of the fetus became compelling only at the point of viability, defined as the point at which the fetus can survive independently of its mother. Even after the point of viability, the state cannot favor the life of the fetus over the life or health of the pregnant woman. Under the right of privacy, physicians must be free to use their "medical judgment for the preservation of the life or health of the mother." On the same day that the Court decided Roe, it also decided Doe v. Bolton, in which the Court defined health very broadly: "The medical judgment may be exercised in the light of all factors—physical, emotional, psychological, familial, and the womans age—relevant to the well-being of the patient. All these factors may relate to health. This allows the attending physician the room he needs to make his best medical judgment.": 1200–01 Public opinion shifted in America following television personality Sherri Finkbines discovery during her fifth month of pregnancy that she had been exposed to thalidomide. Unable to obtain a legal abortion in the United States, she traveled to Sweden. From 1962 to 1965, an outbreak of German measles left 15,000 babies with severe birth defects. In 1967, the American Medical Association publicly supported liberalization of abortion laws. A National Opinion Research Center poll in 1965 showed 73% supported abortion when the mothers life was at risk, 57% when birth defects were present and 59% for pregnancies resulting from rape or incest. Cancer The rate of cancer during pregnancy is 0.02–1%, and in many cases, cancer of the mother leads to consideration of abortion to protect the life of the mother, or in response to the potential damage that may occur to the fetus during treatment. This is particularly true for cervical cancer, the most common type of which occurs in 1 of every 2,000–13,000 pregnancies, for which initiation of treatment "cannot co-exist with preservation of fetal life (unless neoadjuvant chemotherapy is chosen)". Very early stage cervical cancers (I and IIa) may be treated by radical hysterectomy and pelvic lymph node dissection, radiation therapy, or both, while later stages are treated by radiotherapy. Chemotherapy may be used simultaneously. Treatment of breast cancer during pregnancy also involves fetal considerations, because lumpectomy is discouraged in favor of modified radical mastectomy unless late-term pregnancy allows follow-up radiation therapy to be administered after the birth.Exposure to a single chemotherapy drug is estimated to cause a 7.5–17% risk of teratogenic effects on the fetus, with higher risks for multiple drug treatments. Treatment with more than 40 Gy of radiation usually causes spontaneous abortion. Exposure to much lower doses during the first trimester, especially 8 to 15 weeks of development, can cause intellectual disability or microcephaly, and exposure at this or subsequent stages can cause reduced intrauterine growth and birth weight. Exposures above 0.005–0.025 Gy cause a dose-dependent reduction in IQ. It is possible to greatly reduce exposure to radiation with abdominal shielding, depending on how far the area to be irradiated is from the fetus.The process of birth itself may also put the mother at risk. According to Li et al., "[v]aginal delivery may result in dissemination of neoplastic cells into lymphovascular channels, haemorrhage, cervical laceration and implantation of malignant cells in the episiotomy site, while abdominal delivery may delay the initiation of non-surgical treatment." History and religion Since ancient times, abortions have been done using a number of methods, including herbal medicines acting as abortifacients, sharp tools through the use of force, or through other traditional medicine methods. Induced abortion has a long history and can be traced back to civilizations as varied as ancient China (abortifacient knowledge is often attributed to the mythological ruler Shennong), ancient India since its Vedic age, ancient Egypt with its Ebers Papyrus (c. 1550 BCE), and the Roman Empire in the time of Juvenal (c. 200 CE). One of the earliest known artistic representations of abortion is in a bas relief at Angkor Wat (c. 1150). Found in a series of friezes that represent judgment after death in Hindu and Buddhist culture, it depicts the technique of abdominal abortion.In Judaism (Genesis 2:7), the fetus is not considered to have a human soul until it is safely outside of the woman, is viable, and has taken its first breath. The fetus is considered valuable property of the woman and not a human life while in the womb (Exodus 21:22–23). While Judaism encourages people to be fruitful and multiply by having children, abortion is allowed and is deemed necessary when a pregnant womans life is in danger. Several religions, including Judaism, which disagree that human life begins at conception, support the legality of abortion on religious freedom grounds.Some medical scholars and abortion opponents have suggested that the Hippocratic Oath forbade physicians in Ancient Greece from performing abortions; other scholars disagree with this interpretation, and state that the medical texts of Hippocratic Corpus contain descriptions of abortive techniques right alongside the Oath. The physician Scribonius Largus wrote in 43 CE that the Hippocratic Oath prohibits abortion, as did Soranus of Ephesus, although apparently not all doctors adhered to it strictly at the time. According to Soranus 1st or 2nd century CE work Gynaecology, one party of medical practitioners banished all abortives as required by the Hippocratic Oath; the other party to which he belonged was willing to prescribe abortions only for the sake of the mothers health. In Politics (350 BCE), Aristotle condemned infanticide as a means of population control. He preferred abortion in such cases, with the restriction that it "must be practised on it before it has developed sensation and life; for the line between lawful and unlawful abortion will be marked by the fact of having sensation and being alive."In the Catholic Church, opinion was divided on how serious abortion was in comparison with such acts as contraception, oral sex, and sex in marriage for pleasure rather than procreation.: 155–167  The Catholic Church did not begin vigorously opposing abortion until the 19th century. As early as ~100 A.D., the Didache taught that abortion was sinful. Several historians argue that prior to the 19th century most Catholic authors did not regard termination of pregnancy before quickening or ensoulment as an abortion. Among these authors were the Doctors of the Church, such as St. Augustine, St. Thomas Aquinas, and St. Alphonsus Liguori. Pope Sixtus V (r. 1585–90) was the only Pope before Pope Pius IX (in his 1869 bull, Apostolicae Sedis) to institute a Church policy labeling all abortion as homicide and condemning abortion regardless of the stage of pregnancy.: 362–364 : 157–158  Sixtus V 1588 pronouncement was reversed in 1591 by Pope Gregory XIV. In the recodification of 1917 Code of Canon Law, Apostolicae Sedis was strengthened, in part to remove a possible reading that excluded excommunication of the mother. Statements made in the Catechism of the Catholic Church, the codified summary of the Churchs teachings, considers abortion from the moment of conception as homicide and called for the end of legal abortion.A 2014 Guttmacher survey of abortion patients in the United States found that many reported a religious affiliation: 24% were Catholic while 30% were Protestant. A 1995 survey reported that Catholic women are as likely as the general population to terminate a pregnancy, Protestants are less likely to do so, and evangelical Christians are the least likely to do so. A 2019 Pew Research Center study found that most Christian denominations were against overturning Roe v. Wade, which in the United States legalized abortion, at around 70%, except White Evangelicals at 35%.In Islam, abortion is traditionally permitted until a point in time when Muslims believe the soul enters the fetus, considered by various theologians to be at conception, 40 days after conception, 120 days after conception, or quickening. Abortion is largely heavily restricted or forbidden in areas of high Islamic faith such as the Middle East and North Africa. Abortion has been a fairly common practice, and was not always illegal or controversial until the 19th century. Under common law, including early English common law dating back to Edward Coke in 1648, abortion was generally permitted before quickening (14–26 weeks after conception, or betweeth the fourth and sixth month), and at womens discretion; it was whether abortion was performed after quickening that determined if it was a crime. In Europe and North America, abortion techniques advanced starting in the 17th century; the conservatism of most in the medical profession with regards to sexual matters prevented the wide expansion of abortion techniques. Other medical practitioners in addition to some physicians advertised their services, and they were not widely regulated until the 19th century when the practice, sometimes called restellism, was banned in both the United States and the United Kingdom.Church groups, as well as physicians, were highly influential in anti-abortion movements, and religious groups more so since the 20th century. Some of the early anti-abortion laws punished only the doctor or abortionist, and while women could be criminally tried for a self-induced abortion, they were rarely prosecuted in general. In the United States, some argued that abortion was more dangerous than childbirth until about 1930 when incremental improvements in abortion procedures relative to childbirth made abortion safer. Others maintain that in the 19th century early abortions under the hygienic conditions in which midwives usually worked were relatively safe. Several scholars argue that, despite improved medical procedures, the period from the 1930s until the 1970s saw more zealous enforcement of anti-abortion laws, and concomitantly an increasing control of abortion providers by organized crime.Soviet Russia (1919), Iceland (1935), and Sweden (1938) were among the first countries to legalize certain or all forms of abortion. In Nazi Germany (1935), a law permitted abortions for those deemed "hereditarily ill", while women considered of German stock were specifically prohibited from having abortions. Preceding the Nazi German example was that of some 19th-century physicians, one of the most famous and consequential being Horatio Storer, who argued for anti-abortion laws on racist and pseudoscientific grounds. Beginning in the second half of the 20th century, abortion was legalized in a greater number of countries. Society and culture Abortion debate Induced abortion has long been the source of considerable debate. Ethical, moral, philosophical, biological, religious and legal issues surrounding abortion are related to value systems. Opinions of abortion may be about fetal rights, governmental authority, and womens rights. In both public and private debate, arguments presented in favor of or against abortion access focus on either the moral permissibility of an induced abortion, or justification of laws permitting or restricting abortion. The World Medical Association Declaration on Therapeutic Abortion notes, "circumstances bringing the interests of a mother into conflict with the interests of her unborn child create a dilemma and raise the question as to whether or not the pregnancy should be deliberately terminated." Abortion debates, especially pertaining to abortion laws, are often spearheaded by groups advocating one of these two positions. Groups who favor greater legal restrictions on abortion, including complete prohibition, most often describe themselves as "pro-life" while groups who are against such legal restrictions describe themselves as "pro-choice". Modern abortion law Current laws pertaining to abortion are diverse. Religious, moral, and cultural factors continue to influence abortion laws throughout the world. The right to life, the right to liberty, the right to security of person, and the right to reproductive health are major issues of human rights that sometimes constitute the basis for the existence or absence of abortion laws. In jurisdictions where abortion is legal, certain requirements must often be met before a woman may obtain a legal abortion (an abortion performed without the womans consent is considered feticide). These requirements usually depend on the age of the fetus, often using a trimester-based system to regulate the window of legality, or as in the U.S., on a doctors evaluation of the fetus viability. Some jurisdictions require a waiting period before the procedure, prescribe the distribution of information on fetal development, or require that parents be contacted if their minor daughter requests an abortion. Other jurisdictions may require that a woman obtain the consent of the fetus father before aborting the fetus, that abortion providers inform women of health risks of the procedure—sometimes including "risks" not supported by the medical literature—and that multiple medical authorities certify that the abortion is either medically or socially necessary. Many restrictions are waived in emergency situations. China, which has ended their one-child policy, and now has a two child policy, has at times incorporated mandatory abortions as part of their population control strategy.Other jurisdictions ban abortion almost entirely. Many, but not all, of these allow legal abortions in a variety of circumstances. These circumstances vary based on jurisdiction, but may include whether the pregnancy is a result of rape or incest, the fetus development is impaired, the womans physical or mental well-being is endangered, or socioeconomic considerations make childbirth a hardship. In countries where abortion is banned entirely, such as Nicaragua, medical authorities have recorded rises in maternal death directly and indirectly due to pregnancy as well as deaths due to doctors fears of prosecution if they treat other gynecological emergencies. Some countries, such as Bangladesh, that nominally ban abortion, may also support clinics that perform abortions under the guise of menstrual hygiene. This is also a terminology in traditional medicine. In places where abortion is illegal or carries heavy social stigma, pregnant women may engage in medical tourism and travel to countries where they can terminate their pregnancies. Women without the means to travel can resort to providers of illegal abortions or attempt to perform an abortion by themselves.The organization Women on Waves has been providing education about medical abortions since 1999. The NGO created a mobile medical clinic inside a shipping container, which then travels on rented ships to countries with restrictive abortion laws. Because the ships are registered in the Netherlands, Dutch law prevails when the ship is in international waters. While in port, the organization provides free workshops and education; while in international waters, medical personnel are legally able to prescribe medical abortion drugs and counseling. Sex-selective abortion Sonography and amniocentesis allow parents to determine sex before childbirth. The development of this technology has led to sex-selective abortion, or the termination of a fetus based on its sex. The selective termination of a female fetus is most common. Sex-selective abortion is partially responsible for the noticeable disparities between the birth rates of male and female children in some countries. The preference for male children is reported in many areas of Asia, and abortion used to limit female births has been reported in Taiwan, South Korea, India, and China. This deviation from the standard birth rates of males and females occurs despite the fact that the country in question may have officially banned sex-selective abortion or even sex-screening. In China, a historical preference for a male child has been exacerbated by the one-child policy, which was enacted in 1979.Many countries have taken legislative steps to reduce the incidence of sex-selective abortion. At the International Conference on Population and Development in 1994 over 180 states agreed to eliminate "all forms of discrimination against the girl child and the root causes of son preference", conditions also condemned by a PACE resolution in 2011. The World Health Organization and UNICEF, along with other United Nations agencies, have found that measures to reduce access to abortion are much less effective at reducing sex-selective abortions than measures to reduce gender inequality. Anti-abortion violence In a number of cases, abortion providers and these facilities have been subjected to various forms of violence, including murder, attempted murder, kidnapping, stalking, assault, arson, and bombing. Anti-abortion violence is classified by both governmental and scholarly sources as terrorism. In the U.S. and Canada, over 8,000 incidents of violence, trespassing, and death threats have been recorded by providers since 1977, including over 200 bombings/arsons and hundreds of assaults. The majority of abortion opponents have not been involved in violent acts. In the United States, four physicians who performed abortions have been murdered: David Gunn (1993), John Britton (1994), Barnett Slepian (1998), and George Tiller (2009). Also murdered, in the U.S. and Australia, have been other personnel at abortion clinics, including receptionists and security guards such as James Barrett, Shannon Lowney, Lee Ann Nichols, and Robert Sanderson. Woundings (e.g., Garson Romalis) and attempted murders have also taken place in the United States and Canada. Hundreds of bombings, arsons, acid attacks, invasions, and incidents of vandalism against abortion providers have occurred. Notable perpetrators of anti-abortion violence include Eric Robert Rudolph, Scott Roeder, Shelley Shannon, and Paul Jennings Hill, the first person to be executed in the United States for murdering an abortion provider.Legal protection of access to abortion has been brought into some countries where abortion is legal. These laws typically seek to protect abortion clinics from obstruction, vandalism, picketing, and other actions, or to protect women and employees of such facilities from threats and harassment. Far more common than physical violence is psychological pressure. In 2003, Chris Danze organized anti-abortion organizations throughout Texas to prevent the construction of a Planned Parenthood facility in Austin. The organizations released the personal information online of those involved with construction, sent them up to 1200 phone calls a day and contacted their churches. Some protestors record women entering clinics on camera. Non-human examples Spontaneous abortion occurs in various animals. For example, in sheep it may be caused by stress or physical exertion, such as crowding through doors or being chased by dogs. In cows, abortion may be caused by contagious disease, such as brucellosis or Campylobacter, but can often be controlled by vaccination. Eating pine needles can also induce abortions in cows. Several plants, including broomweed, skunk cabbage, poison hemlock, and tree tobacco, are known to cause fetal deformities and abortion in cattle: 45–46  and in sheep and goats.: 77–80  In horses, a fetus may be aborted or resorbed if it has lethal white syndrome (congenital intestinal aganglionosis). Foal embryos that are homozygous for the dominant white gene (WW) are theorized to also be aborted or resorbed before birth. In many species of sharks and rays, stress-induced abortions occur frequently on capture.Viral infection can cause abortion in dogs. Cats can experience spontaneous abortion for many reasons, including hormonal imbalance. A combined abortion and spaying is performed on pregnant cats, especially in trap–neuter–return programs, to prevent unwanted kittens from being born. Female rodents may terminate a pregnancy when exposed to the smell of a male not responsible for the pregnancy, known as the Bruce effect.Abortion may also be induced in animals, in the context of animal husbandry. For example, abortion may be induced in mares that have been mated improperly, or that have been purchased by owners who did not realize the mares were pregnant, or that are pregnant with twin foals. Feticide can occur in horses and zebras due to male harassment of pregnant mares or forced copulation, although the frequency in the wild has been questioned. Male gray langur monkeys may attack females following male takeover, causing miscarriage. See also Abortion doula Forced abortion Notes References Bibliography External links First-trimester abortion in women with medical conditions. US Department of Health and Human Services Safe abortion: Technical & policy guidance for health systems, World Health Organization (2015)

