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You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

I'm curious about the meaning of the medical term 'Soft tissue injury.' Can you give me some insights?

A soft tissue injury is the damage of muscles, ligaments and tendons throughout the body. Common soft tissue injuries usually occur from a sprain, strain, a one-off blow resulting in a contusion or overuse of a particular part of the body. Soft tissue injuries can result in pain, swelling, bruising and loss of function. Signs and symptoms Sprains A sprain is a type of acute injury which results from the stretching or tearing of a ligament. Depending on the severity of the sprain, the movement on the joint can be compromised since ligaments aid in the stability and support of joints. Sprains are commonly seen in vulnerable areas such as the wrists, knees and ankles. They can occur from movements such as falling on an outstretched hand or a twisting of the ankle or foot.The severity of a sprain can be classified: Grade 1: Only some of the fibers in the ligament are torn, and the injured site is moderately painful and swollen. Function in the joint will be unaffected for the most part. Grade 2: Many of the ligament fibers are torn, and pain and swelling is moderate. The functionality of the joint is compromised. Grade 3: The soft tissue is completely torn, and functionality and strength on the joint is completely compromised. In most cases, surgery is needed to repair the damage. Strains A strain is a type of acute injury that occurs to the muscle or tendon. Similar to sprains, it can vary in severity, from a stretching of the muscle or tendon to a complete tear of the tendon from the muscle. Some of the most common places that strains occur are in the foot, back of the leg (hamstring), or back. Bruising (contusion) A contusion is the discoloration of the skin, which results from underlying muscle fibers and connective tissue being crushed. This can happen in a variety of ways such as a direct blow to the skin, or a fall taken against a hard surface. The discoloration in the skin is present when blood begins to pool around the injury. Tendinitis Tendinitis is a type of overuse injury to the tendons, which demonstrates signs of inflammation of tendons around a joint. Tendinitis is the most common cause of shoulder pain and also leg pain . Tendinitis occurs when there is repetitive stress on the subacromial bursa, which causes the bones to make contact with the tendons and irritate them. Diagnosis Classifications Acute injuries Any type of injury that occurs to the body through sudden trauma, such as a fall, twist or blow to the body. A few examples of this type of injury would be sprains, strains and contusions. Overuse injuries An overuse injury occurs when a certain activity is repeated frequently and the body does not have enough time to recover between occurrences. Examples include bursitis and tendinitis. Commonly injured tissues With examples of each. Parentheses indicate location in body LigamentsAnterior cruciate ligament (knee), medial collateral ligament (knee), ulnar collateral ligaments (wrist/hand), interspinous ligaments (vertebrae)MusclesBiceps brachii (upper arm), rectus femoris (thigh), transverse abdominis (abdominals)TendonsPatellar tendon (knee), calcaneal/Achilles tendon (foot/lower leg), biceps tendon (shoulder/elbow)NervesBrachial plexus (shoulder), ulnar nerve (elbow/hand), peroneal nerve (ankle/foot), cranial nerves I-XII(head)BonesFemur (leg), humerus (arm), ribs (torso), metatarsals I-VI (foot), metacarpals I-VI (hand)CartilageMenisci (knee), intervertebral discs (spine), acetabulum (hip) Management RICE method The RICE method is an effective procedure used in the initial treatment of a soft tissue injury. Rest It is suggested that the patient take a break from the activity that caused the injury in order to give the injury time to heal. Ice The injury should be iced on and off in 20 minute intervals, avoiding direct contact of the ice with the skin. Compression Bandaging the injury will compress it, and prevent any further bleeding or swelling from occurring. Elevation Elevating the injury above the heart while resting will aid in the reduction of swelling. No HARM protocol This mnemonic indicates what not to do within the first 48–72 hours after the injury in order to speed up the recovery process. Heat Applying heat to the injured area can cause blood flow and swelling to increase. Alcohol Alcohol can inhibit the ability to feel if the injury is becoming more aggravated, as well as increasing blood flow and swelling. Re-injury Avoid any activities that could aggravate the injury and cause further damage. Massage Massaging an injured area can promote blood flow and swelling, and potentially cause more damage if done too early. Treatment If severe pain persists after the first 24hours it is recommended that an individual consult with a professional who can make a diagnosis and implement a treatment plan so the patient can return to everyday activities. To make a full diagnosis, a professional may use nerve conduction studies to localize nerve dysfunction (e.g. carpal tunnel syndrome), assess severity, and help with prognosis. Electrodiagnosis also helps differentiate between myopathy and neuropathy. Using the RICE method can somewhat be controversial as the science behind using ice is not necessarily very clear. On one hand, ice diminishes pain, metabolism, and muscle spasms. It also minimizes the inflammatory process and edema, which helps one recover from a soft-tissue injury. However, creatine kinase-MB isoform and myoglobin levels circulating in the blood increased after exercising. Ice impedes the recovery process by keeping the Creatine kinase-MB isoform and myoglobin levels increased 2–3 days post exercise. It is therefore important to weigh the pros and cons before applying any treatment, including the use of ice. Ultimately, the best method of imaging soft tissue is magnetic resonance imaging (MRI), though it is cost-prohibitive and carries a high false positive rate. References Sources Flegel, Melinda J. (2004). Sport first aid: A coach’s guide to preventing and responding to injuries. Hong Kong, Japan: Human Kinetics. Lindsay, R., Watson, G., Hickmont, D., Broadfoot, A., & Bruynel, L. (1994). Treat your own strains sprains and bruises. New Zealand: Spinal Publications. Lovering, R.M. (2008). "Physical therapy and related interventions". In P.M. Tiidus (ed.), Skeletal muscle damage and repair (pp. 219–230). United States of America: Human Kinetics. Prentice, William E. "Tissue Response to Injury", Principles of Athletic Training: A Competency Based Approach. 14th ed. New York: McGraw Hill Companies, 2011. 260–277. Subotnick, Steven (1991). Sports and Exercise Injuries: Conventional, Homeopathic and Alternative Treatments. California, United States of America: North Atlantic Books.

