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Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, altitude sickness, periodic paralysis, idiopathic intracranial hypertension (raised brain pressure of unclear cause), urine alkalinization, and heart failure. It may be used long term for the treatment of open angle glaucoma and short term for acute angle closure glaucoma until surgery can be carried out. It is taken by mouth or injection into a vein. Acetazolamide is a first generation carbonic anhydrase inhibitor and it decreases the ocular fluid and osmolality in the eye to decrease intraocular pressure.Common side effects include numbness, ringing in the ears, loss of appetite, vomiting, and sleepiness. It is not recommended in those with significant kidney problems, liver problems, or who are allergic to sulfonamides. Acetazolamide is in the diuretic and carbonic anhydrase inhibitor families of medication. It works by decreasing the formation of hydrogen ions and bicarbonate from carbon dioxide and water.Acetazolamide came into medical use in 1952. It is on the World Health Organizations List of Essential Medicines. Acetazolamide is available as a generic medication. Medical uses It is used in the treatment of glaucoma, drug-induced edema, heart failure-induced edema, epilepsy and in reducing intraocular pressure after surgery. It has also been used in the treatment of altitude sickness, Ménières disease, increased intracranial pressure and neuromuscular disorders.In epilepsy, the main use of acetazolamide is in menstrual-related epilepsy and as an add on to other treatments in refractory epilepsy.

Though various websites on the internet report that acetazolamide can be used to treat dural ectasia in individuals with Marfan Syndrome, the only supporting evidence for this assertion exists from a small study of 14 patients which was not peer-reviewed or submitted for publication. Several published cases of intracranial hypotension related to Marfan syndrome would warrant caution in using acetazolamide in these patients unless there is a clear indication, as it could lower intracranial pressure further. A 2012 review and meta-analysis found that there was "limited supporting evidence" but that acetazolamide "may be considered" for the treatment of central (as opposed to obstructive) sleep apnea.It has also been used to prevent methotrexate-induced kidney damage by alkalinizing the urine, hence speeding up methotrexate excretion by increasing its solubility in urine. There is some evidence to support its use to prevent hemiplegic migraine. Open-Angle Glaucoma Acetazolamide is used in the treatment of open-angle glaucoma. The carbonic anhydrase inhibitor is able to decrease ocular fluid and osmolality of the fluid in the humor of the eye and decrease intraocular pressure in the eye. The medication comes in the form of an oral tablet used for this indication. High altitude sickness Acetazolamide is also used for the treatment of acute mountain sickness. In the prevention or treatment of mountain sickness, acetazolamide inhibits the ability of the kidneys to reabsorb bicarbonate, the conjugate base of carbonic acid. Increasing the amount of bicarbonate excreted in the urine leads to acidification of the blood.

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In the Southern Hemisphere, the tropical cyclone year begins on July 1 and runs all year-round encompassing the tropical cyclone seasons, which run from November 1 until the end of April, with peaks in mid-February to early March.Of various modes of variability in the climate system, El Niño–Southern Oscillation has the largest impact on tropical cyclone activity. Most tropical cyclones form on the side of the subtropical ridge closer to the equator, then move poleward past the ridge axis before recurving into the main belt of the Westerlies. When the subtropical ridge position shifts due to El Niño, so will the preferred tropical cyclone tracks. Areas west of Japan and Korea tend to experience much fewer September–November tropical cyclone impacts during El Niño and neutral years. During La Niña years, the formation of tropical cyclones, along with the subtropical ridge position, shifts westward across the western Pacific Ocean, which increases the landfall threat to China and much greater intensity in the Philippines. The Atlantic Ocean experiences depressed activity due to increased vertical wind shear across the region during El Niño years. Tropical cyclones are further influenced by the Atlantic Meridional Mode, the Quasi-biennial oscillation and the Madden–Julian oscillation. Influence of climate change Climate change can affect tropical cyclones in a variety of ways: an intensification of rainfall and wind speed, a decrease in overall frequency, an increase in the frequency of very intense storms and a poleward extension of where the cyclones reach maximum intensity are among the possible consequences of human-induced climate change.

Autoantibodies A number of specific antibodies found in the blood (antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti-liver kidney microsomal antibodies (LKM-1, LKM-2, LKM-3), anti soluble liver antigen (SLA), liver–pancreas antigen (LP), and anti-mitochondrial antibody (AMA)) are of use, as is finding an increased immunoglobulin G level. The presence of anti-mitochondrial antibody is more suggestive of primary biliary cholangitis. Hypergammaglobulinemia is also of diagnostic value. Histology Autoimmune hepatitis can be characterized histologically by the following nonspecific findings: Portal mononuclear cell infiltrate that invades the boundary surrounding the portal triad and infiltrates the surrounding lobule. Periportal lesions, also known as interface hepatitis, that spare the biliary tree (may include centrizonal necrosis). Bile duct abnormalities (cholangitis, ductal injury, ductular reaction) can be seen and should prompt evaluation for primary biliary cholangitis or sarcoidosis if granulomas are observed. Plasma cell infiltrate, rosettes of hepatocytes, and multinucleated giant cells. Varying degrees of fibrosis (except in the mildest form of autoimmune hepatitis). Bridging fibrosis that connects the portal and central areas can distort the structure of the hepatic lobule and result in cirrhosis. Diagnostic scoring The Internal Autoimmune Hepatitis Group developed a standardized scoring system for clinical diagnosis in population studies but lacks value in individualized cases. A simplified scoring system for clinical use incorporates titers of autoantibodies, total IgG levels, liver histology, and the exclusion of viral hepatitis for diagnostic scoring. Classification On the basis of detected autoantibodies, autoimmune hepatitis can be classified into three subtypes but have no distinct clinical presentations. Type 1 autoimmune hepatitis.

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A person will typically have these conversations with their doctor and ultimately record their preferences in an advance healthcare directive. An advance healthcare directive is a legal document that either documents a persons decisions about desired treatment or indicates who a person has entrusted to make their care decisions for them. The two main types of advanced directives are a living will and durable power of attorney for healthcare. A living will includes a persons decisions regarding their future care, a majority of which address resuscitation and life support but may also delve into a patients’ preferences regarding hospitalization, pain control, and specific treatments that they may undergo in the future. The living will will typically take effect when a patient is terminally ill with low chances of recovery. A durable power of attorney for healthcare allows a person to appoint another individual to make healthcare decisions for them under a specified set of circumstances. Combined directives, such as the "Five Wishes", that include components of both the living will and durable power of attorney for healthcare, are being increasingly utilized. Advanced care planning often includes preferences for CPR initiation, nutrition (tube feeding), as well as decisions about the use of machines to keep a person breathing, or support their heart or kidneys. Many studies have reported benefits to patients who complete advanced care planning, specifically noting the improved patient and surrogate satisfaction with communication and decreased clinician distress.

Changes in breathing (indicate neurologic compromise and impending death) and accumulation of upper airway secretions (resulting in crackling and gurgling breath sounds) Decreased need for food and fluids, and loss of appetite (caused by the bodys need to conserve energy and its decreasing ability to use food and fluids properly). Decreased oral intake and impaired swallowing (caused by general physical weakness and metabolic disturbances, including but not limited to hypercalcemia) Loss of bladder or bowel control (caused by the relaxing of muscles in the pelvic area). Darkened urine or decreased amount of urine (caused by slowing of kidney function and/or decreased fluid intake). Skin becoming cool to the touch, particularly the hands and feet; skin may become bluish in color, especially on the underside of the body (caused by decreased circulation to the extremities). Rattling or gurgling sounds while breathing, which may be loud (death rattle); breathing that is irregular and shallow; decreased number of breaths per minute; breathing that alternates between rapid and slow (caused by congestion from decreased fluid consumption, a buildup of waste products in the body, and/or a decrease in circulation to the organs). Turning of the head toward a light source (caused by decreasing vision). Increased difficulty controlling pain (caused by progression of the disease). Involuntary movements (called myoclonus), increased heart rate, hypertension followed by hypotension, and loss of reflexes in the legs and arms are additional signs that the end of life is near.

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Difficulty swallowing or breathing (signs of angioedema), allergic reaction (anaphylaxis) Hyperkalemia (2.2% in adult clinical trials) Fatigue (1% or more) Diarrhea (1% or more) Some severe skin reactions have been reported rarely, including toxic epidermal necrolysis and Stevens–Johnson syndrome; causal relationship has not been established.People taking lisinopril for the treatment of myocardial infarction may experience the following side effects: Hypotension (5.3%) Kidney dysfunction (1.3%)People taking lisinopril for the treatment of heart failure may experience the following side effects: Hypotension (3.8%) Dizziness (12% at low dose – 19% at high dose) Chest pain (2.1%) Fainting (5–7%) Hyperkalemia (3.5% at low dose – 6.4% at high dose) Difficulty swallowing or breathing (signs of angioedema), allergic reaction (anaphylaxis) Fatigue (1% or more) Diarrhea (1% or more) Some severe skin reactions have been reported rarely, including toxic epidermal necrolysis and Stevens–Johnson syndrome; a causal relationship has not been established. Agranulocytosis Overdose In one reported overdose, the half-life of lisinopril was prolonged to 14.9 hours. The case report of the event estimates that the individual consumed between 420 and 500 mg of lisinopril and survived. In cases of overdosage, it can be removed from circulation by dialysis. Interactions Dental care ACE-inhibitors like lisinopril are considered to be generally safe for people undergoing routine dental care, though the use of lisinopril prior to dental surgery is more controversial, with some dentists recommending discontinuation the morning of the procedure. People may present to dental care suspicious of an infected tooth, but the swelling around the mouth may be due to lisinopril-induced angioedema, prompting emergency and medical referral. Pharmacology Lisinopril is the lysine-analog of enalapril.

Lisinopril is a medication of the angiotensin-converting enzyme (ACE) inhibitor and is used to treat high blood pressure, heart failure, and after heart attacks. For high blood pressure it is usually a first-line treatment. It is also used to prevent kidney problems in people with diabetes mellitus. Lisinopril is taken by mouth. Full effect may take up to four weeks to occur.Common side effects include headache, dizziness, feeling tired, cough, nausea, and rash. Serious side effects may include low blood pressure, liver problems, high blood potassium, and angioedema. Use is not recommended during the entire duration of pregnancy as it may harm the baby. Lisinopril works by inhibiting the renin–angiotensin–aldosterone system.Lisinopril was patented in 1978 and approved for medical use in the United States in 1987. It is available as a generic medication. In 2020, it was the fourth most commonly prescribed medication in the United States, with more than 88 million prescriptions. In July 2016, an oral solution formulation of lisinopril was approved for use in the United States. Structure–activity relationships Lisinopril has a proline group that is responsible for the availability of the drug in oral formulation. The carboxylate group interacts with zinc ions to inhibit the ACE enzyme found in the kidneys and lungs. The other substituents participate in binding the same enzyme. Unlike Captopril, another ACE Inhibitor, Lisinopril lacks a thiol group. Medical uses Lisinopril is typically used for the treatment of high blood pressure, congestive heart failure, and diabetic nephropathy and after acute myocardial infarction (heart attack).

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Oculodentodigital syndrome (ODD syndrome) is an extremely rare genetic condition that typically results in small eyes, underdeveloped teeth, and syndactyly and malformation of the fourth and fifth fingers. It is considered a kind of ectodermal dysplasia. Signs and symptoms People with ODD syndrome often have a characteristic appearance. Visible features of the condition include: small teeth that are prone to dental caries because of underdeveloped tooth enamel; a long, thin nose; unusually small eyes; and type III syndactyly of the fourth and fifth fingers.Iris atrophy and glaucoma are more common than average. The size of the eyes often interferes with learning to read; special eyeglasses may be required. Hair may be fine, thin, dry, or fragile; in some families, it is curly.Neurologic abnormalities may be seen in adults. The neurologic changes may appear earlier in each subsequent generation and can include abnormal white matter, conductive deafness, and various kinds of paresis, including ataxia, spastic paraplegia, difficulty controlling the eyes, and bladder and bowel disturbances. Genetics ODD is typically an autosomal dominant condition, but can be inherited as a recessive trait. It is generally believed to be caused by a mutation in the gene GJA1, which codes for the gap junction protein connexin 43. Slightly different mutations in this gene may explain the different way the condition manifests in different families. Most people inherit this condition from one of their parents, but new cases do arise through novel mutations.

Research Equivocal preliminary results from small studies exist for: Other dyskinesias Huntingtons chorea Spasmodic torticollis Dystonia See also Biperiden (bicyclic ring) Cycrimine (cyclopentanyl instead of cyclohexanyl) Gamfexine Procyclidine References This article incorporates public domain material from Toxnet:Trihexyphenidyl. United States Department of Health and Human Services. Retrieved 8 May 2017.

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One of the regions responsible for the symptoms of idic(15) syndrome is the critical PWS/AS-region named after the Prader-Willi and/or Angelman syndromes. Isodicentric chromosome 15 and autism For more than 12 years, scientists have noticed that some individuals with autism also have idic(15). In fact, idic(15) is the most frequently identified chromosome problem in individuals with autism. (A chromosome anomaly involves extra or missing chromosomal material, not changes within the genes such as Fragile X syndrome). It is suggested that the co-occurrence of autism and idic(15) is not by chance. There may be a gene or genes in the 15q11-q13 region that is/are related to the development of autism in some individuals.Genetic research studies of individuals without chromosome anomalies also support this idea that an autism-related gene may be present in 15q11.2-q13.1 Specifically, research studies found that certain DNA markers from the (15q1.2-q13.1) region were found more often in individuals with autism than in individuals without autism. Although these DNA markers are too small to be genes, they suggest that researchers may be getting close to finding an autism gene in this region.A recent study reported the introduction of two extra copies of just a single gene present in the 15q11.2-q13.1 region, Ube3a, into mice to model the gene copy number expressed in the brain in idic(15). These mice displayed autism-related behavioral deficits including impaired social interaction, reduced ultrasonic vocal communication, and increased repetitive behavior (self-grooming). Diagnosis The extra chromosome in people with idic(15) can be easily detected through chromosome analysis (karyotyping). Additional tests are usually required.

Isodicentric 15, also called marker chromosome 15 syndrome, idic(15), partial tetrasomy 15q, or inverted duplication 15 (inv dup 15), is a chromosome abnormality in which a child is born with extra genetic material from chromosome 15. People with idic(15) are typically born with 47 chromosomes in their body cells, instead of the normal 46. The extra chromosome, which is classified as a small supernumerary marker chromosome, is made up of a piece of chromosome 15 that has been duplicated end-to-end like a mirror image. It is the presence of this extra genetic material that is thought to account for the symptoms seen in some people with idic(15). Individuals with idic(15) have a total of four copies of this chromosome 15 region instead of the usual two copies (1 copy each on the maternal and paternal chromosomes). The syndrome is also often referred to by the term Chromosome 15q11.2-q13.1 Duplication Syndrome, shortened to Dup15q Syndrome, or marker chromosome 15 syndrome (mainly in the United States). Dup15q Syndrome includes both idic(15) and interstitial 15q11.2-q13.1, another type of duplication that causes similar clinical traits. The extra chromosome is occasionally found in the mosaic state, i.e. some of the cells carry the marker chromosome. However, mostly because of the markers instability and tendency to be lost during cell division (mitosis), some cells are completely normal with 46 chromosomes. Occasionally, cells may have more than one idic(15), resulting in 48 or 49 chromosomes in all or some of their cells.

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Exotropia is a form of strabismus where the eyes are deviated outward. It is the opposite of esotropia and usually involves more severe axis deviation than exophoria. People with exotropia often experience crossed diplopia. Intermittent exotropia is a fairly common condition. "Sensory exotropia" occurs in the presence of poor vision in one eye. Infantile exotropia (sometimes called "congenital exotropia") is seen during the first year of life, and is less common than "essential exotropia" which usually becomes apparent several years later. The brains ability to see three-dimensional objects depends on proper alignment of the eyes. When both eyes are properly aligned and aimed at the same target, the visual portion of the brain fuses the two forms from the two eyes into a single image. When one eye turns inward, outward, upward, or downward, two different pictures are sent to the brain. Thus, the brain can no longer fuse the two images coming from the two eyes. This causes loss of depth perception and binocular vision. The term is from Greek exo meaning "outward" and trope meaning "a turning". Signs and symptoms The earliest sign of exotropia is usually a noticeable outward deviation of the eye. This sign may at first be intermittent, occurring when a child is daydreaming, not feeling well, or tired. It may also be more noticeable when the child looks at something in the distance. Squinting or frequent rubbing of the eyes is also common with exotropia. The child probably will not mention seeing double, i.e., double vision or diplopia.

Six muscles control eye movement, four that move the eye up and down and two that move it left and right. All these muscles must be coordinated and working properly for the brain to see a single image. When one or more of these muscles does not work properly, some form of strabismus may occur. Strabismus is more common in children with disorders that affect the brain such as cerebral palsy, Down syndrome, hydrocephalus, and brain tumors. One study has found that children with exotropia are three times more likely to develop a psychiatric disorder in comparison with the general population. Treatment A comprehensive eye examination including an ocular motility (i.e., eye movement) evaluation and an evaluation of the internal ocular structures allows an eye doctor to accurately diagnose exotropia. Although glasses and/or patching therapy, exercises, or prisms may reduce or help control the outward-turning eye in some children, surgery is often required. A common form of exotropia is known as "convergence insufficiency" that responds well to orthoptic vision therapy including exercises. This disorder is characterized by an inability of the eyes to work together when used for near viewing, such as reading. Instead of the eyes focusing together on the near object, one deviates outward. Consecutive exotropia arises after an initial esotropia. Most often it results from surgical overcorrection of the initial esotropia. It can be addressed with further surgery or with vision therapy; vision therapy has shown promising results if the consecutive exotropia is intermittent, alternating, and of small magnitude.

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A 2013 review article reported additional but weaker links to the loci of the genes TNFSF4 (rs7553711), Cathepsin H (rs34593439), and P2RY11-DNMT1 (rs2305795). Another gene locus that has been associated with narcolepsy is EIF3G (rs3826784). H1N1 Influenza Type 1 narcolepsy is caused by hypocretin/orexin neuronal loss. T-cells have been demonstrated to be cross-reactive to both a particular piece of the hemagglutinin flu protein of the pandemic 2009 H1N1 and the amidated terminal ends of the secreted hypocretin peptides.Genes associated with narcolepsy mark the particular HLA heterodimer (DQ0602) involved in presentation of these antigens and modulate expression of the specific T cell receptor segments (TRAJ24 and TRBV4-2) involved in T cell receptor recognition of these antigens, suggesting causality.A link between GlaxoSmithKlines H1N1 flu vaccine Pandemrix and narcolepsy has been found in both children and adults. In 2010, Finlands National Institute of Health and Welfare recommended that Pandemrix vaccinations be suspended pending further investigation into narcolepsy. In 2018, it was demonstrated that T-cells stimulated by Pandemrix were cross-reactive by molecular mimicry with part of the hypocretin peptide, the loss of which is associated with type I narcolepsy. Pathophysiology Loss of neurons Orexin, otherwise known as hypocretin, is a neuropeptide that acts within the brain to regulate appetite and wakefulness as well as a number of other cognitive and physiological processes. Loss of these orexin-producing neurons causes narcolepsy and most individuals with narcolepsy have a reduced number of these neurons in their brains. Selective destruction of the HCRT/OX neurons with preservation of proximate structures suggests a highly specific autoimmune pathophysiology.

The study also included the high rate of consanguinous marriages as a prevailing factor for these disorders, as well as the extremely low rate of diagnosis-related pregnancy terminations throughout the region. Research The fibrocartilaginous effects of fibrochondrogenesis on chondrocytes has shown potential as a means to produce therapeutic cellular biomaterials via tissue engineering and manipulation of stem cells, specifically human embryonic stem cells.Utilization of these cells as curative cartilage replacement materials on the cellular level has shown promise, with beneficial applications including the repair and healing of damaged knee menisci and synovial joints; temporomandibular joints, and vertebra. See also Fibrocyte Boomerang dysplasia Cystic fibrosis References == External links ==

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The condition does not typically lead to hydrocephalus, however, because there is no difference in pressure between various parts of the brain. However, those who have deep cerebral venous sinus thrombosis or oedema at basal ganglia are more prone to hydrocephalus development.Any blood clot forms due to an imbalance between coagulation (the formation of the insoluble blood protein fibrin) and fibrinolysis. The three major mechanisms for such an imbalance are enumerated in Virchows triad: alterations in normal blood flow, injury to the blood vessel wall, and alterations in the constitution of blood (hypercoagulability). Most cases of cerebral venous sinus thrombosis are due to hypercoagulability. The inflammatory response and prolonged immobilization of patients with COVID-19 may also help explain the formation of CVST.It is possible for the clot to break off and migrate (embolise) to the lungs, causing a pulmonary embolism. An analysis of earlier case reports concludes that this occurs in about 10% of cases, but has a very poor prognosis.Central venous thromboses usually involve the dural sinuses with or without involvement of the cortical veins; isolated cortical venous thromboses are extremely rare with only about 100 cases reported. Treatment Various studies have investigated the use of anticoagulation to suppress blood clot formation in cerebral venous sinus thrombosis. Before these trials had been conducted, there had been a concern that small areas of hemorrhage in the brain would bleed further as a result of treatment; the studies showed that this concern was unfounded.

Notable cases U.S. Secretary of State Hillary Clinton was hospitalized on December 30, 2012, for anticoagulation treatment of venous thrombosis of the right transverse sinus, which is located at the base of the brain. Clintons thrombotic episode was discovered on an MRI scan done for follow-up of a cerebral concussion she had sustained 2.5 weeks previously, when she fell while suffering from gastroenteritis. References External links "Intracranial venous thrombosis – Patient UK". UCH Institute for Child Health. "Clinical guideline Cerebral Venous Sinus Thrombosis in Children". Archived from the original on 2 February 2009. Retrieved 28 October 2007.

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The best response to fibrinolytic drugs is within a couple of hours, before the fibrin meshwork of the thrombus has been fully developed. Organization and recanalization involves the ingrowth of smooth muscle cells, fibroblasts and endothelium into the fibrin-rich thrombus. If recanalization proceeds it provides capillary-sized channels through the thrombus for continuity of blood flow through the entire thrombus but may not restore sufficient blood flow for the metabolic needs of the downstream tissue. See also Thrombogenicity (the tendency to clot) National Blood Clot Alliance Hemorrhoid References External links Muscle Relaxing Drugs Can Reduce Lethal Blood Clots Archived 2009-02-04 at the Wayback Machine Air Pollution Triggers Blood Clots - US Study.

Voxelotor, sold under the brand name Oxbryta, is a medication used for the treatment of sickle cell disease. Developed by Global Blood Therapeutics, voxelotor is the first hemoglobin oxygen-affinity modulator. Voxelotor has been shown to have disease-modifying potential by increasing hemoglobin levels and decreasing hemolysis indicators in sickle cell patients. It has a safe profile in sickle cell patients and healthy volunteers, without any dose-limiting toxicity.In November 2019, voxelotor received accelerated approval in the United States for the treatment of sickle cell disease (SCD) for those twelve years of age and older. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. In December 2021, voxelotor received accelerated approval in the United States for the treatment of sickle cell disease (SCD) for those aged four to eleven years. Side effects Common side effects include headache, diarrhea, abdominal pain, nausea, fatigue, rash and pyrexia (fever). History Voxelotor was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in November 2019. The FDA granted the application for voxelotor fast track designation and orphan drug designation.The approval of voxelotor was based on the results of a clinical trial with 274 participants with sickle cell disease.The FDA granted the approval of Oxbryta to Global Blood Therapeutics.

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Drug induced pigmentation may take on many different appearances, one of the most common being a change in the color, or pigmentation, of the skin. Presentation Cause Drug-induced pigmentation of the skin may occur as a consequence of drug administration, and the mechanism may be postinflammatory hyperpigmentation in some cases, but frequently is related to actual deposition of the offending drug in the skin. : 125–6 The incidence of this change varies, and depends on the type of medication involved. Some of the most common drugs involved are NSAIDs, antimalarials, psychotropic drugs, Amiodarone, cytotoxic drugs, tetracyclines, and heavy metals such as silver and gold (which must be ingested, not just worn). Pathophysiology There are 4 possible mechanisms to how this change may occur: Accumulation of melanin, the skin pigment Accumulation of drug or one of its products under any layer of the skin (usually the dermis or epidermis) Accumulation of iron throughout the dermis from drug-induced post-inflammatory changes The synthesis of special pigments, under direct influence of the drug See also Skin lesion References == External links ==

A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defective. Congenital disorders of glycosylation are sometimes known as CDG syndromes. They often cause serious, sometimes fatal, malfunction of several different organ systems (especially the nervous system, muscles, and intestines) in affected infants. The most common sub-type is PMM2-CDG (formally known as CDG-Ia) where the genetic defect leads to the loss of phosphomannomutase 2 (PMM2), the enzyme responsible for the conversion of mannose-6-phosphate into mannose-1-phosphate. Presentation The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver disease; coagulopathies; failure to thrive (FTT); dysmorphic features (e.g., inverted nipples and subcutaneous fat pads), pericardial effusion, and hypotonia. If an MRI is obtained; cerebellar hypoplasia is a common finding.Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, peripheral neuropathy (PN), strabismus, nystagmus, optic disc pallor, and reduced rod function on electroretinography.Three subtypes PMM2-CDG, PMI-CDG, ALG6-CDG can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy. N-Glycosylation and known defects A biologically very important group of carbohydrates is the asparagine (Asn)-linked, or N-linked, oligosaccharides. Their biosynthetic pathway is very complex and involves a hundred or more glycosyltransferases, glycosidases, transporters and synthases. This plethora allows for the formation of a multitude of different final oligosaccharide structures, involved in protein folding, intracellular transport/localization, protein activity, and degradation/half-life.

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Dorothy Squires In the midst of Sinatras multiple runs on the UK Singles Chart, Welsh singer Dorothy Squires also released a rendition of "My Way" in Summer 1970. Her recording reached number 25 on the UK Singles Chart and re-entered the chart twice more during that year. Elvis Presley Elvis Presley began performing the song in concert during the mid-1970s, despite Ankas suggestions that the song did not suit him. Nevertheless, on January 12 and 14, 1973, Presley sang the song during his satellite show Aloha from Hawaii Via Satellite, beamed live and on deferred basis (for European audiences, who also saw it in prime time), to 43 countries via Intelsat. On October 3, 1977, several weeks after Presleys death, his live recording of "My Way" (recorded for the Elvis In Concert CBS-TV special on June 21, 1977) was released as a single. In the U.S., it reached number 22 on the Billboard Hot 100 pop singles chart in late 1977/early 1978 (higher than Frank Sinatras peak position), number 6 on the Billboard Adult Contemporary chart, and went gold for its successful sales of over a million copies. The following year the single reached number 2 on the Billboard Country singles chart but went all the way to number 1 on the rival Cash Box Country Singles chart. In the UK, it reached number 9 on the UK Singles Chart. Presleys version is featured in the climax of the 2001 film 3000 Miles to Graceland with Kurt Russell and Kevin Costner.

The use of SIT in Zanzibar proved effective in eliminating the entire population of tsetse flies but was expensive and is relatively impractical to use in many of the endemic countries afflicted with African trypanosomiasis.A pilot program in Senegal has reduced the tsetse fly population by as much as 99% by introducing male flies which have been sterilized by exposure to gamma rays.Regular active surveillance, involving detection and prompt treatment of new infections, and tsetse fly control is the backbone of the strategy used to control sleeping sickness. Systematic screening of at-risk communities is the best approach, because case-by-case screening is not practical in endemic regions. Systematic screening may be in the form of mobile clinics or fixed screening centres where teams travel daily to areas of high infection rates. Such screening efforts are important because early symptoms are not evident or serious enough to warrant people with gambiense disease to seek medical attention, particularly in very remote areas. Also, diagnosis of the disease is difficult and health workers may not associate such general symptoms with trypanosomiasis. Systematic screening allows early-stage disease to be detected and treated before the disease progresses, and removes the potential human reservoir. A single case of sexual transmission of West African sleeping sickness has been reported. Treatment First stage The treatment for first-stage disease is fexinidazole by mouth or pentamidine by injection for T. b. gambiense. Suramin by injection is used for T. b. rhodesiense. Second stage Fexinidazole may be used for the second stage of TbG, if the disease is not severe.

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Due to these side effects and its red color, doxorubicin has earned the nickname "red devil" or "red death. "Chemotherapy can cause reactivation of hepatitis B, and doxorubicin-containing regimens are no exception.Doxorubicin and several chemotherapeutic drugs (including cyclophosphamide) can cause a loss of skin pigmentation. Liposomal formulations There is a pegylated (polyethylene glycol coated) liposome-encapsulated form of doxorubicin, developed to treat Kaposis sarcoma The polyethylene glycol coating results in preferential concentration of doxorubicin in the skin. However, this also results in a side effect called palmar plantar erythrodysesthesia (PPE), more commonly known as hand-foot syndrome. Following administration of this form of doxorubicin, small amounts of the drug can leak from capillaries in the palms of the hands and soles of the feet. The result of this leakage is redness, tenderness, and peeling of the skin that can be uncomfortable and even painful. In clinical testing at 50 mg/m2 dosing every 4 weeks, half of people developed hand-foot syndrome. The rate of this side effect limits the dose of this formulation that can be given as compared with plain doxorubicin in the same treatment regimen, thereby limiting potential substitution. Substitution would be desirable because liposome-encapsulated doxorubicin is less cardiotoxic than unencapsulated doxorubicin.

