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Hello Aarogya, explain a situation where Refractive surgery occurs

Refractive surgery

Refractive eye surgery is optional eye surgery used to improve the refractive state of the eye and decrease or eliminate dependency on glasses or contact lenses. This can include various methods of surgical remodeling of the cornea (keratomileusis), lens implantation or lens replacement. The most common methods today use excimer lasers to reshape the curvature of the cornea. Refractive eye surgeries are used to treat common vision disorders such as myopia, hyperopia, presbyopia and astigmatism. History The first theoretical work on the potential of refractive surgery was published in 1885 by Hjalmar August Schiøtz, an ophthalmologist from Norway. In 1930, the Japanese ophthalmologist Tsutomu Sato made the first attempts at performing this kind of surgery, hoping to correct the vision of military pilots. His approach was to make radial cuts in the cornea, correcting effects by up to 6 diopters. The procedure unfortunately produced a high rate of corneal degeneration, however, and was soon rejected by the medical community. The first proficient refractive surgery technique was developed in the Barraquer ophthalmologic clinic (Bogotá, Colombia), in 1963, by Jose Barraquer. His technique, called keratomileusis, meaning corneal reshaping (from Greek κέρας (kéras: horn) and σμίλευσις (smileusis: carving)), enabled the correction, not only of myopia, but also of hyperopia. It involves removing a corneal layer, freezing it so that it could be manually sculpted into the required shape, and finally reimplanting the reshaped layer into the eye. In 1980, Swinger performed first keratomileusis surgery in US. In 1985, Krumeich and Swinger introduced non-freeze keratomileusis technique, it remained a relatively imprecise technique. In 1974 a refractive procedure called Radial Keratotomy (RK) was developed in the USSR by Svyatoslav Fyodorov and later introduced to the United States. RK involves making a number of cuts in the cornea to change its shape and correct refractive errors. The incisions are made with a diamond knife. Following the introduction of RK, doctors routinely corrected nearsightedness, farsightedness, and astigmatism using various applications of incisions on the cornea. Meanwhile, experiments in 1970 using a xenon dimer and in 1975 using noble gas halides resulted in the invention of a type of laser called an excimer laser. While excimer lasers were initially used for industrial purposes, in 1980, Rangaswamy Srinivasan, a scientist of IBM who was using an excimer laser to make microscopic circuits in microchips for informatics equipment, discovered that the excimer could also be used to cut organic tissues with high accuracy without significant thermal damage. The discovery of an effective biological cutting laser, along with the development of computers to control it, enabled the development of new refractive surgery techniques. In 1983, Stephen Trokel, a scientist at Columbia University, in collaboration with Theo Seiler and Srinivasan, performed the first Photorefractive Keratectomy (PRK), or keratomileusis in situ (without separation of corneal layer) in Germany. The first patent for this approach, which later became known as LASIK surgery, was granted by the US Patent Office to Gholam Ali. Peyman, MD on June 20, 1989. It involves cutting a flap in the cornea and pulling it back to expose the corneal bed, then using an excimer laser to ablate the exposed surface to the desired shape, and then replacing the flap. The name LASIK was coined in 1991 by University of Crete and the Vardinoyannion Eye. The patents related to so-called broad-beam LASIK and PRK technologies were granted to US companies including Visx and Summit during 1990–1995 based on the fundamental US patent issued to IBM (1983) which claimed the use of UV laser for the ablation of organic tissues. In 1991, J.T. Lin, Ph.D. (a Chinese Physicist) was granted a US patent for a new technology using a flying-spot for customized LASIK currently used worldwide. The first US patent using an eye-tracking device to prevent decentration in LASIK procedures was granted to another Chinese Physicist, Dr. S. Lai in 1993. Techniques Flap procedures Excimer laser ablation is done under a partial-thickness lamellar corneal flap. Automated lamellar keratoplasty (ALK): The surgeon uses an instrument called a microkeratome to cut a thin flap of the corneal tissue. The flap is lifted like a hinged door, targeted tissue is removed from the corneal stroma, again with the microkeratome, and then the flap is replaced. Laser-assisted in situ Keratomileusis (LASIK): The surgeon uses either a microkeratome or a femtosecond laser to cut a flap of the corneal tissue (usually with a thickness of 100–180 micrometres). The flap is lifted like a hinged door, but in contrast to ALK, the targeted tissue is removed from the corneal stroma with an excimer laser. The flap is subsequently replaced. When the flap is created using an IntraLase brand femtosecond laser, the method is called IntraLASIK; other femtosecond lasers such as the Ziemer create a flap similarly. Femtosecond lasers have numerous advantages over mechanical microkeratome based procedure. Microkeratome related flap complications like incomplete flaps, buttonholes or epithelial erosion are eliminated with femtosecond laser procedure. Absence of microscopic metal fragments from the blade will reduce the risk of lamellar keratitis also.Customized aspheric treatment zone (CATz) is a topography-guided LASIK treatment developed by NIDEK Co. Ltd which ablates the cornea based on patient-specific geometry to address certain disadvantages in conventional wavefront spherocylindrical ablation. The treatment is effective for myopia with astigmatism or otherwise irregular corneas, and reduces symptoms such as glare, halos, and night driving difficulty. Refractive Lenticule Extraction (ReLEx): ReLEx "FLEx" (Femtosecond Lenticule Extraction): A femtosecond laser cuts a lenticule within the corneal stroma. Afterwards, a LASIK-like flap is cut which can be lifted to access the lenticule. This is removed through manual dissection using a blunt spatula and forceps. ReLEx "SMILE" (Small Incision Lenticule Extraction): A newer technique without a flap, a femtosecond laser cuts a lenticule within the corneal stroma. The same laser is used to cut a small incision along the periphery of the lenticlue about 1/5th the size of a standard LASIK flap incision. The surgeon then uses a specially designed instrument to separate and remove the lenticule through the incision, leaving the anterior lamellae of the cornea intact. No excimer laser is used in the "ReLEx-procedures". Surface procedures The excimer laser is used to ablate the most anterior portion of the corneal stroma. These procedures do not require a partial thickness cut into the stroma. Surface ablation methods differ only in the way the epithelial layer is handled. Photorefractive keratectomy (PRK) is an outpatient procedure generally performed with local anesthetic eye drops (as with LASIK/LASEK). It is a type of refractive surgery which reshapes the cornea by removing microscopic amounts of tissue from the corneal stroma, using a computer-controlled beam of light (excimer laser). The difference from LASIK is that the top layer of the epithelium is removed (and a bandage contact lens is used), so no flap is created. Recovery time is longer with PRK than with LASIK, though the outcome (after 3 months) is about the same (very good). More recently, customized ablation has been performed with LASIK, LASEK, and PRK. Transepithelial photorefractive keratectomy (TransPRK) is a laser-assisted eye surgery to correct refraction errors of human eye cornea. It employs excimer laser to ablate outer layer of cornea, epithelium, as well its connective tissue, stroma, to correct eye optical power. Laser Assisted Sub-Epithelium Keratomileusis (LASEK) is a procedure that also changes the shape of the cornea using an excimer laser to ablate the tissue from the corneal stroma, under the corneal epithelium, which is kept mostly intact to act as a natural bandage. The surgeon uses an alcohol solution to loosen then lift a thin layer of the epithelium with a trephine blade (usually with a thickness of 50 micrometres). During the weeks following LASEK, the epithelium heals, leaving no permanent flap in the cornea. This healing process can involve discomfort comparable to that with PRK. EPI-LASIK is a new technique similar to LASEK that uses an epi-keratome (rather than a trephine blade and alcohol), to remove the top layer of the epithelium (usually with thickness of 50 micrometres), which is subsequently replaced. For some people it can provide better results than regular LASEK in that it avoids the possibility of negative effects from the alcohol, and recovery may involve less discomfort. Customized Transepithelial No-touch (C-TEN) is an innovative strategy for corneal surgery that avoids any corneal manipulation via a complete laser-assisted trans-epithelial approach. Since C-TEN is planned on the morphology of each individual eye, it can treat a large variety of corneal pathologies from refractive to therapeutic. C-TEN is sometimes referred to as Advanced Surface Ablation (ASA) Corneal incision procedures Radial keratotomy (RK), developed by Russian ophthalmologist Svyatoslav Fyodorov in 1974, uses spoke-shaped incisions, always made with a diamond knife, to alter the shape of the cornea and reduce myopia or astigmatism; this technique is, in medium to high diopters, usually replaced by other refractive methods. Arcuate keratotomy (AK), also known as Astigmatic keratotomy, uses curvilinear incisions at the periphery of the cornea to correct high levels of non-pathological astigmatism, up to 13 diopters. AK is often used for the correction of high post-keratoplasty astigmatism or post-cataract surgery astigmatism. Limbal relaxing incisions (LRI) are incisions near the outer edge of the iris, used to correct minor astigmatism (typically less than 2 diopters). This is often performed in conjunction with an Intraocular Lens implantation. Other procedures Radial Keratocoagulation, also known as Radial Thermokeratoplasty, was invented in 1985 by Svyatoslav Fyodorov and is used to correct hyperopia by putting a ring of 8 or 16 small burns surrounding the pupil, and steepen the cornea with a ring of collagen constriction. It can also be used to treat selected types of astigmatism. It is now generally replaced by laser thermal keratoplasty/laser thermokeratoplasty. Laser thermal keratoplasty (LTK) is a non-touch thermal keratoplasty performed with a Holmium laser, while conductive keratoplasty (CK) is thermal keratoplasty performed with a high-frequency electric probe. Thermal keratoplasty can also be used to improve presbyopia or reading vision after age 40. Intrastromal corneal ring segments (Intacs) are approved by FDA for treatment of low degrees of myopia. Phakic intraocular lens (PIOL) implantation inside the eye can also be used to change refractive errors. The newest type of intervention is a type of PIOL called the implantable collamer lens (ICL) which uses a biocompatible flexible lens which can be inserted in the eye via a 3 mm incision. The ICL is used to correct myopia ranging from −0.5 to −18 diopters, and +0.5 cylinder power to +6.0 for the Toric ICL models. Generally refractive surgery can be broadly divided into: corneal surgery, scleral surgery, lens related surgery (including phakic IOL implantation, clear lens extraction, photophacoreduction and photophacomodulation for correction of presbyopia) For presbyopia correction, a corneal inlay consisting of a porous black ring surrounding a small clear aperture was originally developed by D. Miller, H. Grey PhD and a group at Acufocus. The inlay is placed under a LASIK flap or in a stromal pocket.Using mid-IR and UV lasers for the treatment of presbyopia by scleral tissue ablation was first proposed and patented by J.T. Lin, Ph.D. in US patents #6,258,082 (in 2001) and #6,824,540 (in 2004). Expectations Research conducted by the Magill Research Center for Vision Correction, Medical University of South Carolina, showed that the overall patient satisfaction rate after primary LASIK surgery was 95.4%. They further differentiated between myopic LASIK (95.3%) and hyperopic LASIK (96.3%). They concluded that the vast majority (95.4%) of patients were satisfied with their outcome after LASIK surgery.Ophthalmologists use various approaches to analyze the results of refractive surgery, and alter their techniques to provide better results in the future. Some of these approaches are programmed into the devices ophthalmologists use to measure the refraction of the eye and the shape of the cornea, such as corneal topography. Risks While refractive surgery is becoming more affordable and safe, it may not be recommended for everybody. People with certain eye diseases involving the cornea or retina, pregnant women, and patients who have medical conditions such as glaucoma, diabetes, uncontrolled vascular disease, or autoimmune disease are not good candidates for refractive surgery. Keratoconus, a progressive thinning of the cornea, is a common corneal disorder. Keratoconus occurring after refractive surgery is called Corneal Ectasia. It is believed that additional thinning of the cornea via refractive surgery may contribute to advancement of the disease that may lead to the need for a corneal transplant. Therefore, keratoconus is a contraindication to refractive surgery. Corneal topography and pachymetry are used to screen for abnormal corneas. Furthermore, some peoples eye shape may not permit effective refractive surgery without removing excessive amounts of corneal tissue. Those considering laser eye surgery should have a full eye examination. Although the risk of complications is decreasing compared to the early days of refractive surgery, there is still a small chance for serious problems. These include vision problems such as ghosting, halos, starbursts, double-vision, and dry-eye syndrome. With procedures that create a permanent flap in the cornea (such as LASIK), there is also the possibility of accidental traumatic flap displacement years after the surgery, with potentially disastrous results if not given prompt medical attention.For patients with strabismus, risks of complications such as diplopia and/or increased strabismus angle need to be evaluated carefully. In case both refractive surgery and strabismus surgery are to be performed, it is recommended that the refractive surgery be done first. Children Pediatric refractive surgery involves other risks than refractive surgery on adults, yet it may be indicated especially for children whose cognitive or visual development is failing due to refractive error, in particular in cases of bilateral high refractive error, anisometropia, anisometric amblyopia or accommodative esotropia.Interventions on young children may require general anaesthesia in order to avoid risks due to involuntary movement, and children have a higher risk of rubbing or manipulating their eyes post-surgically. Changes to refractive error occurring during normal age development need to be accounted for, and children have a higher risk of developing postoperative corneal haze. This risk is particularly relevant with relation to myopic children.One study evaluated the outcome of LASEK interventions on 53 children aged 10 months to 16 years who had anisometropic amblyopia. The choice of LASEK was made as it was felt it would give fewer complications than LASIK and less post-operative pain than PRK. In the intervention, which was performed under general anaesthesia, the refractive error in the weaker eye was corrected to balance the refractive error of the other eye. Strabismus surgery was performed later if required. After one year, over 60% had improved in best corrected visual acuity (BCVA) in the weaker eye. Notably, over 80% showed stereopsis post-operatively whereas less than 40% had showed stereopsis before.In addition to corneal refractive procedures (LASIK, PRK and LASEK), intraocular refractive procedures (phakic intraocular lenses, refractive lens exchange and clear lens extraction) are also performed on children. See also Orthokeratology – contact lenses worn only at night to reshape the eye. References External links DJO|Digital Journal of Ophthalmology

Aarogya, can you share information about a health condition involving Renal colic

Renal colic

Renal colic is a type of abdominal pain commonly caused by obstruction of ureter from dislodged kidney stones. The most frequent site of obstruction is the vesico-ureteric junction (VUJ), the narrowest point of the upper urinary tract. Acute obstruction and the resultant urinary stasis (disruption of urine flow) can distend the ureter (hydroureter) and cause a reflexive peristaltic smooth muscle spasm, which leads to a very intense visceral pain transmitted via the ureteric plexus. Signs and symptoms Renal colic typically begins in the flank and often radiates to below the ribs or the groin. It typically comes in waves due to ureteric peristalsis, but may be constant. It is often described as one of the most severe pains.Although this condition can be very painful, most ureteric stones under 5 mm size will eventually pass into the bladder without needing treatments, and cause no permanent physical damage. The experience is said to be traumatizing due to the severe pain, and the experience of passing blood and clots as well as pieces of stone. In most cases, people with renal colic are advised to drink more water to facilitate passing; in other instances, lithotripsy or endoscopic surgery may be needed. Preventive treatment can be instituted to minimize the likelihood of recurrence. Diagnosis The diagnosis of renal colic is the same as the diagnosis for renal calculus and ureteric stones. Differential diagnosis A renal colic must be differentiated from the following conditions: biliary colic and cholecystitis aortic and iliac aneurysms (in older patients with left-side pain, hypertension or atherosclerosis) interstitial: appendicitis, diverticulitis or peritonitis (in this case patients prefer to lie still rather than being restless) gynaecological: endometriosis, ovarian torsion and ectopic pregnancy testicular torsion Treatment Most small stones are passed spontaneously and only pain management is required. Above 5 mm (0.20 in) the rate of spontaneous stone passage decreases. NSAIDs (non-steroidal anti-inflammatory drugs), such as diclofenac or ibuprofen, and antispasmodics like butylscopolamine are used. Although morphine may be administered to assist with emergency pain management, it is often not recommended as morphine is addictive and raises ureteral pressure, worsening the condition. Vomiting is also considered an important adverse effect of opioids, mainly with pethidine. Oral narcotic medications are also often used.There is typically no antalgic position for the patient (lying down on the non-aching side and applying a hot bottle or towel to the area affected may help). Larger stones may require surgical intervention for their removal, such as shockwave lithotripsy, laser lithotripsy, ureteroscopy or percutaneous nephrolithotomy. Patients can also be treated with alpha blockers in cases where the stone is located in the ureter. References == External links ==

Aarogya what is Rhabdomyosarcoma

Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the tumor are identified as rhabdomyoblasts.There are four subtypes – embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, pleomorphic rhabdomyosarcoma, and spindle cell/sclerosing rhabdomyosarcoma. Embryonal, and alveolar are the main groups, and these types are the most common soft tissue sarcomas of childhood and adolescence. The pleomorphic type is usually found in adults.It is generally considered to be a disease of childhood, as the vast majority of cases occur in those below the age of 18. It is commonly described as one of the small-blue-round-cell tumors of childhood due to its appearance on an H&E stain. Despite being relatively rare, it accounts for approximately 40% of all recorded soft tissue sarcomas. RMS can occur in any soft tissue site in the body, but is primarily found in the head, neck, orbit, genitourinary tract, genitals, and extremities. There are no clear risk factors, but the disease has been associated with some congenital abnormalities. Signs and symptoms vary according to tumor site, and prognosis is closely tied to the location of the primary tumor. Common sites of metastasis include the lungs, bone marrow, and bones. There are many classification systems for RMS and a variety of defined histological types. Embryonal rhabdomyosarcoma is the most common type and comprises about 60% of cases.Outcomes vary considerably, with 5 years survival rates between 35% and 95% depending on the type of RMS involved, so clear diagnosis is critical for effective treatment and management. Accurate and quick diagnosis is often difficult due to the heterogeneity of RMS tumors and a lack of strong genetic markers of the disease, although recent research by UVA Health researchers discovered “multiple lines of evidence supporting [the gene] AVIL is powerful driver for both major types of rhabdomyosarcoma,” according to researcher Hui Li, PhD, of the University of Virginia School of Medicine’s Department of Pathology and UVA Cancer Center. (.) Malfunctions in AVIL, Li and his team found, play an essential role in the development of the two main subtypes of rhabdomyosarcoma. In a scientific paper outlining the findings, he and his colleagues describe rhabdomyosarcoma as “addicted” to the gene’s excess activity. They ultimately label AVIL a “bona fide oncogene” for rhabdomyosarcoma. Treatment usually involves a combination of surgery, chemotherapy, and radiation. Sixty percent to 70% of newly diagnosed patients with nonmetastatic disease can be cured using this combined approach to therapy. Despite aggressive multimodality treatment, less than 20% of patients with metastatic RMS are able to be cured of their disease. Types Given the difficulty in diagnosing rhabdomyosarcoma, definitive classification of subtypes has proven difficult. As a result, classification systems vary by institute and organization. However, rhabdomyosarcoma in the 2020 WHO classification is listed as four histological subtypes: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing. Embryonal Embryonal rhabdomyosarcoma (ERMS) is the most common histological variant, comprising approximately 60–70% of childhood cases. It is most common in children 0–4 years old, with a maximum reported incidence of 4 cases per 1 million children. ERMS is characterized by spindle-shaped cells with a stromal-rich appearance, and the morphology is similar to the developing muscle cells of a 6- to 8-week-old embryo. Tumors often present in the head and neck as well as the genitourinary tract. Embryonal subtype Botryoid rhabdomyosarcoma is almost always found in mucosal lined organs including the vagina, bladder, and nasopharynx (although presentation in the nasopharynx typically affects older children). It often presents in infants younger than a year old, as a round, grape-like mass on the affected organ. Histologically, cells of the botryoid variant are defined by a dense tumor layer under an epithelium (cambium layer). This subtype has a good prognosis.Botryoid rhabdomyosarcoma is also sometimes present in adult women, found in the cervix or uterus. Alveolar Alveolar rhabdomyosarcoma (ARMS) is the second most common type. ARMS comprises approximately 20–25% of RMS-related tumors, and it is equally distributed among all age groups with an incidence of about 1 case per 1 million people ages 0 to 19. For this reason, it is the most common form of RMS observed in young adults and teenagers, who are less prone to the embryonal variant. This type of RMS is characterized by densely-packed, round cells that arrange around spaces similar in shape to pulmonary alveoli, although variants have been discovered without these characteristic alveolar spacings. ARMS tends to form more often in the extremities, trunk, and peritoneum. It is also typically more aggressive than ERMS. Pleomorphic Pleomorphic rhabdomyosarcoma (undifferentiated) rhabdomyosarcoma), also known as anaplastic rhabdomyosarcoma, is defined by the presence of pleomorphic cells with large, lobate hyperchromatic nuclei and multipolar mitotic figures. These tumors display high heterogeneity and extremely poor differentiation. The pleomorphic cells may be diffuse or localized, with the diffuse variation correlating to a worse prognosis. It occurs most often in adults, rarely in children, and is often discovered in the extremities. Due to the lack of discernible separation among cancers of this type, clinicians will often label undiagnosed sarcomas with little to no discernible features as anaplastic RMS. It is the most aggressive type of RMS, and will often require intensive treatment. Spindle cell/sclerosing Spindle cell/sclerosing rhabdomyosarcoma is an added subtype listed in the 2020 WHO classification of soft tissue sarcomas.This subtype is very similar to that of leiomyosarcoma (cancer of the smooth muscle tissue), and it has a fascicular, spindled, and leiomyomatous growth pattern with notable rhabdomyoblastic differentiation . It occurs most commonly in the paratesticular region, and the prognosis for this particular form of RMS is excellent with a reported five-year survival rate of 95%. The sclerosing aspect of this subtype has a hyaline sclerosis and pseudovascular development.Multiple classification systems have been proposed for guiding management and treatment, and the most recent and widely used classification system is the "International Classification of Rhabdomyosarcoma" or ICR. It was created by the IRSG in 1995 after their series of four multi-institutional trials aimed at studying the presentation, histology, epidemiology, and treatment of RMS (IRSG I–IV). The ICR system is based on prognostic indicators identified in IRSG I–IV. Pleomorphic rhabdomyosarcoma usually occurs in adults rather than children, and is therefore not included in this system. Signs and symptoms RMS can occur in almost any soft-tissue site in the body; the most common primary sites are genitourinary (24%), parameningeal (16%), extremity (19%), orbit (9%), other head and neck (10%), and miscellaneous other sites (22%). RMS often presents as a mass, but signs and symptoms can vary widely depending on the site of the primary tumor. Genitourinary tumors may present with hematuria, urinary tract obstruction, and/or a scrotal or vaginal mass. Tumors that arise in the retroperitoneum and mediastinum can become quite large before producing signs and symptoms. Parameningeal tumors may present with cranial nerve dysfunction, symptoms of sinusitis, ear discharge, headaches, and facial pain. Orbital tumors often present with orbital swelling and proptosis. Extremity tumors generally present as a rapidly enlarging, firm mass in the relevant tissue. The cancers prevalence in the head, face, and neck will often allow for earlier signs of the disease simply due to the obvious nature of tumors in these locations. Despite the varying presentation and typically aggressive nature of the disease, RMS has the potential to be diagnosed and treated early. The fourth IRSG study found that 23% of patients were diagnosed in time for a complete resection of their cancer, and 15% had resection with only minimal remnants of the diseased cells. Risk factors Rhabdomyosarcoma is difficult to diagnose. Risk factors that increase the likelihood of this cancer include inherited disorders such as Li-Fraumeni syndrome, Neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Costello syndrome, Noonan syndrome, and DICER1 syndrome. Genetic There are multiple genetic lesions associated with rhabdomyosarcoma, but there has been little consistent data demonstrating an association between specific genetic abnormalities and outcome. However, alveolar and embryonal types of RMS can be distinguished cytogenetically, and identification of specific genetic lesions can allow for accurate classification of the ARMS subtype when the histopathological findings are equivocal or unclear. This is valuable for clinical practice as the alveolar type presents a higher risk to the patient and will often require more aggressive treatment than the embryonal type. Thus, ARMS is also referred to as Fusion Positive rhabdomyosarcoma (FP-RMS). Up to 90% of alveolar RMS cases present with a translocations of t(2;13)(q35, q14) or, less commonly, t(1;13)(p36, q15). Both involve the translocation of a DNA binding domain of either PAX3 or PAX7, a member of the Paired Box family of transcription factors, to a transactivation site on FOXO1 (previously known as FKHR), a member of the forkhead/HNF-3 transcription factor family. The t(2;13) translocation results in a fusion of the PAX3 gene with FOXO1, while the t(1;13) translocation involves the fusion of PAX7 with FOXO1. PAX3 has a demonstrated role in muscle cell development, which supports its potential role in RMS. The t(2;13) translocation can result in the PAX3-FKHR fusion product, which is indicative of classic cystic ARMS. Cases of FP-RMS are associated with a poorer prognosis than fusion-negative RMS.The fusion protein presents a potential therapeutic target, and in recent years more research has been conducted to clarify the role of PAX3-FOXO1 in FP-RMS. PAX3-FOXO1 is now known to drive key oncogenes such as MYC and MYCN by creating long-distance genetic interactions by super enhancers. In this context, PAX3-FOXO1 both (1) drives the expression of MYC, MYCN and even MYOD1 (a transcription factor highly expressed in all RMS subtypes) but also (2) co-binds with these master transcription factors at super enhancers to support cancer growth. Furthermore, it was demonstrated that FP-RMS subtypes were especially sensitive to inhibitors (such as JQ1) of a super enhancer bound protein BRD4.Embryonal RMS usually presents with a loss of heterozygosity (LOH) in the short arm of chromosome 11 (p11,15.5). This region is associated with multiple oncogenes, and the potential loss-of-function of this region is likely associated with the loss of a tumor suppressor. However, the specific consequences of this LOH at (p11,15.5) have yet to be determined. The short arm of chromosome 11 is also the site of the insulin-like growth factor 2 gene (IGF-2), which is often over-expressed in RMS.The loss-of-function of tumor suppressor p53 is associated with many cancers including rhabdomyosarcoma, and approximately 50% of RMS cases have been shown to carry some form of mutation to the P53 gene. Other oncogenes often associated with rhabdomyosarcoma, albeit with less frequency, include NMYC, NRAS, KRAS, P16, and c-Met. One study showed that 35% of embryonal RMS tumors contained activating mutations in either NRAS or KRAS and it is worth noting that ras activation has been shown to block myogenic differentiation, which could help explain its potential role in rhabdomyosarcogenesis. More recently, a mechanistic and epigenetic link between mutant RAS isoforms and a block of myogenic differentiation has been demonstrated. Furthermore, it has been shown that this differentiation block can be overcome with a clinical stage inhibitor of the MAP kinase pathway known as a MEK inhibitor. Diagnosis Rhabdomyosarcoma is often difficult to diagnose due to its similarities to other cancers and varying levels of differentiation. It is loosely classified as one of the small-blue-round-cell tumors due to its appearance on an H&E stain. Other cancers that share this classification include neuroblastoma, Ewing sarcoma, and lymphoma, and a diagnosis of RMS requires confident elimination of these morphologically similar diseases. The defining diagnostic trait for RMS is confirmation of malignant skeletal muscle differentiation with myogenesis (presenting as a plump, pink cytoplasm) under light microscopy. Cross striations may or may not be present. Accurate diagnosis is usually accomplished through immunohistochemical staining for muscle-specific proteins such as myogenin, muscle-specific actin, desmin, D-myosin, and myoD1. Myogenin, in particular, has been shown to be highly specific to RMS, although the diagnostic significance of each protein marker may vary depending on the type and location of the malignant cells. The alveolar type of RMS tends to have stronger muscle-specific protein staining. Electron microscopy may also aid in diagnosis, with the presence of actin and myosin or Z bands pointing to a positive diagnosis of RMS. Classification into types and subtypes is accomplished through further analysis of cellular morphology (alveolar spacings, presence of cambium layer, aneuploidy, etc.) as well as genetic sequencing of tumor cells. Some genetic markers, such as the PAX3-FKHR fusion gene expression in alveolar RMS, can aid in diagnosis. Open biopsy is usually required to obtain sufficient tissue for accurate diagnosis. All findings must be considered in context, as no one trait is a definitive indicator for RMS. Staging Following diagnosis and histopathological analysis, various imaging techniques may be used, including MRI, ultrasound, and a bone scan in order to determine the extent of local invasion and any metastasis. Further investigational techniques may be necessary depending on tumor sites. A parameningeal presentation of RMS will often require a lumbar puncture to rule out metastasis to the meninges. A paratesticular presentation will often require an abdominal CT to rule out local lymph node involvement, and so on. Outcomes are strongly tied to the extent of the disease, and its early mapping is important for treatment planning.The current staging system for rhabdomyosarcoma is unusual relative to most cancers. It utilizes a modified TNM (tumor-nodes-metastasis) system originally developed by the IRSG. This system accounts for tumor size (> or <5 cm), lymph node involvement, tumor site, and presence of metastasis. It grades on a scale of 1 to 4 based on these criteria. In addition, patients are sorted by clinical group (from the clinical groups from the IRSG studies) based on the success of their first surgical resection. The current Childrens Oncology Group protocols for the treatment of RMS categorize patients into one of four risk categories based on tumor grade and clinical group, and these risk categories have been shown to be highly predictive of outcome. Treatment Treatment of rhabdomyosarcoma is a multidisciplinary practice involving the use of surgery, chemotherapy, radiation, and possibly immunotherapy. Surgery is generally the first step in a combined therapeutic approach. Resectability varies depending on tumor site, and RMS often presents in sites that dont allow for full surgical resection without significant morbidity and loss of function. Less than 20% of RMS tumors are fully resected with negative margins. Rhabdomyosarcomas are highly chemosensitive, with approximately 80% of cases responding to chemotherapy. In fact, multi-agent chemotherapy is indicated for all patients with rhabdomyosarcoma. Before the use of adjuvant and neoadjuvant therapy involving chemotherapeutic agents, treatment solely by surgical means had a survival rate of <20%. Modern survival rates with adjuvant therapy are approximately 60–70%.There are two main methods of chemotherapy treatment for RMS. There is the VAC regimen, consisting of vincristine, actinomycin D, and cyclophosphamide, and the IVA regimen, consisting of ifosfamide, vincristine, and actinomycin D. These drugs are administered in 9–15 cycles depending on the staging of the disease and other therapies used. Other drug and therapy combinations may also show additional benefit. Addition of doxorubicin and cisplatin to the VAC regimen was shown to increase survival rates of patients with alveolar-type, early-stage RMS in IRS study III, and this same addition improved survival rates and doubled bladder salvage rates in patients with stage III RMS of the bladder. In children and young adults with stage IV metastatic rhabdomyoscarcoma, a Cochrane review has found no evidence to support the use of high-dose chemotherapy as a standard therapy.Radiation therapy, which kill cancer cells with focused doses of radiation, is often indicated in the treatment of rhabdomyosarcoma, and the exclusion of this treatment from disease management has been shown to increase recurrence rates. Radiation therapy is used when resecting the entirety of the tumor would involve disfigurement or loss of important organs (eye, bladder, etc.). Generally, in any case where a lack of complete resection is suspected, radiation therapy is indicated. Administration is usually following 6–12 weeks of chemotherapy if tumor cells are still present. The exception to this schedule is the presence of parameningeal tumors that have invaded the brain, spinal cord, or skull. In these cases radiation treatment is started immediately. In some cases, special radiation treatment may be required. Brachytherapy, or the placement of small, radioactive "seeds" directly inside the tumor or cancer site, is often indicated in children with tumors of sensitive areas such as the testicles, bladder, or vagina. This reduces scattering and the degree of late toxicity following dosing. Radiation therapy is more often indicated in higher stage classifications. Immunotherapy is a more recent treatment modality that is still in development. This method involves recruiting and training the patients immune system to target the cancer cells. This can be accomplished through administering small molecules designed to pull immune cells towards the tumors, taking immune cells pulled from the patient and training to attack tumors through presentation with tumor antigen, or other experimental methods. A specific example here would be presenting some of the patients dendritic cells, which direct the immune system to foreign cells, with the PAX3-FKHR fusion protein in order to focus the patients immune system to the malignant RMS cells. All cancers, including rhabdomyosarcoma, could potentially benefit from this new, immune-based approach. Prognostic Prognosis in rhabdomyosarcoma patients has been shown to be dependent on age, tumor site, resectability of tumor, tumor size, regional lymph node involvement, presence of metastasis, site and extent of metastasis, and biological and histopathological characteristics of the tumor cells. Survival after recurrence is poor, and new salvage therapy strategies are needed. Epidemiology Rhabdomyosarcoma is the most common soft-tissue sarcoma in children as well as the third most common solid tumor in children. Recent estimates place the incidence of the disease at approximately 4.5 case per 1 million children/adolescents with approximately 250 new cases in the United States each year. With the vast majority of cases of RMS occurring in children or adolescents, two-thirds of reported cases occur in youths under the age of 10. RMS also occurs slightly more often in males than in females, with a ratio of approximately 1.3–1.5:1. In addition, slightly lower prevalence of the disease has been reported in black and Asian children relative to white children. In most cases, there are no clear predisposing risk factors for the development of RMS. It tends to occur sporadically with no obvious cause. However, RMS has been correlated with familial cancer syndromes and congenital abnormalities including neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Li–Fraumeni syndrome, cardio-facio-cutaneous syndrome, and Costello syndrome. It has also been associated with parental use of cocaine and marijuana. History Rhabdomyosarcoma was first described by Weber, a German physician, in 1845, but it wasnt until the paper by Arthur Stout in 1946 that RMS was formally classified. The first thirty years of investigation were conducted by the Intergroup Rhabdomyosarcoma Study Group (IRSG), an independent National Cancer Institute (NCI)-funded cooperative that has become a part of the Childrens Oncology Group. Research Cancer stem cells of rhabdomyosarcoma have been identified and fibroblast growth factor receptor 3 has been suggested as their marker. Preclinical animal studies that try to use conditionally replicating adenoviruses against such cells are in progress. Epigenetic Therapy for rhabdomyosarcoma is becoming more important. A recent study by Bharathy et al. found that deacetylase inhibitor, entinostat works in aggressive subtype, alveolar rhabdomyosarcoma (aRMS) by specifically blocking the activity of HDAC3, thereby preventing epigenetic suppression of a microRNA that inhibits PAX3:FOXO1 translation. These findings and ongoing clinical trials (ADVL1513) shows promise for an effective therapy for some patients with aRMS. See also Rhabdomyoma References Saboo, S. S.; Krajewski, K. M.; Zukotynski, K.; Howard, S.; Jagannathan, J. P.; Hornick, J. L.; Ramaiya, N. (2012). "Imaging Features of Primary and Secondary Adult Rhabdomyosarcoma". American Journal of Roentgenology. 199 (6): W694–W703. doi:10.2214/AJR.11.8213. PMID 23169742. == External links ==

Aarogya, share information about a health condition involving Rheumatic fever

Rheumatic fever

Rheumatic fever (RF) is an inflammatory disease that can involve the heart, joints, skin, and brain. The disease typically develops two to four weeks after a streptococcal throat infection. Signs and symptoms include fever, multiple painful joints, involuntary muscle movements, and occasionally a characteristic non-itchy rash known as erythema marginatum. The heart is involved in about half of the cases. Damage to the heart valves, known as rheumatic heart disease (RHD), usually occurs after repeated attacks but can sometimes occur after one. The damaged valves may result in heart failure, atrial fibrillation and infection of the valves.Rheumatic fever may occur following an infection of the throat by the bacterium Streptococcus pyogenes. If the infection is left untreated, rheumatic fever occurs in up to three percent of people. The underlying mechanism is believed to involve the production of antibodies against a persons own tissues. Due to their genetics, some people are more likely to get the disease when exposed to the bacteria than others. Other risk factors include malnutrition and poverty. Diagnosis of RF is often based on the presence of signs and symptoms in combination with evidence of a recent streptococcal infection.Treating people who have strep throat with antibiotics, such as penicillin, decreases the risk of developing rheumatic fever. In order to avoid antibiotic misuse this often involves testing people with sore throats for the infection; however, testing might not be available in the developing world. Other preventive measures include improved sanitation. In those with rheumatic fever and rheumatic heart disease, prolonged periods of antibiotics are sometimes recommended. Gradual return to normal activities may occur following an attack. Once RHD develops, treatment is more difficult. Occasionally valve replacement surgery or valve repair is required. Otherwise complications are treated as usual.Rheumatic fever occurs in about 325,000 children each year and about 33.4 million people currently have rheumatic heart disease. Those who develop RF are most often between the ages of 5 and 14, with 20% of first-time attacks occurring in adults. The disease is most common in the developing world and among indigenous peoples in the developed world. In 2015 it resulted in 319,400 deaths down from 374,000 deaths in 1990. Most deaths occur in the developing world where as many as 12.5% of people affected may die each year. Descriptions of the condition are believed to date back to at least the 5th century BCE in the writings of Hippocrates. The disease is so named because its symptoms are similar to those of some rheumatic disorders. Signs and symptoms The disease typically develops two to four weeks after a throat infection. Symptoms include: fever, painful joints with those joints affected changing with time, involuntary muscle movements, and occasionally a characteristic non-itchy rash known as erythema marginatum. The heart is involved in about half of the cases. Damage to the heart valves usually occurs only after multiple attacks but may occasionally occur after a single case of RF. The damaged valves may result in heart failure and also increase the risk of atrial fibrillation and infection of the valves. Pathophysiology Rheumatic fever is a systemic disease affecting the connective tissue around arterioles, and can occur after an untreated strep throat infection, specifically due to group A streptococcus (GAS), Streptococcus pyogenes. The similarity between antigens of Streptococcus pyogenes and multiple cardiac proteins can cause a life-threatening type II hypersensitivity reaction. Usually, self reactive B cells remain anergic in the periphery without T cell co-stimulation. During a streptococcal infection, mature antigen-presenting cells such as B cells present the bacterial antigen to CD4+T cells which differentiate into helper T2 cells. Helper T2 cells subsequently activate the B cells to become plasma cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies may also react against the myocardium and joints, producing the symptoms of rheumatic fever. S. pyogenes is a species of aerobic, cocci, gram-positive bacteria that are non-motile, non-spore forming, and forms chains and large colonies.S. pyogenes has a cell wall composed of branched polymers which sometimes contain M protein, a virulence factor that is highly antigenic. The antibodies which the immune system generates against the M protein may cross-react with heart muscle cell protein myosin, heart muscle glycogen and smooth muscle cells of arteries, inducing cytokine release and tissue destruction. However, the only proven cross-reaction is with perivascular connective tissue. This inflammation occurs through direct attachment of complement and Fc receptor-mediated recruitment of neutrophils and macrophages. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen surrounded by lymphocytes and macrophages can be seen on light microscopy. The larger macrophages may become Anitschkow cells or Aschoff giant cells. Rheumatic valvular lesions may also involve a cell-mediated immunity reaction as these lesions predominantly contain T-helper cells and macrophages.In rheumatic fever, these lesions can be found in any layer of the heart causing different types of carditis. The inflammation may cause a serofibrinous pericardial exudate described as "bread-and-butter" pericarditis, which usually resolves without sequelae. Involvement of the endocardium typically results in fibrinoid necrosis and wart formation along the lines of closure of the left-sided heart valves. Warty projections arise from the deposition, while subendocardial lesions may induce irregular thickenings called MacCallum plaques. Rheumatic heart disease Chronic rheumatic heart disease (RHD) is characterized by repeated inflammation with fibrinous repair. The cardinal anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords. It is caused by an autoimmune reaction to Group A β-hemolytic streptococci (GAS) that results in valvular damage. Fibrosis and scarring of valve leaflets, commissures and cusps leads to abnormalities that can result in valve stenosis or regurgitation. The inflammation caused by rheumatic fever, usually during childhood, is referred to as rheumatic valvulitis. About half of patients with rheumatic fever develop inflammation involving valvular endothelium. The majority of morbidity and mortality associated with rheumatic fever is caused by its destructive effects on cardiac valve tissue. The pathogenesis of RHD is complex and not fully understood, but it is known to involve molecular mimicry and genetic predisposition that lead to autoimmune reactions.Molecular mimicry occurs when epitopes are shared between host antigens and Streptococcus antigens. This causes an autoimmune reaction against native tissues in the heart that are incorrectly recognized as "foreign" due to the cross-reactivity of antibodies generated as a result of epitope sharing. The valvular endothelium is a prominent site of lymphocyte-induced damage. CD4+ T cells are the major effectors of heart tissue autoimmune reactions in RHD. Normally, T cell activation is triggered by the presentation of bacterial antigens. In RHD, molecular mimicry results in incorrect T cell activation, and these T lymphocytes can go on to activate B cells, which will begin to produce self-antigen-specific antibodies. This leads to an immune response attack mounted against tissues in the heart that have been misidentified as pathogens. Rheumatic valves display increased expression of VCAM-1, a protein that mediates the adhesion of lymphocytes. Self-antigen-specific antibodies generated via molecular mimicry between human proteins and streptococcal antigens up-regulate VCAM-1 after binding to the valvular endothelium. This leads to the inflammation and valve scarring observed in rheumatic valvulitis, mainly due to CD4+ T cell infiltration.While the mechanisms of genetic predisposition remain unclear, a few genetic factors have been found to increase susceptibility to autoimmune reactions in RHD. The dominant contributors are a component of MHC class II molecules, found on lymphocytes and antigen-presenting cells, specifically the DR and DQ alleles on human chromosome 6. Certain allele combinations appear to increase RHD autoimmune susceptibility. Human leukocyte antigen (HLA) class II allele DR7 (HLA-DR7) is most often associated with RHD, and its combination with certain DQ alleles is seemingly associated with the development of valvular lesions. The mechanism by which MHC class II molecules increase a hosts susceptibility to autoimmune reactions in RHD is unknown, but it is likely related to the role HLA molecules play in presenting antigens to T cell receptors, thus triggering an immune response. Also found on human chromosome 6 is the cytokine TNF-α which is also associated with RHD. High expression levels of TNF-α may exacerbate valvular tissue inflammation, contributing to RHD pathogenesis. Mannose-binding lectin (MBL) is an inflammatory protein involved in pathogen recognition. Different variants of MBL2 gene regions are associated in RHD. RHD-induced mitral valve stenosis has been associated with MBL2 alleles encoding for high production of MBL. Aortic valve regurgitation in RHD patients has been associated with different MBL2 alleles that encode for low production of MBL. Other genes are also being investigated to better understand the complexity of autoimmune reactions that occur in RHD. Diagnosis Modified Jones criteria were first published in 1944 by T. Duckett Jones, MD. They have been periodically revised by the American Heart Association in collaboration with other groups. According to revised Jones criteria, the diagnosis of rheumatic fever can be made when two of the major criteria, or one major criterion plus two minor criteria, are present along with evidence of streptococcal infection: elevated or rising antistreptolysin O titre or anti-DNase B. A recurrent episode is also diagnosed when three minor criteria are present. Exceptions are chorea and indolent carditis, each of which by itself can indicate rheumatic fever. An April 2013 review article in the Indian Journal of Medical Research stated that echocardiographic and Doppler (E & D) studies, despite some reservations about their utility, have identified a massive burden of rheumatic heart disease, which suggests the inadequacy of the 1992 Jones criteria. E & D studies have identified subclinical carditis in patients with rheumatic fever, as well as in follow-ups of rheumatic heart disease patients who initially presented as having isolated cases of Sydenhams chorea. Signs of a preceding streptococcal infection include: recent scarlet fever, raised antistreptolysin O or other streptococcal antibody titre, or positive throat culture. The last revision of 2015 suggested variable diagnostic criteria in low-risk and high-risk populations to avoid overdiagnosis in the first category and underdiagnosis in the last one. Low-risk populations were defined as those with acute rheumatic fever annual incidence ≤2 per 100 000 school-aged children or all-age rheumatic heart disease prevalence of ≤1 per 1000. All other populations were categorised as having a moderate or high risk. Major criteria Joint manifestations are the unique clinical signs that have different implications for different population-risk categories : Only polyarthritis (a temporary migrating inflammation of the large joints, usually starting in the legs and migrating upwards) is considered as a major criterion in low-risk populations, whereas monoarthritis, polyarthritis and polyarthralgia (joint pain without swelling) are all included as major criteria in high-risk populations. Carditis: Carditis can involve the pericardium (pericarditis which resolves without sequelae), some regions of the myocardium (which might not provoke systolic dysfunction), and more consistently the endocardium in the form of valvulitis. Carditis is diagnosed clinically (palpitations, shortness of breath, heart failure, or a new heart murmur) or by echocardiography/Doppler studies revealing mitral or aortic valvulitis. Both of clinical and subclinical carditis are now considered a major criterion. Subcutaneous nodules: Painless, firm collections of collagen fibers over bones or tendons. They commonly appear on the back of the wrist, the outside elbow, and the front of the knees. Erythema marginatum: A long-lasting reddish rash that begins on the trunk or arms as macules, which spread outward and clear in the middle to form rings, which continue to spread and coalesce with other rings, ultimately taking on a snake-like appearance. This rash typically spares the face and is made worse with heat. Sydenhams chorea (St. Vitus dance): A characteristic series of involuntary rapid movements of the face and arms. This can occur very late in the disease for at least three months from onset of infection. Minor criteria Arthralgia: Polyarthralgia in low-risk populations and monoarthralgia in others. However, joint manifestations cannot be considered in both major and minor categories in the same patient. Fever: ≥ 38.5 °C (101.3 °F) in low-incidence populations and ≥ 38 °C (100.4 °F) in high-risk populations. Raised erythrocyte sedimentation rate (≥60 mm in the first hour in lox-risk populations and ≥30 mm/h in others) or C reactive protein (>3.0 mg/dL). ECG showing a prolonged PR interval after accounting for age variability (Cannot be included if carditis is present as a major symptom) Prevention Rheumatic fever can be prevented by effectively and promptly treating strep throat with antibiotics.In those who have previously had rheumatic fever, antibiotics in a preventative manner are occasionally recommended. As of 2017 the evidence to support long term antibiotics in those with underlying disease is poor.The American Heart Association suggests that dental health be maintained, and that people with a history of bacterial endocarditis, a heart transplant, artificial heart valves, or "some types of congenital heart defects" may wish to consider long-term antibiotic prophylaxis. Treatment The management of rheumatic fever is directed toward the reduction of inflammation with anti-inflammatory medications such as aspirin or corticosteroids. Individuals with positive cultures for strep throat should also be treated with antibiotics.Aspirin is the drug of choice and should be given at high doses.One should watch for side effects like gastritis and salicylate poisoning. In children and teenagers, the use of aspirin and aspirin-containing products can be associated with Reyes syndrome, a serious and potentially deadly condition. The risks, benefits, and alternative treatments must always be considered when administering aspirin and aspirin-containing products in children and teenagers. Ibuprofen for pain and discomfort and corticosteroids for moderate to severe inflammatory reactions manifested by rheumatic fever should be considered in children and teenagers. Vaccine No vaccines are currently available to protect against S. pyogenes infection, although research is underway to develop one. Difficulties in developing a vaccine include the wide variety of strains of S. pyogenes present in the environment and the large amount of time and people that will be needed for appropriate trials for safety and efficacy of the vaccine. Infection People with positive cultures for Streptococcus pyogenes should be treated with penicillin as long as allergy is not present. The use of antibiotics will not alter cardiac involvement in the development of rheumatic fever. Some suggest the use of benzathine benzylpenicillin.Monthly injections of long-acting penicillin must be given for a period of five years in patients having one attack of rheumatic fever. If there is evidence of carditis, the length of therapy may be up to 40 years. Another important cornerstone in treating rheumatic fever includes the continual use of low-dose antibiotics (such as penicillin, sulfadiazine, or erythromycin) to prevent recurrence. Inflammation While corticosteroids are often used, evidence to support this is poor. Salicylates are useful for pain.Steroids are reserved for cases where there is evidence of an involvement of the heart. The use of steroids may prevent further scarring of tissue and may prevent the development of sequelae such as mitral stenosis. Heart failure Some patients develop significant carditis which manifests as congestive heart failure. This requires the usual treatment for heart failure: ACE inhibitors, diuretics, beta blockers, and digoxin. Unlike typical heart failure, rheumatic heart failure responds well to corticosteroids. Epidemiology About 33 million people are affected by rheumatic heart disease with an additional 47 million having asymptomatic damage to their heart valves. As of 2010 globally it resulted in 345,000 deaths, down from 463,000 in 1990.In Western countries, rheumatic fever has become fairly rare since the 1960s, probably due to the widespread use of antibiotics to treat streptococcus infections. While it has been far less common in the United States since the beginning of the 20th century, there have been a few outbreaks since the 1980s. The disease is most common among Indigenous Australians (particularly in central and northern Australia), Māori, and Pacific Islanders, and is also common in Sub-Saharan Africa, Latin America, the Indian Subcontinent, and North Africa.Rheumatic fever primarily affects children between ages 5 and 17 years and occurs approximately 20 days after strep throat. In up to a third of cases, the underlying strep infection may not have caused any symptoms.The rate of development of rheumatic fever in individuals with untreated strep infection is estimated to be 3%. The incidence of recurrence with a subsequent untreated infection is substantially greater (about 50%). The rate of development is far lower in individuals who have received antibiotic treatment. Persons who have had a case of rheumatic fever have a tendency to develop flare-ups with repeated strep infections.The recurrence of rheumatic fever is relatively common in the absence of maintenance of low dose antibiotics, especially during the first three to five years after the first episode. Recurrent bouts of rheumatic fever can lead to valvular heart disease. Heart complications may be long-term and severe, particularly if valves are involved. In countries in Southeast-Asia, sub-Saharan Africa, and Oceania, the percentage of people with rheumatic heart disease detected by listening to the heart was 2.9 per 1000 children and by echocardiography it was 12.9 per 1000 children. Echocardiographic screening among children and timely initiation of secondary antibiotic prophylaxis in children with evidence of early stages of rheumatic heart disease may be effective to reduce the burden of rheumatic heart disease in endemic regions. See also Rapid strep test References External links "Jones major criteria". Archived from the original on 4 August 2017.

Aarogya what is Riboflavin

Riboflavin

Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved in energy metabolism, cellular respiration, and antibody production, as well as normal growth and development. The coenzymes are also required for the metabolism of niacin, vitamin B6, and folate. Riboflavin is prescribed to treat corneal thinning, and taken orally, may reduce the incidence of migraine headaches in adults. Riboflavin deficiency is rare and is usually accompanied by deficiencies of other vitamins and nutrients. It may be prevented or treated by oral supplements or by injections. As a water-soluble vitamin, any riboflavin consumed in excess of nutritional requirements is not stored; it is either not absorbed or is absorbed and quickly excreted in urine, causing the urine to have a bright yellow tint. Natural sources of riboflavin include meat, fish and fowl, eggs, dairy products, green vegetables, mushrooms, and almonds. Some countries require its addition to grains. Riboflavin was discovered in 1920, isolated in 1933, and first synthesized in 1935. In its purified, solid form, it is a water-soluble yellow-orange crystalline powder. In addition to its function as a vitamin, it is used as a food coloring agent. Biosynthesis takes place in bacteria, fungi and plants, but not animals. Industrial synthesis of riboflavin was initially achieved using a chemical process, but current commercial manufacturing relies on fermentation methods using strains of fungi and genetically modified bacteria. Definition Riboflavin, also known as vitamin B2, is a water-soluble vitamin and is one of the B vitamins. Unlike folate and vitamin B6, which occur in several chemically related forms known as vitamers, riboflavin is only one chemical compound. It is a starting compound in the synthesis of the coenzymes flavin mononucleotide (FMN, also known as riboflavin-5-phosphate) and flavin adenine dinucleotide (FAD). FAD is the more abundant form of flavin, reported to bind to 75% of the number of flavin-dependent protein encoded genes in the all-species genome (the flavoproteome) and serves as a co-enzyme for 84% of human-encoded flavoproteins.In its purified, solid form, riboflavin is a yellow-orange crystalline powder with a slight odor and bitter taste. It is soluble in polar solvents, such as water and aqueous sodium chloride solutions, and slightly soluble in alcohols. It is not soluble in non-polar or weakly polar organic solvents such as chloroform, benzene or acetone. In solution or during dry storage as a powder, riboflavin is heat stable if not exposed to light. When heated to decompose, it releases toxic fumes containing nitric oxide. Functions Riboflavin is essential to the formation of two major coenzymes, FMN and FAD. These coenzymes are involved in energy metabolism, cell respiration, antibody production, growth and development. Riboflavin is essential for the metabolism of carbohydrates, protein and fats. FAD contributes to conversion of tryptophan to niacin (vitamin B3) and the conversion of vitamin B6 to the coenzyme pyridoxal 5-phosphate requires FMN. Riboflavin is involved in maintaining normal circulating levels of homocysteine; in riboflavin deficiency, homocysteine levels increase, elevating the risk of cardiovascular diseases. Redox reactions Redox reactions are processes that involve the transfer of electrons. The flavin coenzymes support the function of roughly 70-80 flavoenzymes in humans (and hundreds more across all organisms, including those encoded by archeal, bacterial and fungal genomes) that are responsible for one- or two-electron redox reactions which capitalize on the ability of flavins to be converted between oxidized, half-reduced and fully reduced forms. FAD is also required for the activity of glutathione reductase, an essential enzyme in formation of the endogenous antioxidant, glutathione. Micronutrient metabolism Riboflavin, FMN, and FAD are involved in the metabolism of niacin, vitamin B6, and folate. The synthesis of the niacin-containing coenzymes, NAD and NADP, from tryptophan involves the FAD-dependent enzyme, kynurenine 3-monooxygenase. Dietary deficiency of riboflavin can decrease the production of NAD and NADP, thereby promoting niacin deficiency. Conversion of vitamin B6 to its coenzyme, pyridoxal 5-phosphate synthase, involves the enzyme, pyridoxine 5-phosphate oxidase, which requires FMN. An enzyme involved in folate metabolism, 5,10-methylenetetrahydrofolate reductase, requires FAD to form the amino acid, methionine, from homocysteine.Riboflavin deficiency appears to impair the metabolism of the dietary mineral, iron, which is essential to the production of hemoglobin and red blood cells. Alleviating riboflavin deficiency in people who are deficient in both riboflavin and iron improves the effectiveness of iron supplementation for treating iron-deficiency anemia. Synthesis Biosynthesis Biosynthesis takes place in bacteria, fungi and plants, but not animals. The biosynthetic precursors to riboflavin are ribulose 5-phosphate and guanosine triphosphate. The former is converted to L-3,4-dihydroxy-2-butanone-4-phosphate while the latter is transformed in a series of reactions that lead to 5-amino-6-(D-ribitylamino)uracil. These two compounds are then the substrates for the penultimate step in the pathway, catalysed by the enzyme lumazine synthase in reaction EC 2.5.1.78. In the final step of the biosynthesis, two molecules of 6,7-dimethyl-8-ribityllumazine are combined by the enzyme riboflavin synthase in a dismutation reaction. This generates one molecule of riboflavin and one of 5-amino-6-(D-ribitylamino) uracil. The latter is recycled to the previous reaction in the sequence. Conversions of riboflavin to the cofactors FMN and FAD are carried out by the enzymes riboflavin kinase and FAD synthetase acting sequentially. Industrial synthesis The industrial-scale production of riboflavin uses various microorganisms, including filamentous fungi such as Ashbya gossypii, Candida famata and Candida flaveri, as well as the bacteria Corynebacterium ammoniagenes and Bacillus subtilis. B. subtilis that has been genetically modified to both increase the production of riboflavin and to introduce an antibiotic (ampicillin) resistance marker, is employed at a commercial scale to produce riboflavin for feed and food fortification. By 2012, over 4,000 tonnes per annum were produced by such fermentation processes.In the presence of high concentrations of hydrocarbons or aromatic compounds, some bacteria overproduce riboflavin, possibly as a protective mechanism. One such organism is Micrococcus luteus (American Type Culture Collection strain number ATCC 49442), which develops a yellow color due to production of riboflavin while growing on pyridine, but not when grown on other substrates, such as succinic acid. Laboratory synthesis The first total synthesis of riboflavin was carried out by Richard Kuhns group. A substituted aniline, produced by reductive amination using D-ribose, was condensed with alloxan in the final step: Uses Treatment of corneal thinning Keratoconus is the most common form of corneal ectasia, a progressive thinning of the cornea. The condition is treated by corneal collagen cross-linking, which increases corneal stiffness. Cross-linking is achieved by applying a topical riboflavin solution to the cornea, which is then exposed to ultraviolet A light. Migraine prevention In its 2012 guidelines, the American Academy of Neurology stated that high-dose riboflavin (400 mg) is "probably effective and should be considered for migraine prevention," a recommendation also provided by the UK National Migraine Centre. A 2017 review reported that daily riboflavin taken at 400 mg per day for at least three months may reduce the frequency of migraine headaches in adults. Research on high-dose riboflavin for migraine prevention or treatment in children and adolescents is inconclusive, and so supplements are not recommended. Food coloring Riboflavin is used as a food coloring (yellow-orange crystalline powder), and is designated with the E number, E101, in Europe for use as a food additive. Dietary recommendations The National Academy of Medicine updated the Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for riboflavin in 1998. The EARs for riboflavin for women and men aged 14 and over are 0.9 mg/day and 1.1 mg/day, respectively; the RDAs are 1.1 and 1.3 mg/day, respectively. RDAs are higher than EARs to provide adequate intake levels for individuals with higher than average requirements. The RDA during pregnancy is 1.4 mg/day and the RDA for lactating females is 1.6 mg/day. For infants up to the age of 12 months, the Adequate Intake (AI) is 0.3–0.4 mg/day and for children aged 1–13 years the RDA increases with age from 0.5 to 0.9 mg/day. As for safety, the IOM sets tolerable upper intake levels (ULs) for vitamins and minerals when evidence is sufficient. In the case of riboflavin there is no UL, as there is no human data for adverse effects from high doses. Collectively the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes (DRIs).The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL are defined the same as in United States. For women and men aged 15 and older the PRI is set at 1.6 mg/day. The PRI during pregnancy is 1.9 mg/day and the PRI for lactating females is 2.0 mg/day. For children aged 1–14 years the PRIs increase with age from 0.6 to 1.4 mg/day. These PRIs are higher than the U.S. RDAs. The EFSA also considered the maximum safe intake and like the U.S. National Academy of Medicine, decided that there was not sufficient information to set an UL. Safety In humans, there is no evidence for riboflavin toxicity produced by excessive intakes and absorption becomes less efficient as doses increases. Any excess riboflavin is excreted via the kidneys into urine, resulting in a bright yellow color known as flavinuria. During a clinical trial on the effectiveness of riboflavin for treating the frequency and severity of migraines, subjects were given up to 400 mg of riboflavin orally per day for periods of 3–12 months. Abdominal pains and diarrhea were among the side effects reported. Labeling For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For riboflavin labeling purposes 100% of the Daily Value was 1.7 mg, but as of May 27, 2016, it was revised to 1.3 mg to bring it into agreement with the RDA. A table of the old and new adult daily values is provided at Reference Daily Intake. Sources The United States Department of Agriculture, Agricultural Research Service maintains a food composition database from which riboflavin content in hundreds of foods can be searched. The milling of wheat results in an 85% loss of riboflavin, so white flour is enriched in some countries. Riboflavin is also added to baby foods, breakfast cereals, pastas and vitamin-enriched meal replacement products. It is difficult to incorporate riboflavin into liquid products because it has poor solubility in water, hence the requirement for riboflavin-5-phosphate (FMN, also called E101 when used as colorant), a more soluble form of riboflavin. The enrichment of bread and ready-to-eat breakfast cereals contributes significantly to the dietary supply of the vitamin. Free riboflavin is naturally present in animal-sourced foods along with protein-bound FMN and FAD. Cows milk contains mainly free riboflavin, but both FMN and FAD are present at low concentrations. Fortification Some countries require or recommend fortification of grain foods. As of 2021, 56 countries, mostly in North and South America and southeast Africa, require food fortification of wheat flour or maize (corn) flour with riboflavin or riboflavin-5-phosphate sodium. The amounts stipulated range from 1.3 to 5.75 mg/kg. An additional 16 countries have a voluntary fortification program. For example, the Indian government recommends 4.0 mg/kg for "maida" (white) and "atta" (whole wheat) flour. Absorption, metabolism, excretion More than 90% of riboflavin in the diet is in the form of protein-bound FMN and FAD. Exposure to gastric acid in the stomach releases the coenzymes, which are subsequently enzymatically hydrolyzed in the proximal small intestine to release free riboflavin.Absorption occurs via a rapid active transport system, with some additional passive diffusion occurring at high concentrations. Bile salts facilitate uptake, so absorption is improved when the vitamin is consumed with a meal. One small clinical trial in adults reported that the maximum amount of riboflavin that can be absorbed from a single dose is 27 mg. The majority of newly absorbed riboflavin is taken up by the liver on the first pass, indicating that postprandial appearance of riboflavin in blood plasma may underestimate absorption. Three riboflavin transporter proteins have been identified: RFVT1 is present in the small intestine and also in the placenta; RFVT2 is highly expressed in brain and salivary glands; and RFVT3 is most highly expressed in the small intestine, testes, and prostate. Infants with mutations in the genes encoding these transport proteins can be treated with riboflavin administered orally.Riboflavin is reversibly converted to FMN and then FAD. From riboflavin to FMN is the function of zinc-requiring riboflavin kinase; the reverse is accomplished by a phosphatase. From FMN to FAD is the function of magnesium-requiring FAD synthase; the reverse is accomplished by a pyrophosphatase. FAD appears to be an inhibitory end-product that down-regulates its own formation.When excess riboflavin is absorbed by the small intestine, it is quickly removed from the blood and excreted in urine. Urine color is used as a hydration status biomarker and, under normal conditions, correlates with urine specific gravity and urine osmolality. However, riboflavin supplementation in large excess of requirements causes urine to appear more yellow than normal. With normal dietary intake, about two-thirds of urinary output is riboflavin, the remainder having been partially metabolized to hydroxymethylriboflavin from oxidation within cells, and as other metabolites. When consumption exceeds the ability to absorb, riboflavin passes into the large intestine, where it is catabolized by bacteria to various metabolites that can be detected in feces. There is speculation that unabsorbed riboflavin could affect the large intestine microbiome. Deficiency Prevalence Riboflavin deficiency is uncommon in the United States and in other countries with wheat flour or corn meal fortification programs. From data collected in biannual surveys of the U.S. population, for ages 20 and over, 22% of females and 19% of men reported consuming a supplement that contained riboflavin, typically a vitamin-mineral multi-supplement. For the non-supplement users, the dietary intake of adult women averaged 1.74 mg/day and men 2.44 mg/day. These amounts exceed the RDAs for riboflavin of 1.1 and 1.3 mg/day respectively. For all age groups, on average, consumption from food exceeded the RDAs. A 2001-02 U.S. survey reported that less than 3% of the population consumed less than the Estimated Average Requirement of riboflavin. Signs and symptoms Riboflavin deficiency (also called ariboflavinosis) results in stomatitis, symptoms of which include chapped and fissured lips, inflammation of the corners of the mouth (angular stomatitis), sore throat, painful red tongue, and hair loss. The eyes can become itchy, watery, bloodshot, and sensitive to light. Riboflavin deficiency is associated with anemia. Prolonged riboflavin insufficiency may cause degeneration of the liver and nervous system. Riboflavin deficiency may increase the risk of preeclampsia in pregnant women. Deficiency of riboflavin during pregnancy can result in fetal birth defects, including heart and limb deformities. Risk factors People at risk of having low riboflavin levels include alcoholics, vegetarian athletes, and practitioners of veganism. Pregnant or lactating women and their infants may also be at risk, if the mother avoids meat and dairy products. Anorexia and lactose intolerance increase the risk of riboflavin deficiency. People with physically demanding lives, such as athletes and laborers, may require higher riboflavin intake. The conversion of riboflavin into FAD and FMN is impaired in people with hypothyroidism, adrenal insufficiency, and riboflavin transporter deficiency. Causes Riboflavin deficiency is usually found together with other nutrient deficiencies, particularly of other water-soluble vitamins. A deficiency of riboflavin can be primary (i.e. caused by poor vitamin sources in the regular diet) or secondary, which may be a result of conditions that affect absorption in the intestine. Secondary deficiencies are typically caused by the body not being able to use the vitamin, or by an increased rate of excretion of the vitamin. Diet patterns that increase risk of deficiency include veganism and low-dairy vegetarianism. Diseases such as cancer, heart disease and diabetes may cause or exacerbate riboflavin deficiency.There are rare genetic defects that compromise riboflavin absorption, transport, metabolism or use by flavoproteins. One of these is riboflavin transporter deficiency, previously known as Brown-Vialetto-Van Laere syndrome. Variants of the genes SLC52A2 and SLC52A3 which code for transporter proteins RDVT2 and RDVT3, respectively, are defective. Infants and young children present with muscle weakness, cranial nerve deficits including hearing loss, sensory symptoms including sensory ataxia, feeding difficulties, and respiratory distress caused by a sensorimotor axonal neuropathy and cranial nerve pathology. When untreated, infants with riboflavin transporter deficiency have labored breathing and are at risk of dying in the first decade of life. Treatment with oral supplementation of high amounts of riboflavin is lifesaving.Other inborn errors of metabolism include riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency, also known as a subset of glutaric acidemia type 2, and the C677T variant of the methylenetetrahydrofolate reductase enzyme, which in adults has been associated with risk of high blood pressure. Diagnosis and assessment The assessment of riboflavin status is essential for confirming cases with non-specific symptoms whenever deficiency is suspected. Total riboflavin excretion in healthy adults with normal riboflavin intake is about 120 micrograms per day, while excretion of less than 40 micrograms per day indicates deficiency. Riboflavin excretion rates decrease as a person ages, but increase during periods of chronic stress and the use of some prescription drugs.Indicators used in humans are erythrocyte glutathione reductase (EGR), erythrocyte flavin concentration and urinary excretion. The erythrocyte glutathione reductase activity coefficient (EGRAC) provides a measure of tissue saturation and long-term riboflavin status. Results are expressed as an activity coefficient ratio, determined by enzyme activity with and without the addition of FAD to the culture medium. An EGRAC of 1.0 to 1.2 indicates that adequate amounts of riboflavin are present; 1.2 to 1.4 is considered low, greater than 1.4 indicates deficient. For the less sensitive "erythrocyte flavin method", values greater than 400 nmol/L are considered adequate and values below 270 nmol/L are considered deficient. Urinary excretion is expressed as nmol of riboflavin per gram of creatinine. Low is defined as in the range of 50 to 72 nmol/g. Deficient is below 50 nmol/g. Urinary excretion load tests have been used to determine dietary requirements. For adult men, as oral doses were increased from 0.5 mg to 1.1 mg, there was a modest linear increase in urinary riboflavin, reaching 100 micrograms for a subsequent 24-hour urine collection. Beyond a load dose of 1.1 mg, urinary excretion increased rapidly, so that with a dose of 2.5 mg, urinary output was 800 micrograms for a 24-hour urine collection. History The name "riboflavin" comes from "ribose" (the sugar whose reduced form, ribitol, forms part of its structure) and "flavin", the ring-moiety which imparts the yellow color to the oxidized molecule (from Latin flavus, "yellow"). The reduced form, which occurs in metabolism along with the oxidized form, appears as orange-yellow needles or crystals. The earliest reported identification, predating any concept of vitamins as essential nutrients, was by Alexander Wynter Blyth. In 1897, Blyth isolated a water-soluble component of cows milk whey, which he named "lactochrome", that fluoresced yellow-green when exposed to light.In the early 1900s, several research laboratories were investigating constituents of foods, essential to maintain growth in rats. These constituents were initially divided into fat-soluble "vitamine" A and water-soluble "vitamine" B. (The "e" was dropped in 1920.) Vitamin B was further thought to have two components, a heat-labile substance called B1 and a heat-stable substance called B2. Vitamin B2 was tentatively identified to be the factor necessary for preventing pellagra, but that was later confirmed to be due to niacin (vitamin B3) deficiency. The confusion was due to the fact that riboflavin (B2) deficiency causes stomatitis symptoms similar to those seen in pellagra, but without the widespread peripheral skin lesions. For this reason, early in the history of identifying riboflavin deficiency in humans the condition was sometimes called "pellagra sine pellagra" (pellagra without pellagra).In 1935, Paul Gyorgy, in collaboration with chemist Richard Kuhn and physician T. Wagner-Jauregg, reported that rats kept on a B2-free diet were unable to gain weight. Isolation of B2 from yeast revealed the presence of a bright yellow-green fluorescent product that restored normal growth when fed to rats. The growth restored was directly proportional to the intensity of the fluorescence. This observation enabled the researchers to develop a rapid chemical bioassay in 1933, and then isolate the factor from egg white, calling it ovoflavin. The same group then isolated the a similar preparation from whey and called it lactoflavin. In 1934, Kuhns group identified the chemical structure of these flavins as identical, settled on "riboflavin" as a name, and were also able to synthesize the vitamin.Circa 1937, riboflavin was also referred to as "Vitamin G". In 1938, Richard Kuhn was awarded the Nobel Prize in Chemistry for his work on vitamins, which had included B2 and B6. In 1939, it was confirmed that riboflavin is essential for human health through a clinical trial conducted by William H. Sebrell and Roy E. Butler. Women fed a diet low in riboflavin developed stomatitis and other signs of deficiency, which were reversed when treated with synthetic riboflavin. The symptoms returned when the supplements were stopped. == References ==

Hey Aarogya, explain a scenario commonly referred as Rickets

Rickets

Rickets is a condition that results in weak or soft bones in children, and is caused by either dietary deficiency or genetic causes. Symptoms include bowed legs, stunted growth, bone pain, large forehead, and trouble sleeping. Complications may include bone deformities, bone pseudofractures and fractures, muscle spasms, or an abnormally curved spine.The most common cause of rickets is a vitamin D deficiency, although hereditary genetic forms also exist. This can result from eating a diet without enough vitamin D, dark skin, too little sun exposure, exclusive breastfeeding without vitamin D supplementation, celiac disease, and certain genetic conditions. Other factors may include not enough calcium or phosphorus. The underlying mechanism involves insufficient calcification of the growth plate. Diagnosis is generally based on blood tests finding a low calcium, low phosphorus, and a high alkaline phosphatase together with X-rays.Prevention for exclusively breastfed babies is vitamin D supplements. Otherwise, treatment depends on the underlying cause. If due to a lack of vitamin D, treatment is usually with vitamin D and calcium. This generally results in improvements within a few weeks. Bone deformities may also improve over time. Occasionally surgery may be performed to correct bone deformities. Genetic forms of the disease typically require specialized treatment.Rickets occurs relatively commonly in the Middle East, Africa, and Asia. It is generally uncommon in the United States and Europe, except among certain minority groups. It begins in childhood, typically between the ages of 3 and 18 months old. Rates of disease are equal in males and females. Cases of what is believed to have been rickets have been described since the 1st century, and the condition was widespread in the Roman Empire. The disease was common into the 20th century. Early treatments included the use of cod liver oil. Signs and symptoms Signs and symptoms of dietary deficiency rickets can include bone tenderness, and a susceptibility for bone fractures, particularly greenstick fractures. Early skeletal deformities can arise in infants such as soft, thinned skull bones – a condition known as craniotabes, which is the first sign of rickets; skull bossing may be present and a delayed closure of the fontanelles. Young children may have bowed legs and thickened ankles and wrists; older children may have knock knees. Spinal curvatures of kyphoscoliosis or lumbar lordosis may be present. The pelvic bones may be deformed. A condition known as rachitic rosary can result as the thickening caused by nodules forming on the costochondral joints. This appears as a visible bump in the middle of each rib in a line on each side of the body. This somewhat resembles a rosary, giving rise to its name. The deformity of a pigeon chest may result in the presence of Harrisons groove. Hypocalcemia, a low level of calcium in the blood can result in tetany – uncontrolled muscle spasms. Dental problems can also arise.An X-ray or radiograph of an advanced patient with rickets tends to present in a classic way: the bowed legs (outward curve of long bone of the legs) and a deformed chest. Changes in the skull also occur causing a distinctive "square headed" appearance known as "caput quadratum". These deformities persist into adult life if not treated. Long-term consequences include permanent curvatures or disfiguration of the long bones, and a curved back. Cause Maternal deficiencies may be the cause of overt bone disease from before birth and impairment of bone quality after birth. The primary cause of congenital rickets is vitamin D deficiency in the mothers blood, which the baby shares. Vitamin D ensures that serum phosphate and calcium levels are sufficient to facilitate the mineralization of bone. Congenital rickets may also be caused by other maternal diseases, including severe osteomalacia, untreated celiac disease, malabsorption, pre-eclampsia, and premature birth. Rickets in children is similar to osteoporosis in the elderly, with brittle bones. Pre-natal care includes checking vitamin levels and ensuring that any deficiencies are supplemented.Exclusively breast-fed infants may require rickets prevention by vitamin D supplementation or an increased exposure to sunlight.In sunny countries such as Nigeria, South Africa, and Bangladesh, there is sufficient endogenous vitamin D due to exposure to the sun. However, the disease occurs among older toddlers and children in these countries, which in these circumstances is attributed to low dietary calcium intakes due to a mainly cereal-based diet.Those at higher risk for developing rickets include: Breast-fed infants whose mothers are not exposed to sunlight Breast-fed infants who are not exposed to sunlight Breast-fed babies who are exposed to little sunlight Adolescents, in particular when undergoing the pubertal growth spurt Any child whose diet does not contain enough vitamin D or calciumDiseases causing soft bones in infants, like hypophosphatasia or hypophosphatemia, can also lead to rickets.Strontium is allied with calcium uptake into bones; at excessive dietary levels strontium has a rachitogenic (rickets-producing) action. Sunlight Sunlight, especially ultraviolet light, lets human skin cells convert vitamin D from an inactive to active state. In the absence of vitamin D, dietary calcium is not properly absorbed, resulting in hypocalcaemia, leading to skeletal and dental deformities and neuromuscular symptoms, e.g. hyperexcitability. Foods that contain vitamin D include butter, eggs, fish liver oils, margarine, fortified milk and juice, portabella and shiitake mushrooms, and oily fishes such as tuna, herring, and salmon. A rare X-linked dominant form exists called vitamin D-resistant rickets or X-linked hypophosphatemia.Cases have been reported in Britain in recent years of rickets in children of many social backgrounds caused by insufficient production in the body of vitamin D because the suns ultraviolet light was not reaching the skin due to use of strong sunblock, too much "covering up" in sunlight, or not getting out into the sun. Other cases have been reported among the children of some ethnic groups in which mothers avoid exposure to the sun for religious or cultural reasons, leading to a maternal shortage of vitamin D, and people with darker skin need more sunlight to maintain vitamin D levels. Rickets had historically been a problem in London, especially during the Industrial Revolution. Persistent thick fog and heavy industrial smog permeating the city blocked out significant amounts of sunlight to such an extent that up to 80 percent of children at one time had varying degrees of rickets in one form or the other. It is sometimes known "the English Disease" in some foreign languages (e.g. German: Die englische Krankheit, Dutch: Engelse ziekte, Hungarian: angolkór). Skin color theory Rickets is often a result of vitamin D3 deficiency. The correlation between human skin color and latitude is thought to be the result of positive selection to varying levels of solar ultraviolet radiation. Northern latitudes have selection for lighter skin that allows UV rays to produce vitamin D from 7-dehydrocholesterol. Conversely, latitudes near the equator have selection for darker skin that can block the majority of UV radiation to protect from toxic levels of vitamin D, as well as skin cancer.An anecdote often cited to support this hypothesis is that Arctic populations whose skin is relatively darker for their latitude, such as the Inuit, have a diet that is historically rich in vitamin D. Since these people acquire vitamin D through their diet, there is not a positive selective force to synthesize vitamin D from sunlight.Environment mismatch: vitamin D deficiency arises from a mismatch between an individuals previous and current environment. This risk of mismatch increases with advances in transportation methods and increases in urban population size at high latitudes.Similar to the environmental mismatch when dark-skinned people live at high latitudes, Rickets can also occur in religious communities that require long garments with hoods and veils. These hoods and veils act as sunlight barriers that prevent individuals from synthesizing vitamin D naturally from the sun.In a study by Mithal et al., vitamin D insufficiency of various countries was measured by lower 25-hydroxyvitamin D. 25(OH) D is an indicator of vitamin D insufficiency that can be easily measured. These percentages should be regarded as relative vitamin D levels, and not as predicting evidence for development of rickets. Asian immigrants living in Europe have an increased risk for vitamin D deficiency. Vitamin D insufficiency was found in 40% of non-Western immigrants in the Netherlands, and in more than 80% of Turkish and Moroccan immigrants. The Middle East, despite high rates of sun-exposure, has the highest rates of rickets worldwide. This can be explained by limited sun exposure due to cultural practices and lack of vitamin D supplementation for breast-feeding women. Up to 70% and 80% of adolescent girls in Iran and Saudi Arabia, respectively, have vitamin D insufficiency. Socioeconomic factors that limit a vitamin D rich diet also plays a role. In the United States, vitamin D insufficiency varies dramatically by ethnicity. Among females aged 70 years and older, the prevalence of low serum 25(OH) D levels was 28.5% for non-Hispanic whites, 55% for Mexican Americans, and 68% for non-Hispanic blacks. Among males, the prevalence was 23%, 45%, and 58%, respectively.A systematic review published in the Cochrane Library looked at children up to three years old in Turkey and China and found there was a beneficial association between vitamin D and rickets. In Turkey children getting vitamin D had only a 4% chance of developing rickets compared to children who received no medical intervention. In China, a combination of vitamin D, calcium and nutritional counseling was linked to a decreased risk of rickets.Parents can supplement their nutritional intake with vitamin D enhanced beverages if they feel their child is at risk for vitamin D deficiency.A recent review links rickets disease to exclusive consumption of Neocate baby formula. Diagnosis Rickets may be diagnosed with the help of: Blood tests:Serum calcium may show low levels of calcium, serum phosphorus may be low, and serum alkaline phosphatase may be high from bones or changes in the shape or structure of the bones. This can show enlarged limbs and joints. A bone density scan may be undertaken. Radiography typically show widening of the zones of provisional calcification of the metaphyses secondary to unmineralized osteoid. Cupping, fraying, and splaying of metaphyses typically appears with growth and continued weight bearing. These changes are seen predominantly at sites of rapid growth, including the proximal humerus, distal radius, distal femur and both the proximal and the distal tibia. Therefore, a skeletal survey for rickets can be accomplished with anteroposterior radiographs of the knees, wrists, and ankles. Types Vitamin D-related ricketsVitamin D deficiency Vitamin D-dependent rickets (VDDR)Type 1: insufficiency in activation VDDR1A: 25-Hydroxyvitamin D3 1-alpha-hydroxylase deficiency VDDR1B: CYP2R1 deficiency Type 2: resistance to calcitriol VDDR2A: calcitriol receptor mutation VDDR2B: unknown nuclear ribonucleoprotein interfering with signal transduction Type 3: excessive inactivation (CYP3A4 mutation, dominant) Hypocalcemia-related rickets Hypocalcemia Chronic kidney failure (CKD-BMD) Hypophosphatemia-related rickets Congenital Vitamin D-resistant rickets Autosomal dominant hypophosphatemic rickets (ADHR) Autosomal recessive hypophosphatemic rickets (ARHR) Hypophosphatemia (typically secondary to malabsorption) Fanconis syndrome Secondary to other diseases Tumor-induced osteomalacia McCune-Albright syndrome Epidermal nevus syndrome Dents disease Differential diagnosis Osteochondrodysplasias, also known as genetic bone diseases, may mimic the clinical picture of rickets in regard to the features of bone deformities. The radiologic picture and the laboratory findings of serum calcium, phosphate and alkaline phosphatase are important differentiating factors. Blounts disease is an important differential diagnosis because it causes knee deformities in a similar fashion to rickets namely bow legs or genu varum. Infants with rickets can have bone fractures. This sometimes leads to child abuse allegations. This issue appears to be more common for solely nursing infants of black mothers, in winter in temperate climates, suffering poor nutrition and no vitamin D supplementation. People with darker skin produce less vitamin D than those with lighter skin, for the same amount of sunlight. Treatment Diet and sunlight Treatment involves increasing dietary intake of calcium, phosphates and vitamin D. Exposure to ultraviolet B light (most easily obtained when the sun is highest in the sky), cod liver oil, halibut-liver oil, and viosterol are all sources of vitamin D.A sufficient amount of ultraviolet B light in sunlight each day and adequate supplies of calcium and phosphorus in the diet can prevent rickets. Darker-skinned people need to be exposed longer to the ultraviolet rays. The replacement of vitamin D has been proven to correct rickets using these methods of ultraviolet light therapy and medicine.Recommendations are for 400 international units (IU) of vitamin D a day for infants and children. Children who do not get adequate amounts of vitamin D are at increased risk of rickets. Vitamin D is essential for allowing the body to uptake calcium for use in proper bone calcification and maintenance. Supplementation Sufficient vitamin D levels can also be achieved through dietary supplementation and/or exposure to sunlight. Vitamin D3 (cholecalciferol) is the preferred form since it is more readily absorbed than vitamin D2. Most dermatologists recommend vitamin D supplementation as an alternative to unprotected ultraviolet exposure due to the increased risk of skin cancer associated with sun exposure. Endogenous production with full body exposure to sunlight is approximately 250 µg (10,000 IU) per day.According to the American Academy of Pediatrics (AAP), all infants, including those who are exclusively breast-fed, may need vitamin D supplementation until they start drinking at least 17 US fluid ounces (500 ml) of vitamin D-fortified milk or formula a day. Surgery Occasionally surgery is needed to correct severe and persistent deformities of the lower limbs, especially around the knees namely genu varum and genu valgum. Surgical correction of rachitic deformities can be achieved through osteotomies or guided growth surgery. Guided growth surgery has almost replaced the use of corrective osteotomies. The functional results of guided growth surgery in children with rickets are satisfactory. While bone osteotomies work through acute/immediate correction of the limb deformity, guided growth works through gradual correction. Epidemiology In developed countries, rickets is a rare disease (incidence of less than 1 in 200,000). Recently, cases of rickets have been reported among children who are not fed enough vitamin D.In 2013/2014 there were fewer than 700 cases in England. In 2019 the number of cases hospitalised was said to be the highest in 50 years.Rickets occurs relatively commonly in the Middle East, Africa, and Asia. History Greek physician Soranus of Ephesus, one of the chief representatives of the Methodic school of medicine who practiced in Alexandria and subsequently in Rome, reported deformation of the bones in infants as early as the first and second centuries AD. Rickets was not defined as a specific medical condition until 1645, when an English physician Daniel Whistler gave the earliest known description of the disease. In 1650 a treatise on rickets was published by Francis Glisson, a physician at Caius College, Cambridge, who said it had first appeared about 30 years previously in the counties of Dorset and Somerset. In 1857, John Snow suggested rickets, then widespread in Britain, was being caused by the adulteration of bakers bread with alum. German pediatrician Kurt Huldschinsky successfully demonstrated in the winter of 1918–1919 how rickets could be treated with ultraviolet lamps. The role of diet in the development of rickets was determined by Edward Mellanby between 1918 and 1920. In 1923, American physician Harry Steenbock demonstrated that irradiation by ultraviolet light increased the vitamin D content of foods and other organic materials. Steenbocks irradiation technique was used for foodstuffs, but most memorably for milk. By 1945, rickets had all but been eliminated in the United States. Etymology The word rickets may be from the Old English word wrickken (to twist), although because this is conjectured, several major dictionaries simply say "origin unknown". The name rickets is plural in form but usually singular in construction. The Greek word rachitis (ῥαχίτης, meaning in or of the spine) was later adopted as the scientific term for rickets, due chiefly to the words similarity in sound. See also Hypervitaminosis D References External links Media related to Rickets at Wikimedia Commons

Aarogya what is Rocky Mountain spotted fever

Rocky Mountain spotted fever

Rocky Mountain spotted fever (RMSF) is a bacterial disease spread by ticks. It typically begins with a fever and headache, which is followed a few days later with the development of a rash. The rash is generally made up of small spots of bleeding and starts on the wrists and ankles. Other symptoms may include muscle pains and vomiting. Long-term complications following recovery may include hearing loss or loss of part of an arm or leg.The disease is caused by Rickettsia rickettsii, a type of bacterium that is primarily spread to humans by American dog ticks, Rocky Mountain wood ticks, and brown dog ticks. Rarely the disease is spread by blood transfusions. Diagnosis in the early stages is difficult. A number of laboratory tests can confirm the diagnosis but treatment should be begun based on symptoms. It is within a group known as spotted fever rickettsiosis, together with Rickettsia parkeri rickettsiosis, Pacific Coast tick fever, and rickettsialpox.Treatment of RMSF is with the antibiotic doxycycline. It works best when started early and is recommended in all age groups, as well as during pregnancy. Antibiotics are not recommended for prevention. Approximately 0.5% of people who are infected die as a result. Before the discovery of tetracycline in the 1940s, more than 10% of those with RMSF died.Fewer than 5,000 cases are reported a year in the United States, most often in June and July. It has been diagnosed throughout the contiguous United States, Western Canada, and parts of Central and South America. Rocky Mountain spotted fever was first identified in the 1800s in the Rocky Mountains. Signs and symptoms Spotted fever can be very difficult to diagnose in its early stages, due to the similarity of symptoms with many different diseases.People infected with R. rickettsii usually notice symptoms following an incubation period of one to two weeks after a tick bite. The early clinical presentation of Rocky Mountain spotted fever is nonspecific and may resemble a variety of other infectious and noninfectious diseases. Initial symptoms: Fever Nausea Emesis (vomiting) Severe headache Muscle pain MalaiseLater signs and symptoms: Maculopapular rash Petechial rash Abdominal pain Joint pain Conjunctivitis ForgetfulnessThe classic triad of findings for this disease are fever, rash, and history of tick bite. However, this combination is often not identified when patients initially present for care. The rash has a centripetal, or "inward" pattern of spread, meaning it begins at the extremities and courses towards the trunk. Rash The rash first appears two to five days after the onset of fever, and it is often quite subtle. Younger patients usually develop the rash earlier than older patients. Most often the rash begins as small, flat, pink, nonitchy spots (macules) on the wrists, forearms, and ankles. These spots turn pale when pressure is applied and eventually become raised on the skin. The characteristic red, spotted (petechial) rash of Rocky Mountain spotted fever is usually not seen until the sixth day or later after onset of symptoms, but this type of rash occurs in only 35 to 60% of patients with Rocky Mountain spotted fever. The rash involves the palms or soles in as many as 80% of people. However, this distribution may not occur until later on in the course of the disease. As many as 15% of patients may never develop a rash. Complications People can develop permanent disabilities including "cognitive deficits, ataxia, hemiparesis, blindness, deafness, or amputation following gangrene". Cause Ticks are the natural hosts of the disease, serving as both reservoirs and vectors of R. rickettsii. Ticks transmit the bacteria primarily by their bites. Less commonly, infections may occur following exposure to crushed tick tissues, fluids, or tick feces. A female tick can transmit R. rickettsii to her eggs in a process called transovarial transmission. Ticks can also become infected with R. rickettsii while feeding on blood from the host in either the larval or nymphal stage. After the tick develops into the next stage, the R. rickettsii may be transmitted to the second host during the feeding process. Furthermore, male ticks may transfer R. rickettsii to female ticks through body fluids or spermatozoa during the mating process. These types of transmission represent how generations or life stages of infected ticks are maintained. Once infected, the tick can carry the pathogen for life.Rickettsiae are transmitted through saliva injected while a tick is feeding. Unlike Lyme disease and other tick-borne pathogens that require a prolonged attachment period to establish infection, a person can become infected with R. rickettsii in a feeding time as short as 2 hours. In general, about 1-3% of the tick population carries R. rickettsii, even in areas where the majority of human cases are reported. Therefore, the risk of exposure to a tick carrying R. rickettsii is low.The disease is spread by the American dog tick (Dermacentor variabilis), Rocky Mountain wood tick (D. andersoni), brown dog tick (Rhipicephalus sanguineus), and Amblyomma sculptum. Not all of these are of equal importance, and most are restricted to certain geographic areas. The two major vectors of R. rickettsii in the United States are the American dog tick and the Rocky Mountain wood tick. American dog ticks are widely distributed east of the Rocky Mountains and they also occur in limited areas along the Pacific Coast. Dogs and medium-sized mammals are the preferred hosts of an adult American dog tick, although it feeds readily on other large mammals, including human beings. This tick is the most commonly identified species responsible for transmitting R. rickettsii to humans. Rocky Mountain wood ticks (D. andersoni) are found in the Rocky Mountain states and in southwestern Canada. The lifecycle of this tick may require up to three years for its completion. The adult ticks feed primarily on large mammals. The larvae and nymphs feed on small rodents.Other tick species have been shown to be naturally infected with R. rickettsii or serve as experimental vectors in the laboratory. These species are likely to play only a minor role in the ecology of R. rickettsii. Pathophysiology Entry into host Rickettsia rickettsii can be transmitted to human hosts through the bite of an infected tick. As with other bacterium transmitted via ticks, the process generally requires a period of attachment of 4 to 6 hours. However, in some cases a Rickettsia rickettsii infection has been contracted by contact with tick tissues or fluids. Then, the bacteria induce their internalization into host cells via a receptor-mediated invasion mechanism.Researchers believe that this mechanism is similar to that of Rickettsia conorii. This species of Rickettsia uses an abundant cell surface protein called OmpB to attach to a host cell membrane protein called Ku70. It has previously been reported that Ku70 migrates to the host cell surface in the presence of "Rickettsia". Then, Ku70 is ubiquitinated by c-Cbl, an E3 ubiquitin ligase. This triggers a cascade of signal transduction events resulting in the recruitment of Arp2/3 complex. CDC42, protein tyrosine kinase, phosphoinositide 3-kinase, and Src-family kinases then activate Arp2/3. This causes the alteration of local host cytoskeletal actin at the entry site as part of a zipper mechanism. Then, the bacteria is phagocytosized by the host cell and enveloped by a phagosome.Studies have suggested that rOmpB is involved in this process of adhesion and invasion. Both rOmpA and rOmpB are members of a family of surface cell antigens (Sca) which are autotransporter proteins; they act as ligands for the Omp proteins and are found throughout the rickettsiae. Exit from host cell The cytosol of the host cell contains nutrients, adenosine triphosphate, amino acids, and nucleotides which are used by the bacteria for growth. For this reason, as well as to avoid phagolysosomal fusion and death, rickettsiae must escape from the phagosome. To escape from the phagosome, the bacteria secrete phospholipase D and hemolysin C. This causes disruption of the phagosomal membrane and allows the bacteria to escape. Following generation time in the cytoplasm of the host cells, the bacteria utilizes actin based motility to move through the cytosol.RickA, expressed on the rickettsial surface, activates Arp2/3 and causes actin polymerization. The rickettsiae use the actin to propel themselves throughout the cytosol to the surface of the host cell. This causes the host cell membrane to protrude outward and invaginate the membrane of an adjacent cell. The bacteria are then taken up by the neighboring cell in a double membrane vacuole that the bacteria can subsequently lyse, enabling spread from cell to cell without exposure to the extracellular environment. Consequences of infection Rickettsia rickettsii initially infect blood vessel endothelial cells, but eventually migrate to vital organs such as the brain, skin, and the heart via the blood stream. Bacterial replication in host cells causes endothelial cell proliferation and inflammation, resulting in mononuclear cell infiltration into blood vessels and subsequent red blood cell leakage into surrounding tissues. The characteristic rash observed in Rocky Mountain spotted fever is the direct result of this localized replication of rickettsia in blood vessel endothelial cells. Diagnosis This disease can be diagnosed by a doctor with and without the use of lab testing. Lab tests are not always relied upon because treatment may be necessary before the results are returned.Abnormal laboratory findings seen in patients with Rocky Mountain spotted fever may include a low platelet count, low blood sodium concentration, or elevated liver enzyme levels. Serology testing and skin biopsy are considered to be the best methods of diagnosis. Although immunofluorescent antibody assays are considered some of the best serology tests available, most antibodies that fight against R. rickettsii are undetectable on serology tests during the first seven days after infection.Differential diagnosis includes dengue, leptospirosis, chikungunya, and Zika fever. Treatment Appropriate antibiotic treatment should be started immediately when there is a suspicion of Rocky Mountain spotted fever. Treatment should not be delayed for laboratory confirmation of disease as early initiation of treatment of Rocky Mountain spotted fever is associated with lower mortality. Failure to respond to a tetracycline argues against a diagnosis of Rocky Mountain spotted fever. Severely ill people may require longer periods before their fever resolves, especially if they have experienced damage to multiple organ systems. Preventive therapy in healthy people who have had recent tick bites is not recommended and may only delay the onset of disease.Doxycycline (a tetracycline) is the drug of choice for patients with Rocky Mountain spotted fever. According to the CDC, "Doctors often avoid prescribing doxycycline to young children because of a warning that tooth staining may occur when used in children less than 8 years old. ..Misperceptions about the use of doxycycline for children prevent kids from getting lifesaving treatment" of rickettsial diseases. "Delay in treatment of rickettsial diseases may lead to severe illness or death. Children are five times more likely than adults to die from RMSF." A 2013 study shows that "short courses of…doxycycline can be used in children without causing tooth staining or weakening of tooth enamel." The CDC observed that "clearer language on the drug label may help avoid hesitation in prescribing life-saving doxycycline to children."Treatment typically consists of 100 milligrams every 12 hours, or for children under 45 kg (99 lb) at 4 mg/kg of body weight per day in two divided doses. Treatment should be continued for at least three days after the fever subsides, and until there is unequivocal evidence of clinical improvement. This will be generally for a minimum time of five to ten days. Severe or complicated outbreaks may require longer treatment courses. Chloramphenicol is an alternative drug that can be used to treat Rocky Mountain spotted fever, specifically in pregnancy. However, this drug may be associated with a wide range of side effects, and careful monitoring of blood levels is required. Prognosis Rocky Mountain spotted fever can be a very severe illness and patients often require hospitalization. Because R. rickettsii infects the cells lining blood vessels throughout the body, severe manifestations of this disease may involve the respiratory system, central nervous system, gastrointestinal system, or kidneys. Long-term health problems following acute Rocky Mountain spotted fever infection include partial paralysis of the lower extremities, gangrene requiring amputation of fingers, toes, or arms or legs, hearing loss, loss of bowel or bladder control, movement disorders, and language disorders. These complications are most frequent in persons recovering from severe, life-threatening disease, often following lengthy hospitalizations. Epidemiology There are between 500 and 2500 cases of Rocky Mountain spotted fever reported in the United States per year, and in only about 20% can the tick be found.Host factors associated with severe or fatal Rocky Mountain spotted fever include advanced age, male sex, African or Caribbean background, long-term excessive alcohol use and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Deficiency of G6PD is a genetic condition affecting about 12 percent of the Afro-American male population. Deficiency in this enzyme is associated with a high proportion of severe cases of Rocky Mountain spotted fever. This is a rare clinical complication that is often fatal within five days of the onset of the disease. In the early 1940s, outbreaks were described in the Mexican states of Sinaloa, Sonora, Durango, and Coahuila driven by dogs and Rhipicephalus sanguineus sensu lato, the brown dog tick. Over the ensuing 100 years case fatality rates were 30%–80%. In 2015, there was an abrupt rise in Sonora cases with 80 fatal cases. From 2003 to 2016, cases increased to 1394 with 247 deaths. History Rocky Mountain spotted fever (or "black measles" because of its characteristic rash) was recognized in the early 1800s, and in the last 10 years of the 1800s (1890–1900) it became very common, especially in the Bitterroot Valley of Montana. The disease was originally noted to be concentrated on the west-side of the Bitterroot river. Though it would be decades before scientists discovered the tick as the carrier of the disease, in as early as 1866, Doctor John B. Buker (establishing a practice in Missoula, MT) noticed a tick embedded in the skin of one of his patients. His notes were later studied as part of later research.In 1901, Dr. A. F. Longeway was appointed to solve "the black measles problem" in Montana. He in turn enlisted his friend, Dr. Earl Strain to help him. Strain suspected that the illness was from ticks. In 1906, Howard T. Ricketts, a pathologist recruited from the University of Chicago, was the first to establish the identity of the infectious organism (the organism smaller than a bacterium and larger than a virus) that causes this disease. He and others characterized the basic epidemiological features of the disease, including the role of tick vectors. Their studies found that Rocky Mountain spotted fever is caused by Rickettsia rickettsii, named in Rickettss honor. Ricketts died of typhus (another rickettsial disease) in Mexico in 1910, shortly after completing his studies on Rocky Mountain spotted fever. Prior to 1922, Doctors McCray and McClintic both died while doing research on Rocky Mountain spotted fever, as did an aide of Noguchi Hideyo at the Rockefeller Institute. Research began in 1922 in western Montana, in the Bitterroot Valley around Hamilton, Montana, after the Governors daughter and his son-in-law died of the fever. However, prior to that, in 1917, Dr. Lumford Fricks introduced herds of sheep into the Bitterroot Valley. His hypothesis was that the sheep would eat the tall grasses where ticks lived and bred. Past Assistant Surgeon R.R. Spencer of the Hygienic Laboratory of the U.S. Public Health Service was ordered to the region, and he led a research team at an abandoned schoolhouse through about 1924. Spencer was assisted by R. R. Parker, Bill Gettinger, Henry Cowan, Henry Greenup, Elmer Greenup, Gene Hughes, Salsbury, Kerlee, and others, of whom Gettinger, Cowan and Kerlee died of Rocky Mountain spotted fever. Through a series of discoveries, the team found that a previous blood meal was necessary to make the tick deadly to its hosts, as well as other facets of the disease. On May 19, 1924, Spencer put a large dose of mashed wood ticks, from lot 2351B, and some weak carbolic acid into his arm by injection. This vaccine worked, and for some years after it was used by people in that region to convert the illness from one with high fatality rate (albeit low incidence) to one that could be either prevented entirely (for many of them) or modified to a non-deadly form (for the rest). Today there is no commercially available vaccine for RMSF because, unlike in the 1920s when Spencer and colleagues developed one, antibiotics are now available to treat the disease, so prevention by vaccination is no longer the sole defense against likely death. Much of the early research was conducted at Rocky Mountain Laboratories a part of the National Institute of Allergy and Infectious Diseases. The schoolhouse laboratory of 1922–1924, filled with ticks in various phases of the life cycle, is identifiable in retrospect as a biohazard, although the team did not fully appreciate it at first. The deaths of Gettinger and Cowan, and the near death of the janitors son, were the results of inadequate biocontainment, but in the 1920s, the elaborate biocontainment systems of today had not been invented. Society Research into this disease in Montana is a sub-plot of the 1937 film Green Light, starring Errol Flynn. Some of the researchers who perished are mentioned by name and their photographs are shown. Rocky Mountain spotted fever is a big part of the 1947 Republic Pictures movie Driftwood, starring Walter Brennan, James Bell, Dean Jagger, Natalie Wood, and Hobart Cavanaugh. In December 2013, hockey player Shane Doan was diagnosed with Rocky Mountain spotted fever, and returned to play in January 2014. Other names Some synonyms for Rocky Mountain spotted fever in other countries include "tick typhus," "Tobia fever" (Colombia), "São Paulo fever" or "febre maculosa" (Brazil), and "fiebre manchada" (Mexico). References External links "Rocky Mountain spotted fever". Centers for Disease Control. 2018-10-26.

Hey Aarogya, explain a scenario commonly referred as Rosacea

Rosacea

Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarged nose may occur in severe disease, a condition known as rhinophyma.The cause of rosacea is unknown. Risk factors are believed to include a family history of the condition. Factors that may potentially worsen the condition include heat, exercise, sunlight, cold, spicy food, alcohol, menopause, psychological stress, or steroid cream on the face. Diagnosis is based on symptoms.While not curable, treatment usually improves symptoms. Treatment is typically with metronidazole, doxycycline, minocycline, or tetracycline. When the eyes are affected, azithromycin eye drops may help. Other treatments with tentative benefit include brimonidine cream, ivermectin cream, and isotretinoin. Dermabrasion or laser surgery may also be used. The use of sunscreen is typically recommended.Rosacea affects between 1% and 10% of people. Those affected are most often 30 to 50 years old and female. People with paler skin or European ancestry are more frequently affected. The condition was described in The Canterbury Tales in the 1300s, and possibly as early as the 200s BC by Theocritus. Signs and symptoms Rosacea typically begins with reddening of the skin in symmetrical patches near the center of the face. Common signs can depend on age and sex: flushing and red swollen patches are common in the young, small and visible dilated blood vessels in older individuals, and swelling of the nose is common in men. Other signs include lumps on the skin (papules or pustules) and swelling of the face. Many people experience stinging or burning pain and rarely itching.Skin problems tend to be aggravated by particular trigger factors, that differ for different people. Common triggers are ultraviolet light, heat, cold, or certain foods or beverages. Erythematotelangiectatic rosacea Erythematotelangiectatic rosacea rosacea (also known as "vascular rosacea") is characterized by prominent history of prolonged (over 10 minutes) flushing reaction to various stimuli, such as emotional stress, hot drinks, alcohol, spicy foods, exercise, cold or hot weather, or hot baths and showers. Glandular rosacea In glandular rosacea, men with thick sebaceous skin predominate, a disease in which the papules are edematous, and the pustules are often 0.5 to 1.0 cm in size, with nodulocystic lesions often present. Cause The exact cause of rosacea is unknown. Triggers that cause episodes of flushing and blushing play a part in its development. Exposure to temperature extremes, strenuous exercise, heat from sunlight, severe sunburn, stress, anxiety, cold wind, and moving to a warm or hot environment from a cold one, such as heated shops and offices during the winter, can each cause the face to become flushed. Certain foods and drinks can also trigger flushing, such as alcohol, foods and beverages containing caffeine (especially hot tea and coffee), foods high in histamines, and spicy foods.Medications and topical irritants have also been known to trigger rosacea flares. Some acne and wrinkle treatments reported to cause rosacea include microdermabrasion and chemical peels, as well as high dosages of isotretinoin, benzoyl peroxide, and tretinoin. Steroid-induced rosacea is caused by the use of topical steroids. These steroids are often prescribed for seborrheic dermatitis. Dosage should be slowly decreased and not immediately stopped to avoid a flare-up. Cathelicidins In 2007, Richard Gallo and colleagues noticed that patients with rosacea had high levels of the antimicrobial peptide cathelicidin and elevated levels of stratum corneum tryptic enzymes (SCTEs). Antibiotics have been used in the past to treat rosacea, but they may only work because they inhibit some SCTEs. Demodex folliculitis and Demodex mites Studies of rosacea and Demodex mites have revealed that some people with rosacea have increased numbers of the mite, especially those with steroid-induced rosacea. Demodex folliculitis (demodicidosis, also known as "mange" in animals) is a condition that may have a "rosacea-like" appearance.A 2007, National Rosacea Society-funded study demonstrated that Demodex folliculorum mites may be a cause or exacerbating factor in rosacea. The researchers identified Bacillus oleronius as distinct bacterium associated with Demodex mites. When analyzing blood samples using a peripheral blood mononuclear cell proliferation assay, they discovered that B. oleronius stimulated an immune system response in 79 percent of 22 patients with subtype 2 (papulopustular) rosacea, compared with only 29% of 17 subjects without the disorder. They concluded, "The immune response results in inflammation, as evident in the papules (bumps) and pustules (pimples) of subtype 2 rosacea. This suggests that the B. oleronius bacteria found in the mites could be responsible for the inflammation associated with the condition." Intestinal bacteria Small intestinal bacterial overgrowth (SIBO) was demonstrated to have greater prevalence in rosacea patients and treating it with locally acting antibiotics led to rosacea lesion improvement in two studies. Conversely in rosacea patients who were SIBO negative, antibiotic therapy had no effect. The effectiveness of treating SIBO in rosacea patients may suggest that gut bacteria play a role in the pathogenesis of rosacea lesions. Diagnosis Most people with rosacea have only mild redness and are never formally diagnosed or treated. No test for rosacea is known. In many cases, simple visual inspection by a trained health-care professional is sufficient for diagnosis. In other cases, particularly when pimples or redness on less-common parts of the face is present, a trial of common treatments is useful for confirming a suspected diagnosis. The disorder can be confused or co-exist with acne vulgaris or seborrheic dermatitis. The presence of a rash on the scalp or ears suggests a different or co-existing diagnosis because rosacea is primarily a facial diagnosis, although it may occasionally appear in these other areas. Classification Four rosacea subtypes exist, and a patient may have more than one subtype:: 176  Erythematotelangiectatic rosacea exhibits permanent redness (erythema) with a tendency to flush and blush easily. Also small, widened blood vessels visible near the surface of the skin (telangiectasias) and possibly intense burning, stinging, and itching are common. People with this type often have sensitive skin. Skin can also become very dry and flaky. In addition to the face, signs can also appear on the ears, neck, chest, upper back, and scalp. Papulopustular rosacea presents with some permanent redness with red bumps (papules); some pus-filled pustules can last 1–4 days or longer. This subtype is often confused with acne. Phymatous rosacea is most commonly associated with rhinophyma, an enlargement of the nose. Signs include thickening skin, irregular surface nodularities, and enlargement. Phymatous rosacea can also affect the chin (gnathophyma), forehead (metophyma), cheeks, eyelids (blepharophyma), and ears (otophyma). Telangiectasias may be present. In ocular rosacea, affected eyes and eyelids may appear red due to telangiectasias and inflammation, and may feel dry, irritated, or gritty. Other symptoms include foreign-body sensations, itching, burning, stinging, and sensitivity to light. Eyes can become more susceptible to infection. About half of the people with subtypes 1–3 also have eye symptoms. Blurry vision and vision loss can occur if the cornea is affected. Variants Variants of rosacea include:: 689  Pyoderma faciale, also known as rosacea fulminans, is a conglobate, nodular disease that arises abruptly on the face. Rosacea conglobata is a severe rosacea that can mimic acne conglobata, with hemorrhagic nodular abscesses and indurated plaques. Phymatous rosacea is a cutaneous condition characterized by overgrowth of sebaceous glands. Phyma is Greek for swelling, mass, or bulb, and these can occur on the face and ears.: 693 Treatment The type of rosacea a person has informs the choice of treatment. Mild cases are often not treated at all, or are simply covered up with normal cosmetics. Therapy for the treatment of rosacea is not curative, and is best measured in terms of reduction in the amount of facial redness and inflammatory lesions, a decrease in the number, duration, and intensity of flares, and concomitant symptoms of itching, burning, and tenderness. The two primary modalities of rosacea treatment are topical and oral antibiotic agents. Laser therapy has also been classified as a form of treatment. While medications often produce a temporary remission of redness within a few weeks, the redness typically returns shortly after treatment is suspended. Long-term treatment, usually 1–2 years, may result in permanent control of the condition for some patients. Lifelong treatment is often necessary, although some cases resolve after a while and go into a permanent remission. Other cases, if left untreated, worsen over time. Some people has also reported better results after changing diet. This is not confirmed by medical studies, even though some studies relate the histamine production to outbreak of rosacea. Behavior Avoiding triggers that worsen the condition can help reduce the onset of rosacea, but alone will not normally lead to remission except in mild cases. Keeping a journal is sometimes recommended to help identify and reduce food and beverage triggers. Because sunlight is a common trigger, avoiding excessive exposure to the sun is widely recommended. Some people with rosacea benefit from daily use of a sunscreen; others opt for wearing hats with broad brims. Like sunlight, emotional stress can also trigger rosacea. People who develop infections of the eyelids must practice frequent eyelid hygiene. Managing pretrigger events such as prolonged exposure to cool environments can directly influence warm-room flushing. Medications Medications with good evidence include topical ivermectin and azelaic acid creams and brimonidine, and doxycycline and isotretinoin by mouth. Lesser evidence supports topical metronidazole cream and tetracycline by mouth.Metronidazole is thought to act through anti-inflammatory mechanisms, while azelaic acid is thought to decrease cathelicidin production. Oral antibiotics of the tetracycline class such as doxycycline, minocycline, and oxytetracycline are also commonly used and thought to reduce papulopustular lesions through anti-inflammatory actions rather than through their antibacterial capabilities.Using alpha-hydroxy acid peels may help relieve redness caused by irritation, and reduce papules and pustules associated with rosacea. Oral antibiotics may help to relieve symptoms of ocular rosacea. If papules and pustules persist, then sometimes isotretinoin can be prescribed. The flushing and blushing that typically accompany rosacea are typically treated with the topical application of alpha agonists such as brimonidine and less commonly oxymetazoline or xylometazoline.A review found that ivermectin was more effective than alternatives for treatment of papulopustular acne rosacea. An ivermectin cream has been approved by the FDA, as well as in Europe, for the treatment of inflammatory lesions of rosacea. The treatment is based upon the hypothesis that parasitic mites of the genus Demodex play a role in rosacea. In a clinical study, ivermectin reduced lesions by 83% over 4 months, as compared to 74% under a metronidazole standard therapy. Quassia amara extract at 4% demonstrated to have clinical efficacy for rosacea. When compared to metronidazole 0.75% as usual care in a randomized, double-blinded clinical trial, Quassia amara extract at 4% demonstrated earlier onset of action, including improvement in telangiectasia, flushing, and papules. Quassia amara showed a sustained reduction of global assessment score at day 42 (reduced to 4.68 from baseline 7.65) compared to metronidazole at day 42 (reduced to 6.32 from baseline 7.2), p<0.001. Laser Evidence for the use of laser and intense pulsed-light therapy in rosacea is poor. Outcomes The highly visible nature of rosacea symptoms are often psychologically challenging for those affected. People with rosacea can experience issues with self-esteem, socializing, and changes to their thoughts, feelings, and coping mechanisms. Epidemiology Rosaceae affects around 5% of people worldwide. Incidence varies by ethnicity, and is particularly prevalent in those with Celtic heritage. Men and women are equally like to develop rosacea. See also Seborrheic dermatitis Keratosis pilaris References External links Rosacea at Curlie Rosacea photo library at Dermnet Questions and Answers about Rosacea, from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases

Aarogya, elaborate on Roughness

Roughness

Roughness may refer to: Surface roughness, the roughness of a surface Roughness length, roughness as applied in meteorology International Roughness Index, the roughness of a road Hydraulic roughness, the roughness of land and waterway features Roughness (psychophysics) in psychoacoustics refers to the level of dissonance The roughness of a line or surface, measured numerically by the Hausdorff dimension Roughness/resel, the resel/roughness of an image/volume Unnecessary roughness, a type of foul in gridiron football See also Surface finish

Aarogya, elaborate on Nematode infection

Nematode infection

A nematode infection is a type of helminthiasis caused by organisms in the nematode phylum.An example is enterobiasis. Several antinematodal agents are available. References == External links ==

Hi Aarogya, explain a situation where Salmonellosis occurs

Salmonellosis

Salmonellosis is a symptomatic infection caused by bacteria of the Salmonella type. It is also a food-borne disease and are defined as diseases, usually either infectious or toxic in nature, caused by agents that enter the body through the ingestion of food. In humans, the most common symptoms are diarrhea, fever, abdominal cramps, and vomiting. Symptoms typically occur between 12 hours and 36 hours after exposure, and last from two to seven days. Occasionally more significant disease can result in dehydration. The old, young, and others with a weakened immune system are more likely to develop severe disease. Specific types of Salmonella can result in typhoid fever or paratyphoid fever.There are two species of Salmonella: Salmonella bongori and Salmonella enterica with many subspecies. However, subgroups and serovars within a species may be substantially different in their ability to cause disease. This suggests that epidemiologic classification of organisms at the subspecies level may improve management of Salmonella and similar pathogens.Both vegetarian and non-vegetarian populations are susceptible to Salmonella infections due to the consumption of contaminated meat and milk. Infection is usually spread by eating contaminated meat, eggs, water or milk. Other foods may spread the disease if they have come into contact with manure. A number of pets including cats, dogs, and reptiles can also carry and spread the infection. Diagnosis is by a stool test or blood tests.Efforts to prevent the disease include the proper washing, preparation, and cooking of food to appropriate temperature. Mild disease typically does not require specific treatment. More significant cases may require treatment of electrolyte problems and intravenous fluid replacement. In those at high risk or in whom the disease has spread outside the intestines, antibiotics are recommended.Salmonellosis is one of the most common causes of diarrhea globally. In 2015, 90,300 deaths occurred from nontyphoidal salmonellosis, and 178,000 deaths from typhoidal salmonellosis. In the United States, about 1.35 million cases and 450 deaths occur from non-typhoidal salmonellosis a year. In Europe, it is the second most common foodborne disease after campylobacteriosis. Signs and symptoms Enteritis After a short incubation period of a few hours to one day, the bacteria multiply in the small intestine, causing an intestinal inflammation (enteritis). Most people with salmonellosis develop diarrhea, fever, vomiting, and abdominal cramps 12 to 72 hours after infection. Diarrhea is often watery and non-bloody but may be mucoid and bloody. In most cases, the illness lasts four to seven days, and does not require treatment. In some cases, though, the diarrhea may be so severe that the patient becomes dangerously dehydrated and must be hospitalized. At the hospital, the patient may receive fluids intravenously to treat the dehydration, and may be given medications to provide symptomatic relief, such as fever reduction. In severe cases, the Salmonella infection may spread from the intestines to the blood stream, and then to other body sites, and can cause death, unless the person is treated promptly with antibiotics.In otherwise healthy adults, the symptoms can be mild. Normally, no sepsis occurs, but it can occur exceptionally as a complication in the immunocompromised. However, in people at risk such as infants, small children, and the elderly, Salmonella infections can become very serious, leading to complications. In infants, dehydration can cause a state of severe toxicity. Extraintestinal localizations are possible, especially Salmonella meningitis in children, osteitis, etc. Children with sickle-cell anemia who are infected with Salmonella may develop osteomyelitis. Treatment of osteomyelitis, in this case, will be to use fluoroquinolones (ciprofloxacin, levofloxacin, etc., and nalidixic acid).Those whose only symptom is diarrhea usually completely recover, but their bowel habits may not return to normal for several months. Typhoid fever Typhoid fever occurs when Salmonella bacteria enter the lymphatic system and cause a systemic form of salmonellosis. Endotoxins first act on the vascular and nervous apparatus, resulting in increased permeability and decreased tone of the vessels, upset thermal regulation, vomiting, and diarrhea. In severe forms of the disease, enough liquid and electrolytes are lost to upset the fluid balance, cause an electrolyte imbalance, decrease the circulating blood volume and arterial pressure, and cause hypovolemic shock. Septic shock may also develop. Shock of mixed character (with signs of both hypovolemic and septic shock) are more common in severe salmonellosis. Oliguria and azotemia develop in severe cases as a result of renal involvement due to hypoxia and toxemia. Long-term Salmonellosis is associated with later irritable bowel syndrome and inflammatory bowel disease. Evidence however does not support it being a direct cause of the latter.A small number of people afflicted with salmonellosis experience reactive arthritis, which can last months or years and can lead to chronic arthritis. In sickle-cell anemia, osteomyelitis due to Salmonella infection is much more common than in the general population. Though Salmonella infection is frequently the cause of osteomyelitis in people with sickle-cell, it is not the most common cause, which is Staphylococcus infection.Those infected may become asymptomatic carriers, but this is relatively uncommon, with shedding observed in only 0.2 to 0.6% of cases after a year. Causes Contaminated food, often having no unusual look or smell Poor kitchen hygiene, especially problematic in institutional kitchens and restaurants because this can lead to a significant outbreak Excretions from either sick or infected but apparently clinically healthy people and animals (especially dangerous are caregivers and animals) Polluted surface water and standing water (such as in shower hoses or unused water dispensers) Unhygienically thawed poultry (the meltwater contains many bacteria) An association with reptiles (pet tortoises, snakes, iguanas, and aquatic turtles) is well described. Amphibians such as frogsSalmonella bacteria can survive for some time without a host; they are frequently found in polluted water, with contamination from the excrement of carrier animals being particularly important.The European Food Safety Authority highly recommends that when handling raw turkey meat, consumers and people involved in the food supply chain should pay attention to personal and food hygiene.An estimated 142,000 Americans are infected each year with Salmonella Enteritidis from chicken eggs, and about 30 die. The shell of the egg may be contaminated with Salmonella by feces or environment, or its interior (yolk) may be contaminated by penetration of the bacteria through the porous shell or from a hen whose infected ovaries contaminate the egg during egg formation.Nevertheless, such interior egg yolk contamination is theoretically unlikely. Even under natural conditions, the rate of infection was very small (0.6% in a study of naturally contaminated eggs and 3.0% among artificially and heavily infected hens). Prevention The US Food and Drug Administration (FDA) has published guidelines to help reduce the chance of food-borne salmonellosis. Food must be cooked to 145–165 °F (63–74 °C), and liquids such as soups or gravies should be boiled when reheating. Freezing kills some Salmonella, but it is not sufficient to reliably reduce them below infectious levels. While Salmonella is usually heat-sensitive, it acquires heat-resistance in high-fat environments such as peanut butter. Vaccine Antibodies against nontyphoidal Salmonella were first found in Malawi children in research published in 2008. The Malawian researchers identified an antibody that protects children against bacterial infections of the blood caused by nontyphoidal Salmonella. A study at Queen Elizabeth Hospital in Blantyre found that children up to two years old develop antibodies that aid in killing the bacteria. This could lead to a possible Salmonella vaccine for humans.A 2014 study tested a vaccine on chickens which offered efficient protection against salmonellosis.Vaccination of chickens against Salmonella essentially wiped out the disease in the United Kingdom. A similar approach was considered in the United States, but the Food and Drug Administration decided not to mandate vaccination of hens. Industrial hygiene Since 2011, Denmark has had three cases of human salmonella poisoning. The country eradicated salmonella without vaccines and antibiotics by focusing on eliminating the infection from "breeder stocks", implementing various measures to prevent infection, and taking a zero-tolerance policy towards salmonella in chickens. Treatment Electrolytes may be replenished with oral rehydration supplements (typically containing salts sodium chloride and potassium chloride).Appropriate antibiotics, such as ceftriaxone, may be given to kill the bacteria, but are not necessary in most cases. Azithromycin has been suggested to be better at treating typhoid in resistant populations than both fluoroquinolone drugs and ceftriaxone. There are recommendations on choice of antibiotic to avoid promoting antibiotic resistance.There is no evidence of benefit of treating healthy people with diarrhea due to non-typhoidal salmonellosis. However, the evidence for the very young, very old or people with severe diseases are uncertain. Epidemiology United States Salmonellosis annually causes, per CDC estimation, about 1.2 million illnesses, 23,000 hospitalizations, and 450 deaths in the United States every year. About 142,000 people in the United States are infected each year with Salmonella Enteritidis specifically from chicken eggs, and about 30 die.In 2010, an analysis of death certificates in the United States identified a total of 1,316 Salmonella-related deaths from 1990 to 2006. These were predominantly among older adults and those who were immunocompromised. The U.S. government reported as many as 20% of all chickens were contaminated with Salmonella in the late 1990s, and 16.3% were contaminated in 2005.The United States has struggled to control salmonella infections, with the rate of infection rising from 2001 to 2011. In 1998, the USDA moved to close plants if salmonella was found in excess of 20 percent, which was the industrys average at the time, for three consecutive tests. Texas-based Supreme Beef Processors, Inc. sued on the argument that Salmonella is naturally occurring and ultimately prevailed when a federal appeals court affirmed a lower court. These issues were highlighted in a proposed Kevins Law (formally proposed as the Meat and Poultry Pathogen Reduction and Enforcement Act of 2003), of which components were included the Food Safety Modernization Act passed in 2011, but that law applies only to the FDA and not the USDA. The USDA proposed a regulatory initiative in 2011 to Office of Management and Budget.Salmonella is found in 8% of the chicken parts tested by the USDA and 25% of ground chicken. Europe An outbreak of salmonellosis started in Northern Europe in July 2012, caused by Salmonella thompson. The infections were linked to smoked salmon from the manufacturer Foppen, where the contamination had occurred. Most infections were reported in the Netherlands; over 1060 infections with this subspecies and four fatalities were confirmed.A case of widespread infection was detected mid-2012 in seven EU countries. Over 400 people had been infected with Salmonella enterica serovar Stanley (S. Stanley) that usually appears in the regions of Southeast Asia. After several DNA analyses seemed to point to a specific Belgian strain, the "Joint ECDC/E FSA Rapid Risk Assessment" report detected turkey production as the source of infection.In Germany, food poisoning infections must be reported. Between 1990 and 2005, the number of officially recorded cases decreased from about 200,000 to about 50,000. Elsewhere In March 2007, around 150 people were diagnosed with salmonellosis after eating tainted food at a governors reception in Krasnoyarsk, Russia. Over 1,500 people attended the ball on March 1 and fell ill as a consequence of ingesting Salmonella-tainted sandwiches.About 150 people were sickened by Salmonella-tainted chocolate cake produced by a major bakery chain in Singapore in December 2007.South Africa reported contamination of its poultry carcasses by Salmonella. Egypt showed that Salmonella was predominant in poultry along with other non-typhoid strains. In Indonesia, the isolation of Salmonella Typhi was the main focus, while other serovars were also included from poultry. In India, Salmonella was predominant in poultry. Romania reported Salmonella serovars in poultry that affect humans. History Both salmonellosis and the microorganism genus Salmonella derive their names from a modern Latin coining after Daniel E. Salmon (1850–1914), an American veterinary surgeon. He had help from Theobald Smith, and together they found the bacterium in pigs.Salmonella enterica was possibly the cause of the 1576 cocliztli epidemic in New Spain. Four-inch regulation The "Four-inch regulation" or "Four-inch law" is a colloquial name for a regulation issued by the U.S. FDA in 1975, restricting the sale of turtles with a carapace length less than four inches (10 cm).The regulation was introduced, according to the FDA, "because of the public health impact of turtle-associated salmonellosis". Cases had been reported of young children placing small turtles in their mouths, which led to the size-based restriction. Regulation elsewhere FSSAI regulation The FSSAI has been established under the Food Safety and Standards Act, 2006, which is a consolidating statute related to food safety and regulation in India. FSSAI is responsible for protecting and promoting public health through the regulation and supervision of food safety. The major importance of the FSSAI License is that it ensures that the food is verified chemically and hence is safe to consume. Health before wealth is a common quote as well as fact. Therefore, anything related directly to health is a matter of great sensitivity. See also 1984 Rajneeshee bioterror attack 2012 salmonella outbreak 2018 outbreak of Salmonella List of foodborne illness outbreaks References External links CDC website, Division of Bacterial and Mycotic Diseases, Disease Listing: Salmonellosis

Aarogya, give me a short description about Scabies

Scabies

Scabies (also known as the seven-year itch) is a contagious skin infestation by the mite Sarcoptes scabiei. The most common symptoms are severe itchiness and a pimple-like rash. Occasionally, tiny burrows may appear on the skin. In a first-ever infection, the infected person will usually develop symptoms within two to six weeks. During a second infection, symptoms may begin within 24 hours. These symptoms can be present across most of the body or just certain areas such as the wrists, between fingers, or along the waistline. The head may be affected, but this is typically only in young children. The itch is often worse at night. Scratching may cause skin breakdown and an additional bacterial infection in the skin.Scabies is caused by infection with the female mite Sarcoptes scabiei var. hominis, an ectoparasite. The mites burrow into the skin to live and deposit eggs. The symptoms of scabies are due to an allergic reaction to the mites. Often, only between 10 and 15 mites are involved in an infection. Scabies is most often spread during a relatively long period of direct skin contact with an infected person (at least 10 minutes) such as that which may occur during sex or living together. Spread of the disease may occur even if the person has not developed symptoms yet. Crowded living conditions, such as those found in child-care facilities, group homes, and prisons, increase the risk of spread. Areas with a lack of access to water also have higher rates of disease. Crusted scabies is a more severe form of the disease. It typically only occurs in those with a poor immune system and people may have millions of mites, making them much more contagious. In these cases, spread of infection may occur during brief contact or by contaminated objects. The mite is very small and usually not directly visible. Diagnosis is based on the signs and symptoms.A number of medications are available to treat those infected, such as ivermectin or permethrin, crotamiton, and lindane creams. Sexual contacts within the last month and people who live in the same house should also be treated at the same time. Bedding and clothing used in the last three days should be washed in hot water and dried in a hot dryer. As the mite does not live for more than three days away from human skin, more washing is not needed. Symptoms may continue for two to four weeks following treatment. If after this time symptoms continue, retreatment may be needed.Scabies is one of the three most common skin disorders in children, along with ringworm and bacterial skin infections. As of 2015, it affects about 204 million people (2.8% of the world population). It is equally common in both sexes. The young and the old are more commonly affected. It also occurs more commonly in the developing world and tropical climates. The word scabies is from Latin: scabere, to scratch. Other animals do not spread human scabies. Infection in other animals is typically caused by slightly different but related mites and is known as sarcoptic mange. Signs and symptoms The characteristic symptoms of a scabies infection include intense itching and superficial burrows. Because the host develops the symptoms as a reaction to the mites presence over time, typically a delay of four to six weeks occurs between the onset of infestation and the onset of itching. Similarly, symptoms often persist for one to several weeks after successful eradication of the mites. As noted, those re-exposed to scabies after successful treatment may exhibit symptoms of the new infestation in a much shorter period—as little as one to four days. Itching In the classic scenario, the itch is made worse by warmth, and is usually experienced as being worse at night, possibly because distractions are fewer. As a symptom, it is less common in the elderly. Rash The superficial burrows of scabies usually occur in the area of the finger webs, feet, ventral wrists, elbows, back, buttocks, and external genitals. Except in infants and the immunosuppressed, infection generally does not occur in the skin of the face or scalp. The burrows are created by excavation of the adult mite in the epidermis. Acropustulosis, or blisters and pustules on the palms and soles of the feet, are characteristic symptoms of scabies in infants. In most people, the trails of the burrowing mites are linear or S-shaped tracks in the skin often accompanied by rows of small, pimple-like mosquito or insect bites. These signs are often found in crevices of the body, such as on the webs of fingers and toes, around the genital area, in stomach folds of the skin, and under the breasts.Symptoms typically appear two to six weeks after infestation for individuals never before exposed to scabies. For those having been previously exposed, the symptoms can appear within several days after infestation. However, symptoms may appear after several months or years. Crusted scabies The elderly, disabled, and people with impaired immune systems, such as those with HIV/AIDS, cancer, or those on immunosuppressive medications, are susceptible to crusted scabies (also called Norwegian scabies). On those with weaker immune systems, the host becomes a more fertile breeding ground for the mites, which spread over the hosts body, except the face. The mites in crusted scabies are not more virulent than in noncrusted scabies; however, they are much more numerous (up to two million). People with crusted scabies exhibit scaly rashes, slight itching, and thick crusts of skin that contain large numbers of scabies mites. For this reason, persons with crusted scabies are more contagious to others than those with typical scabies. Such areas make eradication of mites particularly difficult, as the crusts protect the mites from topical miticides/scabicides, necessitating prolonged treatment of these areas. Cause Scabies mite In the 18th century, Italian biologists Giovanni Cosimo Bonomo and Diacinto Cestoni (1637–1718) described the mite now called Sarcoptes scabiei, variety hominis, as the cause of scabies. Sarcoptes is a genus of skin parasites and part of the larger family of mites collectively known as scab mites. These organisms have eight legs as adults, and are placed in the same phylogenetic class (Arachnida) as spiders and ticks.S. scabiei mites are under 0.5 mm in size, but are sometimes visible as pinpoints of white. Gravid females tunnel into the dead, outermost layer (stratum corneum) of a hosts skin and deposit eggs in the shallow burrows. The eggs hatch into larvae in three to ten days. These young mites move about on the skin and molt into a "nymphal" stage, before maturing as adults, which live three to four weeks in the hosts skin. Males roam on top of the skin, occasionally burrowing into the skin. In general, the total number of adult mites infesting a healthy hygienic person with noncrusted scabies is small, about 11 females in burrows, on average.The movement of mites within and on the skin produces an intense itch, which has the characteristics of a delayed cell-mediated inflammatory response to allergens. IgE antibodies are present in the serum and the site of infection, which react to multiple protein allergens in the body of the mite. Some of these cross-react to allergens from house dust mites. Immediate antibody-mediated allergic reactions (wheals) have been elicited in infected persons, but not in healthy persons; immediate hypersensitivity of this type is thought to explain the observed far more rapid allergic skin response to reinfection seen in persons having been previously infected (especially having been infected within the previous year or two). Transmission Scabies is contagious and can be contracted through prolonged physical contact with an infested person. This includes sexual intercourse, although a majority of cases are acquired through other forms of skin-to-skin contact. Less commonly, scabies infestation can happen through the sharing of clothes, towels, and bedding, but this is not a major mode of transmission; individual mites can survive for only two to three days, at most, away from human skin at room temperature. As with lice, a latex condom is ineffective against scabies transmission during intercourse, because mites typically migrate from one individual to the next at sites other than the sex organs.Healthcare workers are at risk of contracting scabies from patients, because they may be in extended contact with them. Pathophysiology The symptoms are caused by an allergic reaction of the hosts body to mite proteins, though exactly which proteins remains a topic of study. The mite proteins are also present from the gut, in mite feces, which are deposited under the skin. The allergic reaction is both of the delayed (cell-mediated) and immediate (antibody-mediated) type, and involves IgE (antibodies are presumed to mediate the very rapid symptoms on reinfection). The allergy-type symptoms (itching) continue for some days, and even several weeks, after all mites are killed. New lesions may appear for a few days after mites are eradicated. Nodular lesions from scabies may continue to be symptomatic for weeks after the mites have been killed.Rates of scabies are negatively related to temperature and positively related to humidity. Diagnosis Scabies may be diagnosed clinically in geographical areas where it is common when diffuse itching presents along with either lesions in two typical spots or itchiness is present in another household member. The classical sign of scabies is the burrow made by a mite within the skin. To detect the burrow, the suspected area is rubbed with ink from a fountain pen or a topical tetracycline solution, which glows under a special light. The skin is then wiped with an alcohol pad. If the person is infected with scabies, the characteristic zigzag or S pattern of the burrow will appear across the skin; however, interpreting this test may be difficult, as the burrows are scarce and may be obscured by scratch marks. A definitive diagnosis is made by finding either the scabies mites or their eggs and fecal pellets. Searches for these signs involve either scraping a suspected area, mounting the sample in potassium hydroxide and examining it under a microscope, or using dermoscopy to examine the skin directly. Differential diagnosis Symptoms of early scabies infestation mirror other skin diseases, including dermatitis, syphilis, erythema multiforme, various urticaria-related syndromes, allergic reactions, ringworm-related diseases, and other ectoparasites such as lice and fleas. Prevention of passing on scabies to other people Mass-treatment programs that use topical permethrin or oral ivermectin have been effective in reducing the prevalence of scabies in a number of populations. No vaccine is available for scabies. The simultaneous treatment of all close contacts is recommended, even if they show no symptoms of infection (asymptomatic), to reduce rates of recurrence. Since mites can survive for only two to three days without a host, other objects in the environment pose little risk of transmission except in the case of crusted scabies. Therefore, cleaning is of little importance. Rooms used by those with crusted scabies require thorough cleaning. Management Treatment A number of medications are effective in treating scabies. Treatment should involve the entire household, and any others who have had recent, prolonged contact with the infested individual. Options to control itchiness include antihistamines and prescription anti-inflammatory agents. Bedding, clothing and towels used during the previous three days should be washed in hot water and dried in a hot dryer.Treatment protocols for crusted scabies are significantly more intense than for common scabies. Permethrin Permethrin, a pyrethroid insecticide, is the most effective treatment for scabies, and remains the treatment of choice. It is applied from the neck down, usually before sleep, and left on for about eight to 14 hours, then washed off in the morning. Care should be taken to coat the entire skin surface, not just symptomatic areas; any patch of skin left untreated can provide a "safe haven" for one or more mites to survive. One application is normally sufficient, as permethrin kills eggs and hatchlings, as well as adult mites, though many physicians recommend a second application three to seven days later as a precaution. Crusted scabies may require multiple applications, or supplemental treatment with oral ivermectin (below). Permethrin may cause slight irritation of the skin that is usually tolerable. Ivermectin Oral ivermectin is effective in eradicating scabies, often in a single dose. It is the treatment of choice for crusted scabies, and is sometimes prescribed in combination with a topical agent. It has not been tested on infants, and is not recommended for children under six years of age.Topical ivermectin preparations have been shown to be effective for scabies in adults, though only one such formulation is available in the United States at present, and it is not FDA-approved as a scabies treatment. It has also been useful for sarcoptic mange (the veterinary analog of human scabies).One review found that the efficacy of permethrin is similar to that of systemic or topical ivermectin. A separate review found that although oral ivermectin is usually effective for treatment of scabies, it does have a higher treatment failure rate than topical permethrin. Another review found that oral ivermectin provided a reasonable balance between efficacy and safety. A study has demonstrated that scabies is markedly reduced in populations taking ivermectin regularly; the drug is widely used for treating scabies and other parasitic diseases particularly among the poor and disadvantaged in the tropics, beginning with the developer Merck providing the drug at no cost to treat onchocerciasis from 1987. Others Other treatments include lindane, benzyl benzoate, crotamiton, malathion, and sulfur preparations. Lindane is effective, but concerns over potential neurotoxicity have limited its availability in many countries. It is banned in California, but may be used in other states as a second-line treatment. Sulfur ointments or benzyl benzoate are often used in the developing world due to their low cost; Some 10% sulfur solutions have been shown to be effective, and sulfur ointments are typically used for at least a week, though many people find the odor of sulfur products unpleasant. Crotamiton has been found to be less effective than permethrin in limited studies. Crotamiton or sulfur preparations are sometimes recommended instead of permethrin for children, due to concerns over dermal absorption of permethrin. Communities Scabies is endemic in many developing countries, where it tends to be particularly problematic in rural and remote areas. In such settings, community-wide control strategies are required to reduce the rate of disease, as treatment of only individuals is ineffective due to the high rate of reinfection. Large-scale mass drug administration strategies may be required where coordinated interventions aim to treat whole communities in one concerted effort. Although such strategies have shown to be able to reduce the burden of scabies in these kinds of communities, debate remains about the best strategy to adopt, including the choice of drug.The resources required to implement such large-scale interventions in a cost-effective and sustainable way are significant. Furthermore, since endemic scabies is largely restricted to poor and remote areas, it is a public health issue that has not attracted much attention from policy makers and international donors. Epidemiology Scabies is one of the three most common skin disorders in children, along with tinea and pyoderma. As of 2010, it affects about 100 million people (1.5% of the population) and its frequency is not related to gender. The mites are distributed around the world and equally infect all ages, races, and socioeconomic classes in different climates. Scabies is more often seen in crowded areas with unhygienic living conditions. Globally as of 2009, an estimated 300 million cases of scabies occur each year, although various parties claim the figure is either over- or underestimated. About 1–10% of the global population is estimated to be infected with scabies, but in certain populations, the infection rate may be as high as 50–80%. History Scabies has been observed in humans since ancient times. Archeological evidence from Egypt and the Middle East suggests scabies was present as early as 494 BC. In the fourth century BC, Aristotle reported on "lice" that "escape from little pimples if they are pricked" – a description consistent with scabies. Arab physician, Ibn Zuhr is believed to have been the first to provide a clinical description of the scabies mites.The Roman encyclopedist and medical writer Aulus Cornelius Celsus (c. 25 BC – 50 AD) is credited with naming the disease "scabies" and describing its characteristic features. The parasitic etiology of scabies was documented by the Italian physician Giovanni Cosimo Bonomo (1663–1696) in his 1687 letter, "Observations concerning the fleshworms of the human body". Bonomos description established scabies as one of the first human diseases with a well-understood cause.In Europe in the late 19th through mid-20th centuries, a sulfur-bearing ointment called by the medical eponym of Wilkinsons ointment was widely used for topical treatment of scabies. The contents and origins of several versions of the ointment were detailed in correspondence published in the British Medical Journal in 1945. Society and culture The International Alliance for the Control of Scabies was started in 2012, and brings together over 150 researchers, clinicians, and public-health experts from more than 15 countries. It has managed to bring the global health implications of scabies to the attention of the World Health Organization. Consequently, the WHO has included scabies on its official list of neglected tropical diseases and other neglected conditions. Scabies in animals Scabies may occur in a number of domestic and wild animals; the mites that cause these infestations are of different subspecies from the one typically causing the human form. These subspecies can infest animals that are not their usual hosts, but such infections do not last long. Scabies-infected animals experience severe itching and secondary skin infections. They often lose weight and become frail.The most frequently diagnosed form of scabies in domestic animals is sarcoptic mange, caused by the subspecies Sarcoptes scabiei canis, most commonly in dogs and cats. Sarcoptic mange is transmissible to humans who come into prolonged contact with infested animals, and is distinguished from human scabies by its distribution on skin surfaces covered by clothing. Scabies-infected domestic fowl develop what is known as "scaly leg". Domestic animals that have gone feral and have no veterinary care are frequently affected by scabies and a host of other ailments. Nondomestic animals have also been observed to develop scabies. Gorillas, for instance, are known to be susceptible to infection by contact with items used by humans.Scabies is also a concern for cattle. Research Moxidectin is being evaluated as a treatment for scabies. It is established in veterinary medicine to treat a range of parasites, including sarcoptic mange. Its advantage over ivermectin is its longer half life in humans and, thus, potential duration of action.Tea tree oil appears to be effective in the laboratory setting. References External links American Academy of Dermatology pamphlet on Scabies Scabies FAQ from the National Pediculosis Association

Aarogya, give me a short description about Schilling test

Schilling test

The Schilling test was a medical investigation used for patients with vitamin B12 (cobalamin) deficiency. The purpose of the test was to determine how well a patient is able to absorb B12 from their intestinal tract. The test is now considered obsolete and is rarely performed, and is no longer available at many medical centers. It is named for Robert F. Schilling. Process The Schilling test has multiple stages. As noted below, it can be done at any time after vitamin B12 supplementation and body store replacement, and some clinicians recommend that in severe deficiency cases, at least several weeks of vitamin repletion be done before the test (more than one B12 shot, and also oral folic acid), in order to ensure that impaired absorption of B12 (with or without intrinsic factor) is not occurring due to damage to the intestinal mucosa from the B12 and folate deficiency themselves. Stage 1: oral vitamin B12 plus intramuscular vitamin B12 (without IF) In the first part of the test, the patient is given radiolabeled vitamin B12 to drink or eat. The most commonly used radiolabels are 57Co and 58Co. An intramuscular injection of unlabeled vitamin B12 is given an hour later. This is not enough to replete or saturate body stores of B12. The purpose of the single injection is to temporarily saturate B12 receptors in the liver with enough normal vitamin B12 to prevent radioactive vitamin B12 binding in body tissues (especially in the liver), so that if absorbed from the G.I. tract, it will pass into the urine. The patients urine is then collected over the next 24 hours to assess the absorption. Normally, the ingested radiolabeled vitamin B12 will be absorbed into the body. Since the body already has liver receptors for transcobalamin/vitamin B12 saturated by the injection, much of the ingested vitamin B12 will be excreted in the urine. A normal result shows at least 10% of the radiolabeled vitamin B12 in the urine over the first 24 hours. In patients with pernicious anemia or with deficiency due to impaired absorption, less than 10% of the radiolabeled vitamin B12 is detected.The normal test will result in a higher amount of the radiolabeled cobalamin in the urine because it would have been absorbed by the intestinal epithelium, but passed into the urine because all hepatic B12 receptors were occupied. An abnormal result is caused by less of the labeled cobalamin to appear in the urine because it will remain in the intestine and be passed into the feces. Stage 2: vitamin B12 and intrinsic factor If an abnormality is found, i.e. the B12 in the urine is only present in low levels, the test is repeated, this time with additional oral intrinsic factor. If this second urine collection is normal, this shows a lack of intrinsic factor production. This is by definition pernicious anemia. A low result on the second test implies abnormal intestinal absorption (malabsorption), which could be caused by coeliac disease, biliary disease, Whipples disease, small bowel bacterial overgrowth syndrome, fish tapeworm infestation (Diphyllobothrium latum), or liver disease. Malabsorption of B12 can be caused by intestinal dysfunction from a low vitamin level in-and-of-itself (see below), causing test result confusion if repletion has not been done for some days previously. Stage 3: vitamin B12 and antibiotics This stage is useful for identifying patients with bacterial overgrowth syndrome. The physician will provide you a course of 2 weeks of antibiotics to eliminate any possible bacterial overgrowth and repeat the test to check whether radio-labeled Vitamin B12 would be found in urine or not. Stage 4: vitamin B12 and pancreatic enzymes This stage, in which pancreatic enzymes are administered, can be useful in identifying patients with pancreatic insufficiency. The physician will give you 3 days of pancreatic enzymes followed by repeating the test to check if radio-labeled Vitamin B12 would be detected in urine. Combined stage 1 and stage 2 In some versions of the Schilling test, B12 can be given both with and without intrinsic factor at the same time, using different cobalt radioisotopes 57Co and 58Co, which have different radiation signatures, in order to differentiate the two forms of B12. This is performed with the Dicopac kitset. This allows for only a single radioactive urine collection. Complications Note that the B12 shot which begins the Schilling test is enough to go a considerable way toward treating B12 deficiency, so the test is also a partial treatment for B12 deficiency. Also, the classic Schilling test can be performed at any time, even after full B12 repletion and correction of the anemia, and it will still show if the cause of the B12 deficiency was intrinsic-factor related. In fact, some clinicians have suggested that folate and B12 replacement for several weeks be normally performed before a Schilling test is done, since folate and B12 deficiencies are both known to interfere with intestinal cell function, and thus cause malabsorption of B12 on their own, even if intrinsic factor is being made. This state would then tend to cause a false-positive test for both simple B12 and intrinsic factor-related B12 malabsorption. Several weeks of vitamin replacement are necessary, before epithelial damage to the G.I. tract from B12 deficiency is corrected. Many labs have stopped performing the Schilling test, due to lack of production of the cobalt radioisotopes and labeled-B12 test substances. Also, injection replacement of B12 has become relatively inexpensive, and can be self-administered by patients, as well as megadose oral B12. Since these are the same treatments which would be administered for most causes of B12 malabsorption even if the exact cause were identified, the diagnostic test may be omitted without damage to the patient (so long as follow-up treatment and occasional serum B12 testing is not allowed to lapse). It is possible for use of other radiopharmaceuticals to interfere with interpretation of the test. Diagnoses References External links MedlinePlus Encyclopedia: 003572

