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Aarogya, What does Paracetamol poisoning mean

Paracetamol poisoning

Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These include feeling tired, abdominal pain, or nausea. This is typically followed by a couple of days without any symptoms, after which yellowish skin, blood clotting problems, and confusion occurs as a result of liver failure. Additional complications may include kidney failure, pancreatitis, low blood sugar, and lactic acidosis. If death does not occur, people tend to recover fully over a couple of weeks. Without treatment, death from toxicity occurs 4 to 18 days later.Paracetamol poisoning can occur accidentally or as an attempt to die by suicide. Risk factors for toxicity include alcoholism, malnutrition, and the taking of certain other hepatotoxic medications. Liver damage results not from paracetamol itself, but from one of its metabolites, N-acetyl-p-benzoquinone imine (NAPQI). NAPQI decreases the livers glutathione and directly damages cells in the liver. Diagnosis is based on the blood level of paracetamol at specific times after the medication was taken. These values are often plotted on the Rumack-Matthew nomogram to determine level of concern.Treatment may include activated charcoal if the person seeks medical help soon after the overdose. Attempting to force the person to vomit is not recommended. If there is a potential for toxicity, the antidote acetylcysteine is recommended. The medication is generally given for at least 24 hours. Psychiatric care may be required following recovery. A liver transplant may be required if damage to the liver becomes severe. The need for transplant is often based on low blood pH, high blood lactate, poor blood clotting, or significant hepatic encephalopathy. With early treatment liver failure is rare. Death occurs in about 0.1% of cases.Paracetamol poisoning was first described in the 1960s. Rates of poisoning vary significantly between regions of the world. In the United States more than 100,000 cases occur a year. In the United Kingdom it is the medication responsible for the greatest number of overdoses. Young children are most commonly affected. In the United States and the United Kingdom, paracetamol is the most common cause of acute liver failure. Signs and symptoms The signs and symptoms of paracetamol toxicity occur in three phases. The first phase begins within hours of overdose, and consists of nausea, vomiting, a pale appearance, and sweating. However, patients often have no specific symptoms or only mild symptoms in the first 24 hours of poisoning. Rarely, after massive overdoses, patients may develop symptoms of metabolic acidosis and coma early in the course of poisoning.The second phase occurs between 24 hours and 72 hours following overdose and consists of signs of increasing liver damage. In general, damage occurs in liver cells as they metabolize the paracetamol. The individual may experience right upper quadrant abdominal pain. The increasing liver damage also changes biochemical markers of liver function; International normalized ratio (INR) and the liver transaminases ALT and AST rise to abnormal levels. Acute kidney failure may also occur during this phase, typically caused by either hepatorenal syndrome or multiple organ dysfunction syndrome. In some cases, acute kidney failure may be the primary clinical manifestation of toxicity. In these cases, it has been suggested that the toxic metabolite is produced more in the kidneys than in the liver.The third phase follows at 3 to 5 days, and is marked by complications of massive liver necrosis leading to fulminant liver failure with complications of coagulation defects, low blood sugar, kidney failure, hepatic encephalopathy, brain swelling, sepsis, multiple organ failure, and death. If the third phase is survived, the liver necrosis runs its course, and liver and kidney function typically return to normal in a few weeks. The severity of paracetamol toxicity varies depending on the dose and whether appropriate treatment is received. Cause The toxic dose of paracetamol is highly variable. In general the recommended maximum daily dose for healthy adults is 4 grams. Higher doses lead to increasing risk of toxicity. In adults, single doses above 10 grams or 200 mg/kg of bodyweight, whichever is lower, have a reasonable likelihood of causing toxicity. Toxicity can also occur when multiple smaller doses within 24 hours exceed these levels. Following a dose of 1 gram of paracetamol four times a day for two weeks, patients can expect an increase in alanine transaminase in their liver to typically about three times the normal value. It is unlikely that this dose would lead to liver failure. Studies have shown significant hepatotoxicity is uncommon in patients who have taken greater than normal doses over 3 to 4 days. In adults, a dose of 6 grams a day over the preceding 48 hours could potentially lead to toxicity, while in children acute doses above 200 mg/kg could potentially cause toxicity. Acute paracetamol overdose in children rarely causes illness or death, and it is very uncommon for children to have levels that require treatment, with chronic larger-than-normal doses being the major cause of toxicity in children.Intentional overdosing (self-poisoning, with suicidal intent) is frequently implicated in paracetamol toxicity. In a 2006 review, paracetamol was the most frequently ingested compound in intentional overdosing.In rare individuals, paracetamol toxicity can result from normal use. This may be due to individual ("idiosyncratic") differences in the expression and activity of certain enzymes in one of the metabolic pathways that handle paracetamol (see paracetamols metabolism). Risk factors A number of factors can potentially increase the risk of developing paracetamol toxicity. Chronic excessive alcohol consumption can induce CYP2E1, thus increasing the potential toxicity of paracetamol. In one study of patients with liver injury, 64% reported alcohol intakes of greater than 80 grams a day, while 35% took 60 grams a day or less. Whether chronic alcoholism should be considered a risk factor has been debated by some clinical toxicologists. For chronic alcohol users, acute alcohol ingestion at the time of a paracetamol overdose may have a protective effect. For non-chronic alcohol users, acute alcohol consumption had no protective effect. Fasting is a risk factor, possibly because of depletion of liver glutathione reserves. The concomitant use of the CYP2E1 inducer isoniazid increases the risk of hepatotoxicity, though whether 2E1 induction is related to the hepatotoxicity in this case is unclear. Concomitant use of other drugs that induce CYP enzymes, such as antiepileptics including carbamazepine, phenytoin, and barbiturates, have also been reported as risk factors. Pathophysiology When taken in normal therapeutic doses, paracetamol has been shown to be safe. Following a therapeutic dose, it is mostly converted to nontoxic metabolites via Phase II metabolism by conjugation with sulfate and glucuronide, with a small portion being oxidized via the cytochrome P450 enzyme system. Cytochromes P450 2E1 and 3A4 convert approximately 5% of paracetamol to a highly reactive intermediary metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione to form cysteine and mercapturic acid conjugates.In cases of paracetamol overdose, the sulfate and glucuronide pathways become saturated, and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become depleted, as the demand for glutathione is higher than its regeneration. NAPQI therefore remains in its toxic form in the liver and reacts with cellular membrane molecules, resulting in widespread hepatocyte damage and death, leading to acute liver necrosis. In animal studies, the livers stores of glutathione must be depleted to less than 70% of normal levels before liver toxicity occurs. Diagnosis A persons history of taking paracetamol is somewhat accurate for the diagnosis. The most effective way to diagnose poisoning is by obtaining a blood paracetamol level. A drug nomogram developed in 1975, called the Rumack-Matthew nomogram, estimates the risk of toxicity based on the serum concentration of paracetamol at a given number of hours after ingestion. To determine the risk of potential hepatotoxicity, the paracetamol level is traced along the nomogram. Use of a timed serum paracetamol level plotted on the nomogram appears to be the best marker indicating the potential for liver injury. A paracetamol level drawn in the first four hours after ingestion may underestimate the amount in the system because paracetamol may still be in the process of being absorbed from the gastrointestinal tract. Therefore, a serum level taken before 4 hours is not recommended.Clinical or biochemical evidence of liver toxicity may develop in one to four days, although, in severe cases, it may be evident in 12 hours. Right-upper-quadrant tenderness may be present and can aid in diagnosis. Laboratory studies may show evidence of liver necrosis with elevated AST, ALT, bilirubin, and prolonged coagulation times, particularly an elevated prothrombin time. After paracetamol overdose, when AST and ALT exceed 1000 IU/L, paracetamol-induced hepatotoxicity can be diagnosed. In some cases, the AST and ALT levels can exceed 10,000 IU/L. Detection in body fluids Paracetamol may be quantified in blood, plasma, or urine as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths. The concentration in serum after a typical dose of paracetamol usually peaks below 30 mg/L, which equals 200 μmol/L. Levels of 30–300 mg/L (200–2000 μmol/L) are often observed in overdose patients. Postmortem blood levels have ranged from 50 to 400 mg/L in persons dying due to acute overdosage. Automated colorimetric techniques, gas chromatography and liquid chromatography are currently in use for the laboratory analysis of the drug in physiological specimens. Prevention Limitation of availability Limiting the availability of paracetamol tablets has been attempted in some countries. In the UK, sales of over-the-counter paracetamol are restricted to packs of 32 x 500 mg tablets in pharmacies, and 16 x 500 mg tablets in non-pharmacy outlets. Pharmacists may provide up to 100 tablets for those with chronic conditions at the pharmacists discretion. In Ireland, the limits are 24 and 12 tablets, respectively. Subsequent study suggests that the reduced availability in large numbers had a significant effect in reducing poisoning deaths from paracetamol overdose.One suggested method of prevention is to make paracetamol a prescription-only medicine, or to remove it entirely from the market. However, overdose is a relatively minor problem; for example, 0.08% of the UK population (over 50 thousand people) present with paracetamol overdose each year. In contrast, paracetamol is a safe and effective medication that is taken without complications by millions of people. In addition, alternative pain relief medications such as aspirin are more toxic in overdose, whereas non-steroidal anti-inflammatory drugs are associated with more adverse effects following normal use. Combination with other agents One strategy for reducing harm done by acetaminophen overdoses is selling paracetamol pre-combined in tablets either with an emetic or an antidote. Paradote was a tablet sold in the UK which combined 500 mg paracetamol with 100 mg methionine, an amino acid formerly used in the treatment of paracetamol overdose. There have been no studies so far on the effectiveness of paracetamol when given in combination with its most commonly used antidote, acetylcysteine.Calcitriol, the active metabolite of vitamin D3, appears to be a catalyst for glutathione production. Calcitriol was found to increase glutathione levels in rat astrocyte primary cultures on average by 42%, increasing glutathione protein concentrations from 29 nmol/mg to 41 nmol/mg, 24 and 48 hours after administration; it continued to have an influence on glutathione levels 96 hours after administration. It has been proposed that co-administration of calcitriol, via injection, may improve treatment outcomes. Paracetamol replacements Paracetamol ester prodrug with L-pyroglutamic acid (PCA), a biosynthetic precursor of glutathione, has been synthesized to reduce paracetamol hepatotoxicity and improve bioavailability. The toxicological studies of different paracetamol esters show that L-5-oxo-pyrrolidine-2-paracetamol carboxylate reduces toxicity after administration of an overdose of paracetamol to mice. The liver glutathione values in mice induced by intraperitoneal injection of the ester are superimposable with the GSH levels recorded in untreated mice control group. The mice group treated with an equivalent dose of paracetamol showed a significative decrease of glutathione of 35% (p<0.01 vs untreated control group). The oral LD50 was found to be greater than 2000 mg kg-1, whereas the intraperitoneal LD50 was 1900 mg kg-1. These results taken together with the good hydrolysis and bioavailability data show that this ester is a potential candidate as a prodrug of paracetamol. Treatment Gastric decontamination In adults, the initial treatment for paracetamol overdose is gastrointestinal decontamination. Paracetamol absorption from the gastrointestinal tract is complete within two hours under normal circumstances, so decontamination is most helpful if performed within this timeframe. Gastric lavage, better known as stomach pumping, may be considered if the amount ingested is potentially life-threatening and the procedure can be performed within 60 minutes of ingestion. Activated charcoal is the most common gastrointestinal decontamination procedure as it adsorbs paracetamol, reducing its gastrointestinal absorption. Administering activated charcoal also poses less risk of aspiration than gastric lavage.It appears that the most benefit from activated charcoal is gained if it is given within 30 minutes to two hours of ingestion. Administering activated charcoal later than 2 hours can be considered in patients that may have delayed gastric emptying due to co-ingested drugs or following ingestion of sustained- or delayed-release paracetamol preparations. Activated charcoal should also be administered if co-ingested drugs warrant decontamination. There was reluctance to give activated charcoal in paracetamol overdose, because of the concern that it may also absorb the oral antidote acetylcysteine. Studies have shown that 39% less acetylcysteine is absorbed into the body when they are administered together. There are conflicting recommendations regarding whether to change the dosing of oral acetylcysteine after the administration of activated charcoal, and even whether the dosing of acetylcysteine needs to be altered at all. Intravenous acetylcysteine has no interaction with activated charcoal. Inducing vomiting with syrup of ipecac has no role in paracetamol overdose because the vomiting it induces delays the effective administration of activated charcoal and oral acetylcysteine. Liver injury is extremely rare after acute accidental ingestion in children under 6 years of age. Children with accidental exposures do not require gastrointestinal decontamination with either gastric lavage, activated charcoal, or syrup of ipecac. Acetylcysteine Acetylcysteine, also called N-acetylcysteine or NAC, works to reduce paracetamol toxicity by replenishing body stores of the antioxidant glutathione. Glutathione reacts with the toxic NAPQI metabolite so that it does not damage cells and can be safely excreted. NAC was usually given following a treatment nomogram (one for patients with risk factors, and one for those without) but the use of the nomogram is no longer recommended as the evidence base to support the use of risk factors was poor and inconsistent and many of the risk factors are imprecise and difficult to determine with sufficient certainty in clinical practice. Cysteamine and methionine have also been used to prevent hepatotoxicity, although studies show that both are associated with more adverse effects than acetylcysteine. Additionally, acetylcysteine has been shown to be a more effective antidote, particularly in patients presenting greater than 8 hours post-ingestion and for those who present with liver failure symptoms.If the person presents less than eight hours after paracetamol overdose, then acetylcysteine significantly reduces the risk of serious hepatotoxicity and guarantees survival. If acetylcysteine is started more than 8 hours after ingestion, there is a sharp decline in its effectiveness because the cascade of toxic events in the liver has already begun, and the risk of acute liver necrosis and death increases dramatically. Although acetylcysteine is most effective if given early, it still has beneficial effects if given as late as 48 hours after ingestion. If the person presents more than eight hours after the paracetamol overdose, then activated charcoal is not useful, and acetylcysteine is started immediately. In earlier presentations, charcoal can be given when the patient arrives and acetylcysteine is initiated while waiting for the paracetamol level results to return from the laboratory.In United States practice, intravenous (IV) and oral administration are considered to be equally effective and safe if given within 8 hours of ingestion. However, IV is the only recommended route in Australasian and British practice. Oral acetylcysteine is given as a 140 mg/kg loading dose followed by 70 mg/kg every four hours for 17 more doses, and if the patient vomits within 1 hour of dose, the dose must be repeated. Oral acetylcysteine may be poorly tolerated due to its unpleasant taste, odor, and its tendency to cause nausea and vomiting. If repeated doses of charcoal are indicated because of another ingested drug, then subsequent doses of charcoal and acetylcysteine should be staggered.Intravenous acetylcysteine is given as a continuous infusion over 20 hours for a total dose 300 mg/kg. Recommended administration involves infusion of a 150 mg/kg loading dose over 15 to 60 minutes, followed by a 50 mg/kg infusion over four hours; the last 100 mg/kg are infused over the remaining 16 hours of the protocol. Intravenous acetylcysteine has the advantage of shortening hospital stay, increasing both doctor and patient convenience, and allowing administration of activated charcoal to reduce absorption of both the paracetamol and any co-ingested drugs without concerns about interference with oral acetylcysteine. Intravenous dosing varies with weight, specifically in children. For patients less than 20 kg, the loading dose is 150 mg/kg in 3 mL/kg diluent, administered over 60 minutes; the second dose is 50 mg/kg in 7 mL/kg diluent over 4 hours; and the third and final dose is 100 mg/kg in 14 mL/kg diluent over 16 hours.The most common adverse effect to acetylcysteine treatment is an anaphylactoid reaction, usually manifested by rash, wheeze, or mild hypotension. May cause infertility or death. Adverse reactions are more common in people treated with IV acetylcysteine, occurring in up to 20% of patients. Anaphylactoid reactions are more likely to occur with the first infusion (the loading dose). Rarely, severe life-threatening reactions may occur in predisposed individuals, such as patients with asthma or atopic dermatitis, and may be characterized by respiratory distress, facial swelling, and even death.If an anaphylactoid reaction occurs the acetylcysteine is temporarily halted or slowed and antihistamines and other supportive care is administered. For example, a nebulised beta-agonist like salbutamol may be indicated in the event of significant bronchospasm (or prophylactically in patients with a history of bronchospasm secondary to acetylcysteine). It is also important to closely monitor fluids and electrolytes. Liver transplant In people who develop acute liver failure or who are otherwise expected to die from liver failure, the mainstay of management is liver transplantation. Liver transplants are performed in specialist centers. The most commonly used criteria for liver transplant were developed by physicians at Kings College Hospital in London. Patients are recommended for transplant if they have an arterial blood pH less than 7.3 after fluid resuscitation or if a patient has Grade III or IV encephalopathy, a prothrombin time greater than 100 seconds, and a serum creatinine greater than 300 mmol/L In a 24-hour period. Other forms of liver support have been used including partial liver transplants. These techniques have the advantage of supporting the patient while their own liver regenerates. Once liver function returns immunosuppressive drugs are commenced and they have to take immunosuppressive medication for the rest of their lives. Prognosis The mortality rate from paracetamol overdose increases two days after the ingestion, reaches a maximum on day four, and then gradually decreases. Acidosis is the most important single indicator of probable mortality and the need for transplantation. A mortality rate of 95% without transplant was reported in patients who had a documented pH less than 7.30. Other indicators of poor prognosis include chronic kidney disease (stage 3 or worse), hepatic encephalopathy, a markedly elevated prothrombin time, or an elevated blood lactic acid level (lactic acidosis). One study has shown that a factor V level less than 10% of normal indicated a poor prognosis (91% mortality), whereas a ratio of factor VIII to factor V of less than 30 indicated a good prognosis (100% survival). Patients with a poor prognosis are usually identified for likely liver transplantation. Patients that do not die are expected to fully recover and have a normal life expectancy and quality of life. Epidemiology Many over-the-counter and prescription-only medications contain paracetamol. Because of its wide availability paired with comparably high toxicity, (compared to ibuprofen and aspirin) there is a much higher potential for overdose. Paracetamol toxicity is one of the most common causes of poisoning worldwide. In the United States, the United Kingdom, Australia, and New Zealand, paracetamol is the most common cause of drug overdoses. Additionally, in both the United States and the United Kingdom it is the most common cause of acute liver failure.In England and Wales an estimated 41,200 cases of paracetamol poisoning occurred in 1989 to 1990, with a mortality of 0.40%. It is estimated that 150 to 200 deaths and 15 to 20 liver transplants occur as a result of poisoning each year in England and Wales. Paracetamol overdose results in more calls to poison control centers in the US than overdose of any other pharmacological substance, accounting for more than 100,000 calls, as well as 56,000 emergency room visits, 2,600 hospitalizations, and 458 deaths due to acute liver failure per year. A study of cases of acute liver failure between November 2000 and October 2004 by the Centers for Disease Control and Prevention in the USA found that paracetamol was the cause of 41% of all cases in adults, and 25% of cases in children. References External links Gerth, Jeff; T. Christian Miller (September 20, 2013). "Use Only as Directed". ProPublica. Retrieved October 12, 2013.