Hello Aarogya, explain a situation where Premenstrual dysphoric disorder occurs

Premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by emotional, cognitive, and physical symptoms that cause significant distress or impairment in menstruating women during the luteal phase of the menstrual cycle. The symptoms occur in the luteal phase, (between ovulation and menses), improve within a few days after the onset of menses, and are minimal or absent in the week after menses. PMDD has a profound impact on a persons quality of life and dramatically increases the risk of suicidal ideation and even suicide attempts. Many females of reproductive age experience discomfort or mild mood changes prior to menstruation. However, 5-8% experience severe premenstrual syndrome causing significant distress or functional impairment. Within this population of reproductive age, some women will meet the criteria for PMDD. PMDD is most common from age 25–35, but can occur anytime during a womans reproductive years.The exact cause of PMDD is currently unknown. However, because the symptoms are only present during ovulatory cycles and resolve after menses, it is believed to be caused by fluctuations in gonadal sex hormones or variations in sensitivity to sex hormones.In 2017, researchers at the National Institutes of Health discovered that women with PMDD have genetic changes that make their emotional regulatory pathways more sensitive to estrogen and progesterone, as well as their chemical derivatives. The researchers believe that this increased sensitivity may be responsible for PMDD symptoms.Some studies have suggested that those with PMDD are more at risk of developing postpartum depression after pregnancy, but other evidence has been found to suggest against that notion. PMDD was added to the list of depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders in 2013. It has 11 main symptoms, and a woman has to exhibit at least five to be diagnosed with PMDD. Roughly 20% of women have some symptoms of PMDD, but either have less than five or do not have functional impairment.First line treatment for PMDD is with selective serotonin reuptake inhibitors (SSRIs). Hormonal therapy with oral contraceptives that contain drospirenone have demonstrated efficiency in reducing PMDD symptoms as well. Cognitive behavioral therapy, whether in combination with SSRIs or alone, has shown to be effective in reducing impairment. Dietary modifications and exercise may also be helpful, but studies investigating these treatments have not demonstrated efficacy in reducing PMDD symptoms. Signs and symptoms Clinicians consider mood symptoms, physical symptoms and impact on the patients life in making the diagnosis of PMDD. Mood symptoms include emotional lability (rapidly changing emotions, sensitivity to rejection, etc.), irritability and anger that may lead to conflict, anxiety, feeling on edge, hopelessness, difficulty concentrating, appetite changes, sleeping more or less than usual, or feeling out of control. The physical symptoms are similar to the symptoms of PMS. These include breast tenderness or swelling, joint pain, muscle pain, gaining weight, or feeling bloated.Because of the broad variety in clinical presentation, the onset of symptoms only during or around the luteal phase is key for diagnosing someone with PMDD rather than any other mood disorders. PMDD follows a predictable, cyclic pattern. Symptoms begin in the late luteal phase of the menstrual cycle (after ovulation) and end or are markedly reduced shortly after menstruation begins. On average, the symptoms last six days but can start up to two weeks before menses, meaning symptoms can be felt for up to three weeks out of a cycle. Severe symptoms can begin and worsen until the onset of menstruation, with many not feeling relief until a few days after menstruation ends. The most intense symptoms occurring in the week and days leading up to the first day of menstrual blood flow. The symptoms usually cease shortly after the start of the menstrual period or a few days after it ends. Various symptom and severity tracking questionnaires exist to document presence and severity of symptoms throughout consecutive menstrual cycles.The International Society for the Study of Premenstrual Disorders (ISPMD) defines two categories of premenstrual disorders: core PMD and variant PMD. Core PMD has six characteristics, all mainly focusing on the cyclical nature of PMDD and its typical onset pre-menses tracked over the course of more than two menstrual cycles. The four classified Variant PMDs involve more unexpected variables that cause the onset of premenstrual distress; such as, PMD with absent menstruation or premenstrual exacerbation, wherein the symptoms of another preexisting psychological disorder may be heightened as a result of PMDD onset. Epidemiology About 5-8% of women of reproductive age experience severe premenstrual syndrome; most of these women also meet criteria for PMDD. PMDD is most common from age 25–35, but can occur anytime during a womans reproductive years.Among females of reproductive age living in India, the prevalence of PMDD is 8%. Pathophysiology PMDD mood symptoms are only present in menstruating women. Thus, symptoms do not occur during pregnancy, after menopause, or in women who have anovulatory cycles. Other mood disorders typically persist across all reproductive life events and are independent of a womans menstrual cycle.The current consensus on the cause of PMDD is a combination of heightened sensitivity to fluctuating levels of certain hormones (i.e. the reproductive hormones), environmental stress, and genetic predisposition. The sex steroids—estrogen and progesterone—are neuroactive; they have been noted in rat models to be involved in serotonin pathways. Serotonin is involved in mood regulation alongside estrogen, whose receptors are found in the prefrontal cortex and hippocampus—the regions most known for their involvement in regulating ones mood and cognition overall.While the timing of symptoms suggests hormonal fluctuations as the cause of PMDD, a demonstrable hormonal imbalance in women with PMDD has not been identified. In fact, levels of reproductive hormones and their metabolites in women with and without PMDD are indistinguishable. It is instead hypothesized that women with PMDD are more sensitive to normal levels of hormone fluctuations, predominantly estrogen and progesterone, which produces biochemical events in the nervous system that cause the premenstrual symptoms. These symptoms are more predominant in women who have a predisposition to the disorder.It is apparent that the premenstrual disorders are biologically driven and are not only psychological or cultural phenomena. PMDD has been reported by menstruating women worldwide, indicating a biological basis that is not geographically selective. Most psychologists infer that this disorder is caused by both a reaction to hormone flux and also genetic components. There is evidence of heritability of (retrospectively-reported) premenstrual symptoms from several twin and family studies done in the 1990s, with the heritability of PMDD proving to be about 56%. Genetic factors While whether or not this disorder has a specific genetic basis is still being discussed in the academic community and the possible genetic factors contributing to PMDD have yet to be thoroughly researched, there has recently been multiple genetic factors identified that contribute to the moodiness, depression, irritability, increased appetite, trouble sleeping, acne, fluid retention, headaches, nausea, and other symptoms that are all associated with this disorder. Many studies have noted that a polymorphism of the brain-derived neurotrophic factor gene (BDNF), a gene that helps support neurons in their function and survival in the brain by creating a protein that helps in the growth, maturation, and maintenance of these cells, may play a role in causing PMDD symptoms. This is because the result of this polymorphism mimics the hallmarks of PMDD: volatile moods, depression and irritability centered around the menstrual cycle. This gene has been studied extensively in its association with depression and, promisingly for PMDD research, mice homozygous for the BDNF polymorphism exhibited anxiety-like traits that fluctuated and changed around the mices estrus, analogous to the humans menstruation, therefore mimicking some of the symptoms of PMDD. Risk Factors Environmental stressors have also been found to prospectively increase risk for PMDD symptoms. Environmental components such as stress, hormonal fluctuation, and epigenetics play a key role in the pathology and onset of the disorder. Some studies have noted evidence of interpersonal trauma (domestic violence, physical or emotional trauma, or substance abuse) or seasonal changes (making PMDD potentially comorbid with Seasonal Affective Disorder) having an impact on PMDD risk. But the most common pre-existing disorder found in those diagnosed with PMDD is major depression, wherein they either actually had it or were misdiagnosed when they should have only been diagnosed with PMDD. Finally, an easily modifiable risk factor for PMDD is cigarette smoking. One meta-analysis found dramatically increased risk of developing PMDD in menstruating women who smoke. Relationship to pregnancy and menopause Women with PMDD usually see their symptoms disappear while they are pregnant. Premenstrual dysphoric disorder is primarily a mood disorder that is associated with onset of menstruation; pregnancy, menopause, and hysterectomies all cause menstruation to cease, thereby stopping the proposed sex steroid-/serotonin-caused symptoms from occurring. Although one might expect a higher rate of postpartum depression among those with PMDD, a large study of women with prospectively-confirmed PMDD did not find a higher prevalence of postpartum depression than in controls. If a woman had experienced PPD beforehand, there was found to be a less-than 12% chance of PMDD pathology emerging—hardly any differentiation from the regular population of those who have never experienced postpartum depression. However, PMDD symptoms can get worse following pregnancy, or other associated events such as birth and miscarriage. Mental Health Comorbidities in PMDD The lifetime incidence of other psychiatric disorders is high among women with PMDD. An older review article (2002) utilizing the previous edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) used studies from 1966 to 2002 on PMS and mental health disorders and selected for patients who retrospectively met the diagnostic criteria for PMDD and found that Major Depressive Disorder, Seasonal affective disorder, and generalized anxiety disorder often co-occur in PMDD. Another systematic review study suggests that patients with bipolar disorder, type I or II, have a higher incidence of PMDD. While the diagnosis of PMDD requires a mental health provider to determine that the symptoms a woman is facing is not due to an underlying mental or physical health condition, it is important to note that other conditions often co-occur and impact the quality of life and treatment plan for people with PMDD. Suicidality in Premenstrual Dysphoric Disorder Previous links to suicidality and PMS have been made, but women with PMDD are more likely still to consider and attempt suicide even when controlling for mental health comorbidities. Despite the increase in suicidal ideation and attempts in this population, the data currently suggests that suicidal ideation or action is not more likely to occur during the late luteal phase when PMDD symptoms would occur. It is difficult to study whether treatment reduces suicidality because of the multifaceted reasons provided for suicidal ideation. However, treatment has been well documented to reduce physical and emotional symptoms of PMDD. Diagnosis Diagnostic criteria for PMDD are provided by a number of expert medical guides. Diagnosis can be supported by having women who are seeking treatment for PMDD use a daily charting method to record their symptoms. Daily charting helps to distinguish when mood disturbances are experienced and allows PMDD to be more easily distinguished from other mood disorders. With PMDD, mood symptoms are present only during the luteal phase, or last two weeks, of the menstrual cycle. While PMDD mood symptoms are of a cyclical nature, other mood disorders are variable or constant over time. Although there is a lack of consensus on the most efficient instrument by which to confirm a PMDD diagnosis, several validated scales for recording premenstrual symptoms include the Calendar of Premenstrual Experiences (COPE), Daily Record of Severity of Problems (DRSP), and Prospective Record of the Severity of Menstruation (PRISM). In the context of research, standardized numerical cutoffs are often applied to verify the diagnosis. The difficulty of diagnosing PMDD is one reason that it can be challenging for lawyers to cite the disorder as a defense of crime, in the very rare cases where PMDD is allegedly associated with criminal violence. DSM-5 The DSM-5 which established seven criteria (A through G) for the diagnosis of PMDD which is paraphrased below. There is overlap between the criteria for PMDD in the DSM-5 and the criteria found in the Daily Record of Severity of Problems (DRSP).According to the DSM-5, a diagnosis of PMDD requires the presence of at least five of these symptoms with one of the symptoms being numbers 1–4. These symptoms should occur during the week before menses and remit after initiation of menses. In order to meet criteria for the diagnosis, the symptoms should be charted prospectively for two consecutive ovulation cycles in order to confirm a temporal and cyclical nature of the symptoms. The symptoms should also be severe enough to affect normal work, school, social activities, and/or relationships with others. The symptoms of Criteria A-C must have been met for most menstrual cycles that occurred in the preceding year, and have to have cause significant impairment in family, work, school, or social functioning. (Criterion D). Timing Criterion A: During most menstrual cycles throughout the past year, at least 5 of the symptoms outlined in Criterion B and Criterion C must be present in the final week before the onset of menses, must start to improve within a few days after the onset of menses, and become minimal or absent in the week post-menses. Symptoms Criterion B: One (or more) of the following symptoms must be present: Marked affective lability (e.g., mood swings, feeling suddenly sad or tearful, or increased sensitivity to rejection) Marked irritability or anger or increased interpersonal conflicts Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts Marked anxiety, tension, and/or feelings of being keyed up or on edgeCriterion C: One (or more) of the following symptoms must be present additionally, to reach a total of 5 symptoms when combined with present symptoms from Criterion B above: Decreased interest in usual activities (e.g., work, school, friends, hobbies). Subjective difficulty in concentration. Lethargy, easy fatigability, or marked lack of energy. Marked change in appetite; overeating; or specific food cravings. Hypersomnia or insomnia. A sense of being overwhelmed or out of control. Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of "bloating," or weight gain.Severity Criterion D: The symptoms observed in Criteria A-C are associated with clinically significant distress or interference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home). Consideration of Other Psychiatric Disorders Criterion E: The disturbance is not merely an exacerbation of the symptoms of another disorder, such as major depressive disorder, panic disorder, persistent depressive disorder (Dysthymia), or a personality disorder—although it may co-occur with any of these disorders.Confirmation of the Disorder Criterion F: Criterion A should be confirmed by prospective daily ratings during at least two symptomatic cycles. The diagnosis may be made provisionally prior to this confirmation. Criterion G: The symptoms are not attributable to the physiological effects of a substance (e.g., drug abuse, a medication, other treatments) or another medical condition (e.g., hyperthyroidism). Clinically significant distress is not defined explicitly by the DSM-IV, where it has been critiqued by multiple scholars as being too vague, and potentially detrimental for those who have symptoms of depression, anxiety, or other mood disorders because they do not meet the clinical significance requirement. ICD 11 Diagnostic criteria for PMDD are also provided by the 2016 World Health Organizations International Classification of Diseases (ICD-11-CM): GA34.41 Premenstrual dysphoric disorder Description During a majority of menstrual cycles within the past year, a pattern of mood symptoms (depressed mood, irritability), somatic symptoms (lethargy, joint pain, overeating), or cognitive symptoms (concentration difficulties, forgetfulness) that begin several days before the onset of menses, start to improve within a few days after the onset of menses, and then become minimal or absent within approximately 1 week following the onset of menses. The temporal relationship of the symptoms and luteal and menstrual phases of the cycle may be confirmed by a prospective symptom diary. The symptoms are severe enough to cause significant distress or significant impairment in personal, family, social, educational, occupational or other important areas of functioning and do not represent the exacerbation of a mental disorder. Royal College of Obstetricians and Gynecologists and the International Society for the Study of Premenstrual Disorders Other organizations that have published diagnostic criteria for PMDD include the Royal College of Obstetricians and Gynecologists and the International Society for the Study of Premenstrual Disorders (ISPMD). The ISPMD was a consensus group established by an international multidisciplinary group of experts. The groups diagnostic criteria for PMDD focuses on the cyclic nature of the symptoms occurring during the luteal phase of the menstrual cycle, as well as the symptoms being absent after menstruation and before ovulation and causing significant impairment. The ISPMD diagnostic criteria for PMDD do not specify symptom characteristics or number of symptoms. Differential diagnosis A critical part of diagnosing PMDD is ruling out underlying psychiatric disorder or physical illness that can cause similar symptoms. That exhibits premenstrual exacerbation, the menopausal transition, hyperthyroidism, hypothyroidism, as well as other mood disorders. Furthermore, many medical disorders are worsened prior to ordering menses, but these typically do not present strictly during the luteal phase. Mood disorders – there is potential for patients to have psychiatric disorders with superimposed PMDD or psychiatric disorders. In order to establish the timeline of symptoms required for a diagnosis of PMDD symptoms need to be tracked using scales like the Calendar of Premenstrual Experiences or the Daily Record of Severity of Problems.Menopausal transition – affective symptoms associated with the menopausal transition most commonly start when menstrual cycle starts to become irregular or anovulatory whereas PMDD symptoms occur during the luteal phase of ovulatory cycles. Thyroid disorders—patients with both hyperthyroidism and hypothyroidism may present with affective symptoms. The patients history is very important to determine whether the provider should suspect thyroid disorders. Patients should also have thyroid hormone levels checked to ensure no underlying thyroid disorder is present. Treatment Medication Several medications have been shown to effectively reduce the physical and emotional symptoms of PMDD. Antidepressant Treatment Selective serotonin reuptake inhibitors (SSRIs) are the first-line medication. Women taking SSRIs to ease PMDD generally report >50% alleviation in symptoms, which was significant improvement compared to placebo. Two approaches to dosing have been studied: continuous dosing (daily) and luteal dosing (14 days before menstruation and discontinuing at the onset of menses). Both dosing schedules have similar effectiveness with some recent studies demonstrating greater symptom control with continuous dosing. This gives patients control of how they want to dose their medication in alliance with their mental health provider. Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) have also been studied in the treatment of PMDD and shown efficacy in reducing symptoms. These are an alternative for patients who do not respond to SSRIs. However, they are more likely to be dosed continuously due to SNRI discontinuation syndrome - a flu-like feeling caused by dropping blood levels of SNRI. Anxiolytics Two medications typically given to reduce acute anxiety have been studied in treatment for PMDD: alprazolam (Xanax) and buspirone. Alprazolam carries a risk of abuse and causes central nervous system depression and results of clinical trials have not shown benefit to treatment. Buspirone showed lower efficacy than SSRI, but may be used as an adjunctive treatment or alternative if SSRI side effects are intolerable to the patient. Psychotherapy Cognitive behavioral therapy (CBT) has been shown to be effective for reducing premenstrual symptoms in women with (retrospectively-reported) PMS. CBT is an evidence-based approach for treating depression and focuses on the link between mood, thoughts, and actions to help women address current issues and symptoms. When CBT was compared to SSRI alone or in combination with SSRI, groups receiving CBT had significant improvement of PMS symptoms. Through the practice of CBT, women are better able to recognize and modify recurrent issues as well as thought and behavior patterns that interfere with functioning well or that make depressive symptoms worse. However, a recent meta-analysis suggests that existing psychotherapies may be primarily useful for reducing impairment (rather than symptom severity) in PMDD. Hormonal Treatment Oral contraceptives have been effective in reducing PMS symptoms, but only certain formulations have proven to be modestly effective in the treatment of PMDD. Transdermal estrogen and intrauterine devices containing levonorgestrel have also had modest efficacy.Another FDA approved treatment for PMDD is the oral contraceptive with ethinylestradiol and drospirenone (a novel progestin) taken on a 24-4 schedule (24 active pills, 4 inactive pills). It has been shown that hormonal birth control containing drospirenone and low levels of estrogen helps relieve severe PMDD symptoms, for at least the first three months that it is used. The idea behind using oral contraceptives is to suppress ovulation, therefore suppressing sex hormone fluctuations. Another treatment, typically used when other options have failed, is injection of a gonadotropin-releasing hormone(GnRH) agonist with adjunctive estrogen and progesterone or tibolone. This is a last resort because GnRH antagonists can cause medical menopause by shutting down the bodys pathway for reproductive hormones called the hypothalamic, pituitary, gonadal axis. As a result, GnRH therapy presents increased risk of osteopenia (decreased bone density) and cardiovascular disease. This therapy is often reserved for patients considering surgical menopause to test the outcome of the surgery. Surgical Menopause In a minority of patient who meet specific criteria and drug-based treatments are ineffective or produce significant side effects, hysterectomy and bilateral oophorectomy followed by estrogen replacement therapy is an option Typically, the uterus is removed during the same surgery, and the women is prescribed a low-dose estrogen patch to reduce the symptoms produced by surgically induced menopause. There are five guidelines that should be considered before undergoing a surgical treatment. The vast majority of women with PMDD will not require surgical treatment to experience resolution of symptoms. The diagnosis of PMDD must be confirmed GnRH agonist therapy must be the only medical therapy that has been effective and it must have been effective continuously for a minimum of six months Tolerance of estrogen replacement therapy has been tested The woman does not desire further children The womans age warrants several more years of therapy Adjunctive and Alternative Treatments Other proposed treatments include dietary modification, herbal remedies including St Johns Wort and chasteberry, acupuncture, and exercise. Some evidence suggests caffeine, sugar and alcohol intake may increase PMS symptoms. A review article claimed significant improvement of PMS symptoms with herbal treatments and acupuncture but the studies selected for review did not stratify severity of symptoms. Finally, the American College of Obstetricians and Gynecologists recommends regular aerobic exercise to reduce PMS symptoms. History In the 18th century, there were early accounts of weeping and other symptoms recurring almost every month, and in 1822 Prichard gave this description: "Many women … display a degree of excitement and irritation … at the period of menstruation; these are chiefly females of very irritable habits. In such instances, … an unusual vehemence of feeling and expression is observed … or there is torpor and dejection of mind with a despondent disposition". In 1827 a German mother was acquitted of infanticide on the grounds of menstrual mood disorder. Premenstrual tension was also described in the French literature of the early 19th century. Nearly one hundred years later, there were American descriptions of a cyclic personality change appearing 10–14 days before, and ending dramatically at the menses.The diagnostic category was discussed in the DSM-IIIR (1987), in which the proposed condition was named "Late Luteal Phase Dysphoric Disorder" and was included in the appendix as a proposed diagnostic category needing further study. Preparations for the DSM-IV led to debate about whether to keep the category at all, only keep it in the appendix, or remove it entirely; the reviewers determined that the condition was still too poorly studied and defined, so it was kept in the appendix but elaborated with diagnostic criteria to aid further study.As preparations were underway in 1998 for the DSM-IV-TR, the conversation changed, as Eli Lilly and Company paid for a large clinical trial of fluoxetine as a potential treatment for the condition that was then conducted by Canadian academics and published in the New England Journal of Medicine in 1995. Other studies have been conducted as well, wherein all found that approximately 60% of women with PMDD in the trials improved with the drug; representatives from Lilly & Co. and the FDA participated in the discussion.Various strong stances were taken in said discussion. Sally Severino, a psychiatrist, argued that because symptoms were more prevalent in the United States, PMDD was a culture-bound syndrome and not a biological condition; she also claimed it unnecessarily pathologized the hormonal changes of the menstrual cycle. Jean Endicott, another psychiatrist and chair of the committee, has argued that it was a valid condition from which women suffer and should be diagnosed and treated, and has claimed that if the symptoms were felt by males, far more effort and research would have been done by that moment. In the end the committee kept PMDD in the appendix.The decision has been criticized as being driven by Lillys financial interests, and possibly by financial interests of members of the committee who had received funding from Lilly. Paula Caplan, a psychologist who had served on the committee for the DSM-IV, noted at the time of the DSM-IV-TR decision that there was evidence that calcium supplements could treat PMDD but the committee gave it no attention. She had also claimed that the diagnostic category is harmful to women with PMDD, leading them to believe they are mentally ill, and potentially leading others to mistrust them in situations as important as job promotions or child custody cases. She has called PMDD a fake disorder. Nada Stotland has expressed concern that women with PMDD may actually have a more serious condition like major depressive disorder or may be facing difficult circumstances—such domestic abuse—and therefore may have their true issues remain undiagnosed and mismanaged if their gynecologist diagnoses them with PMDD and gives them drugs to treat it.The validity of PMDD was once more heavily debated when it came time to create the DSM-5 in 2008. In the end it was moved out of the appendix and into the main text as a formal category. A review in the Journal of Clinical Psychiatry published in 2014 examined the arguments against inclusion, which it summarized as: the PMDD label will harm women economically, politically, legally, and domestically; there is no equivalent hormone-based medical label for males; the research on PMDD is faulty; PMDD is a culture-bound condition; PMDD is due to situational, rather than biological, factors; and PMDD was fabricated by pharmaceutical companies for financial gain.Each argument was addressed and researchers found: No evidence of harm; no equivalent hormone-driven disorder has been discovered in men despite research seeking it; the research base has matured and many more reputable studies have been performed; several cases of PMDD have been reported or identified; a small minority of women do have the condition; and while there has been financial conflict of interest, it has not made the available research unusable.It concluded that women have historically been under-treated and told that they were making their symptoms up, and that the formal diagnostic criteria would spur more funding, research, diagnosis and treatment for women with PMDD. References External links Premenstrual dysphoric disorder at Curlie Bhatia SC, Bhatia SK (October 2002). "Diagnosis and treatment of premenstrual dysphoric disorder". American Family Physician. 66 (7): 1239–48. PMID 12387436. International Association for Premenstrual Disorders (IAPMD)

Do you know what is Premenstrual syndrome, Aarogya

Premenstrual syndrome

Premenstrual syndrome (PMS) refers to emotional and physical symptoms that regularly occur in the one to two weeks before the start of each menstrual period. Symptoms resolve around the time menstrual bleeding begins. Different women experience different symptoms. The common emotional symptoms include irritability and mood changes. The common physical symptoms include acne, tender breasts, bloating, and feeling tired. These are nonspecific symptoms and may be seen in women without PMS. Often PMS-related symptoms are present for about six days. An individuals pattern of symptoms may change over time. Symptoms do not occur during pregnancy or following menopause.Diagnosis requires a consistent pattern of emotional and physical symptoms occurring after ovulation and before menstruation to a degree that interferes with normal life. Emotional symptoms must not be present during the initial part of the menstrual cycle. A daily list of symptoms over a few months may help in diagnosis. Other disorders that cause similar symptoms need to be excluded before a diagnosis is made.The cause of PMS is unknown, but the underlying mechanism is believed to involve changes in hormone levels. Reducing salt, alcohol, caffeine, and stress along with increasing exercise is typically all that is recommended in those with mild symptoms. Calcium and vitamin D supplementation may be useful in some. Anti-inflammatory drugs such as ibuprofen or naproxen may help with physical symptoms. In those with more significant symptoms birth control pills or the diuretic spironolactone may be useful.Up to 80% of women report having some symptoms after ovulation and before the beginning of menstruation, but these symptoms generally do not cause substantial disruption. These symptoms qualify as PMS in approximately 20 to 30% of pre-menopausal women. Premenstrual dysphoric disorder (PMDD) is a more severe form of PMS that has greater psychological symptoms. PMDD affects 3 to 8% of pre-menopausal individuals. Antidepressant medication of the selective serotonin reuptake inhibitors class may be used for PMDD in addition to the usual measures for PMS. Signs and symptoms More than 200 different symptoms have been associated with PMS. Common emotional and non-specific symptoms include stress, anxiety, difficulty with sleep, headache, feeling tired, mood swings, increased emotional sensitivity, and changes in interest in sex. Problems with concentration and memory may occur. There may also be depression or anxiety.Physical symptoms associated with the menstrual cycle – but not necessarily with PMS, which is symptoms that appear before menstruation, rather than during menstruation – include bloating, lower back pain, cramps in the pelvic area, constipation/diarrhea, swelling or tenderness in the breasts, cyclic acne (acne that appears and disappears at predictable times during the menstrual cycle), joint or muscle pain, and food cravings. The exact symptoms and their intensity vary significantly from person to person, and even somewhat from cycle to cycle and over time. Most people with premenstrual syndrome experience only a few of the possible symptoms, in a relatively predictable pattern.Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome affecting 3–8% of menstruating women. Causes While PMS is linked to the luteal phase, the causes of PMS are not clear, but several factors may be involved. Changes in hormones during the menstrual cycle seem to be an important factor, with changing hormone levels affecting some more than others. PMS occurs more often in those who are in their late 20s and early 40s, have at least one child, have a family history of depression, and have a past medical history of either postpartum depression or a mood disorder. Diagnosis There are no laboratory tests or unique physical findings to verify the diagnosis of PMS. The three key features are: The chief complaint is one or more of the emotional symptoms associated with PMS. Irritability, tension, or unhappiness are typical emotional symptoms. Symptoms appear predictably during the luteal (premenstrual) phase, reduce or disappear predictably shortly before or during menstruation, and remain absent during the follicular (preovulatory) phase. The symptoms must be severe enough to interfere with the person’s everyday life.Mild PMS is common, and more severe symptoms would qualify as PMDD. PMS is not listed in the DSM-IV, unlike PMDD. To document a pattern and determine if it is PMDD, potentially affected women may keep a prospective record of their symptoms on a calendar for at least two menstrual cycles. This will help to establish if the symptoms are, indeed, limited to the premenstrual time, predictably recurring, and disruptive to normal functioning. A number of standardized instruments have been developed to describe PMS, including the Calendar of Premenstrual syndrome Experiences (COPE), the Prospective Record of the Impact and Severity of Menstruation (PRISM), and the Visual Analogue Scales (VAS).Other conditions that may better explain symptoms must be excluded. A number of medical conditions are subject to exacerbation at menstruation, a process called menstrual magnification. These conditions may lead women who do not have PMS to incorrectly believe that they have PMS, when the underlying disorder is some other medical problem, such as anemia, hypothyroidism, eating disorders and substance abuse. A key feature is that these conditions may also be present outside of the luteal phase. Conditions that can be magnified perimenstrually include depression or other affective disorders, migraine, seizure disorders, fatigue, irritable bowel syndrome, asthma, and allergies. Problems with other aspects of the female reproductive system must be excluded, including dysmenorrhea (pain during the menstrual period, rather than before it), endometriosis, perimenopause, and adverse effects produced by oral contraceptive pills.The National Institute of Mental Health research definition compares the intensity of symptoms from cycle days 5 to 10 to the six-day interval before the onset of the menstrual period. To qualify as PMS, symptom intensity must increase at least 30% in the six days before menstruation. Additionally, this pattern must be documented for at least two consecutive cycles. Management Many treatments have been tried in PMS. Reducing salt, caffeine, and stress along with increasing exercise is typically all that is recommended in those with mild symptoms. Calcium and vitamin D supplementation may be useful in some. Anti-inflammatories such as naproxen may help with physical symptoms. A healthy diet, reduced consumption of salt, caffeine and alcohol, and regular exercise may be effective for women in controlling water retention. In those with more significant symptoms birth control pills may be useful.Diuretics have been used to handle water retention. Spironolactone has been shown in some studies to be useful. Antidepressants SSRIs like fluoxetine, sertraline can be used to treat severe PMS. Those with PMS may be able to take medication only on the days when symptoms are expected to occur. Although intermittent therapy might be more acceptable to some, this might be less effective than continuous regimens. Side effect such as nausea and weakness are however relatively common. Hormonal medications Hormonal contraception is commonly used; common forms include the combined oral contraceptive pill and the contraceptive patch. This class of medication may cause PMS-related symptoms in some and may reduce physical symptoms in others. They do not relieve emotional symptoms.Progesterone support has been used for many years but evidence of its efficacy is inadequate.Gonadotropin-releasing hormone agonists can be useful in severe forms of PMS but have their own set of significant potential side effects. Alternative medicine Tentative evidence supports vitamin B6 and chasteberry. Data are insufficient to determine an effect of St. Johns wort, soy, vitamin E, and saffron. Evening primrose oil may be useful.There is tentative evidence that acupressure and acupuncture may help to reduce PMS symptoms and improve women quality of life. Prognosis PMS is generally a stable diagnosis, with susceptible individuals experiencing the same symptoms at the same intensity near the end of each cycle for years. Treatment for specific symptoms is usually effective. Even without treatment, symptoms tend to decrease in perimenopausal women. However, those who experience PMS or PMDD are more likely to have significant symptoms associated with menopause, such as hot flashes. Epidemiology PMS, in which mild to moderate symptoms affect some facet of the persons life, occurs in about 20 to 30% of premenopausal women; the more severe symptoms of PMDD affect 3 to 8% of premenopausal women.Among females of reproductive age living in India, the prevalence of PMS is 43%; the prevalence among adolescents is even higher. History PMS was originally seen as an imagined disease. Women who reported its symptoms were often told it was "all in their head". Womans reproductive organs were thought to have complete control over them. Women were warned not to divert needed energy away from the uterus and ovaries. This view of limited energy very quickly ran up against a reality in 19th century America that young girls worked extremely long and hard hours in factories; newspapers in the 19th century were peppered with remedies to help in the "tyrannous processes" of the menstrual cycle. In 1873 Edward Clarke published an influential book titled Sex in Education. Clarke came to the conclusion that female operatives suffer less than schoolgirls because they "work their brain less". This suggested that they have stronger bodies and a reproductive "apparatus more normally constructed". Feminists later took opposition to Clarkes argument that women should not leave the private sphere by showing that women could function in the world outside the home in spite of natural body functions.The formal medical description of premenstrual syndrome (PMS) and the more severe, related diagnosis of premenstrual dysphoric disorder (PMDD) goes back at least 70 years to a paper presented at the New York Academy of Medicine by Robert T. Frank titled "Hormonal Causes of Premenstrual Tension". The specific term premenstrual syndrome appears to date from an article published in 1953 by Dalton and Greene in the British Medical Journal. Since then, PMS has been a continuous presence in popular culture, occupying a place that is larger than the research attention accorded it as a medical diagnosis. Some have argued that women are partially responsible for the medicalization of PMS. They claim that women are partially responsible for legitimizing this disorder and have thus contributed to the social construction of PMS as an illness. It has also been suggested that the public debate over PMS and PMDD was impacted by organizations who had a stake in the outcome including feminists, the American Psychiatric Association, physicians and scientists. Until the 1950s, there was little research done surrounding PMS and it was not seen as a social problem. By the 1980s, however, viewing PMS in a social context had begun to take place. Alternative views Some supporters of PMS as a social construct believe PMDD and PMS to be unrelated issues: according to them, PMDD is a product of brain chemistry, and PMS is a product of a hypochondriatic culture, i.e. a culture-bound syndrome. Most studies on PMS and PMDD rely solely on self-reporting. According to sociologist Carol Tavris, Western women are socially conditioned to expect PMS or to at least know of its existence, and they, therefore, report their symptoms accordingly. The anthropologist Emily Martin argues that PMS is a cultural phenomenon that continues to grow in a positive feedback loop, and thus is a social construction that contributes to learned helplessness or convenient excuse. Tavris says that PMS is blamed as an explanation for rage or sadness. The decision to call PMDD an illness has been criticized as inappropriate medicalization. In both cases, they are referring to the emotional aspects, not the normal physical symptoms that are present. See also Menstrual leave References External links U.S. Department of Health & Human Services Direct Online Health Encyclopaedia: Premenstrual syndrome (UK) at NHS "Premenstrual Syndrome (PMS) (Premenstrual Tension)" at Merck Manual