A finger is a limb of the body and a type of digit, an organ of manipulation and sensation found in the hands of most of the Tetrapods, so also with humans and other primates. Most land vertebrates have five fingers (Pentadactyly). Land vertebrate fingers The five-rayed anterior limbs of terrestrial vertebrates can be derived phylogenetically from the pectoral fins of fish. Within the taxa of the terrestrial vertebrates, the basic pentadactyl plan, and thus also the fingers and phalanges, undergo many variations.Morphologically the different fingers of terrestrial vertebrates are homolog. The wings of birds and those of bats are not homologous, they are analogue flight organs. However, the phalanges within them are homologous.Chimpanzees have lower limbs that are specialized for manipulation, and (arguably) have fingers on their lower limbs as well. In the case of Primates in general, the digits of the hand are overwhelmingly referred to as "fingers". Primate fingers have both fingernails and fingerprints.Research has been carried out on the embryonic development of domestic chickens showing that an interdigital webbing forms between the tissues that become the toes, which subsequently regresses by apoptosis. If apoptosis fails to occur, the interdigital skin remains intact. Many animals have developed webbed feet or skin between the fingers from this like the Wallaces flying frog. Human fingers Usually humans have five digits, the bones of which are termed phalanges, on each hand, although some people have more or fewer than five due to congenital disorders such as polydactyly or oligodactyly, or accidental or intentional amputations.

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Regional bodies dedicated to controlling Chagas disease arose through support of the Pan American Health Organization, with the Initiative of the Southern Cone for the Elimination of Chagas Diseases launching in 1991, followed by the Initiative of the Andean countries (1997), Initiative of the Central American countries (1997), and the Initiative of the Amazon countries (2004). Research Treatments Fexinidazole, an antiparasitic drug approved for treating African trypanosomiasis, has shown activity against Chagas disease in animal models. As of 2019, it is undergoing phase II clinical trials for chronic Chagas disease in Spain. Other drug candidates include GNF6702, a proteasome inhibitor that is effective against Chagas disease in mice and is undergoing preliminary toxicity studies, and AN4169, which has had promising results in animal models.A number of experimental vaccines have been tested in animals. In addition to subunit vaccines, some approaches have involved vaccination with attenuated T. cruzi parasites or organisms that express some of the same antigens as T. cruzi but do not cause human disease, such as Trypanosoma rangeli or Phytomonas serpens. DNA vaccination has also been explored. As of 2019, vaccine research has mainly been limited to small animal models. Diagnostic tests As of 2018, standard diagnostic tests for Chagas disease were limited in their ability to measure the effectiveness of antiparasitic treatment, as serological tests may remain positive for years after T. cruzi is eliminated from the body, and PCR may give false-negative results when the parasite concentration in the blood is low.

The prevalence varies widely within European countries due to differing immigration patterns. Italy has the second highest prevalence, followed by the Netherlands, the United Kingdom, and Germany. History T. cruzi likely circulated in South American mammals long before the arrival of humans on the continent. T. cruzi has been detected in ancient human remains across South America, from a 9000-year-old Chinchorro mummy in the Atacama Desert, to remains of various ages in Minas Gerais, to an 1100-year-old mummy as far north as the Chihuahuan Desert near the Rio Grande. Many early written accounts describe symptoms consistent with Chagas disease, with early descriptions of the disease sometimes attributed to Miguel Diaz Pimenta (1707), Luís Gomes Ferreira (1735), and Theodoro J. H. Langgaard (1842).The formal description of Chagas disease was made by Carlos Chagas in 1909 after examining a two-year-old girl with fever, swollen lymph nodes, and an enlarged spleen and liver. Upon examination of her blood, Chagas saw trypanosomes identical to those he had recently identified from the hindgut of triatomine bugs and named Trypanosoma cruzi in honor of his mentor, Brazilian physician Oswaldo Cruz. He sent infected triatomine bugs to Cruz in Rio de Janeiro, who showed the bite of the infected triatomine could transmit T. cruzi to marmoset monkeys as well. In just two years, 1908 and 1909, Chagas published descriptions of the disease, the organism that caused it, and the insect vector required for infection.

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: 266  Logographic writing systems, such as Chinese characters, have extensive symbol use; and these also pose problems for dyslexic learners. Pathophysiology For most people who are right-hand dominant, the left hemisphere of their brain is more specialized for language processing. With regard to the mechanism of dyslexia, fMRI studies suggest that this specialization is less pronounced or absent in people with dyslexia. In other studies, dyslexia is correlated with anatomical differences in the corpus callosum, the bundle of nerve fibers that connects the left and right hemispheres.Data via diffusion tensor MRI indicate changes in connectivity or in gray matter density in areas related to reading and language. Finally, the left inferior frontal gyrus has shown differences in phonological processing in people with dyslexia. Neurophysiological and imaging procedures are being used to ascertain phenotypic characteristics in people with dyslexia, thus identifying the effects of dyslexia-related genes. Dual route theory The dual-route theory of reading aloud was first described in the early 1970s. This theory suggests that two separate mental mechanisms, or cognitive routes, are involved in reading aloud. One mechanism is the lexical route, which is the process whereby skilled readers can recognize known words by sight alone, through a "dictionary" lookup procedure. The other mechanism is the nonlexical or sublexical route, which is the process whereby the reader can "sound out" a written word. This is done by identifying the words constituent parts (letters, phonemes, graphemes) and applying knowledge of how these parts are associated with each other, for example, how a string of neighboring letters sound together.

Neural bases for the visual lexicon and for auditory verbal short-term memory components have been proposed, with some implication that the observed neural manifestation of developmental dyslexia is task-specific (i.e., functional rather than structural). fMRIs of people with dyslexia indicate an interactive role of the cerebellum and cerebral cortex as well as other brain structures in reading.The cerebellar theory of dyslexia proposes that impairment of cerebellum-controlled muscle movement affects the formation of words by the tongue and facial muscles, resulting in the fluency problems that some people with dyslexia experience. The cerebellum is also involved in the automatization of some tasks, such as reading. The fact that some children with dyslexia have motor task and balance impairments could be consistent with a cerebellar role in their reading difficulties. However, the cerebellar theory has not been supported by controlled research studies. Genetics Research into potential genetic causes of dyslexia has its roots in post-autopsy examination of the brains of people with dyslexia. Observed anatomical differences in the language centers of such brains include microscopic cortical malformations known as ectopias, and more rarely, vascular micro-malformations, and microgyrus—a smaller than usual size for the gyrus. The previously cited studies and others suggest that abnormal cortical development, presumed to occur before or during the sixth month of fetal brain development, may have caused the abnormalities. Abnormal cell formations in people with dyslexia have also been reported in non-language cerebral and subcortical brain structures.

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The operation is usually performed under a general anaesthetic.In most cases this is done as a day case without the need for an overnight stay. References == External links ==

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by generalized absence of sweating without other autonomic and neurologic dysfunction.AIGA is classified into 3 subgroups: idiopathic pure sudomotor failure (IPSF), sweat gland failure (SGF), and sudomotor neuropathy, with each subgroup presenting a different pathogenesis. Diagnosis Quantitative sudomotor axon reflex test and microneurography are used in the diagnosis of AIGA. However, these refined methods are mostly used for research purposes and not generally available.Skin biopsy analysis may play a crucial role in the identification of AIGA subgroups. See also Hypohidrosis References == External links ==

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Less commonly, FL presents as extra-nodal masses in the skin, thyroid gland, salivary gland, breast, testicles. spleen, liver, and/or lung. Regardless of the type of presentation, FL is usually (~80% of cases) at an advanced stage at diagnosis as indicated by involvement of the bone marrow (50% to 70% of cases), multiple lymph nodes in different parts of the body, and/or other tissues. A minority (<33%) of FL patients present with B symptoms, i.e. recurrent unexplained fevers, recurrent night sweats, and/or weight loss ≥10% in the past 6 months. Generally, the disease has an indolent and prolonged course with a median life expectancy of 15–20 years: a large percentage of patients die from other causes than their FL disease. However, each year, including the early years after diagnosis, some 2-3% of FL cases transform to t-FL; Median survival has been ~4.5 years after the onset of this transformation.There are less common subtypes of FL that differ not only in their presentation but also in their histopathology, genetic abnormalities, and course. These subtypes, which are now (i.e. primary gastrointestinal tract FL) or may in the future (pediatric-type FL) be considered distinctive diseases, are: Duodenal-type follicular lymphoma Duodenal-type follicular lymphoma (DFL) was initially considered to be a type of Primary gastrointestinal tract (GI tract) follicular lymphoma (PGTFL), i.e. a follicular lymphoma in which GI tract lesions were prominent parts of the disease.

Currently used indicators for this include the diseases: 1) histology; 2) subtype; 3) predicted indolence and potential for transformation; and 4) extent of disease as measured by clinical examinations, bone marrow biopsy to determine bone marrow involvement, and PET/CT imaging of the chest, abdomen, pelvis, and any areas outside of these regions if physical examination suggests involvement. Some suggested guidelines using these parameters to indicate the prognosis and need for treatment in FL include: The WHO criteria using histological grade (see previous section): Patients with Grades 1, 2, and 3A disease are predicted to have the same low risk prognosis that is seen in cases of typical FL while patients with grade 3B disease are predicted to have the high risk prognosis typical of t-FL. The Follicular Lymphoma International Prognostic Index (FLIPI): FLIPI uses the following criteria: age ≥60 years; Ann Arbor disease stage III (i.e. lesions located both above and below the thoracic diaphragm) or IV (i.e. disseminated lesions involving one or more non-lymphatic organs); blood hemoglobin <12 gram/deciliter; serum lactose dehydrogenase level above normal; and involvement of >4 lymph nodes. Patients positive for 0–1, 2, or ≥3 of these factors are classified as in low, intermediate, and high risk group, respectively, and after treatment with regimens that include rituximab have 2 year predicted progression free survivals of 84, 72, and 65%, respectively, and overall survivals of 98, 94, and 87%, respectively. The FLIP2 index.

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Once these solvents or gases are inhaled, the extensive capillary surface of the lungs rapidly absorb the solvent or gas, and blood levels peak rapidly. The intoxication effects occur so quickly that the effects of inhalation can resemble the intensity of effects produced by intravenous injection of other psychoactive drugs.Ethanol is also inhaled, either by vaporizing it by pouring it over dry ice in a narrow container and inhaling with a straw or by pouring alcohol in a corked bottle with a pipe, and then using a bicycle pump to make a spray. Alcohol can be vaporized using a simple container and open-flame heater. Medical devices such as asthma nebulizers and inhalers were also reported as means of application. The practice gained popularity in 2004, with the marketing of the device dubbed AWOL (Alcohol without liquid), a play on the military term AWOL (Absent Without Leave). AWOL, created by British businessman Dominic Simler, was first introduced in Asia and Europe, and then in the United States in August 2004. AWOL was used by nightclubs, at gatherings and parties, and it garnered attraction as a novelty, as people enjoyed passing it around in a group. AWOL uses a nebulizer, a machine that agitates the liquid into an aerosol. AWOLs official website states that "AWOL and AWOL 1 are powered by Electrical Air Compressors while AWOL 2 and AWOL 3 are powered by electrical oxygen generators", which refer to a couple of mechanisms used by the nebulizer drug delivery device for inhalation.

Inhalant use, especially glue-sniffing, is widely associated with the late-1970s punk youth subculture in the UK and North America. Raymond Cochrane and Douglas Carroll claim that when glue sniffing became widespread in the late 1970s, it was "adopted by punks because public [negative] perceptions of sniffing fitted in with their self-image" as rebels against societal values. While punks at first used inhalants "experimentally and as a cheap high, adult disgust and hostility [to the practice] encouraged punks to use glue sniffing as a way of shocking society." As well, using inhalants was a way of expressing their anti-corporatist DIY (do it yourself) credo; by using inexpensive household products as inhalants, punks did not have to purchase industrially manufactured liquor or beer. One history of the punk subculture argues that "substance abuse was often referred to in the music and did become synonymous with the genre, glue-sniffing especially" because the youths "faith in the future had died and that the youth just didnt care anymore" due to the "awareness of the threat of nuclear war and a pervasive sense of doom." In a BBC interview with a person who was a punk in the late 1970s, they said that "there was a real fear of imminent nuclear war—people were sniffing glue knowing that it could kill them, but they didnt care because they believed that very soon everybody would be dead anyway." A number of 1970s punk rock and 1980s hardcore punk songs refer to inhalant use.

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Beta-blockers may slow the heart rate to a dangerous level if prescribed with calcium channel blocker-type medications. Bradycardia is also part of the mammalian diving reflex. Diagnosis A diagnosis of bradycardia in adults is based on a heart rate less than 60 BPM, although some studies use a heart rate of less than 50 BPM. This is determined usually either by palpation or ECG. If symptoms occur, a determination of electrolytes may be helpful in determining the underlying cause. Management The treatment of bradycardia is dependent on whether or not the person is stable or unstable. Stable Emergency treatment is not needed if the person is asymptomatic or minimally symptomatic. Unstable If a person is unstable, the initial recommended treatment is intravenous atropine. Doses less than 0.5 mg should not be used, as this may further decrease the rate. If this is not effective, intravenous inotrope infusion (dopamine, epinephrine) or transcutaneous pacing should be used. Transvenous pacing may be required if the cause of the bradycardia is not rapidly reversible.In children, giving oxygen, supporting their breathing, and chest compressions are recommended. Epidemiology In clinical practice, elderly people over age 65 and young athletes of both sexes may have sinus bradycardia. The US Centers for Disease Control and Prevention reported in 2011 that 15.2% of adult males and 6.9% of adult females had clinically-defined bradycardia (a resting pulse rate below 60 BPM). Society and culture Records Daniel Green holds the world record for the slowest heartbeat in a healthy human, with a heart rate measured in 2014 of 26 BPM.

These include; the patients age, acuity of their signs and symptoms, associated neurological conditions, and family history of hereditary forms of cerebellar degeneration. A diagnosis for cerebellar degeneration is regarded after any of the aforementioned signs and symptoms surface. For genetically classified forms of cerebellar degeneration, genetic testing can be carried out in order to confirm or deny the diagnosis, where this form of testing is only possible if the gene responsible for the cause of the condition is recognised. In saying this, for most conditions the genetic cause of cerebellar degeneration is unidentified, hence these patients cannot proceed with genetic testing. In cases where cerebellar degeneration is acquired, a diagnosis can be established using imaging methods such as computerised tomography (CT scans) and magnetic resonance imaging (MRI), necessary to detect brain abnormalities in patients with cerebellar degeneration. Treatment Like any other disease, treatment for cerebellar degeneration is contingent on the underlying cause, unique to each patient. As of present time, hereditary forms of cerebellar degeneration are incurable, though they can be managed. Management is centred around coping with symptoms and improving a patients quality of life. In these cases, immediate management of inherited cerebellum damage should involve consultation with a neurologist, followed by specific management approaches based on the signs and symptoms experienced by each unique patient. These management approaches aim to provide supportive care to the patient, consisting of physical therapy to strengthen muscles, occupational therapy, and speech pathology.

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Other laboratory findings in Lassa fever include lymphocytopenia (low white blood cell count), thrombocytopenia (low platelets), and elevated aspartate transaminase levels in the blood. Lassa fever virus can also be found in cerebrospinal fluid. Prevention Control of the Mastomys rodent population is impractical, so measures focus on keeping rodents out of homes and food supplies, encouraging effective personal hygiene, storing grain and other foodstuffs in rodent-proof containers, and disposing of garbage far from the home to help sustain clean households. Gloves, masks, laboratory coats, and goggles are advised while in contact with an infected person, to avoid contact with blood and body fluids. These issues in many countries are monitored by a department of public health. In less developed countries, these types of organizations may not have the necessary means to effectively control outbreaks. Vaccine There is no vaccine for humans as of 2019. Researchers at the United States Army Medical Research Institute of Infectious Diseases facility had a promising vaccine candidate in 2002. They have developed a replication-competent vaccine against Lassa virus based on recombinant vesicular stomatitis virus vectors expressing the Lassa virus glycoprotein. After a single intramuscular injection, test primates have survived lethal challenge, while showing no clinical symptoms. Treatment Treatment is directed at addressing dehydration and improving symptoms. All persons suspected of Lassa fever infection should be admitted to isolation facilities and their body fluids and excreta properly disposed of. Medications The antiviral medication ribavirin has been recommended, but evidence to support its use is weak.

The virus was first described in 1969 from a case in the town of Lassa, in Borno State, Nigeria. Lassa fever is relatively common in West Africa including the countries of Nigeria, Liberia, Sierra Leone, Guinea, and Ghana. There are about 300,000 to 500,000 cases which result in 5,000 deaths a year. Signs and symptoms Onset of symptoms is typically 7 to 21 days after exposure. In 80% of those who are infected few or no symptoms occur. These mild symptoms may include fever, tiredness, weakness, and headache. In 20% of people more severe symptoms such as bleeding gums, breathing problems, vomiting, chest pain, or dangerously low blood pressure may occur. Long term complications may include hearing loss. In those who are pregnant, miscarriage may occur in 95% of child-bearing women. Lassa fever can be difficult to distinguish clinically from other viral hemorrhagic fevers, such as Ebola virus disease. A combination of pharyngitis, pain behind the sternum, presence of excess protein in the urine and fever can indicate Lassa fever with higher specificity.In cases in which death occurs, this typically occurs within 14 days of onset. About 1% of all Lassa virus infections result in death. Approximately 15%-20% of those who have required hospitalization for Lassa fever die. The risk of death is greater in those who are pregnant. A "Swollen baby syndrome" may occur in newborns, infants and toddlers with pitting edema, abdominal distension and bleeding. Cause Virology Lassa virus is a member of the Arenaviridae, a family of negative-sense, single-stranded RNA viruses.

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Contraindications and patient factors Docetaxel is contraindicated for use with patients with a baseline neutrophil count less than 1500 cells/µL, a history of severe hypersensitivity reactions to docetaxel or polysorbate 80, severe liver impairment and pregnant or breast-feeding women.Side effects are experienced more frequently by patients of 65 years or older, but dosage is usually not decreased. Kidney failure is thought not to be a significant factor for docetaxel dosage adjustment. Patients with hepatic insufficiency resulting in serum bilirubin greater than the upper limit of normal (ULN) should not be administered docetaxel, though this is not a stated contraindication. Dosage should be reduced by 20% in people who develop grade 3 or 4 diarrhea following exposure to docetaxel, hepatotoxicity defined by liver enzymes at levels greater than five times the ULN, and grade 2 palmer-planter toxicity.Paediatric trials of docetaxel have been limited, and so safety of use in patients under 16 years has not been established. Pregnancy Based on the limited data available, docetaxel appears to be safe in pregnancy if administered during the second and third trimesters; however, maternal and fetal risks should be weighed against benefits to determine the appropriate course of action. As with all chemotherapeutic agents, docetaxel administered to pregnant animals causes a variety of embryofetal toxicities, including death, when given during the period of organogenesis. Yet adequate studies investigating maternal and fetal effects in humans are lacking.

It is normally appropriate to send a draft copy of the minutes to all the members in advance of the meeting so that the meeting is not delayed by a reading of the draft. See also Diary Gazette References Citations Sources Further reading American Institute of Parliamentarians (2014). The Complete Minutes Manual. American Institute of Parliamentarians. Archived from the original on 2016-10-14. Retrieved 2016-03-01. National Association of Parliamentarians (2009). Pathways to Proficiency - What Was Done at the Meeting: A Guide to Minutes. Independence, MO: National Association of Parliamentarians. ISBN 9781884048562. Mina, Eli (2004). Minas Guide to Minute Taking. Vancouver (Canada): Eli Mina Consulting. ISBN 978-0973442809.

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Initially, diuretics lower blood pressure by decreasing cardiac output and reducing plasma and extracellular fluid volume. Eventually, cardiac output returns to normal, and plasma and extracellular fluid volume return to slightly less than normal, but a reduction in peripheral vascular resistance is maintained, thus resulting in an overall lower blood pressure. The reduction in intravascular volume induces an elevation in plasma renin activity and aldosterone secretion, further contributing to the potassium loss associated with thiazide diuretic therapy. Pharmacokinetics Chlortalidone is slowly absorbed from the gastrointestinal tract after oral ingestion. It has a long half-life and therefore a prolonged diuretic action, which results in continued diuretic effects despite a skipped dose. This prolonged action of chlortalidone despite missing doses may account for the higher efficacy of chlortalidone compared to the shorter half-life medication, hydrochlorothiazide. Chlortalidone is eliminated from the body mostly by the kidney, as unchanged drug. Thus, in persons with diminished kidney function, the clearance of chlortalidone is reduced and the elimination half-life is increased.As with other thiazide diuretics, chlortalidone crosses the placenta and is excreted in breast milk. Chlortalidone may suppress lactation, and has been used for this indication. Due to its long half-life, chlortalidone may accumulate in newborns via breast milk, despite receiving only about 6% of the maternal weight-adjusted dose. Chemistry Chlortalidone is in the sulfamoylbenzamide class. As it lacks the benzothiadiazine structure of the thiazide-type diuretics, it is called a thiazide-like diuretic.

Hyperuricemia, high levels of uric acid in the blood Hyperglycemia, high blood sugar is more common in persons who are magnesium deficient Hyperlipidemia, high cholesterol and triglycerides Headache Nausea/vomiting Photosensitivity increased susceptibility to sunburn of skin with sun exposure Photoonycholysis detachment of nails from nailbed with sun exposure Weight gain Gout; approximately doubles the risk PancreatitisThe frequency and severity of these adverse effects is much reduced when chlortalidone is used at lower doses (e.g., 12.5 mg per day). Mechanism of action Chlortalidone reduces reabsorption of sodium and chloride primarily through inhibition of the Na+/Cl− symporter in the apical membrane of distal convoluted tubule cells in the kidney. Although chlortalidone is often referred to as a "thiazide-like" diuretic, it is unlike thiazide diuretics in that, in addition to its inhibition of the Na+/Cl− symporter, it also strongly inhibits multiple isoforms of carbonic anhydrase. Some of chlortalidones diuretic effect is also due to this inhibition of carbonic anhydrase in the proximal tubule. Chronic exposure to chlortalidone decreases the glomerular filtration rate. Chlortalidones diuretic effect is diminished in persons with kidney impairment. By increasing the delivery of sodium to the distal renal tubule, chlortalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism (i.e. apical ROMK/Na channels coupled with basolateral Na+/K ATPases). This can result in a low blood concentration of potassium and chloride as well as a mild metabolic alkalosis; however, the diuretic effect of chlortalidone is not affected by the acid-base balance of the person being treated. There is uncertainty about the mechanism of the blood pressure-lowering effect that occurs during chronic exposure to chlortalidone.

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Findings of hypertelorism (widely spaced eyes), bifid or split uvula, and skin findings such as easy bruising or abnormal scars may distinguish Loeys–Dietz from Marfan syndrome.Affected individuals often develop immune system related problems such as allergies to food, asthma, hay fever, and inflammatory disorders such as eczema or inflammatory bowel disease.Findings of Loeys–Dietz syndrome may include: Skeletal/spinal malformations: craniosynostosis, Scoliosis, spinal instability and spondylolisthesis, Kyphosis Sternal abnormalities: pectus excavatum, pectus carinatum Contractures of fingers and toes (camptodactyly) Long fingers and lax joints Weakened or missing eye muscles (strabismus) Club foot Premature fusion of the skull bones (craniosynostosis) Joint hypermobility Congenital heart problems including patent ductus arteriosus (connection between the aorta and the lung circulation) and atrial septal defect (connection between heart chambers) Translucency of the skin with velvety texture Abnormal junction of the brain and medulla (Arnold–Chiari malformation) Bicuspid aortic valves Criss-crossed pulmonary arteries Cause Types (old nomenclature) Several genetic causes of Loeys–Dietz syndrome have been identified. A de novo mutation in TGFB3, a ligand of the TGF β pathway, was identified in an individual with a syndrome presenting partially overlapping symptoms with Marfan Syndrome and Loeys–Dietz Syndrome. Diagnosis Diagnosis involves consideration of physical features and genetic testing. Presence of split uvula is a differentiating characteristic from Marfan Syndrome, as well as the severity of the heart defects. Loeys–Dietz Syndrome patients have more severe heart involvement and it is advised that they be treated for enlarged aorta earlier due to the increased risk of early rupture in Loeys–Dietz patients.

When heated to decomposition it emits very toxic fumes of hydrogen chloride and nitrogen oxides. History Nitrogen mustards arose from the derivatization of sulphur mustard gas after military personnel exposed to it during World War I were observed to have decreased white blood cell counts. Since the sulphur mustard gas was too toxic to be used in humans, Gilman hypothesized that by reducing the electrophilicity of the agent, which made it highly chemically reactive towards electron-rich groups, then less toxic drugs could be obtained. To this end, he made analogues that were less electrophilic by exchanging the sulphur with a nitrogen, leading to the nitrogen mustards.With an acceptable therapeutic index in humans, nitrogen mustards were first introduced in the clinic in 1946. Aliphatic mustards were developed first, such as mechlorethamine hydrochloride (mustine hydrochloride), which is still used in the clinic today. In the 1950s, aromatic mustards like chlorambucil were introduced as less toxic alkylating agents than the aliphatic nitrogen mustards, proving to be less electrophilic and react with DNA more slowly. Additionally, these agent can be administered orally, a significant advantage. Chlorambucil was first synthesized by Everett et al. References External links Leukeran (manufacturers website) "Chlorambucil". Drug Information Portal. U.S. National Library of Medicine.

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When the uterine muscles contract, they constrict the blood supply to the tissue of the endometrium, which, in turn, breaks down and dies. These uterine contractions continue as they squeeze the old, dead endometrial tissue through the cervix and out of the body through the vagina. These contractions, and the resulting temporary oxygen deprivation to nearby tissues, are thought to be responsible for the pain or cramps experienced during menstruation. Compared with non-dysmnenorrhic individuals, those with primary dysmenorrhea have increased activity of the uterine muscle with increased contractility and increased frequency of contractions. Diagnosis The diagnosis of dysmenorrhea is usually made simply on a medical history of menstrual pain that interferes with daily activities. However, there is no universally accepted standard technique for quantifying the severity of menstrual pains. There are various quantification models, called menstrual symptometrics, that can be used to estimate the severity of menstrual pains as well as correlate them with pain in other parts of the body, menstrual bleeding and degree of interference with daily activities. Further work-up Once a diagnosis of dysmenorrhea is made, further workup is required to search for any secondary underlying cause of it, in order to be able to treat it specifically and to avoid the aggravation of a perhaps serious underlying cause. Further work-up includes a specific medical history of symptoms and menstrual cycles and a pelvic examination. Based on results from these, additional exams and tests may be motivated, such as: Gynecologic ultrasonography Laparoscopy Management Treatments that target the mechanism of pain include non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal contraceptives.

NSAIDs inhibit prostaglandin production. With long-term treatment, hormonal birth control reduces the amount of uterine fluid/tissue expelled from the uterus. Thus resulting in shorter, less painful menstruation. These drugs are typically more effective than treatments that do not target the source of the pain (e.g. acetaminophen). Regular physical activity may limit the severity of uterine cramps. NSAIDs Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen are effective in relieving the pain of primary dysmenorrhea. They can have side effects of nausea, dyspepsia, peptic ulcer, and diarrhea. Hormonal birth control Use of hormonal birth control may improve symptoms of primary dysmenorrhea. A 2009 systematic review found limited evidence that the low or medium doses of estrogen contained in the birth control pill reduces pain associated with dysmenorrhea. In addition, no differences between different birth control pill preparations were found.Norplant and Depo-provera are also effective, since these methods often induce amenorrhea. The intrauterine system (Mirena IUD) may be useful in reducing symptoms. Other A review indicated the effectiveness of transdermal nitroglycerin. Reviews indicated magnesium supplementation seemed to be effective. A review indicated the usefulness of using calcium channel blockers. Heat is effective compared to NSAIDs and is a preferred option by many patients, as it is easy to access and has no known side effects.Tamoxifen has been used effectively to reduce uterine contractility and pain in dysmenorrhea patients.There is some evidence that exercises performed 3 times a week for about 45 to 60 minutes, without particular intensity, reduces menstrual pain.

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In other diseases Prion-like domains have been found in a variety of other mammalian proteins. Some of these proteins have been implicated in the ontogeny of age-related neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U), Alzheimers disease, Parkinsons disease, and Huntingtons disease. They are also implicated in some forms of systemic amyloidosis including AA amyloidosis that develops in humans and animals with inflammatory and infectious diseases such as tuberculosis, Crohns disease, rheumatoid arthritis, and HIV/AIDS. AA amyloidosis, like prion disease, may be transmissible. This has given rise to the prion paradigm, where otherwise harmless proteins can be converted to a pathogenic form by a small number of misfolded, nucleating proteins.The definition of a prion-like domain arises from the study of fungal prions. In yeast, prionogenic proteins have a portable prion domain that is both necessary and sufficient for self-templating and protein aggregation. This has been shown by attaching the prion domain to a reporter protein, which then aggregates like a known prion. Similarly, removing the prion domain from a fungal prion protein inhibits prionogenesis. This modular view of prion behaviour has led to the hypothesis that similar prion domains are present in animal proteins, in addition to PrP. These fungal prion domains have several characteristic sequence features. They are typically enriched in asparagine, glutamine, tyrosine and glycine residues, with an asparagine bias being particularly conducive to the aggregative property of prions. Historically, prionogenesis has been seen as independent of sequence and only dependent on relative residue content.