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I've come across the term 'Rifapentine' in a medical context, but I'm not sure what it means. Can you clarify?

Rifapentine, sold under the brand name Priftin, is an antibiotic used in the treatment of tuberculosis. In active tuberculosis it is used together with other antituberculosis medications. In latent tuberculosis it is typically used with isoniazid. It is taken by mouth.Common side effects include low neutrophil counts in the blood, elevated liver enzymes, and white blood cells in the urine. Serious side effects may include liver problems or Clostridium difficile associated diarrhea. It is unclear if use during pregnancy is safe. Rifapentine is in the rifamycin family of medication and works by blocking DNA-dependent RNA polymerase.Rifapentine was approved for medical use in the United States in 1998. It is on the World Health Organizations List of Essential Medicines. In many areas of the world it is not easy to get as of 2015. Medical uses A systematic review of regimens for prevention of active tuberculosis in HIV-negative individuals with latent TB found that a weekly, directly observed regimen of rifapentine with isoniazid for three months was as effective as a daily, self-administered regimen of isoniazid for nine months. The three-month rifapentine-isoniazid regimen had higher rates of treatment completion and lower rates of hepatotoxicity. However, the rate of treatment-limiting adverse events was higher in the rifapentine-isoniazid regimen compared to the nine-month isoniazid regimen. Pregnancy Rifapentine has been assigned a pregnancy category C by the U.S. Food and Drug Administration (FDA). Rifapentine in pregnant women has not been studied, but animal reproduction studies have resulted in fetal harm and were teratogenic. 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). CPNP belongs to the nitrosamine class of compounds, some of which are classified as probable or possible human carcinogens (substances that could cause cancer), based on laboratory tests such as rodent carcinogenicity studies. Although there are no data available to directly evaluate the carcinogenic potential of CPNP, information available on closely related nitrosamine compounds was used to calculate lifetime exposure limits for CPNP.As of January 2021, the FDA continues to investigate the presence of 1-methyl-4-nitrosopiperazine (MNP) in rifampin or 1-cyclopentyl-4-nitrosopiperazine (CPNP) in rifapentine approved for sale in the US. See also Rifampicin Isoniazid Rifamycin Rifabutin References External links "Rifapentine". Drug Information Portal. U.S. National Library of Medicine.

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Please help me grasp the concept behind the medical term 'Dolichocephaly.'

Dolichocephaly (derived from the Ancient Greek δολιχός long and κεφαλή head) is a condition where the head is longer than would be expected, relative to its width. In humans, scaphocephaly is a form of dolichocephaly. Dolichocephalic dogs (such as German Shepherds) have elongated noses. This makes them vulnerable to fungal diseases of the nose such as aspergillosis. In humans the anterior–posterior diameter (length) of dolichocephaly head is more than the transverse diameter (width).It can be present in cases of Sensenbrenner syndrome, Crouzon syndrome, Sotos syndrome, CMFTD as well as Marfan syndrome. See also Brachycephaly Cephalic index Plagiocephaly References == External links ==

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I've encountered the term 'De Quervain syndrome' while reading about medical topics. What does it refer to exactly?