Hello Aarogya, explain a situation where Acromegaly occurs

Acromegaly

Acromegaly is a disorder that results from excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be an enlargement of the forehead, jaw, and nose. Other symptoms may include joint pain, thicker skin, deepening of the voice, headaches, and problems with vision. Complications of the disease may include type 2 diabetes, sleep apnea, and high blood pressure.Acromegaly is usually caused by the pituitary gland producing excess growth hormone. In more than 95% of cases the excess production is due to a benign tumor, known as a pituitary adenoma. The condition is not inherited from a persons parents. Acromegaly is rarely due to a tumor in another part of the body. Diagnosis is by measuring growth hormone after a person has consumed a glucose solution, or by measuring insulin-like growth factor I in the blood. After diagnosis, medical imaging of the pituitary is carried out to determine if an adenoma is present. If excess growth hormone is produced during childhood, the result is the condition gigantism rather than acromegaly, and it is characterized by excessive height.Treatment options include surgery to remove the tumor, medications, and radiation therapy. Surgery is usually the preferred treatment; the smaller the tumor, the more likely surgery will be curative. If surgery is contraindicated or not curative, somatostatin analogues or GH receptor antagonists may be used. Radiation therapy may be used if neither surgery nor medications are completely effective. Without treatment, life expectancy is reduced by 10 years; with treatment, life expectancy is not reduced.Acromegaly affects about 3 per 50,000 people. It is most commonly diagnosed in middle age. Males and females are affected with equal frequency. It was first described in the medical literature by Nicolas Saucerotte in 1772. The term is from the Greek ἄκρον (akron) meaning "extremity", and μέγα (mega) meaning "large". Signs and symptoms Features that may result from a high level of GH or expanding tumor include: Headaches – often severe and prolonged Soft tissue swelling visibly resulting in enlargement of the hands, feet, nose, lips, and ears, and a general thickening of the skin Soft tissue swelling of internal organs, notably the heart with the attendant weakening of its muscularity, and the kidneys, also the vocal cords resulting in a characteristic thick, deep voice and slowing of speech Generalized expansion of the skull at the fontanelle Pronounced brow protrusion, often with ocular distension (frontal bossing) Pronounced lower jaw protrusion (prognathism) with attendant macroglossia (enlargement of the tongue) and teeth spacing Hypertrichosis, hyperpigmentation and hyperhidrosis may occur in these people.: 499  Skin tags Carpal tunnel syndrome Complications Problems with bones and joints, including osteoarthritis, nerve compression syndrome due to bony overgrowth, and carpal tunnel syndrome Hypertension Diabetes mellitus Cardiomyopathy, potentially leading to heart failure Colorectal cancer Sleep Apnea Thyroid nodules and thyroid cancer Hypogonadism Compression of the optic chiasm by the growth of pituitary adenoma leading to visual problems Causes Pituitary adenoma About 98% of cases of acromegaly are due to the overproduction of growth hormone by a benign tumor of the pituitary gland called an adenoma. These tumors produce excessive growth hormone and compress surrounding brain tissues as they grow larger. In some cases, they may compress the optic nerves. Expansion of the tumor may cause headaches and visual disturbances. In addition, compression of the surrounding normal pituitary tissue can alter production of other hormones, leading to changes in menstruation and breast discharge in women and impotence in men because of reduced testosterone production.A marked variation in rates of GH production and the aggressiveness of the tumor occurs. Some adenomas grow slowly and symptoms of GH excess are often not noticed for many years. Other adenomas grow rapidly and invade surrounding brain areas or the sinuses, which are located near the pituitary. In general, younger people tend to have more aggressive tumors.Most pituitary tumors arise spontaneously and are not genetically inherited. Many pituitary tumors arise from a genetic alteration in a single pituitary cell that leads to increased cell division and tumor formation. This genetic change, or mutation, is not present at birth but is acquired during life. The mutation occurs in a gene that regulates the transmission of chemical signals within pituitary cells; it permanently switches on the signal that tells the cell to divide and secrete growth hormones. The events within the cell that cause disordered pituitary cell growth and GH oversecretion currently are the subject of intensive research.Pituitary adenomas and diffuse somatomammotroph hyperplasia may result from somatic mutations activating GNAS, which may be acquired or associated with McCune-Albright syndrome. Other tumors In a few people, acromegaly is caused not by pituitary tumors, but by tumors of the pancreas, lungs, and adrenal glands. These tumors also lead to an excess of GH, either because they produce GH themselves or, more frequently, because they produce GHRH (growth hormone-releasing hormone), the hormone that stimulates the pituitary to make GH. In these people, the excess GHRH can be measured in the blood and establishes that the cause of the acromegaly is not due to a pituitary defect. When these nonpituitary tumors are surgically removed, GH levels fall and the symptoms of acromegaly improve.In people with GHRH-producing, non-pituitary tumors, the pituitary still may be enlarged and may be mistaken for a tumor. Therefore, it is important that physicians carefully analyze all "pituitary tumors" removed from people with acromegaly so as to not overlook the possibility that a tumor elsewhere in the body is causing the disorder. Diagnosis If acromegaly is suspected, medical laboratory investigations followed by medical imaging if the lab tests are positive confirms or rules out the presence of this condition. IGF1 provides the most sensitive lab test for the diagnosis of acromegaly, and a GH suppression test following an oral glucose load, which is a very specific lab test, will confirm the diagnosis following a positive screening test for IGF1. A single value of the GH is not useful in view of its pulsatility (levels in the blood vary greatly even in healthy individuals). GH levels taken 2 hours after a 75- or 100-gram glucose tolerance test are helpful in the diagnosis: GH levels are suppressed below 1 μg/L in normal people, and levels higher than this cutoff are confirmatory of acromegaly.Other pituitary hormones must be assessed to address the secretory effects of the tumor, as well as the mass effect of the tumor on the normal pituitary gland. They include thyroid stimulating hormone (TSH), gonadotropic hormones (FSH, LH), adrenocorticotropic hormone, and prolactin.An MRI of the brain focusing on the sella turcica after gadolinium administration allows for clear delineation of the pituitary and the hypothalamus and the location of the tumor. A number of other overgrowth syndromes can result in similar problems. Differential diagnosis Pseudoacromegaly is a condition with the usual acromegaloid features, but without an increase in growth hormone and IGF-1. It is frequently associated with insulin resistance. Cases have been reported due to minoxidil at an unusually high dose. It can also be caused by a selective post receptor defect of insulin signalling, leading to the impairment of metabolic, but preservation of mitogenic, signalling. Treatment The goals of treatment are to reduce GH production to normal levels thereby reversing or ameliorating the signs and symptoms of acromegaly, to relieve the pressure that the growing pituitary tumor exerts on the surrounding brain areas, and to preserve normal pituitary function. Currently, treatment options include surgical removal of the tumor, drug therapy, and radiation therapy of the pituitary. Medications Somatostatin analogues The primary current medical treatment of acromegaly is to use somatostatin analogues – octreotide (Sandostatin) or lanreotide (Somatuline). These somatostatin analogues are synthetic forms of a brain hormone, somatostatin, which stops GH production. The long-acting forms of these drugs must be injected every 2 to 4 weeks for effective treatment. Most people with acromegaly respond to this medication. In many people with acromegaly, GH levels fall within one hour and headaches improve within minutes after the injection. Octreotide and lanreotide are effective for long-term treatment. Octreotide and lanreotide have also been used successfully to treat people with acromegaly caused by non-pituitary tumors.Somatostatin analogues are also sometimes used to shrink large tumors before surgery.Because octreotide inhibits gastrointestinal and pancreatic function, long-term use causes digestive problems such as loose stools, nausea, and gas in one third of people. In addition, approximately 25 percent of people with acromegaly develop gallstones, which are usually asymptomatic. In some cases, octreotide treatment can cause diabetes due to the fact that somatostatin and its analogues can inhibit the release of insulin. With an aggressive adenoma that is not able to be operated on, there may be a resistance to octreotide and in which case a second generation SSA, pasireotide, may be used for tumor control. However, insulin and glucose levels should be carefully monitored as pasireotide has been associated with hyperglycemia by reducing insulin secretion. Dopamine agonists For those who are unresponsive to somatostatin analogues, or for whom they are otherwise contraindicated, it is possible to treat using one of the dopamine agonists, bromocriptine or cabergoline. As tablets rather than injections, they cost considerably less. These drugs can also be used as an adjunct to somatostatin analogue therapy. They are most effective in those whose pituitary tumours cosecrete prolactin. Side effects of these dopamine agonists include gastrointestinal upset, nausea, vomiting, light-headedness when standing, and nasal congestion. These side effects can be reduced or eliminated if medication is started at a very low dose at bedtime, taken with food, and gradually increased to the full therapeutic dose. Bromocriptine lowers GH and IGF-1 levels and reduces tumor size in fewer than half of people with acromegaly. Some people report improvement in their symptoms although their GH and IGF-1 levels still are elevated. Growth hormone receptor antagonists The latest development in the medical treatment of acromegaly is the use of growth hormone receptor antagonists. The only available member of this family is pegvisomant (Somavert). By blocking the action of the endogenous growth hormone molecules, this compound is able to control the disease activity of acromegaly in virtually everyone with acromegaly. Pegvisomant has to be administered subcutaneously by daily injections. Combinations of long-acting somatostatin analogues and weekly injections of pegvisomant seem to be equally effective as daily injections of pegvisomant. Surgery Surgical removal of the pituitary tumor is usually effective in lowering growth hormone levels. Two surgical procedures are available for use. The first is endonasal transsphenoidal surgery, which involves the surgeon reaching the pituitary through an incision in the nasal cavity wall. The wall is reached by passing through the nostrils with microsurgical instruments. The second method is transsphenoidal surgery during which an incision is made into the gum beneath the upper lip. Further incisions are made to cut through the septum to reach the nasal cavity, where the pituitary is located. Endonasal transsphenoidal surgery is a less invasive procedure with a shorter recovery time than the older method of transsphenoidal surgery, and the likelihood of removing the entire tumor is greater with reduced side effects. Consequently, endonasal transsphenoidal surgery is the more common surgical choice.These procedures normally relieve the pressure on the surrounding brain regions and lead to a lowering of GH levels. Surgery is most successful in people with blood GH levels below 40 ng/ml before the operation and with pituitary tumors no larger than 10 mm in diameter. Success depends on the skill and experience of the surgeon. The success rate also depends on what level of GH is defined as a cure. The best measure of surgical success is the normalization of GH and IGF-1 levels. Ideally, GH should be less than 2 ng/ml after an oral glucose load. A review of GH levels in 1,360 people worldwide immediately after surgery revealed that 60% had random GH levels below 5 ng/ml. Complications of surgery may include cerebrospinal fluid leaks, meningitis, or damage to the surrounding normal pituitary tissue, requiring lifelong pituitary hormone replacement.Even when surgery is successful and hormone levels return to normal, people must be carefully monitored for years for possible recurrence. More commonly, hormone levels may improve, but not return completely to normal. These people may then require additional treatment, usually with medications. Radiation therapy Radiation therapy has been used both as a primary treatment and combined with surgery or drugs. It is usually reserved for people who have tumor remaining after surgery. These people often also receive medication to lower GH levels. Radiation therapy is given in divided doses over four to six weeks. This treatment lowers GH levels by about 50 percent over 2 to 5 years. People monitored for more than 5 years show significant further improvement. Radiation therapy causes a gradual loss of production of other pituitary hormones with time. Loss of vision and brain injury, which have been reported, are very rare complications of radiation treatments. Selection of treatment The initial treatment chosen should be individualized depending on the persons characteristics, such as age and tumor size. If the tumor has not yet invaded surrounding brain tissues, removal of the pituitary adenoma by an experienced neurosurgeon is usually the first choice. After surgery, a person must be monitored long-term for increasing GH levels.If surgery does not normalize hormone levels or a relapse occurs, a doctor will usually begin additional drug therapy. The current first choice is generally octreotide or lanreotide; however, bromocriptine and cabergoline are both cheaper and easier to administer. With all of these medications, long-term therapy is necessary, because their withdrawal can lead to rising GH levels and tumor re-expansion.Radiation therapy is generally used for people whose tumors are not completely removed by surgery, for people who are not good candidates for surgery because of other health problems, and for people who do not respond adequately to surgery and medication. Prognosis Life expectancy of people with acromegaly is dependent on how early the disease is detected. Life expectancy after the successful treatment of early disease is equal to that of the general population. Acromegaly can often go on for years before diagnosis, resulting in poorer outcome, and it is suggested that the better the growth hormone is controlled, the better the outcome. Upon successful surgical treatment, headaches and visual symptoms tend to resolve. One exception is sleep apnea, which is present in around 70% of cases, but does not tend to resolve with successful treatment of growth hormone level. While hypertension is a complication of 40% of cases, it typically responds well to regular regimens of blood pressure medication. Diabetes that occurs with acromegaly is treated with the typical medications, but successful lowering of growth hormone levels often alleviates symptoms of diabetes. Hypogonadism without gonad destruction is reversible with treatment. Acromegaly is associated with a slightly elevated risk of cancer. Notable people Famous people with acromegaly include: Daniel Cajanus (1704–1749), "The Finnish Goliath". His natural size portrait and femur are still extant. His height was estimated to have been 247 cm (8 1"). Mary Ann Bevan (1874–1933), an English woman, who after developing acromegaly, toured the sideshow circuit as "the ugliest woman in the world". André the Giant (born André Roussimoff, 1946–1993), French professional wrestler and actor Salvatore Baccaro (1932–1984), Italian character actor. Active in B-movies, comedies, and horrors because of his peculiar features and spontaneous sympathy Paul Benedict (1938–2008), American actor. Best known for portraying Harry Bentley, The Jeffersons English next door neighbour Big Show (born Paul Wight; 1972), American professional wrestler and actor, had his pituitary tumor removed in 1991. Eddie Carmel, born Oded Ha-Carmeili (1936–1972), Israeli-born entertainer with gigantism and acromegaly, popularly known as "The Jewish Giant" Ted Cassidy (1932–1979), American actor. Best known for portraying Lurch in the TV sitcom The Addams Family Rondo Hatton (1894–1946), American journalist and actor. A Hollywood favorite in B-movie horror films of the 1930s and 1940s. Hattons disfigurement, due to acromegaly, developed over time, beginning during his service in World War I. Sultan Kösen, the worlds tallest man Maximinus Thrax, Roman emperor (c.  173, reigned 235–238). Descriptions, as well as depictions, indicate acromegaly, though remains of his body are yet to be found. The Great Khali (born Dalip Singh Rana), Indian professional wrestler, is best known for his tenure with WWE. He had his pituitary tumor removed in 2012 at age 39. Primo Carnera (1906–1967), nicknamed the Ambling Alp, was an Italian professional boxer and wrestler who reigned as the boxing World Heavyweight Champion from 29 June 1933 to 14 June 1934. Maurice Tillet (1903–1954), Russian-born French professional wrestler, is better known by his ring name, the French Angel. Richard Kiel (1939–2014), actor, "Jaws" from two James Bond movies and Mr. Larson in Happy Gilmore Pío Pico, the last Mexican Governor of California (1801–1894), manifested acromegaly without gigantism between at least 1847 and 1858. Some time after 1858, signs of the growth hormone-producing tumor disappeared along with all the secondary effects the tumor had caused in him. He looked normal in his 90s. His remarkable recovery is likely an example of spontaneous selective pituitary tumor apoplexy. Earl Nightingale (March 12, 1921 – March 25, 1989) was an American radio speaker and author, dealing mostly with the subjects of human character development, motivation, and meaningful existence. He was the voice during the early 1950s of Sky King, the hero of a radio adventure series, and was a WGN radio program host from 1950 to 1956. Nightingale was the author of The Strangest Secret, which economist Terry Savage has termed "…one of the great motivational books of all time." Nightingale’s daughter, Pamela, mentioned her father had acromegaly during a podcast about her father that aired in June 2022. Tony Robbins, motivational speaker Carel Struycken, Dutch actor, 2.13 m (7.0 ft), is best known for playing Lurch in The Addams Family film trilogy, The Giant in Twin Peaks, Lwaxana Trois silent Servant Mr. Homn in Star Trek: The Next Generation, and The Moonlight Man in Geralds Game, based on the Stephen King book. Peter Mayhew (1944–2019), British-American actor, was diagnosed with gigantism at age eight. Best known for portraying Chewbacca in the Star Wars film series. Irwin Keyes, American actor. Best known for portraying Hugo Mojoloweski, Georges occasional bodyguard on The Jeffersons Morteza Mehrzad, Iranian Paralympian and medalist. Member of the Iranian sitting volleyball team. Top scorer in the 2016 gold medal match Neil McCarthy, British actor. Known for roles in Zulu, Time Bandits, and many British television series Nikolai Valuev, Russian politician and former professional boxer Antônio "Bigfoot" Silva, Brazilian kickboxer and mixed martial arts fighter. (Leonel) Edmundo Rivero, Argentine tango singer, composer and impresarioIt has been argued that Lorenzo de Medici (1449–92) may have had acromegaly. Historical documents and portraits, as well as a later analysis of his skeleton, support the speculation. Pianist and composer Sergei Rachmaninoff, noted for his hands that could comfortably stretch a 13th on the piano, was never diagnosed with acromegaly in his lifetime, but a medical article from 2006 suggests that he might have had it.The Bogdanoff twins had shown some signs of acromegaly and their continued denials that they had plastic surgery that greatly altered their facial appearance made some consider the disease. However, acromegaly was not proven before they died. See also Hypothalamic–pituitary–somatic axis Macrognathism References External links Acromegaly at Curlie 2011 American Association of Clinical Endocrinologists Guideline Archived 29 August 2017 at the Wayback Machine Endocrine and Metabolic Diseases Information Service