PrPSc always causes prion disease. Although the exact 3D structure of PrPSc is not known, it has a higher proportion of β-sheet structure in place of the normal α-helix structure. Aggregations of these abnormal isoforms form highly structured amyloid fibers, which accumulate to form plaques. The end of each fiber acts as a template onto which free protein molecules may attach, allowing the fiber to grow. Under most circumstances, only PrP molecules with an identical amino acid sequence to the infectious PrPSc are incorporated into the growing fiber. However, rare cross-species transmission is also possible. Normal function of PrP The physiological function of the prion protein remains poorly understood. While data from in vitro experiments suggest many dissimilar roles, studies on PrP knockout mice have provided only limited information because these animals exhibit only minor abnormalities. In research done in mice, it was found that the cleavage of PrP in peripheral nerves causes the activation of myelin repair in Schwann cells and that the lack of PrP proteins caused demyelination in those cells. PrP and regulated cell death MAVS, RIP1, and RIP3 are prion-like proteins found in other parts of the body. They also polymerise into filamentous amyloid fibers which initiate regulated cell death in the case of a viral infection to prevent the spread of virions to other, surrounding cells. PrP and long-term memory A review of evidence in 2005 suggested that PrP may have a normal function in maintenance of long-term memory.

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Complication Epilepsy can be dangerous when seizure occurs at certain times. The possibility of drowning and having car accident is higher. It is also dangerous when seizure occurs during pregnancy. Certain anti-epileptic medications increase the risk of birth defects. It is also found that people with epilepsy are more likely to have psychological problems. Other complications include aspiration pneumonia and difficulty learning. Management Epilepsy is usually treated with daily medication once a second seizure has occurred, while medication may be started after the first seizure in those at high risk for subsequent seizures. Supporting peoples self management of their condition may be useful. In drug-resistant cases different management options may be looked at including a special diet, the implantation of a neurostimulator, or neurosurgery. First aid Rolling people with an active tonic-clonic seizure onto their side and into the recovery position helps prevent fluids from getting into the lungs. Putting fingers, a bite block or tongue depressor in the mouth is not recommended as it might make the person vomit or result in the rescuer being bitten. Efforts should be taken to prevent further self-injury. Spinal precautions are generally not needed.If a seizure lasts longer than 5 minutes or if there are more than two seizures in an hour without a return to a normal level of consciousness between them, it is considered a medical emergency known as status epilepticus. This may require medical help to keep the airway open and protected; a nasopharyngeal airway may be useful for this.

The ILAE considers doing so is perfectly allowable, so long as it is clear what definition is being used. Classification In contrast to the classification of seizures which focuses on what happens during a seizure, the classification of epilepsies focuses on the underlying causes. When a person is admitted to hospital after an epileptic seizure the diagnostic workup results preferably in the seizure itself being classified (e.g. tonic-clonic) and in the underlying disease being identified (e.g. hippocampal sclerosis). The name of the diagnosis finally made depends on the available diagnostic results and the applied definitions and classifications (of seizures and epilepsies) and its respective terminology. The International League Against Epilepsy (ILAE) provided a classification of the epilepsies and epileptic syndromes in 1989 as follows: This classification was widely accepted but has also been criticized mainly because the underlying causes of epilepsy (which are a major determinant of clinical course and prognosis) were not covered in detail. In 2010 the ILAE Commission for Classification of the Epilepsies addressed this issue and divided epilepsies into three categories (genetic, structural/metabolic, unknown cause) that were refined in their 2011 recommendation into four categories and a number of subcategories reflecting recent technologic and scientific advances. A revised, operational classification of seizure types has been introduced by the ILAE. It allows more clearly understood terms and clearly defines focal and generalized onset dichotomy, when possible, even without observing the seizures based on description by patient or observers.

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Therefore 400,000 units of penicillin V is 250 mg.The use of units to prescribe penicillin is a historical accident and is largely obsolete outside of the US. Since the original penicillin was an ill-defined mixture of active compounds (an amorphous yellow powder), the potency of each batch of penicillin varied from batch to batch. It was therefore impossible to prescribe 1 g of penicillin because the activity of 1 g of penicillin from one batch would be different from the activity from another batch. After manufacture, each batch of penicillin had to be standardised against a known unit of penicillin: each glass vial was then filled with the number of units required. In the 1940s, a vial of 5,000 Oxford units was standard, but the depending on the batch, could contain anything from 15 mg to 20 mg of penicillin. Later, a vial of 1,000,000 international units became standard, and this could contain 2.5 g to 3 g of natural penicillin (a mixture of penicillin I, II, III, and IV and natural impurities). With the advent of pure penicillin G preparations (a white crystalline powder), there is little reason to prescribe penicillin in units. The "unit" of penicillin has had three previous definitions, and each definition was chosen as being roughly equivalent to the previous one. Oxford or Florey unit (1941). This was originally defined as the minimum amount of penicillin dissolved in 50 ml of meat extract that would inhibit the growth of a standard strain of Staphylococcus aureus (the Oxford Staphylococcus).

Nedocromil sodium is a medication considered as mast cell stabilizer which acts to prevent wheezing, shortness of breath, and other breathing problems caused by asthma. It is administered by an inhaler under the brand name Tilade, and as an eye drop under the brand name Alocril. The effects of nedocromil versus asthma are gradual rather than fast-acting and it is not indicated for acute respiratory distress compared to fast acting bronchodilators like albuterol or other well-known inhaler medications. Liquid preparations of nedocromil are available in the UK under the name Rapitil for use for allergic eye reactions. Nedocromil sodium has been shown to be effective in alleviating symptoms of allergic conjunctivitis.Nedocromil is classified as a benzopyrone. Nedocromil acts as a mast cell stabilizer, inhibits the degranulation of mast cells, prevents release of histamine and tryptase, so preventing the synthesis of prostaglandins and leukotrienes. US Production of inhaled nedocromil ceased in April 2008 because it used CFCs as propellant. References Media related to Nedocromil at Wikimedia Commons

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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.

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.

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These scores (0–3) are used in the OLGA staging assessment in each 10 compartment: Treatment Antacids are a common treatment for mild to medium gastritis. When antacids do not provide enough relief, medications such as H2 blockers and proton-pump inhibitors that help reduce the amount of acid are often prescribed.Cytoprotective agents are designed to help protect the tissues that line the stomach and small intestine. They include the medications sucralfate and misoprostol. If NSAIDs are being taken regularly, one of these medications to protect the stomach may also be taken. Another cytoprotective agent is bismuth subsalicylateSeveral regimens are used to treat H. pylori infection. Most use a combination of two antibiotics and a proton pump inhibitor. Sometimes bismuth is added to the regimen. History In 1,000 A.D, Avicenna first gave the description of stomach cancer. In 1728, German physician Georg Ernst Stahl first coined the term "gastritis". Italian anatomical pathologist Giovanni Battista Morgagni further described the characteristics of gastric inflammation. He described the characteristics of erosive or ulcerative gastritis and erosive gastritis. Between 1808 and 1831, French physician François-Joseph-Victor Broussais gathered information from the autopsies of dead French soldiers. He described chronic gastritis as "Gastritide" and erroneously believed that gastritis was the cause of ascites, typhoid fever, and meningitis. In 1854, Charles Handfield Jones and Wilson Fox described the microscopic changes of stomach inner lining in gastritis which existed in diffuse and segmental forms. In 1855, Baron Carl von Rokitansky first described hypertrophic gastritis. In 1859, British physician, William Brinton first described about acute, subacute, and chronic gastritis.

Since 1992, chronic gastritis lesions are classified according to the Sydney system. Metaplasia Mucous gland metaplasia, the reversible replacement of differentiated cells, occurs in the setting of severe damage of the gastric glands, which then waste away (atrophic gastritis) and are progressively replaced by mucous glands. Gastric ulcers may develop; it is unclear if they are the causes or the consequences. Intestinal metaplasia typically begins in response to chronic mucosal injury in the antrum and may extend to the body. Gastric mucosa cells change to resemble intestinal mucosa and may even assume absorptive characteristics. Intestinal metaplasia is classified histologically as complete or incomplete. With complete metaplasia, gastric mucosa is completely transformed into small-bowel mucosa, both histologically and functionally, with the ability to absorb nutrients and secrete peptides. In incomplete metaplasia, the epithelium assumes a histologic appearance closer to that of the large intestine and frequently exhibits dysplasia. Diagnosis Often, a diagnosis can be made based on patients description of their symptoms. Other methods which may be used to verify gastritis include: Blood tests: Blood cell count Presence of H. pylori Liver, kidney, gallbladder, or pancreas functions Urinalysis Stool sample, to look for blood in the stool X-rays Endoscopy, to check for stomach lining inflammation and mucous erosion Stomach biopsy, to test for gastritis and other conditionsThe OLGA staging frame of chronic gastritis on histopathology. Atrophy is scored as the percentage of atrophic glands and scored on a four-tiered scale. No atrophy (0%) = score 0; mild atrophy (1–30%) = score 1; moderate atrophy (31–60%) = score 2; 9 severe atrophy (>60%) = score 3.

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Other competing theories around the turn of the century included one penned by Malcom in 1907, in which the assertion was that prolonged vasoconstriction led to the pathophysiological signs and symptoms of shock. In the following World War I, research concerning shock resulted in experiments by Walter B. Cannon of Harvard and William M. Bayliss of London in 1919 that showed that an increase in permeability of the capillaries in response to trauma or toxins was responsible for many clinical manifestations of shock. In 1972 Hinshaw and Cox suggested the classification system for shock which is still used today. References == External links ==

Carney complex and its subsets LAMB syndrome and NAME syndrome are autosomal dominant conditions comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity. It is distinct from Carneys triad. Approximately 7% of all cardiac myxomas are associated with Carney complex. Presentation The spotty skin pigmentation and lentigines occur most commonly on the face, especially on the lips, eyelids, conjunctiva and oral mucosa. Cardiac myxomas may lead to embolic strokes and heart failure and may present with fever, joint pain, shortness of breath, diastolic rumble and tumor plop. Myxomas may also occur outside the heart, usually in the skin and breast. Endocrine tumors may manifest as disorders such as Cushing syndrome. The most common endocrine gland manifestation is an ACTH-independent Cushings syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). The LAMB acronym refers to lentigines, atrial myxomas, and blue nevi. NAME refers to nevi, atrial myxoma, myxoid neurofibromas, and ephelides.Testicular cancer, particularly Sertoli cell type, is associated with Carney syndrome. Thyroid and pancreas cancer may also occur.Although J Aidan Carney also described Carneys triad it is entirely different. Pathophysiology Carney complex is most commonly caused by mutations in the PRKAR1A gene on chromosome 17 (17q23-q24) which may function as a tumor-suppressor gene.

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Galantamines competitive inhibition of acetylcholinesterase and allosteric nicotinic modulation serves as a dual mechanism of action.To reduce the prevalence of negative side effects associated with galantamine, such as nausea and vomiting, a dose-escalation scheme may be used. The use of a dose-escalation scheme has been well accepted in countries where galantamine is used. A dose-escalation scheme for Alzheimers treatment involves a recommended starting dosage of 4 mg galantamine tablets given twice a day (8 mg/day). After a minimum of 4 weeks, the dosage may then be increased to 8 mg given twice a day (16 mg/day). After a minimum of 4 weeks at 16 mg/day, the treatment may be increased to 12 mg given twice a day (24 mg/day). Dosage increases are based upon the assessment of clinical benefit as well as tolerability of the previous dosage. If treatment is interrupted for more than three days, the process is usually restarted, beginning at the starting dosage, and re-escalating to the current dose. It has been found that a dosage between 16–24 mg/day is the optimal dosage. Available forms The product is supplied in prescription form only in twice-a-day tablets, in once-a-day extended-release capsules, and in oral solution. Side effects Galantamines side effect profile was similar to that of other cholinesterase inhibitors, with gastrointestinal symptoms being the most notable and most commonly observed. One study reports higher proportions of patients treated with galantamine experiencing nausea and vomiting as opposed to the placebo group.

It has been proposed that the drugs Circe used were an extract from Datura stramonium (also known as jimsonweed), which causes memory loss and delirium. This would give a basis for the snowdrops use as an antidote, as Datura stramonium is anticholinergic, while galantamine is an acetylcholinesterase inhibitor. Medical uses Galantamine is indicated for the treatment of mild to moderate vascular dementia and Alzheimers. In the United States, it is approved by the Food and Drug Administration as safe and effective for the treatment of mild to moderate dementia. As with other cholinesterase inhibitors, galantamine may not be effective for treating mild cognitive impairment.The FDA considers galantamine to have dual status as a prescription drug and as a OTC dietary supplement. Alzheimers disease Alzheimers disease is characterized by the impairment of cholinergic function. One hypothesis is that this impairment contributes to the cognitive deficits caused by the disease. This hypothesis forms the basis for use of galantamine as a cholinergic enhancer in the treatment of Alzheimers. Galantamine inhibits acetylcholinesterase, an enzyme which hydrolyzes acetylcholine. As a result of acetylcholinesterase inhibition, galantamine increases the availability of acetylcholine for synaptic transmission. Additionally, galantamine binds to the allosteric sites of nicotinic receptors, which causes a conformational change. This allosteric modulation increases the nicotinic receptors response to acetylcholine. The activation of presynaptic nicotinic receptors increases the release of acetylcholine, further increasing the availability of acetylcholine.

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Causes Typical causes of microcytic anemia include: Childhood Iron deficiency anemia by far the most common cause of anemia in general and of microcytic anemia in particular Thalassemia Adulthood Iron deficiency anemia Thalassemia Anemia of chronic diseaseRare hereditary causes of microcytic anemia include sideroblastic anemia and other X-linked anemias, hereditary hypotransferrinemia, hereditary aceruloplasminemia, erythropoietic protoporphyria, iron-refractory iron deficiency anemia, and other thalassemic mutations (such as hemoglobin E and hemoglobin Lepore syndrome).Rare acquired causes of microcytic anemia include lead poisoning, zinc deficiency, copper deficiency, alcohol, and certain medications.Other causes that are typically thought of as causing normocytic anemia or macrocytic anemia must also be considered, as the presence of two or more causes of anemia can distort the typical picture. Iron Deficiency Anemia Nearly half of all anemia cases are due to iron deficiency as it is the most common nutritional disorder. Although it is a common nutritional disorder, most causes of iron deficiency anemia (IDA) are due to blood loss. It is also more common to occur among children and females who are menstruating but can occur to any individual of any age. As well as a low MCV, diagnostic criteria includes low serum ferritin levels and transferrin saturation may also be used. Non-pharmacological measures to treat IDA include increasing sources of dietary iron, especially from heme sources such are liver, seafood, and red meats. However, these measures often take a great deal of time longer to replete iron stores compared to pharmacological agents such as iron supplements which are the mainstay of treatment.

Pharmacological agents may also be required in cases where deficiency is more severe, in cases where iron loss exceeds dietary intake, and in individuals who follow a plant-based diet as non-heme sources often have lower bioavailability. When oral iron supplements are used, they should be taken on an empty stomach to increase absorption This might increase the risk of side effects however, such as nausea and epigastric pain. Anemia of Chronic Disease Anemia of chronic disease (ACD) is the second most common cause of anemia after IDA. It usually occurs in individuals that have chronic inflammation due to a medical condition. Both diagnosis and treatment can be difficult as there may be an overlap with iron deficiency and thus it is a diagnosis of exclusion. Since ACD is caused by an underlying disorder, complete resolution of the condition is unlikely and we focus on controlling the inflammatory disorder rather than treating the ACD itself. Potential inflammatory conditions that can cause ACD are pulmonary tuberculosis, rheumatoid arthritis, and malignancies among many others. Thalassemia Thalassemia is an inherited condition that has variants in alpha or beta globin genes that result in lower levels of globin chains required to make hemoglobin, resulting in alpha thalassemia or beta thalassemia, respectively. Diagnosis is made by DNA analysis for alpha thalassemia and hemoglobin analysis for beta thalassemia. Management of thalassemia involves chronic transfusions that maintain a hemoglobin level that reduces symptoms of anemia as well as suppresses extramedullary hematopoiesis which can lead to multiple morbidities.

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Respiratory arrest is a sickness caused by apnea (cessation of breathing) or respiratory dysfunction severe enough it will not sustain the body (such as agonal breathing). Prolonged apnea refers to a patient who has stopped breathing for a long period of time. If the heart muscle contraction is intact, the condition is known as respiratory arrest. An abrupt stop of pulmonary gas exchange lasting for more than five minutes may damage vital organs especially the brain, possibly permanently. Lack of oxygen to the brain causes loss of consciousness. Brain injury is likely if respiratory arrest goes untreated for more than three minutes, and death is almost certain if more than five minutes. Damage may be reversible if treated early enough. Respiratory arrest is a life-threatening medical emergency that requires immediate medical attention and management. To save a patient in respiratory arrest, the goal is to restore adequate ventilation and prevent further damage. Management interventions include supplying oxygen, opening the airway, and means of artificial ventilation. In some instances, an impending respiratory arrest could be predetermined by signs the patient is showing, such as the increased work of breathing. Respiratory arrest will ensue once the patient depletes their oxygen reserves and loses the effort to breathe. Respiratory arrest should be distinguished from respiratory failure. The former refers to the complete cessation of breathing, while respiratory failure is the inability to provide adequate ventilation for the bodys requirements.

Children with the more severe form of MPS IV may not live beyond their twenties or thirties. Cause Morquio syndrome is inherited from an autosomal recessive inherited gene. Every person has two copies of the genes needed to break down keratan sulfate, but only one healthy copy is needed. Both parents pass down one defective copy to their child, resulting in a child with no functional copies of the gene. As such, the body is incapable breaking down keratan sulfate for disposal. The incompletely broken down GAGs remain stored in cells in the body, causing progressive damage. Babies may show little sign of the disease, but as more and more cells become damaged, symptoms start to appear. Diagnosis Classification This syndrome has two forms, A and B, referred to as Morquio A and Morquio B syndrome or MPS IVA and MPS IVB. The two forms are distinguished by the gene product involved; Type A involves a malfunction in the GALNS gene, while Type B involves a malfunction of the GLB1 gene. Treatment The treatment for Morquio syndrome consists of prenatal identification and of enzyme replacement therapy. On 12 February 2014, the US Food and Drug Administration approved the drug elosulfase alfa (Vimizim) for treating Type A. Currently, there is no treatment for Type B. Prognosis The lifespan of patients with Morquio syndrome is variable and depends on the subtype. Type A is generally severe, with a life expectancy in the 20s to 30s.

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During depressive episodes, BP-II patients tend to show higher rates of psychomotor agitation, guilt, shame, suicidal ideation, and suicide attempts. BP-II patients have shown higher lifetime comorbidity rates of phobias, anxiety disorders, substance use, and eating disorders. In addition, there is a higher correlation between BP-II patients and family history of psychiatric illness, including major depression and substance-related disorders compared to BP-I. The occurrence rate of psychiatric illness in first degree relatives of BP-II patients was 26.5%, versus 15.4% in BP-I patients. Management Although BP-II is a prevalent condition associated with morbidity and mortality, there has been an absence of robust clinical trials and systematic reviews that investigate the efficacy of pharmacologic treatments for the hypomanic and depressive phases of BP-II. Thus, the current treatment guidelines for the symptoms of BP-II are derived and extrapolated from the treatment guidelines in BP-I, along with limited randomized controlled trials published in the literature. : 1697 The treatment of BP-II consists of the following: treatment of hypomania, treatment of major depression, and maintenance therapy for the prevention of relapse of hypomania or depression. As BP-II is a chronic condition, the goal of treatment is to achieve remission of symptoms and prevention of self-harm in patients. Treatment modalities of BP-II include medication-based pharmacotherapy, along with various forms of psychotherapy. Medications The most common pharmacologic agents utilized in the treatment of BP-II includes mood stabilizers, antipsychotics, and antidepressants.

Hydrometra is a genus of water measurers in the family Hydrometridae. There are more than 120 described species in Hydrometra. See also List of Hydrometra species References Further reading == External links ==

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The fibrous sutures specifically allow the deformation of the skull during birth and absorb mechanical forces during childhood They also allow the necessary expansion during brain growth.In the very first years of life the sutures serve as the most important centers of growth in the skull. The growth of the brain and the patency of the sutures depend on each other. Brain growth pushes the two sides of the patent sutures away from each other, thereby enabling growth of the neurocranium. This means that the neurocranium can only grow if the sutures remain open. The neurocranium will not grow when the forces induced by brain growth are not there. This will occur for example when the intracranial pressure drops; the sutures do not experience stretching anymore causing them to fuse. Diagnosis The evaluation of a child suspected to have craniosynostosis is preferentially performed in a craniofacial center. The three main elements of analysis include medical history, physical examination and radiographic analysis.Medical history should in any case include questions about risk factors during pregnancy, the familial rate and the presence of symptoms of elevated intracranial pressure (ICP). Elevated ICP Symptoms of increased intracranial pressure – such as headache and vomiting – should be questioned after. An elevation of ICP can be present in 4 to 20% of the children where only a single suture is affected. The incidence of ICP in children with more than one suture involved can be as high as 62%. However, even though the children are affected, symptoms are not always present.

observed a FGFR3 mutation in as many as 31% of the cases with nonsyndromic coronal synostosis, thus showing that FGFR abnormalities play an important role in nonsyndromic craniosynostosis.In terms of syndromic craniosynostosis not only do FGFR3 and TWIST genes feature, but also FGFR1 and in particular FGFR2, which has been reported in 90% of the syndromic craniosynostoses such as Apert, Crouzon, Peiffer and Jackson–Weiss. The mutations can be divided into mutations that lead to gain of function (in FGFR genes) and mutations that lead to loss of function (in TWIST genes). Craniosynostosis is therefore likely the result of a disturbance in the fine balance that regulates the multiplication and maturation of the precursor bone cells in the cranial sutures.The familial rate, which is different for nonsyndromic and syndromic cases, provides an important clue. In the nonsyndromic cases, a positive family history is found in 2% of the cases with sagittal suture closure and in 6% to 11% of the cases with coronal suture closure. Cranial sutures The mesenchyme above the meninges undergoes intramembranous ossification forming the neurocranium. The neurocranium consists of several bones, which are united and at the same time separated by fibrous sutures. This allows movement of the separate bones in relation to one another; the infant skull is still malleable.

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This life-threatening scenario is complicated by other medical problems such as pneumonia, severe infections, blood clots in the lungs, and bleeding in the digestive tract in 60% of those who require artificial ventilation. Autonomic dysfunction The autonomic or involuntary nervous system, which is involved in the control of body functions such as heart rate and blood pressure, is affected in two-thirds of people with Guillain–Barré syndrome, but the impact is variable. Twenty percent may experience severe blood-pressure fluctuations and irregularities in the heart beat, sometimes to the point that the heart beat stops and requires pacemaker-based treatment. Other associated problems are abnormalities in perspiration and changes in the reactivity of the pupils. Autonomic nervous system involvement can affect even those who do not have severe muscle weakness. Causes Infection onset Two-thirds of people with Guillain–Barré syndrome have experienced an infection before the onset of the condition. Most commonly, these are episodes of gastroenteritis or a respiratory tract infection. In many cases, the exact nature of the infection can be confirmed. Approximately 30% of cases are provoked by Campylobacter jejuni bacteria, which cause diarrhea. A further 10% are attributable to cytomegalovirus (CMV, HHV-5). Despite this, only very few people with Campylobacter or CMV infections develop Guillain–Barré syndrome (0.25–0.65 per 1000 and 0.6–2.2 per 1000 episodes, respectively). The strain of Campylobacter involved may determine the risk of GBS; different forms of the bacteria have different lipopolysaccharides on their surface, and some may induce illness (see below) while others will not.Links between other infections and GBS are less certain.

Characteristic findings in Guillain–Barré syndrome are an elevated protein level, usually greater than 0.55 g/L, and fewer than 10 white blood cells per cubic millimeter of fluid ("albuminocytological dissociation"). This pattern distinguishes Guillain–Barré syndrome from other conditions (such as lymphoma and poliomyelitis) in which both the protein and the cell count are elevated. Elevated CSF protein levels are found in approximately 50% of patients in the first 3 days after onset of weakness, which increases to 80% after the first week.Repeating the lumbar puncture during the disease course is not recommended. The protein levels may rise after treatment has been administered. Neurophysiology Directly assessing nerve conduction of electrical impulses can exclude other causes of acute muscle weakness, as well as distinguish the different types of Guillain–Barré syndrome. Needle electromyography (EMG) and nerve conduction studies may be performed. In the first two weeks, these investigations may not show any abnormality. Neurophysiology studies are not required for the diagnosis.Formal criteria exist for each of the main subtypes of Guillain–Barré syndrome (AIDP and AMAN/AMSAN, see below), but these may misclassify some cases (particularly where there is reversible conduction failure) and therefore changes to these criteria have been proposed. Sometimes, repeated testing may be helpful. Clinical subtypes A number of subtypes of Guillain–Barré syndrome are recognized. Despite this, many people have overlapping symptoms that can make the classification difficult in individual cases. All types have partial forms.

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See also Torpor Notes References C. Lafosse, Zakboek Neuropsychologische Symptomatologie, p. 37, ISBN 90-334-3995-6. == External links ==

Surgery Vestibulectomy, during which the nerve fibers to the area are cut out, may be recommended if other treatments have not been found to be effective. There have been no high quality studies looking at surgery as a treatment. While improvement has been noted in 60% to 90%, those who were treated without surgery improved in 40 to 80% of cases. Epidemiology The percentage of women affected is not entirely clear, but estimates range as high as 16%. Many other conditions that are not truly vulvodynia (diagnosis is made by ruling out other causes of vulvar pain) could be confused with it. Vulvar pain is a quite frequent complaint in womens health clinics. Vulvodynia is a new term in the medical literature. References External links Vulvodynia at Curlie

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History In 1945, the ophthalmologist David Glendenning Cogan (1908–1993) first described the "nonsyphilitic interstitial keratitis and vestibuloauditory symptoms" that would later bear his name. In 1963, the atypical form of Cogan syndrome, also known as "Logan Syndrome" was first described. References Further reading Haynes BF, Kaiser-Kupfer MI, Mason P, Fauci AS (November 1980). "Cogan syndrome: studies in thirteen patients, long-term follow-up, and a review of the literature". Medicine. 59 (6): 426–41. doi:10.1097/00005792-198011000-00003. PMID 6969345. Gluth MB, Baratz KH, Matteson EL, Driscoll CL (April 2006). "Cogan syndrome: a retrospective review of 60 patients throughout a half century". Mayo Clinic Proceedings. 81 (4): 483–8. doi:10.4065/81.4.483. PMID 16610568. Norton EW, Cogan DG (May 1959). "Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms; a long-term follow-up". Archives of Ophthalmology. 61 (5): 695–7. doi:10.1001/archopht.1959.00940090697004. PMID 13636563. Bicknell JM, Holland JV (March 1978). "Neurologic manifestations of Cogan syndrome". Neurology. 28 (3): 278–81. doi:10.1212/wnl.28.3.278. PMID 305011. S2CID 22367876. Casselman JW, Majoor MH, Albers FW (January 1994). "MR of the inner ear in patients with Cogan syndrome". American Journal of Neuroradiology. 15 (1): 131–8. PMC 8332073. PMID 8141044. Allen NB, Cox CC, Cobo M, et al. (March 1990). "Use of immunosuppressive agents in the treatment of severe ocular and vascular manifestations of Cogans syndrome". The American Journal of Medicine. 88 (3): 296–301. doi:10.1016/0002-9343(90)90157-9. PMID 2309745. Kundell SP, Ochs HD (July 1980). "Cogan syndrome in childhood". The Journal of Pediatrics. 97 (1): 96–8. doi:10.1016/s0022-3476(80)80142-9. PMID 7381656. == External links ==

Simeticone (INN), also known as simethicone (USAN), is an anti-foaming agent used to reduce bloating, discomfort or pain caused by excessive gas. Medical uses Simeticone is used to relieve the symptoms of excessive gas in the gastrointestinal tract, namely bloating, burping, and flatulence. While there is a lack of conclusive evidence that simeticone is effective for this use, ⁣ studies have shown that it can relieve symptoms of functional dyspepsia and functional bloating.It has not been fully established that simeticone is useful to treat colic in babies, and it is not recommended for this purpose. A study in the United Kingdom reported that according to parental perception simeticone helped infant colic in some cases.Simeticone can also be used for suspected postoperative abdominal discomfort in infants. Side effects Simeticone does not have any serious side effects. Two uncommon side effects (occurring in 1 in 100 to 1 in 1,000 patients) are constipation and nausea. Pharmacology Simeticone is a non-systemic surfactant which decreases the surface tension of gas bubbles in the GI tract. This allows gas bubbles to leave the GI tract as flatulence or belching. Simeticone does not reduce or prevent the formation of gas. Its effectiveness has been shown in several in vitro studies. Chemistry Simethicone is a mixture of dimethicone and silicon dioxide. Names The INN name is "simeticone", which was added to the INN recommended list in 1999.Simeticone is marketed under many brand names and in many combination drugs; it is also marketed as a veterinary drug. == References ==

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Testicle: an infarction of a testicle is commonly caused by testicular torsion and may require removal of the affected testicle(s) if not undone by surgery quickly enough. Eye: an infarction can occur to the central retinal artery which supplies the retina causing sudden visual loss. Bowel: Bowel infarction is generally caused by mesenteric ischemia due to blockages in the arteries or veins that supply the bowel. Associated diseases Diseases commonly associated with infarctions include: Peripheral artery occlusive disease (the most severe form of which is gangrene) Antiphospholipid syndrome Sepsis Giant-cell arteritis (GCA) Hernia Volvulus Sickle-cell disease References External links Media related to Infarction at Wikimedia Commons The dictionary definition of infarction at Wiktionary

Because ML I is classified as a sialidosis, it is sometimes referred to as sialidosis type II. A rarer form of sialidosis – sialidosis type 1– occurs in children and adolescents and is often referred to as the juvenile form of the disorder. Children usually begin to show symptoms during the second decade of life, and myoclonus and cherry-red macules are often the initial symptoms. Patients usually develop seizures and progressive deterioration of coordinated muscular and mental activities. Pathophysiology The role of sialidase is to remove a particular form of sialic acid (a sugar molecule) from sugar-protein complexes (referred to as glycoproteins), which allows the cell to function properly. Because the enzyme is deficient, small chains containing the sugar-like material accumulate in neurons, bone marrow, and various cells that defend the body against infection. Diagnosis The detection of high urinary sialyl oligosaccharides and the confirmation of lysosomal enzyme deficiency in leukocytes or cultured fibroblasts make the diagnosis. Management Treatment of sialidosis is similar to the other progressive myoclonic epilepsy disorders, which consists of managing seizures and myoclonus along with palliative, supportive, and rehabilitative care. See also Fucosidosis Sialic acid Neuraminidase Mucolipidosis Lysosomal storage disease Notes References mucolipidoses at NINDS - article derived from detail sheet available here External links Sialidosis type 1 and 3 at NIHs Office of Rare Diseases Sialidosis at NIHs Office of Rare Diseases

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In these cases, the antibodies which the persons immune system developed to attack the group A streptococci are also able to attack the persons own tissues. The following complications result, depending on which tissues in the persons body are targeted by those antibodies. Acute rheumatic fever: This is a complication that results 2–6 weeks after a group A streptococcal infection of the upper respiratory tract. It presents in developing countries, where antibiotic treatment of streptococcal infections is less common, as a febrile illness with several clinical manifestations, which are organized into what is called the Jones criteria. These criteria include arthritis, carditis, neurological issues, and skin findings. Diagnosis also depends on evidence of a prior group A streptococcal infection in the upper respiratory tract (as seen in streptococcal pharyngitis and scarlet fever). The carditis is the result of the immunologic response targeting the persons heart tissue, and it is the most serious sequelae that develops from acute rheumatic fever. When this involvement of the heart tissue occurs, it is called rheumatic heart disease. In most cases of rheumatic heart disease, the mitral valve is affected, ultimately leading to mitral stenosis. The link to rheumatic fever and heart disease is a particular concern in Australia, because of the high prevalence of these diseases in Aboriginal and Torres Strait Islander communities. Poststreptococcal glomerulonephritis: This is inflammation of the kidney, which presents 1–2 weeks after a group A streptococcal pharyngitis.