De Quervain syndrome is mucoid degeneration of two tendons that control movement of the thumb and their tendon sheath. This results in pain and tenderness on the thumb side of the wrist. Radial abduction of the thumb is painful. On occasion, there is uneven movement or triggering the thumb with radial abduction. Symptoms can come on gradually or be noted suddenly.There is speculation that the problem is related to use of the hand, but this is not supported by experimental evidence. Humans tend to misinterpret painful activities as causing the problem to get worse and this misinterpretation is associated with greater pain intensity. For this reason, its better not to blame activity without strong scientific support. The diagnosis is generally based on symptoms and physical examination. Diagnosis is supported if pain increases when the wrist is bent inwards while a person is grabbing their thumb within a fist.There is some evidence that the natural history of de Quervain tendinopathy is resolution over a period of about 1 year. Symptomatic alleviation (palliative treatment) is provided mainly by splinting the thumb and wrist. Pain medications such as NSAIDs can also be considered. Steroid injections are commonly used, but are not proved to alter the natural history of the condition. Surgery to release the first dorsal component is an option. It may be most common in middle age. Signs and symptoms Symptoms are pain and tenderness at the radial side of the wrist, fullness or thickening over the thumb side of the wrist, and difficulty gripping with the affected side of the hand. The onset is often gradual. Pain is made worse by movement of the thumb and wrist, and may radiate to the thumb or the forearm. Causes The cause of de Quervains disease is not established. Evidence regarding a possible relation with activity and occupation is debated. A systematic review of potential risk factors discussed in the literature did not find any evidence of a causal relationship with activity or occupation. However, researchers in France found personal and work-related factors were associated with de Quervains disease in the working population; wrist bending and movements associated with the twisting or driving of screws were the most significant of the work-related factors. Proponents of the view that De Quervain syndrome is a repetitive strain injury consider postures where the thumb is held in abduction and extension to be predisposing factors. Workers who perform rapid repetitive activities involving pinching, grasping, pulling or pushing have been considered at increased risk. These movements are associated with many types of repetitive housework such as chopping vegetables, stirring and scrubbing pots, vacuuming, cleaning surfaces, drying dishes, pegging out washing, mending clothes, gardening, harvesting and weeding. Specific activities that have been postulated as potential risk factors include intensive computer mouse use, trackball use, and typing, as well as some pastimes, including bowling, golf, fly-fishing, piano-playing, sewing, and knitting.Women are diagnosed more often than men. The syndrome commonly occurs during and, even more so, after pregnancy. Contributory factors may include hormonal changes, fluid retention and—again, more debatably and potentially harmfully—increased housework and lifting. Pathophysiology De Quervain syndrome involves noninflammatory thickening of the tendons and the synovial sheaths that the tendons run through. The two tendons concerned are those of the extensor pollicis brevis and abductor pollicis longus muscles. These two muscles run side by side and function to bring the thumb away from the hand; the extensor pollicis brevis brings the thumb outwards radially, and the abductor pollicis longus brings the thumb forward away from the palm. De Quervain tendinopathy affects the tendons of these muscles as they pass from the forearm into the hand via a fibro-osseous tunnel (the first dorsal compartment). Evaluation of histopathological specimens shows a thickening and myxoid degeneration consistent with a chronic degenerative process, as opposed to inflammation. The pathology is identical in de Quervain seen in new mothers. Diagnosis De Quervain syndrome is diagnosed clinically, based on history and physical examination, though diagnostic imaging such as X-ray may be used to rule out fracture, arthritis, or other causes, based on the persons history and presentation. The modified Eichoff maneuver, commonly called the Finkelsteins test, is a physical exam maneuver used to diagnose de Quervain syndrome. To perform the test, the examiner grasps and ulnar deviates the hand when the person has their thumb held within their fist. If sharp pain occurs along the distal radius (top of forearm, about an inch below the wrist), de Quervains syndrome is likely. While a positive Finkelsteins test is often considered pathognomonic for de Quervain syndrome, the maneuver can also cause pain in those with osteoarthritis at the base of the thumb. Differential diagnosis Differential diagnoses include: Osteoarthritis of the trapezio-metacarpal joint Intersection syndrome—pain will be more towards the middle of the back of the forearm and about 2–3 inches below the wrist, usually with associated crepitus. Wartenbergs syndrome: The primary symptom is paresthesia (numbness/tingling). Treatment As with many musculoskeletal conditions, the management of de Quervains disease is determined more by convention than scientific data. A systematic review and meta-analysis published in 2013 found that corticosteroid injection seems to be an effective form of conservative management of de Quervains syndrome in approximately 50% of patients, although more research is needed regarding the extent of any clinical benefits. Efficacy data are relatively sparse and it is not clear whether benefits affect the overall natural history of the illness. One of the most common causes of corticosteroid injection failure are subcompartments of the extensor pollicis brevis tendon.Most tendinoses are self-limiting and the same is likely to be true of de Quervains although further study is needed.Palliative treatments include a splint that immobilized the wrist and the thumb to the interphalangeal joint and anti-inflammatory medication or acetaminophen. Systematic review and meta-analysis do not support the use of splinting over steroid injections.Surgery (in which the sheath of the first dorsal compartment is opened longitudinally) is documented to provide relief in most patients. The most important risk is to the radial sensory nerve. A small incision is made and the dorsal extensor retinaculum is identified. Once it has been identified the release is performed longitudinally along the tendon. This is done to prevent potential subluxation of the 1st compartment tendons. Next the abductor pollicis longus (APL) and extensor pollicis brevis (EPB) are identified and the compartments are released.Some occupational and physical therapists suggest alternative lifting mechanics based on the theory that the condition is due to repetitive use of the thumbs during lifting. Physical/Occupational therapy can suggest activities to avoid based on the theory that certain activities might exacerbate ones condition, as well as instruct on strengthening exercises based on the theory that this will contribute to better form and use of other muscle groups, which might limit irritation of the tendons.Some occupational and physical therapists use other treatments, in conjunction with Therapeutic Exercises, based on the rationale that they reduce inflammation and pain and promote healing: UST, SWD, or other deep heat treatments, as well as TENS, acupuncture, or infrared light therapy, and cold laser treatments. However, the pathology of the condition is not inflammatory changes to the synovial sheath and inflammation is secondary to the condition from friction. Teaching patients to reduce their secondary inflammation does not treat the underlying condition but may reduce their pain; which is helpful when trying to perform the prescribed exercise interventions. Getting Physical Therapy before surgery has shown to reduce overall cost of therapy. History From the original description of the illness in 1895 until the first description of corticosteroid injection by Jarrod Ismond in 1955, it appears that the only treatment offered was surgery. Since approximately 1972, the prevailing opinion has been that of McKenzie (1972) who suggested that corticosteroid injection was the first line of treatment and surgery should be reserved for unsuccessful injections. Eponym It is named after the Swiss surgeon Fritz de Quervain who first identified it in 1895. It should not be confused with de Quervains thyroiditis, another condition named after the same person. Society and culture BlackBerry thumb is a neologism that refers to a form of repetitive strain injury (RSI) caused by the frequent use of the thumbs to press buttons on PDAs, smartphones, or other mobile devices. The name of the condition comes from the BlackBerry, a brand of smartphone that debuted in 1999, although there are numerous other similar eponymous conditions that exist such as "Wiiitis", "Nintendinitis", "Playstation thumb", "texting thumb", "cellphone thumb", "smartphone thumb", "Android thumb", and "iPhone thumb". The medical name for the condition is De Quervain syndrome and is associated with the tendons connected to the thumb through the wrist. Causes for the condition extend beyond smartphones and gaming consoles to include activities like golf, racket sports, and lifting.Symptoms of BlackBerry thumb include aching and throbbing pain in the thumb and wrist. In severe cases, it can lead to temporary disability of the affected hand, particularly the ability to grip objects.One hypothesis is that the thumb does not have the dexterity the other four fingers have and is therefore not well-suited to high speed touch typing. See also Mobile phone overuse Nomophobia References == External links ==

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The term 'Pseudohyperaldosteronism' keeps coming up in medical discussions. What does it stand for?