Could you describe Primary biliary cholangitis, to me Aarogya

Primary biliary cholangitis

Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver, a condition called cholestasis. Further slow damage to the liver tissue can lead to scarring, fibrosis, and eventually cirrhosis. Common symptoms are tiredness, itching, and in more advanced cases, jaundice. In early cases, the only changes may be those seen in blood tests.PBC is a relatively rare disease, affecting up to one in 3,000–4,000 people. It is much more common in women, with a sex ratio of at least 9:1 female to male.The condition has been recognised since at least 1851, and was named "primary biliary cirrhosis" in 1949. Because cirrhosis is a feature only of advanced disease, a change of its name to "primary biliary cholangitis" was proposed by patient advocacy groups in 2014. Signs and symptoms People with PBC experience fatigue (80%); this is a nonspecific symptom and can be debilitating, with a huge impact on quality of life. Its pathogenesis is still unknown, and is quite challenging to explore its specificity and to treat. Comorbidities that could contribute or worsen fatigue, such as depression, hypothyroidism, anaemia, obesity, or medication side effects, should be promptly identified and treated. Dry skin and dry eyes are also common. Itching (pruritus) occurs in 20–70% of cases, and can develop at any stage of the disease; it does not correlate with progression of liver disease, and may even improve or disappear as the disease advances. It is typically mild-to-moderate in intensity. Given the impact on quality of life and night sleep, pruritus is correlated with fatigue. It can rarely be severe, nonresponsive to medical therapy, and requiring liver transplant. Pruritus is characteristically intermittent, worse at night, and improves during summer. People with more severe PBC may have jaundice (yellowing of the eyes and skin). PBC impairs bone density and the risk of fracture increases. Xanthelasma (skin lesions around the eyes) or other xanthoma may be present as a result of increased cholesterol levels.PBC can eventually progress to cirrhosis of the liver. This, in turn, may lead to a number of symptoms or complications, including: Fluid retention in the abdomen (ascites) in more advanced disease Enlarged spleen in more advanced disease Oesophageal varices in more advanced disease Hepatic encephalopathy, including coma in extreme cases in more advanced disease.People with PBC may also sometimes have the findings of an associated extrahepatic autoimmune disorder such as thyroid disease or rheumatoid arthritis or Sjögrens syndrome (in up to 80% of cases). Causes PBC has an immunological basis, and is classified as an autoimmune disorder. It results from a slow, progressive destruction of the small bile ducts of the liver, with the intralobular ducts and the canals of Hering (intrahepatic ductules) being affected early in the disease. Most people with PBC (more than 90%) have antimitochondrial antibodies (AMAs) against pyruvate dehydrogenase complex (PDC-E2), an enzyme complex found in the mitochondria. People who are negative for AMAs are usually found to be positive when more sensitive methods of detection are used.People with PBC may also have been diagnosed with another autoimmune disease, such as a rheumatological, endocrinological, gastrointestinal, pulmonary, or dermatological condition, suggesting shared genetic and immune abnormalities. Common associations include Sjögrens syndrome, systemic sclerosis, rheumatoid arthritis, lupus, hypothyroidism, and coeliac disease.A genetic predisposition to disease has been thought to be important for some time. Evidence for this includes cases of PBC in family members, identical twins both having the condition (concordance), and clustering of PBC with other autoimmune diseases. In 2009, a Canadian-led group of investigators reported in the New England Journal of Medicine results from the first PBC genome-wide association study. This research revealed parts of the IL12 signaling cascade, particularly IL12A and IL12RB2 polymorphisms, to be important in the aetiology of the disease in addition to the HLA region. In 2012, two independent PBC association studies increased the total number of genomic regions associated to 26, implicating many genes involved in cytokine regulation such as TYK2, SH2B3 and TNFSF11.A study of over 2,000 patients identified a gene, POGLUT1, that appeared to be associated with this condition. Earlier studies have also suggested that this gene may be involved. The implicated protein is an endoplasmic reticulum O-glucosyltransferase. An environmental Gram-negative Alphaproteobacterium — Novosphingobium aromaticivorans has been associated with this disease, with several reports suggesting an aetiological role for this organism. The mechanism appears to be a cross-reaction between the proteins of the bacterium and the mitochondrial proteins of the liver cells. The gene encoding CD101 may also play a role in host susceptibility to this disease.A failure of immune tolerance against the mitochondrial pyruvate dehydrogenase complex (PDC-E2) is a primary cause, with shedding of the antigen into apoptotic bodies or "apotopes" leading to the anatomic localization. Such autoreactivity may also be the case with other proteins, including the gp210 and p62 nuclear pore proteins. Gp210 has increased expression in the bile duct of anti-gp210 positive patients, and these proteins may be associated with prognosis. Diagnosis Most patients are currently diagnosed when asymptomatic, having been referred to the hepatologist for abnormal liver function tests (mostly raised GGT or alkaline phosphatase) performed for annual screening blood tests. Other frequent scenarios include screening of patients with nonliver autoimmune diseases, e.g. rheumatoid arthritis, or investigation of elevated cholesterol, evaluation of itch or unresolved cholestasis post partum. Diagnosing PBC is generally straightforward. The basis for a definite diagnosis are: Abnormalities in liver enzyme tests are usually present and elevated gamma-glutamyl transferase and alkaline phosphatase are found in early disease. Elevations in bilirubin occur in advanced disease. Antimitochondrial antibodies are the characteristic serological marker for PBC, being found in 90–95% of patients and only 1% of controls. PBC patients have AMA against pyruvate dehydrogenase complex (PDC-E2), an enzyme complex that is found in the mitochondria. Those people who are AMA negative but with disease similar to PBC have been found to have AMAs when more sensitive detection methods are employed. Other auto-antibodies may be present:Antinuclear antibody measurements are not diagnostic for PBC because they are not specific, but may have a role in prognosis. Anti-glycoprotein-210 antibodies, and to a lesser degree anti-p62 antibodies, correlate with the diseases progression toward end-stage liver failure. Anti-gp210 antibodies are found in 47% of PBC patients. Anti-centromere antibodies often correlate with developing portal hypertension. Anti-np62 and anti-sp100 are also found in association with PBC.Abdominal ultrasound, magnetic resonance cholangiopancreatography or a CT scan is usually performed to rule out blockage to the bile ducts. This may be needed if a condition causing secondary biliary cirrhosis, such as other biliary duct disease or gallstones, needs to be excluded. A liver biopsy may help, and if uncertainty remains as in some patients, an endoscopic retrograde cholangiopancreatography, an endoscopic investigation of the bile duct, may be performed.Given the high specificity of serological markers, liver biopsy is not necessary for the diagnosis of PBC; however, it is still necessary when PBC-specific antibodies are absent, or when co-existent autoimmune hepatitis or nonalcoholic steatohepatitis is suspected. Liver biopsy can be useful to stage the disease for fibrosis and ductopenia. Finally, it may also be appropriate in the presence of other extrahepatic comorbidities. Liver biopsy On microscopic examination of liver biopsy specimens, PBC is characterized by chronic, nonsuppurative inflammation, which surrounds and destroys interlobular and septal bile ducts. These histopathologic findings in primary biliary cholangitis include: Inflammation of the bile ducts, characterized by intraepithelial lymphocytes Periductal epithelioid granulomas. Proliferation of bile ductules Fibrosis (scarring)The Ludwig and Scheuer scoring systems have historically been used to stratify four stages of PBC, with stage 4 indicating the presence of cirrhosis. In the new system of Nakanuma, the stage of disease is based on fibrosis, bile duct loss, and features of cholestasis, i.e. deposition of orcein-positive granules, whereas the grade of necroinflammatory activity is based on cholangitis and interface hepatitis. The accumulation of orcein-positive granules occurs evenly across the PBC liver, which means that staging using the Nakanuma system is more reliable regarding sampling variability. Liver biopsy for the diagnosis and staging of PBC lost favour after the evidence of a patchy distribution of the duct lesions and fibrosis across the organ. The widespread availability of noninvasive measures of fibrosis means that liver biopsy for staging of PBC is somewhat obsolete. Liver biopsy does, however, remain useful in certain settings. The main indications are to confirm the diagnosis of PBC when PBC-specific antibodies are absent and confirm a diagnosis of PBC with AIH features (i.e. overlap PBC-AIH). Liver biopsy is also useful to assess the relative contribution of each liver injury when a comorbid liver disease is present, such as non-alcoholic steatohepatitis. In patients with inadequate response to UDCA, liver biopsy may provide the explanation and could undoubtedly inform risk stratification. For example, it may identify a previously unsuspected variant syndrome, steatohepatitis, or interface hepatitis of moderate or greater severity. It is also useful in AMA and ANA-specific antibody negative cholestatic patients to indicate an alternative process, e.g. sarcoidosis, small duct PSC, adult idiopathic ductopenia. Histopathology stages (by Ludwig and Scheuer systems) Stage 1 – portal stage: Normal-sized triads, portal inflammation, subtle bile duct damage: Granulomas are often detected in this stage. Stage 2 – periportal stage: Enlarged triads, periportal fibrosis and/or inflammation, typically characterized by the finding of a proliferation of small bile ducts Stage 3 – septal stage: Active and/or passive fibrous septa Stage 4 – biliary cirrhosis: Nodules present, garland or jigsaw puzzle pattern Treatment Cholestasis Medical therapy of PBC targets disease progression and symptom control. The first-line treatment for PBC is ursodeoxycholic acid (UDCA). UDCA has been the only drug available for two decades and more recently obeticholic acid (OCA), a semi-synthetic hydrophobic bile acid analogue, has been licensed in patients failing UDCA response or intolerant to UDCA. Several other agents have been studied, including immunosuppressants, but robust evidence of benefit is lacking.UDCA improves liver enzyme levels, slows down histological progression, and improves liver transplant-free survival. UDCA also reduces the need for liver transplantation. UDCA should be taken at a dose of 13 to 15 mg per kg of body weight per day, usually in two divided doses each day. Liver chemistries usually improve within a few weeks of starting UDCA, and 90% of any benefit is observed after 6–9 months of therapy. Liver chemistries should be re-evaluated after 1 year of treatment. UDCA is usually continued lifelong. Up to 40% of people do not respond to treatment with UDCA. Patients with PBC who have an inadequate response to UDCA or those few (less than 3%) who are intolerant to UDCA are candidates for second-line therapies. Obeticholic acid (OCA) is FDA-approved for the treatment of PBC in individuals intolerant or unresponsive to UDCA. OCA is a farnesoid X receptor agonist, and results in increased bile flow (choleresis). OCA is started at 5 mg daily, and liver chemistries should be rechecked after 3 months of treatment. If the liver chemistries remain elevated, then the dose of OCA may be increased to 10 mg per day. The most common side effect of OCA is pruritus. Fibric acid derivatives, or fibrates, are agonists of the peroxisome proliferator activator receptor (PPAR), a nuclear receptor involved in several metabolic pathways. While fibrates are approved for the treatment of hypertriglyceridemia, they exert anticholestatic effects and have been studied for the treatment of PBC. Among the fibrates, bezafibrate and fenofibrate, PPAR-alpha selective agonists, have been extensively studied as therapeutic agents because of their potential ability to decrease bile acid synthesis and bile acid-related hepatic inflammation. A randomized, controlled trial in 2018 showed its efficacy in patients with inadequate response to UDCA. While fibrates can be considered as off-label treatment for PBC that does not respond to UDCA, they should not be used in decompensated cirrhosis.Several additional medications have been investigated as potential treatments for PBC, and found to be ineffective as single agents (monotherapy), including: chlorambucil, colchicine, cyclosporine, corticosteroids, azathioprine, malotilate, methotrexate, mycophenolate mofetil, penicillamine, and thalidomide. Budesonide may be used as an off-label treatment for PBC, although its efficacy is controversial. Itching Pruritus is a common symptom in people with PBC. First-line treatment of pruritus consists of anion-exchange resins, such as cholestyramine, colestipol, or colesevalam. These anion-exchange resins are nonabsorbed, highly positively charged substances that bind bile acids, which are negatively charged anions. Anion-exchange resins relieve itching caused by excess bile acids in circulation by binding bile acids in the gut and facilitating elimination. Bloating or constipation may occur with anion-exchange resins. Cholestyramine may affect absorption of UDCA; if cholestyramine is necessary, it should be taken at least 60 minutes before or 4 hours after UDCA is taken.Treatment options for pruritus that does not improve with anion-exchange resins include: rifampicin, naltrexone, or sertraline. Rifampicin may rarely cause drug induced liver injury and should be avoided if serum bilirubin is elevated (greater than 2.5 mg/dL). Liver enzymes should be monitored after starting rifampin. Rifampicin induces enzymes, resulting in numerous potential drug-drug interactions. Opioid antagonists may cause a self-limited opioid withdrawal like reaction, with abdominal pain, elevated blood pressure, tachycardia, goose bumps, nightmares, and depersonalization. To avoid such reactions, the dose should start low and gradually be increased. Other therapies Fatigue is a nonspecific but often-reported symptom in PBC, and represents an unmet need since no therapies are licensed. A structured approach to management, quantifying fatigue and its impacts (through the use of disease-specific tools such as the PBC-40 quality-of-life measures), addressing contributing and exacerbating factors, and supporting patients to cope with its impact is effective. Drugs such as coenzyme Q and rituximab have been shown to be ineffective. A graded programme of exercise helps some individuals. People with PBC may have poor lipid-dependent absorption of oil-soluble vitamins (A, D, E, and K). Appropriate supplementation is recommended when bilirubin is elevated. People with PBC are at elevated risk of developing osteoporosis as compared to the general population and others with liver disease. Screening and treatment of this complication is an important part of the management of PBC. As in all liver diseases, consumption of alcohol should be restricted or eliminated. In patients with advanced liver disease, the only curative therapy is liver transplant. Outcomes are favourable, with five-year patient survival rates better than for most other indications for LT (80–85%). Prognosis The introduction of UDCA has dramatically changed the pattern and the course of the disease. Numerous trials and observational studies have demonstrated its efficacy on liver biochemistry, histological progression, and transplant-free survival.Among the UDCA-treated patients, the degree of the liver biochemistry improvement, i.e. the UDCA-response, identifies patients with different long-term prognosis. In the absence of cirrhosis, people who experience an improvement of liver enzymes to the normal range on treatment with UDCA have excellent survival, which may be similar to the general population. Survival is significantly reduced though, in those with abnormal liver biochemistry on treatment. The two most important parameters in evaluating response to UDCA are alkaline phosphatase and total bilirubin. Qualitative and quantitative definitions of UDCA-response have been developed, based on changes of bilirubin, transaminases and ALP, after a period of 6 to 24 months of treatment with UDCA at 13–15 mg/kg/day.Patients at diagnosis can be risk-stratified based on the probability of UDCA-response. This is relevant to identify patients who would be eligible for second-line therapies before waiting for the treatment failure under UDCA, with potential impact on disease course.Hepatocellular carcinoma (HCC) is infrequent in PBC. Recent large-scale cohort studies highlighted that the lack of UDCA-response after 12 months of therapy and male sex are associated with increased future risk of developing HCC in PBC. After liver transplant, the recurrence of disease may be as high as 18% at five years, and up to 30% at 10 years. No consensus exists on risk factors for recurrence of the disease. Epidemiology Epidemiologic studies report heterogeneous incidence rates of 0.33 to 5.8 per 100,000 inhabitants per year, and prevalence rates of 1.9 to 40.2 per 100,000 inhabitants. Such figures, in particular the prevalence, have shown some increase in the last decades. Improvement of diagnostic tools, increasing disease awareness, and digitised patient registration with facilitation of case-findings, along with improved survival, likely contributed to the rising prevalence rates. The disease has been described worldwide, though North America and Northern Europe have shown the highest incidence and prevalence rates. Whether a true variation in disease prevalence exists among populations of different geographical areas and of different ethnicity or if this is a consequence of a difference in study quality is unknown. PBC is more common in women, with a female:male ratio of at least 9:1. The peak incidence of PBC is in the fifth decade of life. In some areas of the US and UK, the prevalence is estimated to be as high as one in 4,000. This is much more common than in South America or Africa, which may be due to better recognition in the US and UK. First-degree relatives may have as much as a 500 times increase in prevalence, but if this risk is greater in the same-generation relatives or the one that follows is debated. PBC is considered a prime example of the female preponderance in autoimmunity with a female to male ratio of up to 9:1, confirmed by large cohort studies, although some recent data, using administrative registries, suggest an increasing male prevalence. Major defects of sex chromosomes, i.e. enhanced monosomy X in female patients and an enhanced Y chromosome loss in male patients, have been described and might well explain the greater female predisposition to develop PBC.An association of a greater incidence of PBC at latitudes more distant from the Equator is similar to the pattern seen in multiple sclerosis.Typical disease onset is between 30 and 60 years, though cases have been reported of patients diagnosed at the ages of 15 and 93. Prevalence of PBC in women over the age of 45 years could exceed one in an estimated 800 individuals. History The first report of the disease dates back 1851 by Addison and Gull, who described a clinical picture of progressive jaundice in the absence of mechanical obstruction of the large bile ducts. Ahrens et al. in 1950 published the first detailed description of 17 patients with this condition, and coined the term "primary biliary cirrhosis". In 1959, Dame Sheila Sherlock reported a further series of PBC patients and recognised that the disease could be diagnosed in a precirrhotic stage and proposed the term "chronic intrahepatic cholestasis" as more appropriate description of this disease, but this nomenclature failed to gain acceptance, and the term "primary biliary cirrhosis" lasted for decades. In 2014, to correct the inaccuracy and remove the social stigmata of cirrhosis, as well as all the misunderstanding, disadvantages, and discrimination emanating from this misnomer in daily life for patients, international liver associations agreed to rename the disease "primary biliary cholangitis", as it is now known. Society and culture Support groups PBC Foundation The PBC Foundation is a UK-based international charity offering support and information to people with PBC and their families and friends. It campaigns for increasing recognition of the disorder, improved diagnosis, and treatments, and estimates over 8,000 people are undiagnosed in the UK. The Foundation has supported research into PBC including the development of the PBC-40 quality of life measure published in 2004 and helped establish the PBC Genetics Study. It was founded by Collette Thain in 1996, after she was diagnosed with the condition. Thain was awarded an MBE Order of the British Empire in 2004 for her work with the Foundation. The PBC Foundation helped initiate the name change campaign in 2014. PBCers Organization The PBCers Organization is a US-based nonprofit patient support group that was founded by Linie Moore in 1996; it advocates for greater awareness of the disease and new treatments. It supported the name change initiative. References External links Primary Biliary Cirrhosis page from the National Digestive Diseases Information Clearinghouse Alagille syndrome

Aarogya, elaborate on Primary biliary cholangitis

Primary biliary cholangitis

Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver, a condition called cholestasis. Further slow damage to the liver tissue can lead to scarring, fibrosis, and eventually cirrhosis. Common symptoms are tiredness, itching, and in more advanced cases, jaundice. In early cases, the only changes may be those seen in blood tests.PBC is a relatively rare disease, affecting up to one in 3,000–4,000 people. It is much more common in women, with a sex ratio of at least 9:1 female to male.The condition has been recognised since at least 1851, and was named "primary biliary cirrhosis" in 1949. Because cirrhosis is a feature only of advanced disease, a change of its name to "primary biliary cholangitis" was proposed by patient advocacy groups in 2014. Signs and symptoms People with PBC experience fatigue (80%); this is a nonspecific symptom and can be debilitating, with a huge impact on quality of life. Its pathogenesis is still unknown, and is quite challenging to explore its specificity and to treat. Comorbidities that could contribute or worsen fatigue, such as depression, hypothyroidism, anaemia, obesity, or medication side effects, should be promptly identified and treated. Dry skin and dry eyes are also common. Itching (pruritus) occurs in 20–70% of cases, and can develop at any stage of the disease; it does not correlate with progression of liver disease, and may even improve or disappear as the disease advances. It is typically mild-to-moderate in intensity. Given the impact on quality of life and night sleep, pruritus is correlated with fatigue. It can rarely be severe, nonresponsive to medical therapy, and requiring liver transplant. Pruritus is characteristically intermittent, worse at night, and improves during summer. People with more severe PBC may have jaundice (yellowing of the eyes and skin). PBC impairs bone density and the risk of fracture increases. Xanthelasma (skin lesions around the eyes) or other xanthoma may be present as a result of increased cholesterol levels.PBC can eventually progress to cirrhosis of the liver. This, in turn, may lead to a number of symptoms or complications, including: Fluid retention in the abdomen (ascites) in more advanced disease Enlarged spleen in more advanced disease Oesophageal varices in more advanced disease Hepatic encephalopathy, including coma in extreme cases in more advanced disease.People with PBC may also sometimes have the findings of an associated extrahepatic autoimmune disorder such as thyroid disease or rheumatoid arthritis or Sjögrens syndrome (in up to 80% of cases). Causes PBC has an immunological basis, and is classified as an autoimmune disorder. It results from a slow, progressive destruction of the small bile ducts of the liver, with the intralobular ducts and the canals of Hering (intrahepatic ductules) being affected early in the disease. Most people with PBC (more than 90%) have antimitochondrial antibodies (AMAs) against pyruvate dehydrogenase complex (PDC-E2), an enzyme complex found in the mitochondria. People who are negative for AMAs are usually found to be positive when more sensitive methods of detection are used.People with PBC may also have been diagnosed with another autoimmune disease, such as a rheumatological, endocrinological, gastrointestinal, pulmonary, or dermatological condition, suggesting shared genetic and immune abnormalities. Common associations include Sjögrens syndrome, systemic sclerosis, rheumatoid arthritis, lupus, hypothyroidism, and coeliac disease.A genetic predisposition to disease has been thought to be important for some time. Evidence for this includes cases of PBC in family members, identical twins both having the condition (concordance), and clustering of PBC with other autoimmune diseases. In 2009, a Canadian-led group of investigators reported in the New England Journal of Medicine results from the first PBC genome-wide association study. This research revealed parts of the IL12 signaling cascade, particularly IL12A and IL12RB2 polymorphisms, to be important in the aetiology of the disease in addition to the HLA region. In 2012, two independent PBC association studies increased the total number of genomic regions associated to 26, implicating many genes involved in cytokine regulation such as TYK2, SH2B3 and TNFSF11.A study of over 2,000 patients identified a gene, POGLUT1, that appeared to be associated with this condition. Earlier studies have also suggested that this gene may be involved. The implicated protein is an endoplasmic reticulum O-glucosyltransferase. An environmental Gram-negative Alphaproteobacterium — Novosphingobium aromaticivorans has been associated with this disease, with several reports suggesting an aetiological role for this organism. The mechanism appears to be a cross-reaction between the proteins of the bacterium and the mitochondrial proteins of the liver cells. The gene encoding CD101 may also play a role in host susceptibility to this disease.A failure of immune tolerance against the mitochondrial pyruvate dehydrogenase complex (PDC-E2) is a primary cause, with shedding of the antigen into apoptotic bodies or "apotopes" leading to the anatomic localization. Such autoreactivity may also be the case with other proteins, including the gp210 and p62 nuclear pore proteins. Gp210 has increased expression in the bile duct of anti-gp210 positive patients, and these proteins may be associated with prognosis. Diagnosis Most patients are currently diagnosed when asymptomatic, having been referred to the hepatologist for abnormal liver function tests (mostly raised GGT or alkaline phosphatase) performed for annual screening blood tests. Other frequent scenarios include screening of patients with nonliver autoimmune diseases, e.g. rheumatoid arthritis, or investigation of elevated cholesterol, evaluation of itch or unresolved cholestasis post partum. Diagnosing PBC is generally straightforward. The basis for a definite diagnosis are: Abnormalities in liver enzyme tests are usually present and elevated gamma-glutamyl transferase and alkaline phosphatase are found in early disease. Elevations in bilirubin occur in advanced disease. Antimitochondrial antibodies are the characteristic serological marker for PBC, being found in 90–95% of patients and only 1% of controls. PBC patients have AMA against pyruvate dehydrogenase complex (PDC-E2), an enzyme complex that is found in the mitochondria. Those people who are AMA negative but with disease similar to PBC have been found to have AMAs when more sensitive detection methods are employed. Other auto-antibodies may be present:Antinuclear antibody measurements are not diagnostic for PBC because they are not specific, but may have a role in prognosis. Anti-glycoprotein-210 antibodies, and to a lesser degree anti-p62 antibodies, correlate with the diseases progression toward end-stage liver failure. Anti-gp210 antibodies are found in 47% of PBC patients. Anti-centromere antibodies often correlate with developing portal hypertension. Anti-np62 and anti-sp100 are also found in association with PBC.Abdominal ultrasound, magnetic resonance cholangiopancreatography or a CT scan is usually performed to rule out blockage to the bile ducts. This may be needed if a condition causing secondary biliary cirrhosis, such as other biliary duct disease or gallstones, needs to be excluded. A liver biopsy may help, and if uncertainty remains as in some patients, an endoscopic retrograde cholangiopancreatography, an endoscopic investigation of the bile duct, may be performed.Given the high specificity of serological markers, liver biopsy is not necessary for the diagnosis of PBC; however, it is still necessary when PBC-specific antibodies are absent, or when co-existent autoimmune hepatitis or nonalcoholic steatohepatitis is suspected. Liver biopsy can be useful to stage the disease for fibrosis and ductopenia. Finally, it may also be appropriate in the presence of other extrahepatic comorbidities. Liver biopsy On microscopic examination of liver biopsy specimens, PBC is characterized by chronic, nonsuppurative inflammation, which surrounds and destroys interlobular and septal bile ducts. These histopathologic findings in primary biliary cholangitis include: Inflammation of the bile ducts, characterized by intraepithelial lymphocytes Periductal epithelioid granulomas. Proliferation of bile ductules Fibrosis (scarring)The Ludwig and Scheuer scoring systems have historically been used to stratify four stages of PBC, with stage 4 indicating the presence of cirrhosis. In the new system of Nakanuma, the stage of disease is based on fibrosis, bile duct loss, and features of cholestasis, i.e. deposition of orcein-positive granules, whereas the grade of necroinflammatory activity is based on cholangitis and interface hepatitis. The accumulation of orcein-positive granules occurs evenly across the PBC liver, which means that staging using the Nakanuma system is more reliable regarding sampling variability. Liver biopsy for the diagnosis and staging of PBC lost favour after the evidence of a patchy distribution of the duct lesions and fibrosis across the organ. The widespread availability of noninvasive measures of fibrosis means that liver biopsy for staging of PBC is somewhat obsolete. Liver biopsy does, however, remain useful in certain settings. The main indications are to confirm the diagnosis of PBC when PBC-specific antibodies are absent and confirm a diagnosis of PBC with AIH features (i.e. overlap PBC-AIH). Liver biopsy is also useful to assess the relative contribution of each liver injury when a comorbid liver disease is present, such as non-alcoholic steatohepatitis. In patients with inadequate response to UDCA, liver biopsy may provide the explanation and could undoubtedly inform risk stratification. For example, it may identify a previously unsuspected variant syndrome, steatohepatitis, or interface hepatitis of moderate or greater severity. It is also useful in AMA and ANA-specific antibody negative cholestatic patients to indicate an alternative process, e.g. sarcoidosis, small duct PSC, adult idiopathic ductopenia. Histopathology stages (by Ludwig and Scheuer systems) Stage 1 – portal stage: Normal-sized triads, portal inflammation, subtle bile duct damage: Granulomas are often detected in this stage. Stage 2 – periportal stage: Enlarged triads, periportal fibrosis and/or inflammation, typically characterized by the finding of a proliferation of small bile ducts Stage 3 – septal stage: Active and/or passive fibrous septa Stage 4 – biliary cirrhosis: Nodules present, garland or jigsaw puzzle pattern Treatment Cholestasis Medical therapy of PBC targets disease progression and symptom control. The first-line treatment for PBC is ursodeoxycholic acid (UDCA). UDCA has been the only drug available for two decades and more recently obeticholic acid (OCA), a semi-synthetic hydrophobic bile acid analogue, has been licensed in patients failing UDCA response or intolerant to UDCA. Several other agents have been studied, including immunosuppressants, but robust evidence of benefit is lacking.UDCA improves liver enzyme levels, slows down histological progression, and improves liver transplant-free survival. UDCA also reduces the need for liver transplantation. UDCA should be taken at a dose of 13 to 15 mg per kg of body weight per day, usually in two divided doses each day. Liver chemistries usually improve within a few weeks of starting UDCA, and 90% of any benefit is observed after 6–9 months of therapy. Liver chemistries should be re-evaluated after 1 year of treatment. UDCA is usually continued lifelong. Up to 40% of people do not respond to treatment with UDCA. Patients with PBC who have an inadequate response to UDCA or those few (less than 3%) who are intolerant to UDCA are candidates for second-line therapies. Obeticholic acid (OCA) is FDA-approved for the treatment of PBC in individuals intolerant or unresponsive to UDCA. OCA is a farnesoid X receptor agonist, and results in increased bile flow (choleresis). OCA is started at 5 mg daily, and liver chemistries should be rechecked after 3 months of treatment. If the liver chemistries remain elevated, then the dose of OCA may be increased to 10 mg per day. The most common side effect of OCA is pruritus. Fibric acid derivatives, or fibrates, are agonists of the peroxisome proliferator activator receptor (PPAR), a nuclear receptor involved in several metabolic pathways. While fibrates are approved for the treatment of hypertriglyceridemia, they exert anticholestatic effects and have been studied for the treatment of PBC. Among the fibrates, bezafibrate and fenofibrate, PPAR-alpha selective agonists, have been extensively studied as therapeutic agents because of their potential ability to decrease bile acid synthesis and bile acid-related hepatic inflammation. A randomized, controlled trial in 2018 showed its efficacy in patients with inadequate response to UDCA. While fibrates can be considered as off-label treatment for PBC that does not respond to UDCA, they should not be used in decompensated cirrhosis.Several additional medications have been investigated as potential treatments for PBC, and found to be ineffective as single agents (monotherapy), including: chlorambucil, colchicine, cyclosporine, corticosteroids, azathioprine, malotilate, methotrexate, mycophenolate mofetil, penicillamine, and thalidomide. Budesonide may be used as an off-label treatment for PBC, although its efficacy is controversial. Itching Pruritus is a common symptom in people with PBC. First-line treatment of pruritus consists of anion-exchange resins, such as cholestyramine, colestipol, or colesevalam. These anion-exchange resins are nonabsorbed, highly positively charged substances that bind bile acids, which are negatively charged anions. Anion-exchange resins relieve itching caused by excess bile acids in circulation by binding bile acids in the gut and facilitating elimination. Bloating or constipation may occur with anion-exchange resins. Cholestyramine may affect absorption of UDCA; if cholestyramine is necessary, it should be taken at least 60 minutes before or 4 hours after UDCA is taken.Treatment options for pruritus that does not improve with anion-exchange resins include: rifampicin, naltrexone, or sertraline. Rifampicin may rarely cause drug induced liver injury and should be avoided if serum bilirubin is elevated (greater than 2.5 mg/dL). Liver enzymes should be monitored after starting rifampin. Rifampicin induces enzymes, resulting in numerous potential drug-drug interactions. Opioid antagonists may cause a self-limited opioid withdrawal like reaction, with abdominal pain, elevated blood pressure, tachycardia, goose bumps, nightmares, and depersonalization. To avoid such reactions, the dose should start low and gradually be increased. Other therapies Fatigue is a nonspecific but often-reported symptom in PBC, and represents an unmet need since no therapies are licensed. A structured approach to management, quantifying fatigue and its impacts (through the use of disease-specific tools such as the PBC-40 quality-of-life measures), addressing contributing and exacerbating factors, and supporting patients to cope with its impact is effective. Drugs such as coenzyme Q and rituximab have been shown to be ineffective. A graded programme of exercise helps some individuals. People with PBC may have poor lipid-dependent absorption of oil-soluble vitamins (A, D, E, and K). Appropriate supplementation is recommended when bilirubin is elevated. People with PBC are at elevated risk of developing osteoporosis as compared to the general population and others with liver disease. Screening and treatment of this complication is an important part of the management of PBC. As in all liver diseases, consumption of alcohol should be restricted or eliminated. In patients with advanced liver disease, the only curative therapy is liver transplant. Outcomes are favourable, with five-year patient survival rates better than for most other indications for LT (80–85%). Prognosis The introduction of UDCA has dramatically changed the pattern and the course of the disease. Numerous trials and observational studies have demonstrated its efficacy on liver biochemistry, histological progression, and transplant-free survival.Among the UDCA-treated patients, the degree of the liver biochemistry improvement, i.e. the UDCA-response, identifies patients with different long-term prognosis. In the absence of cirrhosis, people who experience an improvement of liver enzymes to the normal range on treatment with UDCA have excellent survival, which may be similar to the general population. Survival is significantly reduced though, in those with abnormal liver biochemistry on treatment. The two most important parameters in evaluating response to UDCA are alkaline phosphatase and total bilirubin. Qualitative and quantitative definitions of UDCA-response have been developed, based on changes of bilirubin, transaminases and ALP, after a period of 6 to 24 months of treatment with UDCA at 13–15 mg/kg/day.Patients at diagnosis can be risk-stratified based on the probability of UDCA-response. This is relevant to identify patients who would be eligible for second-line therapies before waiting for the treatment failure under UDCA, with potential impact on disease course.Hepatocellular carcinoma (HCC) is infrequent in PBC. Recent large-scale cohort studies highlighted that the lack of UDCA-response after 12 months of therapy and male sex are associated with increased future risk of developing HCC in PBC. After liver transplant, the recurrence of disease may be as high as 18% at five years, and up to 30% at 10 years. No consensus exists on risk factors for recurrence of the disease. Epidemiology Epidemiologic studies report heterogeneous incidence rates of 0.33 to 5.8 per 100,000 inhabitants per year, and prevalence rates of 1.9 to 40.2 per 100,000 inhabitants. Such figures, in particular the prevalence, have shown some increase in the last decades. Improvement of diagnostic tools, increasing disease awareness, and digitised patient registration with facilitation of case-findings, along with improved survival, likely contributed to the rising prevalence rates. The disease has been described worldwide, though North America and Northern Europe have shown the highest incidence and prevalence rates. Whether a true variation in disease prevalence exists among populations of different geographical areas and of different ethnicity or if this is a consequence of a difference in study quality is unknown. PBC is more common in women, with a female:male ratio of at least 9:1. The peak incidence of PBC is in the fifth decade of life. In some areas of the US and UK, the prevalence is estimated to be as high as one in 4,000. This is much more common than in South America or Africa, which may be due to better recognition in the US and UK. First-degree relatives may have as much as a 500 times increase in prevalence, but if this risk is greater in the same-generation relatives or the one that follows is debated. PBC is considered a prime example of the female preponderance in autoimmunity with a female to male ratio of up to 9:1, confirmed by large cohort studies, although some recent data, using administrative registries, suggest an increasing male prevalence. Major defects of sex chromosomes, i.e. enhanced monosomy X in female patients and an enhanced Y chromosome loss in male patients, have been described and might well explain the greater female predisposition to develop PBC.An association of a greater incidence of PBC at latitudes more distant from the Equator is similar to the pattern seen in multiple sclerosis.Typical disease onset is between 30 and 60 years, though cases have been reported of patients diagnosed at the ages of 15 and 93. Prevalence of PBC in women over the age of 45 years could exceed one in an estimated 800 individuals. History The first report of the disease dates back 1851 by Addison and Gull, who described a clinical picture of progressive jaundice in the absence of mechanical obstruction of the large bile ducts. Ahrens et al. in 1950 published the first detailed description of 17 patients with this condition, and coined the term "primary biliary cirrhosis". In 1959, Dame Sheila Sherlock reported a further series of PBC patients and recognised that the disease could be diagnosed in a precirrhotic stage and proposed the term "chronic intrahepatic cholestasis" as more appropriate description of this disease, but this nomenclature failed to gain acceptance, and the term "primary biliary cirrhosis" lasted for decades. In 2014, to correct the inaccuracy and remove the social stigmata of cirrhosis, as well as all the misunderstanding, disadvantages, and discrimination emanating from this misnomer in daily life for patients, international liver associations agreed to rename the disease "primary biliary cholangitis", as it is now known. Society and culture Support groups PBC Foundation The PBC Foundation is a UK-based international charity offering support and information to people with PBC and their families and friends. It campaigns for increasing recognition of the disorder, improved diagnosis, and treatments, and estimates over 8,000 people are undiagnosed in the UK. The Foundation has supported research into PBC including the development of the PBC-40 quality of life measure published in 2004 and helped establish the PBC Genetics Study. It was founded by Collette Thain in 1996, after she was diagnosed with the condition. Thain was awarded an MBE Order of the British Empire in 2004 for her work with the Foundation. The PBC Foundation helped initiate the name change campaign in 2014. PBCers Organization The PBCers Organization is a US-based nonprofit patient support group that was founded by Linie Moore in 1996; it advocates for greater awareness of the disease and new treatments. It supported the name change initiative. References External links Primary Biliary Cirrhosis page from the National Digestive Diseases Information Clearinghouse Alagille syndrome