Karelitz and Stempien discovered that extracts from human serum globulin and placental globulin can be used as lightening agents for scarlet fever and this was used later as the basis for the Dick test. The association of scarlet fever and bacteriophages was described in 1926 by Cantacuzène (Ioan Cantacuzino) and Bonciu.An antitoxin for scarlet fever was developed in 1924. The first toxin which causes this disease was cloned and sequenced in 1986 by Weeks and Ferretti. The discovery of penicillin and its subsequent widespread use has significantly reduced the mortality of this once feared disease. Reports of cases of scarlet fever have been on the rise in countries including England, Wales, South Korea, Vietnam, China, and Hong Kong in recent years. Researchers are unsure as to what has caused the spike in cases of the disease. The Dick test The Dick test, invented in 1924 by George F. Dick and Gladys Dick, was used to identify those susceptible to scarlet fever. The Dick test consisted of injecting a diluted strain of the streptococci known to cause scarlet fever into a persons skin. A local reaction in the skin at the site of injection appeared in people who were susceptible to developing scarlet fever. The reaction was most notable around 24 hours after the injection but could be seen as early as 4 hours. If no reaction was seen in the skin, then that person was assumed to have already developed immunity to the disease and was not at risk of developing it. References == External links ==

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The most common parasites implicated are Angiostrongylus cantonensis, Gnathostoma spinigerum, Schistosoma, as well as the conditions cysticercosis, toxocariasis, baylisascariasis, paragonimiasis, and a number of rarer infections and noninfective conditions. Non-infectious Meningitis may occur as the result of several non-infectious causes: spread of cancer to the meninges (malignant or neoplastic meningitis) and certain drugs (mainly non-steroidal anti-inflammatory drugs, antibiotics and intravenous immunoglobulins). It may also be caused by several inflammatory conditions, such as sarcoidosis (which is then called neurosarcoidosis), connective tissue disorders such as systemic lupus erythematosus, and certain forms of vasculitis (inflammatory conditions of the blood vessel wall), such as Behçets disease. Epidermoid cysts and dermoid cysts may cause meningitis by releasing irritant matter into the subarachnoid space. Rarely, migraine may cause meningitis, but this diagnosis is usually only made when other causes have been eliminated. Mechanism The meninges comprise three membranes that, together with the cerebrospinal fluid, enclose and protect the brain and spinal cord (the central nervous system). The pia mater is a delicate impermeable membrane that firmly adheres to the surface of the brain, following all the minor contours. The arachnoid mater (so named because of its spider-web-like appearance) is a loosely fitting sac on top of the pia mater. The subarachnoid space separates the arachnoid and pia mater membranes and is filled with cerebrospinal fluid. The outermost membrane, the dura mater, is a thick durable membrane, which is attached to both the arachnoid membrane and the skull.

The greatest period of growth is during the end of the second trimester, between 20–26 weeks.A measure of mass volume divided by head circumference, termed cystic adenomatoid malformation volume ratio (CVR) has been developed to predict the risk of hydrops. The lung mass volume is determined using the formula (length × width × anteroposterior diameter ÷ 2), divided by head circumference. With a CVR greater than 1.6 being considered high risk. Fetuses with a CVR less than 1.6 and without a dominant cyst have less than a 3% risk of hydrops. After delivery, if the patient is symptomatic, resection is mandated. If the infant is asymptomatic, the need for resection is a subject of debate, though it is usually recommended. Development of recurrent infections, rhabdomyosarcoma, adenocarcinomas in situ within the lung malformation have been reported. Treatment In most cases, a fetus with CPAM is closely monitored during pregnancy and the CPAM is removed via surgery after birth. Most babies with a CPAM are born without complication and are monitored during the first few months. Many patients have surgery, typically before their first birthday, because of the risk of recurrent lung infections associated with CPAMs. Some pediatric surgeons can safely remove these lesions using very tiny incisions using minimally invasive surgical techniques (thoracoscopy). However, some CPAM patients live a full life without any complication or incident. It is hypothesized that there are thousands of people living with an undetected CPAM. Through ultrasound testing employed in recent years, many more patients are aware that they live with this condition.

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Often the result of strain, including sneezing, coughing, vomiting or other kind of strain Nose Epistaxis – nosebleed Mouth Tooth eruption – losing a tooth Hematemesis – vomiting fresh blood Hemoptysis – coughing up blood from the lungs Lungs Pulmonary hemorrhage Gastrointestinal Upper gastrointestinal bleed Lower gastrointestinal bleed Occult gastrointestinal bleed Urinary tract Hematuria – blood in the urine from urinary bleeding Gynecologic Vaginal bleeding Postpartum hemorrhage Breakthrough bleeding Ovarian bleeding – This is a potentially catastrophic and not so rare complication among lean patients with polycystic ovary syndrome undergoing transvaginal oocyte retrieval. Anus Melena – upper gastrointestinal bleeding Hematochezia – lower gastrointestinal bleeding, or brisk upper gastrointestinal bleeding Vascular Ruptured aneurysm Aortic transection Iatrogenic injury Causes Bleeding arises due to either traumatic injury, underlying medical condition, or a combination. Traumatic injury Traumatic bleeding is caused by some type of injury. There are different types of wounds which may cause traumatic bleeding. These include: Abrasion – Also called a graze, this is caused by transverse action of a foreign object against the skin, and usually does not penetrate below the epidermis. Excoriation – In common with Abrasion, this is caused by mechanical destruction of the skin, although it usually has an underlying medical cause. Hematoma – Caused by damage to a blood vessel that in turn causes blood to collect in an enclosed area. Laceration – Irregular wound caused by blunt impact to soft tissue overlying hard tissue or tearing such as in childbirth. In some instances, this can also be used to describe an incision. Incision – A cut into a body tissue or organ, such as by a scalpel, made during surgery.

Amitriptyline/chlordiazepoxide, sold under the brand names Limbitrol and Limbitrol DS, is a combination of amitriptyline (Elavil), a tricyclic antidepressant, and chlordiazepoxide (Librium), a benzodiazepine, which is approved for the treatment of moderate to severe depression associated with moderate to severe anxiety in the United States. It contains 12.5 to 25 mg amitriptyline and 5 to 10 mg chlordiazepoxide per tablet. == References ==

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Although the innate immune response does not play a significant role in these processes, the adaptive immune response, in particular virus-specific cytotoxic T lymphocytes(CTLs), contributes to most of the liver injury associated with HBV infection. CTLs eliminate HBV infection by killing infected cells and producing antiviral cytokines, which are then used to purge HBV from viable hepatocytes. Although liver damage is initiated and mediated by the CTLs, antigen-nonspecific inflammatory cells can worsen CTL-induced immunopathology, and platelets activated at the site of infection may facilitate the accumulation of CTLs in the liver. Diagnosis The tests, called assays, for detection of hepatitis B virus infection involve serum or blood tests that detect either viral antigens (proteins produced by the virus) or antibodies produced by the host. Interpretation of these assays is complex.The hepatitis B surface antigen (HBsAg) is most frequently used to screen for the presence of this infection. It is the first detectable viral antigen to appear during infection. However, early in an infection, this antigen may not be present and it may be undetectable later in the infection as it is being cleared by the host. The infectious virion contains an inner "core particle" enclosing viral genome. The icosahedral core particle is made of 180 or 240 copies of the core protein, alternatively known as hepatitis B core antigen, or HBcAg. During this window in which the host remains infected but is successfully clearing the virus, IgM antibodies specific to the hepatitis B core antigen (anti-HBc IgM) may be the only serological evidence of disease.

This is because in comparison to their previous lifestyle where they would engage in strenuous physical activity daily and have meals that are low in fat and high in fiber, the Westernized lifestyle has less physical activity and the diet includes high levels of carbohydrates and fats. Age related changes Android fat distributions change across life course. The main changes in women are associated with menopause. Premenopausal women tend to show a more gynoid fat distribution than post-menopausal women - this is associated with a drop in oestrogen levels. An android fat distribution becomes more common post-menopause, where oestrogen is at its lowest levels. Older men show android fat distributions more often than younger men which may be due to lifestyle changes, or hormonal changes related to age. Older adults have a greater waist-to-hip ratio than young adults which indicates high levels of android fat in older adults. Computed tomography studies show that older adults have a two-fold increase in visceral fat compared to young adults. These changes in android fat distribution in older adults occurs in the absence of any clinical diseases. == References ==

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A further study concluded that activated charcoal (4 g) does not influence gas formation in vitro or in vivo. Other authors reported that activated charcoal was effective. A study in 8 dogs concluded activated charcoal (unknown oral dose) reduced hydrogen sulfide levels by 71%. In combination with yucca schidigera, and zinc acetate, this was increased to an 86% reduction in hydrogen sulfide, although flatus volume and number was unchanged. An early study reported activated charcoal (unknown oral dose) prevented a large increase in the number of flatus events and increased breath hydrogen concentrations that normally occur following a gas-producing meal.Garments and external devices In 1998, Chester "Buck" Weimer of Pueblo, Colorado, received a patent for the first undergarment that contained a replaceable charcoal filter. The undergarments are air-tight and provide a pocketed escape hole in which a charcoal filter can be inserted. In 2001 Weimer received the Ig Nobel Prize for Biology for his invention.A similar product was released in 2002, but rather than an entire undergarment, consumers are able to purchase an insert similar to a pantiliner that contains activated charcoal. The inventors, Myra and Brian Conant of Mililani, Hawaii, still claim on their website to have discovered the undergarment product in 2002 (four years after Chester Weimer filed for a patent for his product), but state that their tests "concluded" that they should release an insert instead. Incontinence Flatus incontinence where there is involuntary passage of gas, is a type of faecal incontinence, and is managed similarly.

Pain and bloating While not affecting the production of the gases themselves, surfactants (agents that lower surface tension) can reduce the disagreeable sensations associated with flatulence, by aiding the dissolution of the gases into liquid and solid faecal matter. Preparations containing simethicone reportedly operate by promoting the coalescence of smaller bubbles into larger ones more easily passed from the body, either by burping or flatulence. Such preparations do not decrease the total amount of gas generated in or passed from the colon, but make the bubbles larger and thereby allowing them to be passed more easily.Other drugs including prokinetics, lubiprostone, antibiotics and probiotics are also used to treat bloating in patients with functional bowel disorders such as irritable bowel syndrome, and there is some evidence that these measures may reduce symptoms.A flexible tube, inserted into the rectum, can be used to collect intestinal gas in a flatus bag. This method is occasionally needed in a hospital setting, when the patient is unable to pass gas normally. Volume One method of reducing the volume of flatus produced is dietary modification, reducing the amount of fermentable carbohydrates. This is the theory behind diets such as the low-FODMAP diet (a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, alcohols, and polyols).Most starches, including potatoes, corn, noodles, and wheat, produce gas as they are broken down in the large intestine. Intestinal gas can be reduced by fermenting the beans, and making them less gas-inducing, or by cooking them in the liquor from a previous batch.

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Certain genetic variations within the TPMT gene can lead to decreased or absent TPMT enzyme activity, and individuals who are homozygous or heterozygous for these types of genetic variations may have increased levels of TGN metabolites and an increased risk of severe bone marrow suppression (myelosuppression) when receiving azathioprine. In many ethnicities, TPMT polymorphisms that result in decreased or absent TPMT activity occur with a frequency of approximately 5%, meaning that about 0.25% of patients are homozygous for these variants. However, an assay of TPMT activity in red blood cells or a TPMT genetic test can identify patients with reduced TPMT activity, allowing for the adjustment of azathioprine dose or avoidance of the drug entirely. The FDA-approved drug label for azathioprine recommends testing for TPMT activity to identify patients at risk for myelotoxicity. Indeed, testing for TPMT activity is one of the few examples of pharmacogenetics being translated into routine clinical care. Missense SNP in NUDT15 (e.g., rs116855232, inducing R139C)) has been identified to be a causal factor for AZA-induced leukopenia through a genome wide association study (GWAS) in East Asians. Cancers Azathioprine is listed as a human carcinogen in the 12th Report on Carcinogens by the National Toxicology Program of U.S. Department of Health and Human Services, asserting that it is "known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans."

Because actively replicating cells (such as cancer cells and the T cells and B cells of the immune system) are most active in synthesizing purine, making new DNA, these cells are most strongly affected. A portion of the nucleotides is additionally phosphorylated to the triphosphate forms. These bind to GTP-binding protein Rac1, blocking synthesis of the protein Bcl-xL, thus sending activated T cells and mononuclear cells into apoptosis (programmed cell death). Increased apoptosis of mononuclear cells is seen in inflammatory bowel disease patients treated with azathioprine. Chemistry Azathioprine is a thiopurine linked to a second heterocycle (an imidazole derivative) via a thioether. It is a pale yellow solid with a slightly bitter taste and a melting point of 238–245 °C. It is practically insoluble in water and only slightly soluble in lipophilic solvents such as chloroform, ethanol, and diethylether. It dissolves in alkaline aqueous solutions, where it hydrolyzes to 6-mercaptopurine.Azathioprine is synthesized from 5-chloro-1-methyl-4-nitro-1H-imidazole and 6-mercaptopurine in dimethyl sulfoxide. The synthesis of the former starts with an amide from methylamine and diethyl oxalate, which is then cyclized and chlorinated with phosphorus pentachloride; the nitro group is introduced with nitric and sulfuric acid. History Azathioprine was synthesized by George Herbert Hitchings and Gertrude Elion in 1957 (named BW 57-322) to produce 6-MP in a metabolically active, but masked form, and at first used as a chemotherapy drug.Robert Schwartz investigated the effect of 6-MP on the immune response in 1958 and discovered that it profoundly suppresses the formation of antibodies when given to rabbits together with antigens.

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Osteoporotic bone marrow defect is a condition which may be found in the body of the mandible. It is usually painless and found during routine radiographs. It appears as a poorly defined radiolucency (dark area) where there was a previous history of an extraction of a tooth. It may resemble a metastatic disease. It is a localized increase of hematopoietic bone marrow that creates a radiolucent radiographic defect. They occur more commonly in women in the midyears and show a predilection for the molar region of the mandible. They are especially common in extraction sites. Scattered trabeculae may extend short distances into the defect or, in some instances, through it, giving the defect a fairly characteristic appearance. Naturally there are no clinical symptoms. Cause The cause remains unknown. Diagnosis Differential diagnosis This defect may easily be mistaken for a cyst or tumor. Biopsy is required to rule these out. Treatment No treatment is required. References Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001.

Posaconazole or isavuconazole can be used as third-line agent for people with chronic pulmonary aspergillosis who are intolerant of or developed resistance to the first- and second-line agents. Regular chest X-rays, serological and mycological parameters, and quality of life questionnaires are used to monitor treatment progress. It is important to monitor the blood levels of antifungals to ensure optimal dosing as individuals vary in their absorption levels of these medications. Prognosis References == External links ==

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In transgenic mice, that are a model for human-like lipoprotein metabolism, adding D-PUFAs to diet indeed reduced body weight gain, improved cholesterol handling and reduced atherosclerotic damage to the aorta. miRNA MicroRNAs (miRNAs) have complementary sequences in the 3 UTR and 5 UTR of target mRNAs of protein-coding genes, and cause mRNA cleavage or repression of translational machinery. In diseased vascular vessels, miRNAs are dysregulated and highly expressed. miR-33 is found in cardiovascular diseases. It is involved in atherosclerotic initiation and progression including lipid metabolism, insulin signaling and glucose homeostatis, cell type progression and proliferation, and myeloid cell differentiation. It was found in rodents that the inhibition of miR-33 will raise HDL level and the expression of miR-33 is down-regulated in humans with atherosclerotic plaques.miR-33a and miR-33b are located on intron 16 of human sterol regulatory element-binding protein 2 (SREBP2) gene on chromosome 22 and intron 17 of SREBP1 gene on chromosome 17. miR-33a/b regulates cholesterol/lipid homeostatis by binding in the 3UTRs of genes involved in cholesterol transport such as ATP binding cassette (ABC) transporters and enhance or represses its expression. Study have shown that ABCA1 mediates transport of cholesterol from peripheral tissues to Apolipoprotein-1 and it is also important in the reverse cholesterol transport pathway, where cholesterol is delivered from peripheral tissue to the liver, where it can be excreted into bile or converted to bile acids prior to excretion. Therefore, we know that ABCA1 plays an important role in preventing cholesterol accumulation in macrophages.

Vilas, Román; Ceballos, Francisco C.; Al-Soufi, Laila; González-García, Raúl; Moreno, Carlos; Moreno, Manuel; Villanueva, Laura; Ruiz, Luis; Mateos, Jesús; González, David; Ruiz, Jennifer; Cinza, Aitor; Monje, Florencio; Álvarez, Gonzalo (17 November 2019). "Is the Habsburg jaw related to inbreeding?". Annals of Human Biology. 46 (7–8): 553–561. doi:10.1080/03014460.2019.1687752. PMID 31786955. S2CID 208536371. Vioarsdóttir, US; OHiggins, O; Stringer, C (2002). "A geometric morphometric study of regional differences in the ontogeny of the modern human facial skeleton". J. Anat. 201 (3): 211–229. doi:10.1046/j.1469-7580.2002.00092.x. PMC 1570912. PMID 12363273. Wolff, G; Wienker, T F; Sander, H (1 February 1993). "On the genetics of mandibular prognathism: analysis of large European noble families". Journal of Medical Genetics. 30 (2): 112–116. doi:10.1136/jmg.30.2.112. PMC 1016265. PMID 8445614. External links The dictionary definition of prognathism at Wiktionary

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NBTE usually occurs during a hypercoagulable state such as system-wide bacterial infection, or pregnancy, though it is also sometimes seen in patients with venous catheters. NBTE may also occur in patients with cancers, particularly mucinous adenocarcinoma where Trousseau syndrome can be encountered. Typically NBTE does not cause many problems on its own, but parts of the vegetations may break off and embolize to the heart or brain, or they may serve as a focus where bacteria can lodge, thus causing infective endocarditis.Another form of sterile endocarditis is termed Libman–Sacks endocarditis; this form occurs more often in patients with lupus erythematosus and is thought to be due to the deposition of immune complexes. Like NBTE, Libman-Sacks endocarditis involves small vegetations, while infective endocarditis is composed of large vegetations. These immune complexes precipitate an inflammation reaction, which helps to differentiate it from NBTE. Also unlike NBTE, Libman-Sacks endocarditis does not seem to have a preferred location of deposition and may form on the undersurfaces of the valves or even on the endocardium. References Further reading Meine TJ, Nettles RE, Anderson DJ, Cabell CH, Corey GR, Sexton DJ, Wang A (2001). "Cardiac conduction abnormalities in endocarditis defined by the Duke criteria". American Heart Journal. 142 (2): 280–285. doi:10.1067/mhj.2001.116964. PMID 11479467. Tissières P, Gervaix A, Beghetti M, Jaeggi ET (2003). "Value and limitations of the von Reyn, Duke, and modified Duke criteria for the diagnosis of infective endocarditis in children". Pediatrics. 112 (6 Pt 1): e467–e471. doi:10.1542/peds.112.6.e467. PMID 14654647. External links Endocarditis at Curlie

Anetoderma is a localized laxity of the skin with herniation or outpouching resulting from abnormal dermal elastic tissue. Anetoderma comes in three types: Primary anetoderma Jadassohn–Pellizzari anetoderma is a benign condition with focal loss of dermal elastic tissue. Jadassohn-Pellizzari is one of two major classifications of primary anetoderma, the other being Schweninger–Buzzi anetoderma. The difference between the two is that Jadassohn–Pellizzari anetoderma is preceded by inflammatory lesions. Schweninger–Buzzi anetoderma is a cutaneous condition characterized by loss of dermal elastic tissue. Secondary anetoderma Familial anetoderma See also List of cutaneous conditions References == External links ==

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McLean was a second-year medical student at Johns Hopkins University, and was working under the guidance of Howell investigating pro-coagulant preparations, when he isolated a fat-soluble phosphatide anticoagulant in canine liver tissue. In 1918, Howell coined the term heparin for this type of fat-soluble anticoagulant. In the early 1920s, Howell isolated a water-soluble polysaccharide anticoagulant, which he also termed heparin, although it was different from the previously discovered phosphatide preparations. McLeans work as a surgeon probably changed the focus of the Howell group to look for anticoagulants, which eventually led to the polysaccharide discovery. In the 1930s, several researchers were investigating heparin. Erik Jorpes at Karolinska Institutet published his research on the structure of heparin in 1935, which made it possible for the Swedish company Vitrum AB to launch the first heparin product for intravenous use in 1936. Between 1933 and 1936, Connaught Medical Research Laboratories, then a part of the University of Toronto, perfected a technique for producing safe, nontoxic heparin that could be administered to patients, in a saline solution. The first human trials of heparin began in May 1935, and, by 1937, it was clear that Connaughts heparin was safe, easily available, and effective as a blood anticoagulant. Prior to 1933, heparin was available in small amounts, was extremely expensive and toxic, and, as a consequence, of no medical value.Heparin production experienced a break in the 1990s. Until then, heparin was mainly obtained from cattle tissue, which was a by-product of the meat industry, especially in North America.

The rate of inactivation of these proteases by AT can increase by up to 1000-fold due to the binding of heparin. Heparin binds to AT via a specific pentasaccharide sulfation sequence contained within the heparin polymer: GlcNAc/NS(6S)-GlcA-GlcNS(3S,6S)-IdoA(2S)-GlcNS(6S)The conformational change in AT on heparin-binding mediates its inhibition of factor Xa. For thrombin inhibition, however, thrombin must also bind to the heparin polymer at a site proximal to the pentasaccharide. The highly negative charge density of heparin contributes to its very strong electrostatic interaction with thrombin. The formation of a ternary complex between AT, thrombin, and heparin results in the inactivation of thrombin. For this reason, heparins activity against thrombin is size-dependent, with the ternary complex requiring at least 18 saccharide units for efficient formation. In contrast, antifactor Xa activity via AT requires only the pentasaccharide-binding site. This size difference has led to the development of low-molecular-weight heparins (LMWHs) and fondaparinux as anticoagulants. Fondaparinux targets anti-factor Xa activity rather than inhibiting thrombin activity, with the aim of facilitating a more subtle regulation of coagulation and an improved therapeutic index. It is a synthetic pentasaccharide, whose chemical structure is almost identical to the AT binding pentasaccharide sequence that can be found within polymeric heparin and heparan sulfate. With LMWH and fondaparinux, the risk of osteoporosis and heparin-induced thrombocytopenia (HIT) is reduced. Monitoring of the activated partial thromboplastin time is also not required and does not reflect the anticoagulant effect, as APTT is insensitive to alterations in factor Xa.

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Techniques such as RT-PCR, multiplex genomic PCR, and sequence analysis (cDNA and genomic DNA), used for the diagnosis of genetic diseases, are performed on a research basis. If RT-PCR tests result in cDNA showing the absence of an entire exon or exons, then multiplex genomic PCR testing is performed. Multiplex genomic PCR testing amplifies the nine exons of the HPRT1 gene as eight PCR products. If the exon in question is deleted, the corresponding band will be missing from the multiplex PCR. However, if the exon is present, the exon is sequenced to identify the mutation, therefore causing exclusion of the exon from cDNA. If no cDNA is created by RT-PCR, then multiplex PCR is performed on the notion that most or all of the gene is obliterated. Treatment Treatment for LNS is symptomatic. Gout can be treated with allopurinol to control excessive amounts of uric acid. Kidney stones may be treated with lithotripsy, a technique for breaking up kidney stones using shock waves or laser beams. There is no standard treatment for the neurological symptoms of LNS. Some may be relieved with the drugs carbidopa/levodopa, diazepam, phenobarbital, or haloperidol.It is essential that the overproduction of uric acid be controlled in order to reduce the risk of nephropathy, nephrolithiasis, and gouty arthritis. The drug allopurinol is utilized to stop the conversion of oxypurines into uric acid, and prevent the development of subsequent arthritic tophi (produced after having chronic gout), kidney stones, and nephropathy, the resulting kidney disease.

Signs of self-injurious behavior (SIB), results of pedigree analysis and novel molecular biology with genetic testing (called as Diagnostic triad for LNS), often confirms the diagnosis. Suspicion often comes about when the developmental delay of the individual is associated with hyperuricemia. Otherwise, the diagnosis should be alleged when developmental delay is associated with kidney stones (nephrolithiasis) or blood in the urine (hematuria), caused by uric acid stones. For the most part, Lesch–Nyhan syndrome is first suspected when self-inflicted injury behavior develops. However, self-injurious behaviors occur in other conditions, including nonspecific intellectual disability, autism, Rett syndrome, Cornelia de Lange syndrome, Tourette syndrome, familial dysautonomia, choreoacanthocytosis, sensory neuropathy including hereditary sensory neuropathy type 1, and several psychiatric conditions. Of these, only individuals with Lesch–Nyhan syndrome, de Lange syndrome, and familial dysautonomia recurrently display loss of tissue as a consequence. Biting the fingers and lips is a definitive feature of Lesch–Nyhan syndrome; in other syndromes associated with self-injury, the behaviors usually consist of head banging and nonspecific self-mutilation, but not biting of the cheeks, lips and fingers. Lesch–Nyhan syndrome ought to be clearly considered only when self-injurious behavior takes place in conjunction with hyperuricemia and neurological dysfunction. Diagnostic approach The urate to creatinine (breakdown product of creatine phosphate in muscle) concentration ratio in urine is elevated. This is a good indicator of acid overproduction. For children under ten years of age with LNS, a urate to creatinine ratio above two is typically found. Twenty-four-hour urate excretion of more than 20 mg/kg is also typical but is not diagnostic.

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One meta analysis has found that caffeine consumption is associated with a reduced risk of type 2 diabetes. Regular caffeine consumption may reduce the risk of developing Parkinsons disease and may slow the progression of Parkinsons disease.Caffeine increases intraocular pressure in those with glaucoma but does not appear to affect normal individuals.The DSM-5 also includes other caffeine-induced disorders consisting of caffeine-induced anxiety disorder, caffeine-induced sleep disorder and unspecified caffeine-related disorders. The first two disorders are classified under "Anxiety Disorder" and "Sleep-Wake Disorder" because they share similar characteristics. Other disorders that present with significant distress and impairment of daily functioning that warrant clinical attention but do not meet the criteria to be diagnosed under any specific disorders are listed under "Unspecified Caffeine-Related Disorders". Overdose Consumption of 1–1.5 grams (1,000–1,500 mg) per day is associated with a condition known as caffeinism. Caffeinism usually combines caffeine dependency with a wide range of unpleasant symptoms including nervousness, irritability, restlessness, insomnia, headaches, and palpitations after caffeine use.Caffeine overdose can result in a state of central nervous system overstimulation known as caffeine intoxication, a clinically significant temporary condition that develops during, or shortly after, the consumption of caffeine. This syndrome typically occurs only after ingestion of large amounts of caffeine, well over the amounts found in typical caffeinated beverages and caffeine tablets (e.g., more than 400–500 mg at a time).