Hello Aarogya, could you help me understand about Schistosomiasis

Schistosomiasis

Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever, is a disease caused by parasitic flatworms called schistosomes. The urinary tract or the intestines may be infected. Symptoms include abdominal pain, diarrhea, bloody stool, or blood in the urine. Those who have been infected for a long time may experience liver damage, kidney failure, infertility, or bladder cancer. In children, it may cause poor growth and learning difficulty.The disease is spread by contact with fresh water contaminated with the parasites. These parasites are released from infected freshwater snails. The disease is especially common among children in developing countries, as they are more likely to play in contaminated water. Other high-risk groups include farmers, fishermen, and people using unclean water during daily living. It belongs to the group of helminth infections. Diagnosis is by finding eggs of the parasite in a persons urine or stool. It can also be confirmed by finding antibodies against the disease in the blood.Methods of preventing the disease include improving access to clean water and reducing the number of snails. In areas where the disease is common, the medication praziquantel may be given once a year to the entire group. This is done to decrease the number of people infected, and consequently, the spread of the disease. Praziquantel is also the treatment recommended by the World Health Organization for those who are known to be infected.Schistosomiasis affected about 236.6 million people worldwide in 2019. An estimated 4,400 to 200,000 people die from it each year. The disease is most commonly found in Africa, Asia, and South America. Around 700 million people, in more than 70 countries, live in areas where the disease is common. In tropical countries, schistosomiasis is second only to malaria among parasitic diseases with the greatest economic impact. Schistosomiasis is listed as a neglected tropical disease. Signs and symptoms Many individuals do not experience symptoms. If symptoms do appear, they usually take 4–6 weeks from the time of infection. The first symptom of the disease may be a general feeling of illness. Within 12 hours of infection, an individual may complain of a tingling sensation or light rash, commonly referred to as "swimmers itch", due to irritation at the point of entrance. The rash that may develop can mimic scabies and other types of rashes. Other symptoms can occur 2–10 weeks later and can include fever, aching, a cough, diarrhea, chills, or gland enlargement. These symptoms can also be related to avian schistosomiasis, which does not cause any further symptoms in humans.The manifestations of schistosomal infection vary over time as the cercariae, and later adult worms and their eggs, migrate through the body. If eggs migrate to the brain or spinal cord, seizures, paralysis, or spinal-cord inflammation are possible. Acute Infection Manifestation of acute infection from schistosoma include cercarial dermatitis (hours to days) and acute schistosomiasis (2–8 weeks). Cercarial dermatitis The first potential reaction is an itchy, maculopapular rash that results from cercariae penetrating the skin within the first 12 hours to days of cercarial skin penetration. The first time a non-sensitized person is exposed, the rashes are usually mild with an associated prickling sensation that quickly disappear on its own since this is a type of hypersensitivity reaction. In sensitized people who have previously been infected, the rash can develop into itchy, red, raised lesions (papules) with some turning into fluid-filled lesions (vesicles). Previous infections with cercariae causes a faster developing and worse presentation of dermatitis due to the stronger immune response. The round bumps are usually one to three centimeters across. Because people living in affected areas have often been repeatedly exposed, acute reactions are more common in tourists and migrants. The rash can occur between the first few hours and a week after exposure, and they normally resolve on their own in around 7–10 days. For human schistosomiasis, A similar type of dermatitis called "swimmers itch" can also be caused by cercariae from animal trematodes that often infect birds. Cercarial dermatitis is not contagious and can not be transmitted from person-to-person.Symptoms may include: Flat, red rash Small red, raised pimples Small red blisters Prickling or tingling sensation, burning, itching of the skinScratching the rash can lead to secondary bacterial infection of the skin, thus it is important to refrain from scratching. Some common treatments for itching include corticosteroid cream, anti-itch lotion, application of cool compresses to rash, bathing in Epsom salts or baking soda, and in severe itching cases, prescription strength cream and lotions. Oral antihistamines can also help relieve the itching. Acute Schistosomiasis (Katayama fever) Acute schistosomiasis (Katayama fever) may occur weeks or months (around 2–8 weeks) after the initial infection as a systemic reaction against migrating schistosomulae as they pass through the bloodstream through the lungs to the liver and also against the antigens of eggs. Similarly to swimmers itch, Katayama fever is more commonly seen in people with their first infection such as migrants and tourists, and it is associated with heavy infection. It is seen, however, in native residents of China infected with S. japonicum. S. japonicum can cause acute schistosomiasis in chronically infected population, and it can lead to a more severe form of acute schistosomiasis.Symptoms may include: Dry cough with changes on chest X-ray Fever Fatigue Muscle aches Headache Malaise Abdominal pain Diarrhea Enlargement of both the liver and the spleen HivesAcute schistosomiasis usually self-resolves in 2–8 weeks in most cases., but a small proportion of people have persistent weight loss, diarrhea, diffuse abdominal pain, and rash.Complications may include: Spinal cord inflammation (transverse myelitis) may occur if worms or eggs travel to the spinal cord during this acute phase of infection.Treatment may include: Corticosteroid such as prednisone is used to alleviate the hypersensitivity reaction and reduce inflammation Praziquantel can be administered to kill the adult schistosomes to prevent chronic infection in addition to corticosteroid therapy. Praziquantel is not effective to recent infection as it only targets the adult worms, but not the premature schistosomulae. Therefore, a repeat treatment of Praziquantel several weeks after initial infection may be warranted. It is recommended to treat with Praziquantel 4–6 weeks after initial exposure since it targets adult worms. Chronic Infection In long-established disease, adult worms lay eggs that can cause inflammatory reactions. The eggs secrete proteolytic enzymes that help them migrate to the bladder and intestines to be shed. The enzymes also cause an eosinophilic inflammatory reaction when eggs get trapped in tissues or embolize to the liver, spleen, lungs, or brain. The long-term manifestations are dependent on the species of schistosome, as the adult worms of different species migrate to different areas. Many infections are mildly symptomatic, with anemia and malnutrition being common in endemic areas. Intestinal schistosomiasis The worms of S. mansoni and S. japonicum migrate to the veins of the gastrointestinal tract and liver. Eggs in the gut wall can lead to pain, blood in the stool, and diarrhea (especially in children). Severe disease can lead to narrowing of the colon or rectum.In intestinal schistosomiasis, eggs become lodged in the intestinal wall during their migration from the mesenteric venules to the intestinal lumen, and the trapped eggs cause an immune system reaction called a granulomatous reaction. They mostly affect the large bowel and rectum, and involvement of the small bowel is more rare. This immune response can lead to obstruction of the colon and blood loss. The infected individual may have what appears to be a potbelly. There is a strong correlation between morbidity of intestinal schistosomiasis and the intensities of infection. In cases of light infections, symptoms may be mild and can go unrecognized. The most common species to cause intestinal schistosomiasis are S. mansoni and S. japonicum, however, S. mekongi and S. intercalatum can also cause this disease.Symptoms may include: Abdominal pain and discomfort Loss of appetite Mucous diarrhea with or without gross blood Blood in feces that is not visibly present (fecal occult blood) Abdominal distentionComplications may include: Intestinal polyps Intestinal ulcers Iron deficient anemia Fistula Bowel strictures (narrowing of colon or rectum) Protein-losing enteropathy Partial or complete bowel obstruction Appendicitis (rare)Approximately 10-50% of people living in endemic regions of S. mansoni and S. japonicum develop intestinal schistosomiasis. S. mansoni infection epidemiologically overlaps with high HIV prevalence in Sub-Saharan Africa, where gastrointestinal schistosomiasis has been linked to increased HIV transmission. Hepatosplenic Schistosomiasis Eggs also migrate to the liver leading to fibrosis in 4 to 8% of people with chronic infection, mainly those with long-term heavy infection.Eggs can become lodged in the liver, leading to portal hypertension, splenomegaly, the buildup of fluid in the abdomen, and potentially life-threatening dilations or swollen areas in the esophagus or gastrointestinal tract that can tear and bleed profusely (esophageal varices). This condition can be separated into two distinct phases: inflammatory hepatic schistosomiasis (early inflammatory reaction) and chronic hepatic schistosomiasis. Most common species to cause this condition are S. mansoni, S. japonicum, and S. mekongi. Inflammatory hepatic schistosomiasis This condition occurs mainly in children and adolescents due to early immune reaction to eggs trapped within the periportal and presinusoidal spaces of the liver creating numerous granulomas. Liver function is not affected, and the severity of liver and spleen enlargement is correlated to the intensity of the infection. It is characterized by an enlarged left lobe of the liver with a sharp edge and enlarged spleen with nodules. The enlargement of liver and spleen is usually mild, but in severe cases, they can enlarge to the level of the belly button and even into the pelvis. Chronic (fibrotic) hepatic schistosomiasis This is a late stage liver disease that occurs mainly in young and middle-aged adults who have been chronically infected with a heavy infection and whose immune regulation of fibrosis is not functioning properly. It affects only a small proportion of people who are infected. Liver function and liver architecture are not affected unlike cirrhosis. The pathogenesis of this disease is caused by deposition of collagen and extracellular matrix proteins within the periportal space, which leads to liver portal fibrosis and enlarged fibrotic portal tracts (Symmers pipe stem fibrosis). The periportal fibrosis physically compress the portal vein leading to portal hypertension (increased portal venous pressure), increased pressure of the splenic vein, and subsequent enlargement of the spleen. Portal hypertension can also increase the pressure in portosystemic anastomoses (vessel connections between the portal circulation and systemic circulation) leading to esophageal varices and caput medusae. These portosystemic anastomoses also allows a pathway for the eggs to travel to locations such as the lungs, spinal cord, or brain. Co-infection with hepatitis is common in regions endemic to schistosomiasis with Hepatitis B or Hepatitis C, and co-infection with Hepatitis C is associated with more rapid liver deterioration and worse outcome. Fibrotic hepatic schistosomiasis caused by S. mansoni usually develops in around 5–15 years, while it can take less time for S. japonicum. Symptoms may include: Esophageal varices (can cause life-threatening esophageal variceal bleed) Ascites (end-stage) Caput medusae Enlarged spleen and liver Complications may include: Neuroschistosomiasis due to portosystemic anastomoses from portal hypertension Pulmonary Schistosomiasis due to portosystemic anastomoses from portal hypertension Pulmonary schistosomiasis Portal hypertension secondary to hepatosplenic schistosomiasis can cause vessel connections between the portal (liver and gut) circulation and systemic circulation to develop, which creates a pathway for the eggs and worms to travel to the lungs. The eggs can be deposited around the alveolar capillary beds and causes granulomatous inflammation of the pulmonary arterioles followed by fibrosis. This leads to high blood pressure in the pulmonary circulation system (pulmonary hypertension), increased pressure in the right heart, enlargement of the pulmonary artery and right atria, and thickening of the right ventricular wall.Symptoms of pulmonary hypertension may include: Shortness of breath Chest pain Feeling tired Fainting during physical exertion Urogenital schistosomiasis The worms of S. haematobium migrate to the veins around the bladder and ureters where they reproduce. S. haematobium can produce up to 3000 eggs per day, these eggs migrate from the veins to the bladder and ureter lumens, but up to 50 percent of them can become trapped in the surrounding tissues causing granulomatous inflammation, polyps formation, and ulceration of bladder, ureter, and genital tract tissues. This can lead to blood in the urine 10 to 12 weeks after infection. Over time, fibrosis can lead to obstruction of the urinary tract, hydronephrosis, and kidney failure. Bladder cancer diagnosis and mortality are generally elevated in affected areas; efforts to control schistosomiasis in Egypt have led to decreases in the bladder cancer rate. The risk of bladder cancer appears to be especially high in male smokers, perhaps due to chronic irritation of the bladder lining allowing it to be exposed to carcinogens from smoking.In women, genitourinary disease can also include genital lesions that may lead to increased rates of HIV transmission. If lesions involve the fallopian tubes or ovaries, it may lead to infertility. If the reproductive organs in male are affected, there could be blood in the sperm.Urinary symptoms may include: Blood in the urine - blood is usually seen at the end of an urine stream (most common symptom) Painful urination Increase frequency of urination Protein in the urine Secondary urinary tract infection Secondary kidney infectionGenital symptoms may include: Inflammation and ulceration of uterine cervix, vagina, or vulva Blood in the sperm Infertility in femaleKidney function is unaffected in many cases, and the lesions are reversible with proper treatment to eliminate the worms. Neuroschistosomiasis Central nervous system lesions occur occasionally due to inflammation and granuloma development around eggs or worms that find their way to the brain or spinal cord through the circulatory system, and they can potentially develop irreversible scarring without proper treatment. Cerebral granulomatous disease may be caused by S. japonicum eggs in the brain during both the acute and chronic phase of the disease. Communities in China affected by S. japonicum have rates of seizures eight times higher than baseline. Cerebral granulomatous infection may also be caused by S. mansoni. In situ egg deposition following the anomalous migration of the adult worm, which appears to be the only mechanism by which Schistosoma can reach the central nervous system in people with schistosomiasis. The destructive action on the nervous tissue and the mass effect produced by a large number of eggs surrounded by multiple, large granulomas in circumscribed areas of the brain characterize the pseudotumoral form of neuroschistosomiasis and are responsible for the appearance of clinical manifestations: headache, hemiparesis, altered mental status, vertigo, visual abnormalities, seizures, and ataxia. Similarly, granulomatous lesions from S. mansoni and S. haematobium eggs in the spinal cord can lead to transverse myelitis (inflammation of the spinal cord) with flaccid paraplegia. In cases with advanced hepatosplenic and urinary schistosomiasis, the continuous embolization of eggs from the portal mesenteric system (S. mansoni) or portal mesenteric-pelvic system (S. haematobium) to the brain, results in a sparse distribution of eggs associated with scant periovular inflammatory reaction, usually with little or no clinical significance.Spinal cord inflammation (transverse myelitis) symptoms may include: Paralysis of the lower extremities Loss of bowel or urinary control Loss of sensation below the level of the lesion Pain below the level of the lesionCerebral granulomatous infection symptoms may include: Seizures Headaches Motor impairment Sensory impairment Cerebellar symptomsUnsteady gait Inability to stand or sit without support Uncoordinated movements Scanning speech Irregular eye movementsCorticosteroids is used to prevent permanent neurological damage from the inflammatory response to the eggs, and sometimes anticonvulsant is needed to stop the seizures. Corticosteroid is given prior to administration of Praziquantel. Transmission and life cycle Infected individuals release Schistosoma eggs into water via their fecal material or urine. After larvae hatch from these eggs, the larvae infect a very specific type of freshwater snail. For example, in S. haematobium and S. intercalatum it is snails of the genus Bulinus, in S. mansoni it is Biomphalaria, and in S. japonicum it is Oncomelania. The Schistosoma larvae undergo the next phase of their lifecycles in these snails, spending their time reproducing and developing. Once this step has been completed, the parasite leaves the snail and enters the water column. The parasite can live in the water for only 48 hours without a mammalian host. Once a host has been found, the worm enters its blood vessels. For several weeks, the worm remains in the vessels, continuing its development into its adult phase. When maturity is reached, mating occurs and eggs are produced. Eggs enter the bladder/intestine and are excreted through urine and feces and the process repeats. If the eggs do not get excreted, they can become engrained in the body tissues and cause a variety of problems such as immune reactions and organ damage. While transmission typically occurs only in countries where the freshwater snails are endemic, a case in Germany was reported where a man got Schistosoma by an infected snail in his aquarium.Humans encounter larvae of the Schistosoma parasite when they enter contaminated water while bathing, playing, swimming, washing, fishing, or walking through the water. Life Cycle The excretion Schistosome eggs in urine or feces depending on species The hatching of the eggs leading to release of the free-swimming, ciliated larvae called miracidia Miracidia find and penetrate the snails, which are the intermediate hosts (specific species of snails is dependent on the species of schistosoma) Within the snails, two successive generations of sporocysts occur Sporocyts gives rise to the infective free-swimming larvae with forked tails called cercariae, and they leave the snails to enter the water Cercariae finds the human hosts and penetrate their skin Upon entrance into the human hosts, cercariae lose their tails and become schistosomulae The schistosomulae travels to the lungs and heart via the venous circulation They migrate to the portal venous system of the liver where they mature into the adult form with two separate sexes The adult male and female are paired together, exits the liver via portal venous system, and travel to the venous systems of the intestines or bladder (species dependent) and produce eggs S. japonicum - superior mesenteric veins (but can also inhabit inferior mesenteric veins) S. mansoni - inferior mesenteric veins (but can also inhabit superior mesenteric veins) S. haematobium - vesicular and pelvic venous plexus of the bladder (occasionally rectal venules) S. intercalatum and S. guineensis - inferior mesenteric plexus (lower portion of the bowels compared to S. mansoni)Schistosomes can live an average of 3–5 years, and the eggs can survive for more than 30 years after infection. Other hosts Schistosomiasis is also a concern of cattle husbandry and mice. O-methyl-threonine is weakly effective in mouse schistosomiasis but is not in use. Pathogenesis The infectious stage starts when the free-swimming larval form of the schistosome, cercariae, penetrates the human skin using their suckers, proteolytic enzymes, and tail movements; the cercariae transformed into schistosomulae by losing its tail and subsequently travels to the heart and lungs through venous system until it eventually reach the liver where it will mature into the adult form. The diseases caused by the schistomes are characterized into acute schistosomiasis and chronic schistosomiasis, and they can vary dependent on the species of schistosome.Acute Infection Minutes to days after initial infection: Cercerial dermatitis (Swimmers itch) - swimmers itch is caused by a localized allergic reaction at the sites of skin penetration by the cercariae causing an inflammatory reaction that is characterized by itchy red pimples and blisters. Few weeks to months after initial infection: Acute Schistosomiasis (Katayamas Fever) - the exact pathophysiology of this disease remains unknown. It has been hypothesized to be caused by a systemic immune response due to immune complex formation (Type III hypersensivity) with the foreign antigens on the migratory schistosomula and the eggs, and the subsequent deposition of these complexes on various tissues leading to activation of an autoimmune response. Acute schistosomiasis caused by S. mansoni and S. haematobium generally affect people who have been infected for the first time such as tourists visiting endemic regions. In contrast, cases of acute schistosomiasis caused by S. japonicum can occur in reinfection to population who reside in endemic regions, and they occur in higher incidences and can have worse prognosis. It was proposed that the large amount of egg antigens released by S. japonicum interact with antibodies leading to the formation of high volume of immune complexes, which cause enlargement of the lymph tissues. This sequence of events can lead to clinical manifestation of fever, enlargement of spleen and liver due to fibrosis, portal hypertension, and death.Chronic Infection The clinical manifestations of chronic infection is mainly caused by immune reaction to the eggs entrapment within tissues resulting in granuloma formation and chronic inflammation. Adult worms live together in pairs (one male and female), sexually reproduce, and lay eggs in the veins around the intestines and bladder depending on the species, and these eggs can rupture the wall of the veins to escape to the surrounding tissues. The eggs make their way through the tissues to the intestinal or bladder lumen with help of proteolytic enzymes, however, a large amount of eggs are unable to finish their journey and remained stuck within the tissues where they can elicit an immune response. The miracidia in these eggs can then release antigens that stimulate an inflammatory immune response. The miracidia within the eggs live for around 6–8 weeks before they die and stop releasing the antigens. The granulomatous response is a cellular immune response mediated by CD4+ T cells, neutrophils, eosinophils, lymphocytes, macrophages, and monocytes, and this chronic inflammatory response elicited by the eggs can cause fibrosis, tissue destruction, and granuloma nodules that disrupt the functions of the organs involved. Th1 helper cell response is prominent releasing cytokines such as IFN-γ during the early phases of infection, and it transitions to Th2 response leading to increase in level of IgE, IL-4, and eosinophils as egg production progresses. In chronic infections, the Th2 response shifts to increasing the level of IL-10, IL-13, and IgG4, which reverses the progression of the granulomas and lead to collagen deposition at the sites of the granulomas. The specific clinical symptoms and severity of the disease this causes depends on the type of schistosome infection, duration of infection, number of eggs, and the organ at which the eggs are deposited. The amount of eggs entrapped in the tissues will continue to increase if the schistosoma are not eliminated. Diagnosis Identification of eggs in stools Diagnosis of infection is confirmed by the identification of eggs in stools. Eggs of S. mansoni are about 140 by 60 µm in size and have a lateral spine. The diagnosis is improved through the use of the Kato-Katz technique, a semiquantitative stool examination technique. Other methods that can be used are enzyme-linked immunosorbent assay, circumoval precipitation test, and alkaline phosphatase immunoassay.Microscopic identification of eggs in stool or urine is the most practical method for diagnosis. Stool examination should be performed when infection with S. mansoni or S. japonicum is suspected, and urine examination should be performed if S. haematobium is suspected. Eggs can be present in the stool in infections with all Schistosoma species. The examination can be performed on a simple smear (1 to 2 mg of fecal material). Because eggs may be passed intermittently or in small numbers, their detection is enhanced by repeated examinations or concentration procedures, or both. In addition, for field surveys and investigational purposes, the egg output can be quantified by using the Kato-Katz technique (20 to 50 mg of fecal material) or the Ritchie technique. Eggs can be found in the urine in infections with S. haematobium (recommended time for collection: between noon and 3 PM) and with S. japonicum. Quantification is possible by using filtration through a nucleopore filter membrane of a standard volume of urine followed by egg counts on the membrane. Tissue biopsy (rectal biopsy for all species and biopsy of the bladder for S. haematobium) may demonstrate eggs when stool or urine examinations are negative.Identification of microhematuria in urine using urine reagent strips is more accurate than circulating antigen tests in the identification of active schistosomiasis in endemic areas. Antibody detection Antibody detection can be useful to indicate schistosome infection in people who have traveled to areas where schistosomiasis is common and in whom eggs cannot be demonstrated in fecal or urine specimens. Test sensitivity and specificity vary widely among the many tests reported for the serologic diagnosis of schistosomiasis and are dependent on both the type of antigen preparations used (crude, purified, adult worm, egg, cercarial) and the test procedure.At the U.S. Centers for Disease Control and Prevention, a combination of tests with purified adult worm antigens is used for antibody detection. All serum specimens are tested by FAST-ELISA using S. mansoni adult microsomal antigen. A positive reaction (greater than 9 units/µl serum) indicates infection with Schistosoma species. Sensitivity for S. mansoni infection is 99%, 95% for S. haematobium infection, and less than 50% for S. japonicum infection. Specificity of this assay for detecting schistosome infection is 99%. Because test sensitivity with the FAST-ELISA is reduced for species other than S. mansoni, immunoblots of the species appropriate to the persons travel history are also tested to ensure detection of S. haematobium and S. japonicum infections. Immunoblots with adult worm microsomal antigens are species-specific, so a positive reaction indicates the infecting species. The presence of antibody is indicative only of schistosome infection at some time and cannot be correlated with clinical status, worm burden, egg production, or prognosis. Where a person has traveled can help determine which Schistosoma species to test for by immunoblot.In 2005, a field evaluation of a novel handheld microscope was undertaken in Uganda for the diagnosis of intestinal schistosomiasis by a team led by Russell Stothard from the Natural History Museum of London, working with the Schistosomiasis Control Initiative, London. Molecular diagnostics Polymerase chain reaction (PCR) based testing is accurate and rapid. However, it is not frequently used in countries where the disease is common due to the cost of the equipment and the technical expertise required to run the tests. Using a microscope to detect eggs costs about US$0.40 per test whereas PCR is about $US 7 per test as of 2019. Loop-mediated isothermal amplification are being studied as they are lower cost. LAMP testing is not commercially available as of 2019. Laboratory testing S. haematobium screening in the community can be done by using urine dip-stick to check for hematuria, and the stool guaiac test can be used to test for blood in the stool for potential S. mansoni and S. japonicum infection. For travelers or migrants in endemic regions, complete blood count with differential can be used to identify a high level of eosinophil in the blood, which could be indicative of an acute infection. Liver function test can be ordered if hepatosplenic schistosomiasis is suspected, and a subsequent hepatitis test panel can be ordered if liver function test is abnormal. Tissue biopsy If other diagnostic methods of schistosomiasis have failed to detect the infection, but there is still a high suspicion for schistosomiasis, tissue biopsy from the rectum, bladder, and liver can be obtained to look for schistosome eggs within the tissue samples. Imaging Imaging modalities such as x-rays, ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) can be utilized to evaluate for severity of schistosomiasis and damages of the infected organs. For example, x-ray and CT scans of the chest can be used to detect lesions in the lungs from pulmonary schistosomiasis, and pelvic x-ray can reveal calcification of the bladder in chronic urinary schistosomiasis. Ultrasound may be used to look for abnormalities in the liver and spleen in hepatosplenic schistosomiasis, and CT scan of the liver is a good tool to look for calcification in the liver associated with S. japonicum infection. CT scan can also be used to assess damages from the schistosomiasis infection in the intestinal, urogenital, and central nervous system. MRI is used to evaluate schistosomiasis of the central nervous system, liver, and genital.PET/CT scan that identifies tissues with higher metabolic activity have been used to help diagnose schistosomiasis in rare cases. This is due to the high level of inflammation caused by the schistosomal eggs, which increases the metabolic rate of the surrounding tissues. Prevention Many countries are working towards eradicating the disease. The World Health Organization is promoting these efforts. In some cases, urbanization, pollution, and the consequent destruction of snail habitat have reduced exposure, with a subsequent decrease in new infections. The elimination of snail populations using molluscicides had been attempted to prevent schistosomiasis in the past, but it was an expensive process that often only reduce but not eliminate the snail population. The drug praziquantel is used for prevention in high-risk populations living in areas where the disease is common. The Centers for Disease Control and Prevention advises avoiding drinking or coming into contact with contaminated water in areas where schistosomiasis is common.A 2014 review found tentative evidence that increasing access to clean water and sanitation reduces schistosome infection.Other important preventive measures include hygiene education leading to behavioral change and sanitary engineering to ensure safe water supply. Preventive chemotherapy For schistosomiasis control, World Health Organization recommends preventive chemotherapy, which is treatment of entire affected population and periodic treatment of all groups at high-risk at acquiring schistosomiasis with use of Praziquantel. In 2019, 44.5% of people with schistosomiasis was treated globally, and 67.2% of school-aged children needed preventive chemotherapy received treatment. Snails, dams, and prawns For many years from the 1950s onwards, vast dams and irrigation schemes were constructed, causing a massive rise in water-borne infections from schistosomiasis. The detailed specifications laid out in various United Nations documents since the 1950s could have minimized this problem. Irrigation schemes can be designed to make it hard for the snails to colonize the water and to reduce the contact with the local population. Even though guidelines on how to design these schemes to minimise the spread of the disease had been published years before, the designers were unaware of them. The dams appear to have reduced the population of the large migratory prawn Macrobrachium, which eats the snails. After the construction of fourteen large dams, greater increases in schistosomiasis occurred in the historical habitats of native prawns than in other areas. Further, at the 1986 Diama Dam on the Senegal River, restoring prawns upstream of the dam reduced both snail density and the human schistosomiasis reinfection rate. Integrated strategy in China In China, the national strategy for schistosomiasis control has shifted three times since it was first initiated: transmission control strategy (from mid-1950s to early 1980s), morbidity control strategy (from mid-1980s to 2003), and the "new integrated strategy" (2004 to present). The morbidity control strategy focused on synchronous chemotherapy for humans and bovines and the new strategy developed in 2004 intervenes in the transmission pathway of schistosomiasis, mainly including replacement of bovines with machines, prohibition of grazing cattle in the grasslands, improving sanitation, installation of fecal-matter containers on boats, praziquantel drug therapy, snail control, and health education. A 2018 review found that the "new integrated strategy" was highly effective to reduce the rate of S. japonicum infection in both humans and the intermediate host snails and reduced the infection risk by 3–4 times relative to the conventional strategy. Treatment Two drugs, praziquantel and oxamniquine, are available for the treatment of schistosomiasis. They are considered equivalent in relation to efficacy against S. mansoni and safety. Because of praziquantels lower cost per treatment, and oxaminiquines lack of efficacy against the urogenital form of the disease caused by S. haematobium, in general praziquantel is considered the first option for treatment. Praziquantel can be safely used in pregnant women and young children. The treatment objective is to cure the disease and to prevent the evolution of the acute to the chronic form of the disease. All cases of suspected schistosomiasis should be treated regardless of presentation because the adult parasite can live in the host for years.Schistosomiasis is treatable by taking by mouth a single dose of the drug praziquantel annually.Praziquantel only eliminates the adult schistosomes, but it is not effective in killing the eggs and immature worms. Live eggs can be excreted by the infected individuals for weeks after treatment with Praziquantel. The immature worms can survive and grow up to be adult schistosomes after Praziquantel therapy. Thus, it is important to have repeated schistosomiasis testing of the stool and/or urine around 4–6 weeks after Praziquantel therapy. Treatment of Praziquantel may be repeated to ensure complete elimination of the parasite.The WHO has developed guidelines for community treatment based on the impact the disease has on children in villages in which it is common: When a village reports more than 50 per cent of children have blood in their urine, everyone in the village receives treatment. When 20 to 50 percent of children have bloody urine, only school-age children are treated. When fewer than 20 percent of children have symptoms, mass treatment is not implemented.Other possible treatments include a combination of praziquantel with metrifonate, artesunate, or mefloquine. A Cochrane review found tentative evidence that when used alone, metrifonate was as effective as praziquantel. Mefloquine, which has previously been used to treat and prevent malaria, was recognised in 2008–2009 to be effective against Schistosoma.Historically, antimony potassium tartrate remained the treatment of choice for schistosomiasis until the development of praziquantel in the 1980s.Post-treatment monitoring Osteopontin (OPN) is a promising tool for monitoring Praziquantel efficacy and post-treatment fibrosis regression as (OPN) expression is modulated by Schistosoma mansoni egg antigens and its levels correlate with severity of schistosomiasis fibrosis and portal hypertension in mice and humans. Praziquantel (PZQ) pharmacotherapy reduces systemic OPN levels and liver collagen content in mice. Epidemiology The disease is found in tropical countries in Africa, the Caribbean, eastern South America, Southeast Asia, and the Middle East. S. mansoni is found in parts of South America and the Caribbean, Africa, and the Middle East; S. haematobium in Africa and the Middle East; and S. japonicum in the Far East. S. mekongi and S. intercalatum are found locally in Southeast Asia and central West Africa, respectively.The disease is endemic in about 75 developing countries and mainly affects people living in rural agricultural and peri-urban areas. Infection estimates In 2010, approximately 238 million people were infected with schistosomiasis, 85 percent of whom live in Africa. An earlier estimate from 2006 had put the figure at 200 million people infected. As of the latest WHO record, 236.6 million people were infected in 2019. In many of the affected areas, schistosomiasis infects a large proportion of children under 14 years of age. An estimated 600 to 700 million people worldwide are at risk from the disease because they live in countries where the organism is common. In 2012, 249 million people were in need of treatment to prevent the disease. This likely makes it the most common parasitic infection with malaria second and causing about 207 million cases in 2013.S. haematobium, the infectious agent responsible for urogenital schistosomiasis, infects over 112 million people annually in Sub-Saharan Africa alone. It is responsible for 32 million cases of dysuria, 10 million cases of hydronephrosis, and 150,000 deaths from kidney failure annually, making S. haematobium the worlds deadliest schistosome. Deaths Estimates regarding the number of deaths vary. Worldwide, the Global Burden of Disease Study issued in 2010 estimated 12,000 direct deaths while the WHO in 2014 estimated more than 200,000 annual deaths related to schistosomiasis. Another 20 million have severe consequences from the disease. It is the most deadly of the neglected tropical diseases. History The most ancient evidence of schistosomiasis dates back to more than 6000 years ago. Studies conducted on human skeletal remains found in northern Syria (5800–4000 BC), demonstrated the evidence of a terminal spined schistosome from the pelvic sediment of skeletal remains. Even if these evidence comes from Syria, it has been suggested that the cradle of schistosomes lies in the region of African great lakes, an area in which both the parasites and their intermediate hosts are in an active state of evolution. Subsequently, it is believed that schistosomiasis have spread to Egypt as a result of the importation of monkeys and slaves during reign of the fifth dynasty of pharaohs (~ 2494–2345 BC).Schistosomiasis is known as bilharzia or bilharziosis in many countries, after German physician Theodor Bilharz, who first described the cause of urinary schistosomiasis in 1851.The first physician who described the entire disease cycle was the Brazilian parasitologist Pirajá da Silva in 1908. The earliest known case of infection was discovered in 2014, belonging to a child who lived 6,200 years ago.It was a common cause of death for Egyptians in the Greco-Roman Period.In 2016 more than 200 million people needed treatment but only 88 million people were actually treated for schistosomiasis. Etymology Schistosomiasis is named for the genus of parasitic flatworm Schistosoma, whose name means split body. The name Bilharzia comes from Theodor Bilharz, a German pathologist working in Egypt in 1851 who first discovered these worms. Society and culture Schistosomiasis is endemic in Egypt, exacerbated by the countrys dam and irrigation projects along the Nile. From the late 1950s through the early 1980s, infected villagers were treated with repeated injections of tartar emetic. Epidemiological evidence suggests that this campaign unintentionally contributed to the spread of hepatitis C via unclean needles. Egypt has the worlds highest hepatitis C infection rate, and the infection rates in various regions of the country closely track the timing and intensity of the anti-schistosomiasis campaign. From ancient times to the early 20th century, schistosomiasis symptom of blood in the urine was seen as a male version of menstruation in Egypt and was thus viewed as a rite of passage for boys.Among human parasitic diseases, schistosomiasis ranks second behind malaria in terms of socio-economic and public health importance in tropical and subtropical areas. Research A proposed vaccine against S. haematobium infection called "Bilhvax" underwent a phase 3 clinical trial among children in Senegal: the results, reported in 2018, showed that it was not effective despite provoking some immune response. Using CRISPR gene editing technology, researchers decreased the symptoms due to schistosomiasis in an animal model. See also Angiostrongyliasis, another disease transmitted by snails References External links Schistosomiasis at Curlie River of Hope — documentary about the rise of schistosomiasis along the Senegal river (video, 47 mins) Schistosomiasis information for travellers from IAMAT (International Association for Medical Assistance to Travellers)

Hello Aarogya, what is Scorpion sting

Scorpion sting

A scorpion sting is an injury caused by the stinger of a scorpion resulting in the medical condition known as scorpionism, which may vary in severity. The anatomical part of the scorpion that delivers the sting is called a "telson". In typical cases, scorpion stings usually result in pain, paresthesia, and variable swelling. In serious cases, scorpion stings may involve the envenomation of humans by toxic scorpions, which may result in extreme pain, serious illness, or even death depending on the toxicity of the venom.Most scorpion stings range in severity from minor swelling to medically significant lesions, with only a few able to cause severe allergic, neurotic or necrotic reactions. However, scorpion stings account for approximately 3,000 deaths a year worldwide. The Brazilian yellow scorpion (Tityus serrulatus) is one species known for being especially dangerous, being responsible for most scorpion sting fatalities in South America.Scorpion stings are seen all over the world but are predominantly seen in the tropical and subtropical areas. In the Western hemisphere, these areas include Mexico, northern South America and southeast Brazil. In the Eastern hemisphere, these regions include Sub-Saharan Africa, the Middle East, and the Indian subcontinent. Characteristics and side effects The byproducts of some arthropods may be used as an aphrodisiac. Some of these arthropods whose byproduct may be used as medicines can be found in North America. Across North America, the Arizona bark scorpion (Centruroides sculpturatus) has proven to be the most venomous scorpion. While stings from this species will rarely result in death, side effects can include numbness, tingling, convulsions, difficult breathing, and occasionally, paralysis. These side effects may last up to 72 hours after injection of the venom. It is also observed that penile erection may occur after being stung. The pain of a sting from the Arizona Bark Scorpion has been compared to being struck by a bolt of lightning or electrical current. These symptoms may become visible 4 to 7 minutes after envenomation. Envenomation of a human by a scorpion may affect the sympathetic or parasympathetic systems depending on the species of scorpion. Some of the more severe side effects include respiratory distress syndrome, pulmonary edema, cardiac dysfunction, impaired hemostasis, pancreatitis, and multiple organ failure. Additionally, treatment of the sting depends on the severity of the incident, which is classified as mild, moderate, or severe. This treatment is composed of three different aspects of the sting: symptomatic measures, vital functions support, and injection antivenom. Not all envenomations result in systemic complications; only a small proportion of stings have this effect on the victim. Mechanism The composition of scorpion venom consists of different compounds of varying concentrations. The compounds consist of neurotoxins, cardiotoxin, nephrotoxin, hemolytic toxic, phosphodiesterases, phospholipase, histamine, serotonin, etc. Of these different toxins, the most important and most potent one is the neurotoxin concentration. This compound has neuromuscular and neuroautonomic effects, as well as damages the surrounding local tissue. Neurotoxins work to change voltage-dependent sodium channels, resulting in prolonged neuronal and neuromuscular activity. This prolonged activity of sodium channels results in an erection. There may be nerve damage due to the stabilization of voltage-dependent sodium channels in the open conformation. This position leads to the prolonged and continuous firing of neurons in the somatic, sympathetic, and parasympathetic nervous systems. Continuous firing of neurons causes over excitation and prevents the transmission of normal nerve impulses down the axon.The venom composition of the deathstalker scorpion contains neurotoxins which are almost completely responsible for this symptom. The poison from this scorpion contain 4 components: chlorotoxin, charybdotoxin, scyllatoxin, and agitoxins. Upon injection with the venom, sacral parasympathetic nerve are stimulated causing a change in the neuronal transmission in vascular and nonvascular smooth muscles. The compound known as the vasoactive intestinal polypeptide (VIP) is the main transmitter. This polypeptide is realized from nerves found long the erectile tissue of the corpus calosum. VIP is the strongest relaxant of penile smooth muscle structure, resulting in an erection upon envenomation. This is the proposed mechanics for all scorpion of the family Buthidae, whose venom composition contains these compounds. Epidemiology Overview Scorpions are nocturnal animals that typically live in deserts, mountains, caves, and under rocks. It is when they are disturbed that they attack. Scorpions that possess the ability to inject toxic venom with their sting belong to the family Buthidae. The Middle East and North Africa are home to the deadliest scorpions, belonging to the genus Buthus, Leiurus, Androctonus, and Hottentotta. In South America, the deadliest scorpion belongs to genus Tityus. In India and Mexico, the deadliest scorpions involved in scorpionism are Mesobuthus and Centruroides, respectively. Weather, seasons, and climate Scorpions are nocturnal arachnids that have shown a seasonal pattern that is also related to climate. Specifically in Central America, scorpion attacks are mostly seen during the hot months of the year, noting that in Argentina this occurs in the months of October to April. Additionally, a rainy climate may also change the frequency of scorpion incidents. Lower levels of rainfall, specifically precipitation below 30 mm/month, can be associated with fewer scorpion stings, whereas rainfall greater than 30 mm/month shows no relationship to incident rate. This could be due to potentially disruptive effects of rainfall on scorpion habitat. Central America In Central America, most scorpion stings are mildly toxic to humans. However, Panama has reported an incidence of 52 cases per 100,000 people in 2007. Between 1998 and 2006, 28 people have died as result of scorpion stings. In Panama, the taxa of scorpions responsible for these deaths belong to the genus Tityus. This scorpion species is also found in parts of northern South America. Historically, the presence of these scorpions in Panama could be due to the closure of the Panamanian isthmus, thus allowing for the migration of the scorpions from Panama into the northern part of South America. Tityus pachyurus is among the most important scorpionist species. Envenomation by this scorpion is characterized by intense local pain, that usually does not result in tissue injury. Scorpions possess venom glands located at the distal extremity of their abdomen. There are currently 1,400 known species of scorpions and each possesses venom glands. However, of these 1,400 species, only 25 are known to be dangerous enough to humans to potentially cause death upon envenomation. Other countries in Central America are habitat to the scorpion genus Centruroides. Species in this genus are only mildly toxic to humans even though they have ion channel-active toxins in their venom. == References ==

Hello Aarogya, what is Scurvy

Scurvy

Scurvy is a disease resulting from a lack of vitamin C (ascorbic acid). Early symptoms of deficiency include weakness, feeling tired and sore arms and legs. Without treatment, decreased red blood cells, gum disease, changes to hair, and bleeding from the skin may occur. As scurvy worsens there can be poor wound healing, personality changes, and finally death from infection or bleeding.It takes at least a month of little to no vitamin C in the diet before symptoms occur. In modern times, scurvy occurs most commonly in people with mental disorders, unusual eating habits, alcoholism, and older people who live alone. Other risk factors include intestinal malabsorption and dialysis. While many animals produce their own vitamin C, humans and a few others do not. Vitamin C is required to make the building blocks for collagen. Diagnosis is typically based on physical signs, X-rays, and improvement after treatment.Treatment is with vitamin C supplements taken by mouth. Improvement often begins in a few days with complete recovery in a few weeks. Sources of vitamin C in the diet include citrus fruit and a number of vegetables, including red peppers, broccoli, and tomatoes. Cooking often decreases the residual amount of vitamin C in foods.Scurvy is rare compared to other nutritional deficiencies. It occurs more often in the developing world in association with malnutrition. Rates among refugees are reported at 5 to 45 percent. Scurvy was described as early as the time of ancient Egypt. It was a limiting factor in long-distance sea travel, often killing large numbers of people. During the Age of Sail, it was assumed that 50 percent of the sailors would die of scurvy on a major trip. A Scottish surgeon in the Royal Navy, James Lind, is generally credited with proving that scurvy can be successfully treated with citrus fruit in 1753. Nevertheless, it was not until 1795 that health reformers such as Gilbert Blane persuaded the Royal Navy to routinely give lemon juice to its sailors. Signs and symptoms Early symptoms are malaise and lethargy. After one to three months, patients develop shortness of breath and bone pain. Myalgias may occur because of reduced carnitine production. Other symptoms include skin changes with roughness, easy bruising and petechiae, gum disease, loosening of teeth, poor wound healing, and emotional changes (which may appear before any physical changes). Dry mouth and dry eyes similar to Sjögrens syndrome may occur. In the late stages, jaundice, generalised edema, oliguria, neuropathy, fever, convulsions, and eventual death are frequently seen. Cause Scurvy, including subclinical scurvy, is caused by a deficiency of dietary vitamin C since humans are unable to metabolically synthesize vitamin C. Provided the diet contains sufficient vitamin C, the lack of working L-gulonolactone oxidase (GULO) enzyme has no significance, and in modern Western societies, scurvy is rarely present in adults, although infants and elderly people are affected. Virtually all commercially available baby formulas contain added vitamin C, preventing infantile scurvy. Human breast milk contains sufficient vitamin C, if the mother has an adequate intake. Commercial milk is pasteurized, a heating process that destroys the natural vitamin C content of the milk.Scurvy is one of the accompanying diseases of malnutrition (other such micronutrient deficiencies are beriberi and pellagra) and thus is still widespread in areas of the world depending on external food aid. Although rare, there are also documented cases of scurvy due to poor dietary choices by people living in industrialized nations. Pathogenesis Vitamins are essential to the production and use of enzymes that are involved in ongoing processes throughout the human body. Ascorbic acid is needed for a variety of biosynthetic pathways, by accelerating hydroxylation and amidation reactions. In the synthesis of collagen, ascorbic acid is required as a cofactor for prolyl hydroxylase and lysyl hydroxylase. These two enzymes are responsible for the hydroxylation of the proline and lysine amino acids in collagen. Hydroxyproline and hydroxylysine are important for stabilizing collagen by cross-linking the propeptides in collagen. Collagen is a primary structural protein in the human body, necessary for healthy blood vessels, muscle, skin, bone, cartilage, and other connective tissues. Defective connective tissue leads to fragile capillaries, resulting in abnormal bleeding, bruising, and internal hemorrhaging. Collagen is an important part of bone, so bone formation is also affected. Teeth loosen, bones break more easily, and once-healed breaks may recur. Defective collagen fibrillogenesis impairs wound healing. Untreated scurvy is invariably fatal. Diagnosis Diagnosis is typically based on physical signs, X-rays, and improvement after treatment. Differential diagnosis Various childhood onset disorders can mimic the clinical and X-ray picture of scurvy such as: Rickets Osteochondrodysplasias especially osteogenesis imperfecta Blounts disease Osteomyelitis Prevention Scurvy can be prevented by a diet that includes uncooked vitamin C-rich foods such as amla, bell peppers (sweet peppers), blackcurrants, broccoli, chili peppers, guava, kiwifruit, and parsley. Other sources rich in vitamin C are fruits such as lemons, limes, oranges, papaya, and strawberries. It is also found in vegetables, such as brussels sprouts, cabbage, potatoes, and spinach. Some fruits and vegetables not high in vitamin C may be pickled in lemon juice, which is high in vitamin C. Nutritional supplements which provide ascorbic acid well in excess of what is required to prevent scurvy may cause adverse health effects.Some animal products, including liver, muktuk (whale skin), oysters, and parts of the central nervous system, including the adrenal medulla, brain, and spinal cord, contain large amounts of vitamin C, and can even be used to treat scurvy. Fresh meat from animals, notable internal organs, contains enough vitamin C to prevent scurvy, and even partly treat it. .Scotts 1902 Antarctic expedition used lightly fried seal meat and liver, whereby complete recovery from incipient scurvy was reported to have taken less than two weeks. Treatment Scurvy will improve with doses of vitamin C as low as 10 mg per day though doses of around 100 mg per day are typically recommended. Most people make a full recovery within 2 weeks. History Symptoms of scurvy have been recorded in Ancient Egypt as early as 1550 BCE. In Ancient Greece, the physician Hippocrates (460-370 BCE) described symptoms of scurvy, specifically a "swelling and obstruction of the spleen." In 406 CE, the Chinese monk Faxian wrote that ginger was carried on Chinese ships to prevent scurvy.The knowledge that consuming foods containing vitamin C is a cure for scurvy has been repeatedly forgotten and rediscovered into the early 20th century. Early modern era In the 13th century, the Crusaders frequently developed scurvy. In the 1497 expedition of Vasco da Gama, the curative effects of citrus fruit were already known and confirmed by Pedro Álvares Cabral and his crew in 1507.The Portuguese planted fruit trees and vegetables in Saint Helena, a stopping point for homebound voyages from Asia, and left their sick, who had scurvy and other ailments, to be taken home by the next ship if they recovered.In 1500, one of the pilots of Cabrals fleet bound for India noted that in Malindi, its king offered the expedition fresh supplies such as lambs, chickens, and ducks, along with lemons and oranges, due to which "some of our ill were cured of scurvy".Unfortunately, these travel accounts did not stop further maritime tragedies caused by scurvy, first because of the lack of communication between travelers and those responsible for their health, and because fruits and vegetables could not be kept for long on ships.In 1536, the French explorer Jacques Cartier, exploring the St. Lawrence River, used the local natives knowledge to save his men who were dying of scurvy. He boiled the needles of the arbor vitae tree (eastern white cedar) to make a tea that was later shown to contain 50 mg of vitamin C per 100 grams. Such treatments were not available aboard ship, where the disease was most common. In February 1601, Captain James Lancaster, while sailing to Sumatra, landed on the northern coast of Madagascar specifically to obtain lemons and oranges for his crew to stop scurvy. Captain Lancaster conducted an experiment using four ships under his command. One ships crew received routine doses of lemon juice while the other three ships did not receive any such treatment. As a result, members of the non-treated ships started to contract scurvy, with many dying as a result.During the Age of Exploration (between 1500 and 1800), it has been estimated that scurvy killed at least two million sailors. Jonathan Lamb wrote: "In 1499, Vasco da Gama lost 116 of his crew of 170; In 1520, Magellan lost 208 out of 230;...all mainly to scurvy."In 1579, the Spanish friar and physician Agustin Farfán published a book in which he recommended oranges and lemons for scurvy, a remedy that was already known in the Spanish Navy.In 1593, Admiral Sir Richard Hawkins advocated drinking orange and lemon juice as a means of preventing scurvy.In 1614, John Woodall, Surgeon General of the East India Company, published The Surgions Mate as a handbook for apprentice surgeons aboard the companys ships. He repeated the experience of mariners that the cure for scurvy was fresh food or, if not available, oranges, lemons, limes, and tamarinds. He was, however, unable to explain the reason why, and his assertion had no impact on the prevailing opinion of the influential physicians of the age, that scurvy was a digestive complaint. Apart from ocean travel, even in Europe, until the late Middle Ages, scurvy was common in late winter, when few green vegetables, fruits and root vegetables were available. This gradually improved with the introduction from the Americas of potatoes; by 1800, scurvy was virtually unheard of in Scotland, where it had previously been endemic.: 11 18th century In 2009, a handwritten household book authored by a Cornishwoman in 1707 was discovered in a house in Hasfield, Gloucestershire, containing a "Recp.t for the Scurvy" amongst other largely medicinal and herbal recipes. The recipe consisted of extracts from various plants mixed with a plentiful supply of orange juice, white wine or beer.In 1734, Leiden-based physician Johann Bachstrom published a book on scurvy in which he stated, "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens; which is alone the primary cause of the disease", and urged the use of fresh fruit and vegetables as a cure.It was not until 1747 that James Lind formally demonstrated that scurvy could be treated by supplementing the diet with citrus fruit, in one of the first controlled clinical experiments reported in the history of medicine. As a naval surgeon on HMS Salisbury, Lind had compared several suggested scurvy cures: hard cider, vitriol, vinegar, seawater, oranges, lemons, and a mixture of balsam of Peru, garlic, myrrh, mustard seed and radish root. In A Treatise on the Scurvy (1753) Lind explained the details of his clinical trial and concluded "the results of all my experiments was, that oranges and lemons were the most effectual remedies for this distemper at sea." However, the experiment and its results occupied only a few paragraphs in a work that was long and complex and had little impact. Lind himself never actively promoted lemon juice as a single cure. He shared medical opinion at the time that scurvy had multiple causes – notably hard work, bad water, and the consumption of salt meat in a damp atmosphere which inhibited healthful perspiration and normal excretion – and therefore required multiple solutions. Lind was also sidetracked by the possibilities of producing a concentrated rob of lemon juice by boiling it. This process destroyed the vitamin C and was therefore unsuccessful.During the 18th century, scurvy killed more British sailors than wartime enemy action. It was mainly by scurvy that George Anson, in his celebrated voyage of 1740–1744, lost nearly two-thirds of his crew (1,300 out of 2,000) within the first 10 months of the voyage. The Royal Navy enlisted 184,899 sailors during the Seven Years War; 133,708 of these were "missing" or died from disease, and scurvy was the leading cause.Although throughout this period sailors and naval surgeons were increasingly convinced that citrus fruits could cure scurvy, the classically trained physicians who determined medical policy dismissed this evidence as merely anecdotal, as it did not conform to their theories of disease. Literature championing the cause of citrus juice, therefore, had no practical impact. The medical theory was based on the assumption that scurvy was a disease of internal putrefaction brought on by faulty digestion caused by the hardships of life at sea and the naval diet. Although this basic idea was given different emphases by successive theorists, the remedies they advocated (and which the navy accepted) amounted to little more than the consumption of fizzy drinks to activate the digestive system, the most extreme of which was the regular consumption of elixir of vitriol – sulphuric acid taken with spirits and barley water, and laced with spices. In 1764, a new and similarly inaccurate theory on scurvy appeared. Advocated by Dr David MacBride and Sir John Pringle, Surgeon General of the Army and later President of the Royal Society, this idea was that scurvy was the result of a lack of fixed air in the tissues which could be prevented by drinking infusions of malt and wort whose fermentation within the body would stimulate digestion and restore the missing gases. These ideas received wide and influential backing, when James Cook set off to circumnavigate the world (1768–1771) in HM Bark Endeavour, malt and wort were top of the list of the remedies he was ordered to investigate. The others were beer, Sauerkraut (a good source of vitamin C) and Linds rob. The list did not include lemons.Cook did not lose a single man to scurvy, and his report came down in favour of malt and wort, although it is now clear that the reason for the health of his crews on this and other voyages was Cooks regime of shipboard cleanliness, enforced by strict discipline, as well as frequent replenishment of fresh food and greenstuffs. Another beneficial rule implemented by Cook was his prohibition of the consumption of salt fat skimmed from the ships copper boiling pans, then a common practice elsewhere in the Navy. In contact with air, the copper formed compounds that prevented the absorption of vitamins by the intestines.The first major long distance expedition that experienced virtually no scurvy was that of the Spanish naval officer Alessandro Malaspina, 1789–1794. Malaspinas medical officer, Pedro González, was convinced that fresh oranges and lemons were essential for preventing scurvy. Only one outbreak occurred, during a 56-day trip across the open sea. Five sailors came down with symptoms, one seriously. After three days at Guam all five were healthy again. Spains large empire and many ports of call made it easier to acquire fresh fruit.Although towards the end of the century MacBrides theories were being challenged, the medical authorities in Britain remained committed to the notion that scurvy was a disease of internal putrefaction and the Sick and Hurt Board, run by administrators, felt obliged to follow its advice. Within the Royal Navy, however, opinion – strengthened by first-hand experience of the use of lemon juice at the siege of Gibraltar and during Admiral Rodneys expedition to the Caribbean – had become increasingly convinced of its efficacy. This was reinforced by the writings of experts like Gilbert Blane and Thomas Trotter and by the reports of up-and-coming naval commanders. With the coming of war in 1793, the need to eliminate scurvy acquired a new urgency. But the first initiative came not from the medical establishment but from the admirals. Ordered to lead an expedition against Mauritius, Rear Admiral Gardner was uninterested in the wort, malt and elixir of vitriol which were still being issued to ships of the Royal Navy, and demanded that he be supplied with lemons, to counteract scurvy on the voyage. Members of the Sick and Hurt Board, recently augmented by two practical naval surgeons, supported the request, and the Admiralty ordered that it be done. There was, however, a last minute change of plan, and the expedition against Mauritius was cancelled. On 2 May 1794, only HMS Suffolk and two sloops under Commodore Peter Rainier sailed for the east with an outward bound convoy, but the warships were fully supplied with lemon juice and the sugar with which it had to be mixed. In March 1795, it was reported that the Suffolk had arrived in India after a four-month voyage without a trace of scurvy and with a crew that was healthier than when it set out. The effect was immediate. Fleet commanders clamoured also to be supplied with lemon juice, and by June the Admiralty acknowledged the groundswell of demand in the navy and agreed to a proposal from the Sick and Hurt Board that lemon juice and sugar should in future be issued as a daily ration to the crews of all warships.It took a few years before the method of distribution to all ships in the fleet had been perfected and the supply of the huge quantities of lemon juice required to be secured, but by 1800, the system was in place and functioning. This led to a remarkable health improvement among the sailors and consequently played a critical role in gaining the advantage in naval battles against enemies who had yet to introduce the measures. Scurvy was not only a disease of seafarers. The only colonists of Australia suffered greatly because of the lack of fresh fruit and vegetables in the winter. There the disease was called Spring fever or Spring disease and described an often fatal condition associated with skin lesions, bleeding gums and lethargy. It was eventually identified as scurvy and the remedies already in use at sea implemented. 19th century The surgeon-in-chief of Napoleons army at the Siege of Alexandria (1801), Baron Dominique-Jean Larrey, wrote in his memoirs that the consumption of horse meat helped the French to curb an epidemic of scurvy. The meat was cooked but was freshly obtained from young horses bought from Arabs, and was nevertheless effective. This helped to start the 19th-century tradition of horse meat consumption in France.Lauchlin Rose patented a method used to preserve citrus juice without alcohol in 1867, creating a concentrated drink known as Roses lime juice. The Merchant Shipping Act of 1867 required all ships of the Royal Navy and Merchant Navy to provide a daily lime ration of one pound to sailors to prevent scurvy. The product became nearly ubiquitous, hence the term "limey", first for British sailors, then for English immigrants within the former British colonies (particularly America, New Zealand and South Africa), and finally, in old American slang, all British people.The plant Cochlearia officinalis, also known as "common scurvygrass", acquired its common name from the observation that it cured scurvy, and it was taken on board ships in dried bundles or distilled extracts. Its very bitter taste was usually disguised with herbs and spices; however, this did not prevent scurvygrass drinks and sandwiches from becoming a popular fad in the UK until the middle of the nineteenth century, when citrus fruits became more readily available.West Indian limes began to supplement lemons, when Spains alliance with France against Britain in the Napoleonic Wars made the supply of Mediterranean lemons problematic, and because they were more easily obtained from Britains Caribbean colonies and were believed to be more effective because they were more acidic. It was the acid, not the (then-unknown) Vitamin C that was believed to cure scurvy. In fact, the West Indian limes were significantly lower in Vitamin C than the previous lemons and further were not served fresh but rather as lime juice, which had been exposed to light and air, and piped through copper tubing, all of which significantly reduced the Vitamin C. Indeed, a 1918 animal experiment using representative samples of the Navy and Merchant Marines lime juice showed that it had virtually no antiscorbutic power at all.The belief that scurvy was fundamentally a nutritional deficiency, best treated by consumption of fresh food, particularly fresh citrus or fresh meat, was not universal in the 19th and early 20th centuries, and thus sailors and explorers continued to have scurvy into the 20th century. For example, the Belgian Antarctic Expedition of 1897–1899 became seriously affected by scurvy when its leader, Adrien de Gerlache, initially discouraged his men from eating penguin and seal meat. In the Royal Navys Arctic expeditions in the 19th century it was widely believed that scurvy was prevented by good hygiene on board ship, regular exercise, and maintaining the morale of the crew, rather than by a diet of fresh food. Navy expeditions continued to be plagued by scurvy even while fresh (not jerked or tinned) meat was well known as a practical antiscorbutic among civilian whalers and explorers in the Arctic. Even cooking fresh meat did not entirely destroy its antiscorbutic properties, especially as many cooking methods failed to bring all the meat to high temperature. The confusion is attributed to a number of factors: while fresh citrus (particularly lemons) cured scurvy, lime juice that had been exposed to light, air and copper tubing did not – thus undermining the theory that citrus cured scurvy; fresh meat (especially organ meat and raw meat, consumed in arctic exploration) also cured scurvy, undermining the theory that fresh vegetable matter was essential to preventing and curing scurvy; increased marine speed via steam shipping, and improved nutrition on land, reduced the incidence of scurvy – and thus the ineffectiveness of copper-piped lime juice compared to fresh lemons was not immediately revealed.In the resulting confusion, a new hypothesis was proposed, following the new germ theory of disease – that scurvy was caused by ptomaine, a waste product of bacteria, particularly in tainted tinned meat. Infantile scurvy emerged in the late 19th century because children were being fed pasteurized cows milk, particularly in the urban upper class. While pasteurization killed bacteria, it also destroyed vitamin C. This was eventually resolved by supplementing with onion juice or cooked potatoes. Native Americans helped save some newcomers from scurvy by directing them to eat wild onions. 20th century By the early 20th century, when Robert Falcon Scott made his first expedition to the Antarctic (1901–1904), the prevailing theory was that scurvy was caused by "ptomaine poisoning", particularly in tinned meat. However, Scott discovered that a diet of fresh meat from Antarctic seals cured scurvy before any fatalities occurred.In 1907, an animal model which would eventually help to isolate and identify the "antiscorbutic factor" was discovered. Axel Holst and Theodor Frølich, two Norwegian physicians studying shipboard beriberi contracted by ships crews in the Norwegian Fishing Fleet, wanted a small test mammal to substitute for the pigeons then used in beriberi research. They fed guinea pigs their test diet of grains and flour, which had earlier produced beriberi in their pigeons, and were surprised when classic scurvy resulted instead. This was a serendipitous choice of animal. Until that time, scurvy had not been observed in any organism apart from humans and had been considered an exclusively human disease. Certain birds, mammals, and fish are susceptible to scurvy, but pigeons are unaffected, since they can synthesize ascorbic acid internally. Holst and Frølich found they could cure scurvy in guinea pigs with the addition of various fresh foods and extracts. This discovery of an animal experimental model for scurvy, which was made even before the essential idea of "vitamins" in foods had been put forward, has been called the single most important piece of vitamin C research.In 1915, New Zealand troops in the Gallipoli Campaign had a lack of vitamin C in their diet which caused many of the soldiers to contract scurvy. It is thought that scurvy is one of many reasons that the Allied attack on Gallipoli failed.Vilhjalmur Stefansson, an arctic explorer who had lived among the Inuit, proved that the all-meat diet they consumed did not lead to vitamin deficiencies. He participated in a study in New Yorks Bellevue Hospital in February 1928, where he and a companion ate only meat for a year while under close medical observation, yet remained in good health.In 1927, Hungarian biochemist Albert Szent-Györgyi isolated a compound he called "hexuronic acid". Szent-Györgyi suspected hexuronic acid, which he had isolated from adrenal glands, to be the antiscorbutic agent, but he could not prove it without an animal-deficiency model. In 1932, the connection between hexuronic acid and scurvy was finally proven by American researcher Charles Glen King of the University of Pittsburgh. Kings laboratory was given some hexuronic acid by Szent-Györgyi and soon established that it was the sought-after anti-scorbutic agent. Because of this, hexuronic acid was subsequently renamed ascorbic acid. 21st century Rates of scurvy in most of the world are low. Those most commonly affected are malnourished people in the developing world and the homeless. There have been outbreaks of the condition in refugee camps. Case reports in the developing world of those with poorly healing wounds have occurred. Human trials Notable human dietary studies of experimentally induced scurvy were conducted on conscientious objectors during World War II in Britain and in the United States on Iowa state prisoner volunteers in the late 1960s. These studies both found that all obvious symptoms of scurvy previously induced by an experimental scorbutic diet with extremely low vitamin C content could be completely reversed by additional vitamin C supplementation of only 10 mg per day. In these experiments, no clinical difference was noted between men given 70 mg vitamin C per day (which produced blood levels of vitamin C of about 0.55 mg/dl, about 1⁄3 of tissue saturation levels), and those given 10 mg per day (which produced lower blood levels). Men in the prison study developed the first signs of scurvy about 4 weeks after starting the vitamin C-free diet, whereas in the British study, six to eight months were required, possibly because the subjects were pre-loaded with a 70 mg/day supplement for six weeks before the scorbutic diet was fed.Men in both studies, on a diet devoid or nearly devoid of vitamin C, had blood levels of vitamin C too low to be accurately measured when they developed signs of scurvy, and in the Iowa study, at this time were estimated (by labeled vitamin C dilution) to have a body pool of less than 300 mg, with daily turnover of only 2.5 mg/day. In other animals Most animals and plants are able to synthesize vitamin C through a sequence of enzyme-driven steps, which convert monosaccharides to vitamin C. However, some mammals have lost the ability to synthesize vitamin C, notably simians and tarsiers. These make up one of two major primate suborders, haplorrhini, and this group includes humans. The strepsirrhini (non-tarsier prosimians) can make their own vitamin C, and these include lemurs, lorises, pottos, and galagos. Ascorbic acid is also not synthesized by at least two species of caviidae, the capybara and the guinea pig. There are known species of birds and fish that do not synthesize their own vitamin C. All species that do not synthesize ascorbate require it in the diet. Deficiency causes scurvy in humans, and somewhat similar symptoms in other animals.Animals that can contract scurvy all lack the L-gulonolactone oxidase (GULO) enzyme, which is required in the last step of vitamin C synthesis. The genomes of these species contain GULO as pseudogenes, which serve as insight into the evolutionary past of the species. Name In babies, scurvy is sometimes referred to as Barlows disease, named after Thomas Barlow, a British physician who described it in 1883. However, Barlows disease may also refer to mitral valve prolapse (Barlows syndrome), first described by John Brereton Barlow in 1966. References Further reading == External links ==

Hello Aarogya, could you help me understand about Seasonal affective disorder

Seasonal affective disorder

Seasonal affective disorder (SAD) is a mood disorder subset, in which people who have normal mental health throughout most of the year exhibit depressive symptoms at the same time each year, most commonly in winter. Common symptoms include sleeping too much, having little to no energy, and overeating. The condition in the summer can include heightened anxiety.In the Diagnostic and Statistical Manual of Mental Disorders DSM-IV and DSM-5, its status was changed. It is no longer classified as a unique mood disorder, but is now a specifier, called "with seasonal pattern", for recurrent major depressive disorder that occurs at a specific time of the year, and fully remits otherwise. Although experts were initially skeptical, this condition is now recognized as a common disorder. However, the validity of SAD has been questioned by a 2016 analysis by the Center for Disease Control, in which no links were detected between depression and seasonality or sunlight exposure. In the United States, the percentage of the population affected by SAD ranges from 1.4% of the population in Florida, to 9.9% in Alaska. SAD was formally described and named in 1984, by Norman E. Rosenthal and colleagues at the National Institute of Mental Health. History SAD was first systematically reported and named in the early 1980s, by Norman E. Rosenthal, M.D., and his associates at the National Institute of Mental Health (NIMH). Rosenthal was initially motivated by his desire to discover the cause of his own experience of depression during the dark days of the northern US winter, called polar night. He theorized that the reduction in available natural light during winter was the cause. Rosenthal and his colleagues then documented the phenomenon of SAD in a placebo-controlled study utilizing light therapy. A paper based on this research was published in 1984. Although Rosenthals ideas were initially greeted with skepticism, SAD has become well recognized, and his 1993 book, Winter Blues has become the standard introduction to the subject.Research on SAD in the United States began in 1979, when Herb Kern, a research engineer, had also noticed that he felt depressed during the winter months. Kern suspected that scarcer light in winter was the cause, and discussed the idea with scientists at the NIMH who were working on bodily rhythms. They were intrigued, and responded by devising a lightbox to treat Kerns depression. Kern felt much better within a few days of treatments, as did other patients treated in the same way. Signs and symptoms SAD is a type of major depressive disorder, and those with the condition may exhibit any of the associated symptoms, such as feelings of hopelessness and worthlessness, thoughts of suicide, loss of interest in activities, withdrawal from social interaction, sleep and appetite problems, difficulty with concentrating and making decisions, decreased libido, a lack of energy, or agitation. Symptoms of winter SAD often include falling asleep earlier or in less than 5 minutes in the evening, oversleeping or difficulty waking up in the morning, nausea, and a tendency to overeat, often with a craving for carbohydrates, which leads to weight gain. SAD is typically associated with winter depression, but springtime lethargy or other seasonal mood patterns are not uncommon. Although each individual case is different, in contrast to winter SAD, people who experience spring and summer depression may be more likely to show symptoms such as insomnia, decreased appetite and weight loss, and agitation or anxiety. Bipolar disorder With seasonal pattern is a specifier for bipolar and related disorders, including bipolar I disorder and bipolar II disorder. Most people with SAD experience major depressive disorder, but as many as 20% may have a bipolar disorder. It is important to distinguish between diagnoses because there are important treatment differences. In these cases, people who have the With seasonal pattern specifier may experience a depressive episode either due to major depressive disorder or as part of bipolar disorder during the winter and remit in the summer. Around 25% of patients with bipolar disorder may present with a depressive seasonal pattern, which is associated with bipolar II disorder, rapid cycling, eating disorders, and more depressive episodes. Differences in biological sex display distinct clinical characteristics associated to seasonal pattern: males present with more Bipolar II disorder and a higher number of depressive episodes, and females with rapid cycling and eating disorders. Cause In many species, activity is diminished during the winter months, in response to the reduction in available food, the reduction of sunlight (especially for diurnal animals), and the difficulties of surviving in cold weather. Hibernation is an extreme example, but even species that do not hibernate often exhibit changes in behavior during the winter. The preponderance of women with SAD suggests that the response may also somehow regulate reproduction.Various proximate causes have been proposed. One possibility is that SAD is related to a lack of serotonin, and serotonin polymorphisms could play a role in SAD, although this has been disputed. Mice incapable of turning serotonin into N-acetylserotonin (by serotonin N-acetyltransferase) appear to express "depression-like" behavior, and antidepressants such as fluoxetine increase the amount of the enzyme serotonin N-acetyltransferase, resulting in an antidepressant-like effect. Another theory is that the cause may be related to melatonin, which is produced in dim light and darkness by the pineal gland, since there are direct connections, via the retinohypothalamic tract and the suprachiasmatic nucleus, between the retina and the pineal gland. Melatonin secretion is controlled by the endogenous circadian clock, but can also be suppressed by bright light.One study looked at whether some people could be predisposed to SAD based on personality traits. Correlations between certain personality traits, higher levels of neuroticism, agreeableness, openness, and an avoidance-oriented coping style, appeared to be common in those with SAD. Pathophysiology Seasonal mood variations are believed to be related to light. An argument for this view is the effectiveness of bright-light therapy. SAD is measurably present at latitudes in the Arctic region, such as northern Finland (64°00′N), where the rate of SAD is 9.5%. Cloud cover may contribute to the negative effects of SAD. There is evidence that many patients with SAD have a delay in their circadian rhythm, and that bright light treatment corrects these delays which may be responsible for the improvement in patients.The symptoms of it mimic those of dysthymia or even major depressive disorder. There is also potential risk of suicide in some patients experiencing SAD. One study reports 6–35% of people with the condition required hospitalization during one period of illness. At times, patients may not feel depressed, but rather lack energy to perform everyday activities.Subsyndromal Seasonal Affective Disorder is a milder form of SAD experienced by an estimated 14.3% (vs. 6.1% SAD) of the U.S. population. The blue feeling experienced by both those with SAD and with SSAD can usually be dampened or extinguished by exercise and increased outdoor activity, particularly on sunny days, resulting in increased solar exposure. Connections between human mood, as well as energy levels, and the seasons are well documented, even in healthy individuals. Diagnosis According to the American Psychiatric Association DSM-IV criteria, Seasonal Affective Disorder is not regarded as a separate disorder. It is called a "course specifier" and may be applied as an added description to the pattern of major depressive episodes in patients with major depressive disorder or patients with bipolar disorder. The "Seasonal Pattern Specifier" must meet four criteria: depressive episodes at a particular time of the year; remissions or mania/hypomania at a characteristic time of year; these patterns must have lasted two years with no nonseasonal major depressive episodes during that same period; and these seasonal depressive episodes outnumber other depressive episodes throughout the patients lifetime. The Mayo Clinic describes three types of SAD, each with its own set of symptoms. Management Treatments for classic (winter-based) seasonal affective disorder include light therapy, medication, ionized-air administration, cognitive-behavioral therapy, and carefully timed supplementation of the hormone melatonin. Light therapy Photoperiod-related alterations of the duration of melatonin secretion may affect the seasonal mood cycles of SAD. This suggests that light therapy may be an effective treatment for SAD. Light therapy uses a lightbox, which emits far more lumens than a customary incandescent lamp. Bright white "full spectrum" light at 10,000 lux, blue light at a wavelength of 480 nm at 2,500 lux or green (actually cyan or blue-green) light at a wavelength of 500 nm at 350 lux are used, with the first-mentioned historically preferred.Bright light therapy is effective with the patient sitting a prescribed distance, commonly 30–60 cm, in front of the box with her/his eyes open, but not staring at the light source, for 30–60 minutes. A study published in May 2010 suggests that the blue light often used for SAD treatment should perhaps be replaced by green or white illumination. Discovering the best schedule is essential. One study has shown that up to 69% of patients find lightbox treatment inconvenient, and as many as 19% stop use because of this.Dawn simulation has also proven to be effective; in some studies, there is an 83% better response when compared to other bright light therapy. When compared in a study to negative air ionization, bright light was shown to be 57% effective vs. dawn simulation 50%. Patients using light therapy can experience improvement during the first week, but increased results are evident when continued throughout several weeks. Certain symptoms like hypersomnia, early insomnia, social withdrawal, and anxiety resolve more rapidly with light therapy than with cognitive behavioral therapy. Most studies have found it effective without use year round, but rather as a seasonal treatment lasting for several weeks, until frequent light exposure is naturally obtained.Light therapy can also consist of exposure to sunlight, either by spending more time outside or using a computer-controlled heliostat to reflect sunlight into the windows of a home or office. Although light therapy is the leading treatment for seasonal affective disorder, prolonged direct sunlight or artificial lights that dont block the ultraviolet range should be avoided, due to the threat of skin cancer.The evidence base for light therapy as a preventive treatment for seasonal affective disorder is limited. The decision to use light therapy to treat people with a history of winter depression before depressive symptoms begin should be based on a persons preference of treatment. Medication SSRI (selective serotonin reuptake inhibitor) antidepressants have proven effective in treating SAD. Effective antidepressants are fluoxetine, sertraline, or paroxetine. Both fluoxetine and light therapy are 67% effective in treating SAD, according to direct head-to-head trials conducted during the 2006 Can-SAD study. Subjects using the light therapy protocol showed earlier clinical improvement, generally within one week of beginning the clinical treatment. Bupropion extended-release has been shown to prevent SAD for one in four people, but has not been compared directly to other preventive options in trials. In a 2021 updated Cochrane review of second-generation antidepressant medications for the treatment of SAD, a definitive conclusion could not be drawn, due to lack of evidence, and the need for larger randomized controlled trials.Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression.Another explanation is that vitamin D levels are too low when people do not get enough Ultraviolet-B on their skin. An alternative to using bright lights is to take vitamin D supplements. However, studies did not show a link between vitamin D levels and depressive symptoms in elderly Chinese, nor among elderly British women given only 800IU when 6,000IU is needed. 5-HTP (an amino acid that helps to produce serotonin, and is often used to help those with depression) has also been suggested as a supplement that may help treat the symptoms of SAD, by lifting mood, and regulating sleep schedule for those with the condition. However, those who take antidepressants are not advised to take 5-HTP, as antidepressant medications may combine with the supplement to create dangerously high levels of serotonin – potentially resulting in serotonin syndrome. Other treatments Depending upon the patient, one treatment (e.g., lightbox) may be used in conjunction with another (e.g., medication).Negative air ionization, which involves releasing charged particles into the sleep environment, has been found effective, with a 47.9% improvement if the negative ions are in sufficient density (quantity).Physical exercise has shown to be an effective form of depression therapy, particularly when in addition to another form of treatment for SAD. One particular study noted marked effectiveness for treatment of depressive symptoms, when combining regular exercise with bright light therapy. Patients exposed to exercise which had been added to their treatments in 20 minutes intervals on the aerobic bike during the day, along with the same amount of time underneath the UV light were seen to make a quick recovery.Of all the psychological therapies aimed at the prevention of SAD, cognitive-behaviour therapy, typically involving thought records, activity schedules and a positive data log, has been the subject of the most empirical work. However, evidence for CBT or any of the psychological therapies aimed at preventing SAD remains inconclusive. Epidemiology Nordic countries Winter depression is a common slump in the mood of some inhabitants of most of the Nordic countries. Iceland, however, seems to be an exception. A study of more than 2000 people there found the prevalence of seasonal affective disorder and seasonal changes in anxiety and depression to be unexpectedly low in both sexes. The studys authors suggested that propensity for SAD may differ due to some genetic factor within the Icelandic population. A study of Canadians of wholly Icelandic descent also showed low levels of SAD. It has more recently been suggested that this may be attributed to the large amount of fish traditionally eaten by Icelandic people. In 2007, about 90 kilograms of fish per person was consumed per year in Iceland, as opposed to about 24 kilograms in the US and Canada, rather than to genetic predisposition; a similar anomaly is noted in Japan, where annual fish consumption in recent years averages about 60 kilograms per capita. Fish are high in vitamin D. Fish also contain docosahexaenoic acid (DHA), which help with a variety of neurological dysfunctions. Other countries In the United States, a diagnosis of seasonal affective disorder was first proposed by Norman E. Rosenthal, M.D. in 1984. Rosenthal wondered why he became sluggish during the winter after moving from sunny South Africa to (cloudy in winter) New York. He started experimenting increasing exposure to artificial light, and found this made a difference. In Alaska it has been established that there is a SAD rate of 8.9%, and an even greater rate of 24.9% for subsyndromal SAD. Around 20% of Irish people are affected by SAD, according to a survey conducted in 2007. The survey also shows women are more likely to be affected by SAD than men. An estimated 3% of the population in the Netherlands experience winter SAD. See also Diurnal Cycle Seasonal effects on suicide rates Seasonal Pattern Assessment Questionnaire Vitamin D deficiency References External links Seasonal Affective Disorder at Curlie USA National Institute of Mental Health webpages https://www.nimh.nih.gov/health/topics/seasonal-affective-disorder/index.shtml

Hi Aarogya, explain a situation where Seborrhoeic dermatitis occurs

Seborrhoeic dermatitis

Seborrhoeic dermatitis, sometimes inaccurately referred to as seborrhoea, is a long-term skin disorder. Symptoms include red, scaly, greasy, itchy, and inflamed skin. Areas of the skin rich in oil-producing glands are often affected including the scalp, face, and chest. It can result in social or self-esteem problems. In babies, when the scalp is primarily involved, it is called cradle cap. Dandruff is a milder form of the condition without inflammation.The cause is unclear but believed to involve a number of genetic and environmental factors. Risk factors include poor immune function, Parkinsons disease, and alcoholic pancreatitis. The condition may worsen with stress or during the winter. The Malassezia yeast is believed to play a role. It is not a result of poor hygiene. Diagnosis is typically based on the symptoms. The condition is not contagious.The typical treatment is antifungal cream and anti-inflammatory agents. Specifically, ketoconazole or ciclopirox are effective. It is unclear if other antifungals, such as miconazole, are equally effective as they have been poorly studied. Other options may include salicylic acid, coal tar, benzoyl peroxide, and phototherapy.The condition is most common in infants within the first 3 months or in adults aged 30 to 70 years. In adults between 1% and 10% of people are affected. Males are more often affected than females. Up to 70% of babies may be affected at some point in time. Signs and symptoms Seborrhoeic dermatitis symptoms appear gradually, and usually the first signs are flaky skin and scalp. Symptoms occur most commonly anywhere on the skin of the scalp, behind the ears, on the face, and in areas where the skin folds. Flakes may be yellow, white or grayish. Redness and flaking may also occur on the skin near the eyelashes, on the forehead, around the sides of the nose, on the chest, and on the upper back. In more severe cases, yellowish to reddish scaly pimples appear along the hairline, behind the ears, in the ear canal, on the eyebrows, on the bridge of the nose, around the nose, on the chest, and on the upper back.Commonly, patients experience mild redness, scaly skin lesions and in some cases hair loss. Other symptoms include patchy scaling or thick crusts on the scalp, red, greasy skin covered with flaky white or yellow scales, itching, soreness and yellow or white scales that may attach to the hair shaft.Seborrhoeic dermatitis can occur in infants younger than three months and it causes a thick, oily, yellowish crust around the hairline and on the scalp. Itching is not common among infants. Frequently, a stubborn diaper rash accompanies the scalp rash. Causes The cause of seborrhoeic dermatitis has not been fully clarified.In addition to the presence of Malassezia, genetic, environmental, hormonal, and immune-system factors are necessary for and/or modulate the expression of seborrhoeic dermatitis. The condition may be aggravated by illness, psychological stress, fatigue, sleep deprivation, change of season, and reduced general health. In children and babies, excessive vitamin A intake or issues with Δ6-desaturase enzymes have been correlated with increased risk. Seborrhoeic dermatitis-like eruptions are also associated with vitamin B6 deficiency. Those with immunodeficiency (especially infection with HIV) and with neurological disorders such as Parkinsons disease (for which the condition is an autonomic sign) and stroke are particularly prone to it. Climate Low humidity and low temperature are responsible for high frequency of seborrheic dermatitis. Fungi The condition is thought to be due to a local inflammatory response to over-colonization by Malassezia fungi species in sebum-producing skin areas including the scalp, face, chest, back, underarms, and groin. This is based on observations of high counts of Malassezia species in skin affected by seborrhoeic dermatitis and on the effectiveness of antifungals in treating the condition. Such species of Malassezia include M. furfur (formerly Pityrosporum ovale), M. globosa, M. restricta, M. sympodialis, and M. slooffiae. Although Malassezia appears to be the central predisposing factor in seborrhoeic dermatitis, it is thought that other factors are necessary for the presence of Malassezia to result in the pathology characteristic of the condition. This is based on the fact that summer growth of Malassezia in the skin alone does not result in seborrhoeic dermatitis. Besides antifungals, the effectiveness of anti-inflammatory drugs, which reduce inflammation, and antiandrogens, which reduce sebum production, provide further insights into the pathophysiology of seborrhoeic dermatitis. Eunuchs, owing to their low androgen levels and small sebaceous glands, do not develop seborrheic dermatitis. Management Humidity A humidifier can be used to prevent low indoor humidity during winter (especially with indoor heating), and dry season. And a dehumidifier can be used during seasons with excessive humidity. Medications A variety of different types of medications are able to reduce symptoms of seborrhoeic dermatitis. These include certain antifungals, anti-inflammatory agents like corticosteroids and nonsteroidal anti-inflammatory drugs, antiandrogens, and antihistamines, among others. Antifungals Regular use of an over-the-counter or prescription antifungal shampoo or cream may help those with recurrent episodes. The topical antifungal medications ketoconazole and ciclopirox have the best evidence. It is unclear if other antifungals are equally effective as this has not been sufficiently studied. Antifungals that have been studied and found to be effective in the treatment of seborrhoeic dermatitis include ketoconazole, fluconazole, miconazole, bifonazole, sertaconazole, clotrimazole, flutrimazole, ciclopirox, terbinafine, butenafine, selenium sulfide, and lithium salts such as lithium gluconate and lithium succinate. Topical climbazole appears to have little effectiveness in the treatment of seborrhoeic dermatitis. Systemic therapy with oral antifungals including itraconazole, fluconazole, ketoconazole, and terbinafine is effective. Anti-inflammatory treatments Topical corticosteroids have been shown to be effective in short-term treatment of seborrhoeic dermatitis and are as effective or more effective than antifungal treatment with azoles. There is also evidence for the effectiveness of calcineurin inhibitors like tacrolimus and pimecrolimus as well as lithium salt therapy.Oral immunosuppressive treatment, such as with prednisone, has been used in short courses as a last resort in seborrhoeic dermatitis due to its potential side effects. Antiandrogens Seborrhoea, which is sometimes associated with seborrhoeic dermatitis, is recognized as an androgen-sensitive condition – that is, it is caused or aggravated by androgen sex hormones such as testosterone and dihydrotestosterone – and is a common symptom of hyperandrogenism (e.g., that seen in polycystic ovary syndrome). In addition, seborrhoea, as well as acne, are commonly associated with puberty due to the steep increase of androgen levels at that time.In accordance with the involvement of androgens in seborrhoea, antiandrogens, such as cyproterone acetate, spironolactone, flutamide, and nilutamide, are highly effective in alleviating the condition. As such, they are used in the treatment of seborrhoea, particularly severe cases. While beneficial in seborrhoea, effectiveness may vary with different antiandrogens; for instance, spironolactone (which is regarded as a relatively weak antiandrogen) has been found to produce a 50% improvement after three months of treatment, whereas flutamide has been found to result in an 80% improvement within three months. Cyproterone acetate, similarly more potent and effective than spironolactone, results in considerable improvement or disappearance of acne and seborrhoea in 90% of patients within three months.Systemic antiandrogen therapy is generally used to treat seborrhoea only in women, not in men, as these medications can result in feminization (e.g., gynecomastia), sexual dysfunction, and infertility in males. In addition, antiandrogens theoretically have the potential to feminize male fetuses in pregnant women and, for this reason, are usually combined with effective birth control in sexually active women who can or may become pregnant. Antihistamines Antihistamines are used primarily to reduce itching, if present. However, research studies suggest that some antihistamines have anti-inflammatory properties. Other treatments Coal tar can be effective. Although no significant increased risk of cancer in human treatment with coal tar shampoos has been found, caution is advised since coal tar is carcinogenic in animals, and heavy human occupational exposures do increase cancer risks. Isotretinoin, a sebosuppressive agent, may be used to reduce sebaceous gland activity as a last resort in refractory disease. However, isotretinoin has potentially serious side effects, and few patients with seborrhoeic dermatitis are appropriate candidates for therapy. Keratolytics like topical urea Metronidazole Topical 4% nicotinamide Phototherapy Another potential option is natural and artificial UV radiation since it can curb the growth of Malassezia yeast. Some recommend photodynamic therapy using UV-A and UV-B laser or red and blue LED light to inhibit the growth of Malassezia fungus and reduce seborrhoeic inflammation. Epidemiology Seborrhoeic dermatitis affects 1 to 5% of the general population. It is slightly more common in men, but affected women tend to have more severe symptoms. The condition usually recurs throughout a persons lifetime. Seborrhoeic dermatitis can occur in any age group but usually starts at puberty and peaks in incidence at around 40 years of age. It can reportedly affect as many as 31% of older people. Severity is worse in dry climates. Seborrhoeic dermatitis is common in this with alcoholism, between 7 and 11 percent, which is twice the normal expected occurrence. See also Seborrheic keratosis Eczema herpeticum, condition that primarily manifests in childhood References External links American Academy of Dermatology: Seborrheic dermatitis

Aarogya what is Seborrheic keratosis

Seborrheic keratosis

A seborrheic keratosis is a non-cancerous (benign) skin tumour that originates from cells in the outer layer of the skin. Like liver spots, seborrheic keratoses are seen more often as people age.The tumours (also called lesions) appear in various colours, from light tan to black. They are round or oval, feel flat or slightly elevated, like the scab from a healing wound, and range in size from very small to more than 2.5 centimetres (1 in) across. They can often come in association with other skin conditions, including basal cell carcinoma. Rarely seborrheic keratosis and basal cell carcinoma occur at the same location. At clinical examination the differential diagnosis includes warts and melanoma. Because only the top layers of the epidermis are involved, seborrheic keratoses are often described as having a "pasted on" appearance. Some dermatologists refer to seborrheic keratoses as "seborrheic warts", because they resemble warts, but strictly speaking the term "warts" refers to lesions that are caused by human papillomavirus. Cause The cause of seborrheic keratosis is not known. The only definitive association is that its prevalence increases with age. Diagnosis Visual diagnosis is made by the "stuck on" appearance, horny pearls or cysts embedded in the structure. Darkly pigmented lesions can be challenging to distinguish from nodular melanomas. Furthermore, thin seborrheic keratoses on facial skin can be very difficult to differentiate from lentigo maligna even with dermatoscopy. Clinically, epidermal nevi are similar to seborrheic keratoses in appearance. Epidermal nevi are usually present at or near birth. Condylomas and warts can clinically resemble seborrheic keratoses, and dermatoscopy can be helpful. On the penis and genital skin, condylomas and seborrheic keratoses can be difficult to differentiate, even on biopsy.A study examining over 4,000 biopsied skin lesions identified as seborrheic keratoses showed 3.1% were malignancies. Two thirds of those were squamous cell carcinoma. To date, the gold standard in the diagnosis of seborrheic keratosis is represented by the histolopathologic analysis of a skin biopsy. Subtypes Seborrheic keratoses may be divided into the following types: Main differential diagnoses Dermatosis papulosa nigra (DPN) is a condition of many small, benign skin lesions on the face, a condition generally presenting on dark-skinned individuals.: 638–9  DPN is extremely common, affecting up to 30% of Black people in the US. Treatment No treatment of seborrheic keratoses is necessary, except for aesthetic reasons. Generally, lesions can be treated with electrodesiccation and curettage, or cryosurgery. When correctly performed, removal of seborrheic keratoses will not cause much visible scarring. Epidemiology Seborrheic keratosis is the most common benign skin tumor. Incidence increases with age. There is less prevalence in people with darker skin. In large-cohort studies, 100% of the patients over age 50 had at least one seborrheic keratosis. Onset is usually in middle age, although they are common in younger patients too—found in 12% of 15-year-olds to 25-year-olds—making the term "senile keratosis" a misnomer. See also The sign of Leser-Trélat Notes References External links DermAtlas 185

Hello Aarogya , Do you know what is Sézary disease,

Sézary disease

Sézary disease, or Sézary syndrome, is a type of cutaneous T-cell lymphoma that was first described by Albert Sézary. The affected T cells, known as Sézarys cells or Lutzner cells, have pathological quantities of mucopolysaccharides. Sézary disease is sometimes considered a late stage of mycosis fungoides with lymphadenopathy. Signs and symptoms Sézary disease and mycosis fungoides are cutaneous T-cell lymphomas having a primary manifestation in the skin. The diseases origin is a peripheral CD4+ T-lymphocyte, although rarer CD8+/CD4- cases have been observed. Epidermotropism (lymphocytes residing in the epidermis) by neoplastic CD4+ lymphocytes with the formation of Pautriers microabscesses is the hallmark sign of the disease. Although the condition can affect people of all ages, it is commonly diagnosed in adults over age 60. The dominant signs and symptoms of the disease are: Generalized erythroderma– redness of the skin Lymphadenopathy – swollen, enlarged lymph nodes Atypical T cells – malignant lymphocytes known as "Sézary cells" seen in the peripheral blood with typical cerebriform nuclei (brain-shaped, convoluted nuclei) Hepatosplenomegaly– enlarged liver and spleen Palmoplantar keratoderma – thickening of the palms of the hands, and soles of the feet Diagnosis Those who have Sézary disease often present with skin lesions that do not heal with normal medication. A blood test generally reveals any change in the levels of lymphocytes in the blood, which is often associated with a cutaneous T-cell lymphoma. Finally, a biopsy of a skin lesion can be performed to rule out any other causes.The immunohistochemical features are very similar to those presented in mycosis fungoides except for the following differences: More monotonous cellular infiltrates (large, clustered atypical pagetoid cells) in Sézary syndrome Sometimes absent epidermotropism Increased lymph node involvement with infiltrates of Sézary syndrome. Treatment Treatment typically includes some combination of photodynamic therapy, radiation therapy, chemotherapy, and biologic therapy.Treatments are often used in combination with phototherapy and chemotherapy, though pure chemotherapy is rarely used today. No single treatment type has revealed clear-cut benefits in comparison to others, treatment for all cases remains problematic. Radiation therapy A number of types of radiation therapy may be used including total skin electron therapy. While this therapy does not generally result in systemic toxic effects it can produce side effects involving the skin. It is only available at a few institutions. Chemotherapy Romidepsin, vorinostat and a few others are a second-line drug for cutaneous T-cell lymphoma. Mogamulizumab has been approved in Japan and the United States. Epidemiology In the Western population, there are around 3 cases of Sézary syndrome per 1,000,000 people. Sézary disease is more common in males with a ratio of 2:1, and the mean age of diagnosis is between 55 and 60 years of age. See also List of cutaneous conditions References External links Sezary Syndrome lymphoma information

What does Shigellosis mean Aarogya

Shigellosis

Shigellosis is an infection of the intestines caused by Shigella bacteria. Symptoms generally start one to two days after exposure and include diarrhea, fever, abdominal pain, and feeling the need to pass stools even when the bowels are empty. The diarrhea may be bloody. Symptoms typically last five to seven days and it may take several months before bowel habits return entirely to normal. Complications can include reactive arthritis, sepsis, seizures, and hemolytic uremic syndrome.Shigellosis is caused by four specific types of Shigella. These are typically spread by exposure to infected feces. This can occur via contaminated food, water, or hands or sexual contact. Contamination may be spread by flies or when changing diapers (nappies). Diagnosis is by stool culture.The risk of infection can be reduced by properly washing the hands. There is no vaccine. Shigellosis usually resolves without specific treatment. Rest, and sufficient fluids by mouth, are recommended. Bismuth subsalicylate may help with the symptoms; however, medications that slow the bowels such as loperamide are not recommended. In severe cases antibiotics may be used but resistance is common. Commonly used antibiotics include ciprofloxacin and azithromycin.A 2005 report by the World Health Organization estimated that shigellosis occurs in at least 80 million people and results in about 700,000 deaths a year globally. Most cases occur in the developing world. Young children are most commonly affected. Outbreaks of disease may occur in childcare settings and schools. It is also relatively common among travelers. In the United States about half a million cases occur a year. Signs and symptoms Signs and symptoms may range from mild abdominal discomfort to full-blown dysentery characterized by cramps, diarrhea, with slimy-consistent stools, fever, blood, pus, or mucus in stools or tenesmus. Onset time is 12 to 96 hours, and recovery takes 5 to 7 days. Infections are associated with mucosal ulceration, rectal bleeding, and drastic dehydration. Reactive arthritis and hemolytic uremic syndrome are possible sequelae that have been reported in the aftermath of shigellosis.The most common neurological symptom includes seizures. Cause Bacteria Shigellosis is caused by a bacterial infection with Shigella, a bacterium that is genetically similar to and was once classified as E. coli. There are three serogroups and one serotype of Shigella: Shigella flexneri Shigella boydii Shigella dysenteriae and Shigella sonnei (serotype)The probability of being infected by any given strain of Shigella varies around the world. For instance, S. sonnei is the most common in the United States, while S. dysenteriae and S. boydii are rare in the U.S. Transmission Shigella is transmitted through the fecal-oral route of individuals infected with the disease, whether or not they are exhibiting symptoms. Long-term carriers of the bacteria are rare. The bacteria can infect not just humans but other primates as well. Mechanism Upon ingestion, the bacteria pass through the gastrointestinal tract until they reach the small intestine. There they begin to multiply until they reach the large intestine. In the large intestine, the bacteria cause cell injury and the beginning stages of Shigellosis via two main mechanisms: direct invasion of epithelial cells in the large intestine and production of enterotoxin 1 and enterotoxin 2.Unlike other bacteria, Shigella is not destroyed by the gastric acid in the stomach. As a result, it takes only 10 to 200 cells to cause an infection. This infectious dose is several order of magnitudes smaller than that of other species of bacteria (e.g. cholera, caused by the bacterium Vibrio cholerae, has an infectious dose between 108 and 1011 cells). Diagnosis The diagnosis of shigellosis is made by isolating the organism from diarrheal fecal sample cultures. Shigella species are negative for motility and are generally not lactose fermenters, but S. sonnei can ferment lactose. They typically do not produce gas from carbohydrates (with the exception of certain strains of S. flexneri) and tend to be overall biochemically inert. Shigella should also be urea hydrolysis negative. When inoculated to a triple sugar iron slant, they react as follows: K/A, gas -, and H2S -. Indole reactions are mixed, positive and negative, with the exception of S. sonnei, which is always indole negative. Growth on Hektoen enteric agar produces bluish-green colonies for Shigella and bluish-green colonies with black centers for Salmonella. Prevention Simple precautions can be taken to prevent getting shigellosis: wash hands before handling food and thoroughly cook all food before eating. The primary prevention methods are improved sanitation and personal and food hygiene, but a low-cost and efficacious vaccine would complement these methods.Since shigellosis is spread very quickly among children, keeping infected children out of daycare for 24 hours after their symptoms have disappeared, will decrease the occurrence of shigellosis in daycares. Vaccine Currently, no licensed vaccine targeting Shigella exists. Several vaccine candidates for Shigella are in various stages of development including live attenuated, conjugate, ribosomal, and proteosome vaccines. Shigella has been a longstanding World Health Organization target for vaccine development, and sharp declines in age-specific diarrhea/dysentery attack rates for this pathogen indicate that natural immunity does develop following exposure; thus, vaccination to prevent the disease should be feasible. Shigellosis is resistant to many antibiotics used to treat the disease, so vaccination is an important part of the strategy to reduce morbidity and mortality. Treatment Treatment consists mainly of replacing fluids and salts lost because of diarrhea. Replacement by mouth is satisfactory for most people, but some may need to receive fluids intravenously. Antidiarrheal drugs (such as diphenoxylate or loperamide) may prolong the infection and should not be used. Antibiotics Antibiotics should only be used in severe cases or for certain populations with mild symptoms (elderly, immunocompromised, food service industry workers, child care workers). For Shigella-associated diarrhea, antibiotics shorten the length of infection, but they are usually avoided in mild cases because many Shigella strains are becoming resistant to common antibiotics. Furthermore, effective medications are often in short supply in developing countries, which carry the majority of the disease burden from Shigella. Antidiarrheal agents may worsen the sickness, and should be avoided.In most cases, the disease resolves within four to eight days without antibiotics. Severe infections may last three to six weeks. Antibiotics, such as trimethoprim-sulfamethoxazole, ciprofloxacin may be given when the person is very young or very old, when the disease is severe, or when the risk of the infection spreading to other people is high. Additionally, ampicillin (but not amoxicillin) was effective in treating this disease previously, but now the first choice of drug is pivmecillinam. Epidemiology Insufficient data exist, but it is estimated to have caused the death of 34,000 children under the age of five in 2013, and 40,000 deaths in people over five years of age. Shigella also causes about 580,000 cases annually among travelers and military personnel from industrialized countries.An estimated 500,000 cases of shigellosis occur annually in the United States. Infants, the elderly, and the critically ill are susceptible to the most severe symptoms of disease, but all humans are susceptible to some degree. Individuals with acquired immune deficiency syndrome (AIDS) are more frequently infected with Shigella. Shigellosis is a more common and serious condition in the developing world; fatality rates of shigellosis epidemics in developing countries can be 5–15%.Orthodox Jewish communities (OJCs) are a known risk group for shigellosis; Shigella sonnei is cyclically epidemic in these communities in Israel, with sporadic outbreaks occurring elsewhere in among these communities. "Through phylogenetic and genomic analysis, we showed that strains from outbreaks in OJCs outside of Israel are distinct from strains in the general population and relate to a single multidrug-resistant sublineage of S. sonnei that prevails in Israel. Further Bayesian phylogenetic analysis showed that this strain emerged approximately 30 years ago, demonstrating the speed at which antimicrobial drug–resistant pathogens can spread widely through geographically dispersed, but internationally connected, communities." See also Gastroenteritis Shiga-like toxin Shiga toxin Travelers diarrhea References External links CDCs Shigellosis Page Vaccine Resource Library: Shigellosis and enterotoxigenic Escherichia coli (ETEC)

Hi Aarogya, explain a situation where Short bowel syndrome occurs

Short bowel syndrome

Short bowel syndrome (SBS, or simply short gut) is a rare malabsorption disorder caused by a lack of functional small intestine. The primary symptom is diarrhea, which can result in dehydration, malnutrition, and weight loss. Other symptoms may include bloating, heartburn, feeling tired, lactose intolerance, and foul-smelling stool. Complications can include anemia and kidney stones.Most cases are due to the surgical removal of a large portion of the small intestine. This is most often required due to Crohns disease in adults and necrotising enterocolitis in young children. Other causes include damage to the small intestine from other means and being born with an abnormally short intestine. It usually does not develop until less than 2 m (6.6 ft) of the normally 6.1 m (20 ft) small intestine remains.Treatment may include a specific diet, medications, or surgery. The diet may include slightly salty and slightly sweet liquids, vitamin and mineral supplements, small frequent meals, and the avoidance of high fat food. Occasionally nutrients need to be given through an intravenous line, known as parenteral nutrition. Medications used may include antibiotics, antacids, loperamide, teduglutide, and growth hormone. Different types of surgery, including an intestinal transplant, may help some people.Short bowel syndrome newly occurs in about three per million people each year. There are estimated to be about 15,000 people with the condition in the United States. The prevalence in the United States is approximately 30 cases per million and in Europe it is approximately 1.4 cases per million (but the rate varies widely between countries). The prevalence of short bowel syndrome has increased by more than 2 fold in the last 40 years. It is classified as a rare disease by the European Medicines Agency. Outcomes depend on the amount of bowel remaining and whether or not the small bowel remains connected with the large bowel. Signs and symptoms The symptoms of short bowel syndrome can include: Abdominal pain Diarrhea and steatorrhea (oily, bulky stool, which can be malodorous) Fluid depletion Weight loss and malnutrition FatiguePersons with short bowel syndrome may have complications caused by malabsorption of vitamins and minerals, such as deficiencies in vitamins A, D, E, K, B9 (folic acid), and B12, calcium, magnesium, iron, and zinc. These may appear as anemia, hyperkeratosis (scaling of the skin), easy bruising, muscle spasms, poor blood clotting, and bone pain. Causes Short bowel syndrome in adults and children is most commonly caused by surgery (intestinal resection). In those who undergo intestinal resection, approximately 15% eventually develop small bowel syndrome (75% of those due to 1 large resection and 25% due to multiple separate intestinal resections). This surgery may be done for: Crohns disease, an inflammatory disorder of the digestive tract Mesenteric ischemia, embolic or thrombotic events that may occur in the arteries or veins that supply or drain the intestines respectively, leading to disruption of blood supply to the intestines and ischemia. Volvulus, a twisting of the small intestine often caused by intestinal malrotation that quickly cuts off blood supply and leads to tissue death Tumors of the small intestine Radiation enteropathy, radiation injury to the small intestine, due to radiation therapy for cancer Injury or trauma to the small intestine Necrotizing enterocolitis (premature newborn) Bypass surgery to treat obesity Surgery to remove diseases or damaged portion of the small intestineSome children are also born with an abnormally short small intestine, known as congenital short bowel.Surgical complications, requiring re-surgery, are a common cause of small bowel syndrome, contributing up to 50% of cases based on some estimates. These surgical complications include internal hernias, volvuli, ischemia or profound hypotension. Pathophysiology The length of the small intestine can vary greatly, from as short as 2.75 m (9.0 ft) to as long as 10.49 m (34.4 ft). On average it is about 6.1 m (20 ft). Due to this variation it is recommended that following surgery the amount of bowel remaining be specified rather than the amount removed.Short bowel syndrome usually develops when there is less than 2 meters (6.6 feet) of the small intestine left to absorb sufficient nutrients.The resection of specific areas of the small bowel can lead to distinct symptoms in short bowel syndrome. The resection of the ileum leads to a malabsorption of vitamin B12, bile acids and the fat soluble vitamins A, D, E and K. Loss of the distal ileum also leads to loss of inhibitory hormones; leading to gastric hypersecretion, intestinal hypermotility (decreases in the intestinal transit time) leading to secretory diarrhea and macronutrient, micronutrient, vitamin and mineral deficiencies. Loss of the ileocecal valve leads to small intestinal bacterial overgrowth(SIBO) as bacterial flora normally found in the large intestines migrate proximally and colonize the small intestines leading to further malabsorption. SIBO leads to malabsorption as the bacteria colonizing the small intestine metabolize nutrients, directly competing with the intestinal absorption of nutrients. The bacteria colonizing the small intestines in SIBO may also cause bile acid deconjugation leading to malabsorption of lipids.In a process called intestinal adaptation, physiological changes to the remaining portion of the small intestine occur to increase its absorptive capacity. These changes usually take place over 1-2 years. These changes include: Enlargement (increased diameter) and lengthening of the villi found in the lining Increase in the diameter of the small intestine Slow down in peristalsis or movement of food through the small intestine (an increase in the transit time) to increase the time available for nutrient absorptionOsteoporosis is a very common comorbidity in people with short bowel syndrome who are on parenteral nutrition, with an estimated prevalence of 57-67%. The contributing factors to the osteoporosis include malnutrition, vitamin D deficiency due to malabsorption and vitamin D deficiency due to scarce sunlight exposure due to chronic disability. Diagnosis Definition Intestinal failure is decreased intestinal function such that nutrients, water, and electrolytes are not sufficiently absorbed. Short bowel syndrome is when there is less than 2 m (6.6 ft) of working bowel and is the most common cause of intestinal failure. Treatments Symptoms of short bowel syndrome are usually addressed with medication. These include: Anti-diarrheal medicine (e.g. loperamide, codeine) Vitamin, mineral supplements and L-glutamine powder mixed with water H2 blocker and proton pump inhibitors to reduce stomach acid Lactase supplement (to improve the bloating and diarrhea associated with lactose intolerance)In 2004, the USFDA approved a therapy that reduces the frequency and volume of total parenteral nutrition (TPN), comprising: NutreStore (oral solution of glutamine) and Zorbtive (growth hormone, of recombinant DNA origin, for injection) together with a specialized oral diet. After 24 weeks of successful Phase III patient treatment trials, Teduglutide was shown to be relatively safe and effective with varying degrees of benefits and adverse effects per patient. Adequate safety evaluations prove to be difficult due to a limited sample size available for study, however. In 2012, an advisory panel to the USFDA voted unanimously to approve for treatment of SBS the agent teduglutide, a glucagon-like peptide-2 analog developed by NPS Pharmaceuticals, who intend to market the agent in the United States under the brandname Gattex. Teduglutide had been previously approved for use in Europe and is marketed under the brand Revestive by Nycomed.Surgical procedures to lengthen dilated bowel include the Bianchi procedure, where the bowel is cut in half and one end is sewn to the other, and a newer procedure called serial transverse enteroplasty (STEP), where the bowel is cut and stapled in a zigzag pattern. Heung Bae Kim, MD, and Tom Jaksic, MD, both of Childrens Hospital Boston, devised the STEP procedure in the early 2000s. The procedure lengthens the bowel of children with SBS and may allow children to avoid the need for intestinal transplantation. As of June 2009, Kim and Jaksic have performed 18 STEP procedures. The Bianchi and STEP procedures are usually performed by pediatric surgeons at quaternary hospitals who specialize in small bowel surgery. Prognosis After resection; having a remnant small bowel length of less than 75 cm and a remaining large bowel length of less than 57% of the original length are both associated with subsequent dependence on parenteral nutrition.There is no cure for short bowel syndrome except transplant. In newborn infants, the 4-year survival rate on parenteral nutrition is approximately 70%. In newborn infants with less than 10% of expected intestinal length, 5 year survival is approximately 20%. Some studies suggest that much of the mortality is due to a complication of the total parenteral nutrition (TPN), especially chronic liver disease. Much hope is, as of 2006, vested in Omegaven, a type of lipid TPN feed, in which recent case reports suggest the risk of liver disease is much lower.Although promising, small intestine transplant has a mixed success rate, with postoperative mortality rate of up to 30%. One-year and 4-year survival rate are 90% and 60%, respectively. See also Bowel-associated dermatosis–arthritis syndrome, another syndrome that can result from small-bowel bypass (or other causes) References External links Short bowel syndrome at Curlie National Digestive Diseases Information Clearinghouse - Short Bowel Syndrome Archived 2014-03-21 at the Wayback Machine

Hello Aarogya, explain a situation where Hypersalivation occurs

Hypersalivation

Hypersalivation, or ptyalism, also known as sialorrhea or hypersialosis is the excessive production of saliva. It has also been defined as increased amount of saliva in the mouth, which may also be caused by decreased clearance of saliva.Hypersalivation can contribute to drooling if there is an inability to keep the mouth closed or difficulty in swallowing (dysphagia) the excess saliva, which can lead to excessive spitting. Hypersalivation also often precedes emesis (vomiting), where it accompanies nausea (a feeling of needing to vomit). Causes Excessive production Conditions that can cause saliva overproduction include: Rabies Pellagra (niacin or Vitamin B3 deficiency) Gastroesophageal reflux disease, in such cases specifically called a water brash (a loosely defined lay term), and is characterized by a sour fluid or almost tasteless saliva in the mouth Gastroparesis (main symptoms are nausea, vomiting, and reflux) Pregnancy Fluoride therapy Excessive starch intake Anxiety (common sign of separation anxiety in dogs) Pancreatitis Liver disease Serotonin syndrome Mouth ulcers Oral infections Sjögren syndrome (an early symptom in some patients)Medications that can cause overproduction of saliva include: aripiprazole clozapine pilocarpine ketamine potassium chlorate risperidone pyridostigmineSubstances that can cause hypersalivation include: mercury copper organophosphates (insecticide) arsenic nicotine thallium Decreased clearance Causes of decreased clearance of saliva include: Infections such as tonsillitis, retropharyngeal and peritonsillar abscesses, epiglottitis and mumps. Problems with the jaw, e.g., fracture or dislocation Radiation therapy Neurologic disorders such as Amyotrophic lateral sclerosis, myasthenia gravis, Parkinsons disease, multiple system atrophy, rabies, bulbar paralysis, bilateral facial nerve palsy, and hypoglossal nerve palsy Treatment Hypersalivation is optimally treated by treating or avoiding the underlying cause. Mouthwash and tooth brushing may have drying effects.In the palliative care setting, anticholinergics and similar drugs that would normally reduce the production of saliva causing a dry mouth could be considered for symptom management: scopolamine, atropine, propantheline, hyoscine, amitriptyline, glycopyrrolate.As of 2008, it is unclear if medication for people who have too much saliva due to clozapine treatment is useful. References == External links ==

Hey Aarogya, explain a situation where Night terror occurs

Night terror

Night terror, also called sleep terror, is a sleep disorder causing feelings of panic or dread and typically occurring during the first hours of stage 3–4 non-rapid eye movement (NREM) sleep and lasting for 1 to 10 minutes. It can last longer, especially in children. Sleep terror is classified in the category of NREM-related parasomnias in the International Classification of Sleep Disorders. There are two other categories: REM-related parasomnias and other parasomnias. Parasomnias are qualified as undesirable physical events or experiences that occur during entry into sleep, during sleep, or during arousal from sleep.Sleep terrors usually begin in childhood and usually decrease as age increases. Factors that may lead to sleep terrors are young age, sleep deprivation, medications, stress, fever, and intrinsic sleep disorders. The frequency and severity differ among individuals; the interval between episodes can be as long as weeks and as short as minutes or hours. This has created a situation in which any type of nocturnal attack or nightmare may be confused with and reported as a night terror.Night terrors tend to happen during periods of arousal from delta sleep, or slow-wave sleep. Delta sleep occurs most often during the first half of a sleep cycle, which indicates that people with more delta-sleep activity are more prone to night terrors. However, they can also occur during daytime naps. Night terrors can often be mistaken for confusional arousal.While nightmares (bad dreams during REM sleep that cause feelings of horror or fear) are relatively common during childhood, night terrors occur less frequently. The prevalence of sleep terrors in general is unknown. The number of small children who experience sleep terror episodes (distinct from sleep terror disorder, which is recurrent and causes distress or impairment) are estimated at 36.9% at 18 months of age and at 19.7% at 30 months. In adults, the prevalence is lower, at only 2.2%. Night terrors have been known since ancient times, although it was impossible to differentiate them from nightmares until rapid eye movement was studied. Signs and symptoms The universal feature of night terrors is inconsolability, very similar to that of a panic attack. During night terror bouts, people are usually described as "bolting upright" with their eyes wide open and a look of fear and panic on their faces. They will often yell, scream, or attempt to speak, though such speech is often incomprehensible. Furthermore, they will usually sweat, exhibit rapid breathing, and have a rapid heart rate (autonomic signs). In some cases, individuals are likely to have even more elaborate motor activity, such as a thrashing of limbs—which may include punching, swinging, or fleeing motions. There is a sense that the individuals are trying to protect themselves and/or escape from a possible threat of bodily injury. Although people may seem to be awake during a night terror, they will appear confused, be inconsolable and/or unresponsive to attempts to communicate with them, and may not recognize others familiar to them. Occasionally, when a person with a night terror is awakened, they will lash out at the one awakening them, which can be dangerous to that individual. Most people who experience this do not remember the incident the next day, although brief dream images or hallucinations may occur and be recalled. Sleepwalking is also common during night-terror bouts, as sleepwalking and night terrors are different manifestations of the same parasomnia. Both children and adults may display behaviour indicative of attempting to escape; some may thrash about or get out of bed and begin walking or running around aimlessly while inconsolable, increasing the risk of accidental injury. The risk of injury to others may be exacerbated by inadvertent provocation by nearby people, whose efforts to calm the individual may result in a physically violent response from the individual as they attempt to escape.During lab tests, subjects are known to have very high voltages of electroencephalography (EEG) delta activity, an increase in muscle tone, and a doubled or faster heart rate. Brain activities during a typical episode show theta and alpha activity when monitored with an EEG. Episodes can include tachycardia. Night terrors are also associated with intense autonomic discharge of tachypnea, flushing, diaphoresis, and mydriasis—that is, unconscious or involuntary rapid breathing, reddening of the skin, profuse sweating, and dilation of the pupils. Abrupt but calmer arousal from NREM sleep, short of a full night-terror episode, is also common. In children with night terrors, there is no increased occurrence of psychiatric diagnoses. However, in adults with night terrors there is a close association with psychopathology and mental disorders. There may be an increased occurrence of night terrors—particularly among those with post-traumatic stress disorder (PTSD) and generalized anxiety disorder (GAD). It is also likely that some personality disorders may occur in individuals with night terrors, such as dependent, schizoid, and borderline personality disorders. There have been some symptoms of depression and anxiety that have increased in individuals that have frequent night terrors. Low blood sugar is associated with both pediatric and adult night terrors. A study of adults with thalamic lesions of the brain and brainstem have been occasionally associated with night terrors. Night terrors are closely linked to sleepwalking and frontal lobe epilepsy. Children Night terrors typically occur in children between the ages of three and twelve years, with a peak onset in children aged three and a half years old. An estimated 1–6% of children experience night terrors. Children of both sexes and all ethnic backgrounds are affected equally. In children younger than three and a half years old, peak frequency of night terrors is at least one episode per week. Among older children, peak frequency of night terrors is one or two episodes per month. The children will most likely have no recollection of the episode the next day. Pediatric evaluation may be sought to exclude the possibility that the night terrors are caused by seizure disorders or breathing problems. Most children will outgrow sleep terrors. Adults Night terrors in adults have been reported in all age ranges. Though the symptoms of night terrors in adolescents and adults are similar, the cause, prognosis and treatment are qualitatively different. These night terrors can occur each night if the individual does not eat a proper diet, get the appropriate amount or quality of sleep (e.g. sleep apnea), is enduring stressful events, or if he or she remains untreated. Adult night terrors are much less common, and often respond to treatments to rectify causes of poor quality or quantity of sleep. Night terrors are classified as a mental and behavioral disorder in the ICD. A study done about night terrors in adults showed that other psychiatric symptoms were prevalent in most patients experiencing night terrors hinting at the comorbidity of the two. There is some evidence of a link between night terrors and hypoglycemia.When a night terror happens, it is typical for a person to wake up yelling and kicking and to be able to recognize what he or she is saying. The person may even run out of the house (more common among adults) which can then lead to violent actions. It has been found that some adults who have been on a long-term intrathecal clonidine therapy show side effects of night terrors, such as feelings of terror early in the sleep cycle. This is due to the possible alteration of cervical/brain clonidine concentration. In adults, night terrors can be symptomatic of neurological disease and can be further investigated through an MRI procedure. Causes There is some evidence that a predisposition to night terrors and other parasomnias may be congenital. Individuals frequently report that past family members have had either episodes of sleep terrors or sleepwalking. In some studies, a ten-fold increase in the prevalence of night terrors in first-degree biological relatives has been observed—however, the exact link to inheritance is not known. Familial aggregation has been found suggesting that there is an autosomal mode of inheritance. In addition, some laboratory findings suggest that sleep deprivation and having a fever can increase the likelihood of a night terror episode occurring. Other contributing factors include nocturnal asthma, gastroesophageal reflux, central nervous system medications, and a constricted nasal passage. Special consideration must be used when the subject with narcolepsy, as there may be a link. There have been no findings that show a cultural difference between manifestations of night terrors, though it is thought that the significance and cause of night terrors differ within cultures. Also, older children and adults provide highly detailed and descriptive images associated with their sleep terrors compared to younger children, who either cannot recall or only vaguely remember. Sleep terrors in children are also more likely to occur in males than females; in adults, the ratio between sexes is equal. A longitudinal study examined twins, both identical and fraternal, and found that a significantly higher concordance rate of night terror was found in identical twins than in fraternal.Though the symptoms of night terrors in adolescents and adults are similar, their causes, prognoses, and treatments are qualitatively different. There is some evidence that suggests that night terrors can occur if the individual does not eat a proper diet, does not get the appropriate amount or quality of sleep (e.g., because of sleep apnea), or is enduring stressful events. Adults who have experienced sexual abuse are more likely to receive a diagnosis of sleep disorders, including night terrors. Overall, though, adult night terrors are much less common and often respond best to treatments that rectify causes of poor quality or quantity of sleep. Diagnosis The DSM-5 diagnostic criteria for sleep terror disorder requires: Recurrent periods where the individual abruptly but not completely wakes from sleep, usually occurring during the first third major period of sleep. The individual experiences intense fear with a panicky scream at the beginning and symptoms of autonomic arousal, such as increased heart rate, heavy breathing, and increased perspiration. The individual cannot be soothed or comforted during the episode. The individual is unable or almost unable to remember images of the dream (only a single visual scene for example). The episode is completely forgotten. The occurrence of the sleep terror episode causes clinically significant distress or impairment in the individuals functioning. The disturbance is not due to the effects of a substance, general medical condition or medication. Coexisting mental or medical disorders do not explain the episodes of sleep terrors. Differential diagnosis Night terrors are distinct from nightmares. In fact, in nightmares there are almost never vocalization or agitation, and if there are any, they are less strong in comparison to night terrors. In addition, nightmares appear ordinarily during REM sleep in contrast to night terrors, which occur in NREM sleep. Finally, individuals with nightmares can wake up completely and easily and have clear and detailed memories of their dreams.A distinction between night terrors and epileptic seizure is required. Indeed, an epileptic seizure could happen during the night but also during the day. To make the difference between both of them, an EEG can be done and if there are some anomalies on it, it would rather be an epileptic seizure. Assessment The assessment of sleep terrors is similar to the assessment of other parasomnias and must include: When the episode occurs during the sleep period Age of onset How often these episodes occur (frequency) and how long they last for (duration) Description of the episode, including behavior, emotions, and thoughts during and after the event How responsive the patient is to external stimuli during the episode How conscious or aware the patient is, when awakened from an episode If the episode is remembered afterwards The triggers or precipitating factors Sleep–wake pattern and sleep environment Daytime sleepiness Other sleep disorders that might be present Family history for NREM parasomnias and other sleep disorders Medical, psychiatric, and neurological history Medication and substance use historyAdditionally, a home video might be helpful for a proper diagnosis. A polysomnography in the sleep laboratory is recommended for ruling out other disorders, however, sleep terrors occur less frequently in the sleep laboratory than at home and a polysomnography can therefore be unsuccessful at recording the sleep terror episode. Treatment In most children, night terrors eventually subside and do not need to be treated. It may be helpful to reassure the child and their family that they will outgrow this disorder.The duration of one episode is mostly brief but it may last longer if parents try to wake up the child. Awakening the child may make their agitation stronger. For all these reasons, it is important to let the sleep terror episode fade away and to just be vigilant in order for them not to fall to the ground.Considering an episode could be violent, it may be advisable to secure the environment in which the child sleeps. Windows should be closed and potentially dangerous items should be removed from the bedroom, and additionally, alarms can be installed and the child placed in a downstairs bedroom.There is some evidence to suggest that night terrors can result from lack of sleep or poor sleeping habits. In these cases, it can be helpful to improve the amount and quality of sleep which the child is getting. It is also important to have a good sleep hygiene, if a child has night terrors parents could try to change their sleep hygiene. Another option could be to adapt childs naps so that they are not too long or too short. Then, excessive stress or conflicts in a childs life could also have an impact on their sleep too, so to have some strategies to cope with stress combined with psychotherapy could decrease the frequency of the episodes. A polysomnography can be recommended if the child continues to have a lot of night terror episodes.Hypnosis could be efficient. Sleepers could become less sensitive to their sleep terrors.One technique is to wake up just before the sleep terrors begin. When they appear regularly, this method can prevent their appearance.Psychotherapy or counseling might be helpful in some cases. If all these methods are not enough, benzodiazepines (such as diazepam) or tricyclic antidepressants may be used; however, medication is only recommended in extreme cases. Widening the nasal airway by surgical removal of the adenoid was previously considered and demonstrated to be effective; nowadays, however, invasive treatments are generally avoided. Research A small study of paroxetine found some benefit.Another small trial found benefit with L-5-hydroxytryptophan (L-5-HTP). See also Ephialtes (illness) Horror and terror Sleep paralysis References External links Night Terror Resource Center National Library of Medicine - Medical Subject Headings: Night Terrors