Aarogya, What does Actinic keratosis mean

Actinic keratosis

Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin. Actinic keratosis is a disorder (-osis) of epidermal keratinocytes that is induced by ultraviolet (UV) light exposure (actin-). These growths are more common in fair-skinned people and those who are frequently in the sun. They are believed to form when skin gets damaged by UV radiation from the sun or indoor tanning beds, usually over the course of decades. Given their pre-cancerous nature, if left untreated, they may turn into a type of skin cancer called squamous cell carcinoma. Untreated lesions have up to a 20% risk of progression to squamous cell carcinoma, so treatment by a dermatologist is recommended. Actinic keratoses characteristically appear as thick, scaly, or crusty areas that often feel dry or rough. Size commonly ranges between 2 and 6 millimeters, but they can grow to be several centimeters in diameter. Notably, AKs are often felt before they are seen, and the texture is sometimes compared to sandpaper. They may be dark, light, tan, pink, red, a combination of all these, or have the same color as the surrounding skin. Given the causal relationship between sun exposure and AK growth, they often appear on a background of sun-damaged skin and in areas that are commonly sun-exposed, such as the face, ears, neck, scalp, chest, backs of hands, forearms, or lips. Because sun exposure is rarely limited to a small area, most people who have an AK have more than one.If clinical examination findings are not typical of AK and the possibility of in situ or invasive squamous cell carcinoma (SCC) cannot be excluded based on clinical examination alone, a biopsy or excision can be considered for definitive diagnosis by histologic examination of the lesional tissue. Multiple treatment options for AK are available. Photodynamic therapy (PDT) is one option the treatment of numerous AK lesions in a region of the skin, termed field cancerization. It involves the application of a photosensitizer to the skin followed by illumination with a strong light source. Topical creams, such as 5-fluorouracil or imiquimod, may require daily application to affected skin areas over a typical time course of weeks. Cryotherapy is frequently used for few and well-defined lesions, but undesired skin lightening, or hypopigmentation, may occur at the treatment site. By following up with a dermatologist, AKs can be treated before they progress to skin cancer. If cancer does develop from an AK lesion, it can be caught early with close monitoring, at a time when treatment is likely to have a high cure rate. Signs and symptoms Actinic keratoses (AKs) most commonly present as a white, scaly plaque of variable thickness with surrounding redness; they are most notable for having a sandpaper-like texture when felt with a gloved hand. Skin nearby the lesion often shows evidence of solar damage characterized by notable pigmentary alterations, being yellow or pale in color with areas of hyperpigmentation; deep wrinkles, coarse texture, purpura and ecchymoses, dry skin, and scattered telangiectasias are also characteristic.Photoaging leads to an accumulation of oncogenic changes, resulting in a proliferation of mutated keratinocytes that can manifest as AKs or other neoplastic growths. With years of sun damage, it is possible to develop multiple AKs in a single area on the skin. This condition is termed field cancerization. The lesions are usually asymptomatic, but can be tender, itch, bleed, or produce a stinging or burning sensation. AKs are typically graded in accordance with their clinical presentation: Grade I (easily visible, slightly palpable), Grade II (easily visible, palpable), and Grade III (frankly visible and hyperkeratotic). Variants Actinic keratoses can have various clinical presentations, often characterized as follows: Classic (or common): Classic AKs present as white, scaly macules, papules or plaques of various thickness, often with surrounding erythema. They are usually 2–6mm in diameter but can sometimes reach several centimeters in diameter. Hypertrophic (or hyperkeratotic): Hypertrophic AKs (HAKs) appears as a thicker scale or rough papule or plaque, often adherent to an erythematous base. Classic AKs can progress to become HAKs, and HAKs themselves can be difficult to distinguish from malignant lesions. Atrophic: Atrophic AKs lack an overlying scale, and therefore appear as a nonpalpable change in color (or macule). They are often smooth and red and are less than 10mm in diameter. AK with cutaneous horn: A cutaneous horn is a keratinic projection with its height at least one-half of its diameter, often conical in shape. They can be seen in the setting of actinic keratosis as a progression of an HAK, but are also present in other skin conditions. 38–40% of cutaneous horns represent AKs. Pigmented AK: Pigmented AKs are rare variants that often present as macules or plaques that are tan to brown in color. They can be difficult to distinguish from a solar lentigo or lentigo maligna. Actinic cheilitis: When an AK forms on the lip, it is called actinic cheilitis. This usually presents as a rough, scaly patch on the lip, often accompanied by the sensation of dry mouth and symptomatic splitting of the lips. Bowenoid AK: Usually presents as a solitary, erythematous, scaly patch or plaque with well-defined borders. Bowenoid AKs are differentiated from Bowens disease by degree of epithelial involvement as seen on histology.The presence of ulceration, nodularity, or bleeding should raise concern for malignancy. Specifically, clinical findings suggesting an increased risk of progression to squamous cell carcinoma can be recognized as "IDRBEU": I (induration/inflammation), D (diameter > 1 cm), R (rapid enlargement), B (bleeding), E (erythema), and U (ulceration). AKs are usually diagnosed clinically, but because they are difficult to clinically differentiate from squamous cell carcinoma, any concerning features warrant biopsy for diagnostic confirmation. Causes The most important cause of AK formation is solar radiation, through a variety of mechanisms. Mutation of the p53 tumor suppressor gene, induced by UV radiation, has been identified as a crucial step in AK formation. This tumor suppressor gene, located on chromosome 17p132, allows for cell cycle arrest when DNA or RNA is damaged. Dysregulation of the p53 pathway can thus result in unchecked replication of dysplastic keratinocytes, thereby serving as a source of neoplastic growth and the development of AK, as well as possible progression from AK to skin cancer. Other molecular markers that have been associated with the development of AK include the expression of p16ink4, p14, the CD95 ligand, TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors, and loss of heterozygosity.Evidence also suggests that the human papillomavirus (HPV) plays a role in the development of AKs. The HPV virus has been detected in AKs, with measurable HPV viral loads (one HPV-DNA copy per less than 50 cells) measured in 40% of AKs. Similar to UV radiation, higher levels of HPV found in AKs reflect enhanced viral DNA replication. This is suspected to be related to the abnormal keratinocyte proliferation and differentiation in AKs, which facilitate an environment for HPV replication. This in turn may further stimulate the abnormal proliferation that contributes to the development of AKs and carcinogenesis. Ultraviolet radiation It is thought that ultraviolet (UV) radiation induces mutations in the keratinocytes of the epidermis, promoting the survival and proliferation of these atypical cells. Both UV-A and UV-B radiation have been implicated as causes of AKs. UV-A radiation (wavelength 320–400 nm) reaches more deeply into the skin and can lead to the generation of reactive oxygen species, which in turn can damage cell membranes, signaling proteins, and nucleic acids. UV-B radiation (wavelength 290–320 nm) causes thymidine dimer formation in DNA and RNA, leading to significant cellular mutations. In particular, mutations in the p53 tumor suppressor gene have been found in 30–50% of AK lesion skin samples.UV radiation has also been shown to cause elevated inflammatory markers such as arachidonic acid, as well as other molecules associated with inflammation. Eventually, over time these changes lead to the formation of AKs. Several predictors for increased AK risk from UV radiation have been identified: Extent of sun exposure: Cumulative sun exposure leads to an increased risk for development of AKs. In one U.S. study, AKs were found in 55% of fair-skinned men with high cumulative sun exposure, and in only 19% of fair-skinned men with low cumulative sun exposure in an age-matched cohort (the percents for women in this same study were 37% and 12% respectively). Furthermore, the use of sunscreen (SPF 17 or higher) has been found to significantly reduce the development of AK lesions, and also promotes the regression of existing lesions. History of sunburn: Studies show that even a single episode of painful sunburn as a child can increase an individuals risk of developing AK as an adult. Six or more painful sunburns over the course of a lifetime was found to be significantly associated with the likelihood of developing AK. Skin pigmentation Melanin is a pigment in the epidermis that functions to protect keratinocytes from the damage caused by UV radiation; it is found in higher concentrations in the epidermis of darker-skinned individuals, affording them protection against the development of AKs. Fair-skinned individuals have a significantly increased risk of developing AKs when compared to olive-skinned individuals (odds ratios of 14.1 and 6.5, respectively), and AKs are uncommon in dark-skinned people of African descent. Other phenotypic features seen in fair-skinned individuals that are associated with an increased propensity to develop AKs include: Freckling Light hair and eye color Propensity to sunburn Inability to tan Other risk factors Immunosuppression: People with a compromised immune system from medical conditions (such as AIDS) or immunosuppressive therapy (such as chronic immunosuppression after organ transplantation, or chemotherapy for cancer) are at increased risk for developing AKs. They may develop AK at an earlier age or have an increased number of AK lesions compared to immunocompetent people. Human papillomavirus (HPV): The role of HPV in the development of AK remains unclear, but evidence suggests that infection with the betapapillomavirus type of HPV may be associated with an increased likelihood of AK. Genodermatoses: Certain genetic disorders interfere with DNA repair after sun exposure, thereby putting these individuals at higher risk for the development of AKs. Examples of such genetic disorders include xeroderma pigmentosum and Bloom syndrome. Balding: AKs are commonly found on the scalps of balding men. The degree of baldness seems to be a risk factor for lesion development, as men with severe baldness were found to be seven times more likely to have 10 or more AKs when compared to men with minimal or no baldness. This observation can be explained by an absence of hair causing a larger proportion of scalp to be exposed to UV radiation if other sun protection measures are not taken. Diagnosis Physicians usually diagnose actinic keratosis by doing a thorough physical examination, through a combination of visual observation and touch. However a biopsy may be necessary when the keratosis is large in diameter, thick, or bleeding, in order to make sure that the lesion is not a skin cancer. Actinic keratosis may progress to invasive squamous cell carcinoma (SCC) but both diseases can present similarly upon physical exam and can be difficult to distinguish clinically. Histological examination of the lesion from a biopsy or excision may be necessary to definitively distinguish AK from in situ or invasive SCC. In addition to SCCs, AKs can be mistaken for other cutaneous lesions including seborrheic keratoses, basal cell carcinoma, lichenoid keratosis, porokeratosis, viral warts, erosive pustular dermatosis of the scalp, pemphigus foliaceus, inflammatory dermatoses like psoriasis, or melanoma. Biopsy A lesion biopsy is performed if the diagnosis remains uncertain after a clinical physical exam, or if there is suspicion that the AK might have progressed to squamous cell carcinoma. The most common tissue sampling techniques include shave or punch biopsy. When only a portion of the lesion can be removed due to its size or location, the biopsy should sample tissue from the thickest area of the lesion, as SCCs are most likely to be detected in that area. If a shave biopsy is performed, it should extend through to the level of the dermis in order to provide sufficient tissue for diagnosis; ideally, it would extend to the mid-reticular dermis. Punch biopsy usually extends to the subcutaneous fat when the entire length of the punch blade is utilized. Histopathology On histologic examination, actinic keratoses usually show a collection of atypical keratinocytes with hyperpigmented or pleomorphic nuclei, extending to the basal layer of the epidermis. A "flag sign" is often described, referring to alternating areas of orthokeratosis and parakeratosis. Epidermal thickening and surrounding areas of sun-damaged skin are often seen. The normal ordered maturation of the keratinocytes is disordered to varying degrees: there may be widening of the intracellular spaces, cytologic atypia such as abnormally large nuclei, and a mild chronic inflammatory infiltrate.Specific findings depend on the clinical variant and particular lesion characteristics. The seven major histopathologic variants are all characterized by atypical keratinocytic proliferation beginning in the basal layer and confined to the epidermis; they include: Hypertrophic: Notable for marked hyperkeratosis, often with evident parakeratosis. Keratinocytes in the stratum malphigii may show a loss of polarity, pleomorphism, and anaplasia. Some irregular downward proliferation into the uppermost dermis may be observed, but does not represent frank invasion. Atrophic: With slight hyperkeratosis and overall atrophic changes to the epidermis; the basal layer shows cells with large, hyperchromatic nuclei in close proximity to each other. These cells have been observed to proliferate into the dermis as buds and duct-like structures. Lichenoid: Demonstrate a band-like lymphocytic infiltrate in the papillary dermis, directly beneath the dermal-epidermal junction. Achantholytic: Intercellular clefts or lacunae in the lowermost epidermal layer that result from anaplastic changes; these produce dyskeratotic cells with disrupted intercellular bridges. Bowenoid: This term is controversial and usually refers to full-thickness atypia, microscopically indistinguishable from Bowens Disease. However most dermatologists and pathologists will use it in reference to tissue samples that are notable for small foci of atypia that involve the full thickness of the epidermis, in the background of a lesion that is otherwise consistent with an AK. Epidermolytic: With granular degeneration. Pigmented: Show pigmentation in the basal layer of the epidermis, similar to a solar lentigo. Dermoscopy Dermoscopy is a noninvasive technique utilizing a handheld magnifying device coupled with a transilluminating lift. It is often used in the evaluation of cutaneous lesions but lacks the definitive diagnostic ability of biopsy-based tissue diagnosis. Histopathologic exam remains the gold standard. Polarized contact dermoscopy of AKs occasionally reveals a "rosette sign," described as four white points arranged in a clover pattern, often localized to within a follicular opening. It is hypothesized that the "rosette sign" corresponds histologically to the changes of orthokeratosis and parakeratosis known as the "flag sign." Non-pigmented AKs: linear or wavy vascular patterning, or a "strawberry pattern," described as unfocused vessels between hair follicles, with white-haloed follicular openings. Pigmented AKs: gray to brown dots or globules surrounding follicular openings, and annular-granular rhomboidal structures; often difficult to differentiate from lentigo maligna. Prevention Ultraviolet radiation is believed to contribute to the development of actinic keratoses by inducing mutations in epidermal keratinocytes, leading to proliferation of atypical cells. Therefore, preventive measures for AKs are targeted at limiting exposure to solar radiation, including: Limiting extent of sun exposure Avoid sun exposure during noontime hours between 10:00 AM and 2:00 PM when UV light is most powerful Minimize all time in the sun, since UV exposure occurs even in the winter and on cloudy days Using sun protection Applying sunscreens with SPF ratings 30 or greater that also block both UVA and UVB light, at least every 2 hours and after swimming or sweating Applying sunscreen at least 15 minutes before going outside, as this allows time for the sunscreen to be absorbed appropriately by the skin Wearing sun protective clothing such as hats, sunglasses, long-sleeved shirts, long skirts, or trousersRecent research implicating human papillomavirus (HPV) in the development of AKs suggests that HPV prevention might in turn help prevent development of AKs, as UV-induced mutations and oncogenic transformation are likely facilitated in cases of active HPV infection. A key component of HPV prevention includes vaccination, and the CDC currently recommends routine vaccination in all children at age 11 or 12.There is some data that in individuals with a history of non-melanoma skin cancer, a low-fat diet can serve as a preventative measure against future actinic keratoses. Management There are a variety of treatment options for AK depending on the patient and the clinical characteristics of the lesion. AKs show a wide range of features, which guide decision-making in choosing treatment. As there are multiple effective treatments, patient preference and lifestyle are also factors that physicians consider when determining the management plan for actinic keratosis. Regular follow-up is advisable after any treatment to make sure no new lesions have developed and that old ones are not progressing. Adding topical treatment after a procedure may improve outcomes. Medication Topical medications are often recommended for areas where multiple or ill-defined AKs are present, as the medication can easily be used to treat a relatively large area. Fluorouracil cream Topical fluorouracil (5-FU) destroys AKs by blocking methylation of thymidylate synthetase, thereby interrupting DNA and RNA synthesis. This in turn prevents the proliferation of dysplastic cells in AK. Topical 5-FU is the most utilized treatment for AK, and often results in effective removal of the lesion. Overall, there is a 50% efficacy rate resulting in 100% clearance of AKs treated with topical 5-FU. 5-FU may be up to 90% effective in treating non-hyperkeratotic lesions. While topical 5-FU is a widely used and cost-effective treatment for AKs and is generally well tolerated, its potential side-effects can include: pain, crusting, redness, and local swelling. These adverse effects can be mitigated or minimized by reducing the frequency of application or taking breaks between uses. The most commonly used application regimen consists of applying a layer of topical cream to the lesion twice a day after washing; duration of treatment is typically 2–4 weeks to thinner skin like the cheeks and up to 8 weeks for the arms; treatment of up to 8 weeks has demonstrated a higher cure rate. Imiquimod cream Imiquimod is a topical immune-enhancing agent licensed for the treatment of genital warts. Imiquimod stimulates the immune system through the release and up-regulation of cytokines. Treatment with Imiquimod cream applied 2–3 times per week for 12 to 16 weeks was found to result in complete resolution of AKs in 50% of people, compared to 5% of controls. The Imiquimod 3.75% cream has been validated in a treatment regimen consisting of daily application to entire face and scalp for two 2-week treatment cycles, with a complete clearance rate of 36%.While the clearance rate observed with the Imiquimod 3.75% cream was lower than that observed with the 5% cream (36 and 50 percent, respectively), there are lower reported rates of adverse reactions with the 3.75% cream: 19% of individuals using Imiquimod 3.75% cream reported adverse reactions including local erythema, scabbing, and flaking at the application site, while nearly a third of individuals using the 5% cream reported the same types of reactions with Imiquimod treatment. However, it is ultimately difficult to compare the efficacy of the different strength creams directly, as current study data varies in methodology (e.g. duration and frequency of treatment, and amount of skin surface area covered). Ingenol mebutate gel Ingenol mebutate is a newer treatment for AK used in Europe and the United States. It works in two ways, first by disrupting cell membranes and mitochondria resulting cell death, and then by inducing antibody-dependent cellular cytotoxicity to eliminate remaining tumor cells. A 3-day treatment course with the 0.015% gel is recommended for the scalp and face, while a 2-day treatment course with the 0.05% gel is recommended for the trunk and extremities. Treatment with the 0.015% gel was found to completely clear 57% of AK, while the 0.05% gel had a 34% clearance rate. Advantages of ingenol mebutate treatment include the short duration of therapy and a low recurrence rate. Local skin reactions including pain, itching and redness can be expected during treatment with ingenol mebutate. This treatment was derived from the petty spurge, Euphorbia peplus which has been used as a traditional remedy for keratosis. Diclofenac sodium gel Topical diclofenac sodium gel is a nonsteroidal anti-inflammatory drug that is thought to work in the treatment of AK through its inhibition of the arachidonic acid pathway, thereby limiting the production of prostaglandins which are thought to be involved in the development of UVB-induced skin cancers. Recommended duration of therapy is 60 to 90 days with twice daily application. Treatment of facial AK with diclofenac gel led to complete lesion resolution in 40% of cases. Common side effects include dryness, itching, redness, and rash at the site of application. Retinoids Topical retinoids have been studied in the treatment of AK with modest results, and the American Academy of Dermatology does not currently recommend this as first-line therapy. Treatment with adapalene gel daily for 4 weeks, and then twice daily thereafter for a total of nine months led to a significant but modest reduction in the number AKs compared to placebo; it demonstrated the additional advantage of improving the appearance of photodamaged skin.Topical tretinoin is ineffective as treatment for reducing the number of AKs. For secondary prevention of AK, systemic, low-dose acitretin was found to be safe, well tolerated and moderately effective in chemoprophylaxis for skin cancers in kidney transplant patients. Acitretin is a viable treatment option for organ transplant patients according to expert opinion. Tirbanibulin Tirbanibulin (Klisyri) was approved for medical use in the United States in December 2020, for the treatment of actinic keratosis on the face or scalp. Procedures Cryotherapy Liquid nitrogen (−195.8 °C) is the most commonly used destructive therapy for the treatment of AK in the United States. It is a well-tolerated office procedure that does not require anesthesia.Cryotherapy is particularly indicated for cases where there are fewer than 15 thin, well-demarcated lesions. Caution is encouraged for thicker, more hyperkeratotic lesions, as dysplastic cells may evade treatment. Treatment with both cryotherapy and field treatment can be considered for these more advanced lesions. Cryotherapy is generally performed using an open-spray technique, wherein the AK is sprayed for several seconds.The process can be repeated multiple times in one office visit, as tolerated. Cure rates from 67 to 99 percent have been reported, depending on freeze time and lesion characteristics. Disadvantages include discomfort during and after the procedure; blistering, scarring and redness; hypo- or hyperpigmentation; and destruction of healthy tissue. Photodynamic therapy AKs are one of the most common dermatologic lesions for which photodynamic therapy, including topical methyl aminolevulinate (MAL) or 5-aminolevulinic acid (5-ALA), is indicated.Treatment begins with preparation of the lesion, which includes scraping away scales and crusts using a dermal curette. A thick layer of topical MAL or 5-ALA cream is applied to the lesion and a small area surrounding the lesion, which is then covered with an occlusive dressing and left for a period of time. During this time the photosensitizer accumulates in the target cells within the AK lesion. The dressings are then removed and the lesion is treated with light at a specified wavelength. Multiple treatment regimens using different photosensitizers, incubation times, light sources, and pretreatment regimens have been studied and suggest that longer incubation times lead to higher rates of lesion clearance. Photodynamic therapy is gaining in popularity. It has been found to have a 14% higher likelihood of achieving complete lesion clearance at 3 months compared to cryotherapy, and seems to result in superior cosmetic outcomes when compared to cryotherapy or 5-FU treatment. Photodynamic therapy can be particularly effective in treating areas with multiple AK lesions. Surgical techniques Surgical excision: Excision should be reserved for cases when the AK is a thick, horny papule, or when deeper invasion is suspected and histopathologic diagnosis is necessary. It is a rarely utilized technique for AK treatment. Shave excision and curettage (sometimes followed by electrodesiccation when deemed appropriate by the physician): This technique is often used for treatment of AKs, and particularly for lesions appearing more similar to squamous cell carcinoma, or those that are unresponsive to other treatments. The surface of the lesion can be scraped away using a scalpel, or the base can be removed with a curette. Tissue can be evaluated histopathologically under the microscope, but specimens acquired using this technique are not often adequate to determine whether a lesion is invasive or intraepidermal. Dermabrasion: Dermabrasion is useful in the treatment of large areas with multiple AK lesions. The process involves using a hand-held instrument to "sand" the skin, removing the stratum corneum layer of the epidermis. Diamond fraises or wire brushes revolving at high speeds are used. The procedure can be quite painful and requires procedural sedation and anesthetic, necessitating a hospital stay. One-year clearance rates with dermabrasion treatment are as high as 96%, but diminish drastically to 54% at five years. Laser therapy Laser therapy using carbon dioxide (CO2) or erbium:yttrium aluminum garnet (Er:YAG) lasers is a treatment approach being utilized with increased frequency, and sometimes in conjunction with computer scanning technology. Laser therapy has not been extensively studied, but current evidence suggests it may be effective in cases involving multiple AKs refractive to medical therapy, or AKs located in cosmetically sensitive locations such as the face. The CO2 laser has been recommended for extensive actinic cheilitis that has not responded to 5-FU. Chemical peels A chemical peel is a topically applied agent that wounds the outermost layer of the skin, promoting organized repair, exfoliation, and eventually the development of smooth and rejuvenated skin. Multiple therapies have been studied. A medium-depth peel may effectively treat multiple non-hyperkeratotic AKs. It can be achieved with 35% to 50% trichloroacetic acid (TCA) alone or at 35% in combination with Jessners solution in a once-daily application for a minimum of 3 weeks; 70% glycolic acid (α-hydroxy acid); or solid CO2. When compared to treatment with 5-FU, chemical peels have demonstrated similar efficacy and increased ease of use with similar morbidity. Chemical peels must be performed in a controlled clinic environment and are recommended only for individuals who are able to comply with follow-up precautions, including avoidance of sun exposure. Furthermore, they should be avoided in individuals with a history of HSV infection or keloids, and in those who are immunosuppressed or who are taking photosensitizing medications. Prognosis Untreated AKs follow one of three paths: they can either persist as AKs, regress, or progress to invasive skin cancer, as AK lesions are considered to be on the same continuum with squamous cell carcinoma (SCC). AK lesions that regress also have the potential to recur. Progression: The overall risk of an AK turning into invasive cancer is low. In average-risk individuals, likelihood of an AK lesion progressing to SCC is less than 1% per year. Despite this low rate of progression, studies suggest that a full 60% of SCCs arise from pre-existing AKs, reinforcing the idea that these lesions are closely related. Regression: Reported regression rates for single AK lesions have ranged between 15 and 63% after one year. Recurrence: Recurrence rates after 1 year for single AK lesions that have regressed range between 15 and 53%. Clinical course Given the aforementioned differering clinical outcomes, it is difficult to predict the clinical course of any given actinic keratosis. AK lesions may also come and go—in a cycle of appearing on the skin, remaining for months, and then disappearing. Often they will reappear in a few weeks or months, particularly after unprotected sun exposure. Left untreated, there is a chance that the lesion will advance to become invasive. Although it is difficult to predict whether an AK will advance to become squamous cell carcinoma, it has been noted that squamous cell carcinomas originate in lesions formerly diagnosed as AKs with frequencies reported between 65 and 97%. Epidemiology Actinic keratosis is very common, with an estimated 14% of dermatology visits related to AKs. It is seen more often in fair-skinned individuals, and rates vary with geographical location and age. Other factors such as exposure to ultraviolet (UV) radiation, certain phenotypic features, and immunosuppression can also contribute to the development of AKs. Men are more likely to develop AK than women, and the risk of developing AK lesions increases with age. These findings have been observed in multiple studies, with numbers from one study suggesting that approximately 5% of women ages 20–29 develop AK compared to 68% of women ages 60–69, and 10% of men ages 20–29 develop AK compared to 79% of men ages 60–69.Geography seems to play a role in the sense that individuals living in locations where they are exposed to more UV radiation throughout their lifetime have a significantly higher risk of developing AK. Much of the literature on AK comes from Australia, where the prevalence of AK is estimated at 40–50% in adults over 40, as compared to the United States and Europe, where prevalence is estimated at under 11–38% in adults. One study found that those who immigrated to Australia after age 20 had fewer AKs than native Australians in all age groups. Research Diagnostically, researchers are investigating the role of novel biomarkers to assist in determining which AKs are more likely to develop into cutaneous or metastatic SCC. Upregulation of matrix metalloproteinases (MMP) is seen in many different types of cancers, and the expression and production of MMP-7 in particular has been found to be elevated in SCC specifically. The role of serin peptidase inhibitors (Serpins) is also being investigated. SerpinA1 was found to be elevated in the keratinocytes of SCC cell lines, and SerpinA1 upregulation was correlated with SCC tumor progression in vivo. Further investigation into specific biomarkers could help providers better assess prognosis and determine best treatment approaches for particular lesions. In terms of treatment, a number of medications are being studied. Resiquimod is a TLR 7/8 agonist that works similarly to imiquimod, but is 10 to 100 times more potent; when used to treat AK lesions, complete response rates have range from 40 to 74%. Afamelanotide is a drug that induces the production of melanin by melanocytes to act as a protective factor against UVB radiation. It is being studied to determine its efficacy in preventing AKs in organ transplant patients who are on immunosuppressive therapy. Epidermal growth factor receptor (EGFR) inhibitors such as gefitinib, and anti-EGFR antibodies such as cetuximab are used in the treatment of various types of cancers, and are currently being investigated for potential use in the treatment and prevention of AKs. See also Age spot Freckle Lentigo Squamous cell carcinoma List of cutaneous conditions References == External links ==