Aarogya, can you share information about a health condition involving CD30+ cutaneous T-cell lymphoma

CD30+ cutaneous T-cell lymphoma

CD30+ cutaneous T-cell lymphoma, also known as primary cutaneous anaplastic large cell lymphoma, is a cutaneous (skin) condition characterized by solitary or localized skin lesions that have a tendency to ulcerate.: 738 See also Cutaneous T-cell lymphoma Secondary cutaneous CD30+ large cell lymphoma List of cutaneous conditions References == External links ==

Hey Aarogya, explain a scenario commonly referred as Proctitis

Proctitis

Proctitis is an inflammation of the anus and the lining of the rectum, affecting only the last 6 inches of the rectum. Signs and symptoms A common symptom is a continual urge to have a bowel movement—the rectum could feel full or have constipation. Another is tenderness and mild irritation in the rectum and anal region. A serious symptom is pus and blood in the discharge, accompanied by cramps and pain during the bowel movement. If there is severe bleeding, anemia can result, showing symptoms such as pale skin, irritability, weakness, dizziness, brittle nails, and shortness of breath.Symptoms are ineffectual straining to empty the bowels, diarrhea, rectal bleeding and possible discharge, a feeling of not having adequately emptied the bowels, involuntary spasms and cramping during bowel movements, left-sided abdominal pain, passage of mucus through the rectum, and anorectal pain. Sexually transmitted proctitis Gonorrhea (Gonococcal proctitis) This is the most common cause. Strongly associated with anal intercourse. Symptoms include soreness, itching, bloody or pus-like discharge, or diarrhea. Other rectal problems that may be present are anal warts, anal tears, fistulas, and hemorrhoids.Chlamydia (chlamydia proctitis) Accounts for twenty percent of cases. People may show no symptoms, mild symptoms, or severe symptoms. Mild symptoms include rectal pain with bowel movements, rectal discharge, and cramping. With severe cases, people may have discharge containing blood or pus, severe rectal pain, and diarrhea. Some people have rectal strictures, a narrowing of the rectal passageway. The narrowing of the passageway may cause constipation, straining, and thin stools.Herpes Simplex Virus 1 and 2 (herpes proctitis) Symptoms may include multiple vesicles that rupture to form ulcers, tenesmus, rectal pain, discharge, hematochezia. The disease may run its natural course of exacerbations and remissions but is usually more prolonged and severe in patients with immunodeficiency disorders. Presentations may resemble dermatitis or decubitus ulcers in debilitated, bedridden patients. A secondary bacterial infection may be present.Syphilis (syphilitic proctitis) The symptoms are similar to other causes of infectious proctitis; rectal pain, discharge, and spasms during bowel movements, but some people may have no symptoms. Syphilis occurs in three stages. The primary stage: One painless sore, less than an inch across, with raised borders found at the site of sexual contact, and during acute stages of infection, the lymph nodes in the groin become diseased, firm, and rubbery. The secondary stage: A contagious diffuse rash that may appear over the entire body, particularly on the hands and feet. The third stage: Occurs late in the course of syphilis and affects mostly the heart and nervous system. Causes Proctitis has many possible causes. It may occur idiopathically (idiopathic proctitis, that is, arising spontaneously or from an unknown cause). Other causes include damage by irradiation (for example in radiation therapy for cervical cancer and prostate cancer) or as a sexually transmitted infection, as in lymphogranuloma venereum and herpes proctitis. Studies suggest a celiac disease-associated "proctitis" can result from an intolerance to gluten. A common cause is engaging in anal sex with partner(s) infected with sexual transmitted diseases in men who have sex with men. Shared enema usage has been shown to facilitate the spread of Lymphogranuloma venereum proctitis. Diagnosis Doctors can diagnose proctitis by looking inside the rectum with a proctoscope or a sigmoidoscope. A biopsy is taken, in which the doctor scrapes a tiny piece of tissue from the rectum, and this tissue is then examined by microscopy. The physician may also take a stool sample to test for infections or bacteria. If the physician suspects that the patient has Crohns disease or ulcerative colitis, colonoscopy or barium enema X-rays are used to examine areas of the intestine. Treatment Treatment for proctitis varies depending on severity and the cause. For example, the physician may prescribe antibiotics for proctitis caused by bacterial infection. If the proctitis is caused by Crohns disease or ulcerative colitis, the physician may prescribe the drug 5-aminosalicyclic acid (5ASA) or corticosteroids applied directly to the area in enema or suppository form, or taken orally in pill form. Enema and suppository applications are usually more effective, but some patients may require a combination of oral and rectal applications. Another treatment available is that of fiber supplements such as Metamucil. Taken daily these may restore regularity and reduce pain associated with proctitis. Chronic radiation proctitis is usually treated first-line with sucralfate enemas. These are non-invasive and are effective in diffuse, distal disease. Other treatments may include mesalamine suppositories, vitamin E, hyperbaric oxygen, or short chain fatty acid enemas; however these treatments are only supported by observational or anecdotal evidence. See also Paraproctitis References External links eMedicine

Aarogya, What does Prostatitis mean

Prostatitis

Prostatitis is inflammation of the prostate gland. Prostatitis is classified into acute, chronic, asymptomatic inflammatory prostatitis, and chronic pelvic pain syndrome. In the United States, prostatitis is diagnosed in 8% of all male urologist visits and 1% of all primary care physician visits for male genitourinary symptoms. Classification The term prostatitis refers to inflammation of the tissue of the prostate gland. It may occur as an appropriate physiological response to an infection, or it may occur in the absence of infection.In 1999, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) devised a new classification system. For more specifics about each type of prostatitis, including information on symptoms, treatment, and prognosis, follow the links to the relevant full articles. In 1968, Meares and Stamey determined a classification technique based upon the culturing of bacteria. This classification is no longer used. The conditions are distinguished by the different presentation of pain, white blood cells (WBCs) in the urine, duration of symptoms and bacteria cultured from the urine. To help express prostatic secretions that may contain WBCs and bacteria, prostate massage is sometimes used. See also Interstitial cystitis — a related disease Granulomatous prostatitis IgG4-related prostatitis Male accessory gland infection (MAGI) References External links Prostatitis Self Assessment Calculator

Hey Aarogya , Do you know what is Pruritus ani,

Pruritus ani

Pruritus ani is the irritation of the skin at the exit of the rectum, known as the anus, causing the desire to scratch. The intensity of anal itching increases from moisture, pressure, and rubbing caused by clothing and sitting. At worst, anal itching causes intolerable discomfort that often is accompanied by burning and soreness. It is estimated that up to 5% of the population of the United States experiences this type of discomfort daily. Causes If a specific cause for pruritus ani is found it is classified as "secondary pruritus ani". If a specific cause is not found it is classified as "idiopathic pruritus ani". The irritation can be caused by intestinal parasites, anal perspiration, frequent liquid stools, diarrhea, residual stool deposits, or the escape of small amounts of stool as a result of incontinence or flatulence. Another cause is yeast infection or candidiasis. Some diseases increase the possibility of yeast infections, such as diabetes mellitus or HIV infection. Treatment with antibiotics can bring about a disturbance of the natural balance of intestinal flora, and lead to perianal thrush, a yeast infection affecting the anus. Psoriasis also can be present in the anal area and cause irritation. Abnormal passageways (fistulas) from the small intestine or colon to the skin surrounding the anus can form as a result of disease (such as Crohns disease), acting as channels which may allow leakage of irritating fluids to the anal area. Other problems that can contribute to anal itching include pinworms, hemorrhoids, tears of the anal skin near the mucocutaneous junction (fissures), and skin tags (abnormal local growth of anal skin). Aside from diseases relative to the condition, a common view suggests that the initial cause of the itch may have passed, and that the illness is in fact prolonged by what is known as an itch-scratch-itch cycle. It states that scratching the itch encourages the release of inflammatory chemicals, which worsen redness, intensifies itchiness and increases the area covered by dry skin, thereby causing a snowball effect. Some authorities describe “psychogenic pruritus” or "functional itch disorder", where psychological factors may contribute to awareness of itching. Ingestion of pinworm eggs leads to enterobiasis, indicative of severe itching around the anus from migration of gravid females from the bowel. Severe cases of enterobiasis result in hemorrhage and eczema. Diagnosis Diagnosis is usually done with a careful examination of the anus and the patients history. If the presentation or physical findings are atypical, biopsies can be done.In case of long-lasting symptoms, above all in patients over 50 years of age, a colonoscopy is useful to rule out a colonic polyp or tumor, that can show pruritus ani as first symptom. Treatment The goal of treatment is asymptomatic, intact, dry, clean perianal skin with reversal of morphological changes. For pruritus ani of unknown cause (idiopathic pruritus ani) treatment typically begins with measures to reduce irritation and trauma to the perianal area. Stool softeners can help prevent constipation. If this is not effective topical steroids or injected methylene blue may be tried. Another treatment option that has been met with success in small-scale trials is the application of a very mild (.006) topical capsaicin cream. This strength cream is not typically commercially available and therefore must be diluted by a pharmacist or end-user. If the itchiness is secondary to another condition such as infection or psoriasis these are typically treated.A successful treatment option for chronic idiopathic pruritus ani has been documented using a clean, dry and apply (if necessary) method. The person is instructed to follow this procedure every time the urge to scratch occurs. The treatment makes the assumption that there is an unidentified bacteria in the feces that causes irritation and itching when the feces makes contact with the anal and perianal skin during defecation, flatulation or anal leakage (particularly during sleep). Cleaning the area with warm water, avoiding all soaps and even baby wipes, then drying the area, ideally with a hair dryer to avoid irritation or failing that simply patting gently with a clean, dry, towel. If persons with pruritus ani do not need to scratch after these steps they are instructed to do nothing else. If the urge to scratch is still present they are instructed to apply a topical steroid cream which has antibiotic and antifungal properties. This will address a skin condition which may have become infected. Apply such a cream as directed by your medical professional but usually twice a day for one to two weeks. After this, they must maintain their clean and dry regime and apply an emollient ointment (not cream) to moisturize the skin. This should be applied after each bowel movement and at night. Continue until no longer needed. At any time, persons may use antihistamine treatments orally, to control the itching. See also Pruritus scroti Pruritus vulvae Perianal candidiasis References External links Siddiqi S, Vijay V, Ward M, Mahendran R, Warren S (September 2008). "Pruritus ani". Annals of the Royal College of Surgeons of England. 90 (6): 457–463. doi:10.1308/003588408X317940. PMC 2647235. PMID 18765023.

Hello Aarogya, what is Pseudobulbar affect

Pseudobulbar affect

Pseudobulbar affect (PBA), or emotional incontinence, is a type of emotional disturbance characterized by uncontrollable episodes of crying, laughing, anger or other emotional displays. PBA occurs secondary to a neurologic disorder or brain injury. Patients may find themselves crying uncontrollably at something that is only moderately sad, being unable to stop themselves for several minutes. Episodes may also be mood-incongruent: a patient may laugh uncontrollably when angry or frustrated, for example. Sometimes, the episodes may switch between emotional states, resulting in the patient crying uncontrollably before dissolving into fits of laughter. The pseudobulbar affect, also referred to as emotional lability, should not be confused with labile mood or labile emotions that stem from emotional instability – affective dysregulation – commonly seen in mental illnesses and certain personality disorders. Signs and symptoms The cardinal feature of the disorder is a pathologically lowered threshold for exhibiting the behavioral response of laughter, crying, anger or all of the above. An affected individual exhibits episodes of laughter, crying, anger or a combination of these without an apparent motivating stimulus or in response to stimuli that would not have elicited such an emotional response before the onset of their underlying neurologic disorder. In some patients, the emotional response is exaggerated in intensity but is provoked by a stimulus with an emotional valence congruent with the character of the emotional display. For example, a sad stimulus provokes a pathologically exaggerated weeping response instead of a sigh, which the patient normally would have exhibited in that particular instance. However, in some other patients, the character of the emotional display can be incongruent with, and even contradictory to, the emotional valence of the provoking stimulus or may be incited by a stimulus with no clear valence. For example, a patient may laugh in response to sad news or cry in response to stimuli with no emotional undertone, or, once provoked, the episodes may switch from laughing to crying or vice versa.The symptoms of PBA can be severe, with persistent and unremitting episodes. Characteristics include: The onset can be sudden and unpredictable, and has been described by some patients as coming on like a seizure; The outbursts have a typical duration of a few seconds to several minutes; and, The outbursts may happen several times a day.Many people with neurologic disorders exhibit uncontrollable episodes of laughing, crying, or anger that are either exaggerated or contradictory to the context in which they occur. Where patients have significant cognitive deficits (e.g., Alzheimers) it can be unclear whether it is true PBA as opposed to a grosser form of emotional dysregulation, but patients with intact cognition often report the symptom as disturbing. Patients report that their episodes are at best only partially amenable to voluntary control, and unless they experience a severe change of mental status, as in traumatic brain injury they often have insight into their problem and judge their emotional displays as inappropriate and out of character. The clinical effect of PBA can be severe, with unremitting and persistent symptoms that can be disabling to patients, and may significantly affect quality of life for caregivers. Social impact While not as profoundly disabling as the physical symptoms of these diseases, PBA may significantly influence individuals social functioning and their relationships with others. Such sudden, frequent, extreme, uncontrollable emotional outbursts may lead to social withdrawal and interfere with activities of daily living, social and professional pursuits, and reduce overall healthcare. For example, patients with ALS and MS are often cognitively normal. However, the appearance of uncontrollable emotions is commonly associated with many additional neurological disorders such as attention deficit/hyperactivity disorder, Parkinsons disease, cerebral palsy, autism, epilepsy, and migraines. This may lead to avoidance of social interactions for the patient, which in turn impairs their coping mechanisms and their careers. Depression PBA may often be misdiagnosed as clinical depression or bipolar disorder; however, many clear distinctions exist. In depressive and bipolar disorders, crying, anger or laughter are typically indicative of mood, whereas the pathological displays of crying which occur in PBA are often in contrast to the underlying mood, or greatly in excess of the mood or eliciting stimulus. In addition, a key to differentiating depression from PBA is duration: PBA episodes are sudden, occurring in an episodic manner, while crying in depression is a more sustained presentation and closely relates to the underlying mood state. The level of control that one has over the crying, anger or other emotional displays in PBA is minimal or nonexistent, whereas for those with depression, the emotional expression (typically crying) can be modulated by the situation. Similarly, the trigger for episodes of crying in patients with PBA may be nonspecific, minimal or inappropriate to the situation, but in depression the stimulus is specific to the mood-related condition. These differences are outlined in the adjacent Table. In some cases, depressed mood and PBA may co-exist. Since depression is one of the most common emotional changes in patients with neurodegenerative disease or post-stroke sequelae, it is often comorbid with PBA. Comorbidity implies that depression is distinct from PBA and is not necessary for, nor does it exclude, a diagnosis of PBA. Causes The specific pathophysiology involved in this frequently debilitating condition is still under investigation; the primary pathogenic mechanisms of PBA remain controversial. One hypothesis, established by early researchers such as Wilson and Oppenheim, placed emphasis on the role of the corticobulbar pathways in modulating emotional expression in a top-down model, and theorized that PBA occurs when bilateral lesions in the descending corticobulbar tract cause failure of voluntary control of emotion, which leads to the disinhibition, or release, of laughing/crying centers in the brainstem. Other theories implicate the prefrontal cortex. Secondary condition PBA is a condition that occurs secondary to neurological disease or brain injury, and is thought to result from disruptions of neural networks that control the generation and regulation of motor output of emotions. PBA is most commonly observed in people with neurologic injuries such as traumatic brain injury (TBI) and stroke, and neurologic diseases such as dementias including Alzheimers disease, attention deficit/hyperactivity disorder (ADHD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Parkinsons disease (PD). It has been reported as a symptom of hyperthyroidism, Graves disease, or hypothyroidism in combination with depression.PBA has also been observed in association with a variety of other brain disorders, including brain tumors, Wilsons disease, syphilitic pseudobulbar palsy, and various encephalitides. Rarer conditions associated with PBA include gelastic epilepsy, dacrystic epilepsy, central pontine myelinolysis, olivopontinocerebellar atrophy, lipid storage diseases, chemical exposure (e.g., nitrous oxide and insecticides), fou rire prodromique, and Angelman syndrome. It is hypothesized that these primary neurologic injuries and diseases affect chemical signaling in the brain, which in turn disrupts the neurologic pathways that control emotional expression. Stroke PBA is one of the most frequently reported post-stroke behavioral disorders, with a range of reported prevalence rates from 28% to 52%. The higher prevalence rates tend to be reported in stroke patients who are older or who have a history of prior stroke. The relationship between post-stroke depression and PBA is complicated, because the depressive syndrome also occurs with high frequency in stroke survivors. Post-stroke patients with PBA are more depressed than post-stroke patients without PBA, and the presence of a depressive syndrome may exacerbate the weeping side of PBA symptoms. Multiple sclerosis Recent studies suggest that approximately 10% of patients with multiple sclerosis (MS) will experience at least one episode of emotional lability. PBA is generally associated with later stages of the disease (chronic progressive phase). PBA in MS patients is associated with more severe intellectual deterioration, physical disability, and neurological disability. Amyotrophic lateral sclerosis A study designed specifically to survey for prevalence found that 49% of patients with amyotrophic lateral sclerosis (ALS) also had PBA. PBA does not appear to be associated with duration of ALS. It is a symptom of ALS that many patients are unaware of and do not receive information about from their physician. Traumatic brain injury One study of 301 consecutive cases in a clinic setting reported a 5% prevalence. PBA occurred in patients with more severe head injury, and coincided with other neurological features suggestive of pseudobulbar palsy.The Brain Injury Association of America (BIAA) indicates that approximately 80% of survey respondents experience symptoms of PBA. Results from a recent investigation estimate the prevalence of PBA associated with traumatic brain injury to exceed more than 55% of survivors. Treatment Education of patients, families, and caregivers is an important component of the appropriate treatment of PBA. Crying associated with PBA may be incorrectly interpreted as depression; laughter may be embarrassing, anger can be debilitating. It is therefore critical for families and caregivers to recognize the pathological nature of PBA and the reassurance that this is an involuntary syndrome that is manageable. Traditionally, antidepressants such as sertraline, fluoxetine, citalopram, nortriptyline and amitriptyline have been prescribed with some efficacy. Medication Dextromethorphan hydrobromide affects the signals in the brain that trigger the cough reflex. It is used as a cough suppressant, although it can sometimes be used, medicinally, as a pain reliever, and is also used as a recreational drug.Quinidine sulfate affects the way the heart beats, and is generally used in people with certain heart rhythm disorders. It is also used to treat malaria. Quinidine sulfate, as a metabolic inhibitor, "increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P450 2D6, which catalyzes a major biotransformation pathway for dextromethorphan," enabling therapeutic dextromethorphan concentrations.Dextromethorphan/quinidine is a combination of these two generic drugs, and is the first FDA-approved drug for the treatment of PBA, approved on October 29, 2010.For this multicenter study, the "Objectives...[were] to evaluate the safety, tolerability, and efficacy of two different doses of AVP-923 [Dextromethorphan/quinidine combination]...when compared to placebo." The conditions and results of that study are as follows: At one study site, a total of 326 participants received one of three dose options. "METHODS: In a 12-week randomized, double-blind trial, ALS and MS patients with clinically significant PBA" were given a twice-daily dose of one of the following: placebo (N=109) dextromethorphan hydrobromide 30 mg/quinidine sulfate 10 mg (N=110) Nuedexta – dextromethorphan hydrobromide 20 mg/quinidine sulfate 10 mg (N=107)283 patients (86.8%) completed the study. The number of PBA episodes (laughing, crying or aggressive outbursts) were 47% and 49% lower (based on the trials outcome measures), respectively, for the drug-combination options than for the placebo. The "mean CNS-LS scores" decreased by 8.2 points for both drug-combination options, vs a decrease of 5.7 points for the placebo. Overall, the trial showed a statistically significant benefit from taking a combination of dextromethorphan and quinidine, with both dosages being safe and well tolerated. For a secondary objective measuring a participants "perceived health status...measuring eight health concepts: vitality, physical functioning, bodily pain, general health perceptions, physical role-, emotional role-, social role functioning, and mental health," the higher dosage showed improvement, especially on measures of social functioning and mental health. Epidemiology Prevalence estimates place the number of people with PBA between 1.5 and 2 million in the United States alone, which would be less than 1% of the U.S. population even at the high end of the estimate. Some argue that the number is probably higher and that clinicians underdiagnose PBA. However, the prevalence estimate of 2 million is based on an online survey. Self-selected computer-savvy patients in at-risk groups evaluated their own symptoms and submitted their self-diagnoses. No doctor or clinic confirmed the data. Motivation to participate could have been influenced by the presence of symptoms, which would have skewed the results. The actual prevalence could very well be quite a bit lower than estimated. History The Expression of the Emotions in Man and Animals by Charles Darwin was published in 1872. In Chapter VI, "Special Expressions of Man: Suffering and Weeping", Darwin discusses cultural variations in the acceptability of weeping and the wide differences in individual responses to suffering. The chapter contains the following sentence: We must not, however, lay too much stress on the copious shedding of tears by the insane, as being due to the lack of all restraint; for certain brain-diseases, as hemiplegia, brain-wasting, and senile decay, have a special tendency to induce weeping. Terminology Historically, there have been a variety of terms used for the disorder, including pseudobulbar affect, pathological laughter and crying, emotional lability, emotionalism, emotional dysregulation, or more recently, involuntary emotional expression disorder. The term pseudobulbar (pseudo- + bulbar) came from the idea that the symptoms seemed similar to those caused by a bulbar lesion (that is, a lesion in the medulla oblongata). Terms such as forced crying, involuntary crying, pathological emotionality, and emotional incontinence have also been used, although less frequently. In popular culture Arthur Fleck, the central character of the 2019 film Joker, displays signs of pseudobulbar affect, which are said to be what Joaquin Phoenix used as inspiration for his characters signature laugh. In the 2019 movie Parasite, the character Ki-woo sustains head trauma, and although it is not clearly mentioned that hes affected by pseudobulbar affect, he mentions not being able to stop laughing when thinking about all the events that occur in the movie. In the medical television show House, season 7, episode 8 ("Small Sacrifices"), the character Ramon Silva, played by Kuno Becker displays pseudobulbar affect, with uncontrollable incongruent laughter, while having the Marburg variety of multiple sclerosis. In season 3, episode 9 of The Good Fight, the character Brenda DeCarlo, an external auditor, displays pseudobulbar affect, with uncontrollable incongruent laughter. See also Affect (psychology) Affect display References External links "Pseudobulbar affect and stroke" on the National Stroke Association website