There is no evidence that coffee stunts a childs growth. The American Academy of Pediatrics recommends that caffeine consumption is not appropriate for children and adolescents and should be avoided. This recommendation is based on a clinical report released by American Academy of Pediatrics in 2011 with a review of 45 publications from 1994 to 2011 and includes inputs from various stakeholders (Pediatricians, Committee on nutrition, Canadian Pediatric Society, Centers for Disease Control & Prevention, Food and Drug Administration, Sports Medicine & Fitness committee, National Federations of High School Associations). For children age 12 and under, Health Canada recommends a maximum daily caffeine intake of no more than 2.5 milligrams per kilogram of body weight. Based on average body weights of children, this translates to the following age-based intake limits: Adolescents Health Canada has not developed advice for adolescents because of insufficient data. However, they suggest that daily caffeine intake for this age group be no more than 2.5 mg/kg body weight. This is because the maximum adult caffeine dose may not be appropriate for light-weight adolescents or for younger adolescents who are still growing. The daily dose of 2.5 mg/kg body weight would not cause adverse health effects in the majority of adolescent caffeine consumers. This is a conservative suggestion since older and heavier-weight adolescents may be able to consume adult doses of caffeine without experiencing adverse effects.

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Rectal palpation usually reveals an enlarged, exquisitely tender, swollen prostate gland, which is firm, warm, and, occasionally, irregular to the touch. C-reactive protein is elevated in most cases.Prostate biopsies are not indicated as the (clinical) features (described above) are diagnostic. The histologic correlate of acute prostatitis is a neutrophilic infiltration of the prostate gland.Acute prostatitis is associated with a transiently elevated PSA, i.e., the PSA is increased during an episode of acute prostatitis and then decreases again after it has resolved. PSA testing is not indicated in the context of uncomplicated acute prostatitis. Other diagnostic method is sonography Treatment Antibiotics are the first line of treatment in acute prostatitis. Antibiotics usually resolve acute prostatitis infections in a very short time, however a minimum of two to four weeks of therapy is recommended to eradicate the offending organism completely. Appropriate antibiotics should be used, based on the microbe causing the infection. Some antibiotics have very poor penetration of the prostatic capsule, others, such as ciprofloxacin, trimethoprim/sulfamethoxazole, and tetracyclines such as doxycycline penetrate prostatic tissue well. In acute prostatitis, penetration of the prostate is not as important as for category II because the intense inflammation disrupts the prostate-blood barrier. It is more important to choose a bactericidal antibiotic (kills bacteria, e.g., a fluoroquinolone antibiotic) rather than a bacteriostatic antibiotic (slows bacterial growth, e.g. tetracycline) for acute potentially life-threatening infections.Severely ill patients may need hospitalization, while nontoxic patients can be treated at home with bed rest, analgesics, stool softeners, and hydration.

Men with acute prostatitis complicated by urinary retention are best managed with a suprapubic catheter or intermittent catheterization. Lack of clinical response to antibiotics should raise the suspicion of an abscess and prompt an imaging study such as a transrectal ultrasound (TRUS). Prognosis Full recovery without sequelae is usual. References External links Prostatitis at Curlie

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Estonia had the highest death rate from alcohol in Europe in 2015 at 8.8 per 100,000 population. In the United States, 30% of people admitted to hospital have a problem related to alcohol.Within the medical and scientific communities, there is a broad consensus regarding alcoholism as a disease state. For example, the American Medical Association considers alcohol a drug and states that "drug addiction is a chronic, relapsing brain disease characterized by compulsive drug seeking and use despite often devastating consequences. It results from a complex interplay of biological vulnerability, environmental exposure, and developmental factors (e.g., stage of brain maturity)." Alcoholism has a higher prevalence among men, though, in recent decades, the proportion of female alcoholics has increased. Current evidence indicates that in both men and women, alcoholism is 50–60% genetically determined, leaving 40–50% for environmental influences. Most alcoholics develop alcoholism during adolescence or young adulthood. Prognosis Alcoholism often reduces a persons life expectancy by around ten years. The most common cause of death in alcoholics is from cardiovascular complications. There is a high rate of suicide in chronic alcoholics, which increases the longer a person drinks. Approximately 3–15% of alcoholics commit suicide, and research has found that over 50% of all suicides are associated with alcohol or drug dependence. This is believed to be due to alcohol causing physiological distortion of brain chemistry, as well as social isolation. Suicide is also very common in adolescent alcohol abusers, with 25% of suicides in adolescents being related to alcohol abuse.

Diagnosis Prevention Due to the shape of the stomach and position of the esophagus, sleep-related laryngospasms may be prevented by sleeping on the left side, which can help in keeping stomach acid from entering the esophagus and reaching the vocal cords.When laryngospasm is coincident with a cold or flu, it may be helpful for some with the condition to take acid reflux medication to limit the irritants in the area. If a cough is present, then treat a wet cough; but limit coughing whenever possible, as it is only likely to trigger a spasm. Drink water or tea to keep the area from drying up. Saline drops also help to keep the area moist. Pseudoephederine may also help to clear any mucus that may cause coughing and thereby triggering more spasms. Treatment Minor laryngospasm will generally resolve spontaneously in the majority of cases.Laryngospasm in the operating room is treated by hyperextending the patients neck and administering assisted ventilation with 100% oxygen. In more severe cases it may require the administration of an intravenous muscle relaxant, such as Succinylcholine, and reintubation.When gastroesophageal reflux disease (GERD) is the trigger, treatment of GERD can help manage laryngospasm. Proton pump inhibitors such as Dexlansoprazole (Dexilant), Esomeprazole (Nexium), and Lansoprazole (Prevacid) reduce the production of stomach acids, making reflux fluids less irritant.

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There is a known combination of acetylsalicylic acid, paracetamol and codeine phosphate hemihydrate named Aspaco that is allowed without a medical prescription but its case is signed with an exclamation red symbol which means that driving wont be allowed during treatment. There are no sanctions whether the drug is given without a prescription. The Russian Federation According to ITAR-Tass and Austria Presse-Agentur, OTC availability of codeine products was rescinded nationwide in 2012 because of the discovery of the Krokodil method of underground desomorphine synthesis. Opponents of the move point out that codeine has not been available OTC in 22 of Russias regions for years and the demand will call forth its own supply, meaning that only legitimate end users are negatively affected (activist quoted in Pravda story on issue). South Africa Codeine is available over the counter in South Africa. Certain pharmacies require people to write down their name and address to ensure they are not buying too much over a short period although many do not require this at all. According to Lochan Naidoo, the former president of the National Narcotics Control Board, making the drugs more difficult to obtain could lead to even worse problems where people in withdrawal would turn to illicit drugs to get their fix. Although codeine is freely available, South Africa has a fairly low annual prevalence rate of opiate use at 0.3% compared to the United States at 0.57% where all opiates are strictly regulated. Sri Lanka Codeine preparations are available as over the counter pharmacy medicines in Sri Lanka.

It is on the World Health Organizations List of Essential Medicines. Codeine occurs naturally and makes up about 2% of opium. Medical uses Pain Codeine is used to treat mild to moderate pain. It is commonly used to treat post-surgical dental pain.Weak evidence indicates that it is useful in cancer pain, but it may have increased adverse effects, especially constipation, compared to other opioids. The American Academy of Pediatrics does not recommend its use in children due to side effects. The FDA lists age under 12 years old as a contraindication to use. Cough Codeine is used to relieve coughing. Evidence does not support its use for acute cough suppression in children. In Europe, it is not recommended as a cough medicine in those under 12 years of age. Some tentative evidence shows it can reduce a chronic cough in adults. Diarrhea It is used to treat diarrhea and diarrhea-predominant irritable bowel syndrome, although loperamide (which is available without a prescription for milder diarrhea), diphenoxylate, paregoric, or even laudanum are more frequently used to treat severe diarrhea. Formulations Codeine is marketed as both a single-ingredient drug and in combination preparations with paracetamol (as co-codamol: e.g., brands Paracod, Panadeine, and the Tylenol-with-codeine series, including Tylenol 3 and 1, 2, and 4); with aspirin (as co-codaprin); or with ibuprofen (as Nurofen Plus). These combinations provide greater pain relief than either agent alone (drug synergy). Codeine is also commonly marketed in products containing codeine with other pain killers or muscle relaxers, as well as codeine mixed with phenacetin (Emprazil with codeine No.

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According to the Gospels, Jesus healed the two blind men of Galilee, the blind man of Bethsaida, the blind man of Jericho and the man who was born blind. The parable of the blind men and an elephant has crossed between many religious traditions and is part of Jain, Buddhist, Sufi and Hindu lore. In various versions of the tale, a group of blind men (or men in the dark) touch an elephant to learn what it is like. Each one feels a different part, but only one part, such as the side or the tusk. They then compare notes and learn that they are in complete disagreement. "Three Blind Mice" is a medieval English nursery rhyme about three blind mice whose tails are cut off after chasing the farmers wife. The work is explicitly incongruous, ending with the comment Did you ever see such a sight in your life, As three blind mice? Modern times Poet John Milton, who went blind in mid-life, composed "On His Blindness", a sonnet about coping with blindness. The work posits that [those] who best Bear [God]s mild yoke, they serve him best. The Dutch painter and engraver Rembrandt often depicted scenes from the apocryphal Book of Tobit, which tells the story of a blind patriarch who is healed by his son, Tobias, with the help of the archangel Raphael.Slaver-turned-abolitionist John Newton composed the hymn "Amazing Grace" about a wretch who "once was lost, but now am found, Was blind, but now I see."

Bertolottis syndrome is a commonly missed cause of back pain which occurs due to lumbosacral transitional vertebrae (LSTV). It is a congenital condition but is not usually symptomatic until ones later twenties or early thirties. However, there are a few cases of Bertolottis that become symptomatic at a much earlier age. It is named for Mario Bertolotti, an Italian physician who first described it in 1917. Presentation A chronic, persistent low back pain along with buttock pain is the most important presentation. Radicular pain is observed. Pathophysiology Bertolottis syndrome is characterized by sacralization of the lowest lumbar vertebral body and lumbarization of the uppermost sacral segment. It involves a total or partial unilateral or bilateral fusion of the transverse process of the lowest lumbar vertebra to the sacrum, leading to the formation of a transitional 5th lumbar vertebra. Of importance is that this syndrome will result in a pain generating 4th lumbar disc resulting in a "sciatic" type of a pain correlating to the 5th lumbar nerve root. Usually the transitional vertebra will have a "spatulated" transverse process on one side resulting in articulation or partial articulation with the sacrum or at time the ilium and in some cases with both. This results in limited / altered motion at the lumbo-sacral articulation. This loss of motion will then be compensated for at segments superior to the transitional vertebra resulting in accelerated degeneration and strain through the L4 disc level which can become symptomatic and inflame the adjacent L5 nerve root resulting in "sciatic" or radicular pain patterns.

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digoxin) are at higher risk for changes in heart rhythm if their potassium levels get too high. The 2017 clinical practice guidelines of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines list amiloride as a "secondary" oral antihypertensive, with minimal efficacy. For people with resistant hypertension, already taking a thiazide diuretic, an angiotensin converting enzyme inhibitor (ACE-i) or an angiotensin II receptor blocker (ARB), and a calcium channel blocker, the addition of amiloride (or spironolactone) was better at reducing blood pressure than adding a beta-blocker (bisoprolol) or an alpha-1 blocker (doxazosin). When combined with hydrochlorothiazide, the addition of amiloride had positive effects on blood pressure and blood sugar tolerance. Amiloride may therefore be useful for preventing the metabolic side effects of thiazide diuretics, allowing for the use of higher thiazide doses (in line with how they were originally studied).Amiloride is the treatment of choice for Liddle phenotype, which is characterized by high blood pressure, low blood potassium, and metabolic alkalosis in conjunction with a low plasma renin activity and a low aldosterone. Some people with the Liddle phenotype have Liddle syndrome, which involves a genetic mutation resulting in upregulation of the epithelial sodium channel (ENaC), located in the apical membrane of polarized epithelial cells in the late distal tubule and collecting duct of the kidney.

Research directions include determining the exact mechanism of the disease, improving animal models to aid with research, testing of medications and their delivery to treat symptoms or slow the progression of the disease, and studying procedures such as stem-cell therapy with the goal of replacing damaged or lost neurons. Signs and symptoms Signs and symptoms of Huntingtons disease most commonly become noticeable between the ages of 30 and 50 years, but they can begin at any age, and present as a triad of motor, cognitive, and psychiatric symptoms. In 50% of cases, the psychiatric symptoms appear first. Their progression is often described in early stages, middle stages, and late stages with an earlier prodromal phase. In the early stages, subtle personality changes, problems in cognition, and physical skills, irritability, and mood swings occur, all of which may go unnoticed, and these usually precede the motor symptoms. Almost everyone with HD eventually exhibits similar physical symptoms, but the onset, progression, and extent of cognitive and behavioral symptoms vary significantly between individuals.The most characteristic initial physical symptoms are jerky, random, and uncontrollable movements called chorea. Many people are not aware of their involuntary movements, or impeded by them. Chorea may be initially exhibited as general restlessness, small unintentionally initiated or uncompleted motions, lack of coordination, or slowed saccadic eye movements. These minor motor abnormalities usually precede more obvious signs of motor dysfunction by at least three years. The clear appearance of symptoms such as rigidity, writhing motions, or abnormal posturing appear as the disorder progresses.

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If rifapentine or rifampin are used in late pregnancy, coagulation should be monitored due to a possible increased risk of maternal postpartum hemorrhage and infant bleeding. Adverse effects Common side effects include allergic reaction, anemia, neutropenia, elevated transaminases, and pyuria. Overdoses have been associated with hematuria and hyperuricemia. Contraindications Rifapentine should be avoided in patients with an allergy to the rifamycin class of drugs. This drug class includes rifampicin and rifabutin. Interactions Rifapentine induces metabolism by CYP3A4, CYP2C8 and CYP2C9 enzymes. It may be necessary to adjust the dosage of drugs metabolized by these enzymes if they are taken with rifapentine. Examples of drugs that may be affected by rifapentine include warfarin, propranolol, digoxin, protease inhibitors and birth control pills. Chemical structure The chemical structure of rifapentine is similar to that of rifamycin, with the notable substitution of a methyl group for a cyclopentane (C5H9) group. History Rifapentine was first synthesized in 1965, by the same company that produced rifampicin. The drug was approved by the U.S. Food and Drug Administration (FDA) in June 1998. It is made from rifampicin.Rifapentine was granted orphan drug designation by the FDA in June 1995, and by the European Commission in June 2010. Society and culture Cancer-causing impurities In August 2020, the U.S. Food and Drug Administration (FDA) became aware of nitrosamine impurities in certain samples of rifapentine. The FDA and manufacturers are investigating the origin of these impurities in rifapentine, and the agency is developing testing methods for regulators and industry to detect the 1-cyclopentyl-4-nitrosopiperazine (CPNP).

Unlike mesoblastic nephroma, clear cell sarcoma of the kidney presents with metastasis, particularly to bone, in 5-6% of cases; it histology is diverse and has been mistaken for mesoblastic nephroma. One chromosomal translocations t,(10;17)(q22;p13), has been repeatedly reported to be associated with clear cell sarcoma of the kidney. Infantile myofibromatosis is a fibrous tumor of infancy and childhood most commonly presenting during the first 2 years of life as a single subcutaneous nodule of the head and neck region or less commonly as multiple lesions of skin, muscle, bone, and in ~33% of these latter cases, visceral organs. All of these lesions have an excellent prognosis and can regress spontaneously except for those in which there is visceral involvement where the prognosis is poor. While infantile myofibromatosis and classic mesoblastic nephroma have been suggested to be the same diseases because of their very similar histology, studies on the distribution of cell-type markers (i.e. cyclin D1 and Beta-catenin) indicate that they have different cellular origins. Treatment Based on a survey of >800, surgical removal of the entire involved kidney plus the peri-renal fat appeared curative for the majority of all types of mesoblastic nephroma; the patient overall survival rate was 94%. Of the 4% of non-survivors, half were due to surgical or chemotherapeutic treatments. Another 4% of these patients suffered relapses, primarily in the local area of surgery rare cases of relapse due to lung or bone metastasis.. About 60% of these recurrent cases had a complete remission following further treatment.

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As absorption and reabsorption of glycine, proline and hydroxyproline occurs through PAT1 as well, it is believed to play another role in expressing the malabsorptive iminoglycinuria phenotype. Recent reports, however, suggest a more diminished role from PAT1 in some cases of the disorder.While PAT2 is strongly indicated as the primary mutagen responsible for iminoglycinuria, the variability of the phenotype is found to be instituted by three modifying genetic mutations. The major one among these is believed to be system IMINO.Defined as the sodium-dependent proline transporter not inhibited by alanine, system IMINO, believed to be formed by the SLC6A20 (SIT1) gene, is a crucial mammalian transport mechanism responsible for both renal reabsorption and intestinal absorption of proline and other imino acids, such as hydroxyproline and pipecolate. The mRNA sequence for SIT1 is expressed in a great deal of the gastrointestinal tract, including the stomach, duodenum, jejunum, ileum, cecum and colon. It is also found in the kidney, optical choroid, and parts of the central nervous system such the brain and microglial cells.Reduced penetrance is a phenomenon where a fully inherited genetic trait, such as a disease or disorder, fails to exhibit the expected phenotype. This has been reported in some cases of iminoglycinuria. Here, system IMINO is thought to play a role in reduced penetrance of iminoglycinuria by compensating for imino acid malabsorption related specifically to mutations of PAT2.

Conversely, SIT1 mutations are believed to result in full expression of iminoglycinuria in some cases where heterozygous mutations of PAT2 would otherwise have only been sufficient to cause hyperglycinuria.Two other transport systems are believed to play subsequent roles in iminoglycinuria, when mutations in them are present. The neutral amino acid transporter SLC6A19 (affecting glycine, proline, and other neutral amino acids like cysteine and tryptophan), associated with Hartnup disease, plays a role in iminoglycinuria as a modifier to PAT2 mutations and is also directly affected by the actions of SIT1. The glycine-specific transporter, SLC6A18, also has an effect on the iminoglycinuria phenotype by either compounding or compensating for failures of glycine transport.To summarize, iminoglycinuria is primarily expressed by homozygous mutations of the PAT2 renal transporter, while the overall iminoglycinuria phenotype may be modified by normal or defective activity of SIT1 (IMINO), SLC6A19 and SLC6A18. Diagnosis Treament See also Pipecolic acid Facilitated diffusion Oral rehydration therapy References == External links ==

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Mifepristone showed no detectable anti-HIV activity in clinical trials.Mifepristone showed initial promise in psychotic major depression, a difficult-to-treat form of depression, but a phase-III clinical trial was terminated early due to lack of efficacy. It has been studied in bipolar disorder, post traumatic stress disorder, and anorexia nervosa. References External links "Mifepristone". Drug Information Portal. U.S. National Library of Medicine.

Norethisterone acetate (NETA), also known as norethindrone acetate and sold under the brand name Primolut-Nor among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication available in low-dose and high-dose formulations and is used alone or in combination with an estrogen. It is ingested orally.Side effects of NETA include menstrual irregularities, headaches, nausea, breast tenderness, mood changes, acne, increased hair growth, and others. NETA is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has weak androgenic and estrogenic activity and no other important hormonal activity. The medication is a prodrug of norethisterone in the body.NETA was patented in 1957 and was introduced for medical use in 1964. It is sometimes referred to as a "first-generation" progestin. NETA is marketed widely throughout the world. It is available as a generic medication. Medical uses NETA is used as a hormonal contraceptive in combination with estrogen, in the treatment of gynecological disorders such as abnormal uterine bleeding, and as a component of menopausal hormone therapy for the treatment of menopausal symptoms. Available forms NETA is available in the form of tablets for use by mouth both alone and in combination with estrogens including estradiol, estradiol valerate, and ethinylestradiol.

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Rarely, a gallstone can become impacted in the ileocecal valve that joins the caecum and the ileum, causing gallstone ileus (mechanical ileus).Complications from delayed surgery include pancreatitis, empyema, and perforation of the gallbladder, cholecystitis, cholangitis, and obstructive jaundice.Biliary pain in the absence of gallstones, known as postcholecystectomy syndrome, may severely affect the patients quality of life, even in the absence of disease progression. Causes Biliary pain is most frequently caused by obstruction of the common bile duct or the cystic duct by a gallstone. However, the presence of gallstones is a frequent incidental finding and does not always necessitate treatment, in the absence of identifiable disease. Furthermore, biliary pain may be associated with functional disorders of the biliary tract, so-called acalculous biliary pain (pain without stones), and can even be found in patients post-cholecystectomy (removal of the gallbladder), possibly as a consequence of dysfunction of the biliary tree and the sphincter of Oddi. Acute episodes of biliary pain may be induced or exacerbated by certain foods, most commonly those high in fat. Risk factors Cholesterol gallstone formation risk factors include age, female sex, family history, race, pregnancy, parity, obesity, hormonal birth control, diabetes mellitus, cirrhosis, prolonged fasting, rapid weight loss, total parenteral nutrition, ileal disease and impaired gallbladder emptying.Patients that have gallstones and biliary colic are at increased risk for complications, including cholecystitis.

While a number of side effects have been associated with sublingual immunotherapy, serious adverse effects are very rare (about 1.4/100000 doses), and there has not been a reported fatality. There have been a small number of reports of anaphylaxis. The majority of side effects are local and usually resolve within a few days. They include swelling of the mouth, tongue or lip, throat irritation, nausea, abdominal pain, vomiting, diarrhea, heartburn, and uvular edema. It is not yet clear if there are any risk factors that might increase a persons susceptibility to these adverse effects. Sublingual immunotherapy appears to be better tolerated than subcutaneous immunotherapy and causes fewer side effects. The safety of sublingual immunotherapy has not been studied extensively in people with chronic immunodeficiency or autoimmune disorders. Oral Oral immunotherapy (OIT) involves feeding an allergic individual increasing amounts of a food allergen in order to raise the threshold which triggers a reaction. Long-term, many study participants still experienced mild allergic reactions or needed to regularly consume the allergen to maintain desensitivity. Additionally, oral immunotherapy is known to have an increased risk in the probability of needing epinephrine in patients who take it. Transdermal Transdermal immunotherapy (TDIT) involves skin-induced suppression via epicutaneous (EC) application of an antigen in order to raise the threshold which triggers a reaction. Mechanism of action In desensitization immunotherapy the aim is to induce or restore tolerance to the allergen by reducing its tendency to induce IgE production. People are desensitized through the administration of escalating doses of allergen that gradually decreases the IgE-dominated response.

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Treatment Medication Treatment with selective estrogen receptor modulators (SERMs) alone or in addition to self-administered injections of hCG aim to correct hormonal imbalances caused by anabolic steroid use and can help prevent or reverse testicular atrophy for some people. Surgery People who have testicular atrophy due to testicular torsion are immediately referred to surgery regardless of the ultrasound findings, since delays rapidly decrease the rate of recovery. The consequences of not treating will result in decreased fertility and may result in the need of an orchiectomy, a surgical procedure to remove one or both testicles. While immediate treatment can reduce the recovery time for the testes, there is still a chance of the testes to undergo atrophy a second time. Performance of an orchiectomy on individuals diagnosed with testicular atrophy has a possible negative impact on their testosterone levels in the long term. As a result, these individuals are typically monitored for the reoccurrence of testicular atrophy and low testosterone levels. Lifestyle modifications In addition to drug therapies and surgical interventions to treat testicular atrophy, lifestyle modifications might also be recommended by healthcare providers. Most lifestyle modifications target factors that contribute to infertility in people with testes. Limiting or abstaining from alcohol intake, smoking, and drugs such as anabolic steroids, cannabis, or opioids can help with infertility. Additionally, diet modifications might be encouraged to reach a more balanced diet, such as a higher intake of fish, fruits, vegetables, nuts, seeds, whole grains, and healthier oils, such as olive oil and canola oil.

The most perceptible sign of testicular atrophy is shrinkage of the testicle(s).Signs and symptoms before puberty include: lack of development of pubic hair lack of development of facial hair lack of penis growth lower testosteroneTestosterone is a hormone that is found primarily in a portion of the male-assigned reproductive system called the testes and is normally measured in nanograms per deciliter. Testosterone is in charge of the growth and production of many sexual attributes in people with testes, including facial hair, pubic hair, penis size, vocal and muscle mass changes, regulation of sex drive, and sperm production. Normal testosterone levels in people with testes who have not yet hit puberty are less than 20 nanograms per deciliter. Low testosterone can be defined as hypogonadism in people with testes. Hypogonadism in people with testes is established as the hormonal inhibition of testosterone that can either be inherited or acquired at a later stage in life. Under the circumstances of pre-pubescent hypogonadism, many sexual developmental characteristics may be altered. Testosterone affects hair growth by regulating the follicle itself, which in turn affects the specific growth phases of the hair follicle. As a person with testes hits puberty, androgen, a steroid sex hormone, is produced at an increased rate, which creates terminal hair follicles. Terminal hair follicles create thicker and more pigmented hair which is also regulated by testosterone production. Testosterone also impacts pre-pubescent penis size by providing penile tissue with girth and density. The drop in testosterone values is mainly due to significant impairment of Leydig cells brought upon by hypogonadism.

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chimeric antigen receptor T cells directed against CD19) in adult patients with DLBCL, NOS who have relapsed after or are refractory to two or more lines of systemic therapy. The Committee for Orphan Medicinal Products of the European Medicines Agency recommends tisagenlecleucel retain its orphan drug designation. The USA Food and Drug Administration (FDA) has also approved the use of this drug for relapsed or refractory DLBCL of the large B-cell lymphoma subtype in patients who have failed after two or more lines of systemic therapy. Monoclonal antibodies directed against CD19, CD22, CD30, and PD-L1 have been developed for use as immunotherapeutic agents in other hematological malignancies and are being or plan to be tested for their usefulness in DLBCL, NOS. In August 2020, the FDA approved the humanized Fc-modified cytolytic CD19 targeting monoclonal antibody tafasitamab in combination with lenalidomide as a treatment for adult patients with relapsed or refractory DLBCL. In April 2021, the FDA approved the CD19-directed antibody-drug conjugate loncastuximab tesirine as a treatment for adult patients with relapsed or refractory DLBCL after systemic therapy. Emerging therapies Neoplastic cell expression of CD30 in DLBCL, NOS is a favorable prognostic indicator; in these cases, brentuximab vedotin may be a useful addition to chemotherapy treatment protocols. This agent is a CD30-targeting antibody that delivers a toxin, monomethyl auristatin E, to CD30-expressing cells, has therapeutic efficacy against other CD30-expressing lymphomas, and may prove useful in treating the 10–15% of DLBCL, NOS cases expressing this protein.

African histoplasmosis Alternariosis Antibiotic candidiasis (iatrogenic candidiasis) Black piedra Candidal intertrigo Candidal onychomycosis Candidal paronychia Candidal vulvovaginitis Candidid Chromoblastomycosis (chromomycosis, cladosporiosis, Fonsecas disease, Pedrosos disease, phaeosporotrichosis, verrucous dermatitis) Chronic mucocutaneous candidiasis Coccidioidomycosis (California disease, desert rheumatism, San Joaquin Valley fever, valley fever) Congenital cutaneous candidiasis Cryptococcosis Dermatophytid Diaper candidiasis Disseminated coccidioidomycosis (coccidioidal granuloma) Distal subungual onychomycosis Entomophthoromycosis Erosio interdigitalis blastomycetica Favus Fungal folliculitis (majocchi granuloma) Fusariosis Geotrichosis Granuloma gluteale infantum Histoplasmosis (cave disease, Darlings disease, Ohio Valley disease, reticuloendotheliosis) Hyalohyphomycosis Kerion Lobomycosis (keloidal blastomycosis, lacaziosis, Lobos disease) Mucormycosis Mycetoma (Madura foot, maduromycosis) North American blastomycosis (blastomycetic dermatitis, blastomycosis, Gilchrists disease) Onychomycosis (dermatophytic onychomycosis, ringworm of the nail, tinea unguium) Oral candidiasis (thrush) Otomycosis Perianal candidiasis Perlèche (angular cheilitis) Phaeohyphomycosis Piedra (trichosporosis) Pityrosporum folliculitis Primary cutaneous aspergillosis Primary cutaneous coccidioidomycosis Primary cutaneous histoplasmosis Primary pulmonary coccidioidomycosis Primary pulmonary histoplasmosis Progressive disseminated histoplasmosis Proximal subungual onychomycosis Rhinosporidiosis South American blastomycosis (Brazilian blastomycosis, paracoccidioidal granuloma, paracoccidioidomycosis) Sporotrichosis (rose-gardeners disease) Systemic candidiasis Tinea barbae (barbers itch, ringworm of the beard, tinea sycosis) Tinea capitis (herpes tonsurans, ringworm of the hair, ringworm of the scalp, scalp ringworm, tinea tonsurans) Tinea corporis (ringworm, tinea circinata, tinea glabrosa) Tinea corporis gladiatorum Tinea cruris (crotch itch, eczema marginatum, gym itch, jock itch, ringworm of the groin) Tinea faciei Tinea imbricata (tokelau) Tinea incognito Tinea manuum Tinea nigra (superficial phaeohyphomycosis, tinea nigra palmaris et plantaris) Tinea pedis (athletes foot, ringworm of the foot) Tinea versicolor (dermatomycosis furfuracea, pityriasis versicolor, tinea flava) White piedra White superficial onychomycosis Zygomycosis (phycomycosis) Parasitic infestations, stings, and bites Parasitic infestations, stings, and bites in humans are caused by several groups of organisms belonging to the following phyla: Annelida, Arthropoda, Bryozoa, Chordata, Cnidaria, Cyanobacteria, Echinodermata, Nemathelminthes, Platyhelminthes, and Protozoa.