Aarogya, share information about a health condition involving Congenital adrenal hyperplasia

Congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex. Most of these disorders involve excessive or deficient production of hormones such as glucocorticoids, mineralocorticoids, or sex steroids, and can alter development of primary or secondary sex characteristics in some affected infants, children, or adults. It is one of the most common autosomal recessive disorders in humans. Types CAH can occur in various forms. The clinical presentation of each form is different and depends to a large extent on the underlying enzyme defect, its precursor retention, and deficient products. Classical forms appear in infancy, and nonclassical forms appear in late childhood. The presentation in patients with classic CAH can be further subdivided into two forms: salt-wasting and simple-virilizing, depending on whether mineralocorticoid deficiency presents or absents, respectively (you should put absents before presents to straight the meaning of respectively). This subtyping is often not clinically meaningful, though, because all patients lose salt to some degree, and clinical presentations may overlap. Classic Salt-wasting In 75% of cases of severe enzyme deficiency, insufficient aldosterone production can lead to salt wasting, failure to thrive, and potentially fatal hypovolemia and shock. A missed diagnosis of salt-loss CAH is related to the increased risk of early neonatal morbidity and death. Simple-virilizing The main feature of CAH in newborn females is the abnormal development of the external genitalia, which has varying degrees of virilization. According to clinical practice guidelines, for newborns found to have bilateral inaccessible gonads, CAH evaluation should be considered. If virilizing CAH cannot be identified and treated, both boys and girls may undergo rapid postnatal growth and virilization. Nonclassic In addition to the salt-wasting and simple-virilizing forms of CAH diagnosed in infancy, a mild or "nonclassic" form exists, which is characterized by varying degrees of postnatal androgen excess, but is sometimes asymptomatic. The nonclassic form may be noticed in late childhood and may lead to accelerated growth, premature sexual maturation, acne, and secondary polycystic ovary syndrome. In adult males, early balding and infertility may suggest the diagnosis. The nonclassic form is characterized by mild subclinical impairment of cortisol synthesis; serum cortisol concentration is usually normal. Signs and symptoms The symptoms of CAH vary depending upon the form of CAH and the sex of the patient. Symptoms can include: Due to inadequate mineralocorticoids: Vomiting due to salt-wasting, leading to dehydration and deathDue to excess androgens: In extreme virilization, an elongated clitoris with a phallic-like structure is seen. Ambiguous genitalia, in some infants, occurs such that initially identifying external genitalia as "male" or "female" is difficult. Early pubic hair and rapid growth occurs in childhood. Precocious puberty or failure of puberty to occur (sexual infantilism: absent or delayed puberty) Excessive facial hair, virilization, and/or menstrual irregularity in adolescence Infertility due to anovulation Clitoromegaly, enlarged clitoris and shallow vaginaDue to insufficient androgens and estrogens: Undervirilization in XY males can result in apparently female external genitalia. In females, hypogonadism can cause sexual infantilism or abnormal pubertal development, infertility, and other reproductive system abnormalities. Genetics CAH results from mutations of genes for enzymes mediating the biochemical steps of production of mineralocorticoids, glucocorticoids, or sex steroids from cholesterol by the adrenal glands (steroidogenesis).Each form of CAH is associated with a specific defective gene. The most common type (95% of cases) involves the gene for 21-hydroxylase, which is found on 6p21.3 as part of the HLA complex; 21-hydroxylase deficiency results from a unique mutation with two highly homologous near-copies in series consisting of an active gene (CYP21A2) and an inactive pseudogene (CYP21A1P). Mutant alleles result from recombination between the active and pseudogenes (gene conversion). About 5% of cases of CAH are due to defects in the gene encoding 11β-hydroxylase and consequent 11β-hydroxylase deficiency. Other, more rare forms of CAH are caused by mutations in genes, including HSD3B2 (3β-hydroxysteroid dehydrogenase 2), CYP17A1 (17α-hydroxylase/17,20-lyase), CYP11A1 (P450scc; cholesterol side-chain cleavage enzyme), STAR (steroidogenic acute regulatory protein; StAR), CYB5A (cytochrome b5), and CYPOR (cytochrome P450 oxidoreductase; POR). Expressivity Further variability is introduced by the degree of enzyme inefficiency produced by the specific alleles each patient has. Some alleles result in more severe degrees of enzyme inefficiency. In general, severe degrees of inefficiency produce changes in the fetus and problems in prenatal or perinatal life. Milder degrees of inefficiency are usually associated with excessive or deficient sex hormone effects in childhood or adolescence, while the mildest forms of CAH interfere with ovulation and fertility in adults. Diagnosis Clinical evaluation Female infants with classic CAH have ambiguous genitalia due to exposure to high concentrations of androgens in utero. CAH due to 21-hydroxylase deficiency is the most common cause of ambiguous genitalia in genotypically normal female infants (46XX). Less severely affected females may present with early pubarche. Young women may present with symptoms of polycystic ovarian syndrome (oligomenorrhea, polycystic ovaries, hirsutism).Males with classic CAH generally have no signs of CAH at birth. Some may present with hyperpigmentation, due to co-secretion with melanocyte-stimulating hormone, and possible penile enlargement. Age of diagnosis of males with CAH varies and depends on the severity of aldosterone deficiency. Boys with salt-wasting disease present early with symptoms of hyponatremia and hypovolemia. Boys with non-salt-wasting disease present later with signs of virilization.In rarer forms of CAH, males are undermasculinized and females generally have no signs or symptoms at birth. Laboratory studies Genetic analysis can be helpful to confirm a diagnosis of CAH, but it is not necessary if classic clinical and laboratory findings are present. In classic 21-hydroxylase deficiency, laboratory studies will show: Hypoglycemia (due to hypocortisolism) - One of cortisols many functions is to increase blood glucose levels. This occurs via a combination of several mechanisms, including (a) the stimulation of gluconeogesis (i.e. the creation of new glucose) in the liver, (b) the promotion of glycogenolysis (i.e. the breakdown of glycogen into glucose), and (c) the prevention of glucose leaving the bloodstream via the downregulation of GLUT-4 receptors (which normally promote movement of glucose from the bloodstream into adipose and muscle tissues). Therefore, when cortisol is deficient, these processes (effectively) occur in the reverse direction. Although there are compensatory mechanisms that mitigate the impact of hypocortisolism, they are limited in their extent and the net effect is still hypoglycemia. Hyponatremia (due to hypoaldosteronism) - Aldosterone is the end product of the renin-angiotensin-aldosterone system that regulates blood pressure via blood pressure surveillance in the Kidney Juxtaglomerular apparatus. Aldosterone normally functions to increase sodium retention (which brings water as well) in exchange for potassium. Thus, lack of aldosterone causes hyperkalemia and hyponatremia. In fact, this is a distinguishing point from 11-hydroxylase deficiency, in which one of the increased products is 11-deoxycorticosterone that has weak mineralocorticoid activity. In 11-hydroxylase deficiency, 11-deoxycorticosterone is produced in such excess that it acts to retain sodium at the expense of potassium. It is this reason that patients with 11-hydroxylase deficiency do not show salt wasting (although sometimes they do in infancy), and instead have hypertension/water retention and sometimes hypokalemia. Hyperkalemia (due to hypoaldosteronism) Elevated 17α-hydroxyprogesteroneClassic 21-hydroxylase deficiency typically causes 17α-hydroxyprogesterone blood levels >242 nmol/L. (For comparison, a full-term infant at three days of age should have <3 nmol/L. Many neonatal screening programs have specific reference ranges by weight and gestational age because high levels may be seen in premature infants without CAH.) Salt-wasting patients tend to have higher 17α-hydroxyprogesterone levels than non-salt-wasting patients. In mild cases, 17α-hydroxyprogesterone may not be elevated in a particular random blood sample, but it will rise during a corticotropin stimulation test. Classification Cortisol is an adrenal steroid hormone required for normal endocrine function. Production begins in the second month of fetal life. Poor cortisol production is a hallmark of most forms of CAH. Inefficient cortisol production results in rising levels of ACTH, because cortisol feeds back to inhibit ACTH production, so loss of cortisol results in increased ACTH. This increased ACTH stimulation induces overgrowth (hyperplasia) and overactivity of the steroid-producing cells of the adrenal cortex. The defects causing adrenal hyperplasia are congenital (i.e. present at birth). Cortisol deficiency in CAH is usually partial, and not the most serious problem for an affected person. Synthesis of cortisol shares steps with synthesis of mineralocorticoids such as aldosterone, androgens such as testosterone, and estrogens such as estradiol. The resulting excessive or deficient production of these three classes of hormones produce the most important problems for people with CAH. Specific enzyme inefficiencies are associated with characteristic patterns of over- or underproduction of mineralocorticoids or sex steroids. Since the 1960s, most endocrinologists have referred to the forms of CAH by the traditional names in the left column, which generally correspond to the deficient enzyme activity. As exact structures and genes for the enzymes were identified in the 1980s, most of the enzymes were found to be cytochrome P450 oxidases and were renamed to reflect this. In some cases, more than one enzyme was found to participate in a reaction, and in other cases, a single enzyme mediated in more than one reaction. Variation in different tissues and mammalian species also was found. In all its forms, congenital adrenal hyperplasia due to 21-hydroxylase deficiency accounts for about 95% of diagnosed cases of CAH. Unless another specific enzyme is mentioned, "CAH" in nearly all contexts refers to 21-hydroxylase deficiency. (The terms "salt-wasting CAH", and "simple virilizing CAH" usually refer to subtypes of this condition.) CAH due to deficiencies of enzymes other than 21-hydroxylase present many of the same management challenges, as 21-hydroxylase deficiency, but some involve mineralocorticoid excess or sex steroid deficiency. Screening Currently, in the United States and over 40 other countries, every child born is screened for 21-hydroxylase CAH at birth. This test detects elevated levels of 17α-hydroxyprogesterone (17-OHP). Detecting high levels of 17-OHP enables early detection of CAH. Newborns detected early enough can be placed on medication and live relatively normal lives.The screening process, however, is characterized by a high false-positive rate. In one study, CAH screening had the lowest positive predictive value (111 true-positive cases among 20,647 abnormal screening results in a 2-year period, or 0.53%, compared with 6.36% for biotinidase deficiency, 1.84% for congenital hypo-thyroidism, 0.56% for classic galactosemia, and 2.9% for phenylketonuria). According to this estimate, 200 unaffected newborns required clinical and laboratory follow-up for every true case of CAH.In 2020, Wael AbdAlmageed from USC Information Sciences Institute and Mimi Kim from USC Keck School Of Medicine led a joint study in which they used deep learning technology to analyze the facial morphology and features of CAH patients compared to control. In this cross-sectional study of 102 patients with CAH and 144 control participants, deep learning methods achieved a mean area under the receiver operating characteristic curve of 92% for predicting CAH from facial images. Facial features distinguished patients with CAH from controls, and analyses of facial regions found that the nose and upper face were most contributory. The findings suggest that facial morphologic features, as analyzed by deep neural network techniques, can be used as a phenotypic biomarker to predict CAH. Treatment Since the clinical manifestations of each form of CAH are unique and depend to a large extent on the underlying enzyme defects, their precursor retention and defective products, the therapeutic goal of CAH is to replenish insufficient adrenal hormones and suppress excess of precursors.Treatment of all forms of CAH may include any of: Supplying enough glucocorticoid to reduce hyperplasia and overproduction of androgens or mineralocorticoids Providing replacement mineralocorticoid and extra salt if the person is deficient Providing replacement testosterone or estrogens at puberty if the person is deficient Additional treatments to optimize growth by delaying puberty or delaying bone maturation If CAH is caused by the deficiency of the 21-hydroxylase enzyme, then treatment aims to normalize levels of main substrate of the enzyme - 17α-hydroxyprogesterone. Epidemiology The incidence varies ethnically. In the United States, congenital adrenal hyperplasia in its classic form is particularly common in Native Americans and Yupik Inuit (incidence 1⁄280). Among American Caucasians, the incidence of the classic form is about 1⁄15,000).Continued treatment and wellness are enhanced by education and follow up. History Before 20th century An Italian anatomist, Luigi De Crecchio (1832-1894) provided the earliest known description of a case of probable CAH. I propose in this narrative that it is sometimes extremely difficult and even impossible to determine sex during life. In one of the anatomical theaters of the hospital..., there arrived toward the end of January a cadaver which in life was the body of a certain Joseph Marzo... The general physiognomy was decidedly male in all respects. There were no feminine curves to the body. There was a heavy beard. There was some delicacy of structure with muscles that were not very well developed... The distribution of pubic hair was typical of the male. Perhaps the lower extremities were somewhat delicate, resembling the female, and were covered with hair... The penis was curved posteriorly and measured 6 cm, or with stretching, 10 cm. The corona was 3 cm long and 8 cm in circumference. There was an ample prepuce. There was a first grade hypospadias... There were two folds of skin coming from the top of the penis and encircling it on either side. These were somewhat loose and resembled labia majora. De Crecchio then described the internal organs, which included a normal vagina, uterus, fallopian tubes, and ovaries. It was of the greatest importance to determine the habits, tendencies, passions, and general character of this individual... I was determined to get as complete a story as possible, determined to get at the base of the facts and to avoid undue exaggeration which was rampant in the conversation of many of the people present at the time of the dissection. He interviewed many people and satisfied himself that Joseph Marzo "conducted himself within the sexual area exclusively as a male", even to the point of contracting the "French disease" on two occasions. The cause of death was another in a series of episodes of vomiting and diarrhea.This account was translated by Alfred Bongiovanni from De Crecchio ("Sopra un caso di apparenzi virili in una donna". Morgagni 7:154–188, 1865) in 1963 for an article in The New England Journal of Medicine. 20th and 21st centuries The association of excessive sex steroid effects with diseases of the adrenal cortex have been recognized for over a century. The term "adrenogenital syndrome" was applied to both sex-steroid producing tumors and severe forms of CAH for much of the 20th century, before some of the forms of CAH were understood. Congenital adrenal hyperplasia, which also dates to the first half of the century, has become the preferred term to reduce ambiguity and to emphasize the underlying pathophysiology of the disorders. Much modern understanding and treatment of CAH comes from research conducted at Johns Hopkins Medical School in Baltimore in the middle of the 20th century. Lawson Wilkins, "founder" of pediatric endocrinology, worked out the apparently paradoxical pathophysiology: that hyperplasia and overproduction of adrenal androgens resulted from impaired capacity for making cortisol. He reported use of adrenal cortical extracts to treat children with CAH in 1950. Genital reconstructive surgery was also pioneered at Hopkins. After application of karyotyping to CAH and other intersex disorders in the 1950s, John Money, JL Hampson, and JG Hampson persuaded both the scientific community and the public that sex assignment should not be based on any single biological criterion, and gender identity was largely learned and has no simple relationship with chromosomes or hormones. See Intersex for a fuller history, including recent controversies over reconstructive surgery. Hydrocortisone, fludrocortisone, and prednisone were available by the late 1950s. By 1980, all of the relevant steroids could be measured in blood by reference laboratories for patient care. By 1990, nearly all specific genes and enzymes had been identified. The last decade, though, has seen a number of new developments, discussed more extensively in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: Debate over the value of genital reconstructive surgery and changing standards Debate over sex assignment of severely virilized XX infants New treatments to improve height outcomes Newborn screening programs to detect CAH at birth Increasing attempts to treat CAH before birth Society and culture People with CAH Notable people with CAH include: Jeff Cagandahan is a Filipino who successfully appealed for a change of name and gender on his birth certificate. Lisa Lee Dark Betsy Driver Casimir Pulaski, hypothesized based on examination of remains See also Disorders of sex development Inborn errors of steroid metabolism Intersex List of vaginal anomalies 5α-Reductase 2 deficiency Androgen insensitivity syndrome References Further reading Han, Thang S.; Walker, Brian R.; Arlt, Wiebke; Ross, Richard J. (17 December 2013). "Treatment and health outcomes in adults with congenital adrenal hyperplasia". Nature Reviews Endocrinology. 10 (2): 115–124. doi:10.1038/nrendo.2013.239. PMID 24342885. S2CID 6090764Figure 2: The adrenal steroidogenesis pathway.{{cite journal}}: CS1 maint: postscript (link) External links Congenital adrenal hyperplasia at Curlie