Hello Aarogya, could you help me understand about Smallpox

Smallpox

Smallpox was an infectious disease caused by one of two virus variants, Variola major and Variola minor. The agent of variola virus (VARV) belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) certified the global eradication of the disease in 1980, making it the only human disease to be eradicated.The initial symptoms of the disease included fever and vomiting. This was followed by formation of ulcers in the mouth and a skin rash. Over a number of days, the skin rash turned into the characteristic fluid-filled blisters with a dent in the center. The bumps then scabbed over and fell off, leaving scars. The disease was spread between people or via contaminated objects. Prevention was achieved mainly through the smallpox vaccine. Once the disease had developed, certain antiviral medication may have helped. The risk of death was about 30%, with higher rates among babies. Often, those who survived had extensive scarring of their skin, and some were left blind.The earliest evidence of the disease dates to around 1500 BCE in Egyptian mummies. The disease historically occurred in outbreaks. In 18th-century Europe, it is estimated that 400,000 people died from the disease per year, and that one-third of all cases of blindness were due to smallpox. Smallpox is estimated to have killed up to 300 million people in the 20th century and around 500 million people in the last 100 years of its existence. Earlier deaths included six European monarchs. As recently as 1967, 15 million cases occurred a year.Inoculation for smallpox appears to have started in China around the 1500s. Europe adopted this practice from Asia in the first half of the 18th century. In 1796, Edward Jenner introduced the modern smallpox vaccine. In 1967, the WHO intensified efforts to eliminate the disease. Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest in 2011. The term "smallpox" was first used in Britain in the early 16th century to distinguish the disease from syphilis, which was then known as the "great pox". Other historical names for the disease include pox, speckled monster, and red plague. Classification There are two forms of the smallpox virus. Variola major is the severe and most common form, with a more extensive rash and higher fever. Variola minor is a less common presentation, causing less severe disease, typically discrete smallpox, with historical death rates of 1% or less. Subclinical (asymptomatic) infections with Variola virus were noted but were not common. In addition, a form called variola sine eruptione (smallpox without rash) was seen generally in vaccinated persons. This form was marked by a fever that occurred after the usual incubation period and could be confirmed only by antibody studies or, rarely, by viral culture. In addition, there were two very rare and fulminating types of smallpox, the malignant (flat) and hemorrhagic forms, which were usually fatal. Signs and symptoms The initial symptoms were similar to other viral diseases that are still extant, such as influenza and the common cold: fever of at least 38.3 °C (101 °F), muscle pain, malaise, headache and fatigue. As the digestive tract was commonly involved, nausea, vomiting, and backache often occurred. The early prodromal stage usually lasted 2–4 days. By days 12–15, the first visible lesions – small reddish spots called enanthem – appeared on mucous membranes of the mouth, tongue, palate, and throat, and the temperature fell to near-normal. These lesions rapidly enlarged and ruptured, releasing large amounts of virus into the saliva.Smallpox virus tended to attack skin cells, causing the characteristic pimples, or macules, associated with the disease. A rash developed on the skin 24 to 48 hours after lesions on the mucous membranes appeared. Typically the macules first appeared on the forehead, then rapidly spread to the whole face, proximal portions of extremities, the trunk, and lastly to distal portions of extremities. The process took no more than 24 to 36 hours, after which no new lesions appeared. At this point, variola major infection could take several very different courses, which resulted in four types of smallpox disease based on the Rao classification: ordinary, modified, malignant (or flat), and hemorrhagic smallpox. Historically, ordinary smallpox had an overall fatality rate of about 30%, and the malignant and hemorrhagic forms were usually fatal. The modified form was almost never fatal. In early hemorrhagic cases, hemorrhages occurred before any skin lesions developed. The incubation period between contraction and the first obvious symptoms of the disease was around 12 days. Ordinary Ninety percent or more of smallpox cases among unvaccinated persons were of the ordinary type. In this form of the disease, by the second day of the rash the macules had become raised papules. By the third or fourth day, the papules had filled with an opalescent fluid to become vesicles. This fluid became opaque and turbid within 24–48 hours, resulting in pustules. By the sixth or seventh day, all the skin lesions had become pustules. Between seven and ten days the pustules had matured and reached their maximum size. The pustules were sharply raised, typically round, tense, and firm to the touch. The pustules were deeply embedded in the dermis, giving them the feel of a small bead in the skin. Fluid slowly leaked from the pustules, and by the end of the second week, the pustules had deflated and began to dry up, forming crusts or scabs. By day 16–20 scabs had formed over all of the lesions, which had started to flake off, leaving depigmented scars.Ordinary smallpox generally produced a discrete rash, in which the pustules stood out on the skin separately. The distribution of the rash was most dense on the face, denser on the extremities than on the trunk, and denser on the distal parts of the extremities than on the proximal. The palms of the hands and soles of the feet were involved in most cases. Sometimes, the blisters merged into sheets, forming a confluent rash, which began to detach the outer layers of skin from the underlying flesh. Patients with confluent smallpox often remained ill even after scabs had formed over all the lesions. In one case series, the case-fatality rate in confluent smallpox was 62 percent. Modified Referring to the character of the eruption and the rapidity of its development, modified smallpox occurred mostly in previously vaccinated people. It was rare in unvaccinated people, with one case study showing 1–2% of modified cases compared to around 25% in vaccinated people. In this form, the prodromal illness still occurred but may have been less severe than in the ordinary type. There was usually no fever during the evolution of the rash. The skin lesions tended to be fewer and evolved more quickly, were more superficial, and may not have shown the uniform characteristic of more typical smallpox. Modified smallpox was rarely, if ever, fatal. This form of variola major was more easily confused with chickenpox. Malignant In malignant-type smallpox (also called flat smallpox) the lesions remained almost flush with the skin at the time when raised vesicles would have formed in the ordinary type. It is unknown why some people developed this type. Historically, it accounted for 5–10 percent of cases, and most (72 percent) were children. Malignant smallpox was accompanied by a severe prodromal phase that lasted 3–4 days, prolonged high fever, and severe symptoms of viremia. The prodromal symptoms continued even after the onset of the rash. The rash on the mucous membranes (enanthem) was extensive. Skin lesions matured slowly, were typically confluent or semi-confluent, and by the seventh or eighth day, they were flat and appeared to be buried in the skin. Unlike ordinary-type smallpox, the vesicles contained little fluid, were soft and velvety to the touch, and may have contained hemorrhages. Malignant smallpox was nearly always fatal and death usually occurred between the 8th and 12th day of illness. Often, a day or two before death, the lesions turned ashen gray, which, along with abdominal distension, was a bad prognostic sign. This form is thought to be caused by deficient cell-mediated immunity to smallpox. If the person recovered, the lesions gradually faded and did not form scars or scabs. Hemorrhagic Hemorrhagic smallpox is a severe form accompanied by extensive bleeding into the skin, mucous membranes, gastrointestinal tract, and viscera. This form develops in approximately two percent of infections and occurs mostly in adults. Pustules do not typically form in hemorrhagic smallpox. Instead, bleeding occurs under the skin, making it look charred and black, hence this form of the disease is also referred to as variola nigra or "black pox". Hemorrhagic smallpox has very rarely been caused by Variola minor. While bleeding may occur in mild cases and not affect outcomes, hemorrhagic smallpox is typically fatal. Vaccination does not appear to provide any immunity to either form of hemorrhagic smallpox and some cases even occurred among people that were revaccinated shortly before. It has two forms. Early The early or fulminant form of hemorrhagic smallpox (referred to as purpura variolosa) begins with a prodromal phase characterized by a high fever, severe headache, and abdominal pain. The skin becomes dusky and erythematous, and this is rapidly followed by the development of petechiae and bleeding in the skin, conjunctiva and mucous membranes. Death often occurs suddenly between the fifth and seventh days of illness, when only a few insignificant skin lesions are present. Some people survive a few days longer, during which time the skin detaches and fluid accumulates under it, rupturing at the slightest injury. People are usually conscious until death or shortly before. Autopsy reveals petechiae and bleeding in the spleen, kidney, serous membranes, skeletal muscles, pericardium, liver, gonads and bladder. Historically, this condition was frequently misdiagnosed, with the correct diagnosis made only at autopsy. This form is more likely to occur in pregnant women than in the general population (approximately 16% of cases in unvaccinated pregnant women were early hemorrhagic smallpox, versus roughly 1% in nonpregnant women and adult males). The case fatality rate of early hemorrhagic smallpox approaches 100%. Late There is also a later form of hemorrhagic smallpox (referred to late hemorrhagic smallpox, or variolosa pustula hemorrhagica). The prodrome is severe and similar to that observed in early hemorrhagic smallpox, and the fever persists throughout the course of the disease. Bleeding appears in the early eruptive period (but later than that seen in purpura variolosa), and the rash is often flat and does not progress beyond the vesicular stage. Hemorrhages in the mucous membranes appear to occur less often than in the early hemorrhagic form. Sometimes the rash forms pustules which bleed at the base and then undergo the same process as in ordinary smallpox. This form of the disease is characterized by a decrease in all of the elements of the coagulation cascade and an increase in circulating antithrombin. This form of smallpox occurs anywhere from three to 25 percent of fatal cases, depending on the virulence of the smallpox strain. Most people with the late-stage form die within eight to 10 days of illness. Among the few who recover, the hemorrhagic lesions gradually disappear after a long period of convalescence. The case fatality rate for late hemorrhagic smallpox is around 90-95%. Pregnant women are slightly more likely to experience this form of the disease, though not as much as early hemorrhagic smallpox. Cause Smallpox was caused by infection with Variola virus, which belongs to the family Poxviridae, subfamily Chordopoxvirinae, and genus Orthopoxvirus. Evolution The date of the appearance of smallpox is not settled. It most probably evolved from a terrestrial African rodent virus between 68,000 and 16,000 years ago. The wide range of dates is due to the different records used to calibrate the molecular clock. One clade was the Variola major strains (the more clinically severe form of smallpox) which spread from Asia between 400 and 1,600 years ago. A second clade included both Alastrim minor (a phenotypically mild smallpox) described from the American continents and isolates from West Africa which diverged from an ancestral strain between 1,400 and 6,300 years before present. This clade further diverged into two subclades at least 800 years ago.A second estimate has placed the separation of variola from Taterapox (an Orthopoxvirus of some African rodents including gerbils) at 3,000 to 4,000 years ago. This is consistent with archaeological and historical evidence regarding the appearance of smallpox as a human disease which suggests a relatively recent origin. If the mutation rate is assumed to be similar to that of the herpesviruses, the divergence date of variola from Taterapox has been estimated to be 50,000 years ago. While this is consistent with the other published estimates, it suggests that the archaeological and historical evidence is very incomplete. Better estimates of mutation rates in these viruses are needed. Examination of a strain that dates from c. 1650 found that this strain was basal to the other presently sequenced strains. The mutation rate of this virus is well modeled by a molecular clock. Diversification of strains only occurred in the 18th and 19th centuries. Virology Variola is a large brick-shaped virus measuring approximately 302 to 350 nanometers by 244 to 270 nm, with a single linear double stranded DNA genome 186 kilobase pairs (kbp) in size and containing a hairpin loop at each end. The two classic varieties of smallpox are variola major and variola minor. Four orthopoxviruses cause infection in humans: variola, vaccinia, cowpox, and monkeypox. Variola infects only humans in nature, although primates and other animals have been infected in an experimental setting. Vaccinia, cowpox, and monkeypox viruses can infect both humans and other animals in nature.The life cycle of poxviruses is complicated by having multiple infectious forms, with differing mechanisms of cell entry. Poxviruses are unique among human DNA viruses in that they replicate in the cytoplasm of the cell rather than in the nucleus. To replicate, poxviruses produce a variety of specialized proteins not produced by other DNA viruses, the most important of which is a viral-associated DNA-dependent RNA polymerase. Both enveloped and unenveloped virions are infectious. The viral envelope is made of modified Golgi membranes containing viral-specific polypeptides, including hemagglutinin. Infection with either variola major or variola minor confers immunity against the other. Variola Major The more common, infectious form of the virus comes from the Variola major strain. Variola minor Variola minor, also called alastrim, was a less common form of the virus, and much less deadly. Although Variola minor had the same incubation period and pathogenetic stages as smallpox, it is believed to have had a mortality rate of less than 1%, as compared to smallpoxs 30%. Like Variola major, Variola minor was spread through inhalation of the virus in the air, which could occur through face-to-face contact or through fomites. Infection with Variola minor conferred immunity against the more dangerous variola major. Because variola minor was a less debilitating disease than smallpox, patients were more frequently ambulant and thus able to infect others more rapidly. As such, Variola minor swept through the United States, Great Britain, and South Africa in the early 20th century, becoming the dominant form of the disease in those areas and thus rapidly decreasing mortality rates. Along with Variola major, the minor form has now been totally eradicated from the globe. The last case of indigenous Variola minor was reported in a Somali cook, Ali Maow Maalin, in October 1977, and smallpox was officially declared eradicated worldwide in May 1980. Variola minor was also called white pox, kaffir pox, Cuban itch, West Indian pox, milk pox, and pseudovariola. Genome composition The genome of Variola major is about 186,000 base pairs in length. It is made from linear double stranded DNA and contains the coding sequence for about 200 genes. The genes are usually not overlapping and typically occur in blocks that point towards the closer terminal region of the genome. The coding sequence of the central region of the genome is highly consistent across orthopoxviruses, and the arrangement of genes is consistent across chordopoxvirusesThe center of the variola genome contains the majority of the essential viral genes, including the genes for structural proteins, DNA replication, transcription, and mRNA synthesis. The ends of the genome vary more across strains and species of orthopoxviruses. These regions contain proteins that modulate the hosts immune systems, and are primarily responsible for the variability in virulence across the orthopoxvirus family. These terminal regions in poxviruses are inverted terminal repetitions (ITR) sequences. These sequences are identical but oppositely oriented on either end of the genome, leading to the genome being a continuous loop of DNA Components of the ITR sequences include an incompletely base paired A/T rich hairpin loop, a region of roughly 100 base pairs necessary for resolving concatomeric DNA (a stretch of DNA containing multiple copies of the same sequence), a few open reading frames, and short tandemly repeating sequences of varying number and length. The ITRs of poxviridae vary in length across strains and species. The coding sequence for most of the viral proteins in Variola major have at least 90% similarity with the genome of Vaccinia, a related virus used for vaccination against smallpox. Gene expression Gene expression of variola occurs entirely within the cytoplasm of the host cell, and follows a distinct progression during infection. After entry of an infectious virion into a host cell, synthesis of viral mRNA can be detected within 20 minutes. About half of the viral genome is transcribed prior to the replication of viral DNA. The first set of expressed genes are transcribed by pre-existing viral machinery packaged within the infecting virion. These genes encode the factors necessary for viral DNA synthesis and for transcription of the next set of expressed genes. Unlike most DNA viruses, DNA replication in variola and other poxviruses takes place within the cytoplasm of the infected cell. The exact timing of DNA replication after infection of a host cell varies across the poxviridae. Recombination of the genome occurs within actively infected cells. Following the onset of viral DNA replication, an intermediate set of genes codes for transcription factors of late gene expression. The products of the later genes include transcription factors necessary for transcribing the early genes for new virions, as well as viral RNA polymerase and other essential enzymes for new viral particles. These proteins are then packaged into new infectious virions capable of infecting other cells. Research Two live samples of Variola major remain, one in the United States at the CDC in Atlanta, and one at the Vector Institute in Koltsovo, Russia. Research with the remaining virus samples is tightly controlled, and each research proposal must be approved by the WHO and the World Health Assembly (WHA). Most research on poxviruses is performed using the closely related Vaccinia virus as a model organism. Vaccinia virus, which is used to vaccinate for smallpox, is also under research as a viral vector for vaccines for unrelated diseases.The genome of Variola major was first sequenced in its entirety in the 1990s. The complete coding sequence is publicly available online.The current reference sequence for Variola major was sequenced from a strain that circulated in India in 1967. In addition, there are sequences for samples of other strains that were collected during the WHO eradication campaign. A genome browser for a complete database of annotated sequences of Variola and other poxviruses is publicly available through the Viral Bioinformatics Resource Center. Genetic engineering The WHO currently bans genetic engineering of the smallpox virus. However, in 2004, a committee advisory to the WHO voted in favor of allowing editing of the genome of the two remaining samples of Variola major to add a marker gene. This gene, called GFP, or green fluorescent protein, would cause live samples of the virus to glow green under fluorescent light. The insertion of this gene, which would not influence the virulence of the virus, would be the only allowed modification of the genome. The committee stated the proposed modification would aid in research of treatments by making it easier to assess whether a potential treatment was effective in killing viral samples. The recommendation could only take effect if approved by the WHA. When the WHA discussed the proposal in 2005, it refrained from taking a formal vote on the proposal, stating that it would review individual research proposals one at a time. Addition of the GFP gene to the Vaccinia genome is routinely performed during research on the closely related Vaccinia virus. Controversies The public availability of variolas complete sequence has raised concerns about the possibility of illicit synthesis of infectious virus. Vaccinia, a cousin of the smallpox virus, was artificially synthesized in 2002 by NIH scientists. They used a previously established method that involved using a recombinant viral genome to create a self-replicating bacterial plasmid that produced viral particles.In 2016, another group synthesized the horsepox virus using publicly available sequence data for horsepox. The researchers argued that their work would be beneficial to creating a safer and more effective vaccine for smallpox, although an effective vaccine is already available. The horsepox virus had previously seemed to have gone extinct, raising concern about potential revival of Variola major and causing other scientists to question their motives. Critics found it especially concerning that the group was able to recreate viable virus in a short time frame with relatively little cost or effort. Although the WHO bans individual laboratories from synthesizing more than 20% of the genome at a time, and purchases of smallpox genome fragments are monitored and regulated, a group with malicious intentions could compile, from multiple sources, the full synthetic genome necessary to produce viable virus. Transmission Transmission occurred through inhalation of airborne Variola virus, usually droplets expressed from the oral, nasal, or pharyngeal mucosa of an infected person. It was transmitted from one person to another primarily through prolonged face-to-face contact with an infected person, usually, within a distance of 1.8 m (6 feet), but could also be spread through direct contact with infected bodily fluids or contaminated objects (fomites) such as bedding or clothing. Rarely, smallpox was spread by virus carried in the air in enclosed settings such as buildings, buses, and trains. The virus can cross the placenta, but the incidence of congenital smallpox was relatively low. Smallpox was not notably infectious in the prodromal period and viral shedding was usually delayed until the appearance of the rash, which was often accompanied by lesions in the mouth and pharynx. The virus can be transmitted throughout the course of the illness, but this happened most frequently during the first week of the rash when most of the skin lesions were intact. Infectivity waned in 7 to 10 days when scabs formed over the lesions, but the infected person was contagious until the last smallpox scab fell off.Smallpox was highly contagious, but generally spread more slowly and less widely than some other viral diseases, perhaps because transmission required close contact and occurred after the onset of the rash. The overall rate of infection was also affected by the short duration of the infectious stage. In temperate areas, the number of smallpox infections was highest during the winter and spring. In tropical areas, seasonal variation was less evident and the disease was present throughout the year. Age distribution of smallpox infections depended on acquired immunity. Vaccination immunity declined over time and was probably lost within thirty years. Smallpox was not known to be transmitted by insects or animals and there was no asymptomatic carrier state. Mechanism Once inhaled, the variola virus invaded the mucus membranes of the mouth, throat, and respiratory tract. From there, it migrated to regional lymph nodes and began to multiply. In the initial growth phase, the virus seemed to move from cell to cell, but by around the 12th day, widespread lysis of infected cells occurred and the virus could be found in the bloodstream in large numbers, a condition known as viremia. This resulted in the second wave of multiplication in the spleen, bone marrow, and lymph nodes. Diagnosis The clinical definition of ordinary smallpox is an illness with acute onset of fever equal to or greater than 38.3 °C (101 °F) followed by a rash characterized by firm, deep-seated vesicles or pustules in the same stage of development without other apparent cause. When a clinical case was observed, smallpox was confirmed using laboratory tests. Microscopically, poxviruses produce characteristic cytoplasmic inclusion bodies, the most important of which are known as Guarnieri bodies, and are the sites of viral replication. Guarnieri bodies are readily identified in skin biopsies stained with hematoxylin and eosin, and appear as pink blobs. They are found in virtually all poxvirus infections but the absence of Guarnieri bodies could not be used to rule out smallpox. The diagnosis of an orthopoxvirus infection can also be made rapidly by electron microscopic examination of pustular fluid or scabs. All orthopoxviruses exhibit identical brick-shaped virions by electron microscopy. If particles with the characteristic morphology of herpesviruses are seen this will eliminate smallpox and other orthopoxvirus infections. Definitive laboratory identification of Variola virus involved growing the virus on chorioallantoic membrane (part of a chicken embryo) and examining the resulting pock lesions under defined temperature conditions. Strains were characterized by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Serologic tests and enzyme linked immunosorbent assays (ELISA), which measured Variola virus-specific immunoglobulin and antigen were also developed to assist in the diagnosis of infection.Chickenpox was commonly confused with smallpox in the immediate post-eradication era. Chickenpox and smallpox could be distinguished by several methods. Unlike smallpox, chickenpox does not usually affect the palms and soles. Additionally, chickenpox pustules are of varying size due to variations in the timing of pustule eruption: smallpox pustules are all very nearly the same size since the viral effect progresses more uniformly. A variety of laboratory methods were available for detecting chickenpox in the evaluation of suspected smallpox cases. Prevention The earliest procedure used to prevent smallpox was inoculation with variola minor (known as variolation after the introduction of smallpox vaccine to avoid possible confusion), which likely occurred in India, Africa, and China well before the practice arrived in Europe. The idea that inoculation originated in India has been challenged, as few of the ancient Sanskrit medical texts described the process of inoculation. Accounts of inoculation against smallpox in China can be found as early as the late 10th century, and the procedure was widely practiced by the 16th century, during the Ming dynasty. If successful, inoculation produced lasting immunity to smallpox. Because the person was infected with Variola virus, a severe infection could result, and the person could transmit smallpox to others. Variolation had a 0.5–2 percent mortality rate, considerably less than the 20–30 percent mortality rate of the disease. Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers.Lady Mary Wortley Montagu observed smallpox inoculation during her stay in the Ottoman Empire, writing detailed accounts of the practice in her letters, and enthusiastically promoted the procedure in England upon her return in 1718. According to Voltaire (1742), the Turks derived their use of inoculation from neighbouring Circassia. Voltaire does not speculate on where the Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years". In 1721, Cotton Mather and colleagues provoked controversy in Boston by inoculating hundreds. After publishing The present method of inoculating for the small-pox in 1767, Dr Thomas Dimsdale was invited to Russia to variolate the Empress Catherine the Great of Russia and her son, Grand Duke Paul, which he successfully did in 1768. In 1796, Edward Jenner, a doctor in Berkeley, Gloucestershire, rural England, discovered that immunity to smallpox could be produced by inoculating a person with material from a cowpox lesion. Cowpox is a poxvirus in the same family as variola. Jenner called the material used for inoculation vaccine from the root word vacca, which is Latin for cow. The procedure was much safer than variolation and did not involve a risk of smallpox transmission. Vaccination to prevent smallpox was soon practiced all over the world. During the 19th century, the cowpox virus used for smallpox vaccination was replaced by the vaccinia virus. Vaccinia is in the same family as cowpox and variola but is genetically distinct from both. The origin of the vaccinia virus and how it came to be in the vaccine are not known. The current formulation of the smallpox vaccine is a live virus preparation of the infectious vaccinia virus. The vaccine is given using a bifurcated (two-pronged) needle that is dipped into the vaccine solution. The needle is used to prick the skin (usually the upper arm) several times in a few seconds. If successful, a red and itchy bump develops at the vaccine site in three or four days. In the first week, the bump becomes a large blister (called a "Jennerian vesicle") which fills with pus and begins to drain. During the second week, the blister begins to dry up, and a scab forms. The scab falls off in the third week, leaving a small scar.The antibodies induced by the vaccinia vaccine are cross-protective for other orthopoxviruses, such as monkeypox, cowpox, and variola (smallpox) viruses. Neutralizing antibodies are detectable 10 days after first-time vaccination and seven days after revaccination. Historically, the vaccine has been effective in preventing smallpox infection in 95 percent of those vaccinated. Smallpox vaccination provides a high level of immunity for three to five years and decreasing immunity thereafter. If a person is vaccinated again later, the immunity lasts even longer. Studies of smallpox cases in Europe in the 1950s and 1960s demonstrated that the fatality rate among persons vaccinated less than 10 years before exposure was 1.3 percent; it was 7 percent among those vaccinated 11 to 20 years prior, and 11 percent among those vaccinated 20 or more years before infection. By contrast, 52 percent of unvaccinated persons died. There are side effects and risks associated with the smallpox vaccine. In the past, about 1 out of 1,000 people vaccinated for the first time experienced serious, but non-life-threatening, reactions, including toxic or allergic reaction at the site of the vaccination (erythema multiforme), spread of the vaccinia virus to other parts of the body, and spread to other individuals. Potentially life-threatening reactions occurred in 14 to 500 people out of every 1 million people vaccinated for the first time. Based on past experience, it is estimated that 1 or 2 people in 1 million (0.000198 percent) who receive the vaccine may die as a result, most often the result of postvaccinial encephalitis or severe necrosis in the area of vaccination (called progressive vaccinia).Given these risks, as smallpox became effectively eradicated and the number of naturally occurring cases fell below the number of vaccine-induced illnesses and deaths, routine childhood vaccination was discontinued in the United States in 1972 and was abandoned in most European countries in the early 1970s. Routine vaccination of health care workers was discontinued in the U.S. in 1976, and among military recruits in 1990 (although military personnel deploying to the Middle East and Korea still receive the vaccination). By 1986, routine vaccination had ceased in all countries. It is now primarily recommended for laboratory workers at risk for occupational exposure. However, the possibility of smallpox virus being used as a biological weapon has rekindled interest in the development of newer vaccines. The smallpox vaccine is also used to protect against monkeypox, of which the smallpox vaccine also protects against. Treatment Smallpox vaccination within three days of exposure will prevent or significantly lessen the severity of smallpox symptoms in the vast majority of people. Vaccination four to seven days after exposure can offer some protection from disease or may modify the severity of the disease. Other than vaccination, treatment of smallpox is primarily supportive, such as wound care and infection control, fluid therapy, and possible ventilator assistance. Flat and hemorrhagic types of smallpox are treated with the same therapies used to treat shock, such as fluid resuscitation. People with semi-confluent and confluent types of smallpox may have therapeutic issues similar to patients with extensive skin burns.In July 2018, the Food and Drug Administration approved tecovirimat, the first drug approved for treatment of smallpox. Antiviral treatments have improved since the last large smallpox epidemics, and studies suggest that the antiviral drug cidofovir might be useful as a therapeutic agent. The drug must be administered intravenously, and may cause serious kidney toxicity.ACAM2000 is a smallpox vaccine developed by Acambis. It was approved for use in the United States by the U.S. FDA on August 31, 2007. It contains live vaccinia virus, cloned from the same strain used in an earlier vaccine, Dryvax. While the Dryvax virus was cultured in the skin of calves and freeze-dried, ACAM2000s virus is cultured in kidney epithelial cells (Vero cells) from an African green monkey. Efficacy and adverse reaction incidence are similar to Dryvax. The vaccine is not routinely available to the US public; it is, however, used in the military and maintained in the Strategic National Stockpile.In June 2021, brincidofovir was approved for medical use in the United States for the treatment of human smallpox disease caused by variola virus. Prognosis The mortality rate from variola minor is approximately 1%, while the mortality rate from variola major is approximately 30%.Ordinary type-confluent is fatal about 50–75% of the time, ordinary-type semi-confluent about 25–50% of the time, in cases where the rash is discrete the case-fatality rate is less than 10%. The overall fatality rate for children younger than 1 year of age is 40–50%. Hemorrhagic and flat types have the highest fatality rates. The fatality rate for flat or late hemorrhagic type smallpox is 90% or greater and nearly 100% is observed in cases of early hemorrhagic smallpox. The case-fatality rate for variola minor is 1% or less. There is no evidence of chronic or recurrent infection with Variola virus. In cases of flat smallpox in vaccinated people, the condition was extremely rare but less lethal, with one case series showing a 66.7% death rate.In fatal cases of ordinary smallpox, death usually occurs between days 10-16 of the illness. The cause of death from smallpox is not clear, but the infection is now known to involve multiple organs. Circulating immune complexes, overwhelming viremia, or an uncontrolled immune response may be contributing factors. In early hemorrhagic smallpox, death occurs suddenly about six days after the fever develops. The cause of death in early hemorrhagic cases is commonly due to heart failure and pulmonary edema. In late hemorrhagic cases, high and sustained viremia, severe platelet loss and poor immune response were often cited as causes of death. In flat smallpox modes of death are similar to those in burns, with loss of fluid, protein and electrolytes, and fulminating sepsis. Complications Complications of smallpox arise most commonly in the respiratory system and range from simple bronchitis to fatal pneumonia. Respiratory complications tend to develop on about the eighth day of the illness and can be either viral or bacterial in origin. Secondary bacterial infection of the skin is a relatively uncommon complication of smallpox. When this occurs, the fever usually remains elevated.Other complications include encephalitis (1 in 500 patients), which is more common in adults and may cause temporary disability; permanent pitted scars, most notably on the face; and complications involving the eyes (2% of all cases). Pustules can form on the eyelid, conjunctiva, and cornea, leading to complications such as conjunctivitis, keratitis, corneal ulcer, iritis, iridocyclitis, and atrophy of the optic nerve. Blindness results in approximately 35-40% of eyes affected with keratitis and corneal ulcer. Hemorrhagic smallpox can cause subconjunctival and retinal hemorrhages. In 2-5% of young children with smallpox, virions reach the joints and bone, causing osteomyelitis variolosa. Bony lesions are symmetrical, most common in the elbows, legs, and characteristically cause separation of the epiphysis and marked periosteal reactions. Swollen joints limit movement, and arthritis may lead to limb deformities, ankylosis, malformed bones, flail joints, and stubby fingers.Between 65 and 80% of survivors are marked with deep pitted scars (pockmarks), most prominent on the face. History Disease emergence The earliest credible clinical evidence of smallpox is found in the descriptions of smallpox-like disease in medical writings from ancient India (as early as 1500 BCE), and China (1122 BCE), as well as a study of the Egyptian mummy of Ramses V, who died more than 3000 years ago (1145 BCE). It has been speculated that Egyptian traders brought smallpox to India during the 1st millennium BCE, where it remained as an endemic human disease for at least 2000 years. Smallpox was probably introduced into China during the 1st century CE from the southwest, and in the 6th century was carried from China to Japan. In Japan, the epidemic of 735–737 is believed to have killed as much as one-third of the population. At least seven religious deities have been specifically dedicated to smallpox, such as the god Sopona in the Yoruba religion in West Africa. In India, the Hindu goddess of smallpox, Shitala, was worshipped in temples throughout the country.A different viewpoint is that smallpox emerged 1588 CE and the earlier reported cases were incorrectly identified as smallpox.The timing of the arrival of smallpox in Europe and south-western Asia is less clear. Smallpox is not clearly described in either the Old or New Testaments of the Bible or in the literature of the Greeks or Romans. While some have identified the Plague of Athens – which was said to have originated in "Ethiopia" and Egypt – or the plague that lifted Carthages 396 BCE siege of Syracuse – with smallpox, many scholars agree it is very unlikely such a serious disease as variola major would have escaped being described by Hippocrates if it had existed in the Mediterranean region during his lifetime.While the Antonine Plague that swept through the Roman Empire in 165–180 CE may have been caused by smallpox, Saint Nicasius of Rheims became the patron saint of smallpox victims for having supposedly survived a bout in 450, and Saint Gregory of Tours recorded a similar outbreak in France and Italy in 580, the first use of the term variola. Other historians speculate that Arab armies first carried smallpox from Africa into Southwestern Europe during the 7th and 8th centuries. In the 9th century the Persian physician, Rhazes, provided one of the most definitive descriptions of smallpox and was the first to differentiate smallpox from measles and chickenpox in his Kitab fi al-jadari wa-al-hasbah (The Book of Smallpox and Measles). During the Middle Ages several smallpox outbreaks occurred in Europe. However, smallpox had not become established there until the population growth and mobility marked by the Crusades allowed it to do so. By the 16th century, smallpox had become entrenched across most of Europe, where it had a mortality rate as high as 30 percent. This endemic occurrence of smallpox in Europe is of particular historical importance, as successive exploration and colonization by Europeans tended to spread the disease to other nations. By the 16th century, smallpox had become a predominant cause of morbidity and mortality throughout much of the world. There were no credible descriptions of smallpox-like disease in the Americas before the westward exploration by Europeans in the 15th century CE. Smallpox was introduced into the Caribbean island of Hispaniola in 1507, and into the mainland in 1520, when Spanish settlers from Hispaniola arrived in Mexico, inadvertently carrying smallpox with them. Because the native Amerindian population had no acquired immunity to this new disease, their peoples were decimated by epidemics. Such disruption and population losses were an important factor in the Spanish achieving conquest of the Aztecs and the Incas. Similarly, English settlement of the east coast of North America in 1633 in Plymouth, Massachusetts was accompanied by devastating outbreaks of smallpox among Native American populations, and subsequently among the native-born colonists. Case fatality rates during outbreaks in Native American populations were as high as 90%. Smallpox was introduced into Australia in 1789 and again in 1829, though colonial surgeons, who by 1829 were attempting to distinguish between smallpox and chickenpox (which could be almost equally fatal to Aborigines), were divided as to whether the 1829–1830 epidemic was chickenpox or smallpox. Although smallpox was never endemic on the continent, it has been described as the principal cause of death in Aboriginal populations between 1780 and 1870. By the mid-18th century, smallpox was a major endemic disease everywhere in the world except in Australia and small islands untouched by outside exploration. In 18th century Europe, smallpox was a leading cause of death, killing an estimated 400,000 Europeans each year. Up to 10 percent of Swedish infants died of smallpox each year, and the death rate of infants in Russia might have been even higher. The widespread use of variolation in a few countries, notably Great Britain, its North American colonies, and China, somewhat reduced the impact of smallpox among the wealthy classes during the latter part of the 18th century, but a real reduction in its incidence did not occur until vaccination became a common practice toward the end of the 19th century. Improved vaccines and the practice of re-vaccination led to a substantial reduction in cases in Europe and North America, but smallpox remained almost unchecked everywhere else in the world. By the mid-20th century, variola minor occurred along with variola major, in varying proportions, in many parts of Africa. Patients with variola minor experience only a mild systemic illness, are often ambulant throughout the course of the disease, and are therefore able to more easily spread disease. Infection with v. minor induces immunity against the more deadly variola major form. Thus, as v. minor spread all over the US, into Canada, the South American countries, and Great Britain, it became the dominant form of smallpox, further reducing mortality rates. Eradication The first clear reference to smallpox inoculation was made by the Chinese author Wan Quan (1499–1582) in his Dòuzhěn xīnfǎ (痘疹心法) published in 1549, with earliest hints of the practice in China during the 10th century. In China, powdered smallpox scabs were blown up the noses of the healthy. People would then develop a mild case of the disease and from then on were immune to it. The technique did have a 0.5–2.0% mortality rate, but that was considerably less than the 20–30% mortality rate of the disease itself. Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers. Voltaire (1742) reports that the Chinese had practiced smallpox inoculation "these hundred years". Variolation had also been witnessed in Turkey by Lady Mary Wortley Montagu, who later introduced it in the UK.An early mention of the possibility of smallpoxs eradication was made in reference to the work of Johnnie Notions, a self-taught inoculator from Shetland, Scotland. Notions found success in treating people from at least the late 1780s through a method devised by himself despite having no formal medical background. His method involved exposing smallpox pus to peat smoke, burying it in the ground with camphor for up to 8 years, and then inserting the matter into a persons skin using a knife, and covering the incision with a cabbage leaf. He was reputed not to have lost a single patient. Arthur Edmondston, in writings on Notions technique that were published in 1809, stated, "Had every practitioner been as uniformly successful in the disease as he was, the small-pox might have been banished from the face of the earth, without injuring the system, or leaving any doubt as to the fact." The English physician Edward Jenner demonstrated the effectiveness of cowpox to protect humans from smallpox in 1796, after which various attempts were made to eliminate smallpox on a regional scale. In Russia in 1796, the first child to receive this treatment was bestowed the name "Vaccinov" by Catherine the Great, and was educated at the expense of the nation.The introduction of the vaccine to the New World took place in Trinity, Newfoundland in 1800 by Dr. John Clinch, boyhood friend and medical colleague of Jenner. As early as 1803, the Spanish Crown organized the Balmis expedition to transport the vaccine to the Spanish colonies in the Americas and the Philippines, and establish mass vaccination programs there. The U.S. Congress passed the Vaccine Act of 1813 to ensure that safe smallpox vaccine would be available to the American public. By about 1817, a robust state vaccination program existed in the Dutch East Indies.On August 26, 1807, Bavaria became the first country in the world to introduce compulsory vaccinations. Baden followed in 1809, Prussia in 1815, Württemberg in 1818, Sweden in 1816 and the German Empire in 1874 through the Reichs Vaccination Act. In Lutheran Sweden, the Protestant clergy played a pioneering role in voluntary smallpox vaccination as early as 1800. The first vaccination was carried out in Liechtenstein in 1801, and from 1812 it was mandatory to vaccinate.In British India a program was launched to propagate smallpox vaccination, through Indian vaccinators, under the supervision of European officials. Nevertheless, British vaccination efforts in India, and in Burma in particular, were hampered by indigenous preference for inoculation and distrust of vaccination, despite tough legislation, improvements in the local efficacy of the vaccine and vaccine preservative, and education efforts. By 1832, the federal government of the United States established a smallpox vaccination program for Native Americans. In 1842, the United Kingdom banned inoculation, later progressing to mandatory vaccination. The British government introduced compulsory smallpox vaccination by an Act of Parliament in 1853.In the United States, from 1843 to 1855, first Massachusetts and then other states required smallpox vaccination. Although some disliked these measures, coordinated efforts against smallpox went on, and the disease continued to diminish in the wealthy countries. In Northern Europe a number of countries had eliminated smallpox by 1900, and by 1914, the incidence in most industrialized countries had decreased to comparatively low levels. Vaccination continued in industrialized countries as protection against reintroduction until the mid to late 1970s. Australia and New Zealand are two notable exceptions; neither experienced endemic smallpox and never vaccinated widely, relying instead on protection by distance and strict quarantines. The first hemisphere-wide effort to eradicate smallpox was made in 1950 by the Pan American Health Organization. The campaign was successful in eliminating smallpox from all countries of the Americas except Argentina, Brazil, Colombia, and Ecuador. In 1958 Professor Viktor Zhdanov, Deputy Minister of Health for the USSR, called on the World Health Assembly to undertake a global initiative to eradicate smallpox. The proposal (Resolution WHA11.54) was accepted in 1959. At this point, 2 million people were dying from smallpox every year. Overall, the progress towards eradication was disappointing, especially in Africa and in the Indian subcontinent. In 1966 an international team, the Smallpox Eradication Unit, was formed under the leadership of an American, Donald Henderson. In 1967, the World Health Organization intensified the global smallpox eradication by contributing $2.4 million annually to the effort, and adopted the new disease surveillance method promoted by Czech epidemiologist Karel Raška. In the early 1950s, an estimated 50 million cases of smallpox occurred in the world each year. To eradicate smallpox, each outbreak had to be stopped from spreading, by isolation of cases and vaccination of everyone who lived close by. This process is known as "ring vaccination". The key to this strategy was the monitoring of cases in a community (known as surveillance) and containment. The initial problem the WHO team faced was inadequate reporting of smallpox cases, as many cases did not come to the attention of the authorities. The fact that humans are the only reservoir for smallpox infection and that carriers did not exist played a significant role in the eradication of smallpox. The WHO established a network of consultants who assisted countries in setting up surveillance and containment activities. Early on, donations of vaccine were provided primarily by the Soviet Union and the United States, but by 1973, more than 80 percent of all vaccine was produced in developing countries. The Soviet Union provided one and a half billion doses between 1958 and 1979, as well as the medical staff.The last major European outbreak of smallpox was in 1972 in Yugoslavia, after a pilgrim from Kosovo returned from the Middle East, where he had contracted the virus. The epidemic infected 175 people, causing 35 deaths. Authorities declared martial law, enforced quarantine, and undertook widespread re-vaccination of the population, enlisting the help of the WHO. In two months, the outbreak was over. Prior to this, there had been a smallpox outbreak in May–July 1963 in Stockholm, Sweden, brought from the Far East by a Swedish sailor; this had been dealt with by quarantine measures and vaccination of the local population.By the end of 1975, smallpox persisted only in the Horn of Africa. Conditions were very difficult in Ethiopia and Somalia, where there were few roads. Civil war, famine, and refugees made the task even more difficult. An intensive surveillance and containment and vaccination program was undertaken in these countries in early and mid-1977, under the direction of Australian microbiologist Frank Fenner. As the campaign neared its goal, Fenner and his team played an important role in verifying eradication. The last naturally occurring case of indigenous smallpox (Variola minor) was diagnosed in Ali Maow Maalin, a hospital cook in Merca, Somalia, on 26 October 1977. The last naturally occurring case of the more deadly Variola major had been detected in October 1975 in a three-year-old Bangladeshi girl, Rahima Banu.The global eradication of smallpox was certified, based on intense verification activities, by a commission of eminent scientists on 9 December 1979 and subsequently endorsed by the World Health Assembly on 8 May 1980. The first two sentences of the resolution read: Having considered the development and results of the global program on smallpox eradication initiated by WHO in 1958 and intensified since 1967 … Declares solemnly that the world and its peoples have won freedom from smallpox, which was a most devastating disease sweeping in epidemic form through many countries since earliest time, leaving death, blindness and disfigurement in its wake and which only a decade ago was rampant in Africa, Asia and South America. Costs and benefits The cost of the eradication effort, from 1967 to 1979, was roughly US$300 million. Roughly a third came from the developed world, which had largely eradicated smallpox decades earlier. The United States, the largest contributor to the program, has reportedly recouped that investment every 26 days since in money not spent on vaccinations and the costs of incidence. Post-eradication The last case of smallpox in the world occurred in an outbreak in the United Kingdom in 1978. A medical photographer, Janet Parker, contracted the disease at the University of Birmingham Medical School and died on 11 September 1978. Although it has remained unclear how Parker became infected, the source of the infection was established to be the smallpox virus grown for research purposes at the Medical School laboratory. All known stocks of smallpox worldwide were subsequently destroyed or transferred to two WHO-designated reference laboratories with BSL-4 facilities – the United States Centers for Disease Control and Prevention (CDC) and the Soviet Unions (now Russias) State Research Center of Virology and Biotechnology VECTOR.WHO first recommended destruction of the virus in 1986 and later set the date of destruction to be 30 December 1993. This was postponed to 30 June 1999. Due to resistance from the U.S. and Russia, in 2002 the World Health Assembly agreed to permit the temporary retention of the virus stocks for specific research purposes. Destroying existing stocks would reduce the risk involved with ongoing smallpox research; the stocks are not needed to respond to a smallpox outbreak. Some scientists have argued that the stocks may be useful in developing new vaccines, antiviral drugs, and diagnostic tests; a 2010 review by a team of public health experts appointed by WHO concluded that no essential public health purpose is served by the U.S. and Russia continuing to retain virus stocks. The latter view is frequently supported in the scientific community, particularly among veterans of the WHO Smallpox Eradication Program.On March 31, 2003, smallpox scabs were found inside an envelope in an 1888 book on Civil War medicine in Santa Fe, New Mexico. The envelope was labeled as containing scabs from a vaccination and gave scientists at the CDC an opportunity to study the history of smallpox vaccination in the United States. On July 1, 2014, six sealed glass vials of smallpox dated 1954, along with sample vials of other pathogens, were discovered in a cold storage room in an FDA laboratory at the National Institutes of Health location in Bethesda, Maryland. The smallpox vials were subsequently transferred to the custody of the CDC in Atlanta, where virus taken from at least two vials proved viable in culture. After studies were conducted, the CDC destroyed the virus under WHO observation on February 24, 2015.In 2017, Canadian scientists recreated an extinct horse pox virus to demonstrate that the smallpox virus can be recreated in a small lab at a cost of about $100,000, by a team of scientists without specialist knowledge. This makes the retention controversy irrelevant since the virus can be easily recreated even if all samples are destroyed. Although the scientists performed the research to help development of new vaccines as well as trace smallpoxs history, the possibility of the techniques being used for nefarious purposes was immediately recognized, raising questions on dual use research and regulations.In September 2019, the Russian lab housing smallpox samples experienced a gas explosion that injured one worker. It did not occur near the virus storage area, and no samples were compromised, but the incident prompted a review of risks to containment. Society and culture Biological warfare In 1763, Pontiacs War broke out as a Native American confederacy led by Pontiac attempted to counter British control over the Great Lakes region. A group of Native American warriors laid siege to British-held Fort Pitt on June 22. In response, Henry Bouquet, the commander of the fort, ordered his subordinate Simeon Ecuyer to give smallpox-infested blankets from the infirmary to a Delaware delegation outside the fort. Bouquet had discussed this with his superior, Sir Jeffrey Amherst, who wrote to Bouquet stating: "Could it not be contrived to send the small pox among the disaffected tribes of Indians? We must on this occasion use every stratagem in our power to reduce them." Bouquet agreed with the proposal, writing back that "I will try to inocculate [sic] the Indians by means of Blankets that may fall in their hands". On 24 June 1763, William Trent, a local trader and commander of the Fort Pitt militia, wrote, "Out of our regard for them, we gave them two Blankets and an Handkerchief out of the Small Pox Hospital. I hope it will have the desired effect." The effectiveness of this effort to broadcast the disease is unknown. There are also accounts that smallpox was used as a weapon during the American Revolutionary War (1775–1783).According to a theory put forward in Journal of Australian Studies (JAS) by independent researcher Christopher Warren, Royal Marines used smallpox in 1789 against indigenous tribes in New South Wales. This theory was also considered earlier in Bulletin of the History of Medicine and by David Day. However it is disputed by some medical academics, including Professor Jack Carmody, who in 2010 claimed that the rapid spread of the outbreak in question was more likely indicative of chickenpox—a more infectious disease which, at the time, was often confused, even by surgeons, with smallpox, and may have been comparably deadly to Aborigines and other peoples without natural immunity to it. Carmody noted that in the 8-month voyage of the First Fleet and the following 14 months there were no reports of smallpox amongst the colonists and that, since smallpox has an incubation period of 10–12 days, it is unlikely it was present in the First Fleet; however, Warren argued in the JAS article that the likely source was bottles of smallpox virus possessed by First Fleet surgeons. Ian and Jennifer Glynn, in The life and death of smallpox, confirm that bottles of "variolous matter" were carried to Australia for use as a vaccine, but think it unlikely the virus could have survived till 1789. In 2007, Christopher Warren offered evidence that the British smallpox may have been still viable. However, the only non-Aborigine reported to have died in this outbreak was a seaman called Joseph Jeffries, who was recorded as being of "American Indian" origin.W. S. Carus, an expert in biological weapons, has written that there is circumstantial evidence that smallpox was deliberately introduced to the Aboriginal population. However Carmody and the Australian National Universitys Boyd Hunter continue to support the chickenpox hypothesis. In a 2013 lecture at the Australian National University, Carmody pointed out that chickenpox, unlike smallpox, was known to be present in the Sydney Cove colony. He also suggested that all c. 18th century (and earlier) identifications of smallpox outbreaks were dubious because: "surgeons … would have been unaware of the distinction between smallpox and chickenpox – the latter having traditionally been considered a milder form of smallpox." During World War II, scientists from the United Kingdom, United States, and Japan (Unit 731 of the Imperial Japanese Army) were involved in research into producing a biological weapon from smallpox. Plans of large scale production were never carried through as they considered that the weapon would not be very effective due to the wide-scale availability of a vaccine.In 1947, the Soviet Union established a smallpox weapons factory in the city of Zagorsk, 75 km to the northeast of Moscow. An outbreak of weaponized smallpox occurred during testing at a facility on an island in the Aral Sea in 1971. General Prof. Peter Burgasov, former Chief Sanitary Physician of the Soviet Army and a senior researcher within the Soviet program of biological weapons, described the incident: On Vozrozhdeniya Island in the Aral Sea, the strongest recipes of smallpox were tested. Suddenly I was informed that there were mysterious cases of mortalities in Aralsk. A research ship of the Aral fleet came to within 15 km of the island (it was forbidden to come any closer than 40 km). The lab technician of this ship took samples of plankton twice a day from the top deck. The smallpox formulation – 400 gr. of which was exploded on the island – "got her" and she became infected. After returning home to Aralsk, she infected several people including children. All of them died. I suspected the reason for this and called the Chief of General Staff of the Ministry of Defense and requested to forbid the stop of the Alma-Ata–Moscow train in Aralsk. As a result, the epidemic around the country was prevented. I called Andropov, who at that time was Chief of KGB, and informed him of the exclusive recipe of smallpox obtained on Vozrazhdenie Island. Others contend that the first patient may have contracted the disease while visiting Uyaly or Komsomolsk-on-Ustyurt, two cities where the boat docked.Responding to international pressures, in 1991 the Soviet government allowed a joint U.S.–British inspection team to tour four of its main weapons facilities at Biopreparat. The inspectors were met with evasion and denials from the Soviet scientists and were eventually ordered out of the facility. In 1992, Soviet defector Ken Alibek alleged that the Soviet bioweapons program at Zagorsk had produced a large stockpile – as much as twenty tons – of weaponized smallpox (possibly engineered to resist vaccines, Alibek further alleged), along with refrigerated warheads to deliver it. Alibeks stories about the former Soviet programs smallpox activities have never been independently verified. In 1997, the Russian government announced that all of its remaining smallpox samples would be moved to the Vector Institute in Koltsovo. With the breakup of the Soviet Union and unemployment of many of the weapons programs scientists, U.S. government officials have expressed concern that smallpox and the expertise to weaponize it may have become available to other governments or terrorist groups who might wish to use virus as means of biological warfare. Specific allegations made against Iraq in this respect proved to be false.Concern has been expressed by some that artificial gene synthesis could be used to recreate the virus from existing digital genomes, for use in biological warfare. Insertion of the synthesized smallpox DNA into existing related pox viruses could theoretically be used to recreate the virus. The first step to mitigating this risk, it has been suggested, should be to destroy the remaining virus stocks to enable unequivocal criminalization of any possession of the virus. Notable cases Famous historical figures who contracted smallpox include Lakota Chief Sitting Bull, Ramses V, the Kangxi Emperor (survived), Shunzhi Emperor and Tongzhi Emperor of China, Emperor Komei of Japan (died of smallpox in 1867), and Date Masamune of Japan (who lost an eye to the disease). Cuitláhuac, the 10th tlatoani (ruler) of the Aztec city of Tenochtitlan, died of smallpox in 1520, shortly after its introduction to the Americas, and the Incan emperor Huayna Capac died of it in 1527 (causing a civil war of succession in the Inca empire and the eventual conquest by the Spaniards). More recent public figures include Guru Har Krishan, 8th Guru of the Sikhs, in 1664, Louis I of Spain in 1724 (died), Peter II of Russia in 1730 (died), George Washington (survived), Louis XV of France in 1774 (died) and Maximilian III Joseph of Bavaria in 1777 (died). Prominent families throughout the world often had several people infected by and/or perish from the disease. For example, several relatives of Henry VIII of England survived the disease but were scarred by it. These include his sister Margaret, his wife Anne of Cleves, and his two daughters: Mary I in 1527 and Elizabeth I in 1562. Elizabeth tried to disguise the pockmarks with heavy makeup. Mary, Queen of Scots, contracted the disease as a child but had no visible scarring. In Europe, deaths from smallpox often changed dynastic succession. Louis XV of France succeeded his great-grandfather Louis XIV through a series of deaths of smallpox or measles among those higher in the succession line. He himself died of the disease in 1774. Peter II of Russia died of the disease at 14 years of age. Also, before becoming emperor, Peter III of Russia caught the virus and suffered greatly from it. He was left scarred and disfigured. His wife, Catherine the Great, was spared but fear of the virus clearly had its effects on her. She feared for the safety of her son, Paul, so much that she made sure that large crowds were kept at bay and sought to isolate him. Eventually, she decided to have herself inoculated by a British doctor, Thomas Dimsdale. While this was considered a controversial method at the time, she succeeded. Paul was later inoculated as well. Catherine then sought to have inoculations throughout her empire stating: "My objective was, through my example, to save from death the multitude of my subjects who, not knowing the value of this technique, and frightened of it, were left in danger." By 1800, approximately 2 million inoculations were administered in the Russian Empire.In China, the Qing dynasty had extensive protocols to protect Manchus from Pekings endemic smallpox. U.S. Presidents George Washington, Andrew Jackson, and Abraham Lincoln all contracted and recovered from the disease. Washington became infected with smallpox on a visit to Barbados in 1751. Jackson developed the illness after being taken prisoner by the British during the American Revolution, and though he recovered, his brother Robert did not. Lincoln contracted the disease during his presidency, possibly from his son Tad, and was quarantined shortly after giving the Gettysburg address in 1863.Famous theologian Jonathan Edwards died of smallpox in 1758 following an inoculation.Soviet leader Joseph Stalin fell ill with smallpox at the age of seven. His face was badly scarred by the disease. He later had photographs retouched to make his pockmarks less apparent.Hungarian poet Ferenc Kölcsey, who wrote the Hungarian national anthem, lost his right eye to smallpox. Tradition and religion In the face of the devastation of smallpox, various smallpox gods and goddesses have been worshipped throughout parts of the Old World, for example in China and India. In China, the smallpox goddess was referred to as Tou-Shen Niang-Niang (Chinese: 痘疹娘娘). Chinese believers actively worked to appease the goddess and pray for her mercy, by such measures as referring to smallpox pustules as "beautiful flowers" as a euphemism intended to avert offending the goddess, for example (the Chinese word for smallpox is 天花, literally "heaven flower"). In a related New Years Eve custom it was prescribed that the children of the house wear ugly masks while sleeping, so as to conceal any beauty and thereby avoid attracting the goddess, who would be passing through sometime that night. If a case of smallpox did occur, shrines would be set up in the homes of the victims, to be worshipped and offered to as the disease ran its course. If the victim recovered, the shrines were removed and carried away in a special paper chair or boat for burning. If the patient did not recover, the shrine was destroyed and cursed, to expel the goddess from the house.In the Yoruba language smallpox is known as ṣọpọná, but it was also written as shakpanna, shopona, ṣhapana, and ṣọpọnọ. The word is a combination of 3 words, the verb ṣán, meaning to cover or plaster (referring to the pustules characteristic of smallpox), kpa or pa, meaning to kill, and enia, meaning human. Roughly translated, it means One who kills a person by covering them with pustules. Among the Yorùbá people of West Africa, and also in Dahomean religion, Trinidad, and in Brazil, The deity Sopona, also known as Obaluaye, is the deity of smallpox and other deadly diseases (like leprosy, HIV/AIDS, and fevers). One of the most feared deities of the orisha pantheon, smallpox was seen as a form of punishment from Shopona. Worship of Shopona was highly controlled by his priests, and it was believed that priests could also spread smallpox when angered. However, Shopona was also seen as a healer who could cure the diseases he inflicted, and he was often called upon his victims to heal them. The British government banned the worship of the god because it was believed his priests were purposely spreading smallpox to their opponents.Indias first records of smallpox can be found in a medical book that dates back to 400 CE. This book describes a disease that sounds exceptionally like smallpox. India, like China and the Yorùbá, created a goddess in response to its exposure to smallpox. The Hindu goddess Shitala was both worshipped and feared during her reign. It was believed that this goddess was both evil and kind and had the ability to inflict victims when angered, as well as calm the fevers of the already affected. Portraits of the goddess show her holding a broom in her right hand to continue to move the disease and a pot of cool water in the other hand in an attempt to soothe patients. Shrines were created where many Indian natives, both healthy and not, went to worship and attempt to protect themselves from this disease. Some Indian women, in an attempt to ward off Shitala, placed plates of cooling foods and pots of water on the roofs of their homes.In cultures that did not recognize a smallpox deity, there was often nonetheless a belief in smallpox demons, who were accordingly blamed for the disease. Such beliefs were prominent in Japan, Europe, Africa, and other parts of the world. Nearly all cultures who believed in the demon also believed that it was afraid of the color red. This led to the invention of the so-called red treatment, where patients and their rooms would be decorated in red. The practice spread to Europe in the 12th century and was practiced by (among others) Charles V of France and Elizabeth I of England. Afforded scientific credibility through the studies by Niels Ryberg Finsen showing that red light reduced scarring, this belief persisted even until the 1930s. See also List of epidemics Population history of indigenous peoples of the Americas#Depopulation from disease References Further reading External links Smallpox Biosafety: A Website About Destruction of Smallpox Virus Stocks Detailed CIDRAP Smallpox overview Agent Fact Sheet: Smallpox, Center for Biosecurity Smallpox Images and Diagnosis Synopsis Archived 29 July 2008 at the Wayback Machine Virus Pathogen Database and Analysis Resource (ViPR): Poxviridae Episode 1 (of 4): Vaccines of the BBC Four and PBS show: Extra Life: A Short History of Living Longer (2021)

Hey Aarogya, explain a scenario commonly referred as Snakebite

Snakebite

A snakebite is an injury caused by the bite of a snake, especially a venomous snake. A common sign of a bite from a venomous snake is the presence of two puncture wounds from the animals fangs. Sometimes venom injection from the bite may occur. This may result in redness, swelling, and severe pain at the area, which may take up to an hour to appear. Vomiting, blurred vision, tingling of the limbs, and sweating may result. Most bites are on the hands, arms, or legs. Fear following a bite is common with symptoms of a racing heart and feeling faint. The venom may cause bleeding, kidney failure, a severe allergic reaction, tissue death around the bite, or breathing problems. Bites may result in the loss of a limb or other chronic problems or even death.The outcome depends on the type of snake, the area of the body bitten, the amount of snake venom injected, the general health of the person bitten and whether or not anti-venom serum has been administered by a doctor in a timely manner. Problems are often more severe in children than adults, due to their smaller size. Allergic reactions to snake venom can further complicate outcomes and can include anaphylaxis, requiring additional treatment and in some cases resulting in death.Snakes bite, both as a method of hunting, and as a means of protection. Risk factors for bites include working outside with ones hands such as in farming, forestry, and construction. Snakes commonly involved in envenomations include elapids (such as kraits, cobras and mambas), vipers, and sea snakes. The majority of snake species do not have venom and kill their prey by squeezing them. Venomous snakes can be found on every continent except Antarctica. Determining the type of snake that caused a bite is often not possible. The World Health Organization says snakebites are a "neglected public health issue in many tropical and subtropical countries", and in 2017, the WHO categorized snakebite envenomation as a Neglected Tropical Disease (Category A). The WHO also estimates that between 4.5 and 5.4 million people are bitten each year, and of those figures 40-50% develop some kind of clinical illness as a result. Furthermore, the death toll of such an injury could range between 80,000 and 130,000 people per year. The purpose was to encourage research, expand accessibility of antivenoms, and improve snakebite management in "developing countries".Prevention of snake bites can involve wearing protective footwear, avoiding areas where snakes live, and not handling snakes. Treatment partly depends on the type of snake. Washing the wound with soap and water and holding the limb still is recommended. Trying to suck out the venom, cutting the wound with a knife, or using a tourniquet is not recommended. Antivenom is effective at preventing death from bites; however, antivenoms frequently have side effects. The type of antivenom needed depends on the type of snake involved. When the type of snake is unknown, antivenom is often given based on the types known to be in the area. In some areas of the world, getting the right type of antivenom is difficult and this partly contributes to why they sometimes do not work. An additional issue is the cost of these medications. Antivenom has little effect on the area around the bite itself. Supporting the persons breathing is sometimes also required.The number of venomous snakebites that occur each year may be as high as five million. They result in about 2.5 million envenomations and 20,000 to 125,000 deaths. The frequency and severity of bites vary greatly among different parts of the world. They occur most commonly in Africa, Asia, and Latin America, with rural areas more greatly affected. Deaths are relatively rare in Australia, Europe and North America. For example, in the United States, about seven to eight thousand people per year are bitten by venomous snakes (about one in 40 thousand people) and about five people die (about one death per 65 million people). Signs and symptoms The most common first symptom of all snakebites is an overwhelming fear, which may contribute to other symptoms, and may include nausea and vomiting, diarrhea, vertigo, fainting, tachycardia, and cold, clammy skin. Snake bites can have a variety of different signs and symptoms depending on their species.Dry snakebites and those inflicted by a non-venomous species may still cause severe injury. The bite may become infected from the snakes saliva. The fangs sometimes harbor pathogenic microbial organisms, including Clostridium tetani, and may require an updated tetanus immunization.Most snakebites, from either a venomous or a non-venomous snake, will have some type of local effect. Minor pain and redness occur in over 90 percent of cases, although this varies depending on the site. Bites by vipers and some cobras may be extremely painful, with the local tissue sometimes becoming tender and severely swollen within five minutes. This area may also bleed and blister, and may lead to tissue necrosis. Other common initial symptoms of pit viper and viper bites include lethargy, bleeding, weakness, nausea, and vomiting. Symptoms may become more life-threatening over time, developing into hypotension, tachypnea, severe tachycardia, severe internal bleeding, altered sensorium, kidney failure, and respiratory failure.Bites by some snakes, such as the kraits, coral snake, Mojave rattlesnake, and the speckled rattlesnake, may cause little or no pain, despite their serious and potentially life-threatening venom. Some people report experiencing a "rubbery", "minty", or "metallic" taste after being bitten by certain species of rattlesnake. Spitting cobras and rinkhalses can spit venom in a persons eyes. This results in immediate pain, ophthalmoparesis, and sometimes blindness. Some Australian elapids and most viper envenomations will cause coagulopathy, sometimes so severe that a person may bleed spontaneously from the mouth, nose, and even old, seemingly healed wounds. Internal organs may bleed, including the brain and intestines, and ecchymosis (bruising) of the skin is often seen.The venom of elapids, including sea snakes, kraits, cobras, king cobra, mambas, and many Australian species, contains toxins which attack the nervous system, causing neurotoxicity. The person may present with strange disturbances to their vision, including blurriness. Paresthesia throughout the body, as well as difficulty in speaking and breathing, may be reported. Nervous system problems will cause a huge array of symptoms, and those provided here are not exhaustive. If not treated immediately they may die from respiratory failure.Venom emitted from some types of cobras, almost all vipers and some sea snakes causes necrosis of muscle tissue. Muscle tissue will begin to die throughout the body, a condition known as rhabdomyolysis. Rhabdomyolysis can result in damage to the kidneys as a result of myoglobin accumulation in the renal tubules. This, coupled with hypotension, can lead to acute kidney injury, and, if left untreated, eventually death.Snakebite is also known to cause depression and post-traumatic stress disorder in a high proportion of people who survive. Cause In the developing world most snakebites occur in those who work outside such as farmers, hunters, and fishermen. They often happen when a person steps on the snake or approaches it too closely. In the United States and Europe snakebites most commonly occur in those who keep them as pets.The type of snake that most often delivers serious bites depends on the region of the world. In Africa, it is mambas, Egyptian cobras, puff adders, and carpet vipers. In the Middle East, it is carpet vipers and elapids. In Latin America, it is snakes of the Bothrops and Crotalus types, the latter including rattlesnakes. In North America, rattlesnakes are the primary concern, and up to 95% of all snakebite-related deaths in the United States are attributed to the western and eastern diamondback rattlesnakes. In South Asia, it was previously believed that Indian cobras, common kraits, Russells viper, and carpet vipers were the most dangerous; other snakes, however, may also cause significant problems in this area of the world. Pathophysiology Since envenomation is completely voluntary, all venomous snakes are capable of biting without injecting venom into a person. Snakes may deliver such a "dry bite" rather than waste their venom on a creature too large for them to eat, a behaviour called venom metering. However, the percentage of dry bites varies among species: 80 percent of bites inflicted by sea snakes, which are normally timid, do not result in envenomation, whereas only 25 percent of pit viper bites are dry. Furthermore, some snake genera, such as rattlesnakes, significantly increase the amount of venom injected in defensive bites compared to predatory strikes.Some dry bites may also be the result of imprecise timing on the snakes part, as venom may be prematurely released before the fangs have penetrated the person. Even without venom, some snakes, particularly large constrictors such as those belonging to the Boidae and Pythonidae families, can deliver damaging bites; large specimens often cause severe lacerations, or the snake itself pulls away, causing the flesh to be torn by the needle-sharp recurved teeth embedded in the person. While not as life-threatening as a bite from a venomous species, the bite can be at least temporarily debilitating and could lead to dangerous infections if improperly dealt with.While most snakes must open their mouths before biting, African and Middle Eastern snakes belonging to the family Atractaspididae are able to fold their fangs to the side of their head without opening their mouth and jab a person. Snake venom It has been suggested that snakes evolved the mechanisms necessary for venom formation and delivery sometime during the Miocene epoch. During the mid-Tertiary, most snakes were large ambush predators belonging to the superfamily Henophidia, which use constriction to kill their prey. As open grasslands replaced forested areas in parts of the world, some snake families evolved to become smaller and thus more agile. However, subduing and killing prey became more difficult for the smaller snakes, leading to the evolution of snake venom. Other research on Toxicofera, a hypothetical clade thought to be ancestral to most living reptiles, suggests an earlier time frame for the evolution of snake venom, possibly to the order of tens of millions of years, during the Late Cretaceous.Snake venom is produced in modified parotid glands normally responsible for secreting saliva. It is stored in structures called alveoli behind the animals eyes, and ejected voluntarily through its hollow tubular fangs. Venom in many snakes, such as pit vipers, affects virtually every organ system in the human body and can be a combination of many toxins, including cytotoxins, hemotoxins, neurotoxins, and myotoxins, allowing for an enormous variety of symptoms. Snake venom may cause cytotoxicity as various enzymes including hyaluronidases, collagenases, proteinases and phospholipases lead to breakdown (dermonecrosis) and injury of local tissue and inflammation which leads to pain, edema and blister formation. Metalloproteinases further lead to breakdown of the extracellular matrix (releasing inflammatory mediators) and cause microvascular damage, leading to hemorrhage, skeletal muscle damage (necrosis), blistering and further dermonecrosis. The metalloproteinase release of the inflammatory mediators leads to pain, swelling and white blood cell (leukocyte) infiltration. The lymphatic system may be damaged by the various enzymes contained in the venom leading to edema; or the lymphatic system may also allow the venom to be carried systemically. Snake venom may cause muscle damage or myotoxicity via the enzyme phospholipase A2 which disrupts the plasma membrane of muscle cells. This damage to muscle cells may cause rhabdomyolysis, respiratory muscle compromise, or both. Other enzymes such as bradykinin potentiating peptides, natriuretic peptides, vascular endothelial growth factors, proteases can also cause hypotension or low blood pressure. Toxins in snake venom can also cause kidney damage (nephrotoxicity) via the same inflammatory cytokines. The toxins cause direct damage to the glomeruli in the kidneys as well as causing protein deposits in Bowmans capsule. Or the kidneys may be indirectly damaged by envenomation due to shock, clearance of toxic substances such as immune complexes, blood degradation products or products of muscle breakdown (rhabdomyolysis).In venom-induced consumption coagulopathy, toxins in snake venom promote hemorrhage via activation, consumption and subsequent depletion of clotting factors in the blood. These clotting factors normally work as part of the coagulation cascade in the blood to form blood clots and prevent hemorrhage. Toxins in snake venom (especially the venom of new world pit vipers (the family crotalina)) may also cause low platelets (thrombocytopenia) or altered platelet function also leading to bleeding.Snake venom is known to cause neuromuscular paralysis, usually as a flaccid paralysis that is descending; starting at the facial muscles, causing ptosis or drooping eyelids and dysarthria or poor articulation of speech, and descending to the respiratory muscles causing respiratory compromise. The neurotoxins can either bind to and block membrane receptors at the post-synaptic neurons or they can be taken up into the pre-synaptic neuron cells and impair neurotransmitter release. Venom toxins that are taken up intra-cellularly, into the cells of the pre-synaptic neurons are much more difficult to reverse using anti-venom as they are inaccessible to the anti-venom when they are intracellular.The strength of venom differs markedly between species and even more so between families, as measured by median lethal dose (LD50) in mice. Subcutaneous LD50 varies by over 140-fold within elapids and by more than 100-fold in vipers. The amount of venom produced also differs among species, with the Gaboon viper able to potentially deliver from 450 to 600 milligrams of venom in a single bite, the most of any snake. Opisthoglyphous colubrids have venom ranging from life-threatening (in the case of the boomslang) to barely noticeable (as in Tantilla). Prevention Snakes are most likely to bite when they feel threatened, are startled, are provoked, or when they have been cornered. Snakes are likely to approach residential areas when attracted by prey, such as rodents. Regular pest control can reduce the threat of snakes considerably. It is beneficial to know the species of snake that are common in local areas, or while travelling or hiking. Africa, Australia, the Neotropics, and South Asia in particular are populated by many dangerous species of snake. Being aware of—and ultimately avoiding—areas known to be heavily populated by dangerous snakes is strongly recommended.When in the wilderness, treading heavily creates ground vibrations and noise, which will often cause snakes to flee from the area. However, this generally only applies to vipers, as some larger and more aggressive snakes in other parts of the world, such as mambas and cobras, will respond more aggressively. If presented with a direct encounter, it is best to remain silent and motionless. If the snake has not yet fled, it is important to step away slowly and cautiously.The use of a flashlight when engaged in camping activities, such as gathering firewood at night, can be helpful. Snakes may also be unusually active during especially warm nights when ambient temperatures exceed 21 °C (70 °F). It is advised not to reach blindly into hollow logs, flip over large rocks, and enter old cabins or other potential snake hiding-places. When rock climbing, it is not safe to grab ledges or crevices without examining them first, as snakes are cold-blooded and often sunbathe atop rock ledges.In the United States, more than 40 percent of people bitten by snake intentionally put themselves in harms way by attempting to capture wild snakes or by carelessly handling their dangerous pets—40 percent of that number had a blood alcohol level of 0.1 percent or more.It is also important to avoid snakes that appear to be dead, as some species will actually roll over on their backs and stick out their tongue to fool potential threats. A snakes detached head can immediately act by reflex and potentially bite. The induced bite can be just as severe as that of a live snake. As a dead snake is incapable of regulating the venom injected, a bite from a dead snake can often contain large amounts of venom. Treatment It may be difficult to determine if a bite by any species of snake is life-threatening. A bite by a North American copperhead on the ankle is usually a moderate injury to a healthy adult, but a bite to a childs abdomen or face by the same snake may be fatal. The outcome of all snakebites depends on a multitude of factors: the type of snake, the size, physical condition, and temperature of the snake, the age and physical condition of the person, the area and tissue bitten (e.g., foot, torso, vein or muscle), the amount of venom injected, the time it takes for the person to find treatment, and finally the quality of that treatment. An overview of systematic reviews on different aspects of snakebite management found that the evidence base from majority of treatment modalities is low quality. An analysis of World Health Organization guidelines found that they are of low quality, with inadequate stakeholder involvement and poor methodological rigour. Snake identification Identification of the snake is important in planning treatment in certain areas of the world, but is not always possible. Ideally the dead snake would be brought in with the person, but in areas where snake bite is more common, local knowledge may be sufficient to recognize the snake. However, in regions where polyvalent antivenoms are available, such as North America, identification of snake is not a high priority item. Attempting to catch or kill the offending snake also puts one at risk for re-envenomation or creating a second person bitten, and generally is not recommended.The three types of venomous snakes that cause the majority of major clinical problems are vipers, kraits, and cobras. Knowledge of what species are present locally can be crucial, as is knowledge of typical signs and symptoms of envenomation by each type of snake. A scoring system can be used to try to determine the biting snake based on clinical features, but these scoring systems are extremely specific to particular geographical areas and might be compromised by the presence of escaped or released non-native species. First aid Snakebite first aid recommendations vary, in part because different snakes have different types of venom. Some have little local effect, but life-threatening systemic effects, in which case containing the venom in the region of the bite by pressure immobilization is desirable. Other venoms instigate localized tissue damage around the bitten area, and immobilization may increase the severity of the damage in this area, but also reduce the total area affected; whether this trade-off is desirable remains a point of controversy. Because snakes vary from one country to another, first aid methods also vary. Many organizations, including the American Medical Association and American Red Cross, recommend washing the bite with soap and water. Australian recommendations for snake bite treatment recommend against cleaning the wound. Traces of venom left on the skin/bandages from the strike can be used in combination with a snake bite identification kit to identify the species of snake. This speeds determination of which antivenom to administer in the emergency room. Pressure immobilization As of 2008, clinical evidence for pressure immobilization via the use of an elastic bandage is limited. It is recommended for snakebites that have occurred in Australia (due to elapids which are neurotoxic). It is not recommended for bites from non-neurotoxic snakes such as those found in North America and other regions of the world. The British military recommends pressure immobilization in all cases where the type of snake is unknown.The object of pressure immobilization is to contain venom within a bitten limb and prevent it from moving through the lymphatic system to the vital organs. This therapy has two components: pressure to prevent lymphatic drainage, and immobilization of the bitten limb to prevent the pumping action of the skeletal muscles. Antivenom Until the advent of antivenom, bites from some species of snake were almost universally fatal. Despite huge advances in emergency therapy, antivenom is often still the only effective treatment for envenomation. The first antivenom was developed in 1895 by French physician Albert Calmette for the treatment of Indian cobra bites. Antivenom is made by injecting a small amount of venom into an animal (usually a horse or sheep) to initiate an immune system response. The resulting antibodies are then harvested from the animals blood. Antivenom is injected into the person intravenously, and works by binding to and neutralizing venom enzymes. It cannot undo damage already caused by venom, so antivenom treatment should be sought as soon as possible. Modern antivenoms are usually polyvalent, making them effective against the venom of numerous snake species. Pharmaceutical companies which produce antivenom target their products against the species native to a particular area. Although some people may develop serious adverse reactions to antivenom, such as anaphylaxis, in emergency situations this is usually treatable and hence the benefit outweighs the potential consequences of not using antivenom. Giving adrenaline (epinephrine) to prevent adverse reactions to antivenom before they occur might be reasonable in cases where they occur commonly. Antihistamines do not appear to provide any benefit in preventing adverse reactions. Chronic Complications Chronic health effects of snakebite include but is not limited to non-healing and chronic ulcers, musculoskeletal disorders, amputations, chronic kidney disease, and other neurological and endocrine complications. The treatment of chronic complications of snakebite has not been well researched and there a systems approach consisting of a multi-component intervention. Outmoded The following treatments, while once recommended, are considered of no use or harmful, including tourniquets, incisions, suction, application of cold, and application of electricity. Cases in which these treatments appear to work may be the result of dry bites. Application of a tourniquet to the bitten limb is generally not recommended. There is no convincing evidence that it is an effective first-aid tool as ordinarily applied. Tourniquets have been found to be completely ineffective in the treatment of Crotalus durissus bites, but some positive results have been seen with properly applied tourniquets for cobra venom in the Philippines. Uninformed tourniquet use is dangerous, since reducing or cutting off circulation can lead to gangrene, which can be fatal. The use of a compression bandage is generally as effective, and much safer. Cutting open the bitten area, an action often taken prior to suction, is not recommended since it causes further damage and increases the risk of infection; the subsequent cauterization of the area with fire or silver nitrate (also known as infernal stone) is also potentially threatening. Sucking out venom, either by mouth or with a pump, does not work and may harm the affected area directly. Suction started after three minutes removes a clinically insignificant quantity—less than one-thousandth of the venom injected—as shown in a human study. In a study with pigs, suction not only caused no improvement but led to necrosis in the suctioned area. Suctioning by mouth presents a risk of further poisoning through the mouths mucous tissues. The helper may also release bacteria into the persons wound, leading to infection. Immersion in warm water or sour milk, followed by the application of snake-stones (also known as la Pierre Noire), which are believed to draw off the poison in much the way a sponge soaks up water. Application of a one-percent solution of potassium permanganate or chromic acid to the cut, exposed area. The latter substance is notably toxic and carcinogenic. Drinking abundant quantities of alcohol following the cauterization or disinfection of the wound area. Use of electroshock therapy in animal tests has shown this treatment to be useless and potentially dangerous.In extreme cases, in remote areas, all of these misguided attempts at treatment have resulted in injuries far worse than an otherwise mild to moderate snakebite. In worst-case scenarios, thoroughly constricting tourniquets have been applied to bitten limbs, completely shutting off blood flow to the area. By the time the person finally reached appropriate medical facilities their limbs had to be amputated. In development Several new drugs and treatments are under development for snakebite. For instance, the metal chelator dimercaprol has recently been shown to potently antagonize the activity of Zn2+-dependent snake venom metalloproteinases in vitro. New monoclonal antibodies, polymer gels and a small molecule inhibitor called Varespladib are in development. Epidemiology Estimates vary from 1.2 to 5.5 million snakebites, 421,000 to 2.5 million envenomings, and 20,000 to 125,000 deaths. Since reporting is not mandatory in much of the world, the data on the frequency of snakebites is not precise. Many people who survive bites have permanent tissue damage caused by venom, leading to disability. Most snake envenomings and fatalities occur in South Asia, Southeast Asia, and sub-Saharan Africa, with India reporting the most snakebite deaths of any country.Most snakebites are caused by non-venomous snakes. Of the roughly 3,000 known species of snake found worldwide, only 15% are considered dangerous to humans. Snakes are found on every continent except Antarctica. The most diverse and widely distributed snake family, the colubrids, has approximately 700 venomous species, but only five genera—boomslangs, twig snakes, keelback snakes, green snakes, and slender snakes—have caused human fatalities.Worldwide, snakebites occur most frequently in the summer season when snakes are active and humans are outdoors. Agricultural and tropical regions report more snakebites than anywhere else. In the United States, those bitten are typically male and between 17 and 27 years of age. Children and the elderly are the most likely to die. Mechanics When venomous snakes bite a target, they secrete venom through their venom delivery system. The venom delivery system generally consists of two venom glands, a compressor muscle, venom ducts, a fang sheath, and fangs. The primary and accessory venom glands store the venom quantities required during envenomation. The compressor muscle contracts during bites to increase the pressure throughout the venom delivery system. The pressurized venom travels through the primary venom duct to the secondary venom duct that leads down through the fang sheath and fang. The venom is then expelled through the exit orifice of the fang. The total volume and flow rate of venom administered into a target varies widely, sometimes as much as an order of magnitude. One of the largest factors is snake species and size, larger snakes have been shown to administer larger quantities of venom. Predatory vs. defensive bites Snake bites are classified as either predatory or defensive in nature. During defensive strikes, the rate of venom expulsion and total volume of venom expelled is much greater than during predatory strikes. Defensive strikes can have 10 times as much venom volume expelled at 8.5 times the flow rate. This can be explained by the snakes need to quickly subdue a threat. While employing similar venom expulsion mechanics, predatory strikes are quite different from defensive strikes. Snakes usually release the prey shortly after the envenomation allowing the prey to run away and die. Releasing prey prevents retaliatory damage to the snake. The venom scent allows the snake to relocate the prey once it is deceased. The amount of venom injected has been shown to increase with the mass of the prey animal. Larger venom volumes allow snakes to effectively euthanize larger prey while remaining economical during strikes against smaller prey. This is an important skill as venom is a metabolically expensive resource. Venom Metering Venom metering is the ability of a snake to have neurological control over the amount of venom released into a target during a strike based on situational cues. This ability would prove useful as venom is a limited resource, larger animals are less susceptible to the effects of venom, and various situations require different levels of force. There is a lot of evidence to support the venom metering hypothesis. For example, snakes frequently use more venom during defensive strikes, administer more venom to larger prey, and are capable of dry biting. A dry bite is a bite from a venomous snake that results in very little or no venom expulsion, leaving the target asymptomatic. However, there is debate among many academics about venom metering in snakes. The alternative to venom metering is the pressure balance hypothesis. The pressure balance hypothesis cites the retraction of the fang sheath as the many mechanism for producing outward venom flow from the venom delivery system. When isolated, fang sheath retraction has experimentally been shown to induce very high pressures in the venom delivery system. A similar method was used to stimulate the compressor musculature, the main muscle responsible for the contraction and squeezing of the venom glad, and then measuring the induced pressures. It was determined that the pressure created from the fang sheath retraction was at times an order of magnitude greater than those created by the compressor musculature. Snakes do not have direct neurological control of the fang sheath, it can only be retracted as the fangs enter a target and the targets skin and body provide substantial resistance to retract the sheath. For these reasons, the pressure balance hypothesis concludes that external factors, mainly the bite and physical mechanics, are responsible for the quantity of venom expelled. Venom Spitting Venom spitting is another venom delivery method that is unique to some Asiatic and African cobras. In venom spitting, a stream of venom is propelled at very high pressures outwards up to 3 meters. The venom stream is usually aimed at the eyes and face of the target as a deterrent for predators. There are non-spitting cobras that provide useful information on the unique mechanics behind venom spitting. Unlike the elongated oval shaped exit orifices of non-spitting cobras, spitting cobras have circular exit orifice at their fang tips. This combined with the ability to partially retract their fang sheath by displacing the palato-maxillary arch and contracting the adductor mandibulae, allows the spitting cobras to create large pressures within the venom delivery system. While venom spitting is a less common venom delivery system, the venom can still cause the effects if ingested. Society and culture Snakes were both revered and worshipped and feared by early civilizations. The ancient Egyptians recorded prescribed treatments for snakebites as early as the Thirteenth Dynasty in the Brooklyn Papyrus, which includes at least seven venomous species common to the region today, such as the horned vipers. In Judaism, the Nehushtan was a pole with a snake made of copper fixed upon it. The object was regarded as a divinely empowered instrument of God that could bring healing to Jews bitten by venomous snakes while they were wandering in the desert after their exodus from Egypt. Healing was said to occur by merely looking at the object as it was held up by Moses. Historically, snakebites were seen as a means of execution in some cultures. Reportedly, in Southern Han during Chinas Five Dynasties and Ten Kingdoms period and in India a form of capital punishment was to throw people into snake pits, leaving people to die from multiple venomous bites. According to popular belief, the Egyptian queen Cleopatra VII committed suicide by let herself be bitten by an asp—likely an Egyptian cobra—after hearing of Mark Antonys death, while contemporary ancient authors rather assume a direct application of poison. Snakebite as a surreptitious form of murder has been featured in stories such as Sir Arthur Conan Doyles The Adventure of the Speckled Band, but actual occurrences are virtually unheard of, with only a few documented cases. It has been suggested that Boris III of Bulgaria, who was allied to Nazi Germany during World War II, may have been killed with snake venom, although there is no definitive evidence. At least one attempted suicide by snakebite has been documented in medical literature involving a puff adder bite to the hand. Research In 2018, the World Health Organization listed snakebite envenoming as a neglected tropical disease. In 2019, they launched a strategy to prevent and control snakebite envenoming, which involved a program targeting affected communities and their health systems. Other animals Several animals acquired immunity against venom of snakes that occur in the same habitat. This has been documented in some humans as well. References Bibliography Further reading External links WHO Snake Antivenoms Database Organization (2016). Guidelines for the management of snakebites. Regional Office for South-East Asia, World Health Organization. hdl:10665/249547. ISBN 9789290225300.

Hello Aarogya, explain a situation where Spasmodic dysphonia occurs

Spasmodic dysphonia

Spasmodic dysphonia, also known as laryngeal dystonia, is a disorder in which the muscles that generate a persons voice go into periods of spasm. This results in breaks or interruptions in the voice, often every few sentences, which can make a person difficult to understand. The persons voice may also sound strained or they may be nearly unable to speak. Onset is often gradual and the condition is lifelong.The cause is unknown. Risk factors may include family history. Triggers may include an upper respiratory infection, injury to the larynx, overuse of the voice, and psychological stress. The underlying mechanism is believed to typically involve the central nervous system, specifically the basal ganglia. Diagnosis is typically made following examination by a team of healthcare providers. It is a type of focal dystonia.While there is no cure, treatment may improve symptoms. Most commonly this involves injecting botulinum toxin into the affected muscles of the larynx. This generally results in improvement for a few months. Other measures include voice therapy, counselling, and amplification devices. If this is not effective, surgery may be considered; however, evidence to support surgery is limited.The disorder affects an estimated 2 per 100,000 people. Women are more commonly affected. Onset is typically between the ages of 30 and 50. Severity is variable between people. In some, work and social life are affected. Life expectancy is, however, normal. Signs and symptoms Symptoms of spasmodic dysphonia can come on suddenly or gradually appear over the span of years. They can come and go for hours or even weeks at a time, or remain consistent. Gradual onset can begin with the manifestation of a hoarse voice quality, which may later transform into a voice quality described as strained with breaks in phonation. These phonation breaks have been compared to stuttering in the past, but there is a lack of research in support of spasmodic dysphonia being classified as a fluency disorder. It is commonly reported by people with spasmodic dysphonia that symptoms almost only occur on vocal sounds that require phonation. Symptoms are less likely to occur at rest, while whispering, or on speech sounds that do not require phonation. It is hypothesized this occurs because of an increase in sporadic, sudden, and prolonged tension found in the muscles around the larynx during phonation. This tension affects the abduction and adduction (opening and closing) of the vocal folds. Consequently, the vocal folds are unable to retain subglottal air pressure (required for phonation) and breaks in phonation can be heard throughout the speech of people with spasmodic dysphonia.Regarding types of spasmodic dysphonia, the main characteristic of spasmodic dysphonia, breaks in phonation, is found along with other varying symptoms. The voice quality of adductor spasmodic dysphonia can be described as “strained-strangled” from tension in the glottal region. Voice quality for abductor spasmodic dysphonia can be described as breathy from variable widening of the glottal region. Vocal tremor may also be seen in spasmodic dysphonia. A mix and variance of these symptoms are found in mixed spasmodic dysphonia.Symptoms of spasmodic dysphonia typically appear in middle aged people, but have also been seen in people in their twenties, with symptoms emerging as young as teenage years. Cause Although the exact cause of spasmodic dysphonia is still unknown, epidemiological, genetic, and neurological pathogenic factors have been proposed in recent research.Risk factors include: Being female Being middle aged Having a family history of neurological diseases (e.g., tremor, dystonia, meningitis, and other neurological diseases) Stressful events Upper respiratory tract infections Sinus and throat illnesses Heavy voice use Cervical dystonia Childhood measles or mumps Pregnancy and parturitionIt has not been established whether these factors directly affect the development of spasmodic dysphonia (SD), however these factors could be used to identify possible and/or at-risk patients.Researchers have also explored the possibility of a genetic component to SD. Three genes have been identified that may be related to the development of focal or segmental dystonia: TUBB4A, THAP1 and TOR1A genes. However, a recent study that examined the mutation of these three genes in 86 SD patients found that only 2.3% of the patients had novel/rare variants in THAP1 but none in TUBB4A and TOR1A. Evidence of a genetic contribution for dystonia involving the larynx is still weak and more research is needed in order to establish a causal relationship between SD and specific genes.SD is a neurological disorder rather than a disorder of the larynx, and as in other forms of dystonia, interventions at the end organ (i.e., larynx) have not offered a definitive cure, only symptomatic relief. The pathophysiology underlying dystonia is becoming better understood as a result of discoveries about genetically based forms of the disorder, and this approach is the most promising avenue to a long-term solution.SD is classified as a neurological disorder. However, because the voice can sound normal or near normal at times, some practitioners believe it to be psychogenic; that is, originating in the affected persons mind rather than from a physical cause. This was especially true in the 19th and 20th centuries. No medical organizations or groups take this position. A comparison of SD patients compared with vocal fold paralysis (VFP) patients found that 41.7% of the SD patients met the DSM-IV criteria for psychiatric comorbidity compared with 19.5% of the VFP group. However, another study found the opposite, with SD patients having significantly less psychiatric comorbidity compared to VFP patients: "The prevalence of major psychiatric cases varied considerably among the groups, from a low of seven percent (1/14) for spasmodic dysphonia, to 29.4 percent (5/17) for functional dysphonia, to a high of 63.6 percent (7/11) for vocal cord paralysis." A review in the journal Swiss Medicine Weekly states that "Psychogenic causes, a psychological disequilibrium, and an increased tension of the laryngeal muscles are presumed to be one end of the spectrum of possible factors leading to the development of the disorder". Alternatively, many investigations into the condition feel that the psychiatric comorbidity associated with voice disorders is a result of the social isolation and anxiety that patients with these conditions feel as a consequence of their difficulty with speech, as opposed to the cause of their dysphonia. The opinion that SD is psychogenic is not upheld by experts in the scientific community.SD is formally classified as a movement disorder; it is a type of focal dystonia known as laryngeal dystonia. Diagnosis Diagnosis of spasmodic dysphonia requires a multidisciplinary team and consideration of both perceptual and physiological factors. There is currently no universally accepted diagnostic test for spasmodic dysphonia, which presents a challenge for diagnosis. Additionally, diagnostic criteria have not been agreed upon as the distinguishing features of this disorder have not been well-characterized.A team of professionals including a speech-language pathologist, an otolaryngologist, and a neurologist, are typically involved in spasmodic dysphonia assessment and diagnosis. The speech-language pathologist conducts a speech assessment including case history questions to gather information about voice use and symptoms. This is followed by clinical observation and perceptual rating of voice characteristics such as voice breaks or strain, which are selectively present in normal speech over other voice activities such as whispering or laughing. Symptoms also vary across types of spasmodic dysphonia. For example, voiced sounds are more affected in adductor spasmodic dysphonia, while unvoiced sounds are more affected in abductor spasmodic dysphonia. Following speech assessment, the otolaryngologist conducts a flexible transnasal laryngoscopy to view the vocal folds and activity of the muscles controlling them in order to eliminate other possible causes of the voice disorder. In spasmodic dysphonia, producing long vowels or speaking sentences results in muscle spasms which are not observed during other vocal activities such as coughing, breathing, or whispering. To evaluate the individual for any other neurological problems, this examination is followed up with an assessment by the neurologist. Voice quality symbol The voice quality symbol for spasmodic dysphonia is ꟿ. Differential diagnosis Because spasmodic dysphonia shares many characteristics with other voice disorders, misdiagnosis frequently occurs. A common misdiagnosis is muscle tension dysphonia, a functional voice disorder which results from use of the voice, rather than a structural abnormality. Some parameters can help guide the clinician towards a decision. In muscle tension dysphonia, the vocal folds are typically hyperadducted in constant way, not in a spasmodic way. Additionally, the voice difficulties found in spasmodic dysphonia can be task specific, as opposed to those found in muscle tension dysphonia. Being able to differentiate between muscle tension dysphonia and spasmodic dysphonia is important because muscle tension dysphonia typically responds well to behavioural voice treatment but spasmodic dysphonia does not. This is crucial to avoid providing inappropriate treatment, but in some cases a trial of behavioural voice treatment can also be helpful to establish a differential diagnosis.Spasmodic dysphonia can also be misdiagnosed as voice tremor. The movements that are found in this disorder are typically rhythmic in nature, as opposed to the muscle spasms of spasmodic dysphonia. It is important to note that voice tremor and spasmodic dysphonia can co-occur in some patients.Differential diagnosis is particularly important for determining appropriate interventions, as the type and cause of the disorder determine the most effective treatment. Differences in treatment effectiveness are present even between the types of spasmodic dysphonia. Diagnosis of spasmodic dysphonia is often delayed due to these challenges, which in turn presents difficulties in choosing the proper interventions. Types The three types of spasmodic dysphonia (SD) are adductor spasmodic dysphonia, abductor spasmodic dysphonia, and mixed spasmodic dysphonia. A fourth type called whispering dysphonia has also been proposed. Adductor spasmodic dysphonia is the most common type. Adductor spasmodic dysphonia Adductor spasmodic dysphonia (ADSD) is the most common type, affecting around 87% of individuals with SD. In ADSD, sudden involuntary muscle movements or spasms cause the vocal folds (or vocal cords) to squeeze together and stiffen. As the name suggests, these spasms occur in the adductor muscles of the vocal folds, specifically the thyroarytenoid and the lateral cricoarytenoid. These spasms make it difficult for the vocal folds to vibrate and produce voice. Words are often cut off or are difficult to start because of the muscle spasms. Therefore, speech may be choppy but differs from stuttering. The voice of an individual with adductor spasmodic dysphonia is commonly described as strained or strangled and full of effort. Surprisingly, the spasms are usually absent while laughing, speaking at a high pitch, or speaking while singing, but singers can experience a loss of range or the inability to produce certain notes of a scale or with projection. Stress, however, often makes the muscle spasms more severe. Abductor spasmodic dysphonia Abductor spasmodic dysphonia (ABSD) is the second most common type, affecting around 13% of individuals with SD. In ABSD, sudden involuntary muscle movements or spasms cause the vocal folds to open. As the name suggests, these spasms occur in the single abductor muscle of the vocal folds, called the posterior cricoarytenoid. The vocal folds cannot vibrate when they are open. The open position of the vocal folds also allows air to escape from the lungs during speech. As a result, the voices of these individuals often sound weak, quiet, and breathy or whispery. As with adductor spasmodic dysphonia, the spasms are often absent during activities such as laughing or singing, but singers can experience a loss of range or the inability to produce certain notes of a scale or with projection. Mixed spasmodic dysphonia Mixed spasmodic dysphonia is the most rare type. Mixed spasmodic dysphonia involves both muscles that open the vocal folds and those that close them and therefore has features of both adductor and abductor spasmodic dysphonia. Some researchers believe that a subset of cases classified as mixed spasmodic dysphonia may actually be ADSD or ABSD subtype with the addition of compensatory voice behaviours that make it appear mixed. This further adds to the difficulty in achieving accurate diagnosis. Whispering dysphonia A fourth type has also been described. This appears to be caused by mutations in the TUBB4 gene on the short arm of chromosome 19 (19p13.2-p13.3). This gene encodes a tubulin gene. The pathophysiology of this condition has yet to be determined. Treatment There are a number of potential treatments for spasmodic dysphonia, including Botox, voice therapy, and surgery. A number of medications have also been tried including anticholinergics (such as benztropine) which have been found to be effective in 40-50% of people, but which are associated with a number of side effects. Botulinum toxin Botulinum toxin (Botox) is often used to improve some symptoms of spasmodic dysphonia through weakening or paralyzing the vocal folds, thus preventing muscle spasms. The level of evidence for its use is currently limited; little is known about optimal dosage, frequency of injections, or exact location of injection. However, it remains a choice for many people due to the predictability and low chance of long term side effects. It results in periods of some improvement, with the duration of benefit lasting for 10–12 weeks on average before symptoms return to baseline. Repeat injection is required to sustain good vocal production, as results are only temporary. Some transient side effects observed in adductor spasmodic dysphonia include reduced speaking volume, difficulty swallowing, and a breathy and hoarse voice quality. While treatment outcomes are generally positive, it is presently unclear whether this treatment approach is more or less effective than others. Voice therapy Voice therapy appears to be ineffective in cases of true spasmodic dysphonia. However, as it is difficult to distinguish between spasmodic dysphonia and functional dysphonias, and misdiagnosis is relatively common, trial of voice therapy is often recommended before more invasive procedures are tried. Some also state that it is useful for mild symptoms and as an add-on to botox therapy and others report success in more severe cases. Laryngeal manual therapy, which is massaging of the neck and cervical structures, also shows positive results for intervention of functional dysphonia. Surgery If other measures are not effective, surgery may be considered; however, evidence to support surgery as a treatment for SD is limited. Treatment outcomes are generally positive, though more research is required to determine its effectiveness. Post-surgery voices can be imperfect and about 15% of people have significant difficulties. If symptoms do recur, this typically happens in the first 12 months. As of 2011, surgery was rarely used as a treatment approach for SD. Surgical approaches include recurrent laryngeal nerve resection, selective laryngeal adductor denervation-reinnervation (SLAD-R), thyroplasty, thyroarytenoid myectomy, and laryngeal nerve crush. Recurrent laryngeal nerve resection involves removing a section of the recurrent laryngeal nerve. Recurrent laryngeal nerve avulsion is a more drastic removal of sections of the nerve, and has positive outcomes of 80% at three years. SLAD-R is effective specifically for adductor spasmodic dysphonia, for which it has shown good outcomes in about 80% of people at 8 years. Thyroplasty changes the position or length of the vocal folds. History Initial surgical efforts to treat the condition were published in 1976 by Herbert Dedo and involved cutting of the recurrent laryngeal nerve. Notable cases Scott Adams, creator of the comic strip Dilbert Johnny Bush, country and western musician and songwriter Susan Collins, U.S. Senator from Maine Keath Fraser, Canadian author who has documented the challenges and treatment of his condition in the book The Voice Gallery: Travels With a Glass Throat (2002) Chip Hanauer, American hydroplane racing driver Robert F. Kennedy Jr., political and environmental activist, son of Robert F. Kennedy Mary Lou Lord, indie folk musician Benny Martin (1928–2001), American bluegrass fiddler, affected from 1980 to 1997 Darryl McDaniels of the rap group Run DMC Jenny Morris (OAM), New Zealand-born Australian pop, rock singer-songwriter Diane Rehm, American public radio talk show host Mark Stuart, American Christian rock musician, of Audio Adrenaline Linda Thompson, British folk-rock musician Aleesha Rome, causing her to quit her singing career. References == External links ==

Hey Aarogya!, what is Spider bite

Spider bite

A spider bite, also known as arachnidism, is an injury resulting from the bite of a spider. The effects of most bites are not serious. Most bites result in mild symptoms around the area of the bite. Rarely they may produce a necrotic skin wound or severe pain.: 455 Most spiders do not cause bites that are of importance. For a bite to be significant, substantial envenomation is required. Bites from the widow spiders involve a neurotoxic venom which produces a condition known as latrodectism. Symptoms may include pain which may be at the bite or involve the chest and abdomen, sweating, muscle cramps and vomiting among others. Bites from the recluse spiders cause the condition loxoscelism, in which local necrosis of the surrounding skin and widespread breakdown of red blood cells may occur. Headaches, vomiting and a mild fever may also occur. Other spiders that can cause significant bites include the Australian funnel-web spider and South American wandering spider.Efforts to prevent bites include clearing clutter and the use of pesticides. Most spider bites are managed with supportive care such as nonsteroidal anti-inflammatory drugs (including ibuprofen) for pain and antihistamines for itchiness. Opioids may be used if the pain is severe. While an antivenom exists for black widow spider venom, it is associated with anaphylaxis and therefore not commonly used in the United States. Antivenom against funnel web spider venom improves outcomes. Surgery may be required to repair the area of injured skin from some recluse bites.Spider bites may be overdiagnosed or misdiagnosed. In many reports of spider bites it is unclear if a spider bite actually occurred. Historically a number of conditions were attributed to spider bites. In the Middle Ages a condition claimed to arise from spider bites was tarantism, where people danced wildly. While necrosis has been attributed to the bites of a number of spiders, good evidence only supports this for recluse spiders. Signs and symptoms Almost all spiders are venomous, but not all spider bites result in the injection of venom. Pain from non-venomous bites, so-called "dry bites", typically lasts for 5 to 60 minutes while pain from envenomating spider bites may last for longer than 24 hours. Bleeding also may occur with a bite. Signs of a bacterial infection due to a spider bite occur infrequently (0.9%).A study of 750 definite spider bites in Australia indicated that 6% of spider bites cause significant effects, the vast majority of these being redback spider bites causing significant pain lasting more than 24 hours. Activation of the sympathetic nervous system can lead to sweating, high blood pressure and gooseflesh.Most recluse spider bites are minor with little or no necrosis. However, a small number of bites produce necrotic skin lesions. First pain and tenderness at the site begin. The redness changes over two to three days to a bluish sinking patch of dead skin—the hallmark of necrosis. The wound heals slowly over months but usually completely. Rarely, bites may cause widespread symptoms, with occasional fatalities.There are a few spiders that can bite human skin and cause a skin reaction, but spiders are blamed for many more reactions. In particular the misdiagnosis of infections and other skin ailments are commonly attributed to brown recluses. Cause Spiders do not feed on humans and typically bites occur as a defense mechanism. This can occur from unintentional contact or trapping of the spider. Most spiders have fangs too small to penetrate human skin. Most bites by species large enough for their bites to be noticeable will have no serious medical consequences.Medically significant spider venoms include various combinations and concentrations of necrotic agents, neurotoxins, and pharmacologically active compounds such as serotonin. Worldwide only two spider venoms have impact on humans—those of the widow and recluse spiders. Unlike snake and scorpion envenomation, widow and recluse species bites rarely have fatal consequences. In addition to the widespread widow and recluse spiders, some spider families found exclusively in remote tropical regions have a lethal neurotoxic venom: the wandering spider in Brazil and the funnel web in Australia. However, due to limited contact between these spiders and humans, deaths have always been rare, and since the introduction of anti-venom in Australia, there have been no funnel web related deaths. Pathophysiology A primary concern of the bite of a spider is the effect of its venom. A spider envenomation occurs whenever a spider injects venom into the skin. Not all spider bites involve injection of venom, and the amount of venom injected can vary based on the type of spider and the circumstances of the encounter. The mechanical injury from a spider bite is not a serious concern for humans. However, it is generally the toxicity of spider venom that poses the most risk to human beings; several spiders are known to have venom that can cause injury to humans in the amounts that a spider could inject when biting. While venoms are by definition toxic substances, most spiders do not have venom that is directly toxic (in the quantities delivered) to require medical attention and, of those that do, severity is typically mild. Spider venoms work on one of two fundamental principles; they are either neurotoxic (attacking the nervous system) or necrotic (attacking tissues surrounding the bite). In some cases, the venom affects vital organs and systems. The venoms of the widow spiders, Brazilian wandering spider and Australian funnel-web are neurotoxic. Heart muscle damage is an unusual complication of widow venom that may lead to death. Pulmonary edema, which is fluid accumulation in the lungs, is a feared and potentially serious but uncommon complication of funnel-web venom. Recluse and South African sand spider venoms are necrotic. Recluse venom may also cause severe hemolysis (destruction of red blood cells), though this is typically uncommon. Diagnosis Reliable diagnoses of spider bites require three conditions: first, there should be clinical effects of the bite at the time or soon afterwards, although there are no symptoms universally diagnostic of a spider bite, and bites by some spiders, e.g. Loxosceles species, may initially be painless; second, the spider should be collected, either at the time of the bite or immediately afterwards; and third, the spider should be identified by an expert arachnologist.Spider bites are commonly misdiagnosed. A review published in 2016 showed that 78% of 134 published medical case studies of supposed spider bites did not meet the necessary criteria for a spider bite to be verified. In the case of the two genera with the highest reported number of bites, Loxosceles and Latrodectus, spider bites were not verified in over 90% of the reports. Even when verification had occurred, details of the treatment and its effects were often lacking. Unverified bite reports likely represent many other conditions, both infectious and non-infectious, which can be confused with spider bites. Many of these conditions are far more common and more likely to be the source of necrotic wounds. An affected person may think that a wound is a spider bite when it is actually an infection with methicillin-resistant Staphylococcus aureus (MRSA). False reports of spider bites in some cases have led to misdiagnosis and mistreatment, with potentially life-threatening consequences. Prevention Efforts to prevent bites include clearing clutter and the use of pesticides.OSHA recommends that workers take following measures to prevent spider bite: Wear a long-sleeved shirt, hat, gloves, and boots when handling boxes, firewood, lumber, rocks, etc. Inspect and shake out clothing and shoes before getting dressed. Use insect repellents, such as DEET or Picaridin, on clothing and footwear. Management Most spider bites are harmless, and require no specific treatment. Treatment of bites may depend on the type of spider; thus, capture of the spider—either alive, or in a well-preserved condition, is useful.Treatment of spider bites includes washing the wound with soap and water and ice to reduce inflammation. Analgesics and antihistamines may be used; however, antibiotics are not recommended unless there is also a bacterial infection present. Black widow post-envenomation treatment seeks to control resulting pain and nausea. In the case of bites by widow spiders, Australian funnel-web spiders, or Brazilian wandering spiders, medical attention should be sought immediately as in some cases the bites of these spiders develop into a medical emergency. Antivenom is available for severe widow and funnel-web envenomation. Necrosis In almost all cases, recluse bites are self-limited and typically heal without any medical intervention. Recommendations to limit the extent of damage include elevation and immobilization of the affected limb, application of ice. Both local wound care, and tetanus prophylaxis, are simple standards. There is no established treatment for more extensive necrosis. Many therapies have been used including hyperbaric oxygen, dapsone, antihistamines (e.g., cyproheptadine), antibiotics, dextran, glucocorticoids, vasodilators, heparin, nitroglycerin, electric shock, curettage, surgical excision, and antivenom. None of these treatments conclusively show benefit. Studies have shown surgical intervention is ineffective and may worsen outcome. Excision may delay wound healing, cause abscesses, and lead to objectionable scarring.Dapsone, an antibiotic, is commonly used in the United States and Brazil for the treatment of necrosis. There have been conflicting reports with some supporting its efficacy and others have suggested it should no longer be used routinely, if at all. Antivenom Use of antivenom for severe spider bites may be indicated, especially in the case of neurotoxic venoms. Effective antivenoms exist for Latrodectus, Atrax, and Phoneutria venom. Antivenom in the United States is in intravenous form but is rarely used, as anaphylactic reaction to the antivenom has resulted in deaths. In Australia, antivenom in intramuscular form was once commonly used, but use has declined. In 2014 some doubt as to antivenom effectiveness has been raised. In South America an antivenom is available for Loxosceles bites, and it appears antivenom may be the most promising therapy for recluse bites. However, in experimental trials recluse antivenom is more effective when given early, and patients often do not present for 24 or more hours after envenomation, possibly limiting the effect of such intervention. Epidemiology Estimating the number of spider bites that occur is difficult as the spider involvement may not be confirmed or identified. Several researchers recommend only evaluating verified bites: those that have an eyewitness to the bite, the spider is brought in, and identified by expert. With "suspected arachnidism" the diagnosis came without a spider positively identified. Africa Several Latrodectus species (button spiders) live in Africa. South Africa also has six-eyed sand spiders (Hexophthalma species), whose bite may potentially cause skin necrosis. Physicians are advised that the diagnosis may be difficult without a spider. Australia Bites by the redbacks (Latrodectus hasselti) number a few thousand yearly throughout the country. Antivenom use is frequent but declining. Children may have fewer complications from bites. Funnel web spider bites are few 30–40 per year and 10% requiring intervention. The Sydney funnel web and related species are only on the east coast of Australia. Europe In Switzerland about ten to one hundred spider bites occur per one million people per year. During epidemics of latrodectism from the European black widow upwards of 150 bites a year were documented. North America The American Association of Poison Control Centers reported that they received calls regarding nearly 10,000 spider bites in 1994. The spiders of most concern in North America are brown recluse spiders, with nearly 1,500 bites in 2013 and black widow spiders with 1,800 bites. The native habitat of brown recluse spiders is in the southern and central United States, as far north as Iowa. Encounters with brown recluse outside this native region are very rare and bites are thought to be suspect. A dozen major complications were reported in 2013. South America Numerous spider bites are recorded in Brazil with 5000+ annually. Loxosceles species are responsible for the majority of reports. Accidents are concentrated in the southern state of Parana with rates as high as 1 per 1,000 people. Bite from Phoneutria (Brazilian wandering spider) number in the thousands with most being mild. Severe effects are noted in 0.5% of cases, mostly in children. History Recorded treatment from the 1890s for spider bites in general was rubbing in tobacco juice to the bitten skin, similar to some of the traditional uses of the tobacco plant for various bites and stings from Central and South America. Wild dancing and music was the cure for tarantism—the frenzy was believed to arise from the bite of a spider. An antivenom was developed against wolf spiders in Brazil and used for decades. Wolf spiders have since been exonerated—they never caused illness. See also ArachnoServer database Raventoxin Vanillotoxin References External links Medical Journal of Australia article gives statistics on the most frequent biters and the most serious bites. CDC – Venomous Spiders – NIOSH Workplace Safety and Health Topic

Hey Aarogya, explain a situation where Spontaneous bacterial peritonitis occurs

Spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis (SBP) is the development of a bacterial infection in the peritoneum, despite the absence of an obvious source for the infection. It is specifically an infection of the ascitic fluid – an increased volume of peritoneal fluid. Ascites is most commonly a complication of cirrhosis of the liver. It can also occur in patients with nephrotic syndrome. SBP has a high mortality rate.The diagnosis of SBP requires paracentesis, a sampling of the peritoneal fluid taken from the peritoneal cavity. If the fluid contains large numbers of white blood cells known as neutrophils (>250 cells/µL), infection is confirmed and antibiotics will be given, without waiting for culture results. In addition to antibiotics, infusions of albumin are usually administered.Other life-threatening complications such as kidney malfunction and increased liver insufficiency can be triggered by spontaneous bacterial peritonitis. 30% of SBP patients develop kidney malfunction, one of the strongest predictors for mortality. Where there are signs of this development albumin infusion will also be given.Spontaneous fungal peritonitis (SFP) can also occur and this can sometimes accompany a bacterial infection. Signs and symptoms Signs and symptoms of spontaneous bacterial peritonitis (SBP) include fevers, chills, nausea, vomiting, abdominal pain and tenderness, general malaise, altered mental status, and worsening ascites. Thirteen percent of patients have no signs or symptoms. In cases of acute or chronic liver failure SBP is one of the main triggers for hepatic encephalopathy, and where there is no other clear causal indication for this, SBP may be suspected.These symptoms can also be the same for a spontaneous fungal peritonitis (SFP) and therefore make a differentiation difficult. Delay of diagnosis can delay antifungal treatment and lead to a higher mortality rate. Causes SBP is most commonly caused by gram-negative E. coli, followed by Klebsiella. Common gram-positive bacteria identified include species of Streptococcus, Staphylococcus, and Enterococcus. The percentage of gram-positive bacteria responsible has been increasing.A spontaneous fungal infection can often follow a spontaneous bacterial infection that has been treated with antibiotics. The use of antibiotics can result in an excessive growth of fungi in the gut flora which can then translocate into the peritoneal cavity. Although fungi are much larger than bacteria, the increased intestinal permeability resulting from advanced cirrhosis makes their translocation easier. SFP is mostly caused by species of Candida and most commonly by Candida albicans. Pathophysiology H2 antagonists and proton-pump inhibitors are medications that decrease or suppress the secretion of acid by the stomach. Their use in treating cirrhosis is associated with the development of SBP. Bacterial translocation is thought to be the key mechanism for the development of SBP. Small intestinal bacterial overgrowth which may be implicated in this translocation, is found in a large percentage of those with cirrhosis. With respect to compromised host defenses, patients with severe acute or chronic liver disease are often deficient in complement and may also have malfunctioning of the neutrophilic and reticuloendothelial systems.As for the significance of ascitic fluid proteins, it was demonstrated that cirrhotic patients with ascitic protein concentrations below 1 g/dL were 10 times more likely to develop SBP than individuals with higher concentrations. It is thought that the antibacterial, or opsonic, activity of ascitic fluid is closely correlated with the protein concentration. Additional studies have confirmed the validity of the ascitic fluid protein concentration as the best predictor of the first episode of SBP.In nephrotic syndrome, SBP can frequently affect children but only very rarely can it affect adults. Diagnosis Infection of the peritoneum causes an inflammatory reaction with a subsequent increase in the number of neutrophils in the fluid. Diagnosis is made by paracentesis (needle aspiration of the ascitic fluid); SBP is diagnosed if the fluid contains neutrophils at greater than 250 cells per mm3 (equals a cell count of 250 x106/L) fluid in the absence of another reason for this (such as inflammation of one of the internal organs or a perforation).The fluid is also cultured to identify bacteria. If the sample is sent in a plain sterile container, 40% of samples will identify an organism, while if the sample is sent in a bottle with culture medium, the sensitivity increases to 72–90%. Prevention All people with cirrhosis might benefit from antibiotics (oral fluoroquinolone norfloxacin) if: Ascitic fluid protein <1.0 g/dL. Patients with fluid protein <15 g/L and either Child-Pugh score of at least 9 or impaired renal function may also benefit. Previous SBPPeople with cirrhosis admitted to the hospital should receive prophylactic antibiotics if: They have bleeding esophageal varicesStudies on the use of rifaximin in cirrhotic patients, have suggested that its use may be effective in preventing spontaneous bacterial peritonitis. Treatment Antibiotics Although there is no high-quality evidence, the third-generation cephalosporins are considered the standard empirical treatment for spontaneous bacterial peritonitis in people with cirrhosis.In practice, cefotaxime is the agent of choice for treatment of SBP. After confirmation of SBP, hospital admission is usually advised for observation and intravenous antibiotic therapy.Where there is a risk of kidney malfunction developing in a syndrome called hepatorenal syndrome, intravenous albumin is usually administered too. Paracentesis may be repeated after 48 hours to ensure control of infection. After recovery from a single episode of SBP, indefinite prophylactic antibiotics are recommended. Prokinetics The addition of a prokinetic drug to an antibiotic regimen reduces the incidence of spontaneous bacterial peritonitis possibly via decreasing small intestinal bacterial overgrowth. Intravenous albumin A randomized controlled trial found that intravenous albumin on the day of admission and on hospital day 3 can reduce kidney impairment. Epidemiology Patients with ascites underwent routine paracentesis, the incidence of active SBP ranged from 10% to 27% at the time of hospital admission. History SBP was first described in 1964 by Harold O. Conn. References == External links ==

Hey Aarogya , Do you know what is Sporotrichosis,

Sporotrichosis

Sporotrichosis, also known as rose handlers disease, is a fungal infection that affects skin, lungs, bone and joint, and can be widespread. It presents with firm painless nodules that later ulcerate. It can be localized or widespread. The disease progresses over a week to several months after the initial exposure to the fungus. Serious complications can also develop in people who have a weakened immune system.Sporotrichosis is caused by fungi of the Sporothrix schenckii species complex. Because S. schenckii is naturally found in soil, hay, sphagnum moss, and plants, it usually affects farmers, gardeners, and agricultural workers. It enters through small cuts in the skin to cause the infection. In case of sporotrichosis affecting the lungs, the fungal spores enter by breathing in. Sporotrichosis can also be acquired from handling cats with the disease; it is an occupational hazard for veterinarians.Treatment depends on the site and extent of infection. Topical antifungals can be applied to skin lesions. Deep infection in lungs may require surgery. Medications used include Itraconazole, posaconazole and amphotericin B. With treatment most people recover. The outcome may not be so good if there is a weak immune system or widespread disease.The causal fungus is found worldwide. The species was named for Benjamin Schenck, a medical student who in 1896 was the first to isolate it from a human specimen.It has been reported in cats, mules, dogs, mice and rats. Signs and symptoms Cutaneous or skin sporotrichosisThis is the most common form of this disease. Symptoms of this form include nodular lesions or bumps in the skin, at the point of entry and also along lymph nodes and vessels. The lesion starts off small and painless, and ranges in color from pink to purple. Left untreated, the lesion becomes larger and look similar to a boil and more lesions will appear, until a chronic ulcer develops.Usually, cutaneous sporotrichosis lesions occur in the finger, hand, and arm.Pulmonary sporotrichosisThis rare form of the disease occur when S. schenckii spores are inhaled. Symptoms of pulmonary sporotrichosis include productive coughing, nodules and cavitations of the lungs, fibrosis, and swollen hilar lymph nodes. Patients with this form of sporotrichosis are susceptible to developing tuberculosis and pneumoniaDisseminated sporotrichosisWhen the infection spreads from the primary site to secondary sites in the body, the disease develops into a rare and critical form called disseminated sporotrichosis. The infection can spread to joints and bones (called osteoarticular sporotrichosis) as well as the central nervous system and the brain (called sporotrichosis meningitis).The symptoms of disseminated sporotrichosis include weight loss, anorexia, and appearance of bony lesions. Complications Sporotrichosis lesions on the skin can become infected with bacteria. Cellulitis may also occur. Diagnosis Sporotrichosis is a chronic disease with slow progression and often subtle symptoms. It is difficult to diagnose, as many other diseases share similar symptoms and therefore must be ruled out. Patients with sporotrichosis will have antibody against the fungus S. schenckii, however, due to variability in sensitivity and specificity, it may not be a reliable diagnosis for this disease. The confirming diagnosis remains culturing the fungus from the skin, sputum, synovial fluid, and cerebrospinal fluid. Smears should be taken from the draining tracts and ulcers. Cats with sporotrichosis are unique in that the exudate from their lesions may contain numerous organisms. This makes cytological evaluation of exudate a valuable diagnostic tool in this species. Exudate is pyogranulomatous and phagocytic cells may be packed with yeast forms. These are variable in size, but many are cigar-shaped. Differential diagnosis Differential diagnosis includes: leishmaniasis, nocardiosis, mycobacterium marinum, cat-scratch disease, leprosy, syphilis, sarcoidosis and tuberculosis. Prevention The majority of sporotrichosis cases occur when the fungus is introduced through a cut or puncture in the skin while handling vegetation containing the fungal spores. Prevention of this disease includes wearing long sleeves and gloves while working with soil, hay bales, rose bushes, pine seedlings, and sphagnum moss. The risk of sporotrichosis in cats is increased in male cats that roam outdoors. Accordingly, the risk may be reduced by keeping cats indoors or neutering them. Isolating infected animals can also be a preventive measure. The risk of spread from infected cats to humans can be reduced by appropriate biosafety measures, including wearing protective equipment when handling a cat with suspected sporotrichosis and by washing hands, arms and clothing after handling the cat. Treatment Treatment of sporotrichosis depends on the severity and location of the disease. The following are treatment options for this condition: Oral potassium iodidePotassium iodide is an anti-fungal drug that is widely used as a treatment for cutaneous sporotrichosis. Despite its wide use, there is no high-quality evidence for or against this practice. Further studies are needed to assess the efficacy and safety of oral potassium iodide in the treatment of sporotrichosis.Itraconazole (Sporanox) and fluconazoleThese are antifungal drugs. Itraconazole is currently the drug of choice and is significantly more effective than fluconazole. Fluconazole should be reserved for patients who cannot tolerate itraconazole.Amphotericin BThis antifungal medication is delivered intravenously. Many patients, however, cannot tolerate Amphotericin B due to its potential side effects of fever, nausea, and vomiting. Lipid formulations of amphotericin B are usually recommended instead of amphotericin B deoxycholate because of a better adverse-effect profile. Amphotericin B can be used for severe infection during pregnancy. For children with disseminated or severe disease, amphotericin B deoxycholate can be used initially, followed by itraconazole.In case of sporotrichosis meningitis, the patient may be given a combination of Amphotericin B and 5-fluorocytosine/Flucytosine.Terbinafine500mg and 1000mg daily dosages of terbinafine for twelve to 24 weeks has been used to treat cutaneous sporotrichosis.Newer triazolesSeveral studies have shown that posaconazole has in vitro activity similar to that of amphotericin B and itraconazole; therefore, it shows promise as an alternative therapy. However, voriconazole susceptibility varies. Because the correlation between in vitro data and clinical response has not been demonstrated, there is insufficient evidence to recommend either posaconazole or voriconazole for treatment of sporotrichosis at this time.SurgeryIn cases of bone infection and cavitary nodules in the lungs, surgery may be necessary.Heat therapyHeat creates higher tissue temperatures, which may inhibit fungus growth while the immune system counteracts the infection. The "pocket warmer" used for this purpose has the advantage of being able to maintain a constant temperature of 44 degrees-45 degrees C on the skin surface for several hours, while permitting unrestricted freedom of movement. The duration of treatment depends on the type of lesion, location, depth, and size. Generally, local application for 1-2 h per day, or in sleep time, for 5-6 weeks seems to be sufficient. Other animals Sporotrichosis can be diagnosed in domestic and wild mammals. In veterinary medicine it is most frequently seen in cats and horses. Cats have a particularly severe form of cutaneous sporotrichosis. Infected cats may exhibit abscesses, cellulitis, or draining wounds that fail to respond to antibiotic treatment.Sporotrichosis can spread from nonhuman animals to humans (zoonosis). Infected cats in particular exude large quantities of Sporothrix organisms from their skin leasions and can spread the infection to people who handle them. Although cats are the most common animal source, the infection has also been known to spread to humans from dogs, rats, squirrels, and armadillos. See also Mucormycosis List of cutaneous conditions References External links Sporotrichosis by Health in Plain English (with pictures) Sporotrichosis by Centers for Disease Control and Prevention (CDC)

Hey Aarogya, could you help me understand about Strabismus

Strabismus

Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a large part of childhood, it may result in amblyopia, or lazy eyes, and loss of depth perception. If onset is during adulthood, it is more likely to result in double vision.Strabismus can occur due to muscle dysfunction, farsightedness, problems in the brain, trauma or infections. Risk factors include premature birth, cerebral palsy and a family history of the condition. Types include esotropia, where the eyes are crossed ("cross eyed"); exotropia, where the eyes diverge ("lazy eyed" or "wall eyed"); and hypertropia or hypotropia where they are vertically misaligned. They can also be classified by whether the problem is present in all directions a person looks (comitant) or varies by direction (incomitant). Diagnosis may be made by observing the light reflecting from the persons eyes and finding that it is not centered on the pupil. This is known as the Hirschberg reflex. Another condition that produces similar symptoms is a cranial nerve disease.Treatment depends on the type of strabismus and the underlying cause. This may include the use of glasses and possibly surgery. Some types benefit from early surgery. Strabismus occurs in about 2% of children. The term comes from the Ancient Greek word στραβισμός (strabismós), meaning a squinting. Other terms for the condition include "squint" and "cast of the eye". "Wall-eye" has been used when the eyes turn away from each other. Signs and symptoms When observing a person with strabismus, the misalignment of the eyes may be quite apparent. A person with a constant eye turn of significant magnitude is very easy to notice. However, a small magnitude or intermittent strabismus can easily be missed upon casual observation. In any case, an eye care professional can conduct various tests, such as cover testing, to determine the full extent of the strabismus.Symptoms of strabismus include double vision and eye strain. To avoid double vision, the brain may adapt by ignoring one eye. In this case, often no noticeable symptoms are seen other than a minor loss of depth perception. This deficit may not be noticeable in someone who has had strabismus since birth or early childhood, as they have likely learned to judge depth and distances using monocular cues. However, a constant unilateral strabismus causing constant suppression is a risk for amblyopia in children. Small-angle and intermittent strabismus are more likely to cause disruptive visual symptoms. In addition to headaches and eye strain, symptoms may include an inability to read comfortably, fatigue when reading, and unstable or "jittery" vision. Psychosocial effects People of all ages who have noticeable strabismus may experience psychosocial difficulties. Attention has also been drawn to potential socioeconomic impact resulting from cases of detectable strabismus. A socioeconomic consideration exists as well in the context of decisions regarding strabismus treatment, including efforts to re-establish binocular vision and the possibility of stereopsis recovery.One study has shown that strabismic children commonly exhibit behaviors marked by higher degrees of inhibition, anxiety, and emotional distress, often leading to outright emotional disorders. These disorders are often related to a negative perception of the child by peers. This is due not only to an altered aesthetic appearance, but also because of the inherent symbolic nature of the eye and gaze, and the vitally important role they play in an individuals life as social components. For some, these issues improved dramatically following strabismus surgery. Notably, strabismus interferes with normal eye contact, often causing embarrassment, anger, and feelings of awkwardness, thereby affecting social communication in a fundamental way, with a possible negative effect on self esteem.Children with strabismus, particularly those with exotropia, an outward turn, may be more likely to develop a mental health disorder than normal-sighted children. Researchers have theorized that esotropia (an inward turn) was not found to be linked to a higher propensity for mental illness due to the age range of the participants, as well as the shorter follow-up time period; esotropic children were monitored to a mean age of 15.8 years, compared with 20.3 years for the exotropic group.A subsequent study with participants from the same area monitored people with congenital esotropia for a longer time period; results indicated that people who are esotropic were also more likely to develop mental illness of some sort upon reaching early adulthood, similar to those with constant exotropia, intermittent exotropia, or convergence insufficiency. The likelihood was 2.6 times that of controls. No apparent association with premature birth was observed, and no evidence was found linking later onset of mental illness to psychosocial stressors frequently encountered by those with strabismus.Investigations have highlighted the impact that strabismus may typically have on quality of life. Studies in which subjects were shown images of strabismic and non-strabismic persons showed a strong negative bias towards those visibly displaying the condition, clearly demonstrating the potential for future socioeconomic implications with regard to employability, as well as other psychosocial effects related to an individuals overall happiness.Adult and child observers perceived a right heterotropia as more disturbing than a left heterotropia, and child observers perceived an esotropia as "worse" than an exotropia. Successful surgical correction of strabismus, for adult as well as children, has been shown to have a significantly positive effect on psychological well-being.Very little research exists regarding coping strategies employed by adult strabismics. One study categorized coping methods into three subcategories: avoidance (refraining from participation in an activity), distraction (deflecting attention from the condition), and adjustment (approaching an activity differently). The authors of the study suggested that individuals with strabismus may benefit from psychosocial support such as interpersonal skills training. No studies have evaluated whether psychosocial interventions have had any benefits on individuals undergoing strabismus surgery. Pathophysiology The extraocular muscles control the position of the eyes. Thus, a problem with the muscles or the nerves controlling them can cause paralytic strabismus. The extraocular muscles are controlled by cranial nerves III, IV, and VI. An impairment of cranial nerve III causes the associated eye to deviate down and out and may or may not affect the size of the pupil. Impairment of cranial nerve IV, which can be congenital, causes the eye to drift up and perhaps slightly inward. Sixth nerve palsy causes the eyes to deviate inward and has many causes due to the relatively long path of the nerve. Increased cranial pressure can compress the nerve as it runs between the clivus and brain stem. Also, if the doctor is not careful, twisting of the babys neck during forceps delivery can damage cranial nerve VI.Evidence indicates a cause for strabismus may lie with the input provided to the visual cortex. This allows for strabismus to occur without the direct impairment of any cranial nerves or extraocular muscles.Strabismus may cause amblyopia due to the brain ignoring one eye. Amblyopia is the failure of one or both eyes to achieve normal visual acuity despite normal structural health. During the first seven to eight years of life, the brain learns how to interpret the signals that come from an eye through a process called visual development. Development may be interrupted by strabismus if the child always fixates with one eye and rarely or never fixates with the other. To avoid double vision, the signal from the deviated eye is suppressed, and the constant suppression of one eye causes a failure of the visual development in that eye.Also, amblyopia may cause strabismus. If a great difference in clarity occurs between the images from the right and left eyes, input may be insufficient to correctly reposition the eyes. Other causes of a visual difference between right and left eyes, such as asymmetrical cataracts, refractive error, or other eye disease, can also cause or worsen strabismus.Accommodative esotropia is a form of strabismus caused by refractive error in one or both eyes. Due to the near triad, when a person engages accommodation to focus on a near object, an increase in the signal sent by cranial nerve III to the medial rectus muscles results, drawing the eyes inward; this is called the accommodation reflex. If the accommodation needed is more than the usual amount, such as with people with significant hyperopia, the extra convergence can cause the eyes to cross. Diagnosis During an eye examination, a test such as cover testing or the Hirschberg test is used in the diagnosis and measurement of strabismus and its impact on vision. Retinal birefringence scanning can be used for screening of young children for eye misalignment. A Cochrane review to examine different types of diagnosis test found only one study. This study used a photoscreener which was found to have high specificity (accurate in identifying those without the condition) but low sensitivity (inaccurate in identifying those with the condition).Several classifications are made when diagnosing strabismus. Latency Strabismus can be manifest (-tropia) or latent (-phoria). A manifest deviation, or heterotropia (which may be eso-, exo-, hyper-, hypo-, cyclotropia or a combination of these), is present while the person views a target binocularly, with no occlusion of either eye. The person is unable to align the gaze of each eye to achieve fusion. A latent deviation, or heterophoria (eso-, exo-, hyper-, hypo-, cyclophoria or a combination of these), is only present after binocular vision has been interrupted, typically by covering one eye. This type of person can typically maintain fusion despite the misalignment that occurs when the positioning system is relaxed. Intermittent strabismus is a combination of both of these types, where the person can achieve fusion, but occasionally or frequently falters to the point of a manifest deviation. Onset Strabismus may also be classified based on time of onset, either congenital, acquired, or secondary to another pathological process. Many infants are born with their eyes slightly misaligned, and this is typically outgrown by six to 12 months of age. Acquired and secondary strabismus develop later. The onset of accommodative esotropia, an overconvergence of the eyes due to the effort of accommodation, is mostly in early childhood. Acquired non-accommodative strabismus and secondary strabismus are developed after normal binocular vision has developed. In adults with previously normal alignment, the onset of strabismus usually results in double vision. Any disease that causes vision loss may also cause strabismus, but it can also result from any severe and/or traumatic injury to the affected eye. Sensory strabismus is strabismus due to vision loss or impairment, leading to horizontal, vertical or torsional misalignment or to a combination thereof, with the eye with poorer vision drifting slightly over time. Most often, the outcome is horizontal misalignment. Its direction depends on the persons age at which the damage occurs: people whose vision is lost or impaired at birth are more likely to develop esotropia, whereas people with acquired vision loss or impairment mostly develop exotropia. In the extreme, complete blindness in one eye generally leads to the blind eye reverting to an anatomical position of rest.Although many possible causes of strabismus are known, among them severe and/or traumatic injuries to the affected eye, in many cases no specific cause can be identified. This last is typically the case when strabismus is present since early childhood.Results of a U.S. cohort study indicate that the incidence of adult-onset strabismus increases with age, especially after the sixth decade of life, and peaks in the eighth decade of life, and that the lifetime risk of being diagnosed with adult-onset strabismus is approximately 4%. Laterality Strabismus may be classified as unilateral if the one eye consistently deviates, or alternating if either of the eyes can be seen to deviate. Alternation of the strabismus may occur spontaneously, with or without subjective awareness of the alternation. Alternation may also be triggered by various tests during an eye exam. Unilateral strabismus has been observed to result from a severe or traumatic injury to the affected eye. Direction and latency Horizontal deviations are classified into two varieties, using prefixes: eso- describes inward or convergent deviations towards the midline, while exo- describes outward or divergent misalignment. Vertical deviations are also classified into two varieties, using prefixes: hyper- is the term for an eye whose gaze is directed higher than the fellow eye, while hypo- refers to an eye whose gaze is directed lower. Finally, the prefix cyclo- refers to torsional strabismus, which occurs when the eyes rotate around the anterior-posterior axis to become misaligned and is quite rare. These five directional prefixes are combined with -tropia (if manifest) or -phoria (if latent) to describe various types of strabismus. For example, a constant left hypertropia exists when a persons left eye is always aimed higher than the right. A person with an intermittent right esotropia has a right eye that occasionally drifts toward the persons nose, but at other times is able to align with the gaze of the left eye. A person with a mild exophoria can maintain fusion during normal circumstances, but when the system is disrupted, the relaxed posture of the eyes is slightly divergent. Other considerations Strabismus can be further classified as follows: Paretic strabismus is due to paralysis of one or several extraocular muscles. Nonparetic strabismus is not due to paralysis of extraocular muscles. Comitant (or concomitant) strabismus is a deviation that is the same magnitude regardless of gaze position. Noncomitant (or incomitant) strabismus has a magnitude that varies as the person shifts his or her gaze up, down, or to the sides.Nonparetic strabismus is generally concomitant. Most types of infant and childhood strabismus are comitant. Paretic strabismus can be either comitant or noncomitant. Incomitant strabismus is almost always caused by a limitation of ocular rotations that is due to a restriction of extraocular eye movement (ocular restriction) or due to extraocular muscle paresis. Incomitant strabismus cannot be fully corrected by prism glasses, because the eyes would require different degrees of prismatic correction dependent on the direction of the gaze. Incomitant strabismus of the eso- or exo-type are classified as "alphabet patterns": they are denoted as A- or V- or more rarely λ-, Y- or X-pattern depending on the extent of convergence or divergence when the gaze moves upward or downward. These letters of the alphabet denote ocular motility pattern that have a similarity to the respective letter: in the A-pattern there is (relatively speaking) more convergence when the gaze is directed upwards and more divergence when it is directed downwards, in the V-pattern it is the contrary, in the λ-, Y- and X-patterns there is little or no strabismus in the middle position but relatively more divergence in one or both of the upward and downward positions, depending on the "shape" of the letter.Types of incomitant strabismus include: Duane syndrome, horizontal gaze palsy, and congenital fibrosis of the extraocular muscles.When the misalignment of the eyes is large and obvious, the strabismus is called large-angle, referring to the angle of deviation between the lines of sight of the eyes. Less severe eye turns are called small-angle strabismus. The degree of strabismus can vary based on whether the person is viewing a distant or near target. Strabismus that sets in after eye alignment had been surgically corrected is called consecutive strabismus. Differential diagnosis Pseudostrabismus is the false appearance of strabismus. It generally occurs in infants and toddlers whose bridge of the nose is wide and flat, causing the appearance of esotropia due to less sclera being visible nasally. With age, the bridge of the childs nose narrows and the folds in the corner of the eyes become less prominent. Management Retinoblastoma may also result in abnormal light reflection from the eye. Strabismus is usually treated with a combination of eyeglasses, vision therapy, and surgery, depending on the underlying reason for the misalignment. As with other binocular vision disorders, the primary goal is comfortable, single, clear, normal binocular vision at all distances and directions of gaze.Whereas amblyopia (lazy eye), if minor and detected early, can often be corrected with use of an eye patch on the dominant eye or vision therapy, the use of eye patches is unlikely to change the angle of strabismus. Glasses In cases of accommodative esotropia, the eyes turn inward due to the effort of focusing far-sighted eyes, and the treatment of this type of strabismus necessarily involves refractive correction, which is usually done via corrective glasses or contact lenses, and in these cases surgical alignment is considered only if such correction does not resolve the eye turn. In case of strong anisometropia, contact lenses may be preferable to spectacles because they avoid the problem of visual disparities due to size differences (aniseikonia) which is otherwise caused by spectacles in which the refractive power is very different for the two eyes. In a few cases of strabismic children with anisometropic amblyopia, a balancing of the refractive error eyes via refractive surgery has been performed before strabismus surgery was undertaken.Early treatment of strabismus when the person is a baby may reduce the chance of developing amblyopia and depth perception problems. However, a review of randomized controlled trials concluded that the use of corrective glasses to prevent strabismus is not supported by existing research. Most children eventually recover from amblyopia if they have had the benefit of patches and corrective glasses. Amblyopia has long been considered to remain permanent if not treated within a critical period, namely before the age of about seven years; however, recent discoveries give reason to challenge this view and to adapt the earlier notion of a critical period to account for stereopsis recovery in adults. Eyes that remain misaligned can still develop visual problems. Although not a cure for strabismus, prism lenses can also be used to provide some temporary comfort and to prevent double vision from occurring. Glasses affect the position by changing the persons reaction to focusing. Prisms change the way light, and therefore images, strike the eye, simulating a change in the eye position. Surgery Strabismus surgery does not remove the need for a child to wear glasses. Currently it is unknown whether there are any differences for completing strabismus surgery before or after amblyopia therapy in children.Strabismus surgery attempts to align the eyes by shortening, lengthening, or changing the position of one or more of the extraocular eye muscles. The procedure can typically be performed in about an hour, and requires about six to eight weeks for recovery. Adjustable sutures may be used to permit refinement of the eye alignment in the early postoperative period. It is unclear if there are differences between adjustable versus non-adjustable sutures as it has not been sufficiently studied. An alternative to the classical procedure is minimally invasive strabismus surgery (MISS) that uses smaller incisions than usual. Medication Medication is used for strabismus in certain circumstances. In 1989, the US FDA approved botulinum toxin therapy for strabismus in people over 12 years old. Most commonly used in adults, the technique is also used for treating children, in particular children affected by infantile esotropia. The toxin is injected in the stronger muscle, causing temporary and partial paralysis. The treatment may need to be repeated three to four months later once the paralysis wears off. Common side effects are double vision, droopy eyelid, overcorrection, and no effect. The side effects typically resolve also within three to four months. Botulinum toxin therapy has been reported to be similarly successful as strabismus surgery for people with binocular vision and less successful than surgery for those who have no binocular vision. Prognosis When strabismus is congenital or develops in infancy, it can cause amblyopia, in which the brain ignores input from the deviated eye. Even with therapy for amblyopia, stereoblindness may occur. The appearance of strabismus may also be a cosmetic problem. One study reported 85% of adult with strabismus "reported that they had problems with work, school, and sports because of their strabismus." The same study also reported 70% said strabismus "had a negative effect on their self-image." A second operation is sometimes required to straighten the eyes. Other animals Siamese cats and related breeds are prone to having crossed eyes. Research suggests this is a behavioral compensation for developmental abnormalities in the routing of nerves in the optic chiasm.Strabismus may also occur in dogs, most often due to imbalanced muscle tone of the muscles surrounding the eye. Some breeds such as the Shar Pei are genetically predisposed to the condition. Treatment may involve surgery or therapy to strengthen the muscles. References Further reading Donahue SP, Buckley EG, Christiansen SP, Cruz OA, Dagi LR (August 2014). "Difficult problems: strabismus". Journal of American Association for Pediatric Ophthalmology and Strabismus. 18 (4): e41. doi:10.1016/j.jaapos.2014.07.132. External links AAO Complex strabismus simulator UC Davis strabismus simulator

Hello Aarogya, explain a situation where Strongyloidiasis occurs

Strongyloidiasis

Strongyloidiasis is a human parasitic disease caused by the nematode called Strongyloides stercoralis, or sometimes the closely related S. fülleborni. These helminths belong to a group of nematodes called roundworms. These intestinal worms can cause a number of symptoms in people, principally skin symptoms, abdominal pain, diarrhea and weight loss, but also many other specific and vague symptoms in disseminated disease, and severe life-threatening conditions through hyperinfection. In some people, particularly those who require corticosteroids or other immunosuppressive medication, Strongyloides can cause a hyperinfection syndrome that can lead to death if untreated. The diagnosis is made by blood and stool tests. The medication ivermectin is widely used to treat strongyloidiasis. Strongyloidiasis is a type of soil-transmitted helminthiasis. Low estimates postulate it to affect 30–100 million people worldwide, mainly in tropical and subtropical countries, while higher estimates conservatively extrapolate that infection is upwards to or above 370 million people. It belongs to the group of neglected tropical diseases, and worldwide efforts are aimed at eradicating the infection. Signs and symptoms Strongyloides infection occurs in five forms. As the infection continues and the larvae matures, there may be respiratory symptoms (Löfflers syndrome). The infection may then become chronic with mainly digestive symptoms. On reinfection (when larvae migrate through the body) from the skin to the lungs and finally to the small intestine, there may be respiratory, skin and digestive symptoms. Finally, the hyperinfection syndrome causes symptoms in many organ systems, including the central nervous system. Uncomplicated disease Frequently asymptomatic. Gastrointestinal system symptoms include abdominal pain and diarrhea and/or conversely constipation. Pulmonary symptoms (including Löfflers syndrome) can occur during pulmonary migration of the filariform larvae. Pulmonary infiltrate may be present through radiological investigation. Dermatologic manifestations include urticarial rashes in the buttocks and waist areas as well as larva currens. Eosinophilia is generally present. Strongyloidiasis can become chronic and then become completely asymptomatic. Disseminated disease Disseminated strongyloidiasis occurs when patients with chronic strongyloidiasis become immunosuppressed. There is a distinction to be made between dissemination and hyperinfection. It is mainly a semantic distinction. There can be mild dissemination where the worm burden is relatively lower yet causes insidious symptoms, or extreme dissemination that the term hyperinfection is used to describe. Thus hyperinfection of varying levels of severe dissemination may present with abdominal pain, distension, shock, pulmonary and neurologic complications, sepsis, haemorrhage, malabsorption, and depending on the combination, degree, number, and severity of symptoms, is potentially fatal. The worms enter the bloodstream from the bowel wall, simultaneously allowing entry of bowel bacteria such as Escherichia coli. This may cause symptoms such as sepsis (bloodstream infection), and the bacteria may spread to other organs where they may cause localized infection such as meningitis. Dissemination without hyperinfection may present to a lesser degree the above and many other symptoms.Dissemination can occur many decades after the initial infection and has been associated with high dose corticosteroids, organ transplant, any other instances and causes of immunosuppression, HIV, lepromatous leprosy, tertiary syphilis, aplastic anemia, malnutrition, advanced tuberculosis and radiation poisoning. It is often recommended that patients being started on immunosuppression be screened for chronic strongyloidiasis; however, this is often impractical (screen tests are often unavailable) and in developed countries, the prevalence of chronic strongyloidiasis is very small, so screening is usually not cost-effective, except in endemic areas. The reality of global travel and need for modern advanced healthcare, even in the so-called "developed world", necessitates that in non-endemic areas there is easily accessible testing and screening for neglected tropical diseases such as strongyloidiasis.It is important to note that there is not necessarily any eosinophilia in the disseminated disease. Absence of eosinophilia in an infection limited to the gastrointestinal tract may indicate poor prognosis. Eosinophilia is often absent in disseminated infection. Steroids will also suppress eosinophilia, while leading to dissemination and potential hyperinfection.Escalated disseminated infections caused by immunosuppression can result in a wide variety and variable degree of disparate symptoms depending on the condition and other biological aspects of the individual, that may emulate other diseases or diagnoses. In addition to the many palpable gastrointestinal and varied other symptoms drastic cachexia amidst lassitude is often present, although severe disseminated infections can occur in individuals without weight loss regardless of body mass index. Diagnosis Diagnosis rests on the microscopic identification of larvae (rhabditiform and occasionally filariform) in the stool or duodenal fluid. Examination of many samples may be necessary, and not always sufficient, because direct stool examination is relatively insensitive, with a single sample only able to detect larvae in about 25% of cases. It can take 4 weeks from initial infection to the passage of larvae in the stool. The stool can be examined in wet mounts: directly after concentration (formalin-ethyl acetate) after recovery of the larvae by the Baermann funnel technique after culture by the Harada-Mori filter paper technique after culture in agar platesCulture techniques are the most sensitive, but are not routinely available in the West. In the UK, culture is available at either of the Schools of Tropical Medicine in Liverpool or London. Direct examination must be done on stool that is freshly collected and not allowed to cool down, because hookworm eggs hatch on cooling and the larvae are very difficult to distinguish from Strongyloides.Finding Strongyloides in the stool is negative in up to 70% of tests. It is important to undergo frequent stool sampling as well as duodenal biopsy if a bad infection is suspected. The duodenal fluid can be examined using techniques such as the Enterotest string or duodenal aspiration. Larvae may be detected in sputum from patients with disseminated strongyloidiasis. Given the poor ability of stool examination to diagnose Strongyloides, detecting antibodies by ELISA can be useful. Serology can cross-react with other parasites, remain positive for years after successful treatment or be falsely negative in immunocompromised patients. Infected patients will also often have an elevated eosinophil count, with an average of absolute eosinophil count of 1000 in one series. Eosinophilia of a gastrointestinal infection may fluctuate in response to larval output, or may be permanently lacking in some disseminated infections. Hence lack of eosinophilia is not evidence of absence of infection. The combination of clinical suspicion, a positive antibody and a peripheral eosinophilia can be strongly suggestive of infection.It would be greatly useful to have significant advances in the sensitivity of the means of diagnosis, as it would also solve the challenging problem of proof of cure. If definitive diagnosis is solved then it stands to reason that proof of cure becomes easily realizable. Treatment The consensus drug of choice for the treatment of uncomplicated strongyloidiasis is ivermectin. However, even if it is considered the main drug of choice, recent studies have illustrated the challenges in ivermectin curing strongyloidiasis. Ivermectin does not kill the Strongyloides larvae, only the adult worms, therefore repeat dosing may be necessary to properly eradicate the infection. There is an auto-infective cycle of roughly two weeks in which ivermectin should be re-administered; however, additional dosing may still be necessary as it will not kill Strongyloides in the blood or larvae deep within the bowels or diverticula. Other drugs that can be effective are albendazole and thiabendazole (25 mg/kg twice daily for 5 days—400 mg maximum (generally)). All patients who are at risk of disseminated strongyloidiasis should be treated. The optimal duration of treatment for patients with disseminated infections is not clear.Treatment of strongyloidiasis can be difficult and if ceasing treatment before being entirely cleared Strongyloides via the autoinfective cycle has been known to live in individuals for decades; even after initial or inadequate sustained treatment. Continued treatment, blood and stool monitoring thus may be necessary even if symptoms temporarily resolve. As cited earlier, due to the fact that some infections are insidiously asymptomatic, and relatively expensive bloodwork is often inconclusive via false-positives or false-negatives, just as stool samples can be unreliable in diagnoses, there is yet unfortunately no real gold standard for proof of cure, mirroring the lack of an efficient and reliable methodology of diagnosis. An objective eradication standard for strongyloidiasis is elusive given the high degree of suspicion needed to even begin treatment, the sometimes difficulty of the only definitive diagnostic criteria of detecting and isolating larvae or adult Strongyloides, the importance of early diagnosis, particularly before steroid treatments, and the very wide variability and exclusion/inclusion of differing collections of diffuse symptoms. Disregarding mis-ascribing bonafide delusional parasitosis disorders, strongyloidiasis should be more well known among medical professionals and have serious consideration for broad educational campaigns in effected geographic locales both within the semi-tropical developed world and otherwise, as well as in the tropical developing world where, among many other neglected tropical diseases, it is endemic.Government programs are needed to help decontaminate endemic areas and to help effected populations from infection. Furthermore, progress is required in establishing financial support to facilitate and cover affordable medications for individuals in effected at-risk regions and communities to help continuing treatments.There are conflicting reports on effective drug treatments. Ivermectin ineffectiveness and rising drug resistance has been documented. Albendazole is noted by the WHO as being the least effective. Thiabendazole can have severe side effects and is unavailable in many countries. Major inroads are required to advance the development of successful medications and drug protocols for strongyloidiasis and other neglected tropical diseases.Contagiousness via textiles, unlike Enterobius vermicularis, is unfounded. As is, generally speaking, person to person contagiousness of asymptomatic and disseminated infection. It has rarely been transmitted through organ transplantation. Married Vietnam War veterans who were infected, yet never developed significant hyperinfection, lived for multiple decades with non-debilitating disseminated infection, without treatment, with wives who failed to ever contract infection. Contraction occurs overwhelmingly from skin exposure to any contaminated soil, contaminated potting soil, contaminated waters, lack of sanitation, or environmental factors as potential vectors. Nearly never to extraordinarily very rarely documented is transmission from person to person (besides from infected male homosexual sex), other than closeness of contact to the productive coughing of a very ill hyperinfected individual. It has been shown possible to occur in that situation, or potentially other similar scenarios, it is speculated via pulmonary secretions of a direly hyperinfected individual. In which case treatment for others may be indicated, if deemed necessary by proximity, symptoms, precautions, probable exposures to the same vectors, or through screening of serology and stool samples, until infection is eradicated.Before administering steroids at least somewhat screening for infection in even remotely potentially susceptible individuals in order to prevent escalating the infection is advised. As not doing so in certain cohorts can have extremely high mortality rates from inadvertently caused hyperinfection via immunosuppression of application of certain steroids. Thus extreme caution with respect to iatrogenic risks is crucial to avoiding deaths or other adverse consequences in treatment, that of course prefigures a correct diagnosis. People with high exposure to Strongyloides stercoralis may mitigate the risk of strongyloidiasis hyperinfection associated with corticosteroid treatment, with the presumptive use of ivermectin. Such hyperinfection has been a particular concern during the COVID-19 pandemic because of the use of corticosteroids for treatment of COVID-19 symptoms. The CDC and other international bodies recommend the use of ivermectin for refugees from areas which have a risk of strongyloidiasis.During the 1940s, the treatment of choice was enteric coated tablets of 60 mg gentian violet, three times daily, for 16 days. The cure rate was reported to be only about 50 to 70 percent, requiring repeat courses. It is possible the cure rate was even less than that published in the literature, due to the difficulty in positively diagnosing infection. Epidemiology Low estimates postulate it to affect 30–100 million people worldwide, mainly in tropical and subtropical countries, while higher estimates conservatively extrapolate that infection is upwards to or above 370 million people. It belongs to the group of neglected tropical diseases, and worldwide efforts are aimed at eradicating the infection. History The disease was first recognized in 1876 by the French physician Louis Alexis Normand, working in the naval hospital in Toulon; he identified the adult worms, and sent them to Arthur Réné Jean Baptiste Bavay, chief inspector for health, who observed that these were the adult forms of the larvae found in the stool. In 1883 the German parasitologist Rudolf Leuckart made initial observations on the life cycle of the parasite, and Belgian physician Paul Van Durme (building on observations by the German parasitologist Arthur Looss) described the mode of infection through the skin. The German parasitologist Friedrich Fülleborn described autoinfection and the way by which strongyloidiasis involves the intestine. Interest in the condition increased in the 1940s when it was discovered that those who had acquired the infection abroad and then received immunosuppression developed hyperinfestation syndrome. References External links Strongyloidiasis. U.S. Centers for Disease Control and Prevention (CDC)

Hi Aarogya, explain a situation where Sympathetic ophthalmia occurs

Sympathetic ophthalmia

Sympathetic ophthalmia (SO), also called spared eye injury, is a diffuse granulomatous inflammation of the uveal layer of both eyes following trauma to one eye. It can leave the affected person completely blind. Symptoms may develop from days to several years after a penetrating eye injury. It typically results from a delayed hypersensitivity reaction. Signs and symptoms Eye floaters and loss of accommodation are among the earliest symptoms. The disease may progress to severe inflammation of the uveal layer of the eye (uveitis) with pain and sensitivity of the eyes to light. The affected eye often remains relatively painless while the inflammatory disease spreads through the uvea, where characteristic focal infiltrates in the choroid named Dalén–Fuchs nodules can be seen. The retina, however, usually remains uninvolved, although perivascular cuffing of the retinal vessels with inflammatory cells may occur. Swelling of the optic disc (papilledema), secondary glaucoma, vitiligo, and poliosis of the eyelashes may accompany SO. Pathophysiology Sympathetic ophthalmia is currently thought to be an autoimmune inflammatory response toward ocular antigens, specifically a delayed hypersensitivity to melanin-containing structures from the outer segments of the photoreceptor layer of the retina. The immune system, which normally is not exposed to ocular proteins, is introduced to the contents of the eye following traumatic injury. Once exposed, it senses these antigens as foreign, and begins attacking them. The onset of this process can be from days to years after the inciting traumatic event. Diagnosis Diagnosis is clinical, seeking a history of eye injury. An important differential diagnosis is Vogt–Koyanagi–Harada syndrome (VKH), which is thought to have the same pathogenesis, without a history of surgery or penetrating eye injury. Still experimental, skin tests with soluble extracts of human or bovine uveal tissue are said to elicit delayed hypersensitivity responses in these patients. Additionally, circulating antibodies to uveal antigens have been found in patients with SO and VKH, as well as those with long-standing uveitis, making this a less than specific assay for SO and VKH. Treatment Because SO is so rarely encountered following eye injury, even when the injured eye is retained, the first choice of treatment may not be enucleation or evisceration, especially if there is a chance that the injured eye may regain some function. Additionally, with current advanced surgical techniques, many eyes once considered nonviable now have a fair prognosis. However, only if the injured eye has completely lost its vision and has no potential for any visual recovery, prevention of SO is done by enucleation of the injured eye preferably within the first 2 weeks of injury. Evisceration—the removal of the contents of the globe while leaving the sclera and extraocular muscles intact—is easier to perform, offers long-term orbital stability, and is more aesthetically pleasing, i.e., a greater measure of movement of the prosthesis and thus a more natural appearance. There is concern, however, that evisceration may lead to a higher incidence of SO compared to enucleation. Several retrospective studies involving over 3,000 eviscerations, however, have failed to identify a single case of SO. Once SO is developed, immunosuppressive therapy is the mainstay of treatment. When initiated promptly following injury, it is effective in controlling the inflammation and improving the prognosis. Mild cases may be treated with local application of corticosteroids and pupillary dilators. More severe or progressive cases require high-dose systemic corticosteroids for months to years. Patients who become resistant to corticosteroids or develop side effects of long-term corticosteroid therapy (osteoporosis and pathologic fractures, mental status changes, etc.), may be candidates for therapy with chlorambucil, cyclophosphamide, or ciclosporin. Epidemiology Sympathetic ophthalmia is rare, affecting 0.2% to 0.5% of non-surgical eye wounds, and less than 0.01% of surgical penetrating eye wounds. There are no gender or racial differences in incidence of SO. History Although descriptions of sympathetic ophthalmia can be found in ancient Greek texts, modern understanding of SO derives from the works of Scotlands William MacKenzie who characterized and named the disease sympathetic ophthalmitis. At MacKenzies time, oral mercury and leeches applied to the conjunctiva were the treatments of choice for SO.It is thought that Louis Braille, who injured one of his eyes as a child, lost vision in his other eye owing to SO. James Thurbers adult blindness was also diagnosed as sympathetic ophthalmia deriving from the loss of an eye when he was six years old. See also Vogt–Koyanagi–Harada disease References == External links ==

Aarogya, What does Eucestoda mean

Eucestoda

Eucestoda, commonly referred to as tapeworms, is the larger of the two subclasses of flatworms in the class Cestoda (the other subclass is Cestodaria). Larvae have six posterior hooks on the scolex (head), in contrast to the ten-hooked Cestodaria. All tapeworms are endoparasites of vertebrates, living in the digestive tract or related ducts. Examples are the pork tapeworm (Taenia solium) with a human definitive host, and pigs as the secondary host, and Moniezia expansa, the definitive hosts of which are ruminants. Body structure Adult Eucestoda have a white-opaque dorso-ventrally flattened appearance, and are elongated, ranging in length from a few millimeters to 25 meters. Almost all members, except members of the orders Caryophyllidea and Spathebothriidea, are polyzoic with repeated sets of reproductive organs down the body length, and almost all members, except members of the order Dioecocestidae, are protandral hermaphrodites. Most except caryophyllideans consist of a few to 4000 proglottids (segments) that show a characteristic body differentiation pattern into scolex (head), neck, and strobila.The scolex, located at the anterior end, is a small (usually less than 1 mm) holdfast organ with specific systems for fastening itself to materials: rostrum, acetabula, suckers, bothria, grooves, and hooks. The small neck region, directly behind the scolex, consists of an undifferentiated tissue region of proglottid proliferation, leading into a zone of increasing and continuous proglottid differentiation. As such, the main and largest section of the body, the strobila, consists of a chain of increasingly mature proglottids. These cytological processes are not well understood at present. Members of the Eucestoda have no mouth or digestive tract, and instead absorb nutrients through a layer of microtriches over the tegument at the shared body wall surface. In addition to the body wall, several other systems are common to the whole length of the tapeworm, including excretory canals, nerve fibers, and longitudinal muscles. The excretory system is responsible for osmoregulation and consists of blind-ending flame bulbs communicating through a duct system. The nervous system, often referred to as a "ladder system," is a system of longitudinal connectives and transverse ring commissures. Reproduction The reproductive systems develop progressively along the differentiated proglottids of the strobila region, with each proglottid developing one or two sets of sexual organs that differentiate at different times in a species-specific pattern, usually male-first. Thus, moving in the posterior direction of the continuously maturing proglottid chain, there are proglottids with mature male reproductive organs, then proglottids with mature female reproductive organs, and then proglottids with fertilized eggs in the uterus, a condition commonly referred to as "gravid." Proglottids An atrium on the lateral margin of each proglottid contains the openings to both the male and female genital ducts. Follicular testes produce sperm, which are carried by a system of ducts to the cirrus, an eversible copulatory organ that usually has a hypodermic system of spines and a holdfast system of hooks. The main specialized female reproductive organs are an ovary that produces eggs and a vitellarium that produces yolk cells. Yolk cells travel in a duct system to the oviduct, where, in a modified region, the ovum is enclosed in a shell with yolk cells. After the gonads and their ducts have finished maturing, the female reproductive organs begin to mature. The oviduct develops a vagina and enlarges into the uterus, where fertilization and embryonic development occur.Egg formation is a result of copulation. A proglottid can copulate with itself, with other proglottids in the same worm, or with proglottids in other worms, and hypodermic fertilization sometimes occurs. When a gravid proglottid that is distended with an embryo reaches the end of the strobila, it detaches and passes out of the host intact with feces, with or without some tissue degeneration. In the order Pseudophyllidea, the uterus has a pore and the proglottid sheds the shelled embryo, only becoming detached when exhausted.Some members of the Eucestoda (such as Echinococcus, Sparganum, Taenia multiceps sp., and Mesocestoides sp.) can reproduce asexually through budding, which initiates a metagenesis of alternating sexually and asexually reproducing generations. Life stages A tapeworm can live from a few days to over 20 years. Eucestoda ontogenesis continues through metamorphosing in different larval stages inside different hosts. The initial six-hooked embryo, known as an oncosphere or hexacanth, forms through cleavage. In the order Pseudophyllidea, it remains enclosed in a ciliated embryophore. The embryo continues to develop in other host species, with two intermediate hosts generally needed. It gains entry to its first intermediate host by being eaten. Except for members of the order Taeniidae, the first intermediate host is an arthropod, and except for in the case of Archigetes spp. (which can attain sexual maturity in freshwater oligochaeta), the second host is usually a fish, but can be another invertebrate or vertebrate. After the scolex has differentiated and matured in the larval stage, growth will stop until a vertebrate eats the intermediate host, and then the strobila develops. Adult tapeworms often have a high final host specificity, with some species only found in one host vertebrate. Common infective species Medical importance Taeniasis Taeniasis is an infection within the intestines by adult tapeworms belonging to the genus Taenia. It is due to eating contaminated undercooked beef or pork. There are generally no or only mild symptoms. Symptoms may occasionally include weight loss or abdominal pain. Segments of tapeworm may be seen in the stool. Cysticercosis Cysticercosis is a tissue infection caused by the young form of the pork tapeworm. Infection occurs through swallowing or antiperistaltic contractions during regurgitation carrying eggs or gravid proglottids to the stomach. At this point, larvae hatch when exposed to enzymes and penetrate the intestinal wall, travelling through the body through blood vessels to tissues like the brain, the eye, muscles, and the nervous system (called neurocysticercosis).At these sites, the parasites lodge and form cysts, a condition called cysticercosis, producing inflammatory reactions and clinical issues when they die, sometimes causing serious or fatal damage. In the eye, the parasites can cause visual loss, and infection of the spine and adjacent leptomeninges can cause paresthesias, pain, or paralysis. Echinococcosis (hydatid disease) Humans become accidental hosts to worms of the genus Echinococcus, playing no role in the worms biological cycle. This can result in echinococcosis, also called hydatid disease. Humans (usually children) become infected by direct contact with dogs and eating food contaminated with dog feces. Common sites of infection are the liver, the lungs, muscles, bones, kidneys, and the spleen.Eggs hatch in the gastrointestinal tract after the consumption of contaminated food, after which the larvae travel to the liver through portal circulation. Here, the larvae are trapped and usually develop into hydatid cysts. While the liver is the first filter for trapping them, the lungs act as the second filter site, trapping most of the larvae that are not trapped by the liver. Some larvae escape from the lungs to cause cysts in other tissues.When a larva becomes established in tissue, it develops into a "bladderworm" or "hydatid" and can cause various cancer-like cysts that may rupture and interact with nearby organs. Most cases are asymptomatic, and the mortality rate is low, but various complications from these interactions may lead to debilitating illness. Hymenolepiasis Arthropods are intermediate hosts of Hymenolepis nana, otherwise known as the "dwarf tapeworm," while humans are used as final hosts. Humans become infected and develop hymenolepiasis through eating infected arthropods, ingesting eggs in water inhabited by arthropods, or from dirty hands. This is a common and widespread intestinal worm.While light infections are usually asymptomatic, autoinfection through eating the eggs of worms in the intestines is possible, and it can lead to hyperinfection. Humans can also become hyperinfected through ingesting grain products contaminated by infected insects. Infections involving more than two thousand worms can cause many different gastrointestinal symptoms and allergic responses. Common symptoms include chronic urticaria, skin eruption, and phlyctenular keratoconjunctivitis. Diphyllobothriasis Diphyllobothriasis is caused by infection with Diphyllobothrium latum (also known as the "broad tapeworm" or "fish tapeworm") and related species. Humans become infected by eating raw, undercooked, or marinated fish acting as a second intermediate or paratenic host harboring metacestodes or plerocercoid larvae.Clinical symptoms are due to the large size of the tapeworm, which often reaches a length exceeding 15 m (49 ft). The most common symptom is pernicious anemia, caused by the absorption of vitamin B12 by the worm. Other symptoms include various intestinal issues, slight leukocytosis, and eosinophilia. Sparganosis Sparganosis is caused by the plerocercoid larvae of the tapeworm Spirometra. Humans become infected by drinking contaminated water, eating raw or poorly cooked infected flesh, or from using poultices of raw infected flesh (usually raw pork or snake) on skin or mucous membranes.The most common symptom is a painful, slowly growing nodule in the subcutaneous tissues, which may migrate. Infection in the eye area can cause pain, irritation, edema, and excess watering. When the orbital tissues become infected, the swelling can cause blindness. An infected bowel may become perforated. Brain infection can cause granulomas, hematomas, and abscesses. Subdivisions The evolutionary history of the Eucestoda has been studied using ribosomal RNA, mitochondrial and other DNA, and morphological analysis and continues to be revised. "Tetraphyllidea" is seen to be paraphyletic; "Pseudophyllidea" has been broken up into two orders, Bothriocephalidea and Diphyllobothriidea. Hosts, whose phylogeny often mirrors that of the parasites (Fahrenholzs rule), are indicated in italics and parentheses, the life-cycle sequence (where known) shown by arrows as (intermediate host1 [→ intermediate host2 ] → definitive host). Alternatives, generally for different species within an order, are shown in square brackets. References Bale, James F. "Cysticercosis." Current Treatment Options in Neurology. 2000. pp. 355–360. Dunn, J., and Philip E. S. Palmer. "Sparganosis." Seminars in Roentgenology. 1998. pp. 86–88. Esteban, J. G., Munoz-Antoli, C., and R. Toledo. "Human Infection by a "Fish Tapeworm," Diphyllobothrium latum, in a Non-Endemic Country." Infection. 2014. pp. 191–194. Kim, Bong Jin, et al. "Heavy Hymenoleptis nana Infection Possibly Through Organic Food: Report of a Case." The Korean Journal of Parasitology. 2014. pp. 85–87. Mehlhorn, Heinz. "Eucestoda Classification." Encyclopedia of Parasitology. 2008. pp. 495–497. Rohde, Klaus. "Eucestoda." AccessScience. McGraw-Hill Ryerson. Usharani, A., et al. "Case Reports of Hydatid Disease." Journal of Epidemiology and Global Health. 2013. p. 63–66.