Pseudohyperaldosteronism (also pseudoaldosteronism) is a medical condition which mimics the effects of elevated aldosterone (hyperaldosteronism) by presenting with high blood pressure (hypertension), low blood potassium levels (hypokalemia), metabolic alkalosis, and low levels of plasma renin activity (PRA). However, unlike hyperaldosteronism, this conditions exhibits low or normal levels of aldosterone in the blood. Causes include genetic disorders (e.g. Apparent mineralocorticoid excess syndrome, Liddles syndrome, and types of Congenital adrenal hyperplasia), acquired conditions (e.g. Cushings syndrome and mineralocorticoid-producing adrenal tumors), metabolic disorders, and dietary imbalances including excessive consumption of licorice. Confirmatory diagnosis depends on the specific root cause and may involve blood tests, urine tests, or genetic testing; however, all forms of this condition exhibit abnormally low concentrations of both plasma renin activity (PRA) and plasma aldosterone concentration (PAC) which differentiates this group of conditions from other forms of secondary hypertension. Treatment is tailored to the specific cause and focuses on symptom control, blood pressure management, and avoidance of triggers. Presentation The presentation of pseudohyperaldosteronism varies depending on the cause. The genetic conditions such as Liddles syndrome and Congenital adrenal hyperplasia present in childhood or earlier in life than the acquired causes which can present at any age. Adult patients present with clinical history of resistant hypertension despite typical medical therapy and lifestyle changes. Hypertension may be asymptomatic or may lead to symptoms such as headache, dizziness, vision changes, or kidney disease. Symptoms of hypokalemia include fatigue, muscular weakness, and increased urine production. Causes This condition has several known causes including genetic disorders, acquired conditions, metabolic derangements, and dietary imbalances. All causes mimic the effects of elevated aldosterone without raising aldosterone levels but achieve this through varying mechanisms. Genetic forms Genetic disorders that lead to this condition include Liddles syndrome, Apparent mineralocorticoid excess (AME), and two types of Congenital adrenal hyperplasia (CAH). Liddles syndrome is autosomal dominant disorder affecting epithelial sodium channels (ENaC) in the distal tubules of the kidneys. In this disorder, a gain of function mutation decreases ENaC degradation leading to increased renal absorption of sodium and water. Apparent mineralocorticoid excess genetic forms include autosomal recessive disorders with mutations lowering the activity of the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (11-β-HSD2). These mutations limit the ability of 11-β-HSD2 to transform active cortisol to the less active cortisone. Excess cortisol is then able to bind and activate mineralocorticoid receptors due to receptor cross-reactivity leading to aldosterone-like effects. Congenital Adrenal Hyperplasia is an autosomal recessive disorder with multiple types, two of which lead to pseudohyperaldosteronism. Deficiency of 11-beta-hydroxylase blocks the conversion of 11-deoxycorticosterone (DOC) to corticosterone leading to an excess of DOC which acts as a mineralocorticoid similar to aldosterone. Deficiency of 17-alpha-hydroxylase blocks the conversion of pregnenolone and progesterone to their 17-a-hydroxy forms leading to increased mineralocorticoid production. Acquired forms Some causes of pseudohyperaldosteronism can be acquired throughout life with examples including adrenal tumors and Ectopic ACTH syndrome. Adrenal tumor subtypes include adrenal adenomas that produce 11-deoxycorticosterone (DOC) leading to increased mineralocorticoid activity without elevated aldosterone. Ectopic ACTH syndrome describes conditions leading to excess production of adrenocorticotropic hormone (ACTH) subsequently leading to mineralocorticoid production. This can arise in ectopic forms of Cushings syndrome associated with small-cell lung cancers and other ACTH-producing tumors. The excess ACTH can saturate the 11-β-HSD2 enzyme leading to decreased conversion of cortisol to cortisone and increased mineralocorticoid effects. Metabolic and dietary forms Metabolic causes include conditions of glucocorticoid resistance and from mineralocorticoid excess which can occur following high-dose corticosteroid therapy. Dietary causes include overconsumption of licorice-containing products. Glycyrrhetinic acid in licorice inhibits the 11-β-HSD2 enzyme resulting in inappropriate stimulation of the mineralocorticoid receptor by cortisol leading to aldosterone-like effects. Diagnosis In patients with hypertension, diagnostic clues pointing to pseudohyperaldosteronism can be found on routine labwork. These include low serum potassium (hypokalemia), elevated serum sodium (hypernatremia), and elevated serum bicarbonate (metabolic alkalosis). Urine studies may show elevated urine potassium (kaliuresis). To further differentiate between hyperaldosteronism and pseudohyperaldosteronism, studies including plasma renin activity (PRA) and plasma aldosterone concentration (PAC) can be obtained. Pseudohyperaldosteronism will exhibit low levels of both PRA and PAC while hyperaldosteronism will demonstrate elevated PAC. Confirmatory tests to diagnose the specific forms of pseudohyperaldosteronism vary depending on the cause. The genetic conditions such as Liddles syndrome and CAH can be confirmed with genetic tests for the affected genes. CAH can also be confirmed by analyzing enzyme levels following ACTH stimulation testing. AME can be diagnosed with a 24 hour urine collection exhibiting an increased ratio of urinary cortisol to urinary cortisone. Treatment Specific treatment of pseudohyperaldosteronism depends on the inciting cause. General management focuses on countering the effects of excess mineralocorticoid activity to achieve adequate blood pressure control and avoid end-organ damage and cardiovascular mortality. In some cases, specific antihypertensive medications may be recommended. In Liddles syndrome, ENaC-binding potassium-sparing diuretics (e.g. amiloride or triamterene) are used to counter the excess ENaC activity. In AME, the mineralocorticoid receptor-binding potassium-sparing diuretics (e.g. spironolactone or eplerenone) are used to limit aldosterone receptor activity. Other medications such as glucocorticoids are added in AME and CAH to inhibit ACTH and further cortisol production. Lifestyle changes such as a low sodium diet are also used for managing hypertension, and cessation of licorice intake is recommended in cases of licorice overconsumption. See also Apparent mineralocorticoid excess syndrome Primary aldosteronism Secondary hypertension References == External links ==

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I'd like to learn more about the medical term 'Crigler–Najjar syndrome.' Can you provide some details?