Can you describe Adrenocortical carcinoma, to me Aarogya

Adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is an aggressive cancer originating in the cortex (steroid hormone-producing tissue) of the adrenal gland. Adrenocortical carcinoma is remarkable for the many hormonal syndromes that can occur in patients with steroid hormone-producing ("functional") tumors, including Cushings syndrome, Conn syndrome, virilization, and feminization. Adrenocortical carcinoma has often invaded nearby tissues or metastasized to distant organs at the time of diagnosis, and the overall 5-year survival rate is about 50%.Adrenocortical carcinoma is a rare tumor, with incidence of one to two per million population annually. It has a bimodal distribution by age, with cases clustering in children under 5 and in adults 30–40 years old. The widely used angiotensin-II-responsive steroid-producing cell line H295R was originally isolated from a tumor diagnosed as adrenocortical carcinoma. Signs and symptoms Adrenocortical carcinoma may present differently in children and adults. Most tumors in children are functional, and virilization is by far the most common presenting symptom(s), followed by Cushings syndrome and precocious puberty. Among adults presenting with hormonal syndromes, Cushings syndrome alone is most common, followed by mixed Cushings and virilization (glucocorticoid and androgen overproduction). Feminization and Conn syndrome (mineralocorticoid excess) occur in less than 10% of cases. Rarely, pheochromocytoma-like hypersecretion of catecholamines has been reported in adrenocortical cancers. Nonfunctional tumors (about 40%, authorities vary) usually present with abdominal or flank pain, varicocele, and renal vein thrombosis or they may be asymptomatic and detected incidentally.All patients with suspected ACC should be carefully evaluated for signs and symptoms of hormonal syndromes. For Cushings syndrome (glucocorticoid excess), these include weight gain, muscle wasting, purple lines on the abdomen, a fatty "buffalo hump" on the neck, a "moon-like" face, and thinning, fragile skin. Virilism (androgen excess) is most obvious in women, and may produce excess facial and body hair, acne, enlargement of the clitoris, deepening of the voice, coarsening of facial features, cessation of menstruation. Conn syndrome (mineralcorticoid excess) is marked by high blood pressure, which can result in headache and hypokalemia (low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations), low plasma renin activity, and high serum aldosterone. Feminization (estrogen excess) is most readily noted in men, and includes breast enlargement, decreased libido, and impotence. Pathophysiology The main etiologic factor of ACC is unknown, although families with Li–Fraumeni syndrome, caused by an inherited inactivation mutation in TP53, have increased risk. Several genes have been shown to be recurrently mutated, including TP53, CTNNB1, MEN1, PRKAR1A, RPL22, and DAXX. The telomerase gene TERT is often amplified while ZNRF3 and CDKN2A are often homozygously deleted. The genes h19, insulin-like growth factor II (IGF-II), and p57kip2 are important for fetal growth and development. They are located on chromosome 11p. Expression of the h19 gene is markedly reduced in both nonfunctioning and functioning adrenal cortical carcinomas, especially in tumors producing cortisol and aldosterone. Also, a loss occurs of activity of the p57kip2 gene product in virilizing adenomas and adrenal cortical carcinomas. In contrast, IGF-II gene expression has been shown to be high in adrenal cortical carcinomas. Finally, c-myc gene expression is relatively high in neoplasms, and it is often linked to poor prognosis.Bilateral adrenocortical tumors are less common than unilateral. The majority of bilateral tumours can be distinguished according to size and aspect of the nodules: primary pigmented nodular adrenocortical disease, which can be sporadic or part of Carney complex, and primary bilateral macro nodular adrenal hyperplasia.Metastasis is most commonly to the liver and lung. Diagnosis Laboratory findings Hormonal syndromes should be confirmed with laboratory testing. Laboratory findings in Cushing syndrome include increased serum glucose (blood sugar) and increased urine cortisol. Adrenal virilism is confirmed by the finding of an excess of serum androstenedione and dehydroepiandrosterone. Findings in Conn syndrome include low serum potassium, low plasma renin activity, and high serum aldosterone. Feminization is confirmed with the finding of excess serum estrogen. Imaging Radiological studies of the abdomen, such as CT scans and magnetic resonance imaging are useful for identifying the site of the tumor, differentiating it from other diseases, such as adrenocortical adenoma, and determining the extent of invasion of the tumor into surrounding organs and tissues. On CT, it shows heterogeneous appearance due to necrosis, calcifications, and haemorrhage. After contrast injection, it shows peripheral enhancement. Invasion of adjacent structures such as kidney, vena cava, liver, and retroperitoneal lymph nodes are also common.On MRI, it shows low intensity on T1-weighted images, and high T2 signal with strong heterogeneous contrast enhancement and slow washout. Haemorrhagic areas may show high T1-signal. Pathology Adrenal tumors are often not biopsied prior to surgery, so diagnosis is confirmed on examination of the surgical specimen by a pathologist. Grossly, ACCs are often large, with a tan-yellow cut surface, and areas of hemorrhage and necrosis. On microscopic examination, the tumor usually displays sheets of atypical cells with some resemblance to the cells of the normal adrenal cortex. The presence of invasion and mitotic activity help differentiate small cancers from adrenocortical adenomas. Several relatively rare variants of ACC include: Oncocytic adrenal cortical carcinoma Myxoid adrenal cortical carcinoma Carcinosarcoma Adenosquamous adrenocortical carcinoma Clear cell adrenal cortical carcinoma Differential diagnosis Differential diagnosis includes: Adrenocortical adenoma Renal cell carcinoma Pheochromocytoma Hepatocellular carcinomaAdrenocortical carcinomas are most commonly distinguished from adrenocortical adenomas (their benign counterparts) by the Weiss system, as follows: Total score indicates: 0-2: Adrenocortical adenoma 3: Undetermined 4-9: Adrenocortical carcinoma Treatment The only curative treatment is complete surgical excision of the tumor, which can be performed even in the case of invasion into large blood vessels, such as the renal vein or inferior vena cava. The 5-year survival rate after successful surgery is 50–60%, but unfortunately, many patients are not surgical candidates. Radiation therapy and radiofrequency ablation may be used for palliation in patients who are not surgical candidates. Minimally invasive surgical techniques remain controversial due to the absence of long-term data, with a particular concern for rates of recurrence and peritoneal carcinomatosis.Chemotherapy regimens typically include the drug mitotane, an inhibitor of steroid synthesis, which is toxic to cells of the adrenal cortex, as well as standard cytotoxic drugs. A retrospective analysis showed a survival benefit for mitotane in addition to surgery when compared to surgery alone.The two most common regimens are cisplatin, doxorubicin, etoposide (EDP) + mitotane, and streptozotocin + mitotane. The FIRM-ACT trial demonstrated higher rates of response and longer progression-free survival with EDP + mitotane than with streptozotocin + mitotane. Prognosis ACC, generally, carries a poor prognosis, with an overall 5-year survival rate of about 50%. Five-year disease-free survival for a complete resection of a stage I–III ACC is about 30%. The most important prognostic factors are age of the patient and stage of the tumor. Poor prognostic factors include mitotic activity, venous invasion, weight of 50 g or more, diameter of 6.5 cm or more, Ki-67/MIB1 labeling index of 4% or more, and p53 positive.In its malignancy, adrenocortical carcinoma is unlike most tumours of the adrenal cortex, which are benign (adenomas) and only occasionally cause Cushings syndrome. References == External links ==

Aarogya , Do you know what is Alcohol withdrawal syndrome,

Alcohol withdrawal syndrome

Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. More severe symptoms may include seizures, hallucinations, and delirium tremens (DTs). Symptoms typically begin around six hours following the last drink, are worst at 24 to 72 hours, and improve by seven days.Alcohol withdrawal may occur in those who are alcohol dependent. This may occur following a planned or unplanned decrease in alcohol intake. The underlying mechanism involves a decreased responsiveness of GABA receptors in the brain. The withdrawal process is typically followed using the Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar).The typical treatment of alcohol withdrawal is with benzodiazepines such as chlordiazepoxide or diazepam. Often the amounts given are based on a persons symptoms. Thiamine is recommended routinely. Electrolyte problems and low blood sugar should also be treated. Early treatment improves outcomes.In the Western world about 15% of people have problems with alcoholism at some point in time. Alcohol depresses the central nervous system, slowing cerebral messaging and altering the way signals are sent and received. Progressively larger amounts of alcohol are needed to achieve the same physical and emotional results. The drinker eventually must consume alcohol just to avoid the physical cravings and withdrawal symptoms. About half of people with alcoholism will develop withdrawal symptoms upon reducing their use, with four percent developing severe symptoms. Among those with severe symptoms up to 15% die. Symptoms of alcohol withdrawal have been described at least as early as 400 BC by Hippocrates. It is not believed to have become a widespread problem until the 1700s. Signs and symptoms Signs and symptoms of alcohol withdrawal occur primarily in the central nervous system. The severity of withdrawal can vary from mild symptoms such as insomnia, trembling, and anxiety to severe and life-threatening symptoms such as alcoholic hallucinosis, delirium tremens, and autonomic instability.Withdrawal usually begins 6 to 24 hours after the last drink. It can last for up to one week. To be classified as alcohol withdrawal syndrome, patients must exhibit at least two of the following symptoms: increased hand tremor, insomnia, nausea or vomiting, transient hallucinations (auditory, visual or tactile), psychomotor agitation, anxiety, generalized tonic–clonic seizures, and autonomic instability.The severity of symptoms is dictated by a number of factors, the most important of which are degree of alcohol intake, length of time the individual has been using alcohol, and previous history of alcohol withdrawal. Symptoms are also grouped together and classified: Alcohol hallucinosis: patients have transient visual, auditory, or tactile hallucinations, but are otherwise clear. Withdrawal seizures: seizures occur within 48 hours of alcohol cessations and occur either as a single generalized tonic-clonic seizure or as a brief episode of multiple seizures. Delirium tremens: hyperadrenergic state, disorientation, tremors, diaphoresis, impaired attention/consciousness, and visual and auditory hallucinations. Progression Six to 12 hours after the ingestion of the last drink, withdrawal symptoms such as shaking, headache, sweating, anxiety, nausea or vomiting may occur. Twelve to 24 hours after cessation, the condition may progress to such major symptoms as confusion, hallucinations (with awareness of reality), while less severe symptoms may persist and develop including tremor, agitation, hyperactivity and insomnia.At 12 to 48 hours following the last ethanol ingestion, the possibility of generalized tonic–clonic seizures should be anticipated, occurring in 3-5% of cases. Meanwhile, none of the earlier withdrawal symptoms will typically have abated. Seizures carry the risk of major complications and death for the alcoholic.Although the persons condition usually begins to improve after 48 hours, withdrawal symptoms sometimes continue to increase in severity and advance to the most severe stage of withdrawal, delirium tremens. This occurs in 5 to 20% of patients experiencing detoxification and one third of untreated cases, which is characterized by hallucinations that are indistinguishable from reality, severe confusion, seizures, high blood pressure, and fever that can persist anywhere from 4 to 12 days. Protracted withdrawal A protracted alcohol withdrawal syndrome occurs in many alcoholics when withdrawal symptoms continue beyond the acute withdrawal stage but usually at a subacute level of intensity and gradually decreasing with severity over time. This syndrome is sometimes referred to as the post-acute-withdrawal syndrome. Some withdrawal symptoms can linger for at least a year after discontinuation of alcohol. Symptoms can include a craving for alcohol, inability to feel pleasure from normally pleasurable things (known as anhedonia), clouding of sensorium, disorientation, nausea and vomiting or headache.Insomnia is a common protracted withdrawal symptom that persists after the acute withdrawal phase of alcohol. Insomnia has also been found to influence relapse rate. Studies have found that magnesium or trazodone can help treat the persisting withdrawal symptom of insomnia in recovering alcoholics. Insomnia can be difficult to treat in these individuals because many of the traditional sleep aids (e.g., benzodiazepine receptor agonists and barbiturate receptor agonists) work via a GABAA receptor mechanism and are cross-tolerant with alcohol. However, trazodone is not cross-tolerant with alcohol. The acute phase of the alcohol withdrawal syndrome can occasionally be protracted. Protracted delirium tremens has been reported in the medical literature as a possible but unusual feature of alcohol withdrawal. Pathophysiology Chronic use of alcohol leads to changes in brain chemistry especially in the GABAergic system. Various adaptations occur such as changes in gene expression and down regulation of GABAA receptors. During acute alcohol withdrawal, changes also occur such as upregulation of alpha4 containing GABAA receptors and downregulation of alpha1 and alpha3 containing GABAA receptors. Neurochemical changes occurring during alcohol withdrawal can be minimized with drugs which are used for acute detoxification. With abstinence from alcohol and cross-tolerant drugs these changes in neurochemistry may gradually return towards normal. Adaptations to the NMDA system also occur as a result of repeated alcohol intoxication and are involved in the hyper-excitability of the central nervous system during the alcohol withdrawal syndrome. Homocysteine levels, which are elevated during chronic drinking, increase even further during the withdrawal state, and may result in excitotoxicity. Alterations in ECG (in particular an increase in QT interval) and EEG abnormalities (including abnormal quantified EEG) may occur during early withdrawal. Dysfunction of the hypothalamic–pituitary–adrenal axis and increased release of corticotropin-releasing hormone occur during both acute as well as protracted abstinence from alcohol and contribute to both acute and protracted withdrawal symptoms. Anhedonia/dysphoria symptoms, which can persist as part of a protracted withdrawal, may be due to dopamine underactivity. Kindling Kindling is a phenomenon where repeated alcohol detoxifications leads to an increased severity of the withdrawal syndrome. For example, binge drinkers may initially experience no withdrawal symptoms, but with each period of alcohol use followed by cessation, their withdrawal symptoms intensify in severity and may eventually result in full-blown delirium tremens with convulsive seizures. Alcoholics who experience seizures during detoxification are more likely to have had previous episodes of alcohol detoxification than patients who did not have seizures during withdrawal. In addition, people with previous withdrawal syndromes are more likely to have more medically complicated alcohol withdrawal symptoms.Kindling can cause complications and may increase the risk of relapse, alcohol-related brain damage and cognitive deficits. Chronic alcohol misuse and kindling via multiple alcohol withdrawals may lead to permanent alterations in the GABAA receptors. The mechanism behind kindling is sensitization of some neuronal systems and desensitization of other neuronal systems which leads to increasingly gross neurochemical imbalances. This in turn leads to more profound withdrawal symptoms including anxiety, convulsions and neurotoxicity.Binge drinking is associated with increased impulsivity, impairments in spatial working memory and impaired emotional learning. These adverse effects are believed to be due to the neurotoxic effects of repeated withdrawal from alcohol on aberrant neuronal plasticity and cortical damage. Repeated periods of acute intoxication followed by acute detoxification has profound effects on the brain and is associated with an increased risk of seizures as well as cognitive deficits. The effects on the brain are similar to those seen in alcoholics who have detoxified repeatedly but not as severe as in alcoholics who have no history of prior detox. Thus, the acute withdrawal syndrome appears to be the most important factor in causing damage or impairment to brain function. The brain regions most sensitive to harm from binge drinking are the amygdala and prefrontal cortex.People in adolescence who experience repeated withdrawals from binge drinking show impairments of long-term nonverbal memory. Alcoholics who have had two or more alcohol withdrawals show more frontal lobe cognitive dysfunction than those who have experienced one or no prior withdrawals. Kindling of neurons is the proposed cause of withdrawal-related cognitive damage. Kindling from repeated withdrawals leads to accumulating neuroadaptive changes. Kindling may also be the reason for cognitive damage seen in binge drinkers. Diagnosis Many hospitals use the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol in order to assess the level of withdrawal present and therefore the amount of medication needed. When overuse of alcohol is suspected but drinking history is unclear, testing for elevated values of carbohydrate-deficient transferrin or gammaglutamyl transferase can help make the diagnosis of alcohol overuse and dependence more clear. The CIWA has also been shortened (now called the CIWA-Ar), while retaining its validity and reliability, to help assess patients more efficiently due to the life-threatening nature of alcohol withdrawal.Other conditions that may present similarly include benzodiazepine withdrawal syndrome (a condition also mainly caused by GABAA receptor adaptation). Treatment Benzodiazepines are effective for the management of symptoms as well as the prevention of seizures. Certain vitamins are also an important part of the management of alcohol withdrawal syndrome. In those with severe symptoms inpatient care is often required. In those with lesser symptoms treatment at home may be possible with daily visits with a health care provider. Benzodiazepines Benzodiazepines are the most commonly used medication for the treatment of alcohol withdrawal and are generally safe and effective in suppressing symptoms of alcohol withdrawal. This class of medication is generally effective in symptoms control, but need to be used carefully. Although benzodiazepines have a long history of successfully treating and preventing withdrawal, there is no consensus on the ideal one to use. The most commonly used agents are long-acting benzodiazepines, such as chlordiazepoxide and diazepam. These are believed to be superior to other benzodiazepines for treatment of delirium and allow for longer periods between doses. However, benzodiazepines with intermediate half-lives like lorazepam may be safer in people with liver problems. Benzodiazepines showed a protective benefit against alcohol withdrawal symptoms, in particular seizure, compared to other common methods of treatment.The primary debate between use of long-acting benzodiazepines and short-acting is that of ease of use. Longer-acting drugs, such as diazepam, can be administered less frequently. However, evidence does exist that "symptom-triggered regimens" such as those used when treating with lorazepam, are as safe and effective, but have decreased treatment duration and medication quantity used.Although benzodiazepines are very effective at treating alcohol withdrawal, they should be carefully used. Benzodiazepines should only be used for brief periods in alcoholics who are not already dependent on them, as they share cross tolerance with alcohol. There is a risk of replacing an alcohol addiction with benzodiazepine dependence or adding another addiction. Furthermore, disrupted GABA benzodiazepine receptor function is part of alcohol dependence and chronic benzodiazepines may prevent full recovery from alcohol induced mental effects. The combination of benzodiazepines and alcohol can amplify the adverse psychological effects of each other causing enhanced depressive effects on mood and increase suicidal actions and are generally contraindicated except for alcohol withdrawal. Vitamins Alcoholics are often deficient in various nutrients, which can cause severe complications during alcohol withdrawal, such as the development of Wernicke syndrome. To help to prevent Wernicke syndrome, these individuals should be administered a multivitamin preparation with sufficient quantities of thiamine and folic acid. During alcohol withdrawal, the prophylactic administration of thiamine, folic acid, and pyridoxine intravenously is recommended before starting any carbohydrate-containing fluids or food. These vitamins are often combined into a banana bag for intravenous administration. Anticonvulsants Very limited evidence indicates that topiramate or pregabalin may be useful in the treatment of alcohol withdrawal syndrome. Limited evidence supports the use of gabapentin or carbamazepine for the treatment of mild or moderate alcohol withdrawal as the sole treatment or as combination therapy with other medications; however, gabapentin does not appear to be effective for treatment of severe alcohol withdrawal and is therefore not recommended for use in this setting. A 2010 Cochrane review similarly reported that the evidence to support the role of anticonvulsants over benzodiazepines in the treatment of alcohol withdrawal is not supported. Paraldehyde combined with chloral hydrate showed superiority over chlordiazepoxide with regard to life-threatening side effects and carbamazepine may have advantages for certain symptoms. Long term anticonvulsant medications are not usually recommended in those who have had prior seizures due to withdrawal. Prevention of further drinking There are three medications used to help prevent a return to drinking: naltrexone, acamprosate, and disulfiram. They are used after withdrawal has occurred. Other Clonidine may be used in combination with benzodiazepines to help some of the symptoms. No conclusions can be drawn concerning the efficacy or safety of baclofen for alcohol withdrawal syndrome due to the insufficiency and low quality of the evidence.Antipsychotics, such as haloperidol, are sometimes used in addition to benzodiazepines to control agitation or psychosis. Antipsychotics may potentially worsen alcohol withdrawal as they lower the seizure threshold. Clozapine, olanzapine, or low-potency phenothiazines (such as chlorpromazine) are particularly risky; if used, extreme caution is required.While intravenous ethanol could theoretically be used, evidence to support this use, at least in those who are very sick, is insufficient. Prognosis Failure to manage the alcohol withdrawal syndrome appropriately can lead to permanent brain damage or death. It has been proposed that brain damage due to alcohol withdrawal may be prevented by the administration of NMDA antagonists, calcium antagonists, and glucocorticoid antagonists. Substances impairing recovery Continued use of benzodiazepines may impair recovery from psychomotor and cognitive impairments from alcohol. Cigarette smoking may slow down or interfere with recovery of brain pathways in recovering alcoholics. References External links CIWA-Ar for Alcohol Withdrawal Alcohol Detox Guidelines Example Archived 19 August 2019 at the Wayback Machine