Hi Aarogya, could you help me understand about Tendinopathy

Tendinopathy

Tendinopathy, a type of tendon disorder that results in pain, swelling, and impaired function. The pain is typically worse with movement. It most commonly occurs around the shoulder (rotator cuff tendinitis, biceps tendinitis), elbow (tennis elbow, golfers elbow), wrist, hip, knee (jumpers knee, popliteus tendinopathy), or ankle (Achilles tendinitis).Causes may include an injury or repetitive activities. Less common causes include infection, arthritis, gout, thyroid disease, diabetes and the use of Quinolone_antibiotic medicines. Groups at risk include people who do manual labor, musicians, and athletes. Diagnosis is typically based on symptoms, examination, and occasionally medical imaging. A few weeks following an injury little inflammation remains, with the underlying problem related to weak or disrupted tendon fibrils.Treatment may include rest, NSAIDs, splinting, and physiotherapy. Less commonly steroid injections or surgery may be done. About 80% of patients recover completely within six months. Tendinopathy is relatively common. Older people are more commonly affected. It results in a large amount of missed work. Signs and symptoms Symptoms include tenderness on palpation, swelling, and pain, often when exercising or with a specific movement. Cause Causes may include an injury or repetitive activities. Groups at risk include people who do manual labor, musicians, and athletes. Less common causes include infection, arthritis, gout, thyroid disease, and diabetes. Despite the injury of the tendon, there are roads to healing which includes rehabilitation therapy and/or surgery. Obesity, or more specifically, adiposity or fatness, has also been linked to an increasing incidence of tendinopathy.Quinolone antibiotics are associated with increased risk of tendinitis and tendon rupture. A 2013 review found the incidence of tendon injury among those taking fluoroquinolones to be between 0.08 and 0.2%. Fluoroquinolones most frequently affect large load-bearing tendons in the lower limb, especially the Achilles tendon which ruptures in approximately 30 to 40% of cases. Types Achilles tendinitis Calcific tendinitis Patellar tendinitis (jumpers knee) Pathophysiology As of 2016 the pathophysiology of tendinopathy is poorly understood. While inflammation appears to play a role, the relationships among changes to the structure of tissue, the function of tendons, and pain are not understood and there are several competing models, none of which have been fully validated or falsified. Molecular mechanisms involved in inflammation includes release of inflammatory cytokines like IL-1β which reduces the expression of type I collagen mRNA in human tenocytes and causes extracellular matrix degradation in the tendon.There are multifactorial theories that could include: tensile overload, tenocyte related collagen synthesis disruption, load-induced ischemia, neural sprouting, thermal damage, and adaptive compressive responses. The intratendinous sliding motion of fascicles and shear force at interfaces of fascicles could be an important mechanical factor for the development of tendinopathy and predispose tendons to rupture.The most commonly accepted cause for this condition is seen to be an overuse syndrome in combination with intrinsic and extrinsic factors leading to what may be seen as a progressive interference or the failing of the innate healing response. Tendinopathy involves cellular apoptosis, matrix disorganization and neovascularization.Classic characteristics of "tendinosis" include degenerative changes in the collagenous matrix, hypercellularity, hypervascularity, and a lack of inflammatory cells which has challenged the original misnomer "tendinitis".Histological findings include granulation tissue, microrupture, degenerative changes, and there is no traditional inflammation. As a consequence, "lateral elbow tendinopathy or tendinosis" is used instead of "lateral epicondylitis".Examination of tennis elbow tissue reveals noninflammatory tissue, so the term "angiofibroblastic tendinosis" is used.Cultures from tendinopathic tendons contain an increased production of type III collagen.Longitudinal sonogram of the lateral elbow displays thickening and heterogeneity of the common extensor tendon that is consistent with tendinosis, as the ultrasound reveals calcifications, intrasubstance tears, and marked irregularity of the lateral epicondyle. Although the term "epicondylitis" is frequently used to describe this disorder, most histopathologic findings of studies have displayed no evidence of an acute, or a chronic inflammatory process. Histologic studies have demonstrated that this condition is the result of tendon degeneration, which causes normal tissue to be replaced by a disorganized arrangement of collagen. Therefore, the disorder is more appropriately referred to as "tendinosis" or "tendinopathy" rather than "tendinitis".Colour Doppler ultrasound reveals structural tendon changes, with vascularity and hypo-echoic areas that correspond to the areas of pain in the extensor origin.Load-induced non-rupture tendinopathy in humans is associated with an increase in the ratio of collagen III:I proteins, a shift from large to small diameter collagen fibrils, buckling of the collagen fascicles in the tendon extracellular matrix, and buckling of the tenocyte cells and their nuclei. Diagnosis Symptoms can vary from aches or pains and local joint stiffness, to a burning that surrounds the whole joint around the inflamed tendon. In some cases, swelling occurs along with heat and redness, and there may be visible knots surrounding the joint. With this condition, the pain is usually worse during and after activity, and the tendon and joint area can become stiff the following day as muscles tighten from the movement of the tendon. Many patients report stressful situations in their life in correlation with the beginnings of pain which may contribute to the symptoms. Medical imaging Ultrasound imaging can be used to evaluate tissue strain, as well as other mechanical properties. Ultrasound-based techniques are becoming more popular because of its affordability, safety, and speed. Ultrasound can be used for imaging tissues, and the sound waves can also provide information about the mechanical state of the tissue. Treatment Treatment of tendon injuries is largely conservative. Use of non-steroidal anti-inflammatory drugs (NSAIDs), rest, and gradual return to exercise is a common therapy. Resting assists in the prevention of further damage to the tendon. Ice, compression and elevation are also frequently recommended. Physical therapy, occupational therapy, orthotics or braces may also be useful. Initial recovery is typically within 2 to 3 days and full recovery is within 3 to 6 months. Tendinosis occurs as the acute phase of healing has ended (6–8 weeks) but has left the area insufficiently healed. Treatment of tendinitis helps reduce some of the risks of developing tendinosis, which takes longer to heal.There is tentative evidence that low-level laser therapy may also be beneficial in treating tendinopathy. The effects of deep transverse friction massage for treating tennis elbow and lateral knee tendinitis is unclear. NSAIDs NSAIDs may be used to help with pain. They however do not alter long term outcomes. Other types of pain medication, like paracetamol, may be just as useful. Steroids Steroid injections have not been shown to have long term benefits but have been shown to be more effective than NSAIDs in the short term. They appear to have little benefit in tendinitis of the rotator cuff. There are some concerns that they may have negative effects. Other injections There is insufficient evidence on the routine use of injection therapies (autologous blood, platelet-rich plasma, deproteinised haemodialysate, aprotinin, polysulphated glycosaminoglycan, skin derived fibroblasts etc.) for treating Achilles tendinopathy. As of 2014 there was insufficient evidence to support the use of platelet-rich therapies for treating musculoskeletal soft tissue injuries such as ligament, muscle and tendon tears and tendinopathies. Prognosis Initial recovery is usually within 2 to 3 months, and full recovery usually within 3 to 6 months. About 80% of people will fully recover within 12 months. Epidemiology Tendon injury and resulting tendinopathy are responsible for up to 30% of consultations to sports doctors and other musculoskeletal health providers. Tendinopathy is most often seen in tendons of athletes either before or after an injury but is becoming more common in non-athletes and sedentary populations. For example, the majority of patients with Achilles tendinopathy in a general population-based study did not associate their condition with a sporting activity. In another study the population incidence of Achilles tendinopathy increased sixfold from 1979–1986 to 1987–1994. The incidence of rotator cuff tendinopathy ranges from 0.3% to 5.5% and annual prevalence from 0.5% to 7.4%. Terminology Tendinitis is a very common, but misleading term. By definition, the suffix "-itis" means "inflammation of". Inflammation is the bodys local response to tissue damage which involves red blood cells, white blood cells, blood proteins with dilation of blood vessels around the site of injury. Tendons are relatively avascular. Corticosteroids are drugs that reduce inflammation. Corticosteroids can be useful to relieve chronic tendinopathy pain, improve function, and reduce swelling in the short term. However, there is a greater risk of long-term recurrence. They are typically injected along with a small amount of a numbing drug called lidocaine. Research shows that tendons are weaker following corticosteroid injections. Tendinitis is still a very common diagnosis, though research increasingly documents that what is thought to be tendinitis is usually tendinosis.Anatomically close but separate conditions are: Enthesitis, wherein there is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is associated with HLA B27 arthropathies such as ankylosing spondylitis, psoriatic arthritis, and reactive arthritis. Apophysitis, inflammation of the bony attachment, generally associated with overuse among growing children. Research The use of a nitric oxide delivery system (glyceryl trinitrate patches) applied over the area of maximal tenderness was found to reduce pain and increase range of motion and strength.A promising therapy involves eccentric loading exercises involving lengthening muscular contractions. Other animals Bowed tendon is a horsemans term for tendinitis (inflammation) and tendinosis (degeneration), most commonly seen in the superficial digital flexor tendon in the front leg of horses. Mesenchymal stem cells, derived from a horses bone marrow or fat, are currently being used for tendon repair in horses. References External links Questions and Answers about Bursitis and Tendinitis - US National Institute of Arthritis and Musculoskeletal and Skin Diseases

Aarogya , Do you know what is Tenosynovial giant cell tumor,

Tenosynovial giant cell tumor

Tenosynovial giant cell tumor (TGCT) is a group of rare, typically non-malignant tumors of the joints. TGCT tumors often develop from the lining of joints (also known as synovial tissue).: 100 : 245 Common symptoms of TGCT include swelling, pain, stiffness and reduced mobility in the affected joint or limb.: 102  This group of tumors can be divided into different subsets according to their site, growth pattern, and prognosis.: 361  Localized TGCT is sometimes referred to as giant cell tumor of the tendon sheath;: 100  diffuse TGCT is also called pigmented villonodular synovitis (PVNS).: 102 Classification Classification for TGCT encompasses two subtypes that can be divided according to site – within a joint (intra-articular) or outside of the joint (extra-articular) – and growth pattern (localized or diffuse) of the tumor(s).: 100 : 361  Localized and diffuse subsets of TGCT differ in their prognosis, clinical presentation, and biological behavior, but share a similar manner of disease development.: 100 Localized TGCT Localized TGCT is sometimes referred to as localized pigmented villonodular synovitis (L-PVNS), giant cell tumor of the tendon sheath (GCT-TS), nodular tenosynovitis, localized nodular tenosynovitis, and L-TGCT.: 1 : 100 The localized form of TGCT is more common.: 100 : 245  Localized TGCT tumors are typically 0.5 cm-4 cm),: 101  develop over years,: 100  are benign and non-destructive to the surrounding tissue, and may reoccur in the affected area.: 101  The most common symptom is painless swelling.: 101  Localized TGCT most often occurs in fingers, but can also occur in other joints. Diffuse TGCT Diffuse TGCT is sometimes referred to as pigmented villonodular synovitis (PVNS), conventional PVNS, and D-TGCT.: 1 : 361 : 1 : 102 Diffuse TGCT occurs less frequently and is locally aggressive (in some cases, tumors may infiltrate surrounding soft tissue).: 245 : 1 : 102 : 1  It most commonly affects people under 40 years old, though the age of occurrence varies.: 102  Diffuse TGCT may occur inside a joint (intra-articular) or outside of a joint (extra-articular). Intra-articular tumors typically occur in the knee (approximately 75% of cases) and hip (approximately 15% of cases).: 102  Extra-articular tumors are usually found in the knee, thigh, and foot.: 101  Symptoms include swelling, pain, sensitivity, and/or limited range of motion.: 102  The rate of reoccurrence is estimated to be 18-46% for intra-articular tumors and 33-50% for extra-articular tumors.: 103 : 1 Complications Diffuse TGCT is locally aggressive and can spread to surrounding tissues, causing bone erosion and tissue damage. If not treated early, it can spread to areas outside the joint, extra-articular, and potentially cause permanent loss of range as well as intense pain. Mechanism TGCT tumors grow due to genetic overexpression of colony stimulating factor 1. This causes colony-stimulating factor-1 receptor (CSF1R) cells to accumulate in the joint tissue. Diagnosis TGCT can be diagnosed by magnetic resonance imaging (MRI), by biopsy, or during surgery. The disorder is difficult to identify and is often not diagnosed for years due to nonspecific symptoms or a general paucity of symptoms. TGCT cases are often misdiagnosed as osteoarthritis, localized trauma, sports injuries, xanthomas, or other conditions. One study of 122 diffuse TGCT patients found that the average delay in diagnosis was 2.9 years. Treatment Surgery has been the most common form of treatment for both localized: 101 : 361  and diffuse TGCT.: 103 : 361 : 1  After surgery, patients may receive physical therapy in order to help rehabilitate affected joints. However, recurrence of TGCT after surgery is common, with a higher rate of recurrence for diffuse TGCT than for localized TGCT.: 361  In cases of recurrent or resistant disease, multiple surgeries, total joint arthroplasties, or amputation may be required.: 1 A multidisciplinary approach, supplementing surgery with radiotherapy or other treatments, can also improve outcomes in cases of recurrent TGCT. In the late 2010s, treatment with CSF1R inhibitors emerged as an option that may help improve functionality for patients with recurrent TGCT or TGCT that is not easily managed by surgery.: 361 Epidemiology A study conducted in the Netherlands estimated that the worldwide incidence of TGCT is 43 cases per million person-years. The majority – 39 cases per million person-years – were estimated to be localized TGCT; the remaining 4 cases per million person-years were estimated to be diffuse TGCT. TGCT can occur in patients of any age, but people with localized TGCT are typically between 30 and 50 years old,: 100–101  while diffuse TGCT tends to affect people under the age of 40.: 102–103 See also Fibroma of tendon sheath List of cutaneous conditions References == External links ==

Hello Aarogya, explain a situation where Tetanus occurs

Tetanus

Tetanus, also known as lockjaw, is a bacterial infection caused by Clostridium tetani, and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually lasts a few minutes. Spasms occur frequently for three to four weeks. Some spasms may be severe enough to fracture bones. Other symptoms of tetanus may include fever, sweating, headache, trouble swallowing, high blood pressure, and a fast heart rate. Onset of symptoms is typically three to twenty-one days following infection. Recovery may take months. About ten percent of cases prove to be fatal.C. tetani is commonly found in soil, saliva, dust, and manure. The bacteria generally enter through a break in the skin such as a cut or puncture wound by a contaminated object. They produce toxins that interfere with normal muscle contractions. Diagnosis is based on the presenting signs and symptoms. The disease does not spread between people.Tetanus can be prevented by immunization with the tetanus vaccine. In those who have a significant wound and have had fewer than three doses of the vaccine, both vaccination and tetanus immune globulin are recommended. The wound should be cleaned and any dead tissue should be removed. In those who are infected, tetanus immune globulin or, if unavailable, intravenous immunoglobulin (IVIG) is used. Muscle relaxants may be used to control spasms. Mechanical ventilation may be required if a persons breathing is affected.Tetanus occurs in all parts of the world but is most frequent in hot and wet climates where the soil has a high organic content. In 2015 there were about 209,000 infections and about 59,000 deaths globally. This is down from 356,000 deaths in 1990. In the US there are about 30 cases per year, almost all of which have not been vaccinated. An early description of the disease was made by Hippocrates in the 5th century BC. The cause of the disease was determined in 1884 by Antonio Carle and Giorgio Rattone at the University of Turin, and a vaccine was developed in 1924. Signs and symptoms Tetanus often begins with mild spasms in the jaw muscles—also known as lockjaw. Similar spasms can also be a feature of trismus. The spasms can also affect the facial muscles resulting in an appearance called risus sardonicus. Chest, neck, back, abdominal muscles and buttocks may be affected. Back muscle spasms often cause arching, called opisthotonus. Sometimes the spasms affect muscles that help with breathing, which can lead to breathing problems.Prolonged muscular action causes sudden, powerful, and painful contractions of muscle groups, called tetany. These episodes can cause fractures and muscle tears. Other symptoms include fever, headache, restlessness, irritability, feeding difficulties, breathing problems, burning sensation during urination, urinary retention and loss of stool control.Even with treatment, about 10% of people who contract tetanus die. The mortality rate is higher in unvaccinated people and people over 60 years of age. Incubation period The incubation period of tetanus may be up to several months, but is usually about ten days. In general, the farther the injury site is from the central nervous system, the longer the incubation period. The shorter the incubation period, the more severe the symptoms. In trismus nascentium (i.e. neonatal tetanus), symptoms usually appear from 4 to 14 days after birth, averaging about 7 days. On the basis of clinical findings, four different forms of tetanus have been described. Generalized tetanus Generalized tetanus is the most common type of tetanus, representing about 80% of cases. The generalized form usually presents with a descending pattern. The first sign is trismus or lockjaw, and the facial spasms are called risus sardonicus, followed by stiffness of the neck, difficulty in swallowing, and rigidity of pectoral and calf muscles. Other symptoms include elevated temperature, sweating, elevated blood pressure, and episodic rapid heart rate. Spasms may occur frequently and last for several minutes with the body shaped into a characteristic form called opisthotonos. Spasms continue for up to four weeks, and complete recovery may take months. Neonatal tetanus Neonatal tetanus (trismus nascentium) is a form of generalized tetanus that occurs in newborns, usually those born to mothers who themselves have not been vaccinated. If the mother has been vaccinated against tetanus, the infants acquire passive immunity and are thus protected. It usually occurs through infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile instrument. As of 1998 neonatal tetanus was common in many developing countries and was responsible for about 14% (215,000) of all neonatal deaths. In 2010 the worldwide death toll was 58,000 newborns. As the result of a public health campaign, the death toll from neonatal tetanus was reduced by 90% between 1990 and 2010, and by 2013 the disease had been largely eliminated from all but 25 countries. Neonatal tetanus is rare in developed countries. Local tetanus Local tetanus is an uncommon form of the disease, in which people have persistent contraction of muscles in the same anatomic area as the injury. The contractions may persist for many weeks before gradually subsiding. Local tetanus is generally milder; only about 1% of cases are fatal, but it may precede the onset of generalized tetanus. Cephalic tetanus Cephalic tetanus is the rarest form of the disease (0.9–3% of cases) and is limited to muscles and nerves in the head. It usually occurs after trauma to the head area, including skull fracture, laceration, eye injury, dental extraction, and otitis media, but it has been observed from injuries to other parts of the body. Paralysis of the facial nerve is most frequently implicated, which may cause lockjaw, facial palsy, or ptosis, but other cranial nerves can also be affected. Cephalic tetanus may progress to a more generalized form of the disease. Due to its rarity, clinicians may be unfamiliar with the clinical presentation and may not suspect tetanus as the illness. Treatment can be complicated as symptoms may be concurrent with the initial injury that caused the infection. Cephalic tetanus is more likely than other forms of tetanus to be fatal, with the progression to generalized tetanus carrying a 15–30% case fatality rate. Cause Tetanus is caused by the tetanus bacterium Clostridium tetani. Tetanus is an international health problem, as C. tetani endospores are ubiquitous. Endospores can be introduced into the body through a puncture wound (penetrating trauma). Due to C. tetani being an anaerobic bacterium, it and its endospores thrive in environments that lack oxygen, such as a puncture wound. With the changes in oxygen levels, the drumstick-shaped endospore can result in quick spread.The disease occurs almost exclusively in persons inadequately immunized. It is more common in hot, damp climates with soil rich in organic matter. Manure-treated soils may contain spores, as they are widely distributed in the intestines and feces of many animals such as horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens. In agricultural areas, a significant number of human adults may harbor the organism.The spores can also be found on skin surfaces and in contaminated heroin. Heroin users, particularly those who inject the drug subcutaneously, appear to be at high risk of contracting tetanus. Rarely, tetanus can be contracted through surgical procedures, intramuscular injections, compound fractures, and dental infections. Animal bites can transmit tetanus.Tetanus is often associated with rust, especially rusty nails. Although rust itself does not cause tetanus, objects that accumulate rust are often found outdoors or in places that harbor anaerobic bacteria. Additionally, the rough surface of rusty metal provides crevices for dirt containing C. tetani, while a nail affords a means to puncture skin and deliver endospores deep within the body at the site of the wound. An endospore is a non-metabolizing survival structure that begins to metabolize and cause infection once in an adequate environment. Hence, stepping on a nail (rusty or not) may result in a tetanus infection, as the low-oxygen (anaerobic) environment may exist under the skin, and the puncturing object can deliver endospores to a suitable environment for growth. It is a common misconception that rust itself is the cause and that a puncture from a rust-free nail is not a risk. Pathophysiology Tetanus neurotoxin (TeNT) binds to the presynaptic membrane of the neuromuscular junction, is internalized and is transported back through the axon until it reaches the central nervous system. Here, it selectively binds to and is transported into inhibitory neurons via endocytosis. It then leaves the vesicle for the neuron cytosol where it cleaves vesicle associated membrane protein (VAMP) synaptobrevin, which is necessary for membrane fusion of small synaptic vesicles (SSVs). SSVs carry neurotransmitter to the membrane for release, so inhibition of this process blocks neurotransmitter release.Tetanus toxin specifically blocks the release of the neurotransmitters GABA and glycine from inhibitory neurons. These neurotransmitters keep overactive motor neurons from firing and also play a role in the relaxation of muscles after contraction. When inhibitory neurons are unable to release their neurotransmitters, motor neurons fire out of control and muscles have difficulty relaxing. This causes the muscle spasms and spastic paralysis seen in tetanus infection.The tetanus toxin, tetanospasmin, is made up of a heavy chain and a light chain. There are three domains, each of which contributes to the pathophysiology of the toxin. The heavy chain has two of the domains. The N-terminal side of the heavy chain helps with membrane translocation, and the C-terminal side helps the toxin locate the specific receptor site on the correct neuron. The light chain domain cleaves the VAMP protein once it arrives in the inhibitory neuron cytosol.There are four main steps in tetanuss mechanism of action: binding to the neuron, internalization of the toxin, membrane translocation, and cleavage of the target VAMP. Neurospecific binding The toxin travels from the wound site to the neuromuscular junction through the bloodstream where it binds to the presynaptic membrane of a motor neuron. The heavy chain C-terminal domain aids in the binding to the correct site, recognizing and binding to the correct glycoproteins and glycolipids in the presynaptic membrane. The toxin binds to a site that will be taken into the neuron as an endocytic vesicle that will travel down the axon, past the cell body, and down the dendrites to the dendritic terminal at the spine and central nervous system. Here it will be released into the synaptic cleft and allowed to bind with the presynaptic membrane of inhibitory neurons in a similar manner seen with the binding to the motor neuron. Internalization Tetanus toxin is then internalized again via endocytosis, this time in an acidic vesicle. In a mechanism not well understood, depolarization caused by the firing of the inhibitory neuron causes the toxin to be pulled into the neuron inside vesicles. Membrane translocation The toxin then needs a way to get out of the vesicle and into the neuron cytosol for it to act on its target. The low pH of the vesicle lumen causes a conformational change in the toxin, shifting it from a water-soluble form to a hydrophobic form. With the hydrophobic patches exposed, the toxin can slide into the vesicle membrane. The toxin forms an ion channel in the membrane that is nonspecific for Na+, K+, Ca2+, and Cl− ions. There is a consensus among experts that this new channel is involved in the translocation of the toxins light chain from the inside of the vesicle to the neuron cytosol, but the mechanism is not well understood or agreed upon. It has been proposed that the channel could allow the light chain (unfolded from the low pH environment) to leave through the toxin pore, or that the pore could alter the electrochemical gradient enough, by letting in or out ions, to cause osmotic lysis of the vesicle, spilling the vesicles contents. Enzymatic target cleavage The light chain of the tetanus toxin is zinc-dependent protease. It shares a common zinc protease motif (His-Glu-Xaa-Xaa-His) that researchers hypothesized was essential for target cleavage until this was more recently confirmed by experiment: when all zinc was removed from the neuron with heavy metal chelators, the toxin was inhibited, only to be reactivated when the zinc was added back in. The light chain binds to VAMP and cleaves it between Gln76 and Phe77. Without VAMP, vesicles holding the neurotransmitters needed for motor neuron regulation (GABA and glycine) cannot be released, causing the above-mentioned deregulation of motor neurons and muscle tension. Diagnosis There are currently no blood tests for diagnosing tetanus. The diagnosis is based on the presentation of tetanus symptoms and does not depend upon isolation of the bacterium, which is recovered from the wound in only 30% of cases and can be isolated from people without tetanus. Laboratory identification of C. tetani can be demonstrated only by production of tetanospasmin in mice. Having recently experienced head trauma may indicate cephalic tetanus if no other diagnosis has been made.The "spatula test" is a clinical test for tetanus that involves touching the posterior pharyngeal wall with a soft-tipped instrument and observing the effect. A positive test result is the involuntary contraction of the jaw (biting down on the "spatula") and a negative test result would normally be a gag reflex attempting to expel the foreign object. A short report in The American Journal of Tropical Medicine and Hygiene states that, in an affected subject research study, the spatula test had a high specificity (zero false-positive test results) and a high sensitivity (94% of infected people produced a positive test). Prevention Unlike many infectious diseases, recovery from naturally acquired tetanus does not usually result in immunity. This is due to the extreme potency of the tetanospasmin toxin. Tetanospasmin will likely be lethal before it will provoke an immune response.Tetanus can be prevented by vaccination with tetanus toxoid. The CDC recommends that adults receive a booster vaccine every ten years, and standard care practice in many places is to give the booster to any person with a puncture wound who is uncertain of when he or she was last vaccinated, or if he or she has had fewer than three lifetime doses of the vaccine. The booster may not prevent a potentially fatal case of tetanus from the current wound, however, as it can take up to two weeks for tetanus antibodies to form.In children under the age of seven, the tetanus vaccine is often administered as a combined vaccine, DPT/DTaP vaccine, which also includes vaccines against diphtheria and pertussis. For adults and children over seven, the Td vaccine (tetanus and diphtheria) or Tdap (tetanus, diphtheria, and acellular pertussis) is commonly used.The World Health Organization certifies countries as having eliminated maternal or neonatal tetanus. Certification requires at least two years of rates of less than 1 case per 1,000 live births. In 1998 in Uganda, 3,433 tetanus cases were recorded in newborn babies; of these, 2,403 died. After a major public health effort, Uganda in 2011 was certified as having eliminated maternal and neonatal tetanus. Post-exposure prophylaxis Tetanus toxoid can be given in case of suspected exposure to tetanus. In such cases, it can be given with or without tetanus immunoglobulin (also called tetanus antibodies or tetanus antitoxin). It can be given as intravenous therapy or by intramuscular injection.The guidelines for such events in the United States for non-pregnant people 11 years and older are as follows: Treatment Mild tetanus Mild cases of tetanus can be treated with: Tetanus immunoglobulin (TIG), also called tetanus antibodies or tetanus antitoxin. It can be given as intravenous therapy or by intramuscular injection. Antibiotic therapy to reduce toxin production. Metronidazole intravenous (IV) is a preferred treatment. Benzodiazepines can be used to control muscle spasms. Options include diazepam and lorazepam, oral or IV. Severe tetanus Severe cases will require admission to intensive care. In addition to the measures listed above for mild tetanus: Human tetanus immunoglobulin injected intrathecally (which increases clinical improvement from 4% to 35%) Tracheotomy and mechanical ventilation for 3 to 4 weeks. Tracheotomy is recommended for securing the airway because the presence of an endotracheal tube is a stimulus for spasm Magnesium sulfate, as an intravenous infusion, to control spasm and autonomic dysfunction Diazepam as a continuous IV infusion The autonomic effects of tetanus can be difficult to manage (alternating hyper- and hypotension hyperpyrexia/hypothermia) and may require IV labetalol, magnesium, clonidine, or nifedipineDrugs such as diazepam or other muscle relaxants can be given to control the muscle spasms. In extreme cases it may be necessary to paralyze the person with curare-like drugs and use a mechanical ventilator.To survive a tetanus infection, the maintenance of an airway and proper nutrition are required. An intake of 3,500 to 4,000 calories and at least 150 g of protein per day is often given in liquid form through a tube directly into the stomach (percutaneous endoscopic gastrostomy), or through a drip into a vein (parenteral nutrition). This high-caloric diet maintenance is required because of the increased metabolic strain brought on by the increased muscle activity. Full recovery takes 4 to 6 weeks because the body must regenerate destroyed nerve axon terminals.The antibiotic of choice is metronidazole. It can be given as intravenously, by mouth, or by rectum. Of likewise efficiency is penicillin, but some raise the concern of provoking spasms because it inhibits GABA receptor, which is already affected by tetanospasmin. Epidemiology In 2013 it caused about 59,000 deaths – down from 356,000 in 1990. Tetanus – in particular, the neonatal form – remains a significant public health problem in non-industrialized countries with 59,000 newborns worldwide dying in 2008 as a result of neonatal tetanus. In the United States, from 2000 through 2007 an average of 31 cases were reported per year. Nearly all of the cases in the United States occur in unimmunized individuals or individuals who have allowed their inoculations to lapse. History Tetanus was well known to ancient civilizations who recognized the relationship between wounds and fatal muscle spasms. In 1884, Arthur Nicolaier isolated the strychnine-like toxin of tetanus from free-living, anaerobic soil bacteria. The etiology of the disease was further elucidated in 1884 by Antonio Carle and Giorgio Rattone, two pathologists of the University of Turin, who demonstrated the transmissibility of tetanus for the first time. They produced tetanus in rabbits by injecting pus from a person with fatal tetanus into their sciatic nerves and testing their reactions while tetanus was spreading.In 1891, C. tetani was isolated from a human victim by Kitasato Shibasaburō, who later showed that the organism could produce disease when injected into animals and that the toxin could be neutralized by specific antibodies. In 1897, Edmond Nocard showed that tetanus antitoxin induced passive immunity in humans, and could be used for prophylaxis and treatment. Tetanus toxoid vaccine was developed by P. Descombey in 1924, and was widely used to prevent tetanus induced by battle wounds during World War II. Etymology The word tetanus comes from the Ancient Greek: τέτανος, romanized: tetanos, lit. taut, which is further from the Ancient Greek: τείνειν, romanized: teinein, lit. to stretch. Research There is insufficient evidence that tetanus can be treated or prevented by vitamin C. This is at least partially due to the fact that historically trials conducted trying to look for a possible connection between vitamin C and helping tetanus patients were of poor quality. See also Renshaw cell Tetanized state Tetanospasmin References External links Tetanus Information from Medline Plus Tetanus Surveillance -- United States, 1998-2000 (Data and Analysis) "Tetanus". MedlinePlus. U.S. National Library of Medicine.

Would you describe Thrombocythemia, to me Aarogya

Thrombocythemia

Thrombocythemia is a condition of high platelet (thrombocyte) count in the blood. Normal count is in the range of 150x109 to 450x109 platelets per liter of blood, but investigation is typically only considered if the upper limit exceeds 750x109/L. When the cause is unknown, the term thrombocythemia is used, as either primary thrombocythemia or essential thrombocythemia. The condition arises from a fault in the bone marrow cells leading to over-production of platelets but the cause of the fault is unknown, and this type is not common.When the cause is known such as another disorder or disease, the term thrombocytosis is preferred, as either secondary or reactive thrombocytosis. Reactive thrombocytosis is the most common type and though it can often have no symptoms it can sometimes predispose to thrombosis. In contrast, thrombocytopenia refers to abnormally low blood platelet numbers in the blood. Signs and symptoms High platelet counts do not necessarily signal any clinical problems, and can be picked up on a routine full blood count. However, it is important that a full medical history be elicited to ensure that the increased platelet count is not due to a secondary process. Often, it occurs in tandem with an inflammatory disease as the principal stimulants of platelet production (e.g. thrombopoietin) are elevated in these clinical states as part of the acute phase reaction. High platelet counts can occur in patients with polycythemia vera (high red blood cell counts), and is an additional risk factor for complications.A very small number of people report symptoms of erythromelalgia, a burning sensation and redness of the extremities that resolves with cooling, or aspirin or both.Scientific literature sometimes excludes thrombocytosis from the scope of thrombophilia by definition, but practically, by the definition of thrombophilia as an increased predisposition to thrombosis, thrombocytosis (especially primary thrombocytosis) is a potential cause of thrombophilia. Conversely, secondary thrombocytosis very rarely causes thrombotic complications. Causes Reactive thrombocythemia is the most common cause of a high platelet count. It accounts for 88% to 97% of thrombocythemia cases in adults, and near 100% in children. In adults, acute infection, tissue damage, chronic inflammation and malignancy are the common causes of reactive thrombocythemia. Usually, one or more of these conditions is present in more than 75% of the cases with reactive thrombocythemia. Causes for reactive thrombocythemia in children are similar to adults. In addition, hemolytic anemia and thalassemia are often present in children living in the Middle East. Other causes of reactive thrombocythemia include: post surgery, iron deficiency, drugs, and rebound effect after bone marrow suppression.The SARS disease caused thrombocytosis.Once the reactive causes of thrombocythemia are ruled out, clonal thrombocythemia should be considered. The most common cause of clonal thrombocythemia is a myeloproliferative neoplasm. These include: essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, and primary myelofibrosis.Extremely rare causes of thrombocythemia are spurious causes. This is due to the presence of structures resembling platelets in the blood such as needle-like cryoglobulin crystals, cytoplasmic fragments of circulating leukemic cells, bacteria, and red blood cell microvesicles. These structures are counted as platelets by the automated machine counter; therefore, causing the platelet number to be falsely elevated. However, such error can be avoided by doing a peripheral blood smear. Diagnosis Laboratory tests might include: full blood count, liver enzymes, renal function and erythrocyte sedimentation rate.If the cause for the high platelet count remains unclear, bone marrow biopsy is often undertaken, to differentiate whether the high platelet count is reactive or essential. Treatment Often, no treatment is required or necessary for reactive thrombocytosis. In cases of reactive thrombocytosis of more than 1,000x109/L, it may be considered to administer daily low dose aspirin (such as 65 mg) to minimize the risk of stroke or thrombosis.However, in essential thrombocythemia where platelet counts are over 750x109/L or 1,000x109/L, especially if there are other risk factors for thrombosis, treatment may be needed. Selective use of aspirin at low doses is thought to be protective. Extremely high platelet counts can be treated with hydroxyurea (a cytoreducing agent) or anagrelide (Agrylin).In Janus kinase 2 positive disorders, ruxolitinib (Jakafi) can be effective. References Schafer AI (March 2004). "Thrombocytosis". N. Engl. J. Med. 350 (12): 1211–9. doi:10.1056/NEJMra035363. PMID 15028825. == External links ==

Hello Aarogya, what is Tinea barbae

Tinea barbae

Tinea barbae is a fungal infection of the hair. Tinea barbae is due to a dermatophytic infection around the bearded area of men. Generally, the infection occurs as a follicular inflammation, or as a cutaneous granulomatous lesion, i.e. a chronic inflammatory reaction. It is one of the causes of folliculitis. It is most common among agricultural workers, as the transmission is more common from animal-to-human than human-to-human. The most common causes are Trichophyton mentagrophytes and T. verrucosum. Signs and symptoms Main symptoms that occur when affected with tinea barbae is pimple or blister amongst affected area, swelling and redness around infected area, red and lumpy skin on infected area. Crusting around hairs in infected area will occur, hairs on infected area will also be effortless to pull out. Tinea barbae can be itchy or painful to touch but these symptoms do not always occur. Transmission The transmission of tinea barbae to humans occurs through contact of an infected animal to the skin of a human. Infection can occasionally be transmitted through contact of infected animal hair on human skin. Tinea barbae is very rarely transmitted through human to human contact but is not completely impossible. Diagnosis Diagnosis of tinea barbae will firstly include questions being asked from doctors about interactions with farm animals and lifestyle experiences. Doctor will then gain knowledge on possible disease by microscopy, this is viewing the skin under a microscope to get an enlarge view of infected area. Skin scraping and removal of hairs on infected area will occur for medical examination. To acquire causation of tinea barbae putting infected area under ultraviolet light can achieve this, as infection caused by animal and human contact will not show up as fluorescent under the ultraviolet light, compared to other causes of this disease. Treatment Treatment can vary with severity of the infection. Moderate cases of tinea barbae can be treated with topical antifungal medications. Topical antifungal medications will come in the form of cream, which can normally be obtained over the counter. More serious cases of tinea barbae warrant an oral antifungal medication. References == External links ==

Aarogya what is Tinea capitis

Tinea capitis

Tinea capitis (also known as "herpes tonsurans", "ringworm of the hair", "ringworm of the scalp", "scalp ringworm", and "tinea tonsurans") is a cutaneous fungal infection (dermatophytosis) of the scalp. The disease is primarily caused by dermatophytes in the genera Trichophyton and Microsporum that invade the hair shaft. The clinical presentation is typically single or multiple patches of hair loss, sometimes with a black dot pattern (often with broken-off hairs), that may be accompanied by inflammation, scaling, pustules, and itching. Uncommon in adults, tinea capitis is predominantly seen in pre-pubertal children, more often boys than girls. At least eight species of dermatophytes are associated with tinea capitis. Cases of Trichophyton infection predominate from Central America to the United States and in parts of Western Europe. Infections from Microsporum species are mainly in South America, Southern and Central Europe, Africa and the Middle East. The disease is infectious and can be transmitted by humans, animals, or objects that harbor the fungus. The fungus can also exist in a carrier state on the scalp, without clinical symptomatology. Treatment of tinea capitis requires an oral antifungal agent; griseofulvin is the most commonly used drug, but other newer antimycotic drugs, such as terbinafine, itraconazole, and fluconazole have started to gain acceptance. Symptoms It may appear as thickened, scaly, and sometimes boggy swellings, or as expanding raised red rings (ringworm). Common symptoms are severe itching of the scalp, dandruff, and bald patches where the fungus has rooted itself in the skin. It often presents identically to dandruff or seborrheic dermatitis. The highest incidence in the United States of America is in American boys of school age.There are three type of tinea capitis, microsporosis, trichophytosis, and favus; these are based on the causative microorganism, and the nature of the symptoms. In microsporosis, the lesion is a small red papule around a hair shaft that later becomes scaly; eventually the hairs break off 1–3 mm above the scalp. This disease used to be caused primarily by Microsporum audouinii, but in Europe, M. canis is more frequently the causative fungus. The source of this fungus is typically sick cats and kittens; it may be spread through person to person contact, or by sharing contaminated brushes and combs. In the United States, Trichophytosis is usually caused by Trichophyton tonsurans, while T. violaceum is more common in Eastern Europe, Africa, and India. This fungus causes dry, non-inflammatory patches that tend to be angular in shape. When the hairs break off at the opening of the follicle, black dots remain. Favus is caused by T. schoenleinii, and is endemic in South Africa and the Middle East. It is characterized by a number of yellowish, circular, cup-shaped crusts (scutula) grouped in patches like a piece of honeycomb, each about the size of a split pea, with a hair projecting in the center. These increase in size and become crusted over, so that the characteristic lesion can only be seen around the edge of the scab. Pathophysiology From the site of inoculation, the fungus grows down into the stratum corneum, where it invades keratin. Dermatophytes are unique in that they produce keratinase, which enables them to use keratin as a nutrient source. Infected hairs become brittle, and after three weeks, the clinical presentation of broken hairs is evident.There are three types of infection: Ectothrix: Characterized by the growth of fungal spores (arthroconidia) on the exterior of the hair shaft. Infected hairs usually fluoresce greenish-yellow under a Wood lamp (blacklight). Associated with Microsporum canis, Microsporum gypseum, Trichophyton equinum, and Trichophyton verrucosum. Endothrix: Similar to ectothrix, but characterized by arthroconidia restricted to the hair shaft, and restricted to anthropophilic bacteria. The cuticle of the hair remains intact and clinically this type does not have fluorescence. Associated with Trichophyton tonsurans and Trichophyton violaceum, which are anthropophilic. Favus: Causes crusting on the surface of the skin, combined with hair loss. Associated with Trichophyton schoenleini. Diagnosis Tinea capitis may be difficult to distinguish from other skin diseases that cause scaling, such as psoriasis and seborrhoeic dermatitis; the basis for the diagnosis is positive microscopic examination and microbial culture of epilated hairs. Woods lamp examination will reveal bright green to yellow-green fluorescence of hairs infected by M. canis, M. audouinii, M. rivalieri, and M. ferrugineum and a dull green or blue-white color of hairs infected by T. schoenleinii. Individuals with M. canis infection trichoscopy will show characteristic small comma hairs. Histopathology of scalp biopsy shows fungi sparsely distributed in the stratum corneum and hyphae extending down the hair follicle, placed on the surface of the hair shaft. These findings are occasionally associated with inflammatory tissue reaction in the local tissue. Treatment The treatment of choice by dermatologists is a safe and inexpensive oral medication, griseofulvin, a secondary metabolite of the fungus Penicillium griseofulvin. This compound is fungistatic (inhibiting the growth or reproduction of fungi) and works by affecting the microtubular system of fungi, interfering with the mitotic spindle and cytoplasmic microtubules. The recommended pediatric dosage is 10 mg/kg/day for 6–8 weeks, although this may be increased to 20 mg/kg/d for those infected by T. tonsurans, or those who fail to respond to the initial 6 weeks of treatment. Unlike other fungal skin infections that may be treated with topical therapies like creams applied directly to the affected area, griseofulvin must be taken orally to be effective; this allows the drug to penetrate the hair shaft where the fungus lives. The effective therapy rate of this treatment is generally high, in the range of 88–100%. Other oral antifungal treatments for tinea capitis also frequently reported in the literature include terbinafine, itraconazole, and fluconazole; these drugs have the advantage of shorter treatment durations than griseofulvin. A 2016 meta-analysis of randomized controlled trials found that terbinafine, itraconazole and fluconazole were at least equally effective as griseofulvin for children infected with Trichophyton, and terbinafine is more effective than griseofulvin for children with T. tonsurans infection. However, concerns have been raised about the possibility of rare side effects like liver toxicity or interactions with other drugs; furthermore, the newer drug treatments tend to be more expensive than griseofulvin.On September 28, 2007, the U.S. Food and Drug Administration stated that Lamisil (Terbinafine hydrochloride, by Novartis AG) is a new treatment approved for use by children aged 4 years and older. The antifungal granules can be sprinkled on a childs food to treat the infection. Lamisil carries hepatotoxic risk, and can cause a metallic taste in the mouth. Epidemiology Tinea capitis caused by species of Microsporum and Trichophyton is a contagious disease that is endemic in many countries. Affecting primarily pre-pubertal children between 6 and 10 years, it is more common in males than females; rarely does the disease persist past age sixteen. Because spread is thought to occur through direct contact with affected individuals, large outbreaks have been known to occur in schools and other places where children are in close quarters; however, indirect spread through contamination with infected objects (fomites) may also be a factor in the spread of infection. In the US, tinea capitis is thought to occur in 3-8% of the pediatric population; up to one-third of households with contact with an infected person may harbor the disease without showing any symptoms.The fungal species responsible for causing tinea capitis vary according to the geographical region, and may also change over time. For example, Microsporum audouinii was the predominant etiological agent in North America and Europe until the 1950s, but now Trichophyton tonsurans is more common in the US, and becoming more common in Europe and the United Kingdom. This shift is thought to be due to the widespread use of griseofulvin, which is more effective against M. audounii than T. tonsurans; also, changes in immigration patterns and increases in international travel have likely spread T. tonsurans to new areas. Another fungal species that has increased in prevalence is Trichophyton violaceum, especially in urban populations of the United Kingdom and Europe. See also List of cutaneous conditions Ringworm affair Footnotes References Richardson M. (2003). Fungal Infection: Diagnosis and Management. Cambridge, MA: Blackwell Publishers. ISBN 1-4051-1578-5. == External links ==

Do you know what is Tinea corporis, Aarogya

Tinea corporis

Tinea corporis is a fungal infection of the body, similar to other forms of tinea. Specifically, it is a type of dermatophytosis (or ringworm) that appears on the arms and legs, especially on glabrous skin; however, it may occur on any superficial part of the body. Signs and symptoms It may have a variety of appearances; most easily identifiable are the enlarging raised red rings with a central area of clearing (ringworm). The same appearances of ringworm may also occur on the scalp (tinea capitis), beard area (tinea barbae) or the groin (tinea cruris, known as jock itch or dhobi itch). Other classic features of tinea corporis include: Itching occurs on infected area. The edge of the rash appears elevated and is scaly to touch. Sometimes the skin surrounding the rash may be dry and flaky. Almost invariably, there will be hair loss in areas of the infection. Causes Tinea corporis is caused by a tiny fungus known as dermatophyte. These tiny organisms normally live on the superficial skin surface, and when the opportunity is right, they can induce a rash or infection.The disease can also be acquired by person-to-person transfer usually via direct skin contact with an infected individual. Animal-to-human transmission is also common. Ringworm commonly occurs on pets (dogs, cats) and the fungus can be acquired while petting or grooming an animal. Ringworm can also be acquired from other animals such as horses, pigs, ferrets and cows. The fungus can also be spread by touching inanimate objects like personal care products, bed linen, combs, athletic gear, or hair brushes contaminated by an affected person.Individuals at high risk of acquiring ringworm include those who: Live in crowded, humid conditions. Sweat excessively, as sweat can produce a humid wet environment where the pathogenic fungi can thrive. This is most common in the armpits, groin creases and skin folds of the abdomen. Participate in close contact sports like soccer, rugby, or wrestling. Wear tight, constrictive clothing with poor aeration. Have a weakened immune system (e.g., those infected with HIV or taking immunosuppressive drugs). Diagnosis Superficial scrapes of skin examined underneath a microscope may reveal the presence of a fungus. This is done by utilizing a diagnostic method called KOH test, wherein the skin scrapings are placed on a slide and immersed on a dropful of potassium hydroxide solution to dissolve the keratin on the skin scrappings thus leaving fungal elements such as hyphae, septate or yeast cells viewable. If the skin scrapings are negative and a fungus is still suspected, the scrapings are sent for culture. Because the fungus grows slowly, the culture results do take several days to become positive. Prevention Because fungi prefer warm, moist environments, preventing ringworm involves keeping skin dry and avoiding contact with infectious material. Basic prevention measures include: Washing hands after handling animals, soil, and plants. Avoiding touching characteristic lesions on other people. Wearing loose-fitting clothing. Practicing good hygiene when participating in sports that involve physical contact with other people. Treatment Most cases are treated by application of topical antifungal creams to the skin, but in extensive or difficult to treat cases, systemic treatment with oral medication may be required. The over-the-counter options include tolnaftate, as well as ketoconazole (available as Nizoral shampoo that can be applied topically). Among the available prescription drugs, the evidence is best for terbinafine and naftifine, but other agents may also work.Topical antifungals are applied to the lesion twice a day for at least 3 weeks. The lesion usually resolves within 2 weeks, but therapy should be continued for another week to ensure the fungus is completely eradicated. If there are several ringworm lesions, the lesions are extensive, complications such as secondary infection exist, or the patient is immunocompromised, oral antifungal medications can be used. Oral medications are taken once a day for 7 days and result in higher clinical cure rates. The antifungal medications most commonly used are itraconazole, terbinafine, and ketoconazole.The benefits of the use of topical steroids in addition to an antifungal is unclear. There might be a greater cure rate but no guidelines currently recommend its addition. The effect of Whitfields ointment is also unclear. Prognosis Tinea corporis is moderately contagious and can affect both humans and pets. If a person acquires it, the proper measures must be taken to prevent it from spreading. Young children in particular should be educated about the infection and preventive measures: avoid skin to skin contact with infected persons and animals, wear clothing that allows the skin to breathe, and dont share towels, clothing or combs with others. If pets are kept in the household or premises, the animal should be checked for tinea, especially if hair loss in patches is noticed or the pet is scratching excessively. The majority of people who have acquired tinea know how uncomfortable the infection can be. However, the fungus can easily be treated and prevented in individuals with a healthy immune system. Society and culture When the dermatophytic infection presents in wrestlers, with skin lesions typically found on the head, neck, and arms it is sometimes called tinea corporis gladiatorum. See also Fungal folliculitis References == External links ==

Aarogya, elaborate on Tinea cruris

Tinea cruris

Tinea cruris, also known as jock itch, is a common type of contagious, superficial fungal infection of the groin region, which occurs predominantly but not exclusively in men and in hot-humid climates.Typically, over the upper inner thighs, there is an intensely itchy red raised rash with a scaly well-defined curved border. It is often associated with athletes foot and fungal nail infections, excessive sweating and sharing of infected towels or sports clothing. It is uncommon in children.Its appearance may be similar to some other rashes that occur in skin folds including candidal intertrigo, erythrasma, inverse psoriasis and seborrhoeic dermatitis. Tests may include microscopy and culture of skin scrapings.Treatment is with topical antifungal medications and is particularly effective if symptoms have recent onset. Prevention of recurrences include treating concurrent fungal infections and taking measures to avoid moisture build-up including keeping the groin region dry, avoiding tight clothing and losing weight if obese. Names Other names include "jock rot", "dhobi itch", "crotch itch", "scrot rot", "gym itch", "ringworm of groin" and "eczema marginatum". Signs and symptoms Typically, over the upper inner thighs, there is a red raised rash with a scaly well-defined border. There may be some blistering and weeping, and the rash can reach near to the anus. The distribution is usually on both sides of the groin and the center may be lighter in colour. The rash may appear reddish, tan, or brown, with flaking, rippling, peeling, iridescence, or cracking skin.If the person is hairy, hair follicles can become inflamed resulting in some bumps (papules, nodules and pustules) within the plaque. The plaque may reach the scrotum in men and the labia majora and mons pubis in women. The penis is usually unaffected unless there is immunodeficiency or there has been use of steroids.Affected people usually experience intense itching in the groin which can extend to the anus. Causes Tinea cruris is often associated with athletes foot and fungal nail infections. Rubbing from clothing, excessive sweating, diabetes and obesity are risk factors. It is contagious and can be transmitted person-to-person by skin-to-skin contact or by contact with contaminated sports clothing and sharing towels.The type of fungus involved may vary in different parts of the world; for example, Trichophyton rubrum and Epidermophyton floccosum are common in New Zealand. Less commonly Trichophyton mentagrophytes and Trichophyton verrucosum are involved. Trichophyton interdigitale has also been implicated. Diagnosis Tests are usually not needed to make a diagnosis, but if required, may include microscopy and culture of skin scrapings, a KOH examination to check for fungus or skin biopsy. Differential diagnosis The symptoms of tinea cruris may be similar to other causes of itch in the groin. Its appearance may be similar to some other rashes that occur in skin folds including candidal intertrigo, erythrasma, inverse psoriasis and seborrhoeic dermatitis. Prevention To prevent recurrences of tinea cruris, concurrent fungal infections such as athletes foot need to be treated. Also advised are measures to avoid moisture build-up including keeping the groin region dry, avoiding tight clothing and losing weight if obese. People with athletes foot or tinea cruris can prevent spread by not lending their towels to others. Treatment Tinea cruris is treated by applying antifungal medications of the allylamine or azole type to the groin region. Studies suggest that allylamines (naftifine and terbinafine) are a quicker but more expensive form of treatment compared to azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, sulconazole). If the symptoms have been present for long or the condition worsens despite applying creams, terbinafine or itraconazole can be given by mouth.The benefits of the use of topical steroids in addition to an antifungal is unclear. There might be a greater cure rate but no guidelines currently recommend its addition. The effect of Whitfields ointment is also unclear, but when given, it is prescribed at half strength.Wearing cotton underwear and socks, in addition to keeping the groin dry and using antifungal powders are helpful. Prognosis and complications Tinea cruris is not life-threatening and treatment is effective, particularly if the symptoms have not been present for long. However, recurrence may occur. The intense itch may lead to lichenification and secondary bacterial infection. Irritant and allergic contact dermatitis may be caused by applied medications. Epidemiology Tinea cruris is common in hot-humid climates and is the second most common clinical presentation for dermatophytosis. It is uncommon in children. References External links eMedicineHealth.com

Aarogya, can you share information about a health condition involving Tinea nigra

Tinea nigra

Tinea nigra, also known as superficial phaeohyphomycosis and Tinea nigra palmaris et plantaris, is a superficial fungal infection, a type of phaeohyphomycosis rather than a tinea, that causes usually a single 1–5 cm dark brown-black, non-scaly, flat, painless patch on the palms of the hands and the soles of the feet of healthy people. There may be multiple spots. The macules occasionally extend to the fingers, toes, and nails, and may be reported on the chest, neck, or genital area.: 311  Tinea nigra infections can present with multiple macules that can be mottled or velvety in appearance, and may be oval or irregular in shape. The macules can be anywhere from a few mm to several cm in size.Most cases are caused by Hortaea werneckii, a pigmented fungus, which is a dark yeast found in sewage, soil, rotting vegetation and wood and in places with a high salt content such as moldy salted fish and on beaches, where contact with sand may result in transmission. Infection is by direct contact and the fungus enters and remains in the outer dead layer of skin with little or no skin inflammation. The infection does not invade deeper tissues.Diagnosis is by visualisation, dermoscopy, and microscopy and culture of skin scrapings. Differential diagnosis includes Addisons disease, syphilis, pinta, yaws, melanoma, lentigines, lichen planus of the palms, and junctional melanocytes nevus. Treatment is with topical Whitfields ointment or salicylic acid ointment. Topical antifungals or oral itraconazole are other options. Scraping the lesion can be curative. Prevention is by general hygiene measures.It is uncommon. It generally occurs in tropical and subtropical countries of Central and South America, the Caribbean, Europe, South East Asia, Australia and the Far East. The disease was first described by Alexandre Cerqueira from Brazil in 1891. No cases in animals have been reported. Causes This infection is caused by the fungus formerly classified as Cladosporium werneckii, but more recently classified as Hortaea werneckii. The causative organism has also been described as Phaeoannellomyces werneckii. Tinea nigra is extremely superficial and can be removed from the skin by forceful scraping. It tends to appear in areas where eccrine sweat glands are highly concentrated. Infections generally start to appear on the skin around 2–7 weeks post inoculation. The ability of H. werneckii to tolerate high salt concentrations and acidic conditions allows it to flourish inside the stratum corneum. H. wernickii tends remain localized in one spot or region, and produces darkly-colored, brown macules on the skin due to the production of a melanin-like substance. Diagnosis Diagnosis of tinea nigra is made based on microscopic examination of stratum corneum skin scrapings obtained by using a scalpel. The scrapings are mixed with potassium hydroxide (KOH). The KOH lyses the nonfungal debris. The skin scrapings are cultured on Sabourauds agar at 25°C and allowed to grow for about a week. H. werneckii can generally be distinguished due to its two-celled yeast form and the presence of septate hyphae with thick, darkly pigmented walls. Treatment Treatment consists of topical application of dandruff shampoo, which contains selenium sulfide, over the skin. Topical antifungal imidazoles such as ketoconazole, itraconazole, and miconazole may also be used. Imidazoles are generally used twice daily for a two-week period. This is the same treatment plan for tinea or pityriasis versicolor. Other treatment methods include the use of epidermal tape stripping, Undecylenic acid, and other topical agents such as ciclopirox. Once a tinea nigra infection has been eradicated from the host, it is not likely to reoccur. Epidemiology Tinea nigra is commonly found in Africa, Asia, Central America, and South America. It is typically not found in the United States or Europe, although cases have been documented in the Southeastern United States. People of all ages can be infected; however, it is generally more apparent in children and younger adults. Females are three times more likely than males to become infected. See also List of cutaneous conditions References External links DermAtlas 1049165786 DermNet fungal/tinea-nigra

Aarogya, What does Athletes foot mean

Athletes foot

Athletes foot, known medically as tinea pedis, is a common skin infection of the feet caused by a fungus. Signs and symptoms often include itching, scaling, cracking and redness. In rare cases the skin may blister. Athletes foot fungus may infect any part of the foot, but most often grows between the toes. The next most common area is the bottom of the foot. The same fungus may also affect the nails or the hands. It is a member of the group of diseases known as tinea.Athletes foot is caused by a number of different fungi, including species of Trichophyton, Epidermophyton, and Microsporum. The condition is typically acquired by coming into contact with infected skin, or fungus in the environment. Common places where the fungi can survive are around swimming pools and in locker rooms. They may also be spread from other animals. Usually diagnosis is made based on signs and symptoms; however, it can be confirmed either by culture or seeing hyphae using a microscope.Athletes foot is not limited to just athletes: it can be caused by going barefoot in public showers, letting toenails grow too long, wearing shoes that are too tight, and not changing socks daily. It can be treated with topical antifungal medications such as clotrimazole or, for persistent infections, using oral antifungal medications such as terbinafine. Topical creams are typically recommended to be used for four weeks. Keeping infected feet dry and wearing sandals also assists with treatment.Athletes foot was first medically described in 1908. Globally, athletes foot affects about 15% of the population. Males are more often affected than females. It occurs most frequently in older children or younger adults. Historically it is believed to have been a rare condition that became more frequent in the 20th century due to the greater use of shoes, health clubs, war, and travel. Signs and symptoms Athletes foot is divided into four categories or presentations: chronic interdigital, plantar (chronic scaly; aka "moccasin foot"), acute ulcerative, and vesiculobullous. "Interdigital" means between the toes. "Plantar" here refers to the sole of the foot. The ulcerative condition includes macerated lesions with scaly borders. Maceration is the softening and breaking down of skin due to extensive exposure to moisture. A vesiculobullous disease is a type of mucocutaneous disease characterized by vesicles and bullae (blisters). Both vesicles and bullae are fluid-filled lesions, and they are distinguished by size (vesicles being less than 5–10 mm and bulla being larger than 5–10 mm, depending upon what definition is used).Athletes foot occurs most often between the toes (interdigital), with the space between the fourth and fifth digits (the little toe and the fore toe) most commonly affected. Cases of interdigital athletes foot caused by Trichophyton rubrum may be symptomless, it may itch, or the skin between the toes may appear red or ulcerative (scaly, flaky, with soft and white if skin has been kept wet), with or without itching. An acute ulcerative variant of interdigital athletes foot caused by T. mentagrophytes is characterized by pain, maceration of the skin, erosions and fissuring of the skin, crusting, and an odor due to secondary bacterial infection.Plantar athletes foot (moccasin foot) is also caused by T. rubrum which typically causes asymptomatic, slightly erythematous plaques (areas of redness of the skin) to form on the plantar surface (sole) of the foot that are often covered by fine, powdery hyperkeratotic scales.The vesiculobullous type of athletes foot is less common and is usually caused by T. mentagrophytes and is characterized by a sudden outbreak of itchy blisters and vesicles on an erythematous base, usually appearing on the sole of the foot. This subtype of athletes foot is often complicated by secondary bacterial infection by Streptococcus pyogenes or Staphylococcus aureus. Complications As the disease progresses, the skin may crack, leading to bacterial skin infection and inflammation of the lymphatic vessels. If allowed to grow for too long, athletes foot fungus may spread to infect the toenails, feeding on the keratin in them, a condition called onychomycosis.Because athletes foot may itch, it may also elicit the scratch reflex, causing the host to scratch the infected area before they realize it. Scratching can further damage the skin and worsen the condition by allowing the fungus to more easily spread and thrive. The itching sensation associated with athletes foot can be so severe that it may cause hosts to scratch vigorously enough to inflict excoriations (open wounds), which are susceptible to bacterial infection. Further scratching may remove scabs, inhibiting the healing process. Scratching infected areas may also spread the fungus to the fingers and under the fingernails. If not washed away soon enough, it can infect the fingers and fingernails, growing in the skin and in the nails (not just underneath). After scratching, it can be spread to wherever the person touches, including other parts of the body and to ones environment. Scratching also causes infected skin scales to fall off into ones environment, leading to further possible spread. When athletes foot fungus or infested skin particles spread to ones environment (such as to clothes, shoes, bathroom, etc.) whether through scratching, falling, or rubbing off, not only can they infect other people, they can also reinfect (or further infect) the host they came from. For example, infected feet infest ones socks and shoes which further expose the feet to the fungus and its spores when worn again.The ease with which the fungus spreads to other areas of the body (on ones fingers) poses another complication. When the fungus is spread to other parts of the body, it can easily be spread back to the feet after the feet have been treated. And because the condition is called something else in each place it takes hold (e.g., tinea corporis (ringworm) or tinea cruris (jock itch)), persons infected may not be aware it is the same disease. Some individuals may experience an allergic response to the fungus called an id reaction in which blisters or vesicles can appear in areas such as the hands, chest, and arms. Treatment of the underlying infection typically results in the disappearance of the id reaction. Causes Athletes foot is a form of dermatophytosis (fungal infection of the skin), caused by dermatophytes, fungi (most of which are mold) which inhabit dead layers of skin and digest keratin. Dermatophytes are anthropophilic, meaning these parasitic fungi prefer human hosts. Athletes foot is most commonly caused by the molds known as Trichophyton rubrum and T. mentagrophytes, but may also be caused by Epidermophyton floccosum. Most cases of athletes foot in the general population are caused by T. rubrum; however, the majority of athletes foot cases in athletes are caused by T. mentagrophytes. Transmission According to the UKs National Health Service, "Athletes foot is very contagious and can be spread through direct and indirect contact." The disease may spread to others directly when they touch the infection. People can contract the disease indirectly by coming into contact with contaminated items (clothes, towels, etc.) or surfaces (such as bathroom, shower, or locker room floors). The fungi that cause athletes foot can easily spread to ones environment. Fungi rub off of fingers and bare feet, but also travel on the dead skin cells that continually fall off the body. Athletes foot fungi and infested skin particles and flakes may spread to socks, shoes, clothes, to other people, pets (via petting), bed sheets, bathtubs, showers, sinks, counters, towels, rugs, floors, and carpets. When the fungus has spread to pets, it can subsequently spread to the hands and fingers of people who pet them. If a pet frequently gnaws upon itself, it might not be fleas it is reacting to, it may be the insatiable itch of tinea. One way to contract athletes foot is to get a fungal infection somewhere else on the body first. The fungi causing athletes foot may spread from other areas of the body to the feet, usually by touching or scratching the affected area, thereby getting the fungus on the fingers, and then touching or scratching the feet. While the fungus remains the same, the name of the condition changes based on where on the body the infection is located. For example, the infection is known as tinea corporis ("ringworm") when the torso or limbs are affected or tinea cruris (jock itch or dhobi itch) when the groin is affected. Clothes (or shoes), body heat, and sweat can keep the skin warm and moist, just the environment the fungus needs to thrive. Risk factors Besides being exposed to any of the modes of transmission presented above, there are additional risk factors that increase ones chance of contracting athletes foot. Persons who have had athletes foot before are more likely to become infected than those who have not. Adults are more likely to catch athletes foot than children. Men have a higher chance of getting athletes foot than women. People with diabetes or weakened immune systems are more susceptible to the disease. HIV/AIDS hampers the immune system and increases the risk of acquiring athletes foot. Hyperhidrosis (abnormally increased sweating) increases the risk of infection and makes treatment more difficult. Diagnosis When visiting a doctor, the basic diagnosis procedure applies. This includes checking the patients medical history and medical record for risk factors, a medical interview during which the doctor asks questions (such as about itching and scratching), and a physical examination. Athletes foot can usually be diagnosed by visual inspection of the skin and by identifying less obvious symptoms such as itching of the affected area. If the diagnosis is uncertain, direct microscopy of a potassium hydroxide preparation of a skin scraping (known as a KOH test) can confirm the diagnosis of athletes foot and help rule out other possible causes, such as candidiasis, pitted keratolysis, erythrasma, contact dermatitis, eczema, or psoriasis. Dermatophytes known to cause athletes foot will demonstrate multiple septate branching hyphae on microscopy.A Woods lamp (black light), although useful in diagnosing fungal infections of the scalp (tinea capitis), is not usually helpful in diagnosing athletes foot, since the common dermatophytes that cause this disease do not fluoresce under ultraviolet light. Prevention There are several preventive foot hygiene measures that can prevent athletes foot and reduce recurrence. Some of these include: keeping the feet dry; clipping toenails short; using a separate nail clipper for infected toenails; using socks made from well-ventilated cotton or synthetic moisture wicking materials (to soak moisture away from the skin to help keep it dry); avoiding tight-fitting footwear; changing socks frequently; and wearing sandals while walking through communal areas such as gym showers and locker rooms.According to the Centers for Disease Control and Prevention, "Nails should be clipped short and kept clean. Nails can house and spread the infection." Recurrence of athletes foot can be prevented with the use of antifungal powder on the feet.The fungi (molds) that cause athletes foot require warmth and moisture to survive and grow. There is an increased risk of infection with exposure to warm, moist environments (e.g., occlusive footwear—shoes or boots that enclose the feet) and in shared humid environments such as communal showers, shared pools, and treatment tubs. Chlorine bleach is a disinfectant and common household cleaner that kills mold. Cleaning surfaces with a chlorine bleach solution prevents the disease from spreading from subsequent contact. Cleaning bathtubs, showers, bathroom floors, sinks, and counters with bleach helps prevent the spread of the disease, including reinfection. Keeping socks and shoes clean (using bleach in the wash) is one way to prevent fungi from taking hold and spreading. Avoiding the sharing of boots and shoes is another way to prevent transmission. Athletes foot can be transmitted by sharing footwear with an infected person. Hand-me-downs and purchasing used shoes are other forms of shoe-sharing. Not sharing also applies to towels, because, though less common, fungi can be passed along on towels, especially damp ones. Treatment Athletes foot resolves without medication (resolves by itself) in 30–40% of cases. Topical antifungal medication consistently produces much higher rates of cure.Conventional treatment typically involves thoroughly washing the feet daily or twice daily, followed by the application of a topical medication. Because the outer skin layers are damaged and susceptible to reinfection, topical treatment generally continues until all layers of the skin are replaced, about 2–6 weeks after symptoms disappear. Keeping feet dry and practicing good hygiene (as described in the above section on prevention) is crucial for killing the fungus and preventing reinfection. Treating the feet is not always enough. Once socks or shoes are infested with fungi, wearing them again can reinfect (or further infect) the feet. Socks can be effectively cleaned in the wash by adding bleach or by washing in water 60 °C (140 °F). Washing with bleach may help with shoes, but the only way to be absolutely certain that one cannot contract the disease again from a particular pair of shoes is to dispose of those shoes.To be effective, treatment includes all infected areas (such as toenails, hands, torso, etc.). Otherwise, the infection may continue to spread, including back to treated areas. For example, leaving fungal infection of the nail untreated may allow it to spread back to the rest of the foot, to become athletes foot once again. Allylamines such as terbinafine are considered more efficacious than azoles for the treatment of athletes foot.Severe or prolonged fungal skin infections may require treatment with oral antifungal medication. Topical treatments There are many topical antifungal drugs useful in the treatment of athletes foot including: miconazole nitrate, clotrimazole, tolnaftate (a synthetic thiocarbamate), terbinafine hydrochloride, butenafine hydrochloride and undecylenic acid. The fungal infection may be treated with topical antifungal agents, which can take the form of a spray, powder, cream, or gel. Topical application of an antifungal cream such as butenafine once daily for one week or terbinafine once daily for two weeks is effective in most cases of athletes foot and is more effective than application of miconazole or clotrimazole. Plantar-type athletes foot is more resistant to topical treatments due to the presence of thickened hyperkeratotic skin on the sole of the foot. Keratolytic and humectant medications such as urea, salicyclic acid (Whitfields ointment), and lactic acid are useful adjunct medications and improve penetration of antifungal agents into the thickened skin. Topical glucocorticoids are sometimes prescribed to alleviate inflammation and itching associated with the infection.A solution of 1% potassium permanganate dissolved in hot water is an alternative to antifungal drugs. Potassium permanganate is a salt and a strong oxidizing agent. Oral treatments For severe or refractory cases of athletes foot oral terbinafine is more effective than griseofulvin. Fluconazole or itraconazole may also be taken orally for severe athletes foot infections. The most commonly reported adverse effect from these medications is gastrointestinal upset. Epidemiology Globally, fungal infections affect about 15% of the population and 20% of adults. Athletes foot is common in individuals who wear unventilated (occlusive) footwear, such as rubber boots or vinyl shoes. Countries and regions where going barefoot is more common experience much lower rates of athletes foot than do populations which habitually wear shoes; as a result, the disease has been called "a penalty of civilization". Studies have demonstrated that men are infected 2–4 times more often than women. See also Toenail fungus, tinea unguium, an infection affecting the toenails Trench foot, due to moisture and decay References External links Media related to Athletes foot at Wikimedia Commons "Athletes Foot". MedlinePlus. U.S. National Library of Medicine.

Aarogya, can you share information about a health condition involving Tinea versicolor

Tinea versicolor

Tinea versicolor (also pityriasis versicolor) is a condition characterized by a skin eruption on the trunk and proximal extremities. The majority of tinea versicolor is caused by the fungus Malassezia globosa, although Malassezia furfur is responsible for a small number of cases. These yeasts are normally found on the human skin and become troublesome only under certain circumstances, such as a warm and humid environment, although the exact conditions that cause initiation of the disease process are poorly understood.The condition pityriasis versicolor was first identified in 1846. Versicolor comes from the Latin versāre to turn + color. It is also commonly referred to as Peter Elams disease in many parts of South Asia. Signs and symptoms The symptoms of this condition include: Occasional fine scaling of the skin producing a very superficial ash-like scale Pale, dark tan, or pink in color, with a reddish undertone that can darken when the patient is overheated, such as in a hot shower or during/after exercise. Tanning typically makes the affected areas contrast more starkly with the surrounding skin. Sharp borderPityriasis versicolor is more common in hot, humid climates or in those who sweat heavily, so it may recur each summer.The yeasts can often be seen under the microscope within the lesions and typically have a so-called "spaghetti and meatball appearance" as the round yeasts produce filaments. In people with dark skin tones, pigmentary changes such as hypopigmentation (loss of color) are common, while in those with lighter skin color, hyperpigmentation (increase in skin color) is more common. These discolorations have led to the term "sun fungus". Pathophysiology In cases of tinea versicolor caused by the fungus Malassezia furfur, lightening of the skin occurs due to the funguss production of azelaic acid, which has a slight bleaching effect. Diagnosis Tinea versicolor may be diagnosed by a potassium hydroxide (KOH) preparation and lesions may fluoresce copper-orange when exposed to Woods lamp. The differential diagnosis for tinea versicolor infection includes: Progressive macular hypomelanosis Pityriasis alba Pityriasis rosea Seborrheic dermatitis Erythrasma Vitiligo Leprosy Syphilis Post-inflammatory hypopigmentation Treatment Treatments for tinea versicolor include: Topical antifungal medications containing selenium sulfide are often recommended. Ketoconazole (Nizoral ointment and shampoo) is another treatment. It is normally applied to dry skin and washed off after 10 minutes, repeated daily for two weeks. Ciclopirox (ciclopirox olamine) is an alternative treatment to ketoconazole, as it suppresses growth of the yeast Malassezia furfur. Initial results show similar efficacy to ketoconazole with a relative increase in subjective symptom relief due to its inherent anti-inflammatory properties. Other topical antifungal agents such as clotrimazole, miconazole, terbinafine, or zinc pyrithione can lessen symptoms in some patients. Additionally, hydrogen peroxide has been known to lessen symptoms and, on certain occasions, remove the problem, although permanent scarring has occurred with this treatment in some people. Clotrimazole is also used combined with selenium sulfide. Oral medications are viewed as a second-line of treatment for pityriasis versicolor in the event of widespread, severe, recalcitrant or recurrent cases. Systemic therapies include itraconazole (200 mg daily for seven days) and fluconazole (150 to 300 mg weekly dose for 2 to 4 weeks) that are preferred to oral ketoconazole which is no longer approved due to its potential hepatotoxic sides effects. The single-dose regimens and pulse therapy regimens can be made more effective by having the patient exercise 1–2 hours after the dose, to induce sweating. The sweat is allowed to evaporate, and showering is delayed for a day, leaving a film of the medication on the skin. Epidemiology This skin disease commonly affects adolescents and young adults, especially in warm and humid climates. The yeast is thought to feed on skin oils (lipids), as well as dead skin cells. Infections are more common in people who have seborrheic dermatitis, dandruff, and hyperhidrosis. References External links Media related to Tinea versicolor at Wikimedia Commons

Hey Aarogya!, what is Tocolytic

Tocolytic

Tocolytics (also called anti-contraction medications or labor suppressants) are medications used to suppress premature labor (from Greek τόκος tókos, "childbirth", and λύσις lúsis, "loosening"). Preterm birth accounts for 70% of neonatal deaths. Therefore, tocolytic therapy is provided when delivery would result in premature birth, postponing delivery long enough for the administration of glucocorticoids, which accelerate fetal lung maturity but may require one to two days to take effect. Commonly used tocolytic medications include β2 agonists, calcium channel blockers, NSAIDs, and magnesium sulfate. These can assist in delaying preterm delivery by suppressing uterine muscle contractions and their use is intended to reduce fetal morbidity and mortality associated with preterm birth. The suppression of contractions is often only partial and tocolytics can only be relied on to delay birth for a matter of days. Depending on the tocolytic used, the pregnant woman or fetus may require monitoring (e.g., blood pressure monitoring when nifedipine is used as it reduces blood pressure; cardiotocography to assess fetal well-being). In any case, the risk of preterm labor alone justifies hospitalization. Indications Tocolytics are used in preterm labor, which refers to when a baby is born too early before 37 weeks of pregnancy. As preterm birth represents one of the leading causes of neonatal morbidity and mortality, the goal is to prevent neonatal morbidity and mortality through delaying delivery and increasing gestational age by gaining more time for other management strategies like corticosteroids therapy that may help with fetus lung maturity. Tocolytics are considered for women with confirmed preterm labor between 24 and 34 weeks of gestation age and used in conjunction with other therapies that may include corticosteroids administration, fetus neuroprotection, and safe transfer to facilities. Types of agents There is no clear first-line tocolytic agent. Current evidence suggests that first line treatment with β2 agonists, calcium channel blockers, or NSAIDs to prolong pregnancy for up to 48 hours is the best course of action to allow time for glucocorticoid administration.Various types of agents are used, with varying success rates and side effects. Some medications are not specifically approved by the U.S. Food and Drug Administration (FDA) for use in stopping uterine contractions in preterm labor, instead being used off-label. Calcium-channel blockers (such as nifedipine) and oxytocin antagonists (such as atosiban) may delay delivery by 2 to 7 days, depending on how quickly the medication is administered. NSAIDs (such as indomethacin) and calcium channel blockers (such as nifedipine) are the most likely to delay delivery for 48 hours, with the least amount of maternal and neonatal side effects. Otherwise, tocolysis is rarely successful beyond 24 to 48 hours because current medications do not alter the fundamentals of labor activation. However, postponing premature delivery by 48 hours appears sufficient to allow pregnant women to be transferred to a center specialized for management of preterm deliveries, and thus administer corticosteroids for the possibility to reduce neonatal organ immaturity.The efficacy of β-adrenergic agonists, atosiban, and indomethacin is a decreased odds ratio (OR) of delivery within 24 hours of 0.54 (95% confidence interval (CI): 0.32-0.91) and 0.47 within 48 hours (OR 0.47, 95% CI: 0.30-0.75).Antibiotics were thought to delay delivery, but no studies have shown any evidence that using antibiotics during preterm labor effectively delays delivery or reduces neonatal morbidity. Antibiotics are used in people with premature rupture of membranes, but this is not characterized as tocolysis. Contraindications to tocolytics In addition to drug-specific contraindications, several general factors may contraindicate delaying childbirth with the use of tocolytic medications. Fetus is older than 34 weeks gestation Fetus weighs less than 2.5 kg, or has intrauterine growth restriction (IUGR) or placental insufficiency Lethal congenital or chromosomal abnormalities Cervical dilation is greater than 4 centimeters Chorioamnionitis or intrauterine infection is present Pregnant woman has severe pregnancy-induced hypertension, severe eclampsia/preeclampsia, active vaginal bleeding, placental abruption, a cardiac disease, or another condition which indicates that the pregnancy should not continue. Maternal hemodynamic instability with bleeding Intrauterine fetal demise, lethal fetal anomaly, or non-reassuring fetal status Future direction of tocolytics Most tocolytics are currently being used off-label. The future direction of the development of tocolytics agents should be directed toward better efficacy in intentionally prolonging pregnancy. This will potentially result in less maternal, fetal, and neonatal adverse effects when delaying preterm childbirth. A few tocolytic alternatives worth pursuing include Barusiban, a last generation of oxytocin receptor antagonists, as well as COX-2 inhibitors. More studies on the use of multiple tocolytics must be directed to research overall health outcomes rather than solely pregnancy prolongation. See also Labor induction == References ==

Aarogya, could you share information about a health condition involving Tourette syndrome

Tourette syndrome

Tourette syndrome or Tourettes syndrome (abbreviated as TS or Tourettes) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) tic. Common tics are blinking, coughing, throat clearing, sniffing, and facial movements. These are typically preceded by an unwanted urge or sensation in the affected muscles known as a premonitory urge, can sometimes be suppressed temporarily, and characteristically change in location, strength, and frequency. Tourettes is at the more severe end of a spectrum of tic disorders. The tics often go unnoticed by casual observers. Tourettes was once regarded as a rare and bizarre syndrome and has popularly been associated with coprolalia (the utterance of obscene words or socially inappropriate and derogatory remarks). It is no longer considered rare; about 1% of school-age children and adolescents are estimated to have Tourettes, and coprolalia occurs only in a minority. There are no specific tests for diagnosing Tourettes; it is not always correctly identified, because most cases are mild, and the severity of tics decreases for most children as they pass through adolescence. Therefore, many go undiagnosed or may never seek medical attention. Extreme Tourettes in adulthood, though sensationalized in the media, is rare, but for a small minority, severely debilitating tics can persist into adulthood. Tourettes does not affect intelligence or life expectancy. There is no cure for Tourettes and no single most effective medication. In most cases, medication for tics is not necessary, and behavioral therapies are the first-line treatment. Education is an important part of any treatment plan, and explanation alone often provides sufficient reassurance that no other treatment is necessary. Other conditions, such as attention deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD), are more likely to be present among those who are referred to specialty clinics than they are among the broader population of persons with Tourettes. These co-occurring conditions often cause more impairment to the individual than the tics; hence it is important to correctly distinguish co-occurring conditions and treat them. Tourette syndrome was named by French neurologist Jean-Martin Charcot for his intern, Georges Gilles de la Tourette, who published in 1885 an account of nine patients with a "convulsive tic disorder". While the exact cause is unknown, it is believed to involve a combination of genetic and environmental factors. The mechanism appears to involve dysfunction in neural circuits between the basal ganglia and related structures in the brain. Classification Most published research on Tourette syndrome originates in the United States; in international TS research and clinical practice, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is preferred over the World Health Organization (WHO) classification, which is criticized in the 2021 European Clinical Guidelines. In the fifth version of the DSM (DSM-5), published in 2013, Tourette syndrome is classified as a motor disorder (a disorder of the nervous system that causes abnormal and involuntary movements). It is listed in the neurodevelopmental disorder category. Tourettes is at the more severe end of the spectrum of tic disorders; its diagnosis requires multiple motor tics and at least one vocal tic to be present for more than a year. Tics are sudden, repetitive, nonrhythmic movements that involve discrete muscle groups, while vocal (phonic) tics involve laryngeal, pharyngeal, oral, nasal or respiratory muscles to produce sounds. The tics must not be explained by other medical conditions or substance use.Other conditions on the spectrum include persistent (chronic) motor or vocal tics, in which one type of tic (motor or vocal, but not both) has been present for more than a year; and provisional tic disorder, in which motor or vocal tics have been present for less than one year. The fifth edition of the DSM replaced what had been called transient tic disorder with provisional tic disorder, recognizing that "transient" can only be defined in retrospect. Some experts believe that TS and persistent (chronic) motor or vocal tic disorder should be considered the same condition, because vocal tics are also motor tics in the sense that they are muscular contractions of nasal or respiratory muscles.Tourette syndrome is defined only slightly differently by the WHO; in its ICD-11, the International Statistical Classification of Diseases and Related Health Problems, Tourette syndrome is classified as a disease of the nervous system and a neurodevelopmental disorder, and only one motor tic is required for diagnosis. Older versions of the ICD called it "combined vocal and multiple motor tic disorder [de la Tourette]".Genetic studies indicate that tic disorders cover a spectrum that is not recognized by the clear-cut distinctions in the current diagnostic framework. Since 2008, studies have suggested that Tourettes is not a unitary condition with a distinct mechanism, as described in the existing classification systems. Instead, the studies suggest that subtypes should be recognized to distinguish "pure TS" from TS that is accompanied by attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD) or other disorders, similar to the way that subtypes have been established for other conditions, such as type 1 and type 2 diabetes. Elucidation of these subtypes awaits fuller understanding of the genetic and other causes of tic disorders. Characteristics Tics Tics are movements or sounds that take place "intermittently and unpredictably out of a background of normal motor activity", having the appearance of "normal behaviors gone wrong". The tics associated with Tourettes wax and wane; they change in number, frequency, severity, anatomical location, and complexity; each person experiences a unique pattern of fluctuation in their severity and frequency. Tics may also occur in "bouts of bouts", which also vary among people. The variation in tic severity may occur over hours, days, or weeks. Tics may increase when someone is experiencing stress, fatigue, anxiety, or illness, or when engaged in relaxing activities like watching TV. They sometimes decrease when an individual is engrossed in or focused on an activity like playing a musical instrument.In contrast to the abnormal movements associated with other movement disorders, the tics of Tourettes are nonrhythmic, often preceded by an unwanted urge, and temporarily suppressible. Over time, about 90% of individuals with Tourettes feel an urge preceding the tic, similar to the urge to sneeze or scratch an itch. The urges and sensations that precede the expression of a tic are referred to as premonitory sensory phenomena or premonitory urges. People describe the urge to express the tic as a buildup of tension, pressure, or energy which they ultimately choose consciously to release, as if they "had to do it" to relieve the sensation or until it feels "just right". The urge may cause a distressing sensation in the part of the body associated with the resulting tic; the tic is a response that relieves the urge in the anatomical location of the tic. Examples of this urge are the feeling of having something in ones throat, leading to a tic to clear ones throat, or a localized discomfort in the shoulders leading to shrugging the shoulders. The actual tic may be felt as relieving this tension or sensation, similar to scratching an itch or blinking to relieve an uncomfortable feeling in the eye. Some people with Tourettes may not be aware of the premonitory urge associated with tics. Children may be less aware of it than are adults, but their awareness tends to increase with maturity; by the age of ten, most children recognize the premonitory urge.Premonitory urges which precede the tic make suppression of the impending tic possible. Because of the urges that precede them, tics are described as semi-voluntary or "unvoluntary", rather than specifically involuntary; they may be experienced as a voluntary, suppressible response to the unwanted premonitory urge. The ability to suppress tics varies among individuals, and may be more developed in adults than children. People with tics are sometimes able to suppress them for limited periods of time, but doing so often results in tension or mental exhaustion. People with Tourettes may seek a secluded spot to release the suppressed urge, or there may be a marked increase in tics after a period of suppression at school or work. Children may suppress tics while in the doctors office, so they may need to be observed when not aware of being watched.Complex tics related to speech include coprolalia, echolalia and palilalia. Coprolalia is the spontaneous utterance of socially objectionable or taboo words or phrases. Although it is the most publicized symptom of Tourettes, only about 10% of people with Tourettes exhibit it, and it is not required for a diagnosis. Echolalia (repeating the words of others) and palilalia (repeating ones own words) occur in a minority of cases. Complex motor tics include copropraxia (obscene or forbidden gestures, or inappropriate touching), echopraxia (repetition or imitation of another persons actions) and palipraxia (repeating ones own movements). Onset and progression There is no typical case of Tourette syndrome, but the age of onset and the severity of symptoms follow a fairly reliable course. Although onset may occur anytime before eighteen years, the typical age of onset of tics is from five to seven, and is usually before adolescence. A 1998 study from the Yale Child Study Center showed that tic severity increased with age until it reached its highest point between ages eight and twelve. Severity declines steadily for most children as they pass through adolescence, when half to two-thirds of children see a dramatic decrease in tics.In people with TS, the first tics to appear usually affect the head, face, and shoulders, and include blinking, facial movements, sniffing and throat clearing. Vocal tics often appear months or years after motor tics but can appear first. Among people who experience more severe tics, complex tics may develop, including "arm straightening, touching, tapping, jumping, hopping and twirling". There are different movements in contrasting disorders (for example, the autism spectrum disorders), such as self-stimulation and stereotypies.The severity of symptoms varies widely among people with Tourettes, and many cases may be undetected. Most cases are mild and almost unnoticeable; many people with TS may not realize they have tics. Because tics are more commonly expressed in private, Tourette syndrome may go unrecognized, and casual observers might not notice tics. Most studies of TS involve males, who have a higher prevalence of TS than females, and gender-based differences are not well studied; a 2021 review suggested that the characteristics and progression for females, particularly in adulthood, may differ and better studies are needed.Most adults with TS have mild symptoms and do not seek medical attention. While tics subside for the majority after adolescence, some of the "most severe and debilitating forms of tic disorder are encountered" in adults. In some cases, what appear to be adult-onset tics can be childhood tics re-surfacing. Co-occurring conditions Because people with milder symptoms are unlikely to be referred to specialty clinics, studies of Tourettes have an inherent bias towards more severe cases. When symptoms are severe enough to warrant referral to clinics, ADHD and OCD are often also found. In specialty clinics, 30% of those with TS also have mood or anxiety disorders or disruptive behaviors. In the absence of ADHD, tic disorders do not appear to be associated with disruptive behavior or functional impairment, while impairment in school, family, or peer relations is greater in those who have more comorbid conditions. When ADHD is present along with tics, the occurrence of conduct disorder and oppositional defiant disorder increases. Aggressive behaviors and angry outbursts in people with TS are not well understood; they are not associated with severe tics, but are connected with the presence of ADHD. ADHD may also contribute to higher rates of anxiety, and aggression and anger control problems are more likely when both OCD and ADHD co-occur with Tourettes.Compulsions that resemble tics are present in some individuals with OCD; "tic-related OCD" is hypothesized to be a subgroup of OCD, distinguished from non-tic related OCD by the type and nature of obsessions and compulsions. Compared to the more typical compulsions of OCD without tics that relate to contamination, tic-related OCD presents with more "counting, aggressive thoughts, symmetry and touching" compulsions. Compulsions associated with OCD without tics are usually related to obsessions and anxiety, while those in tic-related OCD are more likely to be a response to a premonitory urge. There are increased rates of anxiety and depression in those adults with TS who also have OCD.Among individuals with TS studied in clinics, between 2.9% and 20% had autism spectrum disorders, but one study indicates that a high association of autism and TS may be partly due to difficulties distinguishing between tics and tic-like behaviors or OCD symptoms seen in people with autism.Not all people with Tourettes have ADHD or OCD or other comorbid conditions, and estimates of the rate of pure TS or TS-only vary from 15% to 57%; in clinical populations, a high percentage of those under care do have ADHD. Children and adolescents with pure TS are not significantly different from their peers without TS on ratings of aggressive behaviors or conduct disorders, or on measures of social adaptation. Similarly, adults with pure TS do not appear to have the social difficulties present in those with TS plus ADHD.Among those with an older age of onset, more substance abuse and mood disorders are found, and there may be self-injurious tics. Adults who have severe, often treatment-resistant tics are more likely to also have mood disorders and OCD. Coprolalia is more likely in people with severe tics plus multiple comorbid conditions. Neuropsychological function There are no major impairments in neuropsychological function among people with Tourettes, but conditions that occur along with tics can cause variation in neurocognitive function. A better understanding of comorbid conditions is needed to untangle any neuropsychological differences between TS-only individuals and those with comorbid conditions.Only slight impairments are found in intellectual ability, attentional ability, and nonverbal memory—but ADHD, other comorbid disorders, or tic severity could account for these differences. In contrast with earlier findings, visual motor integration and visuoconstructive skills are not found to be impaired, while comorbid conditions may have a small effect on motor skills. Comorbid conditions and severity of tics may account for variable results in verbal fluency, which can be slightly impaired. There might be slight impairment in social cognition, but not in the ability to plan or make decisions. Children with TS-only do not show cognitive deficits. They are faster than average for their age on timed tests of motor coordination, and constant tic suppression may lead to an advantage in switching between tasks because of increased inhibitory control.Learning disabilities may be present, but whether they are due to tics or comorbid conditions is controversial; older studies that reported higher rates of learning disability did not control well for the presence of comorbid conditions. There are often difficulties with handwriting, and disabilities in written expression and math are reported in those with TS plus other conditions. Causes The exact cause of Tourettes is unknown, but it is well established that both genetic and environmental factors are involved. Genetic epidemiology studies have shown that Tourettes is highly heritable, and 10 to 100 times more likely to be found among close family members than in the general population. The exact mode of inheritance is not known; no single gene has been identified, and hundreds of genes are likely involved. Genome-wide association studies were published in 2013 and 2015 in which no finding reached a threshold for significance; a 2019 meta-analysis found only a single genome-wide significant locus on chromosome 13, but that result was not found in broader samples. Twin studies show that 50 to 77% of identical twins share a TS diagnosis, while only 10 to 23% of fraternal twins do. But not everyone who inherits the genetic vulnerability will show symptoms. A few rare highly penetrant genetic mutations have been found that explain only a small number of cases in single families (the SLITRK1, HDC, and CNTNAP2 genes).Psychosocial or other non-genetic factors—while not causing Tourettes—can affect the severity of TS in vulnerable individuals and influence the expression of the inherited genes. Pre-natal and peri-natal events increase the risk that a tic disorder or comorbid OCD will be expressed in those with the genetic vulnerability. These include paternal age; forceps delivery; stress or severe nausea during pregnancy; and use of tobacco, caffeine, alcohol, and cannabis during pregnancy. Babies who are born premature with low birthweight, or who have low Apgar scores, are also at increased risk; in premature twins, the lower birthweight twin is more likely to develop TS.Autoimmune processes may affect the onset of tics or exacerbate them. Both OCD and tic disorders are hypothesized to arise in a subset of children as a result of a post-streptococcal autoimmune process. Its potential effect is described by the controversial hypothesis called PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections), which proposes five criteria for diagnosis in children. PANDAS and the newer pediatric acute-onset neuropsychiatric syndrome (PANS) hypotheses are the focus of clinical and laboratory research, but remain unproven. There is also a broader hypothesis that links immune-system abnormalities and immune dysregulation with TS.Some forms of OCD may be genetically linked to Tourettes, although the genetic factors in OCD with and without tics may differ. The genetic relationship of ADHD to Tourette syndrome, however, has not been fully established. A genetic link between autism and Tourettes has not been established as of 2017. Mechanism The exact mechanism affecting the inherited vulnerability to Tourettes is not well established. Tics are believed to result from dysfunction in cortical and subcortical brain regions: the thalamus, basal ganglia and frontal cortex. Neuroanatomic models suggest failures in circuits connecting the brains cortex and subcortex; imaging techniques implicate the frontal cortex and basal ganglia. In the 2010s, neuroimaging and postmortem brain studies, as well as animal and genetic studies, made progress towards better understanding the neurobiological mechanisms leading to Tourettes. These studies support the basal ganglia model, in which neurons in the striatum are activated and inhibit outputs from the basal ganglia.Cortico-striato-thalamo-cortical (CSTC) circuits, or neural pathways, provide inputs to the basal ganglia from the cortex. These circuits connect the basal ganglia with other areas of the brain to transfer information that regulates planning and control of movements, behavior, decision-making, and learning. Behavior is regulated by cross-connections that "allow the integration of information" from these circuits. Involuntary movements may result from impairments in these CSTC circuits, including the sensorimotor, limbic, language and decision making pathways. Abnormalities in these circuits may be responsible for tics and premonitory urges.The caudate nuclei may be smaller in subjects with tics compared to those without tics, supporting the hypothesis of pathology in CSTC circuits in Tourettes. The ability to suppress tics depends on brain circuits that "regulate response inhibition and cognitive control of motor behavior". Children with TS are found to have a larger prefrontal cortex, which may be the result of an adaptation to help regulate tics. It is likely that tics decrease with age as the capacity of the frontal cortex increases. Cortico-basal ganglia (CBG) circuits may also be impaired, contributing to "sensory, limbic and executive" features. The release of dopamine in the basal ganglia is higher in people with Tourettes, implicating biochemical changes from "overactive and dysregulated dopaminergic transmissions".Histamine and the H3 receptor may play a role in the alterations of neural circuitry. A reduced level of histamine in the H3 receptor may result in an increase in other neurotransmitters, causing tics. Postmortem studies have also implicated "dysregulation of neuroinflammatory processes". Diagnosis According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Tourettes may be diagnosed when a person exhibits both multiple motor tics and one or more vocal tics over a period of one year. The motor and vocal tics need not be concurrent. The onset must have occurred before the age of 18 and cannot be attributed to the effects of another condition or substance (such as cocaine). Hence, other medical conditions that include tics or tic-like movements—for example, autism or other causes of tics—must be ruled out.Patients referred for a tic disorder are assessed based on their family history of tics, vulnerability to ADHD, obsessive–compulsive symptoms, and a number of other chronic medical, psychiatric and neurological conditions. In individuals with a typical onset and a family history of tics or OCD, a basic physical and neurological examination may be sufficient. There are no specific medical or screening tests that can be used to diagnose Tourettes; the diagnosis is usually made based on observation of the individuals symptoms and family history, and after ruling out secondary causes of tic disorders (tourettism).Delayed diagnosis often occurs because professionals mistakenly believe that TS is rare, always involves coprolalia, or must be severely impairing. The DSM has recognized since 2000 that many individuals with Tourettes do not have significant impairment; diagnosis does not require the presence of coprolalia or a comorbid condition, such as ADHD or OCD. Tourettes may be misdiagnosed because of the wide expression of severity, ranging from mild (in the majority of cases) or moderate, to severe (the rare but more widely recognized and publicized cases). About 20% of people with Tourette syndrome do not realize that they have tics.Tics that appear early in the course of TS are often confused with allergies, asthma, vision problems, and other conditions. Pediatricians, allergists and ophthalmologists are among the first to see or identify a child as having tics, although the majority of tics are first identified by the childs parents. Coughing, blinking, and tics that mimic unrelated conditions such as asthma are commonly misdiagnosed. In the UK, there is an average delay of three years between symptom onset and diagnosis. Differential diagnosis Tics that may appear to mimic those of Tourettes—but are associated with disorders other than Tourettes—are known as tourettism and are ruled out in the differential diagnosis for Tourette syndrome. The abnormal movements associated with choreas, dystonias, myoclonus, and dyskinesias are distinct from the tics of Tourettes in that they are more rhythmic, not suppressible, and not preceded by an unwanted urge. Developmental and autism spectrum disorders may manifest tics, other stereotyped movements, and stereotypic movement disorder. The stereotyped movements associated with autism typically have an earlier age of onset; are more symmetrical, rhythmical and bilateral; and involve the extremities (for example, flapping the hands).If another condition might better explain the tics, tests may be done; for example, if there is diagnostic confusion between tics and seizure activity, an EEG may be ordered. An MRI can rule out brain abnormalities, but such brain imaging studies are not usually warranted. Measuring thyroid-stimulating hormone blood levels can rule out hypothyroidism, which can be a cause of tics. If there is a family history of liver disease, serum copper and ceruloplasmin levels can rule out Wilsons disease. The typical age of onset of TS is before adolescence. In teenagers and adults with an abrupt onset of tics and other behavioral symptoms, a urine drug screen for stimulants might be requested.Increasing episodes of tic-like behavior among teenagers (predominantly adolescent girls) were reported in several countries during the COVID-19 pandemic. Researchers linked their occurrence to followers of certain TikTok or YouTube artists. Described in 2006 as psychogenic, abrupt-onset movements resembling tics are referred to as a functional movement disorder or functional tic-like movements. Functional tic-like movements can be difficult to distinguish from tics that have an organic (rather than psychological) cause. They may occur alone or co-exist in individuals with tic disorders. These tics are inconsistent with the classic tics of TS in several ways: the premonitory urge (present in 90% of those with tics disorders) is absent in functional tic-like movements; the suppressibility seen in tic disorders is lacking; there is no family or childhood history of tics and there is a female predominance in functional tics, with a later-than-typical age of first presentation; onset is more abrupt than typical with movements that are more suggestible; and there is less co-occurring OCD or ADHD and more co-occurring disorders. Functional tics are "not fully sterotypical", do not respond to medications, do not demonstrate the classic waxing and waning pattern of Tourettic tics, and do not progress in the typical fashion, in which tics often first appear in the face and gradually move to limbs.Other conditions that may manifest tics include Sydenhams chorea; idiopathic dystonia; and genetic conditions such as Huntingtons disease, neuroacanthocytosis, pantothenate kinase-associated neurodegeneration, Duchenne muscular dystrophy, Wilsons disease, and tuberous sclerosis. Other possibilities include chromosomal disorders such as Down syndrome, Klinefelter syndrome, XYY syndrome and fragile X syndrome. Acquired causes of tics include drug-induced tics, head trauma, encephalitis, stroke, and carbon monoxide poisoning. The extreme self-injurious behaviors of Lesch-Nyhan syndrome may be confused with Tourette syndrome or stereotypies, but self-injury is rare in TS even in cases of violent tics. Most of these conditions are rarer than tic disorders and a thorough history and examination may be enough to rule them out without medical or screening tests. Screening for other conditions Although not all those with Tourettes have comorbid conditions, most presenting for clinical care exhibit symptoms of other conditions along with their tics. ADHD and OCD are the most common, but autism spectrum disorders or anxiety, mood, personality, oppositional defiant, and conduct disorders may also be present. Learning disabilities and sleep disorders may be present; higher rates of sleep disturbance and migraine than in the general population are reported. A thorough evaluation for comorbidity is called for when symptoms and impairment warrant, and careful assessment of people with TS includes comprehensive screening for these conditions.Comorbid conditions such as OCD and ADHD can be more impairing than tics, and cause greater impact on overall functioning. Disruptive behaviors, impaired functioning, or cognitive impairment in individuals with comorbid Tourettes and ADHD may be accounted for by the ADHD, highlighting the importance of identifying comorbid conditions. Children and adolescents with TS who have learning difficulties are candidates for psychoeducational testing, particularly if the child also has ADHD. Management There is no cure for Tourettes. There is no single most effective medication, and no one medication effectively treats all symptoms. Most medications prescribed for tics have not been approved for that use, and no medication is without the risk of significant adverse effects. Treatment is focused on identifying the most troubling or impairing symptoms and helping the individual manage them. Because comorbid conditions are often a larger source of impairment than tics, they are a priority in treatment. The management of Tourettes is individualized and involves shared decision-making between the clinician, patient, family and caregivers. Practice guidelines for the treatment of tics were published by the American Academy of Neurology in 2019.Education, reassurance and psychobehavioral therapy are often sufficient for the majority of cases. In particular, psychoeducation targeting the patient and their family and surrounding community is a key management strategy. Watchful waiting "is an acceptable approach" for those who are not functionally impaired. Symptom management may include behavioral, psychological and pharmacological therapies. Pharmacological intervention is reserved for more severe symptoms, while psychotherapy or cognitive behavioral therapy (CBT) may ameliorate depression and social isolation, and improve family support. The decision to use behavioral or pharmacological treatment is "usually made after the educational and supportive interventions have been in place for a period of months, and it is clear that the tic symptoms are persistently severe and are themselves a source of impairment in terms of self-esteem, relationships with the family or peers, or school performance". Psychoeducation and social support Knowledge, education and understanding are uppermost in management plans for tic disorders, and psychoeducation is the first step. A childs parents are typically the first to notice their tics; they may feel worried, imagine that they are somehow responsible, or feel burdened by misinformation about Tourettes. Effectively educating parents about the diagnosis and providing social support can ease their anxiety. This support can also lower the chance that their child will be unnecessarily medicated or experience an exacerbation of tics due to their parents emotional state.People with Tourettes may suffer socially if their tics are viewed as "bizarre". If a child has disabling tics, or tics that interfere with social or academic functioning, supportive psychotherapy or school accommodations can be helpful. Even children with milder tics may be angry, depressed or have low self-esteem as a result of increased teasing, bullying, rejection by peers or social stigmatization, and this can lead to social withdrawal. Some children feel empowered by presenting a peer awareness program to their classmates. It can be helpful to educate teachers and school staff about typical tics, how they fluctuate during the day, how they impact the child, and how to distinguish tics from naughty behavior. By learning to identify tics, adults can refrain from asking or expecting a child to stop ticcing, because "tic suppression can be exhausting, unpleasant, and attention-demanding and can result in a subsequent rebound bout of tics".Adults with TS may withdraw socially to avoid stigmatization and discrimination because of their tics. Depending on their countrys healthcare system, they may receive social services or help from support groups. Behavioral Behavioral therapies using habit reversal training (HRT) and exposure and response prevention (ERP) are first-line interventions in the management of Tourette syndrome, and have been shown to be effective. Because tics are somewhat suppressible, when people with TS are aware of the premonitory urge that precedes a tic, they can be trained to develop a response to the urge that competes with the tic. Comprehensive behavioral intervention for tics (CBIT) is based on HRT, the best researched behavioral therapy for tics. TS experts debate whether increasing a childs awareness of tics with HRT/CBIT (as opposed to ignoring tics) can lead to more tics later in life.When disruptive behaviors related to comorbid conditions exist, anger control training and parent management training can be effective. CBT is a useful treatment when OCD is present. Relaxation techniques, such as exercise, yoga and meditation may be useful in relieving the stress that can aggravate tics. Beyond HRT, the majority of behavioral interventions for Tourettes (for example, relaxation training and biofeedback) have not been systematically evaluated and are not empirically supported. Medication Children with tics typically present when their tics are most severe, but because the condition waxes and wanes, medication is not started immediately or changed often. Tics may subside with education, reassurance and a supportive environment. When medication is used, the goal is not to eliminate symptoms. Instead, the lowest dose that manages symptoms without adverse effects is used, because adverse effects may be more disturbing than the symptoms being treated with medication.The classes of medication with proven efficacy in treating tics—typical and atypical neuroleptics—can have long-term and short-term adverse effects. Some antihypertensive agents are also used to treat tics; studies show variable efficacy but a lower side effect profile than the neuroleptics. The antihypertensives clonidine and guanfacine are typically tried first in children; they can also help with ADHD symptoms, but there is less evidence that they are effective for adults. The neuroleptics risperidone and aripiprazole are tried when antihypertensives are not effective, and are generally tried first for adults. Because of lower side effects, aripiprazole is preferred over other antipsychotics. The most effective medication for tics is haloperidol, but it has a higher risk of side effects. Methylphenidate can be used to treat ADHD that co-occurs with tics, and can be used in combination with clonidine. Selective serotonin reuptake inhibitors are used to manage anxiety and OCD. Other Complementary and alternative medicine approaches, such as dietary modification, neurofeedback and allergy testing and control have popular appeal, but they have no proven benefit in the management of Tourette syndrome. Despite this lack of evidence, up to two-thirds of parents, caregivers and individuals with TS use dietary approaches and alternative treatments and do not always inform their physicians.There is low confidence that tics are reduced with tetrahydrocannabinol, and insufficient evidence for other cannabis-based medications in the treatment of Tourettes. There is no good evidence supporting the use of acupuncture or transcranial magnetic stimulation; neither is there evidence supporting intravenous immunoglobulin, plasma exchange, or antibiotics for the treatment of PANDAS.Deep brain stimulation (DBS) has become a valid option for individuals with severe symptoms that do not respond to conventional therapy and management, although it is an experimental treatment. Selecting candidates who may benefit from DBS is challenging, and the appropriate lower age range for surgery is unclear; it is potentially useful in less than 3% of individuals. The ideal brain location to target has not been identified as of 2019. Pregnancy A quarter of women report that their tics increase before menstruation; however, studies have not shown consistent evidence of a change in frequency or severity of tics related to pregnancy or hormonal levels. Overall, symptoms in women respond better to haloperidol than they do for men.Most women find they can withdraw from medication during pregnancy without much trouble. When needed, medications are used at the lowest doses possible. During pregnancy, neuroleptic medications are avoided when possible because of the risk of pregnancy complications. When needed, olanzapine, risperidone and quetiapine are most often used as they have not been shown to cause fetal abnormalities. One report found that haloperidol could be used during pregnancy, to minimize the side effects in the mother, including low blood pressure, and anticholinergic effects, although it may cross the placenta.If severe tics might interfere with administration of local anesthesia, other anesthesia options are considered. Neuroleptics in low doses may not affect the breastfed infant, but most medications are avoided. Clonidine and amphetamines may be present in breast milk. Prognosis Tourette syndrome is a spectrum disorder—its severity ranges from mild to severe. Symptoms typically subside as children pass through adolescence. In a group of ten children at the average age of highest tic severity (around ten or eleven), almost four will see complete remission by adulthood. Another four will have minimal or mild tics in adulthood, but not complete remission. The remaining two will have moderate or severe tics as adults, but only rarely will their symptoms in adulthood be more severe than in childhood.Regardless of symptom severity, individuals with Tourettes have a normal life span. Symptoms may be lifelong and chronic for some, but the condition is not degenerative or life-threatening. Intelligence among those with pure TS follows a normal curve, although there may be small differences in intelligence in those with comorbid conditions. The severity of tics early in life does not predict their severity in later life. There is no reliable means of predicting the course of symptoms for a particular individual, but the prognosis is generally favorable. By the age of fourteen to sixteen, when the highest tic severity has typically passed, a more reliable prognosis might be made.Tics may be at their highest severity when they are diagnosed, and often improve as an individuals family and friends come to better understand the condition. Studies report that almost eight out of ten children with Tourettes experience a reduction in the severity of their tics by adulthood, and some adults who still have tics may not be aware that they have them. A study that used video to record tics in adults found that nine out of ten adults still had tics, and half of the adults who considered themselves tic-free displayed evidence of mild tics. Quality of life People with Tourettes are affected by the consequences of tics and by the efforts to suppress them. Head and eye tics can interfere with reading or lead to headaches, and forceful tics can lead to repetitive strain injury. Severe tics can lead to pain or injuries; as an example, a rare cervical disc herniation was reported from a neck tic. Some people may learn to camouflage socially inappropriate tics or channel the energy of their tics into a functional endeavor.A supportive family and environment generally give those with Tourettes the skills to manage the disorder. Outcomes in adulthood are associated more with the perceived significance of having tics as a child than with the actual severity of the tics. A person who was misunderstood, punished or teased at home or at school is likely to fare worse than a child who enjoyed an understanding environment. The long-lasting effects of bullying and teasing can influence self-esteem, self-confidence, and even employment choices and opportunities. Comorbid ADHD can severely affect the childs well-being in all realms, and extend into adulthood.Factors impacting quality of life change over time, given the natural fluctuating course of tic disorders, the development of coping strategies, and a persons age. As ADHD symptoms improve with maturity, adults report less negative impact in their occupational lives than do children in their educational lives. Tics have a greater impact on adults psychosocial function, including financial burdens, than they do on children. Adults are more likely to report a reduced quality of life due to depression or anxiety; depression contributes a greater burden than tics to adults quality of life compared to children. As coping strategies become more effective with age, the impact of OCD symptoms seems to diminish. Epidemiology Tourette syndrome is a common but underdiagnosed condition that reaches across all social, racial and ethnic groups. It is three to four times more frequent in males than in females. Observed prevalence rates are higher among children than adults because tics tend to remit or subside with maturity and a diagnosis may no longer be warranted for many adults. Up to 1% of the overall population experiences tic disorders, including chronic tics and transient (provisional or unspecified) tics in childhood. Chronic tics affect 5% of children and transient tics affect up to 20%.Many individuals with tics do not know they have tics, or do not seek a diagnosis, so epidemiological studies of TS "reflect a strong ascertainment bias" towards those with co-occurring conditions. The reported prevalence of TS varies "according to the source, age, and sex of the sample; the ascertainment procedures; and diagnostic system", with a range reported between 0.15% and 3.0% for children and adolescents. Sukhodolsky, et al. wrote in 2017 that the best estimate of TS prevalence in children was 1.4%. Both Robertson and Stern states that the prevalence in children is 1%. The prevalence of TS in the general population is estimated as 0.3% to 1.0%. According to turn of the century census data, these prevalence estimates translated to half a million children in the US with TS and half a million people in the UK with TS, although symptoms in many older individuals would be almost unrecognizable.Tourette syndrome was once thought to be rare: in 1972, the US National Institutes of Health (NIH) believed there were fewer than 100 cases in the United States, and a 1973 registry reported only 485 cases worldwide. However, numerous studies published since 2000 have consistently demonstrated that the prevalence is much higher. Recognizing that tics may often be undiagnosed and hard to detect, newer studies use direct classroom observation and multiple informants (parents, teachers and trained observers), and therefore record more cases than older studies. As the diagnostic threshold and assessment methodology have moved towards recognition of milder cases, the estimated prevalence has increased.Because of the high male prevalence of TS, there is limited data on females from which conclusion about gender-based differences can be drawn; caution may be warranted in extending conclusions to females regarding the characteristics and treatment of tics based on studies of mostly males. A 2021 review stated that females may see a later peak than males in symptoms, with less remission over time, along with a higher prevalence of anxiety and mood disorders. History A French doctor, Jean Marc Gaspard Itard, reported the first case of Tourette syndrome in 1825, describing the Marquise de Dampierre, an important woman of nobility in her time. In 1884, Jean-Martin Charcot, an influential French physician, assigned his student and intern Georges Gilles de la Tourette, to study patients with movement disorders at the Salpêtrière Hospital, with the goal of defining a condition distinct from hysteria and chorea. In 1885, Gilles de la Tourette published an account in Study of a Nervous Affliction of nine people with "convulsive tic disorder", concluding that a new clinical category should be defined. The eponym was bestowed by Charcot after and on behalf of Gilles de la Tourette, who later became Charcots senior resident.Following the 19th-century descriptions, a psychogenic view prevailed and little progress was made in explaining or treating tics until well into the 20th century. The possibility that movement disorders, including Tourette syndrome, might have an organic origin was raised when an encephalitis lethargica epidemic from 1918 to 1926 was linked to an increase in tic disorders.During the 1960s and 1970s, as the beneficial effects of haloperidol on tics became known, the psychoanalytic approach to Tourette syndrome was questioned. The turning point came in 1965, when Arthur K. Shapiro—described as "the father of modern tic disorder research"—used haloperidol to treat a person with Tourettes, and published a paper criticizing the psychoanalytic approach. In 1975, The New York Times headlined an article with "Bizarre outbursts of Tourettes disease victims linked to chemical disorder in brain", and Shapiro said: "The bizarre symptoms of this illness are rivaled only by the bizarre treatments used to treat it."During the 1990s, a more neutral view of Tourettes emerged, in which a genetic predisposition is seen to interact with non-genetic and environmental factors. The fourth revision of the DSM (DSM-IV) in 1994 added a diagnostic requirement for "marked distress or significant impairment in social, occupational, or other important areas of functioning", which led to an outcry from TS experts and researchers, who noted that many people were not even aware they had TS, nor were they distressed by their tics; clinicians and researchers resorted to using the older criteria in research and practice. In 2000, the American Psychiatric Association revised its diagnostic criteria in the fourth text revision of the DSM (DSM-IV-TR) to remove the impairment requirement, recognizing that clinicians often see people who have Tourettes without distress or impairment. Society and culture Not everyone with Tourettes wants treatment or a cure, especially if that means they may lose something else in the process. The researchers Leckman and Cohen believe that there may be latent advantages associated with an individuals genetic vulnerability to developing Tourette syndrome that may have adaptive value, such as heightened awareness and increased attention to detail and surroundings.Accomplished musicians, athletes, public speakers and professionals from all walks of life are found among people with Tourettes. The athlete Tim Howard, described by the Chicago Tribune as the "rarest of creatures—an American soccer hero", and by the Tourette Syndrome Association as the "most notable individual with Tourette Syndrome around the world", says that his neurological makeup gave him an enhanced perception and an acute focus that contributed to his success on the field.Samuel Johnson is a historical figure who likely had Tourette syndrome, as evidenced by the writings of his friend James Boswell. Johnson wrote A Dictionary of the English Language in 1747, and was a prolific writer, poet, and critic. There is little support for speculation that Mozart had Tourettes: the potentially coprolalic aspect of vocal tics is not transferred to writing, so Mozarts scatological writings are not relevant; the composers available medical history is not thorough; the side effects of other conditions may be misinterpreted; and "the evidence of motor tics in Mozarts life is doubtful".Likely portrayals of TS or tic disorders in fiction predating Gilles de la Tourettes work are "Mr. Pancks" in Charles Dickenss Little Dorrit and "Nikolai Levin" in Leo Tolstoys Anna Karenina. The entertainment industry has been criticized for depicting those with Tourette syndrome as social misfits whose only tic is coprolalia, which has furthered the publics misunderstanding and stigmatization of those with Tourettes. The coprolalic symptoms of Tourettes are also fodder for radio and television talk shows in the US and for the British media. High-profile media coverage focuses on treatments that do not have established safety or efficacy, such as deep brain stimulation, and alternative therapies involving unstudied efficacy and side effects are pursued by many parents. Research directions Research since 1999 has advanced knowledge of Tourettes in the areas of genetics, neuroimaging, neurophysiology, and neuropathology, but questions remain about how best to classify it and how closely it is related to other movement or psychiatric disorders. Modeled after genetic breakthroughs seen with large-scale efforts in other neurodevelopmental disorders, three groups are collaborating in research of the genetics of Tourettes: The Tourette Syndrome Association International Consortium for Genetics (TSAICG) Tourette International Collaborative Genetics Study (TIC Genetics) European Multicentre Tics in Children Studies (EMTICS)Compared to the progress made in gene discovery in certain neurodevelopmental or mental health disorders—autism, schizophrenia and bipolar disorder—the scale of related TS research is lagging in the United States due to funding. Notes References Book sources Further reading External links Tourette syndrome at Curlie

Give me a short description about Toxoplasmosis , Aarogya

Toxoplasmosis

Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii, an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or months of mild, flu-like illness such as muscle aches and tender lymph nodes. In a small number of people, eye problems may develop. In those with a weak immune system, severe symptoms such as seizures and poor coordination may occur. If a person becomes infected during pregnancy, a condition known as congenital toxoplasmosis may affect the child.Toxoplasmosis is usually spread by eating poorly cooked food that contains cysts, exposure to infected cat feces, and from an infected woman to their baby during pregnancy. Rarely, the disease may be spread by blood transfusion. It is not otherwise spread between people. The parasite is known to reproduce sexually only in the cat family. However, it can infect most types of warm-blooded animals, including humans. Diagnosis is typically by testing blood for antibodies or by testing the amniotic fluid in pregnant people for the parasites DNA.Prevention is by properly preparing and cooking food. Pregnant people are also recommended not to clean cat litter boxes or, if they must, to wear gloves and wash their hands afterwards. Treatment of otherwise healthy people is usually not needed. During pregnancy, spiramycin or pyrimethamine/sulfadiazine and folinic acid may be used for treatment.Up to half of the worlds population is infected by toxoplasmosis, but have no symptoms. In the United States, approximately 11% of people have been infected, while in some areas of the world this is more than 60%. Approximately 200,000 cases of congenital toxoplasmosis occur a year. Charles Nicolle and Louis Manceaux first described the organism in 1908. In 1941, transmission during pregnancy from a pregnant parent to their baby was confirmed. There is tentative evidence that infection may affect peoples behavior. Signs and symptoms Infection has three stages: Acute Acute toxoplasmosis is often asymptomatic in healthy adults. However, symptoms may manifest and are often influenza-like: swollen lymph nodes, headaches, fever, and fatigue, or muscle aches and pains that last for a month or more. It is rare for a human with a fully functioning immune system to develop severe symptoms following infection. People with weakened immune systems are likely to experience headache, confusion, poor coordination, seizures, lung problems that may resemble tuberculosis or Pneumocystis jiroveci pneumonia (a common opportunistic infection that occurs in people with AIDS), or chorioretinitis caused by severe inflammation of the retina (ocular toxoplasmosis). Young children and immunocompromised people, such as those with HIV/AIDS, those taking certain types of chemotherapy, or those who have recently received an organ transplant, may develop severe toxoplasmosis. This can cause damage to the brain (encephalitis) or the eyes (necrotizing retinochoroiditis). Infants infected via placental transmission may be born with either of these problems, or with nasal malformations, although these complications are rare in newborns. The toxoplasmic trophozoites causing acute toxoplasmosis are referred to as tachyzoites, and are typically found in various tissues and body fluids, but rarely in blood or cerebrospinal fluid.Swollen lymph nodes are commonly found in the neck or under the chin, followed by the armpits and the groin. Swelling may occur at different times after the initial infection, persist, and recur for various times independently of antiparasitic treatment. It is usually found at single sites in adults, but in children, multiple sites may be more common. Enlarged lymph nodes will resolve within 1–2 months in 60% of cases. However, a quarter of those affected take 2–4 months to return to normal, and 8% take 4–6 months. A substantial number (6%) do not return to normal until much later. Latent Due to the absence of obvious symptoms, hosts easily become infected with T. gondii and develop toxoplasmosis without knowing it. Although mild, flu-like symptoms occasionally occur during the first few weeks following exposure, infection with T. gondii produces no readily observable symptoms in healthy human adults. In most immunocompetent people, the infection enters a latent phase, during which only bradyzoites (in tissue cysts) are present; these tissue cysts and even lesions can occur in the retinas, alveolar lining of the lungs (where an acute infection may mimic a Pneumocystis jirovecii infection), heart, skeletal muscle, and the central nervous system (CNS), including the brain. Cysts form in the CNS (brain tissue) upon infection with T. gondii and persist for the lifetime of the host. Most infants who are infected while in the womb have no symptoms at birth, but may develop symptoms later in life.Reviews of serological studies have estimated that 30–50% of the global population has been exposed to and may be chronically infected with latent toxoplasmosis, although infection rates differ significantly from country to country. This latent state of infection has recently been associated with numerous disease burdens, neural alterations, and subtle gender-dependent behavioral changes in immunocompetent humans, as well as an increased risk of motor vehicle collisions. Skin While rare, skin lesions may occur in the acquired form of the disease, including roseola and erythema multiforme-like eruptions, prurigo-like nodules, urticaria, and maculopapular lesions. Newborns may have punctate macules, ecchymoses, or "blueberry muffin" lesions. Diagnosis of cutaneous toxoplasmosis is based on the tachyzoite form of T. gondii being found in the epidermis. It is found in all levels of the epidermis, is about 6 by 2 μm and bow-shaped, with the nucleus being one-third of its size. It can be identified by electron microscopy or by Giemsa staining tissue where the cytoplasm shows blue, the nucleus red. Cause Parasitology In its lifecycle, T. gondii adopts several forms. Tachyzoites are responsible for acute infection; they divide rapidly and spread through the tissues of the body. Tachyzoites are also known as "tachyzoic merozoites", a descriptive term that conveys more precisely the parasitological nature of this stage. After proliferating, tachyzoites convert into bradyzoites, which are inside latent intracellular tissue cysts that form mainly in the muscles and brain. The formation of cysts is in part triggered by the pressure of the host immune system. The bradyzoites (also called "bradyzoic merozoites") are not responsive to antibiotics. Bradyzoites, once formed, can remain in the tissues for the lifespan of the host. In a healthy host, if some bradyzoites convert back into active tachyzoites, the immune system will quickly destroy them. However, in immunocompromised individuals, or in fetuses, which lack a developed immune system, the tachyzoites can run rampant and cause significant neurological damage.The parasites survival is dependent on a balance between host survival and parasite proliferation. T. gondii achieves this balance by manipulating the hosts immune response, reducing the hosts immune response, and enhancing the parasites reproductive advantage. Once it infects a normal host cell, it resists damage caused by the hosts immune system, and changes the hosts immune processes.As it forces its way into the host cell, the parasite forms a parasitophorous vacuole (PV) membrane from the membrane of the host cell. The PV encapsulates the parasite, and is both resistant to the activity of the endolysosomal system, and can take control of the hosts mitochondria and endoplasmic reticulum.When first invading the cell, the parasite releases ROP proteins from the bulb of the rhoptry organelle. These proteins translocate to the nucleus and the surface of the PV membrane where they can activate STAT pathways to modulate the expression of cytokines at the transcriptional level, bind and inactivate PV membrane destroying IRG proteins, among other possible effects. Additionally, certain strains of T. gondii can secrete a protein known as GRA15, activating the NF-κB pathway, which upregulates the pro-inflammatory cytokine IL-12 in the early immune response, possibly leading to the parasites latent phase. The parasites ability to secrete these proteins depends on its genotype and affects its virulence.The parasite also influences an anti-apoptotic mechanism, allowing the infected host cells to persist and replicate. One method of apoptosis resistance is by disrupting pro-apoptosis effector proteins, such as BAX and BAK. To disrupt these proteins, T. gondii causes conformational changes to the proteins, which prevent the proteins from being transported to various cellular compartments where they initiate apoptosis events. T. gondii does not, however, cause downregulation of the pro-apoptosis effector proteins.T. gondii also has the ability to initiate autophagy of the hosts cells. This leads to a decrease in healthy, uninfected cells, and consequently fewer host cells to attack the infected cells. Research by Wang et al finds that infected cells lead to higher levels of autophagosomes in normal and infected cells. Their research reveals that T. gondii causes host cell autophagy using a calcium-dependent pathway. Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells.The mechanisms above allow T. gondii to persist in a host. Some limiting factors for the toxoplasma is that its influence on the host cells is stronger in a weak immune system and is quantity-dependent, so a large number of T. gondii per host cell cause a more severe effect. The effect on the host also depends on the strength of the host immune system. Immunocompetent individuals do not normally show severe symptoms or any at all, while fatality or severe complications can result in immunocompromised individuals.Since the parasite can change the hosts immune response, it may also have an effect, positive or negative, on the immune response to other pathogenic threats. This includes, but is not limited to, the responses to infections by Helicobacter felis, Leishmania major, or other parasites, such as Nippostrongylus brasiliensis. Transmission Toxoplasmosis is generally transmitted through the mouth when Toxoplasma gondii oocysts or tissue cysts are accidentally eaten. Congenital transmittance from mother to fetus can also occur. Transmission may also occur during the solid organ transplant process or hematogenous stem cell transplants.Oral transmission may occur through: Ingestion of raw or partly cooked meat, especially pork, lamb, or venison containing Toxoplasma cysts: Infection prevalence in countries where undercooked meat is traditionally eaten has been related to this transmission method. Tissue cysts may also be ingested during hand-to-mouth contact after handling undercooked meat, or from using knives, utensils, or cutting boards contaminated by raw meat. Ingestion of unwashed fruit or vegetables that have been in contact with contaminated soil containing infected cat feces. Ingestion of cat feces containing oocysts: This can occur through hand-to-mouth contact following gardening, cleaning a cats litter box, contact with childrens sandpits; the parasite can survive in the environment for months. Ingestion of untreated, unfiltered water through direct consumption or utilization of water for food preparation. Ingestion of unpasteurized milk and milk products, particularly goats milk. Ingestion of raw seafood.Cats excrete the pathogen in their feces for a number of weeks after contracting the disease, generally by eating an infected intermediate host that could include mammals (like rodents) or birds. Oocyst shedding usually starts from the third day after ingestion of infected intermediate hosts, and may continue for weeks. The oocysts are not infective when excreted. After about a day, the oocyst undergoes a process called sporulation and becomes potentially pathogenic. In addition to cats, birds and mammals including human beings are also intermediate hosts of the parasite and are involved in the transmission process. However the pathogenicity varies with the age and species involved in infection and the mode of transmission of T. gondii.Toxoplasmosis may also be transmitted through solid organ transplants. Toxoplasma-seronegative recipients who receive organs from recently infected Toxoplasma-seropositive donors are at risk. Organ recipients who have latent toxoplasmosis are at risk of the disease reactivating in their system due to the immunosuppression occurring during solid organ transplant. Recipients of hematogenous stem cell transplants may experience higher risk of infection due to longer periods of immunosuppression.Heart and lung transplants provide the highest risk for toxoplasmosis infection due to the striated muscle making up the heart, which can contain cysts, and risks for other organs and tissues vary widely. Risk of transmission can be reduced by screening donors and recipients prior to the transplant procedure and providing treatment. Pregnancy precautions Congenital toxoplasmosis is a specific form of toxoplasmosis in which an unborn fetus is infected via the placenta. Congenital toxoplasmosis is associated with fetal death and miscarriage, and in infants, it is associated with hydrocephalus, cerebral calcifications and chorioretinitis, leading to encephalopathy and possibly blindness. A positive antibody titer indicates previous exposure and immunity, and largely ensures the unborn fetus safety. A simple blood draw at the first prenatal doctor visit can determine whether or not a woman has had previous exposure and therefore whether or not she is at risk. If a woman receives her first exposure to T. gondii while pregnant, the fetus is at particular risk.Not much evidence exists around the effect of education before pregnancy to prevent congenital toxoplasmosis. However educating parents before the baby is born has been suggested to be effective because it may improve food, personal and pet hygiene. More research is needed to find whether antenatal education can reduce congenital toxoplasmosis.For pregnant women with negative antibody titers, indicating no previous exposure to T. gondii, serology testing as frequent as monthly is advisable as treatment during pregnancy for those women exposed to T. gondii for the first time dramatically decreases the risk of passing the parasite to the fetus. Since a babys immune system does not develop fully for the first year of life, and the resilient cysts that form throughout the body are very difficult to eradicate with antiprotozoans, an infection can be very serious in the young.Despite these risks, pregnant women are not routinely screened for toxoplasmosis in most countries, for reasons of cost-effectiveness and the high number of false positives generated; Portugal, France, Austria, Uruguay, and Italy are notable exceptions, and some regional screening programmes operate in Germany, Switzerland and Belgium. As invasive prenatal testing incurs some risk to the fetus (18.5 pregnancy losses per toxoplasmosis case prevented), postnatal or neonatal screening is preferred. The exceptions are cases where fetal abnormalities are noted, and thus screening can be targeted.Pregnant women should avoid handling raw meat, drinking raw milk (especially goat milk) and be advised to not eat raw or undercooked meat regardless of type. Because of the obvious relationship between Toxoplasma and cats it is also often advised to avoid exposure to cat feces, and refrain from gardening (cat feces are common in garden soil) or at least wear gloves when so engaged. Most cats are not actively shedding oocysts, since they get infected in the first six months of their life, when they shed oocysts for a short period of time (1–2 weeks.) However, these oocysts get buried in the soil, sporulate and remain infectious for periods ranging from several months to more than a year. Numerous studies have shown living in a household with a cat is not a significant risk factor for T. gondii infection, though living with several kittens has some significance.In 2006, a Czech research team discovered women with high levels of toxoplasmosis antibodies were significantly more likely to give birth to baby boys than baby girls. In most populations, the birth rate is around 51% boys, but people infected with T. gondii had up to a 72% chance of a boy. Diagnosis Diagnosis of toxoplasmosis in humans is made by biological, serological, histological, or molecular methods, or by some combination of the above. Toxoplasmosis can be difficult to distinguish from primary central nervous system lymphoma. It mimics several other infectious diseases so clinical signs are non-specific and are not sufficiently characteristic for a definite diagnosis. As a result, the possibility of an alternate diagnosis is supported by a failed trial of antimicrobial therapy (pyrimethamine, sulfadiazine, and folinic acid (USAN: leucovorin)), i.e., if the drugs produce no effect clinically and no improvement on repeat imaging. T. gondii may also be detected in blood, amniotic fluid, or cerebrospinal fluid by using polymerase chain reaction. T. gondii may exist in a host as an inactive cyst that would likely evade detection.Serological testing can detect T. gondii antibodies in blood serum, using methods including the Sabin–Feldman dye test (DT), the indirect hemagglutination assay, the indirect fluorescent antibody assay (IFA), the direct agglutination test, the latex agglutination test (LAT), the enzyme-linked immunosorbent assay (ELISA), and the immunosorbent agglutination assay test (IAAT).The most commonly used tests to measure IgG antibody are the DT, the ELISA, the IFA, and the modified direct agglutination test. IgG antibodies usually appear within a week or two of infection, peak within one to two months, then decline at various rates. Toxoplasma IgG antibodies generally persist for life, and therefore may be present in the bloodstream as a result of either current or previous infection.To some extent, acute toxoplasmosis infections can be differentiated from chronic infections using an IgG avidity test, which is a variation on the ELISA. In the first response to infection, toxoplasma-specific IgG has a low affinity for the toxoplasma antigen; in the following weeks and month, IgG affinity for the antigen increases. Based on the IgG avidity test, if the IgG in the infected individual has a high affinity, it means that the infection began three to five months before testing. This is particularly useful in congenital infection, where pregnancy status and gestational age at time of infection determines treatment.In contrast to IgG, IgM antibodies can be used to detect acute infection but generally not chronic infection. The IgM antibodies appear sooner after infection than the IgG antibodies and disappear faster than IgG antibodies after recovery. In most cases, T. gondii-specific IgM antibodies can first be detected approximately a week after acquiring primary infection and decrease within one to six months; 25% of those infected are negative for T. gondii-specific IgM within seven months. However, IgM may be detectable months or years after infection, during the chronic phase, and false positives for acute infection are possible. The most commonly used tests for the measurement of IgM antibody are double-sandwich IgM-ELISA, the IFA test, and the immunosorbent agglutination assay (IgM-ISAGA). Commercial test kits often have low specificity, and the reported results are frequently misinterpreted.In 2021, twenty commercial anti-Toxoplasma IgG assays were evaluated in a systematic review, in comparison with an accepted reference method. Most of them were enzyme-immunoassays, followed by agglutination tests, immunochromatographic tests, and a Western-Blot assay. The mean sensitivity of IgG assays ranged from 89.7% to 100% for standard titers and from 13.4% to 99.2% for low IgG titers. A few studies pointed out the ability of some methods, especially WB to detect IgG early after primary infection. The specificity of IgG assays was generally high, ranging from 91.3% to 100%; and higher than 99% for most EIA assays. The positive predictive value (PPV) was not a discriminant indicator among methods, whereas significant disparities (87.5%–100%) were reported among negative predictive values (NPV), a key-parameter assessing the ability to definitively rule out a Toxoplasma infection in patients at-risk for opportunistic infections. Congenital Recommendations for the diagnosis of congenital toxoplasmosis include: prenatal diagnosis based on testing of amniotic fluid and ultrasound examinations; neonatal diagnosis based on molecular testing of placenta and cord blood and comparative mother-child serologic tests and a clinical examination at birth; and early childhood diagnosis based on neurologic and ophthalmologic examinations and a serologic survey during the first year of life. During pregnancy, serological testing is recommended at three week intervals.Even though diagnosis of toxoplasmosis heavily relies on serological detection of specific anti-Toxoplasma immunoglobulin, serological testing has limitations. For example, it may fail to detect the active phase of T. gondii infection because the specific anti-Toxoplasma IgG or IgM may not be produced until after several weeks of infection. As a result, a pregnant woman might test negative during the active phase of T. gondii infection leading to undetected and therefore untreated congenital toxoplasmosis. Also, the test may not detect T. gondii infections in immunocompromised patients because the titers of specific anti-Toxoplasma IgG or IgM may not rise in this type of patient.Many PCR-based techniques have been developed to diagnose toxoplasmosis using clinical specimens that include amniotic fluid, blood, cerebrospinal fluid, and tissue biopsy. The most sensitive PCR-based technique is nested PCR, followed by hybridization of PCR products. The major downside to these techniques is that they are time-consuming and do not provide quantitative data.Real-time PCR is useful in pathogen detection, gene expression and regulation, and allelic discrimination. This PCR technique utilizes the 5 nuclease activity of Taq DNA polymerase to cleave a nonextendible, fluorescence-labeled hybridization probe during the extension phase of PCR. A second fluorescent dye, e.g., 6-carboxy-tetramethyl-rhodamine, quenches the fluorescence of the intact probe. The nuclease cleavage of the hybridization probe during the PCR releases the effect of quenching resulting in an increase of fluorescence proportional to the amount of PCR product, which can be monitored by a sequence detector.Toxoplasmosis cannot be detected with immunostaining. Lymph nodes affected by Toxoplasma have characteristic changes, including poorly demarcated reactive germinal centers, clusters of monocytoid B cells, and scattered epithelioid histiocytes. The classic triad of congenital toxoplasmosis includes: chorioretinitis, hydrocephalus, and intracranial arteriosclerosis. Other consequences include sensorineural deafness, seizures, and intellectual disability.Congenital toxoplasmosis may also impact a childs hearing. Up to 30% of newborns have some degree of sensorineural hearing loss. The childs communication skills may also be affected. A study published in 2010 looked at 106 patients, all of whom received toxoplasmosis treatment prior to 2.5 months. Of this group, 26.4% presented with language disorders. Treatment Treatment is recommended for people with serious health problems, such as people with HIV whose CD4 counts are under 200 cells/mm3. Trimethoprim/sulfamethoxazole is the drug of choice to prevent toxoplasmosis, but not for treating active disease. A 2012 study shows a promising new way to treat the active and latent form of this disease using two endochin-like quinolones. Acute The medications prescribed for acute toxoplasmosis are the following: Pyrimethamine – an antimalarial medication Sulfadiazine – an antibiotic used in combination with pyrimethamine to treat toxoplasmosis Combination therapy is usually given with folic acid supplements to reduce incidence of thrombocytopaenia. Combination therapy is most useful in the setting of HIV. Clindamycin Spiramycin – an antibiotic used most often for pregnant women to prevent the infection of their children.(other antibiotics, such as minocycline, have seen some use as a salvage therapy). If infected during pregnancy, spiramycin is recommended in the first and early second trimesters while pyrimethamine/sulfadiazine and leucovorin is recommended in the late second and third trimesters. Latent In people with latent toxoplasmosis, the cysts are immune to these treatments, as the antibiotics do not reach the bradyzoites in sufficient concentration. The medications prescribed for latent toxoplasmosis are: Atovaquone – an antibiotic that has been used to kill Toxoplasma cysts inside AIDS patients Clindamycin – an antibiotic that, in combination with atovaquone, seemed to optimally kill cysts in mice Congenital When a pregnant woman is diagnosed with acute toxoplasmosis, amniocentesis can be used to determine whether the fetus has been infected or not. When a pregnant woman develops acute toxoplasmosis, the tachyzoites have approximately a 30% chance of entering the placental tissue, and from there entering and infecting the fetus. As gestational age at the time of infection increases, the chance of fetal infection also increases.If the parasite has not yet reached the fetus, spiramycin can help to prevent placental transmission. If the fetus has been infected, the pregnant woman can be treated with pyrimethamine and sulfadiazine, with folinic acid, after the first trimester. They are treated after the first trimester because pyrimethamine has an antifolate effect, and lack of folic acid can interfere with fetal brain formation and cause thrombocytopaenia. Infection in earlier gestational stages correlates with poorer fetal and neonatal outcomes, particularly when the infection is untreated.Newborns who undergo 12 months of postnatal anti-toxoplasmosis treatment have a low chance of sensorineural hearing loss. Information regarding treatment milestones for children with congenital toxoplasmosis have been created for this group. Epidemiology T. gondii infections occur throughout the world, although infection rates differ significantly by country. For women of childbearing age, a survey of 99 studies within 44 countries found the areas of highest prevalence are within Latin America (about 50–80%), parts of Eastern and Central Europe (about 20–60%), the Middle East (about 30–50%), parts of Southeast Asia (about 20–60%), and parts of Africa (about 20–55%).In the United States, data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004 found 9.0% of US-born persons 12–49 years of age were seropositive for IgG antibodies against T. gondii, down from 14.1% as measured in the NHANES 1988–1994. In the 1999–2004 survey, 7.7% of US-born and 28.1% of foreign-born women 15–44 years of age were T. gondii seropositive. A trend of decreasing seroprevalence has been observed by numerous studies in the United States and many European countries. Toxoplasma gondii is considered the second leading cause of foodborne-related deaths and the fourth leading cause of foodborne-related hospitalizations in the United States.The protist responsible for toxoplasmosis is T. gondii. There are three major types of T. gondii responsible for the patterns of toxoplasmosis throughout the world. There are types I, II, and III. These three types of T. gondii have differing effects on certain hosts, mainly mice and humans due to their variation in genotypes. Type I: virulent in mice and humans, seen in people with AIDS. Type II: non-virulent in mice, virulent in humans (mostly Europe and North America), seen in people with AIDS. Type III: non-virulent in mice, virulent mainly in animals but seen to a lesser degree in humans as well.Current serotyping techniques can only separate type I or III from type II parasites.Because the parasite poses a particular threat to fetuses when it is contracted during pregnancy, much of the global epidemiological data regarding T. gondii comes from seropositivity tests in women of childbearing age. Seropositivity tests look for the presence of antibodies against T. gondii in blood, so while seropositivity guarantees one has been exposed to the parasite, it does not necessarily guarantee one is chronically infected. History Toxoplasma gondii was first described in 1908 by Nicolle and Manceaux in Tunisia, and independently by Splendore in Brazil. Splendore reported the protozoan in a rabbit, while Nicolle and Manceaux identified it in a North African rodent, the gundi (Ctenodactylus gundi). In 1909 Nicolle and Manceaux differentiated the protozoan from Leishmania. Nicolle and Manceaux then named it Toxoplasma gondii after the curved shape of its infectious stage (Greek root toxon= bow).The first recorded case of congenital toxoplasmosis was in 1923, but it was not identified as caused by T. gondii. Janků (1923) described in detail the autopsy results of an 11-month-old boy who had presented to hospital with hydrocephalus. The boy had classic marks of toxoplasmosis including chorioretinitis (inflammation of the choroid and retina of the eye). Histology revealed a number of "sporocytes", though Janků did not identify these as T. gondii.It was not until 1937 that the first detailed scientific analysis of T. gondii took place using techniques previously developed for analyzing viruses. In 1937 Sabin and Olitsky analyzed T. gondii in laboratory monkeys and mice. Sabin and Olitsky showed that T. gondii was an obligate intracellular parasite and that mice fed T. gondii-contaminated tissue also contracted the infection. Thus Sabin and Olitsky demonstrated T. gondii as a pathogen transmissible between animals. T. gondii was first described as a human pathogen in 1939 at Babies Hospital in New York City. Wolf, Cowen and Paige identified T. gondii infection in an infant girl delivered full-term by Caesarean section. The infant developed seizures and had chorioretinitis in both eyes at three days. The infant then developed encephalomyelitis and died at one month of age. Wolf, Cowen and Paige isolated T. gondii from brain tissue lesions. Intracranial injection of brain and spinal cord samples into mice, rabbits and rats produced encephalitis in the animals. Wolf, Cowen and Page reviewed additional cases and concluded that T. gondii produced recognizable symptoms and could be transmitted from mother to child.The first adult case of toxoplasmosis was reported in 1940 with no neurological signs. Pinkerton and Weinman reported the presence of Toxoplasma in a 22-year-old man from Peru who died from a subsequent bacterial infection and fever.In 1948, a serological dye test was created by Sabin and Feldman based on the ability of the patients antibodies to alter staining of Toxoplasma. The Sabin Feldman Dye Test is now the gold standard for identifying Toxoplasma infection.Transmission of Toxoplasma by eating raw or undercooked meat was demonstrated by Desmonts et al. in 1965 Paris. Desmonts observed that the therapeutic consumption of raw beef or horse meat in a tuberculosis hospital was associated with a 50% per year increase in Toxoplasma antibodies. This means that more T. gondii was being transmitted through the raw meat. In 1974, Desmonts and Couvreur showed that infection during the first two trimesters produces most harm to the fetus, that transmission depended on when mothers were infected during pregnancy, that mothers with antibodies before pregnancy did not transmit the infection to the fetus, and that spiramycin lowered the transmission to the fetus.Toxoplasma gained more attention in the 1970s with the rise of immune-suppressant treatment given after organ or bone marrow transplants and the AIDS epidemic of the 1980s. Patients with lowered immune system function are much more susceptible to disease. Society and culture "Crazy cat-lady" "Crazy cat-lady syndrome" is a term coined by news organizations to describe scientific findings that link the parasite Toxoplasma gondii to several mental disorders and behavioral problems. The suspected correlation between cat ownership in childhood and later development of schizophrenia suggested that further studies were needed to determine a risk factor for children; however, later studies showed that T. gondii was not a causative factor in later psychoses. Researchers also found that cat ownership does not strongly increase the risk of a T. gondii infection in pregnant women.The term crazy cat-lady syndrome draws on both stereotype and popular cultural reference. It was originated as instances of the aforementioned afflictions were noted amongst the populace. A cat lady is a cultural stereotype of a woman who compulsively hoards and dotes upon cats. The biologist Jaroslav Flegr is a proponent of the theory that toxoplasmosis affects human behaviour. Notable cases Tennis player Arthur Ashe developed neurological problems from toxoplasmosis (and was later found to be HIV-positive). Actor Merritt Butrick was HIV-positive and died from toxoplasmosis as a result of his already-weakened immune system. Pedro Zamora, reality television personality and HIV/AIDS activist, was diagnosed with toxoplasmosis as a result of his immune system being weakened by HIV. Prince François, Count of Clermont, pretender to the throne of France had congenital toxoplasmosis; his disability caused him to be overlooked in the line of succession. Actress Leslie Ash contracted toxoplasmosis in the second month of pregnancy. British middle-distance runner Sebastian Coe contracted toxoplasmosis in 1983, which was probably transmitted by a cat while he trained in Italy. Tennis player Martina Navratilova experienced toxoplasmosis during the 1982 US Open. Other animals Although T. gondii has the capability of infecting virtually all warm-blooded animals, susceptibility and rates of infection vary widely between different genera and species. Rates of infection in populations of the same species can also vary widely due to differences in location, diet, and other factors. Although infection with T. gondii has been noted in several species of Asian primates, seroprevalence of T. gondii antibodies were found for the first time in toque macaques (Macaca sinica) that are endemic to the island of Sri Lanka.Australian marsupials are particularly susceptible to toxoplasmosis. Wallabies, koalas, wombats, pademelons and small dasyurids can be killed by it, with eastern barred bandicoots typically dying within about 3 weeks of infection.It is estimated that 23% of wild swine worldwide are seropositive for T. gondii. Seroprevalence varies across the globe with the highest seroprevalence in North America (32%) and Europe (26%) and the lowest in Asia (13%) and South America (5%). Geographical regions located at higher latitudes and regions that experience warmer, humid climates are associated with increased seroprevalence of T. gondii among wild boar. Wild boar infected with T. gondii pose a potential health risk for humans who consume their meat. Livestock Among livestock, pigs, sheep and goats have the highest rates of chronic T. gondii infection. The prevalence of T. gondii in meat-producing animals varies widely both within and among countries, and rates of infection have been shown to be dramatically influenced by varying farming and management practices. For instance, animals kept outdoors or in free-ranging environments are more at risk of infection than animals raised indoors or in commercial confinement operations. Pigs Worldwide, the percentage of pigs harboring viable parasites has been measured to be 3–71.43% and in the United States (via bioassay in mice or cats) to be as high as 92.7% and as low as 0%, depending on the farm or herd. Surveys of seroprevalence (T. gondii antibodies in blood) are more common, and such measurements are indicative of the high relative seroprevalence in pigs across the world. Neonatal piglets have been found to experience the entire range of severity, including progression to stillbirth.: 95  This was especially demonstrated in the foundational Thiptara et al. 2006, reporting a litter birth of three stillborns and six live in Thailand. This observation has been relevant not only to that country but to toxoplasmosis control in porciculture around the world.: 95 Sheep Along with pigs, sheep and goats are among the most commonly infected livestock of epidemiological significance for human infection. Prevalence of viable T. gondii in sheep tissue has been measured (via bioassay) to be as high as 78% in the United States, and a 2011 survey of goats intended for consumption in the United States found a seroprevalence of 53.4%. Chickens Due to a lack of exposure to the outdoors, chickens raised in large-scale indoor confinement operations are not commonly infected with T. gondii. Free-ranging or backyard-raised chickens are much more commonly infected. A survey of free-ranging chickens in the United States found its prevalence to be 17–100%, depending on the farm. Because chicken meat is generally cooked thoroughly before consumption, poultry is not generally considered to be a significant risk factor for human T. gondii infection. Cattle Although cattle and buffalo can be infected with T. gondii, the parasite is generally eliminated or reduced to undetectable levels within a few weeks following exposure. Tissue cysts are rarely present in buffalo meat or beef, and meat from these animals is considered to be low-risk for harboring viable parasites. Horses Horses are considered resistant to chronic T. gondii infection. However, viable cells have been isolated from US horses slaughtered for export, and severe human toxoplasmosis in France has been epidemiologically linked to the consumption of horse meat. Domestic cats In 1942, the first case of feline toxoplasmosis was diagnosed and reported in a domestic cat in Middletown, New York. The investigators isolated oocysts from feline feces and found that the oocysts could be infectious for up to 12 months in the environment.The seroprevalence of T. gondii in domestic cats, worldwide has been estimated to be around 30–40% and exhibits significant geographical variation. In the United States, no official national estimate has been made, but local surveys have shown levels varying between 16% and 80%. A 2012 survey of 445 purebred pet cats and 45 shelter cats in Finland found an overall seroprevalence of 48.4%, while a 2010 survey of feral cats from Giza, Egypt found a seroprevalence rate of 97.4%. Another survey from Colombia recorded seroprevalence of 89.3%, whereas a Chinese (Guangdong) study found just a 2.1% prevalence.T. gondii infection rates in domestic cats vary widely depending on the cats diets and lifestyles. Feral cats that hunt for their food are more likely to be infected than domestic cats, and naturally also depends on the prevalence of T. gondii-infected prey such as birds and small mammals.Most infected cats will shed oocysts only once in their lifetimes, for a period of about one to two weeks. This shedding can release millions of oocysts, each capable of spreading and surviving for months. An estimated 1% of cats at any given time are actively shedding oocysts.It is difficult to control the cat population with the infected oocysts due to lack of an effective vaccine. This remains a challenge in most cases and the programs that are readily available are questionable in efficacy. Rodents Infection with T. gondii has been shown to alter the behavior of mice and rats in ways thought to increase the rodents chances of being preyed upon by cats. Infected rodents show a reduction in their innate aversion to cat odors; while uninfected mice and rats will generally avoid areas marked with cat urine or with cat body odor, this avoidance is reduced or eliminated in infected animals. Moreover, some evidence suggests this loss of aversion may be specific to feline odors: when given a choice between two predator odors (cat or mink), infected rodents show a significantly stronger preference to cat odors than do uninfected controls.In rodents, T. gondii–induced behavioral changes occur through epigenetic remodeling in neurons associated with observed behaviors; for example, it modifies epigenetic methylation to induce hypomethylation of arginine vasopressin-related genes in the medial amygdala to greatly decrease predator aversion. Similar epigenetically induced behavioral changes have also been observed in mouse models of addiction, where changes in the expression of histone-modifying enzymes via gene knockout or enzyme inhibition in specific neurons produced alterations in drug-related behaviors. Widespread histone–lysine acetylation in cortical astrocytes appears to be another epigenetic mechanism employed by T. gondii.T. gondii-infected rodents show a number of behavioral changes beyond altered responses to cat odors. Rats infected with the parasite show increased levels of activity and decreased neophobic behavior. Similarly, infected mice show alterations in patterns of locomotion and exploratory behavior during experimental tests. These patterns include traveling greater distances, moving at higher speeds, accelerating for longer periods of time, and showing a decreased pause-time when placed in new arenas. Infected rodents have also been shown to have lower anxiety, using traditional models such as elevated plus mazes, open field arenas, and social interaction tests. Marine mammals A University of California, Davis study of dead sea otters collected from 1998 to 2004 found toxoplasmosis was the cause of death for 13% of the animals. Proximity to freshwater outflows into the ocean was a major risk factor. Ingestion of oocysts from cat feces is considered to be the most likely ultimate source. Surface runoff containing wild cat feces and litter from domestic cats flushed down toilets are possible sources of oocysts. These same sources may have also introduced the toxoplasmosis infection to the endangered Hawaiian monk seal. Infection with the parasite has contributed to the death of at least four Hawaiian monk seals. A Hawaiian monk seals infection with T. gondii was first noted in 2004. The parasites spread threatens the recovery of this highly endangered pinniped. The parasites have been found in dolphins and whales. Researchers Black and Massie believe anchovies, which travel from estuaries into the open ocean, may be helping to spread the disease. Giant panda Toxoplasma gondii has been reported as the cause of death of a giant panda kept in a zoo in China, who died in 2014 of acute gastroenteritis and respiratory disease. Although seemingly anecdotal, this report emphasizes that all warm-blooded species are likely to be infected by T. gondii, including endangered species such as the giant panda. Research Chronic infection with T. gondii has traditionally been considered asymptomatic in people with normal immune function. Some evidence suggests latent infection may subtly influence a range of human behaviors and tendencies, and infection may alter the susceptibility to or intensity of a number of psychiatric or neurological disorders.In most of the current studies where positive correlations have been found between T. gondii antibody titers and certain behavioral traits or neurological disorders, T. gondii seropositivity tests are conducted after the onset of the examined disease or behavioral trait; that is, it is often unclear whether infection with the parasite increases the chances of having a certain trait or disorder, or if having a certain trait or disorder increases the chances of becoming infected with the parasite. Groups of individuals with certain behavioral traits or neurological disorders may share certain behavioral tendencies that increase the likelihood of exposure to and infection with T. gondii; as a result, it is difficult to confirm causal relationships between T. gondii infections and associated neurological disorders or behavioral traits. Mental health Some evidence links T. gondii to schizophrenia. Two 2012 meta-analyses found that the rates of antibodies to T. gondii in people with schizophrenia were 2.7 times higher than in controls. T. gondii antibody positivity was therefore considered an intermediate risk factor in relation to other known risk factors. Cautions noted include that the antibody tests do not detect toxoplasmosis directly, most people with schizophrenia do not have antibodies for toxoplasmosis, and publication bias might exist. While the majority of these studies tested people already diagnosed with schizophrenia for T. gondii antibodies, associations between T. gondii and schizophrenia have been found prior to the onset of schizophrenia symptoms. Sex differences in the age of schizophrenia onset may be explained in part by a second peak of T. gondii infection incidence during ages 25–30 in females only. Although a mechanism supporting the association between schizophrenia and T. gondii infection is unclear, studies have investigated a molecular basis of this correlation. Antipsychotic drugs used in schizophrenia appear to inhibit the replication of T. gondii tachyzoites in cell culture. Supposing a causal link exists between T. gondii and schizophrenia, studies have yet to determine why only some individuals with latent toxoplasmosis develop schizophrenia; some plausible explanations include differing genetic susceptibility, parasite strain differences, and differences in the route of the acquired T. gondii infection.Correlations have also been found between antibody titers to T. gondii and OCD, as well as suicide among people with mood disorders including bipolar disorder. Positive antibody titers to T. gondii appear to be uncorrelated with major depression or dysthymia. Although there is a correlation between T. gondii and many psychological disorders, the underlying mechanism is unclear. A 2016 study of 236 persons with high levels of toxoplasmosis antibodies found that "there was little evidence that T. gondii was related to increased risk of psychiatric disorder, poor impulse control, personality aberrations or neurocognitive impairment". Neurological disorders Latent infection has been linked to Parkinsons disease and Alzheimers disease.Individuals with multiple sclerosis show infection rates around 15% lower than the general public. Traffic accidents Latent T. gondii infection in humans has been associated with a higher risk of automobile accidents, potentially due to impaired psychomotor performance or enhanced risk-taking personality profiles. Climate change Climate change has been reported to affect the occurrence, survival, distribution and transmission of T. gondii. T. gondii has been identified in the Canadian arctic, a location that was once too cold for its survival. Higher temperatures increase the survival time of T. gondii. More snowmelt and precipitation can increase the amount of T. gondii oocysts that are transported via river flow. Shifts in bird, rodent, and insect populations and migration patterns can impact the distribution of T. gondii due to their role as reservoir and vector. Urbanization and natural environmental degradation are also suggested to affect T. gondii transmission and increase risk of infection. See also Toxoplasmic chorioretinitis TORCH infection Pyrimethamine References Parts of this article are taken from the public domain CDC factsheet: Toxoplasmosis Bibliography Weiss, L. M.; Kim, K. (28 April 2011). Toxoplasma gondii: The Model Apicomplexan. Perspectives and Methods. Academic Press. ISBN 978-0-08-047501-1. Retrieved 12 March 2013. Dubey, J. P. (2016). Toxoplasmosis of Animals and Humans (2nd ed.). Boca Raton: CRC Press. pp. xvii+313. ISBN 978-1-4200-9237-0. OCLC 423572366. ISBN 1-4200-9236-7 ISBN 9781420092363 Dubey JP, Lindsay DS, Speer CA (April 1998). "Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts". Clinical Microbiology Reviews. 11 (2): 267–299. doi:10.1128/CMR.11.2.267. PMC 106833. PMID 9564564. Jaroslav Flegr (2011). Pozor, Toxo!. Academia, Prague, Czech Republic. ISBN 978-80-200-2022-2. External links How a cat-borne parasite infects humans (National Geographic) Toxoplasmosis at Merck Manual of Diagnosis and Therapy Professional Edition Toxoplasmosis at Health Protection Agency (HPA), United Kingdom Pictures of Toxoplasmosis Medical Image Database Video-Interview with Professor Robert Sapolsky on Toxoplasmosis and its effect on human behavior (24:27 min) "Toxoplasmosis". MedlinePlus. U.S. National Library of Medicine.