Aarogya what is Pud

Pud

Pud may refer to: Pudding, a typically sweet food Comic strip mascot for Dubble Bubble A nickname of Albert Kent, a Canadian football coach and olympic rower A nickname of Philip J. Kaplan, an American entrepreneur Pud Galvin, a Hall of Fame Major League Baseball pitcher Pood or pud, an old Russian unit of weight slang shortened version of "pudendum"PUD can be an acronym for Planned Unit Development Public Utility District, a consumer co-op owned utility Peptic Ulcer Disease

Please give me a short description about Pulmonary hypertension , Aarogya

Pulmonary hypertension

Pulmonary hypertension (PH or PHTN) is a condition of increased blood pressure in the arteries of the lungs. Symptoms include shortness of breath, fainting, tiredness, chest pain, swelling of the legs, and a fast heartbeat. The condition may make it difficult to exercise. Onset is typically gradual.A patient is deemed to have pulmonary hypertension if the pulmonary mean arterial pressure is greater than 25mmHg at rest, or greater than 30mmHg during exercise.The cause is often unknown. Risk factors include a family history, prior blood clots in the lungs, HIV/AIDS, sickle cell disease, cocaine use, chronic obstructive pulmonary disease, sleep apnea, living at high altitudes, and problems with the mitral valve. The underlying mechanism typically involves inflammation and subsequent remodeling of the arteries in the lungs. Diagnosis involves first ruling out other potential causes.There is currently no cure for pulmonary hypertension, although research on a cure is ongoing. Treatment depends on the type of disease. A number of supportive measures such as oxygen therapy, diuretics, and medications to inhibit blood clotting may be used. Medications specifically used to treat pulmonary hypertension include epoprostenol, treprostinil, iloprost, bosentan, ambrisentan, macitentan, and sildenafil. Lung transplantation may be an option in severe cases.The frequency of occurrence is estimated at 1,000 new cases per year in the United States. Females are more often affected than males. Onset is typically between 20 and 60 years of age. Pulmonary hypertension was identified by Ernst von Romberg in 1891. Classification According to WHO classification there are 5 groups of PH, where Group I (pulmonary arterial hypertension) is further subdivided into Group I and Group I classes. The most recent WHO classification system (with adaptations from the more recent ESC/ERS guidelines shown in italics) can be summarized as follows:WHO Group I – Pulmonary arterial hypertension (PAH) Idiopathic Heritable (BMPR2, ALK1, SMAD9, caveolin 1, KCNK3 mutations) Drug- and toxin-induced (e.g., methamphetamine, amphetamine, or cocaine use ) Associated conditions:Connective tissue disease, HIV infection, Portal hypertension, Congenital heart diseases, SchistosomiasisWHO Group I – Pulmonary veno-occlusive disease (PVOD), pulmonary capillary hemangiomatosis (PCH) Idiopathic Heritable (EIF2AK4 mutations) Drugs, toxins and radiation-induced Associated conditions:connective tissue disease, HIV infectionWHO Group I" – Persistent pulmonary hypertension of the newborn WHO Group II – Pulmonary hypertension secondary to left heart disease Left ventricular systolic dysfunction Left ventricular diastolic dysfunction Valvular heart disease Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathy Congenital/acquired pulmonary venous stenosisWHO Group III – Pulmonary hypertension due to lung disease, chronic hypoxia Chronic obstructive pulmonary disease (COPD) Interstitial lung disease Mixed restrictive and obstructive pattern pulmonary diseases Sleep-disordered breathing Alveolar hypoventilation disorders Chronic exposure to high altitude Developmental abnormalitiesWHO Group IV – chronic arterial obstruction Chronic thromboembolic pulmonary hypertension (CTEPH) Other pulmonary artery obstructions Angiosarcoma or other tumor within the blood vessels Arteritis Congenital pulmonary artery stenosis Parasitic infection (hydatidosis)WHO Group V – Pulmonary hypertension with unclear or multifactorial mechanisms Hematologic diseases: chronic hemolytic anemia (including sickle cell disease) Systemic diseases: sarcoidosis, pulmonary Langerhans cell histiocytosis: lymphangioleiomyomatosis, neurofibromatosis, vasculitis Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid diseases Others: pulmonary tumoral thrombotic microangiopathy, fibrosing mediastinitis, chronic kidney failure, segmental pulmonary hypertension (pulmonary hypertension restricted to one or more lobes of the lungs) Signs and symptoms The symptoms of pulmonary hypertension include the following: Less common signs/symptoms include non-productive cough and exercise-induced nausea and vomiting. Coughing up of blood may occur in some patients, particularly those with specific subtypes of pulmonary hypertension such as heritable pulmonary arterial hypertension, Eisenmenger syndrome and chronic thromboembolic pulmonary hypertension. Pulmonary venous hypertension typically presents with shortness of breath while lying flat or sleeping (orthopnea or paroxysmal nocturnal dyspnea), while pulmonary arterial hypertension (PAH) typically does not.Other typical signs of pulmonary hypertension include an accentuated pulmonary component of the second heart sound, a right ventricular third heart sound, and parasternal heave indicating a hypertrophied right ventricle. Signs of systemic congestion resulting from right-sided heart failure include jugular venous distension, ascites, and hepatojugular reflux. Evidence of tricuspid insufficiency and pulmonic regurgitation is also sought and, if present, is consistent with the presence of pulmonary hypertension. Causes Pulmonary hypertension is a pathophysiologic condition with many possible causes. Indeed, this condition frequently accompanies severe heart or lung conditions. A 1973 World Health Organization meeting was the first attempt to classify pulmonary hypertension by its cause, and a distinction was made between primary PH (resulting from a disease of the pulmonary arteries) and secondary PH (resulting secondary to other, non-vascular causes). Further, primary PH was divided into the "arterial plexiform", "veno-occlusive" and "thromboembolic" forms. In 1998, a second conference at Évian-les-Bains addressed the causes of secondary PH. Subsequent third, fourth, and fifth (2013) World Symposia on PAH have further defined the classification of PH. The classification continues to evolve based on improved understanding of the disease mechanisms.Most recently in 2015, the WHO guidelines were updated by the European Society of Cardiology (ESC) and European Respiratory Society (ERS). These guidelines are endorsed by the International Society for Heart and Lung Transplantation, and provide the current framework for understanding and treatment of pulmonary hypertension. Genetics Mutations in several genes have been associated with this condition these include bone morphogenetic protein receptor type 2 (BMPR2) and eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4). Pathogenesis The pathogenesis of pulmonary arterial hypertension (WHO Group I) involves the narrowing of blood vessels connected to and within the lungs. This makes it harder for the heart to pump blood through the lungs, as it is much harder to make water flow through a narrow pipe as opposed to a wide one. Over time, the affected blood vessels become stiffer and thicker, in a process known as fibrosis. The mechanisms involved in this narrowing process include vasoconstriction, thrombosis, and vascular remodeling (excessive cellular proliferation, fibrosis, and reduced apoptosis/programmed cell death in the vessel walls, caused by inflammation, disordered metabolism and dysregulation of certain growth factors). This further increases the blood pressure within the lungs and impairs their blood flow. In common with other types of pulmonary hypertension, these changes result in an increased workload for the right side of the heart. The right ventricle is normally part of a low pressure system, with systolic ventricular pressures that are lower than those that the left ventricle normally encounters. As such, the right ventricle cannot cope as well with higher pressures, and although right ventricular adaptations (hypertrophy and increased contractility of the heart muscle) initially help to preserve stroke volume, ultimately these compensatory mechanisms are insufficient; the right ventricular muscle cannot get enough oxygen to meet its needs and right heart failure follows. As the blood flowing through the lungs decreases, the left side of the heart receives less blood. This blood may also carry less oxygen than normal. Therefore, it becomes harder and harder for the left side of the heart to pump to supply sufficient oxygen to the rest of the body, especially during physical activity. During the end-systolic volume phase of the cardiac cycle, the Gaussian curvature and the mean curvature of right ventricular endocardial wall of PH patients was found to be significantly different as compared to controls.In PVOD (WHO Group I), pulmonary blood vessel narrowing occurs preferentially (though not exclusively) in post-capillary venous blood vessels. PVOD shares several characteristics with PAH, but there are also some important differences, for example differences in prognosis and response to medical therapy.Persistent pulmonary hypertension of the newborn occurs when the circulatory system of a newborn baby fails to adapt to life outside the womb; it is characterized by high resistance to blood flow through the lungs, right-to-left cardiac shunting and severe hypoxemia.Pathogenesis in pulmonary hypertension due to left heart disease (WHO Group II) is completely different in that constriction or damage to the pulmonary blood vessels is not the issue. Instead, the left heart fails to pump blood efficiently, leading to pooling of blood in the lungs and back pressure within the pulmonary system. This causes pulmonary edema and pleural effusions. In the absence of pulmonary blood vessel narrowing, the increased back pressure is described as isolated post-capillary pulmonary hypertension (older terms include passive or proportionate pulmonary hypertension or pulmonary venous hypertension). However, in some patients, the raised pressure in the pulmonary vessels triggers a superimposed component of vessel narrowing, which further increases the workload of the right side of the heart. This is referred to as post-capillary pulmonary hypertension with a pre-capillary component or combined post-capillary and pre-capillary pulmonary hypertension (older terms include reactive or out-of-proportion pulmonary hypertension).In pulmonary hypertension due to lung diseases and/or hypoxia (WHO Group III), low levels of oxygen in the alveoli (due to respiratory disease or living at high altitude) cause constriction of the pulmonary arteries. This phenomenon is called hypoxic pulmonary vasoconstriction and it is initially a protective response designed to stop too much blood flowing to areas of the lung that are damaged and do not contain oxygen. When the alveolar hypoxia is widespread and prolonged, this hypoxia-mediated vasoconstriction occurs across a large portion of the pulmonary vascular bed and leads to an increase in pulmonary arterial pressure, with thickening of the pulmonary vessel walls contributing to the development of sustained pulmonary hypertension. Prolonged hypoxia also induces the transcription factor HIF1A, which directly activates downstream growth factor signaling that causes irreversible proliferation and remodeling of pulmonary arterial endothelial cells, leading to chronic pulmonary arterial hypertension.In CTEPH (WHO Group IV), the initiating event is thought to be blockage or narrowing of the pulmonary blood vessels with unresolved blood clots; these clots can lead to increased pressure and shear stress in the rest of the pulmonary circulation, precipitating structural changes in the vessel walls (remodeling) similar to those observed in other types of severe pulmonary hypertension. This combination of vessel occlusion and vascular remodeling once again increases the resistance to blood flow and so the pressure within the system rises. Molecular pathology The molecular mechanism of pulmonary arterial hypertension (PAH) is not known yet, but it is believed that the endothelial dysfunction results in a decrease in the synthesis of endothelium-derived vasodilators such as nitric oxide and prostacyclin. Moreover, there is a stimulation of the synthesis of vasoconstrictors such as thromboxane and vascular endothelial growth factor (VEGF). These result in a severe vasoconstriction and vascular smooth muscle and adventitial hypertrophy characteristic of patients with PAH. Nitric oxide-soluble guanylate cyclase pathway In normal conditions, the vascular endothelial nitric oxide synthase produces nitric oxide from L-arginine in the presence of oxygen.This nitric oxide diffuses into neighboring cells (including vascular smooth muscle cells and platelets), where it increases the activity of the enzyme soluble guanylate cyclase, leading to increased formation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). The cGMP then activates cGMP-dependent kinase or PKG (protein kinase G). Activated PKG promotes vasorelaxation (via a reduction of intracellular calcium levels), alters the expression of genes involved in smooth muscle cell contraction, migration and differentiation, and inhibits platelet activation. Nitric oxide–soluble guanylate cyclase signaling also leads to anti-inflammatory effects.Phosphodiesterase type 5 (PDE5), which is abundant in the pulmonary tissue, hydrolyzes the cyclic bond of cGMP. Consequently, the concentration of cGMP (and thus PKG activity) decreases. Endothelin Endothelin-1 is a peptide (comprising 21 amino acids) that is produced in endothelial cells. It acts on the endothelin receptors ETA and ETB in various cell types including vascular smooth muscle cells and fibroblasts, leading to vasoconstriction, hypertrophy, proliferation, inflammation, and fibrosis. It also acts on ETB receptors in endothelial cells; this leads to the release of both vasoconstrictors and vasodilators from those cells, and clears endothelin-1 from the system. Prostacyclin (and thromboxane) Prostacyclin is synthesized from arachidonic acid in endothelial cells. In vascular smooth muscle cells, prostacyclin binds mainly to the prostaglandin I receptor. This sends a signal to increase adenylate cyclase activity, which leads to increased synthesis of cyclic adenosine monophosphate (cAMP). This in turn leads to increased cAMP-dependent protein kinase or PKA (protein kinase A) activity, ultimately promoting vasodilation and inhibiting cell proliferation. Prostacyclin signaling also leads to anti-thrombotic, anti-fibrotic, and anti-inflammatory effects. Levels of cAMP (which mediates most of the biological effects of prostacyclin) are reduced by phosphodiesterases 3 and 4. The vasoconstrictor thromboxane is also synthesized from arachidonic acid. In PAH, the balance is shifted away from synthesis of prostacyclin towards synthesis of thromboxane. Other pathways The three pathways described above are all targeted by currently available medical therapies for PAH. However, several other pathways have been identified that are also altered in PAH and are being investigated as potential targets for future therapies. For example, the mitochondrial enzyme pyruvate dehydrogenase kinase (PDK) is pathologically activated in PAH, causing a metabolic shift from oxidative phosphorylation to glycolysis and leading to increased cell proliferation and impaired apoptosis. Expression of vasoactive intestinal peptide, a potent vasodilator with anti-inflammatory and immune-modulatory roles, is reduced in PAH, while expression of its receptor is increased. Plasma levels of serotonin, which promotes vasoconstriction, hypertrophy and proliferation, are increased in patients with PAH, although the role played by serotonin in the pathogenesis of PAH remains uncertain. The expression or activity of several growth factors (including platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor) is increased and contributes to vascular remodeling in PAH. Other factors underlying the proliferative state of pulmonary vascular smooth muscle cells include OPG and TRAIL. Focusing only on the pulmonary vasculature provides an incomplete picture of PAH; the ability of the right ventricle to adapt to the increased workload varies between patients and is an important determinant of survival. The molecular pathology of PAH in the right ventricle is therefore also being investigated, and recent research has shifted to consider the cardiopulmonary unit as a single system rather than two separate systems. Importantly, right ventricular remodeling is associated with increased apoptosis; this is in contrast to pulmonary vascular remodeling which involves inhibition of apoptosis. Diagnosis In terms of the diagnosis of pulmonary hypertension, it has five major types, and a series of tests must be performed to distinguish pulmonary arterial hypertension from venous, hypoxic, thromboembolic, or unclear multifactorial varieties. PAH is diagnosed after exclusion of other possible causes of pulmonary hypertension. Physical examination A physical examination is performed to look for typical signs of pulmonary hypertension (described above), and a detailed family history is established to determine whether the disease might be heritable. A history of exposure to drugs such as benfluorex (a fenfluramine derivative), dasatinib, cocaine, methamphetamine, ethanol leading to cirrhosis, and tobacco leading to emphysema is considered significant. Use of selective serotonin reuptake inhibitors during pregnancy (particularly late pregnancy) is associated with an increased risk of the baby developing persistent pulmonary hypertension of the newborn. Echocardiography If pulmonary hypertension is suspected based on the above assessments, echocardiography is performed as the next step. A meta-analysis of Doppler echocardiography for predicting the results of right heart catheterization reported a sensitivity and specificity of 88% and 56%, respectively. Thus, Doppler echocardiography can suggest the presence of pulmonary hypertension, but right heart catheterization (described below) remains the gold standard for diagnosis of PAH. Echocardiography can also help to detect congenital heart disease as a cause of pulmonary hypertension. Exclude other diseases If the echocardiogram is compatible with a diagnosis of pulmonary hypertension, common causes of pulmonary hypertension (left heart disease and lung disease) are considered and further tests are performed accordingly. These tests generally include electrocardiography (ECG), pulmonary function tests including lung diffusion capacity for carbon monoxide and arterial blood gas measurements, X-rays of the chest and high-resolution computed tomography (CT) scanning. Ventilation/perfusion scintigraphy If heart disease and lung disease have been excluded, a ventilation/perfusion scan is performed to rule out CTEPH. If unmatched perfusion defects are found, further evaluation by CT pulmonary angiography, right heart catheterization, and selective pulmonary angiography is performed. CT scan Signs of pulmonary hypertension on CT scan of the chest are: Enlargement of the pulmonary trunk (measured at its bifurcation). It is, however, a poor predictor of pulmonary hypertension in patients with interstitial lung disease.A diameter of more than 27 mm for women and 29 mm for men is suggested as a cutoff. A cutoff of 31.6 mm may be a more statistically robust in individuals without interstitial lung disease.Increased ratio of the diameter of the main pulmonary artery (pulmonary trunk) to the ascending aorta (measured at its bifurcation).A ratio of 1.0 is suggested as a cutoff in adults. Cutoff ~1.09 in children.Increased diameter ratio of segmental arteries to bronchi. This finding in three or four lobes, in the presence of a dilated pulmonary trunk (≥29 mm), and absence of significant structural lung disease confers a specificity of 100% for pulmonary hypertension. Mural calcification in central pulmonary arteries is most frequently seen in patients with Eisenmengers syndrome. Right heart catheterization Although pulmonary arterial pressure (PAP) can be estimated on the basis of echocardiography, pressure measurements with a Swan-Ganz catheter inserted through the right side of the heart provide the most definite assessment.[42] Pulmonary hypertension is defined as a mean PAP of at least 20 mm Hg (3300 Pa) at rest, and PAH is defined as precapillary pulmonary hypertension (i.e. mean PAP ≥ 20 mm Hg with pulmonary arterial occlusion pressure [PAOP] ≤ 15 mm Hg and pulmonary vascular resistance [PVR] > 3 Wood Units). PAOP and PVR cannot be measured directly with echocardiography. Therefore, diagnosis of PAH requires right-sided cardiac catheterization. A Swan-Ganz catheter can also measure the cardiac output; this can be used to calculate the cardiac index, which is far more important in measuring disease severity than the pulmonary arterial pressure.Mean PAP (mPAP) should not be confused with systolic PAP (sPAP), which is often reported on echocardiogram reports. A systolic pressure of 40 mm Hg typically implies a mean pressure of more than 25 mm Hg. Roughly, mPAP = 0.61•sPAP + 2. Due to the invasive nature of this procedure, the use of computational fluid dynamics based hemodynamic indices have been postulated. Other For people considered likely to have PAH based on the above tests, the specific associated condition is then determined based on the physical examination, medical/family history and further specific diagnostic tests (for example, serological tests to detect underlying connective tissue disease, HIV infection or hepatitis, ultrasonography to confirm the presence of portal hypertension, echocardiography/cardiac magnetic resonance imaging for congenital heart disease, laboratory tests for schistosomiasis, and high-resolution CT for PVOD and pulmonary capillary hemangiomatosis). Routine lung biopsy is discouraged in patients with PAH, because of the risk to the patient and because the findings are unlikely to alter the diagnosis and treatment. Treatment Treatment of pulmonary hypertension is determined by whether the PH is arterial, venous, hypoxic, thromboembolic, or miscellaneous. If it is caused by left heart disease, the treatment is to optimize left ventricular function by the use of medication or to repair/replace the mitral valve or aortic valve. Patients with left heart failure or hypoxemic lung diseases (groups II or III pulmonary hypertension) should not routinely be treated with vasoactive agents including prostanoids, phosphodiesterase inhibitors, or endothelin antagonists, as these are approved for the different condition called primary pulmonary arterial hypertension. To make the distinction, doctors at a minimum will conduct cardiac catheterization of the right heart, echocardiography, chest CT, a six-minute walk test, and pulmonary function testing. Using treatments for other kinds of pulmonary hypertension in patients with these conditions can harm the patient and wastes substantial medical resources.High-dose calcium channel blockers are useful in only 5% of IPAH patients who are vasoreactive by Swan-Ganz catheter. Unfortunately, calcium channel blockers have been largely misused, being prescribed to many patients with non-vasoreactive PAH, leading to excess morbidity and mortality. The criteria for vasoreactivity have changed. Only those patients whose mean pulmonary artery pressure falls by more than 10 mm Hg to less than 40 mm Hg with an unchanged or increased cardiac output when challenged with adenosine, epoprostenol, or nitric oxide are considered vasoreactive. Of these, only half of the patients are responsive to calcium channel blockers in the long term.A number of agents have recently been introduced for primary and secondary PAH. The trials supporting the use of these agents have been relatively small, and the only measure consistently used to compare their effectivity is the "six-minute walk test". Many have no data on mortality benefit or time to progression. Vasoactive substances Many pathways are involved in the abnormal proliferation and contraction of the smooth muscle cells of the pulmonary arteries in patients with pulmonary arterial hypertension. Three of these pathways are important since they have been targeted with drugs — endothelin receptor antagonists, phosphodiesterase type 5 (PDE-5) inhibitors, and prostacyclin derivatives. Prostaglandins Prostacyclin (prostaglandin I2) is commonly considered the most effective treatment for PAH. Epoprostenol (synthetic prostacyclin) is given via continuous infusion that requires a semi-permanent central venous catheter. This delivery system can cause sepsis and thrombosis. Prostacyclin is unstable, and therefore has to be kept on ice during administration. Since it has a half-life of 3 to 5 minutes, the infusion has to be continuous, and interruption can be fatal. Other prostanoids have therefore been developed. Treprostinil can be given intravenously or subcutaneously, but the subcutaneous form can be very painful. An increased risk of sepsis with intravenous Remodulin has been reported by the CDC. Iloprost is also used in Europe intravenously and has a longer half life. Iloprost was the only inhaled form of prostacyclin approved for use in the US and Europe, until the inhaled form of treprostinil was approved by the FDA in July 2009. Endothelin receptor antagonists Moderate quality evidence suggests that endothelin receptor antagonists improve exercise capacity and decrease symptoms severity. The dual (ETA and ETB) endothelin receptor antagonist bosentan was approved in 2001. Sitaxentan (Thelin) was approved for use in Canada, Australia, and the European Union, but not in the United States. In 2010, Pfizer withdrew Thelin worldwide because of fatal liver complications. A similar drug, ambrisentan is marketed as Letairis in the U.S. by Gilead Sciences. s Phosphodiesterase type 5 inhibitors The U.S. FDA approved sildenafil, a selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5), for the treatment of PAH in 2005. It is marketed for PAH as Revatio. In 2009, they also approved tadalafil, another PDE5 inhibitor, marketed under the name Adcirca. PDE5 inhibitors are believed to increase pulmonary artery vasodilation, and inhibit vascular remodeling, thus lowering pulmonary arterial pressure and pulmonary vascular resistance.Tadalafil is taken orally, as well as sildenafil, and it is rapidly absorbed (serum levels are detectable at 20 minutes). The T1/2 (biological half-life) hovers around 17.5 hours in healthy subjects. Moreover, if we consider pharmacoeconomic implications, patients that take tadalafil would pay two-thirds of the cost of sildenafil therapy. However, there are some adverse effects of this drug such as headache, diarrhea, nausea, back pain, dyspepsia, flushing and myalgia. Activators of soluble guanylate cyclase Soluble guanylate cyclase (sGC) is the intracellular receptor for NO. As of April 2009, the sGC activators cinaciguat and riociguat were undergoing clinical trials for the treatment of PAH. Surgical Atrial septostomy is a surgical procedure that creates a communication between the right and left atria. It relieves pressure on the right side of the heart, but at the cost of lower oxygen levels in blood (hypoxia). Lung transplantation replaces a chronic condition with the ongoing need for treatment. There is a post-surgical median survival of just over five years.Pulmonary thromboendarterectomy (PTE) is a surgical procedure that is used for chronic thromboembolic pulmonary hypertension. It is the surgical removal of an organized thrombus (clot) along with the lining of the pulmonary artery; it is a very difficult, major procedure that is currently performed in a few select centers. Monitoring Established clinical practice guidelines dictate the frequency of pulmonary nodule evaluation and surveillance, patients are normally monitored through commonly available tests such as: Prognosis PAH is considered a universally fatal illness, although survival time may vary between individuals. The prognosis of pulmonary arterial hypertension (WHO Group I) has an untreated median survival of 2–3 years from time of diagnosis, with the cause of death usually being right ventricular failure (cor pulmonale). The survival time is variable and depends on many factors. A recent outcome study of those patients who had started treatment with bosentan (Tracleer) showed that 89% of patients were alive at 2 years. With new therapies, survival rates are increasing. For 2,635 patients enrolled in The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry) from March 2006 to December 2009, 1-, 3-, 5-, and 7-year survival rates were 85%, 68%, 57%, and 49%, respectively. For patients with idiopathic/familial PAH, survival rates were 91%, 74%, 65%, and 59%. Levels of mortality are very high in pregnant women with severe pulmonary arterial hypertension (WHO Group I). Pregnancy is sometimes described as contraindicated in these women. Epidemiology The epidemiology of IPAH is about 125–150 deaths per year in the U.S., and worldwide the incidence is similar at 4 cases per million. However, in parts of Europe (France), indications are 6 cases per million of IPAH. Females have a higher incidence rate than males (2–9:1).Other forms of PH are far more common. In systemic scleroderma, the incidence has been estimated to be 8 to 12% of all patients; in rheumatoid arthritis it is rare. However, in systemic lupus erythematosus it is 4 to 14%, and in sickle cell disease, it ranges from 20 to 40%. Up to 4% of people who develop a pulmonary embolism go on to develop chronic thromboembolic disease including pulmonary hypertension. A small percentage of patients with COPD develop pulmonary hypertension with no other disease to explain the high pressure. On the other hand, obesity-hypoventilation syndrome is very commonly associated with right heart failure due to pulmonary hypertension. Research For people that inherited the disease, gene therapy is being studied. Notable cases Elaine Kaufman, American restaurateur Ina Balin, American Broadway and TV actress Chloe Temtchine, American singer-songwriter Natalie Cole, American singer See also Pulmonary Hypertension Association Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) References Further reading Rubin LJ, Badesch DB (August 2005). "Evaluation and management of the patient with pulmonary arterial hypertension". Annals of Internal Medicine. 143 (4): 282–92. CiteSeerX 10.1.1.463.8466. doi:10.7326/0003-4819-143-4-200508160-00009. PMID 16103472. S2CID 28841269. Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, et al. (November 2015). "Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society". Circulation. 132 (21): 2037–99. doi:10.1161/CIR.0000000000000329. PMID 26534956. S2CID 7412370. External links The Merck Manual Home Edition: Pulmonary Hypertension