Hey Aarogya, could you help me understand about Alopecia areata

Alopecia areata

Alopecia areata, also known as spot baldness, is a condition in which hair is lost from some or all areas of the body. Often, it results in a few bald spots on the scalp, each about the size of a coin. Psychological stress and illness are possible factors in bringing on alopecia areata in individuals at risk, but in most cases there is no obvious trigger. People are generally otherwise healthy. In a few cases, all the hair on the scalp is lost (alopecia totalis), or all body hair is lost (alopecia universalis). Hair loss can be permanent, or temporary. It is distinctive from pattern hair loss, which is common among males. Alopecia areata is believed to be an autoimmune disease resulting from a breach in the immune privilege of the hair follicles. Risk factors include a family history of the condition. Among identical twins, if one is affected, the other has about a 50% chance of also being affected. The underlying mechanism involves failure by the body to recognize its own cells, with subsequent immune-mediated destruction of the hair follicle.No cure for the condition is known. Efforts may be used to try to speed hair regrowth, such as cortisone injections. Sunscreen, head coverings to protect from cold and sun, and glasses, if the eyelashes are missing, are recommended. In some cases, the hair regrows, and the condition does not reoccur. In others, hair loss and regrowth occurs over years. Among those in whom all body hair is lost, fewer than 10% recover.About 0.15% of people are affected at any one time, and 2% of people are affected at some point in time. Onset is usually in childhood. Females are affected at higher rates than males. Signs and symptoms Typical first symptoms of alopecia areata are small bald patches. The underlying skin is unscarred and looks superficially normal. Although these patches can take many shapes, they are usually round or oval. Alopecia areata most often affects the scalp and beard, but may occur on any part of the body with hair. Different areas of the skin may exhibit hair loss and regrowth at the same time. The disease may also go into remission for a time, or may be permanent. It is common in children.The area of hair loss may tingle or be mildly painful. The hair tends to fall out over a short period of time, with the loss commonly occurring more on one side of the scalp than the other.Exclamation point hairs, narrower along the length of the strand closer to the base, producing a characteristic "exclamation point" appearance, are often present. These hairs are very short (3–4 mm), and can be seen surrounding the bald patches.When healthy hair is pulled out, at most a few should come out, and ripped hair should not be distributed evenly across the tugged portion of the scalp. In cases of alopecia areata, hair tends to pull out more easily along the edge of the patch where the follicles are already being attacked by the bodys immune system than away from the patch where they are still healthy.Nails may have pitting or trachyonychia. Causes Alopecia areata is thought to be a systemic autoimmune disorder in which the body attacks its own anagen hair follicles and suppresses or stops hair growth. For example, T cell lymphocytes cluster around affected follicles, causing inflammation and subsequent hair loss. Hair follicles in a normal state are thought to be kept secure from the immune system, a phenomenon called immune privilege. A breach in this immune privilege state is considered as the cause of alopecia areata. A few cases of babies being born with congenital alopecia areata have been reported.Alopecia areata is not contagious. It occurs more frequently in people who have affected family members, suggesting heredity may be a factor. Strong evidence of genetic association with increased risk for alopecia areata was found by studying families with two or more affected members. This study identified at least four regions in the genome that are likely to contain these genes. In addition, alopecia areata shares genetic risk factors with other autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, and celiac disease. It may be the only manifestation of celiac disease.Endogenous retinoids metabolic defect is a key part of the pathogenesis of the alopecia areata.In 2010, a genome-wide association study was completed that identified 129 single nucleotide polymorphisms that were associated with alopecia areata. The genes that were identified include those involved in controlling the activation and proliferation of regulatory T cells, cytotoxic T lymphocyte-associated antigen 4, interleukin-2, interleukin-2 receptor A, and Eos (also known as Ikaros family zinc finger 4), as well as the human leukocyte antigen. The study also identified two genes, PRDX5 and STX17, that are expressed in the hair follicle. Diagnosis Alopecia areata is usually diagnosed based on clinical features. Trichoscopy may aid in establishing the diagnosis. In alopecia areata, trichoscopy shows regularly distributed "yellow dots" (hyperkeratotic plugs), small exclamation-mark hairs, and "black dots" (destroyed hairs in the hair follicle opening).Oftentimes, however, discrete areas of hair loss surrounded by exclamation mark hairs is sufficient for clinical diagnosis of alopecia areata. Sometimes, reddening of the skin, erythema, may also be present in the balding area.A biopsy is rarely needed to make the diagnosis or aid in the management of alopecia areata. Histologic findings may include peribulbar lymphocytic infiltration resembling a "swarm of bees", a shift in the anagen-to-telogen ratio towards telogen, and dilated follicular infundibulae. Other helpful findings can include pigment incontinence in the hair bulb and follicular stelae. Occasionally, in inactive alopecia areata, no inflammatory infiltrates are found. Classification Commonly, alopecia areata involves hair loss in one or more round spots on the scalp. Hair may also be lost more diffusely over the whole scalp, in which case the condition is called diffuse alopecia areata. Alopecia areata monolocularis describes baldness in only one spot. It may occur anywhere on the head. Alopecia areata multilocularis refers to multiple areas of hair loss. Ophiasis refers to hair loss in the shape of a wave at the circumference of the head. The disease may be limited only to the beard, in which case it is called alopecia areata barbae. If the person loses all the hair on the scalp, the disease is then called alopecia areata totalis. If all body hair, including pubic hair, is lost, the diagnosis then becomes alopecia areata universalis.Alopecia areata totalis and universalis are rare. Treatment The objective assessment of treatment efficacy is very difficult and spontaneous remission is unpredictable, but if the affected area is patched, the hair may regrow spontaneously in many cases. None of the existing therapeutic options are curative or preventive.In cases of severe hair loss, limited success has been achieved by using the corticosteroid medications clobetasol or fluocinonide, corticosteroid injections, or cream. Application of corticosteroid creams to the affected skin is less effective and takes longer to produce results. Steroid injections are commonly used in sites where the areas of hair loss on the head are small or especially where eyebrow hair has been lost. Whether they are effective is uncertain. Some other medications that have been used are minoxidil, Elocon (mometasone) ointment (steroid cream), irritants (anthralin or topical coal tar), and topical immunotherapy ciclosporin, sometimes in different combinations. Topical corticosteroids frequently fail to enter the skin deeply enough to affect the hair bulbs, which are the treatment target, and small lesions typically also regrow spontaneously. Oral corticosteroids may decrease the hair loss, but only for the period during which they are taken, and these medications can cause serious side effects. No one treatment is effective in all cases, and some individuals may show no response to any treatment. Few treatments have been well evaluated. A 2008 meta-analysis of oral and topical corticosteroids, topical ciclosporin, photodynamic therapy, and topical minoxidil showed no benefit of hair growth compared with placebo, especially with regard to long-term benefits. For more severe cases, recent studies have shown promising results with the individual use of the immunosuppressant Methotrexate or adjunct use with corticosteroids. However, as relapse of the condition may occur long-term treatment is recommended.When alopecia areata is associated with celiac disease, treatment with a gluten-free diet allows for complete and permanent regrowth of scalp and other body hair in many people, but in others, remissions and recurrences are seen. This improvement is probably due to the normalization of the immune response as a result of gluten withdrawal from the diet.In June 2022, the U.S. Food and Drug Administration (FDA) authorized baricitinib for the treatment of severe alopecia areata. Prognosis In most cases that begin with a small number of patches of hair loss, hair grows back after a few months to a year. In cases with a greater number of patches, hair can either grow back or progress to alopecia areata totalis or, in rare cases, alopecia areata universalis.No loss of body function occurs, and the effects of alopecia areata are psychological (loss of self-image due to hair loss), although these can be severe. Loss of hair also means the scalp burns more easily in the sun. Patients may also have aberrant nail formation because keratin forms both hair and nails.Hair may grow back and then fall out again later. This may not indicate a recurrence of the condition, but rather a natural cycle of growth-and-shedding from a relatively synchronised start; such a pattern will fade over time. Episodes of alopecia areata before puberty predispose to chronic recurrence of the condition.Alopecia can be the cause of psychological stress. Because hair loss can lead to significant changes in appearance, individuals with it may experience social phobia, anxiety, and depression. Epidemiology The condition affects 0.1%–0.2% of the population, with a lifetime risk of 1%-2%. and is more common in females.Alopecia areata occurs in people who are otherwise healthy and have no other skin disorders. Initial presentation most commonly occurs in the early childhood, late teenage years, or young adulthood, but can happen at any ages. Patients also tend to have a slightly higher incidence of conditions related to the immune system, such as asthma, allergies, atopic dermatitis, and hypothyroidism. Research Many medications are being studied. Some of these medications are approved for other diseases, others are not available outside of studies. In 2014, preliminary findings showing that oral ruxolitinib, a drug approved by the US Food and Drug Administration (FDA) for bone marrow disorder myelofibrosis, restored hair growth in three individuals with long-standing and severe disease. The medicine costs almost US$10,000 a month. History Alopecia areata and alopecia barbae have been identified by some as the biblical nethek condition that is part of the greater tzaraath family of skin disorders; the said disorders are purported to being discussed in the Book of Leviticus, chapter 13. Notable people Actor Anthony Carrigan, athlete of American Ninja Warrior fame Kevin Bull, Australian politician Peter Dutton, Australian actor Alan Fletcher, Congresswoman Ayanna Pressley, K-pop singer Peniel Shin of BtoB, and actresses Jada Pinkett Smith, and May Calamawy all have some form of alopecia areata. See also Noncicatricial alopecia Trichotillomania References External links National Institute of Arthritis and Musculoskeletal and Skin Diseases at NIH DermAtlas 42

Aarogya, give me a short description about Altitude sickness

Altitude sickness

Altitude sickness, the mildest form being acute mountain sickness (AMS), is the harmful effect of high altitude, caused by rapid exposure to low amounts of oxygen at high elevation. People can respond to high altitude in different ways. Symptoms may include headaches, vomiting, tiredness, confusion, trouble sleeping, and dizziness. Acute mountain sickness can progress to high-altitude pulmonary edema (HAPE) with associated shortness of breath or high-altitude cerebral edema (HACE) with associated confusion. Chronic mountain sickness may occur after long-term exposure to high altitude.Altitude sickness typically occurs only above 2,500 metres (8,000 ft), though some are affected at lower altitudes. Risk factors include a prior episode of altitude sickness, a high degree of activity, and a rapid increase in elevation. Diagnosis is based on symptoms and is supported in those who have more than a minor reduction in activities. It is recommended that at high altitude any symptoms of headache, nausea, shortness of breath, or vomiting be assumed to be altitude sickness.Prevention is by gradually increasing elevation by no more than 300 metres (1,000 ft) per day. Being physically fit does not decrease the risk. Treatment is generally by descending and sufficient fluids. Mild cases may be helped by ibuprofen, acetazolamide, or dexamethasone. Severe cases may benefit from oxygen therapy and a portable hyperbaric bag may be used if descent is not possible. Treatment efforts, however, have not been well studied.AMS occurs in about 20% of people after rapidly going to 2,500 metres (8,000 ft) and 40% of people going to 3,000 metres (10,000 ft). While AMS and HACE occurs equally frequently in males and females, HAPE occurs more often in males. The earliest description of altitude sickness is attributed to a Chinese text from around 30 BCE which describes "Big Headache Mountains", possibly referring to the Karakoram Mountains around Kilik Pass. Signs and symptoms People have different susceptibilities to altitude sickness; for some otherwise healthy people, acute altitude sickness can begin to appear at around 2,000 metres (6,600 ft) above sea level, such as at many mountain ski resorts, equivalent to a pressure of 80 kilopascals (0.79 atm). This is the most frequent type of altitude sickness encountered. Symptoms often manifest within ten hours of ascent and generally subside within two days, though they occasionally develop into the more serious conditions. Symptoms include headache, confusion, fatigue, stomach illness, dizziness, and sleep disturbance. Exertion may aggravate the symptoms.Those individuals with the lowest initial partial pressure of end-tidal pCO2 (the lowest concentration of carbon dioxide at the end of the respiratory cycle, a measure of a higher alveolar ventilation) and corresponding high oxygen saturation levels tend to have a lower incidence of acute mountain sickness than those with high end-tidal pCO2 and low oxygen saturation levels. Primary symptoms Headaches are the primary symptom used to diagnose altitude sickness, although a headache is also a symptom of dehydration. A headache occurring at an altitude above 2,400 metres (7,900 ft) – a pressure of 76 kilopascals (0.75 atm) – combined with any one or more of the following symptoms, may indicate altitude sickness: Severe symptoms Symptoms that may indicate life-threatening altitude sickness include: Pulmonary edema (fluid in the lungs) Symptoms similar to bronchitis Persistent dry cough Fever Shortness of breath even when restingCerebral edema (swelling of the brain) Headache that does not respond to analgesics Unsteady gait Gradual loss of consciousness Increased nausea and vomiting Retinal hemorrhageThe most serious symptoms of altitude sickness arise from edema (fluid accumulation in the tissues of the body). At very high altitude, humans can get either high-altitude pulmonary edema (HAPE), or high-altitude cerebral edema (HACE). The physiological cause of altitude-induced edema is not conclusively established. It is currently believed, however, that HACE is caused by local vasodilation of cerebral blood vessels in response to hypoxia, resulting in greater blood flow and, consequently, greater capillary pressures. On the other hand, HAPE may be due to general vasoconstriction in the pulmonary circulation (normally a response to regional ventilation-perfusion mismatches) which, with constant or increased cardiac output, also leads to increases in capillary pressures. For those with HACE, dexamethasone may provide temporary relief from symptoms in order to keep descending under their own power.HAPE can progress rapidly and is often fatal. Symptoms include fatigue, severe dyspnea at rest, and cough that is initially dry but may progress to produce pink, frothy sputum. Descent to lower altitudes alleviates the symptoms of HAPE. HACE is a life-threatening condition that can lead to coma or death. Symptoms include headache, fatigue, visual impairment, bladder dysfunction, bowel dysfunction, loss of coordination, paralysis on one side of the body, and confusion. Descent to lower altitudes may save those affected by HACE. Cause Altitude sickness can first occur at 1,500 metres (4,900 ft), with the effects becoming severe at extreme altitudes (greater than 5,500 metres (18,000 ft)). Only brief trips above 6,000 metres (20,000 ft) are possible and supplemental oxygen is needed to avert sickness. As altitude increases, the available amount of oxygen to sustain mental and physical alertness decreases with the overall air pressure, though the relative percentage of oxygen in air, at about 21%, remains practically unchanged up to 21,000 metres (69,000 ft). The RMS velocities of diatomic nitrogen and oxygen are very similar and thus no change occurs in the ratio of oxygen to nitrogen until stratospheric heights. Dehydration due to the higher rate of water vapor lost from the lungs at higher altitudes may contribute to the symptoms of altitude sickness.The rate of ascent, altitude attained, amount of physical activity at high altitude, as well as individual susceptibility, are contributing factors to the onset and severity of high-altitude illness. Altitude sickness usually occurs following a rapid ascent and can usually be prevented by ascending slowly. In most of these cases, the symptoms are temporary and usually abate as altitude acclimatization occurs. However, in extreme cases, altitude sickness can be fatal. High altitude illness can be classified according to the altitude: high (1,500–3,500 metres (4,900–11,500 ft)), very high (3,500–5,500 metres (11,500–18,000 ft)) and extreme (above 5,500 metres (18,000 ft)). High altitude At high altitude, 1,500 to 3,500 metres (4,900 to 11,500 ft), the onset of physiological effects of diminished inspiratory oxygen pressure (PiO2) includes decreased exercise performance and increased ventilation (lower arterial partial pressure of carbon dioxide: PCO2). While arterial oxygen transport may be only slightly impaired the arterial oxygen saturation (SaO2) generally stays above 90%. Altitude sickness is common between 2,400 and 4,000 metres (7,900 and 13,100 ft) because of the large number of people who ascend rapidly to these altitudes. Very high altitude At very high altitude, 3,500 to 5,500 metres (11,500 to 18,000 ft), maximum SaO2 falls below 90% as the arterial PO2 falls below 60mmHg. Extreme hypoxemia may occur during exercise, during sleep, and in the presence of high altitude pulmonary edema or other acute lung conditions. Severe altitude illness occurs most commonly in this range. Extreme altitude Above 5,500 metres (18,000 ft), marked hypoxemia, hypocapnia, and alkalosis are characteristic of extreme altitudes. Progressive deterioration of physiologic function eventually outstrips acclimatization. As a result, no permanent human habitation occurs above 6,000 metres (20,000 ft). A period of acclimatization is necessary when ascending to extreme altitude; abrupt ascent without supplemental oxygen for other than brief exposures invites severe altitude sickness. Mechanism The physiology of altitude sickness centres around the alveolar gas equation; the atmospheric pressure is low, but there is still 20.9% oxygen. Water vapour still occupies the same pressure too—this means that there is less oxygen pressure available in the lungs and blood. Compare these two equations comparing the amount of oxygen in blood at altitude: The hypoxia leads to an increase in minute ventilation (hence both low CO2, and subsequently bicarbonate), Hb increases through haemoconcentration and erythrogenesis. Alkalosis shifts the haemoglobin dissociation constant to the left, 2,3-BPG increases to counter this. Cardiac output increases through an increase in heart rate.The bodys response to high altitude includes the following: ↑ Erythropoietin → ↑ hematocrit and haemoglobin ↑ 2,3-BPG (allows ↑ release of O2 and a right shift on the Hb-O2 disassociation curve) ↑ kidney excretion of bicarbonate (use of acetazolamide can augment for treatment) Chronic hypoxic pulmonary vasoconstriction (can cause right ventricular hypertrophy)People with high-altitude sickness generally have reduced hyperventilator response, impaired gas exchange, fluid retention or increased sympathetic drive. There is thought to be an increase in cerebral venous volume because of an increase in cerebral blood flow and hypocapnic cerebral vasoconstriction causing oedema. Diagnosis Altitude sickness is typically self-diagnosed since symptoms are consistent: nausea, vomiting, headache, and can generally be deduced from a rapid change in altitude or oxygen levels. However, some symptoms may be confused with dehydration. Some severe cases may require professional diagnosis which can be assisted with multiple different methods such as using an MRI or CT scan to check for abnormal buildup of fluids in the lung or brain. Prevention Ascending slowly is the best way to avoid altitude sickness. Avoiding strenuous activity such as skiing, hiking, etc. in the first 24 hours at high altitude may reduce the symptoms of AMS. Alcohol and sleeping pills are respiratory depressants, and thus slow down the acclimatization process and should be avoided. Alcohol also tends to cause dehydration and exacerbates AMS. Thus, avoiding alcohol consumption in the first 24–48 hours at a higher altitude is optimal. Pre-acclimatization Pre-acclimatization is when the body develops tolerance to low oxygen concentrations before ascending to an altitude. It significantly reduces risk because less time has to be spent at altitude to acclimatize in the traditional way. Additionally, because less time has to be spent on the mountain, less food and supplies have to be taken up. Several commercial systems exist that use altitude tents, so called because they mimic altitude by reducing the percentage of oxygen in the air while keeping air pressure constant to the surroundings. Examples of pre-acclimation measures include remote ischaemic preconditioning, using hypobaric air breathing in order to simulate altitude, and positive end-expiratory pressure. Altitude acclimatization Altitude acclimatization is the process of adjusting to decreasing oxygen levels at higher elevations, in order to avoid altitude sickness. Once above approximately 3,000 metres (10,000 ft) – a pressure of 70 kilopascals (0.69 atm) – most climbers and high-altitude trekkers take the "climb-high, sleep-low" approach. For high-altitude climbers, a typical acclimatization regimen might be to stay a few days at a base camp, climb up to a higher camp (slowly), and then return to base camp. A subsequent climb to the higher camp then includes an overnight stay. This process is then repeated a few times, each time extending the time spent at higher altitudes to let the body adjust to the oxygen level there, a process that involves the production of additional red blood cells. Once the climber has acclimatized to a given altitude, the process is repeated with camps placed at progressively higher elevations. The rule of thumb is to ascend no more than 300 m (1,000 ft) per day to sleep. That is, one can climb from 3,000 m (9,800 ft) (70 kPa or 0.69 atm) to 4,500 m (15,000 ft) (58 kPa or 0.57 atm) in one day, but one should then descend back to 3,300 m (10,800 ft) (67.5 kPa or 0.666 atm) to sleep. This process cannot safely be rushed, and this is why climbers need to spend days (or even weeks at times) acclimatizing before attempting to climb a high peak. Simulated altitude equipment such as altitude tents provide hypoxic (reduced oxygen) air, and are designed to allow partial pre-acclimation to high altitude, reducing the total time required on the mountain itself. Altitude acclimatization is necessary for some people who move rapidly from lower altitudes to higher altitudes . Medications The drug acetazolamide (trade name Diamox) may help some people making a rapid ascent to sleeping altitude above 2,700 metres (9,000 ft), and it may also be effective if started early in the course of AMS. Acetazolamide can be taken before symptoms appear as a preventive measure at a dose of 125 mg twice daily. The Everest Base Camp Medical Centre cautions against its routine use as a substitute for a reasonable ascent schedule, except where rapid ascent is forced by flying into high altitude locations or due to terrain considerations. The Centre suggests a dosage of 125 mg twice daily for prophylaxis, starting from 24 hours before ascending until a few days at the highest altitude or on descending; with 250 mg twice daily recommended for treatment of AMS. The Centers for Disease Control and Prevention (CDC) suggest the same dose for prevention of 125 mg acetazolamide every 12 hours. Acetazolamide, a mild diuretic, works by stimulating the kidneys to secrete more bicarbonate in the urine, thereby acidifying the blood. This change in pH stimulates the respiratory center to increase the depth and frequency of respiration, thus speeding the natural acclimatization process. An undesirable side-effect of acetazolamide is a reduction in aerobic endurance performance. Other minor side effects include a tingle-sensation in hands and feet. Although a sulfonamide; acetazolamide is a non-antibiotic and has not been shown to cause life-threatening allergic cross-reactivity in those with a self-reported sulfonamide allergy. Dosage of 1000 mg/day will produce a 25% decrease in performance, on top of the reduction due to high-altitude exposure. The CDC advises that Dexamethasone be reserved for treatment of severe AMS and HACE during descents, and notes that Nifedipine may prevent HAPE.There is insufficient evidence to determine the safety of sumatriptan and if it may help prevent altitude sickness. Despite their popularity, antioxidant treatments have not been found to be effective medications for prevention of AMS. Interest in phosphodiesterase inhibitors such as sildenafil has been limited by the possibility that these drugs might worsen the headache of mountain sickness. A promising possible preventive for altitude sickness is myo-inositol trispyrophosphate (ITPP), which increases the amount of oxygen released by hemoglobin. Prior to the onset of altitude sickness, ibuprofen is a suggested non-steroidal anti-inflammatory and painkiller that can help alleviate both the headache and nausea associated with AMS. It has not been studied for the prevention of cerebral edema (swelling of the brain) associated with extreme symptoms of AMS. Over-the-counter herbal supplements and traditional medicines Herbal supplements and traditional medicines are sometimes suggested to prevent high altitude sickness including ginkgo biloba, R crenulata, minerals such as iron, antacids, and hormonal-based supplements such as medroxyprogesterone and erythropoietin. Medical evidence to support the effectiveness and safety of these approaches is often contradictory or lacking. Indigenous peoples of the Americas, such as the Aymaras of the Altiplano, have for centuries chewed coca leaves to try to alleviate the symptoms of mild altitude sickness. This therapy has not yet been proven effective in a clinical study. In Chinese and Tibetan traditional medicine, an extract of the root tissue of Radix rhodiola is often taken in order to prevent the symptoms of high altitude sickness, however, no clear medical studies have confirmed the effectiveness or safety of this extract. Oxygen enrichment In high-altitude conditions, oxygen enrichment can counteract the hypoxia related effects of altitude sickness. A small amount of supplemental oxygen reduces the equivalent altitude in climate-controlled rooms. At 3,400 metres (11,200 ft) (67 kPa or 0.66 atm), raising the oxygen concentration level by 5% via an oxygen concentrator and an existing ventilation system provides an effective altitude of 3,000 m (10,000 ft) (70 kPa or 0.69 atm), which is more tolerable for those unaccustomed to high altitudes.Oxygen from gas bottles or liquid containers can be applied directly via a nasal cannula or mask. Oxygen concentrators based upon pressure swing adsorption (PSA), VSA, or vacuum-pressure swing adsorption (VPSA) can be used to generate the oxygen if electricity is available. Stationary oxygen concentrators typically use PSA technology, which has performance degradations at the lower barometric pressures at high altitudes. One way to compensate for the performance degradation is to use a concentrator with more flow capacity. There are also portable oxygen concentrators that can be used on vehicular DC power or on internal batteries, and at least one system commercially available measures and compensates for the altitude effect on its performance up to 4,000 m (13,000 ft). The application of high-purity oxygen from one of these methods increases the partial pressure of oxygen by raising the FiO2 (fraction of inspired oxygen). Other methods Increased water intake may also help in acclimatization to replace the fluids lost through heavier breathing in the thin, dry air found at altitude, although consuming excessive quantities ("over-hydration") has no benefits and may cause dangerous hyponatremia. Treatment The only reliable treatment, and in many cases the only option available, is to descend. Attempts to treat or stabilize the patient in situ (at altitude) are dangerous unless highly controlled and with good medical facilities. However, the following treatments have been used when the patients location and circumstances permit: Oxygen may be used for mild to moderate AMS below 3,700 metres (12,000 ft) and is commonly provided by physicians at mountain resorts. Symptoms abate in 12 to 36 hours without the need to descend. For more serious cases of AMS, or where rapid descent is impractical, a Gamow bag, a portable plastic hyperbaric chamber inflated with a foot pump, can be used to reduce the effective altitude by as much as 1,500 m (5,000 ft). A Gamow bag is generally used only as an aid to evacuate severe AMS patients, not to treat them at altitude. Acetazolamide 250 mg twice daily dosing assists in AMS treatment by quickening altitude acclimatization. A study by the Denali Medical Research Project concluded: "In established cases of acute mountain sickness, treatment with acetazolamide relieves symptoms, improves arterial oxygenation, and prevents further impairment of pulmonary gas exchange." The folk remedy for altitude sickness in Ecuador, Peru and Bolivia is a tea made from the coca plant. See mate de coca. Steroids can be used to treat the symptoms of pulmonary or cerebral edema, but do not treat the underlying AMS. Two studies in 2012 showed that ibuprofen 600 milligrams three times daily was effective at decreasing the severity and incidence of AMS; it was not clear if HAPE or HACE was affected. Paracetamol (acetaminophen) has also shown to be as good as ibuprofen for altitude sickness when tested on climbers ascending Everest. See also References External links Travel at High Altitude: a free booklet about how to keep healthy at altitude. Available in many languages. Merck Manual entry on altitude sickness Altitude Illness Clinical Guide for Physicians