Hello Aarogya, what is Trachoma

Trachoma

Trachoma is an infectious disease caused by bacterium Chlamydia trachomatis. The infection causes a roughening of the inner surface of the eyelids. This roughening can lead to pain in the eyes, breakdown of the outer surface or cornea of the eyes, and eventual blindness. Untreated, repeated trachoma infections can result in a form of permanent blindness when the eyelids turn inward.The bacteria that cause the disease can be spread by both direct and indirect contact with an affected persons eyes or nose. Indirect contact includes through clothing or flies that have come into contact with an affected persons eyes or nose. Children spread the disease more often than adults. Poor sanitation, crowded living conditions, and not enough clean water and toilets also increase spread.Efforts to prevent the disease include improving access to clean water and treatment with antibiotics to decrease the number of people infected with the bacterium. This may include treating, all at once, whole groups of people in whom the disease is known to be common. Washing, by itself, is not enough to prevent disease, but may be useful with other measures. Treatment options include oral azithromycin and topical tetracycline. Azithromycin is preferred because it can be used as a single oral dose. After scarring of the eyelid has occurred, surgery may be required to correct the position of the eyelashes and prevent blindness.Globally, about 80 million people have an active infection. In some areas, infections may be present in as many as 60–90% of children. Among adults, it more commonly affects women than men – likely due to their closer contact with children. The disease is the cause of decreased vision in 2.2 million people, of whom 1.2 million are completely blind. Trachoma is a public health problem in 44 countries across Africa, Asia, and Central and South America, with 136.9 million people at risk. It results in US$8 billion of economic losses a year. It belongs to a group of diseases known as neglected tropical diseases. Signs and symptoms The bacterium has an incubation period of 6 to 12 days, after which the affected individual experiences symptoms of conjunctivitis, or irritation similar to "pink eye". Blinding endemic trachoma results from multiple episodes of reinfection that maintains the intense inflammation in the conjunctiva. Without reinfection, the inflammation gradually subsides.The conjunctival inflammation is called "active trachoma" and usually is seen in children, especially preschool children. It is characterized by white lumps in the undersurface of the upper eyelid (conjunctival follicles or lymphoid germinal centres) and by nonspecific inflammation and thickening often associated with papillae. Follicles may also appear at the junction of the cornea and the sclera (limbal follicles). Active trachoma often can be irritating and have a watery discharge. Bacterial secondary infection may occur and cause a purulent discharge.The later structural changes of trachoma are referred to as "cicatricial trachoma". These include scarring in the eyelid (tarsal conjunctiva) that leads to distortion of the eyelid with buckling of the lid (tarsus) so the lashes rub on the eye (trichiasis). These lashes can lead to corneal opacities and scarring and then to blindness. Linear scars present in the sulcus subtarsalis are called Arlts lines (named after Carl Ferdinand von Arlt). In addition, blood vessels and scar tissue can invade the upper cornea (pannus). Resolved limbal follicles may leave small gaps in the pannus (Herberts pits).Most commonly, children with active trachoma do not present with any symptoms, as the low-grade irritation and ocular discharge is just accepted as normal, but further symptoms may include: Eye discharge Swollen eyelids Trichiasis (misdirected eyelashes) Swelling of lymph nodes in front of the ears Sensitivity to bright lights Increased heart rate Further ear, nose, and throat complications.The major complication or the most important one is corneal ulcer occurring due to rubbing by concentrations, or trichiasis with superimposed bacterial infection. Cause Trachoma is caused by Chlamydia trachomatis, serotypes (serovars) A, B, and C. It is spread by direct contact with eye, nose, and throat secretions from affected individuals, or contact with fomites (inanimate objects that carry infectious agents), such as towels and/or washcloths, that have had similar contact with these secretions. Flies can also be a route of mechanical transmission. Untreated, repeated trachoma infections result in entropion (the inward turning of the eyelids), which may result in blindness due to damage to the cornea. Children are the most susceptible to infection due to their tendency to get dirty easily, but the blinding effects or more severe symptoms are often not felt until adulthood.Blinding endemic trachoma occurs in areas with poor personal and family hygiene. Many factors are indirectly linked to the presence of trachoma including lack of water, absence of latrines or toilets, poverty in general, flies, close proximity to cattle, and crowding. The final common pathway, though, seems to be the presence of dirty faces in children, facilitating the frequent exchange of infected ocular discharge from one childs face to another. Most transmission of trachoma occurs within the family. Diagnosis McCallans classification McCallan in 1908 divided the clinical course of trachoma into four stages: WHO classification The World Health Organization recommends a simplified grading system for trachoma. The Simplified WHO Grading System is summarized below: Trachomatous inflammation, follicular (TF)—Five or more follicles of >0.5 mm on the upper tarsal conjunctiva Trachomatous inflammation, intense (TI)—Papillary hypertrophy and inflammatory thickening of the upper tarsal conjunctiva obscuring more than half the deep tarsal vessels Trachomatous scarring (TS)—Presence of scarring in tarsal conjunctiva. Trachomatous trichiasis (TT)—At least one ingrown eyelash touching the globe, or evidence of epilation (eyelash removal) Corneal opacity (CO)—Corneal opacity blurring part of the pupil margin Prevention Although trachoma was eliminated from much of the developed world in the 20th century (Australia being a notable exception), this disease persists in many parts of the developing world, particularly in communities without adequate access to water and sanitation. Environmental measures Environmental improvement: Modifications in water use, fly control, latrine use, health education, and proximity to domesticated animals have all been proposed to reduce transmission of C. trachomatis. These changes pose numerous challenges for implementation. These environmental changes are likely to ultimately affect the transmission of ocular infection by means of lack of facial cleanliness. Particular attention is required for environmental factors that limit clean faces. A systematic review examining the effectiveness of environmental sanitary measures on the prevalence of active trachoma in endemic areas showed that use of insecticide spray resulted in significant reductions of trachoma and fly density in some studies. Health education also resulted in reductions of active trachoma when implemented. Improved water supply did not result in a reduction of trachoma incidence. Antibiotics WHO Guidelines recommend that a region should receive community-based, mass antibiotic treatment when the prevalence of active trachoma among one- to nine-year-old children is greater than 10%. Subsequent annual treatment should be administered for three years, at which time the prevalence should be reassessed. Annual treatment should continue until the prevalence drops below 5%. At lower prevalences, antibiotic treatment should be family-based. Management Antibiotics Azithromycin (single oral dose of 20 mg/kg) or topical tetracycline (1% eye ointment twice a day for six weeks). Azithromycin is preferred because it is used as a single oral dose. Although it is expensive, it is generally used as part of the international donation program organized by Pfizer. Azithromycin can be used in children from the age of six months and in pregnancy. As a community-based antibiotic treatment, some evidence suggests that oral azithromycin was more effective than topical tetracycline, but no consistent evidence supported either oral or topical antibiotics as being more effective. Antibiotic treatment reduces the risk of active trachoma in individuals infected with chlamydial trachomatis. Surgery For individuals with trichiasis, a bilamellar tarsal rotation procedure is warranted to direct the lashes away from the globe. Evidence suggests that use of a lid clamp and absorbable sutures would result in reduced lid contour abnormalities and granuloma formulation after surgery. Early intervention is beneficial as the rate of recurrence is higher in more advanced disease. Lifestyle measures The WHO-recommended SAFE strategy includes: Surgery to correct advanced stages of the disease Antibiotics to treat active infection, using azithromycin Facial cleanliness to reduce disease transmission Environmental change to increase access to clean water and improved sanitationChildren with visible nasal discharge, discharge from the eyes, or flies on their faces are at least twice as likely to have active trachoma as children with clean faces. Intensive community-based health education programs to promote face-washing can reduce the rates of active trachoma, especially intense trachoma. If an individual is already infected, washing ones face is encouraged, especially a child, to prevent reinfection. Some evidence shows that washing the face combined with topical tetracycline might be more effective in reducing severe trachoma compared to topical tetracycline alone. The same trial found no statistical benefit of eye washing alone or in combination with tetracycline eye drops in reducing follicular trachoma amongst children. Prognosis If not treated properly with oral antibiotics, the symptoms may escalate and cause blindness, which is the result of ulceration and consequent scarring of the cornea. Surgery may also be necessary to fix eyelid deformities. Without intervention, trachoma keeps families in a cycle of poverty, as the disease and its long-term effects are passed from one generation to the next. Epidemiology As of 2011, about 21 million people are actively affected by trachoma, with around 2.2 million people being permanently blind or have severe visual impairment from trachoma. An additional 7.3 million people are reported to have trichiasis. 51 countries are currently classified as endemic for blinding trachoma. Of these, Africa is considered the worst affected area, with over 85% of all known active cases of trachoma. Within the continent, South Sudan and Ethiopia have the highest prevalence. In many of these communities, women are three times more likely than men to be blinded by the disease, due to their roles as caregivers in the family. Approximately 158 million people are living in areas were trachoma is common. An additional 229 million live where trachoma could potentially occur. Australia is the only developed country that has trachoma. In 2008, trachoma was found in half of Australias very remote communities. Elimination In 1996, the WHO launched its Alliance for the Global Elimination of Trachoma by 2020, and in 2006, the WHO officially set 2020 as the target to eliminate trachoma as a public-health problem. The International Coalition for Trachoma Control has produced maps and a strategic plan called 2020 INSight that lays out actions and milestones to achieve global elimination of blinding trachoma by 2020. The program recommends the SAFE protocol for blindness prevention: Surgery for trichiasis, Antibiotics to clear infection, Facial cleanliness, and Environmental improvement to reduce transmission. This includes sanitation infrastructure to reduce the open presence of human feces that can breed flies.As of 2018, Cambodia, Ghana, Iran, Laos, Mexico, Nepal, Morocco, and Oman have been certified as having eliminated trachoma as a public-health problem; China, Gambia, Iran, Iraq, and Myanmar make that claim, but have not sought certification. Eradication of the bacterium that causes the disease is seen as impractical; the WHO definition of "eliminated as a public-health problem" means less than 5% of children have any symptoms, and less than 0.1% of adults have vision loss. Having already donated more doses (about 700 million since 2002) of the drug than it has sold during the same time period, the drug company Pfizer has agreed to donate azithromycin until 2025, if necessary, for elimination of the disease. The campaign unexpectedly found distribution of azithromycin to very poor children reduced their early death rate by up to 25%. History The disease is one of the earliest known eye afflictions, having been identified in Egypt as early as 15 BC.Its presence was also recorded in ancient China and Mesopotamia. Trachoma became a problem as people moved into crowded settlements or towns where hygiene was poor. It became a particular problem in Europe in the 19th century. After the Egyptian Campaign (1798–1802) and the Napoleonic Wars (1798–1815), trachoma was rampant in the army barracks of Europe and spread to those living in towns as troops returned home. Stringent control measures were introduced, and by the early 20th century, trachoma was essentially controlled in Europe, although cases were reported until the 1950s. Today, most victims of trachoma live in underdeveloped and poverty-stricken countries in Africa, the Middle East, and Asia.In the United States, the Centers for Disease Control says, "No national or international surveillance [for trachoma] exists. Blindness due to trachoma has been eliminated from the United States. The last cases were found among Native American populations and in Appalachia, and those in the boxing, wrestling, and sawmill industries (prolonged exposure to combinations of sweat and sawdust often led to the disease). In the late 19th and early 20th centuries, trachoma was the main reason for an immigrant coming through Ellis Island to be deported."In 1913, President Woodrow Wilson signed an act designating funds for the eradication of the disease. Immigrants who attempted to enter the U.S. through Ellis Island, New York, had to be checked for trachoma. During this time, treatment for the disease was by topical application of copper sulfate. By the late 1930s, a number of ophthalmologists reported success in treating trachoma with sulfonamide antibiotics. In 1948, Vincent Tabone (who was later to become the President of Malta) was entrusted with the supervision of a campaign in Malta to treat trachoma using sulfonamide tablets and drops.Due to improved sanitation and overall living conditions, trachoma virtually disappeared from the industrialized world by the 1950s, though it continues to plague the developing world to this day. Epidemiological studies were conducted in 1956–63 by the Trachoma Control Pilot Project in India under the Indian Council for Medical Research. This potentially blinding disease remains endemic in the poorest regions of Africa, Asia, and the Middle East and in some parts of Latin America and Australia. Currently, 8 million people are visually impaired as a result of trachoma, and 41 million have an active infection. Of the 54 countries that the WHO cited as still having blinding trachoma occurring, Australia is the only developed country—Australian Aboriginal people who live in remote communities with inadequate sanitation are still blinded by this infectious eye disease.Indias Health and Family Welfare Minister JP Nadda declared India free of infective trachoma in 2017. Etymology The term is derived from New Latin trāchōma, from Greek τράχωμα trākhōma, from τραχύς trākhus "rough". Economics The economic burden of trachoma is huge, particularly with regard to covering treatment costs and productivity losses as a result of increased visual impairment, and in some cases, permanent blindness. The global estimated cost of trachoma is reported between $US2.9 and 5.3 billion each year. By including the cost for trichiasis treatment, the estimated overall cost for the disease increases to about $US 8 billion. References External links CDC Disease Info trachomaCelia W. Dugger (31 March 2006), "Preventable Disease Blinds Poor in Third World", The New York Times Photographs of trachoma patients Trachoma Atlas International Trachoma Initiative

Hey Aarogya , Do you know what is Travelers diarrhea,

Travelers diarrhea

Travelers diarrhea (TD) is a stomach and intestinal infection. TD is defined as the passage of unformed stool (one or more by some definitions, three or more by others) while traveling. It may be accompanied by abdominal cramps, nausea, fever, headache and bloating. Occasionally bloody diarrhea may occur. Most travelers recover within three to four days with little or no treatment. About 10% of people may have symptoms for a week.Bacteria are responsible for more than half of cases, typically via foodborne illness and waterborne diseases. The bacteria enterotoxigenic Escherichia coli (ETEC) are typically the most common except in Southeast Asia, where Campylobacter is more prominent. About 10 to 20 percent of cases are due to norovirus. Protozoa such as Giardia may cause longer term disease. The risk is greatest in the first two weeks of travel and among young adults. People affected are more often from the developed world.Recommendations for prevention include eating only properly cleaned and cooked food, drinking bottled water, and frequent hand washing. The oral cholera vaccine, while effective for cholera, is of questionable use for travelers diarrhea. Preventive antibiotics are generally discouraged. Primary treatment includes rehydration and replacing lost salts (oral rehydration therapy). Antibiotics are recommended for significant or persistent symptoms, and can be taken with loperamide to decrease diarrhea. Hospitalization is required in less than 3 percent of cases.Estimates of the percentage of people affected range from 20 to 50 percent among travelers to the developing world. TD is particularly common among people traveling to Asia (except for Japan and Singapore), the Middle East, Africa, Mexico, and Central and South America. The risk is moderate in Southern Europe, Russia, and China. TD has been linked to later irritable bowel syndrome and Guillain–Barré syndrome. It has colloquially been known by a number of names, including "Montezumas revenge," the "Nile runs" and "Delhi belly". Signs and symptoms The onset of TD usually occurs within the first week of travel, but may occur at any time while traveling, and even after returning home, depending on the incubation period of the infectious agent. Bacterial TD typically begins abruptly, but Cryptosporidium may incubate for seven days, and Giardia for 14 days or more, before symptoms develop. Typically, a traveler experiences four to five loose or watery bowel movements each day. Other commonly associated symptoms are abdominal cramping, bloating, fever, and malaise. Appetite may decrease significantly. Though unpleasant, most cases of TD are mild, and resolve in a few days without medical intervention.Blood or mucus in the diarrhea, significant abdominal pain, or high fever suggests a more serious cause, such as cholera, characterized by a rapid onset of weakness and torrents of watery diarrhea with flecks of mucus (described as "rice water" stools). Medical care should be sought in such cases; dehydration is a serious consequence of cholera, and may trigger serious sequelae—including, in rare instances, death—as rapidly as 24 hours after onset if not addressed promptly. Causes Infectious agents are the primary cause of travelers diarrhea. Bacterial enteropathogens cause about 80% of cases. Viruses and protozoans account for most of the rest.The most common causative agent isolated in countries surveyed has been enterotoxigenic Escherichia coli (ETEC). Enteroaggregative E. coli is increasingly recognized. Shigella spp. and Salmonella spp. are other common bacterial pathogens. Campylobacter, Yersinia, Aeromonas, and Plesiomonas spp. are less frequently found. Mechanisms of action vary: some bacteria release toxins which bind to the intestinal wall and cause diarrhea; others damage the intestines themselves by their direct presence.Brachyspira pilosicoli pathogen also appears to be responsible for many chronic intermittent watery diarrhea and is only diagnosed through colonic biopsies and microscopic discovery of a false brush border on H&E or Warthin silver stain: its brush-border is stronger and longer that Brachyspira aalborgis brush-border. It is unfortunately often not diagnosed as coproculture does not allow growth and 16S PCR panel primers do not match Brachyspira sequences.While viruses are associated with less than 20% of adult cases of travelers diarrhea, they may be responsible for nearly 70% of cases in infants and children. Diarrhea due to viral agents is unaffected by antibiotic therapy, but is usually self-limited. Protozoans such as Giardia lamblia, Cryptosporidium and Cyclospora cayetanensis can also cause diarrhea. Pathogens commonly implicated in travelers diarrhea appear in the table in this section.A subtype of travelers diarrhea afflicting hikers and campers, sometimes known as wilderness diarrhea, may have a somewhat different frequency of distribution of pathogens. Risk factors The primary source of infection is ingestion of fecally contaminated food or water. Attack rates are similar for men and women.The most important determinant of risk is the travelers destination. High-risk destinations include developing countries in Latin America, Africa, the Middle East, and Asia. Among backpackers, additional risk factors include drinking untreated surface water and failure to maintain personal hygiene practices and clean cookware. Campsites often have very primitive (if any) sanitation facilities, making them potentially as dangerous as any developing country.Although travelers diarrhea usually resolves within three to five days (mean duration: 3.6 days), in about 20% of cases, the illness is severe enough to require bedrest, and in 10%, the illness duration exceeds one week. For those prone to serious infections, such as bacillary dysentery, amoebic dysentery, and cholera, TD can occasionally be life-threatening. Others at higher-than-average risk include young adults, immunosuppressed persons, persons with inflammatory bowel disease or diabetes, and those taking H2 blockers or antacids. Immunity Travelers often get diarrhea from eating and drinking foods and beverages that have no adverse effects on local residents. This is due to immunity that develops with constant, repeated exposure to pathogenic organisms. The extent and duration of exposure necessary to acquire immunity has not been determined; it may vary with each individual organism. A study among expatriates in Nepal suggests that immunity may take up to seven years to develop—presumably in adults who avoid deliberate pathogen exposure. Conversely, immunity acquired by American students while living in Mexico disappeared, in one study, as quickly as eight weeks after cessation of exposure. Prevention Sanitation Recommendations include avoidance of questionable foods and drinks, on the assumption that TD is fundamentally a sanitation failure, leading to bacterial contamination of drinking water and food. While the effectiveness of this strategy has been questioned, given that travelers have little or no control over sanitation in hotels and restaurants, and little evidence supports the contention that food vigilance reduces the risk of contracting TD, guidelines continue to recommend basic, common-sense precautions when making food and beverage choices: Maintain good hygiene and use only safe water for drinking and brushing teeth. Safe beverages include bottled water, bottled carbonated beverages, and water boiled or appropriately treated by the traveler (as described below). Caution should be exercised with tea, coffee, and other hot beverages that may be only heated, not boiled. In restaurants, insist that bottled water be unsealed in your presence; reports of locals filling empty bottles with untreated tap water and reselling them as purified water have surfaced. When in doubt, a bottled carbonated beverage is the safest choice, since it is difficult to simulate carbonation when refilling a used bottle. Avoid ice, which may not have been made with safe water. Avoid green salads, because the lettuce and other uncooked ingredients are unlikely to have been washed with safe water. Avoid eating raw fruits and vegetables unless cleaned and peeled personally.If handled properly, thoroughly cooked fresh and packaged foods are usually safe. Raw or undercooked meat and seafood should be avoided. Unpasteurized milk, dairy products, mayonnaise, and pastry icing are associated with increased risk for TD, as are foods and beverages purchased from street vendors and other establishments where unhygienic conditions may be present. Water Although safe bottled water is now widely available in most remote destinations, travelers can treat their own water if necessary, or as an extra precaution. Techniques include boiling, filtering, chemical treatment, and ultraviolet light; boiling is by far the most effective of these methods. Boiling rapidly kills all active bacteria, viruses, and protozoa. Prolonged boiling is usually unnecessary; most microorganisms are killed within seconds at water temperature above 55–70 °C (130–160 °F). The second-most effective method is to combine filtration and chemical disinfection. Filters eliminate most bacteria and protozoa, but not viruses. Chemical treatment with halogens—chlorine bleach, tincture of iodine, or commercial tablets—have low-to-moderate effectiveness against protozoa such as Giardia, but work well against bacteria and viruses. UV light is effective against both viruses and cellular organisms, but only works in clear water, and it is ineffective unless manufacturers instructions are carefully followed for maximum water depth/distance from UV source, and for dose/exposure time. Other claimed advantages include short treatment time, elimination of the need for boiling, no taste alteration, and decreased long-term cost compared with bottled water. The effectiveness of UV devices is reduced when water is muddy or turbid; as UV is a type of light, any suspended particles create shadows that hide microorganisms from UV exposure. Medications Bismuth subsalicylate four times daily reduces rates of travelers diarrhea. Though many travelers find a four-times-per-day regimen inconvenient, lower doses have not been shown to be effective. Potential side effects include black tongue, black stools, nausea, constipation, and ringing in the ears. Bismuth subsalicylate should not be taken by those with aspirin allergy, kidney disease, or gout, nor concurrently with certain antibiotics such as the quinolones, and should not be taken continuously for more than three weeks. Some countries do not recommend it due to the risk of rare but serious side effects.A hyperimmune bovine colostrum to be taken by mouth is marketed in Australia for prevention of ETEC-induced TD. As yet, no studies show efficacy under actual travel conditions.Though effective, antibiotics are not recommended for prevention of TD in most situations because of the risk of allergy or adverse reactions to the antibiotics, and because intake of preventive antibiotics may decrease effectiveness of such drugs should a serious infection develop subsequently. Antibiotics can also cause vaginal yeast infections, or overgrowth of the bacterium Clostridium difficile, leading to pseudomembranous colitis and its associated severe, unrelenting diarrhea.Antibiotics may be warranted in special situations where benefits outweigh the above risks, such as immunocompromised travelers, chronic intestinal disorders, prior history of repeated disabling bouts of TD, or scenarios in which the onset of diarrhea might prove particularly troublesome. Options for prophylactic treatment include the quinolone antibiotics (such as ciprofloxacin), azithromycin, and trimethoprim/sulfamethoxazole, though the latter has proved less effective in recent years. Rifaximin may also be useful. Quinolone antibiotics may bind to metallic cations such as bismuth, and should not be taken concurrently with bismuth subsalicylate. Trimethoprim/sulfamethoxazole should not be taken by anyone with a history of sulfa allergy. Vaccination The oral cholera vaccine, while effective for prevention of cholera, is of questionable use for prevention of TD. A 2008 review found tentative evidence of benefit. A 2015 review stated it may be reasonable for those at high risk of complications from TD. Several vaccine candidates targeting ETEC or Shigella are in various stages of development. Probiotics One 2007 review found that probiotics may be safe and effective for prevention of TD, while another review found no benefit. A 2009 review confirmed that more study is needed, as the evidence to date is mixed. Treatment Most cases of TD are mild and resolve in a few days without treatment, but severe or protracted cases may result in significant fluid loss and dangerous electrolytic imbalance. Dehydration due to diarrhea can also alter the effectiveness of medicinal and contraceptive drugs. Adequate fluid intake (oral rehydration therapy) is therefore a high priority. Commercial rehydration drinks are widely available; alternatively, purified water or other clear liquids are recommended, along with salty crackers or oral rehydration salts (available in stores and pharmacies in most countries) to replenish lost electrolytes. Carbonated water or soda, left open to allow dissipation of the carbonation, is useful when nothing else is available. In severe or protracted cases, the oversight of a medical professional is advised. Antibiotics If diarrhea becomes severe (typically defined as three or more loose stools in an eight-hour period), especially if associated with nausea, vomiting, abdominal cramps, fever, or blood in stools, medical treatment should be sought. Such patients may benefit from antimicrobial therapy. A 2000 literature review found that antibiotic treatment shortens the duration and severity of TD; most reported side effects were minor, or resolved on stopping the antibiotic.The antibiotic recommended varies based upon the destination of travel. Trimethoprim–sulfamethoxazole and doxycycline are no longer recommended because of high levels of resistance to these agents. Antibiotics are typically given for three to five days, but single doses of azithromycin or levofloxacin have been used. Rifaximin and rifamycin are approved in the U.S. for treatment of TD caused by ETEC. If diarrhea persists despite therapy, travelers should be evaluated for bacterial strains resistant to the prescribed antibiotic, possible viral or parasitic infections, bacterial or amoebic dysentery, Giardia, helminths, or cholera. Antimotility agents Antimotility drugs such as loperamide and diphenoxylate reduce the symptoms of diarrhea by slowing transit time in the gut. They may be taken to slow the frequency of stools, but not enough to stop bowel movements completely, which delays expulsion of the causative organisms from the intestines. They should be avoided in patients with fever, bloody diarrhea, and possible inflammatory diarrhea. Adverse reactions may include nausea, vomiting, abdominal pain, hives or rash, and loss of appetite. Antimotility agents should not, as a rule, be taken by children under age two. Epidemiology An estimated 10 million people—20 to 50% of international travelers—develop TD each year. It is more common in the developing world, where rates exceed 60%, but has been reported in some form in virtually every travel destination in the world. Society and culture Moctezumas revenge is a colloquial term for travelers diarrhea contracted in Mexico. The name refers to Moctezuma II (1466–1520), the Tlatoani (ruler) of the Aztec civilization who was overthrown by the Spanish conquistador Hernán Cortés in the early 16th century, thereby bringing large portions of what is now Mexico and Central America under the rule of the Spanish crown. Wilderness diarrhea Wilderness diarrhea, also called wilderness-acquired diarrhea (WAD) or backcountry diarrhea, refers to diarrhea among backpackers, hikers, campers and other outdoor recreationalists in wilderness or backcountry situations, either at home or abroad. It is caused by the same fecal microorganisms as other forms of travelers diarrhea, usually bacterial or viral. Since wilderness campsites seldom provide access to sanitation facilities, the infection risk is similar to that of any developing country. Water treatment, good hygiene, and dish washing have all been shown to reduce the incidence of WAD. See also Diarrhea References This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention. External links "Travelers Diarrhea". Centers for Disease Control and Prevention.

Hey Aarogya!, what is Trichinosis

Trichinosis

Trichinosis, also known as trichinellosis, is a parasitic disease caused by roundworms of the Trichinella type. During the initial infection, invasion of the intestines can result in diarrhea, abdominal pain, and vomiting. Migration of larvae to muscle, which occurs about a week after being infected, can cause swelling of the face, inflammation of the whites of the eyes, fever, muscle pains, and a rash. Minor infection may be without symptoms. Complications may include inflammation of heart muscle, central nervous system involvement, and inflammation of the lungs.Trichinosis is mainly spread when undercooked meat containing Trichinella cysts is eaten. In North America this is most often bear, but infection can also occur from pork, boar, and dog meat. Several species of Trichinella can cause disease, with T. spiralis being the most common. After being eaten, the larvae are released from their cysts in the stomach. They then invade the wall of the small intestine, where they develop into adult worms. After one week, the females release new larvae that migrate to voluntarily controlled muscles, where they form cysts. The diagnosis is usually based on symptoms and confirmed by finding specific antibodies in the blood, or larvae on tissue biopsy.The best way to prevent trichinosis is to fully cook meat. A food thermometer can verify that the temperature inside the meat is high enough. Infection is typically treated with antiparasitic medication such as albendazole or mebendazole. Rapid treatment may kill adult worms and thereby stop further worsening of symptoms. Both medications are considered safe, but have been associated with side effects such as bone marrow suppression. Their use during pregnancy or in children under the age of 2 years is poorly studied, but appears to be safe. Treatment with steroids is sometimes also required in severe cases. Without treatment, symptoms typically resolve within three months.Worldwide, about 10,000 infections occur a year. At least 55 countries including the United States, China, Argentina, and Russia have had recently documented cases. While the disease occurs in the tropics, it is less common there. Rates of trichinosis in the United States have decreased from about 400 cases per year in the 1940s to 20 or fewer per year in the 2000s. The risk of death from infection is low. Signs and symptoms The great majority of trichinosis infections have either minor or no symptoms and no complications. The two main phases for the infection are enteral (affecting the intestines) and parenteral (outside the intestines). The symptoms vary depending on the phase, species of Trichinella, quantity of encysted larvae ingested, age, sex, and host immunity. Enteral phase A large burden of adult worms in the intestines promotes symptoms such as nausea, heartburn, dyspepsia, and diarrhea from two to seven days after infection, while small worm burdens generally are asymptomatic. Eosinophilia presents early and increases rapidly. Parenteral phase The severity of symptoms caused by larval migration from the intestines depends on the number of larvae produced. As the larvae migrate through tissue and vessels, the bodys inflammatory response results in edema, muscle pain, fever, and weakness. A classic sign of trichinosis is periorbital edema, swelling around the eyes, which may be caused by vasculitis. Splinter hemorrhage in the nails is also a common symptom.They may very rarely cause enough damage to produce serious neurological deficits (such as ataxia or respiratory paralysis) from worms entering the central nervous system (CNS), which is compromised by trichinosis in 10–24% of reported cases of cerebral venous sinus thrombosis, a very rare form of stroke (three or four cases per million annual incidence in adults). Trichinosis can be fatal depending on the severity of the infection; death can occur 4–6 weeks after the infection, and is usually caused by myocarditis, encephalitis, or pneumonia. Cause The classical agent is T. spiralis (found worldwide in many carnivorous and omnivorous animals, both domestic and sylvatic (wild), but seven primarily sylvatic species of Trichinella also are now recognized: Species and characteristics T. spiralis is most adapted to swine, most pathogenic in humans, and is cosmopolitan in distribution. T. britovi is the second-most common species to infect humans; it is distributed throughout Europe, Asia, and northern and western Africa, usually in wild carnivores, crocodiles, birds, wild boar, and domesticated pigs. T. murrelli also infects humans, especially from black bear meat; it is distributed among wild carnivores in North America. T. nativa, which has a high resistance to freezing, is found in the Arctic and subarctic regions; reservoir hosts include polar bears, Arctic foxes, walruses, and other wild game. T. nelsoni, found in East African predators and scavengers, has been documented to cause a few human cases. T. papuae infects both mammals and reptiles, including crocodiles, humans, and wild and domestic pigs; this species, found in Papua New Guinea and Thailand, is also nonencapsulated. T. pseudospiralis infects birds and mammals, and has demonstrated infection in humans; it is a nonencapsulated species. T. zimbabwensis can infect mammals, and possibly humans; this nonencapsulated species was detected in crocodiles in Africa. Taxonomy Kingdom: Animalia Phylum: Nematoda Class: Adenophorea Order: Trichurida Family: Trichinellidae Genus: Trichinella Lifecycle The typical lifecycle for T. spiralis involves humans, pigs, and rodents. A pig becomes infected when it eats infectious cysts in raw meat, often porcine carrion or a rat (sylvatic cycle). A human becomes infected by consuming raw or undercooked infected pork (domestic cycle). In the stomach, the cysts from infected undercooked meat are acted on by pepsin and hydrochloric acid, which help release the larvae from the cysts into the stomach. The larvae then migrate to the small intestine, and burrow into the intestinal mucosa, where they molt four times before becoming adults.Thirty to 34 hours after the cysts were originally ingested, the adults mate, and within five days produce larvae. Adult worms can only reproduce for a limited time, because the immune system eventually expels them from the small intestine. The larvae then use their piercing mouthpart, called the "stylet", to pass through the intestinal mucosa and enter the lymphatic vessels, and then enter the bloodstream.The larvae travel by capillaries to various organs, such as the retina, myocardium, or lymph nodes; however, only larvae that migrate to skeletal muscle cells survive and encyst. The larval host cell becomes a nurse cell, in which the larva will be encapsulated, potentially for the life of the host, waiting for the host to be eaten. The development of a capillary network around the nurse cell completes encystation of the larva. Trichinosis is not soil-transmitted, as the parasite does not lay eggs, nor can it survive long outside a host. Diagnosis Diagnosis of trichinosis is confirmed by a combination of exposure history, clinical diagnosis, and laboratory testing. Exposure history An epidemiological investigation can be done to determine a patients exposure to raw infected meat. Often, an infection arises from home-preparation of contaminated meat, in which case microscopy of the meat may be used to determine the infection. Exposure determination does not have to be directly from a laboratory-confirmed infected animal. Indirect exposure criteria include the consumption of products from a laboratory-confirmed infected animal, or sharing of a common exposure with a laboratory-confirmed infected human. Clinical diagnosis Clinical presentation of the common trichinosis symptoms may also suggest infection. These symptoms include eye puffiness, splinter hemorrhage, nonspecific gastroenteritis, and muscle pain. The case definition for trichinosis at the European Center for Disease Control states, "at least three of the following six: fever, muscle soreness and pain, gastrointestinal symptoms, facial edema, eosinophilia, and subconjunctival, subungual, and retinal hemorrhages." Laboratory testing Blood tests and microscopy can be used to aid in the diagnosis of trichinosis. Blood tests include a complete blood count for eosinophilia, creatine phosphokinase activity, and various immunoassays such as ELISA for larval antigens. Prevention Legislation Laws and rules for food producers may improve food safety for consumers, such as the rules established by the European Commission for inspections, rodent control, and improved hygiene. A similar protocol exists in the United States, in the USDA guidelines for farms and slaughterhouse responsibilities in inspecting pork. Education and training Public education about the dangers of consuming raw and undercooked meat, especially pork, may reduce infection rates. Hunters are also an at-risk population due to their contact and consumption of wild game, including bear. As such, many states, such as New York, require the completion of a course in such matters before a hunting license can be obtained. Meat testing Testing methods are available for both individual carcasses and monitoring of the herds. Artificial digestion method is usually used for the testing of individual carcasses, while the testing for specific antibodies is usually used for herd monitoring. Food preparation Larvae may be killed by the heating or irradiation of raw meat. Freezing is normally only effective for T. spiralis, since other species, such as T. nativa, are freeze-resistant and can survive long-term freezing. All meat (including pork) can be safely prepared by cooking to an internal temperature of 165 °F (74 °C) or higher for 15 seconds or more. Wild game: Wild game meat must be cooked thoroughly (see meat preparation above) Freezing wild game does not kill all trichinosis larval worms, because the worm species that typically infests wild game can resist freezing. Pork: Freezing cuts of pork less than 6 inches thick for 20 days at 5 °F (−15 °C) or three days at −4 °F (−20 °C) kills T. spiralis larval worms; but this will not kill other trichinosis larval worm species, such as T. nativa, if they have infested the pork food supply (which is unlikely, due to geography).Pork can be safely cooked to a slightly lower temperature, provided that the internal meat temperature is at least as hot for at least as long as listed in the USDA table below. Nonetheless, allowing a margin of error for variation in internal temperature within a particular cut of pork, which may have bones that affect temperature uniformity, is prudent. In addition, kitchen thermometers have measurement error that must be considered. Pork may be cooked for significantly longer and at a higher uniform internal temperature than listed below to be safe. Unsafe and unreliable methods of cooking meat include the use of microwave ovens, curing, drying, and smoking, as these methods are difficult to standardize and control. Pig farming Incidence of infection can be reduced by: Keeping pigs in clean pens, with floors that can be washed (such as concrete) Not allowing hogs to eat carcasses of other animals, including rats, which may be infected with Trichinella Cleaning meat grinders thoroughly when preparing ground meats Control and destruction of meat containing trichinae, e.g., removal and proper disposal of porcine diaphragms prior to public sale of meatThe US Centers for Disease Control and Prevention make the following recommendation: "Curing (salting), drying, smoking, or microwaving meat does not consistently kill infective worms." However, under controlled commercial food processing conditions, some of these methods are considered effective by the USDA.The USDA Animal and Plant Health Inspection Service (APHIS) is responsible for the regulations concerning the importation of swine from foreign countries. The Foreign Origin Meat and Meat Products, Swine section covers swine meat (cooked, cured and dried, and fresh). APHIS developed the National Trichinae Certification Program; this is a voluntary "preharvest" program for U.S. swine producers "that will provide documentation of swine management practices" to reduce the incidence of Trichinella in swine. The CDC reports 0.013% of U.S. swine are infected with Trichinella. Treatment As with most diseases, early treatment is better and decreases the risk of developing disease. If larvae do encyst in skeletal muscle cells, they can remain infectious for months to years. Primary treatment Early administration of anthelmintics, such as mebendazole or albendazole, decreases the likelihood of larval encystation, particularly if given within three days of infection. However, most cases are diagnosed after this time. In humans, mebendazole (200–400 mg three times a day for three days) or albendazole (400 mg twice a day for 8–14 days) is given to treat trichinosis. These drugs prevent newly hatched larvae from developing, but should not be given to pregnant women or children under two years of age.Medical references from the 1940s described no specific treatment for trichinosis at the time, but intravenous injection of calcium salts was found to be useful in managing symptoms related to severe toxemia from the infection.. Secondary treatment After infection, steroids, such as prednisone, may be used to relieve muscle pain associated with larval migration. Vaccine research Researchers trying to develop a vaccine for Trichinella have tried using either "larval extracts, excretory–secretory antigen, DNA, or recombinant antigen protein." Currently, no marketable vaccine is available for trichinosis, but experimental mouse studies have suggested possibilities. In one study, microwaved Trichinella larvae were used to immunize mice (orally or intraperitoneally), which were subsequently infected. Depending on the dosage and frequency of immunization, results ranged from a decreased larval count to complete protection from trichinosis. Another study used extracts and excretory–secretory products from first-stage larvae to produce an oral vaccine. To prevent gastric acids from dissolving the antigens before reaching the small intestine, scientists encapsulated the antigens in microcapsules. This vaccine significantly increased CD4+ cell levels, and increased antigen-specific serum IgGq and IgA, resulting in a statistically significant reduction in the average number of adult worms in the small intestines of mice. The significance of this approach is that, if the white blood cells in the small intestine have been exposed to Trichinella antigens (through vaccination), when an individual does get infected, the immune system will respond to expel the worms from the small intestine fast enough to prevent the female worms from releasing their larvae. A DNA vaccine tested on mice "induced a muscle larva burden reduction in BALB/c mice by 29% in response to T. spiralis infection". Epidemiology About 11 million humans are infected with Trichinella; T. spiralis is the species responsible for most of these infections. Infection was once very common, but this disease is now rare in the developed world, but two known outbreaks occurred in 2015. In the first outbreak, around 40 people were infected in Liguria, Italy, during a New Years Eve celebration. The second outbreak in France was associated with pork sausages from Corsica, which were eaten raw, affecting 14 people in total. The incidence of trichinosis in the U.S. has decreased dramatically in the past century from an average of 400 cases per year mid-20th century down to an annual average of 20 cases per year (2008–10). The number of cases has decreased because of legislation prohibiting the feeding of raw meat garbage to hogs, increased commercial and home freezing of pork, and the public awareness of the danger of eating raw or undercooked pork products.China reports around 10,000 cases every year, so is the country with the highest number of cases. In China, between 1964 and 1998, over 20,000 people became infected with trichinosis, and more than 200 people died.Trichinosis is common in developing countries where meat fed to pigs is raw or undercooked, but infections also arise in developed countries in Europe where raw or undercooked pork, wild boar and horse meat may be consumed as delicacies.In the developing world, most infections are associated with undercooked pork. For example, in Thailand, between 200 and 600 cases are reported annually around the Thai New Year. This is mostly attributable to a particular delicacy, larb, which calls for undercooked pork as part of the recipe.In parts of Eastern Europe, the World Health Organization reports, some swine herds have trichinosis infection rates above 50%, with correspondingly large numbers of human infections. United States Historically, pork products were thought to have the most risk of infecting humans with T. spiralis. However, a trichinosis surveillance conducted between 1997 and 2001 showed a higher percentage of cases caused by consumption of wild game (the sylvatic transmission cycle). This is thought to be due to the Federal Swine Health Protection Act (Public Law 96-468) that was passed by Congress in 1980. Prior to this act, swine were fed garbage that could potentially be infected by T. spiralis. This act was put in place to prevent trichinella-contaminated food from being given to swine. Additionally, other requirements were put in place, such as rodent control, limiting commercial swine contact with wildlife, maintaining good hygiene, and removing dead pigs from pens immediately.Between 2002 and 2007, 11 trichinosis cases were reported to the CDC each year on average in the United States, and 2008–10 averaged 20 cases per year; these were mostly the result of consuming undercooked game (sylvatic transmission) or home-reared pigs (domestic transmission). Religious groups The kashrut and halal dietary laws of Judaism and Islam prohibit eating pork. In the 19th century, when the association between trichinosis and undercooked pork was first established, this association was suggested to be the reason for the prohibition, reminiscent of the earlier opinion of medieval Jewish philosopher Maimonides that food forbidden by Jewish law was "unwholesome". This theory was controversial, and eventually fell out of favor. Reemergence The disappearance of the pathogen from domestic pigs has led to a relaxation of legislation and control efforts by veterinary public health systems. Trichinosis has lately been thought of as a re-emerging zoonosis, supplemented by the increased distribution of meat products, political changes, a changing climate, and increasing sylvatic transmission.Major sociopolitical changes can produce conditions that favor the resurgence of Trichinella infections in swine and, consequently, in humans. For instance, "the overthrow of the social and political structures in the 1990s" in Romania led to an increase in the incidence rate of trichinosis. History As early as 1835, trichinosis was known to have been caused by a parasite, but the mechanism of infection was unclear at the time. A decade later, American scientist Joseph Leidy pinpointed undercooked meat as the primary vector for the parasite, and two decades afterwards, this hypothesis was fully accepted by the scientific community. Parasite The circumstances surrounding the first observation and identification of T. spiralis are controversial, due to a lack of records. In 1835, James Paget, a first-year medical student, first observed the larval form of T. spiralis, while witnessing an autopsy at St. Bartholomew’s Hospital in London. Paget took special interest in the presentation of muscle with white flecks, described as a "sandy diaphragm". Although Paget is most likely the first person to have noticed and recorded these findings, the parasite was named and published in a report by his professor, Richard Owen, who is now credited for the discovery of the T. spiralis larval form. Lifecycle A series of experiments conducted between 1850 and 1870 by the German researchers Rudolf Virchow, Rudolf Leuckart, and Friedrich Albert von Zenker, which involved feeding infected meat to a dog and performing the subsequent necropsy, led to the discovery of the lifecycle of Trichinella. Through these experiments, Virchow was able to describe the development and infectivity of T. spiralis. Research The International Commission on Trichinellosis (ICT) was formed in Budapest in 1958. Its mission is to exchange information on the epidemiology, biology, pathophysiology, immunology, and clinical aspects of trichinosis in humans and animals. Prevention is a primary goal. Since the creation of the ICT, its members (more than 110 from 46 countries) have regularly gathered and worked together during meetings held every four years: the International Conference on Trichinellosis. See also List of parasites (human) Nurse cell References External links International Commission on trichinellosis web pages CDC Department of Parasitic Diseases – Trichinosis Jokelainen P, Näreaho A, Hälli O, Heinonen M, Sukura A (June 2012). "Farmed wild boars exposed to Toxoplasma gondii and Trichinella spp". Vet. Parasitol. 187 (1–2): 323–27. doi:10.1016/j.vetpar.2011.12.026. PMID 22244535.

Do you know what is Trichomoniasis, Aarogya

Trichomoniasis

Trichomoniasis (trich) is an infectious disease caused by the parasite Trichomonas vaginalis. About 70% of affected people do not have symptoms when infected. When symptoms occur, they typically begin 5 to 28 days after exposure. Symptoms can include itching in the genital area, a bad smelling thin vaginal discharge, burning with urination, and pain with sex. Having trichomoniasis increases the risk of getting HIV/AIDS. It may also cause complications during pregnancy.Trichomoniasis is a sexually transmitted infection (STI) which is most often spread through vaginal, oral, or anal sex. It can also spread through genital touching. People who are infected may spread the disease even when symptoms are not present. Diagnosis is by finding the parasite in the vaginal fluid using a microscope, culturing the vaginal fluid or urine, or testing for the parasites DNA. If present, other STIs should be tested for.Methods of prevention include not having sex, using condoms, not douching, and being tested for STIs before having sex with a new partner. Although not caused by a bacteria, trichomoniasis can be cured with certain antibiotics (metronidazole, tinidazole, secnidazole). Sexual partners should also be treated. About 20% of people get infected again within three months of treatment.There were about 122 million new cases of trichomoniasis in 2015. In the United States, there are about 2 million women affected. It occurs more often in women than men. Trichomonas vaginalis was first identified in 1836 by Alfred Donné. It was first recognized as causing this disease in 1916. Signs and symptoms Most people infected with Trichomonas vaginalis do not have any symptoms and can be undetected for years. Symptoms experienced include pain, burning or itching in the penis, urethra (urethritis), or vagina (vaginitis). Discomfort for both sexes may increase during intercourse and urination. For women there may also be a yellow-green, itchy, frothy, foul-smelling ("fishy" smell) vaginal discharge. In rare cases, lower abdominal pain can occur. Symptoms usually appear within 5 to 28 days of exposure. Sometimes trichomoniasis can be confused with chlamydia because the symptoms are similar. Complications Trichomoniasis is linked to several serious complications. Trichomoniasis is associated with increased risk of transmission and infection of HIV. Trichomoniasis may cause a woman to deliver a low-birth-weight or premature infant. The role of Trichomonas infection in causing cervical cancer is unclear, although trichomonas infection may be associated with co-infection with high-risk strains of HPV. T. vaginalis infection in males has been found to cause asymptomatic urethritis and prostatitis. In the prostate, it may create chronic inflammation that may eventually lead to prostate cancer. Causes The human genital tract is the only reservoir for this species. Trichomonas is transmitted through sexual or genital contact.The single-celled protozoan produces mechanical stress on host cells and then ingests cell fragments after cell death. Genetic sequence A draft sequence of the Trichomonas genome was published on January 12, 2007, in the journal Science confirming that the genome has at least 26,000 genes, a similar number to the human genome. An additional approximately 34,000 unconfirmed genes, including thousands that are part of potentially transposable elements, brings the gene content to well over 60,000. Diagnosis There are three main ways to test for trichomoniasis. The first is known as saline microscopy. This is the most commonly used method and requires an endocervical, vaginal, or penile swab specimen for examination under a microscope. The presence of one or multiple trichomonads constitutes a positive result. This method is cheap but has a low sensitivity (60–70%) often due to an inadequate sample, resulting in false negatives. The second diagnostic method is culture, which has historically been the "gold standard" in infectious disease diagnosis. Trichomonas vaginalis culture tests are relatively cheap; however, sensitivity is still somewhat low (70–89%). The third method includes the nucleic acid amplification tests (NAATs) which are more sensitive. These tests are more costly than microscopy and culture, and are highly sensitive (80–90%). Prevention Use of male condoms or female condoms may help prevent the spread of trichomoniasis, although careful studies have never been done that focus on how to prevent this infection. Infection with trichomoniasis through water is unlikely because Trichomonas vaginalis dies in water after 45–60 minutes, in thermal water after 30 minutes to 3 hours and in diluted urine after 5–6 hours.Currently there are no routine standard screening requirements for the general U.S. population receiving family planning or STI testing. The Centers for Disease Control and Prevention (CDC) recommends trichomoniasis testing for females with vaginal discharge and can be considered for females at higher risk for infection or of HIV-positive serostatus.The advent of new, highly specific and sensitive trichomoniasis tests present opportunities for new screening protocols for both men and women. Careful planning, discussion, and research are required to determine the cost-efficiency and most beneficial use of these new tests for the diagnosis and treatment of trichomoniasis in the U.S., which can lead to better prevention efforts.A number of strategies have been found to improve follow-up for STI testing including email and text messaging as reminders of appointments. Screening Evidence from a randomized controlled trials for screening pregnant women who do not have symptoms for infection with trichomoniasis and treating women who test positive for the infection have not consistently shown a reduced risk of preterm birth. Further studies are needed to verify this result and determine the best method of screening. In the US, screening of pregnant women without any symptoms is only recommended in those with HIV as Trichomonas infection is associated with increased risk of transmitting HIV to the fetus. Treatment Treatment for both pregnant and non-pregnant women is usually with metronidazole, by mouth once. Caution should be used in pregnancy, especially in the first trimester. Sexual partners, even if they have no symptoms, should also be treated. Single oral dose of nitroimidazole is sufficient to kill the parasites.For 95–97% of cases, infection is resolved after one dose of metronidazole. Studies suggest that 4–5% of trichomonas cases are resistant to metronidazole, which may account for some "repeat" cases. Without treatment, trichomoniasis can persist for months to years in women, and is thought to improve without treatment in men. Women living with HIV infection have better cure rates if treated for seven days rather than with one dose.Topical treatments are less effective than oral antibiotics due to Skenes gland and other genitourinary structures acting as a reservoir. Epidemiology There were about 58 million cases of trichomoniasis in 2013. It is more common in women (2.7%) than males (1.4%). It is the most common non-viral STI in the U.S., with an estimated 3.7 million prevalent cases and 1.1 million new cases per year. It is estimated that 3% of the general U.S. population is infected, and 7.5–32% of moderate-to-high risk (including incarcerated) populations. References External links Trichomoniasis at Centers for Disease Control and Prevention Vaginitis/Vaginal infection fact sheet from the National Institute of Allergies and Infections. The first version of this article was taken from this public domain resource. eMedicine Health Trichomoniasis Archived 2008-05-22 at the Wayback Machine

Hello Aarogya , Do you know what is Tricyclic antidepressant overdose,

Tricyclic antidepressant overdose

Tricyclic antidepressant overdose is poisoning caused by excessive medication of the tricyclic antidepressant (TCA) type. Symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest. If symptoms have not occurred within six hours of exposure they are unlikely to occur.TCA overdose may occur by accident or purposefully in an attempt to cause death. The toxic dose depends on the specific TCA. Most are non-toxic at less than 5 mg/kg except for desipramine, nortriptyline, and trimipramine, which are generally non-toxic at less than 2.5 mg/kg. In small children one or two pills can be fatal. An electrocardiogram (ECG) should be included in the assessment when there is concern of an overdose.In overdose activated charcoal is often recommended. People should not be forced to vomit. In those who have a wide QRS complex (> 100 ms) sodium bicarbonate is recommended. If seizures occur benzodiazepines should be given. In those with low blood pressure intravenous fluids and norepinephrine may be used. The use of intravenous lipid emulsion may also be tried.In the early 2000s TCAs were one of the most common cause of poisoning. In the United States in 2004 there were more than 12,000 cases. In the United Kingdom they resulted in about 270 deaths a year. An overdose from TCAs was first reported in 1959. Signs and symptoms The peripheral autonomic nervous system, central nervous system and the heart are the main systems that are affected following overdose. Initial or mild symptoms typically develop within 2 hours and include tachycardia, drowsiness, a dry mouth, nausea and vomiting, urinary retention, confusion, agitation, and headache. More severe complications include hypotension, cardiac rhythm disturbances, hallucinations, and seizures. Electrocardiogram (ECG) abnormalities are frequent and a wide variety of cardiac dysrhythmias can occur, the most common being sinus tachycardia and intraventricular conduction delay resulting in prolongation of the QRS complex and the PR/QT intervals. Seizures, cardiac dysrhythmias, and apnea are the most important life-threatening complications. Cause Tricyclics have a narrow therapeutic index, i.e., the therapeutic dose is close to the toxic dose. Factors that increase the risk of toxicity include advancing age, cardiac status, and concomitant use of other drugs. However, serum drug levels are not useful for evaluating risk of arrhythmia or seizure in tricyclic overdose. Pathophysiology Most of the toxic effects of TCAs are caused by four major pharmacological effects. TCAs have anticholinergic effects, cause excessive blockade of norepinephrine reuptake at the preganglionic synapse, direct alpha adrenergic blockade, and importantly they block sodium membrane channels with slowing of membrane depolarization, thus having quinidine-like effects on the myocardium. Diagnosis A specific blood test to verify toxicity is not typically available. An electrocardiogram (ECG) should be included in the assessment when there is concern of an overdose. Treatment People with symptoms are usually monitored in an intensive care unit for a minimum of 12 hours, with close attention paid to maintenance of the airways, along with monitoring of blood pressure, arterial pH, and continuous ECG monitoring. Supportive therapy is given if necessary, including respiratory assistance and maintenance of body temperature. Once a person has had a normal ECG for more than 24 hours they are generally medically clear. Decontamination Initial treatment of an acute overdose includes gastric decontamination. This is achieved by giving activated charcoal, which adsorbs the drug in the gastrointestinal tract either by mouth or via a nasogastric tube. Activated charcoal is most useful if given within 1 to 2 hours of ingestion. Other decontamination methods such as stomach pumps, ipecac induced emesis, or whole bowel irrigation are generally not recommended in TCA poisoning. Stomach pumps may be considered within an hour of ingestion but evidence to support the practice is poor. Medication Administration of intravenous sodium bicarbonate as an antidote has been shown to be an effective treatment for resolving the metabolic acidosis and cardiovascular complications of TCA poisoning. If sodium bicarbonate therapy fails to improve cardiac symptoms, conventional antidysrhythmic drugs or magnesium can be used to reverse any cardiac abnormalities. However, no benefit has been shown from Class 1 antiarrhythmic drugs; it appears they worsen the sodium channel blockade, slow conduction velocity, and depress contractility and should be avoided in TCA poisoning. Low blood pressure is initially treated with fluids along with bicarbonate to reverse metabolic acidosis (if present), if the blood pressure remains low despite fluids then further measures such as the administration of epinephrine, norepinephrine, or dopamine can be used to increase blood pressure.Another potentially severe symptom is seizures: Seizures often resolve without treatment but administration of a benzodiazepine or other anticonvulsive may be required for persistent muscular overactivity. There is no role for physostigmine in the treatment of tricyclic toxicity as it may increase cardiac toxicity and cause seizures. In cases of severe TCA overdose that are refractory to conventional therapy, intravenous lipid emulsion therapy has been reported to improve signs and symptoms in moribund patients with toxicities involving several types of lipophilic substances, therefore lipids may have a role in treating severe cases of refractory TCA overdose. Dialysis Tricyclic antidepressants are highly protein bound and have a large volume of distribution; therefore removal of these compounds from the blood with hemodialysis, hemoperfusion or other techniques are unlikely to be of any significant benefit. Epidemiology Studies in the 1990s in Australia and the United Kingdom showed that between 8 and 12% of drug overdoses were following TCA ingestion. TCAs may be involved in up to 33% of all fatal poisonings, second only to analgesics. Another study reported 95% of deaths from antidepressants in England and Wales between 1993 and 1997 were associated with tricyclic antidepressants, particularly dothiepin and amitriptyline. It was determined there were 5.3 deaths per 100,000 prescriptions.Sodium channel blockers such as Dilantin should not be used in the treatment of TCA overdose as the Na+ blockade will increase the QTI. References == External links ==

Hey Aarogya, could you help me understand about Trigeminal neuralgia

Trigeminal neuralgia

Trigeminal neuralgia (TN or TGN), also called Fothergill Disease, Tic Douloureux, or Trifacial Neuralgia is a long-term pain disorder that affects the trigeminal nerve, the nerve responsible for sensation in the face and motor functions such as biting and chewing. It is a form of neuropathic pain. There are two main types: typical and atypical trigeminal neuralgia. The typical form results in episodes of severe, sudden, shock-like pain in one side of the face that lasts for seconds to a few minutes. Groups of these episodes can occur over a few hours. The atypical form results in a constant burning pain that is less severe. Episodes may be triggered by any touch to the face. Both forms may occur in the same person. It is regarded as one of the most painful disorders known to medicine, and often results in depression.The exact cause is unknown, but believed to involve loss of the myelin of the trigeminal nerve. This might occur due to compression from a blood vessel as the nerve exits the brain stem, multiple sclerosis, stroke, or trauma. Less common causes include a tumor or arteriovenous malformation. It is a type of nerve pain. Diagnosis is typically based on the symptoms, after ruling out other possible causes such as postherpetic neuralgia.Treatment includes medication or surgery. The anticonvulsant carbamazepine or oxcarbazepine is usually the initial treatment, and is effective in about 90% of people. Side effects are frequently experienced that necessitate drug withdrawal in as many as 23% of patients. Other options include lamotrigine, baclofen, gabapentin, amitriptyline and pimozide. Opioids are not usually effective in the typical form. In those who do not improve or become resistant to other measures, a number of types of surgery may be tried.It is estimated that 1 in 8,000 people per year develop trigeminal neuralgia. It usually begins in people over 50 years old, but can occur at any age. Women are more commonly affected than men. The condition was first described in detail in 1773 by John Fothergill. Signs and symptoms This disorder is characterized by episodes of severe facial pain along the trigeminal nerve divisions. The trigeminal nerve is a paired cranial nerve that has three major branches: the ophthalmic nerve (V1), the maxillary nerve (V2), and the mandibular nerve (V3). One, two, or all three branches of the nerve may be affected. Trigeminal neuralgia most commonly involves the middle branch (the maxillary nerve or V2) and lower branch (mandibular nerve or V3) of the trigeminal nerve.An individual attack usually lasts from a few seconds to several minutes or hours, but these can repeat for hours with very short intervals between attacks. In other instances, only 4–10 attacks are experienced daily. The episodes of intense pain may occur paroxysmally. To describe the pain sensation, people often describe a trigger area on the face so sensitive that touching or even air currents can trigger an episode; however, in many people, the pain is generated spontaneously without any apparent stimulation. It affects lifestyle as it can be triggered by common activities such as eating, talking, shaving and brushing teeth. The wind, chewing, and talking can aggravate the condition in many patients. The attacks are said, by those affected, to feel like stabbing electric shocks, burning, sharp, pressing, crushing, exploding or shooting pain that becomes intractable.The pain also tends to occur in cycles with remissions lasting months or even years. Pain attacks are known to worsen in frequency or severity over time, in some people. Pain may migrate to other branches over time but in some people remains very stable.Bilateral (occurring on both sides) trigeminal neuralgia is very rare except for trigeminal neuralgia caused by multiple sclerosis (MS). This normally indicates problems with both trigeminal nerves, since one nerve serves the left side of the face and the other serves the right side. Occasional reports of bilateral trigeminal neuralgia reflect successive episodes of unilateral (only one side) pain switching the side of the face rather than pain occurring simultaneously on both sides.Rapid spreading of the pain, bilateral involvement or simultaneous participation with other major nerve trunks (such as Painful Tic Convulsif of nerves V & VII or occurrence of symptoms in the V and IX nerves) may suggest a systemic cause. Systemic causes could include multiple sclerosis or expanding cranial tumors.The severity of the pain makes it difficult to wash the face, shave, and perform good oral hygiene. The pain has a significant impact on activities of daily living especially as those affected live in fear of when they are going to get their next attack of pain and how severe it will be. It can lead to severe depression and anxiety.However, not all people will have the symptoms described above and there are variants of TN. One of which is atypical trigeminal neuralgia ("trigeminal neuralgia, type 2" or trigeminal neuralgia with concomitant pain), based on a recent classification of facial pain. In these instances there is also a more prolonged lower severity background pain that can be present for over 50% of the time and is described more as a burning or prickling, rather than a shock. Trigeminal pain can also occur after an attack of herpes zoster. Post-herpetic neuralgia has the same manifestations as in other parts of the body. Herpes zoster oticus typically presents with inability to move many facial muscles, pain in the ear, taste loss on the front of the tongue, dry eyes and mouth, and a vesicular rash. Less than 1% of varicella zoster infections involve the facial nerve and result in this occurring.Trigeminal deafferentation pain (TDP), also termed anesthesia dolorosa, or colloquially as phantom face pain, is from intentional damage to a trigeminal nerve following attempts to surgically fix a nerve problem. This pain is usually constant with a burning sensation and numbness. TDP is very difficult to treat as further surgeries are usually ineffective and possibly detrimental to the person. Causes The trigeminal nerve is a mixed cranial nerve responsible for sensory data such as tactition (pressure), thermoception (temperature), and nociception (pain) originating from the face above the jawline; it is also responsible for the motor function of the muscles of mastication, the muscles involved in chewing but not facial expression.Several theories exist to explain the possible causes of this pain syndrome. It was once believed that the nerve was compressed in the opening from the inside to the outside of the skull; but leading research indicates that it is an enlarged or lengthened blood vessel – most commonly the superior cerebellar artery – compressing or throbbing against the microvasculature of the trigeminal nerve near its connection with the pons. Such a compression can injure the nerves protective myelin sheath and cause erratic and hyperactive functioning of the nerve. This can lead to pain attacks at the slightest stimulation of any area served by the nerve as well as hinder the nerves ability to shut off the pain signals after the stimulation ends. This type of injury may rarely be caused by an aneurysm (an outpouching of a blood vessel); by an AVM (arteriovenous malformation); by a tumor; such as an arachnoid cyst or meningioma in the cerebellopontine angle; or by a traumatic event, such as a car accident.Short-term peripheral compression is often painless. Persistent compression results in local demyelination with no loss of axon potential continuity. Chronic nerve entrapment results in demyelination primarily, with progressive axonal degeneration subsequently. It is, "therefore widely accepted that trigeminal neuralgia is associated with demyelination of axons in the Gasserian ganglion, the dorsal root, or both." It has been suggested that this compression may be related to an aberrant branch of the superior cerebellar artery that lies on the trigeminal nerve. Further causes, besides an aneurysm, multiple sclerosis or cerebellopontine angle tumor, include: a posterior fossa tumor, any other expanding lesion or even brainstem diseases from strokes.Trigeminal neuralgia is found in 3–4% of people with multiple sclerosis, according to data from seven studies. It has been theorized that this is due to damage to the spinal trigeminal complex. Trigeminal pain has a similar presentation in patients with and without MS.Postherpetic neuralgia, which occurs after shingles, may cause similar symptoms if the trigeminal nerve is damaged, called Ramsay Hunt syndrome type 2. When there is no apparent structural cause, the syndrome is called idiopathic. Diagnosis Trigeminal neuralgia is diagnosed via the result of neurological and physical tests, as well as the individuals medical history. Management As with many conditions without clear physical or laboratory diagnosis, TN is sometimes misdiagnosed. A person with TN will sometimes seek the help of numerous clinicians before a firm diagnosis is made.There is evidence that points towards the need to quickly treat and diagnose TN. It is thought that the longer a patient has TN, the harder it may be to reverse the neural pathways associated with the pain.The differential diagnosis includes temporomandibular disorder. Since triggering may be caused by movements of the tongue or facial muscles, TN must be differentiated from masticatory pain that has the clinical characteristics of deep somatic rather than neuropathic pain. Masticatory pain will not be arrested by a conventional mandibular local anesthetic block. One quick test a dentist might perform is a conventional inferior dental local anaesthetic block, if the pain is in this branch, as it will not arrest masticatory pain but will TN. Medical The anticonvulsant carbamazepine is the first line treatment; second line medications include baclofen, lamotrigine, oxcarbazepine, phenytoin, topiramate, gabapentin and pregabalin. Uncontrolled trials have suggested that clonazepam and lidocaine may be effective. Antidepressant medications, such as amitriptyline have shown good efficacy in treating trigeminal neuralgia, especially if combined with an anti-convulsant drug such as pregabalin. There is some evidence that duloxetine can also be used in some cases of neuropathic pain, especially in patients with major depressive disorder as it is an antidepressant. However, it should, by no means, be considered a first line therapy and should only be tried by specialist advice. There is controversy around opiate use such as morphine and oxycodone for treatment of TN, with varying evidence on its effectiveness for neuropathic pain. Generally, opioids are considered ineffective against TN and thus should not be prescribed. Surgical Microvascular decompression provides freedom from pain in about 75% of patients presenting with drug-resistant trigeminal neuralgia. While there may be pain relief after surgery, there is also a risk of adverse effects, such as facial numbness. Percutaneous radiofrequency thermorhizotomy may also be effective as may stereotactic radiosurgery; however the effectiveness decreases with time.Surgical procedures can be separated into non-destructive and destructive: Non-destructive Microvascular decompression – this involves a small incision behind the ear and some bone removal from the area. An incision through the meninges is made to expose the nerve. Any vascular compressions of the nerve are carefully moved and a sponge-like pad is placed between the compression and nerve, stopping unwanted pulsation and allowing myelin sheath healing. Destructive All destructive procedures will cause facial numbness, post relief, as well as pain relief. Percutaneous techniques which all involve a needle or catheter entering the face up to the origin where the nerve splits into three divisions and then damaging this area, purposely, to produce numbness but also stop pain signals. These techniques are proven effective especially in those where other interventions have failed or in those who are medically unfit for surgery such as the elderly. Balloon compression – inflation of a balloon at this point causing damage and stopping pain signals. Glycerol injection – deposition of a corrosive liquid called glycerol at this point causes damage to the nerve to hinder pain signals. Radiofrequency thermocoagulation rhizotomy – application of a heated needle to damage the nerve at this point. Stereotactic radiosurgery is a form of radiation therapy that focuses high-power energy on a small area of the body Support Psychological and social support has found to play a key role in the management of chronic illnesses and chronic pain conditions, such as trigeminal neuralgia. Chronic pain can cause constant frustration to an individual as well as to those around them. History Trigeminal neuralgia was first described by physician John Fothergill and treated surgically by John Murray Carnochan, both of whom were graduates of the University of Edinburgh Medical School. Historically TN has been called "suicide disease" due to studies by the pioneering forefather in neurosurgery Harvey Cushing involving 123 cases of TN during 1896 and 1912. Often called the "suicide disease" because of the intense pain, higher rates of suicidal ideation in patients with severe migraines, and links to higher rates of depression, anxiety, and sleep disorders, trigeminal neuralgia is pain that spreads over the face and down the neck, triggered by even the slightest breath of wind across the face. Society and culture Some individuals of note with TN include: Four-time British Prime Minister William Gladstone is believed to have had the disease. Entrepreneur and author Melissa Seymour was diagnosed with TN in 2009 and underwent microvascular decompression surgery in a well documented case covered by magazines and newspapers which helped to raise public awareness of the illness in Australia. Seymour was subsequently made a Patron of the Trigeminal Neuralgia Association of Australia. Salman Khan, an Indian film star, was diagnosed with TN in 2011. He underwent surgery in the US. All-Ireland winning Gaelic footballer Christy Toye was diagnosed with the condition in 2013. He spent five months in his bedroom at home, returned for the 2014 season and lined out in another All-Ireland final with his team. Jim Fitzpatrick – former Member of Parliament (MP) for Poplar and Limehouse – disclosed he had trigeminal neuralgia before undergoing neurosurgery. He has openly discussed his condition at parliamentary meetings and is a prominent figure in the TNA UK charity. Jefferson Davis – President of the Confederate States of America Charles Sanders Peirce – American philosopher, scientist and father of pragmatism. Gloria Steinem – American feminist, journalist, and social and political activist Anneli van Rooyen, Afrikaans singer-songwriter popular during the 1980s and 1990s, was diagnosed with atypical trigeminal neuralgia in 2004. During surgical therapy directed at alleviating the condition performed in 2007, Van Rooyen had permanent nerve damage, resulting in her near-complete retirement from performing. H.R., singer of hardcore punk band Bad Brains Aneeta Prem, British author, human rights campaigner, magistrate and the founder and president of Freedom Charity. Aneetas experience of bilateral TN began in 2010, with severe pain and resulting sleep deprivation. Her condition remained undiagnosed until 2017. MVD Surgery to ameliorate the pain on the right-hand side was performed at UCHL in December 2019. Travis Barker, drummer of rock band Blink-182 See also Cluster headache Trigeminal trophic syndrome References External links Trigeminal neuralgia at Curlie Trigeminal Neuralgia at NHS Choices

Would you describe Tropical sprue, to me Aarogya

Tropical sprue

Tropical sprue is a malabsorption disease commonly found in tropical regions, marked with abnormal flattening of the villi and inflammation of the lining of the small intestine. It differs significantly from coeliac sprue. It appears to be a more severe form of environmental enteropathy. Signs and symptoms The illness usually starts with an attack of acute diarrhoea, fever and malaise following which, after a variable period, the patient settles into the chronic phase of diarrhoea, steatorrhoea, weight loss, anorexia, malaise, and nutritional deficiencies. The symptoms of tropical sprue are: Diarrhoea Steatorrhoea or fatty stool (often foul-smelling and whitish in colour) Indigestion Cramps Weight loss and malnutrition FatigueLeft untreated, nutrient and vitamin deficiencies may develop in patients with tropical sprue. These deficiencies may have these symptoms: Vitamin A deficiency: hyperkeratosis or skin scales Vitamin B12 and folic acid deficiencies: anaemia, numbness, and tingling sensation Vitamin D and calcium deficiencies: spasm, bone pain, muscle weakness Vitamin K deficiency: bruises Cause The cause of tropical sprue is not known. It may be caused by persistent bacterial, viral, amoebal, or parasitic infections. Folic acid deficiency, effects of malabsorbed fat on intestinal motility, and persistent small intestinal bacterial overgrowth may combine to cause the disorder. A link between small intestinal bacterial overgrowth and tropical sprue has been proposed to be involved in the aetiology of post-infectious irritable bowel syndrome (IBS). Intestinal immunologic dysfunction, including deficiencies in secretory immunoglobulin A (IgA), may predispose people to malabsorption and bacterial colonization, so tropical sprue may be triggered in susceptible individuals following an acute enteric infection. Diagnosis Diagnosis of tropical sprue can be complicated because many diseases have similar symptoms. The following investigation results are suggestive: Abnormal flattening of villi and inflammation of the lining of the small intestine, observed during an endoscopic procedure. Presence of inflammatory cells (most often lymphocytes) in the biopsy of small intestine tissue. Low levels of vitamins A, B12, E, D, and K, as well as serum albumin, calcium, and folate, revealed by a blood test. Excess fat in the feces (steatorrhoea). Thickened small bowel folds seen on imaging.Tropical sprue is largely limited to within about 30 degrees north and south of the equator. Recent travel to this region is a key factor in diagnosing this disease in residents of countries outside of that geographical region.Other conditions which can resemble tropical sprue need to be differentiated. Coeliac disease (also known as coeliac sprue or gluten sensitive enteropathy), has similar symptoms to tropical sprue, with the flattening of the villi and small intestine inflammation and is caused by an autoimmune disorder in genetically susceptible individuals triggered by ingested gluten. Malabsorption can also be caused by protozoan infections, tuberculosis, HIV/AIDS, immunodeficiency, chronic pancreatitis and inflammatory bowel disease. Environmental enteropathy is a less severe, subclinical condition similar to tropical sprue. Prevention Preventive measures for visitors to tropical areas where the condition exists include steps to reduce the likelihood of gastroenteritis. These may comprise using only bottled water for drinking, brushing teeth, and washing food, and avoiding fruits washed with tap water (or consuming only peeled fruits, such as bananas and oranges). Basic sanitation is necessary to reduce fecal-oral contamination and the impact of environmental enteropathy in the developing world. Treatment Once diagnosed, tropical sprue can be treated by a course of the antibiotic tetracycline or sulphamethoxazole/trimethoprim (co-trimoxazole) for 3 to 6 months. Supplementation of vitamins B12 and folic acid improves appetite and leads to a gain in weight. Prognosis The prognosis for tropical sprue may be excellent after treatment. It usually does not recur in people who get it during travel to affected regions. The recurrence rate for natives is about 20%, but another study showed changes can persist for several years. Epidemiology Tropical sprue is common in the Caribbean, Central and South America, and India and southeast Asia. In the Caribbean, it appeared to be more common in Puerto Rico and Haiti. Epidemics in southern India have occurred. History The disease was first described by William Hillary in 1759 in Barbados. Tropical sprue was responsible for one-sixth of all casualties sustained by the Allied forces in India and Southeast Asia during World War II. The use of folic acid and vitamin B12 in the treatment of tropical sprue was promoted in the late 1940s by Dr. Tom Spies of the University of Alabama, while conducting his research in Cuba and Puerto Rico. == References ==

Hey Aarogya, explain a scenario commonly referred as Tuberculosis management

Tuberculosis management

Tuberculosis management describes the techniques and procedures utilized in treating tuberculosis (TB). The medical standard for active TB is a short course treatment involving a combination of Isoniazid, Rifampicin (also known as Rifampin), Pyrazinamide, and Ethambutol for the first two months. During this initial period, Isoniazid is taken alongside Pyridoxal phosphate to obviate Peripheral neuropathy. Isoniazid is then taken coicident with Rifampicin alone for the remaining four months of treatment. A patient is considered free of all living TB bacteria after six months. Latent tuberculosis or Latent Tuberculosis Infection (LTBI) is treated with three to nine months of Isoniazid alone, this longterm treatment often risks the development of Hepatotoxicity. A combination of Isoniazid plus Rifampicin for a period of three to four months is shown to be an equallly effective method for treating LTBI, while mitigating risks to Hepatotoxicity. Treatment of LTBI is essential in preventing the spread of active TB. Drugs First line All first-line anti-tuberculous drug names have semistandardized three-letter and single-letter abbreviations: ethambutol is EMB or E, isoniazid is INH or H, pyrazinamide is PZA or Z, rifampicin is RMP or R, streptomycin is SM or S.First-line anti-tuberculous drug names are often remembered with the mnemonic "RIPE," referring to the use of a rifamycin (like rifampin), isoniazid, pyrazinamide, and ethambutol. US practice uses abbreviations and names that are not internationally convened: rifampicin is called rifampin and abbreviated RIF; streptomycin is abbreviated STM. Other abbreviations have been widely used (for example, the notations RIF, RFP, and RMP have all been widely used for rifampicin, and the combination regimens have notations such as IRPE, HRZE, RIPE, and IREP that are variously synonyms or near-synonyms, depending on dosage schedules), but for clarity, the semistandardized abbreviations used above are used in the rest of this article. In this system, which the World Health Organization (WHO) supports, "RIPE" is "RHZE". (Both have mnemonic potential, as tuberculosis is named after tubercles (small tubers), and a tuber can be ripe and can be a rhizome.)Drug regimens are similarly abbreviated in a semistandardised manner. The drugs are listed using their single letter abbreviations (in the order given above, which is roughly the order of introduction into clinical practice). A prefix denotes the number of months the treatment should be given for; a subscript denotes intermittent dosing (so 3 means three times a week) and no subscript means daily dosing. Most regimens have an initial high-intensity phase, followed by a continuation phase (also called a consolidation phase or eradication phase): the high-intensity phase is given first, then the continuation phase, the two phases divided by a slash.So, 2HREZ/4HR3means isoniazid, rifampicin, ethambutol, pyrazinamide daily for two months, followed by four months of isoniazid and rifampicin given three times a week.In the US only, streptomycin is not considered a first line drug by ATS/IDSA/CDC because of high rates of resistance. The WHO have made no such recommendation. Second line The second line drugs (WHO groups 2, 3 and 4) are only used to treat disease that is resistant to first line therapy (i.e., for extensively drug-resistant tuberculosis (XDR-TB) or multidrug-resistant tuberculosis (MDR-TB)). A drug may be classed as second-line instead of first-line for one of three possible reasons: it may be less effective than the first-line drugs (e.g., p-aminosalicylic acid); or, it may have toxic side-effects (e.g., cycloserine); or it may be effective, but unavailable in many developing countries (e.g., fluoroquinolones): aminoglycosides (WHO group 2): e.g., amikacin (AMK), kanamycin (KM); polypeptides (WHO group 2): e.g., capreomycin, viomycin, enviomycin; fluoroquinolones (WHO group 3): e.g., ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF); thioamides (WHO group 4): e.g. ethionamide, prothionamide cycloserine (WHO group 4) terizidone (WHO group 5) Third line Third-line drugs (WHO group 5) include drugs that may be useful, but have doubtful or unproven efficacy: rifabutin macrolides: e.g., clarithromycin (CLR); linezolid (LZD); thioacetazone (T); thioridazine; arginine; vitamin D; bedaquiline.These drugs are listed here either because they are not very effective (e.g., clarithromycin) or because their efficacy has not been proven (e.g., linezolid, R207910). Rifabutin is effective, but is not included on the WHO list because for most developing countries, it is impractically expensive. Standard regimen Rationale and evidence Tuberculosis has been treated with combination therapy for over fifty years. Drugs are not used singly (except in latent TB or chemoprophylaxis), and regimens that use only single drugs result in the rapid development of resistance and treatment failure. The rationale for using multiple drugs to treat TB are based on simple probability. The rate of spontaneous mutations that confer resistance to an individual drug are well known: 1 mutation for every 107 cell divisions for EMB, 1 for every 108 divisions for STM and INH, and 1 for every 1010 divisions for RMP.Patients with extensive pulmonary TB have approximately 1012 bacteria in their body, and therefore will probably be harboring approximately 105 EMB-resistant bacteria, 104 STM-resistant bacteria, 104 INH-resistant bacteria and 10² RMP-resistant bacteria. Resistance mutations appear spontaneously and independently, so the chances of them harbouring a bacterium that is spontaneously resistant to both INH and RMP is 1 in 108 × 1 in 1010 = 1 in 1018, and the chances of them harbouring a bacterium that is spontaneously resistant to all four drugs is 1 in 1033. This is, of course, an oversimplification, but it is a useful way of explaining combination therapy.There are other theoretical reasons for supporting combination therapy. The different drugs in the regimen have different modes of action. INH are bacteriocidal against replicating bacteria. EMB is bacteriostatic at low doses, but is used in TB treatment at higher, bactericidal doses. RMP is bacteriocidal and has a sterilizing effect. PZA is only weakly bactericidal, but is very effective against bacteria located in acidic environments, inside macrophages, or in areas of acute inflammation.All TB regimens in use were 18 months or longer until the appearance of rifampicin. In 1953, the standard UK regimen was 3SPH/15PH or 3SPH/15SH2. Between 1965 and 1970, EMB replaced PAS. RMP began to be used to treat TB in 1968 and the BTS study in the 1970s showed that 2HRE/7HR was efficacious. In 1984, a BTS study showed that 2HRZ/4HR was efficacious, with a relapse rate of less than 3% after two years. In 1995, with the recognition that INH resistance was increasing, the British Thoracic Society recommended adding EMB or STM to the regimen: 2HREZ/4HR or 2SHRZ/4HR, which are the regimens currently recommended. The WHO also recommend a six-month continuation phase of HR if the patient is still culture positive after 2 months of treatment (approximately 15% of patients with fully sensitive TB) and for those patients who have extensive bilateral cavitation at the start of treatment. Monitoring, DOTS, and DOTS-Plus DOTS stands for "Directly Observed Treatment, Short-course" and is a major plank in the World Health Organization (WHO) Global Plan to Stop TB. The DOTS strategy focuses on five main points of action. The first element of DOTS involves creating increased sustainable financial services and a short and long-term plan provided by the government, dedicated to eliminating tuberculosis.The World Health Organization helps encourage mobilized funding to reduce poverty standards that will prevent tuberculosis. The second component of the DOTS strategy is case detection, which involves improving the accuracy of laboratory tests for bacteriology and improving communication from labs to doctors and patients. Case detection means that laboratories that detect and test for bacteriology are accurate and communicative to its doctors and patients. The third strategy is to provide standard treatment and patient support. The guidelines to adhere to adequate treatment is to provide pharmaceutical drugs that will help eliminate tuberculosis and follow-up check-ups to ensure that tuberculosis is not a deterring factor in a patients life. There are many cultural barriers as many patients might continue to work under unsanitary living conditions or not have enough money to pay for the treatments. Programs that provide stipends and incentives to allow citizens to seek treatment are also necessary. The fourth element to the DOTS approach is to have a management program that supplies a sustainable long-term supply of reliable antibiotics. Lastly, the fifth component is to record and monitor treatment plans to ensure that the DOTS approach is effective. The DOTS approach not only aims to provide structure for tuberculosis programs, but also to ensure that citizens diagnosed with tuberculosis adhere to protocols which will prevent future bacterial infections.These include government commitment to control TB, diagnosis based on sputum-smear microscopy tests done on patients who actively report TB symptoms, direct observation short-course chemotherapy treatments, a definite supply of drugs, and standardized reporting and recording of cases and treatment outcomes. The WHO advises that all TB patients should have at least the first two months of their therapy observed (and preferably the whole of it observed): this means an independent observer watching patients swallow their anti-TB therapy. The independent observer is often not a healthcare worker and may be a shopkeeper or a tribal elder or similar senior person within that society. DOTS is used with intermittent dosing (thrice weekly or 2HREZ/4HR3). Twice weekly dosing is effective but not recommended by the World Health Organization (WHO), because there is no margin for error (accidentally omitting one dose per week results in once weekly dosing, which is ineffective).Treatment with properly implemented DOTS has a success rate exceeding 95% and prevents the emergence of further multi-drug resistant strains of tuberculosis. Administering DOTS, decreases the possibilities of tuberculosis from recurring, resulting in a reduction in unsuccessful treatments. This is in part due to the fact that areas without the DOTS strategy generally provide lower standards of care. Areas with DOTS administration help lower the number of patients seeking help from other facilities where they are treated with unknown treatments resulting in unknown outcomes. However, if the DOTS program is not implemented or done so incorrectly positive results will be unlikely. For the program to work efficiently and accurately health providers must be fully engaged, links must be built between public and private practitioners, health services must be available to all, and global support is provided to countries trying to reach their TB prevention, and treatment aims. Some researchers suggest that, because the DOTS framework has been so successful in the treatment of tuberculosis in sub-Saharan Africa, DOTS should be expanded to non-communicable diseases such as diabetes mellitus, hypertension, and epilepsy. DOTS-Plus strategy The WHO extended the DOTS programme in 1998 to include the treatment of MDR-TB (called "DOTS-Plus"). Implementation of DOTS-Plus requires the capacity to perform drug-susceptibility testing (not routinely available even in developed countries) and the availability of second-line agents, in addition to all the requirements for DOTS. DOTS-Plus is therefore much more resource-expensive than DOTS, and requires much greater commitment from countries wishing to implement it. Community engagement is a new approach that is being initiated alongside the DOTS individualized treatment. By creating a community for health workers to give support to patients and hospital faculty, the DOTS-plus model also incorporates psychological structural support treatments to help accommodate patients to ensure completion of treatment. Treatment with the new strategy is a total duration of 18–24 months.Monthly surveillance until cultures convert to negative is recommended for DOTS-Plus, but not for DOTS. If cultures are positive or symptoms do not resolve after three months of treatment, it is necessary to re-evaluate the patient for drug-resistant disease or nonadherence to drug regimen. If cultures do not convert to negative despite three months of therapy, some physicians may consider admitting the patient to hospital so as to closely monitor therapy. Extra-pulmonary tuberculosis Tuberculosis not affecting the lungs is called extra-pulmonary tuberculosis. Disease of the central nervous system is specifically excluded from this classification. The United Kingdom and the World Health Organization (WHO) recommendation is 2HREZ/4HR; the US recommendation is 2HREZ/7HR. There is good evidence from randomised-controlled trials to say that in tuberculous lymphadenitis and in TB of the spine, the six-month regimen is equivalent to the nine-month regimen; the US recommendation is therefore not supported by the evidence.Up to 25% of patients with TB of the lymph nodes (TB lymphadenitis) will get worse on treatment before they get better and this usually happens in the first few months of treatment. A few weeks after starting treatment, lymph nodes often start to enlarge, and previously solid lymph nodes may soften and develop into tuberculous cervical lymphadenitis. This should not be interpreted as failure of therapy and is a common reason for patients (and their physicians) to panic unnecessarily. With patience, two to three months into treatment the lymph nodes start to shrink again and re-aspiration or re-biopsy of the lymph nodes is unnecessary: if repeat microbiological studies are ordered, they will show the continued presence of viable bacteria with the same sensitivity pattern, which further adds to the confusion: physicians inexperienced in the treatment of TB will then often add second-line drugs in the belief that the treatment is not working. In these situations, all that is required is re-assurance. Steroids may be useful in resolving the swelling, especially if it is painful, but they are unnecessary. Additional antibiotics are unnecessary and the treatment regimen does not need to be lengthened.There is no evidence that 6 months regimen is inadequate in treating abdominal TB and there is no additional benefits for 9-month regimen for preventing relapse. However, more large scale studies are needed to confirm the above conclusion. Tuberculosis of the central nervous system Central nervous system tuberculosis takes two major forms: tuberculous meningitis and tuberculoma.Tuberculosis may affect the central nervous system (meninges, brain or spinal cord) in which case it is called TB meningitis, TB cerebritis, and TB myelitis respectively; the standard treatment is 12 months of drugs (2HREZ/10HR) and steroid are mandatory.Diagnosis is difficult as CSF culture is positive in less than half of cases, and therefore a large proportion of cases are treated on the basis of clinical suspicion alone. PCR of CSF does not significantly improve the microbiology yield; culture remains the most sensitive method and a minimum of 5 mL (preferably 20 mL) of CSF should be sent for analysis. TB cerebritis (or TB of the brain) may require brain biopsy to make the diagnosis, because the CSF is commonly normal: this is not always available and even when it is, some clinicians would debate whether it is justified putting a patient through such an invasive and potentially dangerous procedure when a trial of anti-TB therapy may yield the same answer; probably the only justification for brain biopsy is when drug-resistant TB is suspected.It is possible that shorter durations of therapy (e.g., six months) may be sufficient to treat TB meningitis, but no clinical trial has addressed this issue. The CSF of patients with treated TB meningitis is commonly abnormal even at 12 months; the rate of resolution of the abnormality bears no correlation with clinical progress or outcome, and is not an indication for extending or repeating treatment; repeated sampling of CSF by lumbar puncture to monitor treatment progress should therefore not be done.Although TB meningitis and TB cerebritis are classified together, the experience of many clinicians is that their progression and response to treatment is not the same. TB meningitis usually responds well to treatment, but TB cerebritis may require prolonged treatment (up to two years) and the steroid course needed is often also prolonged (up to six months). Unlike TB meningitis, TB cerebritis often required repeated CT or MRI imaging of the brain to monitor progress.Central nervous system TB may be secondary to blood-borne spread: therefore some experts advocate the routine sampling of CSF in patients with miliary TB.The anti-TB drugs that are most useful for the treatment of Central nervous system TB are: INH (CSF penetration 100%) RMP (10–20%) EMB (25–50% inflamed meninges only) PZA (100%) STM (20% inflamed meninges only) LZD (20%) Cycloserine (80–100%) Ethionamide (100%) PAS (10–50%) (inflamed meninges only)The use of steroids is routine in TB meningitis (see section below). There is evidence from one poorly designed trial that aspirin may be beneficial, but further work is required before this can be recommended routinely. Steroids The usefulness of corticosteroids (e.g., prednisolone or dexamethasone) in the treatment of TB is proven for TB meningitis and TB pericarditis. The dose for TB meningitis is dexamethasone 8 to 12 mg daily tapered off over six weeks (for those who prefer more precise dosing should refer to Thwaites et al., 2004). The dose for pericarditis is prednisolone 60 mg daily tapered off over four to eight weeks.Steroids may be of temporary benefit in pleurisy, extremely advanced TB, and TB in children: Pleurisy: prednisolone 20 to 40 mg daily tapered off over 4 to 8 weeks Extremely advanced TB: 40 to 60 mg daily tapered off over 4 to 8 weeks TB in children: 2 to 5 mg/kg/day for one week, 1 mg/kg/day the next week, then tapered off over 5 weeksSteroids may be of benefit in peritonitis, miliary disease, tubercular osteomyelitis, TB osteomyelitis, laryngeal TB, lymphadenitis and genitourinary disease, but the evidence is scant and the routine use of steroids cannot be recommended. Steroid treatment in these patients should be considered on a case-by-case basis by the attending physician. The long-term impact of pleural TB on respiratory function is unknown. Therefore, such impact should be quantified first before assessing the need of further clinical trials of corticosteroids with pleural TB.Thalidomide may be of benefit in TB meningitis and has been used in cases where patients have failed to respond to steroid treatment. Non-compliance Patients who take their TB treatment in an irregular and unreliable way are at greatly increased risk of treatment failure, relapse and the development of drug-resistant TB strains.There are variety of reasons why patients fail to take their medication. The symptoms of TB commonly resolve within a few weeks of starting TB treatment and many patients then lose motivation to continue taking their medication. Regular follow-up is important to check on compliance and to identify any problems patients are having with their medication. Patients need to be told of the importance of taking their tablets regularly, and the importance of completing treatment, because of the risk of relapse or drug-resistance developing otherwise.One of the main complaints is the bulkiness of the tablets. The main offender is PZA (the tablets being the size of horse tablets). PZA syrup may be offered as a substitute, or if the size of the tablets is truly an issue and liquid preparations are not available, then PZA can be omitted altogether. If PZA is omitted, the patient should be warned that this results in a significant increase in the duration of treatment (details of regimens omitting PZA are given below). The other complaint is that the medicines must be taken on an empty stomach to facilitate absorption. This can be difficult for patients to follow (for example, shift workers who take their meals at irregular times) and may mean the patient waking up an hour earlier than usual everyday just to take medication. The rules are actually less stringent than many physicians and pharmacists realise: the issue is that the absorption of RMP is reduced if taken with fat, but is unaffected by carbohydrate, protein, or antacids. So the patient can in fact have his or her medication with food as long as the meal does not contain fat or oils (e.g., a cup of black coffee or toast with jam and no butter). Taking the medicines with food also helps ease the nausea that many patients feel when taking the medicines on an empty stomach. The effect of food on the absorption of INH is not clear: two studies have shown reduced absorption with food but one study showed no difference. There is a small effect of food on the absorption of PZA and of EMB that is probably not clinically important.It is possible to test urine for isoniazid and rifampicin levels to check for compliance. The interpretation of urine analysis is based on the fact that isoniazid has a longer half-life than rifampicin: urine positive for isoniazid and rifampicin – patient probably fully compliant urine positive for isoniazid only – patient has taken his medication in the last few days preceding the clinic appointment, but had not yet taken a dose that day. urine positive for rifampicin only – patient has omitted to take his medication the preceding few days, but did take it just before coming to clinic. urine negative for both isoniazid and rifampicin – patient has not taken either medicine for a number of daysIn countries where doctors are unable to compel patients to take their treatment (e.g., the UK), some say that urine testing only results in unhelpful confrontations with patients and does not help increase compliance. In countries where legal measures can be taken to force patients to take their medication (e.g., the US), then urine testing can be a useful adjunct in assuring compliance.RMP colours the urine and all bodily secretions (tears, sweat, etc.) an orange-pink colour and this can be a useful proxy if urine testing is not available (although this colour fades approximately six to eight hours after each dose).In study on cases of extra-pulmonary TB (EPTB), researchers at the University of the Philippines Manila found that similarity of symptoms of EPTB to other diseases results to delayed identification of the disease and late provision of medication. This, ultimately contribute to increasing rates of mortality and incidence rates of EPTB.The World Health Organization (WHO) recommends prescription of fixed-dose combination drugs, to improve adherence to treatment by reducing the number of tablets that need to be taken by people, and also possibly reducing prescribing errors. A Cochrane review, published in 2016, found moderate quality evidence that "there is probably little or no difference in fixed-dose combination drugs compared to single-drug formulations". Treatment adherence strategies As stated above, non-compliance to anti-tuberculin treatment can result in treatment failure or development of drug-resistant tuberculosis. Therefore, overall treatment strategies should be focused on promoting adherence. WHO and the Centers for Disease Control and Prevention (CDC) recommend a multi-faceted patient centered care approach. Public health and private sector practitioners can promote TB treatment adherence by allowing patients to be active partners in making their own treatment decisions; improving patients knowledge and understanding of tuberculosis disease, treatment and potential spread; and by discussing expected interim and long-term outcomes with patients. CDC also recommends use of incentives and enablers. Incentives are monetary rewards for a healthy behavior (e.g.transport or food vouchers), while enablers function to remove economic burdens impeding healthcare access (e.g. grouping clinic visits, providing after hours clinic visits, or home visits). However, more research is needed to determine whether incentives and enablers have a significant effect on long-term treatment adherence for TB. Smartphones are considered to have potential to improve compliance.Individuals with tuberculosis may also benefit from the emotional support of peers and survivors. Advocacy organizations and patient support groups such as STOP TB, TB Alert, Treatment Action Group (TAG) and others work to connect TB survivors. Adverse effects For information on adverse effects of individual anti-TB drugs, please refer to the individual articles for each drug. The relative incidence of major adverse effects has been carefully described: INH 0.49 per hundred patient months RMP 0.43 EMB 0.07 PZA 1.48 All drugs 2.47This works out to an 8.6% risk that any one patient will need to have his drug therapy changed during the course of standard short-course therapy (2HREZ/4HR). The people identified to be most at risk of major adverse side effects in this study were: age >60, females, HIV positive patients, and Asians.It can be extremely difficult identifying which drug is responsible for which side effect, but the relative frequency of each is known. The offending drugs are given in decreasing order of frequency: Thrombocytopenia: Rifampicin (RMP) Neuropathy: Isoniazid (INH) Vertigo: Streptomycin (STM) Hepatitis: Pyrazinamide (PZA), RMP, INH Rash: PZA, RMP, Ethambutol (EMB)Thrombocytopenia is only caused by RMP and no test dosing need be done. Regimens omitting RMP are discussed below. Please refer to the entry on rifampicin for further details. The most frequent cause of neuropathy is INH. The peripheral neuropathy of INH is always a pure sensory neuropathy and finding a motor component to the peripheral neuropathy should always prompt a search for an alternative cause. Once a peripheral neuropathy has occurred, INH must be stopped and pyridoxine should be given at a dose of 50 mg thrice daily. Simply adding high dose pyridoxine to the regimen once neuropathy has occurred will not stop the neuropathy from progressing. Patients at risk of peripheral neuropathy from other causes (diabetes mellitus, alcoholism, renal failure, malnutrition, pregnancy, etc.) should all be given pyridoxine 10 mg daily at the start of treatment. Please refer to the entry on isoniazid for details on other neurological side effects of INH. Rashes are most frequently due to PZA, but can occur with any of the TB drugs. Test dosing using the same regimen as detailed below for hepatitis may be necessary to determine which drug is responsible. Itching RMP commonly causes itching without a rash in the first two weeks of treatment: treatment should not be stopped and the patient should be advised that the itch usually resolves on its own. Short courses of sedative antihistamines such as chlorpheniramine may be useful in alleviating the itch. Fever during treatment can be due to a number of causes. It can occur as a natural effect of tuberculosis (in which case it should resolve within three weeks of starting treatment). Fever can be a result of drug resistance (but in that case the organism must be resistant to two or more of the drugs). Fever may be due to a superadded infection or additional diagnosis (patients with TB are not exempt from getting influenza and other illnesses during the course of treatment). In a few patients, the fever is due to drug allergy. The clinician must also consider the possibility that the diagnosis of TB is wrong. If the patient has been on treatment for more than two weeks and if the fever had initially settled and then come back, it is reasonable to stop all TB medication for 72 hours. If the fever persists despite stopping all TB medication, then the fever is not due to the drugs. If the fever disappears off treatment, then the drugs need to be tested individually to determine the cause. The same scheme as is used for test dosing for drug-induced hepatitis (described below) may be used. The drug most frequently implicated as causing a drug fever is RMP: details are given in the entry on rifampicin. Drug-induced hepatitis Drug-induced hepatitis, from TB treatment, has a mortality rate of around 5%. Three drugs can induce hepatitis: PZA, INH and RMP (in decreasing order of frequency).[1] It is not possible to distinguish between these three causes based purely on signs and symptoms. Test dosing must be carried out to determine which drug is responsible (this is discussed in detail below). Liver function tests (LFTs) should be checked at the start of treatment, but, if normal, need not be checked again; the patient need only be warned of the symptoms of hepatitis. Some clinicians insist on regular monitoring of LFTs while on treatment, and in this instance, tests need only be done two weeks after starting treatment and then every two months thereafter, unless any problems are detected. Elevations in bilirubin must be expected with RMP treatment (RMP blocks bilirubin excretion) and usually resolve after 10 days (liver enzyme production increases to compensate). Isolated elevations in bilirubin can be safely ignored. Elevations in liver transaminases (ALT and AST) are common in the first three weeks of treatment. If the patient is asymptomatic and the elevation is not excessive then no action need be taken; some experts suggest a cut-off of four times the upper limit of normal, but there is no evidence to support this particular number over and above any other number. Some experts consider that treatment should only be stopped if jaundice becomes clinically evident. If clinically significant hepatitis occurs while on TB treatment, then all the drugs should be stopped until the liver transaminases return to normal. If the patient is so ill that TB treatment cannot be stopped, then STM and EMB should be given until the liver transaminases return to normal (these two drugs are not associated with hepatitis). Fulminant hepatitis can occur in the course of TB treatment, but is fortunately rare; emergency liver transplantation may be necessary and deaths do occur. Test dosing for drug-induced hepatitis Drugs should be re-introduced individually. This cannot be done in an outpatient setting, and must be done under close observation. A nurse must be present to take patients pulse and blood pressure at 15-minute intervals for a minimum of four hours after each test dose is given (most problems will occur within six hours of test dosing, if they are going to occur at all). Patients can become very suddenly unwell and access to intensive care facilities must be available. The drugs should be given in this order: Day 1: INH at 1/3 or 1/4 dose Day 2: INH at 1/2 dose Day 3: INH at full dose Day 4: RMP at 1/3 or 1/4 dose Day 5: RMP at 1/2 dose Day 6: RMP at full dose Day 7: EMB at 1/3 or 1/4 dose Day 8: EMB at 1/2 dose Day 9: EMB at full doseNo more than one test dose per day should be given, and all other drugs should be stopped while test dosing is being done. So on day 4, for example, the patient only receives RMP and no other drugs are given. If the patient completes the nine days of test dosing, then it is reasonable to assume that PZA has caused the hepatitis and no PZA test dosing need be done. The reason for using the order for testing drugs is because the two most important drugs for treating TB are INH and RMP, so these are tested first: PZA is the most likely drug to cause hepatitis and is also the drug that can be most easily omitted. EMB is useful when the sensitivity pattern of the TB organism are not known and can be omitted if the organism is known to be sensitive to INH. Regimens omitting each of the standard drugs are listed below. The order in which the drugs are tested can be varied according to the following considerations: The most useful drugs (INH and RMP) should be tested first, because the absence of these drugs from a treatment regimen severely impairs its efficacy. The drugs most likely to be causing the reaction should be tested as late as possible (and possibly need not be tested at all). This avoids rechallenging patients with a drug to which they have already had a (possibly) dangerous adverse reaction.A similar scheme may be used for other adverse effects (such as fever and rash), using similar principles. Dysbiosis caused by HRZE antibiotic treatment Tuberculosis treatment results in changes to the structure of the gut microbiome both during and after treatment in mice and humans. It is currently unknown what the long term effects of this dysbiosis are on systemic immunity. Deviations from the standard regimen There is evidence supporting some deviations from the standard regimen when treating pulmonary TB. Sputum culture-positive patients who are smear-negative at the start of treatment do well with only 4 months of treatment (this has not been validated for HIV-positive patients); sputum culture-negative patients do well on only 3 months of treatment (possibly because some of these patients never had TB at all). It is unwise to treat patients for only three or four months, but all TB physicians will have patients who stop their treatment early (for whatever reason), and it can be reassuring to know that sometimes retreatment is unnecessary. Elderly patients who are already taking a large number of tablets may be offered 9HR, omitting PZA which is the bulkiest part of the regimen. It may not always be necessary to treat with four drugs from the beginning. An example might be a close contact of a patient known to have a fully sensitive strain of tuberculosis: in this case, it is acceptable to use 2HRZ/4HR (omitting EMB and STM) in the expectation that their strain will be INH susceptible also. Indeed, this was previously the recommended standard regimen in many countries until the early 1990s, when isoniazid-resistance rates increased. TB involving the brain or spinal cord (meningitis, encephalitis, etc.) is currently treated with 2HREZ/10HR (12 months of treatment in total), but there is no evidence to say that this is superior to 2HREZ/4HR. There is no difference in relapse rates amongst those who are treated with 6 months or longer period of time. However, more well-designed studies are needed to answer this question. Regimens omitting isoniazid Isoniazid resistance accounts 6.9% of isolates in the UK (2010). Worldwide, it is the most common type of resistance encountered, hence the current recommendation of using HREZ at the beginning of treatment until sensitivities are known. It is useful to know of current reported outbreaks (like the current outbreak of INH-resistant TB in London). If patients are discovered to be infected with an isoniazid-resistant strain of TB having completed 2 months of HREZ, then they should be changed to RE for a further 10 months, and the same thing if the patient is intolerant to isoniazid (although 2REZ/7RE may be acceptable if the patient is well supervised). The US recommendation is 6RZE with the option of adding a quinolone such as moxifloxacin. The level of evidence for all these regimens is poor, and there is little to recommend one over the other. Regimens omitting rifampicin The UK prevalence of rifampicin (RMP) resistance is 1.4%. It is rare for TB strains to be resistant to RMP without also being resistant to INH, which means that rifampicin-resistance usually means resistance to INH as well (that is, MDR-TB). However, RMP intolerance is not uncommon (hepatitis or thrombocytopaenia being the most common reasons for stopping rifampicin). Of the first-line drugs, rifampicin is also the most expensive, and in the poorest countries, regimens omitting rifampicin are therefore often used. Rifampicin is the most potent sterilising drug available for the treatment of tuberculosis and all treatment regimens that omit rifampicin are significantly longer than the standard regimen. The UK recommendation is 18HE or 12HEZ. The US recommendation is 9 to 12HEZ, with the option of adding a quinolone (for example, MXF). Regimens omitting pyrazinamide PZA is a common cause of rash, hepatitis and of painful arthralgia in the HREZ regimen, and can be safely stopped in those patients who are intolerant to it. Isolated PZA resistance is uncommon in M. tuberculosis, but M. bovis is innately resistant to PZA. PZA is not crucial to the treatment of fully sensitive TB, and its main value is in shortening the total treatment duration from nine months to six. An alternative regimen is 2HRE/7HR, for which there is excellent clinical trial evidence. The 1994 US CDC guidelines for tuberculosis erroneously cite Slutkin as evidence that a nine-month regimen using only isoniazid and rifampicin is acceptable, but almost all of the patients in that study received ethambutol for the first two to three months (although this is not obvious from the abstract of that article). This mistake was rectified in the 2003 guidelines.This regimen (2HRE/7HR) is the first-line regimen used to treat M. bovis, since M. bovis is intrinsically resistant to pyrazinamide. Regimens omitting ethambutol EMB intolerance or resistance is rare. If a patient is truly intolerant or is infected with TB that is resistant to EMB, then 2HRZ/4HR is an acceptable regimen. The main motivator for including EMB in the initial two months is because of increasing rates of INH resistance. Tuberculosis and other conditions Liver disease People with alcoholic liver disease are at an increased risk of tuberculosis. The incidence of tuberculous peritonitis is particularly high in patients with cirrhosis of the liver.There are broadly two categories of treatment: A) Cirrhotic patients with essentially normal baseline liver function tests (Childs A Cirrhosis). Such patients may be treated with standard 4 drug regime for 2 months followed by 2 drugs for remaining 4 months (total 6-month treatment). B) Cirrhotic patients altered baseline liver function tests (Childs B & C). According to 2010 WHO guidelines: depending on the severity of the disease and degree of decompensation, the following regimen can be used, by altering the number of hepatotoxic drugs. One or two hepatotoxic drugs may be used in moderately severe disease (e.g., Childs B cirrhosis) whereas hepatotoxic drugs are completely avoided in decompensated Child C cirrhosis. • Two hepatotoxic drugs – 9 months of Isoniazid, Rifampin and Ethambutol (until or unless isoniazid susceptibility is documented) – 2 months of Isoniazid, Rifampin, Ethambutol and Streptomycin followed by 6 months of Isoniazid and Rifampin • One hepatotoxic drug – 2 months of Isoniazid, Ethambutol & Streptomycin followed by 10 months of Isoniazid and Ethambutol • No hepatotoxic drugs – 18–24 months of Streptomycin, Ethambutol and Quinolones Patients with liver disease should have their liver function tests monitored regularly throughout TB treatment. Drug-induced hepatitis is discussed in a separate section above. Pregnancy Pregnancy itself is not a risk factor for TB. Rifampicin makes hormonal contraception less effective, so additional precautions need to be taken for birth control while tuberculosis treatment. Untreated TB in pregnancy is associated with an increased risk of miscarriage and major fetal abnormality, and treatment of pregnant women. The US guidelines recommend omitting PZA when treating TB in pregnancy; the UK and WHO guidelines make no such recommendation, and PZA is commonly used in pregnancy. There is extensive experience with the treatment of pregnant women with TB and no toxic effect of PZA in pregnancy has ever been found. High doses of RMP (much higher than used in humans) causes neural tube defects in animals, but no such effect has ever been found in humans. There may be an increased risk of hepatitis in pregnancy and during the puerperium. It is prudent to advise all women of child-bearing age to avoid getting pregnant until TB treatment is completed. Aminoglycosides (STM, capreomycin, amikacin) should be used with caution in pregnancy, because they may cause deafness in the unborn child. The attending physician must weigh the benefits of treating the mother against the potential harm to the baby, and good outcomes have been reported in children whose mothers were treated with aminoglycosides. Experience in Peru shows that treatment for MDR-TB is not a reason to recommend termination of pregnancy, and that good outcomes are possible. Kidney disease People with kidney failure have a 10 to 30-fold increase in risk of getting TB. People with kidney disease who are being given immunosuppressive medications or are being considered for transplant should be considered for treatment of latent tuberculosis if appropriate. Aminoglycosides (STM, capreomycin and amikacin) should be avoided in patients with mild to severe kidney problems because of the increased risk of damage to the kidneys. If the use of aminoglycosides cannot be avoided (e.g., in treating drug-resistant TB) then serum levels must be closely monitored and the patient warned to report any side-effects (deafness in particular). If a person has end-stage kidney disease and has no useful remaining kidney function, then aminoglycosides can be used, but only if drug levels can be easily measured (often only amikacin levels can be measured). In mild kidney impairment, no change needs to be made in dosing any of the other drugs routinely used in the treatment of TB. In severe chronic kidney disease (GFR<30), the EMB dose should be halved (or avoided altogether). The PZA dose is 20 mg/kg/day (UK recommendation) or three-quarters the normal dose (US recommendation), but not much published evidence is available to support this. When using 2HRZ/4HR in patients on dialysis, the drugs should be given daily during the initial high-intensity phase. In the continuation phase, the drugs should be given at the end of each haemodialysis session and no dose should be taken on non-dialysis days. HIV In patients with HIV, treatment for the HIV should be delayed until TB treatment is completed, if possible. The current UK guidance (provided by the British HIV Association) is CD4 count over 200—delay treatment until the six months of TB treatment are complete. CD4 count 100 to 200—delay treatment until the initial two-month intensive phase of therapy is complete CD4 count less than 100—the situation is unclear and patients should be enrolled in clinical trials examining this question. There is evidence that if these patients are managed by a specialist in both TB and HIV then outcomes are not compromised for either disease.If HIV treatment has to be started while a patient is still on TB treatment, then the advice of a specialist HIV pharmacist should be sought. In general, there is no significant interactions with the NRTIs. Nevirapine should not be used with rifampicin. Efavirenz may be used, but dose used depends on the patients weight (600 mg daily if weight less than 50 kg; 800 mg daily if weight greater than 50 kg). Efavirenz levels should be checked early after starting treatment (unfortunately, this is not a service routinely offered in the US, but is readily available in the UK). The protease inhibitors should be avoided if at all possible: patients on rifamycins and protease inhibitors have an increased risk of treatment failure or relapse.The World Health Organization (WHO) warns against using thioacetazone in patients with HIV, because of the 23% risk of potentially fatal exfoliative dermatitis.According to Caprisa 003 (SAPiT) Study the mortality in patients who were started on anti-retrovirals during TB treatment was 56% lower than those started after TB treatment was completed (hazard ratio 0.44 (95% CI: 0.25 to 0.79); p=0.003). Epilepsy INH may be associated with an increased risk of seizures. Pyridoxine 10 mg daily should be given to all epileptics taking INH. There is no evidence that INH causes seizures in patients who are not epileptic. TB treatment involves numerous drug interactions with anti-epileptic drugs and serum drug levels should be closely monitored. There are serious interactions between rifampicin and carbamazepine, rifampicin and phenytoin, and rifampicin and sodium valproate. The advice of a pharmacist should always be sought. Covid- 19 TB and COVID-19 are a "cursed duet" and need immediate attention. TB should be considered a risk factor for severe COVID disease and patients with TB should be prioritised for COVID-19 preventative efforts, including vaccination. Drug-resistance Definitions Multi-drug resistant tuberculosis (MDR-TB) is defined as TB that is resistant at least to INH and RMP. Isolates that are multi-resistant to any other combination of anti-TB drugs but not to INH and RMP are not classed as MDR-TB. As of Oct 2006, "Extensively drug-resistant tuberculosis" (XDR-TB) is defined as MDR-TB that is resistant to quinolones and also to any one of kanamycin, capreomycin, or amikacin. The old case definition of XDR-TB is MDR-TB that is also resistant to three or more of the six classes of second-line drugs. This definition should no longer be used, but is included here because many older publications refer to it. The principles of treatment for MDR-TB and for XDR-TB are the same. The main difference is that XDR-TB is associated with a much higher mortality rate than MDR-TB, because of a reduced number of effective treatment options. The epidemiology of XDR-TB is currently not well studied, but it is believed that XDR-TB does not transmit easily in healthy populations, but is capable of causing epidemics in populations which are already stricken by HIV and therefore more susceptible to TB infection. Epidemiology of drug-resistant TB A 1997 survey of 35 countries found rates above 2% in about a third of the countries surveyed. The highest rates of drug-resistant TB were in the former USSR, the Baltic states, Argentina, India and China, and was associated with poor or failing national Tuberculosis Control programmes. Likewise, the appearance of high rates of MDR-TB in New York city the early 1990s was associated with the dismantling of public health programmes by the Reagan administration.Paul Farmer points out that the more expensive a treatment, the harder it is for poor countries to get. Farmer sees this as verging on denial of basic human rights. Africa is low in quality of treatment partly because many African cultures lack the concept of time essential to the schedule of administration.MDR-TB can develop in the course of the treatment of fully sensitive TB and this is always the result of patients missing doses or failing to complete a course of treatment. Thankfully, MDR-TB strains appear to be less fit and less transmissible. It has been known of many years that INH-resistant TB is less virulent in guinea pigs, and the epidemiological evidence is that MDR strains of TB do not dominate naturally. A study in Los Angeles found that only 6% of cases of MDR-TB were clustered. This should not be a cause for complacency: it must be remembered that MDR-TB has a mortality rate comparable to lung cancer. It must also be remembered that people who have weakened immune systems (because of diseases such as HIV or because of drugs) are more susceptible to catching TB. Children represent a susceptible population with increasing rates of MDR and XDR-TB. Since diagnosis in pediatric patients is difficult, large number of cases are not properly reported. Cases of pediatric XDR-TB have been reported in most countries including the United States.In 2006 an outbreak of XDR-TB South Africa was first reported as a cluster of 53 patients in a rural hospital in KwaZulu-Natal, with all but one dying. What was particularly worrying was that the mean survival from sputum specimen collection to death was only 16 days and that the majority of patients had never previously received treatment for tuberculosis. This is the epidemic for which the acronym XDR-TB was first used, although TB strains that fulfil the current definition have been identified retrospectively, this was the largest group of linked cases ever found. Since the initial report in September 2006, cases have now been reported in most provinces in South Africa. As of 16 March 2007, there were 314 cases reported, with 215 deaths. It is clear that the spread of this strain of TB is closely associated with a high prevalence of HIV and poor infection control; in other countries where XDR-TB strains have arisen, drug-resistance has arisen from mismanagement of cases or poor patient compliance with drug treatment instead of being transmitted from person to person. This strain of TB does not respond to any of the drugs currently available in South Africa for first- or second-line treatment. It is now clear that the problem has been around for much longer than health department officials have suggested, and is far more extensive. By 23 November 2006, 303 cases of XDR-TB had been reported, of which 263 were in KwaZulu-Natal. Serious thought has been put to isolation procedures that may deny some patients their human rights, but which may be necessary to prevent further spread of this strain of TB. Treatment of MDR-TB The treatment and prognosis of MDR-TB are much more akin to that for cancer than to that for infection. It has a mortality rate of up to 80%, which depends on a number of factors, including How many drugs the organism is resistant to (the fewer the better), How many drugs the patient is given (patients treated with five or more drugs do better), Whether an injectable drug is given or not (it should be given for the first three months at least), The expertise and experience of the physician responsible, How co-operative the patient is with treatment (treatment is arduous and long, and requires persistence and determination on the part of the patient), Whether the patient is HIV positive or not (HIV co-infection is associated with an increased mortality).Treatment courses are a minimum of 18 months and may last years; it may require surgery, though death rates remain high despite optimal treatment. That said, good outcomes are still possible. Treatment courses that are at least 18 months long and which have a directly observed component can increase cure rates to 69%.The treatment of MDR-TB must be undertaken by a physician experienced in the treatment of MDR-TB. Mortality and morbidity in patients treated in non-specialist centres is significantly elevated compared to those patients treated in specialist centres. In addition to the obvious risks (e.g., known exposure to a patient with MDR-TB), risk factors for MDR-TB include male sex, HIV infection, previous incarceration, failed TB treatment, failure to respond to standard TB treatment, and relapse following standard TB treatment. A large proportion of people with MDR-TB are unable to access treatment due to what Paul Farmer describes as an "Outcome Gap". The majority of people struck with MDR-TB live in "resource-poor settings" and are denied treatment because international organizations have refused to make technologies available to countries who cannot afford to pay for treatment, the reason being that second line drugs are to expensive therefore treatment methods for MDR-TB are not sustainable in impoverished nations. Farmer argues that this is social injustice and we cannot allow people to die simply because they are faced with circumstances where they cannot afford "effective therapy".Treatment of MDR-TB must be done on the basis of sensitivity testing: it is impossible to treat such patients without this information. If treating a patient with suspected MDR-TB, the patient should be started on SHREZ+MXF+cycloserine pending the result of laboratory sensitivity testing. A gene probe for rpoB is available in some countries and this serves as a useful marker for MDR-TB, because isolated RMP resistance is rare (except when patients have a history of being treated with rifampicin alone). If the results of a gene probe (rpoB) are known to be positive, then it is reasonable to omit RMP and to use SHEZ+MXF+cycloserine. The reason for maintaining the patient on INH despite the suspicion of MDR-TB is that INH is so potent in treating TB that it is foolish to omit it until there is microbiological proof that it is ineffective. There are also probes available for isoniazid-resistance (katG and mabA-inhA), but these are less widely available. When sensitivities are known and the isolate is confirmed as resistant to both INH and RMP, five drugs should be chosen in the following order (based on known sensitivities): an aminoglycoside (e.g., amikacin, kanamycin) or polypeptide antibiotic (e.g., capreomycin) PZA EMB a fluoroquinolones: moxifloxacin is preferred (ciprofloxacin should no longer be used; rifabutin cycloserine a thioamide: prothionamide or ethionamide PAS a macrolide: e.g., clarithromycin linezolid high-dose INH (if low-level resistance) interferon-γ thioridazine meropenem and clavulanic acidDrugs are placed nearer the top of the list because they are more effective and less toxic; drugs are placed nearer the bottom of the list because they are less effective or more toxic, or more difficult to obtain. Resistance to one drug within a class generally means resistance to all drugs within that class, but a notable exception is rifabutin: rifampicin-resistance does not always mean rifabutin-resistance and the laboratory should be asked to test for it. It is only possible to use one drug within each drug class. If it is difficult finding five drugs to treat then the clinician can request that high level INH-resistance be looked for. If the strain has only low level INH-resistance (resistance at 0.2 mg/L INH, but sensitive at 1.0 mg/L INH), then high dose INH can be used as part of the regimen. When counting drugs, PZA and interferon count as zero; that is to say, when adding PZA to a four drug regimen, you must still choose another drug to make five. It is not possible to use more than one injectable (STM, capreomycin or amikacin), because the toxic effect of these drugs is additive: if possible, the aminoglycoside should be given daily for a minimum of three months (and perhaps thrice weekly thereafter). Ciprofloxacin should not be used in the treatment of tuberculosis if other fluoroquinolones are available.There is no intermittent regimen validated for use in MDR-TB, but clinical experience is that giving injectable drugs for five days a week (because there is no-one available to give the drug at weekends) does not seem to result in inferior results. Directly observed therapy certainly helps to improve outcomes in MDR-TB and should be considered an integral part of the treatment of MDR-TB.Response to treatment must be obtained by repeated sputum cultures (monthly if possible). Treatment for MDR-TB must be given for a minimum of 18 months and cannot be stopped until the patient has been culture-negative for a minimum of nine months. It is not unusual for patients with MDR-TB to be on treatment for two years or more. Patients with MDR-TB should be isolated in negative-pressure rooms, if possible. Patients with MDR-TB should not be accommodated on the same ward as immunosuppressed patients (HIV infected patients, or patients on immunosuppressive drugs). Careful monitoring of compliance with treatment is crucial to the management of MDR-TB (and some physicians insist on hospitalisation if only for this reason). Some physicians will insist that these patients are isolated until their sputum is smear negative, or even culture negative (which may take many months, or even years). Keeping these patients in hospital for weeks (or months) on end may be a practical or physical impossibility and the final decision depends on the clinical judgement of the physician treating that patient. The attending physician should make full use of therapeutic drug monitoring (particularly of the aminoglycosides) both to monitor compliance and to avoid toxic effects. Some supplements may be useful as adjuncts in the treatment of tuberculosis, but for the purposes of counting drugs for MDR-TB, they count as zero (if you already have four drugs in the regimen, it may be beneficial to add arginine or vitamin D or both, but you still need another drug to make five). arginine, some clinical evidence (peanuts are a good source) Vitamin D, (some in-vitro evidence & see Vitamin D and tuberculosis treatment )The drugs listed below have been used in desperation and it is uncertain whether they are effective at all. They are used when it is not possible to find five drugs from the list above. imipenem co-amoxiclav clofazimine prochlorperazine metronidazoleOn 28 December 2012 the US Food and Drug Administration (FDA) approved bedaquiline (marketed as Sirturo by Johnson & Johnson) to treat multi-drug resistant tuberculosis, the first new treatment in 40 years. Sirturo is to be used in a combination therapy for patients who have failed standard treatment and have no other options. Sirturo is an adenosine triphosphate synthase (ATP synthase) inhibitor.The follow drug is experimental compounds that are not commercially available, but which may be obtained from the manufacturer as part of a clinical trial or on a compassionate basis. Their efficacy and safety are unknown: Pretomanid (manufactured by Novartis, developed in partnership with TB Alliance)There is increasing evidence for the role of surgery (lobectomy or pneumonectomy) in the treatment of MDR-TB, although whether this is should be performed early or late is not yet clearly defined. See Modern surgical management Management in Asia The Asia‐Pacific region carries 58% of the global tuberculosis burden, which includes multi drug-resistant tuberculosis. Southeast Asia has high burdens of tuberculosis as a result of inefficient and inadequate health infrastructures. According to the World Health Organization, many Asian countries have high cases of tuberculosis, but their governments will not invest in new technology to treat its patients. Philippines From 2005 to 2009, the IPHO-Maguindanao, a governmental organization in Maguindanao, Philippines, partnered with the Catholic Relief Services (CRS) to increase tuberculosis awareness. CRS implemented a USAID-assisted project to fund tuberculosis testing. Additionally, they launched an "Advocacy, Communication, and Self-Mobilization" project featuring workshops to encourage testing in communities. Citizens attending religious sermons were able to distribute information about tuberculosis and inform their communities on where to seek treatment and how to adhere to treatment protocols The DOTS-Plus strategy, designed to deliver from within familiar local institutions, was successful at conveying information about tuberculosis prevention and treatment. India In 1906, India opened its first air sanatorium for treatment and isolation of TB patients.However, the World Health Organization reviewed the national program in India which lacked funding and treatment regimens that could report accurate tuberculosis case management. By 1945, there were successful immunization screenings due to campaigns that helped spread messages about the prevention of disease. This was also around the same time that the World Health Organization declared tuberculosis to be a global emergency and recommended countries adopt the DOTS strategy. Bangladesh, Cambodia, Thailand In Bangladesh, Cambodia, and Indonesia, there is a diagnostic treatment for latent tuberculosis in children below 5 years of age. The IGRA approach (Interferon Gamma Release Assay) is used in these countries. IGRA testing and diagnosis are whole blood cell tests where fresh blood samples are mixed with antigens and controls. A person infected with tuberculosis will have interferon-gammas in the blood stream when mixed with the antigen. It is a highly accurate but expensive test and is technologically complex for immuno-compromised patients. These developing countries were unable to get rid of tuberculosis effectively because the national health policies did not cover screening and testing for tuberculosis. There were also no programs in place to educate citizens and provide training for healthcare workers. Without the mobilization of sufficient resources and the backing of sustainable government funding, these developing countries failed to adequately provide the treatment and resources necessary to combat tuberculosis. Vietnam According to the WHO, Vietnam ranks 13th on the list of 22 countries with the highest tuberculosis burden in the world. Nearly 400 new cases of TB and 55 deaths occur each day in Vietnam. In 1989, the Ministry of Health in Vietnam addressed the tuberculosis burden by establishing the National Institute of Tuberculosis and Lung Diseases and implemented the DOTS strategy as a national priority. Vietnams health service system consists of four different levels: the central level headed by the Ministry of Health (MOH), provincial health services, district health services, and commune health centers". These departments worked with the National Institute of Tuberculosis and Lung Diseases to ensure that there were treatment and prevention plans for long-term reduction of tuberculosis. In 2002, Vietnam also implemented a communication plan to provide accurate educational information to respond to any barriers or misperceptions about tuberculosis treatment. The government worked with the World Health Organization, Center for Disease and Control Prevention, and local medical non-profits such as Friends for International Tuberculosis Relief to provide information about the causes of TB, sources of infection, how it is transmitted, symptoms, treatment, and prevention. The National Tuberculosis Control Program works closely with the primary health care system at the central, provincial, district, and commune levels which has proven to be an incredibly imperative measure of success. Tuberculosis non-profits in Asia Friends for International TB Relief is a small non-governmental organization whose mission is to help prevent tuberculosis and the spreading of TB. FIT not only diagnoses patients, but also provides preventative tuberculosis detection to pilot a comprehensive patient-centered TB program that aims to stop TB transmission and reduce suffering. The organization focuses on island screening due to the high level of risk and burden the population faces. Through its method of search, treat, prevent, and integrative sustainability, FIT is working closely with most of the population on the island (roughly 2022 patients), and partnered with the Ho Chi Minh City Public Health Association on a pilot that provides active community outreach, patient-centric care and stakeholder engagement.Located in Ha Noi, the National Institute of Tuberculosis and Lung Diseases is responsible for the direction and management of TB control activities at the central level. The institute supports the MOH in developing TB- related strategies, and in handling management and professional guidelines for the system. The provincial level centers diagnose, treat, and manage patients, implement TB policies issued by the NTP, and develop action plans under the guidelines of the Provincial Health Bureau and the provincial TB control committees. The districts are capable of detecting TB and treating patients. All districts have physicians specializing in TB, laboratories, and X-ray equipment and have either a TB department or a TB-communicable diseases department in the district hospital. The district level is also responsible for implementing and monitoring the NTP, and the supervision and management of TB programs in the communes. The commune level provides treatment as prescribed by the district level, administering drugs, and vaccinating children. In TB control, village health workers play critically important roles in identifying suspected TB patients, conducting counseling for examination and tests, paying home visits to patients undergoing treatment, and reporting problems in monthly meetings with the CHC.TB Alliance is a non-governmental organization that is located in South Africa and was discovered in the early 2000s. The NGO is a leading non-profit for global tuberculosis research and development of new TB vaccines. To advance TB development, TB Alliance creates partnerships with private, public, academic, and philanthropic sectors to develop products in underserved communities. In 2019, TB Alliance became the first not-for-profit organization to develop and register an anti-TB drug. TB Alliance also works closely alongside the World Health Organization (WHO), U.S FDA, and the European Medicine Agency (EMA) to endorse regulative policies and treatments that are affordable. FHI 360 is an international tuberculosis non-profit organization funded by USAID to treat and support patients in Myanmar, China, and Thailand. The organization developed an app called DOTsync for healthcare staff to administer antibiotics and monitor the side effects of patients. This is incredibly imperative to eliminating tuberculosis because it allows healthcare workers to have follow-up checkups with patients to ensure that tuberculosis treatments are effective. Operation ASHA is a TB nonprofit organization that was founded in 2006. Located in India and Cambodia, Operation ASHA focuses on the development of "e-Compliance," which is a verification and SMS text messaging system where patients can use their fingerprints to access their medical records and be reminded daily via text when to take their medication. According to Operation ASHA, the e-Compliance treatment successive rate is 85%. Treatment failure Patients who fail treatment must be distinguished from patients who relapse. Patients who responded to treatment and appeared to be cured after completing a course of TB treatment are not classed as treatment failures, but as relapses and are discussed in a separate section below. Patients are said to have failed treatment if they fail to respond to treatment (cough and sputum production persisting throughout the whole of treatment), or only experience a transient response to treatment (the patient gets better at first, but then get worse again, all the while on treatment).It is very uncommon for patients not to respond to TB treatment at all (even transiently), because this implies resistance at base-line to all of the drugs in the regimen. Patients who fail to get any response at all while on treatment should first of all be questioned very closely about whether or not they have been taking their medicines, and perhaps even be admitted to hospital to be observed taking their treatment. Blood or urine samples may be taken to check for malabsorption of TB drugs. If it can be shown that they are fully compliant with their medication, then the probability that they have another diagnosis (perhaps in addition to the diagnosis of TB) is very high. These patients should have their diagnosis carefully reviewed and specimens obtained for TB culture and sensitivity testing. Patients who get better and then get worse again should likewise be questioned very closely about adherence to treatment. If adherence is confirmed then they should be investigated for resistant TB (including MDR-TB), even if a specimen has already been obtained for microbiology before commencing treatment. Prescription or dispensing errors will account for a proportion of patients who fail to respond to treatment. Immune defects are a rare cause of non-response. In a tiny proportion of patients, treatment failure is a reflection of extreme biological variation and no cause is found. Treatment relapse Patients are said to relapse if they improve while on treatment, but become ill again after stopping treatment. Patients who experience only a transient improvement while on treatment, or who never respond to treatment are said to have failed treatment and are discussed above. There is a small relapse rate associated with all treatment regimens, even if the treatment has been taken religiously with 100% compliance (the standard regimen 2HREZ/4HR has a relapse rate of 2 to 3% under trial conditions). The majority of relapses occur within 6 months of finishing treatment. Patients who are more likely to relapse are those who took their medication in an unreliable and irregular fashion. The probability of resistance is higher in those patients who relapse and every effort must be made to obtain a specimen that can be cultured for sensitivities. That said, most patients who relapse do so with a fully sensitive strain and it is possible that these patients have not relapsed, but have instead been re-infected; these patients can be re-treated with the same regimen as before (no drugs need to be added to the regimen and the duration need not be any longer). The WHO recommends a regimen of 2SHREZ/6HRE when microbiology is not available (the majority of countries where TB is highly endemic). This regimen was designed to provide optimal treatment for fully sensitive TB (the most common finding in patients who have relapsed) as well as to cover the possibility of INH-resistant TB (the most common form of resistance found). Because of the lifelong risk of relapse, all patients should be warned of the symptoms of TB relapse upon finishing treatment and given strict instructions to return to their doctor if symptoms recur. Public health and health policy As of 2010, India has more reported cases of TB than any other country. This is in part due to severe mismanagement of diagnosis and treatment of TB within the private health care sector of India that serves about 50% of the population. There are therefore calls for the private sector to engage in the public Revised National Tuberculosis Control Program that has proved effective in reducing TB amongst the patients receiving health care through the government. Additionally, a study by Maurya et al. conducted in 2013 shows evidence that there is a burden of multidrug-resistant tuberculosis in India and change is needed for testing, surveillance, monitoring and management. During the COVID-19 pandemic, 80% fewer TB cases were reported daily in April 2020 in India, reducing the diagnosis and treatment of TB. Trial of therapy In areas where TB is highly endemic, it is not unusual to encounter patient with a fever, but in whom no source of infection is found. The physician may then, after extensive investigation has excluded all other diseases, resort to a trial of TB treatment. The regimen used is HEZ for a minimum of three weeks; RMP and STM are omitted from the regimen because they are broad spectrum antibiotics, whereas the other three first-line drugs treat only mycobacterial infection. Resolution of the fever after three weeks of treatment is good evidence for occult TB and the patient should then be changed to conventional TB treatment (2HREZ/4HR). If the fever does not resolve after three weeks of treatment then it is reasonable to conclude that the patient has another cause for his fever. This approach is not recommended by the WHO and most national guidelines. Surgical treatment Surgery has played an important part in the management of tuberculosis since the 1930s. Historical surgical management The first successful treatments for tuberculosis were all surgical. They were based on the observation that healed tuberculous cavities were all closed. Surgical management was therefore directed at closing open cavities to encourage healing. These procedures were all used in the pre-antibiotic era. There exists a myth that surgeons believed that the purpose was to deprive the organism of oxygen: it was however well known that the organism survives anaerobic conditions. Although these procedures may be considered barbaric by 21st centurys standards, it must be remembered that these treatments represented a potential cure for a disease that at the time had a mortality at least as bad as lung cancer in 2000s. Recurrent or persistent pneumothorax The simplest and earliest procedure was to introduce air into the pleural space so as to collapse the affected lung and therefore the open cavity. There was always spontaneous resolution of the pneumothorax and the procedure had to be repeated every few weeks. Phrenic nerve crush The phrenic nerve (which supplies the diaphragm) was cut or crushed so as to permanently paralyse the diaphragm on that side. The paralysed diaphragm would then rise up and the lung on that side would collapse, thus closing the cavity. Thoracoplasty When the cavity was located in the apex of the lung, thoracoplasty could be performed. Six to eight ribs were broken and pushed into the thoracic cavity to collapse the lung beneath. This was a disfiguring operation, but it avoided the need for repeated procedures. In the Novosibirsk TB Research Institute (Russia), osteoplastic thoracoplasty (a variant of extrapleural thoracoplasty) has been used for the last 50 years for patients with complicated cavitary forms of TB for whom lung resection is contraindicated. Plombage Plombage reduced the need for a disfiguring operation. It involved inserting porcelain balls into the thoracic cavity to collapse the lung underneath.Surgical resections of infected lungs were rarely attempted during the 1930s and 1940s, due to the extremely high perioperative mortality rate. Modern surgical management In modern times, the surgical treatment of tuberculosis is confined to the management of multi-drug resistant TB. A patient with MDR-TB who remains culture positive after many months of treatment may be referred for lobectomy or pneumonectomy with the aim of cutting out the infected tissue. The optimal timing for surgery has not been defined, and surgery still confers significant morbidity. The centre with the largest experience in the US is the National Jewish Medical and Research Center in Denver, Colorado. From 1983 to 2000, they performed 180 operations in 172 patients; of these, 98 were lobectomies, and 82 were pneumonectomies. They report a 3.3% operative mortality, with an additional 6.8% dying following the operation; 12% experienced significant morbidity (particularly extreme breathlessness). Of 91 patients who were culture positive before surgery, only 4 were culture positive after surgery. Some complications of treated tuberculosis like recurrent hemoptysis, destroyed or bronchiectasic lungs and empyema (a collection of pus in the pleural cavity) are also amenable to surgical therapy.In extrapulmonary TB, surgery is often needed to make a diagnosis (rather than to effect a cure): surgical excision of lymph nodes, drainage of abscesses, tissue biopsy, etc. are all examples of this. Samples taken for TB culture should be sent to the laboratory in a sterile pot with no additive (not even water or saline) and must arrive in the laboratory as soon as possible. Where facilities for liquid culture are available, specimens from sterile sites may be inoculated directly following the procedure: this may improve the yield. In spinal TB, surgery is indicated for spinal instability (when there is extensive bony destruction) or when the spinal cord is threatened. Therapeutic drainage of tuberculous abscesses or collections is not routinely indicated and will resolve with adequate treatment. In TB meningitis, hydrocephalus is a potential complication and may necessitate the insertion of a ventricular shunt or drain. Nutrition It is well known that malnutrition is a strong risk factor for becoming unwell with TB, that TB is itself a risk factor for malnutrition, and that malnourished patients with TB (BMI less than 18.5) are at an increased risk of death even with appropriate antibiotic therapy. Knowledge about the association between malnutrition and TB is prevalent in some cultures, and may reduce diagnostic delay and improve adherence to treatment.Although blood levels of some micronutrients may be low in people starting treatment for active tuberculosis, a Cochrane review of thirty-five included trials concluded that there is insufficient research to know whether the routine provision of free food or energy supplements improves tuberculosis treatment outcomes. However, nutritional supplementation probably improves weight gain in some settings. Vitamin D and tuberculosis epidemiology Vitamin D deficiency is a risk factor for tuberculosis, and vitamin D deficiency appears to impair the bodys ability to fight tuberculosis, but there is no clinical evidence to show that treating vitamin D deficiency prevents tuberculosis, although the available evidence is that it ought to. Reduced levels of vitamin D may explain the increased susceptibility of African-Americans to tuberculosis, and may also explain why phototherapy is effective for lupus vulgaris (tuberculosis of the skin) (a finding which won Niels Finsen the Nobel Prize in 1903), because skin exposed to sunlight naturally produces more vitamin D. Concerns that tuberculosis treatment itself decreases vitamin D levels appear not to be an issue in clinical practice.Genetic differences in the vitamin D receptor in West African, Gujarati and Chinese populations have been noted to affect susceptibility to tuberculosis, but there is no data available in any population that shows vitamin D supplementation (that is, giving extra vitamin D to people with normal vitamin D levels) has any effect on susceptibility to TB. Vitamin D and tuberculosis treatment Giving vitamin D to TB patients who are vitamin D deficient may be beneficial in a proportion of patients. When taken as a group, vitamin D supplementation appears to have no benefit when using sputum culture conversion as an endpoint, and giving vitamin D supplements to TB patients who have normal vitamin D levels does not provide any benefit from the point of view of TB. In a subset of patients with the tt genotype of the TaqI vitamin D receptor and who are vitamin D deficient, vitamin D supplementation appears to hasten sputum culture conversion. There are no studies of vitamin D using the gold standard outcome of relapse, so the true benefit of vitamin D is not at present known.It was noted as early as the mid-19th century that cod liver oil (which is rich in vitamin D) improved patients with tuberculosis, and the mechanism for this is probably an enhancement of immune responses to tuberculosis.The addition of vitamin D appears to enhance the ability of monocytes and macrophages to kill M. tuberculosis in vitro as well as ameliorating potentially harmful effects of the human immune system. Another reason Vitamin D can be used as a treatment for mycobacterial infections like tuberculosis is because of pro-anti-inflammatory cytokines that are influenced by vitamin D. Vitamin D has a post-anti-inflammatory effect on tuberculosis. Other arginine has some clinical evidence as an adjuvant. Mycobacterium vaccae has been completed in Phase III trials by Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., injectable Vaccae(TM) and Immunitor LLC., oral tablet Tubivac (V7). Latent tuberculosis The treatment of latent tuberculosis infection (LTBI) is essential to controlling and eliminating TB by reducing the risk that TB infection will progress to disease. The terms "preventive therapy" and "chemoprophylaxis" have been used for decades and are preferred in the UK because it involves giving medication to people who have no active disease and are currently well, the reason for treatment is primarily to prevent people from becoming unwell. The term "latent tuberculosis treatment" is preferred in the US because the medication does not actually prevent infection: it prevents an existing silent infection from becoming active. The feeling in the US is that the term "treatment of LTBI" promotes wider implementation by convincing people that they are receiving treatment for disease. There are no convincing reasons to prefer one term over the other. It is essential that assessment to rule out active TB is carried out before treatment for LTBI is started. To give LTBI treatment to someone with active TB is a serious error: the TB will not be adequately treated and there is a risk of developing drug-resistant strains of TB. There are several treatment regimens available: 9H—Isoniazid for 9 months is the gold standard and is 93% effective. 6H—Isoniazid for 6 months might be adopted by a local TB program based on cost-effectiveness and patient compliance. This is the regimen currently recommended in the UK for routine use. The US guidance exclude this regimen from use in children or persons with radiographic evidence of prior tuberculosis (old fibrotic lesions). (69% effective) 6 to 9H2—A twice-weekly regimen for the above two treatment regimens is an alternative if administered under Directly observed therapy (DOT). 4R—Rifampicin for 4 months is an alternative for those who are unable to take isoniazid or who have had known exposure to isoniazid-resistant TB. 3HR—Isoniazid and rifampicin may be given for 3 months. 2RZ—The 2-month regimen of rifampicin and pyrazinamide is no longer recommended for treatment of LTBI because of the greatly increased risk of drug-induced hepatitis and death. 3RPT/INH - 3-month (12-dose) regimen of weekly rifapentine and isoniazid.Evidence for treatment effectiveness: A 2000 Cochran review containing 11 double-blinded, randomized control trials and 73,375 patients examined six and 12 month courses of isoniazid (INH) for treatment of latent tuberculosis. HIV positive and patients currently or previously treated for tuberculosis were excluded. The main result was a relative risk (RR) of 0.40 (95% confidence interval (CI) 0.31 to 0.52) for development of active tuberculosis over two years or longer for patients treated with INH, with no significant difference between treatment courses of six or 12 months (RR 0.44, 95% CI 0.27 to 0.73 for six months, and 0.38, 95% CI 0.28 to 0.50 for 12 months).A 2013 systematic review published by the Cochrane Collaboration, compared Rifamycins (monotheraphy and combination therapy) to INH monotheraphy as an alternative in preventing active TB in HIV negative populations. The evidence suggested that shorter Rifampicin regimes (3 or 4 months) had higher treatment completion rates and fewer adverse events when compared to INH. However, the overall quality of evidence as per GRADE criteria was low to moderate. Another meta-analysis came to a similar conclusion, namely that rifamycin-containing regimens taken for 3 months or longer had a better profile in preventing TB reactivation. Research There is some evidence from animal and clinical studies that suggests that moxifloxacin-containing regimens as short as four months may be as effective as six months of conventional therapy.Bayer is currently running a phase II clinical trial in collaboration with the TB Alliance to evaluate shorter treatment regimens for TB; encouragingly, Bayer have also promised that if the trials are successful, Bayer will make moxifloxacin affordable and accessible in countries that need it. Another approach for anti-TB drug development, which does not rely on antibiotics, consists of targeting NAD+ synthase, an essential enzyme in tuberculosis bacteria but not in humans. Low level laser therapy for treating tuberculosis is not supported by reliable evidence. History Streptomycin and para-aminosalicylic acid were developed by the mid-1940s. In 1960, Edinburgh City Hospital physician Sir John Crofton, addressed the Royal College of Physicians in London with a lecture titled "Tuberculosis Undefeated", and proposed that "the disease could be conquered, once and for all". With his colleagues at Edinburgh, he recognised that germs that developed only a mild resistance to one drug was significant. His team showed that when treating new cases of TB, strict compliance to a combination of three therapies, or the triple therapy, (streptomycin, para-aminosalicylic acid and isoniazid) could provide a complete cure. It became known as the Edinburgh method and became standard treatment for at least 15 years. In the 1970s it was recognised that combining isoniazid and rifampin could reduce the duration of treatment from 18 to nine months, and in the 1980s the duration of treatment was further shortened by adding pyrazinamide. National and international guidelines See also Modern era ATC code J04 Drugs for treatment of TB Mantoux test Heaf test TB Alliance Tuberculosis management in the era before antituberculosis drugs History of tuberculosis Tuberculosis treatment in Colorado Springs (historical) References This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention. == Further reading ==