Please give me a short description about Ventricular tachycardia , Aarogya

Ventricular tachycardia

Ventricular tachycardia (V-tach or VT) is a fast heart rate arising from the lower chambers of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple episodes over a short period of time are referred to as an electrical storm. Short periods may occur without symptoms, or present with lightheadedness, palpitations, or chest pain. Ventricular tachycardia may result in ventricular fibrillation (VF) and turn into cardiac arrest. This conversion of the VT into VF is called the degeneration of the VT. It is found initially in about 7% of people in cardiac arrest.Ventricular tachycardia can occur due to coronary heart disease, aortic stenosis, cardiomyopathy, electrolyte problems, or a heart attack. Diagnosis is by an electrocardiogram (ECG) showing a rate of greater than 120 beats per minute and at least three wide QRS complexes in a row. It is classified as non-sustained versus sustained based on whether it lasts less than or more than 30 seconds. The term ventricular arrhythmia refers to the group of abnormal cardiac rhythms originating from the ventricle, which includes ventricular tachycardia, ventricular fibrillation, and torsades de pointes.In those who have normal blood pressure and strong pulse, the antiarrhythmic medication procainamide may be used. Otherwise, immediate cardioversion is recommended, preferably with a biphasic DC shock of 200 joules. In those in cardiac arrest due to ventricular tachycardia, cardiopulmonary resuscitation (CPR) and defibrillation is recommended. Biphasic defibrillation may be better than monophasic. While waiting for a defibrillator, a precordial thump may be attempted (However reserved to those who have the prior experience of doing so) in those on a heart monitor who are seen going into an unstable ventricular tachycardia. In those with cardiac arrest due to ventricular tachycardia, survival is about 45%. An implantable cardiac defibrillator or medications such as calcium channel blockers or amiodarone may be used to prevent recurrence. Signs and symptoms While a few seconds may not result in problems, longer periods are dangerous. Short periods may occur without symptoms or present with lightheadedness, palpitations, or chest pain. Ventricular tachycardia may turn into ventricular fibrillation and can result in cardiac arrest. Cause Ventricular tachycardia can occur due to coronary heart disease, aortic stenosis, cardiomyopathy, electrolyte problems (e.g., low blood levels of magnesium or potassium), inherited channelopathies (e.g., long-QT syndrome), catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular dysplasia, alcohol withdrawal syndrome (typically following atrial fibrillation), or a myocardial infarction. Pathophysiology The morphology of the tachycardia depends on its cause and the origin of the re-entry electrical circuit in the heart.In monomorphic ventricular tachycardia, the shape of each heart beat on the ECG looks the same because the impulse is either being generated from increased automaticity of a single point in either the left or the right ventricle, or due to a reentry circuit within the ventricle. The most common cause of monomorphic ventricular tachycardia is scarring of the heart muscle from a previous myocardial infarction (heart attack). This scar cannot conduct electrical activity, so there is a potential circuit around the scar that results in the tachycardia. This is similar to the re-entrant circuits that are the cause of atrial flutter and the re-entrant forms of supraventricular tachycardia. Other rarer congenital causes of monomorphic VT include right ventricular dysplasia, and right and left ventricular outflow tract VT.Polymorphic ventricular tachycardia, on the other hand, is most commonly caused by abnormalities of ventricular muscle repolarization. The predisposition to this problem usually manifests on the ECG as a prolongation of the QT interval. QT prolongation may be congenital or acquired. Congenital problems include long QT syndrome and catecholaminergic polymorphic ventricular tachycardia. Acquired problems are usually related to drug toxicity or electrolyte abnormalities, but can occur as a result of myocardial ischemia. Class III anti-arrhythmic drugs such as sotalol and amiodarone prolong the QT interval and may in some circumstances be pro-arrhythmic. Other relatively common drugs including some antibiotics and antihistamines may also be a danger, in particular in combination with one another. Problems with blood levels of potassium, magnesium and calcium may also contribute. High-dose magnesium is often used as an antidote in cardiac arrest protocols. Diagnosis The diagnosis of ventricular tachycardia is made based on the rhythm seen on either a 12-lead ECG or a telemetry rhythm strip. It may be very difficult to differentiate between ventricular tachycardia and a wide-complex supraventricular tachycardia in some cases. In particular, supraventricular tachycardias with aberrant conduction from a pre-existing bundle branch block are commonly misdiagnosed as ventricular tachycardia. Other rarer phenomena include Ashman beats and antidromic atrioventricular re-entry tachycardias.Various diagnostic criteria have been developed to determine whether a wide complex tachycardia is ventricular tachycardia or a more benign rhythm. In addition to these diagnostic criteria, if the individual has a history of a myocardial infarction, congestive heart failure, or recent angina, the wide complex tachycardia is much more likely to be ventricular tachycardia.The proper diagnosis is important, as the misdiagnosis of supraventricular tachycardia when ventricular tachycardia is present is associated with worse prognosis. This is particularly true if calcium channel blockers, such as verapamil, are used to attempt to terminate a presumed supraventricular tachycardia. Therefore, it is wisest to assume that all wide complex tachycardia is VT until proven otherwise.ECG features of Ventricular Tachycardia in addition to the increased Heart rate are: i) A wide QRS Complex ( Because the ectopics for the generation of the cardiac impulse originates in the Ventricular Myocyte and propagated via the intermyocyte conduction, which is a delayed conduction) ii) A Josephsons sign where there is the notch in the downsloping of the S wave near its nadir.(Considered very specific for the VT). iii) Capture beats (Normal QRS complex in between when the Heart pick up the sinus rhythm from the impulses generated by the SA node), fusion beats ( due to the fusion of the Abnormal and the Normal QRS complexes) which has a unique morphology . iv) Positive or negative concordance. v) Extreme Axis deviation or NORTH WEST axis . ( Axis between -90 to +180 degrees) Classification Ventricular tachycardia can be classified based on its morphology: Monomorphic ventricular tachycardia means that the appearance of all the beats match each other in each lead of a surface electrocardiogram (ECG). Scar-related monomorphic ventricular tachycardia is the most common type and a frequent cause of death in patients having survived a heart attack, especially if they have weak heart muscle. Right ventricular outflow tract (RVOT) tachycardia is a type of monomorphic ventricular tachycardia originating in the right ventricular outflow tract. RVOT morphology refers to the characteristic pattern of this type of tachycardia on an ECG. The source of the re-entry circuit can be identified by evaluating the morphology of the QRS complex in the V1 lead of a surface ECG. If the R wave is dominant (consistent with a right bundle branch block morphology), this indicates the origin of the VT is the left ventricle. Conversely, if the S wave is dominant (consistent with a left bundle branch block morphology, this is consistent with VT originating from the right ventricle or interventricular septum. Polymorphic ventricular tachycardia, on the other hand, has beat-to-beat variations in morphology. This may appear as a cyclical progressive change in cardiac axis, previously referred to by its French name torsades de pointes ("twisting of the spikes"). However, at the current time, the term torsades de pointes is reserved for polymorphic VT occurring in the context of a prolonged resting QT interval.Another way to classify ventricular tachycardias is the duration of the episodes: Three or more beats in a row on an ECG that originate from the ventricle at a rate of more than 120 beats per minute constitute a ventricular tachycardia. If the fast rhythm self-terminates within 30 seconds, it is considered a non-sustained ventricular tachycardia. If the rhythm lasts more than 30 seconds, it is known as a sustained ventricular tachycardia (even if it terminates on its own after 30 seconds).A third way to classify ventricular tachycardia is on the basis of its symptoms: Pulseless VT is associated with no effective cardiac output, hence, no effective pulse, and is a cause of cardiac arrest (see also: pulseless electrical activity [PEA]). In this circumstance, it is best treated the same way as ventricular fibrillation (VF), and is recognized as one of the shockable rhythms on the cardiac arrest protocol. Some VT is associated with reasonable cardiac output and may even be asymptomatic. The heart usually tolerates this rhythm poorly in the medium to long term, and patients may certainly deteriorate to pulseless VT or to VF.Occasionally in ventricular tachycardia, supraventricular impulses are conducted to the ventricles, generating QRS complexes with normal or aberrant supraventricular morphology (ventricular capture). Or, those impulses can be merged with complexes that are originated in the ventricle and produce a summation pattern (fusion complexes).Less common is ventricular tachycardia that occurs in individuals with structurally normal hearts. This is known as idiopathic ventricular tachycardia and in the monomorphic form coincides with little or no increased risk of sudden cardiac death. In general, idiopathic ventricular tachycardia occurs in younger individuals diagnosed with VT. While the causes of idiopathic VT are not known, in general it is presumed to be congenital, and can be brought on by any number of diverse factors. Treatment Therapy may be directed either at terminating an episode of the abnormal heart rhythm or at reducing the risk of another VT episode. The treatment for stable VT is tailored to the specific person, with regard to how well the individual tolerates episodes of ventricular tachycardia, how frequently episodes occur, their comorbidities, and their wishes. Individuals with pulseless VT or unstable VT are hemodynamically compromised and require immediate electric cardioversion to shock them out of the VT rhythm. Cardioversion If a person still has a pulse, it is usually possible to terminate the episode using electric cardioversion. This should be synchronized to the heartbeat if the waveform is monomorphic if possible, in order to avoid degeneration of the rhythm to ventricular fibrillation. An initial energy of 100J is recommended. If the waveform is polymorphic, then higher energies and an unsynchronized shock should be provided (also known as defibrillation). Defibrillation A person with pulseless VT is treated the same as ventricular fibrillation with high-energy (360J with a monophasic defibrillator, or 200J with a biphasic defibrillator) unsynchronised cardioversion (defibrillation). They will be unconscious. The shock may be delivered to the outside of the chest using the two pads of an external defibrillator, or internally to the heart by an implantable cardioverter-defibrillator (ICD) if one has previously been inserted.An ICD may also be set to attempt to overdrive pace the ventricle. Pacing the ventricle at a rate faster than the underlying tachycardia can sometimes be effective in terminating the rhythm. If this fails after a short trial, the ICD will usually stop pacing, charge up and deliver a defibrillation grade shock. Medication For those who are stable with a monomorphic waveform the medications procainamide or sotalol may be used and are better than lidocaine. Evidence does not show that amiodarone is better than procainamide.As a low magnesium level in the blood is a common cause of VT, magnesium sulfate can be given for torsades de pointes or if a low blood magnesium level is found/suspected.Long-term anti-arrhythmic therapy may be indicated to prevent recurrence of VT. Beta-blockers and a number of class III anti-arrhythmics are commonly used, such as the beta-blockers carvedilol, metoprolol, and bisoprolol, and the Potassium-Channel-Blockers amiodarone, dronedarone, bretylium, sotalol, ibutilide, and dofetilide. Angiotensin-converting-enzyme (ACE) inhibitors and aldosterone antagonists are also sometimes used in this setting. Invasive treatment An ICD (implantable cardioverter defibrillator ) is more effective than drug therapy for prevention of sudden cardiac death due to VT and VF, but does not prevent these rhythm from happening. Catheter ablation is a potentially definitive treatment option for those with recurrent VT. Remote magnetic navigation is one effective method to do the procedure.In the past, ablation was often not considered until pharmacological options had been exhausted, often after the patient had developed substantial morbidity from recurrent episodes of VT and ICD shocks. Antiarrhythmic medications can reduce the frequency of ICD therapies, but have efficacy varies and side effects can be significant. Advances in technology and understanding of VT substrates now allow ablation of multiple and unstable VTs with acceptable safety and efficacy, even in patients with advanced heart disease. References == External links ==

Hey Aarogya, explain a situation where Pyogenic granuloma occurs

Pyogenic granuloma

A pyogenic granuloma or lobular capillary hemangioma is a vascular tumor that occurs on both mucosa and skin, and appears as an overgrowth of tissue due to irritation, physical trauma, or hormonal factors. It is often found to involve the gums, skin, or nasal septum, and has also been found far from the head, such as in the thigh.Pyogenic granulomas may be seen at any age, and are more common in females than males. In pregnant women, lesions may occur in the first trimester with an increasing incidence until the seventh month, and are often seen on the gums. Signs and symptoms The appearance of pyogenic granuloma is usually a color ranging from red/pink to purple, grows rapidly, and can be smooth or mushroom-shaped. Younger lesions are more likely to be red because of their high number of blood vessels. Older lesions begin to change into a pink color. Size commonly ranges from a few millimeters to centimeters, though smaller or larger lesions may occur. A pyogenic granuloma can be painful, especially if located in an area of the body where it is constantly disturbed. Pyogenic granulomas can grow rapidly and often bleed profusely with little or no trauma. They may exude an oil-like substance, causing the surface to be damp. This is especially true if the granuloma is located on the scalp.Epulis granulomatosum is a variant of pyogenic granuloma that forms only on gingiva, and is often seen forming in a recent extraction socket. Pyogenic granulomas appear on the gingiva in 75% of cases, more often in the maxillary than mandibular jaw. Anterior areas are more often affected than posterior areas. It can also be found on the lips, tongue, and inner cheek. Poor oral hygiene or trauma are usually precipitating factors.One study has suggested a correlation between pyogenic granulomas and Bartonella seropositivity. However, this association has been questioned by others. The microscopic appearance of a pyogenic granuloma consists of highly vascular granulation tissue. Inflammation is present. The lesion may have a fibrous character if it is older, and the surface may have ulcerations. Pyogenic granulomas rarely occur in the conjunctiva, cornea, or connective tissue of the eye following minor local trauma. Grossly, these mass lesions resemble those occurring at more common sites. The relationship of these lesions to lobular capillary hemangiomas of skin and oropharyngeal mucosa commonly referred to as pyogenic granuloma is uncertain. Associated conditions Due to its overwhelming incidence on the gingiva, the condition is often associated with two other diseases, though not because they occur together. Instead, the three are associated with each other because they appear frequently on gingiva—peripheral giant cell granuloma and peripheral ossifying fibroma. Detailed analysis can be used to distinguish these conditions. Cause Pyogenic granulomas are caused by proliferation of capillaries and are not caused by infection or cancer. Diagnosis A doctor likely can diagnose a pyogenic granuloma based on its appearance, and might perform a biopsy to make a more accurate diagnosis. A biopsy also helps rule out malignant (cancerous) medical conditions that can cause a similar kind of growth. These conditions include squamous-cell carcinoma, basal-cell carcinoma, and melanoma.Histopathological examination shows multiple capillaries (due to the vascular nature of the tumor), neutrophils (pyogenic), and necrotic tissue. Management Although pyogenic granulomas are not infectious or cancer, treatment may be considered because of bleeding or ulceration. Frequently, they are treated with electrodesiccation (cauterization) and curettage (excision), though laser treatment using pulsed dye laser or CO2 laser is often effective.Several reports have demonstrated the efficacy of topical application of the beta-adrenergic antagonist timolol in the treatment of pediatric pyogenic granuloma.Usually, no treatment is used if the pyogenic granuloma occurs during pregnancy, since the lesion may heal spontaneously. Recurrent bleeding in either oral or nasal lesions may necessitate excision and cauterization sooner, however. If aesthetics are a concern, then treatment may be pursued, as well. Usually, only minor surgery may be needed, along with a dental cleaning for oral lesions to remove any calculus or other source of irritation. For nasal lesions, nose-picking should be discouraged. History Pyogenic granulomas were first described in 1897 by two French surgeons, Antonin Poncet and Dor, who named these lesions botryomycosis hominis. Terminology The name "pyogenic granuloma" is misleading, as it is neither pyogenic or a true granuloma. In actuality, it is a capillary hemangioma of lobular subtype, which is why such a lesion is prone to bleeding. It is also not truly pyogenic (pus-producing), as the cause is hormonal or traumatic and has no association with infection or pus production. See also Trumpeters wart List of cutaneous conditions References == External links ==

Aarogya, give me a short description about Vitamin B6

Vitamin B6

Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosphate, serves as a coenzyme in more than 140 enzyme reactions in amino acid, glucose, and lipid metabolism.Plants synthesize pyridoxine as a means of protection from the ultraviolet-B radiation of sunlight and to participate in synthesis of chlorophyll. Animals cannot synthesize any of the various forms of the vitamin, and hence must obtain it via diet, either of plants, or of other animals. There is some absorption of the vitamin produced by intestinal bacteria, but this is not sufficient to meet needs. For adult humans, recommendations from various countries food regulatory agencies are in the range of 1.0 to 2.0 milligrams (mg) per day. These same agencies also recognize ill effects from intakes that are too high, and so set safe upper limits, ranging from as low as 25 mg/day to as high as 100 mg/day depending on the country. Beef, pork, fowl and fish are generally good sources; dairy, eggs, mollusks and crustaceans also contain vitamin B6, but at lower levels. There is enough in a wide variety of plant foods so that a vegetarian or vegan diet does not put consumers at risk for deficiency.Dietary deficiency is rare. Classic clinical symptoms include rash and inflammation around the mouth and eyes, plus neurological effects that include drowsiness and peripheral neuropathy affecting sensory and motor nerves in the hands and feet. In addition to dietary shortfall, deficiency can be the result of anti-vitamin drugs. There are also rare genetic defects that can trigger vitamin B6 deficiency-dependent epileptic seizures in infants. These are responsive to pyridoxal 5-phosphate therapy. Definition Vitamin B6 is a water-soluble vitamin, one of the B vitamins. The vitamin actually comprises a group of six chemically related compounds, i.e., vitamers, that all contain a pyridine ring as their core. These are pyridoxine, pyridoxal, pyridoxamine, and their respective phosphorylated derivatives pyridoxine 5-phosphate, pyridoxal 5-phosphate and pyridoxamine 5-phosphate. Pyridoxal 5-phosphate has the highest biological activity, but the others are convertible to that form. Vitamin B6 serves as a co-factor in more than 140 cellular reactions, mostly related to amino acid biosynthesis and catabolism, but is also involved in fatty acid biosynthesis and other physiological functions. Forms Because of its chemical stability, pyridoxine hydrochloride is the form most commonly given as vitamin B6 dietary supplement. Absorbed pyridoxine (PN) is converted to pyridoxamine 5-phosphate (PMP) by the enzyme pyridoxal kinase, with PMP further converted to pyridoxal 5-phosphate (PLP), the metabolically active form, by the enzymes pyridoxamine-phosphate transaminase or pyridoxine 5-phosphate oxidase, the latter of which also catalyzes the conversion of pyridoxine 5′-phosphate (PNP) to PLP. Pyridoxine 5-phosphate oxidase is dependent on flavin mononucleotide (FMN) as a cofactor produced from riboflavin (vitamin B2). For degradation, in a non-reversible reaction, PLP is catabolized to 4-pyridoxic acid, which is excreted in urine. Synthesis Biosynthesis Two pathways for PLP are currently known: one requires deoxyxylulose 5-phosphate (DXP), while the other does not, hence they are known as DXP-dependent and DXP-independent. These pathways have been studied extensively in Escherichia coli and Bacillus subtilis, respectively. Despite the disparity in the starting compounds and the different number of steps required, the two pathways possess many commonalities. The DXP-dependent pathway: Commercial synthesis The starting material is either the amino acid alanine, or propionic acid converted into alanine via halogenation and amination. Then, the procedure accomplishes the conversion of the amino acid into pyridoxine through the formation of an oxazole intermediate followed by a Diels–Alder reaction, with the entire process referred to as the "oxazole method". The product used in dietary supplements and food fortification is pyridoxine hydrochloride, the chemically stable hydrochloride salt of pyridoxine. Pyridoxine is converted in the liver into the metabolically active coenzyme form pyridoxal 5-phosphate. At present, while the industry mainly utilizes the oxazole method, there is research exploring means of using less toxic and dangerous reagents in the process. Fermentative bacterial biosynthesis methods are also being explored, but are not yet scaled up for commercial production. Functions PLP is involved in many aspects of macronutrient metabolism, neurotransmitter synthesis, histamine synthesis, hemoglobin synthesis and function, and gene expression. PLP generally serves as a coenzyme (cofactor) for many reactions including decarboxylation, transamination, racemization, elimination, replacement, and beta-group interconversion. Amino acid metabolism Transaminases break down amino acids with PLP as a cofactor. The proper activity of these enzymes is crucial for the process of moving amine groups from one amino acid to another. To function as a transaminase coenzyme, PLP bound to a lysine of the enzyme then binds to a free amino acid via formation of a Schiffs base. The process then dissociates the amine group from the amino acid, releasing a keto acid, then transfers the amine group to a different keto acid to create a new amino acid. Serine racemase which synthesizes the neuromodulator D-serine from its enantiomer is a PLP-dependent enzyme. PLP is a coenzyme needed for the proper function of the enzymes cystathionine synthase and cystathionase. These enzymes catalyze reactions in the catabolism of methionine. Part of this pathway (the reaction catalyzed by cystathionase) also produces cysteine. Selenomethionine is the primary dietary form of selenium. PLP is needed as a cofactor for the enzymes that allow selenium to be used from the dietary form. PLP also plays a cofactor role in releasing selenium from selenohomocysteine to produce hydrogen selenide, which can then be used to incorporate selenium into selenoproteins. PLP is required for the conversion of tryptophan to niacin, so low vitamin B6 status impairs this conversion. Neurotransmitters PLP is a cofactor in the biosynthesis of five important neurotransmitters: serotonin, dopamine, epinephrine, norepinephrine, and gamma-aminobutyric acid. Glucose metabolism PLP is a required coenzyme of glycogen phosphorylase, the enzyme necessary for glycogenolysis. Glycogen serves as a carbohydrate storage molecule, primarily found in muscle, liver and brain. Its breakdown frees up glucose for energy. PLP also catalyzes transamination reactions that are essential for providing amino acids as a substrate for gluconeogenesis, the biosynthesis of glucose. Lipid metabolism PLP is an essential component of enzymes that facilitate the biosynthesis of sphingolipids. Particularly, the synthesis of ceramide requires PLP. In this reaction, serine is decarboxylated and combined with palmitoyl-CoA to form sphinganine, which is combined with a fatty acyl-CoA to form dihydroceramide. This compound is then further desaturated to form ceramide. In addition, the breakdown of sphingolipids is also dependent on vitamin B6 because sphingosine-1-phosphate lyase, the enzyme responsible for breaking down sphingosine-1-phosphate, is also PLP-dependent. Hemoglobin synthesis and function PLP aids in the synthesis of hemoglobin, by serving as a coenzyme for the enzyme aminolevulinic acid synthase. It also binds to two sites on hemoglobin to enhance the oxygen binding of hemoglobin. Gene expression PLP has been implicated in increasing or decreasing the expression of certain genes. Increased intracellular levels of the vitamin lead to a decrease in the transcription of glucocorticoids. Vitamin B6 deficiency leads to the increased gene expression of albumin mRNA. Also, PLP influences expression of glycoprotein IIb by interacting with various transcription factors; the result is inhibition of platelet aggregation. In plants Plant synthesis of vitamin B6 contributes to protection from sunlight. Ultraviolet-B radiation (UV-B) from sunlight stimulates plant growth, but in high amounts can increase production of tissue-damaging reactive oxygen species (ROS), i.e., oxidants. Using Arabidopsis thaliana (common name: thale cress), researchers demonstrated that UV-B exposure increased pyridoxine biosynthesis, but in a mutant variety, pyridoxine biosynthesis capacity was not inducible, and as a consequence, ROS levels, lipid peroxidation, and cell proteins associated with tissue damage were all elevated. Biosynthesis of chlorophyll depends on aminolevulinic acid synthase, a PLP-dependent enzyme that uses succinyl-CoA and glycine to generate aminolevulinic acid, a chlorophyll precursor. In addition, plant mutants with severely limited capacity to synthesize vitamin B6 have stunted root growth, because synthesis of plant hormones such as auxin require the vitamin as an enzyme cofactor. Medical uses Isoniazid is an antibiotic used for the treatment of tuberculosis. Common side effect include numbness in the hands and feet, also known as peripheral neuropathy. Co-treatment with vitamin B6 alleviates the numbness.Overconsumption of seeds from Ginkgo biloba can deplete vitamin B6, because the ginkgotoxin is an anti-vitamin (vitamin antagonist). Symptoms include vomiting and generalized convulsions. Ginkgo seed poisoning can be treated with vitamin B6. Dietary recommendations The US National Academy of Medicine updated Dietary Reference Intakes for many vitamins in 1998. Recommended Dietary Allowances (RDAs), expressed as milligrams per day, increase with age from 1.2 to 1.5 mg/day for women and from 1.3 to 1.7 mg/day for men. The RDA for pregnancy is 1.9 mg/day, for lactation, 2.0 mg/day. For children ages 1–13 years the RDA increases with age from 0.5 to 1.0 mg/day. As for safety, Tolerable upper intake levels (ULs) for vitamins and minerals are identified when evidence is sufficient. In the case of vitamin B6 the adult UL is set at 100 mg/day.The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA. For women and men ages 15 and older the PRI is set at 1.6 and 1.7 mg/day, respectively; for pregnancy 1.8 mg/day, for lactation 1.7 mg/day. For children ages 1–14 years the PRIs increase with age from 0.6 to 1.4 mg/day. The EFSA also reviewed the safety question and set its UL at 25 mg/day.The Japanese Ministry of Health, Labour and Welfare updated its vitamin and mineral recommendations in 2015. The adult RDAs are at 1.2 mg/day for women 1.4 mg/day for men. The RDA for pregnancy is 1.4 mg/day, for lactation is 1.5 mg/day. For children ages 1–17 years the RDA increases with age from 0.5 to 1.5 mg/day. The adult UL was set at 40–45 mg/day for women and 50–60 mg/day for men, with the lower values in those ranges for adults over 70 years of age. Safety Adverse effects have been documented from vitamin B6 dietary supplements, but never from food sources. Even though it is a water-soluble vitamin and is excreted in the urine, doses of pyridoxine in excess of the dietary upper limit (UL) over long periods cause painful and ultimately irreversible neurological problems. The primary symptoms are pain and numbness of the extremities. In severe cases, motor neuropathy may occur with "slowing of motor conduction velocities, prolonged F wave latencies, and prolonged sensory latencies in both lower extremities", causing difficulty in walking. Sensory neuropathy typically develops at doses of pyridoxine in excess of 1,000 mg per day, but adverse effects can occur with much less, so intakes over 200 mg/day are not considered safe. Trials with amounts equal to or less than 200 mg/day established that as a "No-observed-adverse-effect level", meaning the highest amount at which no adverse effects were observed. This was divided by two to allow for people who might be extra sensitive to the vitamin, referred to as an "uncertainty factor", resulting in the aforementioned adult UL of 100 mg/day. Labeling For US food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value. For vitamin B6 labeling purposes 100% of the Daily Value was 2.0 mg, but as of May 27, 2016 it was revised to 1.7 mg to bring it into agreement with the adult RDA. A table of the old and new adult daily values is provided at Reference Daily Intake. Sources Bacteria residing in the large intestine are known to synthesize B-vitamins, including B6, but the amounts are not sufficient to meet host requirements, in part because the vitamins are competitively taken up by non-synthesizing bacteria.Vitamin B6 is found in a wide variety of foods. In general, meat, fish and fowl are good sources, but dairy foods and eggs are not (table). Crustaceans and mollusks contain about 0.1 mg/100 grams. Fruit (apples, oranges, pears) contain less than 0.1 mg/100g.Bioavailability from a mixed diet (containing animal- and plant-sourced foods) is estimated at being 75% – higher for PLP from meat, fish and fowl, lower from plants, as those are mostly in the form of pyridoxine glucoside, which has approximately half the bioavailability of animal-sourced B6 because removal of the glucoside by intestinal cells is not 100% efficient. Given lower amounts and lower bioavailability of the vitamin from plants there was a concern that a vegetarian or vegan diet could cause a vitamin deficiency state. However, the results from a population-based survey conducted in the U.S. demonstrated that despite a lower vitamin intake, serum PLP was not significantly different between meat-eaters and vegetarians, suggesting that a vegetarian diet does not pose a risk for vitamin B6 deficiency.Cooking, storage, and processing losses vary, and in some foods may be more than 50% depending on the form of vitamin present in the food. Plant foods lose less during processing, as they contain pyridoxine, which is more stable than the pyridoxal or pyridoxamine forms found in animal-sourced foods. For example, milk can lose 30–70% of its vitamin B6 content when dried. The vitamin is found in the germ and aleurone layer of grains, so there is more in whole wheat bread compared to white bread wheat, and more in brown rice compared to white rice.Most values shown in the table are rounded to nearest tenth of a milligram: Fortification As of 2019, fourteen countries require food fortification of wheat flour, maize flour or rice with vitamin B6 as pyridoxine hydrochloride. Most of these are in southeast Africa or Central America. The amounts stipulated range from 3.0 to 6.5 mg/kg. An additional seven countries, including India, have a voluntary fortification program. India stipulates 2.0 mg/kg. Dietary supplements In the US, multi-vitamin/mineral products typically contain 2 to 4 mg of vitamin B6 per daily serving as pyridoxine hydrochloride, but a few contain more than 25 mg. Many US dietary supplement companies also market a B6-only dietary supplement with 100 mg per daily serving. While the US National Academy of Medicine sets an adult safety UL at 100 mg/day, the European Food Safety Authority sets its UL at 25 mg/day. Health claims The Japanese Ministry of Health, Labour, and Welfare (MHLW) set up the Foods for Specified Health Uses (特定保健用食品; FOSHU) regulatory system in 1991 to individually approve the statements made on food labels concerning the effects of foods on the human body. The regulatory range of FOSHU was later broadened to allow for the certification of capsules and tablets. In 2001, MHLW enacted a new regulatory system, Foods with Health Claims (保健機能食品; FHC), which consists of the existing FOSHU system and the newly established Foods with Nutrient Function Claims (栄養機能表示食品; FNFC), under which claims were approved for any product containing a specified amount per serving of 12 vitamins, including vitamin B6, and two minerals. To make a health claim based on a foods vitamin B6 content, the amount per serving must be in the range of 0.3–25 mg. The allowed claim is: "Vitamin B6 is a nutrient that helps produce energy from protein and helps maintain healthy skin and mucous membranes."In 2010, the European Food Safety Authority (EFSA) published a review of proposed health claims for vitamin B6, disallowing claims for bone, teeth, hair skin and nails, and allowing claims that the vitamin provided for normal homocysteine metabolism, normal energy-yielding metabolism, normal psychological function, reduced tiredness and fatigue, and provided for normal cysteine synthesis.The US Food and Drug Administration (FDA) has several processes for permitting health claims on food and dietary supplement labels. There are no FDA-approved Health Claims or Qualified Health Claims for vitamin B6. Structure/Function Claims can be made without FDA review or approval as long as there is some credible supporting science. Examples for this vitamin are "Helps support nervous system function" and "Supports healthy homocysteine metabolism." Absorption, metabolism and excretion Vitamin B6 is absorbed in the jejunum of the small intestine by passive diffusion. Even extremely large amounts are well absorbed. Absorption of the phosphate forms involves their dephosphorylation catalyzed by the enzyme alkaline phosphatase. Most of the vitamin is taken up by the liver. There, the dephosphorylated vitamins are converted to the phosphorylated PLP, PNP and PMP, with the two latter converted to PLP. In the liver, PLP is bound to proteins, primarily albumin. The PLP-albumin complex is what is released by the liver to circulate in plasma. Protein-binding capacity is the limiting factor for vitamin storage. Total body stores, the majority in muscle, with a lesser amount in liver, have been estimated to be in the range of 61 to 167 mg.Enzymatic processes utilize PLP as a phosphate-donating cofactor. PLP is restored via a salvage pathway that requires three key enzymes, pyridoxal kinase, pyridoxine 5-phosphate oxidase, and phosphatases. Inborn errors in the salvage enzymes are known to cause inadequate levels of PLP in the cell, particularly in neuronal cells. The resulting PLP deficiency is known to cause or implicated in several pathologies, most notably infant epileptic seizures.The end-product of vitamin B6 catabolism is 4-pyridoxic acid, which makes up about half of the B6 compounds in urine. 4-Pyridoxic acid is formed by the action of aldehyde oxidase in the liver. Amounts excreted increase within 1–2 weeks with vitamin supplementation and decrease as rapidly after supplementation ceases. Other vitamin forms excreted in the urine include pyridoxal, pyridoxamine and pyridoxine, and their phosphates. When large doses of pyridoxine are given orally, the proportion of these other forms increases. A small amount of vitamin B6 is also excreted in the feces. This may be a combination of unabsorbed vitamin and what was synthesized by large intestine microbiota. Deficiency Signs and symptoms The classic clinical syndrome for vitamin B6 deficiency is a seborrhoeic dermatitis-like eruption, atrophic glossitis with ulceration, angular cheilitis, conjunctivitis, intertrigo, and neurologic symptoms of somnolence, confusion, and neuropathy (due to impaired sphingosine synthesis) and microcytic anemia (due to impaired heme synthesis).Less severe cases present with metabolic disease associated with insufficient activity of the coenzyme PLP. The most prominent of the lesions is due to impaired tryptophan–niacin conversion. This can be detected based on urinary excretion of xanthurenic acid after an oral tryptophan load. Vitamin B6 deficiency can also result in impaired transsulfuration of methionine to cysteine. The PLP-dependent transaminases and glycogen phosphorylase provide the vitamin with its role in gluconeogenesis, so deprivation of vitamin B6 results in impaired glucose tolerance. Diagnosis The assessment of vitamin B6 status is essential, as the clinical signs and symptoms in less severe cases are not specific. The three biochemical tests most widely used are plasma PLP concentrations, the activation coefficient for the erythrocyte enzyme aspartate aminotransferase, and the urinary excretion of vitamin B6 degradation products, specifically urinary PA. Of these, plasma PLP is probably the best single measure, because it reflects tissue stores. Plasma PLP of less than 10 nmol/l is indicative of vitamin B6 deficiency. A PLP concentration greater than 20 nmol/l has been chosen as a level of adequacy for establishing Estimated Average Requirements and Recommended Daily Allowances in the USA. Urinary PA is also an indicator of vitamin B6 deficiency; levels of less than 3.0 mmol/day is suggestive of vitamin B6 deficiency. Other methods of measurement, including UV spectrometric, spectrofluorimetric, mass spectrometric, thin-layer and high-performance liquid chromatographic, electrophoretic, electrochemical, and enzymatic, have been developed.The classic clinical symptoms for vitamin B6 deficiency are rare, even in developing countries. A handful of cases were seen between 1952 and 1953, particularly in the United States, having occurred in a small percentage of infants who were fed a formula lacking in pyridoxine. Causes A deficiency of vitamin B6 alone is relatively uncommon and often occurs in association with other vitamins of the B complex. Evidence exists for decreased levels of vitamin B6 in women with type 1 diabetes and in patients with systemic inflammation, liver disease, rheumatoid arthritis, and those infected with HIV. Use of oral contraceptives and treatment with certain anticonvulsants, isoniazid, cycloserine, penicillamine, and hydrocortisone negatively impact vitamin B6 status. Hemodialysis reduces vitamin B6 plasma levels. Genetic defects Genetically confirmed diagnoses of diseases affecting vitamin B6 metabolism (ALDH7A1 deficiency, pyridoxine-5-phosphate oxidase deficiency, PLP binding protein deficiency, hyperprolinaemia type II and hypophosphatasia) can trigger vitamin B6 deficiency-dependent epileptic seizures in infants. These are responsive to pyridoxal 5-phosphate therapy. History An overview of the history was published in 2012. In 1934, the Hungarian physician Paul György discovered a substance that was able to cure a skin disease in rats (dermatitis acrodynia). He named this substance vitamin B6, as numbering of the B vitamins was chronological, and pantothenic acid had been assigned vitamin B5 in 1931. In 1938, Richard Kuhn was awarded the Nobel Prize in Chemistry for his work on carotenoids and vitamins, specifically B2 and B6. Also in 1938, Samuel Lepkovsky isolated vitamin B6 from rice bran. A year later, Stanton A. Harris and Karl August Folkers determined the structure of pyridoxine and reported success in chemical synthesis, and then in 1942 Esmond Emerson Snell developed a microbiological growth assay that led to the characterization of pyridoxamine, the aminated product of pyridoxine, and pyridoxal, the formyl derivative of pyridoxine. Further studies showed that pyridoxal, pyridoxamine, and pyridoxine have largely equal activity in animals and owe their vitamin activity to the ability of the organism to convert them into the enzymatically active form pyridoxal-5-phosphate.Following a recommendation of IUPAC-IUB in 1973, vitamin B6 is the official name for all 2-methyl,3-hydroxy,5-hydroxymethylpyridine derivatives exhibiting the biological activity of pyridoxine. Moreover, pyridoxine alone should not to be used as a synonym of vitamin B6. Research Observational studies suggested an inverse correlation between a higher intake of vitamin B6 and all cancers, with the strongest evidence for gastrointestinal cancers. However, evidence from a review of randomized clinical trials did not support a protective effect. The authors noted that high B6 intake may be an indicator of higher consumption of other dietary protective micronutrients. A review and two observational trials reporting lung cancer risk reported that serum vitamin B6 was lower in people with lung cancer compared to people without lung cancer, but did not incorporate any intervention or prevention trials.According to a prospective cohort study the long-term use of vitamin B6 from individual supplement sources at greater than 20 mg per day, which is more than ten times the adult male RDA of 1.7 mg/day, was associated with an increased risk for lung cancer among men. Smoking further elevated this risk. However, a more recent review of this study suggested that a causal relationship between supplemental vitamin B6 and an increased lung cancer risk cannot be confirmed yet.For coronary heart disease, a meta-analysis reported lower relative risk for a 0.5 mg/day increment in dietary vitamin B6 intake. As of 2021, there were no published reviews of randomized clinical trials for coronary heart disease or cardiovascular disease. In reviews of observational and intervention trials, neither higher vitamin B6 concentrations nor treatment showed any significant benefit on cognition and dementia risk. Low dietary vitamin B6 correlated with a higher risk of depression in women but not in men. When treatment trials were reviewed, no meaningful treatment effect for depression was reported, but a subset of trials in pre-menopausal women suggested a benefit, with a recommendation that more research was needed. The results of several trials with children diagnosed as having autism spectrum disorder (ASD) treated with high dose vitamin B6 and magnesium did not result in treatment effect on the severity of symptoms of ASD. References External links The B6 database A database of B6-dependent enzymes at University of Parma Vitamin+B6 at the US National Library of Medicine Medical Subject Headings (MeSH)