Crigler–Najjar syndrome is a rare inherited disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of the heme in red blood cells. The disorder results in a form of nonhemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in infants. The disorder is inherited in an autosomal recessive manner. The annual incidence is estimated at 1 in 1,000,000.This syndrome is divided into types I and II, with the latter sometimes called Arias syndrome. These two types, along with Gilberts syndrome, Dubin–Johnson syndrome, and Rotor syndrome, make up the five known hereditary defects in bilirubin metabolism. Unlike Gilberts syndrome, only a few causes of Crigler–Najjar syndrome are known. Signs and symptoms Jaundice Diarrhea Vomiting Fever Confusion Slurred speech Difficulty swallowing Change in gait, staggering frequent falling Seizures Cause It is caused by abnormalities in the gene coding for uridine diphosphoglucuronate glucuronosyltransferase (UGT1A1). UGT1A1 normally catalyzes the conjugation of bilirubin and glucuronic acid within hepatocytes. Conjugated bilirubin is more water-soluble and is excreted in bile. Diagnosis Type I This is a very rare disease (estimated at 0.6–1.0 per million live births), and consanguinity increases the risk of this condition (other rare diseases may be present). Inheritance is autosomal recessive. Intense jaundice appears in the first days of life and persists thereafter. Type 1 is characterised by a serum bilirubin usually above 345 μmol/L [20 mg/dL] (range 310–755 μmol/L [18–44 mg/dL]) (whereas the reference range for total bilirubin is 2–14 μmol/L [0.1–0.8 mg/dL]). No UDP glucuronosyltransferase 1-A1 expression can be detected in the liver tissue. Hence, there is no response to treatment with phenobarbital, which causes CYP450 enzyme induction. Most patients (type IA) have a mutation in one of the common exons (2 to 5), and have difficulties conjugating several additional substrates (several drugs and xenobiotics). A smaller percentage of patients (type IB) have mutations limited to the bilirubin-specific A1 exon; their conjugation defect is mostly restricted to bilirubin itself. Before the availability of phototherapy, these children died of kernicterus (bilirubin encephalopathy) or survived until early adulthood with clear neurological impairment. Today, therapy includes exchange transfusions in the immediate neonatal period 12 hours/day phototherapy heme oxygenase inhibitors to reduce transient worsening of hyperbilirubinemia (although the effect of the drug decreases over time) oral calcium phosphate and carbonate to form complexes with bilirubin in the gut liver transplantation before the onset of brain damage and before phototherapy becomes ineffective at later age Type II The inheritance patterns of both Crigler–Najjar syndrome types I and II are autosomal recessive.However, type II differs from type I in a number of different aspects: Bilirubin levels are generally below 345 μmol/L [20 mg/dL] (range 100–430 μmol/L [6–24 mg/dL]; thus, overlap may sometimes occur), and some cases are only detected later in life. Because of lower serum bilirubin, kernicterus is rare in type II. Bile is pigmented, instead of pale in type I or dark as normal, and monoconjugates constitute the largest fraction of bile conjugates. UGT1A1 is present at reduced but detectable levels (typically <10% of normal), because of single base pair mutations. Therefore, treatment with phenobarbital is effective, generally with a decrease of at least 25% in serum bilirubin. In fact, this can be used, along with these other factors, to differentiate type I and II. Differential diagnosis Neonatal jaundice may develop in the presence of sepsis, hypoxia, hypoglycemia, hypothyroidism, hypertrophic pyloric stenosis, galactosemia, fructosemia, etc. Hyperbilirubinemia of the unconjugated type may be caused by: increased production hemolysis (e.g., hemolytic disease of the newborn, hereditary spherocytosis, sickle cell disease) ineffective erythropoiesis massive tissue necrosis or large hematomas decreased clearance drug-induced physiological neonatal jaundice and prematurity liver diseases such as advanced hepatitis or cirrhosis breast milk jaundice and Lucey–Driscoll syndrome Crigler–Najjar syndrome and Gilbert syndromeIn Crigler–Najjar syndrome and Gilbert syndrome, routine liver function tests are normal, and hepatic histology usually is normal, too. No evidence for hemolysis is seen. Drug-induced cases typically regress after discontinuation of the substance. Physiological neonatal jaundice may peak at 85–170 μmol/L and decline to normal adult concentrations within two weeks. Prematurity results in higher levels. Treatment Plasmapheresis and phototherapy are used for treatment. Liver transplant is curative. Research A San Francisco-based company named Audentes Therapeutics is currently investigating the treatment of Crigler–Najjar syndrome with one of their gene replacement therapy products, AT342. Preliminary success has been found in early stages of a phase 1/2 clinical trial.One 10-year-old girl with Crigler–Najjar syndrome type I was successfully treated by liver cell transplantation.The homozygous Gunn rat, which lacks the enzyme uridine diphosphate glucuronyltransferase (UDPGT), is an animal model for the study of Crigler–Najjar syndrome. Since only one enzyme is working improperly, gene therapy for Crigler-Najjar is a theoretical option which is being investigated. Eponym The condition is named for John Fielding Crigler (1919 – May 13, 2018), an American pediatrician and Victor Assad Najjar (1914–2002), a Lebanese-American pediatrician. References External links Crigler–Najjar syndrome, type 1 at NIHs Office of Rare Diseases Crigler–Najjar syndrome, type 2 at NIHs Office of Rare Diseases

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I'm curious about the meaning of the medical term 'Belumosudil.' Can you give me some insights?