Hey Aarogya, explain a scenario commonly referred as Typhoid fever

Typhoid fever

Typhoid fever, also known as typhoid, is a disease caused by Salmonella serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several days. This is commonly accompanied by weakness, abdominal pain, constipation, headaches, and mild vomiting. Some people develop a skin rash with rose colored spots. In severe cases, people may experience confusion. Without treatment, symptoms may last weeks or months. Diarrhea may be severe, but is uncommon. Other people may carry the bacterium without being affected, but they are still able to spread the disease. Typhoid fever is a type of enteric fever, along with paratyphoid fever. S. enterica Typhi is believed to infect and replicate only within humans.Typhoid is caused by the bacterium Salmonella enterica subsp. enterica serovar Typhi growing in the intestines, peyers patches, mesenteric lymph nodes, spleen, liver, gallbladder, bone marrow and blood. Typhoid is spread by eating or drinking food or water contaminated with the feces of an infected person. Risk factors include limited access to clean drinking water and poor sanitation. Those who have not yet been exposed to the pathogen and ingest contaminated drinking water or food are most at risk for developing symptoms. Only humans can be infected; there are no known animal reservoirs.Diagnosis is by culturing and identifying S. enterica Typhi from patient samples or detecting an immune response to the pathogen from blood samples. Recently, new advances in large-scale data collection and analysis have allowed researchers to develop better diagnostics, such as detecting changing abundances of small molecules in the blood that may specifically indicate typhoid fever. Diagnostic tools in regions where typhoid is most prevalent are quite limited in their accuracy and specificity, and the time required for a proper diagnosis, the increasing spread of antibiotic resistance, and the cost of testing are also hardships for under-resourced healthcare systems.A typhoid vaccine can prevent about 40% to 90% of cases during the first two years. The vaccine may have some effect for up to seven years. For those at high risk or people traveling to areas where the disease is common, vaccination is recommended. Other efforts to prevent the disease include providing clean drinking water, good sanitation, and handwashing. Until an infection is confirmed as cleared, the infected person should not prepare food for others. Typhoid is treated with antibiotics such as azithromycin, fluoroquinolones, or third-generation cephalosporins. Resistance to these antibiotics has been developing, which has made treatment more difficult.In 2015, 12.5 million new typhoid cases were reported. The disease is most common in India. Children are most commonly affected. Typhoid decreased in the developed world in the 1940s as a result of improved sanitation and the use of antibiotics. Every year about 400 cases are reported in the U.S. and an estimated 6,000 people have typhoid. In 2015, it resulted in about 149,000 deaths worldwide – down from 181,000 in 1990. Without treatment, the risk of death may be as high as 20%. With treatment, it is between 1% and 4%.Typhus is a different disease. Owing to their similar symptoms, they were not recognized as distinct diseases until the 1800s. "Typhoid" means "resembling typhus". Signs and symptoms Classically, the progression of untreated typhoid fever has three distinct stages, each lasting about a week. Over the course of these stages, the patient becomes exhausted and emaciated. In the first week, the body temperature rises slowly, and fever fluctuations are seen with relative bradycardia (Faget sign), malaise, headache, and cough. A bloody nose (epistaxis) is seen in a quarter of cases, and abdominal pain is also possible. A decrease in the number of circulating white blood cells (leukopenia) occurs with eosinopenia and relative lymphocytosis; blood cultures are positive for S. enterica subsp. enterica serovar Typhi. The Widal test is usually negative. In the second week, the person is often too tired to get up, with high fever in plateau around 40 °C (104 °F) and bradycardia (sphygmothermic dissociation or Faget sign), classically with a dicrotic pulse wave. Delirium can occur, where the patient is often calm, but sometimes becomes agitated. This delirium has given typhoid the nickname "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. Rhonchi (rattling breathing sounds) are heard in the base of the lungs. The abdomen is distended and painful in the right lower quadrant, where a rumbling sound can be heard. Diarrhea can occur in this stage, but constipation is also common. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and liver transaminases are elevated. The Widal test is strongly positive, with antiO and antiH antibodies. Blood cultures are sometimes still positive. In the third week of typhoid fever, a number of complications can occur: The fever is still very high and oscillates very little over 24 hours. Dehydration ensues along with malnutrition, and the patient is delirious. A third of affected people develop a macular rash on the trunk. Intestinal haemorrhage due to bleeding in congested Peyers patches occurs; this can be very serious, but is usually not fatal. Intestinal perforation in the distal ileum is a very serious complication and often fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in. Respiratory diseases such as pneumonia and acute bronchitis Encephalitis Neuropsychiatric symptoms (described as "muttering delirium" or "coma vigil"), with picking at bedclothes or imaginary objects. Metastatic abscesses, cholecystitis, endocarditis, and osteitis. Low platelet count (thrombocytopenia) is sometimes seen. Causes Bacteria The Gram-negative bacterium that causes typhoid fever is Salmonella enterica subsp. enterica serovar Typhi. Based on MLST subtyping scheme, the two main sequence types of the S. Typhi are ST1 and ST2, which are widespread globally. Global phylogeographical analysis showed dominance of a haplotype 58 (H58), which probably originated in India during the late 1980s and is now spreading through the world with multi-drug resistance. A more detailed genotyping scheme was reported in 2016 and is now being used widely. This scheme reclassified the nomenclature of H58 to genotype 4.3.1. Transmission Unlike other strains of Salmonella, no animal carriers of typhoid are known. Humans are the only known carriers of the bacterium. S. enterica subsp. enterica serovar Typhi is spread by the fecal-oral route from people who are infected and from asymptomatic carriers of the bacterium. An asymptomatic human carrier is someone who is still excreting typhoid bacteria in their stool a year after the acute stage of the infection. Diagnosis Diagnosis is made by any blood, bone marrow, or stool cultures and with the Widal test (demonstration of antibodies against Salmonella antigens O-somatic and H-flagellar). In epidemics and less wealthy countries, after excluding malaria, dysentery, or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of the Widal test and blood and stool cultures. Widal test The Widal test is used to identify specific antibodies in the serum of people with typhoid by using antigen-antibody interactions.In this test, the serum is mixed with a dead bacterial suspension of salmonella with specific antigens. If the patients serum contains antibodies against those antigens, they get attached to them, forming clumps. If clumping does not occur, the test is negative. The Widal test is time-consuming and prone to significant false positives. It may also be falsely negative in recently infected people. But unlike the Typhidot test, the Widal test quantifies the specimen with titres. Rapid diagnostic tests Rapid diagnostic tests such as Tubex, Typhidot, and Test-It have shown moderate diagnostic accuracy. Typhidot Typhidot is based on the presence of specific IgM and IgG antibodies to a specific 50Kd OMP antigen. This test is carried out on a cellulose nitrate membrane where a specific S. typhi outer membrane protein is attached as fixed test lines. It separately identifies IgM and IgG antibodies. IgM shows recent infection; IgG signifies remote infection. The sample pad of this kit contains colloidal gold-anti-human IgG or gold-anti-human IgM. If the sample contains IgG and IgM antibodies against those antigens, they will react and turn red. The typhidot test becomes positive within 2–3 days of infection. Two colored bands indicate a positive test. A single control band indicates a negative test. A single first fixed line or no band at all indicates an invalid test. Typhidots biggest limitation is that it is not quantitative, just positive or negative. Tubex test The Tubex test contains two types of particles: brown magnetic particles coated with antigen and blue indicator particles coated with O9 antibody. During the test, if antibodies are present in the serum, they will attach to the brown magnetic particles and settle at the base, while the blue indicator particles remain in the solution, producing a blue color, which means the test is positive.If the serum does not have an antibody in it, the blue particles attach to the brown particles and settle at the bottom, producing a colorless solution, which means the test is negative. Prevention Sanitation and hygiene are important to prevent typhoid. It can spread only in environments where human feces can come into contact with food or drinking water. Careful food preparation and washing of hands are crucial to prevent typhoid. Industrialization contributed greatly to the elimination of typhoid fever, as it eliminated the public-health hazards associated with having horse manure in public streets, which led to a large number of flies, which are vectors of many pathogens, including Salmonella spp. According to statistics from the U.S. Centers for Disease Control and Prevention, the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever. Vaccination Two typhoid vaccines are licensed for use for the prevention of typhoid: the live, oral Ty21a vaccine (sold as Vivotif by Crucell Switzerland AG) and the injectable typhoid polysaccharide vaccine (sold as Typhim Vi by Sanofi Pasteur and Typherix by GlaxoSmithKline). Both are efficacious and recommended for travelers to areas where typhoid is endemic. Boosters are recommended every five years for the oral vaccine and every two years for the injectable form. An older, killed whole-cell vaccine is still used in countries where the newer preparations are not available, but this vaccine is no longer recommended for use because it has more side effects (mainly pain and inflammation at the site of the injection). To help decrease rates of typhoid fever in developing nations, the World Health Organization (WHO) endorsed the use of a vaccination program starting in 1999. Vaccination has proven effective at controlling outbreaks in high-incidence areas and is also very cost-effective: prices are normally less than US$1 per dose. Because the price is low, poverty-stricken communities are more willing to take advantage of the vaccinations. Although vaccination programs for typhoid have proven effective, they alone cannot eliminate typhoid fever. Combining vaccines with public-health efforts is the only proven way to control this disease.Since the 1990s, the WHO has recommended two typhoid fever vaccines. The ViPS vaccine is given by injection, and the Ty21a by capsules. Only people over age two are recommended to be vaccinated with the ViPS vaccine, and it requires a revaccination after 2–3 years, with a 55%–72% efficacy. The Ty21a vaccine is recommended for people five and older, lasting 5–7 years with 51%–67% efficacy. The two vaccines have proved safe and effective for epidemic disease control in multiple regions.A version of the vaccine combined with a hepatitis A vaccine is also available.Results of a phase 3 trial of typhoid conjugate vaccine (TCV) in December 2019 reported 81% fewer cases among children. Treatment Oral rehydration therapy The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general. Antibiotics Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin. Otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice. Cefixime is a suitable oral alternative.Properly treated, typhoid fever is not fatal in most cases. Antibiotics such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin, and ciprofloxacin have been commonly used to treat it. Treatment with antibiotics reduces the case-fatality rate to about 1%.Without treatment, some patients develop sustained fever, bradycardia, hepatosplenomegaly, abdominal symptoms, and occasionally pneumonia. In white-skinned patients, pink spots, which fade on pressure, appear on the skin of the trunk in up to 20% of cases. In the third week, untreated cases may develop gastrointestinal and cerebral complications, which may prove fatal in 10%–20% of cases. The highest case fatality rates are reported in children under 4. Around 2%–5% of those who contract typhoid fever become chronic carriers, as bacteria persist in the biliary tract after symptoms have resolved. Surgery Surgery is usually indicated if intestinal perforation occurs. One study found a 30-day mortality rate of 9% (8/88), and surgical site infections at 67% (59/88), with the disease burden borne predominantly by low-resource countries.For surgical treatment, most surgeons prefer simple closure of the perforation with drainage of the peritoneum. Small-bowel resection is indicated for patients with multiple perforations. If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladder should be resected. Cholecystectomy is sometimes successful, especially in patients with gallstones, but is not always successful in eradicating the carrier state because of persisting hepatic infection. Resistance As resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and streptomycin is now common, these agents are no longer used as first–line treatment of typhoid fever. Typhoid resistant to these agents is known as multidrug-resistant typhoid.Ciprofloxacin resistance is an increasing problem, especially in the Indian subcontinent and Southeast Asia. Many centres are shifting from ciprofloxacin to ceftriaxone as the first line for treating suspected typhoid originating in South America, India, Pakistan, Bangladesh, Thailand, or Vietnam. Also, it has been suggested that azithromycin is better at treating resistant typhoid than both fluoroquinolone drugs and ceftriaxone. Azithromycin can be taken by mouth and is less expensive than ceftriaxone, which is given by injection.A separate problem exists with laboratory testing for reduced susceptibility to ciprofloxacin; current recommendations are that isolates should be tested simultaneously against ciprofloxacin (CIP) and against nalidixic acid (NAL), that isolates sensitive to both CIP and NAL should be reported as "sensitive to ciprofloxacin", and that isolates sensitive to CIP but not to NAL should be reported as "reduced sensitivity to ciprofloxacin". But an analysis of 271 isolates found that around 18% of isolates with a reduced susceptibility to fluoroquinolones, the class which CIP belongs (MIC 0.125–1.0 mg/L), would not be detected by this method. Epidemiology In 2000, typhoid fever caused an estimated 21.7 million illnesses and 217,000 deaths. It occurs most often in children and young adults between 5 and 19 years old. In 2013, it resulted in about 161,000 deaths – down from 181,000 in 1990. Infants, children, and adolescents in south-central and Southeast Asia have the highest rates of typhoid. Outbreaks are also often reported in sub-Saharan Africa and Southeast Asia. In 2000, more than 90% of morbidity and mortality due to typhoid fever occurred in Asia. In the U.S., about 400 cases occur each year, 75% of which are acquired while traveling internationally.Before the antibiotic era, the case fatality rate of typhoid fever was 10%–20%. Today, with prompt treatment, it is less than 1%, but 3%–5% of people who are infected develop a chronic infection in the gall bladder. Since S. enterica subsp. enterica serovar Typhi is human-restricted, these chronic carriers become the crucial reservoir, which can persist for decades for further spread of the disease, further complicating its identification and treatment. Lately, the study of S. enterica subsp. enterica serovar Typhi associated with a large outbreak and a carrier at the genome level provides new insight into the pathogenesis of the pathogen.In industrialized nations, water sanitation and food handling improvements have reduced the number of typhoid cases. Developing nations, such as those in parts of Asia and Africa, have the highest rates. These areas lack access to clean water, proper sanitation systems, and proper health-care facilities. In these areas, such access to basic public-health needs is not expected in the near future.In 2004–2005 an outbreak in the Democratic Republic of Congo resulted in more than 42,000 cases and 214 deaths. Since November 2016, Pakistan has had an outbreak of extensively drug-resistant (XDR) typhoid fever.In Europe, a report based on data for 2017 retrieved from The European Surveillance System (TESSy) on the distribution of confirmed typhoid and paratyphoid fever cases found that 22 EU/EEA countries reported a total of 1,098 cases, 90.9% of which were travel-related, mainly acquired during travel to South Asia. History Early descriptions The plague of Athens, during the Peloponnesian War, was most likely an outbreak of typhoid fever. During the war, Athenians retreated into a walled-in city to escape attack from the Spartans. This massive influx of humans into a concentrated space overwhelmed the water supply and waste infrastructure, likely leading to unsanitary conditions as fresh water became harder to obtain and waste became more difficult to collect and remove beyond the city walls. In 2006, examining the remains for a mass burial site from Athens from around the time of the plague (~430 B.C.) revealed that fragments of DNA similar to modern day S. Typhi DNA were detected, whereas Yersinia pestis (plague), Rickettsia prowazekii (typhus), Mycobacterium tuberculosis, cowpox virus, and Bartonella henselae were not detected in any of the remains tested.It is possible that the Roman emperor Augustus Caesar had either a liver abscess or typhoid fever, and survived by using ice baths and cold compresses as a means of treatment for his fever. There is a statue of the Greek physician, Antonius Musa, who treated his fever. Definition and evidence of transmission The French doctors Pierre-Fidele Bretonneau and Pierre-Charles-Alexandre Louis are credited with describing typhoid fever as a specific disease, unique from typhus. Both doctors performed autopsies on individuals who died in Paris due to fever – and indicated that many had lesions on the Peyers patches which correlated with distinct symptoms before death. British medics were skeptical of the differentiation between typhoid and typhus because both were endemic to Britain at that time. However, in France only typhoid was present circulating in the population. Pierre-Charlles-Alexandre Louis also performed case studies and statistical analysis to demonstrate that typhoid was contagious - and that persons who already had the disease seemed to be protected. Afterward, several American doctors confirmed these findings, and then Sir William Jenner convinced any remaining skeptics that typhoid is a specific disease recognizable by lesions in the Peyers patches by examining sixty six autopsies from fever patients and concluding that the symptoms of headaches, diarrhea, rash spots, and abdominal pain were only present in patients which then had intestinal lesions after death; which solidified the association of the disease with the intestinal tract and gave the first clue to the route of transmission.In 1847 William Budd learned of an epidemic of typhoid fever in Clifton, and identified that all 13 of 34 residents who had contracted the disease drew their drinking water from the same well. Notably, this observation was two years prior to John Snow discovering the route of contaminated water as the cause for a cholera outbreak. Budd later became health officer of Bristol and ensured a clean water supply, and documented further evidence of typhoid as a water-borne illness throughout his career. Cause Polish scientist Tadeusz Browicz described a short bacillus in the organs and feces of typhoid victims in 1874. Browicz was able to isolate and grow the bacilli but did not go as far as to insinuate or prove that they caused the disease.In April 1880, three months prior to Eberths publication, Edwin Klebs described short and filamentous bacilli in the Peyers patches in typhoid victims. The bacteriums role in disease was speculated but not confirmed.In 1880, Karl Joseph Eberth described a bacillus that he suspected was the cause of typhoid. Eberth is given credit for discovering the bacterium definitively by successfully isolating the same bacterium from 18 of 40 typhoid victims and failing to discover the bacterium present in any "control" victims of other diseases. In 1884, pathologist Georg Theodor August Gaffky (1850–1918) confirmed Eberths findings. Gaffky isolated the same bacterium as Eberth from the spleen of a typhoid victim, and was able to grow the bacterium on solid media. The organism was given names such as Eberths bacillus, Eberthella Typhi, and Gaffky-Eberth bacillus. Today, the bacillus that causes typhoid fever goes by the scientific name Salmonella enterica serovar Typhi. Chlorination of water Most developed countries had declining rates of typhoid fever throughout the first half of the 20th century due to vaccinations and advances in public sanitation and hygiene. In 1893 attempts were made to chlorinate the water supply in Hamburg, Germany and in 1897 Maidstone, England, was the first town to have its entire water supply chlorinated. In 1905, following an outbreak of typhoid fever, the City of Lincoln, England, instituted permanent water chlorination. The first permanent disinfection of drinking water in the US was made in 1908 to the Jersey City, New Jersey, water supply. Credit for the decision to build the chlorination system has been given to John L. Leal. The chlorination facility was designed by George W. Fuller.Outbreaks in traveling military groups led to the creation of the Lyster bag in 1915; a bag with a faucet which can be hung from a tree or pole, filled with water, and comes with a chlorination tablet to drop into the water. The Lyster bag was essential for the survival of American soldiers in the Vietnam War. Direct transmission and carriers There were several occurrences of milk delivery men spreading typhoid fever throughout the communities they served. Although typhoid is not spread through milk itself, there were several examples of milk distributors in many locations watering their milk down with contaminated water, or cleaning the glass bottles the milk was placed in with contaminated water. Boston had two such cases around the turn of the 20th century. In 1899 there were 24 cases of typhoid traced to a single milkman, whose wife had died of typhoid fever a week before the outbreak. In 1908, J.J. Fallon, who was also a milkman, died of typhoid fever. Following his death and confirmation of the typhoid fever diagnosis, the city conducted an investigation of typhoid symptoms and cases along his route and found evidence of a significant outbreak. A month after the outbreak was first reported, the Boston Globe published a short statement declaring the outbreak over, stating "[a]t Jamaica Plain there is a slight increase, the total being 272 cases. Throughout the city there is a total of 348 cases." There was at least one death reported during this outbreak: Mrs. Sophia S. Engstrom, aged 46. Typhoid continued to ravage the Jamaica Plain neighborhood in particular throughout 1908, and several more people were reported dead due to typhoid fever, although these cases were not explicitly linked to the outbreak. The Jamaica Plain neighborhood at that time was home to many working-class and poor immigrants, mostly from Ireland.The most notorious carrier of typhoid fever, but by no means the most destructive, was Mary Mallon, known as Typhoid Mary. Although other cases of human-to-human spread of typhoid were known at the time, the concept of an asymptomatic carrier, who was able to transmit disease, had only been hypothesized and not yet identified or proven. Mary Mallon became the first known example of an asymptomatic carrier of an infectious disease, making typhoid fever the first known disease being transmissible through asymptomatic hosts. The cases and deaths caused by Mallon were mainly upper-class families in New York City. At the time of Mallons tenure as a personal cook for upper-class families, New York City reported 3,000 to 4,500 cases of typhoid fever annually. In the summer of 1906 two daughters of a wealthy family and maids working in their home became ill with typhoid fever. After investigating their home water sources and ruling out water contamination, the family hired civil engineer George Soper to conduct an investigation of the possible source of typhoid fever in the home. Soper described himself as an "epidemic fighter". His investigation ruled out many sources of food, and led him to question if the cook the family hired just prior to their household outbreak, Mallon, was the source. Since she had already left and begun employment elsewhere, he proceeded to track her down in order to obtain a stool sample. When he was able to finally meet Mallon in person he described her by saying "Mary had a good figure and might have been called athletic had she not been a little too heavy." In recounts of Sopers pursuit of Mallon, his only remorse appears to be that he was not given enough credit for his relentless pursuit and publication of her personal identifying information, stating that the media "rob[s] me of whatever credit belongs to the discovery of the first typhoid fever carrier to be found in America." Ultimately, 51 cases and 3 deaths were suspected to be caused by Mallon.In 1924 the city of Portland, Oregon, experienced an outbreak of typhoid fever, consisting of 26 cases and 5 deaths, all deaths due to intestinal hemorrhage. All cases were concluded to be due to a single milk farm worker, who was shedding large amounts of the typhoid pathogen in his urine. Misidentification of the disease, due to inaccurate Widal test results, delayed identification of the carrier and proper treatment. Ultimately, it took four samplings of different secretions from all of the dairy workers in order to successfully identify the carrier. Upon discovery, the dairy worker was forcibly quarantined for seven weeks, and regular samples were taken, most of the time the stool samples yielding no typhoid and often the urine yielding the pathogen. The carrier was reported as being 72 years old and appearing in excellent health with no symptoms. Pharmaceutical treatment decreased the amount of bacteria secreted, however, the infection was never fully cleared from the urine, and the carrier was released "under orders never again to engage in the handling of foods for human consumption." At the time of release, the authors noted "for more than fifty years he has earned his living chiefly by milking cows and knows little of other forms of labor, it must be expected that the closest surveillance will be necessary to make certain that he does not again engage in this occupation."Overall, in the early 20th century the medical profession began to identify carriers of the disease, and evidence of transmission independent of water contamination. In a 1933 American Medical Association publication, physicians treatment of asymptomatic carriers is best summarized by the opening line "Carriers of typhoid bacilli are a menace". Within the same publication, the first official estimate of typhoid carriers is given: 2 to 5% of all typhoid patients, and distinguished between temporary carriers and chronic carriers. The authors further estimate that there are four to five chronic female carriers to every one male carrier, although offered no data to explain this assertion of a gender difference in the rate of typhoid carriers. As far as treatment, the authors suggest: "When recognized, carriers must be instructed as to the disposal of excreta as well as to the importance of personal cleanliness. They should be forbidden to handle food or drink intended for others, and their movements and whereabouts must be reported to the public health officers". Today, typhoid carriers exist all over the world, but the highest incidence of asymptomatic infection is likely to occur in South/Southeast Asian and Sub-Saharan countries. The Los Angeles County department of public health tracks typhoid carriers and reports the number of carriers identified within the county yearly; between 2006 and 2016 0-4 new cases of typhoid carriers were identified per year. Cases of typhoid fever must be reported within one working day from identification. As of 2018, chronic typhoid carriers must sign a "Carrier Agreement" and are required to test for typhoid shedding twice yearly, ideally every 6 months. Carriers may be released from their agreements upon fulfilling "release" requirements, based on completion of a personalized treatment plan designed with medical professionals. Fecal or gallbladder carrier release requirements: 6 consecutive negative feces and urine specimens submitted at 1-month or greater intervals beginning at least 7 days after completion of therapy. Urinary or kidney carrier release requirements: 6 consecutive negative urine specimens submitted at 1-month or greater intervals beginning at least 7 days after completion of therapy. As of 2016 the male:female ratio of carriers in Los Angeles county was 3:1.Due to the nature of asymptomatic cases, many questions remain about how individuals are able to tolerate infection for long periods of time, how to identify such cases, and efficient options for treatment. Researchers are currently working to understand asymptomatic infection with Salmonella species by studying infections in laboratory animals, which will ultimately lead to improved prevention and treatment options for typhoid carriers. In 2002, Dr. John Gunn described the ability of Salmonella sp. to form biofilms on gallstones in mice, providing a model for studying carriage in the gallbladder. Dr. Denise Monack and Dr. Stanley Falkow described a mouse model of asymptomatic intestinal and systemic infection in 2004, and Dr. Monack went on to demonstrate that a sub-population of superspreaders are responsible for the majority of transmission to new hosts, following the 80/20 rule of disease transmission, and that the intestinal microbiota likely plays a role in transmission. Dr. Monacks mouse model allows long-term carriage of salmonella in mesenteric lymph nodes, spleen and liver. Vaccine development British bacteriologist Almroth Edward Wright first developed an effective typhoid vaccine at the Army Medical School in Netley, Hampshire. It was introduced in 1896 and used successfully by the British during the Second Boer War in South Africa. At that time, typhoid often killed more soldiers at war than were lost due to enemy combat. Wright further developed his vaccine at a newly opened research department at St Marys Hospital Medical School in London from 1902, where he established a method for measuring protective substances (opsonin) in human blood. Wrights version of the typhoid vaccine was produced by growing the bacterium at body temperature in broth, then heating the bacteria to 60 °C to "heat inactivate" the pathogen, killing it, while keeping the surface antigens intact. The heat-killed bacteria was then injected into a patient. To show evidence of the vaccines efficacy, Wright then collected serum samples from patients several weeks post-vaccination, and tested their serums ability to agglutinate live typhoid bacteria. A "positive" result was represented by clumping of bacteria, indicating that the body was producing anti-serum (now called antibodies) against the pathogen.Citing the example of the Second Boer War, during which many soldiers died from easily preventable diseases, Wright convinced the British Army that 10 million vaccine doses should be produced for the troops being sent to the Western Front, thereby saving up to half a million lives during World War I. The British Army was the only combatant at the outbreak of the war to have its troops fully immunized against the bacterium. For the first time, their casualties due to combat exceeded those from disease.In 1909, Frederick F. Russell, a U.S. Army physician, adopted Wrights typhoid vaccine for use with the Army, and two years later, his vaccination program became the first in which an entire army was immunized. It eliminated typhoid as a significant cause of morbidity and mortality in the U.S. military. Typhoid vaccination for members of the American military became mandatory in 1911. Before the vaccine, the rate of typhoid fever in the military was 14,000 or greater per 100,000 soldiers. By World War I, the rate of typhoid in American soldiers was 37 per 100,000.During the second world war, the United States army authorized the use of a trivalent vaccine – containing heat-inactivated Typhoid, Paratyphi A and Paratyphi B pathogens.In 1934, discovery of the Vi capsular antigen by Arthur Felix and Miss S. R. Margaret Pitt enabled development of the safer Vi Antigen vaccine – which is widely in use today. Arthur Felix and Margaret Pitt also isolated the strain Ty2, which became the parent strain of Ty21a, the strain used as a live-attenuated vaccine for typhoid fever today. Antibiotics and resistance Chloramphenicol was isolated from Streptomyces by Dr. David Gotlieb during the 1940s. In 1948 American army doctors tested its efficacy in treating typhoid patients in Kuala Lumpur, Malaysia. Individuals who received a full course of treatment cleared the infection, whereas patients given a lower dose had a relapse. Asymptomatic carriers continued to shed bacilli despite chloramphenicol treatment - only ill patients were improved with chloramphenicol. Resistance to chloramphenicol became frequent in Southeast Asia by the 1950s, and today chloramphenicol is only used as a last resort due to the high prevalence of resistance. Terminology The disease has been referred to by various names, often associated with symptoms, such as gastric fever, enteric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever, pythogenic fever, drain fever and low fever. Notable people Emperor Augustus of Rome (suspected based on historical record but not confirmed), survived. Albert, Prince Consort, husband of Queen Victoria of the United Kingdom, died in 24 days after first record of "feeling horribly ill". Died 14 December 1861 after suffering loss of appetite, insomnia, fever, chills, profuse sweating, vomiting, rash spots, delusions, inability to recognize family members, worsening rash on abdomen, a change in tongue color, then finally a state of extreme fatigue. Attending physician William Jenner, an expert on Typhoid fever at the time, diagnosed him. Edward VII of the UK, son of Queen Victoria, while still Prince of Wales, had a near fatal case of typhoid fever. Tsar Nicholas II of Russia, survived, illness was circa 1900–1901. William Henry Harrison, the 9th President of the United States of America, died 32 days into his term, in 1841. This is the shortest term served by a United States President. Wilbur Wright, co-inventor of the plane with his brother Orville died from typhoid 32 years before Orville. Stephen A. Douglas, political opponent of Abraham Lincoln in 1858 and 1860, died of typhoid on June 3, 1861. Ignacio Zaragoza, Mexican general and politician, died at the age of 33 of typhoid fever on September 8, 1862. William Wallace Lincoln, the son of US president Abraham and Mary Todd Lincoln, died of typhoid in 1862. Martha Bulloch Roosevelt, mother of president Theodore Roosevelt and paternal grandmother of Eleanor Roosevelt, died of typhoid fever in 1884. Mary Mallon, "Typhoid Mary" - see history section, "carriers" for further details Leland Stanford Jr., son of American tycoon and politician A. Leland Stanford and eponym of Leland Stanford Junior University, died of typhoid fever in 1884 at the age of 15. Three of Louis Pasteurs five children died of typhoid fever. Gerard Manley Hopkins, English poet, died of typhoid fever in 1889. Lizzie van Zyl, South African child inmate of the Bloemfontein concentration camp during the Second Boer War, died of typhoid fever in 1901. Dr HJH Tup Scott, captain of the 1886 Australian cricket team that toured England, died of typhoid in 1910. Arnold Bennett, English novelist, died in 1932 of typhoid, two months after drinking a glass of water in a Paris hotel to prove it was safe. Hakaru Hashimoto, Japanese medical scientist, died of typhoid fever in 1934. Outbreaks Plague of Athens (suspected) "Burning Fever" outbreak among indigenous Americans. Between 1607 and 1624, 85% of the population at the James River died from a typhoid epidemic. The World Health Organization estimates the death toll was over 6,000 during this time. Maidstone, Kent outbreak in 1897–1898: 1,847 patients were recorded to have typhoid fever. This outbreak is notable because it was the first time a typhoid vaccine was deployed during a civilian outbreak. Almoth Edward Wrights vaccine was offered to 200 healthcare providers, and of the 84 individuals who received the vaccine none developed typhoid whereas 4 who had not been vaccinated became ill. American army in the Spanish-American war: government records estimate over 21,000 troops had typhoid, resulting in 2,200 deaths. In 1902, guests at mayoral banquets in Southampton and Winchester, England, became ill and four died, including the Dean of Winchester, after consuming oysters. The infection was due to oysters sourced from Emsworth, where the oyster beds had been contaminated with raw sewage. Jamaica Plain neighborhood, Boston in 1908 - linked to milk delivery. See history section, "carriers" for further details. Outbreak in upperclass New Yorkers who employed Mary Mallon - 51 cases and 3 deaths from 1907 to 1915. Aberdeen, Scotland, in summer 1964 - traced back to contaminated canned beef sourced from Argentina sold in markets. More than 500 patients were quarantined in the hospital for a minimum of four weeks, and the outbreak was contained without any deaths. Dushanbe, Tajikistan, in 1996–1997: 10,677 cases reported, 108 deaths Kinshasa, Democratic Republic of the Congo, in 2004: 43,000 cases and over 200 deaths. A prospective study of specimens collected in the same region between 2007 and 2011 revealed about one third of samples obtained from patient samples were resistant to multiple antibiotics. Kampala, Uganda in 2015: 10,230 cases reported See also Typhus fever References == Further reading ==

Would you describe Weight loss, to me Aarogya

Weight loss

Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other connective tissue). Weight loss can either occur unintentionally because of malnourishment or an underlying disease, or from a conscious effort to improve an actual or perceived overweight or obese state. "Unexplained" weight loss that is not caused by reduction in calorific intake or exercise is called cachexia and may be a symptom of a serious medical condition. Intentional Intentional weight loss is the loss of total body mass as a result of efforts to improve fitness and health, or to change appearance through slimming. Weight loss is the main treatment for obesity, and there is substantial evidence this can prevent progression from prediabetes to type 2 diabetes with a 7-10% weight loss and manage cardiometabolic health for diabetic people with a 5-15% weight loss.Weight loss in individuals who are overweight or obese can reduce health risks, increase fitness, and may delay the onset of diabetes. It could reduce pain and increase movement in people with osteoarthritis of the knee. Weight loss can lead to a reduction in hypertension (high blood pressure), however whether this reduces hypertension-related harm is unclear. Weight loss is achieved by adopting a lifestyle in which fewer calories are consumed than are expended. Depression, stress or boredom may contribute to weight increase, and in these cases, individuals are advised to seek medical help. A 2010 study found that dieters who got a full nights sleep lost more than twice as much fat as sleep-deprived dieters. Though hypothesized that supplementation of vitamin D may help, studies do not support this. The majority of dieters regain weight over the long term. According to the UK National Health Service and the Dietary Guidelines for Americans, those who achieve and manage a healthy weight do so most successfully by being careful to consume just enough calories to meet their needs, and being physically active.For weight loss to be permanent, changes in diet and lifestyle must be permanent as well. There is evidence that counseling or exercise alone do not result in weight loss, whereas dieting alone results in meaningful long-term weight loss, and a combination of dieting and exercise provides the best results. Meal replacements, orlistat, a very-low-calorie diet, and primary care intensive medical interventions can also support meaningful weight loss. Techniques Diet and exercise The least intrusive weight loss methods, and those most often recommended, are adjustments to eating patterns and increased physical activity, generally in the form of exercise. The World Health Organization recommends that people combine a reduction of processed foods high in saturated fats, sugar and salt, and reduced caloric intake with an increase in physical activity. Both long-term exercise programs and anti-obesity medications reduce abdominal fat volume. Self-monitoring of diet, exercise, and weight are beneficial strategies for weight loss, particularly early in weight loss programs. Research indicates that those who log their foods about three times per day and about 20 times per month are more likely to achieve clinically significant weight loss.Weight loss depends on maintaining an negative energy balance and not the type of macronutrients (such as carbohydrate) consumed. High protein diets have shown greater efficacy in the short term for people eating ad libitum due to increased thermogenesis and satiety. Medications Other methods of weight loss include use of anti-obesity drugs that decrease appetite, block fat absorption, or reduce stomach volume. Obesity has been resistant to drug-based therapies, with a 2021 review stating that existing medications are "often delivering insufficient efficacy and dubious safety". Bariatric surgery Bariatric surgery may be indicated in cases of severe obesity. Two common bariatric surgical procedures are gastric bypass and gastric banding. Both can be effective at limiting the intake of food energy by reducing the size of the stomach, but as with any surgical procedure both come with their own risks that should be considered in consultation with a physician. Weight loss industry There is a substantial market for products which claim to make weight loss easier, quicker, cheaper, more reliable, or less painful. These include books, DVDs, CDs, cremes, lotions, pills, rings and earrings, body wraps, body belts and other materials, fitness centers, clinics, personal coaches, weight loss groups, and food products and supplements. Dietary supplements, though widely used, are not considered a healthy option for weight loss, and have no clinical evidence of efficacy. Herbal products have not been shown to be effective.In 2008, between US$33 billion and $55 billion was spent annually in the US on weight-loss products and services, including medical procedures and pharmaceuticals, with weight-loss centers taking between 6 and 12 percent of total annual expenditure. Over $1.6 billion per year was spent on weight-loss supplements. About 70 percent of Americans dieting attempts are of a self-help nature.In Western Europe, sales of weight-loss products, excluding prescription medications, topped €1,25 billion (£900 million/$1.4 billion) in 2009.The scientific soundness of commercial diets by commercial weight management organizations varies widely, being previously non-evidence-based, so there is only limited evidence supporting their use, because of high attrition rates. Commercial diets result in modest weight loss in the long term, with similar results regardless of the brand, and similarly to non-commercial diets and standard care. Comprehensive diet programs, providing counseling and targets for calorie intake, are more efficient than dieting without guidance ("self-help"), although the evidence is very limited. The National Institute for Health and Care Excellence devised a set of essential criteria to be met by commercial weight management organizations to be approved. Unintentional Characteristics Unintentional weight loss may result from loss of body fats, loss of body fluids, muscle atrophy, or a combination of these. It is generally regarded as a medical problem when at least 10% of a persons body weight has been lost in six months or 5% in the last month. Another criterion used for assessing weight that is too low is the body mass index (BMI). However, even lesser amounts of weight loss can be a cause for serious concern in a frail elderly person.Unintentional weight loss can occur because of an inadequately nutritious diet relative to a persons energy needs (generally called malnutrition). Disease processes, changes in metabolism, hormonal changes, medications or other treatments, disease- or treatment-related dietary changes, or reduced appetite associated with a disease or treatment can also cause unintentional weight loss. Poor nutrient utilization can lead to weight loss, and can be caused by fistulae in the gastrointestinal tract, diarrhea, drug-nutrient interaction, enzyme depletion and muscle atrophy.Continuing weight loss may deteriorate into wasting, a vaguely defined condition called cachexia. Cachexia differs from starvation in part because it involves a systemic inflammatory response. It is associated with poorer outcomes. In the advanced stages of progressive disease, metabolism can change so that they lose weight even when they are getting what is normally regarded as adequate nutrition and the body cannot compensate. This leads to a condition called anorexia cachexia syndrome (ACS) and additional nutrition or supplementation is unlikely to help. Symptoms of weight loss from ACS include severe weight loss from muscle rather than body fat, loss of appetite and feeling full after eating small amounts, nausea, anemia, weakness and fatigue.Serious weight loss may reduce quality of life, impair treatment effectiveness or recovery, worsen disease processes and be a risk factor for high mortality rates. Malnutrition can affect every function of the human body, from the cells to the most complex body functions, including: immune response; wound healing; muscle strength (including respiratory muscles); renal capacity and depletion leading to water and electrolyte disturbances; thermoregulation; and menstruation.Malnutrition can lead to vitamin and other deficiencies and to inactivity, which in turn may pre-dispose to other problems, such as pressure sores. Unintentional weight loss can be the characteristic leading to diagnosis of diseases such as cancer and type 1 diabetes. In the UK, up to 5% of the general population is underweight, but more than 10% of those with lung or gastrointestinal diseases and who have recently had surgery. According to data in the UK using the Malnutrition Universal Screening Tool (MUST), which incorporates unintentional weight loss, more than 10% of the population over the age of 65 is at risk of malnutrition. A high proportion (10–60%) of hospital patients are also at risk, along with a similar proportion in care homes. Causes Disease-related Disease-related malnutrition can be considered in four categories: Weight loss issues related to specific diseases include: As chronic obstructive pulmonary disease (COPD) advances, about 35% of patients experience severe weight loss called pulmonary cachexia, including diminished muscle mass. Around 25% experience moderate to severe weight loss, and most others have some weight loss. Greater weight loss is associated with poorer prognosis. Theories about contributing factors include appetite loss related to reduced activity, additional energy required for breathing, and the difficulty of eating with dyspnea (labored breathing). Cancer, a very common and sometimes fatal cause of unexplained (idiopathic) weight loss. About one-third of unintentional weight loss cases are secondary to malignancy. Cancers to suspect in patients with unexplained weight loss include gastrointestinal, prostate, hepatobiliary (hepatocellular carcinoma, pancreatic cancer), ovarian, hematologic or lung malignancies. People with HIV often experience weight loss, and it is associated with poorer outcomes. Wasting syndrome is an AIDS-defining condition. Gastrointestinal disorders are another common cause of unexplained weight loss – in fact they are the most common non-cancerous cause of idiopathic weight loss. Possible gastrointestinal etiologies of unexplained weight loss include: celiac disease, peptic ulcer disease, inflammatory bowel disease (crohns disease and ulcerative colitis), pancreatitis, gastritis, diarrhea, chronic mesenteric ischemia and many other GI conditions. Infection. Some infectious diseases can cause weight loss. Fungal illnesses, endocarditis, many parasitic diseases, AIDS, and some other subacute or occult infections may cause weight loss. Renal disease. Patients who have uremia often have poor or absent appetite, vomiting and nausea. This can cause weight loss. Cardiac disease. Cardiovascular disease, especially congestive heart failure, may cause unexplained weight loss. Connective tissue disease Oral, taste or dental problems (including infections) can reduce nutrient intake leading to weight loss. Therapy-related Medical treatment can directly or indirectly cause weight loss, impairing treatment effectiveness and recovery that can lead to further weight loss in a vicious cycle. Many patients will be in pain and have a loss of appetite after surgery. Part of the bodys response to surgery is to direct energy to wound healing, which increases the bodys overall energy requirements. Surgery affects nutritional status indirectly, particularly during the recovery period, as it can interfere with wound healing and other aspects of recovery. Surgery directly affects nutritional status if a procedure permanently alters the digestive system. Enteral nutrition (tube feeding) is often needed. However a policy of nil by mouth for all gastrointestinal surgery has not been shown to benefit, with some weak evidence suggesting it might hinder recovery. Early post-operative nutrition is a part of Enhanced Recovery After Surgery protocols. These protocols also include carbohydrate loading in the 24 hours before surgery, but earlier nutritional interventions have not been shown to have a significant impact. Social conditions Social conditions such as poverty, social isolation and inability to get or prepare preferred foods can cause unintentional weight loss, and this may be particularly common in older people. Nutrient intake can also be affected by culture, family and belief systems. Ill-fitting dentures and other dental or oral health problems can also affect adequacy of nutrition.Loss of hope, status or social contact and spiritual distress can cause depression, which may be associated with reduced nutrition, as can fatigue. Myths Some popular beliefs attached to weight loss have been shown to either have less effect on weight loss than commonly believed or are actively unhealthy. According to Harvard Health, the idea of metabolic rate being the "key to weight" is "part truth and part myth" as while metabolism does affect weight loss, external forces such as diet and exercise have an equal effect. They also commented that the idea of changing ones rate of metabolism is under debate. Diet plans in fitness magazines are also often believed to be effective but may actually be harmful by limiting the daily intake of important calories and nutrients which can be detrimental depending on the person and are even capable of driving individuals away from weight loss. Health effects Obesity increases health risks, including diabetes, cancer, cardiovascular disease, high blood pressure, and non-alcoholic fatty liver disease, to name a few. Reduction of obesity lowers those risks. A 1-kg loss of body weight has been associated with an approximate 1-mm Hg drop in blood pressure. Intentional weight loss is associated with cognitive performance improvements in overweight and obese individuals. See also Anorexia Cigarette smoking for weight loss Dieting Physical exercise Weight gain References External links Weight loss at Curlie Health benefits of losing weight By IQWiG at PubMed Health Weight-control Information Network Archived 12 February 2015 at the Wayback Machine U.S. National Institutes of Health Nutrition in cancer care By NCI at PubMed Health Unintentional weight loss

Could you describe Urethritis, to me Aarogya

Urethritis

Urethritis is the inflammation of the urethra. The most common symptoms include painful or difficult urination and urethral discharge. It is a commonly treatable condition usually caused by infection with bacteria. This bacterial infection is often sexually transmitted, but not in every instance; it can be idiopathic, for example. Some incidence of urethritis can appear asymptomatic as well. Symptoms and signs Symptoms vary based on the cause of the diseases. For infectious causes of urethritis, symptoms may start a few weeks to several months after infection. Non-infectious causes of urethritis commonly show symptoms after a few days. Common symptoms include painful urination, continuous urge to urinate, itching and, urethral discharge. Additional symptoms vary based on assigned sex at birth. AMAB (assigned male at birth) individuals may experience blood in the urine or semen, itching, tenderness, or swelling of the penis, enlarged lymph nodes in the groin area, and/or pain with intercourse or ejaculation. AFAB (assigned female at birth) may experience abdominal pain, pelvic pain, pain with intercourse, or vaginal discharge. Non-gonococcal urethritis typically does not have noticeable symptoms in AFAB individuals, however, the infection can spread to parts of the reproductive system. Complications Serious, yet rare complications associated with Neisseria gonorrhea, may include penile edema, abscessed tissue surrounding the urethra, urethral strictures such as scarring, and penile lymphangitis. If left untreated, the bacteria that cause non-gonococcal urethritis can lead to various complications. In individuals assigned male at birth, complications can lead to epididymitis, reactive arthritis, conjunctivitis, skin lesions, and discharge. In individuals assigned female at birth, complications can lead to pelvic inflammatory disease, chronic pelvic pain, vaginitis, mucopurulent cervicitis, and miscarriages. Causes The disease is classified as either gonococcal urethritis, caused by Neisseria gonorrhoeae, or non-gonococcal urethritis (NGU), most commonly caused by Chlamydia trachomatis, which is accounted for 20-50% of routinely tested cases. NGU, sometimes called nonspecific urethritis (NSU), has both infectious and noninfectious causes. Other causes include: Mycoplasma genitalium: second most common cause accounting for 15-20% of non-gonococcal urethritis Trichomonas vaginalis: accounts for 2-13% of cases in the US; infection is mainly asymptomatic in most cases Adenoviridae Uropathogenic Escherichia coli (UPEC) Herpes simplex virus Cytomegalovirus Reactive arthritis: urethritis is part of the triad of reactive arthritis, which includes arthritis, urethritis, and conjunctivitis. Ureaplasma urealyticum Methicillin-resistant Staphylococcus aureus Group B streptococcus Irritation of the genital area: for example catheter-induced, physical activity, tight clothing or soaps Fungal urethritis in immunosuppressed individual Menopause Diagnosis Urethritis is usually diagnosed through collecting history on the individual and through a physical examination. In AFAB individuals, urethritis can be diagnosed with a number of tests including: urine test, blood test, vaginal culture, cytoscopy, or a nucleic acid test. AFAB individuals will also have abdominal and pelvic exams to check for urethral discharge, and tenderness of the lower abdomen or urethra.In AMAB individuals, urethritis is diagnosed by at least one of the following: mucopurulent or purulent urethral discharge on examination, ≥ 2 white blood cells per oil immersion field from a Gram stain of a urethral swab, or positive leukocyte esterase and/or ≥10 white blood cells per high power field of the first-void urine. Men who meet the criteria for urethritis commonly get nucleic acid amplification testing for Chlamydia trachomatis and Neisseria gonorrhoeae to determine the type of urethritis. AMAB individuals will have an exam on the abdomen, bladder area, penis, and scrotum. Additionally, a digital rectal examination of the prostate may be used if rectal pain is reported or if the individual is of older age. Prevention Primary prevention can be accomplished by the reduction of modifiable risk factors that increase the likelihood of developing urethritis. These factors include, but are not limited to, sexual intercourse (particularly unprotected intercourse) and genital irritation from contact with tight clothing, physical activity, and various irritants such as soap, lotion and spermicides.Bacterial infections leading to gonococcal and non-gonococcal urethritis can be prevented by: sexual abstinence use of barrier contraception, such as condoms pre-exposure vaccination: HPV and Hepatitis B vaccines reducing number of sexual partnersChlorhexidine is an antibacterial agent that covers a wide spectrum of gram-positive and gram-negative bacteria. Rinsing with 15 ml of a 0.12% or 10 ml of 0.2% chlorhexidine solution for 30 seconds produced large and prolonged reductions in salivary bacterial counts within 7 hours of its use. One hypothesis in 2010 posed the potential use of chlorhexidine rinsing before oral sex as a prevention strategy of recurrent non-gonococcal urethritis caused by bacteria entering the urethra from oral cavity following "insertive oral intercourse", particularly in men. However, actual clinical studies are yet to be carried out in order to prove this hypothesis. Treatment Antimicrobials are generally the drug of choice for gonococcal and non-gonococcal infections. The CDC in 2015 suggests using a dual therapy that consists of two antimicrobials that have different mechanisms of action would be an effective treatment strategy for urethritis and it could also potentially slow down antibiotic resistance.A variety of drugs may be prescribed based on the cause of urethritis: Gonococcal urethritis (caused by N. gonorrhoeae): The CDC recommends administering an injection dose of ceftriaxone 250 mg intramuscularly and oral dose of azithromycin 1g simultaneously. Cefixime 400 mg oral single dose can be used as an alternative if ceftriaxone is not available. Non-gonococcal urethritis (caused by Chlamydia trachomatis): The CDC recommends administering an oral single dose of azithromycin 1g or a 7-day course of doxycycline 100 mg orally twice daily.Alternative treatments can also be used when the above options are not available:Erythromycin base 500 mg orally four times daily for 7 days Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days Levofloxacin 500 mg orally once daily for 7 days Ofloxacin 300 mg orally twice daily for 7 daysTreatment for both gonococcal and non-gonococcal urethritis is suggested to be given under direct observation in a clinic or healthcare facility in order to maximize compliance and effectiveness. For non-medication management, proper perineal hygiene should be stressed. This includes avoiding use of vaginal deodorant sprays and proper wiping after urination and bowel movements. Sexual intercourse should be avoided at least 7 days after completion of treatment (and until symptoms resolves, if present). Past and current sexual partners should also be assessed and treated.Individuals displaying persistence or recurrence of symptoms should be instructed for possible re-evaluation. Although there is no standard definition, persistent urethritis is defined as urethritis that has failed to display improvement within the first week of initial therapy. Additionally, recurrent urethritis is defined as urethritis reappearing within 6 weeks after a previous episode of non-gonococcal urethritis. If recurrent symptoms are supported by microscopic evidence of urethritis, then re-treatment is appropriate. The following treatment recommendations are limited and based on clinical experience, expert opinions and guidelines for recurrent or persistent non-gonococcal urethritis: If doxycycline was prescribed as initial therapy, give azithromycin 500 mg or 1 gram for the first day, then give azithromycin 250 mg once daily for 4 days plus metronidazole 400 – 500 mg twice daily for 5 days If azithromycin was prescribed as initial therapy, then give doxycycline 100 mg twice daily for 7 days plus metronidazole 400 – 500 mg twice daily for 5 – 7 days Moxifloxacin 400 mg orally once daily for 7 – 14 days can be given with use of caution, if macrolide-resistant M. genitalium infection is demonstrated Appropriate treatment for these individuals may require further referral to a urologist if symptoms persist after initial treatment. Epidemiology Urethritis is one of the most common sexually transmitted infections found in men. Gonorrhea and chlamydia are the main pathogens causing urethritis. Health organizations break down the rate of urethritis based on its etiology. The estimated global prevalence of gonorrhoea is 0.9% in women and 0.7% in men. An estimated 87 million new infections of gonorrhoea occurred in 2016. Low-income countries have the highest prevalence of gonorrhoea. Gonorrhea is more commonly seen in males than in females and infection rates are higher in adolescents and young adults.The estimated global prevalence of chlamydia, which is the most common cause of non-gonococcal urethritis, is 3.8% in women and 2.7% in men. An estimated 127 million new chlamydia cases occurred in 2016. Upper-middle income countries had the highest prevalence of chlamydia. The rate of chlamydia is around two times higher in females than in males. Rates are also higher among adolescents and young adults. References == External links ==

Hey Aarogya , Do you know what is Sodium bicarbonate,

Sodium bicarbonate

Sodium bicarbonate (IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda, is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cation (Na+) and a bicarbonate anion (HCO3−). Sodium bicarbonate is a white solid that is crystalline, but often appears as a fine powder. It has a slightly salty, alkaline taste resembling that of washing soda (sodium carbonate). The natural mineral form is nahcolite. It is a component of the mineral natron and is found dissolved in many mineral springs. Nomenclature Because it has long been known and widely used, the salt has many different names such as baking soda, bread soda, cooking soda, and bicarbonate of soda and can often be found near baking powder in stores. The term baking soda is more common in the United States, while bicarbonate of soda is more common in Australia, United Kingdom and Ireland. and in many northern/central European countries it is called Natron. Abbreviated colloquial forms such as sodium bicarb, bicarb soda, bicarbonate, and bicarb are common.The word saleratus, from Latin sal æratus (meaning "aerated salt"), was widely used in the 19th century for both sodium bicarbonate and potassium bicarbonate.Its E number food additive code is E500.The prefix bi in bicarbonate comes from an outdated naming system predating molecular knowledge in reference to the two molar equivalents of carbon dioxide (known as carbonic acid in the ancient chemistry language) that potassium hydrocarbonate/bicarbonate releases upon decomposition to (di)potassium carbonate and to potassium oxide (potash). The modern chemical formulas of these compounds now express their precise chemical compositions which were unknown when the name bi-carbonate of potash was coined (see also: bicarbonate). Uses Cooking Leavening In cooking, baking soda is primarily used in baking as a leavening agent. When it reacts with acid, carbon dioxide is released, which causes expansion of the batter and forms the characteristic texture and grain in cakes, quick breads, soda bread, and other baked and fried foods. The acid–base reaction can be generically represented as follows: NaHCO3 + H+ → Na+ + CO2 + H2OAcidic materials that induce this reaction include hydrogen phosphates, cream of tartar, lemon juice, yogurt, buttermilk, cocoa, and vinegar. Baking soda may be used together with sourdough, which is acidic, making a lighter product with a less acidic taste.Heat can also by itself cause sodium bicarbonate to act as a raising agent in baking because of thermal decomposition, releasing carbon dioxide at temperatures above 80 °C (180 °F), as follows: 2 NaHCO3 → Na2CO3 + H2O + CO2When used this way on its own, without the presence of an acidic component (whether in the batter or by the use of a baking powder containing acid), only half the available CO2 is released (one CO2 molecule is formed for every two equivalents of NaHCO3). Additionally, in the absence of acid, thermal decomposition of sodium bicarbonate also produces sodium carbonate, which is strongly alkaline and gives the baked product a bitter, "soapy" taste and a yellow color. Since the reaction occurs slowly at room temperature, mixtures (cake batter, etc.) can be allowed to stand without rising until they are heated in the oven. Baking powder Baking powder, also sold for cooking, contains around 30% of bicarbonate, and various acidic ingredients which are activated by the addition of water, without the need for additional acids in the cooking medium. Many forms of baking powder contain sodium bicarbonate combined with calcium acid phosphate, sodium aluminium phosphate, or cream of tartar. Baking soda is alkaline; the acid used in baking powder avoids a metallic taste when the chemical change during baking creates sodium carbonate. Pyrotechnics Sodium bicarbonate is one of the main components of the common "black snake" firework. The effect is caused by the thermal decomposition, which produces carbon dioxide gas to produce a long snake-like ash as a combustion product of the other main component, sucrose. Sodium bicarbonate is also used to delay combustion reactions by releasing CO2 and H2O when heated, both of which are flame retardants. Mild disinfectant It has weak disinfectant properties, and it may be an effective fungicide against some organisms. Because baking soda will absorb musty smells, it has become a reliable method for used book sellers when making books less malodorous. Fire extinguisher Sodium bicarbonate can be used to extinguish small grease or electrical fires by being thrown over the fire, as heating of sodium bicarbonate releases carbon dioxide. However, it should not be applied to fires in deep fryers; the sudden release of gas may cause the grease to splatter. Sodium bicarbonate is used in BC dry chemical fire extinguishers as an alternative to the more corrosive monoammonium phosphate in ABC extinguishers. The alkaline nature of sodium bicarbonate makes it the only dry chemical agent, besides Purple-K, that was used in large-scale fire suppression systems installed in commercial kitchens. Because it can act as an alkali, the agent has a mild saponification effect on hot grease, which forms a smothering, soapy foam. Neutralization of acids Sodium bicarbonate reacts spontaneously with acids, releasing CO2 gas as a reaction product. It is commonly used to neutralize unwanted acid solutions or acid spills in chemical laboratories. It is not appropriate to use sodium bicarbonate to neutralize base even though it is amphoteric, reacting with both acids and bases. Agriculture Sodium bicarbonate when applied on leaves, can prevent the growth of fungi; however, it does not kill the fungus. Excessive amount of sodium bicarbonate can cause discolouration of fruits (two percent solution) and chlorosis (one percent solution). Medical uses and health Sodium bicarbonate mixed with water can be used as an antacid to treat acid indigestion and heartburn. Its reaction with stomach acid produces salt, water, and carbon dioxide: NaHCO3 + HCl → NaCl + H2O + CO2(g)A mixture of sodium bicarbonate and polyethylene glycol such as PegLyte, dissolved in water and taken orally, is an effective gastrointestinal lavage preparation and laxative prior to gastrointestinal surgery, gastroscopy, etc.Intravenous sodium bicarbonate in an aqueous solution is sometimes used for cases of acidosis, or when insufficient sodium or bicarbonate ions are in the blood. In cases of respiratory acidosis, the infused bicarbonate ion drives the carbonic acid/bicarbonate buffer of plasma to the left, and thus raises the pH. For this reason, sodium bicarbonate is used in medically supervised cardiopulmonary resuscitation. Infusion of bicarbonate is indicated only when the blood pH is markedly low (< 7.1–7.0).HCO3− is used for treatment of hyperkalemia, as it will drive K+ back into cells during periods of acidosis. Since sodium bicarbonate can cause alkalosis, it is sometimes used to treat aspirin overdoses. Aspirin requires an acidic environment for proper absorption, and a basic environment will diminish aspirin absorption in cases of overdose. Sodium bicarbonate has also been used in the treatment of tricyclic antidepressant overdose. It can also be applied topically as a paste, with three parts baking soda to one part water, to relieve some kinds of insect bites and stings (as well as accompanying swelling).Some alternative practitioners, such as Tullio Simoncini, have promoted baking soda as a cancer cure, which the American Cancer Society has warned against due to both its unproven effectiveness and potential danger in use. Edzard Ernst has called the promotion of sodium bicarbonate as a cancer cure "one of the more sickening alternative cancer scams I have seen for a long time".Sodium bicarbonate can be added to local anesthetics, to speed up the onset of their effects and make their injection less painful. It is also a component of Moffetts solution, used in nasal surgery.It has been proposed that acidic diets weaken bones. One systematic meta-analysis of the research shows no such effect. Another also finds that there is no evidence that alkaline diets improve bone health, but suggests that there "may be some value" to alkaline diets for other reasons.Antacid (such as baking soda) solutions have been prepared and used by protesters to alleviate the effects of exposure to tear gas during protests.Similarly to its use in baking, sodium bicarbonate is used together with a mild acid such as tartaric acid as the excipient in effervescent tablets: when such a tablet is dropped in a glass of water, the carbonate leaves the reaction medium as carbon dioxide gas (HCO3− + H+ → H2O + CO2↑ or, more precisely, HCO3− + H3O+ → 2 H2O + CO2↑). This makes the tablet disintegrate, leaving the medication suspended and/or dissolved in the water together with the resulting salt (in this example, sodium tartrate). Personal hygiene Sodium bicarbonate is also used as an ingredient in some mouthwashes. It has anticaries and abrasive properties. It works as a mechanical cleanser on the teeth and gums, neutralizes the production of acid in the mouth, and also acts as an antiseptic to help prevent infections. Sodium bicarbonate in combination with other ingredients can be used to make a dry or wet deodorant. Sodium bicarbonate may be used as a buffering agent, combined with table salt, when creating a solution for nasal irrigation.It is used in eye hygiene to treat blepharitis. This is done by addition of a teaspoon of sodium bicarbonate to cool water that was recently boiled, followed by gentle scrubbing of the eyelash base with a cotton swab dipped in the solution. Veterinary uses Sodium bicarbonate is used as a cattle feed supplement, in particular as a buffering agent for the rumen. Cleaning agent Sodium bicarbonate is used in a process for removing paint and corrosion called sodablasting. As a blasting medium, sodium bicarbonate is used to remove surface contamination from softer and less resilient substrates such as aluminium, copper or timber which could be damaged by silica sand abrasive media.A manufacturer recommends a paste made from baking soda with minimal water as a gentle scouring powder, and is useful in removing surface rust, as the rust forms a water-soluble compound when in a concentrated alkaline solution; cold water should be used, as hot-water solutions can corrode steel. Sodium bicarbonate attacks the thin protective oxide layer that forms on aluminium, making it unsuitable for cleaning this metal. A solution in warm water will remove the tarnish from silver when the silver is in contact with a piece of aluminium foil. Baking soda is commonly added to washing machines as a replacement for water softener and to remove odors from clothes. It is also almost as effective in removing heavy tea and coffee stains from cups as Sodium hydroxide, when diluted with warm water. During the Manhattan Project to develop the nuclear bomb in the early 1940s, the chemical toxicity of uranium was an issue. Uranium oxides were found to stick very well to cotton cloth, and did not wash out with soap or laundry detergent. However, the uranium would wash out with a 2% solution of sodium bicarbonate. Clothing can become contaminated with toxic dust of depleted uranium (DU), which is very dense, hence used for counterweights in a civilian context, and in armour-piercing projectiles. DU is not removed by normal laundering; washing with about 6 ounces (170 g) of baking soda in 2 gallons (7.5 L) of water will help to wash it out. Odor control It is often claimed that baking soda is an effective odor remover, and it is often recommended that an open box be kept in the refrigerator to absorb odor. This idea was promoted by the leading U.S. brand of baking soda, Arm & Hammer, in an advertising campaign starting in 1972. Though this campaign is considered a classic of marketing, leading within a year to more than half of American refrigerators containing a box of baking soda, there is little evidence that it is in fact effective in this application. Chemistry Sodium bicarbonate is an amphoteric compound. Aqueous solutions are mildly alkaline due to the formation of carbonic acid and hydroxide ion: HCO−3 + H2O → H2CO3 + OH−Sodium bicarbonate can often be used as a safer alternative to sodium hydroxide, and as such can be used as a wash to remove any acidic impurities from a "crude" liquid, producing a purer sample. Reaction of sodium bicarbonate and an acid produces a salt and carbonic acid, which readily decomposes to carbon dioxide and water: NaHCO3 + HCl → NaCl + H2CO3 H2CO3 → H2O + CO2(g)Sodium bicarbonate reacts with acetic acid (found in vinegar), producing sodium acetate, water, and carbon dioxide: NaHCO3 + CH3COOH → CH3COONa + H2O + CO2(g)Sodium bicarbonate reacts with bases such as sodium hydroxide to form carbonates: NaHCO3 + NaOH → Na2CO3 + H2O Thermal decomposition At temperatures from 80–100 °C (176–212 °F), sodium bicarbonate gradually decomposes into sodium carbonate, water, and carbon dioxide. The conversion is faster at 200 °C (392 °F): 2 NaHCO3 → Na2CO3 + H2O + CO2Most bicarbonates undergo this dehydration reaction. Further heating converts the carbonate into the oxide (above 850 °C/1,560 °F): Na2CO3 → Na2O + CO2These conversions are relevant to the use of NaHCO3 as a fire-suppression agent ("BC powder") in some dry-powder fire extinguishers. Stability and shelf life If kept cool (room temperature) and dry (an airtight container is recommended to keep out moist air), sodium bicarbonate can be kept without a significant amount of decomposition for at least two or three years. History The word natron has been in use in many languages throughout modern times (in the forms of anatron, natrum and natron) and originated (like Spanish, French and English natron as well as sodium) via Arabic naṭrūn (or anatrūn; cf. the Lower Egyptian “Natrontal” Wadi El Natrun, where a mixture of sodium carbonate and sodium hydrogen carbonate for the dehydration of mummies was used ) from Greek nítron (νίτρον) (Herodotus; Attic lítron (λίτρον)), which can be traced back to ancient Egyptian ntr. The Greek nítron (soda, saltpeter) was also used in Latin (sal) nitrum and in German Salniter (the source of Nitrogen, Nitrat etc.).In 1791, French chemist Nicolas Leblanc produced sodium carbonate, also known as soda ash. The pharmacist Valentin Rose the Younger is credited with the discovery of sodium bicarbonate in 1801 in Berlin. In 1846, two American bakers, John Dwight and Austin Church, established the first factory in the United States to produce baking soda from sodium carbonate and carbon dioxide.Saleratus, potassium or sodium bicarbonate, is mentioned in the novel Captains Courageous by Rudyard Kipling as being used extensively in the 1800s in commercial fishing to prevent freshly caught fish from spoiling.In 1919, US Senator Lee Overman declared that bicarbonate of soda could cure the Spanish flu. In the midst of the debate on 26 January 1919, he interrupted the discussion to announce the discovery of a cure. "I want to say, for the benefit of those who are making this investigation," he reported, "that I was told by a judge of a superior court in the mountain country of North Carolina they have discovered a remedy for this disease." The purported cure implied a critique of modern science and an appreciation for the simple wisdom of simple people. "They say that common baking soda will cure the disease," he continued, "that they have cured it with it, that they have no deaths up there at all; they use common baking soda, which cures the disease." Production Sodium bicarbonate is produced industrially from sodium carbonate: Na2CO3 + CO2 + H2O → 2 NaHCO3It is produced on the scale of about 100,000 tonnes/year (as of 2001) with a worldwide production capacity of 2.4 million tonnes per year (as of 2002). Commercial quantities of baking soda are also produced by a similar method: soda ash, mined in the form of the ore trona, is dissolved in water and treated with carbon dioxide. Sodium bicarbonate precipitates as a solid from this solution.Regarding the Solvay process, sodium bicarbonate is an intermediate in the reaction of sodium chloride, ammonia, and carbon dioxide. The product however shows low purity (75pc). NaCl + CO2 + NH3 + H2O → NaHCO3 + NH4ClAlthough of no practical value, NaHCO3 may be obtained by the reaction of carbon dioxide with an aqueous solution of sodium hydroxide: CO2 + NaOH → NaHCO3 Mining Naturally occurring deposits of nahcolite (NaHCO3) are found in the Eocene-age (55.8–33.9 Mya) Green River Formation, Piceance Basin in Colorado. Nahcolite was deposited as beds during periods of high evaporation in the basin. It is commercially mined using common underground mining techniques such as bore, drum, and longwall mining in a fashion very similar to coal mining.It is also produced by solution mining, pumping heated water through nahcolite beds and crystalizing the dissolved nahcolite through a cooling crystallization process. In popular culture Sodium bicarbonate, as "bicarbonate of soda", was a frequent source of punch lines for Groucho Marx in Marx Brothers movies. In Duck Soup, Marx plays the leader of a nation at war. In one scene, he receives a message from the battlefield that his general is reporting a gas attack, and Groucho tells his aide: "Tell him to take a teaspoonful of bicarbonate of soda and a half a glass of water." In A Night at the Opera, Grouchos character addresses the opening night crowd at an opera by saying of the lead tenor: "Signor Lassparri comes from a very famous family. His mother was a well-known bass singer. His father was the first man to stuff spaghetti with bicarbonate of soda, thus causing and curing indigestion at the same time."In the Joseph L. Mankewicz classic All About Eve, the Max Fabian character (Gregory Ratoff) has an extended scene with Margo Channing (Bette Davis) in which, suffering from heartburn, he requests and then drinks bicarbonate of soda, eliciting a prominent burp. Channing promises to always keep a box of bicarb with Maxs name on it. See also References Bibliography External links International Chemical Safety Card 1044

Aarogya, can you share information about a health condition involving Bacterial vaginosis

Bacterial vaginosis

Bacterial vaginosis (BV) is a disease of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urination may occur. Itching is uncommon. Occasionally, there may be no symptoms. Having BV approximately doubles the risk of infection by a number of sexually transmitted infections, including HIV/AIDS. It also increases the risk of early delivery among pregnant women.BV is caused by an imbalance of the naturally occurring bacteria in the vagina. There is a change in the most common type of bacteria and a hundred to thousand fold increase in total numbers of bacteria present. Typically, bacteria other than Lactobacilli become more common. Risk factors include douching, new or multiple sex partners, antibiotics, and using an intrauterine device, among others. However, it is not considered a sexually transmitted infection and, unlike gonorrhoea and chlamydia, sexual partners are not treated. Diagnosis is suspected based on the symptoms, and may be verified by testing the vaginal discharge and finding a higher than normal vaginal pH, and large numbers of bacteria. BV is often confused with a vaginal yeast infection or infection with Trichomonas.Usually treatment is with an antibiotic, such as clindamycin or metronidazole. These medications may also be used in the second or third trimesters of pregnancy. However, the condition often recurs following treatment. Probiotics may help prevent re-occurrence. It is unclear if the use of probiotics or antibiotics affects pregnancy outcomes.BV is the most common vaginal infection in women of reproductive age. The percentage of women affected at any given time varies between 5% and 70%. BV is most common in parts of Africa and least common in Asia and Europe. In the United States about 30% of women between the ages of 14 and 49 are affected. Rates vary considerably between ethnic groups within a country. While BV-like symptoms have been described for much of recorded history, the first clearly documented case occurred in 1894. Signs and symptoms Although about 50% of women with BV are asymptomatic, common symptoms include increased vaginal discharge that usually smells like fish. The discharge is often white or gray in color. There may be burning with urination. Occasionally, there may be no symptoms.The discharge coats the walls of the vagina, and is usually without significant irritation, pain, or erythema (redness), although mild itching can sometimes occur. By contrast, the normal vaginal discharge will vary in consistency and amount throughout the menstrual cycle and is at its clearest at ovulation—about two weeks before the period starts. Some practitioners claim that BV can be asymptomatic in almost half of affected women, though others argue that this is often a misdiagnosis. Complications Although previously considered a mere nuisance infection, untreated bacterial vaginosis may cause increased susceptibility to sexually transmitted infections, including HIV, and pregnancy complications.It has been shown that HIV-infected women with bacterial vaginosis (BV) are more likely to transmit HIV to their sexual partners than those without BV. There is evidence of an association between BV and increased rates of sexually transmitted infections such as HIV/AIDS. BV is associated with up to a six-fold increase in HIV shedding. BV is a risk factor for viral shedding and herpes simplex virus type 2 infection. BV may increase the risk of infection with or reactivation of human papillomavirus (HPV).In addition, bacterial vaginosis as either pre-existing, or acquired, may increase the risk of pregnancy complications, most notably premature birth or miscarriage. Pregnant women with BV have a higher risk of chorioamnionitis, miscarriage, preterm birth, premature rupture of membranes, and postpartum endometritis. Women with BV who are treated with in vitro fertilization have a lower implantation rate and higher rates of early pregnancy loss. Causes Healthy vaginal microbiota consists of species that neither cause symptoms or infections, nor negatively affect pregnancy. It is dominated mainly by Lactobacillus species. BV is defined by the disequilibrium in the vaginal microbiota, with decline in the number of lactobacilli. While the infection involves a number of bacteria, it is believed that most infections start with Gardnerella vaginalis creating a biofilm, which allows other opportunistic bacteria to thrive.One of the main risks for developing BV is douching, which alters the vaginal microbiota and predisposes women to developing BV. Douching is strongly discouraged by the U.S. Department of Health and Human Services and various medical authorities, for this and other reasons.BV is a risk factor for pelvic inflammatory disease, HIV, sexually transmitted infections (STIs), and reproductive and obstetric disorders or negative outcomes. Although BV can be associated with sexual activity, there is no clear evidence of sexual transmission. It is possible for sexually inactive persons to develop bacterial vaginosis.Also, subclinical iron deficiency may correlate with bacterial vaginosis in early pregnancy. A longitudinal study published in February 2006, in the American Journal of Obstetrics and Gynecology, showed a link between psychosocial stress and bacterial vaginosis persisted even when other risk factors were taken into account. Exposure to the spermicide nonoxynol-9 does not affect the risk of developing bacterial vaginosis. Diagnosis To make a diagnosis of bacterial vaginosis, a swab from inside the vagina should be obtained. These swabs can be tested for: Gram stain which shows the depletion of lactobacilli and overgrowth of Gardnerella vaginalis bacteria. Bacterial vaginosis is usually confirmed by a Gram stain of vaginal secretions. A characteristic "fishy" odor on wet mount. This test, called the whiff test, is performed by adding a small amount of potassium hydroxide to a microscope slide containing the vaginal discharge. A characteristic fishy odor is considered a positive whiff test and is suggestive of bacterial vaginosis. Loss of acidity. To control bacterial growth, the vagina is normally slightly acidic with a pH of 3.8–4.2. A swab of the discharge is put onto litmus paper to check its acidity. A pH greater than 4.5 is considered alkaline and is suggestive of bacterial vaginosis. The presence of clue cells on wet mount. Similar to the whiff test, the test for clue cells is performed by placing a drop of sodium chloride solution on a slide containing vaginal discharge. If present, clue cells can be visualized under a microscope. They are so-named because they give a clue to the reason behind the discharge. These are epithelial cells that are coated with bacteria.Differential diagnosis for bacterial vaginosis includes the following: Normal vaginal discharge. Candidiasis (thrush, or a yeast infection). Trichomoniasis, an infection caused by Trichomonas vaginalis. Aerobic vaginitisThe Center for Disease Control (CDC) defines STIs as "a variety of clinical syndromes and infections caused by pathogens that can be acquired and transmitted through sexual activity." But the CDC does not specifically identify BV as sexually transmitted infection. Amsel criteria In clinical practice BV can be diagnosed using the Amsel criteria: Thin, white, yellow, homogeneous discharge Clue cells on microscopy pH of vaginal fluid >4.5 Release of a fishy odor on adding alkali—10% potassium hydroxide (KOH) solution.At least three of the four criteria should be present for a confirmed diagnosis. A modification of the Amsel criteria accepts the presence of two instead of three factors and is considered equally diagnostic. Gram stain An alternative is to use a Gram-stained vaginal smear, with the Hay/Ison criteria or the Nugent criteria. The Hay/Ison criteria are defined as follows: Grade 1 (Normal): Lactobacillus morphotypes predominate. Grade 2 (Intermediate): Some lactobacilli present, but Gardnerella or Mobiluncus morphotypes also present. Grade 3 (Bacterial Vaginosis): Predominantly Gardnerella and/or Mobiluncus morphotypes. Few or absent lactobacilli. (Hay et al., 1994)Gardnerella vaginalis is the main culprit in BV. Gardnerella vaginalis is a short, Gram-variable rod (coccobacillus). Hence, the presence of clue cells and gram variable coccobacilli are indicative or diagnostic of bacterial vaginosis. Nugent score The Nugent score is now rarely used by physicians due to the time it takes to read the slides and requires the use of a trained microscopist. A score of 0-10 is generated from combining three other scores. The scores are as follows: 0–3 is considered negative for BV 4–6 is considered intermediate 7+ is considered indicative of BV.At least 10–20 high power (1000× oil immersion) fields are counted and an average determined. DNA hybridization testing with Affirm VPIII was compared to the Gram stain using the Nugent criteria. The Affirm VPIII test may be used for the rapid diagnosis of BV in symptomatic women but uses expensive proprietary equipment to read results, and does not detect other pathogens that cause BV, including Prevotella spp, Bacteroides spp, and Mobiluncus spp. The cervicovaginal microbiome measured using 16S rRNA sequencing has the capacity to increase throughput of the Nugent Score and has demonstrate to be directly comparable to clinical Nugent Score measurement. Screening Screening during pregnancy is not recommended in the United States as of 2020. Prevention Some steps suggested to lower the risk include: not douching, avoiding sex, or limiting the number of sex partners.One review concluded that probiotics may help prevent re-occurrence. Another review found that, while there is tentative evidence, it is not strong enough to recommend their use for this purpose.Early evidence suggested that antibiotic treatment of male partners could re-establish the normal microbiota of the male urogenital tract and prevent the recurrence of infection. However, a 2016 Cochrane review found high-quality evidence that treating the sexual partners of women with bacterial vaginosis had no effect on symptoms, clinical outcomes, or recurrence in the affected women. It also found that such treatment may lead treated sexual partners to report increased adverse events. Treatment Antibiotics Treatment is typically with the antibiotics metronidazole or clindamycin. They can be either given by mouth or applied inside the vagina with similar efficacy. About 10% to 15% of people, however, do not improve with the first course of antibiotics and recurrence rates of up to 80% have been documented. Recurrence rates are increased with sexual activity with the same pre-/posttreatment partner and inconsistent condom use although estrogen-containing contraceptives decrease recurrence. When clindamycin is given to pregnant women symptomatic with BV before 22 weeks of gestation the risk of pre-term birth before 37 weeks of gestation is lower.Other antibiotics that may work include macrolides, lincosamides, nitroimidazoles, and penicillins.Bacterial vaginosis is not considered a sexually transmitted infection, and treatment of a male sexual partner of a woman with bacterial vaginosis is not recommended. Probiotics A 2009 Cochrane review found tentative but insufficient evidence for probiotics as a treatment for BV. A 2014 review reached the same conclusion. A 2013 review found some evidence supporting the use of probiotics during pregnancy. The preferred probiotics for BV are those containing high doses of lactobacilli (around 109 CFUs) given in the vagina. Intravaginal administration is preferred to taking them by mouth. Prolonged repetitive courses of treatment appear to be more promising than short courses.The lack of effectiveness of commercially available Lactobacillus probiotics may be because most do not actually contain vaginal lactobacilli strains. LACTIN-V is a live biopharmaceutical medication containing the vaginally important Lactobacillus crispatus which is under development for the treatment of bacterial vaginosis and recurrent urinary tract infections. It has shown initial effectiveness in considerably reducing recurrence of bacterial vaginosis following antibiotic treatment. LACTIN-V is not yet Food and Drug Administration (FDA)-approved or commercially available. Antiseptics Topical antiseptics, for example dequalinium chloride, policresulen, hexetidine or povidone-iodine vaginal suppositories may be applied, if the risk of ascending infections is low (outside of pregnancy and in immunocompetent people without histories of upper genital tract infections). One study found that vaginal irrigations with hydrogen peroxide (3%) resulted in a slight improvement but this was much less than with the use of oral metronidazole. Intravaginal boric acid in conjunction with other medications may be helpful in the treatment of recurrent BV. TOL-463, a formulation of boric acid enhanced with ethylenediaminetetraacetic acid (EDTA), is under development as an intravaginal medication for the treatment of BV and has shown preliminary effectiveness. Epidemiology BV is the most common infection of the vagina in women of reproductive age. The percentage of women affected at any given time varies between 5% and 70%. BV is most common in parts of Africa, and least common in Asia and Europe. In the United States, about 30% of those between the ages of 14 and 49 are affected. Rates vary considerably between ethnic groups within a country. References == External links ==

Hey Aarogya!, what is Nonallergic rhinitis

Nonallergic rhinitis

Nonallergic rhinitis is inflammation of the inner part of the nose that is not caused by an allergy. Nonallergic rhinitis involves symptoms including chronic sneezing or having a congested, drippy nose without an identified allergic reaction. Other common terms for nonallergic rhinitis are vasomotor rhinitis and perennial rhinitis. The prevalence of nonallergic rhinitis in otolaryngology is 40%. Allergic rhinitis is more common than nonallergic rhinitis; however, both conditions have similar presentation, manifestation and treatment. Nasal itching and paroxysmal sneezing are usually associated with nonallergic rhinitis in comparison to allergic rhinitis. Types Rhinitis medicamentosa – rebound nasal congestion suspected to be brought on by extended use of topical decongestants and certain oral medications that constrict blood vessels in the nose. Treatment includes withdrawal of nasal drops, short courses of systemic steroid therapy and in some cases, surgical reduction of turbinates, if they have become hypertrophied. Rhinitis of pregnancy – pregnant women may develop persistent rhinitis due to hormonal changes. Nasal mucous become edematous and block the airway. Some may develop secondary infection and even sinusitis in such cases. Care should be taken while prescribing drugs. Generally, local measures such as limited use of nasal drops, topical steroids and limited surgery (cryosurgery) to turbinates are sufficient to relate the symptoms. Safety of developing fetus is not established for newer antihistamines and they should be avoided. Honeymoon rhinitis – this usually follows sexual excitement, leading to nasal stuffiness. The condition appears to be genetically determined and caused by the presence in the nose of erectile tissue which may become engorged during sexual arousal, as a side effect of the signals from the autonomic nervous system that trigger changes in the genitals of both men and women. A related condition called sexually induced sneezing also exists, where people sneeze, sometimes uncontrollably, when engaging in or even thinking about sexual activity. A phenomenon presumably related to honeymoon rhinitis is the frequent side effect of nasal congestion during the use of Viagra or related phosphodiesterase type 5 antagonists. Gustatory rhinitis – spicy and pungent food may in some people produce rhinorrhea, nasal stuffiness, lacrimation, sweating and flushing of face. It can be relieved by ipratropium bromide nasal spray (an anticholinergic), a few minutes before a meal. Non-air flow rhinitis – it is seen in patients of laryngectomy, tracheostomy and choanal atresia. Nose is not used for air flow and the turbinates become swollen due to loss of vasomotor control. In choanal atresia there is an additional factor of infection due to stagnation of discharge in the nasal cavity which should otherwise drain freely into nasopharynx. Photic sneeze reflex is a reflex condition that causes sneezing in response to looking at bright lights. Presentation Paroxysmal sneezing in morning, especially in morning while getting out of bed. Excessive rhinorrhea – watering discharge from the nose when patient bends forward. Nasal obstruction – bilateral nasal stuffiness alternates from one site to other; this is more marked at night, when the dependent side of nose is often blocked. Postnasal drip. Complications Nonallergic rhinitis cases may subsequently develop polyps, turbinate hypertrophy and sinusitis. Pathophysiology Nasal mucosa has a rich blood supply and has venous sinusoids or "lakes" surrounded by smooth muscle fibers. These smooth muscle fibers act as sphincters and control the filling and emptying of sinusoids. Sympathetic stimulation causes vasoconstriction and shrinkage of mucosa, which leads to decongestion of the nose. Parasympathetic stimulation causes not only excessive secretion from the nasal gland but also vasodilatation and engorgement, which lead to rhinorrhoea and congestion of the nose. The autonomic nervous system, which supplies the nasal mucosa, is under the control of the hypothalamus. Diagnosis Nose examination: The mucosa is usually boggy and edematous with clear mucoid secretions. The turbinates are congested and hypertrophic.Pharynx examination: Mucosal injection and lymphoid hyperplasia involving tonsils, adenoids and base of tongue may be seen. Investigations Absolute eosinophil count, nasal smear, skin and in vitro allergy tests to rule out allergic rhinitis, acoustic rhinometry for measuring nasal patency, smell testing, CT scan in cases of sinus disease and MRI in case of mass lesions. Classification Treatment Medical The avoidance of inciting factors such as sudden changes in temperature, humidity, or blasts of air or dust is helpful. Intranasal application of antihistamines, corticosteroids, or anticholinergics may also be used for vasomotor rhinitis. Intranasal cromolyn sodium may be used in patients older than two years. A Cochrane review concluded that it is unclear whether intranasal corticosteroids, when compared with a placebo, reduce patient‐reported disease severity in people with nonallergic/vasomotor rhinitis due to the low certainty of the evidence available from clinical trials. However, intranasal corticosteroids probably increase risk of nosebleeds.Astelin (azelastine) "is indicated for symptomatic treatment of vasomotor rhinitis including rhinorrhea, nasal congestion, and post nasal drip in adults and children 12 years of age and older." Surgical Reduction of hypertrophied turbinates, correction of nasal septum deviation, removal of polyps, sectioning of the parasympathetic secretomotor fiber to nose (vidian neurectomy) for controlling refractory excessive rhinorrhea. See also Snatiation == References ==

Aarogya , Do you know what is Ventriculitis,

Ventriculitis

Ventriculitis is the inflammation of the ventricles in the brain. The ventricles are responsible for containing and circulating cerebrospinal fluid throughout the brain. Ventriculitis is caused by infection of the ventricles, leading to swelling and inflammation. This is especially prevalent in patients with external ventricular drains and intraventricular stents. Ventriculitis can cause a wide variety of short-term symptoms and long-term side effects ranging from headaches and dizziness to unconsciousness and death if not treated early. It is treated with some appropriate combination of antibiotics in order to rid the patient of the underlying infection. Much of the current research involving ventriculitis focuses specifically around defining the disease and what causes it. This will allow for much more advancement in the subject. There is also a lot of attention being paid to possible treatments and prevention methods to help make this disease even less prevalent and dangerous. Signs and symptoms There is great deal of variety in the symptoms associated with ventriculitis. The symptoms vary based on a number of different factors including severity of inflammation, underlying cause, and the individual patient. Patients often present with headaches, painful cranial pressure, and neck pain early in the progression of the disease. Patients with a more advanced infection have been known to complain of many neurological effects such as dizziness, vertigo, confusion, and slurred speech. Very advanced cases can lead to mental instability, nausea, vomiting, rigors, and temporary loss of consciousness. Many patients with ventriculitis also experience some degree of hydrocephalus, which is the buildup of cerebrospinal fluid due to the inability of the ventricles to reabsorb and correctly circulate the fluid. Brain abscess is another common disorder resulting from the inflammation. If left untreated, ventriculitis can lead to serious inhibition of mental function and even death. The symptoms vary greatly, in part, because of the underlying or causing infection. While the inflammation can cause a number of effects such as those mentioned previously, the base infection could cause other symptoms that dont necessarily have to do with the ventriculitis, itself. One of the challenges doctors face in diagnosing ventriculitis is distinguishing indicative symptoms, in spite of the wide variety of possible presentations of the disease. A great deal of emphasis is being put on research into better and faster ways to diagnose ventriculitis without the delay inherent with microbiological testing of the cerebrospinal fluid.The progression of the disease is also largely dependent on the nature of the specific case. Depending on the underlying infection, the way it entered the brain, and the type and timing of treatment, the infection may spread or withdraw on the order of months or days. Ventriculitis is a very serious condition and should be treated early to ensure as little lasting damage as possible. Cause Ventriculitis is caused by an infection of the ventricles, causing an immune response in the lining, which in turn, leads to inflammation. The ventriculitis, is in truth, a complication of the initial infection or abnormality. The underlying infection can come in the form of a number of different bacteria or viruses. The data seems to point to Staphylococci as the leading bacterial cause of infection leading to ventriculitis being present in about 90% of cases, but generally, what is of more concern is the way the infection entered the ventricles. The brain in its natural state is very protected from infection. The blood–brain barrier serves to keep pathogens from entering the sensitive areas of the brain. However, when those natural defenses are by-passed in the hospital setting, the brain is suddenly exposed to a host of potentially harmful bacteria and viruses. Patients that have had invasive brain surgery or procedures are considered to be the most at risk for experiencing ventriculitis. Two procedures, in particular have been studied extensively due to their high rate of ventriculitis contractions post operation. The first group consists of patients that have had an external ventricular drain implanted to allow physicians to reduce the intracranial pressure they experience. The duration that the drain is implanted varies by necessity, however, the longer the drain is in, the more likely an infection will occur. The second group consists of patients that have an implanted intracranial stent. Both groups of patients have a much higher rate of ventriculitis than the general populace, though there is very little supporting evidence due to the lack of definition of ventriculitis as frequent misdiagnosis. Nearly 25% of patients with an external ventricular drain experience infection-based meningitis or ventriculitis. Diagnosis Ventriculitis is commonly diagnosed using a variety of tests or procedures. When a physician suspects that a patient has ventriculitis, the first step is typically to ascertain the presence of the inflammation using computed tomography (CT) or magnetic resonance imaging (MRI) technology to "take a picture" of the brain. The scans allow physicians to check for "intraventricular debris and pus, abnormal periventricular and subependymal signal intensity, and enhancement of the ventricular lining," all of which indicate the likelihood of ventriculitis. MRIs have been reported as being highly effective and sensitive in detecting such indicators, even from an early stage. After determining whether a patient shows signs of ventriculitis, the doctor may choose to pursue a more specific and useful diagnosis to find the cause of the ventriculitis. This is done by obtaining a sample of cerebrospinal fluid, most commonly via a procedure called a lumbar puncture or spinal tap. For patients with an implanted external ventricular drain, cerebrospinal fluid can be collected from the drains output. After the sample of fluid is obtained, a battery of tests featuring gram staining will be performed to identify any offending pathogen or infection agent. The test will also determine any resistance the pathogen may have to antibiotics. By identifying the viral or bacterial cause of the ventriculitis, doctors are more able to effectively treat the inflammation and infection. This procedure is fairly effective, but is rarely able to isolate anaerobic organisms that may be causing the inflammation, giving cause for further research and procedural development.Though they present with similar symptoms and often occur in tandem, meningitis and ventriculitis are two different diseases, so physicians must be able to distinguish between the two. Meningitis is the inflammation of the protective lining of the central nervous system, called meninges. Because of the similar pathologies and cause of the two types of inflammation, they are difficult to differentiate using chemical testing, but show very different visual effects in both the MRI and CT scans, hence their use as a validation that the patient does, in fact, have ventriculitis and not another, similar condition such as meningitis. Treatment Treatment of ventriculitis is critical. If left untreated, it could lead to severe brain damage and even death in some cases. Currently, the only commonly employed treatments of ventriculitis involve an antibiotic regimen targeting the underlying infection causing the inflammation. Typically, the physician will order the patient be placed on broad-spectrum antibiotics in order to manage the symptoms and control the infection while the cerebrospinal fluid samples are analyzed. When a specific bacterial or viral cause is found, the doctor will change the treatment accordingly. There is some debate as to the most effective antibiotics and the best ways to introduce the drugs (e.g. intravenously, orally, etc.), however it is agreed that drug effectiveness is limited by the difficulty of non-invasively allowing the drugs to enter the cerebrospinal fluid. Should intracranial pressure reach unsafe levels, the patient may need to have cerebrospinal fluid drained. Implanted external ventricular drains are one of the more common ways to manage and monitor the intracranial pressure, however there are several risks involved with such an invasive procedure, including the risk of further infection. There is a great deal of research focused around prevention of ventriculitis. It is crucial that any procedure involving exposing the brain is performed with the utmost care, as infections in the brain are very dangerous and potentially deadly. When patients undergo such procedures, they are often monitored closely over the next several days to ensure that there were no infections and any instance of even a small headache is treated very seriously. It is also necessary to monitor the intracranial pressure of the patients often enough to observe significant changes that could indicate the presence of and infection and ensuing ventriculitis. It is important not to measure the pressure too often, however, as it could in fact lead to infection. Current research Due to the poor definition of the condition that is ventriculitis, there is still a great deal that is not known about this dangerous condition. While other, similar conditions, such as meningitis or encephalitis, have been thoroughly researched, ventriculitis is a very loose grouping of conditions characterized by the fact that the lining of the ventricles is inflamed. Because no solid definition has been accepted across the medical community, research in the subject has been slow to progress. However, most common research into ventriculitis has been focused on the main points of causation, demographic information, and effectiveness of treatments and prevention methods. Causation One of the key areas of research for ventriculitis is discovering and defining exactly what causes it. There are many bacterial and viral infections that could cause inflammation of the ventricles, but researchers are trying to define which are the most common pathogens, the risk levels associated with various medical operations and procedures, and why the symptoms vary so much on a case-by-case basis. Answering these questions will allow doctors to not only better understand ventriculitis, but better treat and prevent it as well. Demographics Currently, there is very little understanding as to who is at increased risk for ventriculitis, other than those who have undergone neurosurgery or procedures involving brain exposure. Even then, current clinical practices cant predict which patients will be affected. In order to predict which populations should be focused on, researchers must gather more case information about who is diagnosed with ventriculitis and how they present. In essence, the medical community must compile data of as many details as possible from each case so that more generalized conclusions may be drawn. Treatment and prevention So little is currently known about how ventriculitis should be defined and those it affects that even less can be known about prevention methods. While treatment is fairly standard for any infection to some degree, prevention is a different matter. One popular theory is the use of prophylactic antibiotics, administered during insertion of external ventricular drains or ventricular stents with the hope of preventing infection. The results of these studies have been more or less inconclusive due to a lack of standardized protocol, showing no significant benefit to using antibiotics as a preventative measure. References == External links ==

Hello Aarogya, explain a situation where Vitamin D deficiency occurs

Vitamin D deficiency

Vitamin D deficiency or hypovitaminosis D is a vitamin D level that is below normal. It most commonly occurs in people when they have inadequate exposure to sunlight, particularly sunlight with adequate ultraviolet B rays (UVB). Vitamin D deficiency can also be caused by inadequate nutritional intake of vitamin D; disorders that limit vitamin D absorption; and disorders that impair the conversion of vitamin D to active metabolites, including certain liver, kidney, and hereditary disorders. Deficiency impairs bone mineralization, leading to bone-softening diseases, such as rickets in children. It can also worsen osteomalacia and osteoporosis in adults, increasing the risk of bone fractures. Muscle weakness is also a common symptom of vitamin D deficiency, further increasing the risk of fall and bone fractures in adults. Vitamin D deficiency is associated with the development of schizophrenia.Vitamin D can be synthesized in the skin under the exposure of UVB from sunlight. Oily fish, such as salmon, herring, and mackerel, are also sources of vitamin D, as are mushrooms. Milk is often fortified with vitamin D; sometimes bread, juices, and other dairy products are fortified with vitamin D. Many multivitamins contain vitamin D in different amounts. Classifications Vitamin D deficiency is typically diagnosed by measuring the concentration of the 25-hydroxyvitamin D in the blood, which is the most accurate measure of stores of vitamin D in the body. One nanogram per millilitre (1 ng/mL) is equivalent to 2.5 nanomoles per litre (2.5 nmol/L). Severe deficiency: <12 ng/mL = <30 nmol/L Deficiency: <20 ng/mL = <50 nmol/L Insufficient: 20–29 ng/mL = 50–75 nmol/L Normal: 30–50 ng/mL = 75–125 nmol/LVitamin D levels falling within this normal range prevent clinical manifestations of vitamin D insufficiency as well as vitamin D toxicity. Signs and symptoms In most cases, vitamin D deficiency is almost asymptomatic. It may only be detected on blood tests but is the cause of some bone diseases and is associated with other conditions: Complications Rickets, a childhood disease characterized by impeded growth and deformity of the long bones. The earliest sign of vitamin D deficiency is craniotabes, abnormal softening or thinning of the skull. Osteomalacia, a bone-thinning disorder that occurs exclusively in adults and is characterized by proximal muscle weakness and bone fragility. Women with vitamin D deficiency who have been through multiple pregnancies are at elevated risk of osteomalacia. Osteoporosis, a condition characterized by reduced bone mineral density and increased bone fragility Increased risk of fracture Muscle aches, weakness, and twitching (fasciculations), due to reduced blood calcium (hypocalcemia) Periodontitis, local inflammatory bone loss that can result in tooth loss. Pre-eclampsia: There has been an association of vitamin D deficiency and women who develop pre-eclampsia in pregnancy. The exact relationship of these conditions is not well understood. Maternal vitamin D deficiency may affect the baby, causing overt bone disease from before birth and impairment of bone quality after birth. Respiratory infections and COVID-19: Vitamin D deficiency may increase the risk of severe acute respiratory infections and COPD. Emerging studies have suggested a link between vitamin D deficiency and COVID-19 symptoms. A review has shown that vitamin D deficiency is not associated with a higher chance of having COVID-19 but is associated with a greater severity of the disease, including 80% increases in the rates of hospitalization and mortality. Schizophrenia: Vitamin D deficiency is associated with the development of schizophrenia. People with schizophrenia generally have lower levels of vitamin D. The environmental risk factors of seasonality of birth, latitude, and migration linked to schizophrenia all implicate vitamin D deficiency, as do other health conditions such as maternal obesity. Vitamin D is essential for the normal development of the nervous system. Maternal vitamin D deficiency can cause prenatal neurodevelopmental defects, which influence neurotransmission, altering brain rhythms and the metabolism of dopamine. Vitamin D receptors, CYP27B1, and CYP24A1 are found in various regions of the brain, showing that vitamin D is a neuroactive, neurosteroid hormone essential for the development of the brain and normal function. Inflammation as a causative factor in schizophrenia is normally suppressed by vitamin D. Risk factors Those most likely to be affected by vitamin D deficiency are people with little exposure to sunlight. Certain climates, dress habits, the avoidance of sun exposure and the use of too much sunscreen protection can all limit the production of vitamin D. Age Elderly people have a higher risk of having a vitamin D deficiency due to a combination of several risk factors, including decreased sunlight exposure, decreased intake of vitamin D in the diet, and decreased skin thickness, which leads to further decreased absorption of vitamin D from sunlight. Fat percentage Since vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) are fat-soluble, humans and other animals with a skeleton need to store some fat. Without fat, the animal will have a hard time absorbing vitamin D2 and vitamin D3, and the lower the fat percentage, the greater the risk of vitamin deficiency, which is true in some athletes who strive to get as lean as possible. Malnutrition Although rickets and osteomalacia are now rare in Britain, osteomalacia outbreaks in some immigrant communities included women with seemingly adequate daylight outdoor exposure wearing typical Western clothing. Having darker skin and reduced exposure to sunshine did not produce rickets unless the diet deviated from a Western omnivore pattern characterized by high intakes of meat, fish, and eggs and low intakes of high-extraction cereals. In sunny countries where rickets occurs among older toddlers and children, the rickets has been attributed to low dietary calcium intakes. This is characteristic of cereal-based diets with limited access to dairy products. Rickets was formerly a major public health problem among the US population; in Denver, almost two-thirds of 500 children had mild rickets in the late 1920s. An increase in the proportion of animal protein in the 20th-century American diet coupled with increased consumption of milk fortified with relatively small quantities of vitamin D coincided with a dramatic decline in the number of rickets cases. One study of children in a hospital in Uganda, however, showed no significant difference in vitamin D levels of malnourished children compared to non-malnourished children. Because both groups were at risk due to darker skin pigmentation, both groups had vitamin D deficiency. Nutritional status did not appear to play a role in this study. Obesity There is an increased risk of vitamin D deficiency in people who are considered overweight or obese based on their body mass index (BMI) measurement. The relationship between these conditions is not well understood. There are different factors that could contribute to this relationship, particularly diet and sunlight exposure. Alternatively, vitamin D is fat-soluble, so excess amounts can be stored in fat tissue and used during winter, when sun exposure is limited. Sun exposure The use of sunscreen with a sun protection factor of 8 can theoretically inhibit more than 95% of vitamin D production in the skin. In practice, however, sunscreen is applied so as to have a negligible effect on vitamin D status. The vitamin D status of those in Australia and New Zealand is unlikely to have been affected by campaigns advocating sunscreen. Instead, wearing clothing is more effective at reducing the amount of skin exposed to UVB and reducing natural vitamin D synthesis. Clothing that covers a large portion of the skin, when worn on a consistent and regular basis, such as the burqa, is correlated with lower vitamin D levels and an increased prevalence of vitamin D deficiency.Regions far from the equator have a high seasonal variation of the amount and intensity of sunlight. In the UK, the prevalence of low vitamin D status in children and adolescents is found to be higher in winter than in summer. Lifestyle factors such as indoor versus outdoor work and time spent in outdoor recreation play an important role. Additionally, vitamin D deficiency has been associated with urbanisation in terms of both air pollution, which blocks UV light, and an increase in the number of people working indoors. The elderly are generally exposed to less UV light due to hospitalisation, immobility, institutionalisation, and being housebound, leading to decreased levels of vitamin D. Darker skin color Because of melanin which enables natural sun protection, dark-skinned people are susceptible to vitamin D deficiency. Three to five times greater sun exposure is necessary for naturally darker skinned people to produce the same amount of vitamin D as those with white skin. Malabsorption Rates of vitamin D deficiency are higher among people with untreated celiac disease, inflammatory bowel disease, exocrine pancreatic insufficiency from cystic fibrosis, and short bowel syndrome, which can all produce problems of malabsorption. Vitamin D deficiency is also more common after surgical procedures that reduce absorption from the intestine, including weight loss procedures. Critical illness Vitamin D deficiency is associated with increased mortality in critical illness. People who take vitamin D supplements before being admitted for intensive care are less likely to die than those who do not take vitamin D supplements. Additionally, vitamin D levels decline during stays in intensive care. Vitamin D3 (cholecalciferol) or calcitriol given orally may reduce the mortality rate without significant adverse effects. Breastfeeding Infants who exclusively breastfeed need a vitamin D supplement, especially if they have dark skin or have minimal sun exposure. The American Academy of Pediatrics recommends that all breastfed infants receive 400 international units (IU) per day of oral vitamin D. Pathophysiology Decreased exposure of the skin to sunlight is a common cause of vitamin D deficiency. People with a darker skin pigment with increased amounts of melanin may have decreased production of vitamin D. Melanin absorbs ultraviolet B radiation from the sun and reduces vitamin D production. Sunscreen can also reduce vitamin D production. Medications may speed up the metabolism of vitamin D, causing a deficiency.The liver is required to transform vitamin D into 25-hydroxyvitamin D. This is an inactive metabolite of vitamin D but is a necessary precursor (building block) to create the active form of vitamin D.The kidneys are responsible for converting 25-hydroxyvitamin D to 1,25-hydroxyvitamin D. This is the active form of vitamin D in the body. Kidney disease reduces 1,25-hydroxyvitamin D formation, leading to a deficiency of the effects of vitamin D.Intestinal conditions that result in malabsorption of nutrients may also contribute to vitamin D deficiency by decreasing the amount of vitamin D absorbed via diet. In addition, a vitamin D deficiency may lead to decreased absorption of calcium by the intestines, resulting in increased production of osteoclasts that may break down a persons bone matrix. In states of hypocalcemia, calcium will leave the bones and may give rise to secondary hyperparathyroidism, which is a response by the body to increase serum calcium levels. The body does this by increasing uptake of calcium by the kidneys and continuing to take calcium away from the bones. If prolonged, this may lead to osteoporosis in adults and rickets in children. Diagnosis The serum concentration of calcifediol, also called 25-hydroxyvitamin D (abbreviated 25(OH)D), is typically used to determine vitamin D status. Most vitamin D is converted to 25(OH)D in the serum, giving an accurate picture of vitamin D status. The level of serum 1,25(OH)D is not usually used to determine vitamin D status because it often is regulated by other hormones in the body such as parathyroid hormone. The levels of 1,25(OH)D can remain normal even when a person may be vitamin D deficient. Serum level of 25(OH)D is the laboratory test ordered to indicate whether or not a person has vitamin D deficiency or insufficiency. It is also considered reasonable to treat at-risk persons with vitamin D supplementation without checking the level of 25(OH)D in the serum, as vitamin D toxicity has only been rarely reported to occur.Levels of 25(OH)D that are consistently above 200 nanograms per milliliter (ng/mL) (or 500 nanomoles per liter, nmol/L) are potentially toxic. Vitamin D toxicity usually results from taking supplements in excess. Hypercalcemia is often the cause of symptoms, and levels of 25(OH)D above 150 ng/mL (375 nmol/L) are usually found, although in some cases 25(OH)D levels may appear to be normal. Periodic measurement of serum calcium in individuals receiving large doses of vitamin D is recommended. Screening The official recommendation from the United States Preventive Services Task Force is that for persons that do not fall within an at-risk population and are asymptomatic, there is not enough evidence to prove that there is any benefit in screening for vitamin D deficiency. Treatment UVB exposure Vitamin-D overdose is impossible from UV exposure: the skin reaches an equilibrium where the vitamin degrades as fast as it is created. Sun tanning Light therapy Exposure to photons (light) at specific wavelengths of narrowband UVB enables the body to produce vitamin D to treat vitamin D deficiency. Supplement In the United States and Canada as of 2016, the amount of vitamin D recommended is 400 IU per day for children, 600 IU per day for adults, and 800 IU per day for people over age 70. The Canadian Paediatric Society recommends that pregnant or breastfeeding women consider taking 2000 IU/day, that all babies who are exclusively breastfed receive a supplement of 400 IU/day, and that babies living north of 55°N get 800 IU/day from October to April.Treating vitamin D deficiency depends on the severity of the deficit. Treatment involves an initial high-dosage treatment phase until the required serum levels are reached, followed by the maintenance of the acquired levels. The lower the 25(OH)D serum concentration is before treatment, the higher is the dosage that is needed in order to quickly reach an acceptable serum level.The initial high-dosage treatment can be given on a daily or weekly basis or can be given in form of one or several single doses (also known as stoss therapy, from the German word Stoß, meaning "push").Therapy prescriptions vary, and there is no consensus yet on how best to arrive at an optimum serum level. While there is evidence that vitamin D3 raises 25(OH)D blood levels more effectively than vitamin D2, other evidence indicates that D2 and D3 are equal for maintaining 25(OH)D status. Initial phase Daily or weekly or monthly dose For treating rickets, the American Academy of Pediatrics (AAP) has recommended that pediatric patients receive an initial two- to three-month treatment of "high-dose" vitamin D therapy. In this regime, the daily dose of cholecalciferol is 1,000 IU for newborns, 1,000 to 5,000 IU for 1- to 12-month-old infants, and 5,000 IU for patients over 1 year of age.For adults, other dosages have been called for. A review of 2008/2009 recommended dosages of 1,000 IU cholecalciferol per 10 ng/mL required serum increase, to be given daily over two to three months. In another proposed cholecalciferol loading dose guideline for vitamin D-deficient adults, a weekly dosage is given, up to a total amount that is proportional to the required serum increase (up to the level of 75 nmL/L) and within certain body weight limits, to body weight.According to new data and practices relevant to vitamin D levels in the general population in France, to establish optimal vitamin D status and frequency of intermittent supplement dosing, patients with or at high risk for osteoporosis and vitamin D deficiency should start supplementation with a loading phase consisting of 50,000 IU weekly of vitamin D for 8 weeks in patients with levels <20 ng/mL and 50,000 IU weekly for 4 weeks in patients with levels between 20 and 30 ng/mL. Subsequently, long-term supplementation should be prescribed as 50,000 IU monthly. Should pharmaceutical forms suitable for daily supplementation become available, patients displaying good treatment adherence could take a daily dose determined based on the 25(OH)D level. Until now, there are no consistent data suggesting the ideal regimen of supplementation with vitamin D, and the question of the ideal time between doses is still of debate. Ish-Shalom et al. performed a study in elderly women to compare the efficacy and safety of a daily dose of 1,500 IU to a weekly dose of 10,500 IU and to a dose of 45,000 IU given every 28 days for two months. They concluded that supplementation with vitamin D can be equally achieved with daily, weekly, or monthly dosing frequencies. Another study comparing daily, weekly, and monthly supplementation of vitamin D in deficient patients was published by Takacs et al. They reported an equal efficacy of 1,000 IU taken daily, 7,000 IU taken weekly, and 30,000 IU taken monthly. Nevertheless, these consistent findings differ from the report by Chel et al., in which a daily dose was more effective than a monthly dose. In that study, the compliance calculation could be questionable since only random samples of the returned medications were counted. In a study by De Niet et al., 60 subjects with vitamin D deficiency were randomized to receive 2,000 IU vitamin D3 daily or 50,000 IU monthly. They reported a similar efficacy of the two dosing frequencies, with the monthly dose providing a more rapid normalization of vitamin D levels. Single-dose therapy Alternatively, a single-dose therapy is used for instance if there are concerns regarding the patients compliance. The single-dose therapy can be given as an injection but is normally given in form of an oral medication. Vitamin D doses and meals The presence of a meal and the fat content of that meal may also be important. Because vitamin D is fat-soluble, it is hypothesized that absorption would be improved if patients are instructed to take their supplement with a meal. Raimundo et al. performed different studies confirming that a high-fat meal increased the absorption of vitamin D3 as measured by serum 25(OH) D. A clinical report indicated that serum 25(OH) D levels increased by an average of 57% over a 2-month to 3-month period in 17 clinic patients after they were instructed to take their usual dose of vitamin D with the largest meal of the day.Another study conducted in 152 healthy men and women concluded that diets rich in monounsaturated fatty acids may improve and those rich in polyunsaturated fatty acids may reduce the effectiveness of vitamin D3 supplements. In another study performed by Cavalier E. et al., 88 subjects received orally a single dose of 50,000 IU of vitamin D3 solubilized in an oily solution as two ampoules each containing 25,000 IU (D‐CURE®, Laboratories SMB SA, Brussels, Belgium) with or without a standardized high‐fat breakfast. No significant difference between fasting vs. fed conditions was observed. Maintenance phase Once the desired serum level has been achieved, be it by a high daily or weekly or monthly dose or by a single-dose therapy, the AAP recommendation calls for a maintenance supplementation of 400 IU for all age groups, with this dosage being doubled for premature infants, dark-skinned infants and children, children who reside in areas of limited sun exposure (>37.5° latitude), obese patients, and those on certain medications. Special cases To maintain blood levels of calcium, therapeutic vitamin D doses are sometimes administered (up to 100,000 IU or 2.5 mg daily) to patients who have had their parathyroid glands removed (most commonly kidney dialysis patients who have had tertiary hyperparathyroidism, but also to patients with primary hyperparathyroidism) or with hypoparathyroidism. Patients with chronic liver disease or intestinal malabsorption disorders may also require larger doses of vitamin D (up to 40,000 IU or 1 mg (1000 micrograms) daily). Co-supplementation with vitamin K The combination of vitamin D and vitamin K supplements has been shown in trials to improve bone quality. As high intake of vitamin D is a cause of raised calcium levels (hypercalcemia), the addition of vitamin K may be beneficial in helping to prevent vascular calcification, particularly in people with chronic kidney disease. Bioavailability Not all D3 deficiencies can be effectively supplemented or treated with vitamin D3 on its own. Older people or those who have fatty liver or metabolic syndrome have a reduced ability to absorb vitamin D3. In addition, in overweight or obese persons, excessive adipose tissue can sequester D3 from the circulation and reduce its access to other tissues. With age or in obesity, metabolic activation of D3 may be reduced by liver steatosis or by microbiome imbalance.For vitamin D3 to perform its hormonal roles, it is converted into its biologically active metabolite, calcifediol, also known as 25-hydroxyvitamin D3, an activation occurring by a hydroxylation reaction in the liver via the cytochrome P450 system, and in the gut microbiome. Epidemiology The estimated percentage of the population with a vitamin D deficiency varies based on the threshold used to define a deficiency. Recommendations for 25(OH)D serum levels vary across authorities, and probably vary based on factors like age; calculations for the epidemiology of vitamin D deficiency depend on the recommended level used.A 2011 Institute of Medicine (IOM) report set the sufficiency level at 20 ng/mL (50 nmol/L), while in the same year The Endocrine Society defined sufficient serum levels at 30 ng/mL and others have set the level as high as 60 ng/mL. As of 2011 most reference labs used the 30 ng/mL standard.: 435 Applying the IOM standard to NHANES data on serum levels, for the period from 1988 to 1994 22% of the US population was deficient, and 36% were deficient for the period between 2001 and 2004; applying the Endocrine Society standard, 55% of the US population was deficient between 1988 and 1994, and 77% were deficient for the period between 2001 and 2004.In 2011 the Centers for Disease Control and Prevention applied the IOM standard to NHANES data on serum levels collected between 2001 and 2006, and determined that 32% of Americans were deficient during that period (8% at risk of deficiency, and 24% at risk of inadequacy). History The role of diet in the development of rickets was determined by Edward Mellanby between 1918 and 1920. In 1921, Elmer McCollum identified an antirachitic substance found in certain fats that could prevent rickets. Because the newly discovered substance was the fourth vitamin identified, it was called vitamin D. The 1928 Nobel Prize in Chemistry was awarded to Adolf Windaus, who discovered the steroid 7-dehydrocholesterol, the precursor of vitamin D. Prior to the fortification of milk products with vitamin D, rickets was a major public health problem. In the United States, milk has been fortified with 10 micrograms (400 IU) of vitamin D per quart since the 1930s, leading to a dramatic decline in the number of rickets cases. Research Some evidence suggests vitamin D deficiency may be associated with a worse outcome for some cancers, but evidence is insufficient to recommend that vitamin D be prescribed for people with cancer. Taking vitamin D supplements has no significant effect on cancer risk. Vitamin D3, however, appears to decrease the risk of death from cancer but concerns with the quality of the data exist.Vitamin D deficiency is thought to play a role in the pathogenesis of non-alcoholic fatty liver disease.Evidence suggests that vitamin D deficiency may be associated with impaired immune function. Those with vitamin D deficiency may have trouble fighting off certain types of infections. It has also been thought to correlate with cardiovascular disease, type 1 diabetes, type 2 diabetes, and some cancers.Review studies have also seen associations between vitamin D deficiency and pre-eclampsia. See also Hypervitaminosis D Vitamin D deficiency in Australia References == External links ==

Please give me a short description about Vitamin E deficiency , Aarogya

Vitamin E deficiency

Vitamin E deficiency in humans is a very rare condition, occurring as a consequence of abnormalities in dietary fat absorption or metabolism rather than from a diet low in vitamin E. Collectively the EARs, RDAs, AIs and ULs for vitamin E and other essential nutrients are referred to as Dietary Reference Intakes (DRIs). Vitamin E deficiency can cause nerve problems due to poor conduction of electrical impulses along nerves due to changes in nerve membrane structure and function. Signs and symptoms Signs of vitamin E deficiency include the following: Neuromuscular problems – such as spinocerebellar ataxia and myopathies. Neurological problems – may include dysarthria, absence of deep tendon reflexes, loss of the ability to sense vibration and detect where body parts are in three dimensional space, and positive Babinski sign. Hemolytic anemia – due to oxidative damage to red blood cells Retinopathy Impairment of the immune response Causes Vitamin E deficiency is rare. There are no records of it from simple lack of vitamin E in a persons diet, but it can arise from physiological abnormalities. It occurs in the people in the following situations: Premature, very low birth weight infants – birth weights less than 1500 grams (3.3 pounds). Rare disorders of fat metabolism – There is a rare genetic condition termed isolated vitamin E deficiency or ataxia with isolated with vitamin E deficiency, caused by mutations in the gene for the tocopherol transfer protein. These individuals have an extremely poor capacity to absorb vitamin E and develop neurological complications that are reversed by high doses of vitamin E. Fat malabsorption – Some dietary fat is needed for the absorption of vitamin E from the gastrointestinal tract. Anyone diagnosed with cystic fibrosis, individuals who have had part or all of their stomach removed or who have had a gastric bypass, and individuals with malabsorptive problems such as Crohns disease, liver disease or exocrine pancreatic insufficiency may not absorb fat (people who cannot absorb fat often pass greasy stools or have chronic diarrhea and bloating). Abetalipoproteinemia is a rare inherited disorder of fat metabolism that results in poor absorption of dietary fat and vitamin E. The vitamin E deficiency associated with this disease causes problems such as poor transmission of nerve impulses and muscle weakness. Diagnosis The U.S. Institute of Medicine defines deficiency as a serum concentration of less than 12 μmol/L. The symptoms can be enough for a diagnosis to be formed. Treatment Treatment is oral vitamin E supplementation. See also Familial isolated vitamin E deficiency Abetalipoproteinemia Tocopherol References == External links ==

Aarogya, give me a short description about Waldenström macroglobulinemia

Waldenström macroglobulinemia

Waldenström macroglobulinemia () is a type of cancer affecting two types of B cells: lymphoplasmacytoid cells and plasma cells. Both cell types are white blood cells. It is characterized by having high levels of a circulating antibody, immunoglobulin M (IgM), which is made and secreted by the cells involved in the disease. Waldenström macroglobulinemia is an "indolent lymphoma" (i.e., one that tends to grow and spread slowly) and a type of lymphoproliferative disease which shares clinical characteristics with the indolent non-Hodgkin lymphomas. It is commonly classified as a form of plasma cell dyscrasia, similar to other plasma cell dyscrasias that, for example, lead to multiple myeloma. Waldenström macroglobulinemia is commonly preceded by two clinically asymptomatic but progressively more pre-malignant phases, IgM monoclonal gammopathy of undetermined significance and smoldering Waldenström macroglobulinemia. The Waldenström macroglobulinemia spectrum of dysplasias differs from other spectrums of plasma cell dyscrasias in that it involves not only aberrant plasma cells but also aberrant lymphoplasmacytoid cells and that it involves IgM while other plasma dyscrasias involve other antibody isoforms.Waldenström macroglobulinemia is a rare disease, with only about 1,500 cases per year in the United States. It occurs more frequently in older adults. While the disease is incurable, it is treatable. Because of its indolent nature, many patients are able to lead active lives, and when treatment is required, may experience years of symptom-free remission. Signs and symptoms Signs and symptoms of Waldenström macroglobulinemia include weakness, fatigue, weight loss, and chronic oozing of blood from the nose and gums. Peripheral neuropathy occurs in 10% of patients. Enlargement of the lymph nodes, spleen, and/or liver are present in 30–40% of cases. Other possible signs and symptoms include blurring or loss of vision, headache, and (rarely) stroke or coma. Causes Waldenström macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B lymphocytes. The most commonly associated mutations, based on whole-genome sequencing of 30 patients, are a somatic mutation in MYD88 (90% of patients) and a somatic mutation in CXCR4 (27% of patients). CXCR4 mutations cause symptomatic hyperviscosity syndrome and high bone marrow activity characteristic of the disease. However, CXCR4 mutation is not associated with splenomegaly, high platelet counts, or different response to therapy, questioning the relevance of CXCR4 in treating patients. An association has been demonstrated with the locus 6p21.3 on chromosome 6. There is a two- to threefold increased risk of Waldenström macroglobulinemia in people with a personal history of autoimmune diseases with autoantibodies, and a particularly elevated risk associated with liver inflammation, human immunodeficiency virus, and rickettsiosis.There are genetic factors, with first-degree relatives of Waldenström macroglobulinemia patients shown to have a highly increased risk of also developing the disease. There is also evidence to suggest that environmental factors, including exposure to farming, pesticides, wood dust, and organic solvents, may influence the development of Waldenström macroglobulinemia. Genetics Although believed to be a sporadic disease, studies have shown increased susceptibility within families, indicating a genetic component. A mutation in gene MYD88 has been found to occur frequently in patients. Waldenström macroglobulinemia cells show only minimal changes in cytogenetic and gene expression studies. Their miRNA signature however differs from their normal counterpart. It is therefore believed that epigenetic modifications play a crucial role in the disease.Comparative genomic hybridization identified the following chromosomal abnormalities: deletions of 6q23 and 13q14, and gains of 3q13-q28, 6p and 18q. FGFR3 is overexpressed. The following signalling pathways have been implicated: CD154/CD40 Akt ubiquitination, p53 activation, cytochrome c release NF-κB WNT/beta-catenin mTOR ERK MAPK Bcl-2The protein Src tyrosine kinase is overexpressed in Waldenström macroglobulinemia cells compared with control B cells. Inhibition of Src arrests the cell cycle at phase G1 and has little effect on the survival of Waldenström macroglobulinemia or normal cells. MicroRNAs involved in Waldenström: increased expression of miRNAs-363*, -206, -494, -155, -184, -542–3p. decreased expression of miRNA-9*.MicroRNA-155 regulates the proliferation and growth of Waldenström macroglobulinemia cells in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-κB pathways.In Waldenström macroglobulinemia cells, histone deacetylases and histone-modifying genes are de-regulated. Bone marrow tumour cells express the following antigen targets CD20 (98.3%), CD22 (88.3%), CD40 (83.3%), CD52 (77.4%), IgM (83.3%), MUC1 core protein (57.8%), and 1D10 (50%). Pathophysiology Symptoms including blurring or loss of vision, headache, and (rarely) stroke or coma are due to the effects of the IgM paraprotein, which may cause autoimmune phenomenon or cryoglobulinemia. Other symptoms of Waldenström macroglobulinemia are due to hyperviscosity syndrome, which is present in 6–20% of patients. This is attributed to the IgM monoclonal protein increasing the viscosity of the blood by forming aggregates to each other, binding water through their carbohydrate component and by their interaction with blood cells. Diagnosis A diagnosis of Waldenström macroglobulinemia depends on a significant monoclonal IgM spike evident in blood tests and malignant cells consistent with the disease in bone marrow biopsy samples. Blood tests show the level of IgM in the blood and the presence of proteins, or tumor markers, that are the key signs of Waldenström macroglobulinemia. A bone marrow biopsy provides a sample of bone marrow, usually from the lower back of the pelvis bone. The sample is extracted through a needle and examined under a microscope. A pathologist identifies the particular lymphocytes that indicate Waldenström macroglobulinemia. Flow cytometry may be used to examine markers on the cell surface or inside the lymphocytes.Additional tests such as computed tomography (CT or CAT) scan may be used to evaluate the chest, abdomen, and pelvis, particularly swelling of the lymph nodes, liver, and spleen. A skeletal survey can help distinguish between Waldenström macroglobulinemia and multiple myeloma. Anemia occurs in about 80% of patients with Waldenström macroglobulinemia. A low white blood cell count, and low platelet count in the blood may be observed. A low level of neutrophils (a specific type of white blood cell) may also be found in some individuals with Waldenström macroglobulinemia.Chemistry tests include lactate dehydrogenase (LDH) levels, uric acid levels, erythrocyte sedimentation rate (ESR), kidney and liver function, total protein levels, and an albumin-to-globulin ratio. The ESR and uric acid level may be elevated. Creatinine is occasionally elevated and electrolytes are occasionally abnormal. A high blood calcium level is noted in approximately 4% of patients. The LDH level is frequently elevated, indicating the extent of Waldenström macroglobulinemia–related tissue involvement. Rheumatoid factor, cryoglobulins, direct antiglobulin test and cold agglutinin titre results can be positive. Beta-2 microglobulin and C-reactive protein test results are not specific for Waldenström macroglobulinemia. Beta-2 microglobulin is elevated in proportion to tumor mass. Coagulation abnormalities may be present. Prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen tests should be performed. Platelet aggregation studies are optional. Serum protein electrophoresis results indicate evidence of a monoclonal spike but cannot establish the spike as IgM. An M component with beta-to-gamma mobility is highly suggestive of Waldenström macroglobulinemia. Immunoelectrophoresis and immunofixation studies help identify the type of immunoglobulin, the clonality of the light chain, and the monoclonality and quantitation of the paraprotein. High-resolution electrophoresis and serum and urine immunofixation are recommended to help identify and characterize the monoclonal IgM paraprotein. The light chain of the monoclonal protein is usually the kappa light chain. At times, patients with Waldenström macroglobulinemia may exhibit more than one M protein. Plasma viscosity must be measured. Results from characterization studies of urinary immunoglobulins indicate that light chains (Bence Jones protein), usually of the kappa type, are found in the urine. Urine collections should be concentrated. Bence Jones proteinuria is observed in approximately 40% of patients and exceeds 1 g/d in approximately 3% of patients. Patients with findings of peripheral neuropathy should have nerve conduction studies and antimyelin associated glycoprotein serology.Criteria for diagnosis of Waldenström macroglobulinemia include: IgM monoclonal gammopathy that excludes chronic lymphocytic leukemia and Mantle cell lymphoma Evidence of anemia, constitutional symptoms, hyperviscosity, swollen lymph nodes, or enlargement of the liver and spleen that can be attributed to an underlying lymphoproliferative disorder. Treatment There is no single accepted treatment for Waldenström macroglobulinemia. There is marked variation in clinical outcome due to gaps in knowledge of the diseases molecular basis. Objective response rates are high (> 80%) but complete response rates are low (0–15%). The medication ibrutinib targets the MYD88 L265P mutation induced activation of Brutons tyrosine kinase. In a cohort study of previously treated patients, ibrutinib induced responses in 91% of patients, and at 2 years 69% of patients had no progression of disease and 95% were alive. Based on this study, the Food and Drug Administration approved ibrutinib for use in Waldenström macroglobulinemia in 2015.There are different treatment flowcharts: Treon and mSMART.Patients with Waldenström macroglobulinemia are at higher risk of developing second cancers than the general population, but it is not yet clear whether treatments are contributory. Watchful waiting In the absence of symptoms, many clinicians will recommend simply monitoring the patient; Waldenström himself stated "let well do" for such patients. These asymptomatic cases are now classified as two successively more pre-malignant phases, IgM monoclonal gammopathy of undetermined significance and smoldering Waldenström macroglobulinemia. But on occasion, the disease can be fatal, as it was to the French president Georges Pompidou, who died in office in 1974. Mohammad Reza Shah Pahlavi, the Shah of Iran, also had Waldenström macroglobulinemia, which resulted in his ill-fated trip to the United States for therapy in 1979, leading to the Iran hostage crisis. First-line Should treatment be started it should address both the paraprotein level and the lymphocytic B-cells.In 2002, a panel at the International Workshop on Waldenströms Macroglobulinemia agreed on criteria for the initiation of therapy. They recommended starting therapy in patients with constitutional symptoms such as recurrent fever, night sweats, fatigue due to anemia, weight loss, progressive symptomatic lymphadenopathy or spleen enlargement, and anemia due to bone marrow infiltration. Complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy, systemic amyloidosis, kidney failure, or symptomatic cryoglobulinemia were also suggested as indications for therapy.Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or vincristine or with thalidomide. Corticosteroids, such as prednisone, may also be used in combination. Plasmapheresis can be used to treat the hyperviscosity syndrome by removing the paraprotein from the blood, although it does not address the underlying disease. Ibrutinib is another agent that has been approved for use in this condition. Combination treatment with Ibrutinib and Rituximab showed significantly higher disease progression free survival than with just Rituximab treatment.Autologous bone marrow transplantation is a treatment option.Zanubrutinib is indicated for the treatment of adults with Waldenström macroglobulinemia. Salvage therapy When primary or secondary resistance invariably develops, salvage therapy is considered. Allogeneic stem cell transplantation can induce durable remissions for heavily pre-treated patients. Drug pipeline As of October 2010, there have been a total of 44 clinical trials on Waldenström macroglobulinemia, excluding transplantation treatments. Of these, 11 were performed on previously untreated patients, 14 in patients with relapsed or refractory Waldenström. A database of clinical trials investigating Waldenström macroglobulinemia is maintained by the National Institutes of Health in the US. Patient stratification Patients with polymorphic variants (alleles) FCGR3A-48 and -158 were associated with improved categorical responses to rituximab-based treatments. Prognosis Current medical treatments result in survival of some longer than 10 years; in part this is because better diagnostic testing means early diagnosis and treatments. Older diagnosis and treatments resulted in published reports of median survival of approximately 5 years from time of diagnosis. Currently, median survival is 6.5 years. In rare instances, Waldenström macroglobulinemia progresses to multiple myeloma.The International Prognostic Scoring System for Waldenströms Macroglobulinemia is a predictive model to characterise long-term outcomes. According to the model, factors predicting reduced survival are: Age > 65 years Hemoglobin ≤ 11.5 g/dL Platelet count ≤ 100×109/L B2-microglobulin > 3 mg/L Serum monoclonal protein concentration > 70 g/LThe risk categories are: Low: ≤ 1 adverse variable except age Intermediate: 2 adverse characteristics or age > 65 years High: > 2 adverse characteristicsFive-year survival rates for these categories are 87%, 68% and 36%, respectively. The corresponding median survival rates are 12, 8, and 3.5 years.The International Prognostic Scoring System for Waldenströms Macroglobulinemia has been shown to be reliable. It is also applicable to patients on a rituximab-based treatment regimen. An additional predictive factor is elevated serum lactate dehydrogenase (LDH). Epidemiology Of cancers involving the lymphocytes, 1% of cases are Waldenström macroglobulinemia.Waldenström macroglobulinemia is a rare disorder, with fewer than 1,500 cases occurring in the United States annually. The median age of onset is between 60 and 65 years, with some cases occurring in late teens. History Waldenström macroglobulinemia was first described by Jan G. Waldenström (1906–1996) in 1944 in two patients with bleeding from the nose and mouth, anemia, decreased levels of fibrinogen in the blood (hypofibrinogenemia), swollen lymph nodes, neoplastic plasma cells in bone marrow, and increased viscosity of the blood due to increased levels of a class of heavy proteins called macroglobulins.For a time, Waldenström macroglobulinemia was considered to be related to multiple myeloma because of the presence of monoclonal gammopathy and infiltration of the bone marrow and other organs by plasmacytoid lymphocytes. The new World Health Organization (WHO) classification, however, places Waldenström macroglobulinemia under the category of lymphoplasmacytic lymphomas, itself a subcategory of the indolent (low-grade) non-Hodgkin lymphomas. Since the 1990s, there have been significant advances in the understanding and treatment of Waldenström macroglobulinemia. See also List of hematologic conditions Waldenström hyperglobulinemic purpura == References ==

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

Wart

Warts are typically small, rough, hard growths that are similar in color to the rest of the skin. They typically do not result in other symptoms, except when on the bottom of the feet, where they may be painful. While they usually occur on the hands and feet, they can also affect other locations. One or many warts may appear. They are not cancerous.Warts are caused by infection with a type of human papillomavirus (HPV). Factors that increase the risk include use of public showers and pools, working with meat, eczema and a weak immune system. The virus is believed to enter the body through skin that has been damaged slightly. A number of types exist, including "common warts", plantar warts, "filiform warts", and genital warts. Genital warts are often sexually transmitted.Without treatment, most types of warts resolve in months to years. A number of treatments may speed resolution, including salicylic acid applied to the skin and cryotherapy. In those who are otherwise healthy, they do not typically result in significant problems. Treatment of genital warts differs from that of other types.Warts are very common, with most people being infected at some point in their lives. The estimated current rate of non-genital warts among the general population is 1–13%. They are more common among young people. Prior to widespread adoption of the HPV vaccine, the estimated rate of genital warts in sexually active women was 12%. Warts have been described at least as far back as 400 BC by Hippocrates. Types A range of types of wart have been identified, varying in shape and site affected, as well as the type of human papillomavirus involved. These include: Common wart (verruca vulgaris), a raised wart with roughened surface, most common on hands, but can grow anywhere on the body. Sometimes known as a Palmer wart or Junior wart. Flat wart (verruca plana), a small, smooth flattened wart, flesh-coloured, which can occur in large numbers; most common on the face, neck, hands, wrists and knees. Filiform or digitate wart, a thread- or finger-like wart, most common on the face, especially near the eyelids and lips. Genital wart (venereal wart, condyloma acuminatum, verruca acuminata), a wart that occurs on the genitalia. Periungual wart, a cauliflower-like cluster of warts that occurs around the nails. Plantar wart (verruca, verruca plantaris), a hard, sometimes painful lump, often with multiple black specks in the center; usually only found on pressure points on the soles of the feet. Mosaic wart, a group of tightly clustered plantar-type warts, commonly on the hands or soles of the feet. Cause Warts are caused by the human papilloma virus (HPV). There are about 130 known types of human papilloma viruses. HPV infects the squamous epithelium, usually of the skin or genitals, but each HPV type is typically only able to infect a few specific areas on the body. Many HPV types can produce a benign growth, often called a "wart" or "papilloma", in the area they infect. Many of the more common HPV and wart types are listed below. Common warts – HPV types 2 and 4 (most common); also types 1, 3, 26, 29, and 57 and others. Cancers and genital dysplasia – "high-risk" HPV types are associated with cancers, notably cervical cancer, and can also cause some vulvar, vaginal, penile, anal and some oropharyngeal cancers. "Low-risk" types are associated with warts or other conditions.High-risk: 16, 18 (cause the most cervical cancer); also 31, 33, 35, 39, 45, 52, 58, 59, and others.Plantar warts (verruca) – HPV type 1 (most common); also types 2, 3, 4, 27, 28, and 58 and others. Anogenital warts (condylomata acuminata or venereal warts) – HPV types 6 and 11 (most common); also types 42, 44 and others.Low-risk: 6, 11 (most common); also 13, 44, 40, 43, 42, 54, 61, 72, 81, 89, and others.Verruca plana (flat warts) – HPV types 3, 10, and 28. Butchers warts – HPV type 7. Hecks disease (focal epithelial hyperplasia) – HPV types 13 and 32. Pathophysiology Common warts have a characteristic appearance under the microscope. They have thickening of the stratum corneum (hyperkeratosis), thickening of the stratum spinosum (acanthosis), thickening of the stratum granulosum, rete ridge elongation, and large blood vessels at the dermoepidermal junction. Diagnosis On dermatoscopic examination, warts will commonly have fingerlike or knoblike extensions. Prevention Gardasil 6 is an HPV vaccine aimed at preventing cervical cancers and genital warts. Gardasil is designed to prevent infection with HPV types 16, 18, 6, and 11. HPV types 16 and 18 currently cause about 70% of cervical cancer cases, and also cause some vulvar, vaginal, penile and anal cancers. HPV types 6 and 11 are responsible for 90% of documented cases of genital warts.Gardasil 9, approved in 2014 protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.HPV vaccines do not currently protect against the virus strains responsible for plantar warts (verrucae). Disinfection The virus is relatively hardy and immune to many common disinfectants. Exposure to 90% ethanol for at least 1 minute, 2% glutaraldehyde, 30% Savlon, and/or 1% sodium hypochlorite can disinfect the pathogen.The virus is resistant to drying and heat, but killed by 100 °C (212 °F) and ultraviolet radiation. Treatment There are many treatments and procedures associated with wart removal. A review of various skin wart treatments concluded that topical treatments containing salicylic acid were more effective than placebo. Cryotherapy appears to be as effective as salicylic acid, but there have been fewer trials. Medication Salicylic acid can be prescribed by a dermatologist in a higher concentration than that found in over-the-counter products. Several over-the-counter products are readily available at pharmacies and supermarkets of roughly two types: adhesive pads treated with salicylic acid, and bottled concentrated salicylic acid and lactic acid solution. Fluorouracil — Fluorouracil cream, a chemotherapy agent sometimes used to treat skin cancer, can be used on particularly resistant warts, by blocking viral DNA and RNA production and repair. Imiquimod is a topical cream that helps the bodys immune system fight the wart virus by encouraging interferon production. It has been approved by the U.S. Food and Drug Administration (FDA) for genital warts. Cantharidin, found naturally in the bodies of many members of the beetle family Meloidae, causes dermal blistering. It is used either by itself or compounded with podophyllin. Not FDA approved, but available through Canada or select US compounding pharmacies. Bleomycin — A more potent chemotherapy drug, can be injected into deep warts, destroying the viral DNA or RNA. Bleomycin is notably not US FDA approved for this purpose. Possible side effects include necrosis of the digits, nail loss and Raynaud syndrome. The usual treatment is one or two injections. Dinitrochlorobenzene (DNCB), like salicylic acid, is applied directly to the wart. Studies show this method is effective with a cure rate of 80%. But DNCB must be used much more cautiously than salicylic acid; the chemical is known to cause genetic mutations, so it must be administered by a physician. This drug induces an allergic immune response, resulting in inflammation that wards off the wart-causing virus. Cidofovir is an antiviral drug which is injected into HPV lesions within the larynx (laryngeal papillomatosis) as an experimental treatment. Verrutop verruca treatment is a topical solution made from a combination of organic acids, inorganic acids, and metal ions. This solution causes the production of nitrites, which act to denature viral proteins and mummify the wart tissue. The difference between Verrutop and other acid treatments is that it does not damage the surrounding skin. Another product available over-the-counter that can aid in wart removal is silver nitrate in the form of a caustic pencil, which is also available at drug stores. In a placebo-controlled study of 70 patients, silver nitrate given over nine days resulted in clearance of all warts in 43% and improvement in warts in 26% one month after treatment compared to 11% and 14%, respectively, in the placebo group. The instructions must be followed to minimize staining of skin and clothing. Occasionally, pigmented scars may develop. Procedures Keratolysis, of dead surface skin cells usually using salicylic acid, blistering agents, immune system modifiers ("immunomodulators"), or formaldehyde, often with mechanical paring of the wart with a pumice stone, blade etc. Electrodesiccation Cryosurgery or cryotherapy, which involves freezing the wart (generally with liquid nitrogen), creating a blister between the wart and epidermal layer after which the wart and the surrounding dead skin fall off. An average of 3 to 4 treatments are required for warts on thin skin. Warts on calloused skin like plantar warts might take dozens or more treatments. Surgical curettage of the wart Laser treatment – often with a pulse dye laser or carbon dioxide (CO2) laser. Pulse dye lasers (wavelength 582 nm) work by selective absorption by blood cells (specifically hemoglobin). CO2 lasers work by selective absorption by water molecules. Pulse dye lasers are less destructive and more likely to heal without scarring. CO2 laser works by vaporizing and destroying tissue and skin. Laser treatments can be painful, expensive (though covered by many insurance plans), and not extensively scarring when used appropriately. CO2 lasers will require local anaesthetic. Pulse dye laser treatment does not need conscious sedation or local anesthetic. It takes 2 to 4 treatments, but can be many more for extreme cases. Typically, 10–14 days are required between treatments. Preventative measures are important. Infrared coagulator – an intense source of infrared light in a small beam like a laser. This works essentially on the same principle as laser treatment. It is less expensive. Like the laser, it can cause blistering, pain and scarring. Intralesional immunotherapy with purified candida, MMR, and tuberculin (PPD) protein appears safe and effective. Duct tape occlusion therapy involves placing a piece of duct tape over the wart. The mechanism of action of this technique still remains unknown. Despite several trials, evidence for the efficacy of duct tape therapy is inconclusive. Despite the mixed evidence for efficacy, the simplicity of the method and its limited side-effects leads some researchers to be reluctant to dismiss it. No intervention. Spontaneous resolution within a few years can be recommended. Alternative medicine Daily application of the latex of Chelidonium majus is a traditional treatment.The acrid yellow sap of Greater Celandine is used as a traditional wart remedy.According to English folk belief, touching toads causes warts; according to a German belief, touching a toad under a full moon cures warts. The most common Northern Hemisphere toads have glands that protrude from their skin that superficially resemble warts. Warts are caused by a virus, and toads do not harbor it. A variety of traditional folk remedies and rituals claim to be able to remove warts. In The Adventures of Tom Sawyer, Mark Twain has his characters discuss a variety of such remedies. Tom Sawyer proposes "spunk-water" (or "stump-water", the water collecting in the hollow of a tree stump) as a remedy for warts on the hand. You put your hand into the water at midnight and say: You then "walk away quick, eleven steps, with your eyes shut, and then turn around three times and walk home without speaking to anybody. Because if you speak the charms busted." This is given as an example to Huckleberry Finns planned remedy, which involves throwing a dead cat into a graveyard as a devil or devils comes to collect a recently buried wicked person. Another remedy involved splitting a bean, drawing blood from the wart and putting it on one of the halves, and burying that half at a crossroads at midnight. The theory of operation is that the blood on the buried bean will draw away the wart. Twain is recognized as an early collector and recorder of genuine American folklore.Similar practices are recorded elsewhere. In Louisiana, one remedy for warts involves rubbing the wart with a potato, which is then buried; when the "buried potato dries up, the wart will be cured". Another remedy similar to Twains is reported from Northern Ireland, where water from a specific well on Rathlin Island is credited with the power to cure warts. History Surviving ancient medical texts show that warts were a documented disease since at least the time of Hippocrates, who lived c. 460 – c. 370 BC. In the book De Medecia by the Roman physician Aulus Cornelius Celsus, who lived c. 25 BC – c. 50 AD, different types of warts were described. Celsus described myrmecia, today recognized as plantar wart, and categorized acrochordon (a skin tag) as wart. In the 13th century, warts were described in books published by the surgeons William of Saliceto and Lanfranc of Milan. The word verruca to describe a wart was introduced by the physician Daniel Sennert, who described warts in his 1636 book Hypomnemata physicae.But the cause of warts was disputed in the medical profession. In the early 18th century the physician Daniel Turner, who published the first book on dermatology, suggested that warts were caused by damaged nerves close to the skin. In the mid 18th century, the surgeon John Hunter popularized the belief that warts were caused by a bacterial syphilis infection. The surgeon Benjamin Bell documented that warts were caused by a disease entirely unrelated to syphilis, and established a causal link between warts and cancer. In the 19th century, the chief physician of Verona hospital established a link between warts and cervical cancer. But in 1874 it was noted by the dermatologist Ferdinand Ritter von Hebra that while various theories were advanced by the medical profession, the "influences causing warts are still very obscure".In 1907 the physician Giuseppe Ciuffo was the first to demonstrate that warts were caused by a virus infection. In 1976 the virologist Harald zur Hausen was the first to discover that warts were caused by the human papillomavirus (HPV). His continuous research established the evidence necessary to develop a HPV vaccine, which first became available in 2006. Other animals References External links Wart photo library, Dermnet

Aarogya , Do you know what is Wernicke encephalopathy,

Wernicke encephalopathy

Wernicke encephalopathy (WE), also Wernickes encephalopathy, or wet brain is the presence of neurological symptoms caused by biochemical lesions of the central nervous system after exhaustion of B-vitamin reserves, in particular thiamine (vitamin B1). The condition is part of a larger group of thiamine deficiency disorders that includes beriberi, in all its forms, and alcoholic Korsakoff syndrome. When it occurs simultaneously with alcoholic Korsakoff syndrome it is known as Wernicke–Korsakoff syndrome.Classically, Wernicke encephalopathy is characterised by a triad of symptoms: ophthalmoplegia, ataxia, and confusion. Around 10% of patients exhibit all three features, and other symptoms may also be present. While it is commonly regarded as a condition peculiar to malnourished people with alcohol misuse, it can be caused by a variety of diseases. It is treated with thiamine supplementation, which can lead to improvement of the symptoms and often complete resolution, particularly in those where alcohol misuse is not the underlying cause. Often other nutrients also need to be replaced, depending on the cause. Wernicke encephalopathy may be present in the general population with a prevalence of around 2%, and is considered underdiagnosed; probably, many cases are in patients who do not have commonly-associated symptoms. Signs and symptoms The classic triad of symptoms found in Wernicke encephalopathy is: ophthalmoplegia (later expanded to other eye movement disorders, most commonly affecting the lateral rectus muscle. Lateral nystagmus is most commonly seen although lateral rectus palsy, usually bilateral, may be seen). ataxia (later expanded to imbalance or any cerebellar signs) confusion (later expanded to other mental changes. Has 82% incidence in diagnosis cases)However, in actuality, only a small percentage of patients experience all three symptoms, and the full triad occurs more frequently among those who have overused alcohol. Also a much more diverse range of symptoms has been found in patients with this condition, including: pupillary changes, retinal hemorrhage, papilledema, impaired vision and hearing, vision loss hearing loss, fatigability, apathy, irritability, drowsiness, psycho and/or motor slowing dysphagia, blush, sleep apnea, epilepsy and stupor lactic acidosis memory impairment, amnesia, depression, psychosis hypothermia, polyneuropathy, hyperhidrosis.Although hypothermia is usually diagnosed with a body temperature of 35 °C / 95° Fahrenheit, or less, incipient cooling caused by deregulation in the central nervous system (CNS) needs to be monitored because it can promote the development of an infection. The patient may report feeling cold, followed by mild chills, cold skin, moderate pallor, tachycardia, hypertension, tremor or piloerection. External warming techniques are advised to prevent hypothermia.Among the frequently altered functions are the cardio circulatory. There may be tachycardia, dyspnea, chest pain, orthostatic hypotension, changes in heart rate and blood pressure. The lack of thiamine sometimes affects other major energy consumers, the myocardium, and also patients may have developed cardiomegaly. Heart failure with lactic acidosis syndrome has been observed. Cardiac abnormalities are an aspect of the WE, which was not included in the traditional approach, and are not classified as a separate disease. Infections have been pointed out as one of the most frequent triggers of death in WE. Furthermore, infections are usually present in pediatric cases.In the last stage other symptoms may occur: hyperthermia, increased muscle tone, spastic paralysis, choreic dyskinesias and coma.Because of the frequent involvement of heart, eyes and peripheral nervous system, several authors prefer to call it Wernicke disease rather than simply encephalopathy.Early symptoms are nonspecific, and it has been stated that WE may present nonspecific findings. In Wernicke Korsakoffs syndrome some single symptoms are present in about one-third. Location of the lesion Depending on the location of the brain lesion different symptoms are more frequent: Brainstem tegmentum. - Ocular: pupillary changes. Extraocular muscle palsy; gaze palsy: nystagmus. Hypothalamus. Medulla: dorsal nuc. of vagus. - Autonomic dysfunction: temperature; cardiocirculatory; respiratory. Medulla: vestibular region. Cerebellum. - Ataxia. Dorsomedial nuc. of thalamus. Mammillary bodies. - Amnestic syndrome for recent memory.Mamillary lesion are characteristic-small petechial hemorrhages are found. Diffuse cerebral dysfunction.- Altered cognition: global confusional state. Brainstem: periaqueductal gray.- Reduction of consciousness Hypothalamic lesions may also affect the immune system, which is known in people who consume excessive amounts of alcohol, causing dysplasias and infections. Korsakoff syndrome Korsakoff syndrome, characterised by memory impairment, confabulation, confusion and personality changes, has a strong and recognised link with WE. A very high percentage of patients with Wernicke–Korsakoff syndrome also have peripheral neuropathy, and many people who consume excess alcohol have this neuropathy without other neurologic signs or symptoms. Korsakoffs occurs much more frequently in WE due to chronic alcoholism. It is uncommon among those who do not consume excessive amounts of alcohol. Up to 80% of WE patients who misuse alcohol develop Korsakoffs syndrome. In Korsakoffs, is usually observed atrophy of the thalamus and the mammillary bodies, and frontal lobe involvement. In a study, half of Wernicke-Korsakoff cases had good recovery from the amnesic state, which may take from 2 months to 10 years. Risk factors Wernicke encephalopathy has classically been thought of as a disease solely of people who drink excessive amounts of alcohol, but it is also found in the chronically undernourished, and in recent years had been discovered post bariatric surgery. Without being exhaustive, the documented causes of Wernicke encephalopathy have included: pancreatitis, liver dysfunction, chronic diarrhea, celiac disease, Crohns disease, uremia, thyrotoxicosis vomiting, hyperemesis gravidarum, malabsorption, gastrointestinal surgery or diseases incomplete parenteral nutrition, starvation/fasting chemotherapy, renal dialysis, diuretic therapy, stem cell/marrow transplantation cancer, AIDS, Creutzfeldt–Jakob disease, febrile infections this disease may even occur in some people with normal, or even high blood thiamine levels, are people with deficiencies in intracellular transport of this vitamin. Selected genetic mutations, including presence of the X-linked transketolase-like 1 gene, SLC19A2 thiamine transporter protein mutations, and the aldehyde dehydrogenase-2 gene, which may predispose to alcohol use disorder. The APOE epsilon-4 allele, involved in Alzheimers disease, may increase the chance of developing neurological symptoms. Pathophysiology Thiamine deficiency and errors of thiamine metabolism are believed to be the primary cause of Wernicke encephalopathy. Thiamine, also called B1, helps to break down glucose. Specifically, it acts as an essential coenzyme to the TCA cycle and the pentose phosphate shunt. Thiamine is first metabolised to its more active form, thiamine diphosphate (TDP), before it is used. The body only has 2–3 weeks of thiamine reserves, which are readily exhausted without intake, or if depletion occurs rapidly, such as in chronic inflammatory states or in diabetes. Thiamine is involved in: Metabolism of carbohydrates, releasing energy. Production of neurotransmitters including glutamic acid and GABA. Lipid metabolism, necessary for myelin production. Amino acid modification. Probably linked to the production of taurine, of great cardiac importance. Neuropathology The primary neurological-related injury caused by thiamine deficiency in WE is three-fold: oxidative damage, mitochondrial injury leading to apoptosis, and directly stimulating a pro-apoptotic pathway. Thiamine deficiency affects both neurons and astrocytes, glial cells of the brain. Thiamine deficiency alters the glutamate uptake of astrocytes, through changes in the expression of astrocytic glutamate transporters EAAT1 and EAAT2, leading to excitotoxicity. Other changes include those to the GABA transporter subtype GAT-3, GFAP, glutamine synthetase, and the Aquaporin 4 channel. Focal lactic acidosis also causes secondary oedema, oxidative stress, inflammation and white matter damage. Pathological anatomy Despite its name, WE is not related to Wernickes area, a region of the brain associated with speech and language interpretation.In most, early lesions completely reversed with immediate and adequate supplementation.Lesions are usually symmetrical in the periventricular region, diencephalon, the midbrain, hypothalamus, and cerebellar vermis. Brainstem lesions may include cranial nerve III, IV, VI and VIII nuclei, the medial thalamic nuclei, and the dorsal nucleus of the vagus nerve. Oedema may be found in the regions surrounding the third ventricle, and fourth ventricle, also appearing petechiae and small hemorrhages. Chronic cases can present the atrophy of the mammillary bodies.Endothelial proliferation, hyperplasia of capillaries, demyelination and neuronal loss can also occur.An altered blood–brain barrier may cause a perturbed response to certain drugs and foods. Diagnosis Diagnosis of Wernicke encephalopathy or disease is made clinically. Caine et al. in 1997 established criteria that Wernicke encephalopathy can be diagnosed in any patient with just two or more of the main symptoms noted above. The sensitivity of the diagnosis by the classic triad was 23% but increased to 85% taking two or more of the four classic features. These criteria are challenged because all the cases he studied were people who drank excessive amounts of alcohol. Some consider it sufficient to suspect the presence of the disease with only one of the principal symptoms. Some British hospital protocols suspect WE with any one of these symptoms: confusion, decreased consciousness level (or unconsciousness, stupor or coma), memory loss, ataxia or unsteadiness, ophthalmoplegia or nystagmus, and unexplained hypotension with hypothermia. The presence of only one sign should be sufficient for treatment.As a much more diverse range of symptoms has been found frequently in patients it is necessary to search for new diagnostic criteria, however Wernicke encephalopathy remains a clinically-diagnosed condition. Neither the MR, nor serum measurements related to thiamine are sufficient diagnostic markers in all cases. However, as described by Zuccoli et al. in several papers the involvement of the cranial nerve nuclei and central gray matter on MRI, is very specific to WE in the appropriate clinical setting. Non-recovery upon supplementation with thiamine is inconclusive.The sensitivity of MR was 53% and the specificity was 93%. The reversible cytotoxic edema was considered the most characteristic lesion of WE. The location of the lesions were more frequently atypical among people who drank appropriate amounts of alcohol, while typical contrast enhancement in the thalamus and the mammillary bodies was observed frequently associated with alcohol misuse. These abnormalities may include: Dorsomedial thalami, periaqueductal gray matter, mamillary bodies, tectal plate and brainstem nuclei are commonly affected. Involvement is always bilateral and symmetric. Value of DWI in the diagnosis of WE is minimal. Axial FLAIR MRI images represent the best diagnostic MRI sequence. Contrast material may highlight involvement of the mamillary bodies.There appears to be very little value for CT scans.Thiamine can be measured using an erythrocyte transketolase activity assay, or by activation by measurement of in vitro thiamine diphosphate levels. Normal thiamine levels do not necessarily rule out the presence of WE, as this may be a patient with difficulties in intracellular transport. Prevention There are hospital protocols for prevention, supplementing with thiamine in the presence of: history of alcohol misuse or related seizures, requirement for IV glucose, signs of malnutrition, poor diet, recent diarrhea or vomiting, peripheral neuropathy, intercurrent illness, delirium tremens or treatment for DTs, and others. Some experts advise parenteral thiamine should be given to all at-risk patients in the emergency department.In the clinical diagnosis should be remembered that early symptoms are nonspecific, and it has been stated that WE may present nonspecific findings. There is consensus to provide water-soluble vitamins and minerals after gastric operations.In some countries certain foods have been supplemented with thiamine, and have reduced WE cases. Improvement is difficult to quantify because they applied several different actions. Avoiding or moderating alcohol consumption and having adequate nutrition reduces one of the main risk factors in developing Wernicke-Korsakoff syndrome.. Treatment Most symptoms will improve quickly if deficiencies are treated early. Memory disorder may be permanent.In patients suspected of WE, thiamine treatment should be started immediately. Blood should be immediately taken to test for thiamine, other vitamins and minerals levels. Following this an immediate intravenous or intramuscular dose of thiamine should be administered two or three times daily. Thiamine administration is usually continued until clinical improvement ceases.Considering the diversity of possible causes and several surprising symptomatologic presentations, and because there is low assumed risk of toxicity of thiamine, because the therapeutic response is often dramatic from the first day, some qualified authors indicate parenteral thiamine if WE is suspected, both as a resource for diagnosis and treatment. The diagnosis is highly supported by the response to parenteral thiamine, but is not sufficient to be excluded by the lack of it. Parenteral thiamine administration is associated with a very small risk of anaphylaxis.People who consume excessive amounts of alcohol may have poor dietary intakes of several vitamins, and impaired thiamine absorption, metabolism, and storage; they may thus require higher doses.If glucose is given, such as in people with an alcohol use disorder who are also hypoglycaemic, thiamine must be given concurrently. If this is not done, the glucose will rapidly consume the remaining thiamine reserves, exacerbating this condition.The observation of edema in MR, and also the finding of inflation and macrophages in necropsied tissues, has led to successful administration of antiinflammatories.Other nutritional abnormalities should also be looked for, as they may be exacerbating the disease. In particular, magnesium, a cofactor of transketolase which may induce or aggravate the disease.Other supplements may also be needed, including: cobalamin, ascorbic acid, folic acid, nicotinamide, zinc, phosphorus (dicalcium phosphate) and in some cases taurine, especially suitable when there cardiocirculatory impairment. Patient-guided nutrition is suggested. In patients with Wernicke-Korsakoff syndrome, even higher doses of parenteral thiamine are recommended. Concurrent toxic effects of alcohol should also be considered. Epidemiology There are no conclusive statistical studies, all figures are based on partial studies. Wernickes lesions were observed in 0.8 to 2.8% of the general population autopsies, and 12.5% of people with an alcohol use disorder. This figure increases to 35% of such individuals if including cerebellar damage due to lack of thiamine.Most autopsy cases were from people with an alcohol use disorder. Autopsy series were performed in hospitals on the material available which is unlikely to be representative of the entire population. Considering the slight affectations, previous to the generation of observable lesions at necropsy, the percentage should be higher. There is evidence to indicate that Wernicke encephalopathy is underdiagnosed. For example, in one 1986 study, 80% of cases were diagnosed postmortem. Is estimated that only 5–14% of patients with WE are diagnosed in life.In a series of autopsy studies held in Recife, Brazil, it was found that only 7 out of 36 had consumed excessive amounts of alcohol, and only a small minority had malnutrition. In a reviewed of 53 published case reports from 2001 to 2011, the relationship with alcohol was also about 20% (10 out of 53 cases).WE is more likely to occur in males than females. Among the minority who are diagnosed, mortality can reach 17%. The main factors triggering death are thought to be infections and liver dysfunctions. History WE was first identified in 1881 by the German neurologist Carl Wernicke, although the link with thiamine was not identified until the 1930s. A similar presentation of this disease was described by the Russian psychiatrist Sergei Korsakoff in a series of articles published 1887–1891. References == External links ==