Hey Aarogya, explain a situation where Rapid eye movement sleep behavior disorder occurs

Rapid eye movement sleep behavior disorder

Rapid eye movement sleep behavior disorder or REM behavior disorder (RBD) is a sleep disorder in which people act out their dreams. It involves abnormal behavior during the sleep phase with rapid eye movement (REM) sleep. The major feature of RBD is loss of muscle atonia (i.e., the loss of paralysis) during otherwise intact REM sleep (during which paralysis is not only normal but necessary). The loss of motor inhibition leads to sleep behaviors ranging from simple limb twitches to more complex integrated movements that can be violent or result in injury to either the individual or their bedmates.RBD is a very strong predictor of progression to a synucleinopathy (usually Parkinsons disease or dementia with Lewy bodies). Melatonin is useful in the treatment of RBD. RBD was first described in 1986. Classification RBD is a parasomnia. It is categorized as either idiopathic or symptomatic. Idiopathic RBD is the term used when RBD is not associated with another ongoing neurological condition. When it results from an identifiable cause, RBD is referred to as symptomatic RBD (and considered a symptom of the underlying disorder). Characteristics RBD is characterized by the dreamer acting out their dreams, with complex behaviors. These dreams often involve screaming, shouting, laughing, crying, arm flailing, kicking, punching, choking, and jumping out of bed. The actions in an episode can result in injuries to oneself or ones bedmate. The sleeping person may be unaware of these movements. Dreams often involve violent or aggressive actions, and an attack theme like being chased by people or animals. Because violence in dreams is more likely to be recalled, this could be an artifact of recall bias or selection bias. The individual with RBD may not be aware of having it. When awakened, people may be able to recall the dream they were having, which will match the actions they were performing.As the first indication of an underlying neurodegenerative disorder or synucleinopathy, symptoms of RBD may begin years or decades before the onset of another condition. Abnormal sleep behaviors may begin decades before any other symptoms, often as the first clinical indication if another condition.Symptomatic RBD can also be associated with narcolepsy, Guillain–Barré syndrome, limbic encephalitis, and Morvans syndrome.Other symptoms found in patients with RBD are reduced motor abilities, posture and gait changes, mild cognitive impairment, alterations in the sense of smell, impairments in color vision, autonomic dysfunction (orthostatic hypotension, constipation, urinary problems and sexual dysfunction), and depression. Causes Rapid eye movement behavior disorder occurs when there is a loss of normal voluntary muscle atonia during REM sleep resulting in motor behavior in response to dream content. It can be caused by adverse reactions to certain drugs or during drug withdrawal; however, it is most often associated with the elderly and in those with neurodegenerative disorders such as Parkinsons disease and other neurodegenerative diseases, for example multiple system atrophy and the Lewy body dementias.The underlying cause of RBD is not well understood, but it is likely that RBD is an early symptom of synucleinopathy rather than a separate disorder. Brainstem circuits that control atonia during REM sleep may be damaged, including those in the pontomedullary brainstem. REM sleep circuits are located in caudal brainstem structures—the same structures that are known to lead to be implicated in the synucleinopathies. Motor deficits like those seen in RBD are known to result from lesions in those circuits.Risk factors for developing RBD are a family history of acting out dreams, prior head injury, farming, exposure to pesticides, low education level, depression, and use of antidepressants.RBD may be acute and sudden in onset if associated with drug treatment or withdrawal (particularly with alcohol withdrawal). Antidepressant medications can induce or aggravate RBD symptoms. Diagnosis There are two ways to diagnose RBD: by documenting a history of complex, dream-enactment sleep behaviors, or by polysomnography recording of these behaviors along with REM sleep atonia loss.RBD may be established from clinical interview as well as several validated questionnaires, when sleep studies cannot be performed. Questionnaires such as the Rapid Eye Movement (REM) sleep Behavior Disorder Screening Questionnaire (RBDSQ), the REM Sleep Behavior Questionnaires – Hong-Kong (RBD-HK), the Mayo Sleep Questionnaire (MSQ) and the Innsbruck REM Sleep Behavior Disorder Inventory are well-validated. Individuals with RBD may not be able to provide a history of dream enactment behavior, so bed partners are also consulted. The REM Sleep Behavior Disorder Single-Question Screen offers diagnostic sensitivity and specificity in the absence of polysomnography with one question: "Have you ever been told, or suspected yourself, that you seem to act out your dreams while asleep (for example, punching, flailing your arms in the air, making running movements, etc.)?" Diagnostic criteria for RBD from the International Classification of Sleep Disorders (ICSD-3) are: Repetition of vocalizations and/or complex motor behaviors during sleep Polysomnography (PSG) show that these behaviors occur during REM sleep If documentation of these behaviors by PSG is not possible, they must at least be assumed to take place during REM sleep based on records of dream enactment REM sleep without atonia (RWA) can be seen in polysomnographic recordings Episodes cannot be explained by another mental disorder, sleep disorder, substance abuse or medication Differential Other conditions are similar to RBD in that individuals exhibit excessive sleep movement and potentially violent behavior. Such disorders include non-REM parasomnias (sleepwalking, sleep terrors), periodic limb movement disorder, severe obstructive sleep apnea, and dissociative disorders. Because of the similarities between the conditions, polysomnography plays an important role in confirming RBD diagnosis. Treatment RBD is treatable (even when the underlying synucleinopathies are not). Melatonin and clonazepam are the most frequently used, and are comparably effective, but melatonin offers a safer alternative, because clonazepam can produce undesirable side effects. Other medications and treatments are available, but have only anecdotal evidence.Medications that may worsen RBD and should be stopped if possible are tramadol, mirtazapine, antidepressants, and beta blockers.In addition to medication, it is wise to secure the sleepers environment by removing potentially dangerous objects from the bedroom and either place a cushion around the bed or move the mattress to the floor for added protection against injuries. In extreme cases, an affected individual has slept in a sleeping bag zipped up to their neck, wearing mittens so they cannot unzip it until they awake.Patients are advised to maintain a normal sleep schedule, avoid sleep deprivation, and keep track of any sleepiness they may have. Treatment includes regulating neurologic symptoms and treating any other sleep disorders that might interfere with sleep. Sleep deprivation, alcohol, certain medications, and other sleep disorders can all increase RBD and should be avoided if possible. Prognosis Patients with RBD are at risk for sleep-related injury.Almost 92% of patients with idiopathic RBD will go on to develop a neurodegenerative disorder. The disorders most strongly associated with RBD are the synucleinopathies, particularly Parkinsons disease, dementia with Lewy bodies, and to a lesser extent, multiple system atrophy. Most people with RBD will convert to a synucleinopathy—usually Parkinsons disease or dementia with Lewy bodies—within 4 to 9 years from diagnosis of RBD, and 11 to 16 years from onset of symptoms. Epidemiology RBD prevalence as of 2017 is estimated to be 0.5–2% overall, and 5–13% of those aged 60 to 99. It is more common in males overall, but equally frequent among men and women below the age of 50. This may partially be due to a referral bias, as violent activity carried out by men is more likely to result in harm and injury and is more likely to be reported than injury to male bed partners by women, or it may reflect a true difference in prevalence as a result of genetic or androgenic factors. Typical onset is in the 50s or 60s.Almost half of those with Parkinsons, at least 88% of those with multiple system atrophy, and about 80% of people with Lewy body dementia have RBD. RBD is a very strong predictor of progression to a synucleinopathy (for example, the Lewy body dementias). On autopsy, up to 98% of individuals with polysomnography-confirmed RBD are found to have a synucleinopathy. History In the 1960s and 1970s, Michel Jouvet described brain lesions in cats that led to loss of atonia in REM sleep. Carlos Schenck and Mark Mahowald and their team in Minnesota first described RBD in 1986. In animals RBD has also been diagnosed in animals; specifically dogs. See also Sleepwalk with Me Pseudobulbar affect Gelastic seizure References Further reading Roguski A, Rayment D, Whone AL, Jones MW, Rolinski M (2020). "A Neurologists Guide to REM Sleep Behavior Disorder". Front Neurol (Review). 11: 610. doi:10.3389/fneur.2020.00610. PMC 7360679. PMID 32733361.

Hello Aarogya, explain a situation where Rapid sequence induction occurs

Rapid sequence induction

In advanced airway management, rapid sequence induction (RSI) – also referred to as rapid sequence intubation or as rapid sequence induction and intubation (RSII) or as crash induction – is a special process for endotracheal intubation that is used where the patient is at a high risk of pulmonary aspiration. It differs from other techniques for inducing general anesthesia in that several extra precautions are taken to minimize the time between giving the induction drugs and securing the tube, during which period the patients airway is essentially unprotected.First described by William Stept and Peter Safar in 1970, "classical" or "traditional" RSI involves pre-filling the patients lungs with a high concentration of oxygen gas; applying cricoid pressure to occlude the esophagus; administering pre-determined doses of rapid-onset sedative and neuromuscular-blocking drugs (traditionally thiopentone and suxamethonium) that induce prompt unconsciousness and paralysis; avoiding any artificial positive-pressure ventilation by mask after the patient stops breathing (to minimize insufflation of air into the stomach, which might otherwise provoke regurgitation); inserting a cuffed endotracheal tube with minimal delay; and then releasing the cricoid pressure after the cuff is inflated, with ventilation being started through the tube. There is no consensus around the precise definition of the term "modified RSI", but it is used to refer to various modifications that deviate from the classic sequence – usually to improve the patients physiological stability during the procedure, at the expense of theoretically increasing the risk of regurgitation. Examples of such modifications include using various alternative drugs, omitting the cricoid pressure, or applying ventilation before the tube has been secured.The procedure is used where general anesthesia must be induced before the patient has had time to fast long enough to empty the stomach; where the patient has a condition that makes aspiration more likely during induction of anesthesia, regardless of how long they have fasted (such as gastroesophageal reflux disease or advanced pregnancy); or where the patient has become unable to protect their own airway even before anesthesia (such as after a traumatic brain injury). The induction drugs classically used for RSI have short durations of action, wearing off after only minutes. This confers a degree of fault tolerance on the procedure when it is used in elective or semi-elective settings: if intubation is unsuccessful, and if the clinical condition allows it, the procedure may be abandoned and the patient should regain the ability to protect their own airway sooner than would be the case under routine methods of induction. Conversely, in emergency settings where the patients condition does not allow for them to be woken up immediately, a failed intubation under RSI places them at very high risk for respiratory compromise. Common medications Premedication Premedication is used to reduce anxiety of those who are going to be intubated and to reduce the anticipated physiological response of the patient during intubation. Midazolam – It is a fast-acting and the most lipophilic of all benzodiazepine and rapidly crosses the blood–brain barrier. It is a gamma-aminobutyric acid (GABA) agonist. Usual doses for midazolam are 1 mg to 2 mg where the older people receive smaller doses and obese people receive higher doses. Midazolam is metabolised in the liver and is excreted through the kidneys. When midazolam is used alone, it has few side effects, but can cause respiratory depression if being used together with fentanyl. Fentanyl – It is a synthetic, centrally-acting opioid. It suppresses pain and sympathetic stimulation. Sympathetic stimulation can cause further injury to those with heart disease, aortic dissection, and aortic aneurysm. Fentanyl is ideal because of its rapid onset, lack of histamine release, high lipophilicity, and short duration of action. The dosage is between 1 and 3 μg/kg. It is metabolised by liver. The most significant side effect is respiratory depression. Atropine – The process of intubation can cause massive stimulation to vagus nerve, causing bradycardia (low heart rate). The people who are at increased risk of bradycardia are neonates and children. This does not happen in adults because sympathetic stimulation overpowers the vagal response. However, for those adults who have received drugs such as beta blocker, calcium channel blocker, and digoxin have an increased risk of developing bradycardia. Atropine is a muscarinic receptor antagonist, thus blocking the vagal response. The dose is 0.01 mg/kg. It has quick onset of action, and common side effects are: increased heart rate, dry mouth, flushing, and urinary retention. Lidocaine – It is used to reduce the sympathetic response in those who have suspected raised intracranial pressure (ICP) or those who received succinylcholine which also causes increase ICP or those with underlying asthma that have bronchospasm. Administration of lidocaine can causes reduction in mean arterial pressure (MAP). The dosage is 1.5 mg/kg. This drug is metabolised by liver. The side effects are: hypotension, arrythmia (irregular heart beat). Lidocaine can further interact with other drugs such as amiodarone and monoamine oxidase inhibitor to cause hypotension, and dronedarone to cause arrhythmia. Induction agents Administration of induction agents followed by neuromuscular blockade agents helps to achieve optimal conditions for intubation. Etomidate – It is an imidazole-derivative that stimulates GABA receptors. The dosage is between 0.2 and 0.6 mg/kg (commonly 20 to 50 mg doses). Dose reduction may be required in those with hypotension. Etomidate has minimal cardiovascular side effects, reduces intracerebral pressure (by reducing cerebral blood flow), and does not cause histamine release. It has quick onset of action, short duration of action, and undergoes hepatic elimination. Myoclonus, pain at the site of the injection, post-operative nausea and vomiting are common. It can also suppresses the production of cortisol and aldosterone. Ketamine – It is highly lipophilic and crosses the blood-brain barrier. It inhibits the binding of glutamine to N-Methyl-D-aspartic acid (NMDA) receptors in Thalamocortical radiations and limbic system, causing amnesia. Through the same blockade of NMDA receptor, ketamine is also effective as a painkiller. The dosage is 1 to 2 mg/kg, usually given at 100 mg. Ketamine is metabolised by liver and excreted through kidneys. The drug lessen the reuptake of the catecholamine, increases heart rate, blood pressure, and cardiac output, thus suitable for those with hypotension. However, it can worsen the cardiac depression and hypotension for those with depletion of catecholamines. Thus, maximum dose of 1.5 mg/kg is need for this situation. For those with head injuries, ketamine does not appear to increase intracranial pressure, while able to maintain the mean arterial pressure. Ketamine also relieves bronchospasm by relaxing bronchiolar smooth muscles. However, it increases oral secretions during intubation. Ketamine is associated with nightmares, delirium, and hallucinations. Propofol – It is a highly lipid-soluble, GABA agonist. The dosage is 1.5 mg/kg (usually 100 to 200 mg). It has quick onset of action, can cross the blood-brain barrier, wide tissue distribution, and can be cleared by the body quickly. In the elderly, the rate of propofol clearance is low. Therefore, lower doses of propofol (50 to 100 mg) should be given. It is suitable in those with kidney or liver impairment and decreases intra-cranial pressure. For those with bronchospasm, propofol also has mild bronchodilating effect. However, propofol can induce hypotension and bradycardia due to its calcium channel blocker and beta blocker properties. At prolonged high propofol dosages, it can induce propofol infusion syndrome. Pain during peripheral administration of propofol can be reduced by using a large bore cannula. Midazolam – Apart as a premedication, midazolam can be used as an induction agent at the dose of 0.2 to 0.3 mg/kg. It has slow onset of action when used alone, but the onset can be improved when using together with an opioid. However, for those with hypotension, midazolam can further reduce the blood pressure and has cardiac depressive effects. Therefore, dose reduction is required for the elderly, and for those with heart and liver failure. Methohexital – This is a GABA agonist. It works by reducing the dissociation of GABA from its receptors. The dosage is 1.5 mg/kg. It is metabolised in liver. However, methohexital can cause respiratory depression, venodilatation, myocardial depression, and hypotension. Additionally, it can also cause reduced cerebral blood flow and histamine release. It can cause distal thrombosis and tissue necrosis if given into the arterial system. Paralytics Paralytics are also known as neuromuscular-blocking drugs (NMB). NMB can reduce the complication rates of rapid sequence induction such as inadequate oxygenation of the blood, airway complications, and instability of the cardiovascular system. NMB can be divided into two types: depolarising and non-depolarising blockers. Depolarising blockers resembles the acetylcholine and activates the motor end-plate of the neuromuscular junction (NMJ). Meanwhile, non-depolarising blockers competitively blocks the NMJ without activating the motor end plate. Depolarising blockers Succinylcholine – This drug has rapid onset of action and fast duration. Its dosages are between 1 and 2 mg/kg body weight with common dosage of 100 mg. The drug can only be kept under room temperature for 14 days. Therefore, for longer shelf life, it has to be kept under temperatures from 3.3 °C (37.9 °F) to 8.7 °C (47.7 °F). When the intravenous access is not obtainable, the 3 to 4 mg/kg of intramuscular doses can be given (usual dose of 300 mg). However, duration of onset will be delayed to 3 to 4 minutes. Repetitive dosages of succinylcholine are discouraged to prevent vagal stimulation which leads to bradycardia. Non-depolarising blockers Rocuronium – The dosage of rocuronium is between 0.6 and 1.2 mg/kg. Since rocuronium has longer duration of onset, caution should be taken for those who are difficult to bag-mask ventilate. Vecuronium – The dosage of this drug is between 0.08 and 0.1 mg/kg. Vecuronium is only used when there is a shortage of drugs such as succinylcholine and rocuronium. Reversal agents Sugammadex – It is used as a reversal agent for rocuronium and vecuronium. It works by encapsulating the paralytic drug thus preventing it from acting on the binding sites. The dose of 16 mg/kg is used for immediate reversal after administration such as during RSI. Doses of 2 mg/kg and 4 mg/kg are used if the patient has twitches evident on a twitch monitor and terminates the rocuronium action within 3 minutes. The FDA initially did not approve Sugammadex due to concerns over potential allergic reactions, however it was subsequently approved on December 15, 2015 for use in the United States. Neostigmine – It can be used to reverse nondepolarizing neuromuscular blocking agents which cannot be reversed with sugammadex, although its onset is much slower. It works by competing with acetylcholine for the binding sites of acetylcholinesterase, which in turn prevents the breaking down of acetylcholine. The dosage is between 0.03 and 0.07 mg/kg. The side effect of this drug is bradycardia. Therefore, glycopyrrolate should be given together with neostigmine to prevent bradycardia. Other medications Thiopental Metaraminol or ephedrine, where hypotension may occur secondary to the sedating drugs. Phenylephrine – This drug is administered to those with hypotension post intubation as a result of lidocaine, midazolam, fentanyl, propofol, and ketamine. The dosages range from 50 to 200 μg in adults. It has quick onset and quick elimination. The common side effect is reflex bradycardia. Technique Rapid sequence intubation refers to the pharmacologically induced sedation and neuromuscular paralysis prior to intubation of the trachea. The technique is a quicker form of the process normally used to induce general anesthesia. A useful framework for describing the technique of RSI is the "seven Ps". Preparation The patient is assessed to predict the difficulty of intubation. Continuous physiological monitoring such as ECG and pulse oximetry is put on the patient. The equipment and drugs for the intubation are planned, including the endotracheal tube size, the laryngoscope size, and drug dosage. Drugs are prepared in syringes. Intravenous access is obtained to deliver the drugs, usually by placing one or two IV cannulae. Preoxygenation The aim of preoxygenation is to replace the nitrogen that forms the majority of the functional residual capacity with oxygen. This provides an oxygen reservoir in the lungs that will delay the depletion of oxygen in the absence of ventilation (after paralysis). For a healthy adult, this can lead to maintaining a blood oxygen saturation of at least 90% for up to 8 minutes. This time will be significantly reduced in obese patients, ill patients and children. Preoxygenation is usually performed by giving 100% oxygen via a tightly fitting face mask. Preoxygenation or a maximum of eight deep breaths over 60 seconds resulting in blood oxygenation is not different from that of quiet breathing volume for 3 minutes.Newer methods of preoxygenation include the use of a nasal cannula placed on the patient at 15 LPM at least 5 minutes prior to the administration of the sedation and paralytic drugs. High flow nasal oxygen has been shown to flush the nasopharynx with oxygen, and then when patients inspire they inhale a higher percentage of inspired oxygen. Small changes in FiO2 create dramatic changes in the availability of oxygen at the alveolus, and these increases result in marked expansion of the oxygen reservoir in the lungs prior to the induction of apnea. After apnea created by RSI the same high flow nasal cannula will help maintain oxygen saturation during efforts securing the tube (oral intubation). The use of nasal oxygen during pre-oxygenation and continued during apnea can prevent hypoxia before and during intubation, even in extreme clinical cases. Pretreatment Pretreatment consists of the medications given to specific groups of high-risk patients 3 minutes before the paralysis stage with the aim of protecting the patient from the adverse effects of introducing the laryngoscope and endotracheal tube. Intubation causes increased sympathetic activity, an increase in intracranial pressure and bronchospasm. Patients with reactive airway disease, increased intracranial pressure, or cardiovascular disease may benefit from pretreatment. Two common medications used in the pretreatment of RSI include Lidocaine and Atropine. Lidocaine has the ability to suppress the cough reflex which in turn may mitigate increased intracranial pressure. For this reason Lidocaine is commonly used as a pretreatment for trauma patients who are suspected of already having an increase in intracranial pressure. Although there is not yet definitive evidence to support this, if proper dosing is used it is safe. The typical dose is 1.5 mg/kg IV given three minutes prior to intubation. Atropine may also be used as a premedication agent in pediatrics to prevent bradycardia caused by hypoxia, laryngoscopy, and succinylcholine. Atropine is a parasympathetic blocker. The common premedication dose for atropine is 0.01–0.02 mg/kg. Paralysis with induction With standard intravenous induction of general anesthesia, the patient typically receives an opioid, and then a hypnotic medication. Generally the patient will be manually ventilated for a short period of time before a neuromuscular blocking agent is administered and the patient is intubated. During rapid sequence induction, the person still receives an IV opioid. However, the difference lies in the fact that the induction drug and neuromuscular blocking agent are administered in rapid succession with no time allowed for manual ventilation.Commonly used hypnotics include thiopental, propofol and etomidate. The neuromuscular blocking agents paralyze all of the skeletal muscles, most notably and importantly in the oropharynx, larynx, and diaphragm. Opioids such as fentanyl may be given to attenuate the responses to the intubation process (accelerated heart rate and increased intracranial pressure). This is supposed to have advantages in patients with ischemic heart disease and those with brain injury (e.g. after traumatic brain injury or stroke). Lidocaine is also theorized to blunt a rise in intracranial pressure during laryngoscopy, although this remains controversial and its use varies greatly. Atropine may be used to prevent a reflex bradycardia from vagal stimulation during laryngoscopy, especially in young children and infants. Despite their common use, such adjunctive medications have not been demonstrated to improve outcomes. Positioning Positioning involves bringing the axes of the mouth, pharynx, and larynx into alignment, leading to whats called the "sniffing" position. The sniffing position can be achieved by placing a rolled towel underneath the head and neck, effectively extending the head and flexing the neck. You are at proper alignment when the ear is inline with the sternum.As described by Brian Arthur Sellick in 1961, cricoid pressure (alternatively known as Sellicks maneuver) may be used to occlude the esophagus with the goal of preventing aspiration. Placement of tube During this stage, laryngoscopy is performed to visualize the glottis. Modern practice involves the passing of a ‘Bougie’, a thin tube, past the vocal cords and over which the endotracheal tube is then passed. The bougie is then removed and an inbuilt cuff at the end of the tube is inflated, (via a thin secondary tube and a syringe), to hold it in place and prevent aspiration of stomach contents. The position of the tube in the trachea can be confirmed in a number of ways, including observing increasing end tidal carbon dioxide, auscultation of both lungs and stomach, chest movement, and misting of the tube. Postintubation management Malpositioning of the endotracheal tube (in a bronchus, above the glottis, or in the esophagus) should be excluded by confirmation of end tidal CO2, auscultation and observation of bilateral chest rise. One important difference between RSI and routine tracheal intubation is that the practitioner does not typically manually assist the ventilation of the lungs after the onset of general anesthesia and cessation of breathing, until the trachea has been intubated and the cuff has been inflated. Additional considerations Age can play a role in whether or not the procedure is warranted, and is commonly needed in younger persons. The clinician that performs RSI must be skilled in tracheal intubation and also in bag valve mask ventilation. Alternative airway management devices must be immediately available, in the event the trachea cannot be intubated using conventional techniques. Such devices include the combitube and the laryngeal mask airway. Invasive techniques such as cricothyrotomy must also be available in the event of inability to intubate the trachea by conventional techniques. RSI is mainly used to intubate patients at high risk of aspiration, mostly due to a full stomach as commonly seen in a trauma setting. Bag ventilation causes distention of stomach which can induce vomiting, so this phase must be quick. The patient is given a sedative and paralytic agent, usually midazolam / suxamethonium / propofol and intubation is quickly attempted with minimal or no manual ventilation. The patient is assessed for predictable intubation difficulties. Laryngoscope blades and endotracheal tubes smaller than would be used in a non-emergency setting are selected. If the patient on initial assessment is found to have a difficult airway, RSI is contraindicated since a failed RSI attempt will leave no option but to ventilate the patient on bag and mask which can lead to vomiting. For these challenging cases, awake fiberoptic intubation is usually preferred. Controversy Since the introduction of RSI, there has been controversy regarding virtually every aspect of this technique, including: choice of intravenous hypnotic agents as well as their dosage and timing of administration dosage and timing of administration of neuromuscular blocking agents avoidance of manual ventilation before tracheal intubation optimal position and whether the head-up, head-down, or horizontal supine position is the safest for induction of anesthesia in full-stomach patients application of cricoid pressure, which is also referred to as the Sellick maneuver. References External links Rapid Sequence Intubation at eMedicine