Belumosudil, sold under the brand name Rezurock among others, is a medication used for the treatment of chronic graft versus host disease (cGvHD).It is in the class of drugs known as serine/threonine kinase inhibitors. Specifically, it is an inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2; ROCK-II). Belumosudil binds to and inhibits the serine/threonine kinase activity of ROCK2. This inhibits ROCK2-mediated signaling pathways which play major roles in pro- and anti-inflammatory immune cell responses. A genomic study in human primary cells demonstrated that the drug also has effects on oxidative phosphorylation, WNT signaling, angiogenesis, and KRAS signaling.The most common side effects include infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma glutamyl transferase increased, lymphocytes decreased, and hypertension.Belumosudil was approved for medical use in the United States in July 2021. Medical uses Belumosudil is indicated for the treatment of people aged 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy. History Originally developed by Surface Logix, Inc, belumosudil was later acquired by Kadmon Corporation. By July 2020, the drug completed Phase II clinical studies for cGvHD, IPF, and psoriasis.cGvHD is a complication that can follow allogeneic stem cell or hematopoietic stem cell transplantation where the transplanted cells (graft) attack healthy cells (host). This causes inflammation and fibrosis in multiple tissues. Two cytokines controlled by the ROCK2 signaling pathway, IL-17 and IL-21, have a major role in the cGvHD response. In a 2016 report using both mouse models and a limited human clinical trial ROCK2 inhibition with belumosudil targeted both the immunologic and fibrotic components of cGvHD and reversed the symptoms of the disease.In October 2017, belumosudil was granted orphan drug status in the United States for treatment of patients with cGvHD.Efficacy of belumosudil was evaluated in clinical trial NCT03640481, a randomized, open-label, multicenter dose-ranging trial that included 65 patients with chronic GVHD who were treated with belumosudil 200 mg taken orally once daily.On 16 July 2021, the U.S. Food and Drug Administration (FDA) approved belumosudil for adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy. Research IPF is a progressive fibrotic disease where the lining of the lungs become thickened and scarred. Increased ROCK activity has been found in the lungs of humans and animals with IPF. Treatment with belumosudil reduced lung fibrosis in a bleomycin mouse model study.Psoriasis is an inflammatory skin condition where patients experiences eruptions and remissions of thickened, erythematous, and scaly patches of skin. Down-regulation of pro-inflammatory responses was observed with KD025 treatment in Phase 2 clinical studies in patients with moderate to severe psoriasis. References External links "Belumosudil". Drug Information Portal. U.S. National Library of Medicine.

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Can you demystify the medical term 'Omphalitis of newborn' for me?

Omphalitis of newborn is the medical term for inflammation of the umbilical cord stump in the neonatal newborn period, most commonly attributed to a bacterial infection. Typically immediately after an infant is born, the umbilical cord is cut with a small remnant (often referred to as the stump) left behind. Normally the stump separates from the skin within 3–45 days after birth. A small amount of pus-like material is commonly seen at the base of the stump and can be controlled by keeping the stump open to air to dry. Certain bacteria can grow and infect the stump during this process and as a result significant redness and swelling may develop, and in some cases the infection can then spread through the umbilical vessels to the rest of the body. While currently an uncommon anatomical location for infection in the newborn in the United States, it has caused significant morbidity and mortality both historically and in areas where health care is less readily available. In general, when this type of infection is suspected or diagnosed, antibiotic treatment is given, and in cases of serious complications surgical management may be appropriate. Signs and symptoms Clinically, neonates with omphalitis present within the first two weeks of life with signs and symptoms of a skin infection (cellulitis) around the umbilical stump (redness, warmth, swelling, pain), pus from the umbilical stump, fever, fast heart rate (tachycardia), low blood pressure (hypotension), somnolence, poor feeding, and yellow skin (jaundice). Omphalitis can quickly progress to sepsis and presents a potentially life-threatening infection. In fact, even in cases of omphalitis without evidence of more serious infection such as necrotizing fasciitis, mortality is high (in the 10% range). Causes Omphalitis is most commonly caused by bacteria. The culprits usually are Staphylococcus aureus, Streptococcus, and Escherichia coli. The infection is typically caused by a combination of these organisms and is a mixed Gram-positive and Gram-negative infection. Anaerobic bacteria can also be involved. Diagnosis In a normal umbilical stump, you first see the umbilicus lose its characteristic bluish-white, moist appearance and become dry and black After several days to weeks, the stump should fall off and leave a pink fleshy wound which continues to heal as it becomes a normal umbilicus.For an infected umbilical stump, diagnosis is usually made by the clinical appearance of the umbilical cord stump and the findings on history and physical examination. There may be some confusion, however, if a well-appearing neonate simply has some redness around the umbilical stump. In fact, a mild degree is common, as is some bleeding at the stump site with detachment of the umbilical cord. The picture may be clouded even further if caustic agents have been used to clean the stump or if silver nitrate has been used to cauterize granulomata of the umbilical stump. Prevention During the 1950s there were outbreaks of omphalitis that then led to anti-bacterial treatment of the umbilical cord stump as the new standard of care. It was later determined that in developed countries keeping the cord dry is sufficient, (known as "dry cord care") as recommended by the American Academy of Pediatrics. The umbilical cord dries more quickly and separates more readily when exposed to air However, each hospital/birthing center has its own recommendations for care of the umbilical cord after delivery. Some recommend not using any medicinal washes on the cord. Other popular recommendations include triple dye, betadine, bacitracin, or silver sulfadiazine. With regards to the medicinal treatments, there is little data to support any one treatment (or lack thereof) over another. However one recent review of many studies supported the use of chlorhexidine treatment as a way to reduce risk of death by 23% and risk of omphalitis by anywhere between 27 and 56% in community settings in underdeveloped countries. This study also found that this treatment increased the time that it would take for the umbilical stump to separate or fall off by 1.7 days. Lastly this large review also supported the notion that in hospital settings no medicinal type of cord care treatment was better at reducing infections compared to dry cord care. Treatment Treatment consists of antibiotic therapy aimed at the typical bacterial pathogens in addition to supportive care for any complications which might result from the infection itself such as hypotension or respiratory failure. A typical regimen will include intravenous antibiotics such as from the penicillin-group which is active against Staphylococcus aureus and an aminoglycoside for activity against Gram-negative bacteria. For particularly invasive infections, antibiotics to cover anaerobic bacteria may be added (such as metronidazole). Treatment is typically for two weeks and often necessitates insertion of a central venous catheter or peripherally inserted central catheter. Epidemiology The current incidence in the United States is somewhere around 0.5% per year; overall, the incidence rate for developed world falls between 0.2 and 0.7%. In developing countries, the incidence of omphalitis varies from 2 to 7 for 100 live births. There does not appear to be any racial or ethnic predilection. Like many bacterial infections, omphalitis is more common in those patients who have a weakened or deficient immune system or who are hospitalized and subject to invasive procedures. Therefore, infants who are premature, sick with other infections such as blood infection (sepsis) or pneumonia, or who have immune deficiencies are at greater risk. Infants with normal immune systems are at risk if they have had a prolonged birth, birth complicated by infection of the placenta (chorioamnionitis), or have had umbilical catheters. References == External links ==

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Can you demystify the medical term 'Pendred syndrome' for me?