Hey Aarogya!, what is Wilms tumor

Wilms tumor

Wilms tumor or Wilms tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children, rarely in adults.; and occurs most commonly as a renal tumor in child patients. It is named after Max Wilms, the German surgeon (1867–1918) who first described it.Approximately 650 cases are diagnosed in the U.S. annually. The majority of cases occur in children with no associated genetic syndromes; however, a minority of children with Wilms tumor have a congenital abnormality. It is highly responsive to treatment, with about 90 percent of children being cured. Signs and symptoms Typical signs and symptoms of Wilms tumor include the following: a painless, palpable abdominal mass loss of appetite abdominal pain fever nausea and vomiting blood in the urine (in about 20% of cases) high blood pressure in some cases (especially if synchronous or metachronous bilateral kidney involvement) Rarely as varicocele Pathogenesis Wilms tumor has many causes, which can broadly be categorized as syndromic and non-syndromic. Syndromic causes of Wilms tumor occur as a result of alterations to genes such as the Wilms Tumor 1 (WT1) or Wilms Tumor 2 (WT2) genes, and the tumor presents with a group of other signs and symptoms. Non-syndromic Wilms tumor is not associated with other symptoms or pathologies. Many, but not all, cases of Wilms tumor develop from nephrogenic rests, which are fragments of tissue in or around the kidney that develop before birth and become cancerous after birth. In particular, cases of bilateral Wilms tumor, as well as cases of Wilms tumor derived from certain genetic syndromes such as Denys-Drash syndrome, are strongly associated with nephrogenic rests. Most nephroblastomas are on one side of the body only and are found on both sides in less than 5% of cases, although people with Denys-Drash syndrome mostly have bilateral or multiple tumors. They tend to be encapsulated and vascularized tumors that do not cross the midline of the abdomen. In cases of metastasis it is usually to the lung. A rupture of Wilms tumor puts the patient at risk of bleeding and peritoneal dissemination of the tumor. In such cases, surgical intervention by a surgeon who is experienced in the removal of such a fragile tumor is imperative.Pathologically, a triphasic nephroblastoma comprises three elements: blastema mesenchyme (stroma) epitheliumWilms tumor is a malignant tumor containing metanephric blastema, stromal and epithelial derivatives. Characteristic is the presence of abortive tubules and glomeruli surrounded by a spindled cell stroma. The stroma may include striated muscle, cartilage, bone, fat tissue, and fibrous tissue. Dysfunction is caused when the tumor compresses the normal kidney parenchyma.The mesenchymal component may include cells showing rhabdomyoid differentiation or malignancy (rhabdomyosarcomatous Wilms).Wilms tumors may be separated into two prognostic groups based on pathologic characteristics: Favorable – Contains well developed components mentioned above Anaplastic – Contains diffuse anaplasia (poorly developed cells) Molecular biology and related conditions Mutations of the WT1 gene which is located on the short arm of chromosome 11 (11p13) are observed in approximately 20% of Wilms tumors, the majority of them being inherited from the germline, while a minority are acquired somatic mutations. In addition at least half of the Wilms tumors with mutations in WT1 also carry acquired somatic mutations in CTNNB1, the gene encoding the proto-oncogene beta-catenin. This latter gene is found on short arm of chromosome 3 (3p22.1). Most cases do not have mutations in any of these genes. An association with H19 has been reported. H19 is a long noncoding RNA located on the short arm of chromosome 11 (11p15.5). Diagnosis The majority of people with Wilms tumor present with an asymptomatic abdominal mass which is noticed by a family member or healthcare professional. Renal tumors can also be found during routine screening in children who have known predisposing clinical syndromes. The diagnostic process includes taking a medical history, a physical exam, and a series of tests including blood, urine, and imaging tests.Once Wilms tumor is suspected, an ultrasound scan is usually done first to confirm the presence of an intrarenal mass. A computed tomography scan or MRI scan can also be used for more detailed imaging. Finally, the diagnosis of Wilms tumor is confirmed by a tissue sample. In most cases, a biopsy is not done first because there is a risk of cancer cells spreading during the procedure. Treatment in North America is nephrectomy or in Europe chemotherapy followed by nephrectomy. A definitive diagnosis is obtained by pathological examination of the nephrectomy specimen. Staging Staging is a standard way to describe the extent of spread of Wilms tumors and to determine prognosis and treatments. Staging is based on anatomical findings and tumor cells pathology. According to the extent of tumor tissue at the time of initial diagnosis, five stages are considered.In Stage I Wilms tumor (43% of cases), all of the following criteria must be met: Tumor is limited to the kidney and is completely excised. The surface of the renal capsule is intact. The tumor is not ruptured or biopsied (open or needle) prior to removal. No involvement of extrarenal or renal sinus lymph-vascular spaces No residual tumor apparent beyond the margins of excision. Metastasis of tumor to lymph nodes not identified.In Stage II (23% of cases), 1 or more of the following criteria must be met: Tumor extends beyond the kidney but is completely excised. No residual tumor apparent at or beyond the margins of excision. Any of the following conditions may also exist: Tumor involvement of the blood vessels of the renal sinus and/or outside the renal parenchyma. Extensive tumor involvement of renal sinus soft tissue.In Stage III (20% of cases), 1 or more of the following criteria must be met: Inoperable primary tumor. Lymph node metastasis. Tumor is present at surgical margins. Tumor spillage involving peritoneal surfaces either before or during surgery, or transected tumor thrombus. The tumor has been biopsied prior to removal or there is local spillage of tumor during surgery, confined to the flank.Stage IV (10% of cases) Wilms tumor is defined by the presence of hematogenous metastases (lung, liver, bone, or brain), or lymph node metastases outside the abdominopelvic region.Stage V (5% of cases) Wilms tumor is defined by bilateral renal involvement at the time of initial diagnosis. For patients with bilateral involvement, an attempt should be made to stage each side according to the above criteria (stage I to III) on the basis of extent of disease prior to biopsy. Treatment and prognosis The overall 5-year survival is estimated to be approximately 90%, but for individuals the prognosis is highly dependent on individual staging and treatment. Early removal tends to promote positive outcomes. Tumor-specific loss-of-heterozygosity (LOH) for chromosomes 1p and 16q identifies a subset of Wilms tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure. Genome-wide copy number and LOH status can be assessed with virtual karyotyping of tumor cells (fresh or paraffin-embedded).Statistics may sometimes show more favorable outcomes for more aggressive stages than for less aggressive stages, which may be caused by more aggressive treatment and/or random variability in the study groups. Also, a stage V tumor is not necessarily worse than a stage IV tumor. In case of relapse of Wilms tumor, the 4-year survival rate for children with a standard-risk has been estimated to be 80%. Epidemiology Wilms tumor is the most common malignant renal tumor in children. There are a number of rare genetic syndromes that have been linked to an increased risk of developing Wilms Tumor. Screening guidelines vary between countries; however health care professionals are recommending regular ultrasound screening for people with associated genetic syndromes.Wilms tumor affects approximately one person per 10,000 worldwide before the age of 15 years. People of African descent may have slightly higher rates of Wilms tumor. The peak age of Wilms tumor is 3 to 4 years and most cases occur before the age of 10 years. A genetic predisposition to Wilms tumor in individuals with aniridia has been established, due to deletions in the p13 band on chromosome 11. History Dr. Sidney Farber, founder of Dana–Farber Cancer Institute, and his colleagues achieved the first remissions in Wilms tumor in the 1950s. By employing the antibiotic actinomycin D in addition to surgery and radiation therapy, they boosted cure rates from 40 to 89 percent.The use of computed tomography scan for the diagnosis of Wilms tumor began in the early 1970s, thanks to the intuition of Dr. Mario Costici, an Italian physician. He discovered that in the direct radiograms and in the urographic images, you can identify determining elements for a differential diagnosis with the Wilms tumor. This possibility was a premise for starting a treatment. See also Hemihypertrophy National Wilms Tumor Study Group (NWTS) Perlman syndrome Virtual Karyotype for 1p and 16q LOH References External links Wilms tumor at Curlie GeneReviews/NCBI/NIH/UW entry on Wilms Tumor Overview Information from National Cancer Institute Cancer.Net Wilms Tumor – Childhood

Hello Aarogya, could you help me understand about Wrinkle

Wrinkle

A wrinkle, also known as a rhytid, is a fold, ridge or crease in an otherwise smooth surface, such as on skin or fabric. Skin wrinkles typically appear as a result of ageing processes such as glycation, habitual sleeping positions, loss of body mass, sun damage, or temporarily, as the result of prolonged immersion in water. Age wrinkling in the skin is promoted by habitual facial expressions, aging, sun damage, smoking, poor hydration, and various other factors. In humans, it can also be prevented to some degree by avoiding excessive solar exposure and through diet (in particular through consumption of carotenoids, tocopherols and flavonoids, vitamins (A, C, D and E), essential omega-3-fatty acids, certain proteins and lactobacilli). Skin Causes for aging wrinkles Development of facial wrinkles is a kind of fibrosis of the skin. Misrepair-accumulation aging theory suggests that wrinkles develop from incorrect repairs of injured elastic fibers and collagen fibers. Repeated extensions and compressions of the skin cause repeated injuries of extracellular fibers in derma. During the repairing process, some of the broken elastic fibers and collagen fibers are not regenerated and restored but replaced by altered fibers. When an elastic fiber is broken in an extended state, it may be replaced by a "long" collagen fiber. Accumulation of "long" collagen fibers makes part of the skin looser and stiffer, and as a consequence, a big fold of skin appears. When a "long" collagen is broken in a compressed state, it may be replaced by a "short" collagen fiber. The "shorter" collagen fibers will restrict the extension of "longer" fibers, and make the “long" fibers in a folding state permanently. A small fold, namely a permanent wrinkle, then appears. Sleep wrinkles Sleep wrinkles are created and reinforced when the face is compressed against a pillow or bed surface in side or stomach sleeping positions during sleep. They appear in predictable locations due to the underlying superficial musculoaponeurotic system (SMAS), and are usually distinct from wrinkles of facial expression. As with wrinkles of facial expression, sleep wrinkles can deepen and become permanent over time, unless the habitual sleeping positions which cause the wrinkles are altered. Water-immersion wrinkling The wrinkles that occur in skin over prolonged exposure to water are sometimes referred to as pruney fingers or water aging. This is a temporary skin condition where the skin on the palms of the hand or feet becomes wrinkly. This wrinkling response may have imparted an evolutionary benefit by providing improved traction in wet conditions, and a better grasp of wet objects. These results were called into question by a 2014 study that failed to reproduce any improvement of handling wet objects with wrinkled fingertips. However, a 2020 study of gripping efficiency found that wrinkles decreased the force required to grip wet objects by 20%, supporting the traction hypothesis.Prior to a 1935 study, the common explanation was based on water absorption in the keratin-laden epithelial skin when immersed in water, causing the skin to expand and resulting in a larger surface area, forcing it to wrinkle. Usually the tips of the fingers and toes are the first to wrinkle because of a thicker layer of keratin and an absence of hairs which secrete the protective oil called sebum. In the 1935 study, however, Lewis and Pickering were studying patients with palsy of the median nerve when they discovered that skin wrinkling did not occur in the areas of the patients skin normally innervated by the damaged nerve. This suggested that the nervous system plays an essential role in wrinkling, so the phenomenon could not be entirely explained simply by water absorption. Recent research shows that wrinkling is related to vasoconstriction. Water probably initiates the wrinkling process by altering the balance of electrolytes in the skin as it diffuses into the hands and soles via their many sweat ducts. This could alter the stability of the membranes of the many neurons that synapse on the many blood vessels underneath skin, causing them to fire more rapidly. Increased neuronal firing causes blood vessels to constrict, decreasing the amount of fluid underneath the skin. This decrease in fluid would cause a decrease in tension, causing the skin to become wrinkly.This insight resulted in bedside tests for nerve damage and vasoconstriction. Wrinkling is often scored with immersion of the hands for 30 minutes in water or EMLA cream with measurements steps of 5 minutes, and counting the number of visible wrinkles in time. Not all healthy persons have finger wrinkling after immersion, so it would be safe to say that sympathetic function is preserved if finger wrinkling after immersion in water is observed, but if the fingers emerge smooth it cannot be assumed that there is a lesion to the autonomic supply or to the peripheral nerves of the hand. Animals with wrinkles Examples of wrinkles can be found in various animal species that grow loose, excess skin, particularly when they are young. Several breeds of dog, such as the Pug and the Shar Pei, have been bred to exaggerate this trait. In dogs bred for fighting, this is the result of selection for loose skin, which confers a protective advantage. Wrinkles are also associated with neoteny, as they are a trait associated with juvenile animals. Techniques for reducing the appearance of aging wrinkles Current evidence suggests that tretinoin decreases cohesiveness of follicular epithelial cells, although the exact mode of action is unknown. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells. Tretinoin is better known by the brand name Retin-A. Topical glycosaminoglycans supplements can help to provide temporary restoration of enzyme balance to slow or prevent matrix breakdown and consequent onset of wrinkle formation. Glycosaminoglycans (GAGs) are produced by the body to maintain structural integrity in tissues and to maintain fluid balance. Hyaluronic acid is a type of GAG that promotes collagen synthesis, repair, and hydration. GAGs serve as a natural moisturizer and lubricant between epidermal cells to inhibit the production of matrix metalloproteinases (MMPs). Dermal fillers are injectable products frequently used to correct wrinkles, and other depressions in the skin. They are often a kind of soft tissue designed to enable injection into the skin for purposes of improving the appearance. The most common products are based on hyaluronic acid and calcium hydroxylapatite. Botulinum toxin is a neurotoxin protein produced by the bacterium Clostridium botulinum. Botox is a specific form of botulinum toxin manufactured by Allergan for both therapeutic and cosmetic use. Besides its cosmetic application, Botox is used in the treatment of other conditions including migraine headache and cervical dystonia (spasmodic torticollis) (a neuromuscular disorder involving the head and neck).Dysport, manufactured by Ipsen, received FDA approval and is now used to treat cervical dystonia as well as glabellar lines in adults. In 2010, another form of botulinum toxin, one free of complexing proteins, became available to Americans. Xeomin received FDA approval for medical indications in 2010 and cosmetic indications in 2011. Botulinum toxin treats wrinkles by immobilizing the muscles which cause wrinkles. It is not appropriate for the treatment of all wrinkles; it is indicated for the treatment of glabellar lines (between the eyebrows) in adults. Any other usage is not approved by the FDA and is considered off-label use. Laser resurfacing is FDA-cleared skin resurfacing procedure in which lasers are used to improve the condition of the skin. Two types of lasers are used to reduce the appearance of fine lines and wrinkles on the face; laser ablation, which removes thin layers of skin, and nonablative lasers that stimulate collagen production. Nonablative lasers are less effective than ablative ones but they are less invasive and recovery time is short. After the procedure people experience temporary redness, itching and swelling. See also Botulinum toxin Injectable filler References External links Skin Ageing at Medline

Aarogya, could you share information about a health condition involving X-linked hypophosphatemia

X-linked hypophosphatemia

X-linked hypophosphatemia (XLH) is an X-linked dominant form of rickets (or osteomalacia) that differs from most cases of dietary deficiency rickets in that vitamin D supplementation does not cure it. It can cause bone deformity including short stature and genu varum (bow-leggedness). It is associated with a mutation in the PHEX gene sequence (Xp.22) and subsequent inactivity of the PHEX protein. PHEX mutations lead to an elevated circulating (systemic) level of the hormone FGF23 which results in renal phosphate wasting, and locally in the extracellular matrix of bones and teeth an elevated level of the mineralization/calcification-inhibiting protein osteopontin. An inactivating mutation in the PHEX gene results in an increase in systemic circulating FGF23, and a decrease in the enzymatic activity of the PHEX enzyme which normally removes (degrades) mineralization-inhibiting osteopontin protein; in XLH, the decreased PHEX enzyme activity leads to an accumulation of inhibitory osteopontin locally in bones and teeth to block mineralization which, along with renal phosphate wasting, both cause osteomalacia and odontomalacia. For both XLH and hypophosphatasia, inhibitor-enzyme pair relationships function to regulate mineralization in the extracellular matrix through a double-negative (inhibiting the inhibitors) activation effect in a manner described as the Stenciling Principle. Both these underlying mechanisms (renal phosphate wasting systemically, and mineralization inhibitor accumulation locally) contribute to the pathophysiology of XLH that leads to soft bones and teeth (hypomineralization, osteomalacia/odontomalacia). The prevalence of the disease is 1 in 20,000.X-linked hypophosphatemia may be lumped in with autosomal dominant hypophosphatemic rickets under general terms such as hypophosphatemic rickets. Hypophosphatemic rickets are associated with at least nine other genetic mutations. Clinical management of hypophosphatemic rickets may differ depending on the specific mutations associated with an individual case, but treatments are aimed at raising phosphate levels to promote normal bone formation. Symptoms and signs The most common symptoms of XLH affect the bones and teeth, causing pain, abnormalities, and osteoarthritis. Symptoms and signs can vary between children and adults and can include: Children Adults Osteomalacia Dental abscesses Limited range of movement (enthesopathy) Short stature Fatigue Fractures / pseudofracture Bone pain Craniostenosis Osteoarthritis Spinal stenosis Hearing loss Depression Genetics XLH is associated with a mutation in the PHEX gene sequence, located on the human X chromosome at location Xp22.2-p22.1. The PHEX protein regulates another protein called fibroblast growth factor 23 (produced from the FGF23 gene). Fibroblast growth factor 23 normally inhibits the kidneys ability to reabsorb phosphate into the bloodstream. Gene mutations in PHEX prevent it from correctly regulating fibroblast growth factor 23. The resulting overactivity of FGF-23 reduces vitamin D 1α-hydroxylation and phosphate reabsorption by the kidneys, leading to hypophosphatemia and the related features of hereditary hypophosphatemic rickets. Also in XLH, where PHEX enzymatic activity is absent or reduced, osteopontin—a mineralization-inhibiting secreted substrate protein found in the extracellular matrix of bone—accumulates in bone (and teeth) to contribute to the osteomalacia (and odontomalacia) as shown in the mouse homolog (Hyp) of XLH and in XLH patients. Biochemically in blood, XLH is recognized by hypophosphatemia and an inappropriately low level of calcitriol (1,25-(OH)2 vitamin D3). Patients often have bowed legs or knock knees in which they usually cannot touch both knees and ankles together at the same time.The disorder is inherited in an X-linked dominant manner. This means the defective gene responsible for the disorder (PHEX) is located on the X chromosome, and only one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who has the disorder. Males are normally hemizygous for the X chromosome, having only one copy. As a result, X-linked dominant disorders usually show higher expressivity in males than females.As the X chromosome is one of the sex chromosomes (the other being the Y chromosome), X-linked inheritance is determined by the sex of the parent carrying a specific gene and can often seem complex. This is because, typically, females have two copies of the X-chromosome and males have only one copy. The difference between dominant and recessive inheritance patterns also plays a role in determining the chances of a child inheriting an X-linked disorder from their parentage. Diagnosis Begin clinical laboratory evaluation of rickets with assessment of serum calcium, phosphate, and alkaline phosphatase levels. In hypophosphatemic rickets, calcium levels may be within or slightly below the reference range; alkaline phosphatase levels will be significantly above the reference range.Carefully evaluate serum phosphate levels in the first year of life, because the concentration reference range for infants (5.0–7.5 mg/dL) is high compared with that for adults (2.7–4.5 mg/dL).Serum parathyroid hormone levels are within the reference range or slightly elevated, while calcitriol levels are low or within the lower reference range. Most importantly, urinary loss of phosphate is above the reference range.The renal tubular reabsorption of phosphate (TRP) in X-linked hypophosphatemia is 60%; normal TRP exceeds 90% at the same reduced plasma phosphate concentration. The TRP is calculated with the following formula:1 - [Phosphate Clearance (CPi) / Creatinine Clearance (Ccr)] X 100 Treatment Oral phosphate, calcitriol; in the event of severe bowing, an osteotomy may be performed to correct the leg shape. The monoclonal antibody burosumab was first licensed in February 2018 by the European Medicines Agency, then licensed by the Food and Drug Administration in the United States of America in June 2018 as the first drug targeting the underlying cause for this condition.The leg deformity can be treated with Ilizarov frames and CAOS. It is also treated with medications including human growth hormone, calcitriol, and phosphate. Society and culture International XLH Alliance – an alliance of international patient groups for individuals affected by XLH and related disorders. Jennyfer Marques Parinos is a Paralympic bronze medalist from Brazil who has XLH. She competes under a class 9 disability. See also Autosomal dominant hypophosphatemic rickets Hypophosphatemia Tumor-induced osteomalacia References External links 00754 at CHORUSHypophosphatemic rickets; XLH; Hypophosphatemia, vitamin D-resistant rickets at NIHs Office of Rare Diseases

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

Xerophthalmia

Xerophthalmia (from Ancient Greek "xērós" (ξηρός) meaning "dry" and "ophthalmos" (οφθαλμός) meaning "eye") is a medical condition in which the eye fails to produce tears. It may be caused by vitamin A deficiency, which is sometimes used to describe that condition, although there may be other causes. Xerophthalmia caused by a severe vitamin A deficiency is described by pathologic dryness of the conjunctiva and cornea. The conjunctiva becomes dry, thick and wrinkled. The first symptom is poor vision at night. If untreated, xerophthalmia can lead to dry eye syndrome, corneal ulceration, and ultimately to blindness as a result of corneal and retinal damage. Xerophthalmia usually implies a destructive dryness of the conjunctival epithelium due to dietary vitamin A deficiency—a rare condition in developed countries, but still causing much damage in developing countries. Other forms of dry eye are associated with aging, poor lid closure, scarring from a previous injury, or autoimmune diseases such as rheumatoid arthritis and Sjögrens syndrome, and these can all cause chronic conjunctivitis. Radioiodine therapy can also induce xerophthalmia, often transiently, although in some patients late onset or persistent xerophthalmia has been observed.The damage to the cornea in vitamin A associated xerophthalmia is quite different from damage to the retina at the back of the globe, a type of damage which can also be due to lack of vitamin A, but which is caused by lack of other forms of vitamin A which work in the visual system. Xerophthalmia from hypovitaminosis A is specifically due to lack of the hormone-like vitamin A metabolite retinoic acid, since (along with certain growth-stunting effects) the condition can be reversed in vitamin A deficient rats by retinoic acid supplementation (however the retinal damage continues). Since retinoic acid cannot be reduced to retinal or retinol, these effects on the cornea must be specific to retinoic acid. This is in keeping with retinoic acids known requirement for good health in epithelial cells, such as those in the cornea. Cause The condition is not congenital and develops over the course of a few months as the lacrimal glands fail to produce tears. Other conditions involved in the progression already stated include the appearance of Bitots spots, which are clumps of keratin debris that build up inside the conjunctiva and night blindness, which precedes corneal ulceration and total blindness. Classification World Health Organization classified xerophthalmia into following stages: XN-Night blindness X1A-Conjunctival xerosis X1B-Bitot spots X2-Corneal xerosis X3A-Corneal ulceration/keratomalacia, involving less than one-third of the cornea X3B-Corneal ulceration/keratomalacia, involving more than one-third of the cornea XS-Corneal scar due to xerophthalmia XF-Xerophthalmic fundus Prevention Prophylaxis consists of periodic administration of Vitamin A supplements. WHO recommended schedule, which is universally recommended is as follows: Infants 6–12 months old and any older children weighing less than 8 kg – 100,000 IU orally every 3–6 months Children over 1 year and under 6 years of age – 200,000 IU orally every 6 months Infants less than 6 months old, who are not being breastfed – 50,000 IU orally should be given before they attain the age of 6 months Treatment Treatment can occur in two ways: treating symptoms and treating the deficiency. Treatment of symptoms usually includes the use of artificial tears in the form of eye drops, increasing the humidity of the environment with humidifiers, and wearing wraparound glasses when outdoors. Treatment of the deficiency can be accomplished with a Vitamin A or multivitamin supplement or by eating foods rich in Vitamin A. Treatment with supplements and/or diet can be successful until the disease progresses as far as corneal ulceration, at which point only an extreme surgery can offer a chance of returning sight. Epidemiology Throughout southeast Asia, estimates are that more than half of children under the age of six years have subclinical vitamin A deficiency and night blindness, with progression to xerophthalmia being the leading cause of preventable childhood blindness. Estimates are that each year there are 350,000 cases of childhood blindness due to vitamin A deficiency. The causes are vitamin A deficiency during pregnancy, followed by low transfer of vitamin A during lactation and infant/child diets low in vitamin A or beta-carotene. The prevalence of pre-school age children who are blind due to vitamin A deficiency is lower than expected from incidence of new cases only because childhood vitamin A deficiency significantly increases all-cause mortality. See also Keratoconjunctivitis Keratoconjunctivitis sicca Keratomalacia, also caused by vitamin A deficiency. References Further reading Jellife DB. "Xerophthalmia: A World-wide Drive for Prevention." Journal of Tropical Pediatrics 1980; 26: ii-iii. 4 November 2009. == External links ==

Hey Aarogya, explain a scenario commonly referred as Xerostomia

Xerostomia

Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side effect of many types of medication. It is more common in older people (mostly because this group tend to take several medications) and in persons who breathe through their mouths. Dehydration, radiotherapy involving the salivary glands, chemotherapy and several diseases can cause reduced salivation (hyposalivation), or a change in saliva consistency and hence a complaint of xerostomia. Sometimes there is no identifiable cause, and there may sometimes be a psychogenic reason for the complaint. Definition Xerostomia is the subjective sensation of dry mouth, which is often (but not always) associated with hypofunction of the salivary glands. The term is derived from the Greek words ξηρός (xeros) meaning "dry" and στόμα (stoma) meaning "mouth". A drug or substance that increases the rate of salivary flow is termed a sialogogue. Hyposalivation is a clinical diagnosis that is made based on the history and examination, but reduced salivary flow rates have been given objective definitions. Salivary gland hypofunction has been defined as any objectively demonstrable reduction in whole and/or individual gland flow rates. An unstimulated whole saliva flow rate in a normal person is 0.3–0.4 ml per minute, and below 0.1 ml per minute is significantly abnormal. A stimulated saliva flow rate less than 0.5 ml per gland in 5 minutes or less than 1 ml per gland in 10 minutes is decreased. The term subjective xerostomia is sometimes used to describe the symptom in the absence of any clinical evidence of dryness. Xerostomia may also result from a change in composition of saliva (from serous to mucous). Salivary gland dysfunction is an umbrella term for the presence of xerostomia, salivary gland hyposalivation, and hypersalivation. Signs and symptoms Hyposalivation may give the following signs and symptoms: Dental caries (xerostomia related caries) – Without the buffering effects of saliva, tooth decay becomes a common feature and may progress much more aggressively than it would otherwise ("rampant caries"). It may affect tooth surfaces that are normally spared, e.g., cervical caries and root surface caries. This is often seen in patients who have had radiotherapy involving the major salivary glands, termed radiation-induced caries. Therefore, it is important that any products used in managing dry mouth symptoms are sugar-free, as the presence of sugars in the mouth support the growth of oral bacteria, resulting in acid production and development of dental caries. Acid erosion. Saliva acts as a buffer and helps to prevent demineralization of teeth. Oral candidiasis – A loss of the antimicrobial actions of saliva may also lead to opportunistic infection with Candida species. Ascending (suppurative) sialadenitis – an infection of the major salivary glands (usually the parotid gland) that may be recurrent. It is associated with hyposalivation, as bacteria are able to enter the ductal system against the diminished flow of saliva. There may be swollen salivary glands even without acute infection, possibly caused by autoimmune involvement. Dysgeusia – altered taste sensation (e.g., a metallic taste) and dysosmia, altered sense of smell. Intraoral halitosis – possibly due to increased activity of halitogenic biofilm on the posterior dorsal tongue (although dysgeusia may cause a complaint of nongenuine halitosis in the absence of hyposalivation). Burning mouth syndrome – a burning or tingling sensation in the mouth. Saliva that appears thick or ropey. Mucosa that appears dry. A lack of saliva pooling in the floor of the mouth during examination. Dysphagia – difficulty swallowing and chewing, especially when eating dry foods. Food may stick to the tissues during eating. The tongue may stick to the palate, causing a clicking noise during speech, or the lips may stick together. Gloves or a dental mirror may stick to the tissues. Fissured tongue with atrophy of the filiform papillae and a lobulated, erythematous appearance of the tongue. Saliva cannot be "milked" (expressed) from the parotid duct. Difficulty wearing dentures, e.g., when swallowing or speaking. There may be generalized mucosal soreness and ulceration of the areas covered by the denture. Mouth soreness and oral mucositis. Lipstick or food may stick to the teeth. A need to sip drinks frequently while talking or eating. Dry, sore, and cracked lips and angles of mouth. Thirst.However, sometimes the clinical findings do not correlate with the symptoms experienced. For example, a person with signs of hyposalivation may not complain of xerostomia. Conversely a person who reports experiencing xerostomia may not show signs of reduced salivary secretions (subjective xerostomia). In the latter scenario, there are often other oral symptoms suggestive of oral dysesthesia ("burning mouth syndrome"). Some symptoms outside the mouth may occur together with xerostomia. These include: Xerophthalmia (dry eyes). Inability to cry. Blurred vision. Photophobia (light intolerance). Dryness of other mucosae, e.g., nasal, laryngeal, and/or genital. Burning sensation. Itching or grittiness. Dysphonia (voice changes).There may also be other systemic signs and symptoms if there is an underlying cause such as Sjögrens syndrome, for example, joint pain due to associated rheumatoid arthritis. Cause The differential of hyposalivation significantly overlaps with that of xerostomia. A reduction in saliva production to about 50% of the normal unstimulated level will usually result in the sensation of dry mouth. Altered saliva composition may also be responsible for xerostomia. Physiologic Salivary flow rate is decreased during sleep, which may lead to a transient sensation of dry mouth upon waking. This disappears with eating or drinking or with oral hygiene. When associated with halitosis, this is sometimes termed "morning breath". Dry mouth is also a common sensation during periods of anxiety, probably owing to enhanced sympathetic drive. Dehydration is known to cause hyposalivation, the result of the body trying to conserve fluid. Physiologic age-related changes in salivary gland tissues may lead to a modest reduction in salivary output and partially explain the increased prevalence of xerostomia in older people. However, polypharmacy is thought to be the major cause in this group, with no significant decreases in salivary flow rate being likely to occur through aging alone. Drug induced Aside from physiologic causes of xerostomia, iatrogenic effects of medications are the most common cause. A medication which is known to cause xerostomia may be termed xerogenic. Over 400 medications are associated with xerostomia. Although drug induced xerostomia is commonly reversible, the conditions for which these medications are prescribed are frequently chronic. The likelihood of xerostomia increases in relation to the total number of medications taken, whether the individual medications are xerogenic or not. The sensation of dryness usually starts shortly after starting the offending medication or after increasing the dose. Anticholinergic, sympathomimetic, or diuretic drugs are usually responsible. Sjögrens syndrome Xerostomia may be caused by autoimmune conditions which damage saliva-producing cells. Sjögrens syndrome is one such disease, and it is associated with symptoms including fatigue, myalgia and arthralgia. The disease is characterised by inflammatory changes in the moisture-producing glands throughout the body, leading to reduced secretions from glands that produce saliva, tears and other secretions throughout the body. Primary Sjögrens syndrome is the combination of dry eyes and xerostomia. Secondary Sjögrens syndrome is identical to primary form but with the addition of a combination of other connective tissue disorders such as systemic lupus erythematosus or rheumatoid arthritis. Celiac disease Xerostomia may be the only symptom of celiac disease, especially in adults, who often have no obvious digestive symptoms. Radiation therapy Radiation therapy for cancers of the head and neck (including brachytherapy for thyroid cancers) where the salivary glands are close to or within the field irradiated is another major cause of xerostomia. A radiation dose of 52 Gy is sufficient to cause severe salivary dysfunction. Radiotherapy for oral cancers usually involves up to 70 Gy of radiation, often given along with chemotherapy which may also have a damaging effect on saliva production. This side effect is a result of radiation damage of the parasympathetic nerves. Formation of salivary gland ducts depends on the secretion of a neuropeptide from the parasympathetic nerves, while development of the end buds of the salivary gland depends on acetylcholine from the parasympathetic nerves. Sicca syndrome "Sicca" simply means dryness. Sicca syndrome is not a specific condition, and there are varying definitions, but the term can describe oral and eye dryness that is not caused by autoimmune diseases (e.g., Sjögren syndrome). Other causes Oral dryness may also be caused by mouth breathing, usually caused by partial obstruction of the upper respiratory tract. Examples include hemorrhage, vomiting, diarrhea, and fever.Alcohol may be involved in the cause of salivary gland disease, liver disease, or dehydration.Smoking is another possible cause. Other recreational drugs such as methamphetamine, cannabis, hallucinogens, or heroin, may be implicated. Hormonal disorders, such as poorly controlled diabetes, chronic graft versus host disease or low fluid intake in people undergoing hemodialysis for renal impairment may also result in xerostomia, due to dehydration.Nerve damage can be a cause of oral dryness. An injury to the face or surgery can cause nerve damage to your head and neck area which can effect the nerves that are associated with the salivary flow.Xerostomia may be a consequence of infection with hepatitis C virus (HCV) and a rare cause of salivary gland dysfunction may be sarcoidosis.Infection with Human Immunodeficiency Virus/Acquired immunodeficiency Syndrome (AIDS) can cause a related salivary gland disease known as Diffuse Infiltrative Lymphocytosis Syndrome (DILS).Similar to taste dysfunction, xerostomia is one of the most prevalent and persistent oral symptoms associated with COVID-19. Despite a close association with COVID-19, xerostomia, dry mouth and hyposalivation tend to be overlooked in COVID-19 patients and survivors, unlike ageusia, dysgeusia and hypogeusia. Diagnostic approach A diagnosis of hyposalivation is based predominantly on the clinical signs and symptoms. The Challacombe scale maybe used to classify the extent of dryness. The rate of the salivary flow in an individuals mouth can also be measured. There is little correlation between symptoms and objective tests of salivary flow, such as sialometry. This test is simple and noninvasive, and involves measurement of all the saliva a patient can produce during a certain time, achieved by dribbling into a container. Sialometery can yield measures of stimulated salivary flow or unstimulated salivary flow. Stimulated salivary flow rate is calculated using a stimulant such as 10% citric acid dropped onto the tongue, and collection of all the saliva that flows from one of the parotid papillae over five or ten minutes. Unstimulated whole saliva flow rate more closely correlates with symptoms of xerostomia than stimulated salivary flow rate. Sialography involves introduction of radio-opaque dye such as iodine into the duct of a salivary gland. It may show blockage of a duct due to a calculus. Salivary scintiscanning using technetium is rarely used. Other medical imaging that may be involved in the investigation include chest x-ray (to exclude sarcoidosis), ultrasonography and magnetic resonance imaging (to exclude Sjögrens syndrome or neoplasia). A minor salivary gland biopsy, usually taken from the lip, may be carried out if there is a suspicion of organic disease of the salivary glands. Blood tests and urinalysis may be involved to exclude a number of possible causes. To investigate xerophthalmia, the Schirmer test of lacrimal flow may be indicated. Slit-lamp examination may also be carried out. Treatment The successful treatment of xerostomia is difficult to achieve and often unsatisfactory. This involves finding any correctable cause and removing it if possible, but in many cases it is not possible to correct the xerostomia itself, and treatment is symptomatic, and also focuses on preventing tooth decay through improving oral hygiene. Where the symptom is caused by hyposalivation secondary to underlying chronic disease, xerostomia can be considered permanent or even progressive. The management of salivary gland dysfunction may involve the use of saliva substitutes and/or saliva stimulants: Saliva substitutes – These are viscous products which are applied to the oral mucosa, which can be found in the form of sprays, gels, oils, mouthwashes, mouth rinses, pastilles or viscous liquids. This includes water, artificial salivas (mucin-based, carboxymethylcellulose-based), and other substances (milk, vegetable oil): Mucin Spray: 4 Trials have been completed on the effects of Mucin Spray on Xerostomia, overall there is no strong evidence showing that Mucin Spray is more effective than a placebo in reducing the symptoms of dry mouth. Mucin Lozenge: Only 1 trial (Gravenmade 1993) has been completed regarding the effectiveness of Mucin Lozenges. Whilst it was assessed as being at high risk of bias, it showed that Mucin Lozenges were ineffective when compared to a placebo. Mucoadhesive Disk: These disks are stuck to the palate and they contain lubricating agents, flavouring agents and some antimicrobial agents. One trial (Kerr 2010) assessed their effectiveness against a placebo disk. Strangely, patients from both groups (placebo and the real disk) reported an increase in subjective oral moistness. No adverse effects were reported. More research is needed in this area before conclusions are drawn. Biotene oral Balance Gel & toothpaste: One trial has been completed (Epstein 1999) regarding the effectiveness of Biotene Oral Balance gel & toothpaste. The results showed that Biotene products were "more effective than control and reduced dry mouth on waking". Saliva stimulants – organic acids (ascorbic acid, malic acid), chewing gum, parasympathomimetic drugs (choline esters, e.g. pilocarpine hydrochloride, cholinesterase inhibitors), and other substances (sugar-free mints, nicotinamide). Medications which stimulate saliva production traditionally have been administered through oral tablets, which the patient goes on to swallow, although some saliva stimulants can also be found in the form of toothpastes. Lozenges, which are retained in the mouth and then swallowed are becoming more and more popular. Lozenges are soft and gentle on the mouth and there is a belief that prolonged contact with the oral mucosa mechanically stimulates saliva production.Pilocarpine: A study by Taweechaisupapong in 2006 showed no statistical significant improvement in oral dryness and saliva production compared to placebo when administering pilocarpine lozenges. Physostigmine Gel: A study by Knosravini in 2009 showed a reduction in the oral dryness and a 5 times increase in saliva following physostigmine treatment. Chewing gum increases saliva production but there is no strong evidence that it improves dry mouth symptoms. The Cochrane oral health group concluded there is insufficient evidence to determine whether pilocarpine or physostigmine are effective treatments for Xerostomia. More research is needed. Dentirol chewing gum (xylitol): A study by Risheim in 1993 showed that when subjects had 2 sticks of gum up to 5 x daily, the gum gave subjective dry mouth symptom relief in approximately 1/3 of participants but no change in SWS (stimulated whole saliva). Profylin lozenge (xylitol/sorbitol):A study by Risheim in 1993 showed that when subjects had 1 lozenge 4 to 8 x daily, Profylin lozenges gave subjective dry mouth symptom relief in approximately 1/3 of participants but no change in SWS (stimulated whole saliva).Saliva substitutes can improve xerostomia, but tend not to improve the other problems associated with salivary gland dysfunction. Parasympathomimetic drugs (saliva stimulants) such as pilocarpine may improve xerostomia symptoms and other problems associated with salivary gland dysfunction, but the evidence for treatment of radiation-induced xerostomia is limited. Both stimulants and substitutes relieve symptoms to some extent. Salivary stimulants are probably only useful in people with some remaining detectable salivary function. A systematic review compromising of 36 randomised controlled trials for the treatment of dry mouth found that there was no strong evidence to suggest that a specific topical therapy is effective. This review also states that topical therapies can be expected to provide only short-term effects, which are reversible. The review reported limited evidence that oxygenated glycerol triester spray was more effective than electrolyte sprays. Sugar free chewing gum increases saliva production but there is no strong evidence that it improves symptoms. Plus, there is no clear evidence to suggest whether chewing gum is more or less effective as a treatment. There is a suggestion that intraoral devices and integrated mouthcare systems may be effective in reducing symptoms, but there was a lack of strong evidence. A systematic review of the management of radiotherapy-induced xerostomia with parasympathomimetic drugs found that there was limited evidence to support the use of pilocarpine in the treatment of radiation-induced salivary gland dysfunction. It was suggested that, barring any contraindications, a trial of the drug be offered in the above group (at a dose of five mg three times per day to minimize side effects). Improvements can take up to twelve weeks. However, pilocarpine is not always successful in improving xerostomia symptoms. The review also concluded that there was little evidence to support the use of other parasympathomimetics in this group. Another systematic review showed, that there is some low-quality evidence to suggest that amifostine prevents the feeling of dry mouth or reduce the risk of moderate to severe xerostomia in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months postradiotherapy). But, it is less clear whether or not this effect is sustained to 12 months postradiotherapy.A 2013 review looking at non-pharmacological interventions reported a lack of evidence to support the effects of electrostimulation devices, or acupuncture, on symptoms of dry mouth. Epidemiology Xerostomia is a very common symptom. A conservative estimate of prevalence is about 20% in the general population, with increased prevalences in females (up to 30%) and the elderly (up to 50%). Estimates of the prevalence of persistent dry mouth vary between 10 and 50%. History Xerostomia has been used as a test to detect lies, which relied on emotional inhibition of salivary secretions to indicate possible incrimination. See also Xerosis (dry skin) References External links University of Illinois at Chicago NIH MedlinePlus Encyclopedia Drymouth Drymouth Drug Database

Could you describe Yersiniosis, to me Aarogya

Yersiniosis

Yersiniosis is an infectious disease caused by a bacterium of the genus Yersinia. In the United States, most yersiniosis infections among humans are caused by Yersinia enterocolitica. Infection with Y. enterocolitica occurs most often in young children. The infection is thought to be contracted through the consumption of undercooked meat products, unpasteurized milk, or water contaminated by the bacteria. It has been also sometimes associated with handling raw chitterlings.Another bacterium of the same genus, Yersinia pestis, is the cause of Plague. Signs and symptoms Infection with Y. enterocolitica can cause a variety of symptoms depending on the age of the person infected. Common symptoms in children are fever, abdominal pain, and diarrhea, which is often bloody. Symptoms typically develop 4 to 7 days after exposure and may last 1 to 3 weeks or longer. In older children and adults, right-sided abdominal pain and fever may be the predominant symptoms, and may be confused with appendicitis. In a small proportion of cases, complications such as skin rash, joint pains, ileitis, erythema nodosum, and sometimes sepsis, acute arthritis or the spread of bacteria to the bloodstream (bacteremia) can occur. Diagnosis Phage typing of bacterial culture or antibodies for F-antigen. Treatment Treatment for gastroenteritis due to Y. enterocolitica is not needed in the majority of cases. Severe infections with systemic involvement (sepsis or bacteremia) often requires aggressive antibiotic therapy; the drugs of choice are doxycycline and an aminoglycoside. Alternatives include cefotaxime, fluoroquinolones, and co-trimoxazole. References == External links ==

Aarogya, can you share information about a health condition involving Zinc deficiency

Zinc deficiency

Zinc deficiency is defined either as insufficient zinc to meet the needs of the body, or as a serum zinc level below the normal range. However, since a decrease in the serum concentration is only detectable after long-term or severe depletion, serum zinc is not a reliable biomarker for zinc status. Common symptoms include increased rates of diarrhea. Zinc deficiency affects the skin and gastrointestinal tract; brain and central nervous system, immune, skeletal, and reproductive systems. Zinc deficiency in humans is caused by reduced dietary intake, inadequate absorption, increased loss, or increased body system use. The most common cause is reduced dietary intake. In the U.S., the Recommended Dietary Allowance (RDA) is 8 mg/day for women and 11 mg/day for men.The highest concentration of dietary zinc is found in oysters, meat, beans, and nuts. Increasing the amount of zinc in the soil and thus in crops and animals is an effective preventive measure. Zinc deficiency may affect up to 2 billion people worldwide. Signs and symptoms Skin, nails and hair Zinc deficiency may manifest as acne, eczema, xerosis (dry, scaling skin), seborrheic dermatitis, or alopecia (thin and sparse hair). It may also impair or possibly prevent wound healing. Mouth Zinc deficiency can manifest as non-specific oral ulceration, stomatitis, or white tongue coating. Rarely it can cause angular cheilitis (sores at the corners of the mouth). Vision, smell and taste Severe zinc deficiency may disturb the sense of smell and taste. Night blindness may be a feature of severe zinc deficiency, although most reports of night blindness and abnormal dark adaptation in humans with zinc deficiency have occurred in combination with other nutritional deficiencies (e.g. vitamin A). Immune system Impaired immune function in people with zinc deficiency can lead to the development of respiratory, gastrointestinal, or other infections, e.g., pneumonia. The levels of inflammatory cytokines (e.g., IL-1β, IL-2, IL-6, and TNF-α) in blood plasma are affected by zinc deficiency and zinc supplementation produces a dose-dependent response in the level of these cytokines. During inflammation, there is an increased cellular demand for zinc and impaired zinc homeostasis from zinc deficiency is associated with chronic inflammation. Diarrhea Zinc deficiency contributes to an increased incidence and severity of diarrhea. Appetite Zinc deficiency may lead to loss of appetite. The use of zinc in the treatment of anorexia has been advocated since 1979 by Bakan. At least 15 clinical trials have shown that zinc improved weight gain in anorexia. A 1994 trial showed that zinc doubled the rate of body mass increase in the treatment of anorexia nervosa. Deficiency of other nutrients such as tyrosine, tryptophan and thiamine could contribute to this phenomenon of "malnutrition-induced malnutrition". Cognitive function and hedonic tone Cognitive functions, such as learning and hedonic tone, are impaired with zinc deficiency. Moderate and more severe zinc deficiencies are associated with behavioral abnormalities, such as irritability, lethargy, and depression (e.g., involving anhedonia). Zinc supplementation produces a rapid and dramatic improvement in hedonic tone (i.e., general level of happiness or pleasure) under these circumstances. Zinc supplementation has been reported to improve symptoms of ADHD and depression. Psychological disorders Low plasma zinc levels have been alleged to be associated with many psychological disorders. Schizophrenia has been linked to decreased brain zinc levels. Evidence suggests that zinc deficiency could play a role in depression. Zinc supplementation may be an effective treatment in major depression. Growth Zinc deficiency in children can cause delayed growth and has been claimed to be the cause of stunted growth in one third of the worlds population. During pregnancy Zinc deficiency during pregnancy can negatively affect both the mother and fetus. Animal studies indicate that maternal zinc deficiency can upset both the sequencing and efficiency of the birth process. An increased incidence of difficult and prolonged labor, hemorrhage, uterine dystocia and placental abruption has been documented in zinc deficient animals. These effects may be mediated by the defective functioning of estrogen via the estrogen receptor, which contains a zinc finger protein. A review of pregnancy outcomes in women with acrodermatitis enteropathica, reported that out of every seven pregnancies, there was one abortion and two malfunctions, suggesting the human fetus is also susceptible to the teratogenic effects of severe zinc deficiency. However, a review on zinc supplementation trials during pregnancy did not report a significant effect of zinc supplementation on neonatal survival.Zinc deficiency can interfere with many metabolic processes when it occurs during infancy and childhood, a time of rapid growth and development when nutritional needs are high. Low maternal zinc status has been associated with less attention during the neonatal period and worse motor functioning. In some studies, supplementation has been associated with motor development in very low birth weight infants and more vigorous and functional activity in infants and toddlers. Testosterone production Zinc is required to produce testosterone. Thus, zinc deficiency can lead to reduced circulating testosterone, which could lead to sexual immaturity (Ananda Parsad, et al.) hypogonadism, and delayed puberty. Causes Dietary deficiency Zinc deficiency can be caused by a diet high in phytate-containing whole grains, foods grown in zinc deficient soil, or processed foods containing little or no zinc. Conservative estimates suggest that 25% of the worlds population is at risk of zinc deficiency.In the U.S., the Recommended Dietary Allowance (RDA) is 8 mg/day for women and 11 mg/day for men. RDA for pregnancy is 11 mg/day. RDA for lactation is 12 mg/day. For infants up to 12 months the RDA is 3 mg/day. For children ages 1–13 years the RDA increases with age from 3 to 8 mg/day. The following table summarizes most of the foods with significant quantities of zinc, listed in order of quantity per serving, unfortified. Note that all of the top 10 entries are meat, beans, or nuts. Recent research findings suggest that increasing atmospheric carbon dioxide concentrations will exacerbate zinc deficiency problems in populations that consume grains and legumes as staple foods. A meta-analysis of data from 143 studies comparing the nutrient content of grasses and legumes grown in ambient and elevated CO2 environments found that the edible portions of wheat, rice, peas and soybeans grown in elevated CO2 contained less zinc and iron. Global atmospheric CO2 concentration is expected to reach 550 p.p.m. in the late 21st century. At this CO2 level the zinc content of these crops was 3.3 to 9.3% lower than that of crops grown in the present atmosphere. A model of the nutritional impact of these lower zinc quantities on the populations of 151 countries predicts that an additional 175 million people could face dietary zinc deficiency as the result of increasing atmospheric CO2. Inadequate absorption Acrodermatitis enteropathica is an inherited deficiency of the zinc carrier protein ZIP4 resulting in inadequate zinc absorption. It presents as growth retardation, severe diarrhea, hair loss, skin rash (most often around the genitalia and mouth) and opportunistic candidiasis and bacterial infections.Numerous small bowel diseases which cause destruction or malfunction of the gut mucosa enterocytes and generalized malabsorption are associated with zinc deficiency. Increased loss Exercising, high alcohol intake, and diarrhea all increase loss of zinc from the body. Changes in intestinal tract absorbability and permeability due, in part, to viral, protozoal, or bacteria pathogens may also encourage fecal losses of zinc. Chronic disease The mechanism of zinc deficiency in some diseases has not been well defined; it may be multifactorial.Wilsons disease, sickle cell disease, chronic kidney disease, chronic liver disease have all been associated with zinc deficiency. It can also occur after bariatric surgery, mercury exposure and tartrazine.Although marginal zinc deficiency is often found in depression, low zinc levels could either be a cause or a consequence of mental disorders and their symptoms. Mechanism As biosystems are unable to store zinc, regular intake is necessary. Excessively low zinc intake can lead to zinc deficiency, which can negatively impact an individuals health. The mechanisms for the clinical manifestations of zinc deficiency are best appreciated by recognizing that zinc functions in the body in three areas: catalytic, structural, and regulatory. Zinc (Zn) is only common in its +2 oxidative state, where it typically coordinates with tetrahedral geometry. It is important in maintaining basic cellular functions such as DNA replication, RNA transcription, cell division and cell activations. However, having too much or too little zinc can cause these functions to be compromised. Zinc is a critical component of the catalytic site of hundreds of kinds of different metalloenzymes in each human being. In its structural role, zinc coordinates with certain protein domains, facilitating protein folding and producing structures such as zinc fingers. In its regulatory role, zinc is involved in the regulation of nucleoproteins and the activity of various inflammatory cells. For example, zinc regulates the expression of metallothionein, which has multiple functions, such as intracellular zinc compartmentalization and antioxidant function. Thus zinc deficiency results in disruption of hundreds of metabolic pathways, causing numerous clinical manifestations, including impaired growth and development, and disruption of reproductive and immune function.Pra1 (pH regulated antigen 1) is a candida albicans protein that scavenges host zinc. Diagnosis Diagnosis is typically made based on clinical suspicion and a low level of zinc in the blood. Any level below 70 mcg/dl (normal 70-120 mcg/dl)is considered as zinc deficiency. Zinc deficiency could be also associated with low alkaline phosphatase since it acts a cofactor for this enzyme.There is a paucity of adequate zinc biomarkers, and the most widely used indicator, plasma zinc, has poor sensitivity and specificity. Classification Zinc deficiency can be classified as acute, as may occur during prolonged inappropriate zinc-free total parenteral nutrition; or chronic, as may occur in dietary deficiency or inadequate absorption. Prevention Five interventional strategies can be used: Adding zinc to soil, called agronomic biofortification, which both increases crop yields and provides more dietary zinc. Adding zinc to food, called food fortification. The Republic of China, India, Mexico and about 20 other countries, mostly on the east coast of sub-Saharan Africa, fortify wheat flour and/or maize flour with zinc. Adding zinc rich foods to diet. The foods with the highest concentration of zinc are proteins, especially animal meats, the highest being oysters. Per ounce, beef, pork, and lamb contain more zinc than fish. The dark meat of a chicken has more zinc than the light meat. Other good sources of zinc are nuts, whole grains, legumes, and yeast. Although whole grains and cereals are high in zinc, they also contain chelating phytates which bind zinc and reduce its bioavailability. Oral repletion via tablets (e.g. zinc gluconate) or liquid (e.g. zinc acetate). Oral zinc supplementation in healthy infants more than six months old has been shown to reduce the duration of any subsequent diarrheal episodes by about 11 hours. Oral repletion via multivitamin/mineral supplements containing zinc gluconate, sulfate, or acetate. It is not clear whether one form is better than another. Epidemiology Zinc deficiency affects about 2.2 billion people around the world. Severe zinc deficiency is rare, and is mainly seen in persons with acrodermatitis enteropathica, a severe defect in zinc absorption due to a congenital deficiency in the zinc carrier protein ZIP4 in the enterocyte. Mild zinc deficiency due to reduced dietary intake is common. Conservative estimates suggest that 25% of the worlds population is at risk of zinc deficiency. Zinc deficiency is thought to be a leading cause of infant mortality.Providing micronutrients, including zinc, to humans is one of the four solutions to major global problems identified in the Copenhagen Consensus from an international panel of economists. History Significant historical events related to zinc deficiency began in 1869 when zinc was first discovered to be essential to the growth of an organism Aspergillus niger. In 1929 Lutz measured zinc in numerous human tissues using the dithizone technique and estimated total body zinc in a 70 kg man to be 2.2 grams. Zinc was found to be essential to the growth of rats in 1933. In 1939 beriberi patients in China were noted to have decreased zinc levels in skin and nails. In 1940 zinc levels in a series of autopsies found it to be present in all tissues examined. In 1942 a study showed most zinc excretion was via the feces. In 1950 a normal serum zinc level was first defined, and found to be 17.3–22.1 micromoles/liter. In 1956 cirrhotic patients were found to have low serum zinc levels. In 1963 zinc was determined to be essential to human growth, three enzymes requiring zinc as a cofactor were described, and a report was published of a 21-year-old Iranian man with stunted growth, infantile genitalia, and anemia which were all reversed by zinc supplementation. In 1972 fifteen Iranian rejected army inductees with symptoms of zinc deficiency were reported: all responded to zinc. In 1973 the first case of acrodermatitis enteropathica due to severe zinc deficiency was described. In 1974 the National Academy of Sciences declared zinc to be an essential element for humans and established a recommended daily allowance. In 1978 the Food and Drug Administration required zinc to be in total parenteral nutrition fluids. In the 1990s there was increasing attention on the role of zinc deficiency in childhood morbidity and mortality in developing countries. In 2002 the zinc transporter protein ZIP4 was first identified as the mechanism for absorption of zinc in the gut across the basolateral membrane of the enterocyte. By 2014 over 300 zinc containing enzymes have been identified, as well as over 1000 zinc containing transcription factors.Phytate was recognized as removing zinc from nutrients given to chicken and swine in 1960. That it can cause human zinc deficiency however was not recognized until Reinholds work in Iran in the 1970s. This phenomenon is central to the high risk of zinc deficiency worldwide. Soils and crops Soil zinc is an essential micronutrient for crops. Almost half of the worlds cereal crops are deficient in zinc, leading to poor crop yields. Many agricultural countries around the world are affected by zinc deficiency. In China, zinc deficiency occurs on around half of the agricultural soils, affecting mainly rice and maize. Areas with zinc deficient soils are often regions with widespread zinc deficiency in humans. A basic knowledge of the dynamics of zinc in soils, understanding of the uptake and transport of zinc in crops and characterizing the response of crops to zinc deficiency are essential steps in achieving sustainable solutions to the problem of zinc deficiency in crops and humans. Biofortification Soil and foliar application of zinc fertilizer can effectively increase grain zinc and reduce the phytate:zinc ratio in grain. People who eat bread prepared from zinc enriched wheat have a significant increase in serum zinc.Zinc fertilization not only increases zinc content in zinc deficient crops, it also increases crop yields. Balanced crop nutrition supplying all essential nutrients, including zinc, is a cost effective management strategy. Even with zinc-efficient varieties, zinc fertilizers are needed when the available zinc in the topsoil becomes depleted. Plant breeding can improve zinc uptake capacity of plants under soil conditions with low chemical availability of zinc. Breeding can also improve zinc translocation which elevates zinc content in edible crop parts as opposed to the rest of the plant. Central Anatolia, in Turkey, was a region with zinc-deficient soils and widespread zinc deficiency in humans. In 1993, a research project found that yields could be increased by 6 to 8-fold and child nutrition dramatically increased through zinc fertilization. Zinc was added to fertilizers. While the product was initially made available at the same cost, the results were so convincing that Turkish farmers significantly increased the use of the zinc-fortified fertilizer (1 percent of zinc) within a few years, despite the repricing of the products to reflect the added value of the content. Nearly ten years after the identification of the zinc deficiency problem, the total amount of zinc-containing compound fertilizers produced and applied in Turkey reached a record level of 300,000 tonnes per annum. It is estimated that the economic benefits associated with the application of zinc fertilizers on zinc deficient soils in Turkey is around US$100 million per year. Zinc deficiency in children has been dramatically reduced. References Further reading Maret W (2013). "Chapter 14 Zinc and the Zinc Proteome". In Banci L (ed.). Metallomics and the Cell. Metal Ions in Life Sciences. Vol. 12. Springer. pp. 479–501. doi:10.1007/978-94-007-5561-1_14. ISBN 978-94-007-5560-4. ISSN 1559-0836. PMID 23595681. External links DermAtlas 228

Aarogya , Do you know what is Zinc deficiency,

Zinc deficiency

Zinc deficiency is defined either as insufficient zinc to meet the needs of the body, or as a serum zinc level below the normal range. However, since a decrease in the serum concentration is only detectable after long-term or severe depletion, serum zinc is not a reliable biomarker for zinc status. Common symptoms include increased rates of diarrhea. Zinc deficiency affects the skin and gastrointestinal tract; brain and central nervous system, immune, skeletal, and reproductive systems. Zinc deficiency in humans is caused by reduced dietary intake, inadequate absorption, increased loss, or increased body system use. The most common cause is reduced dietary intake. In the U.S., the Recommended Dietary Allowance (RDA) is 8 mg/day for women and 11 mg/day for men.The highest concentration of dietary zinc is found in oysters, meat, beans, and nuts. Increasing the amount of zinc in the soil and thus in crops and animals is an effective preventive measure. Zinc deficiency may affect up to 2 billion people worldwide. Signs and symptoms Skin, nails and hair Zinc deficiency may manifest as acne, eczema, xerosis (dry, scaling skin), seborrheic dermatitis, or alopecia (thin and sparse hair). It may also impair or possibly prevent wound healing. Mouth Zinc deficiency can manifest as non-specific oral ulceration, stomatitis, or white tongue coating. Rarely it can cause angular cheilitis (sores at the corners of the mouth). Vision, smell and taste Severe zinc deficiency may disturb the sense of smell and taste. Night blindness may be a feature of severe zinc deficiency, although most reports of night blindness and abnormal dark adaptation in humans with zinc deficiency have occurred in combination with other nutritional deficiencies (e.g. vitamin A). Immune system Impaired immune function in people with zinc deficiency can lead to the development of respiratory, gastrointestinal, or other infections, e.g., pneumonia. The levels of inflammatory cytokines (e.g., IL-1β, IL-2, IL-6, and TNF-α) in blood plasma are affected by zinc deficiency and zinc supplementation produces a dose-dependent response in the level of these cytokines. During inflammation, there is an increased cellular demand for zinc and impaired zinc homeostasis from zinc deficiency is associated with chronic inflammation. Diarrhea Zinc deficiency contributes to an increased incidence and severity of diarrhea. Appetite Zinc deficiency may lead to loss of appetite. The use of zinc in the treatment of anorexia has been advocated since 1979 by Bakan. At least 15 clinical trials have shown that zinc improved weight gain in anorexia. A 1994 trial showed that zinc doubled the rate of body mass increase in the treatment of anorexia nervosa. Deficiency of other nutrients such as tyrosine, tryptophan and thiamine could contribute to this phenomenon of "malnutrition-induced malnutrition". Cognitive function and hedonic tone Cognitive functions, such as learning and hedonic tone, are impaired with zinc deficiency. Moderate and more severe zinc deficiencies are associated with behavioral abnormalities, such as irritability, lethargy, and depression (e.g., involving anhedonia). Zinc supplementation produces a rapid and dramatic improvement in hedonic tone (i.e., general level of happiness or pleasure) under these circumstances. Zinc supplementation has been reported to improve symptoms of ADHD and depression. Psychological disorders Low plasma zinc levels have been alleged to be associated with many psychological disorders. Schizophrenia has been linked to decreased brain zinc levels. Evidence suggests that zinc deficiency could play a role in depression. Zinc supplementation may be an effective treatment in major depression. Growth Zinc deficiency in children can cause delayed growth and has been claimed to be the cause of stunted growth in one third of the worlds population. During pregnancy Zinc deficiency during pregnancy can negatively affect both the mother and fetus. Animal studies indicate that maternal zinc deficiency can upset both the sequencing and efficiency of the birth process. An increased incidence of difficult and prolonged labor, hemorrhage, uterine dystocia and placental abruption has been documented in zinc deficient animals. These effects may be mediated by the defective functioning of estrogen via the estrogen receptor, which contains a zinc finger protein. A review of pregnancy outcomes in women with acrodermatitis enteropathica, reported that out of every seven pregnancies, there was one abortion and two malfunctions, suggesting the human fetus is also susceptible to the teratogenic effects of severe zinc deficiency. However, a review on zinc supplementation trials during pregnancy did not report a significant effect of zinc supplementation on neonatal survival.Zinc deficiency can interfere with many metabolic processes when it occurs during infancy and childhood, a time of rapid growth and development when nutritional needs are high. Low maternal zinc status has been associated with less attention during the neonatal period and worse motor functioning. In some studies, supplementation has been associated with motor development in very low birth weight infants and more vigorous and functional activity in infants and toddlers. Testosterone production Zinc is required to produce testosterone. Thus, zinc deficiency can lead to reduced circulating testosterone, which could lead to sexual immaturity (Ananda Parsad, et al.) hypogonadism, and delayed puberty. Causes Dietary deficiency Zinc deficiency can be caused by a diet high in phytate-containing whole grains, foods grown in zinc deficient soil, or processed foods containing little or no zinc. Conservative estimates suggest that 25% of the worlds population is at risk of zinc deficiency.In the U.S., the Recommended Dietary Allowance (RDA) is 8 mg/day for women and 11 mg/day for men. RDA for pregnancy is 11 mg/day. RDA for lactation is 12 mg/day. For infants up to 12 months the RDA is 3 mg/day. For children ages 1–13 years the RDA increases with age from 3 to 8 mg/day. The following table summarizes most of the foods with significant quantities of zinc, listed in order of quantity per serving, unfortified. Note that all of the top 10 entries are meat, beans, or nuts. Recent research findings suggest that increasing atmospheric carbon dioxide concentrations will exacerbate zinc deficiency problems in populations that consume grains and legumes as staple foods. A meta-analysis of data from 143 studies comparing the nutrient content of grasses and legumes grown in ambient and elevated CO2 environments found that the edible portions of wheat, rice, peas and soybeans grown in elevated CO2 contained less zinc and iron. Global atmospheric CO2 concentration is expected to reach 550 p.p.m. in the late 21st century. At this CO2 level the zinc content of these crops was 3.3 to 9.3% lower than that of crops grown in the present atmosphere. A model of the nutritional impact of these lower zinc quantities on the populations of 151 countries predicts that an additional 175 million people could face dietary zinc deficiency as the result of increasing atmospheric CO2. Inadequate absorption Acrodermatitis enteropathica is an inherited deficiency of the zinc carrier protein ZIP4 resulting in inadequate zinc absorption. It presents as growth retardation, severe diarrhea, hair loss, skin rash (most often around the genitalia and mouth) and opportunistic candidiasis and bacterial infections.Numerous small bowel diseases which cause destruction or malfunction of the gut mucosa enterocytes and generalized malabsorption are associated with zinc deficiency. Increased loss Exercising, high alcohol intake, and diarrhea all increase loss of zinc from the body. Changes in intestinal tract absorbability and permeability due, in part, to viral, protozoal, or bacteria pathogens may also encourage fecal losses of zinc. Chronic disease The mechanism of zinc deficiency in some diseases has not been well defined; it may be multifactorial.Wilsons disease, sickle cell disease, chronic kidney disease, chronic liver disease have all been associated with zinc deficiency. It can also occur after bariatric surgery, mercury exposure and tartrazine.Although marginal zinc deficiency is often found in depression, low zinc levels could either be a cause or a consequence of mental disorders and their symptoms. Mechanism As biosystems are unable to store zinc, regular intake is necessary. Excessively low zinc intake can lead to zinc deficiency, which can negatively impact an individuals health. The mechanisms for the clinical manifestations of zinc deficiency are best appreciated by recognizing that zinc functions in the body in three areas: catalytic, structural, and regulatory. Zinc (Zn) is only common in its +2 oxidative state, where it typically coordinates with tetrahedral geometry. It is important in maintaining basic cellular functions such as DNA replication, RNA transcription, cell division and cell activations. However, having too much or too little zinc can cause these functions to be compromised. Zinc is a critical component of the catalytic site of hundreds of kinds of different metalloenzymes in each human being. In its structural role, zinc coordinates with certain protein domains, facilitating protein folding and producing structures such as zinc fingers. In its regulatory role, zinc is involved in the regulation of nucleoproteins and the activity of various inflammatory cells. For example, zinc regulates the expression of metallothionein, which has multiple functions, such as intracellular zinc compartmentalization and antioxidant function. Thus zinc deficiency results in disruption of hundreds of metabolic pathways, causing numerous clinical manifestations, including impaired growth and development, and disruption of reproductive and immune function.Pra1 (pH regulated antigen 1) is a candida albicans protein that scavenges host zinc. Diagnosis Diagnosis is typically made based on clinical suspicion and a low level of zinc in the blood. Any level below 70 mcg/dl (normal 70-120 mcg/dl)is considered as zinc deficiency. Zinc deficiency could be also associated with low alkaline phosphatase since it acts a cofactor for this enzyme.There is a paucity of adequate zinc biomarkers, and the most widely used indicator, plasma zinc, has poor sensitivity and specificity. Classification Zinc deficiency can be classified as acute, as may occur during prolonged inappropriate zinc-free total parenteral nutrition; or chronic, as may occur in dietary deficiency or inadequate absorption. Prevention Five interventional strategies can be used: Adding zinc to soil, called agronomic biofortification, which both increases crop yields and provides more dietary zinc. Adding zinc to food, called food fortification. The Republic of China, India, Mexico and about 20 other countries, mostly on the east coast of sub-Saharan Africa, fortify wheat flour and/or maize flour with zinc. Adding zinc rich foods to diet. The foods with the highest concentration of zinc are proteins, especially animal meats, the highest being oysters. Per ounce, beef, pork, and lamb contain more zinc than fish. The dark meat of a chicken has more zinc than the light meat. Other good sources of zinc are nuts, whole grains, legumes, and yeast. Although whole grains and cereals are high in zinc, they also contain chelating phytates which bind zinc and reduce its bioavailability. Oral repletion via tablets (e.g. zinc gluconate) or liquid (e.g. zinc acetate). Oral zinc supplementation in healthy infants more than six months old has been shown to reduce the duration of any subsequent diarrheal episodes by about 11 hours. Oral repletion via multivitamin/mineral supplements containing zinc gluconate, sulfate, or acetate. It is not clear whether one form is better than another. Epidemiology Zinc deficiency affects about 2.2 billion people around the world. Severe zinc deficiency is rare, and is mainly seen in persons with acrodermatitis enteropathica, a severe defect in zinc absorption due to a congenital deficiency in the zinc carrier protein ZIP4 in the enterocyte. Mild zinc deficiency due to reduced dietary intake is common. Conservative estimates suggest that 25% of the worlds population is at risk of zinc deficiency. Zinc deficiency is thought to be a leading cause of infant mortality.Providing micronutrients, including zinc, to humans is one of the four solutions to major global problems identified in the Copenhagen Consensus from an international panel of economists. History Significant historical events related to zinc deficiency began in 1869 when zinc was first discovered to be essential to the growth of an organism Aspergillus niger. In 1929 Lutz measured zinc in numerous human tissues using the dithizone technique and estimated total body zinc in a 70 kg man to be 2.2 grams. Zinc was found to be essential to the growth of rats in 1933. In 1939 beriberi patients in China were noted to have decreased zinc levels in skin and nails. In 1940 zinc levels in a series of autopsies found it to be present in all tissues examined. In 1942 a study showed most zinc excretion was via the feces. In 1950 a normal serum zinc level was first defined, and found to be 17.3–22.1 micromoles/liter. In 1956 cirrhotic patients were found to have low serum zinc levels. In 1963 zinc was determined to be essential to human growth, three enzymes requiring zinc as a cofactor were described, and a report was published of a 21-year-old Iranian man with stunted growth, infantile genitalia, and anemia which were all reversed by zinc supplementation. In 1972 fifteen Iranian rejected army inductees with symptoms of zinc deficiency were reported: all responded to zinc. In 1973 the first case of acrodermatitis enteropathica due to severe zinc deficiency was described. In 1974 the National Academy of Sciences declared zinc to be an essential element for humans and established a recommended daily allowance. In 1978 the Food and Drug Administration required zinc to be in total parenteral nutrition fluids. In the 1990s there was increasing attention on the role of zinc deficiency in childhood morbidity and mortality in developing countries. In 2002 the zinc transporter protein ZIP4 was first identified as the mechanism for absorption of zinc in the gut across the basolateral membrane of the enterocyte. By 2014 over 300 zinc containing enzymes have been identified, as well as over 1000 zinc containing transcription factors.Phytate was recognized as removing zinc from nutrients given to chicken and swine in 1960. That it can cause human zinc deficiency however was not recognized until Reinholds work in Iran in the 1970s. This phenomenon is central to the high risk of zinc deficiency worldwide. Soils and crops Soil zinc is an essential micronutrient for crops. Almost half of the worlds cereal crops are deficient in zinc, leading to poor crop yields. Many agricultural countries around the world are affected by zinc deficiency. In China, zinc deficiency occurs on around half of the agricultural soils, affecting mainly rice and maize. Areas with zinc deficient soils are often regions with widespread zinc deficiency in humans. A basic knowledge of the dynamics of zinc in soils, understanding of the uptake and transport of zinc in crops and characterizing the response of crops to zinc deficiency are essential steps in achieving sustainable solutions to the problem of zinc deficiency in crops and humans. Biofortification Soil and foliar application of zinc fertilizer can effectively increase grain zinc and reduce the phytate:zinc ratio in grain. People who eat bread prepared from zinc enriched wheat have a significant increase in serum zinc.Zinc fertilization not only increases zinc content in zinc deficient crops, it also increases crop yields. Balanced crop nutrition supplying all essential nutrients, including zinc, is a cost effective management strategy. Even with zinc-efficient varieties, zinc fertilizers are needed when the available zinc in the topsoil becomes depleted. Plant breeding can improve zinc uptake capacity of plants under soil conditions with low chemical availability of zinc. Breeding can also improve zinc translocation which elevates zinc content in edible crop parts as opposed to the rest of the plant. Central Anatolia, in Turkey, was a region with zinc-deficient soils and widespread zinc deficiency in humans. In 1993, a research project found that yields could be increased by 6 to 8-fold and child nutrition dramatically increased through zinc fertilization. Zinc was added to fertilizers. While the product was initially made available at the same cost, the results were so convincing that Turkish farmers significantly increased the use of the zinc-fortified fertilizer (1 percent of zinc) within a few years, despite the repricing of the products to reflect the added value of the content. Nearly ten years after the identification of the zinc deficiency problem, the total amount of zinc-containing compound fertilizers produced and applied in Turkey reached a record level of 300,000 tonnes per annum. It is estimated that the economic benefits associated with the application of zinc fertilizers on zinc deficient soils in Turkey is around US$100 million per year. Zinc deficiency in children has been dramatically reduced. References Further reading Maret W (2013). "Chapter 14 Zinc and the Zinc Proteome". In Banci L (ed.). Metallomics and the Cell. Metal Ions in Life Sciences. Vol. 12. Springer. pp. 479–501. doi:10.1007/978-94-007-5561-1_14. ISBN 978-94-007-5560-4. ISSN 1559-0836. PMID 23595681. External links DermAtlas 228

Do you know what is Zollinger–Ellison syndrome, Aarogya

Zollinger–Ellison syndrome

Zollinger–Ellison syndrome (Z-E syndrome) is a disease in which tumors cause the stomach to produce too much acid, resulting in peptic ulcers. Symptoms include abdominal pain and diarrhea. The syndrome is caused by a gastrinoma, a neuroendocrine tumor that secretes a hormone called gastrin. Too much gastrin in the blood (hypergastrinemia) results in the overproduction of gastric acid by parietal cells in the stomach. Gastrinomas most commonly arise in the duodenum, pancreas or stomach.In 75% of cases Zollinger–Ellison syndrome occurs sporadically, while in 25% of cases it occurs as part of an autosomal dominant syndrome called multiple endocrine neoplasia type 1 (MEN 1). Signs and symptoms Patients with Zollinger–Ellison syndrome may experience abdominal pain and diarrhea. The diagnosis is also suspected in patients who have severe ulceration of the stomach and small bowel, especially if they fail to respond to treatment. Chronic diarrhea, including steatorrhea (fatty stools) Pain in the esophagus, especially between and after meals at night Nausea Wheezing Vomiting blood Malnourishment Loss of appetite MalabsorptionGastrinomas may occur as single tumors or as multiple small tumors. About one-half to two-thirds of single gastrinomas are malignant tumors that most commonly spread to the liver and to lymph nodes near the pancreas and small bowel. Nearly 25 percent of patients with gastrinomas have multiple tumors as part of a condition called multiple endocrine neoplasia type 1 (MEN 1). MEN I patients have tumors in their pituitary gland and parathyroid glands, in addition to tumors of the pancreas. Pathophysiology Gastrin works on the parietal cells of the gastric glands, causing them to secrete more hydrogen ions into the stomach lumen. In addition, gastrin acts as a trophic factor for parietal cells, causing parietal cell hyperplasia. Normally, hydrogen ion secretion is controlled by a negative feedback loop by gastric cells to maintain a suitable pH, however, the neuroendocrine tumor that is present in individuals with Zollinger–Ellison Syndrome has no regulation, resulting in excessively large amounts of secretion. Thus, there is an increase in the number of acid-secreting cells, and each of these cells produces acid at a higher rate. The increase in acidity contributes to the development of peptic ulcers in the stomach, duodenum (first portion of the small bowel) and occasionally the jejunum (second portion of the small bowel), the last of which is an atypical ulcer. Diagnosis Zollinger–Ellison syndrome may be suspected when the above symptoms prove resistant to treatment when the symptoms are especially suggestive of the syndrome, or when endoscopy is suggestive. The diagnosis is made through several laboratory tests and imaging studies: Secretin stimulation test, which measures evoked gastrin levels. Note that the mechanism underlying this test is in contrast to the normal physiologic mechanism whereby secretin inhibits gastrin release from G cells. Gastrinoma cells release gastrin in response to secretin stimulation, thereby providing a sensitive means of differentiation. Fasting gastrin levels on at least three occasions Gastric acid secretion and pH (normal basal gastric acid secretion is less than 10 mEq/hour; in Zollinger–Ellison patients, it is usually more than 15 mEq/hour) An increased level of chromogranin A is a common marker of neuroendocrine tumors.In addition, the source of the increased gastrin production must be determined using MRI or somatostatin receptor scintigraphy. Treatment Proton pump inhibitors (such as omeprazole and lansoprazole) and histamine H2-receptor antagonists (such as famotidine and ranitidine) are used to slow acid secretion. Once gastric acid is suppressed, symptoms normally improve. Surgery to remove peptic ulcers or tumors might also be considered. Epidemiology The condition most commonly affects people between the ages of 30 and 60. The prevalence is unknown, but estimated to be about 1 in 100,000 people. History Sporadic reports of unusual cases of peptic ulceration in the presence of pancreatic tumors occurred prior to 1955, but R. M. Zollinger and E. H. Ellison, surgeons at Ohio State University, were the first to postulate a causal relationship between these findings. The American Surgical Association meeting in Philadelphia in April 1955 heard the first public description of the syndrome, and Zollinger and Ellison subsequently published their findings in Annals of Surgery. References == External links ==

Hi Aarogya, could you help me understand about Skeletal fluorosis

Skeletal fluorosis

Skeletal fluorosis is a bone disease caused by excessive accumulation of fluoride leading to weakened bones. In advanced cases, skeletal fluorosis causes painful damage to bones and joints. Symptoms Symptoms are mainly promoted in the bone structure. Due to a high fluoride concentration in the body, the bone is hardened and thus less elastic, resulting in an increased frequency of fractures. Other symptoms include thickening of the bone structure and accumulation of bone tissue, which both contribute to impaired joint mobility. Ligaments and cartilage can become ossified. Most patients with skeletal fluorosis show side effects from the high fluoride dose such as ruptures of the stomach lining and nausea. Fluoride can also damage the parathyroid glands, leading to hyperparathyroidism, the uncontrolled secretion of parathyroid hormones. These hormones regulate calcium concentration in the body. An elevated parathyroid hormone concentration results in a depletion of calcium in bone structures and thus a higher calcium concentration in the blood. As a result, bone flexibility decreases making the bone more susceptible to fractures. Causes Common causes of fluorosis include inhalation of fluoride dusts or fumes by workers in industry and consumption of fluoride from drinking water (levels of fluoride in excess of levels that are considered safe.) In India, especially the Nalgonda region (Telangana), a common cause of fluorosis is fluoride-rich drinking water that is sourced from deep-bore wells. Over half of groundwater sources in India have fluoride above recommended levels.Fluorosis can also occur as a result of volcanic activity. The 1783 eruption of the Laki volcano in Iceland is estimated to have killed about 22% of the Icelandic population, and 60% of livestock, as a result of fluorosis and sulfur dioxide gases. The 1693 eruption of Hekla also led to fatalities of livestock under similar conditions. Skeletal fluorosis phases Treatment As of now, there are no established treatments for skeletal fluorosis patients. However, it is reversible in some cases, depending on the progression of the disease. If fluorine intake is stopped, the amount in bone will decrease and be excreted via urine. However, it is a very slow process to eliminate the fluorine from the body completely. Minimal results are seen in patients. Treatment of side effects is also very difficult. For example, a patient with a bone fracture cannot be treated according to standard procedures, because the bone is very brittle. In this case, recovery will take a very long time and a pristine healing cannot be guaranteed. However, further fluorosis can be prevented by drinking defluoridated water. It is recently suggested that drinking of defluoridated water from the "calcium amended-hydroxyapatite" defluoridation method may help in the fluorosis reversal. Defluoridated water from this suggested method provides calcium-enriched alkaline drinking water as generally fluoride contaminated water has a low amount of calcium mineral and drinking alkaline water helps in eliminating the toxic fluoride from the body. Epidemiology In some areas, skeletal fluorosis is endemic. While fluorosis is most severe and widespread in the worlds two most populous countries – India and China – UNICEF estimates that "fluorosis is endemic in at least 25 countries across the globe. The total number of people affected is not known, but a conservative estimate would number in the tens of millions."In India, 20 states have been identified as endemic areas, with an estimated 60 million people at risk and 6 million people disabled; about 600,000 might develop a neurological disorder as a consequence. Effects on animals The histological changes which are induced through fluorine on rats resemble those of humans. See also Dental fluorosis Fluoride poisoning Kaj Roholm References Further reading Fluorosis from drinking very large amounts of tea: Naveen Kakumanu, M.D. & Sudhaker D. Rao, M.B., B.S. (2013-03-21). "Skeletal Fluorosis Due to Excessive Tea Drinking". New England Journal of Medicine. 368 (12): 1140. doi:10.1056/NEJMicm1200995. PMID 23514291.{{cite journal}}: CS1 maint: multiple names: authors list (link) == External links ==

Would you describe Amylase, to me Aarogya

Amylase

An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin amylum) into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of starch but little sugar, such as rice and potatoes, may acquire a slightly sweet taste as they are chewed because amylase degrades some of their starch into sugar. The pancreas and salivary gland make amylase (alpha amylase) to hydrolyse dietary starch into disaccharides and trisaccharides which are converted by other enzymes to glucose to supply the body with energy. Plants and some bacteria also produce amylase. Specific amylase proteins are designated by different Greek letters. All amylases are glycoside hydrolases and act on α-1,4-glycosidic bonds. Classification α-Amylase The α-amylases (EC 3.2.1.1 ) (CAS 9014-71-5) (alternative names: 1,4-α-D-glucan glucanohydrolase; glycogenase) are calcium metalloenzymes. By acting at random locations along the starch chain, α-amylase breaks down long-chain saccharides, ultimately yielding either maltotriose and maltose from amylose, or maltose, glucose and "limit dextrin" from amylopectin. They belong to glycoside hydrolase family 13. Because it can act anywhere on the substrate, α-amylase tends to be faster-acting than β-amylase. In animals, it is a major digestive enzyme, and its optimum pH is 6.7–7.0.In human physiology, both the salivary and pancreatic amylases are α-amylases. The α-amylase form is also found in plants, fungi (ascomycetes and basidiomycetes) and bacteria (Bacillus). β-Amylase Another form of amylase, β-amylase (EC 3.2.1.2 ) (alternative names: 1,4-α-D-glucan maltohydrolase; glycogenase; saccharogen amylase) is also synthesized by bacteria, fungi, and plants. Working from the non-reducing end, β-amylase catalyzes the hydrolysis of the second α-1,4 glycosidic bond, cleaving off two glucose units (maltose) at a time. During the ripening of fruit, β-amylase breaks starch into maltose, resulting in the sweet flavor of ripe fruit. They belong to glycoside hydrolase family 14. Both α-amylase and β-amylase are present in seeds; β-amylase is present in an inactive form prior to germination, whereas α-amylase and proteases appear once germination has begun. Many microbes also produce amylase to degrade extracellular starches. Animal tissues do not contain β-amylase, although it may be present in microorganisms contained within the digestive tract. The optimum pH for β-amylase is 4.0–5.0. γ-Amylase γ-Amylase (EC 3.2.1.3 ) (alternative names: Glucan 1,4-a-glucosidase; amyloglucosidase; exo-1,4-α-glucosidase; glucoamylase; lysosomal α-glucosidase; 1,4-α-D-glucan glucohydrolase) will cleave α(1–6) glycosidic linkages, as well as the last α-1,4 glycosidic bond at the nonreducing end of amylose and amylopectin, yielding glucose. The γ-amylase has the most acidic optimum pH of all amylases because it is most active around pH 3. They belong to a variety of different GH families, such as glycoside hydrolase family 15 in fungi, glycoside hydrolase family 31 of human MGAM, and glycoside hydrolase family 97 of bacterial forms. Uses Fermentation α- and β-amylases are important in brewing beer and liquor made from sugars derived from starch. In fermentation, yeast ingests sugars and excretes ethanol. In beer and some liquors, the sugars present at the beginning of fermentation have been produced by "mashing" grains or other starch sources (such as potatoes). In traditional beer brewing, malted barley is mixed with hot water to create a "mash", which is held at a given temperature to allow the amylases in the malted grain to convert the barleys starch into sugars. Different temperatures optimize the activity of alpha or beta amylase, resulting in different mixtures of fermentable and unfermentable sugars. In selecting mash temperature and grain-to-water ratio, a brewer can change the alcohol content, mouthfeel, aroma, and flavor of the finished beer. In some historic methods of producing alcoholic beverages, the conversion of starch to sugar starts with the brewer chewing grain to mix it with saliva. This practice continues to be practiced in home production of some traditional drinks, such as chhaang in the Himalayas, chicha in the Andes and kasiri in Brazil and Suriname. Flour additive Amylases are used in breadmaking and to break down complex sugars, such as starch (found in flour), into simple sugars. Yeast then feeds on these simple sugars and converts it into the waste products of ethanol and carbon dioxide. This imparts flavour and causes the bread to rise. While amylases are found naturally in yeast cells, it takes time for the yeast to produce enough of these enzymes to break down significant quantities of starch in the bread. This is the reason for long fermented doughs such as sourdough. Modern breadmaking techniques have included amylases (often in the form of malted barley) into bread improver, thereby making the process faster and more practical for commercial use.α-Amylase is often listed as an ingredient on commercially package-milled flour. Bakers with long exposure to amylase-enriched flour are at risk of developing dermatitis or asthma. Molecular biology In molecular biology, the presence of amylase can serve as an additional method of selecting for successful integration of a reporter construct in addition to antibiotic resistance. As reporter genes are flanked by homologous regions of the structural gene for amylase, successful integration will disrupt the amylase gene and prevent starch degradation, which is easily detectable through iodine staining. Medical uses Amylase also has medical applications in the use of pancreatic enzyme replacement therapy (PERT). It is one of the components in Sollpura (liprotamase) to help in the breakdown of saccharides into simple sugars. Other uses An inhibitor of alpha-amylase, called phaseolamin, has been tested as a potential diet aid.When used as a food additive, amylase has E number E1100, and may be derived from pig pancreas or mold fungi. Bacilliary amylase is also used in clothing and dishwasher detergents to dissolve starches from fabrics and dishes. Factory workers who work with amylase for any of the above uses are at increased risk of occupational asthma. Five to nine percent of bakers have a positive skin test, and a fourth to a third of bakers with breathing problems are hypersensitive to amylase. Hyperamylasemia Blood serum amylase may be measured for purposes of medical diagnosis. A higher than normal concentration may reflect any of several medical conditions, including acute inflammation of the pancreas (it may be measured concurrently with the more specific lipase), perforated peptic ulcer, torsion of an ovarian cyst, strangulation, ileus, mesenteric ischemia, macroamylasemia and mumps. Amylase may be measured in other body fluids, including urine and peritoneal fluid. A January 2007 study from Washington University in St. Louis suggests that saliva tests of the enzyme could be used to indicate sleep deficits, as the enzyme increases its activity in correlation with the length of time a subject has been deprived of sleep. History In 1831, Erhard Friedrich Leuchs (1800–1837) described the hydrolysis of starch by saliva, due to the presence of an enzyme in saliva, "ptyalin", an amylase. it was named after the Ancient Greek name for saliva: πτύαλον - ptyalon. The modern history of enzymes began in 1833, when French chemists Anselme Payen and Jean-François Persoz isolated an amylase complex from germinating barley and named it "diastase". It is from this term that all subsequent enzyme names tend to end in the suffix -ase. In 1862, Alexander Jakulowitsch Danilewsky (1838–1923) separated pancreatic amylase from trypsin. Evolution Salivary amylase Saccharides are a food source rich in energy. Large polymers such as starch are partially hydrolyzed in the mouth by the enzyme amylase before being cleaved further into sugars. Many mammals have seen great expansions in the copy number of the amylase gene. These duplications allow for the pancreatic amylase AMY2 to re-target to the salivary glands, allowing animals to detect starch by taste and to digest starch more efficiently and in higher quantities. This has happened independently in mice, rats, dogs, pigs, and most importantly, humans after the agricultural revolution.Following the agricultural revolution 12,000 years ago, human diet began to shift more to plant and animal domestication in place of hunting and gathering. Starch has become a staple of the human diet. Despite the obvious benefits, early humans did not possess salivary amylase, a trend that is also seen in evolutionary relatives of the human, such as chimpanzees and bonobos, who possess either one or no copies of the gene responsible for producing salivary amylase.Like in other mammals, the pancreatic alpha-amylase AMY2 was duplicated multiple times. One event allowed it to evolve salivary specificity, leading to the production of amylase in the saliva (named in humans as AMY1). The 1p21.1 region of human chromosome 1 contains many copies of these genes, variously named AMY1A, AMY1B, AMY1C, AMY2A, AMY2B, and so on.However, not all humans possess the same number of copies of the AMY1 gene. Populations known to rely more on saccharides have a higher number of AMY1 copies than human populations that, by comparison, consume little starch. The number of AMY1 gene copies in humans can range from six copies in agricultural groups such as European-American and Japanese (two high starch populations) to only two to three copies in hunter-gatherer societies such as the Biaka, Datog, and Yakuts.The correlation that exists between starch consumption and number of AMY1 copies specific to population suggest that more AMY1 copies in high starch populations has been selected for by natural selection and considered the favorable phenotype for those individuals. Therefore, it is most likely that the benefit of an individual possessing more copies of AMY1 in a high starch population increases fitness and produces healthier, fitter offspring.This fact is especially apparent when comparing geographically close populations with different eating habits that possess a different number of copies of the AMY1 gene. Such is the case for some Asian populations that have been shown to possess few AMY1 copies relative to some agricultural populations in Asia. This offers strong evidence that natural selection has acted on this gene as opposed to the possibility that the gene has spread through genetic drift.Variations of amylase copy number in dogs mirrors that of human populations, suggesting they acquired the extra copies as they followed humans around. Unlike humans whose amylase levels depend on starch content in diet, wild animals eating a broad range of foods tend to have more copies of amylase. This may have to do with mainly detection of starch as opposed to digestion. == References ==

Hey Aarogya!, what is Ectopic calcification

Ectopic calcification

Ectopic calcification is a pathologic deposition of calcium salts in tissues or bone growth in soft tissues. This can be a symptom of hyperphosphatemia. Formation of osseous tissue in soft tissues such as the lungs, eyes, arteries, or other organs is known as ectopic calcification, dystrophic calcification, or ectopic ossification. Causes Absorption of calcium salts normally occurs in bony tissues and is facilitated by parathyroid hormone and vitamin D. However, increased amounts of parathyroid hormone in the blood result in the deposit of calcium in soft tissues. This can be an indication of hyperparathyroidism, arteriosclerosis, or trauma to tissues. Calcification of muscle can occur after traumatic injury and is known as myositis ossificans. It can be recognized by muscle tenderness and loss of stretch in the affected area. To reduce the risk of calcification after an injury, initiate what is commonly known as "RICE" (rest, ice, compression, and elevation). Diagnosis Typically, the diagnosis of extra-skeletal ectopic calcification is quite straightforward. A physical examination of a suspected area with calcified deposits palpates as hard and rough. To confirm, the calcified tissues can be seen on an x-ray. Prognosis Ectopic ossification of the heart valves is an indicator of future heart problems, hyperparathyroidism, and necrosis of tissues. See also Subepidermal calcified nodule == References ==

Hey Aarogya!, what is Bullous keratopathy

Bullous keratopathy

Bullous keratopathy, also known as pseudophakic bullous keratopathy (PBK), is a pathological condition in which small vesicles, or bullae, are formed in the cornea due to endothelial dysfunction. In a healthy cornea, endothelial cells keeps the tissue from excess fluid absorption, pumping it back into the aqueous humor. When affected by some reason, such as Fuchs dystrophy or a trauma during cataract removal, endothelial cells suffer mortality or damage. The corneal endothelial cells normally do not undergo mitotic cell division, and cell loss results in permanent loss of function. When endothelial cell counts drop too low, the pump starts failing to function and fluid moves anterior into the stroma and epithelium. The excess fluid precipitates swelling of the cornea. As fluid accumulates between the basal epithelium cells, blister like formations form (bullae) and they undergo painful ruptures releasing their fluid content to the surface. These characteristic malformations disrupt vision and create pain sensations. Symptoms Disease begins with vesicles that coalesce. There is severe progressing edema and rupture may occur in 24 hours or less. Bullous keratopathy Treatment Treatment can include hyperosmotic eye drops to reduce swelling (5% sodium chloride), bandage contact lenses to reduce discomfort, glaucoma medications to reduce the flow of fluid into the cornea, and surgical procedures . The most common types of surgical treatment are Descemets stripping automated endothelial keratoplasty (DSAEK) and Descemets membrane endothelial keratoplasty (DMEK). Prognosis Keratopathy is common in older people. Keratopathy occurs after cataract surgery, its incidence has decreased since the advent of intraoperative viscoelastic agents that protect the endothelium. References == External links ==

Hey Aarogya!, what is Hostility

Hostility

Hostility is seen as form of emotionally charged aggressive behavior. In everyday speech it is more commonly used as a synonym for anger and aggression. It appears in several psychological theories. For instance it is a facet of neuroticism in the NEO PI, and forms part of personal construct psychology, developed by George Kelly. Hostility/hospitality For hunter gatherers, every stranger from outside the small tribal group was a potential source of hostility. Similarly, in archaic Greece, every community was in a state of hostility, latent or overt, with every other community - something only gradually tempered by the rights and duties of hospitality.Tensions between the two poles of hostility and hospitality remain a potent force in the 21st century world. Us/them Robert Sapolsky argues that the tendency to form in-groups and out-groups of Us and Them, and to direct hostility at the latter, is inherent in humans. He also explores the possibility raised by Samuel Bowles that intra-group hostility is reduced when greater hostility is directed at Thems, something exploited by insecure leaders when they mobilise external conflicts so as to reduce in-group hostility towards themselves. Non-verbal indicators Automatic mental functioning suggests that among universal human indicators of hostility are the grinding or gnashing of teeth, the clenching and shaking of fists, and grimacing. Desmond Morris would add stamping and thumping.The Haka represents a ritualised set of such non-verbal signs of hostility. Kellys model In psychological terms, George Kelly considered hostility as the attempt to extort validating evidence from the environment to confirm types of social prediction, constructs, that have failed. Instead of reconstructing their constructs to meet disconfirmations with better predictions, the hostile person attempts to force or coerce the world to fit their view, even if this is a forlorn hope, and even if it entails emotional expenditure and/or harm to self or others.In this sense hostility is a form of psychological extortion - an attempt to force reality to produce the desired feedback, even by acting out in bullying by individuals and groups in various social contexts, in order that preconceptions become ever more widely validated. Kellys theory of cognitive hostility thus forms a parallel to Leon Festingers view that there is an inherent impulse to reduce cognitive dissonance.While challenging reality can be a useful part of life, and persistence in the face of failure can be a valuable trait (for instance in invention or discovery), in the case of hostility it is argued that evidence is not being accurately assessed but rather forced into a Procrustean mould in order to maintain ones belief systems and avoid having ones identity challenged. Instead it is claimed that hostility shows evidence of suppression or denial, and is "deleted" from awareness - unfavorable evidence which might suggest that a prior belief is flawed is to various degrees ignored and willfully avoided. See also Antisocial personality disorder Death drive Narcissism of small differences Righteous indignation References External links Quotations related to Hostility at Wikiquote The dictionary definition of hostility at Wiktionary

Hello Aarogya , Do you know what is Cold sensitivity,

Cold sensitivity

Cold sensitivity or cold intolerance is unusual discomfort felt by some people when in a cool environment.There is much variation in the sensitivity to cold experienced by different people, with some putting on many layers of clothing while others in the same environment feel comfortable in one layer.Cold sensitivity may be a symptom of hypothyroidism, anemia, fibromyalgia or vasoconstriction. Vitamin B12 deficiency usually accompanies cold intolerance as well. There are other conditions that may cause a cold intolerance, including low body weight, high body temperature and low blood pressure. There may also be differences in people in the expression of uncoupling proteins, thus affecting their amount of thermogenesis. Psychology may also play a factor in perceived temperature. See also Apparent temperature Thermoception Raynaud syndrome == References ==

Hi Aarogya , Do you know what is Spontaneous coronary artery dissection,

Spontaneous coronary artery dissection

Spontaneous coronary artery dissection (SCAD) is an uncommon but dangerous condition in which one of the arteries that supply the heart spontaneously develops a blood collection, or hematoma, within the artery wall. This leads to a separation and weakening of the walls of the artery. SCAD is a major cause of heart attacks in young, otherwise healthy women without known risk factors. While the exact cause is not yet known, SCAD is likely related to changes that occur during and after pregnancy, as well as other diseases. These changes lead to the dissection of the wall which restricts blood flow to the heart and causes symptoms. SCAD is often diagnosed in the cath lab with angiography, though more advanced confirmatory tests exist. While the risk of death due to SCAD is low, it has a relatively high rate of recurrence leading to further heart attack-like symptoms in the future. It was first described in 1931. Signs and symptoms SCAD often presents like a heart attack in young to middle-aged, healthy women. This pattern usually includes chest pain, rapid heartbeat, shortness of breath, sweating, extreme tiredness, nausea, and dizziness. A minority of people with SCAD may also present in cardiogenic shock (2-5%), ventricular arrhythmias (3-11%), or after sudden cardiac death. Pregnancy- and postpartum-associated SCAD generally have worse outcomes compared to other cases. Causes Risk factors include pregnancy and the postpartum period. Evidence suggests that estrogen- and progesterone-related vascular changes affect the coronary arteries during this period, contributing to SCAD. Some case reports and case series suggest associations with autoimmune inflammatory diseases, but there have not been larger studies to explore this relationship. Underlying heritable conditions such as fibromuscular dysplasia and connective-tissue disorders (e.g., Marfan syndrome, Ehlers–Danlos syndrome, and Loeys–Dietz syndrome) are associated with SCAD, but SCAD otherwise lacks a significant genetic component. SCAD triggers may include severe physical or emotional stress, but many cases have no obvious cause. Pathophysiology SCAD symptoms are the result of a restriction in the size of the affected coronary artery. The dissection leads to a collection of blood, or hematoma, between the layers of the artery wall. The hematoma does not carry oxygen to the heart muscle but instead forms a "false lumen" that restricts the flow of blood through the "true lumen" to the heart muscle. As yet, there is no consensus on why the hematoma develops in the first place.The restriction limits the availability of oxygen and nutrients to the heart muscle, or myocardium. As a result, the myocardium continues to demand oxygen but is not adequately supplied by the coronary artery. This imbalance leads to ischemia, damage, and eventually death of myocardium, causing a heart attack (myocardial infarction). Diagnosis Given the demographics of SCAD, it is important to maintain a high index of suspicion for the condition in otherwise low-risk women presenting with symptoms of acute coronary syndrome. Initial evaluation may show ECG changes of ST elevation, like heart attacks due to other causes. SCAD comprises 2-4% of all cases of acute coronary syndrome.With typically elevated cardiac biomarkers and ECG changes, people will often undergo coronary angiography evaluation. It is important to recognize SCAD through angiography as other confirmatory measures carry increased risks. Angiography There are 3 types of SCAD based on angiographic and anatomical criteria; with the designations based on the location and extent of the hematoma within the walls of the coronary arteries. Type 1 SCAD results from an intimal tear of the coronary artery (a tear of the innermost layer of the arterial wall) creating a false lumen as blood flows into the new space. A type 1 SCAD lesion is seen on angiography or intravascular imaging as a radiolucent flap separating the two flow channels; separating the false lumen from the true lumen of the coronary artery. Type 2 SCAD, the most common type of SCAD lesions, seen in 60-75% of patients, occurs due to an intramural hematoma or a collection of blood in the muscular layer of the coronary artery wall with the absence of intimal tearing. This is seen on coronary angiography as an abrupt change in coronary caliber with a long segment of a diffusely narrowed artery (typically longer than 20 mm). Type 2 SCAD is subdivided into type 2A where the narrowed segment of the coronary artery is flanked by normal caliber segments and type 2B where the stenosis continues to the terminus of a coronary artery. Type 3 SCAD, the least common type, is also due to an intramural hematoma causing coronary stenosis, but the lesions are shorter than as seen in type 2 SCAD, being less than 20 mm in length. Due to the short segment of coronary stenosis in type 3 SCAD, it is often difficult to differentiate type 3 SCAD lesions from coronary stenosis due to atherosclerotic plaques and intra-coronary imaging is often needed to distinguish between the two. Some authors have proposed a fourth designation of SCAD, type 4 SCAD, in which there is a complete intraluminal occlusion of the coronary artery due to any of the previously mentioned types (Type 1–3). Intracoronary imaging Intracoronary imaging (ICI), consisting of intracoronary optical coherence tomography (OCT) and intravascular ultrasound (IVUS) can help distinguish SCAD from an atherosclerotic lesion when it is difficult to do so with angiography. ICI techniques provide a direct view of the walls of the coronary artery to confirm SCAD, but may actually worsen the dissection as the probes are inserted into the damaged area. ICI confers a 3.4% risk of iatrogenic dissection in people with SCAD compared to 0.2% risk in the general population. Between the two ICI methods, OCT - a newer technique - has superior spatial resolution than IVUS and is the preferred technique if ICI is required, but the need to inject extra contrast with OCT poses risk for worsening the dissection. Other methods Some studies propose coronary CT angiography to evaluate SCAD in lower-risk people, with research into the approach ongoing. Management Management depends upon the presenting symptoms. In most people who are hemodynamically stable without high-risk coronary involvement, conservative medical management with blood pressure control is recommended. In these people, especially if angiography demonstrates adequate coronary flow, the most likely course usually leads to spontaneous healing, often within 30 days. Anti-coagulation should be discontinued upon diagnosis of SCAD on coronary angiography as continuation of anti-coagulation may lead to hematoma and dissection propagation.In cases involving high-risk coronaries, hemodynamic instability, or a lack of improvement or worsening after initial attempts at treatment, urgent treatment with coronary stents or coronary artery bypass surgery may be necessary. Stents carry the risk of worsening the dissection or have an increased risk of other complications as the vessel walls in SCAD are already weak due to the disease before introducing the stent. Large studies into coronary artery bypass surgery are lacking, but this approach is used to redirect blood to the heart around the affected area for cases involving the left main coronary artery or when other approaches fail.Angina, or chest pain due to coronary insufficiency may persist for months after SCAD, sometimes even when repeat angiography shows vessel healing. Anti-anginal agents such as nitrates, calcium channel blockers and ranolazine are indicated as anti-anginal pharmacologic agents after SCAD. Control of hypertension is also indicated after SCAD, with beta blockers especially showing a reduction in the recurrence of SCAD. Statins are not recommended in the treatment post-SCAD (in the absence of other indications for statins) as the myocardial infarctions in SCAD are not the result of atherosclerotic plaques. Cardiac rehabilitation is recommended for all patients after myocardial infarction due to SCAD and is associated with a reduction in anginal symptoms increased psychological well-being. Dual antiplatelet therapy should be started after percutaneous coronary intervention (stents) is used to treat SCAD and continued for at least 1 year afterwards. Dual antiplatelet therapy during the acute phase and for at least 1 year after medically treated SCAD may be also used, based on expert consensus.Physical stress is associated with SCAD recurrence but there are no heart rate, blood pressure or weight exercise parameters that are established in those with SCAD. In general, it is recommended that those with SCAD avoid isometric exercise, high intensity endurance training, exercising to the point of exhaustion and activities involving a prolonged Valsalva to reduce the risk of SCAD recurrence.After addressing the SCAD, people are often treated with typical post-heart attack care, though people who are pregnant may need altered therapy due to the possibility of some teratogenic cardiac medications affecting fetal development. Depending on the clinical situation, providers may screen for associated connective tissue diseases. Prognosis People with SCAD have a low in-hospital mortality after treatment. However, the lesion may worsen after leaving the hospital within the first month. One study suggested a 1.2% mortality rate following SCAD but a 19.9% risk for either death, heart attacks, or strokes. Even afterwards, SCAD has a high recurrence risk at 30% within 10 years, often at a different site than the initial lesion - meaning that stents placed in the location of the first lesion may not protect against a second. Given the lack of consensus on the cause of SCAD, prevention of future SCAD may include medical therapy, counseling about becoming pregnant again (for those who had pregnancy-associated SCAD), or avoidance of oral contraceptives - as they contain estrogen and progesterone. Epidemiology SCAD is the most common cause of heart attacks in pregnant and postpartum women. Over 90% of people who develop SCAD are women. It is especially common among women aged 43–52. With angiography and improved recognition of the condition, diagnosis of SCAD has improved since the early 2010s. While prior studies had reported a SCAD prevalence of less than 1% in patients presenting with acute coronary syndrome, more recent data suggests the prevalence of SCAD in acute coronary syndrome patients may be between 2-4%. History SCAD was first described in the year 1931, at postmortem examination, in a 42-year-old woman. Due to a lack of recognition and diagnostic technology though, SCAD literature until the 21st century included only case reports and series. With the recent advent of coronary angiography and intracoronary imaging, recognition and diagnosis of SCAD has greatly increased, especially in the 2010s. See also Dissection (medical) Aortic dissection Kounis syndrome References External links "Spontaneous Coronary Artery Dissection Postpartum" "Spontaneous-Coronary-Artery-Dissection-Case-Series-and-Review"

Hello Aarogya, explain a situation where Bleeding diathesis occurs

Bleeding diathesis

In medicine (hematology), bleeding diathesis is an unusual susceptibility to bleed (hemorrhage) mostly due to hypocoagulability (a condition of irregular and slow blood clotting), in turn caused by a coagulopathy (a defect in the system of coagulation). Therefore, this may result in the reduction of platelets being produced and leads to excessive bleeding. Several types of coagulopathy are distinguished, ranging from mild to lethal. Coagulopathy can be caused by thinning of the skin (Cushings syndrome), such that the skin is weakened and is bruised easily and frequently without any trauma or injury to the body. Also, coagulopathy can be contributed by impaired wound healing or impaired clot formation. Signs and symptoms Complications Following are some complications of coagulopathies, some of them caused by their treatments: Causes While there are several possible causes, they generally result in excessive bleeding and a lack of clotting. Acquired Acquired causes of coagulopathy include anticoagulation with warfarin, liver failure, vitamin K deficiency and disseminated intravascular coagulation. Additionally, the hemotoxic venom from certain species of snakes can cause this condition, for example Bothrops, rattlesnakes and other species of viper. Viral hemorrhagic fevers include dengue hemorrhagic fever and dengue shock syndrome. Leukemia may also cause coagulopathy. Furthermore, cystic fibrosis has been known to cause bleeding diathesis, especially in undiagnosed infants, due to malabsorption of fat soluble vitamins like vitamin K. Autoimmune causes of acquired coagulation disorders There are autoimmune causes of coagulation disorders. They include acquired antibodies to coagulation factors, termed inhibitors of coagulation. The main inhibitor is directed against clotting factor VIII. Another example is antiphospholipid syndrome, an autoimmune, hypercoagulable state. Causes other than coagulation Bleeding diathesis may also be caused by impaired wound healing (as in scurvy), or by thinning of the skin, such as in Cushings syndrome. Genetic Some people lack genes that typically produce the protein coagulation factors that allow normal clotting. Various types of hemophilia and von Willebrand disease are the major genetic disorders associated with coagulopathy. Rare examples are Bernard–Soulier syndrome, Wiskott–Aldrich syndrome and Glanzmanns thrombasthenia. Gene therapy treatments may be a solution as they involve in the insertion of normal genes to replace defective genes causing for the genetic disorder. Gene therapy is a source of active research that hold promise for the future. Diagnosis Comparing coagulation tests Treatments Consult a hematologist and have a regular blood check ups. Have an early diagnostic test for any blood disorders or blood diseases including hemophilia, hemorrhage, and sickle-cell anemia. Prothrombin time and partial thromboplastin time blood tests are useful to investigate the reason behind the excessive bleeding. The PT evaluates coagulation factors I, II, V, VII and X, while the PTT evaluates coagulation factors I, II, V, VIII, IX, X, XI and XII. The analysis of both tests thus helps to diagnose certain disorders.Blood transfusion involves the transfer of plasma containing all the necessary coagulating factors (fibrinogen, prothrombin, thromboplastin) to help restore them and to improve the immune defense of the patient after excessive blood loss. Blood transfusion also caused the transfer of platelets that can work along with coagulating factors for blood clotting to commence.Different drugs can be prescribed depending on the type of disease. Vitamins (K, P and C) are essential in case of obstruction to walls of blood vessels. Also, vitamin K is required for the production of blood clotting factors, hence the injection of vitamin K (phytomenadione) is recommended to boost blood clotting. References == External links ==

Do you know what is Breast development, Aarogya

Breast development

Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a females life. It occurs across several phases, including prenatal development, puberty, and pregnancy. At menopause, breast development ceases and the breasts atrophy. Breast development results in prominent and developed structures on the chest known as breasts in primates, which serve primarily as mammary glands. The process is mediated by an assortment of hormones (and growth factors), the most important of which include estrogen, progesterone, prolactin, and growth hormone. Biochemistry Hormones The master regulators of breast development are the steroid hormones, estrogen and progesterone, growth hormone (GH), mostly via its secretory product, insulin-like growth factor 1 (IGF-1), and prolactin. These regulators induce the expression of growth factors, such as amphiregulin, epidermal growth factor (EGF), IGF-1, and fibroblast growth factor (FGF), which in turn have specific roles in breast growth and maturation.At puberty, gonadotropin-releasing hormone (GnRH) is secreted in a pulsatile manner from the hypothalamus. GnRH induces the secretion of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), from the pituitary gland. The secreted gonadotropins travel through the bloodstream to the ovaries and trigger the secretion of estrogen and progesterone in fluctuating amounts during each menstrual cycle. Growth hormone (GH), which is secreted from the pituitary gland, and insulin-like growth factor 1 (IGF-1), which is produced in the body in response to GH, are growth-mediating hormones. During prenatal development, infancy, and childhood, GH and IGF-1 levels are low, but progressively increase and reach a peak at puberty, with a 1.5- to 3-fold increase in pulsatile GH secretion and a 3-fold or greater increase in serum IGF-1 levels being capable of occurring at this time. In late adolescence and early adulthood, GH and IGF-1 levels significantly decrease, and continue to decrease throughout the rest of life. It has been found that both estrogen and GH are essential for breast development at puberty – in the absence of either, no development will take place. Moreover, most of the role of GH in breast development has been found to be mediated by its induction of IGF-1 production and secretion, as IGF-1 administration rescues breast development in the absence of GH. GH induction of IGF-1 production and secretion occurs in almost all types of tissue in the body, but especially in the liver, which is the source of approximately 80% of circulating IGF-1, as well as locally in the breasts. Although IGF-1 is responsible for most of the role of GH in mediating breast development, GH itself has been found to play a direct, augmenting role as well, as it increases estrogen receptor (ER) expression in breast stromal (connective) tissue, while IGF-1, in contrast, has been found to not do this. In addition to estrogen and GH/IGF-1 both being essential for pubertal breast development, they are synergistic in bringing it about.Despite the apparent necessity of GH/IGF-1 signaling in pubertal breast development however, women with Laron syndrome, in whom the growth hormone receptor (GHR) is defective and insensitive to GH and serum IGF-1 levels are very low, puberty, including breast development, is delayed, although full sexual maturity is always eventually reached. Moreover, breast development and size are normal (albeit delayed) in spite of GH/IGF-1 axis insufficiency, and in some the breasts may actually be large in relation to body size. The relatively large breasts in women with Laron syndrome have been suggested to be due to increased secretion of prolactin (which is known to produce breast enlargement) caused by a drift phenomenon from somatomammotrophic cells in the pituitary gland with a high GH secretion. An animal model of Laron syndrome, the GHR knockout mouse, shows severely impaired ductal outgrowth at 11 weeks of age. However, by 15 weeks, ductal development has caught up with that of normal mice and the ducts have fully distributed throughout the mammary fat pad, although the ducts remain narrower than those of wild-type mice. In any case, female GHR knockout mice can lactate normally. As such, it has been said that the phenotypes of women with Laron syndrome and GHR knockout mice are identical, with diminished body size and delayed sexual maturation accompanied by normal lactation. These data indicate that very low circulating levels of IGF-1 can nonetheless allow for full pubertal breast development. Development of the breasts during the prenatal stage of life is independent of biological sex and sex hormones. During embryonic development, the breast buds, in which networks of tubules are formed, are generated from the ectoderm. These rudimentary tubules will eventually become the matured lactiferous (milk) ducts, which connect the lobules (milk "containers") of the breast, grape-like clusters of alveoli, to the nipples. Until puberty, the tubule networks of the breast buds remain rudimentary and quiescent, and the male and female breast do not show any differences. During puberty in females, estrogen, in conjunction with GH/IGF-1, through activation of ERα specifically (and notably not ERβ or GPER), causes growth of and transformation of the tubules into the matured ductal system of the breasts. Under the influence of estrogen, the ducts sprout and elongate, and terminal end buds (TEBs), bulbous structures at the tips of the ducts, penetrate into the fat pad and branch as the ducts elongate. This continues until a tree-like network of branched ducts that is embedded into and fills the entire fat pad of the breast is formed. In addition to its role in mediating ductal development, estrogen causes stromal tissue to grow and adipose (fat) tissue to accumulate, as well as the nipple-areolar complex to increase in size.Progesterone, in conjunction with GH/IGF-1 similarly to estrogen, affects the development of the breasts during puberty and thereafter as well. To a lesser extent than estrogen, progesterone contributes to ductal development at this time, as evidenced by the findings that progesterone receptor (PR) knockout mice or mice treated with the PR antagonist mifepristone show delayed (albeit eventually normal, due to estrogen acting on its own) ductal growth during puberty and by the fact that progesterone has been found to induce ductal growth on its own in the mouse mammary gland mainly via the induction of the expression of amphiregulin, the same growth factor that estrogen primarily induces to mediate its actions on ductal development. In addition, progesterone produces modest lobuloalveolar development (alveolar bud formation or ductal sidebranching) starting at puberty, specifically through activation of PRB (and notably not PRA), with growth and regression of the alveoli occurring to some degree with each menstrual cycle. However, only rudimentary alveoli develop in response to pre-pregnancy levels of progesterone and estrogen, and lobuloalveolar development will remain at this stage until pregnancy occurs, if it does. In addition to GH/IGF-1, estrogen is required for progesterone to affect the breasts, as estrogen primes the breasts by inducing the expression of the progesterone receptor (PR) in breast epithelial tissue. In contrast to the case of the PR, ER expression in the breast is stable and differs relatively little in the contexts of reproductive status, stage of the menstrual cycle, or exogenous hormonal therapy.During pregnancy, pronounced breast growth and maturation occurs in preparation of lactation and breastfeeding. Estrogen and progesterone levels increase dramatically, reaching levels by late pregnancy that are several hundred-fold higher than usual menstrual cycle levels. Estrogen and progesterone cause the secretion of high levels of prolactin from the anterior pituitary, which reach levels as high as 20 times greater than normal menstrual cycle levels. IGF-1 and IGF-2 levels also increase dramatically during pregnancy, due to secretion of placental growth hormone (PGH). Further ductal development, by estrogen, again in conjunction with GH/IGF-1, occurs during pregnancy. In addition, the concert of estrogen, progesterone (again specifically through PRB), prolactin, and other lactogens such as human placental lactogen (hPL) and PGH, in conjunction with GH/IGF-1, as well as insulin-like growth factor 2 (IGF-2), acting together, mediate the completion of lobuloalveolar development of the breasts during pregnancy. Both PR and prolactin receptor (PRLR) knockout mice fail to show lobuloalveolar development, and progesterone and prolactin have been found to be synergistic in mediating growth of alveoli, demonstrating the essential role of both of these hormones in this aspect of breast development. Growth hormone receptor (GHR) knockout mice also show greatly impaired lobuloalveolar development. In addition to their role in lobuloalveolar growth, prolactin and hPL act to increase the size of the nipple-areolar complex during pregnancy. By the end of the fourth month of pregnancy, at which time lobuloalveolar maturation is complete, the breasts are fully prepared for lactation and breastfeeding.Insulin, glucocorticoids such as cortisol (and by extension adrenocorticotropic hormone (ACTH)), and thyroid hormones such as thyroxine (and by extension thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH)) also play permissive but less well-understood/poorly-characterized roles in breast development during both puberty and pregnancy, and are required for full functional development. Leptin has also been found to be an important factor in mammary gland development, and has been found to promote mammary epithelial cell proliferation.In contrast to the female-associated sex hormones, estrogen and progesterone, the male-associated sex hormones, the androgens, such as testosterone and dihydrotestosterone (DHT), powerfully suppress the action of estrogen in the breasts. At least one way that they do this is by reducing the expression of the estrogen receptor in breast tissue. In the absence of androgenic activity, such as in women with complete androgen insensitivity syndrome (CAIS), modest levels of estrogen (50 pg/mL) are capable of mediating significant breast development, with CAIS women showing breast volumes that are even above-average. The combination of much higher levels of androgens (about 10-fold higher) and much lower levels of estrogen (about 10-fold less), due to the ovaries in females producing high amounts of estrogens but low amounts of androgens and the testes in males producing high amounts of androgens but low amounts of estrogens, are why males generally do not grow prominent or well-developed breasts relative to females.Calcitriol, the hormonally active form of vitamin D, acting through the vitamin D receptor (VDR), has, like the androgens, been reported to be a negative regulator of mammary gland development in mice, for instance, during puberty. VDR knockout mice show more extensive ductal development relative to wild-type mice, as well as precocious mammary gland development. In addition, VDR knockout has also been shown to result in increased responsiveness of mouse mammary gland tissue to estrogen and progesterone, which was represented by increased cell growth in response to these hormones. Conversely however, it has been found that VDR knockout mice show reduced ductal differentiation, represented by an increased number of undifferentiated TEBs, and this finding has been interpreted as indicating that vitamin D may be essential for lobuloalveolar development. As such, calcitriol, via the VDR, may be a negative regulator of ductal development but a positive regulator of lobuloalveolar development in the mammary gland.A possible mechanism of the negative regulatory effects of the VDR on breast development may be indicated by a study of vitamin D3 supplementation in women which found that vitamin D3 suppresses cyclooxygenase-2 (COX-2) expression in the breast, and by doing so, reduces and increases, respectively, the levels of prostaglandin E2 (PGE2) and transforming growth factor β2 (TGF-β2), a known inhibitory factor in breast development. Moreover, suppression of PGE2 in breast tissue is relevant because, via activation of prostaglandin EP receptors, PGE2 potently induces amphiregulin expression in breast tissue, and activation of the EGFR by amphiregulin increases COX-2 expression in breast tissue, in turn resulting in more PGE2, and thus, a self-perpetuating, synergistic cycle of growth amplification due to COX-2 appears to potentially be present in normal breast tissue. Accordingly, overexpression of COX-2 in mammary gland tissue produces mammary gland hyperplasia as well as precocious mammary gland development in female mice, mirroring the phenotype of VDR knockout mice, and demonstrating a strong stimulatory effect of COX-2, which is downregulated by VDR activation, on the growth of the mammary glands. Also in accordance, COX-2 activity in the breasts has been found to be positively associated with breast volume in women. Growth factors Estrogen, progesterone, and prolactin, as well as GH/IGF-1, produce their effects on breast development by modulating the local expression in breast tissue of an assortment of autocrine and paracrine growth factors, including IGF-1, IGF-2, amphiregulin, EGF, FGF, hepatocyte growth factor (HGF), tumor necrosis factor α (TNF-α), tumor necrosis factor β (TNF-β), transforming growth factor α (TGF-α), transforming growth factor β (TGF-β), heregulin, Wnt, RANKL, and leukemia inhibitory factor (LIF). These factors regulate cellular growth, proliferation, and differentiation via activation of intracellular signaling cascades that control cell function, such as Erk, Akt, JNK, and Jak/Stat.Based on research with epidermal growth factor receptor (EGFR) knockout mice, the EGFR, which is the molecular target of EGF, TGF-α, amphiregulin, and heregulin, has, similarly to the insulin-like growth factor-1 receptor (IGF-1R), been found to be essential for mammary gland development. Estrogen and progesterone mediate ductal development mainly through induction of amphiregulin expression, and thus downstream EGFR activation. Accordingly, ERα, amphiregulin, and EGFR knockout mice copy each other phenotypically in regards to their effects on ductal development. Also in accordance, treatment of mice with amphiregulin or other EGFR ligands like TGF-α or heregulin induces ductal and lobuloalveolar development in the mouse mammary gland, actions that occur even in the absence of estrogen and progesterone. As both the IGF-1R and the EGFR are independently essential for mammary gland development, and as combined application of IGF-1 and EGF, through their respective receptors, has been found to synergistically stimulate the growth of human breast epithelial cells, these growth factor systems appear to work together in mediating breast development.Elevated levels of HGF and, to a lesser extent, IGF-1 (by 5.4-fold and 1.8-fold, respectively), in breast stromal tissue, have been found in macromastia, a very rare condition of extremely and excessively large breast size. Exposure of macromastic breast stromal tissue to non-macromastic breast epithelial tissue was found to cause increased alveolar morphogenesis and epithelial proliferation in the latter. A neutralizing antibody for HGF, but not for IGF-1 or EGF, was found to attenuate the proliferation of breast epithelial tissue caused by exposure to macromastic breast stromal cells, potentially directly implicating HGF in the breast growth and enlargement seen in macromastia. Also, a genome-wide association study has highly implicated HGF and its receptor, c-Met, in breast cancer aggressiveness. Lactation Upon parturition (childbirth), estrogen and progesterone rapidly drop to very low levels, with progesterone levels being undetectable. Conversely, prolactin levels remain elevated. As estrogen and progesterone block prolactin-induced lactogenesis by suppressing prolactin receptor (PRLR) expression in breast tissue, their sudden absence results in the commencement of milk production and lactation by prolactin. Expression of the PRLR in breast tissue may increase by as much as 20-fold when estrogen and progesterone levels drop upon childbirth. With suckling from the infant, prolactin and oxytocin are secreted and mediate milk production and letdown, respectively. Prolactin suppresses the secretion of LH and FSH, which in turn results in continued low levels of estrogen and progesterone, and temporary amenorrhea (absence of menstrual cycles) occurs. In the absence of regular, episodic suckling, which keeps prolactin concentrations high, levels of prolactin will quickly drop, the menstrual cycle will resume and hence normal estrogen and progesterone levels will return, and lactation will cease (that is, until next parturition, or until induced lactation (i.e., with a galactogogue), occurs). Breast size and cancer risk Some factors of breast morphology, including their density, are clearly implicated in breast cancer. While breast size is moderately heritable, the relationship between breast size and cancer is uncertain. The genetic variants influencing breast size have not been identified.Through genome-wide association studies, a variety of genetic polymorphisms have been linked to breast size. Some of these include rs7816345 near ZNF703 (zinc finger protein 703); rs4849887 and rs17625845 flanking INHBB (inhibin βB); rs12173570 near ESR1 (ERα); rs7089814 in ZNF365 (zinc finger protein 365); rs12371778 near PTHLH (parathyroid hormone-like hormone); rs62314947 near AREG (amphiregulin); as well as rs10086016 at 8p11.23 (which is in complete linkage disequilibrium with rs7816345) and rs5995871 at 22q13 (contains the MKL1 gene, which has been found to modulate the transcriptional activity of ERα). Many of these polymorphisms are also associated with the risk of developing breast cancer, revealing a potential positive association between breast size and breast cancer risk. However, conversely, some polymorphisms show a negative association between breast size and breast cancer risk. In any case, a meta-analysis concluded that breast size and risk of breast cancer are indeed importantly related.Circulating IGF-1 levels are positively associated with breast volume in women. In addition, the absence of the common 19-repeat allele in the IGF1 gene is also positively associated with breast volume in women, as well as with high IGF-1 levels during oral contraceptive use and with lessening of the normal age-associated decline in circulating IGF-1 concentrations in women. There is great variation in the prevalence of the IGF1 19-repeat allele between ethnic groups, and its absence has been reported to be highest among African-American women.Genetic variations in the androgen receptor (AR) have been linked to both breast volume (as well as body mass index) and breast cancer aggressiveness.COX-2 expression has been positively associated with breast volume and inflammation in breast tissue, as well as with breast cancer risk and prognosis. Rare mutations Women with CAIS, who are completely insensitive to the AR-mediated actions of androgens, have, as a group, above-average sized breasts. This is true despite the fact that they simultaneously have relatively low levels of estrogen, which demonstrates the powerful suppressant effect of androgens on estrogen-mediated breast development.Aromatase excess syndrome, an extremely rare condition characterized by marked hyperestrogenism, is associated with precocious breast development and macromastia in females and similarly precocious gynecomastia (womens breasts) in males. In complete androgen insensitivity syndrome, a condition in which the AR is defective and insensitive to androgens, there is full breast development with breast volumes that are in fact above average in spite of relatively low levels of estrogen (50 pg/mL estradiol). In aromatase deficiency, a form of hypoestrogenism in which aromatase is defective and cannot synthesize estrogen, and in complete estrogen insensitivity syndrome, a condition in which ERα is defective and insensitive to estrogen, breast development is completely absent. See also Breast augmentation Breast enlargement Mammoplasia Premenstrual water retention Thelarche References Further reading Hovey, Russell C.; Aimo, Lucila (2010). "Diverse and Active Roles for Adipocytes During Mammary Gland Growth and Function". Journal of Mammary Gland Biology and Neoplasia. 15 (3): 279–290. doi:10.1007/s10911-010-9187-8. ISSN 1083-3021. PMC 2941079. PMID 20717712. Sun, Susie X.; Bostanci, Zeynep; Kass, Rena B.; Mancino, Anne T.; Rosenbloom, Arlan L.; Klimberg, V. Suzanne; Bland, Kirby I. (2018). "Breast Physiology". The Breast. pp. 37–56.e6. doi:10.1016/B978-0-323-35955-9.00003-9. ISBN 9780323359559.