What does Rat-bite fever mean Aarogya

Rat-bite fever

Rat-bite fever (RBF) is an acute, febrile human illness caused by bacteria transmitted by rodents, in most cases, which is passed from rodent to human by the rodents urine or mucous secretions. Alternative names for rat-bite fever include streptobacillary fever, streptobacillosis, spirillary fever, bogger, and epidemic arthritic erythema. It is a rare disease spread by infected rodents and caused by two specific types of bacteria: Streptobacillus moniliformis, the only reported bacteria that causes RBF in North America (streptobacillary RBF) Spirillum minus, common in Asia (spirillary RBF, also known as sodoku). Most cases occur in Japan, but specific strains of the disease are present in the United States, Europe, Australia, and Africa.Some cases are diagnosed after patients were exposed to the urine or bodily secretions of an infected animal. These secretions can come from the mouth, nose, or eyes of the rodent. The majority of cases are due to the animals bite. It can also be transmitted through food or water contaminated with rat feces or urine. Other animals can be infected with this disease, including weasels, gerbils, and squirrels. Household pets such as dogs or cats exposed to these animals can also carry the disease and infect humans. If a person is bitten by a rodent, it is important to quickly wash and cleanse the wound area thoroughly with antiseptic solution to reduce the risk of infection. Symptoms and signs Symptoms are different for every person depending on the type of rat-bite fever with which the person is infected. Both spirillary and streptobacillary rat-bite fever have a few individual symptoms, although most symptoms are shared. Streptobacillosis is most commonly found in the United States and spirillary rat-bite fever is generally diagnosed in Africa. Rat-bite symptoms are visually seen in most cases and include inflammation around the open sore. A rash can also spread around the area and appear red or purple. Other symptoms associated with streptobacillary rat-bite fever include chills, fever, vomiting, headaches, and muscle aches. Joints can also become painfully swollen and pain can be experienced in the back. Skin irritations such as ulcers or inflammation can develop on the hands and feet. Wounds heal slowly, so symptoms possibly come and go over the course of a few months. Symptoms associated with spirillary rat-bite fever include issues with the lymph nodes, which often swell or become inflamed as a reaction to the infection. The most common locations of lymph node swelling are in the neck, groin, and underarm. Symptoms generally appear within two to ten days of exposure to the infected animal. It begins with the fever and progresses to the rash on the hands and feet within two to four days. The rash appears all over the body with this form but rarely causes joint pain. Causes Two types of Gram-negative, facultatively anaerobic bacteria can cause the infection. Spirillosis Rat-bite fever transmitted by the Gram-negative coiled rod Spirillum minus (also known as Spirillum minor) is rarer, and is found most often in Asia. In Japan, the disease is called sodoku. Symptoms do not manifest for two to four weeks after exposure to the organism, and the wound through which it entered exhibits slow healing and marked inflammation. The fever lasts longer and is recurring, for months in some cases. Rectal pain and gastrointestinal symptoms are less severe or are absent. Penicillin is the most common treatment. Streptobacillosis The streptobacillosis form of rat-bite fever is known by the alternative names Haverhill fever and epidemic arthritic erythema. It is a severe disease caused by Streptobacillus moniliformis, transmitted either by rat bite or ingestion of contaminated products (Haverhill fever). After an incubation period of 2–10 days, Haverhill fever begins with high prostrating fevers, rigors (shivering), headache, and polyarthralgia (joint pain). Soon, an exanthem (widespread rash) appears, either maculopapular (flat red with bumps) or petechial (red or purple spots) and arthritis of large joints can be seen. The organism can be cultivated in blood or articular fluid. The disease can be fatal if untreated in 20% of cases due to malignant endocarditis, meningoencephalitis, or septic shock. Treatment is with penicillin, tetracycline, or doxycycline. Diagnosis This condition is diagnosed by detecting the bacteria in skin, blood, joint fluid, or lymph nodes. Blood antibody tests may also be used. To get a proper diagnosis for rat-bite fever, different tests are run depending on the symptoms being experienced. To diagnosis streptobacillary rat-bite fever, blood or joint fluid is extracted and the organisms living in it are cultured. Diagnosis for spirillary rat bite fever is by direct visualization or culture of spirilla from blood smears or tissue from lesions or lymph nodes. Prevention Eliminating exposure is very important when it comes to disease prevention. When handling rodents or cleaning areas where rodents have been, contact between hand and mouth should be avoided. Hands and face should be washed after contact and any scratches both cleaned and antiseptics applied. The effect of chemoprophylaxis following rodent bites or scratches on the disease is unknown. No vaccines are available for these diseases. Improved conditions to minimize rodent contact with humans are the best preventive measures. Animal handlers, laboratory workers, and sanitation and sewer workers must take special precautions against exposure. Wild rodents, dead or alive, should not be touched and pets must not be allowed to ingest rodents. Those living in the inner cities where overcrowding and poor sanitation cause rodent problems are at risk from the disease. Half of all cases reported are children under 12 living in these conditions. Treatment Treatment with antibiotics is the same for both types of infection. The condition responds to penicillin, and where allergies to it occur, erythromycin or tetracyclines are used. Prognosis When proper treatment is provided for patients with rat-bite fever, the prognosis is positive. Without treatment, the infection usually resolves on its own, although it may take up to a year to do so. A particular strain of rat-bite fever in the United States can progress and cause serious complications that can be potentially fatal. Before antibiotics were used, many cases resulted in death. If left untreated, streptobacillary rat-bite fever can result in infection in the lining of the heart, covering over the spinal cord and brain, or in the lungs. Any tissue or organ throughout the body may develop an abscess. Epidemiology Rat-bite fever (RBF) is a zoonotic disease. It can be directly transmitted by rats, gerbils, and mice (the vectors) to humans by either a bite or scratch or it can be passed from rodent to rodent. The causative bacterial agent of RBF has also been observed in squirrels, ferrets, dogs, and pigs. The most common reservoir of the disease is rats because nearly all domestic and wild rats are colonized by the causative bacterial agent, Streptobacillus moniliformis. Most notably, the Black rat (Rattus rattus) and the Norwegian rat (Rattus norvegicus) are recognized as potential reservoirs due to their common use as laboratory animals or kept as pets. The bacteria Streptobacillus moniliformis is found in the rats upper respiratory tract. Most rats harbor the disease asymptomatically, and signs and symptoms rarely develop. It is estimated that 1 in 10 bites from a rat will result in developing RBF. A person is also at risk of acquiring the bacteria through touching contaminated surfaces with an open wound or mucous membrane or ingestion of contaminated water or food by rodent feces, though this is referred to as Haverhill Fever (epidemic arthritic erythema). RBF is not a contagious disease. That is, it cannot be transferred directly from person to person.Researchers are challenged in understanding the prevalence of RBF. One factor that limits the known number of cases of RBF in the United States is that it is not a reportable disease there. RBF is classified as a notifiable disease, which means it is required by the state to be reported, however, the state is not mandated to provide that information to the United States Centers for Disease Control. Identification of RBF is also hindered due to the presence of two different etiological bacterial agents, Streptobacillus moniliformis and Spirillum minus. RBF caused by Sp. minus is more commonly found in Asia and is termed Sodoku, whereas St. moniliformis is found more often in the United States and in the Western Hemisphere. Although cases of RBF have been reported all over the world, the majority of cases that have been documented are caused by St. moniliformis primarily in the United States, where approximately 200 cases have been identified and reported. Due to increasing population density, this illness is being seen more frequently, as humans have increased their contact with animals and the zoonotic diseases they carry. Most cases of the disease have been reported from densely populated regions, such as big cities. The populations at risk have broadened due to the fact that domestic rats have become a common household pet. In the United States it is estimated that children 5 years and younger are the most at risk, receiving 50% of the total exposure, followed by laboratory personnel and then pet store employees. Other groups at increased risk are people over 65 years old, immunocompromised individuals, and pregnant women.Symptoms of RBF include sudden high temperature fevers with rigors, vomiting, headaches, painful joints/arthritis. A red, bumpy rash develops in about 75% of subjects. Symptoms of RBF can develop between 3 days and 3 weeks after exposure. While symptoms differ between Streptobacillary and Spirillary RBF, both types exhibit an incubation period before symptoms manifest. Due to its symptoms, RBF is often misdiagnosed by clinicians, leading to lingering symptoms and worsening conditions in patients; left untreated the mortality rate (death rate) of RBF is 13%. Even when treated, RBF can lead to migratory polyarthralgia, persistent rash, and fatigue which can persist for weeks to years after initial infection and treatment. See also Pasteurellosis List of cutaneous conditions Zoonosis References Rat Bite Fever (RBF) | CDC Further reading "Rat-bite Fever (RBF)". Centers for Disease Control and Prevention. Retrieved 28 February 2014. Centers for Disease Control Prevention (CDC) (January 2005). "Fatal rat-bite fever—Florida and Washington, 2003". MMWR Morb. Mortal. Wkly. Rep. 53 (51): 1198–202. PMID 15635289. Rat-bite fever (MyOptumHealth.com) Tandon, R; Lee, M; Curran, E; Demierre, MF; Sulis, CA (Dec 15, 2006). "A 26-year-old woman with a rash on her extremities". Clinical Infectious Diseases. 43 (12): 1585–6, 1616–7. doi:10.1086/509574. PMID 17109293. Centers for Disease Control, (CDC) (Jun 8, 1984). "Rat-bite fever in a college student--California". MMWR. Morbidity and Mortality Weekly Report. 33 (22): 318–20. PMID 6427575. == External links ==

Aarogya , Do you know what is Raynaud syndrome,

Raynaud syndrome

Raynaud syndrome, also known as Raynauds phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries causes episodes of reduced blood flow to end arterioles. Typically, the fingers, and less commonly, the toes, are involved. Rarely, the nose, ears, or lips are affected. The episodes classically result in the affected part turning white and then blue. Often, numbness or pain occurs. As blood flow returns, the area turns red and burns. The episodes typically last minutes but can last several hours.Episodes are typically triggered by cold or emotional stress. Primary Raynauds, also known as idiopathic, means that it is spontaneous, of unknown cause, and unrelated to another disease. Secondary Raynauds occurs as a result of another condition and has an older age at onset; episodes are intensely painful and can be asymmetric and associated with skin lesions. Secondary Raynauds can occur due to a connective-tissue disorder such as scleroderma or lupus, injuries to the hands, prolonged vibration, smoking, thyroid problems, and certain medications, such as birth control pills. Diagnosis is typically based on the symptoms.The primary treatment is avoiding the cold. Other measures include the discontinuation of nicotine or stimulant use. Medications for treatment of cases that do not improve include calcium channel blockers and iloprost. Little evidence supports alternative medicine. Severe disease may in rare cases lead to complications, specifically skin sores or gangrene.About 4% of people have the condition. Onset of the primary form is typically between ages 15 and 30 and occurs more frequently in females. The secondary form usually affects older people. Both forms are more common in cold climates. Signs and symptoms The condition can cause localized pain, discoloration (paleness), and sensations of cold and/or numbness. When exposed to cold temperatures, the blood supply to the fingers or toes, and in some cases the nose or earlobes, is markedly reduced; the skin turns pale or white (called pallor) and becomes cold and numb. These events are episodic, and when the episode subsides or the area is warmed, the blood flow returns, and the skin color first turns red (rubor), and then back to normal, often accompanied by swelling, tingling, and a painful "pins and needles" sensation. All three color changes are observed in classic Raynauds. However, not all patients see all of the aforementioned color changes in all episodes, especially in milder cases of the condition. The red flush is due to reactive hyperemia of the areas deprived of blood flow.In pregnancy, this sign normally disappears due to increased surface blood flow. Raynauds has occurred in breastfeeding mothers, causing nipples to turn white and painful. Causes Primary Raynauds disease, or primary Raynauds, is diagnosed if the symptoms are idiopathic, that is, if they occur by themselves and not in association with other diseases. Some refer to primary Raynauds disease as "being allergic to coldness". It often develops in young women in their teens and early adulthood. Primary Raynauds is thought to be at least partly hereditary, although specific genes have not yet been identified.Smoking increases frequency and intensity of attacks, and a hormonal component exists. Caffeine, estrogen, and nonselective beta-blockers are often listed as aggravating factors, but evidence that they should be avoided is not solid. Secondary Raynauds phenomenon, or secondary Raynauds, occurs secondary to a wide variety of other conditions. Secondary Raynauds has a number of associations: Connective tissue disorders: Scleroderma Systemic lupus erythematosus Rheumatoid arthritis Sjögrens syndrome Dermatomyositis Polymyositis Mixed connective tissue disease Cold agglutinin disease Ehlers-Danlos syndrome Eating disorders: Anorexia nervosa Obstructive disorders: Atherosclerosis Buergers disease Takayasus arteritis Subclavian aneurysms Thoracic outlet syndrome Drugs: Beta-blockers Cytotoxic drugs – particularly chemotherapeutics and most especially bleomycin Cyclosporin Bromocriptine Ergotamine Sulfasalazine Anthrax vaccines whose primary ingredient is the Anthrax Protective Antigen Stimulant medications, such as those used to treat ADHD (amphetamine and methylphenidate) OTC pseudoephedrine medications (Chlor-Trimeton, Sudafed, others) Occupation: Jobs involving vibration, particularly drilling and prolonged use of a string trimmer (weed whacker), experience vibration white finger Exposure to vinyl chloride, mercury Exposure to the cold (e.g., by working as a frozen food packer) Others: Physical trauma to the extremities Lyme disease Hypothyroidism Cryoglobulinemia Cancer Chronic fatigue syndrome Reflex sympathetic dystrophy Carpal tunnel syndrome Magnesium deficiency Multiple sclerosis Erythromelalgia (clinically presenting as the opposite of Raynauds, with hot and warm extremities, often co-exists in patients with Raynauds) Chilblains (also clinically presenting as the opposite of Raynauds, with hot and itchy extremities, however it affects smaller areas than erythromelalgia, for instance the tip of a toe rather than the whole foot)Raynauds can precede these other diseases by many years, making it the first presenting symptom. This may be the case in the CREST syndrome, of which Raynauds is a part.Patients with secondary Raynauds can also have symptoms related to their underlying diseases. Raynauds phenomenon is the initial symptom that presents for 70% of patients with scleroderma, a skin and joint disease.When Raynauds phenomenon is limited to one hand or one foot, it is referred to as unilateral Raynauds. This is an uncommon form, and it is always secondary to local or regional vascular disease. It commonly progresses within several years to affect other limbs as the vascular disease progresses. Mechanism Its pathophysiology includes hyperactivation of the sympathetic nervous system causing extreme vasoconstriction of the peripheral blood vessels, leading to tissue hypoxia. Diagnosis Distinguishing Raynauds disease (primary Raynauds) from Raynauds phenomenon (secondary Raynauds) is important. Looking for signs of arthritis or vasculitis, as well as a number of laboratory tests, may separate them. Nail fold capillary examination or "capillaroscopy" is one of the most sensitive methods to diagnose RS with connective tissue disorders, i.e. distinguish a secondary from a primary form objectively.If suspected to be secondary to systemic sclerosis, one tool which may help aid in the prediction of systemic sclerosis is thermography.A careful medical history will seek to identify or exclude possible secondary causes. Digital artery pressures are measured in the arteries of the fingers before and after the hands have been cooled. A decrease of at least 15 mmHg is diagnostic (positive). Doppler ultrasound to assess blood flow Full blood count may reveal a normocytic anaemia suggesting the anaemia of chronic disease or kidney failure. Blood test for urea and electrolytes may reveal kidney impairment. Thyroid function tests may reveal hypothyroidism. Tests for rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, and autoantibody screening may reveal specific causative illnesses or an inflammatory process. Anti-centromere antibodies are common in limited systemic sclerosis (CREST syndrome). Nail fold vasculature (capillaroscopy) can be examined under a microscope.To aid in the diagnosis of Raynauds phenomenon, multiple sets of diagnostic criteria have been proposed. Table 1 below provides a summary of these various diagnostic criteria.Recently, International Consensus Criteria were developed for the diagnosis of primary Raynauds phenomenon by a panel of experts in the fields of rheumatology and dermatology. Management Secondary Raynauds is managed primarily by treating the underlying cause, and as primary Raynauds, avoiding triggers, such as cold, emotional and environmental stress, vibrations and repetitive motions, and avoiding smoking (including passive smoking) and sympathomimetic drugs. Medications Medications can be helpful for moderate or severe disease. Vasodilators – calcium channel blockers, such as the dihydropyridines nifedipine or amlodipine, preferably slow-release preparations – are often first-line treatment. They have the common side effects of headache, flushing, and ankle edema, but these are not typically of sufficient severity to require cessation of treatment. The limited evidence available shows that calcium-channel blockers are only slightly effective in reducing how often the attacks happen. Although, other studies also reveal that CCBs may be effective at decreasing severity of attacks, pain and disability associated with Raynauds phenomenon. People whose disease is secondary to erythromelalgia often cannot use vasodilators for therapy, as they trigger flares causing the extremities to become burning red due to too much blood supply. People with severe disease prone to ulceration or large artery thrombotic events may be prescribed aspirin. Sympatholytic agents, such as the alpha-adrenergic blocker prazosin, may provide temporary relief to secondary Raynauds phenomenon. Losartan can, and topical nitrates may, reduce the severity and frequency of attacks, and the phosphodiesterase inhibitors sildenafil and tadalafil may reduce their severity. Angiotensin receptor blockers or ACE inhibitors may aid blood flow to the fingers, and some evidence shows that angiotensin receptor blockers (often losartan) reduce frequency and severity of attacks, and possibly better than nifedipine. The prostaglandin iloprost is used to manage critical ischemia and pulmonary hypertension in Raynauds phenomenon, and the endothelin receptor antagonist bosentan is used to manage severe pulmonary hypertension and prevent finger ulcers in scleroderma. Statins have a protective effect on blood vessels, and SSRIs such as fluoxetine may help symptoms, but the data is weak. PDE5 inhibitors are used off-label to treat severe ischemia and ulcers in fingers and toes for people with secondary Raynauds phenomenon; as of 2016, their role more generally in Raynauds was not clear. Surgery In severe cases, an endoscopic thoracic sympathectomy procedure can be performed. Here, the nerves that signal the blood vessels of the fingertips to constrict are surgically cut. Microvascular surgery of the affected areas is another possible therapy, but this procedure should be considered as a last resort. A more recent treatment for severe Raynauds is the use of botulinum toxin. The 2009 article studied 19 patients ranging in age from 15 to 72 years with severe Raynauds phenomenon of which 16 patients (84%) reported pain reduction at rest; 13 patients reported immediate pain relief, three more had gradual pain reduction over 1–2 months. All 13 patients with chronic finger ulcers healed within 60 days. Only 21% of the patients required repeated injections. A 2007 article describes similar improvement in a series of 11 patients. All patients had significant relief of pain. Alternative medicine Evidence does not support the use of alternative medicine, including acupuncture and laser therapy. Prognosis The prognosis of primary Raynaud syndrome is often very favorable, with no mortality and little morbidity. However, a minority develops gangrene. The prognosis of secondary Raynaud is dependent on the underlying disease, and how effective blood flow-restoring maneuvers are. References External links What Is Raynauds Disease at National Heart, Lung, and Blood Institute Questions and Answers about Raynauds Phenomenon at National Institutes of Health Bakst R, Merola JF, Franks AG, Sanchez M (October 2008). "Raynauds phenomenon: pathogenesis and management". Journal of the American Academy of Dermatology. 59 (4): 633–53. doi:10.1016/j.jaad.2008.06.004. PMID 18656283.