Pendred syndrome is a genetic disorder leading to congenital bilateral (both sides) sensorineural hearing loss and goitre with euthyroid or mild hypothyroidism (decreased thyroid gland function). There is no specific treatment, other than supportive measures for the hearing loss and thyroid hormone supplementation in case of hypothyroidism. It is named after Vaughan Pendred (1869–1946), the British doctor who first described the condition in an Irish family living in Durham in 1896. It accounts for 7.5% to 15% of all cases of congenital deafness. Signs and symptoms The hearing loss of Pendred syndrome is often, although not always, present from birth, and language acquisition may be a significant problem if deafness is severe in childhood. The hearing loss typically worsens over the years, and progression can be step-wise and related to minor head trauma. In some cases, language development worsens after head injury, demonstrating that the inner ear is sensitive to trauma in Pendred syndrome; this is as a consequence of the widened vestibular aqueducts usual in this syndrome. Vestibular function varies in Pendred syndrome and vertigo can be a feature of minor head trauma. A goitre is present in 75% of all cases. Genetics Pendred syndrome is inherited in an autosomal recessive manner, meaning that one would need to inherit an abnormal gene from each parent to develop the condition. This also means that a sibling of a patient with Pendred syndrome has a 25% chance of also having the condition if the parents are unaffected carriers.It has been linked to mutations in the PDS gene, which codes for the pendrin protein (solute carrier family 26, member 4, SLC26A4). The gene is located on the long arm of chromosome 7 (7q31). Mutations in the same gene also cause enlarged vestibular aqueduct syndrome (EVA or EVAS), another congenital cause of deafness; specific mutations are more likely to cause EVAS, while others are more linked with Pendred syndrome. Pathophysiology SLC26A4 can be found in the cochlea (part of the inner ear), thyroid and the kidney. In the kidney, it participates in the secretion of bicarbonate. However, Pendred syndrome is not known to lead to kidney problems. It functions as an iodide/chloride transporter. In the thyroid, this leads to reduced organification of iodine (i.e. its incorporation into thyroid hormone). Diagnosis People with Pendred syndrome present with a hearing loss either at birth or during childhood. The hearing loss is commonly progressive. In early stages it is usually a mixed hearing loss (both conductive and sensorineural hearing loss) because of a third window effect due to the inner ear malformation (widened vestibular aqueducts). A thyroid goitre may be present in the first decade and is usual towards the end of the second decade. MRI scanning of the inner ear usually shows widened or large vestibular aqueducts with enlarged endolymphatic sacs and may show abnormalities of the cochleae that are known as Mondini dysplasia. Genetic testing to identify the pendrin gene usually establishes the diagnosis. If the condition is suspected, a "perchlorate discharge test" is sometimes performed. This test is highly sensitive, but may also be abnormal in other thyroid conditions. If a goitre is present, thyroid function tests are performed to identify mild cases of thyroid dysfunction even if they are not yet causing symptoms. Treatment No specific treatment exists for Pendred syndrome. If thyroid hormone levels are decreased, thyroid hormone supplements may be required. Patients are advised to take precautions against head injury. References External links GeneReviews/NCBI/NIH/UW entry on Pendred Syndrome/DFNB4 NCBI Genes and Diseases

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

I'm encountering the term 'Autumn' in medical literature. What's its definition?