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This may account for the low prevalence of the illness. There is also a pathological similarity between the endotheliopathy in Susacs syndrome with that seen in juvenile dermatomyositis. Treatment Early and aggressive treatment is important to prevent irreversible neurological damage, hearing loss, or vision loss. Medications used include immunosuppressive agents and corticosteroids such a prednisone, or intravenous immunoglobulins (IVIG). Other drugs that have been used are mycophenolate mofetil (Cellcept), azathioprine (Imuran), cyclophosphamide, rituximab, and anti-TNF therapies.Hearing aids or cochlear implants may be necessary in the event of hearing loss. References Egan RA, Nguyen TH, Gass JDM, Rizzo JF, Tivnan J, Susac JO. Retinal Artery Wall Plaques in Susac Syndrome. American Journal of Ophthalmology 135: 483-6; 2003 Susac JO, Murtagh FR, Egan RA, Berger JR, Fox RJ, Galetta S, Costello F, Lee AG, Bakshi R, Lincoff N, Clark J, Daroff R. MRI Findings in Susac Syndrome. Neurology 61: 1783-1787; 2003 Egan RA, Hills WL, Susac JO. Gass Plaques and Fluorescein Leakage in Susac Syndrome. Journal of Neurological Sciences 299(1-2): 97-100; 2010 Susac JO, Rennebohm RM, Egan RA, Daroff RB. Susac’s Syndrome – Update. Journal of Neurological Sciences 299(1-2): 86-91; 2010 Susac JO. Susac Syndrome: the triad of microangiopathy of the brain and retina with hearing loss in young women. Neurology 44(4): 591-3; 1994 Dörr J, Krautwald S, Wildemann B, Jarius S, Ringelstein M, Duning T, Aktas O, Ringelstein EB, Paul F, Kleffner I. Characteristics of Susac Syndrome: a review of all reported cases.

Susacs syndrome (retinocochleocerebral vasculopathy) is a very rare form of microangiopathy characterized by encephalopathy, branch retinal artery occlusions and hearing loss. The cause is unknown but it is theorized that antibodies are produced against endothelial cells in tiny arteries which leads to damage and the symptoms related to the illness. Despite this being an extremely rare disease, there are 4 registries collecting data on the illness; two are the United States, one in Germany, and one in Portugal. Presentation Susacs syndrome is named for Dr. John Susac (1940–2012), of Winter Haven, Florida, who first described it in 1979. Susacs syndrome is a very rare disease, of unknown cause, and many persons who experience it do not display the bizarre symptoms named here. Their speech can be affected, such as the case of a female of late teens who suffered speech issues and hearing problems, and many experience unrelenting and intense headaches and migraines, some form of hearing loss, and impaired vision. The problem usually corrects itself, but this can take up to five years. In some cases, subjects can become confused. The syndrome usually affects women around the age of 18 years, with female to male ratio of cases of 2:1. William F. Hoyt was the first to call the syndrome "Susac syndrome" and later Robert Daroff asked Dr. Susac to write an editorial in Neurology about the disorder and to use the eponym of Susac syndrome in the title, forever linking this disease with him. Pathogenesis In the March 1979 report in Neurology, Drs.

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Cannabidiol (CBD) is a phytocannabinoid discovered in 1940. It is one of 113 identified cannabinoids in cannabis plants, along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plants extract. As of 2019, clinical research on CBD included studies related to anxiety, cognition, movement disorders, and pain, but there is insufficient high-quality evidence that cannabidiol is effective for these conditions. Nevertheless, CBD is a popular herbal dietary supplement, widely promoted with unproven claims of particular therapeutic benefits. The global market size for CBD was predicted to exceed US$47 billion by 2028.Cannabidiol can be taken internally in multiple ways, including by inhaling cannabis smoke or vapor, by mouth, and as an aerosol spray into the cheek. It may be supplied as CBD oil containing only CBD as the active ingredient (excluding tetrahydrocannabinol [THC] or terpenes), CBD-dominant hemp extract oil, capsules, dried cannabis, or prescription liquid solution. CBD does not have the same psychoactivity as THC, and will negate the psychoactive effects of THC on the body if both are present. As of 2018, the mechanism of action for its biological effects has not been determined. Unlike THC, which acts on the cannabinoid receptor type 1 (CB1) as a partial agonist, CBD instead is a negative allosteric modulator of CB1 receptors.In the United States, the cannabidiol drug Epidiolex was approved by the Food and Drug Administration in 2018 for the treatment of two epilepsy disorders.

United Kingdom Cannabidiol, in an oral-mucosal spray formulation combined with delta-9-tetrahydrocannabinol, is a product available by prescription for the relief of severe spasticity due to multiple sclerosis (where other anti-spasmodics have not been effective).Until 2017, products containing cannabidiol marketed for medical purposes were classed as medicines by the UK regulatory body, the Medicines and Healthcare products Regulatory Agency (MHRA), and could not be marketed without regulatory approval for the medical claims. As of 2018, cannabis oil is legal to possess, buy, and sell in the UK, providing the product does not contain more than 1 milligram of THC and is not advertised as providing a medicinal benefit.In January 2019, the UK Food Standards Agency indicated it would regard CBD products, including CBD oil, as a novel food having no history of use before May 1997, and stated that such products must have authorisation and proven safety before being marketed. The deadline for companies with existing products to submit a full and validated novel foods application with the FSA is 31 March 2021; failure to do so before this date will exclude those companies from selling CBD. New products containing CBD after this deadline will require a fully approved application.In February 2020, the UK FSA advised vulnerable people, such as pregnant women, breastfeeding mothers, and those already taking medication for other medical concerns not to take CBD. The FSA further recommended that healthy adults should not consume more than 70 mg CBD per day.

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Since approximately 2000, these incidents have occurred on a global scale, affecting not only Muslim-majority states in Africa and Asia, but also states with non-Muslim majority such as United States, United Kingdom, France, Germany, Spain, Belgium, Sweden, Russia, Australia, Canada, Sri Lanka, Israel, China, India and Philippines. Such attacks have targeted both Muslims and non-Muslims, however the majority affect Muslims themselves.Terrorism in Pakistan has become a great problem. From the summer of 2007 until late 2009, more than 1,500 people were killed in suicide and other attacks on civilians for reasons attributed to a number of causes—sectarian violence between Sunni and Shia Muslims; easy availability of guns and explosives; the existence of a "Kalashnikov culture"; an influx of ideologically driven Muslims based in or near Pakistan, who originated from various nations around the world and the subsequent war against the pro-Soviet Afghans in the 1980s which blew back into Pakistan; the presence of Islamist insurgent groups and forces such as the Taliban and Lashkar-e-Taiba. On July 2, 2013, in Lahore, 50 Muslim scholars of the Sunni Ittehad Council (SIC) issued a collective fatwa against suicide bombings, the killing of innocent people, bomb attacks, and targeted killings declaring them as Haraam or forbidden.In 2015, the Southern Poverty Law Center released a report on terrorism in the United States. The report (titled The Age of the Wolf) analyzed 62 incidents and found that, between 2009 and 2015, "more people have been killed in America by non-Islamic domestic terrorists than jihadists."

Their terror was directed against Jewish "collaborators", including temple priests, Sadducees, Herodians, and other wealthy elites.The term "terrorism" itself was originally used to describe the actions of the Jacobin Club during the "Reign of Terror" in the French Revolution. "Terror is nothing other than justice, prompt, severe, inflexible", said Jacobin leader Maximilien Robespierre. In 1795, Edmund Burke denounced the Jacobins for letting "thousands of those hell-hounds called Terrorists ... loose on the people" of France. In January 1858, Italian patriot Felice Orsini threw three bombs in an attempt to assassinate French Emperor Napoleon III. Eight bystanders were killed and 142 injured. The incident played a crucial role as an inspiration for the development of the early terrorist groups.Arguably the first organization to use modern terrorist techniques was the Irish Republican Brotherhood, founded in 1858 as a revolutionary Irish nationalist group that carried out attacks in England. The group initiated the Fenian dynamite campaign in 1881, one of the first modern terror campaigns. Instead of earlier forms of terrorism based on political assassination, this campaign used timed explosives with the express aim of sowing fear in the very heart of metropolitan Britain, in order to achieve political gains.Another early terrorist-type group was Narodnaya Volya, founded in Russia in 1878 as a revolutionary anarchist group inspired by Sergei Nechayev and "propaganda by the deed" theorist Carlo Pisacane.

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The advantage of misoprostol is that it can be used for evacuation not only following miscarriage, but also following birth for retained placenta or hemorrhaging.Alternatively, D&C could be performed under ultrasound guidance rather than as a blind procedure. This would enable the surgeon to end scraping the lining when all retained tissue has been removed, avoiding injury.Early monitoring during pregnancy to identify miscarriage can prevent the development of, or as the case may be, the recurrence of AS, as the longer the period after fetal death following D&C, the more likely adhesions may be to occur. Therefore, immediate evacuation following fetal death may prevent IUA.The use of hysteroscopic surgery instead of D&C to remove retained products of conception or placenta is another alternative that could theoretically improve future pregnancy outcomes, although it could be less effective if tissue is abundant. Also, hysteroscopy is not a widely or routinely used technique and requires expertise.There is no data to indicate that suction D&C is less likely than sharp curette to result in Ashermans. A recent article describes three cases of women who developed intrauterine adhesions following manual vacuum aspiration.Intrauterine adhesions also form after hysteroscopic surgery such as myomectomy, polypectomy or septum removal. Mechanical barriers such as Womed Leaf or hyaluronic acid gels can be used to prevent formation of IUA after such adhesiogenic procedures or after D&C. Treatment Fertility may sometimes be restored by removal of adhesions, depending on the severity of the initial trauma and other individual patient factors.

AS can result from other pelvic surgeries including cesarean sections, removal of fibroid tumours (myomectomy) and from other causes such as IUDs, pelvic irradiation, schistosomiasis and genital tuberculosis. Chronic endometritis from genital tuberculosis is a significant cause of severe intrauterine adhesions (IUA) in the developing world, often resulting in total obliteration of the uterine cavity which is difficult to treat.An artificial form of AS can be surgically induced by endometrial ablation in women with excessive uterine bleeding, in lieu of hysterectomy. Diagnosis The history of a pregnancy event followed by a D&C leading to secondary amenorrhea or hypomenorrhea is typical. Hysteroscopy is the gold standard for diagnosis. Imaging by sonohysterography or hysterosalpingography will reveal the extent of the scar formation. Ultrasound is not a reliable method of diagnosing Ashermans Syndrome. Hormone studies show normal levels consistent with reproductive function. Classification Various classification systems were developed to describe Ashermans syndrome (citations to be added), some taking into account the amount of functioning residual endometrium, menstrual pattern, obstetric history and other factors which are thought to play a role in determining the prognoses. With the advent of techniques which allow visualization of the uterus, classification systems were developed to take into account the location and severity of adhesions inside the uterus. This is useful as mild cases with adhesions restricted to the cervix may present with amenorrhea and infertility, showing that symptoms alone do not necessarily reflect severity. Other patients may have no adhesions but amenorrhea and infertility due to a sclerotic atrophic endometrium.

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Fourth stump a position or line one stumps width outside the off stump, i.e. where the wickets fourth stump would be positioned if it existed. Generally refers to the line or pitch of a delivery. A fourth stump line is roughly synonymous with the corridor of uncertainty. Free hit a penalty given in some forms of cricket when a bowler bowls a no-ball. The bowler must bowl another delivery, and the batsman cannot be dismissed by the bowler from that delivery. Between the no-ball and the free hit, the fielders may not change positions (unless the batsmen changed ends on the no-ball). French cricket an informal form of the game, typically played by children. The term "playing French Cricket" can imply that a batsman has not attempted to move their feet and looks ungainly because of this. French Cut (also referred to as a Chinese Cut, Surrey Cut, or Harrow Drive) term for an unintentionally poorly executed shot which results in an inside edge where the ball narrowly misses hitting the stumps. Such unintentional shots can frequently fool the wicket keeper and may often fortunately result in runs. Fritz To be out stumped following a rebound from the wicketkeepers pads on to the stumps. Front foot all opposites of back foot1. (of a batsman) in the batting stance, the foot that is closest to the bowler and furthest from the stumps. 2. (of a shot) played with the batmans weight primarily on that foot. 3.

Tampering scratching, scuffing, or otherwise unnaturally altering the cricket ball outside of its normal wear and tear. When this is done, it is usually by the fielding team, to give their bowler an edge so that the ball might spin or seam more effectively. This is an illegal act in the game. Tape ball An ersatz cricket ball produced by wrapping a tennis ball in electrical tape. Common in informal games on the Indian subcontinent. Target The score that the team batting last has to score to beat their opponents. This is one run more than what the team batting first managed; or, in limited overs cricket, an adjusted value determined by a rain rule. Tea the second of the two intervals during a full days play is known as the tea interval, due to its timing at about tea-time. In matches lasting only an afternoon, the tea interval is usually taken between innings. Teesra A back spin delivery by a finger spin bowler. Ten-wicket match A two-innings match in which a bowler takes ten or more wickets in total. Test cricket (also Test match) The highest level of the sport. Consists of timed matches that last up to five days, with two innings per side. Played between senior international teams which have been granted Test status. Textbook shot A shot played by the batsmen with perfect orthodox technique, exactly as shown in textbooks on batting.

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Dobutamine is a medication used in the treatment of cardiogenic shock (as a result of inadequate tissue perfusion) and severe heart failure. It may also be used in certain types of cardiac stress tests. It is given by IV only, as an injection into a vein or intraosseous as a continuous infusion. The amount of medication needs to be adjusted to the desired effect. Onset of effects is generally seen within 2 minutes. It has a half-life of two minutes. This drug is generally only administered short term, although it may be used for longer periods to relieve symptoms of heart failure in patients awaiting heart transplantation.Common side effects include a fast heart rate, an irregular heart beat, and inflammation at the site of injection. Use is not recommended in those with idiopathic hypertrophic subaortic stenosis. It primarily works by direct stimulation of β1 receptors, which increases the strength of the hearts contractions, leading to a positive ionotrophic effect. Generally it has little effect on a persons heart rate.Dobutamine was approved for medical use in the United States in 1978. It is available as a generic medication. It was initially made from isoproterenol. Medical uses Dobutamine is used to treat acute but potentially reversible heart failure, such as which occurs during cardiac surgery or in cases of septic or cardiogenic shock, on the basis of its positive inotropic action.Dobutamine can be used in cases of congestive heart failure to increase cardiac output.

It is indicated when parenteral therapy is necessary for inotropic support in the short-term treatment of patients with cardiac decompensation due to depressed contractility, which could be the result of either organic heart disease or cardiac surgical procedures. Higher doses are not useful with history of recent ischemic heart disease because it increases heart rate and thus increases myocardial oxygen demand.The drug is also commonly used in the hospital setting as a pharmacologic stress testing agent to identify coronary artery disease. Adverse effects Primary side effects include those commonly seen for β1 active sympathomimetics, such as hypertension, angina, arrhythmia, and tachycardia. Used with caution in atrial fibrillation as it has the effect of increasing the atrioventricular (AV) conduction.The most dangerous side effect of dobutamine is increased risk of arrhythmia, including fatal arrhythmias. Overall, dobutamine tends to produce less tachycardia and peripheral vascular effects than agents such as epinephrine and isoproterenol. Pharmacology Dobutamine is a direct-acting agent whose primary activity results from stimulation of the β1-adrenoceptors of the heart, increasing contractility and cardiac output. Since it does not act on dopamine receptors to inhibit the release of norepinephrine (another α1 agonist), dobutamine is less prone to induce hypertension than is dopamine. Dobutamine is predominantly a β1-adrenergic agonist, with weak β2 activity, and α1 selective activity, although it is used clinically in cases of cardiogenic shock for its β1 inotropic effect in increasing heart contractility and cardiac output.

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However, the sensations in both sexes are extremely pleasurable and are often felt throughout the body, causing a mental state that is often described as transcendental, and with vasocongestion and associated pleasure comparable to that of a full-contractionary orgasm. For example, modern findings support distinction between ejaculation and male orgasm. For this reason, there are views on both sides as to whether these can be accurately defined as orgasms. Achieving orgasm Orgasms can be achieved during a variety of activities, including vaginal, anal or oral sex, non-penetrative sex or masturbation. They may also be achieved by the use of a sex toy, such as a sensual vibrator or an erotic electrostimulation. Achieving orgasm by stimulation of the nipples or other erogenous zones is rarer. Multiple orgasms are also possible, especially in women, but they are also uncommon. Multiple orgasms are orgasms that occur within a short period of one another.In addition to physical stimulation, orgasm can be achieved from psychological arousal alone, such as during dreaming (nocturnal emission for males or females) or by forced orgasm. Orgasm by psychological stimulation alone was first reported among people who had spinal cord injury.

Acral fibrokeratoma (also known as an "Acquired digital fibrokeratoma," and "Acquired periungual fibrokeratoma": 668 ) is a skin lesion characterized by a pinkish, hyperkeratotic, hornlike projection occurring on a finger, toe, or palm. : 609 : 1817 See also Skin lesion List of cutaneous conditions == References ==

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Effective treatment against all stages of the disease may require a combination of medications. Infections without symptoms may be treated with just one antibiotic, and infections with symptoms are treated with two antibiotics.Amoebiasis is present all over the world, though most cases occur in the developing world. About 480 million people are currently infected with about 40 million new cases per year with significant symptoms. This results in the death of between 40,000–100,000 people a year. The first case of amoebiasis was documented in 1875 and in 1891 the disease was described in detail, resulting in the terms amoebic dysentery and amoebic liver abscess. Further evidence from the Philippines in 1913 found that upon swallowing cysts of E. histolytica volunteers developed the disease. Signs and symptoms Most infected people, about 90%, are asymptomatic, but this disease has the potential to become serious. It is estimated that about 40,000 to 100,000 people worldwide die annually due to amoebiasis.Infections can sometimes last for years if there is no treatment. Symptoms take from a few days to a few weeks to develop and manifest themselves, but usually it is about two to four weeks. Symptoms can range from mild diarrhea to dysentery with blood, coupled with intense abdominal pains. Extra-intestinal complications might also arise as a result of invasive infection which includes colitis, liver, lung, or brain abscesses. The blood comes from bleeding lesions created by the amoebae invading the lining of the colon.

E. histolytica cysts have a maximum of four nuclei, while the commensal Entamoeba coli cyst has up to 8 nuclei. Additionally, in E. histolytica, the endosome is centrally located in the nucleus, while it is usually off-center in Entamoeba coli. Finally, chromatoidal bodies in E. histolytica cysts are rounded, while they are jagged in Entamoeba coli. However, other species, Entamoeba dispar and E. moshkovskii, are also commensals and cannot be distinguished from E. histolytica under the microscope. As E. dispar is much more common than E. histolytica in most parts of the world this means that there is a lot of incorrect diagnosis of E. histolytica infection taking place. The WHO recommends that infections diagnosed by microscopy alone should not be treated if they are asymptomatic and there is no other reason to suspect that the infection is actually E. histolytica. Detection of cysts or trophozoites stools under microscope may require examination of several samples over several days to determine if they are present, because cysts are shed intermittently and may not show up in every sample.Typically, the organism can no longer be found in the feces once the disease goes extra-intestinal. Serological tests are useful in detecting infection by E. histolytica if the organism goes extra-intestinal and in excluding the organism from the diagnosis of other disorders. An Ova & Parasite (O&P) test or an E. histolytica fecal antigen assay is the proper assay for intestinal infections.

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Metformin is distributed to (and appears to accumulate in) red blood cells, with a much longer elimination half-life: 17.6 hours (reported as ranging from 18.5 to 31.5 hours in a single-dose study of nondiabetics).Some evidence indicates that liver concentrations of metformin in humans may be two to three times higher than plasma concentrations, due to portal vein absorption and first-pass uptake by the liver in oral administration. Chemistry Metformin hydrochloride (1,1-dimethylbiguanide hydrochloride) is freely soluble in water, slightly soluble in ethanol, but almost insoluble in acetone, ether, or chloroform. The pKa of metformin is 12.4. The usual synthesis of metformin, originally described in 1922, involves the one-pot reaction of dimethylamine hydrochloride and 2-cyanoguanidine over heat. According to the procedure described in the 1975 Aron patent, and the Pharmaceutical Manufacturing Encyclopedia, equimolar amounts of dimethylamine and 2-cyanoguanidine are dissolved in toluene with cooling to make a concentrated solution, and an equimolar amount of hydrogen chloride is slowly added. The mixture begins to boil on its own, and after cooling, metformin hydrochloride precipitates with a 96% yield. Derivatives A new derivative HL156A, also known as IM156, is potential new drug for medical use. History The biguanide class of antidiabetic medications, which also includes the withdrawn agents phenformin and buformin, originates from the French lilac or goats rue (Galega officinalis), a plant used in folk medicine for several centuries.

A choriovitelline placenta is a placenta formed by the yolk sac and chorion. In a choriovitelline placenta, the yolk sac fuses with the chorion and, subsequently, wrinkles develop that hold the embryo to the uterine wall, thus forming the choriovitelline placenta. The chorionic blood vessels are connected with the vitelline blood vessel of the yolk sac. It is a primitive type of placenta found in all marsupials. (However, bandicoots also have a chorioallantoic placenta.) A choriovitelline placenta also forms early in the development of some placental mammals before the chorioallantoic placenta forms and the choriovitelline placenta is resorbed. == References ==

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The resulting inadequate blood flow produces tubular atrophy, interstitial fibrosis, and glomerular alterations (smaller glomeruli with different degrees of hyalinization – from mild to sclerosis of glomeruli) and scarring around the glomeruli (periglomerular fibrosis). In advanced stages, kidney failure will occur. Functional nephrons have dilated tubules, often with hyaline casts in the opening of the tubules. Additional complications often associated with hypertensive nephropathy include glomerular damage resulting in protein and blood in the urine.Hypertensive nephropathy refers to kidney failure that can be attributed to a history of hypertension It is a chronic condition and it is a serious risk factor for the development of end-stage kidney disease (ESKD). However, despite the well-known association between hypertension and chronic kidney disease, the underlying mechanism remains unclear. The two proposed mechanisms of HNs pathophysiology both centre around how the glomerulus, a network of dense capillaries that carries out the kidney filtration process, is affected; with one theory identifying glomerular ischemia as the main contributor to HN and the other identifying glomerular hypertension and glomerular hyperfiltration at the centre of HNs pathogenesis. Glomerular ischemia High blood pressure in the long term can damage the endothelium, commonly known as the blood vessel lining. This leads to a build-up of plaques and they can be deposited in the renal arteries causing stenosis and ischemic kidney disease. In this situation, the kidney supplied blood by the narrowed renal artery suffers from inadequate blood flow, which in turn causes the size of the kidneys to decrease.

Hypertensive kidney disease is a medical condition referring to damage to the kidney due to chronic high blood pressure. It manifests as hypertensive nephrosclerosis (sclerosis referring to the stiffening of renal components). It should be distinguished from renovascular hypertension, which is a form of secondary hypertension, and thus has opposite direction of causation. Signs and symptoms Signs and symptoms of chronic kidney disease, including loss of appetite, nausea, vomiting, itching, sleepiness or confusion, weight loss, and an unpleasant taste in the mouth, may develop. Causes "Hypertensive" refers to high blood pressure and "nephropathy" means damage to the kidney; hence this condition is where chronic high blood pressure causes damages to kidney tissue; this includes the small blood vessels, glomeruli, kidney tubules and interstitial tissues. The tissue hardens and thickens which is known as nephrosclerosis. The narrowing of the blood vessels means less blood is going to the tissue and so less oxygen is reaching the tissue resulting in tissue death (ischemia).Risk factors for HN include poorly controlled, moderate-to-high blood pressure, older age, other kidney disorders, and Afro-Caribbean background, whose exact cause is unclear, as it may be due to either genetic susceptibility or poor health management among people of Afro-Caribbean descent. Mechanism In the kidneys, as a result of benign arterial hypertension, hyaline (pink, amorphous, homogeneous material) accumulates in the walls of small arteries and arterioles, producing the thickening of their walls and the narrowing of the arterial openings, a process known as arteriolosclerosis.

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List of basic calculations Evolution of the Hindu-Arabic digit Brahmic numerals represented 1, 2, and 3 with as many lines. 4 was simplified by joining its four lines into a cross that looks like the modern plus sign. The Shunga would add a horizontal line on top of the digit, and the Kshatrapa and Pallava evolved the digit to a point where the speed of writing was a secondary concern. The Arabs 4 still had the early concept of the cross, but for the sake of efficiency, was made in one stroke by connecting the "western" end to the "northern" end; the "eastern" end was finished off with a curve. The Europeans dropped the finishing curve and gradually made the digit less cursive, ending up with a digit very close to the original Brahmin cross.While the shape of the character for the digit 4 has an ascender in most modern typefaces, in typefaces with text figures the glyph usually has a descender, as, for example, in . On the seven-segment displays of pocket calculators and digital watches, as well as certain optical character recognition fonts, 4 is seen with an open top.Television stations that operate on channel 4 have occasionally made use of another variation of the "open 4", with the open portion being on the side, rather than the top. This version resembles the Canadian Aboriginal syllabics letter ᔦ. The magnetic ink character recognition "CMC-7" font also uses this variety of "4".

Post-surgical: after frontal sinus reconstruction Diagnosis Diagnosis is suspected clinically and is confirmed using cross sectional imaging of the sinuses and brain. The patient typically presents with a headache overlying the frontal sinuses and an associated forehead swelling. This is often preceded by a history of chronic rhinosinusitis.Plain X Rays can be used to demonstrate the location of this swelling, but the gold standard for diagnosis is a cross sectional CT scan of the sinuses and brain, aided by contrast to delineate the abscess itself. Treatment The patient requires admission for intravenous anti-microbial treatment. Definitively, the abscess is drained via a combination of open and/or endoscopic approaches by an otolaryngologist, with the exact approach dependent on surgical skill set. At the very least, the abscess is trephined externally as an emergency. Any associated frontal sinus table fracture can be managed electively. Intracranial extension requires referral to the neurosurgery. References External links Karaman E, Hacizade Y, Isildak H, Kaytaz A (2008). "Potts puffy tumor". J Craniofac Surg. 19 (6): 1694–7. doi:10.1097/SCS.0b013e31818b432e. PMID 19098585.

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Intensity values vary from place to place, depending on distance from the earthquake and underlying rock or soil makeup.The first scale for measuring earthquake magnitudes was developed by Charles F. Richter in 1935. Subsequent scales (see seismic magnitude scales) have retained a key feature, where each unit represents a ten-fold difference in the amplitude of the ground shaking and a 32-fold difference in energy. Subsequent scales are also adjusted to have approximately the same numeric value within the limits of the scale.Although the mass media commonly reports earthquake magnitudes as "Richter magnitude" or "Richter scale", standard practice by most seismological authorities is to express an earthquakes strength on the moment magnitude scale, which is based on the actual energy released by an earthquake. Frequency of occurrence It is estimated that around 500,000 earthquakes occur each year, detectable with current instrumentation. About 100,000 of these can be felt. Minor earthquakes occur nearly constantly around the world in places like California and Alaska in the U.S., as well as in El Salvador, Mexico, Guatemala, Chile, Peru, Indonesia, the Philippines, Iran, Pakistan, the Azores in Portugal, Turkey, New Zealand, Greece, Italy, India, Nepal and Japan. Larger earthquakes occur less frequently, the relationship being exponential; for example, roughly ten times as many earthquakes larger than magnitude 4 occur in a particular time period than earthquakes larger than magnitude 5.

A notable example is Heinrich von Kleists classic novella, The Earthquake in Chile, which describes the destruction of Santiago in 1647. Haruki Murakamis short fiction collection After the Quake depicts the consequences of the Kobe earthquake of 1995. The most popular single earthquake in fiction is the hypothetical "Big One" expected of Californias San Andreas Fault someday, as depicted in the novels Richter 10 (1996), Goodbye California (1977), 2012 (2009) and San Andreas (2015) among other works. Jacob M. Appels widely anthologized short story, A Comparative Seismology, features a con artist who convinces an elderly woman that an apocalyptic earthquake is imminent.Contemporary depictions of earthquakes in film are variable in the manner in which they reflect human psychological reactions to the actual trauma that can be caused to directly afflicted families and their loved ones. Disaster mental health response research emphasizes the need to be aware of the different roles of loss of family and key community members, loss of home and familiar surroundings, loss of essential supplies and services to maintain survival. Particularly for children, the clear availability of caregiving adults who are able to protect, nourish, and clothe them in the aftermath of the earthquake, and to help them make sense of what has befallen them has been shown even more important to their emotional and physical health than the simple giving of provisions.