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

Amblyopia

Amblyopia, also called lazy eye, is a disorder of sight in which the brain fails to fully process input from one eye and over time favors the other eye. It results in decreased vision in an eye that typically appears normal in other respects. Amblyopia is the most common cause of decreased vision in a single eye among children and younger adults.The cause of amblyopia can be any condition that interferes with focusing during early childhood. This can occur from poor alignment of the eyes (strabismic), an eye being irregularly shaped such that focusing is difficult, one eye being more nearsighted or farsighted than the other (refractive), or clouding of the lens of an eye (deprivational). After the underlying cause is addressed, vision is not restored right away, as the mechanism also involves the brain. Amblyopia can be difficult to detect, so vision testing is recommended for all children around the ages of four to five.Early detection improves treatment success. Glasses may be all the treatment needed for some children. If this is not sufficient, treatments which encourage or force the child to use the weaker eye are used. This is done by either using a patch or putting atropine in the stronger eye. Without treatment, amblyopia typically persists. Treatment in adulthood is usually much less effective.Amblyopia begins by the age of five. In adults, the disorder is estimated to affect 1–5% of the population. While treatment improves vision, it does not typically restore it to normal in the affected eye. Amblyopia was first described in the 1600s. The condition may make people ineligible to be pilots or police officers. The word amblyopia is from Greek ἀμβλύς amblys, meaning "blunt", and ὤψ ōps, meaning "sight". Signs and symptoms Many people with amblyopia, especially those who only have a mild form, are not aware they have the condition until tested at older ages, since the vision in their stronger eye is normal. People with amblyopia typically have poor stereo vision, since it requires both eyes. They further may have, on the affected eye, poor pattern recognition, poor visual acuity, and low sensitivity to contrast and motion.Amblyopia is characterized by several functional abnormalities in spatial vision, including reductions in visual acuity, contrast sensitivity function, and vernier acuity, as well as spatial distortion, abnormal spatial interactions, and impaired contour detection. In addition, individuals with amblyopia have binocular abnormalities such as impaired stereoacuity (stereoscopic acuity) and abnormal binocular summation. Also, central vision in amblyopes is more crowded than central vision in normal observers.These deficits are usually specific to the amblyopic eye. Subclinical deficits of the "better" eye have also been demonstrated.People with amblyopia also have problems of binocular vision such as limited stereoscopic depth perception and usually have difficulty seeing the three-dimensional images in hidden stereoscopic displays such as autostereograms. Perception of depth, from monocular cues such as size, perspective, and motion parallax remains normal. Cause Amblyopia has three main causes: Strabismic: by strabismus (misaligned eyes) Refractive: by anisometropia (difference of a certain degree of nearsightedness, farsightedness, or astigmatism), or by significant amount of equal refractive error in both eyes Deprivational: by deprivation of vision early in life by vision-obstructing disorders such as congenital cataract Strabismus Strabismus, sometimes also incorrectly called lazy eye, is a condition in which the eyes are misaligned. Strabismus usually results in normal vision in the preferred sighting (or "fellow") eye (the eye that the person prefers to use), but may cause abnormal vision in the deviating or strabismic eye due to the difference between the images projecting to the brain from the two eyes. Adult-onset strabismus usually causes double vision (diplopia), since the two eyes are not fixed on the same object. Childrens brains are more neuroplastic, so can more easily adapt by suppressing images from one of the eyes, eliminating the double vision. This plastic response of the brain, interrupts the brains normal development, resulting in the amblyopia. Recent evidence points to a cause of infantile strabismus lying with the input to the visual cortex.Those with strabismic amblyopia tend to show ocular motion deficits when reading, even when they use the nonamblyopic eye. In particular, they tend to make more saccades per line than persons with normal stereo vision, and to have a reduced reading speed, especially when reading a text with small font size.Strabismic amblyopia is treated by clarifying the visual image with glasses, or encouraging use of the amblyopic eye with an eyepatch over the dominant eye or pharmacologic penalization of the better eye. Penalization usually consists of applying atropine drops to temporarily paralyze the accommodation reflex, leading to the blurring of vision in the good eye. It also dilates the pupil. This helps to prevent the bullying and teasing associated with wearing a patch, although sometimes application of the eye drops is challenging. The ocular alignment itself may be treated with surgical or nonsurgical methods, depending on the type and severity of the strabismus. Refractive Refractive amblyopia may result from anisometropia (unequal refractive error between the two eyes). Anisometropia exists when there is a difference in the power between the two eyes. The eye which provides the brain with a clearer image typically becomes the dominant eye. The image in the other eye is blurred, which results in abnormal development of one half of the visual system. Refractive amblyopia is usually less severe than strabismic amblyopia and is commonly missed by primary care physicians because of its less dramatic appearance and lack of obvious physical manifestation, such as with strabismus. Given that the refractive correction of anisometropia by means of spectacles typically leads to different image magnification for the two eyes, which may in turn prevent binocular vision, a refractive correction using contact lenses is to be considered. Also pediatric refractive surgery is a treatment option, in particular if conventional approaches have failed due to aniseikonia or lack of compliance or both.Frequently, amblyopia is associated with a combination of anisometropia and strabismus. In some cases, the vision between the eyes can differ to the point where one eye has twice average vision while the other eye is completely blind. Deprivation and occlusion Deprivation amblyopia (amblyopia ex anopsia) results when the ocular media become opaque, such as is the case with congenital cataract or corneal haziness. These opacities prevent adequate visual input from reaching the eye, and disrupt development. If not treated in a timely fashion, amblyopia may persist even after the cause of the opacity is removed. Sometimes, drooping of the eyelid (ptosis) or some other problem causes the upper eyelid to physically occlude a childs vision, which may cause amblyopia quickly. Occlusion amblyopia may be a complication of a hemangioma that blocks some or all of the eye. Other possible causes of deprivation and occlusion amblyopia include obstruction in the vitreous and aphakia. Deprivation amblyopia accounts for less than 3% of all individuals affected by amblyopia. Pathophysiology Amblyopia is a developmental problem in the brain, not any intrinsic, organic neurological problem in the eyeball (although organic problems can lead to amblyopia which can continue to exist after the organic problem has resolved by medical intervention). The part of the brain receiving images from the affected eye is not stimulated properly and does not develop to its full visual potential. This has been confirmed by direct brain examination. David H. Hubel and Torsten Wiesel won the Nobel Prize in Physiology or Medicine in 1981 for their work in showing the extent of the damage to ocular dominance columns produced in kittens by sufficient visual deprivation during the so-called "critical period". The maximum "critical period" in humans is from birth to two years old. Diagnosis Amblyopia is diagnosed by identifying low visual acuity in one or both eyes, out of proportion to the structural abnormality of the eye and excluding other visual disorders as causes for the lowered visual acuity. It can be defined as an interocular difference of two lines or more in acuity (e.g. on Snellen chart) when the eye optics are maximally corrected. In young children, visual acuity is difficult to measure and can be estimated by observing the reactions of the patient when one eye is covered, including observing the patients ability to follow objects with one eye. Stereotests like the Lang stereotest are not reliable exclusion tests for amblyopia. A person who passes the Lang stereotest test is unlikely to have strabismic amblyopia, but could nonetheless have refractive or deprivational amblyopia. Binocular retinal birefringence scanning may be able to identify, already in very young children, amblyopia that is associated with strabismus, microstrabismus, or reduced fixation accuracy. Diagnosis and treatment of amblyopia as early as possible is necessary to keep the vision loss to a minimum. Screening for amblyopia is recommended in all people between three and five years of age. Treatment Treatment of strabismic or anisometropic amblyopia consists of correcting the optical deficit (wearing the necessary spectacle prescription) and often forcing use of the amblyopic eye, by patching the good eye, or instilling topical atropine in the good eye, or both.: 130  Atropine appears to result in similar outcomes to patching. If there is overpatching or overpenalizing the good eye when treating amblyopia, "reverse amblyopia" can result. Eye patching is usually done on a part-time schedule of about 4–6 hours a day. Treatment is continued as long as vision improves. It is not worthwhile continuing to patch for more than 6 months if no improvement continues.Deprivation amblyopia is treated by removing the opacity as soon as possible followed by patching or penalizing the good eye to encourage the use of the amblyopic eye. The earlier the treatment is initiated, the easier and faster the treatment is and the less psychologically damaging. Also, the chance of achieving 20/20 vision is greater if treatment is initiated early.One of the German public health insurance providers, Barmer, has changed its policy to cover, as of 1 April 2014, the cost of software for amblyopic children whose condition did not improve through patching. The app offers dedicated eye exercises that the patient performs while wearing an eyepatch.Evidence for vision therapy is unclear as of 2011. Older age Treatment of individuals age 9 through to adulthood is possible through applied perceptual learning. Tentative evidence shows that perceptual training may be beneficial in adults. Epidemiology Amblyopia occurs in between 2 and 5% of the population in Western countries. In the UK, 90% of visual health appointments in the child concern amblyopia.Depending on the chosen criterion for diagnosis, between 1 and 4% of the children have amblyopia. Research A 2009 study, widely reported in the popular press, has suggested that repetitive transcranial magnetic stimulation may temporarily improve contrast sensitivity and spatial resolution in the affected eye of adults with amblyopia. This approach is still under development, and the results await verification by other researchers. Comparable results may be achieved using different types of brain stimulation, such as anodal transcranial direct current stimulation and theta burst rTMS.A 2013 study concluded that converging evidence indicates decorrelated binocular experience plays a pivotal role in the genesis of amblyopia and the associated residual deficits. Another study of 2013 suggests that playing a version of the popular game Tetris that is modified such that each eye sees separate components of the game may also help to treat this condition in adults. Furthermore, the effects of this kind of therapy may be further enhanced by noninvasive brain stimulation as shown by a recent study using anodal tDCS.A 2014 Cochrane review sought to determine the effectiveness of occlusion treatment on patients with sensory deprivation amblyopia, but no trials were found eligible to be included in the review. However, good outcomes from occlusion treatment for sensory deprivation amblyopia likely rely on compliance with the treatment. References Further reading External links National Eye Institute (NEI) Resource Guide Lazy Eye Site from the National Health Service, UK Look After Your Eyes - patient information on Amblyopia or lazy eye by College of Optometrists