Aarogya , Do you know what is Asterixis,

Asterixis

Asterixis, more colloquially referred to as flapping tremor, is a tremor of the hand when the wrist is extended, sometimes said to resemble a bird flapping its wings. This motor disorder is characterized by an inability to maintain a position, which is demonstrated by jerking movements of the outstretched hands when bent upward at the wrist. The tremor is caused by abnormal function of the diencephalic motor centers in the brain, which regulate the muscles involved in maintaining position. Asterixis is associated with various encephalopathies due especially to faulty metabolism. The term derives from the Greek a, "not" and stērixis, "fixed position". Asterixis is the inability to maintain posture due to a metabolic encephalopathy. This can be elicited on physical exam by having the patient extend their arms and bend their hands back. With a metabolic encephalopathy, the patient is unable to hold their hands back resulting in a “flapping” motion consistent with asterixis. It can be seen in any metabolic encephalopathy e.g. chronic kidney failure, severe congestive heart failure, acute respiratory failure and commonly in decompensated liver failure. Associated conditions and presentation Usually there are brief, arrhythmic interruptions of sustained voluntary muscle contraction causing brief lapses of posture, with a frequency of 3–5 Hz. It is bilateral, but may be asymmetric. Unilateral asterixis may occur with structural brain disease. It can be a sign of hepatic encephalopathy, damage to brain cells presumably due to the inability of the liver to metabolize ammonia to urea. The cause is thought to be predominantly related to abnormal ammonia metabolism. Asterixis is seen most often in drowsy or stuporous patients with metabolic encephalopathies, especially in decompensated cirrhosis or acute liver failure. It is also seen in some patients with kidney failure and azotemia. It can also be a feature of Wilsons disease. Asterixis is also seen in respiratory failure due to carbon dioxide toxicity (hypercapnia). Some drugs are known to cause asterixis, particularly phenytoin (when it is known as phenytoin flap). Other drugs implicated include benzodiazepines, salicylates, barbiturates, valproate, gabapentin, lithium, ceftazidime, and metoclopramide. History R.D. Adams and J.M. Foley first described asterixis in 1949 in patients with severe liver failure and encephalopathy. Initially Foley and Adams referred to asterixis simply as "tremor" but realized that they needed a more appropriate term. On a literature search they found a poorly described phenomenon in similar patients mentioned by German physicians called “jactitations” but the reference was vague. Foley consulted Father Cadigan, a Jesuit classics scholar, who suggested “anisosterixis” (an "negative"–iso "equal"–sterixis "firmness") but Foley shortened this to asterixis due to the former being too difficult to pronounce. They introduced the term in 1953 by way of a medical abstract and later Adams solidified its medical use as he was an author and editor of the widely influential Harrisons Principles of Internal Medicine. References External links Diagram

Hi Aarogya, could you help me understand about Tetraplegia

Tetraplegia

Tetraplegia, also known as quadriplegia, is paralysis caused by illness or injury that results in the partial or total loss of use of all four limbs and torso; paraplegia is similar but does not affect the arms. The loss is usually sensory and motor, which means that both sensation and control are lost. The paralysis may be flaccid or spastic. Signs and symptoms Although the most obvious symptom is impairment of the limbs, functioning is also impaired in the torso. This can mean a loss or impairment in controlling bowel and bladder, sexual function, digestion, breathing and other autonomic functions. Furthermore, sensation is usually impaired in affected areas. This can manifest as numbness, reduced sensation or burning neuropathic pain. Secondarily, because of their depressed functioning and immobility, people with tetraplegia are often more vulnerable to pressure sores, osteoporosis and fractures, frozen joints, spasticity, respiratory complications and infections, autonomic dysreflexia, deep vein thrombosis, and cardiovascular disease.The severity of the condition depends on both the level at which the spinal cord is injured and the extent of the injury. An individual with an injury at C1 (the highest cervical vertebra, at the base of the skull) will probably lose function from the neck down and be ventilator-dependent. An individual with a C7 injury may lose function from the chest down but still retain use of the arms and much of the hands. The extent of the injury is also important. A complete severing of the spinal cord will result in complete loss of function from that vertebra down. A partial severing or even bruising of the spinal cord results in varying degrees of mixed function and paralysis. A common misconception with tetraplegia is that the victim cannot move legs, arms or any of the major function; this is often not the case. Some individuals with tetraplegia can walk and use their hands, as though they did not have a spinal cord injury, while others may use wheelchairs and they can still have function of their arms and mild finger movement; again, that varies on the spinal cord damage.It is common to have movement in limbs, such as the ability to move the arms but not the hands, or to be able to use the fingers but not to the same extent as before the injury. Furthermore, the deficit in the limbs may not be the same on both sides of the body; either left or right side may be more affected, depending on the location of the lesion on the spinal cord. Causes Tetraplegia is caused by damage to the brain or the spinal cord at a high level. The injury, which is known as a lesion, causes the loss of partial or total function of all four limbs, meaning the arms and the legs. Typical causes of this damage are trauma (such as a traffic collision, diving into shallow water, a fall, a sports injury), disease (such as transverse myelitis, Guillain–Barré syndrome, multiple sclerosis, or polio), or congenital disorders (such as muscular dystrophy).Tetraplegia is defined in many ways; C1–C4 usually affects arm movement more so than a C5–C7 injury; however, all tetraplegics have or have had some kind of finger dysfunction. So, it is not uncommon to have a tetraplegic with fully functional arms but no nervous control of their fingers and thumbs. It is possible to have a broken neck without becoming tetraplegic if the vertebrae are fractured or dislocated but the spinal cord is not damaged. Conversely, it is possible to injure the spinal cord without breaking the spine, for example when a ruptured disc or bone spur on the vertebra protrudes into the spinal column. Diagnosis Classification Spinal cord injuries are classified as complete and incomplete by the American Spinal Injury Association (ASIA) classification. The ASIA scale grades patients based on their functional impairment as a result of the injury, grading a patient from A to D. This has considerable consequences for surgical planning and therapy. Complete spinal-cord lesions Pathophysiologically, the spinal cord of a person with tetraplegia can be divided into three segments which can be useful for classifying the injury. First, there is an injured functional medullary segment. This segment has unparalysed, functional muscles; the action of these muscles is voluntary, not permanent and hand strength can be evaluated by the Medical Research Council (MRC) Scale. This scale is used when upper limb surgery is planned, as referred to in the International Classification for hand surgery in tetraplegic patients.A lesional segment (or an injured metamere) consists of denervated corresponding muscles. The lower motor neuron (LMN) of these muscles is damaged. These muscles are hypotonic, atrophic and have no spontaneous contraction. The existence of joint contractures should be monitored.Below the level of the injured metamere, there is an injured sublesional segment with the intact lower motor neuron, which means that medullary reflexes are present, but the upper cortical control is lost. These muscles show some increase in tone when elongated and sometimes spasticity, the trophicity is good. Incomplete spinal-cord lesions Incomplete spinal cord injuries result in varied post injury presentations. There are three main syndromes described, depending on the exact site and extent of the lesion. Central cord syndrome: most of the cord lesion is in the gray matter of the spinal cord, sometimes the lesion continues in the white matter. Brown-Séquard syndrome: hemisection of the spinal cord. Anterior cord syndrome: a lesion of the anterior horns and the anterolateral tracts, with a possible division of the anterior spinal artery.For most patients with ASIA A (complete) tetraplegia, ASIA B (incomplete) tetraplegia and ASIA C (incomplete) tetraplegia, the International Classification level of the patient can be established without great difficulty. The surgical procedures according to the International Classification level can be performed. In contrast, for patients with ASIA D (incomplete) tetraplegia it is difficult to assign an International Classification other than International Classification level X (others). Therefore, it is more difficult to decide which surgical procedures should be performed. A far more personalized approach is needed for these patients. Decisions must be based more on experience than on texts or journals.The results of tendon transfers for patients with complete injuries are predictable. On the other hand, it is well known that muscles lacking normal excitation perform unreliably after surgical tendon transfers. Despite the unpredictable aspect in incomplete lesions, tendon transfers may be useful. The surgeon should be confident that the muscle to be transferred has enough power and is under good voluntary control. Pre-operative assessment is more difficult to assess in incomplete lesions.Patients with an incomplete lesion also often need therapy or surgery before the procedure to restore function to correct the consequences of the injury. These consequences are hypertonicity/spasticity, contractures, painful hyperesthesias and paralyzed proximal upper limb muscles with distal muscle sparing.Spasticity is a frequent consequence of incomplete injuries. Spasticity often decreases function, but sometimes a patient can control the spasticity in a way that it is useful to their function. The location and the effect of the spasticity should be analyzed carefully before treatment is planned. An injection of Botulinum toxin (Botox) into spastic muscles is a treatment to reduce spasticity. This can be used to prevent muscle shortening and early contractures.Over the last ten years, an increase in traumatic incomplete lesions is seen, due to the better protection in traffic. Treatment Upper limb paralysis refers to the loss of function of the elbow and hand. When upper limb function is absent as a result of a spinal cord injury it is a major barrier to regain autonomy. People with tetraplegia should be examined and informed concerning the options for reconstructive surgery of the tetraplegic arms and hands. Prognosis Delayed diagnosis of cervical spine injury has grave consequences for the victim. About one in 20 cervical fractures are missed and about two-thirds of these patients have further spinal-cord damage as a result. About 30% of cases of delayed diagnosis of cervical spine injury develop permanent neurological deficits. In high-level cervical injuries, total paralysis from the neck can result. High-level tetraplegics (C4 and higher) will likely need constant care and assistance in activities of daily living, such as getting dressed, eating and bowel and bladder care. Low-level tetraplegics (C5 to C7) can often live independently.Even with "complete" injuries, in some rare cases, through intensive rehabilitation, slight movement can be regained through "rewiring" neural connections, as in the case of actor Christopher Reeve.In the case of cerebral palsy, which is caused by damage to the motor cortex either before, during (10%), or after birth, some people with tetraplegia are gradually able to learn to stand or walk through physical therapy.Quadriplegics can improve muscle strength by performing resistance training at least three times per week. Combining resistance training with proper nutrition intake can greatly reduce co-morbidities such as obesity and type 2 diabetes. Epidemiology There are an estimated 17,700 spinal cord injuries each year in the United States; the total number of people affected by spinal cord injuries is estimated to be approximately 290,000 people.In the US, spinal cord injuries alone cost approximately US$40.5 billion each year, which is a 317 percent increase from costs estimated in 1998 ($9.7 billion).The estimated lifetime costs for a 25-year-old in 2018 is $3.6 million when affected by low tetraplegia and $4.9 million when affected by high tetraplegia. In 2009, it was estimated that the lifetime care of a 25-year-old rendered with low tetraplegia was about $1.7 million, and $3.1 million with high tetraplegia.There are about 1,000 people affected each year in the UK (~1 in 60,000—assuming a population of 60 million). Terminology The condition of paralysis affecting four limbs is alternately termed tetraplegia or quadriplegia. Quadriplegia combines the Latin root quadra, for "four", with the Greek root πληγία plegia, for "paralysis". Tetraplegia uses the Greek root τετρα tetra for "four". Quadriplegia is the common term in North America; tetraplegia is more commonly used in Europe. See also Clearing the cervical spine Hemiplegia Locked-in syndrome Sexuality after spinal cord injury Spinal cord injury research References Citations External links Tetraplegia at Curlie

Aarogya, could you share information about a health condition involving Menstrual disorder

Menstrual disorder

A menstrual disorder is characterized as any abnormal condition with regards to a persons menstrual cycle. There are many different types of menstrual disorders that vary with signs and symptoms, including pain during menstruation, heavy bleeding, or absence of menstruation. Normal variations can occur in menstrual patterns but generally menstrual disorders can also include periods that come sooner than 21 days apart, more than 3 months apart, or last more than 10 days in duration. Variations of the menstrual cycle are mainly caused by the immaturity of the hypothalamic-pituitary-ovarian (HPO) axis, and early detection and management is required in order to minimize the possibility of complications regarding future reproductive ability.Though menstrual disorders were once considered more of a nuisance problem, they are now widely recognized as having a serious impact on society in the form of days lost from work brought about by the pain and suffering experienced by women. These disorders can arise from physiologic sources (pregnancy etc.), pathologic sources (stress, excessive exercise, weight loss, endocrine or structural abnormalities etc.), or iatrogenic sources (secondary to contraceptive use etc.). Types of menstrual disorders Premenstrual Disorders Premenstrual syndrome (PMS) or premenstrual tension refers to the emotional and physical symptoms that routinely occur in the two weeks leading up to menstruation. Symptoms are usually mild, but 5-8% of women experience moderate to severe symptoms that significantly affect daily activities. Symptoms may include anxiety, irritability, mood swings, depression, headache, food cravings, increased appetite, and bloating. Premenstrual dysphoric disorder (PMDD) is a severe mood disorder that affects cognitive and physical functions in the week leading up to menstruation. Premenstrual dysphoric disorder is diagnosed with at least one affective, or mood, symptom and at least five physical, mood, and/or behavioral symptoms. Disorders of cycle length Normal menstrual cycle length is 22–45 days. Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiologic states of amenorrhoea are seen during pregnancy and lactation (breastfeeding). Outside of the reproductive years there is absence of menses during childhood and after menopause. Irregular menstruation is where there is variation in menstrual cycle length of more than approximately 8 days for a woman. The term metrorrhagia is often used for irregular menstruation that occurs between the expected menstrual periods. Oligomenorrhea is the medical term for infrequent, often light menstrual periods (intervals exceeding 35 days). Polymenorrhea is the medical term for cycles with intervals of 21 days or fewer. Disorders of flow Normal menstrual flow length is 3–7 days. Abnormal uterine bleeding (AUB) is a broad term used to describe any disruption in bleeding that involves the volume, duration, and/or regularity of flow. Bleeding may occur frequently or infrequently, and can occur between periods, after sexual intercourse, and after menopause. Bleeding during pregnancy is excluded. Hypomenorrhea is abnormally light menstrual bleeding. Menorrhagia (meno = prolonged, rrhagia = excessive flow/discharge) is an abnormally heavy and prolonged menstrual period. Metrorrhagia is bleeding at irregular times, especially outside the expected intervals of the menstrual cycle. If there is excessive menstrual and uterine bleeding other than that caused by menstruation, menometrorrhagia (meno = prolonged, metro = time, rrhagia = excessive flow/discharge) may be diagnosed. Causes may be due to abnormal blood clotting, disruption of normal hormonal regulation of periods or disorders of the endometrial lining of the uterus. Depending upon the cause, it may be associated with abnormally painful periods. Disorders of ovulation Disorders of ovulation include oligoovulation and anovulation: Anovulation is absence of ovulation when it would be normally expected (in a post-menarchal, premenopausal woman). Anovulation usually manifests itself as irregularity of menstrual periods, that is, unpredictable variability of intervals, duration, or bleeding. Anovulation can also cause cessation of periods (secondary amenorrhea) or excessive bleeding (dysfunctional uterine bleeding). Oligoovulation is infrequent or irregular ovulation (usually defined as cycles of >35 days or <8 cycles a year). Other menstrual disorders Dysmenorrhea (or dysmenorrhoea), cramps or painful menstruation, involves menstrual periods that are accompanied by either sharp, intermittent pain or dull, aching pain, usually in the pelvis or lower abdomen. Signs and symptoms of menstrual disorders The signs and symptoms of menstrual disorders can cause significant stress. Abnormal uterine bleeding (AUB) has the potential to be one of the most urgent gynecological problems during menstruation. Dysmenorrhea is the most common. Premenstrual Syndrome (PMS) Symptoms may include irritability, bloating, depression, food cravings, aggressiveness, and mood swings. Fluid retention and fluctuating weight gain are also reported.Precipitating risk factors include: stress, alcohol consumption, exercise, smoking, and some medications. Amenorrhea Lack of a menses by the age of 16 where secondary sexual characteristics have developed or by the age of 14 where no secondary sexual characteristics have developed (primary amenorrhea), or lack of a menses for more than 3–6 months after first menstruation cycle. Although missing a period is the main sign, other symptoms can include: excess facial, hair loss, headache, changes to vision, milky discharge from the breasts, or absence of breast development. Abnormal Uterine Bleeding One-third of women will experience abnormal uterine bleeding in their life. Normal menstrual cycle has a frequency of 24 to 38 days, lasts 7 to 9 days, so bleeding that lasts longer could be considered abnormal. Very heavy bleeding (for example, needing to use 1 or more tampons or sanitary pads every hour) is another symptom. Dysmenorrhea Especially painful or persistent menstrual cramping that occurs in the absence of any underlying pelvic disease.Pain radiating to the low back or upper thighs with onset of menstruation and lasting anywhere from 12 to 72 hours. Headache, nausea, vomiting, diarrhea, and fatigue may also accompany the pain. Pain may begin gradually, with the first several years of menses, and then intensified as menstruation becomes regular. Patients who also have secondary amenorrhea report symptoms beginning after age 20 and lasting 5–7 days with progressive worsening of pain over time. Pelvic pain is also reported. Causes of menstrual disorders There are many causes of menstrual disorders, including uterine fibroids, hormonal imbalances, clotting disorders, cancer, sexually-transmitted infections, polycystic ovary syndrome, and genetics. Uterine fibroids are benign, non-cancerous growths in the uterus that affect most women at some point in their lives and usually does not require treatment unless they cause intolerable symptoms. Stress and lifestyle factors commonly impact menstruation, which includes weight changes, dieting, changes in exercise, travel, and illness.Hyperprolactinaemia can also cause menstrual disorders. Amenorrhea There are different causes depending on the type of menstrual(period) disorder. Amenorrhea, or the absence of menstruation, is subdivided into primary and secondary amenorrhea. In primary amenorrhea, in which there is a failure to menstruate by the age of 16 with normal sexual development or by 14 without normal sexual development, causes can be from developmental abnormalities of the uterus, ovaries, or genital tract, or endocrine disorders. In secondary amenorrhea, or the absence of menstruation for greater than 6 months, can be caused by the same reasons as primary amenorrhea, as well as polycystic ovary syndrome, pregnancy, chronic illness, and certain drugs like cocaine and opioids. Hypomenorrhea Causes of hypomenorrhea, or irregular light periods, include periods around menopause, eating disorders, excessive exercise, thyroid dysfunction, uncontrolled diabetes, Cushings syndrome, hormonal birth control, and certain medications to treat epilepsy or mental health conditions. Menorrhagia Causes of menorrhagia, or heavy menstrual bleeding, include polycystic ovary syndrome, uterine fibroids, endometrial polyps, bleeding disorders, and miscarriage. Dysmenorrhea Causes of dysmenorrhea, or menstrual pain, include endometriosis, pelvic scarring due to chlamydia or gonorrhea, and intrauterine devices or IUDs. Primary dysmenorrhea is when there is no underlying cause that is identified, and secondary dysmenorrhea is when the menstrual pain is caused by other conditions such as endometriosis, fibroids, or infection. Diagnosis of menstrual disorders Diagnosis begins with an in-depth medical history and physical exam, including a pelvic exam and sometimes a Pap smear.Additional testing may include but are not limited to blood tests, hormonal tests, ultrasound, gynecologic ultrasound, magnetic resonance imaging (MRI), hysteroscopy, laparoscopy, endometrial biopsy, and dilation and curettage (D&C). Treatment of menstrual disorders Premenstrual syndrome and premenstrual dysphoric disorder Due to the unclear etiology of premenstrual syndrome and premenstrual dysphoric disorder, symptom relief is the primary goal of treatment. Selective serotonin reuptake inhibitors and spironolactone decrease physical and psychological symptoms associated with premenstrual syndrome. Oral contraceptives may ameliorate physical symptoms of breast tenderness and bloating. Ovarian suppression treatment with gonadotropin-releasing hormone agonist as an off-label use may reduce symptoms but have adverse side effects including decreased bone density. Other less commonly use medications such as alprazolam may reduce anxiety symptoms but has potential for dependence, tolerance, and abuse. Pyridoxine, a form of vitamin B6, may be used as a dietary supplement to relieve overall symptoms. Amenorrhea Successful treatment varies depending on the diagnosis of amenorrhea. In patients with functional hypothalamic amenorrhea due to physical or psychological stress, non-pharmacological options include weight gain, resolution of emotional issues, or decreased intensity of exercise. Patients experiencing amenorrhea due to hypothyroidism may be started with thyroid replacement therapy. Dopamine agonists such as bromocriptine are used in patients with pituitary adenomas. Amenorrhea associated with gonadal dysgenesis or a hypoestrogenic state may be treated with oral contraceptives, patches, or vaginal rings.Amenorrhea associated with structural anomalies can be addressed with surgical treatment such as gonadectomy. Menorrhagia Acute management of menstrual bleeding includes hormonal therapy with estrogen or oral contraceptives until bleeding has stopped followed by an oral contraceptive tapering regimen. Adjunctive therapy may include iron supplements and nonsteroidal anti-inflammatory drugs. Patients who do not respond to hormonal therapy may use antifibrinolytics. Procedural therapy such as a suction curettage and intrauterine balloon tamponade are reserved for patients who do not respond to medication therapy and do not put fertility at risk. Life-threatening situations may consider more invasive procedures such as endometrial ablation, uterine artery embolization, and hysterectomy.Long-term management include estrogen-containing therapy and progestin therapy. Dysmenorrhea Primary dysmenorrhea is commonly treated with nonsteroidal anti-inflammatory drugs such as ibuprofen to reduce moderate to severe pain. Other simple analgesics such as aspirin or acetaminophen are less commonly used but may also reduce short-term pain. Supplements including thiamine and vitamin E may reduce pain in younger women. Non-pharmacological interventions such as the use of external heat are also effective at reducing pain. Regular exercises can also reduce pain. See also References External links NIH Putting tampon in painlessly

Aarogya, Please give me a short description about Hyperkinesia

Hyperkinesia

Hyperkinesia refers to an increase in muscular activity that can result in excessive abnormal movements, excessive normal movements, or a combination of both. Hyperkinesia is a state of excessive restlessness which is featured in a large variety of disorders that affect the ability to control motor movement, such as Huntingtons disease. It is the opposite of hypokinesia, which refers to decreased bodily movement, as commonly manifested in Parkinsons disease. Many hyperkinetic movements are the result of improper regulation of the basal ganglia–thalamocortical circuitry. Overactivity of a direct pathway combined with decreased activity of indirect pathway results in activation of thalamic neurons and excitation of cortical neurons, resulting in increased motor output. Often, hyperkinesia is paired with hypotonia, a decrease in muscle tone. Many hyperkinetic disorders are psychological in nature and are typically prominent in childhood. Depending on the specific type of hyperkinetic movement, there are different treatment options available to minimize the symptoms, including different medical and surgical therapies. The word hyperkinesis comes from the Greek hyper, meaning "increased," and kinein, meaning "to move." Classification Basic hyperkinetic movements can be defined as any unwanted, excess movement. Such abnormal movements can be distinguished from each other on the basis of whether or not, or to what degree they are, rhythmic, discrete, repeated, and random. In evaluating the individual with a suspected form of hyperkinesia, the physician will record a thorough medical history, including a clear description of the movements in question, medications prescribed in the past and present, family history of similar diseases, medical history, including past infections, and any past exposure to toxic chemicals. Hyperkinesia is a defining feature of many childhood movement disorders, yet distinctly differs from both hypertonia and negative signs, which are also typically involved in such disorders. Several prominent forms of hyperkinetic movements include: Ataxia The term ataxia refers to a group of progressive neurological diseases that alter coordination and balance. Ataxias are often characterized by poor coordination of hand and eye movements, speech problems, and a wide-set, unsteady gait. Possible causes of ataxias may include stroke, tumor, infection, trauma, or degenerative changes in the cerebellum. These types of hyperkinetic movements can be further classified into two groups. The first group, hereditary ataxias, affect the cerebellum and spinal cord and are passed from one generation to the next through a defective gene. A common hereditary ataxia is Friedreichs ataxia. in contrast, sporadic ataxias occur spontaneously in individuals with no known family history of such movement disorders. Athetosis Athetosis is defined as a slow, continuous, involuntary writhing movement that prevents the individual from maintaining a stable posture. These are smooth, nonrhythmic movements that appear random and are not composed of any recognizable sub-movements. They mainly involve the distal extremities, but can also involve the face, neck, and trunk. Athetosis can occur in the resting state, as well as in conjunction with chorea and dystonia. When combined with o, as in cerebral palsy, the term "choreoathetosis" is frequently used. Chorea Chorea is a continuous, random-appearing sequence of one or more discrete involuntary movements or movement fragments. Although chorea consists of discrete movements, many are often strung together in time, thus making it difficult to identify each movements start and end point. These movements can involve the face, trunk, neck, tongue, and extremities. Unlike dystonic movements, chorea-associated movements are often more rapid, random and unpredictable. Movements are repeated, but not rhythmic in nature. Children with chorea appear fidgety and will often try to disguise the random movements by voluntarily turning the involuntary, abnormal movement into a seemingly more normal, purposeful motion. Chorea may result specifically from disorders of the basal ganglia, cerebral cortex, thalamus, and cerebellum. It has also been associated with encephalitis, hyperthyroidism, anticholinergic toxicity, and other genetic and metabolic disorders. Chorea is also the prominent movement featured in Huntingtons disease. Dystonia Dystonia is a movement disorder in which involuntarily sustained or intermittent muscle contractions cause twisting or repetitive movements, abnormal postures, or both. Such abnormal postures include foot inversion, wrist ulnar deviation, or lordotic trunk twisting. They can be localized to specific parts of the body or be generalized to many different muscle groups. These postures are often sustained for long periods of time and can be combined in time. Dystonic movements can augment hyperkinetic movements, especially when linked to voluntary movements.Blepharospasm is a type of dystonia characterized by the involuntary contraction of the muscles controlling the eyelids. Symptoms can range from a simple increased frequency of blinking to constant, painful eye closure leading to functional blindness.Oromandibular dystonia is a type of dystonia marked by forceful contractions of the lower face, which causes the mouth to open or close. Chewing motions and unusual tongue movements may also occur with this type of dystonia.Laryngeal dystonia or spasmodic dysphonia results from abnormal contraction of muscles in the voice box, resulting in altered voice production. Patients may have a strained-strangled quality to their voice or, in some cases, a whispering or breathy quality.Cervical dystonia (CD) or spasmodic torticollis is characterized by muscle spasms of the head and neck, which may be painful and cause the neck to twist into unusual positions or postures.Writers cramp and musicians cramp is a task-specific dystonia, meaning that it only occurs when performing certain tasks. Writers cramp is a contraction of hand and/or arm muscles that happens only when a patient is writing. It does not occur in other situations, such as when a patient is typing or eating. Musicians cramp occurs only when a musician plays an instrument, and the type of cramp experienced is specific to the instrument. For example, pianists may experience cramping of their hands when playing, while brass players may have cramping or contractions of their mouth muscles. Hemiballismus Typically caused by damage to the subthalamic nucleus or nuclei, hemiballismus movements are nonrhythmic, rapid, nonsuppressible, and violent. They usually occur in an isolated body part, such as the proximal arm. Hemifacial spasm Hemifacial spasm (HFS) is characterized by involuntary contraction of facial muscles, typically occurring only on one side of the face. Like blepharospasm, the frequency of contractions in hemifacial spasm may range from intermittent to frequent and constant. The unilateral blepharospasm of HFS may interfere with routine tasks such as driving. In addition to medication, patients may respond well to treatment with Botox. HFS may be due to vascular compression of the nerves going to the muscles of the face. For these patients, surgical decompression may be a viable option for the improvement of symptoms. Myoclonus Myoclonus is defined as a sequence of repeated, often nonrhythmic, brief, shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles. These movements may be asynchronous, in which several muscles contract variably in time, synchronous, in which muscles contract simultaneously, or spreading, in which several muscles contract sequentially. It is characterized by a sudden, unidirectional movement due to muscle contraction, followed by a relaxation period in which the muscle is no longer contracted. However, when this relaxation phase is decreased, as when muscle contractions become faster, a myoclonic tremor results. Myoclonus can often be associated with seizures, delirium, dementia, and other signs of neurological disease and gray matter damage. Stereotypies Stereotypies are repetitive, rhythmic, simple movements that can be voluntarily suppressed. Like tremors, they are typically back and forth movements, and most commonly occur bilaterally. They often involve fingers, wrists, or proximal portions of the upper extremities. Although, like tics, they can stem from stress or excitement, there is no underlying urge to move associated with stereotypies and these movements can be stopped with distraction. When aware of the movements, the child can also suppress them voluntarily. Stereotypies are often associated with developmental syndromes, including the autism spectrum disorders. Stereotypies are quite common in preschool-aged children and for this reason are not necessarily indicative of neurological pathology on their own. Tardive dyskinesia / tardive dystonia Tardive dyskinesia or tardive dystonia, both referred to as "TD", refers to a wide variety of involuntary stereotypical movements caused by the prolonged use of dopamine receptor-blocking agents. The most common types of these agents are antipsychotics and anti-nausea agents. The classic form of TD refers to stereotypic movements of the mouth, which resemble chewing. However, TD can also appear as other involuntary movements such as chorea, dystonia, or tics. Tics A tic can be defined as a repeated, individually recognizable, intermittent movement or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. These abnormal movements occur with intervening periods of normal movement. These movements are predictable, often triggered by stress, excitement, suggestion, or brief voluntary suppressibility. Many children say that the onset of tics can stem from the strong urge to move. Tics can be either muscular (alter normal motor function) or vocal (alter normal speech) in nature and most commonly involve the face, mouth, eyes, head, neck or shoulder muscles. Tics can also be classified as simple motor tics (a single brief stereotyped movement or movement fragment), complex motor tics (a more complex or sequential movement involving multiple muscle groups), or phonic tics (including simple, brief phonations or vocalizations).When both motor and vocal tics are present and persist for more than one year, a diagnosis of Tourette syndrome (TS) is likely. TS is an inherited neurobehavioral disorder characterized by both motor and vocal tics. Many individuals with TS may also develop obsessions, compulsions, inattention and hyperactivity. TS usually begins in childhood. Up to 5% of the population has tics, but at least 20% of boys will have developed tics at some point in their lifetimes. Tremor A tremor can be defined as a rhythmic, back and forth or oscillating involuntary movement about a joint axis. Tremors are symmetric about a midpoint within the movement, and both portions of the movement occur at the same speed. Unlike the other hyperkinetic movements, tremors lack both the jerking associated movements and posturing.Essential tremor (ET), also known as benign essential tremor, or familial tremor, is the most common movement disorder. It is estimated that 5 percent of people worldwide have this condition, affecting those of all ages but typically staying within families. ET typically affects the hands and arms but can also affect the head, voice, chin, trunk and legs. Both sides of the body tend to be equally affected. The tremor is called an action tremor, becoming noticeable in the arms when they are being used. Patients often report that alcohol helps lessen the symptoms. Primary medical treatments for ET are usually beta-blockers. For patients who fail to respond sufficiently to medication, deep brain stimulation and thalamotomy can be highly effective.A "flapping tremor," or asterixis, is characterized by irregular flapping-hand movement, which appears most often with outstretched arms and wrist extension. Individuals with this condition resemble birds flapping their wings. Volitional hyperkinesia Volitional hyperkinesia refers to any type of involuntary movement described above that interrupts an intended voluntary muscular movement. These movements tend to be jolts that present suddenly during an otherwise smoothly coordinated action of skeletal muscle. Pathophysiology The causes of the majority of the above hyperkinetic movements can be traced to improper modulation of the basal ganglia by the subthalamic nucleus. In many cases, the excitatory output of the subthalamic nucleus is reduced, leading to a reduced inhibitory outflow of the basal ganglia. Without the normal restraining influence of the basal ganglia, upper motor neurons of the circuit tend to become more readily activated by inappropriate signals, resulting in the characteristic abnormal movements.There are two pathways involving basal ganglia-thalamocortical circuitry, both of which originate in the neostriatum. The direct pathway projects to the internal globus pallidus (GPi) and to the substantia nigra pars reticulata (SNr). These projections are inhibitory and have been found to utilize both GABA and substance P. The indirect pathway, which projects to the globus pallidus external (GPe), is also inhibitory and uses GABA and enkephalin. The GPe projects to the subthalamic nucleus (STN), which then projects back to the GPi and GPe via excitatory, glutaminergic pathways. Excitation of the direct pathway leads to disinhibition of the GABAergic neurons of the GPi/SNr, ultimately resulting in activation of thalamic neurons and excitation of cortical neurons. In contrast, activation of the indirect pathway stimulates the inhibitory striatal GABA/enkephalin projection, resulting in suppression of GABAergic neuronal activity. This, in turn, causes disinhibition of the STN excitatory outputs, thus triggering the GPi/SNr inhibitory projections to the thalamus and decreased activation of cortical neurons. While deregulation of either of these pathways can disturb motor output, hyperkinesia is thought to result from overactivity of the direct pathway and decreased activity from the indirect pathway.Hyperkinesia occurs when dopamine receptors, and norepinephrine receptors to a lesser extent, within the cortex and the brainstem are more sensitive to dopamine or when the dopaminergic receptors/neurons are hyperactive. Hyperkinesia can be caused by a large number of different diseases including metabolic disorders, endocrine disorders, heritable disorders, vascular disorders, or traumatic disorders. Other causes include toxins within the brain, autoimmune disease, and infections, which include meningitis.Since the basal ganglia often have many connections with the frontal lobe of the brain, hyperkinesia can be associated with neurobehavioral or neuropsychiatric disorders such as mood changes, psychosis, anxiety, disinhibition, cognitive impairments, and inappropriate behavior.In children, primary dystonia is usually inherited genetically. Secondary dystonia, however, is most commonly caused by dyskinetic cerebral palsy, due to hypoxic or ischemic injury to the basal ganglia, brainstem, cerebellum, and thalamus during the prenatal or infantile stages of development. Chorea and ballism can be caused by damage to the subthalamic nucleus. Chorea can be secondary to hyperthyroidism. Athetosis can be secondary to sensory loss in the distal limbs; this is called pseudoathetosis in adults but is not yet proven in children. Diagnosis Definition There are various terms which refer to specific movement mechanisms that contribute to the differential diagnoses of hyperkinetic disorders. As defined by Hogan and Sternad, "posture" is a nonzero time period during which bodily movement is minimal. When a movement is called "discrete," it means that a new posture is assumed without any other postures interrupting the process. "Rhythmic" movements are those that occur in cycles of similar movements. "Repetitive," "recurrent," and "reciprocal" movements feature a certain bodily or joint position that occur more than once in a period, but not necessarily in a cyclic manner.Overflow refers to unwanted movements that occur during a desired movement. It may occur in situations where the individuals motor intention spreads to either nearby or distant muscles, taking away from the original goal of the movement. Overflow is often associated with dystonic movements and may be due to a poor focusing of muscle activity and inability to suppress unwanted muscle movement. Co-contraction refers to a voluntary movement performed to suppress the involuntary movement, such as forcing ones wrist toward the body to stop it from involuntarily moving away from the body.In evaluating these signs and symptoms, one must consider the frequency of repetition, whether or not the movements can be suppressed voluntarily (either by cognitive decisions, restraint, or sensory tricks), the awareness of the affected individual during the movement events, any urges to make the movements, and if the affected individual feels rewarded after having completed the movement. The context of the movement should also be noted; this means that a movement could be triggered in a certain posture, while at rest, during action, or during a specific task. The movements quality can also be described in observing whether or not the movement can be categorized as a normal movement by an unaffected individual, or one that is not normally made on a daily basis by unaffected individuals. Differential diagnosis Diseases that feature one or more hyperkinetic movements as prominent symptoms include: Huntingtons disease Hyperkinesia, more specifically chorea, is the hallmark symptom of Huntingtons disease, formerly referred to as Huntingtons chorea. Appropriately, chorea is derived from the Greek word, khoros, meaning "dance." The extent of the hyperkinesia exhibited in the disease can vary from solely the little finger to the entire body, resembling purposeful movements but occurring involuntarily. In children, rigidity and seizures are also symptoms. Other hyperkinetic symptoms include: Head turning to shift eye position Facial movements, including grimaces Slow, uncontrolled movements Quick, sudden, sometimes wild jerking movements of the arms, legs, face, and other body parts Unsteady gait Abnormal reflexes "prancing," or a wide walkThe disease is characterized further by the gradual onset of defects in behavior and cognition, including dementia and speech impediments, beginning in the fourth or fifth decades of life. Death usually occurs within 10–20 years after a progressive worsening of symptoms. Caused by the Huntington gene, the disease eventually contributes to selective atrophy of the Caudate nucleus and Putamen, especially of GABAergic and acetylcholinergic neurons, with some additional degeneration of the frontal and temporal cortices of the brain. The disrupted signaling in the basal ganglia network is thought to cause the hyperkinesia. There is no known cure for Huntingtons disease, yet there is treatment available to minimize the hyperkinetic movements. Dopamine blockers, such as haloperidol, tetrabenazine, and amantadine, are often effective in this regard. Wilsons disease Wilsons disease (WD) is a rare inherited disorder in which patients have a problem metabolizing copper. In patients with WD, copper accumulates in the liver and other parts of the body, particularly the brain, eyes and kidneys. Upon accumulation in the brain, patients may experience speech problems, incoordination, swallowing problems, and prominent hyperkinetic symptoms including tremor, dystonia, and gait difficulties. Psychiatric disturbances such as irritability, impulsiveness, aggressiveness, and mood disturbances are also common. Restless leg syndrome Restless leg syndrome is a disorder in which patients feel uncomfortable or unpleasant sensations in the legs. These sensations usually occur in the evening, while the patient is sitting or lying down and relaxing. Patients feel like they have to move their legs to relieve the sensations, and walking generally makes the symptoms disappear. In many patients, this can lead to insomnia and excessive daytime sleepiness. This is a very common problem and can occur at any age.Similarly, the syndrome akathisia ranges from mildly compulsive movement usually in the legs to intense frenzied motion. These movements are partly voluntary, and the individual typically has the ability to suppress them for short amounts of time. Like restless leg syndrome, relief results from movement. Post-stroke repercussions A multitude of movement disorders have been observed after either ischemic or hemorrhagic stroke. Some examples include athetosis, chorea with or without hemiballismus, tremor, dystonia, and segmental or focal myoclonus, although the prevalence of these manifestations after stroke is quite low. The amount of time that passes between stroke event and presentation of hyperkinesia depends on the type of hyperkinetic movement since their pathologies slightly differ. Chorea tends to affect older stroke survivors while dystonia tends to affect younger ones. Men and women have an equal chance of developing the hyperkinetic movements after stroke. Strokes causing small, deep lesions in the basal ganglia, brain stem and thalamus are those most likely to be associated with post-stroke hyperkinesia. Dentatorubral-pallidoluysian atrophy DRPLA is a rare trinucleotide repeat disorder (polyglutamine disease) that can be juvenile-onset (< 20 years), early adult-onset (20–40 years), or late adult-onset (> 40 years). Late adult-onset DRPLA is characterized by ataxia, choreoathetosis and dementia. Early adult-onset DRPLA also includes seizures and myoclonus. Juvenile-onset DRPLA presents with ataxia and symptoms consistent with progressive myoclonus epilepsy (myoclonus, multiple seizure types and dementia). Other symptoms that have been described include cervical dystonia, corneal endothelial degeneration autism, and surgery-resistant obstructive sleep apnea. Management Athetosis, chorea and hemiballismus Before prescribing medication for these conditions which often resolve spontaneously, recommendations have pointed to improved skin hygiene, good hydration via fluids, good nutrition, and installation of padded bed rails with use of proper mattresses. Pharmacological treatments include the typical neuroleptic agents such as fluphenazine, pimozide, haloperidol and perphenazine which block dopamine receptors; these are the first line of treatment for hemiballismus. Quetiapine, sulpiride and olanzapine, the atypical neuroleptic agents, are less likely to yield drug-induced parkinsonism and tardive dyskinesia. Tetrabenazine works by depleting presynaptic dopamine and blocking postsynaptic dopamine receptors, while reserpine depletes the presynaptic catecholamine and serotonin stores; both of these drugs treat hemiballismus successfully but may cause depression, hypotension and parkinsonism. Sodium valproate and clonazepam have been successful in a limited number of cases. Stereotactic ventral intermediate thalamotomy and use of a thalamic stimulator have been shown to be effective in treating these conditions. Essential tremor The medical treatment of essential tremor at the Movement Disorders Clinic at Baylor College of Medicine begins with minimizing stress and tremorgenic drugs along with recommending a restricted intake of beverages containing caffeine as a precaution, although caffeine has not been shown to significantly intensify the presentation of essential tremor. Alcohol amounting to a blood concentration of only 0.3% has been shown to reduce the amplitude of essential tremor in two-thirds of patients; for this reason it may be used as a prophylactic treatment before events during which one would be embarrassed by the tremor presenting itself. Using alcohol regularly and/or in excess to treat tremors is highly inadvisable, as there is a purported correlation between tremor and alcoholism. Alcohol is thought to stabilize neuronal membranes via potentiation of GABA receptor-mediated chloride influx. It has been demonstrated in essential tremor animal models that the food additive 1-octanol suppresses tremors induced by harmaline, and decreases the amplitude of essential tremor for about 90 minutes.Two of the most valuable drug treatments for essential tremor are propranolol, a beta blocker, and primidone, an anticonvulsant. Propranolol is much more effective for hand tremor than head and voice tremor. Some beta-adrenergic blockers (beta blockers) are not lipid-soluble and therefore cannot cross the blood–brain barrier (propranolol being an exception), but can still act against tremors; this indicates that this drugs mechanism of therapy may be influenced by peripheral beta-adrenergic receptors. Primidones mechanism of tremor prevention has been shown significantly in controlled clinical studies. The benzodiazepine drugs such as diazepam and barbiturates have been shown to reduce presentation of several types of tremor, including the essential variety. Controlled clinical trials of gabapentin yielded mixed results in efficacy against essential tremor while topiramate was shown to be effective in a larger double-blind controlled study, resulting in both lower Fahn-Tolosa-Marin tremor scale ratings and better function and disability as compared to placebo.It has been shown in two double-blind controlled studies that injection of botulinum toxin into muscles used to produce oscillatory movements of essential tremors, such as forearm, wrist and finger flexors, may decrease the amplitude of hand tremor for approximately three months and that injections of the toxin may reduce essential tremor presenting in the head and voice. The toxin also may help tremor causing difficulty in writing, although properly adapted writing devices may be more efficient. Due to high incidence of side effects, use of botulinum toxin has only received a C level of support from the scientific community.Deep brain stimulation toward the ventral intermediate nucleus of the thalamus and potentially the subthalamic nucleus and caudal zona incerta nucleus have been shown to reduce tremor in numerous studies. That toward the ventral intermediate nucleus of the thalamus has been shown to reduce contralateral and some ipsilateral tremor along with tremors of the cerebellar outflow, head, resting state and those related to hand tasks; however, the treatment has been shown to induce difficulty articulating thoughts (dysarthria), and loss of coordination and balance in long-term studies. Motor cortex stimulation is another option shown to be viable in numerous clinical trials. Dystonia Treatment of primary dystonia is aimed at reducing symptoms such as involuntary movements, pain, contracture, embarrassment, and to restore normal posture and improve the patients function. This treatment is therefore not neuroprotective. According to the European Federation of Neurological Sciences and Movement Disorder Society, there is no evidence-based recommendation for treating primary dystonia with antidopaminergic or anticholinergic drugs although recommendations have been based on empirical evidence. Anticholinergic drugs prove to be most effective in treating generalized and segmental dystonia, especially if dose starts out low and increases gradually. Generalized dystonia has also been treated with such muscle relaxants as the benzodiazepines. Another muscle relaxant, baclofen, can help reduce spasticity seen in cerebral palsy such as dystonia in the leg and trunk. Treatment of secondary dystonia by administering levodopa in dopamine-responsive dystonia, copper chelation in Wilsons disease, or stopping the administration of drugs that may induce dystonia have been proven effective in a small number of cases. Physical therapy has been used to improve posture and prevent contractures via braces and casting, although in some cases, immobilization of limbs can induce dystonia, which is by definition known as peripherally induced dystonia. There are not many clinical trials that show significant efficacy for particular drugs, so medical of dystonia must be planned on a case-by-case basis. Botulinum toxin B, or Myobloc, has been approved by the US Food and Drug Administration to treat cervical dystonia due to level A evidential support by the scientific community. Surgery known as GPi DBS (Globus Pallidus Pars Interna Deep Brain Stimulation) has come to be popular in treating phasic forms of dystonia, although cases involving posturing and tonic contractions have improved to a lesser extent with this surgery. A follow-up study has found that movement score improvements observed one year after the surgery was maintained after three years in 58% of the cases. It has also been proven effective in treating cervical and cranial-cervical dystonia. Tics Treatment of tics present in conditions such as Tourettes syndrome begins with patient, relative, teacher and peer education about the presentation of the tics. Sometimes, pharmacological treatment is unnecessary and tics can be reduced by behavioral therapy such as habit-reversal therapy and/or counseling. Often this route of treatment is difficult because it depends most heavily on patient compliance. Once pharmacological treatment is deemed most appropriate, lowest effective doses should be given first with gradual increases. The most effective drugs belong to the neuroleptic variety such as monoamine-depleting drugs and dopamine receptor-blocking drugs. Of the monoamine-depleting drugs, tetrabenazine is most powerful against tics and results in fewest side effects. A non-neuroleptic drug found to be safe and effective in treating tics is topiramate. Botulinum toxin injection in affected muscles can successfully treat tics; involuntary movements and vocalizations can be reduced, as well as life-threatening tics that have the potential of causing compressive myelopathy or radiculopathy. Surgical treatment for disabling Tourettes syndrome has been proven effective in cases presenting with self-injury. Deep Brain Stimulation surgery targeting the globus pallidus, thalamus and other areas of the brain may be effective in treating involuntary and possibly life-threatening tics. History In the 16th century, Andreas Vesalius and Francesco Piccolomini were the first to distinguish between white matter, the cortex, and the subcortical nuclei in the brain. About a century later, Thomas Willis noticed that the corpus striatum was typically discolored, shrunken, and abnormally softened in the cadavers of people who had died from paralysis. The view that the corpus striatum played such a large role in motor functions was the most prominent one until the 19th century when electrophysiologic stimulation studies began to be performed. For example, Gustav Fritsch and Eduard Hitzig performed them on dog cerebral cortices in 1870, while David Ferrier performed them, along with ablation studies, on cerebral cortices of dogs, rabbits, cats, and primates in 1876. During the same year, John Hughlings Jackson posited that the motor cortex was more relevant to motor function than the corpus striatum after carrying out clinical-pathologic experiments in humans. Soon it would be discovered that the theory about the corpus striatum would not be completely incorrect.By the late 19th century, a few hyperkinesias such as Huntingtons chorea, post-hemiplegic choreoathetosis, Tourettes syndrome, and some forms of both tremor and dystonia were described in a clinical orientation. However, the common pathology was still a mystery. British neurologist William Richard Gowers called these disorders "general and functional diseases of the nervous system" in his 1888 publication entitled A Manual of Diseases of the Nervous System. It was not until the late 1980s and 1990s that sufficient animal models and human clinical trials were utilized to discover the specific involvement of the basal ganglia in the hyperkinesia pathology. In 1998, Wichmann and Delong made the conclusion that hyperkinesia is associated with decreased output from the basal ganglia, and in contrast, hypokinesia is associated with increased output from the basal ganglia. This generalization, however, still leaves a need for more complex models to distinguish the more nuanced pathologies of the numerous diverse hyperkinesias which are still being studied today.In the 2nd century, Galen was the first to define tremor as "involuntary alternating up-and-down motion of the limbs." Further classification of hyperkinetic movements came in the 17th and 18th centuries by Franciscus Sylvius and Gerard van Swieten. Parkinsons disease was one of the first disorders to be named as a result of the recent classification of its featured hyperkinetic tremor. The subsequent naming of other disorders involving abnormal motions soon followed. Research directions Studies have been done with electromyography to trace skeletal muscle activity in some hyperkinetic disorders. The electromyogram (EMG) of dystonia sometimes shows rapid rhythmic bursts, but these patterns can almost always be produced intentionally. In the myoclonus EMG, there are typically brief, and sometimes rhythmic, bursts or pauses in the recording pattern. When the bursts last for 50 milliseconds or less they are indicative of cortical myoclonus, but when they last up to 200 milliseconds, they are indicative of spinal or brainstem myoclonus. Such bursts can occur in multiple muscles simultaneously quite quickly, but high time resolution must be used in the EMG trace to clearly record them. The bursts recorded for tremor tend to be longer in duration than those of myoclonus, although some types can last for durations within the range for those of myoclonus. Future studies would have to examine the EMGs for tics, athetosis, stereotypies and chorea as there are minimal recordings done for those movements. However, it may be predicted that the EMG for chorea would include bursts varying in duration, timing, and amplitude, while that for tics and stereotypies would take on patterns of voluntary movements.In general, research for treatment of hyperkinesia has most recently been focusing on ameliorating symptoms rather than attempting to correct the pathogenesis of the disease. Therefore, now and in the future it may be beneficial to inform the learning of the diseases pathology through carefully controlled, long-term, observation-based studies. As therapies are supported by proven effectiveness that can be repeated in multiple studies, they are useful, but the clinician may also consider that the best treatments for patients can only be evaluated on a case-by-case basis. It is the interplay of these two facets of neurology and medicine that may bring about significant progress in this field. See also Basal ganglia disease References == External links ==

Hey Aarogya!, what is Vertebral compression fracture

Vertebral compression fracture

A compression fracture is a collapse of a vertebra. It may be due to trauma or due to a weakening of the vertebra (compare with burst fracture). This weakening is seen in patients with osteoporosis or osteogenesis imperfecta, lytic lesions from metastatic or primary tumors, or infection. In healthy patients, it is most often seen in individuals suffering extreme vertical shocks, such as ejecting from an ejection seat. Seen in lateral views in plain x-ray films, compression fractures of the spine characteristically appear as wedge deformities, with greater loss of height anteriorly than posteriorly and intact pedicles in the anteroposterior view. Signs and symptoms Acute fractures will cause severe back pain. Compression fractures which develop gradually, such as in osteoporosis, may initially not cause any symptoms, but will later often lead to back pain and loss of height. Diagnosis Compression fractures are usually diagnosed on spinal radiographs, where a wedge-shaped vertebra may be visible or there may be loss of height of the vertebra. In addition, bone density measurement may be performed to evaluate for osteoporosis. When a tumor is suspected as the underlying cause, or the fracture was caused by severe trauma, CT or MRI scans may be performed. Treatment Conservative treatment Back brace for support while the bone heals—either a Jewett brace for relatively stable and mild injuries, or a thoracic lumbar sacral orthosis (TLSO) for more severe ones. Opioids or non-steroidal anti-inflammatory drugs (NSAIDs) for pain. For osteoporotic patients, calcitonin may be helpful. Surgical Kyphoplasty and vertebroplasty are minimally invasive procedures that inject cement into the bone of the back that is fractured. However, the data examining the effectiveness of these procedures is mixed. References Further reading Zeller, J. L.; Burke, A. E.; Glass, R. M. (2008). "Osteomyelitis". JAMA. 299 (7): 858. doi:10.1001/jama.299.7.858. PMID 18285597. Medscape article on lytic lesions Emedicine article on spinal metastasis == External links ==

Aarogya, could you share information about a health condition involving Lung abscess

Lung abscess

Lung abscess is a type of liquefactive necrosis of the lung tissue and formation of cavities (more than 2 cm) containing necrotic debris or fluid caused by microbial infection. This pus-filled cavity is often caused by aspiration, which may occur during anesthesia, sedation, or unconsciousness from injury. Alcoholism is the most common condition predisposing to lung abscesses. Lung abscess is considered primary (60%) when it results from existing lung parenchymal process and is termed secondary when it complicates another process e.g. vascular emboli or follows rupture of extrapulmonary abscess into lung. Signs and symptoms Onset of symptoms is often gradual, but in necrotizing staphylococcal or gram-negative bacillary pneumonias patients can be acutely ill. Cough, fever with shivering, and night sweats are often present. Cough can be productive of foul smelling purulent mucus (≈70%) or less frequently with blood in one third of cases). Affected individuals may also complain of chest pain, shortness of breath, lethargy and other features of chronic illness.Those with a lung abscess are generally cachectic at presentation. Finger clubbing is present in one third of patients. Dental decay is common especially in alcoholics and children. On examination of the chest there will be features of consolidation such as localized dullness on percussion and bronchial breath sounds. Complications Although rare in modern times, can include spread of infection to other lung segments, bronchiectasis, empyema, and bacteremia with metastatic infection such as brain abscess. Causes Conditions contributing to lung abscessAspiration of oropharyngeal or gastric secretion Septic emboli Necrotizing pneumonia Vasculitis: Granulomatosis with polyangiitis Necrotizing tumors: 8% to 18% are due to neoplasms across all age groups, higher in older people; primary squamous carcinoma of the lung is the most common.OrganismsIn the post-antibiotic era pattern of frequency is changing. In older studies anaerobes were found in up to 90% cases but they are much less frequent now. Anaerobic bacteria: Actinomyces, Peptostreptococcus, Bacteroides, Fusobacterium species, Microaerophilic streptococcus : Streptococcus milleri Aerobic bacteria: Staphylococcus, Klebsiella, Haemophilus, Pseudomonas, Nocardia, Escherichia coli, Streptococcus, Mycobacterium Fungi: Candida, Aspergillus Parasites: Entamoeba histolytica Diagnosis Imaging studies Lung abscesses are often on one side and single involving posterior segments of the upper lobes and the apical segments of the lower lobes as these areas are gravity dependent when lying down. Presence of air-fluid levels implies rupture into the bronchial tree or rarely growth of gas forming organism. Laboratory studies Raised inflammatory markers (high ESR, CRP) are common but nonspecific. Examination of the coughed up mucus is important in any lung infection and often reveals mixed bacterial flora. Transtracheal or transbronchial (via bronchoscopy) aspirates can also be cultured. Fiber optic bronchoscopy is often performed to exclude obstructive lesion; it also helps in bronchial drainage of pus. Management Broad spectrum antibiotic to cover mixed flora is the mainstay of treatment. Pulmonary physiotherapy and postural drainage are also important. Surgical procedures are required in selective patients for drainage or pulmonary resection. The treatment is divided according to the type of abscess, acute or chronic. For acute cases the treatment is antibiotics: if anaerobic: metronidazole or clindamycin if aerobic: beta-lactams, cephalosporins if MRSA or Staphylococcus infection: vancomycin or linezolid postural drainage and chest physiotherapy bronchoscopy is used for the following cases: aspiration or instillation of antibiotics patients with atypical presentation suspected of having underlying foreign body or malignancy Prognosis Most cases respond to antibiotics and prognosis is usually excellent unless there is a debilitating underlying condition. Mortality from lung abscess alone is around 5% and is improving. See also Empyema Bronchiectasis Abscess Pleural effusion References == External links ==

Hello Aarogya , Do you know what is Irritation,

Irritation

Irritation, in biology and physiology, is a state of inflammation or painful reaction to allergy or cell-lining damage. A stimulus or agent which induces the state of irritation is an irritant. Irritants are typically thought of as chemical agents (for example phenol and capsaicin) but mechanical, thermal (heat), and radiative stimuli (for example ultraviolet light or ionising radiations) can also be irritants. Irritation also has non-clinical usages referring to bothersome physical or psychological pain or discomfort. Irritation can also be induced by some allergic response due to exposure of some allergens for example contact dermatitis, irritation of mucosal membranes and pruritus. Mucosal membrane is the most common site of irritation because it contains secretory glands that release mucous which attracts the allergens due to its sticky nature. Chronic irritation is a medical term signifying that afflictive health conditions have been present for a while. There are many disorders that can cause chronic irritation, the majority involve the skin, vagina, eyes and lungs. Irritation in organisms In higher organisms, an allergic response may be the cause of irritation. An allergen is defined distinctly from an irritant, however, as allergy requires a specific interaction with the immune system and is thus dependent on the (possibly unique) sensitivity of the organism involved while an irritant, classically, acts in a non-specific manner. It is a form of stress, but conversely, if one is stressed by unrelated matters, mild imperfections can cause more irritation than usual: one is irritable; see also sensitivity (human). In more basic organisms, the status of pain is the perception of the being stimulated, which is not observable although it may be shared (see gate control theory of pain). It is not proven that oysters can feel pain, but it is known that they react to irritants. When an irritating object becomes trapped within an oysters shell, it deposits layers of calcium carbonate (CaCO3), slowly increasing in size and producing a pearl. This is purely a defense mechanism, to trap a potentially threatening irritant such as a parasite inside its shell, or an attack from outside, injuring the mantle tissue. The oyster creates a pearl sac to seal off the irritation. It has also been observed that an amoeba avoids being prodded with a pin, but there is not enough evidence to suggest how much it feels this. Irritation is apparently the only universal sense shared by even single-celled creatures. It is postulated that most such beings also feel pain, but this is a projection – empathy. Some philosophers, notably René Descartes, denied it entirely, even for such higher mammals as dogs or primates like monkeys; Descartes considered intelligence a pre-requisite for the feeling of pain. Types Eye irritation Modern office work with use of office equipment has raised concerns about possible adverse health effects. Since the 1970s, reports have linked mucosal, skin, and general symptoms to work with self-copying paper. Emission of various particulate and volatile substances has been suggested as specific causes. These symptoms have been related to Sick Building Syndrome, which involves symptoms such as irritation to the eyes, skin, and upper airways, headache and fatigue.The eye is also a source of chronic irritation. Disorders like Sjögrens syndrome, where one does not make tears, can cause a dry eye sensation which feels very unpleasant. The condition is difficult to treat and is lifelong. Besides artificial tears, there is a drug called Restasis which may help.Blepharitis is dryness and itching on the upper eyelids. This condition is often seen in young people and can lead to reddish dry eye and scaly eyebrows. To relieve the itching sensation, one may need to apply warm compresses and use topical corticosteroid creams. Skin Eczema is another cause of chronic irritation and affects millions of individuals. Eczema simply means a dry skin which is itchy. The condition usually starts at an early age and continues throughout life. The major complaint of people with eczema is an itchy dry skin. Sometimes, the itching will be associated with a skin rash. The affected areas are always dry, scaly, reddish and may ooze sometimes. Eczema cannot be cured, but its symptoms can be controlled. One should use moisturizers, use cold compresses and avoid frequent hot showers. There are over the counter corticosteroids creams which can be applied. Sometimes, an anti histamine has to be used to prevent the chronic itching sensations. There are also many individuals who have allergies to a whole host of substances like nuts, hair, dander, plants and fabrics. For these individuals, even the minimal exposure can lead to a full blown skin rash, itching, wheezing and coughing. Unfortunately, other than avoidance, there is no other cure. There are allergy shots which can help desensitize against an allergen but often the results are poor and the treatments are expensive. Most of these individuals with chronic irritation from allergens usually need to take anti histamines or use a bronchodilator to relieve symptoms.Another common irritation disorder in females is intertrigo. This disorder is associated with chronic irritation under folds of skin. This is typically seen under large breasts, groins and folds of the abdomen in obese individuals. Candida quickly grows in warm moist areas of these folds and presents as a chronic itch. Over time, the skin becomes red and often oozes. Perspiration is also a chronic type of irritation which can be very annoying. Besides being socially unacceptable, sweat stain the clothes and can present with a foul odor. In some individuals, the warm moist areas often become easily infected. The best way to treat excess sweating is good hygiene, frequent change of clothes and use of deodorants/antiperspirants. Vaginal irritation One of the most common areas of the body associated with irritation is the vagina. Many women complain of an itch, dryness, or discharge in the perineum at some point in their lives. There are several causes of vaginal irritation including fungal vaginitis (like candida) or trichomoniasis. Often, herpes simplex infection of the mouth or genitalia can be recurrent and prove to be extremely irritating. Sometimes, the irritation can be of the chronic type and it can be so intense that it also causes painful intercourse. Aside from infections, chronic irritation of the vagina may be related to the use of contraceptives and condoms made from latex. The majority of contraceptives are made of synthetic chemicals which can induce allergies, rash and itching. Sometimes the lubricant used for intercourse may cause irritation. Another cause of irritation in women is post menopausal vaginitis. The decline in the female sex hormones leads to development of dryness and itching in the vagina. This is often accompanied by painful sexual intercourse. Cracks and tears often develop on outer aspects of the labia which becomes red from chronic scratching. Post menopausal vaginitis can be treated with short term use of vaginal estrogen pessary and use of a moisturizer. Lungs Individuals who smoke or are exposed to smog or other airborne pollutants can develop a condition known as COPD. In this disorder, there is constant irritation of the breathing tubes (trachea) and the small airways. The constant irritation results in excess production of mucus which makes breathing difficult. Frequently, these individuals wake up in the morning with copious amounts of foul smelling mucus and a cough which lasts all day. Wheeze and heavy phlegm are common findings. COPD is a lifelong disorder and there is no cure. Eventually most people develop recurrent pneumonia, lack any type of endurance, and are unable to work productively. One of the ways to avoid chronic bronchitis is to stop or not smoke. Stomach Gastritis or stomach upset is a common irritating disorder affecting millions of people. Gastritis is basically inflammation of the stomach wall lining and has many causes. Smoking, excess alcohol consumption and the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, account for the majority of causes of gastritis. In some cases, gastritis may develop after surgery, a major burn, infection or emotional stress. The most common symptoms of gastritis include sharp abdominal pain which may radiate to the back. This may be associated with nausea, vomiting, abdominal bloating and a lack of appetite. When the condition is severe it may even result in loss of blood on the stools. The condition often comes and goes for years because most people continue to drink alcohol or use NSAIDs. Treatment includes the use of antacids or acid neutralizing drugs, antibiotics, and avoiding spicy food and alcohol. See also Allergy Irritability (psychology) Itch Stimulus (physiology) == References ==

Hello Aarogya , Do you know what is Voice change,

Voice change

A voice change or voice mutation, sometimes referred to as a voice break or voice crack, commonly refers to the deepening of the voice of people as they reach puberty. Before puberty, both sexes have roughly similar vocal pitch, but during puberty the male voice typically deepens an octave, while the female voice usually deepens only by a few tones.A similar effect is a "voice crack", during which a persons voice suddenly and unintentionally enters a higher register (usually falsetto) for a brief period of time. This may be caused by singing or talking at a pitch outside the persons natural vocal range, stress, fatigue, emotional tension, or the physical changes associated with puberty. An instance of a voice crack (when associated with puberty) lasts for only a moment and generally occurs less frequently as a person grows into maturity. Anatomical changes Most of the voice change begins around puberty. Adult pitch is reached 2–3 years later but the voice does not stabilize until the early years of adulthood. It usually happens months or years before the development of significant facial hair. Under the influence of sex hormones, the voice box, or larynx, grows in both sexes. This growth is far more prominent in males than in females and is more easily perceived. It causes the voice to drop and deepen. Along with the larynx, the vocal folds (vocal cords) grow significantly longer and thicker. The facial bones begin to grow as well. Cavities in the sinuses, the nose, and the back of the throat grow bigger, thus creating more space within the head to allow the voice to resonate. Occasionally, voice change is accompanied by unsteadiness of vocalization in the early stages of untrained voices. Due to the significant drop in pitch to the vocal range, people may unintentionally speak in head voice or even strain their voices using pitches which were previously chest voice, the lowest part of the modal voice register. History Historical changes in the average age of puberty have had profound effects on the composing of music for childrens voices. The composer Joseph Haydn was known for typically singing parts in high pitches throughout his 17th year. Unchanged voices were in high demand for church choirs, which historically excluded women. The British cathedral choir ideal remains based on boy sopranos (or trebles), with the alto part executed by adult countertenors. In German-speaking countries, however, the alto parts are also sung by boys. Historically, a strategy for avoiding the shift altogether was castration. Castrati are first documented in Italian church records from the 1550s. Mozarts Exultate Jubilate, Allegris Miserere and parts of Handels Messiah were written for this voice, whose distinctive timbre was widely exploited in Baroque opera. In 1861, the practice of castration became illegal in Italy, and in 1878 Pope Leo XIII prohibited the hiring of new castrati by the church. The last castrato was Alessandro Moreschi, who served in the Sistine Chapel Choir. Singing Children are able to sing in the same octave as women. When the voices of male teenagers break, they are no longer able to sing in the same octave. For music sung in the same key as women, they can sing in falsetto or drop an octave. See also Puberty Voice masculinization and feminization == References ==

Aarogya, explain a scenario commonly referred as Abdominal pain

Abdominal pain

Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a more serious underlying condition such as appendicitis, leaking or ruptured abdominal aortic aneurysm, diverticulitis, or ectopic pregnancy. In a third of cases the exact cause is unclear.Given that a variety of diseases can cause some form of abdominal pain, a systematic approach to the examination of a person and the formulation of a differential diagnosis remains important. Differential diagnosis The most frequent reasons for abdominal pain are gastroenteritis (13%), irritable bowel syndrome (8%), urinary tract problems (5%), inflammation of the stomach (5%) and constipation (5%). In about 30% of cases, the cause is not determined. About 10% of cases have a more serious cause including gallbladder (gallstones or biliary dyskinesia) or pancreas problems (4%), diverticulitis (3%), appendicitis (2%) and cancer (1%). More common in those who are older, ischemic colitis, mesenteric ischemia, and abdominal aortic aneurysms are other serious causes. Acute abdominal pain Acute abdomen can be defined as severe, persistent abdominal pain of sudden onset that is likely to require surgical intervention to treat its cause. The pain may frequently be associated with nausea and vomiting, abdominal distention, fever and signs of shock. One of the most common conditions associated with acute abdominal pain is acute appendicitis. Selected causes Traumatic: blunt or perforating trauma to the stomach, bowel, spleen, liver, or kidney Inflammatory: Infections such as appendicitis, cholecystitis, pancreatitis, pyelonephritis, Peritonitis, pelvic inflammatory disease, hepatitis, mesenteric adenitis, or a subdiaphragmatic abscess Perforation of a peptic ulcer, a diverticulum, or the caecum Complications of inflammatory bowel disease such as Crohns disease or ulcerative colitis Mechanical: Small bowel obstruction secondary to adhesions caused by previous surgeries, intussusception, hernias, benign or malignant neoplasms Large bowel obstruction caused by colorectal cancer, inflammatory bowel disease, volvulus, fecal impaction or hernia Vascular: occlusive intestinal ischemia, usually caused by thromboembolism of the superior mesenteric artery By system A more extensive list includes the following: Gastrointestinal GI tract Inflammatory: gastroenteritis, appendicitis, gastritis, esophagitis, diverticulitis, Crohns disease, ulcerative colitis, microscopic colitis Obstruction: hernia, intussusception, volvulus, post-surgical adhesions, tumors, severe constipation, hemorrhoids Vascular: embolism, thrombosis, hemorrhage, sickle cell disease, abdominal angina, blood vessel compression (such as celiac artery compression syndrome), superior mesenteric artery syndrome, postural orthostatic tachycardia syndrome Digestive: peptic ulcer, lactose intolerance, celiac disease, food allergies, indigestion Glands Bile system Inflammatory: cholecystitis, cholangitis Obstruction: cholelithiasis, tumours Liver Inflammatory: hepatitis, liver abscess Pancreatic Inflammatory: pancreatitis Renal and urological Inflammation: pyelonephritis, bladder infection Obstruction: kidney stones, urolithiasis, urinary retention, tumours Vascular: left renal vein entrapment Gynaecological or obstetric Inflammatory: pelvic inflammatory disease Mechanical: ovarian torsion Endocrinological: menstruation, Mittelschmerz Tumors: endometriosis, fibroids, ovarian cyst, ovarian cancer Pregnancy: ruptured ectopic pregnancy, threatened abortion Abdominal wall muscle strain or trauma muscular infection neurogenic pain: herpes zoster, radiculitis in Lyme disease, abdominal cutaneous nerve entrapment syndrome (ACNES), tabes dorsalis Referred pain from the thorax: pneumonia, pulmonary embolism, ischemic heart disease, pericarditis from the spine: radiculitis from the genitals: testicular torsion Metabolic disturbance uremia, diabetic ketoacidosis, porphyria, C1-esterase inhibitor deficiency, adrenal insufficiency, lead poisoning, black widow spider bite, narcotic withdrawal Blood vessels aortic dissection, abdominal aortic aneurysm Immune system sarcoidosis vasculitis familial Mediterranean fever Idiopathic irritable bowel syndrome (IBS)(affecting up to 20% of the population, IBS is the most common cause of recurrent and intermittent abdominal pain) By location The location of abdominal pain can provide information about what may be causing the pain. The abdomen can be divided into four regions called quadrants. Locations and associated conditions include: Diffuse Peritonitis Vascular: mesenteric ischemia, ischemic colitis, Henoch-Schonlein purpura, sickle cell disease, systemic lupus erythematosus, polyarteritis nodosa Small bowel obstruction Irritable bowel syndrome Metabolic disorders: ketoacidosis, porphyria, familial Mediterranean fever, adrenal crisis Epigastric Heart: myocardial infarction, pericarditis Stomach: gastritis, stomach ulcer, stomach cancer Pancreas: pancreatitis, pancreatic cancer Intestinal: duodenal ulcer, diverticulitis, appendicitis Right upper quadrant Liver: hepatomegaly, fatty liver, hepatitis, liver cancer, abscess Gallbladder and biliary tract: inflammation, gallstones, worm infection, cholangitis Colon: bowel obstruction, functional disorders, gas accumulation, spasm, inflammation, colon cancer Other: pneumonia, Fitz-Hugh-Curtis syndrome Left upper quadrant Splenomegaly Colon: bowel obstruction, functional disorders, gas accumulation, spasm, inflammation, colon cancer Peri-umbilical (the area around the umbilicus, aka the belly button) Appendicitis Pancreatitis Inferior myocardial infarction Peptic ulcer Diabetic ketoacidosis Vascular: aortic dissection, aortic rupture Bowel: mesenteric ischemia, Celiac disease, inflammation, intestinal spasm, functional disorders, small bowel obstruction Lower abdominal pain Diarrhea Colitis Crohns Dysentery Hernia Right lower quadrant Colon: intussusception, bowel obstruction, appendicitis (McBurneys point) Renal: kidney stone (nephrolithiasis), pyelonephritis Pelvic: cystitis, bladder stone, bladder cancer, pelvic inflammatory disease, pelvic pain syndrome Gynecologic: endometriosis, intrauterine pregnancy, ectopic pregnancy, ovarian cyst, ovarian torsion, fibroid (leiomyoma), abscess, ovarian cancer, endometrial cancer Left lower quadrant Bowel: diverticulitis, sigmoid colon volvulus, bowel obstruction, gas accumulation, Toxic megacolon Right low back pain Liver: hepatomegaly Kidney: kidney stone (nephrolithiasis), complicated urinary tract infection Left low back pain Spleen Kidney: kidney stone (nephrolithiasis), complicated urinary tract infection Low back pain kidney pain (kidney stone, kidney cancer, hydronephrosis) Ureteral stone pain Pathophysiology Abdominal pain can be referred to as visceral pain or peritoneal pain. The contents of the abdomen can be divided into the foregut, midgut, and hindgut. The foregut contains the pharynx, lower respiratory tract, portions of the esophagus, stomach, portions of the duodenum (proximal), liver, biliary tract (including the gallbladder and bile ducts), and the pancreas. The midgut contains portions of the duodenum (distal), cecum, appendix, ascending colon, and first half of the transverse colon. The hindgut contains the distal half of the transverse colon, descending colon, sigmoid colon, rectum, and superior anal canal.Each subsection of the gut has an associated visceral afferent nerve that transmits sensory information from the viscera to the spinal cord, traveling with the autonomic sympathetic nerves. The visceral sensory information from the gut traveling to the spinal cord, termed the visceral afferent, is non-specific and overlaps with the somatic afferent nerves, which are very specific. Therefore, visceral afferent information traveling to the spinal cord can present in the distribution of the somatic afferent nerve; this is why appendicitis initially presents with T10 periumbilical pain when it first begins and becomes T12 pain as the abdominal wall peritoneum (which is rich with somatic afferent nerves) is involved. Diagnosis A thorough patient history and physical examination is used to better understand the underlying cause of abdominal pain. The process of gathering a history may include: Identifying more information about the chief complaint by eliciting a history of present illness; i.e. a narrative of the current symptoms such as the onset, location, duration, character, aggravating or relieving factors, and temporal nature of the pain. Identifying other possible factors may aid in the diagnosis of the underlying cause of abdominal pain, such as recent travel, recent contact with other ill individuals, and for females, a thorough gynecologic history. Learning about the patients past medical history, focusing on any prior issues or surgical procedures. Clarifying the patients current medication regimen, including prescriptions, over-the-counter medications, and supplements. Confirming the patients drug and food allergies. Discussing with the patient any family history of disease processes, focusing on conditions that might resemble the patients current presentation. Discussing with the patient any health-related behaviors (e.g. tobacco use, alcohol consumption, drug use, and sexual activity) that might make certain diagnoses more likely. Reviewing the presence of non-abdominal symptoms (e.g., fever, chills, chest pain, shortness of breath, vaginal bleeding) that can further clarify the diagnostic picture. Using Carnetts sign to differentiate between visceral pain and pain originating in the muscles of the abdominal wall.After gathering a thorough history, one should perform a physical exam in order to identify important physical signs that might clarify the diagnosis, including a cardiovascular exam, lung exam, thorough abdominal exam, and for females, a genitourinary exam.Additional investigations that can aid diagnosis include: Blood tests including complete blood count, basic metabolic panel, electrolytes, liver function tests, amylase, lipase, troponin I, and for females, a serum pregnancy test. Urinalysis Imaging including chest and abdominal X-rays ElectrocardiogramIf diagnosis remains unclear after history, examination, and basic investigations as above, then more advanced investigations may reveal a diagnosis. Such tests include: Computed tomography of the abdomen/pelvis Abdominal or pelvic ultrasound Endoscopy and/or colonoscopy Management The management of abdominal pain depends on many factors, including the etiology of the pain. In the emergency department, a person presenting with abdominal pain may initially require IV fluids due to decreased intake secondary to abdominal pain and possible emesis or vomiting. Treatment for abdominal pain includes analgesia, such as non-opioid (ketorolac) and opioid medications (morphine, fentanyl). Choice of analgesia is dependent on the cause of the pain, as ketorolac can worsen some intra-abdominal processes. Patients presenting to the emergency department with abdominal pain may receive a "GI cocktail" that includes an antacid (examples include omeprazole, ranitidine, magnesium hydroxide, and calcium chloride) and lidocaine. After addressing pain, there may be a role for antimicrobial treatment in some cases of abdominal pain. Butylscopolamine (Buscopan) is used to treat cramping abdominal pain with some success. Surgical management for causes of abdominal pain includes but is not limited to cholecystectomy, appendectomy, and exploratory laparotomy. Emergencies Below is a brief overview of abdominal pain emergencies. Epidemiology Abdominal pain is the reason about 3% of adults see their family physician. Rates of emergency department (ED) visits in the United States for abdominal pain increased 18% from 2006 through to 2011. This was the largest increase out of 20 common conditions seen in the ED. The rate of ED use for nausea and vomiting also increased 18%. References == External links ==

Do you know what is Ischemia, Aarogya

Ischemia

Ischemia or ischaemia is a restriction in blood supply to any tissues, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue i.e. hypoxia and microvascular dysfunction. It also means local hypoxia in a given part of a body sometimes resulting from constriction (such as vasoconstriction, thrombosis or embolism). Ischemia comprises not only insufficiency of oxygen, but also reduced availability of nutrients and inadequate removal of metabolic wastes. Ischemia can be partial (poor perfusion) or total blockage. The inadequate delivery of oxygenated blood to the organs must be resolved either by treating the cause of the inadequate delivery or reducing the oxygen demand of the system that needs it. For example, patients with myocardial ischemia have a decreased blood flow to the heart and are prescribed with medications that reduce chronotrophy and ionotrophy to meet the new level of blood delivery supplied by the stenosed so that it is adequate. Signs and symptoms The signs and symptoms of ischemia vary, as it can occur anywhere in the body and depends on the degree to which blood flow is interrupted. For example, clinical manifestations of acute limb ischemia (which can be summarized as the "six Ps") include pain, pallor, pulseless, paresthesia, paralysis, and poikilothermia.Without immediate intervention, ischemia may progress quickly to tissue necrosis and gangrene within a few hours. Paralysis is a very late sign of acute arterial ischemia and signals the death of nerves supplying the extremity. Foot drop may occur as a result of nerve damage. Because nerves are extremely sensitive to hypoxia, limb paralysis or ischemic neuropathy may persist after revascularization and may be permanent. Cardiac ischemia Cardiac ischemia may be asymptomatic or may cause chest pain, known as angina pectoris. It occurs when the heart muscle, or myocardium, receives insufficient blood flow. This most frequently results from atherosclerosis, which is the long-term accumulation of cholesterol-rich plaques in the coronary arteries. In most Western countries, Ischemic heart disease is the most common cause of death in both men and women, and a major cause of hospital admissions. Bowel Both large and small intestines can be affected by ischemia. The blockage of blood flow to the large intestine (colon) is called ischemic colitis. Ischemia of the small bowel is called mesenteric ischemia. Brain Brain ischemia is insufficient blood flow to the brain, and can be acute or chronic. Acute ischemic stroke is a neurological emergency typically caused by a blood clot blocking blood flow in a vessel in the brain. Chronic ischemia of the brain may result in a form of dementia called vascular dementia. A sudden, brief episode (symptoms lasting only minutes) of ischemia affecting the brain is called a transient ischemic attack (TIA), often called a mini-stroke. TIAs can be a warning of future strokes, with approximately 1/3 of TIA patients having a serious stroke within one year. Limb Inadequate blood supply to a limb may results in acute limb ischemia or chronic limb threatening ischemia. Cutaneous Reduced blood flow to the skin layers may result in mottling or uneven, patchy discoloration of the skin. Kidney Ischemia Kidney Ischemia is a loss of blood flow to the kidney cells. Several physical symptoms include shrinkage of one or both kidneys, renovascular hypertension, acute renal failure, progressive azotemia, and acute pulmonary edema. It is a disease with high mortality rate and high morbidity. Failure to treat could cause chronic kidney disease and a need for renal surgery. Causes Ischemia is a vascular disease involving an interruption in the arterial blood supply to a tissue, organ, or extremity that, if untreated, can lead to tissue death. It can be caused by embolism, thrombosis of an atherosclerotic artery, or trauma. Venous problems like venous outflow obstruction and low-flow states can cause acute arterial ischemia. An aneurysm is one of the most frequent causes of acute arterial ischemia. Other causes are heart conditions including myocardial infarction, mitral valve disease, chronic atrial fibrillation, cardiomyopathies, and prosthesis, in all of which thrombi are prone to develop. Occlusion The thrombi may dislodge and may travel anywhere in the circulatory system, where they may lead to pulmonary embolus, an acute arterial occlusion causing the oxygen and blood supply distal to the embolus to decrease suddenly. The degree and extent of symptoms depend on the size and location of the obstruction, the occurrence of clot fragmentation with embolism to smaller vessels, and the degree of peripheral arterial disease (PAD). Thromboembolism (blood clots) Embolism (foreign bodies in the circulation, e.g. amniotic fluid embolism) Trauma Traumatic injury to an extremity may produce partial or total occlusion of a vessel from compression, shearing, or laceration. Acute arterial occlusion may develop as a result of arterial dissection in the carotid artery or aorta or as a result of iatrogenic arterial injury (e.g., after angiography). Other An inadequate flow of blood to a part of the body may be caused by any of the following: Thoracic outlet syndrome (compression of the brachial plexus) Atherosclerosis (lipid-laden plaques obstructing the lumen of arteries) Hypoglycemia (lower than normal level of glucose) Tachycardia (abnormally rapid beating of the heart) Radiotherapy Hypotension (low blood pressure, e.g. in septic shock, heart failure) Outside compression of a blood vessel, e.g. by a tumor or in the case of superior mesenteric artery syndrome Sickle cell disease (abnormally shaped red blood cells) Induced g-forces which restrict the blood flow and force the blood to the extremities of the body, as in acrobatics and military flying Localized extreme cold, such as by frostbite or improper cold compression therapy Tourniquet application An increased level of glutamate receptor stimulation Arteriovenous malformations and peripheral artery occlusive disease rupture of significant blood vessels supplying a tissue or organ. Anemia vasoconstricts the periphery so that red blood cells can work internally on vital organs such as the heart, brain, etc., thus causing lack of oxygen to the periphery. Premature discontinuation of any oral anticoagulant. Unconsciousness, such as due to the ingestion of excessive doses of central depressants like alcohol or opioids, can result in ischemia of the extremities due to unusual body positions that prevent normal circulation Pathophysiology Ischemia results in tissue damage in a process known as ischemic cascade. The damage is the result of the build-up of metabolic waste products, inability to maintain cell membranes, mitochondrial damage, and eventual leakage of autolyzing proteolytic enzymes into the cell and surrounding tissues. Restoration of blood supply to ischemic tissues can cause additional damage known as reperfusion injury that can be more damaging than the initial ischemia. Reintroduction of blood flow brings oxygen back to the tissues, causing a greater production of free radicals and reactive oxygen species that damage cells. It also brings more calcium ions to the tissues causing further calcium overloading and can result in potentially fatal cardiac arrhythmias and also accelerates cellular self-destruction. The restored blood flow also exaggerates the inflammation response of damaged tissues, causing white blood cells to destroy damaged cells that may otherwise still be viable. Treatment Early treatment is essential to keep the affected organ viable. The treatment options include injection of an anticoagulant, thrombolysis, embolectomy, surgical revascularization, or partial amputation. Anticoagulant therapy is initiated to prevent further enlargement of the thrombus. Continuous IV unfractionated heparin has been the traditional agent of choice.If the condition of the ischemic limb is stabilized with anticoagulation, recently formed emboli may be treated with catheter-directed thrombolysis using intra-arterial infusion of a thrombolytic agent (e.g., recombinant tissue plasminogen activator (tPA), streptokinase, or urokinase). A percutaneous catheter inserted into the femoral artery and threaded to the site of the clot is used to infuse the drug. Unlike anticoagulants, thrombolytic agents work directly to resolve the clot over a period of 24 to 48 hours.Direct arteriotomy may be necessary to remove the clot. Surgical revascularization may be used in the setting of trauma (e.g., laceration of the artery). Amputation is reserved for cases where limb salvage is not possible. If the patient continues to have a risk of further embolization from some persistent source, such as chronic atrial fibrillation, treatment includes long-term oral anticoagulation to prevent further acute arterial ischemic episodes.Decrease in body temperature reduces the aerobic metabolic rate of the affected cells, reducing the immediate effects of hypoxia. Reduction of body temperature also reduces the inflammation response and reperfusion injury. For frostbite injuries, limiting thawing and warming of tissues until warmer temperatures can be sustained may reduce reperfusion injury. Ischemic stroke is at times treated with various levels of statin therapy at hospital discharge, followed by home time, in an attempt to lower the risk of adverse events. Society and culture The Infarct Combat Project (ICP) is an international nonprofit organization founded in 1998 to fight ischemic heart diseases through education and research. Etymology and pronunciation The word ischemia () is from Greek ἴσχαιμος iskhaimos staunching blood, from ἴσχω iskhο keep back, restrain and αἷμα haima blood. See also Infarction Inhibitor protein Trauma triad of death Ischemia-reperfusion injury of the appendicular musculoskeletal system References Bibliography Elizabeth (editor). Oxford Reference: Concise Medical Dictionary (1990, 3rd ed.). Oxford University Press: Market House Books, 1987, 2nd ed., pp. 107, ISBN 978-0-19-281991-8

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

Taste

The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste receptor cells located on taste buds in the oral cavity, mostly on the tongue. Taste, along with olfaction and trigeminal nerve stimulation (registering texture, pain, and temperature), determines flavors of food and other substances. Humans have taste receptors on taste buds and other areas, including the upper surface of the tongue and the epiglottis. The gustatory cortex is responsible for the perception of taste. The tongue is covered with thousands of small bumps called papillae, which are visible to the naked eye. Within each papilla are hundreds of taste buds. The exception to this is the filiform papillae that do not contain taste buds. There are between 2000 and 5000 taste buds that are located on the back and front of the tongue. Others are located on the roof, sides and back of the mouth, and in the throat. Each taste bud contains 50 to 100 taste receptor cells. Taste receptors in the mouth sense the five taste modalities: sweetness, sourness, saltiness, bitterness, and savoriness (also known as savory or umami). Scientific experiments have demonstrated that these five tastes exist and are distinct from one another. Taste buds are able to distinguish between different tastes through detecting interaction with different molecules or ions. Sweet, savoriness, and bitter tastes are triggered by the binding of molecules to G protein-coupled receptors on the cell membranes of taste buds. Saltiness and sourness are perceived when alkali metal or hydrogen ions enter taste buds, respectively.The basic taste modalities contribute only partially to the sensation and flavor of food in the mouth—other factors include smell, detected by the olfactory epithelium of the nose; texture, detected through a variety of mechanoreceptors, muscle nerves, etc.; temperature, detected by thermoreceptors; and "coolness" (such as of menthol) and "hotness" (pungency), through chemesthesis. As the gustatory system senses both harmful and beneficial things, all basic taste modalities are classified as either aversive or appetitive, depending upon the effect the things they sense have on our bodies. Sweetness helps to identify energy-rich foods, while bitterness serves as a warning sign of poisons.Among humans, taste perception begins to fade at an older age because of loss of tongue papillae and a general decrease in saliva production. Humans can also have distortion of tastes (dysgeusia). Not all mammals share the same taste modalities: some rodents can taste starch (which humans cannot), cats cannot taste sweetness, and several other carnivores including hyenas, dolphins, and sea lions, have lost the ability to sense up to four of their ancestral five taste modalities. Basic tastes The gustatory system allows animals to distinguish between safe and harmful food, and to gauge foods’ nutritional value. Digestive enzymes in saliva begin to dissolve food into base chemicals that are washed over the papillae and detected as tastes by the taste buds. The tongue is covered with thousands of small bumps called papillae, which are visible to the naked eye. Within each papilla are hundreds of taste buds. The exception to this are the filiform papillae that do not contain taste buds. There are between 2000 and 5000 taste buds that are located on the back and front of the tongue. Others are located on the roof, sides and back of the mouth, and in the throat. Each taste bud contains 50 to 100 taste receptor cells. The five specific tastes received by taste receptors are saltiness, sweetness, bitterness, sourness, and savoriness, often known by its Japanese name "umami" which translates to ‘deliciousness’. As of the early 20th century, Western physiologists and psychologists believed there were four basic tastes: sweetness, sourness, saltiness, and bitterness. The concept of a "savory" taste was not present in Western science at that time, but was postulated in Japanese research. By the end of the 20th century, the concept of umami was becoming familiar to Western society. One study found that both salt and sour taste mechanisms detect, in different ways, the presence of sodium chloride (salt) in the mouth. However, acids are also detected and perceived as sour. The detection of salt is important to many organisms, but specifically mammals, as it serves a critical role in ion and water homeostasis in the body. It is specifically needed in the mammalian kidney as an osmotically active compound which facilitates passive re-uptake of water into the blood. Because of this, salt elicits a pleasant taste in most humans. Sour and salt tastes can be pleasant in small quantities, but in larger quantities become more and more unpleasant to taste. For sour taste this is presumably because the sour taste can signal under-ripe fruit, rotten meat, and other spoiled foods, which can be dangerous to the body because of bacteria which grow in such media. Additionally, sour taste signals acids, which can cause serious tissue damage. Sweet taste signals the presence of carbohydrates in solution. Since carbohydrates have a very high calorie count (saccharides have many bonds, therefore much energy), they are desirable to the human body, which evolved to seek out the highest calorie intake foods. They are used as direct energy (sugars) and storage of energy (glycogen). However, there are many non-carbohydrate molecules that trigger a sweet response, leading to the development of many artificial sweeteners, including saccharin, sucralose, and aspartame. It is still unclear how these substances activate the sweet receptors and what adaptational significance this has had. The savory taste (known in Japanese as "umami") was identified by Japanese chemist Kikunae Ikeda, which signals the presence of the amino acid L-glutamate, triggers a pleasurable response and thus encourages the intake of peptides and proteins. The amino acids in proteins are used in the body to build muscles and organs, transport molecules (hemoglobin), antibodies, and the organic catalysts known as enzymes. These are all critical molecules, and as such it is important to have a steady supply of amino acids, hence the pleasurable response to their presence in the mouth. Pungency (piquancy or hotness) had traditionally been considered a sixth basic taste. In 2015, researchers suggested a new basic taste of fatty acids called fat taste, although oleogustus and pinguis have both been proposed as alternate terms. Sweetness Sweetness, usually regarded as a pleasurable sensation, is produced by the presence of sugars and substances that mimic sugar. Sweetness may be connected to aldehydes and ketones, which contain a carbonyl group. Sweetness is detected by a variety of G protein coupled receptors (GPCR) coupled to the G protein gustducin found on the taste buds. At least two different variants of the "sweetness receptors" must be activated for the brain to register sweetness. Compounds the brain senses as sweet are compounds that can bind with varying bond strength to two different sweetness receptors. These receptors are T1R2+3 (heterodimer) and T1R3 (homodimer), which account for all sweet sensing in humans and animals.Taste detection thresholds for sweet substances are rated relative to sucrose, which has an index of 1. The average human detection threshold for sucrose is 10 millimoles per liter. For lactose it is 30 millimoles per liter, with a sweetness index of 0.3, and 5-nitro-2-propoxyaniline 0.002 millimoles per liter. “Natural” sweeteners such as saccharides activate the GPCR, which releases gustducin. The gustducin then activates the molecule adenylate cyclase, which catalyzes the production of the molecule cAMP, or adenosine 3, 5-cyclic monophosphate. This molecule closes potassium ion channels, leading to depolarization and neurotransmitter release. Synthetic sweeteners such as saccharin activate different GPCRs and induce taste receptor cell depolarization by an alternate pathway. Sourness Sourness is the taste that detects acidity. The sourness of substances is rated relative to dilute hydrochloric acid, which has a sourness index of 1. By comparison, tartaric acid has a sourness index of 0.7, citric acid an index of 0.46, and carbonic acid an index of 0.06.Sour taste is detected by a small subset of cells that are distributed across all taste buds called Type III taste receptor cells. H+ ions (protons) that are abundant in sour substances can directly enter the Type III taste cells through a proton channel. This channel was identified in 2018 as otopetrin 1 (OTOP1). The transfer of positive charge into the cell can itself trigger an electrical response. Some weak acids such as acetic acid, can also penetrate taste cells; intracellular hydrogen ions inhibit potassium channels, which normally function to hyperpolarize the cell. By a combination of direct intake of hydrogen ions through OTOP1 ion channels (which itself depolarizes the cell) and the inhibition of the hyperpolarizing channel, sourness causes the taste cell to fire action potentials and release neurotransmitter.The most common foods with natural sourness are fruits, such as lemon, lime, grape, orange, tamarind, and bitter melon. Fermented foods, such as wine, vinegar or yogurt, may have sour taste. Children show a greater enjoyment of sour flavors than adults, and sour candy containing citric acid or malic acid is common. Saltiness The simplest receptor found in the mouth is the sodium chloride (salt) receptor. Saltiness is a taste produced primarily by the presence of sodium ions. Other ions of the alkali metals group also taste salty, but the further from sodium, the less salty the sensation is. A sodium channel in the taste cell wall allows sodium cations to enter the cell. This on its own depolarizes the cell, and opens voltage-dependent calcium channels, flooding the cell with positive calcium ions and leading to neurotransmitter release. This sodium channel is known as an epithelial sodium channel (ENaC) and is composed of three subunits. An ENaC can be blocked by the drug amiloride in many mammals, especially rats. The sensitivity of the salt taste to amiloride in humans, however, is much less pronounced, leading to conjecture that there may be additional receptor proteins besides ENaC to be discovered. The size of lithium and potassium ions most closely resemble those of sodium, and thus the saltiness is most similar. In contrast, rubidium and caesium ions are far larger, so their salty taste differs accordingly. The saltiness of substances is rated relative to sodium chloride (NaCl), which has an index of 1. Potassium, as potassium chloride (KCl), is the principal ingredient in salt substitutes and has a saltiness index of 0.6.Other monovalent cations, e.g. ammonium (NH4+), and divalent cations of the alkali earth metal group of the periodic table, e.g. calcium (Ca2+), ions generally elicit a bitter rather than a salty taste even though they, too, can pass directly through ion channels in the tongue, generating an action potential. But the chloride of calcium is saltier and less bitter than potassium chloride, and is commonly used in pickle brine instead of KCl. Bitterness Bitterness is one of the most sensitive of the tastes, and many perceive it as unpleasant, sharp, or disagreeable, but it is sometimes desirable and intentionally added via various bittering agents. Common bitter foods and beverages include coffee, unsweetened cocoa, South American mate, coca tea, bitter gourd, uncured olives, citrus peel, some varieties of cheese, many plants in the family Brassicaceae, dandelion greens, horehound, wild chicory, and escarole. The ethanol in alcoholic beverages tastes bitter, as do the additional bitter ingredients found in some alcoholic beverages including hops in beer and gentian in bitters. Quinine is also known for its bitter taste and is found in tonic water. Bitterness is of interest to those who study evolution, as well as various health researchers since a large number of natural bitter compounds are known to be toxic. The ability to detect bitter-tasting, toxic compounds at low thresholds is considered to provide an important protective function. Plant leaves often contain toxic compounds, and among leaf-eating primates there is a tendency to prefer immature leaves, which tend to be higher in protein and lower in fiber and poisons than mature leaves. Amongst humans, various food processing techniques are used worldwide to detoxify otherwise inedible foods and make them palatable. Furthermore, the use of fire, changes in diet, and avoidance of toxins has led to neutral evolution in human bitter sensitivity. This has allowed several loss of function mutations that has led to a reduced sensory capacity towards bitterness in humans when compared to other species.The threshold for stimulation of bitter taste by quinine averages a concentration of 8 μM (8 micromolar). The taste thresholds of other bitter substances are rated relative to quinine, which is thus given a reference index of 1. For example, brucine has an index of 11, is thus perceived as intensely more bitter than quinine, and is detected at a much lower solution threshold. The most bitter natural substance is amarogentin, a compound present in the roots of the plant Gentiana lutea, and the most bitter substance known is the synthetic chemical denatonium, which has an index of 1,000. It is used as an aversive agent (a bitterant) that is added to toxic substances to prevent accidental ingestion. It was discovered accidentally in 1958 during research on a local anesthetic, by MacFarlan Smith of Gorgie, Edinburgh, Scotland.Research has shown that TAS2Rs (taste receptors, type 2, also known as T2Rs) such as TAS2R38 coupled to the G protein gustducin are responsible for the human ability to taste bitter substances. They are identified not only by their ability to taste for certain "bitter" ligands, but also by the morphology of the receptor itself (surface bound, monomeric). The TAS2R family in humans is thought to comprise about 25 different taste receptors, some of which can recognize a wide variety of bitter-tasting compounds. Over 670 bitter-tasting compounds have been identified, on a bitter database, of which over 200 have been assigned to one or more specific receptors. Recently it is speculated that the selective constraints on the TAS2R family have been weakened due to the relatively high rate of mutation and pseudogenization. Researchers use two synthetic substances, phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) to study the genetics of bitter perception. These two substances taste bitter to some people, but are virtually tasteless to others. Among the tasters, some are so-called "supertasters" to whom PTC and PROP are extremely bitter. The variation in sensitivity is determined by two common alleles at the TAS2R38 locus. This genetic variation in the ability to taste a substance has been a source of great interest to those who study genetics. Gustducin is made of three subunits. When it is activated by the GPCR, its subunits break apart and activate phosphodiesterase, a nearby enzyme, which in turn converts a precursor within the cell into a secondary messenger, which closes potassium ion channels. Also, this secondary messenger can stimulate the endoplasmic reticulum to release Ca2+ which contributes to depolarization. This leads to a build-up of potassium ions in the cell, depolarization, and neurotransmitter release. It is also possible for some bitter tastants to interact directly with the G protein, because of a structural similarity to the relevant GPCR. Umami Umami, or savory, is an appetitive taste. It can be tasted in soy sauce, meat, dashi and consomme. A loanword from Japanese meaning "good flavor" or "good taste", umami (旨味) is considered fundamental to many East Asian cuisines, such as Japanese cuisine. It dates back to the use of fermented fish sauce: garum in ancient Rome and ge-thcup or koe-cheup in ancient China.Umami was first studied in 1907 by Ikeda isolating dashi taste, which he identified as the chemical monosodium glutamate (MSG). MSG is a sodium salt that produces a strong savory taste, especially combined with foods rich in nucleotides such as meats, fish, nuts, and mushrooms.Some savory taste buds respond specifically to glutamate in the same way that "sweet" ones respond to sugar. Glutamate binds to a variant of G protein coupled glutamate receptors. L-glutamate may bond to a type of GPCR known as a metabotropic glutamate receptor (mGluR4) which causes the G-protein complex to activate the sensation of umami. Measuring relative tastes Measuring the degree to which a substance presents one basic taste can be achieved in a subjective way by comparing its taste to a reference substance. Sweetness is subjectively measured by comparing the threshold values, or level at which the presence of a dilute substance can be detected by a human taster, of different sweet substances. Substances are usually measured relative to sucrose, which is usually given an arbitrary index of 1 or 100. Rebaudioside A is 100 times sweeter than sucrose; fructose is about 1.4 times sweeter; glucose, a sugar found in honey and vegetables, is about three-quarters as sweet; and lactose, a milk sugar, is one-half as sweet.The sourness of a substance can be rated by comparing it to very dilute hydrochloric acid (HCl).Relative saltiness can be rated by comparison to a dilute salt solution.Quinine, a bitter medicinal found in tonic water, can be used to subjectively rate the bitterness of a substance. Units of dilute quinine hydrochloride (1 g in 2000 mL of water) can be used to measure the threshold bitterness concentration, the level at which the presence of a dilute bitter substance can be detected by a human taster, of other compounds. More formal chemical analysis, while possible, is difficult.There may not be an absolute measure for pungency, though there are tests for measuring the subjective presence of a given pungent substance in food, such as the Scoville scale for capsaicine in peppers or the Pyruvate scale for pyruvates in garlics and onions. Functional structure Taste is a form of chemoreception which occurs in the specialised taste receptors in the mouth. To date, there are five different types of taste these receptors can detect which are recognized: salt, sweet, sour, bitter, and umami. Each type of receptor has a different manner of sensory transduction: that is, of detecting the presence of a certain compound and starting an action potential which alerts the brain. It is a matter of debate whether each taste cell is tuned to one specific tastant or to several; Smith and Margolskee claim that "gustatory neurons typically respond to more than one kind of stimulus, [a]lthough each neuron responds most strongly to one tastant". Researchers believe that the brain interprets complex tastes by examining patterns from a large set of neuron responses. This enables the body to make "keep or spit out" decisions when there is more than one tastant present. "No single neuron type alone is capable of discriminating among stimuli or different qualities, because a given cell can respond the same way to disparate stimuli." As well, serotonin is thought to act as an intermediary hormone which communicates with taste cells within a taste bud, mediating the signals being sent to the brain. Receptor molecules are found on the top of microvilli of the taste cells. SweetnessSweetness is produced by the presence of sugars, some proteins, and other substances such as alcohols like anethol, glycerol and propylene glycol, saponins such as glycyrrhizin, artificial sweeteners (organic compounds with a variety of structures), and lead compounds such as lead acetate. It is often connected to aldehydes and ketones, which contain a carbonyl group. Many foods can be perceived as sweet regardless of their actual sugar content. For example, some plants such as liquorice, anise or stevia can be used as sweeteners. Rebaudioside A is a steviol glycoside coming from stevia that is 200 times sweeter than sugar. Lead acetate and other lead compounds were used as sweeteners, mostly for wine, until lead poisoning became known. Romans used to deliberately boil the must inside of lead vessels to make a sweeter wine. Sweetness is detected by a variety of G protein-coupled receptors coupled to a G protein that acts as an intermediary in the communication between taste bud and brain, gustducin. These receptors are T1R2+3 (heterodimer) and T1R3 (homodimer), which account for sweet sensing in humans and other animals. SaltinessSaltiness is a taste produced best by the presence of cations (such as Na+, K+ or Li+) and is directly detected by cation influx into glial like cells via leak channels causing depolarisation of the cell.Other monovalent cations, e.g., ammonium, NH+4, and divalent cations of the alkali earth metal group of the periodic table, e.g., calcium, Ca2+, ions, in general, elicit a bitter rather than a salty taste even though they, too, can pass directly through ion channels in the tongue. SournessSourness is acidity, and, like salt, it is a taste sensed using ion channels. Undissociated acid diffuses across the plasma membrane of a presynaptic cell, where it dissociates in accordance with Le Chateliers principle. The protons that are released then block potassium channels, which depolarise the cell and cause calcium influx. In addition, the taste receptor PKD2L1 has been found to be involved in tasting sour. BitternessResearch has shown that TAS2Rs (taste receptors, type 2, also known as T2Rs) such as TAS2R38 are responsible for the ability to taste bitter substances in vertebrates. They are identified not only by their ability to taste certain bitter ligands, but also by the morphology of the receptor itself (surface bound, monomeric). SavorinessThe amino acid glutamic acid is responsible for savoriness, but some nucleotides (inosinic acid and guanylic acid) can act as complements, enhancing the taste.Glutamic acid binds to a variant of the G protein-coupled receptor, producing a savory taste. Further sensations and transmission The tongue can also feel other sensations not generally included in the basic tastes. These are largely detected by the somatosensory system. In humans, the sense of taste is conveyed via three of the twelve cranial nerves. The facial nerve (VII) carries taste sensations from the anterior two thirds of the tongue, the glossopharyngeal nerve (IX) carries taste sensations from the posterior one third of the tongue while a branch of the vagus nerve (X) carries some taste sensations from the back of the oral cavity. The trigeminal nerve (cranial nerve V) provides information concerning the general texture of food as well as the taste-related sensations of peppery or hot (from spices). Pungency (also spiciness or hotness) Substances such as ethanol and capsaicin cause a burning sensation by inducing a trigeminal nerve reaction together with normal taste reception. The sensation of heat is caused by the foods activating nerves that express TRPV1 and TRPA1 receptors. Some such plant-derived compounds that provide this sensation are capsaicin from chili peppers, piperine from black pepper, gingerol from ginger root and allyl isothiocyanate from horseradish. The piquant ("hot" or "spicy") sensation provided by such foods and spices plays an important role in a diverse range of cuisines across the world—especially in equatorial and sub-tropical climates, such as Ethiopian, Peruvian, Hungarian, Indian, Korean, Indonesian, Lao, Malaysian, Mexican, New Mexican, Singaporean, Southwest Chinese (including Sichuan cuisine), Vietnamese, and Thai cuisines. This particular sensation, called chemesthesis, is not a taste in the technical sense, because the sensation does not arise from taste buds, and a different set of nerve fibers carry it to the brain. Foods like chili peppers activate nerve fibers directly; the sensation interpreted as "hot" results from the stimulation of somatosensory (pain/temperature) fibers on the tongue. Many parts of the body with exposed membranes but no taste sensors (such as the nasal cavity, under the fingernails, surface of the eye or a wound) produce a similar sensation of heat when exposed to hotness agents. Coolness Some substances activate cold trigeminal receptors even when not at low temperatures. This "fresh" or "minty" sensation can be tasted in peppermint, spearmint and is triggered by substances such as menthol, anethol, ethanol, and camphor. Caused by activation of the same mechanism that signals cold, TRPM8 ion channels on nerve cells, unlike the actual change in temperature described for sugar substitutes, this coolness is only a perceived phenomenon. Numbness Both Chinese and Batak Toba cooking include the idea of 麻 (má or mati rasa), a tingling numbness caused by spices such as Sichuan pepper. The cuisines of Sichuan province in China and of the Indonesian province of North Sumatra often combine this with chili pepper to produce a 麻辣 málà, "numbing-and-hot", or "mati rasa" flavor. Typical in northern Brazilian cuisine, jambu is an herb used in dishes like tacacá. These sensations, although not taste, fall into a category of chemesthesis. Astringency Some foods, such as unripe fruits, contain tannins or calcium oxalate that cause an astringent or puckering sensation of the mucous membrane of the mouth. Examples include tea, red wine, or rhubarb. Other terms for the astringent sensation are "dry", "rough", "harsh" (especially for wine), "tart" (normally referring to sourness), "rubbery", "hard" or "styptic". Metallicness A metallic taste may be caused by food and drink, certain medicines or amalgam dental fillings. It is generally considered an off flavor when present in food and drink. A metallic taste may be caused by galvanic reactions in the mouth. In the case where it is caused by dental work, the dissimilar metals used may produce a measurable current. Some artificial sweeteners are perceived to have a metallic taste, which is detected by the TRPV1 receptors. Many people consider blood to have a metallic taste. A metallic taste in the mouth is also a symptom of various medical conditions, in which case it may be classified under the symptoms dysgeusia or parageusia, referring to distortions of the sense of taste, and can be caused by medication, including saquinavir, zonisamide, and various kinds of chemotherapy, as well as occupational hazards, such as working with pesticides. Fat taste Recent research reveals a potential taste receptor called the CD36 receptor. CD36 was targeted as a possible lipid taste receptor because it binds to fat molecules (more specifically, long-chain fatty acids), and it has been localized to taste bud cells (specifically, the circumvallate and foliate papillae). There is a debate over whether we can truly taste fats, and supporters of our ability to taste free fatty acids (FFAs) have based the argument on a few main points: there is an evolutionary advantage to oral fat detection; a potential fat receptor has been located on taste bud cells; fatty acids evoke specific responses that activate gustatory neurons, similar to other currently accepted tastes; and, there is a physiological response to the presence of oral fat. Although CD36 has been studied primarily in mice, research examining human subjects ability to taste fats found that those with high levels of CD36 expression were more sensitive to tasting fat than were those with low levels of CD36 expression; this study points to a clear association between CD36 receptor quantity and the ability to taste fat. Other possible fat taste receptors have been identified. G protein-coupled receptors GPR120 and GPR40 have been linked to fat taste, because their absence resulted in reduced preference to two types of fatty acid (linoleic acid and oleic acid), as well as decreased neuronal response to oral fatty acids.Monovalent cation channel TRPM5 has been implicated in fat taste as well, but it is thought to be involved primarily in downstream processing of the taste rather than primary reception, as it is with other tastes such as bitter, sweet, and savory.Proposed alternate names to fat taste include oleogustus and pinguis, although these terms are not widely accepted. The main form of fat that is commonly ingested is triglycerides, which are composed of three fatty acids bound together. In this state, triglycerides are able to give fatty foods unique textures that are often described as creaminess. But this texture is not an actual taste. It is only during ingestion that the fatty acids that make up triglycerides are hydrolysed into fatty acids via lipases. The taste is commonly related to other, more negative, tastes such as bitter and sour due to how unpleasant the taste is for humans. Richard Mattes, a co-author of the study, explained that low concentrations of these fatty acids can create an overall better flavor in a food, much like how small uses of bitterness can make certain foods more rounded. However, a high concentration of fatty acids in certain foods is generally considered inedible. To demonstrate that individuals can distinguish fat taste from other tastes, the researchers separated volunteers into groups and had them try samples that also contained the other basic tastes. Volunteers were able to separate the taste of fatty acids into their own category, with some overlap with savory samples, which the researchers hypothesized was due to poor familiarity with both. The researchers note that the usual "creaminess and viscosity we associate with fatty foods is largely due to triglycerides", unrelated to the taste; while the actual taste of fatty acids is not pleasant. Mattes described the taste as "more of a warning system" that a certain food should not be eaten.There are few regularly consumed foods rich in fat taste, due to the negative flavor that is evoked in large quantities. Foods whose flavor to which fat taste makes a small contribution include olive oil and fresh butter, along with various kinds of vegetable and nut oils. Heartiness Kokumi (, Japanese: kokumi (コク味) from koku (こく)) is translated as "heartiness", "full flavor" or "rich" and describes compounds in food that do not have their own taste, but enhance the characteristics when combined. Alongside the five basic tastes of sweet, sour, salt, bitter and savory, kokumi has been described as something that may enhance the other five tastes by magnifying and lengthening the other tastes, or "mouthfulness".: 290  Garlic is a common ingredient to add flavor used to help define the characteristic kokumi flavors.Calcium-sensing receptors (CaSR) are receptors for "kokumi" substances. Kokumi substances, applied around taste pores, induce an increase in the intracellular Ca concentration in a subset of cells. This subset of CaSR-expressing taste cells are independent from the influenced basic taste receptor cells. CaSR agonists directly activate the CaSR on the surface of taste cells and integrated in the brain via the central nervous system. However, a basal level of calcium, corresponding to the physiological concentration, is necessary for activation of the CaSR to develop the kokumi sensation. Calcium The distinctive taste of chalk has been identified as the calcium component of that substance. In 2008, geneticists discovered a calcium receptor on the tongues of mice. The CaSR receptor is commonly found in the gastrointestinal tract, kidneys, and brain. Along with the "sweet" T1R3 receptor, the CaSR receptor can detect calcium as a taste. Whether the perception exists or not in humans is unknown. Temperature Temperature can be an essential element of the taste experience. Heat can accentuate some flavors and decrease others by varying the density and phase equilibrium of a substance. Food and drink that—in a given culture—is traditionally served hot is often considered distasteful if cold, and vice versa. For example, alcoholic beverages, with a few exceptions, are usually thought best when served at room temperature or chilled to varying degrees, but soups—again, with exceptions—are usually only eaten hot. A cultural example are soft drinks. In North America it is almost always preferred cold, regardless of season. Starchiness A 2016 study suggested that humans can taste starch (specifically, a glucose oligomer) independently of other tastes such as sweetness. However, no specific chemical receptor has yet been found for this taste. Nerve supply and neural connections The glossopharyngeal nerve innervates a third of the tongue including the circumvallate papillae. The facial nerve innervates the other two thirds of the tongue and the cheek via the chorda tympani.The pterygopalatine ganglia are ganglia (one on each side) of the soft palate. The greater petrosal, lesser palatine and zygomatic nerves all synapse here. The greater petrosal, carries soft palate taste signals to the facial nerve. The lesser palatine sends signals to the nasal cavity; which is why spicy foods cause nasal drip. The zygomatic sends signals to the lacrimal nerve that activate the lacrimal gland; which is the reason that spicy foods can cause tears. Both the lesser palatine and the zygomatic are maxillary nerves (from the trigeminal nerve). The special visceral afferents of the vagus nerve carry taste from the epiglottal region of the tongue. The lingual nerve (trigeminal, not shown in diagram) is deeply interconnected with the chorda tympani in that it provides all other sensory info from the anterior ⅔ of the tongue. This info is processed separately (nearby) in the rostal lateral subdivision of the nucleus of the solitary tract (NST). NST receives input from the amygdala (regulates oculomotor nuclei output), bed nuclei of stria terminalis, hypothalamus, and prefrontal cortex. NST is the topographical map that processes gustatory and sensory (temp, texture, etc.) info.Reticular formation (includes Raphe nuclei responsible for serotonin production) is signaled to release serotonin during and after a meal to suppress appetite. Similarly, salivary nuclei are signaled to decrease saliva secretion. Hypoglossal and thalamic connections aid in oral-related movements. Hypothalamus connections hormonally regulate hunger and the digestive system. Substantia innominata connects the thalamus, temporal lobe, and insula. Edinger-Westphal nucleus reacts to taste stimuli by dilating and constricting the pupils.Spinal ganglion are involved in movement. The frontal operculum is speculated to be the memory and association hub for taste.The insula cortex aids in swallowing and gastric motility. Other concepts Supertasters A supertaster is a person whose sense of taste is significantly more sensitive than most. The cause of this heightened response is likely, at least in part, due to an increased number of fungiform papillae. Studies have shown that supertasters require less fat and sugar in their food to get the same satisfying effects. However, contrary to what one might think, these people actually tend to consume more salt than most people. This is due to their heightened sense of the taste of bitterness, and the presence of salt drowns out the taste of bitterness. (This also explains why supertasters prefer salted cheddar cheese over non-salted.) Aftertaste Aftertastes arise after food has been swallowed. An aftertaste can differ from the food it follows. Medicines and tablets may also have a lingering aftertaste, as they can contain certain artificial flavor compounds, such as aspartame (artificial sweetener). Acquired taste An acquired taste often refers to an appreciation for a food or beverage that is unlikely to be enjoyed by a person who has not had substantial exposure to it, usually because of some unfamiliar aspect of the food or beverage, including bitterness, a strong or strange odor, taste, or appearance. Clinical significance Patients with Addisons disease, pituitary insufficiency, or cystic fibrosis sometimes have a hyper-sensitivity to the five primary tastes. Disorders of taste ageusia (complete loss of taste) hypogeusia (reduced sense of taste) dysgeusia (distortion in sense of taste) hypergeusia (abnormally heightened sense of taste)Viruses can also cause loss of taste. About 50% of patients with SARS-CoV-2 (causing COVID-19) experience some type of disorder associated with their sense of smell or taste, including ageusia and dysgeusia. SARS-CoV-1, MERS-CoV and even the flu (influenza virus) can also disrupt olfaction. History Ayurveda, an ancient Indian healing science, has its own tradition of basic tastes, comprising sweet, salty, sour, pungent, bitter & astringent.In the West, Aristotle postulated in c. 350 BC that the two most basic tastes were sweet and bitter. He was one of the first identified persons to develop a list of basic tastes.The Ancient Chinese regarded spiciness as a basic taste. Research The receptors for the basic tastes of bitter, sweet and savory have been identified. They are G protein-coupled receptors. The cells that detect sourness have been identified as a subpopulation that express the protein PKD2L1. The responses are mediated by an influx of protons into the cells but the receptor for sour is still unknown. The receptor for amiloride-sensitive attractive salty taste in mice has been shown to be a sodium channel. There is some evidence for a sixth taste that senses fatty substances.In 2010, researchers found bitter taste receptors in lung tissue, which cause airways to relax when a bitter substance is encountered. They believe this mechanism is evolutionarily adaptive because it helps clear lung infections, but could also be exploited to treat asthma and chronic obstructive pulmonary disease. == See also ==

Give me a short description about Polyarteritis nodosa , Aarogya

Polyarteritis nodosa

Polyarteritis nodosa (PAN) is a systemic necrotizing inflammation of blood vessels (vasculitis) affecting medium-sized muscular arteries, typically involving the arteries of the kidneys and other internal organs but generally sparing the lungs circulation. Small aneurysms are strung like the beads of a rosary, therefore making this "rosary sign" an important diagnostic feature of the vasculitis. PAN is sometimes associated with infection by the hepatitis B or hepatitis C virus. The condition may be present in infants.PAN is a rare disease. With treatment, five-year survival is 80%; without treatment, five-year survival is 13%. Death is often a consequence of kidney failure, myocardial infarction, or stroke. Signs and symptoms PAN may affect nearly every organ system and thus can present with a broad array of signs and symptoms. These manifestations result from ischemic damage to affected organs, often the skin, heart, kidneys, and nervous system. Constitutional symptoms are seen in up to 90% of affected individuals and include fever, fatigue, weakness, loss of appetite, and unintentional weight loss.Skin: The skin may show rashes, swelling, necrotic ulcers, and subcutaneous nodules (lumps). Skin manifestations of PAN include palpable purpura and livedo reticularis in some individuals.Neurologic system: Nerve involvement may cause sensory changes with numbness, pain, burning, and weakness (peripheral neuropathy). Peripheral nerves are often affected, and this most commonly presents as mononeuritis multiplex, which is the most common neurologic sign of PAN. Mononeuritis multiplex develops in more than 70% of patients with polyarteritis nodosa because of damage to arteries supplying large peripheral nerves. Most cases are marked by asymmetric polyneuropathy, but progressive disease can lead to symmetric nerve involvement. Central nervous system involvement may cause strokes or seizures.Renal system: Kidney involvement is common and often leads to death of parts of the kidney. Involvement of the renal artery, which supplies the kidneys with highly oxygenated blood, often leads to high blood pressure in about one-third of cases. deposition of protein or blood in the urine may also be seen. Almost all patients with PAN have renal insufficiency caused by renal artery narrowing, thrombosis, and infarctions. Cardiovascular system: Involvement of the arteries of the heart may cause a heart attack, heart failure, and inflammation of the sac around the heart (pericarditis).Gastrointestinal system: Damage to mesenteric arteries can cause abdominal pain, mesenteric ischemia, and bowel perforation. Abdominal pain may also be seen. Musculoskeletal system: Muscle and joint aches are common. Complications Stroke Heart failure resulting from cardiomyopathy and pericarditis Intestinal necrosis and perforation Causes PAN has no association with anti-neutrophil cytoplasmic antibodies, but about 30% of people with PAN have chronic hepatitis B and deposits containing HBsAg-HBsAb complexes in affected blood vessels, indicating an immune complex-mediated cause in that subset. Infection with the hepatitis C virus and HIV are occasionally discovered in people affected by PAN. PAN has also been associated with underlying hairy cell leukemia. The cause remains unknown in the remaining cases; there may be causal and clinical distinctions between classic idiopathic PAN, the cutaneous forms of PAN, and PAN associated with chronic hepatitis. In children, cutaneous PAN is frequently associated with streptococcal infections, and positive streptococcal serology is included in the diagnostic criteria. Diagnosis No specific lab tests exist for diagnosing polyarteritis nodosa. Diagnosis is generally based on the physical examination and a few laboratory studies that help confirm the diagnosis: CBC (may demonstrate an elevated white blood count) ESR (elevated) Perinuclear pattern of antineutrophil cytoplasmic antibodies (p-ANCA) - not associated with "classic" polyarteritis nodosa, but is present in a form of the disease affecting smaller blood vessels, known as microscopic polyangiitis or leukocytoclastic angiitis Tissue biopsy (reveals inflammation in small arteries, called arteritis) Elevated C-reactive proteinA patient is said to have polyarteritis nodosa if he or she has three of the 10 signs known as the 1990 American College of Rheumatology (ACR) criteria, when a radiographic or pathological diagnosis of vasculitis is made: Weight loss greater than/equal to 4.5 kg Livedo reticularis (a mottled purplish skin discoloration over the extremities or torso) Testicular pain or tenderness (occasionally, a site biopsied for diagnosis) Muscle pain, weakness, or leg tenderness Nerve disease (either single or multiple) Diastolic blood pressure greater than 90 mmHg (high blood pressure) Elevated kidney blood tests (BUN greater than 40 mg/dL or creatinine greater than 1.5 mg/dL) Hepatitis B (not C) virus tests positive (for surface antigen or antibody) Arteriogram (angiogram) showing the arteries that are dilated (aneurysms) or constricted by the blood vessel inflammation Biopsy of tissue showing the arteritis (typically inflamed arteries): The sural nerve is a frequent location for the biopsy. In polyarteritis nodosa, small aneurysms are strung like the beads of a rosary, therefore making this "rosary sign" an important diagnostic feature of the vasculitis. The 1990 ACR criteria were designed for classification purposes only, but their good discriminatory performances, indicated by the initial ACR analysis, suggested their potential usefulness for diagnostic purposes as well. Subsequent studies did not confirm their diagnostic utility, demonstrating a significant dependence of their discriminative abilities on the prevalence of the various vasculitides in the analyzed populations. Recently, an original study, combining the analysis of more than 100 items used to describe patients characteristics in a large sample of vasculitides with a computer simulation technique designed to test the potential diagnostic utility of the various criteria, proposed a set of eight positively or negatively discriminating items to be used as a screening tool for diagnosis in patients suspected of systemic vasculitis. Differential diagnosis Polyarteritis nodosa rarely affects the blood vessels of the lungs and this feature can help to differentiate it from other vasculitides that may have similar signs and symptoms (e.g., granulomatosis with polyangiitis or microscopic polyangiitis). Treatment Treatment involves medications to suppress the immune system, including prednisone and cyclophosphamide. When present, underlying hepatitis B virus infection should be immediately treated. In some cases, methotrexate or leflunomide may be helpful. Some patients have entered a remission phase when a four-dose infusion of rituximab is used before the leflunomide treatment is begun. Therapy results in remissions or cures in 90% of cases. Untreated, the disease is fatal in most cases. The most serious associated conditions generally involve the kidneys and gastrointestinal tract. A fatal course usually involves gastrointestinal bleeding, infection, myocardial infarction, and/or kidney failure.In case of remission, about 60% experience relapse within five years. In cases caused by hepatitis B virus, however, recurrence rate is only around 6%. Epidemiology The condition affects adults more frequently than children and males more frequently than females. Most cases occur between the ages of 40 and 60. Polyarteritis nodosa is more common in people with hepatitis B infection. History The medical eponyms Kussmaul disease or Kussmaul-Maier disease reflect the seminal description of the disease in the medical literature by Adolph Kussmaul and Rudolf Robert Maier. Culture In the 1956 American film Bigger Than Life, the protagonist character played by James Mason is diagnosed with polyarteritis nodosa after experiencing excruciating chest pain and is treated with cortisone. References == External links ==

Give me a short description about Aplastic anemia , Aarogya

Aplastic anemia

Aplastic anemia is a disease in which the body fails to produce blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets.It occurs most frequently in people in their teens and twenties but is also common among the elderly. It can be caused by heredity, immune disease, or exposure to chemicals, drugs, or radiation. However, in about half of cases, the cause is unknown.Aplastic anemia can be definitively diagnosed by bone marrow biopsy. Normal bone marrow has 30–70% blood stem cells, but in aplastic anemia, these cells are mostly gone and are replaced by fat.First-line treatment for aplastic anemia consists of immunosuppressive drugs—typically either anti-lymphocyte globulin or anti-thymocyte globulin—combined with corticosteroids, chemotherapy, and ciclosporin. Hematopoietic stem cell transplantation is also used, especially for patients under 30 years of age with a related, matched marrow donor.Aplastic anemia is known to have caused the deaths of Eleanor Roosevelt and Marie Curie. Signs and symptoms Anemia may lead to fatigue, pale skin, severe bruising, and a fast heart rate.Low platelets are associated with an increased risk of bleeding, bruising, and petechiae, with lower blood counts that impact the ability of the blood to clot. Low white blood cells increase the risk of infections. Causes Aplastic anemia can be caused by immune disease or exposure to certain chemicals, drugs, radiation, or infection; in about half the cases, a definitive cause is unknown. It is not a hereditary condition, nor is it contagious.Aplastic anemia is also sometimes associated with exposure to toxins such as benzene or with the use of certain drugs, including chloramphenicol, carbamazepine, felbamate, phenytoin, quinine, and phenylbutazone. However, the probability that these drugs will lead to aplastic anemia in a given patient is very low. Chloramphenicol treatment is associated with aplasia in less than one in 40,000 treatment courses, and carbamazepine aplasia is even rarer.Exposure to ionizing radiation from radioactive materials or radiation-producing devices is also associated with the development of aplastic anemia. Marie Curie, famous for her pioneering work in the field of radioactivity, died of aplastic anemia after working unprotected with radioactive materials for a long period of time; the damaging effects of ionizing radiation were not then known.Aplastic anemia is present in up to 2% of patients with acute viral hepatitis.One known cause is an autoimmune disorder in which white blood cells attack the bone marrow. Acquired aplastic anemia is a T-cell mediated autoimmune disease, in which regulatory T cells are decreased and T-bet, a transcription factor and key regulator of Th1 development and function, is upregulated in affected T-cells. As a result of active transcription of the interferon gamma (IFN-gamma) gene by T-bet, IFN-gamma levels are increased, which reduces colony formation of hematopoietic progenitor cells in vitro by inducing apoptosis of CD34+ cells in the bone marrow.Short-lived aplastic anemia can also be a result of parvovirus infection. In humans, the P antigen (also known as globoside), one of many cellular receptors that contribute to a persons blood type, is the cellular receptor for parvovirus B19, which causes erythema infectiosum (fifth disease) in children. Because it infects red blood cells as a result of the affinity for the P antigen, parvovirus causes complete cessation of red blood cell production. In most cases, this goes unnoticed, as red blood cells live on average 120 days, and the drop in production does not significantly affect the total number of circulating cells. However, in people with conditions where the cells die early (such as sickle cell disease), parvovirus infection can lead to severe anemia.More frequently, parvovirus B19 is associated with aplastic crisis, which involves only red blood cells (despite the name). Aplastic anemia involves all cell lines. Other viruses that have been linked to the development of aplastic anemia include hepatitis, Epstein-Barr, cytomegalovirus, and HIV. In some animals, aplastic anemia may have other causes. For example, in the ferret (Mustela putorius furo), it is caused by estrogen toxicity, because female ferrets are induced ovulators, so mating is required to bring the female out of heat. Intact females, if not mated, will remain in heat, and after some time the high levels of estrogen will cause the bone marrow to stop producing red blood cells. Diagnosis Aplastic anemia must be differentiated from pure red cell aplasia. In aplastic anemia, the patient has pancytopenia (i.e., also leukopenia and thrombocytopenia) resulting in a decrease of all formed elements. In contrast, pure red cell aplasia is characterized by a reduction in red cells only. The diagnosis can only be confirmed with a bone marrow examination.Before this procedure is undertaken, a patient will generally have had other blood tests to find diagnostic clues, including a complete blood count, renal function and electrolytes, liver enzymes, thyroid function tests, vitamin B12 and folic acid levels. Tests that may aid in determining an etiology for aplastic anemia include: History of iatrogenic exposure to cytotoxic chemotherapy: transient bone marrow suppression Vitamin B12 and folate levels: vitamin deficiency Liver tests: liver diseases Viral studies: viral infections Chest X-ray: infections X-rays, computed tomography (CT) scans, or ultrasound imaging tests: enlarged lymph nodes (sign of lymphoma), kidneys, and bones in arms and hands (abnormal in Fanconi anemia) Antibody test: immune competency Blood tests for paroxysmal nocturnal hemoglobinuria Bone marrow aspirate and biopsy: to rule out other causes of pancytopenia (i.e., neoplastic infiltration or significant myelofibrosis). Pathogenesis For many years, the cause of acquired aplastic anemia was not clear. Now, autoimmune processes are considered to be responsible. The majority of cases are hypothesized to be the result of T-cell-mediated autoimmunity and destruction of the bone marrow, which leads to defective or nearly absent hematopoiesis. It is suggested that unidentified antigens cause a polyclonal expansion of dysregulated CD4+ T cells and overproduction of pro-inflammatory cytokines, such as interferon-γ and tumor necrosis factor-α. Ex vivo bone marrow models show an expansion of dysregulated CD8+ T cell populations. Activated T cells also induce apoptosis in hematopoietic stem cells.Aplastic anemia is associated with increased levels of Th17 cells—which produce pro-inflammatory cytokine IL-17—and interferon-γ-producing cells in the peripheral blood and bone marrow. Th17 cell populations also negatively correlate with regulatory T-cell populations, suppressing auto-reactivity to normal tissues, including the bone marrow. Deep phenotyping of regulatory T-cells showed two subpopulations with specific phenotypes, gene expression signatures, and functions.Studies in patients who responded to immunosuppressive therapy found dominant subpopulations characterized by higher expression of HLA‐DR2 and HLA‐DR15 (mean age of two groups: 34 and 21 years), FOXP3, CD95, and CCR4; lower expression of CD45RA (mean age: 45 years); and expression of the IL‐2/STAT5 pathway. Higher frequency of HLA‐DR2 and HLA‐DR15 may cause augmented presentation of antigens to CD4+ T-cells, resulting in immune‐mediated destruction of the stem cells. In addition, HLA‐DR2-expressing cells augment the release of tumor necrosis factor-α, which plays a role in disease pathology.The hypothesis of aberrant, disordered T‐cell populations as the initiators of aplastic anemia is supported by findings that immunosuppressive therapy for T-cells (for example, anti-thymocyte globulin and ciclosporin) results in a response in up to 80% of severe aplastic anemia patients. CD34+ progenitor cells and lymphocytes in the bone marrow over-express the Fas receptor, the main element in apoptotic signaling. A significant increase in the proportion of apoptotic cells in the bone marrow of aplastic anemia patients has been demonstrated. This suggests that cytokine‐induced and Fas‐mediated apoptosis play roles in bone marrow failure because annihilation of CD34+ progenitor cells leads to hematopoietic stem cell deficiency. Frequently detected autoantibodies A study of blood and bone marrow samples obtained from 18 aplastic anemia patients revealed more than 30 potential specific candidate autoantigens after the serologic screening of a fetal liver library with sera from 8 patients. The human fetal liver cDNA library (chosen because of its high enrichment of CD34+ cells), compared with peripheral blood or the bone marrow, significantly increased the likelihood of detection of possible stem cell autoantigens. ELISA and Western blot analysis revealed that an IgG antibody response to one of the candidate autoantigens, kinectin, was present in a significant number of patients (39%). In contrast, no antibody was detected in 35 healthy volunteers. Antibody was detected in both transfused and transfusion-naive patients, suggesting that antikinectin autoantibody development was not due to transfusion-related alloreactivity. Negative sera from patients with other autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis) showed a specific association of antikinectin antibodies with aplastic anemia. These results support the hypothesis that immune response to kinectin may be involved in the pathophysiology of the disease. Kinectin is a large molecule (1,300 amino acid residues) expressed by CD34+ cells. Several kinectin-derived peptides can be processed and presented by HLA I and can induce antigen-specific CD8+ T-cell responses. Bone marrow microenvironment A critical factor for healthy stem cell production is the bone marrow microenvironment. Important components are stromal cells, the extracellular matrix, and local cytokine gradients. The hematopoietic and non-hematopoietic elements of the bone marrow closely interact with each other and sustain and maintain the balance of hematopoiesis. In addition to low numbers of hematopoietic stem cells, aplastic anemia patients have altered hematopoietic niche: cytotoxic T-cells (polyclonal expansion of dysregulated CD4+ T-cells) trigger apoptosis in bone marrow cells activated T-cells induce apoptosis in hematopoietic stem cells there is abnormal production of interferon-γ, tumor necrosis factor-α, and transforming growth factor overexpression of Fas receptor leads to apoptosis of hematopoietic stem cells poor quality and quantity of regulatory T-cells means failure in suppressing auto-reactivity, which leads to abnormal T-cell expansion due to higher amounts of interferon-γ, macrophages are more frequent in the bone marrow of aplastic anemia patients; interferon-mediated loss of hematopoietic stem cells occurs only in the presence of macrophages interferon-γ can cause direct exhaustion and depletion of hematopoietic stem cells and indirect reduction of their functions through cells that are part of the bone marrow microenvironment (e.g., macrophages and mesenchymal stem cells) increased numbers of B cells produce autoantibodies against hematopoietic stem cells increased numbers of adipocytes and decreased numbers of pericytes also play a role in suppressing hematopoiesis Treatment Treating immune-mediated aplastic anemia involves suppression of the immune system, an effect achieved by daily medicine or, in more severe cases, a bone marrow transplant, a potential cure. The transplanted bone marrow replaces the failing bone marrow cells with new ones from a matching donor. The multipotent stem cells in the bone marrow reconstitute all three blood cell lines, giving the patient a new immune system, red blood cells, and platelets. However, besides the risk of graft failure, there is also a risk that the newly created white blood cells may attack the rest of the body ("graft-versus-host disease"). In young patients with an HLA-matched sibling donor, bone marrow transplant can be considered as a first-line treatment. Patients lacking a matched sibling donor typically pursue immunosuppression as a first-line treatment, and matched, unrelated donor transplants are considered second-line therapy. Treatment often includes a course of antithymocyte globulin (ATG) and several months of treatment with ciclosporin to modulate the immune system. Chemotherapy with agents such as cyclophosphamide may also be effective but is more toxic than ATG. Antibody therapy such as ATG targets T cells, which are believed to attack the bone marrow. Corticosteroids are generally ineffective, though they are used to ameliorate serum sickness caused by ATG. Normally, success is judged by bone marrow biopsy six months after initial treatment with ATG.One prospective study involving cyclophosphamide was terminated early due to a high incidence of mortality from severe infections as a result of prolonged neutropenia.Before the above treatments became available, patients with low leukocyte counts were often confined to a sterile room or bubble (to reduce risk of infection), as in the case of Ted DeVita. Follow-up Full blood counts are required on a regular basis to determine whether the patient is still in remission. Many patients with aplastic anemia also have clones of cells characteristic of paroxysmal nocturnal hemoglobinuria (PNH), a rare disease that causes anemia with thrombocytopenia and/or thrombosis and is sometimes referred to as AA/PNH. Occasionally PNH dominates over time, with the major manifestation of intravascular hemolysis. The overlap of AA and PNH has been speculated to be an escape mechanism by the bone marrow against destruction by the immune system. Flow cytometry testing is performed regularly in people with previous aplastic anemia to monitor for the development of PNH. Prognosis Untreated, severe aplastic anemia has a high risk of death. Modern treatment produces a five-year survival rate that exceeds 85%, with younger age associated with higher survival.Survival rates for stem cell transplants vary depending on the age and availability of a well-matched donor. They are better for patients who have donors that are matched siblings and worse for patients who receive their marrow from unrelated donors. Overall, the five-year survival rate is higher than 75% among recipients of blood marrow transplantation.Older people (who are generally too frail to undergo bone marrow transplants) and people who are unable to find a good bone marrow match have five-year survival rates of up to 35% when undergoing immune suppression.Relapses are common. Relapse following ATG/ciclosporin use can sometimes be treated with a repeated course of therapy. In addition, 10–15% of severe aplastic anemia cases evolve into myelodysplastic syndrome and leukemia. According to one study, 15.9% of children who responded to immunosuppressive therapy eventually relapsed.Milder disease may resolve on its own. Etymology Aplastic is a combination of two ancient Greek elements: a- (meaning "not") and -plasis ("forming into a shape"). Anemia is a combination of the ancient Greek element an- ("not") and -emia (new Latin from the Greek -(h)aimia, meaning "blood"). Epidemiology Aplastic anemia is a rare, noncancerous disorder in which the blood marrow is unable to adequately produce blood cells required for survival. It is estimated that the incidence of aplastic anemia is 0.7–4.1 cases per million people worldwide, with the prevalence between men and women being approximately equal. The incidence rate of aplastic anemia in Asia is 2–3 times higher than it is in the West; the incidence in the United States is 300–900 cases per year. The disease most commonly affects adults aged 15–25 and over the age of 60, but it can be observed in all age groups.The disease is usually acquired during life and not inherited. Acquired cases are often linked to environmental exposures such as chemicals, drugs, and infectious agents that damage the bone marrow and compromise its ability to generate new blood cells. However, in many instances the underlying cause for the disease is not found. This is referred to as idiopathic aplastic anemia and accounts for 75% of cases. This compromises the effectiveness of treatment since treatment of the disease is often aimed at the underlying cause.Those with a higher risk for aplastic anemia include individuals who are exposed to high-dose radiation or toxic chemicals, take certain prescription drugs, have pre-existing autoimmune disorders or blood diseases, or are pregnant. No screening test currently exists for early detection of aplastic anemia. Notable cases Marie Curie Eleanor Roosevelt Donny Schmit Ted DeVita Demetrio Stratos John Dill (British Field Marshal) Robert McFall (asbestos worker from Pittsburgh who unsuccessfully sued his cousin for a transfusion of bone marrow) See also Fanconi anemia Acquired pure red cell aplasia References External links Mayo Clinic MedlinePlus Encyclopedia: 000554—Idiopathic aplastic anemia

Hey Aarogya!, what is Hepatocellular carcinoma

Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.It occurs in the setting of chronic liver inflammation, and is most closely linked to chronic viral hepatitis infection (hepatitis B or C) or exposure to toxins such as alcohol, aflatoxin, or pyrrolizidine alkaloids. Certain diseases, such as hemochromatosis and alpha 1-antitrypsin deficiency, markedly increase the risk of developing HCC. Metabolic syndrome and NASH are also increasingly recognized as risk factors for HCC.As with any cancer, the treatment and prognosis of HCC vary depending on the specifics of tumor histology, size, how far the cancer has spread, and overall health. The vast majority of HCC cases and the lowest survival rates after treatment occur in Asia and sub-Saharan Africa, in countries where hepatitis B infection is endemic and many are infected from birth. The incidence of HCC in the United States and other developing countries is increasing due to an increase in hepatitis C virus infections. It is more than four times as common in males as in females, for unknown reasons. Signs and symptoms Most cases of HCC occur in people who already have signs and symptoms of chronic liver disease. They may present with worsening symptoms or without symptoms at the time of cancer detection. HCC may present with non-specific symptoms such as abdominal pain, nausea, vomiting, or feeling tired. Some symptoms that are more closely associated with liver disease include yellow skin (also called jaundice), abdominal swelling due to fluid in the abdominal cavity, easy bruising from blood clotting abnormalities, loss of appetite, unintentional weight loss, abdominal pain, nausea, vomiting, or feeling tired. Risk factors Since HCC mostly occurs in people with cirrhosis of the liver, risk factors generally include factors which cause chronic liver disease that may lead to cirrhosis. Still, certain risk factors are more highly associated with HCC than others. For example, while heavy alcohol consumption is estimated to cause 60–70% of cirrhosis, the vast majority of HCC occurs in cirrhosis attributed to viral hepatitis (although there may be overlap). Recognized risk factors include: Chronic viral hepatitis (estimated cause of 80% cases globally) Chronic hepatitis B (about 50% cases) Chronic hepatitis C (about 25% cases) Toxins: Alcohol use disorder: the most common cause of cirrhosis Aflatoxin Iron overload state (hemochromatosis) Pyrrolizidine alkaloids Metabolic: Nonalcoholic steatohepatitis: up to 20% progress to cirrhosis Nonalcoholic fatty liver disease Type 2 diabetes (probably aided by obesity) Congenital disorders: Alpha 1-antitrypsin deficiency Wilsons disease (controversial; while some theorise the risk increases, case studies are rare and suggest the opposite where Wilsons disease actually may confer protection) Hemophilia, although statistically associated with higher risk of HCC, this is due to coincident chronic viral hepatitis infection related to repeated blood transfusions over lifetime.The significance of these risk factors varies globally. In regions where hepatitis B infection is endemic, such as southeast China, hepatitis B is the predominant cause. In populations largely protected by hepatitis B vaccination, such as the United States, HCC is most often linked to causes of cirrhosis such as chronic hepatitis C, obesity, and excessive alcohol use.Certain benign liver tumors, such as hepatocellular adenoma, may sometimes be associated with coexisting malignant HCC. Evidence is limited for the true incidence of malignancy associated with benign adenomas; however, the size of hepatic adenoma is considered to correspond to risk of malignancy and so larger tumors may be surgically removed. Certain subtypes of adenoma, particularly those with β-catenin activation mutation, are particularly associated with increased risk of HCC.Chronic liver disease is rare in children and adolescents; however, congenital liver disorders are associated with an increased the chance of developing HCC. Specifically, children with biliary atresia, infantile cholestasis, glycogen-storage diseases, and other cirrhotic diseases of the liver are predisposed to developing HCC in childhood.Young adults afflicted by the rare fibrolamellar variant of hepatocellular carcinoma may have none of the typical risk factors, such as cirrhosis and hepatitis. Diabetes mellitus The risk of hepatocellular carcinoma in type 2 diabetics is greater (from 2.5 to 7.1 times the nondiabetic risk) depending on the duration of diabetes and treatment protocol. A suspected contributor to this increased risk is circulating insulin concentration such that diabetics with poor insulin control or on treatments that elevate their insulin output (both states that contribute to a higher circulating insulin concentration) show far greater risk of hepatocellular carcinoma than diabetics on treatments that reduce circulating insulin concentration. On this note, some diabetics who engage in tight insulin control (by keeping it from being elevated) show risk levels low enough to be indistinguishable from the general population. This phenomenon is thus not isolated to diabetes mellitus type 2, since poor insulin regulation is also found in other conditions such as metabolic syndrome (specifically, when evidence of nonalcoholic fatty liver disease or NAFLD is present) and again evidence of greater risk exists here, too. While there are claims that anabolic steroid abusers are at greater risk (theorized to be due to insulin and IGF exacerbation), the only evidence that has been confirmed is that anabolic steroid users are more likely to have the benign hepatocellular adenomas transform into the more dangerous hepatocellular carcinoma. Pathogenesis Hepatocellular carcinoma, like any other cancer, develops when epigenetic alterations and mutations affecting the cellular machinery cause the cell to replicate at a higher rate and/or result in the cell avoiding apoptosis.In particular, chronic infections of hepatitis B and/or C can aid the development of hepatocellular carcinoma by repeatedly causing the bodys own immune system to attack the liver cells, some of which are infected by the virus, others merely bystanders. Activated immune-system inflammatory cells release free radicals, such as reactive oxygen species and nitric oxide reactive species, which in turn can cause DNA damage and lead to carcinogenic gene mutations. Reactive oxygen species also cause epigenetic alterations at the sites of DNA repair.While this constant cycle of damage followed by repair can lead to mistakes during repair, which in turn lead to carcinogenesis, this hypothesis is more applicable, at present, to hepatitis C. Chronic hepatitis C causes HCC through the stage of cirrhosis. In chronic hepatitis B, however, the integration of the viral genome into infected cells can directly induce a noncirrhotic liver to develop HCC. Alternatively, repeated consumption of large amounts of ethanol can have a similar effect. The toxin aflatoxin from certain Aspergillus species of fungi is a carcinogen and aids carcinogenesis of hepatocellular cancer by building up in the liver. The combined high prevalence of rates of aflatoxin and hepatitis B in settings such as China and West Africa has led to relatively high rates of hepatocellular carcinoma in these regions. Other viral hepatitides such as hepatitis A have no potential to become a chronic infection, thus are not related to HCC. Diagnosis Methods of diagnosis in HCC have evolved with the improvement in medical imaging. The evaluation of both asymptomatic patients and those with symptoms of liver disease involves blood testing and imaging evaluation. Historically, a biopsy of a tumor was required to prove an HCC diagnosis. However, imaging (especially MRI) findings may be conclusive enough to obviate histopathologic confirmation. Screening HCC remains associated with a high mortality rate, in part because initial diagnosis commonly occurs at an advanced stage of disease. As with other cancers, outcomes are significantly improved if treatment is initiated earlier in the disease process. Since the vast majority of HCC cases occur in people with certain chronic liver diseases, especially those with cirrhosis, liver screening is commonly advocated in this population. Specific screening guidelines continue to evolve over time as evidence of its clinical impact becomes available. In the United States, the most commonly observed guidelines are those published by the American Association for the Study of Liver Diseases(AASLD), which recommends ultrasound screenings every six months for people with cirrhosis, with or without measurement of blood levels of tumor marker alpha-fetoprotein (AFP). Elevated levels of AFP are associated with active HCC disease, though their reliability can be inconsistent. At levels >20, sensitivity is 41–65% and specificity is 80–94%. However, at levels >200, sensitivity is 31 and specificity is 99%.On ultrasound, HCC often appears as a small hypoechoic lesion with poorly defined margins and coarse, irregular internal echoes. When the tumor grows, it can sometimes appear heterogeneous with fibrosis, fatty change, and calcifications. This heterogeneity can look similar to cirrhosis and the surrounding liver parenchyma. A systematic review found that the sensitivity was 60% (95% CI 44–76%) and specificity was 97% (95% CI 95–98%) compared with pathologic examination of an explanted or resected liver as the reference standard. The sensitivity increases to 79% with AFP correlation.Controversy remains as to the most effective screening protocols. For example, while some data support decreased mortality related to screening people with hepatitis B infection, the AASLD notes, “There are no randomized trials [for screening] in Western populations with cirrhosis secondary to chronic hepatitis C or fatty liver disease, and thus there is some controversy surrounding whether surveillance truly leads to a reduction in mortality in this population of patients with cirrhosis.” Higher risk people In a person where a higher suspicion of HCC exists, such as a person with symptoms or abnormal blood tests (i.e. alpha-fetoprotein and des-gamma carboxyprothrombin levels), evaluation requires imaging of the liver by CT or MRI scans. Optimally, these scans are performed with intravenous contrast in multiple phases of hepatic perfusion to improve detection and accurate classification of any liver lesions by the interpreting radiologist. Due to the characteristic blood flow pattern of HCC tumors, a specific perfusion pattern of any detected liver lesion may conclusively detect an HCC tumor. Alternatively, the scan may detect an indeterminate lesion and further evaluation may be performed by obtaining a physical sample of the lesion. Imaging Ultrasound, CT scan, and MRI may be used to evaluate the liver for HCC. On CT and MRI, HCC can have three distinct patterns of growth: A single large tumor Multiple tumors Poorly defined tumor with an infiltrative growth patternA systematic review of CT diagnosis found that the sensitivity was 68% (95% CI 55–80%) and specificity was 93% (95% CI 89–96%) compared with pathologic examination of an explanted or resected liver as the reference standard. With triple-phase helical CT, the sensitivity was 90% or higher, but these data have not been confirmed with autopsy studies.However, MRI has the advantage of delivering high-resolution images of the liver without ionizing radiation. HCC appears as a high-intensity pattern on T2-weighted images and a low-intensity pattern on T1-weighted images. The advantage of MRI is that it has improved sensitivity and specificity when compared to ultrasound and CT in cirrhotic patients with whom it can be difficult to differentiate HCC from regenerative nodules. A systematic review found that the sensitivity was 81% (95% CI 70–91%) and specificity was 85% (95% CI 77–93%) compared with pathologic examination of an explanted or resected liver as the reference standard. The sensitivity is further increased if gadolinium contrast-enhanced and diffusion-weighted imaging are combined. MRI is more sensitive and specific than CT.Liver image reporting and data system (LI-RADS) is a classification system for the reporting of liver lesions detected on CT and MRI. Radiologists use this standardized system to report on suspicious lesions and to provide an estimated likelihood of malignancy. Categories range from LI-RADS (LR) 1 to 5, in order of concern for cancer. A biopsy is not needed to confirm the diagnosis of HCC if certain imaging criteria are met. Pathology Macroscopically, liver cancer appears as a nodular or infiltrative tumor. The nodular type may be solitary (large mass) or multiple (when developed as a complication of cirrhosis). Tumor nodules are round to oval, gray or green (if the tumor produces bile), well circumscribed but not encapsulated. The diffuse type is poorly circumscribed and infiltrates the portal veins, or the hepatic veins (rarely).Microscopically, the four architectural and cytological types (patterns) of hepatocellular carcinoma are: fibrolamellar, pseudoglandular (adenoid), pleomorphic (giant cell), and clear cell. In well-differentiated forms, tumor cells resemble hepatocytes, form trabeculae, cords, and nests, and may contain bile pigment in the cytoplasm. In poorly differentiated forms, malignant epithelial cells are discohesive, pleomorphic, anaplastic, and giant. The tumor has a scant stroma and central necrosis because of the poor vascularization. A fifth form – lymphoepithelioma like hepatocellular carcinoma – has also been described. Staging BCLC Staging System The prognosis of HCC is affected by the staging of the tumor and the livers function due to the effects of liver cirrhosis.A number of staging classifications for HCC are available. However, due to the unique nature of the carcinoma to fully encompass all the features that affect the categorization of the HCC, a classification system should incorporate tumor size and number, presence of vascular invasion and extrahepatic spread, liver function (levels of serum bilirubin and albumin, presence of ascites, and portal hypertension) and general health status of the patient (defined by the ECOG classification and the presence of symptoms).Of all the staging classification systems available, the Barcelona Clinic Liver Cancer staging classification encompasses all of the above characteristics. This staging classification can be used to select people for treatment. Important features that guide treatment include: size spread (stage) involvement of liver vessels presence of a tumor capsule presence of extrahepatic metastases presence of daughter nodules vascularity of the tumorMRI is the best imaging method to detect the presence of a tumor capsule. The most common sites of metastasis are the lung, abdominal lymph nodes, and bone. Prevention Since hepatitis B and C are some of the main causes of hepatocellular carcinoma, prevention of infection is key to then prevent HCC. Thus, childhood vaccination against hepatitis B may reduce the risk of liver cancer in the future. In the case of patients with cirrhosis, alcohol consumption is to be avoided. Also, screening for hemochromatosis may be beneficial for some patients. Whether screening those with chronic liver disease for HCC improves outcomes is unclear. Treatment Treatment of hepatocellular carcinoma varies by the stage of disease, a persons likelihood to tolerate surgery, and availability of liver transplant: Curative intention: for limited disease, when the cancer is limited to one or more areas of within the liver, surgically removing the malignant cells may be curative. This may be accomplished by resection the affected portion of the liver (partial hepatectomy) or in some cases by orthotopic liver transplantation of the entire organ. "Bridging" intention: for limited disease which qualifies for potential liver transplantation, the person may undergo targeted treatment of some or all of the known tumor while waiting for a donor organ to become available. "Downstaging" intention: for moderately advanced disease which has not spread beyond the liver, but is too advanced to qualify for curative treatment. The person may be treated by targeted therapies in order to reduce the size or number of active tumors, with the goal of once again qualifying for liver transplant after this treatment. Palliative intention: for more advanced disease, including spread of cancer beyond the liver or in persons who may not tolerate surgery, treatment intended to decrease symptoms of disease and maximize duration of survival.Loco-regional therapy (also referred to as liver-directed therapy) refers to any one of several minimally-invasive treatment techniques to focally target HCC within the liver. These procedures are alternatives to surgery, and may be considered in combination with other strategies, such as a later liver transplantation. Generally, these treatment procedures are performed by interventional radiologists or surgeons, in coordination with a medical oncologist. Loco-regional therapy may refer to either percutaneous therapies (e.g. cryoablation), or arterial catheter-based therapies (chemoembolization or radioembolization). Surgical resection Surgical removal of the tumor is associated with better cancer prognosis, but only 5–15% of patients are suitable for surgical resection due to the extent of disease or poor liver function. Surgery is only considered if the entire tumor can be safely removed while preserving sufficient functional liver to maintain normal physiology. Thus, preoperative imaging assessment is critical to determine both the extent of HCC and to estimate the amount of residual liver remaining after surgery. To maintain liver function, residual liver volume should exceed 25% of total liver volume in a noncirrhotic liver, greater than 40% in a cirrhotic liver. Surgery on diseased or cirrhotic livers is generally associated with higher morbidity and mortality. The overall recurrence rate after resection is 50–60%. The Singapore Liver Cancer Recurrence score can be used to estimate risk of recurrence after surgery. Liver transplantation Liver transplantation, replacing the diseased liver with a cadaveric or a living donor liver, plays an increasing role in treatment of HCC. Although outcomes following liver transplant were initially poor (20%–36% survival rate), outcomes have significantly improved with improvement in surgical techniques and adoption of the Milan criteria at US transplantation centers. Expanded Shanghai criteria in China have resulted in overall survival and disease-free survival rates similar to those achieved using the Milan criteria. Studies from the late 2000s obtained higher survival rates ranging from 67% to 91%.The risks of liver transplantation extend beyond risk of the procedure itself. The immunosuppressive medication required after surgery to prevent rejection of the donor liver also impairs the bodys natural ability to combat dysfunctional cells. If the tumor has spread undetected outside the liver before the transplant, the medication effectively increases the rate of disease progression and decreases survival. With this in mind, liver transplant "can be a curative approach for patients with advanced HCC without extrahepatic metastasis". In fact, among patients with compensated cirrhosis, transplantation is not associated with improved survival compared to hepatectomy, but instead is significantly more expensive. Patient selection is considered a major key for success. Ablation Radiofrequency ablation (RFA) uses high-frequency radio waves to destroy tumor by local heating. The electrodes are inserted into the liver tumor under ultrasound image guidance using percutaneous, laparoscopic or open surgical approach. It is suitable for small tumors (<5 cm). RFA has the best outcomes in patients with a solitary tumor less than 4 cm. Since it is a local treatment and has minimal effect on normal healthy tissue, it can be repeated multiple times. Survival is better for those with smaller tumors. In one study, In one series of 302 patients, the three-year survival rates for lesions >5 cm, 2.1 to 5 cm, and ≤2 cm were 59, 74, and 91%, respectively. A large randomized trial comparing surgical resection and RFA for small HCC showed similar four-year survival and less morbidities for patients treated with RFA. Cryoablation is a technique used to destroy tissue using cold temperature. The tumor is not removed and the destroyed cancer is left to be reabsorbed by the body. Initial results in properly selected patients with unresectable liver tumors are equivalent to those of resection. Cryosurgery involves the placement of a stainless steel probe into the center of the tumor. Liquid nitrogen is circulated through the end of this device. The tumor and a half inch margin of normal liver are frozen to −190 °C for 15 minutes, which is lethal to all tissues. The area is thawed for 10 minutes and then refrozen to −190 °C for another 15 minutes. After the tumor has thawed, the probe is removed, bleeding is controlled, and the procedure is complete. The patient spends the first postoperative night in the intensive care unit and typically is discharged in 3–5 days. Proper selection of patients and attention to detail in performing the cryosurgical procedure are mandatory to achieve good results and outcomes. Frequently, cryosurgery is used in conjunction with liver resection, as some of the tumors are removed while others are treated with cryosurgery. Percutaneous ethanol injection is well tolerated, with high RR in small (<3 cm) solitary tumors; as of 2005, no randomized trial has comparing resection to percutaneous treatments; recurrence rates are similar to those for postresection. However, a comparative study found that local therapy can achieve a 5-year survival rate around 60% for patients with small HCC. Arterial catheter-based treatment Transcatheter arterial chemoembolization (TACE) is performed for unresectable tumors or as a temporary treatment while waiting for liver transplant ("bridge to transplant"). TACE is done by injecting an antineoplastic drug (e.g. cisplatin) mixed with a radio-opaque contrast (e.g. Lipiodol) and an embolic agent (e.g. Gelfoam) into the right or left hepatic artery via the groin artery. The goal of the procedure is to restrict the tumors vascular supply while supplying a targeted chemotherapeutic agent. TACE has been shown to increase survival and to downstage HCC in patients who exceed the Milan criteria for liver transplant. Patients who undergo the procedure are followed with CT scans and may need additional TACE procedures if the tumor persists. As of 2005, multiple trials show objective tumor responses and slowed tumor progression, but questionable survival benefit compared to supportive care; greatest benefit is seen in people with preserved liver function, absence of vascular invasion, and smallest tumors. TACE is not suitable for big tumors (>8 cm), the presence of portal vein thrombus, tumors with a portal-systemic shunt, and patients with poor liver function. Selective internal radiation therapy (SIRT) can be used to destroy the tumor from within (thus minimizing exposure to healthy tissue). Similar to TACE, this is a procedure in which an interventional radiologist selectively injects the artery or arteries supplying the tumor with a chemotherapeutic agent. The agent is typically Yttrium-90 (Y-90) incorporated into embolic microspheres that lodge in the tumor vasculature, causing ischemia and delivering their radiation dose directly to the lesion. This technique allows for a higher, local dose of radiation to be delivered directly to the tumor while sparing normal healthy tissue. While not curative, patients have increased survival. No studies have been done to compare whether SIRT is superior to TACE in terms of survival outcomes, although retrospective studies suggest similar efficacy. Two products are available, SIR-Spheres and TheraSphere. The latter is an FDA-approved treatment for primary liver cancer (HCC) which has been shown in clinical trials to increase the survival rate of low-risk patients. SIR-Spheres are FDA-approved for the treatment of metastatic colorectal cancer, but outside the US, SIR-Spheres are approved for the treatment of any nonresectable liver cancer including primary liver cancer. External beam therapy The role of radiotherapy in the treatment of hepatocellular carcinoma has evolved as technological advancements in treatment delivery and imaging have provided a means for safe and effective radiotherapy delivery in a wide spectrum of HCC patients. In metastatic cases, radiotherapy can be used for palliative care. Proton therapy for unresectable hepatocellular carcinoma was associated with improved survival relative to photon-based radiation therapy which may be driven by decreased incidence of post-treatment liver decompensation and a number of randomized controlled trials are currently ongoing. Systemic In disease which has spread beyond the liver, systemic therapy may be a consideration. In 2007, Sorafenib, an oral multikinase inhibitor, was the first systemic agent approved for first-line treatment of advanced HCC. Trials have found modest improvement in overall survival: 10.7 months vs 7.9 months and 6.5 months vs 4.2 months.The most common side effects of Sorafenib include a hand-foot skin reaction and diarrhea. Sorafenib is thought to work by blocking growth of both tumor cells and new blood vessels. Numerous other molecular targeted drugs are being tested as alternative first- and second-line treatments for advanced HCC.More recently, a host of additional targeted therapies and immune checkpoint inhibitors have been found to be effective against this disease. For instance, in the recent phase III trial IMBrave 150, the combination of atezolizumab and bevacizumab was found to improve both overall and progression-free survival compared to sorafenib alone. Other Portal vein embolization (PVE): This technique is sometimes used to increase the volume of healthy liver, in order to improve chances of survival following surgical removal of diseased liver. For example, embolization of the right main portal vein would result in compensatory hypertrophy of the left lobe, which may qualify the patient for a partial hepatectomy. Embolization is performed by an interventional radiologist using a percutaneous transhepatic approach. This procedure can also serve as a bridge to transplant. High intensity focused ultrasound (HIFU) (as opposed to diagnostic ultrasound) is an experimental technique which uses high-powered ultrasound waves to destroy tumor tissue. A systematic review assessed 12 articles involving a total of 318 patients with hepatocellular carcinoma treated with Yttrium-90 radioembolization. Excluding a study of only one patient, post-treatment CT evaluation of the tumor showed a response ranging from 29 to 100% of patients evaluated, with all but two studies showing a response of 71% or greater. Prognosis The usual outcome is poor because only 10–20% of hepatocellular carcinomas can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually deadly within 3 to 6 months. This is partially due to late presentation with tumors, but also the lack of medical expertise and facilities in the regions with high HCC prevalence. However, survival can vary, and occasionally people survive much longer than 6 months. The prognosis for metastatic or unresectable HCC has improved due to the approval of Sorafenib (Nexavar®) for advanced HCC. Epidemiology HCC is one of the most common tumors worldwide. The epidemiology of HCC exhibits two main patterns, one in North America and Western Europe and another in non-Western countries, such as those in sub-Saharan Africa, Central and Southeast Asia, and the Amazon basin. Males are affected more than females usually, and it is most common between the ages of 30 and 50, Hepatocellular carcinoma causes 662,000 deaths worldwide per year about half of them in China. Africa and Asia In some parts of the world, such as sub-Saharan Africa and Southeast Asia, HCC is the most common cancer, generally affecting men more than women, and with an age of onset between the late teens and 30s. This variability is in part due to the different patterns of hepatitis B and hepatitis C transmission in different populations – infection at or around birth predispose to earlier cancers than if people are infected later. The time between hepatitis B infection and development into HCC can be years, even decades, but from diagnosis of HCC to death, the average survival period is only 5.9 months according to one Chinese study during the 1970-80s, or 3 months (median survival time) in sub-Saharan Africa according to Mansons textbook of tropical diseases. HCC is one of the deadliest cancers in China, where chronic hepatitis B is found in 90% of cases. In Japan, chronic hepatitis C is associated with 90% of HCC cases. Foods infected with Aspergillus flavus (especially peanuts and corns stored during prolonged wet seasons) which produces aflatoxins pose another risk factor for HCC. North America and Western Europe The most common malignant tumors in the liver represent metastases (spread) from tumors which originate elsewhere in the body. Among cancers that originate from liver tissue, HCC is the most common primary liver cancer. In the United States, the US surveillance, epidemiology, and end results database program, shows that HCC accounts for 65% of all cases of liver cancers. As screening programs are in place for high-risk persons with chronic liver disease, HCC is often discovered much earlier in Western countries than in developing regions such as sub-Saharan Africa.Acute and chronic hepatic porphyrias (acute intermittent porphyria, porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria) and tyrosinemia type I are risk factors for hepatocellular carcinoma. The diagnosis of an acute hepatic porphyria (AIP, HCP, VP) should be sought in patients with HCC without typical risk factors of hepatitis B or C, alcoholic liver cirrhosis, or hemochromatosis. Both active and latent genetic carriers of acute hepatic porphyrias are at risk for this cancer, although latent genetic carriers have developed the cancer at a later age than those with classic symptoms. Patients with acute hepatic porphyrias should be monitored for HCC.The incidence of HCC is relatively lower in the Western Hemisphere than in Eastern Asia. However, despite the statistics being low, the diagnosis of HCC has increased since the 1980s and it is continuing to increase, making it one of the rising causes of death due to cancer. The common risk factor for HCC is hepatitis C, along with other health issues. Research Preclinical Mipsagargin (G-202), has orphan drug designation as a treatment during chemotherapy for HCC. It is a thapsigargin-based prodrug with cytotoxic activity used to reduce blood flow to the tumor during treatment. Results from Phase 2 trial recommended G-202 as a first-in-class PSMA-targeted prodrug and that it move to clinical trials.Current research includes the search for the genes that are disregulated in HCC, antiheparanase antibodies, protein markers, non-coding RNAs (such as TUC338) and other predictive biomarkers. As similar research is yielding results in various other malignant diseases, it is hoped that identifying the aberrant genes and the resultant proteins could lead to the identification of pharmacological interventions for HCC.The development of three-dimensional culture methods provides a new approach for preclinical studies of cancer therapy using patient-derived organoids. These miniaturized organoid avatars of a patients tumor recapitulate several features of the original tumor, rendering them an attractive model for drug-sensitivity testing and precision medicine for HCC and other types of primary liver cancer.Furthermore, HCC occurs in patients with liver disease. A biomarker named six-miRNA signature allows effective treatment of patients with HCC and is able to predict its recurrence in the liver. Clinical JX-594, an oncolytic virus, has orphan drug designation for this condition and is undergoing clinical trials. Hepcortespenlisimut-L (Hepko-V5), an oral cancer vaccine, also has US FDA orphan drug designation for HCC. Immunitor Inc. completed a Phase II trial, published in 2017. A randomized trial of people with advanced HCC showed no benefit for the combination of everolimus and pasireotide. See also Hemihypertrophy Oncovirus Portal hypertension References Further reading "Long-term results of liver transplantation for hepatocellular carcinoma: an update of the University of Padova experience". September 23, 2013. Retrieved 6 February 2014. Bruix, Jordi; Sherman, Morris; Practice Guidelines Committee (November 2005). "Management of hepatocellular carcinoma". Hepatology. 42 (5): 1208–1236. doi:10.1002/hep.20933. PMID 16250051. S2CID 5106445. Liu, Chi-leung, M.D., "Hepatic Resection for Hepatocellular Carcinoma", The Hong Kong Medical Diary, Vol.10 No.12, December 2005 Medical Bulletin External links Blue Faery: The Adrienne Wilson Liver Cancer Association (hepatocellular carcinoma patient support site) NCI Liver Cancer Homepage