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Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of cancer. This includes Wilms tumor, rhabdomyosarcoma, Ewings sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer. It is given by injection into a vein.Most people develop side effects. Common side effects include bone marrow suppression, vomiting, mouth ulcers, hair loss, liver problems, infections, and muscle pains. Other serious side effects include future cancers, allergic reactions, and tissue death at the site of injection. Use in pregnancy may harm the baby. Dactinomycin is in the cytotoxic antibiotic family of medications. It is believed to work by blocking the creation of RNA.Dactinomycin was approved for medical use in the United States in 1964. It is on the World Health Organizations List of Essential Medicines. Medical use Actinomycin is a clear, yellowish liquid administered intravenously and most commonly used in treatment of a variety of cancers, including: Gestational trophoblastic neoplasia Wilms tumor Rhabdomyosarcoma Ewings sarcoma Malignant hydatidiform moleSometimes it will be combined with other drugs in chemotherapy regimens, like the VAC regimen (with vincristine and cyclophosphamide) for treating rhabdomyosarcoma and Ewings sarcoma. It is also used as a radiosensitizer in adjunct to radiotherapies, since it can increase the radiosensitivity of tumor cells by inhibiting repair of sublethal radiation damage and delay the onset of the compensatory hyperplasia that occurs following irradiation. Side effects Common adverse drug reaction includes bone marrow suppression, fatigue, hair loss, mouth ulcer, loss of appetite and diarrhea. Actinomycin is a vesicant, if extravasation occurs.

Mechanism In cell biology, actinomycin D is shown to have the ability to inhibit transcription. Actinomycin D does this by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by RNA polymerase. History Actinomycin D was the first antibiotic shown to have anti-cancer activity. It was first isolated by Selman Waksman and his co-worker H. Boyd Woodruff in 1940. It was approved by the U.S. Food and Drug Administration (FDA) on December 10, 1964, and launched by Merck Sharp and Dohme under the trade name Cosmegen. Research use Because actinomycin can bind DNA duplexes, it can also interfere with DNA replication, although other chemicals such as hydroxyurea are better suited for use in the laboratory as inhibitors of DNA synthesis. Actinomycin D and its fluorescent derivative, 7-aminoactinomycin D (7-AAD), are used as stains in microscopy and flow cytometry applications. The affinity of these stains/compounds for GC-rich regions of DNA strands makes them excellent markers for DNA. 7-AAD binds to single stranded DNA; therefore it is a useful tool in determining apoptosis and distinguishing between dead cells and live ones. References External links "Dactinomycin". Drug Information Portal. U.S. National Library of Medicine.

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The last 50 years have been filled with refractory treatment research. As of the early 2000s, longer treatments lasting months to years have been explored in the continued search for permanent removal of abnormal pain. Eponym Dejerine–Roussy syndrome has also been referred to as: "Posterior Thalamic Syndrome", "Retrolenticular Syndrome", "Thalamic Hyperesthetic Anesthesia", "Thalamic Pain Syndrome", "Thalamic Syndrome", "Central Pain Syndrome", and "Central Post-Stroke Syndrome". This condition is not associated with Roussy–Lévy syndrome or Dejerine–Sottas disease, both of which are genetic disorders. See also Central pain syndrome References == External links ==

Nelfinavir, sold under the brand name Viracept, is an antiretroviral medication used in the treatment of HIV/AIDS. Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and like other PIs is almost always used in combination with other antiretroviral drugs. Nelfinavir is an orally bioavailable human immunodeficiency virus HIV-1 protease inhibitor (Ki = 2 nM) and is widely prescribed in combination with HIV reverse transcriptase inhibitors for the treatment of HIV infection.It was patented in 1992 and approved for medical use in 1997. Toxicity Common (>1%) side effects include insulin resistance, hyperglycemia and lipodystrophy.Nelfinavir can produce a range of adverse side effects. Flatulence, diarrhea, or abdominal pain are common (i.e. experienced by more than one in one hundred patients). Fatigue, urination, rash, mouth ulcers, or hepatitis are less frequent effects (experienced by one in one thousand to one in one hundred patients). Nephrolithiasis, arthralgia, leukopenia, pancreatitis, or allergic reactions may occur, but are rare (less than one in one thousand patients) . Other bioactivity Antiviral Nelfinavir inhibits maturation and export of the herpes simplex 1 virus and the Kaposis sarcoma virus. Anti-virulence activity Nelfinavir and simple derivatives have been found to inhibit the production of the virulence factor streptolysin S, a cytolysin produced by the human pathogen Streptococcus pyogenes. Nelfinavir and these related molecules did not exhibit detectable antibiotic activity, but did also inhibit the production of other biologically active molecules, including plantazolicin (antibiotic), listeriolysin S (cytolysin), and clostridiolysin S (cytolysin), by other bacteria. Interactions Nelfinavirs interaction profile is similar to that of other protease inhibitors.

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It has recently been shown that the oxidative stress associated with cigarette smoke can inhibit the activity of HDAC2, thereby blocking the anti-inflammatory effects of corticosteroids.) Pharmacokinetics Absorption When theophylline is administered intravenously, bioavailability is 100%. Distribution Theophylline is distributed in the extracellular fluid, in the placenta, in the mothers milk and in the central nervous system. The volume of distribution is 0.5 L/kg. The protein binding is 40%. The volume of distribution may increase in neonates and those suffering from cirrhosis or malnutrition, whereas the volume of distribution may decrease in those who are obese. Metabolism Theophylline is metabolized extensively in the liver (up to 70%). It undergoes N-demethylation via cytochrome P450 1A2. It is metabolized by parallel first order and Michaelis-Menten pathways. Metabolism may become saturated (non-linear), even within the therapeutic range. Small dose increases may result in disproportionately large increases in serum concentration. Methylation to caffeine is also important in the infant population. Smokers and people with hepatic (liver) impairment metabolize it differently. Both THC and nicotine have been shown to increase the rate of theophylline metabolism. Excretion Theophylline is excreted unchanged in the urine (up to 10%). Clearance of the drug is increased in children (age 1 to 12), teenagers (12 to 16), adult smokers, elderly smokers, as well as in cystic fibrosis, and hyperthyroidism.

Clearance of the drug is decreased in these conditions: elderly, acute congestive heart failure, cirrhosis, hypothyroidism and febrile viral illnesses.The elimination half-life varies: 30 hours for premature neonates, 24 hours for neonates, 3.5 hours for children ages 1 to 9, 8 hours for adult non-smokers, 5 hours for adult smokers, 24 hours for those with hepatic impairment, 12 hours for those with congestive heart failure NYHA class I-II, 24 hours for those with congestive heart failure NYHA class III-IV, 12 hours for the elderly. History Theophylline was first extracted from tea leaves and chemically identified around 1888 by the German biologist Albrecht Kossel. Seven years later, a chemical synthesis starting with 1,3-dimethyluric acid was described by Emil Fischer and Lorenz Ach. The Traube purine synthesis, an alternative method to synthesize theophylline, was introduced in 1900 by another German scientist, Wilhelm Traube. Theophyllines first clinical use came in 1902 as a diuretic. It took an additional 20 years until it was first reported as an asthma treatment. The drug was prescribed in a syrup up to the 1970s as Theostat 20 and Theostat 80, and by the early 1980s in a tablet form called Quibron. References == External links ==

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Loss and social rejection are so painful that these individuals will choose to be alone rather than risk trying to connect with others. Some with this disorder fantasize about idealized, accepting and affectionate relationships because of their desire to belong. They often feel themselves unworthy of the relationships they desire, and shame themselves from ever attempting to begin them. If they do manage to form relationships, it is also common for them to pre-emptively abandon them out of fear of the relationship failing.Individuals with the disorder tend to describe themselves as uneasy, anxious, lonely, unwanted and isolated from others. They often choose jobs of isolation in which they do not have to interact with others regularly. Avoidant individuals also avoid performing activities in public spaces for fear of embarrassing themselves in front of others. Symptoms include: Extreme shyness or anxiety in social situations, though the person feels a strong desire for close relationships Heightened attachment-related anxiety, which may include a fear of abandonment Substance use disorders Comorbidity AvPD is reported to be especially prevalent in people with anxiety disorders, although estimates of comorbidity vary widely due to differences in (among others) diagnostic instruments. Research suggests that approximately 10–50% of people who have panic disorder with agoraphobia have avoidant personality disorder, as well as about 20–40% of people who have social anxiety disorder.

Treatment Treatment of avoidant personality disorder can employ various techniques, such as social skills training, psychotherapy, cognitive therapy, and exposure treatment to gradually increase social contacts, group therapy for practicing social skills, and sometimes drug therapy.A key issue in treatment is gaining and keeping the patients trust since people with an avoidant personality disorder will often start to avoid treatment sessions if they distrust the therapist or fear rejection. The primary purpose of both individual therapy and social skills group training is for individuals with an avoidant personality disorder to begin challenging their exaggerated negative beliefs about themselves.Significant improvement in the symptoms of personality disorders is possible, with the help of treatment and individual effort. Prognosis Being a personality disorder, which is usually chronic and has long-lasting mental conditions, an avoidant personality disorder may not improve with time without treatment. Given that it is a poorly studied personality disorder and in light of prevalence rates, societal costs, and the current state of research, AvPD qualifies as a neglected disorder. Controversy There is debate as to whether avoidant personality disorder (AvPD) is distinct from social anxiety disorder. Both have similar diagnostic criteria and may share a similar causation, subjective experience, course, treatment and identical underlying personality features, such as shyness.It is contended by some that they are merely different conceptualizations of the same disorder, where avoidant personality disorder may represent the more severe form.

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Higher degrees of impairment correlate with the number of previous manic episodes and hospitalizations, and with the presence of psychotic symptoms. Early intervention can slow the progression of cognitive impairment, while treatment at later stages can help reduce distress and negative consequences related to cognitive dysfunction.Despite the overly ambitious goals that are frequently part of manic episodes, symptoms of mania undermine the ability to achieve these goals and often interfere with an individuals social and occupational functioning. One-third of people with BD remain unemployed for one year following a hospitalization for mania. Depressive symptoms during and between episodes, which occur much more frequently for most people than hypomanic or manic symptoms over the course of illness, are associated with lower functional recovery in between episodes, including unemployment or underemployment for both BD-I and BD-II. However, the course of illness (duration, age of onset, number of hospitalizations, and the presence or not of rapid cycling) and cognitive performance are the best predictors of employment outcomes in individuals with bipolar disorder, followed by symptoms of depression and years of education. Recovery and recurrence A naturalistic study in 2003 by Tohen and coworkers from the first admission for mania or mixed episode (representing the hospitalized and therefore most severe cases) found that 50% achieved syndromal recovery (no longer meeting criteria for the diagnosis) within six weeks and 98% within two years. Within two years, 72% achieved symptomatic recovery (no symptoms at all) and 43% achieved functional recovery (regaining of prior occupational and residential status).

The condition was added to the Diagnostic and Statistical Manual of Mental Disorders as posttraumatic stress disorder in 1980. PTSD was considered a severe and ongoing emotional reaction to an extreme psychological trauma, and as such often associated with soldiers, police officers, and other emergency personnel. The stressor may involve threat to life (or viewing the actual death of someone else), serious physical injury, or threat to physical or psychological integrity. In some cases, it can also be from profound psychological and emotional trauma, apart from any actual physical harm or threat. Often, however, the two are combined. By the 1990s, "stress" had become an integral part of modern scientific understanding in all areas of physiology and human functioning, and one of the great metaphors of Western life. Focus grew on stress in certain settings, such as workplace stress, and stress management techniques were developed. The term also became a euphemism, a way of referring to problems and eliciting sympathy without being explicitly confessional, just "stressed out". It came to cover a huge range of phenomena from mild irritation to the kind of severe problems that might result in a real breakdown of health. In popular usage, almost any event or situation between these extremes could be described as stressful.The American Psychological Associations 2015 Stress In America Study found that nationwide stress is on the rise and that the three leading sources of stress were "money", "family responsibility", and "work".

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However, Voltarol Emulgel contains diclofenac diethylammonium, in which a 1.16% concentration is equivalent to a 1% concentration of the sodium salt. In 2016 Voltarol was one of the biggest selling branded over-the-counter medications sold in Great Britain, with sales of £39.3 million.On 14 January 2015, diclofenac oral preparations were reclassified as prescription-only medicines in the UK. The topical preparations are still available without prescription.Diclofenac formulations are available worldwide under many different trade names. Ecological effects Use of diclofenac for animals is controversial due to toxicity when eaten by scavenging birds that eat dead animals; the medication has been banned for veterinary use in several countries.Use of diclofenac in animals has been reported to have led to a sharp decline in the vulture population in the Indian subcontinent – a 95% decline by 2003 and a 99.9% decline by 2008. The mechanism is presumed to be renal failure; however, toxicity may be due to direct inhibition of uric acid secretion in vultures. Vultures eat the carcasses of livestock that have been administered veterinary diclofenac, and are poisoned by the accumulated chemical, as vultures do not have a particular enzyme to break down diclofenac. At a meeting of the National Wildlife Board in March 2005, the Government of India announced it intended to phase out the veterinary use of diclofenac. Meloxicam is a safer alternative to replace use of diclofenac.

It is more expensive than diclofenac, but the cost is dropping as more pharmaceutical companies are beginning to manufacture it.Steppe eagles have the same vulnerability to diclofenac as vultures and may also fall victim to it. Diclofenac has been shown also to harm freshwater fish species such as rainbow trout. In contrast, New World vultures, such as the turkey vulture, can tolerate at least 100 times the level of diclofenac that is lethal to Gyps species. "The loss of tens of millions of vultures over the last decade has had major ecological consequences across the Indian Subcontinent that pose a potential threat to human health. In many places, populations of feral dogs (Canis familiaris) have increased sharply from the disappearance of Gyps vultures as the main scavenger of wild and domestic ungulate carcasses. Associated with the rise in dog numbers is an increased risk of rabies" and casualties of almost 50,000 people. The Government of India cites this as one of the major consequences of a vulture species extinction. A major shift in the transfer of corpse pathogens from vultures to feral dogs and rats could lead to a disease pandemic, causing millions of deaths in a crowded country like India, whereas vultures digestive systems safely destroy many species of such pathogens. Vultures are long-lived and slow to breed. They start breeding only at the age of six and only 50% of young survive.

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There is evidence to support the use of perindopril and indapamide combination over perindopril monotherapy to prevent strokes and improve mortality in patients with a history of stroke, transient ischaemic attack or other cardiovascular disease. With amlodipine The Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BLA) was a 2005 landmark trial that compared the effects of the established therapy of the combination of atenolol and bendroflumethiazide to the new drug combination of amlodipine and perindopril (trade names Viacoram, AceryCal etc.). The study of more than 19 000 patients world-wide was terminated earlier than anticipated because it clearly demonstrated a statistically significant improvement in mortality and cardiovascular outcomes with the newer treatment. The combination of amlodipine and perindopril remains in the current treatment guidelines for hypertension and the outcomes of the ASCOT-BLA trial paved the way for further research into combination therapy and newer agents. Contraindications Children Pregnancy Lactation Situations where a patient has a history of hypersensitivity Kidney failure Precautions Assess kidney function before and during treatment where appropriate. Renovascular hypertension Surgery/anesthesia An analysis on the PROGRESS trial showed that perindopril has key benefits in reducing cardiovascular events by 30% in patients with chronic kidney disease defined as a CrCl <60ml/min. A 2016 and 2017 meta-analysis review looking at ACE inhibitors demonstrated a reduction in cardiovascular events but also slowed the decline of renal failure by 39% when compared to placebo. These studies included patients with moderate to severe kidney disease and those on dialysis. Its renoprotective benefits of decreasing blood pressure and removing filtration pressure is highlighted in a 2016 review.

Temsirolimus, sold under the brand name Torisel, is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) in May 2007, and was also approved by the European Medicines Agency (EMA) in November 2007. It is a derivative and prodrug of sirolimus. Mechanism of action Temsirolimus is a specific inhibitor of mTOR and interferes with the synthesis of proteins that regulate proliferation, growth, and survival of tumor cells. Though temsirolimus shows activity on its own, it is also known to be converted to sirolimus (rapamycin) in vivo; therefore, its activity may be more attributed to its metabolite rather than the prodrug itself (despite claims to the contrary by the manufacturer). Treatment with temsirolimus leads to cell cycle arrest in the G1 phase, and also inhibits tumor angiogenesis by reducing synthesis of VEGF.mTOR (mammalian target of rapamycin) is a kinase enzyme inside the cell that collects and interprets the numerous and varied growth and survival signals received by tumor cells. When the kinase activity of mTOR is activated, its downstream effectors, the synthesis of cell cycle proteins such as cyclin D and hypoxia-inducible factor-1a (HIF-1a) are increased. HIF-1a then stimulates VEGF. Whether or not mTOR kinase is activated, determines whether the tumor cell produces key proteins needed for proliferation, growth, survival, and angiogenesis.mTOR is activated in tumor cells by various mechanisms including growth factor surface receptor tyrosine kinases, oncogenes, and loss of tumor suppressor genes.

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The proportion of pregnancies that ended in induced abortion ranged from about 10% (Israel, the Netherlands and Switzerland) to 30% (Estonia) in the same group, though it might be as high as 36% in Hungary and Romania, whose statistics were deemed incomplete.An American study in 2002 concluded that about half of women having abortions were using a form of contraception at the time of becoming pregnant. Inconsistent use was reported by half of those using condoms and three-quarters of those using the birth control pill; 42% of those using condoms reported failure through slipping or breakage. The Guttmacher Institute estimated that "most abortions in the United States are obtained by minority women" because minority women "have much higher rates of unintended pregnancy". In a 2022 analysis by the Kaiser Family Foundation, while people of color comprise 44% of the population in Mississippi, 59% of the population in Texas, 42% of the population in Louisiana (by the state Health Department), and 35% of the population in Alabama, they comprise 80%, 74%, 72%, and 70% of those receiving abortions.The abortion rate may also be expressed as the average number of abortions a woman has during her reproductive years; this is referred to as total abortion rate (TAR). Gestational age and method Abortion rates also vary depending on the stage of pregnancy and the method practiced.

In China, a historical preference for a male child has been exacerbated by the one-child policy, which was enacted in 1979.Many countries have taken legislative steps to reduce the incidence of sex-selective abortion. At the International Conference on Population and Development in 1994 over 180 states agreed to eliminate "all forms of discrimination against the girl child and the root causes of son preference", conditions also condemned by a PACE resolution in 2011. The World Health Organization and UNICEF, along with other United Nations agencies, have found that measures to reduce access to abortion are much less effective at reducing sex-selective abortions than measures to reduce gender inequality. Anti-abortion violence In a number of cases, abortion providers and these facilities have been subjected to various forms of violence, including murder, attempted murder, kidnapping, stalking, assault, arson, and bombing. Anti-abortion violence is classified by both governmental and scholarly sources as terrorism. In the U.S. and Canada, over 8,000 incidents of violence, trespassing, and death threats have been recorded by providers since 1977, including over 200 bombings/arsons and hundreds of assaults. The majority of abortion opponents have not been involved in violent acts. In the United States, four physicians who performed abortions have been murdered: David Gunn (1993), John Britton (1994), Barnett Slepian (1998), and George Tiller (2009). Also murdered, in the U.S. and Australia, have been other personnel at abortion clinics, including receptionists and security guards such as James Barrett, Shannon Lowney, Lee Ann Nichols, and Robert Sanderson.

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Localised argyria often results from topical use of substances containing silver, such as some kinds of eye drops. Generalized argyria results from chronically swallowing or inhaling silver compounds, either for home medicinal purposes, or as a result of working with silver or silver compounds.While silver is potentially toxic to humans at high doses, the risk of serious harm from low doses, given over a short term, is small. Silver is used in some medical appliances because of its anti-microbial nature, which stems from the oligodynamic effect. Chronic ingestion or inhalation of silver preparations (especially colloidal silver) can lead to argyria in the skin and other organs. This is not life-threatening, but is considered by most to be cosmetically undesirable.The reference dose, published by the United States Environmental Protection Agency in 1991, which represents the estimated daily exposure that is unlikely to incur an appreciable risk of deleterious effects during a lifetime, is 5 µg/(kg·d).Argyria worsens and builds up as exposure to silver continues, and does not resolve once exposure stops. History Since at least the mid-19th century, doctors have known that silver or silver compounds can cause some areas of the skin and other body tissues to turn grey or blue-grey. Argyria occurs in people who ingest or inhale silver in large quantities over a long period (several months to many years). People who work in factories that manufacture silver products can also breathe in silver or its compounds. In the past, some of these workers have become argyric.

Argyria or argyrosis is a condition caused by excessive exposure to chemical compounds of the element silver, or to silver dust. The most dramatic symptom of argyria is that the skin turns blue or blue-grey. It may take the form of generalized argyria or local argyria. Generalized argyria affects large areas over much of the visible surface of the body. Local argyria shows in limited regions of the body, such as patches of skin, parts of the mucous membrane or the conjunctiva. The terms argyria and argyrosis have long been used interchangeably, with argyria being used more frequently. Argyrosis has been used particularly in referring to argyria of the conjunctiva, but the usage has never been consistent and cannot be relied on except where it has been explicitly specified. The term is from the Ancient Greek: ἄργυρος (argyros, silver). Pathophysiology In humans and other animals, chronic intake of silver products commonly leads to gradual accumulation of silver compounds in various parts of the body. As in photography (where silver is useful because of its sensitivity to light), exposure of pale or colourless silver compounds to sunlight decomposes them to silver metal or silver sulfides. Commonly these products deposit as microscopic particles in the skin, in effect a dark pigment. This condition is known as argyria or argyrosis. Chronic intake also may lead to silver pigments depositing in other organs exposed to light, particularly the eyes. In the conjunctiva this is not generally harmful, but it also may affect the lens, leading to serious effects.

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Society and culture In the United States, hyperkalemia is induced by lethal injection in capital punishment cases. Potassium chloride is the last of the three drugs administered and actually causes death. Injecting potassium chloride into the heart muscle disrupts the signal that causes the heart to beat. This same amount of potassium chloride would do no harm if taken orally and not injected directly into the blood. References External links USDA National Nutrient Database for Standard Reference, Release 26 Archived 1 March 2014 at the Wayback Machine List of foods rich in potassium National Kidney Foundation site on potassium content of foods

PMID 25704934. van der Hoeve, J.; Flieringa, H. J. (1 March 1924). "Accommodation". British Journal of Ophthalmology. 8 (3): 97–106. doi:10.1136/bjo.8.3.97. PMC 512904. PMID 18168370.

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Developmental dysfluency, or "normal dysfluency", is a lack of language fluency that occurs during early childhood development. It is commonly observed in children ages 2 to 4 years old. This typically occurs as they begin to learn language and communication skills. Developmental dysfluency refers to speech that is continually interrupted rather than flowing naturally. Developmental dysfluency is most commonly expressed through inconsistencies in speech such as stuttering, repetition, lengthening of sounds and syllables, mistiming, and poor inflection.Speech is a complicated skill involving a series of cognitive and linguistic processes that are both sensorimotor and auditory. As children grow, their language and vocabulary grow exponentially. Dysfluencies in early speech are typical as their speech skills develop. The most common form of dysfluency in children younger than three years is the repetition of one-syllable words or parts of words. Words or syllables are often repeated in the beginning of their sentences as they try to process how to form the rest of the sentence. Language dysfluency may be common in children as they learn basic language skills throughout the crucial development stages in early childhood. Developmental dysfluency is normal in children as they work to acquire language skills and semantic/syntactic processing. About twenty-five percent of children experience some loss in fluency in their linguistic abilities. Some children between the ages of 2 and 6 encounter some obstacles in the path to fluent speech. Fluency in a normal child will typically improve around the age of 4. When attempting to master spoken language, children gradually develop fluent speech.

Monofixation syndrome (MFS) (also: microtropia or microstrabismus) is an eye condition defined by less-than-perfect binocular vision. It is defined by a small angle deviation with suppression of the deviated eye and the presence of binocular peripheral fusion. That is, MFS implies peripheral fusion without central fusion. Aside the manifest small-angle deviation ("tropia"), subjects with MFS often also have a large-angle latent deviation (phoria). Their stereoacuity is often in the range of 3000 to 70 arcsecond, and a small central suppression scotoma of 2 to 5 deg.A rare condition, MFS is estimated to affect only 1% of the general population. There are three distinguishable forms of this condition: primary constant, primary decompensating and consecutive MFS. It is believed that primary MFS is a result of a primary sensorial defect, predisposing to anomalous retinal correspondence.Secondary MFS is a frequent outcome of surgical treatment of congenital esotropia. A study of 1981 showed MFS to result in the vast majority of cases if surgical alignment is reached before the age of 24 months and only in a minority of cases if it is reached later.MFS was first described by Marshall Parks. References == External links ==

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It may have a greater survival benefit for those with bulbar-onset ALS. It may work by decreasing release of the excitatory neurotransmitter glutamate from pre-synaptic neurons. The most common side effects are nausea and a lack of energy (asthenia). People with ALS should begin treatment with riluzole as soon as possible following their diagnosis.Edaravone has been shown to modestly slow the decline in function in a small group of people with early-stage ALS. It may work by protecting motor neurons from oxidative stress. The most common side effects are bruising and gait disturbance. Treatment with edaravone is expensive and requires daily hour-long IV infusions for 10 days in a two-week period.Other medications may be used to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Gabapentin, pregabalin, and tricyclic antidepressants (e.g., amitriptyline) can be used for neuropathic pain, while nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioids can be used for nociceptive pain.Depression can be treated with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants, while benzodiazepines can be used for anxiety. There are no medications to treat cognitive impairment/frontotemporal dementia (FTD); however, SSRIs and antipsychotics can help treat some of the symptoms of FTD. Baclofen and tizanidine are the most commonly used oral drugs for treating spasticity; an intrathecal baclofen pump can be used for severe spasticity.

Secondary airway malacia was defined as airway malacia secondary to esophageal atresia, VATER/VACTERL association (condition with vertebral anomalies, anal atresia, congenital heart disease, tracheoesophageal fistula or esophageal atresia, renourinary anomalies, or radial limb defects), vascular or other external compression of the airways, or specific syndromes. Treatment Time Minimally Invasive, usually in conjunction with Continuous Positive Airflow Pressure. Continuous Positive Airflow Pressure A method of respiratory ventilation. Tracheotomy Surgical procedures on the neck to open a direct airway through an incision in the trachea (the windpipe). Prosthesis Insertion of a prosthesis to keep the bronchial tube open. Notes References Carden, KA, Boiselle, PM, Waltz, DA, et al. (2005) Tracheomalacia and tracheobronchomalacia in children and adults: an in-depth review. Chest 127,984-1005. Clements, B Congenital malformations of the lungs and airways. Taussig, LM Landau, LI eds. Pediatric respiratory medicine 1999,1106-1136 Mosby. St. Louis, MO Austin, J, Ali, T Tracheomalacia and Bronchomalacia in children: pathophysiology, assessment, treatment and anaesthesia management. Paediatr Anaesth 2003;13,3-11 McNamara, VM, Crabbe, DC Tracheomalacia. Paediatr Respir Rev 2004;5,147-154 Benjamin, B Tracheomalacia in infants and children. Ann Otol Rhinol Laryngol 1984;93,438-442 == External links ==

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The fact that cytokine levels are not completely restored indicates there is another pathway activated by cmvIL-10 that is inhibiting cytokine system synthesis. The proposed mechanism is that cmvIL-10 activates PI3K which in turn activates PKB (Akt). PKB may then activate mTOR, which may target Stat3 for phosphorylation on the S727 residue. MHC downregulation Another one of the many ways in which herpes viruses evade the immune system is by down regulation of MHC I and MHC II. This is observed in almost every human herpesvirus. Down regulation of MHC I and MHC II can come about by many different mechanisms, most causing the MHC to be absent from the cell surface. As discussed above, one way is by a viral chemokine homolog such as IL-10. Another mechanism to down regulate MHCs is to encode viral proteins that detain the newly formed MHC in the endoplasmic reticulum (ER). The MHC cannot reach the cell surface and therefore cannot activate the T cell response. The MHCs can also be targeted for destruction in the proteasome or lysosome. The ER protein TAP also plays a role in MHC down regulation. Viral proteins inhibit TAP preventing the MHC from picking up a viral antigen peptide. This prevents proper folding of the MHC and therefore the MHC does not reach the cell surface. Human herpesvirus types Below are the nine (9) distinct viruses in this family known to cause disease in humans. Zoonotic herpesviruses In addition to the herpesviruses considered endemic in humans, some viruses associated primarily with animals may infect humans.

Speciations within sublineages took place in the last 80 million years probably with a major component of cospeciation with host lineages.All the currently known bird and reptile species are alphaherpesviruses. Although the branching order of the herpes viruses has not yet been resolved, because herpes viruses and their hosts tend to coevolve this is suggestive that the alphaherpesviruses may have been the earliest branch.The time of origin of the genus Iltovirus has been estimated to be 200 mya while those of the mardivirus and simplex genera have been estimated to be between 150 and 100 mya. Immune system evasions Herpesviruses are known for their ability to establish lifelong infections. One way this is possible is through immune evasion. Herpesviruses have many different ways of evading the immune system. One such way is by encoding a protein mimicking human interleukin 10 (hIL-10) and another is by downregulation of the major histocompatibility complex II (MHC II) in infected cells. cmvIL-10 Research conducted on cytomegalovirus (CMV) indicates that the viral human IL-10 homolog, cmvIL-10, is important in inhibiting pro-inflammatory cytokine synthesis. The cmvIL-10 protein has 27% identity with hIL-10 and only one conserved residue out of the nine amino acids that make up the functional site for cytokine synthesis inhibition on hIL-10. There is, however, much similarity in the functions of hIL-10 and cmvIL-10. Both have been shown to down regulate IFN-γ, IL-1α, GM-CSF, IL-6 and TNF-α, which are all pro-inflammatory cytokines.