Give me a short description about Amoebiasis , Aarogya

Amoebiasis

Amoebiasis, or amoebic dysentery, is an infection of the intestines caused by a parasitic amoeba Entamoeba histolytica. Amoebiasis can be present with no, mild, or severe symptoms. Symptoms may include lethargy, loss of weight, colonic ulcerations, abdominal pain, diarrhea, or bloody diarrhea. Complications can include inflammation and ulceration of the colon with tissue death or perforation, which may result in peritonitis. Anemia may develop due to prolonged gastric bleeding.Cysts of Entamoeba can survive for up to a month in soil or for up to 45 minutes under fingernails. Invasion of the intestinal lining results in bloody diarrhea. If the parasite reaches the bloodstream it can spread through the body, most frequently ending up in the liver where it can cause amoebic liver abscesses. Liver abscesses can occur without previous diarrhea. Diagnosis is typically made by stool examination using microscopy, but it can be difficult to distinguish E. hystolitica from other harmless entamoeba species. An increased white blood cell count may be present in severe cases. The most accurate test is finding specific antibodies in the blood, but it may remain positive following treatment. Bacterial colitis can result in similar symptoms.Prevention of amoebiasis is by improved sanitation, including separating food and water from faeces. There is no vaccine. There are two treatment options depending on the location of the infection. Amoebiasis in tissues is treated with either metronidazole, tinidazole, nitazoxanide, dehydroemetine or chloroquine, while luminal infection is treated with diloxanide furoate or iodoquinoline. Effective treatment against all stages of the disease may require a combination of medications. Infections without symptoms may be treated with just one antibiotic, and infections with symptoms are treated with two antibiotics.Amoebiasis is present all over the world, though most cases occur in the developing world. About 480 million people are currently infected with about 40 million new cases per year with significant symptoms. This results in the death of between 40,000–100,000 people a year. The first case of amoebiasis was documented in 1875 and in 1891 the disease was described in detail, resulting in the terms amoebic dysentery and amoebic liver abscess. Further evidence from the Philippines in 1913 found that upon swallowing cysts of E. histolytica volunteers developed the disease. Signs and symptoms Most infected people, about 90%, are asymptomatic, but this disease has the potential to become serious. It is estimated that about 40,000 to 100,000 people worldwide die annually due to amoebiasis.Infections can sometimes last for years if there is no treatment. Symptoms take from a few days to a few weeks to develop and manifest themselves, but usually it is about two to four weeks. Symptoms can range from mild diarrhea to dysentery with blood, coupled with intense abdominal pains. Extra-intestinal complications might also arise as a result of invasive infection which includes colitis, liver, lung, or brain abscesses. The blood comes from bleeding lesions created by the amoebae invading the lining of the colon. In about 10% of invasive cases the amoebae enter the bloodstream and may travel to other organs in the body. Most commonly this means the liver, as this is where blood from the intestine reaches first, but they can end up almost anywhere in the body.Onset time is highly variable and the average asymptomatic infection persists for over a year. It is theorized that the absence of symptoms or their intensity may vary with such factors as strain of amoeba, immune response of the host, and perhaps associated bacteria and viruses.In asymptomatic infections, the amoeba lives by eating and digesting bacteria and food particles in the gut, a part of the gastrointestinal tract. It does not usually come in contact with the intestine itself due to the protective layer of mucus that lines the gut. Disease occurs when amoeba comes in contact with the cells lining the intestine. It then secretes the same substances it uses to digest bacteria, which include enzymes that destroy cell membranes and proteins. This process can lead to penetration and digestion of human tissues, resulting first in flask-shaped ulcerations in the intestine. Entamoeba histolytica ingests the destroyed cells by phagocytosis and is often seen with red blood cells (a process known as erythrophagocytosis) inside when viewed in stool samples. Especially in Latin America, a granulomatous mass (known as an amoeboma) may form in the wall of the ascending colon or rectum due to long-lasting immunological cellular response, and is sometimes confused with cancer.The ingestion of one viable cyst may cause an infection.Steroid therapy can occasionally provoke severe amoebic colitis in people with any E. histolytica infection. This bears high mortality: on average more than 50% with severe colitis die. Cause Amoebiasis is an infection caused by the amoeba Entamoeba histolytica. Transmission Amoebiasis is usually transmitted by the fecal-oral route, but it can also be transmitted indirectly through contact with dirty hands or objects as well as by anal-oral contact. Infection is spread through ingestion of the cyst form of the parasite, a semi-dormant and hardy structure found in feces. Any non-encysted amoebae, or trophozoites, die quickly after leaving the body but may also be present in stool: these are rarely the source of new infections. Since amoebiasis is transmitted through contaminated food and water, it is often endemic in regions of the world with limited modern sanitation systems, including México, Central America, western South America, South Asia, and western and southern Africa.Amoebic dysentery is one form of travelers diarrhea, although most travelers diarrhea is bacterial or viral in origin. Pathogenesis Amoebiasis results from tissue destruction induced by the E. histolytica parasite. E. histolytica causes tissue damage by three main events: direct host cell killing, inflammation, and parasite invasion. Diagnosis With colonoscopy it is possible to detect small ulcers of between 3–5mm, but diagnosis may be difficult as the mucous membrane between these areas can look either healthy or inflamed. Trophozoites may be identified at the ulcer edge or within the tissue, using immunohistochemical staining with specific anti-E. histolytica antibodies.Asymptomatic human infections are usually diagnosed by finding cysts shed in the stool. Various flotation or sedimentation procedures have been developed to recover the cysts from fecal matter and stains help to visualize the isolated cysts for microscopic examination. Since cysts are not shed constantly, a minimum of three stools are examined. In symptomatic infections, the motile form (the trophozoite) is often seen in fresh feces. Serological tests exist, and most infected individuals (with symptoms or not) test positive for the presence of antibodies. The levels of antibody are much higher in individuals with liver abscesses. Serology only becomes positive about two weeks after infection. More recent developments include a kit that detects the presence of amoeba proteins in the feces, and another that detects ameba DNA in feces. These tests are not in widespread use due to their expense.Microscopy is still by far the most widespread method of diagnosis around the world. However it is not as sensitive or accurate in diagnosis as the other tests available. It is important to distinguish the E. histolytica cyst from the cysts of nonpathogenic intestinal protozoa such as Entamoeba coli by its appearance. E. histolytica cysts have a maximum of four nuclei, while the commensal Entamoeba coli cyst has up to 8 nuclei. Additionally, in E. histolytica, the endosome is centrally located in the nucleus, while it is usually off-center in Entamoeba coli. Finally, chromatoidal bodies in E. histolytica cysts are rounded, while they are jagged in Entamoeba coli. However, other species, Entamoeba dispar and E. moshkovskii, are also commensals and cannot be distinguished from E. histolytica under the microscope. As E. dispar is much more common than E. histolytica in most parts of the world this means that there is a lot of incorrect diagnosis of E. histolytica infection taking place. The WHO recommends that infections diagnosed by microscopy alone should not be treated if they are asymptomatic and there is no other reason to suspect that the infection is actually E. histolytica. Detection of cysts or trophozoites stools under microscope may require examination of several samples over several days to determine if they are present, because cysts are shed intermittently and may not show up in every sample.Typically, the organism can no longer be found in the feces once the disease goes extra-intestinal. Serological tests are useful in detecting infection by E. histolytica if the organism goes extra-intestinal and in excluding the organism from the diagnosis of other disorders. An Ova & Parasite (O&P) test or an E. histolytica fecal antigen assay is the proper assay for intestinal infections. Since antibodies may persist for years after clinical cure, a positive serological result may not necessarily indicate an active infection. A negative serological result, however, can be equally important in excluding suspected tissue invasion by E. histolytica.Stool antigen detection tests have helped to overcome some of the limitations of stool microscopy. Antigen detection tests are easy to use, but they have variable sensitivity and specificity, especially in low-endemic areas.Polymerase chain reaction (PCR) is considered the gold standard for diagnosis but remains underutilized. Prevention To help prevent the spread of amoebiasis around the home : Wash hands thoroughly with soap and hot running water for at least 10 seconds after using the toilet or changing a babys diaper, and before handling food. Clean bathrooms and toilets often; pay particular attention to toilet seats and taps. Avoid sharing towels or face washers.To help prevent infection: Avoid raw vegetables when in endemic areas, as they may have been fertilized using human feces. Boil water or treat with iodine tablets. Avoid eating street foods especially in public places where others are sharing sauces in one containerGood sanitary practice, as well as responsible sewage disposal or treatment, are necessary for the prevention of E. histolytica infection on an endemic level. E.histolytica cysts are usually resistant to chlorination, therefore sedimentation and filtration of water supplies are necessary to reduce the incidence of infection.E. histolytica cysts may be recovered from contaminated food by methods similar to those used for recovering Giardia lamblia cysts from feces. Filtration is probably the most practical method for recovery from drinking water and liquid foods. E. histolytica cysts must be distinguished from cysts of other parasitic (but nonpathogenic) protozoa and from cysts of free-living protozoa as discussed above. Recovery procedures are not very accurate; cysts are easily lost or damaged beyond recognition, which leads to many falsely negative results in recovery tests. Treatment E. histolytica infections occur in both the intestine and (in people with symptoms) in tissue of the intestine and/or liver. Those with symptoms require treatment with two medications, an amoebicidal tissue-active agent and a luminal cysticidal agent. Individuals that are asymptomatic only need a luminal cysticidal agent. Prognosis In the majority of cases, amoebas remain in the gastrointestinal tract of the hosts. Severe ulceration of the gastrointestinal mucosal surfaces occurs in less than 16% of cases. In fewer cases, the parasite invades the soft tissues, most commonly the liver. Only rarely are masses formed (amoebomas) that lead to intestinal obstruction.(Mistaken for Ca caecum and appendicular mass) Other local complications include bloody diarrhea, pericolic and pericaecal abscess.Complications of hepatic amoebiasis includes subdiaphragmatic abscess, perforation of diaphragm to pericardium and pleural cavity, perforation to abdominal cavital (amoebic peritonitis) and perforation of skin (amoebiasis cutis).Pulmonary amoebiasis can occur from liver lesions by spread through the blood or by perforation of pleural cavity and lung. It can cause lung abscess, pulmono pleural fistula, empyema lung and broncho pleural fistula. It can also reach the brain through blood vessels and cause amoebic brain abscess and amoebic meningoencephalitis. Cutaneous amoebiasis can also occur in skin around sites of colostomy wound, perianal region, region overlying visceral lesion and at the site of drainage of liver abscess.Urogenital tract amoebiasis derived from intestinal lesion can cause amoebic vulvovaginitis (Mays disease), rectovesicle fistula and rectovaginal fistula.Entamoeba histolytica infection is associated with malnutrition and stunting of growth in children. Epidemiology Amoebiasis caused about 55,000 deaths worldwide in 2010, down from 68,000 in 1990. In older textbooks it is often stated that 10% of the worlds population is infected with Entamoeba histolytica. Nevertheless, this means that there are up to 50 million true E. histolytica infections and approximately seventy thousand die each year, mostly from liver abscesses or other complications. Although usually considered a tropical parasite, the first case reported (in 1875) was actually in St Petersburg in Russia, near the Arctic Circle. Infection is more common in warmer areas, but this is because of both poorer hygiene and the parasitic cysts surviving longer in warm moist conditions. History Amoebiasis was first described by Fedor A. Lösch in 1875, in northern Russia. The most dramatic incident in the US was the Chicago Worlds Fair outbreak in 1933, caused by contaminated drinking water. There were more than a thousand cases, with 98 deaths. It has been known since 1897 that at least one non-disease-causing species of Entamoeba existed (Entamoeba coli), but it was first formally recognized by the WHO in 1997 that E. histolytica was two species, despite this having first been proposed in 1925. In addition to the now-recognized E. dispar, evidence shows there are at least two other species of Entamoeba that look the same in humans: E. moshkovskii and Entamoeba bangladeshi. The reason these species havent been differentiated until recently is because of the reliance on appearance.Joel Connolly of the Chicago Bureau of Sanitary Engineering brought the outbreak to an end when he found that defective plumbing permitted sewage to contaminate drinking water. In 1998 there was an outbreak of amoebiasis in the Republic of Georgia. Between 26 May and 3 September 1998, 177 cases were reported, including 71 cases of intestinal amoebiasis and 106 probable cases of liver abscess.The Nicobarese people have attested to the medicinal properties found in Glochidion calocarpum, a plant common to India, saying that its bark and seed are most effective in curing abdominal disorders associated with amoebiasis. Society and culture An outbreak of amoebic dysentery occurs in Diana Gabaldons novel A Breath of Snow and Ashes. References External links Amoebiasis - Centers for Disease Control and Prevention

Hello Aarogya, explain a situation where Anaplasmosis occurs

Anaplasmosis

Anaplasmosis is a tick-borne disease affecting ruminants, dogs, and horses, and is caused by Anaplasma bacteria. Anaplasmosis is an infectious but not contagious disease. Anaplasmosis can be transmitted through mechanical and biological vector processes. Anaplasmosis can also be referred to as "yellow bag" or "yellow fever" because the infected animal can develop a jaundiced look. Other signs of infection include weight loss, diarrhea, paleness of the skin, aggressive behavior, and high fever.Many different tick species can carry the bacteria that cause anaplasmosis. The two major bacterial pathogens are Anaplasma marginale and Anaplasma phagocytophilum. These microorganisms are Gram-negative, and infect red blood cells. Once the host is infected with anaplasmosis, the immune system will try to fight off and kill the infected red blood cells, but will also kill healthy red blood cells. The Anaplasma sparouinense species is responsible for a rare zoonosis, the Sparouine anaplasmosis, detected only in French Guiana, South America. This disease was described from a clandestine gold miner working deep in rainforest. Infection of his red blood cells led to a severe deterioration of his health and required his hospitalization. Molecular typing showed that Anaplasma sparouinense is distinct to all known species and more genetically related to recently described Anaplasma species causing infections in rainforest wild fauna of Brazil.While there are no current live or inactivated vaccines effective for all strains of A. marginale approved by the USDA for anaplasmosis, there are other means of prevention. Tick and fly control for herds of ruminants can be effective but also labor intensive. Chemical methods can also be used, including sanitizing surgical equipment after each use. Tetracycline drugs are the most common treatment for anaplasmosis, and can provide the animal with immunity for a period of time. The disease is more common in the South and West parts of the United States, but is no longer considered a major problem since the use of tetracycline drugs. Transmission Mechanical and biological vector transmission work in different ways but both lead to infection of the red blood cells. Mechanical transmission happens in two ways, one when red blood cells are inoculated with the blood parasite through surgical equipment including needles, dehorners, ear taggers, castrating knives, and tattoo instruments. Another mechanical transmission mode is through the mouthparts of biting flies who carry an Anaplasma species of blood parasite.Biological vector transmission is through ticks that carry a blood parasite able to cause anaplasmosis. The most common Anaplasmosis-causing tick is Ixodes scapularis, also known as the black-legged tick or the deer tick. Ticks who contain species of many different Anaplasma species can transmit this disease through a bite. The blood parasite survives and can multiply in the tick, and can sit dormant for months without being transmitted to an animal. When bitten by a tick carrying a blood parasite, the blood parasite can then enter the new host and cause infection.Once infected with a species of Anaplasma, the parasite multiplies in the blood stream and attaches to red blood cells. The immune system will attempt to kill the infected blood cells but will also kill uninfected red blood cells in the process. The number of red blood cells being destroyed becomes larger than new red blood cells being made, causing the host to become anemic and leading to many other symptoms. Once infected with anaplasmosis, the cattle will always be a carrier of the infectious disease, and calves born from carriers will also carry the disease. Signs and symptoms Classic signs and symptoms of anaplasmosis will not occur until 3–6 weeks after infection. The most common symptoms of anaplasmosis include fever, a decreased number of white blood cells, platelets in the bloodstream, and abnormally elevated levels of liver enzymes. The erythema chronicum migrans rash may be seen with anaplasmosis as it is co-transmitted in 10% of Lyme disease cases. Anemia may be severe and result in cardiovascular changes such as an increase in heart rate. Blood in the urine may occur due to the lysis of red blood cells. General systemic signs include diarrhea, anorexia, and weight loss. Infected animals may develop a jaundiced look which then turns into paleness around the eyes, muzzle, lips, and teats of the cattle.All cattle are susceptible to infection by Anaplasma marginale, but the severity worsens with age increase. Older cattle tend to exhibit the most severe clinical symptoms; cattle aged 1–3 may also show severe symptoms but are able to recover easier. Causes The two major species that cause anaplasmosis in ruminants include Anaplasma marginale and Anaplasma phagocytophilum. Anaplasma marginale is found worldwide and is transmitted by Rhipicephalus ticks. Anaplasma phagocytophilum is also found worldwide, mainly transmitted by Ixodes ticks. Other species that cause anaplasmosis in specific species include: Cattle: Anaplasma centrale - found mainly in South America, Africa and the Middle East Sheep and goats: Anaplasma ovis - found worldwide. There is a prevalence of 82.9% in sheep, and 74.9% in goats. This species is the most prevalent for causing anaplasmosis in sheep and goats, although Anaplasma phagocytophilium can also cause the disease. Anaplasma phagocytophilium has a prevalence of 11.9% in sheep, and 15.2% in goats. Morphology There are many strains of Anaplasma marginale, all with differing morphology, antigenic properties, protein sequence, and ability to be transmitted by ticks. Major surface proteins (MSP) have been found to play a major role in the infection by Anaplasma marginale. Out of the six MSP found on this species, three of the major surface proteins do not seem to differ between all strains, those including MSP1a, MSP4, and MSP5. The msp1a gene, which codes for MSP1a, is used as a marker for the identification of Anaplasma marginale because it has shown to be conserved in the multiplication of rickettsia in cattle and ticks and has been shown to be involved in adhesion to bovine erythrocytes and tick cells.Anaplasma phagocytophilum is a gram-negative bacterium that does not have lipopolysaccharides or peptidoglycan. The outer membrane does not have a capsule, and is coarse with irregular periplasmic spaces. This species was originally included in the genus Ehrlichia (Ehrlichia phagocytophilium), but is now included in the genus Anaplasma (Anaplasma phagocytophilium). Prevention Currently, no live or inactivated vaccines have been approved by the USDA that are effective against all strains of A. marginale. Some vaccines that rely on erythrocyte-derived antigen sources provide immunity or prevent clinical disease, although these do not prevent cattle from being infected with A. marginale. Other means of prevention can include testing all ruminants in a herd and eliminating any individuals who test positive for anaplasmosis, leading to an anaplasmosis-free herd. Vector control measures can also be used. Tick control is widely used in some countries, including Africa, but rarely used in the United States due to the fact that this prevention method is labor-intensive and expensive. In contrast, the control of flies is effective and there are many ways to do this. Chemical agents can be used, sanitation methods (such as cleaning stalls/pens regularly, manure management, and protecting feed), as well as biological control by natural enemies of flies (including bees, mites, parasitoids). Ways to prevent iatrogenic transmission include avoiding re-using of needles and sanitizing medical equipment between uses. Antimicrobial treatment can also be used, although it is more commonly used in the case of active infection. This includes the drugs tetracycline and imidocarb, and is used in healthy ruminants to decrease the clinical effects of an active infection. Treatment The most common source of treatment is the use of tetracycline drugs (including tetracycline, chlortetracycline, oxytetracycline, rolitetracycline, doxycycline, and minocycline) and imidocarb. An injection of tetracycline drugs can give ruminants immunity to Anaplasma species for at least eight months. Imidocarb has been shown to be highly effective against Anaplasma marginale, but has been identified as a possible carcinogen and is not approved in the United States or Europe. Countries such as South Africa, Australia, Israel, and South America have used live vaccines containing infectious Anaplasma centrale to prevent infection of Anaplasma marginale. Live vaccines are prohibited in the United States, and there has been production of vaccines consisting of nonliving Anaplasma marginale pulled from infected bovine erythrocytes, which can provide some immunity but leaves cattle susceptible to other strains of Anaplasma marginale. Supportive therapy such as blood products and fluids may be necessary. Epidemiology In the United States, anaplasmosis is notably present in the South and West, where the tick hosts Ixodes spp. are found. It is also a seemingly increasing antibody in humans in Europe. Although vaccines have been developed, none are currently available in the United States. Early in the 20th century, this disease was considered one of major economic consequence in the Western United States. In the 1980s and 1990s, control of ticks through new acaricides and practical treatment with prolonged-action antibiotics, notably tetracycline, has led to the point where the disease is no longer considered a major problem. The disease affects immunoglobulin G, therefore G-specific antibody levels can be used to diagnose the disease.In 2005, A. ovis was found in reindeer populations in Mongolia. This pathogen and its associated syndrome (characterized by lethargy, fever, and pale mucous membranes) was previously observed in only wild sheep and goats in the region, and is the first observed occurrence of A. ovis in reindeer. In Australia, bovine anaplasmosis, caused by A. marginale, is found in only the northern and eastern parts of Australia where the cattle tick is present. It was probably introduced as early as 1829 by cattle from Indonesia infested with the cattle tick Boophilus microplus.The veterinarian George P. Broussard of New Iberia, Louisiana, conducted important research on anaplasmosis and brucellosis. References == External links ==