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Pyuria is the condition of urine containing white blood cells or pus. Defined as the presence of 6-10 or more neutrophils per high power field of unspun, voided mid-stream urine, it can be a sign of a bacterial urinary tract infection. Pyuria may be present in people with sepsis, or in older people with pneumonia. Others additionally require discoloration, clouding or change in the smell of urine for a pyuria to be present. Without these additional features, there is said to be leukocyturia. Sterile pyuria is urine which contains white blood cells while appearing sterile by standard culturing techniques. It is often caused by sexually transmitted infections, such as gonorrhea, or viruses which will not grow in bacterial cultures. Sterile pyuria is listed as a side effect from some medications such as paracetamol (acetaminophen). Its occurrence is also associated with certain disease processes, such as Kawasaki disease and genitourinary tuberculosis. However, there are many known causes, including systemic or infectious disease, structural and physiological reasons, intrinsic kidney pathology, or drugs. Leukocyturia Under normal conditions, fewer than two million leukocytes are expelled in urine per day. A number greater than two million is called leucocyturia and can be determined when determining the Addis count.However, this method requires a 24-hour urine collection, so it is not practical. Currently, the number of leukocytes is estimated under the microscope for which morning urine is taken.

It has been arbitrarily assumed that a number of over 4-5 leukocytes in the field of vision of the microscope indicates leukocyturia.At the moment, there are also quick test strips available, allowing after wetting a special diagnostic bar, the detection of granulocytes in the urine, as evidenced by the color change of the test strip. The principle of their operation is based on the detection of granulocytes esterases, including leukocytes. This method, however, is burdened with a large number of false positive results (use of antibiotics, such as imipenem, meropenem, clavulanic acid, which is sometimes combined with penicillin derivatives) or false negative (gentamicin, cefalexin, glycosuria, proteinuria).Leukocyturia is a laboratory symptom of many diseases like glomerulonephritis or pyelonephritis. It may occur in the case of diseases of the urinary tract, reproductive system and diseases of the abdominal organs. Leukocyturia is mostly a sign of urinary tract infection, especially if significant bacteriuria is found (for most people, the number of bacteria in a culture is > 10^5) and other symptoms associated with passing urine. The presence of leukocyturia does not indicate the need for antimicrobial therapy yet. Additional images See also Urinalysis Bacteriuria References == External links ==

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This leads to abnormalities in protein production (identified by deranged coagulation) and metabolism by the liver. The deranged protein metabolism leads to the accumulation of waste products such as ammonia in the bloodstream. When these irritate the brain, the person develops hepatic encephalopathy (confusion, coma, seizures and finally life-threatening swelling of the brain). Neuropsychiatric symptoms About half of the people with Wilsons disease have neurological or psychiatric symptoms. Most initially have mild cognitive deterioration and clumsiness, as well as changes in behavior. Specific neurological symptoms usually then follow, often in the form of parkinsonism (cogwheel rigidity, bradykinesia or slowed movements and a lack of balance are the most common parkinsonian features) with or without a typical hand tremor, masked facial expressions, slurred speech, ataxia (lack of coordination) or dystonia (twisting and repetitive movements of part of the body). Seizures and migraine appear to be more common in Wilsons disease. A characteristic tremor described as "wing-beating tremor" is encountered in many people with Wilsons; this is absent at rest but can be provoked by abducting the arms and flexing the elbows toward the midline.Cognition can also be affected in Wilsons disease. This comes in two, not mutually exclusive, categories: frontal lobe disorder (may present as impulsivity, impaired judgement, promiscuity, apathy and executive dysfunction with poor planning and decision making) and subcortical dementia (may present as slow thinking, memory loss and executive dysfunction, without signs of aphasia, apraxia or agnosia).

Kidneys: renal tubular acidosis (Type 2), a disorder of bicarbonate handling by the proximal tubules leads to nephrocalcinosis (calcium accumulation in the kidneys), a weakening of bones (due to calcium and phosphate loss), and occasionally aminoaciduria (loss of essential amino acids needed for protein synthesis). Heart: cardiomyopathy (weakness of the heart muscle) is a rare but recognized problem in Wilsons disease; it may lead to heart failure (fluid accumulation due to decreased pump function) and cardiac arrhythmias (episodes of irregular and/or abnormally fast or slow heart beat). Hormones: hypoparathyroidism (failure of the parathyroid glands leading to low calcium levels), infertility, and recurrent miscarriage. Genetics The Wilsons disease gene (ATP7B) is on chromosome 13 (13q14.3) and is expressed primarily in the liver, kidney, and placenta. The gene codes for a P-type (cation transport enzyme) ATPase that transports copper into bile and incorporates it into ceruloplasmin. Mutations can be detected in 90% of cases. Most (60%) are homozygous for ATP7B mutations (two abnormal copies), and 30% have only one abnormal copy. Ten percent have no detectable mutation.Although 300 mutations of ATP7B have been described, in most populations the cases of Wilsons disease are due to a small number of mutations specific for that population. For instance, in Western populations the H1069Q mutation (replacement of a histidine by a glutamine at position 1069 in the protein) is present in 37–63% of cases, while in China this mutation is very uncommon and R778L (arginine to leucine at 778) is found more often.

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The bioavailability of oral administration of oxycodone averages within a range of 60 to 87%, with rectal administration yielding the same results; intranasal varies between individuals with a mean of 46%.After a dose of conventional (immediate-release) oral oxycodone, the onset of action is 10 to 30 minutes, and peak plasma levels of the drug are attained within roughly 30 to 60 minutes; in contrast, after a dose of OxyContin (an oral controlled-release formulation), peak plasma levels of oxycodone occur in about three hours. The duration of instant-release oxycodone is 3 to 6 hours, although this can be variable depending on the individual. Distribution Oxycodone has a volume of distribution of 2.6L/kg, in the blood it is distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain. At equilibrium the unbound concentration in the brain is threefold higher than the unbound concentration in blood Conventional oral preparations start to reduce pain within 10 to 15 minutes on an empty stomach; in contrast, OxyContin starts to reduce pain within one hour. Metabolism The metabolism of oxycodone in humans occurs in the liver mainly via the cytochrome P450 system and is extensive (about 95%) and complex, with many minor pathways and resulting metabolites. Around 10% (range 8–14%) of a dose of oxycodone is excreted essentially unchanged (unconjugated or conjugated) in the urine. The major metabolites of oxycodone are noroxycodone (70%), noroxymorphone ("relatively high concentrations"), and oxymorphone (5%).

Bednars aphthae is a type of oral ulceration (mouth ulcers) which occurs in infants. The lesions are located on the palate and are caused by trauma. No treatment is required since the lesions heal within a few days.The condition was first described in 1850, by the Austrian physician Alois Bednar (1816-1888). References == External links ==

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A specialty ear splint can also be made to keep the ear compressed, so that the damaged ear is unable to fill thus preventing cauliflower ear. For some athletes, however, a cauliflower ear is considered a badge of courage or experience. Treatment There are many types of treatment for the perichondral hematoma that can lead to cauliflower ear, but the current body of research is unable to identify a single best treatment or protocol. There is definitive evidence that the drainage of this hematoma is better for the prevention of cauliflower deformity when compared to conservative treatment, but the use of bandages and/or splinting after drainage requires more research.Because an acute hematoma can lead to cauliflower ear, prompt evacuation of the blood can prevent permanent deformity. There are many described techniques for the drainage of blood in the acute stage to prevent hematoma, including simple needle drainage, continuous suction devices, placing a wick, and incision and drainage. After the blood has been drained, the prevention of re-accumulation becomes the most pressing issue. This has been achieved with many techniques including: direct pressure dressings, in and out mattress sutures, buttons placed on sutures, thermoplastic splints, sutured cotton balls, and absorbable mattress sutures. The use of simple drainage becomes less useful after six hours from the injury and when there is recurrent trauma. In these cases it has been suggested that open surgical treatment is more effective in returning the cosmetic appearance and prevention of recurrence. The outer ear is prone to infections, so antibiotics are usually prescribed.

When the mutation is present, there is no signal for B cells to undergo class switching, so there is an excess of IgM and little to no other immunoglobulin types produced. Type 4 Immunodeficiency with hyper IgM type 4 is poorly characterized. All that is known is that there is an excess of IgM in the blood, with normal levels of the other immunoglobulins. The exact cause is yet to be determined. Type 5 Immunodeficiency with hyper IgM type 5 is caused by a mutation in the Uracil-DNA glycosylase (UNG) gene, which, like AICDA, is located on chromosome 12. This codes for Uracil DNA Glycosylase, which is responsible for excising previous uracil bases that are due to cytosine deamination, or previous uracil misincorporation from double-stranded previous DNA substrates. This enzyme is also responsible for helping with gene conversion during somatic recombination in B cells. The mutation in the gene causes an enzyme that does not function properly, thus gene conversion does not proceed and class switching cannot occur. See also Monoclonal gammopathy of undetermined significance References == External links ==

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HTML is then cleaved by HTML aldolase (a pyridoxal phosphate requiring enzyme), yielding 4-trimethylaminobutyraldehyde (TMABA) and glycine. TMABA is then dehydrogenated into gamma-butyrobetaine in an NAD+-dependent reaction, catalyzed by TMABA dehydrogenase. Gamma-butyrobetaine is then hydroxylated by gamma butyrobetaine hydroxylase (a zinc binding enzyme) into l-carnitine, requiring iron in the form of Fe2+.Carnitine is involved in transporting fatty acids across the mitochondrial membrane, by forming a long chain acetylcarnitine ester and being transported by carnitine palmitoyltransferase I and carnitine palmitoyltransferase II. Carnitine also plays a role in stabilizing Acetyl-CoA and coenzyme A levels through the ability to receive or give an acetyl group. Tissue distribution of carnitine-biosynthetic enzymes The tissue distribution of carnitine-biosynthetic enzymes in humans indicates TMLD to be active in the liver, heart, muscle, brain and highest in the kidney. HTMLA activity is found primarily in the liver. The rate of TMABA oxidation is greatest in the liver, with considerable activity also in the kidney. Carnitine shuttle system The free-floating fatty acids, released from adipose tissues to the blood, bind to carrier protein molecule known as serum albumin that carry the fatty acids to the cytoplasm of target cells such as the heart, skeletal muscle, and other tissue cells, where they are used for fuel.

Metabolic defects of fatty acid oxidation More than 20 human genetic defects in fatty acid transport or oxidation have been identified. In case of fatty acid oxidation defects, acyl-carnitines accumulate in mitochondria and are transferred into the cytosol, and then into the blood. Plasma levels of acylcarnitine in newborn infants can be detected in a small blood sample by tandem mass spectrometry.When β oxidation is defective because of either mutation or deficiency in carnitine, the ω (omega) oxidation of fatty acids becomes more important in mammals. Actually, the ω Oxidation of Fatty Acids is another pathway for F-A degradation in some species of vertebrates and mammals that occurs in the endoplasmic reticulum of the liver and kidney, it is the oxidation of the ω carbon—the carbon most far from the carboxyl group (in contrast to β {\displaystyle \beta } oxidation which occurs at the carboxyl end of fatty acid, in the mitochondria). Physiological effects As an example of normal synthesis, a 70 kilograms (150 lb) person would produce 11–34 mg of carnitine per day. Adults eating mixed diets of red meat and other animal products ingest some 60–180 mg of carnitine per day, while vegans consume about 10–12 mg per day. Most (54–86%) carnitine obtained from the diet is absorbed in the small intestine before entering the blood.

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There is a suggestion that treatment of factors that modulate pain sensitivity such as mood disorders, anxiety and fatigue, may be important in the treatment of TMD, which often tends to attempt to address the pain directly.Cognitive Behavioral Therapy (CBT) has been used in TMD and has been shown to be efficacious by meta analyses.Hypnosis is suggested by some to be appropriate for TMD. Studies have suggested that it may even be more beneficial than occlusal splint therapy, and has comparable effects to relaxation techniques.Relaxation techniques include progressive muscle relaxation, yoga, and meditation. It has been suggested that TMD involves increased sensitivity to external stimuli leading to an increased sympathetic ("fight or flight") response with cardiovascular and respiratory alterations. Relaxation techniques cause reduced sympathetic activity, including muscle relaxation and reducing sensitivity to external stimuli, and provoke a general sense of well-being and reduced anxiety. Devices Occlusal splints (also termed bite plates or intra-oral appliances) are often used by dentists to treat TMD. They are usually made of acrylic and can be hard or soft. They can be designed to fit onto the upper teeth or the lower teeth. They may cover all the teeth in one arch (full coverage splint) or only some (partial coverage splint). Splints are also termed according to their intended mechanism, such as the anterior positioning splint or the stabilization splint. Although occlusal splints are generally considered a reversible treatment, sometimes partial coverage splints lead to pathologic tooth migration (changes in the position of teeth).

Choreoathetosis is the occurrence of involuntary movements in a combination of chorea (irregular migrating contractions) and athetosis (twisting and writhing). It is caused by many different diseases and agents. It is a symptom of several diseases, including Lesch–Nyhan syndrome, phenylketonuria, and Huntington disease and can be a feature of kernicterus (rapidly increasing unconjugated bilirubin that cross the blood-brain-barrier in infants). Choreoathetosis is also a common presentation of dyskinesia as a side effect of levodopa-carbidopa in the treatment of Parkinson disease.The use of crack cocaine or amphetamines can result in conditions nicknamed crack dancing, or tweaking respectively, described as choreathetoid. See also Ulegyria References == External links ==

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Systemic vasculitides may be classified according to the type of cells involved in the proliferation, as well as the specific type of tissue damage occurring within the vein or arterial walls. Under this classification scheme for systemic vasculitis, Kawasaki disease is considered to be a necrotizing vasculitis (also called necrotizing angiitis), which may be identified histologically by the occurrence of necrosis (tissue death), fibrosis, and proliferation of cells associated with inflammation in the inner layer of the vascular wall.Other diseases involving necrotizing vasculitis include polyarteritis nodosa, granulomatosis with polyangiitis, Henoch–Schönlein purpura, and eosinophilic granulomatosis with polyangiitis.Kawasaki disease may be further classified as a medium-sized vessel vasculitis, affecting medium- and small-sized blood vessels, such as the smaller cutaneous vasculature (veins and arteries in the skin) that range from 50 to 100 µm in diameter. Kawasaki disease is also considered to be a primary childhood vasculitis, a disorder associated with vasculitis that mainly affects children under the age of 18. A recent, consensus-based evaluation of vasculitides occurring primarily in children resulted in a classification scheme for these disorders, to distinguish them and suggest a more concrete set of diagnostic criteria for each. Within this classification of childhood vasculitides, Kawasaki disease is, again, a predominantly medium-sized vessel vasculitis.It can also be classed as an autoimmune form of vasculitis. It is not associated with anti-neutrophil cytoplasmic antibodies, unlike other vasculitic disorders associated with them (such as granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis). This form of categorization is relevant for appropriate treatment.

The criteria are: erythema of the lips or oral cavity or cracking of the lips rash on the trunk swelling or erythema of the hands or feet red eyes (conjunctival injection) swollen lymph node in the neck of at least 15 mmMany children, especially infants, eventually diagnosed with Kawasaki disease, do not exhibit all of the above criteria. In fact, many experts now recommend treating for Kawasaki disease even if only three days of fever have passed and at least three diagnostic criteria are present, especially if other tests reveal abnormalities consistent with Kawasaki disease. In addition, the diagnosis can be made purely by the detection of coronary artery aneurysms in the proper clinical setting. Investigations A physical examination will demonstrate many of the features listed above. Blood tests Complete blood count may reveal normocytic anemia and eventually thrombocytosis. Erythrocyte sedimentation rate will be elevated. C-reactive protein will be elevated. Liver function tests may show evidence of hepatic inflammation and low serum albumin levels.Other optional tests include: Electrocardiogram may show evidence of ventricular dysfunction or, occasionally, arrhythmia due to myocarditis. Echocardiogram may show subtle coronary artery changes or, later, true aneurysms. Ultrasound or computerized tomography may show hydrops (enlargement) of the gallbladder. Urinalysis may show white blood cells and protein in the urine (pyuria and proteinuria) without evidence of bacterial growth. Lumbar puncture may show evidence of aseptic meningitis.

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Antidepressants of the SSRI or SNRI type are the first-line medications used for PTSD and are moderately beneficial for about half of people. Benefits from medication are less than those seen with counselling. It is not known whether using medications and counselling together has greater benefit than either method separately. Medications, other than some SSRIs or SNRIs, do not have enough evidence to support their use and, in the case of benzodiazepines, may worsen outcomes.In the United States, about 3.5% of adults have PTSD in a given year, and 9% of people develop it at some point in their life. In much of the rest of the world, rates during a given year are between 0.5% and 1%. Higher rates may occur in regions of armed conflict. It is more common in women than men.Symptoms of trauma-related mental disorders have been documented since at least the time of the ancient Greeks. A few instances of evidence of post-traumatic illness have been argued to exist from the seventeenth and eighteenth centuries, such as the diary of Samuel Pepys, who described intrusive and distressing symptoms following the 1666 Fire of London. During the world wars, the condition was known under various terms, including shell shock, war nerves, neurasthenia and combat neurosis. The term "post-traumatic stress disorder" came into use in the 1970s in large part due to the diagnoses of U.S. military veterans of the Vietnam War.

In music, an intermezzo (, Italian pronunciation: [interˈmɛddzo], plural form: intermezzi), in the most general sense, is a composition which fits between other musical or dramatic entities, such as acts of a play or movements of a larger musical work. In music history, the term has had several different usages, which fit into two general categories: the opera intermezzo and the instrumental intermezzo. Renaissance intermezzo The Renaissance intermezzo was also called the intermedio. It was a masque-like dramatic piece with music, which was performed between the acts of a play at Italian court festivities on special occasions, especially weddings. By the late 16th century, the intermezzo had become the most spectacular form of dramatic performance, and an important precursor to opera. The most famous examples were created for Medici weddings in 1539, 1565, and 1589. In Baroque Spain the equivalent entremés or paso was a one-act comic scene, often ending in music and dance, between jornadas (acts) of a play. Opera intermezzo The intermezzo, in the 18th century, was a comic operatic interlude inserted between acts or scenes of an opera seria. These intermezzi could be substantial and complete works themselves, though they were shorter than the opera seria which enclosed them; typically they provided comic relief and dramatic contrast to the tone of the bigger opera around them, and often they used one or more of the stock characters from the opera or from the commedia dellarte.

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Accessory breasts, also known as polymastia, supernumerary breasts, or mammae erraticae, is the condition of having an additional breast. Extra breasts may appear with or without nipples or areolae. It is a condition and a form of atavism which is most prevalent in male humans, and often goes untreated as it is mostly harmless. In recent years, many affected women have had a plastic surgery operation to remove the additional breasts, for purely aesthetic reasons. A related condition, in which extra nipples form, is called "supernumerary nipple" or "polythelia". Presentation In some cases, the accessory breast may not be visible at the surface. In these cases, it may be possible to distinguish their appearance from normal breast tissue with MRI. In other cases, accessory breasts have been known to lactate, as illustrated in a drawing showing a child nursing at ectopic breast tissue on the lateral thigh. There is some evidence that the condition may be more common in Native American populations. Cause Polymastia typically occurs in the womb during the development. During normal development, breast tissue will develop along the milk line, and additional tissue will disintegrate and be absorbed into the body. Polymastia occurs when the additional tissue does not disintegrate before birth. This condition can be inherited. See also Artemis § As the Lady of Ephesus (fertility goddess with many breasts) Fleischers syndrome References A Paper on the Appearance of Multiple Mammaries in Humans, R. Eghardt, Oxford University Press (1923) Weird Diseases, B. Hargreaves and M. Wallette, Emu Publishing (2007) == External links ==

Stasis dermatitis refers to the skin changes that occur in the leg as a result of "stasis" or blood pooling from insufficient venous return; the alternative name of varicose eczema comes from a common cause of this being varicose veins.Insufficient venous return results in increased pressure in the capillaries with the result that both fluid and cells may "leak" out of the capillaries. This results in red cells breaking down, with iron containing hemosiderin possibly contributing to the pathology of this entity. Symptoms Stasis dermatitis may be characterized by: Skin that appears thin, brown and tissue-like, with possible skin lesions (macule or patches), red spots, superficial skin irritation and/or darkening and/or thickening of the skin at the ankles or legs Weak skin may ulcerate in some areas and legs, ankles, or other areas may become swollen Open sores, ulcers Itching and/or leg pains Sometimes pain may persist from swollen tissues and may feel like "stabbing" or "needle pricks"If skin continues to deteriorate and breaks down, a venous ulcer (also known as a stasis ulcer) may form. Without proper wound care, open cracks predispose patients for the entry of a bacterial infection, causing cellulitis in the leg. Diagnosis Stasis dermatitis is diagnosed clinically by assessing the appearance of red plaques on the lower legs and the inner side of the ankle. Stasis dermatitis can resemble a number of other conditions, such as cellulitis and contact dermatitis, and at times needs the use of a duplex ultrasound to confirm the diagnosis or if clinical diagnosis alone is not sufficient.

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Other variants are less functional and are termed A-L and N-Z, dependent on whether they run proximal or distal to the M band. The presence of deviant bands on IEF can signify the presence of alpha-1 antitrypsin deficiency. Since the number of identified mutations has exceeded the number of letters in the alphabet, subscripts have been added to most recent discoveries in this area, as in the Pittsburgh mutation described above. As every person has two copies of the A1AT gene, a heterozygote with two different copies of the gene may have two different bands showing on electrofocusing, although heterozygote with one null mutant that abolishes expression of the gene will only show one band. In blood test results, the IEF results are notated as in PiMM, where Pi stands for protease inhibitor and "MM" is the banding pattern of that patient. Alpha-1 antitrypsin levels in the blood depend on the genotype. Some mutant forms fail to fold properly and are, thus, targeted for destruction in the proteasome, whereas others have a tendency to polymerise, being retained in the endoplasmic reticulum.

Relation to true melanoses The condition is unrelated to true melanoses, such as Peutz–Jeghers syndrome and smokers melanosis.Peutz–Jeghers syndrome causes pigmentation of the skin and mucous surfaces with melanin, and polyps in the digestive tract. Non-colonic pseudomelanoses Pseudomelanoses of other parts of the gastrointestinal tract have also been reported, and are of unclear relevance.Patients with colostomies can have melanosis involving the stoma, which is also of no significance. References == External links ==

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: 3 Self-esteem was believed to be a cultural phenomenon of Western individualistic societies since low self-esteem was not found in collectivist countries such as Japan. Concern about low self-esteem and its many presumed negative consequences led California assemblyman John Vasconcellos to work to set up and fund the Task Force on Self-Esteem and Personal and Social Responsibility, in California, in 1986. Vasconcellos argued that this task force could combat many of the states problems – from crime and teen pregnancy to school underachievement and pollution. He compared increasing self-esteem to giving out a vaccine for a disease: it could help protect people from being overwhelmed by lifes challenges. The task force set up committees in many California counties and formed a committee of scholars to review the available literature on self-esteem. This committee found very small associations between low self-esteem and its assumed consequences, ultimately showing that low self-esteem was not the root of all societal problems and not as important as the committee had originally thought. However, the authors of the paper that summarized the review of the literature still believed that self-esteem is an independent variable that affects major social problems. The task force disbanded in 1995, and the National Council for Self-Esteem and later the National Association for Self-Esteem (NASE) was established, taking on the task forces mission. Vasconcellos and Jack Canfield were members of its advisory board in 2003, and members of its masters coalition included Anthony Robbins, Bernie Siegel, and Gloria Steinem.

When children get older, they often realize and report to their parents that they do not actually possess a sense of smell, often to the surprise of their parents. Causes A temporary loss of smell can be caused by a blocked nose or infection. In contrast, a permanent loss of smell may be caused by death of olfactory receptor neurons in the nose or by brain injury in which there is damage to the olfactory nerve or damage to brain areas that process smell (see olfactory system). The lack of the sense of smell at birth, usually due to genetic factors, is referred to as congenital anosmia. Family members of the patient with congenital anosmia are often found with similar histories; this suggests that the anosmia may follow an autosomal dominant pattern. Anosmia may very occasionally be an early sign of a degenerative brain disease such as Parkinsons disease and Alzheimers disease.Another specific cause of permanent loss could be from damage to olfactory receptor neurons because of use of certain types of nasal spray; i.e., those that cause vasoconstriction of the nasal microcirculation. To avoid such damage and the subsequent risk of loss of smell, vasoconstricting nasal sprays should be used only when absolutely necessary and then for only a short amount of time. Non-vasoconstricting sprays, such as those used to treat allergy-related congestion, are safe to use for prescribed periods of time. Anosmia can also be caused by nasal polyps. These polyps are found in people with allergies, histories of sinusitis, and family history.

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HSV-1 most commonly infects the trigeminal ganglia, where it remains latent. If reactivated, it presents as herpes labialis, also known as cold sores. Diagnosis Histopathology The histological appearance of a herpetic infection on the mucosa includes degeneration of stratified squamous epithelial cells, the loss of intercellular connections and inflammatory infiltrate around the capillaries of the dermis layer. An intact herpetic vesicle presents as an intraepithelial blister histologically. This vesicle is caused by rupture and distension of the virally epithelial cells by intracellular oedema and coalescence of disrupted cells.Rupturing of the infected cells cause a great number of viral particles to be released, rendering them the ability to affect adjacent epithelial cells and even the sensory axons of the trigeminal nerve. Histologically, these infected cells have an eosinophilic cytoplasm and large, pale vesicular nuclei, appearing swollen under the microscope. The cytoplasms of the infected cells fuse, collectively forming giant cells with many nuclei. The balloon cells and multi-nucleated giant cells can often be identified in smears taken from an intact vesicle or from one which has been recently ruptured.The lamina propria shows a variable inflammatory infiltrate, the density of which depends on the stage and severity of the disease, and inflammatory cells also extend into the epithelium.Cowdry type A bodies are intranuclear inclusion bodies visible under light microscopy. They show electron dense glycoproteins and viral capsids. Both Cowdry type A bodies can both be found in varicella zoster and herpetic gingivostomatitis, making it impossible to distinguish between both eosinophilic bodies.

Signs and symptoms Current consensus is that atypical anorexia patients are at risk for the same medical complications of anorexia nervosa.Evidence from a study conducted at the University of California San Francisco Eating Disorders Program suggests that atypical anorexia patients are equally likely as anorexia nervosa patients to develop secondary side effects, including bradycardia (decreased heart rate), amenorrhea (stopping of the menstrual period), and electrolyte imbalances. Treatment Treatment for atypical anorexia is very similar to treatment for anorexia nervosa. Increasing calorie intake to a healthy amount is a crucial part of treatment, but patients with severe atypical anorexia are at risk for refeeding syndrome during early recovery, so it is recommended that they are treated in an inpatient facility and slowly adjusted to increased calorie intake by 100-200 additional calories per day. Treatment may also include a variety of therapies that help a patient deal with the depression, anxiety, and other mental symptoms that arise from the eating disorder.In the US, treatment may be complicated by the need to get health insurance plans to pay. Medical coding may be incorrect on requests or may be rejected because payers incorrectly evaluated it under the separate criteria for anorexia nervosa. Epidemiology It is difficult to gauge the true prevalence of atypical anorexia pre-2013 because patients were lumped together under the EDNOS diagnosis. Evidence suggests that atypical anorexia is more prevalent than anorexia nervosa, but individuals experiencing it are less likely to receive care.

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Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnancy, and in newborn babies to keep the ductus arteriosus open. In babies it is used in those with congenital heart defects until surgery can be carried out. It is also used to manage gestational trophoblastic disease. It may be used within the vagina or by injection into a vein.PGE2 synthesis within the body begins with the activation of arachidonic acid (AA) by the enzyme phospholipase A2. Once activated, AA is oxygenated by cyclooxygenase (COX) enzymes to form prostaglandin endoperoxides. Specifically, prostaglandin G2 (PGG2) is modified by the peroxidase moiety of the COX enzyme to produce prostaglandin H2 (PGH2) which is then converted to PGE2.Common side effects of PGE2 include nausea, vomiting, diarrhea, fever, and excessive uterine contraction. In babies there may be decreased breathing and low blood pressure. Caution should be taken in people with asthma or glaucoma and it is not recommended in those who have had a prior C-section. It works by binding and activating the prostaglandin E2 receptor which results in the opening and softening of the cervix and dilation of blood vessels.Prostaglandin E2 was first synthesized in 1970 and approved for medical use by the FDA in the United States in 1977. It is on the World Health Organizations List of Essential Medicines. Prostaglandin E2 works as well as prostaglandin E1 in babies.

In addition, PGE2 inhibits Na+ absorption within the Thick Ascending Limb (TAL) of the Loop of Henle and ADH-mediated water transport in collecting tubules. As a result, blockage of PGE2 synthesis with NSAIDs can limit the efficacy of loop diuretics. Administration Prostaglandin E2 (PGE2) should only be administered by, or under the direct supervision of, a physician and careful monitoring should be performed. PGE2 comes in many dosage forms with varying pharmacokinetic properties. For example PGE2 can come in a gel formulation that requires six hour dosing or it can come as a slow release dinoprostone pessary that does not need to be re-administered and can be taken out if necessary. In a quality improvement project done in UK, the switch from prostaglandin gel to the slow release dinoprostone pessary was able to lower cesarian section rates in women undergoing induction of labor in maternity care.For the vaginal insert (brand name Cervidil), the manufacturer recommends keeping the medication frozen until use since it does not need to be warmed to room temperature. Once the package is open, a water miscible lubricant may be used to insert the medication, using your finger place the device into the vagina and position the device transversely in the posterior vaginal fornix. The person receiving the drug should remain laying down for two hours after administration of the insert is complete.

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