Autumn, also known as fall in American English and Canadian English, is one of the four temperate seasons on Earth. Outside the tropics, autumn marks the transition from summer to winter, in September (Northern Hemisphere) or March (Southern Hemisphere). Autumn is the season when the duration of daylight becomes noticeably shorter and the temperature cools considerably. Day length decreases and night length increases as the season progresses until the Winter Solstice in December (Northern Hemisphere) and June (Southern Hemisphere). One of its main features in temperate climates is the striking change in colour for the leaves of deciduous trees as they prepare to shed. Date definitions Some cultures regard the autumnal equinox as "mid-autumn", while others with a longer temperature lag treat the equinox as the start of autumn. In the English-speaking world of high latitude countries, autumn traditionally began with Lammas Day and ended around Halloween, the approximate mid-points between midsummer, the autumnal equinox, and midwinter. Meteorologists (and Australia and most of the temperate countries in the southern hemisphere) use a definition based on Gregorian calendar months, with autumn being September, October, and November in the northern hemisphere, and March, April, and May in the southern hemisphere. In the higher latitude countries in the Northern Hemisphere, autumn traditionally starts with the September equinox (21 to 24 September) and ends with the winter solstice (21 or 22 December). Popular culture in the United States associates Labor Day, the first Monday in September, as the end of summer and the start of autumn; certain summer traditions, such as wearing white, are discouraged after that date. As daytime and nighttime temperatures decrease, trees change colour and then shed their leaves.Under the traditional East Asian solar term system, autumn starts on or around 8 August and ends on or about 7 November. In Ireland, the autumn months according to the national meteorological service, Met Éireann, are September, October, and November. However, according to the Irish Calendar, which is based on ancient Gaelic traditions, autumn lasts throughout the months of August, September, and October, or possibly a few days later, depending on tradition. In the Irish language, September is known as Meán Fómhair ("middle of autumn") and October as Deireadh Fómhair ("end of autumn"). Persians celebrate the beginning of the autumn as Mehregan to honor Mithra (Mehr). Etymology The word autumn () is derived from Latin autumnus, archaic auctumnus, possibly from the ancient Etruscan root autu- and has within it connotations of the passing of the year. Alternative etymologies include Proto-Indo-European *h₃ewǵ- ("cold") or *h₂sows- ("dry").After the Greek era, the word continued to be used as the Old French word autompne (automne in modern French) or autumpne in Middle English, and was later normalised to the original Latin. In the Medieval period, there are rare examples of its use as early as the 12th century, but by the 16th century, it was in common use. Before the 16th century, harvest was the term usually used to refer to the season, as it is common in other West Germanic languages to this day (cf. Dutch herfst, German Herbst, and Scots hairst). However, as more people gradually moved from working the land to living in towns, the word harvest lost its reference to the time of year and came to refer only to the actual activity of reaping, and autumn, as well as fall, began to replace it as a reference to the season.The alternative word fall for the season traces its origins to old Germanic languages. The exact derivation is unclear, with the Old English fiæll or feallan and the Old Norse fall all being possible candidates. However, these words all have the meaning "to fall from a height" and are clearly derived either from a common root or from each other. The term came to denote the season in 16th-century England, a contraction of Middle English expressions like "fall of the leaf" and "fall of the year". Compare the origin of spring from "spring of the leaf" and "spring of the year".During the 17th century, Englishmen began emigrating to the new North American colonies, and the settlers took the English language with them. While the term fall gradually became nearly obsolete in Britain, it became the more common term in North America.The name backend, a once common name for the season in Northern England, has today been largely replaced by the name autumn. Associations Harvest Association with the transition from warm to cold weather, and its related status as the season of the primary harvest, has dominated its themes and popular images. In Western cultures, personifications of autumn are usually pretty, well-fed females adorned with fruits, vegetables and grains that ripen at this time. Many cultures feature autumnal harvest festivals, often the most important on their calendars. Still-extant echoes of these celebrations are found in the autumn Thanksgiving holiday of the United States and Canada, and the Jewish Sukkot holiday with its roots as a full-moon harvest festival of "tabernacles" (living in outdoor huts around the time of harvest). There are also the many festivals celebrated by indigenous peoples of the Americas tied to the harvest of ripe foods gathered in the wild, the Chinese Mid-Autumn or Moon festival, and many others. The predominant mood of these autumnal celebrations is a gladness for the fruits of the earth mixed with a certain melancholy linked to the imminent arrival of harsh weather. This view is presented in English poet John Keats poem To Autumn, where he describes the season as a time of bounteous fecundity, a time of mellow fruitfulness. In North America, while most foods are harvested during the autumn, foods usually associated with the season include pumpkins (which are integral parts of both Thanksgiving and Halloween) and apples, which are used to make the seasonal beverage apple cider. Melancholia Autumn, especially in poetry, has often been associated with melancholia. The possibilities and opportunities of summer are gone, and the chill of winter is on the horizon. Skies turn grey, the amount of usable daylight drops rapidly, and many people turn inward, both physically and mentally. It has been referred to as an unhealthy season.Similar examples may be found in Irish poet W.B. Yeats poem The Wild Swans at Coole where the maturing season that the poet observes symbolically represents his own ageing self. Like the natural world that he observes, he too has reached his prime and now must look forward to the inevitability of old age and death. French poet Paul Verlaines "Chanson dautomne" ("Autumn Song") is likewise characterised by strong, painful feelings of sorrow. Keats To Autumn, written in September 1819, echoes this sense of melancholic reflection but also emphasises the lush abundance of the season. The song "Autumn Leaves", based on the French song "Les Feuilles mortes", uses the melancholic atmosphere of the season and the end of summer as a metaphor for the mood of being separated from a loved one. Halloween Autumn is associated with Halloween (influenced by Samhain, a Celtic autumn festival), and with it a widespread marketing campaign that promotes it. The Celtic people also used this time to celebrate the harvest with a time of feasting. At the same time though, it was a celebration of death as well. Crops were harvested, livestock were butchered, and Winter was coming.Halloween, 31 October, is in autumn in the northern hemisphere. Television, film, book, costume, home decoration, and confectionery businesses use this time of year to promote products closely associated with such a holiday, with promotions going from late August or early September to 31 October, since their themes rapidly lose strength once the holiday ends, and advertising starts concentrating on Christmas. Other associations In some parts of the northern hemisphere, autumn has a strong association with the end of summer holiday and the start of a new school year, particularly for children in primary and secondary education. "Back to School" advertising and preparations usually occurs in the weeks leading to the beginning of autumn. Thanksgiving Day is a national holiday celebrated in Canada, in the United States, in some of the Caribbean islands and in Liberia. Thanksgiving is celebrated on the second Monday of October in Canada, on the fourth Thursday of November in the United States (where it is commonly regarded as the start of the Christmas and holiday season), and around the same part of the year in other places. Similarly named festival holidays occur in Germany and Japan. Television stations and networks, particularly in North America, traditionally begin their regular seasons in their autumn, with new series and new episodes of existing series debuting mostly during late September or early October (series that debut outside the autumn season are usually known as mid-season replacements). A sweeps period takes place in November to measure Nielsen Ratings. American football is played almost exclusively in the autumn months; at the high school level, seasons run from late August through early November, with some playoff games and holiday rivalry contests being played as late as Thanksgiving. In many American states, the championship games take place in early December. College footballs regular season runs from September through November, while the main professional circuit, the National Football League, plays from September through to early January. Summer sports, such as association football (in Northern America, East Asia, Argentina, and South Africa), Canadian football, stock car racing, tennis, golf, cricket, and professional baseball, wrap up their seasons in early to late autumn; Major League Baseballs championship World Series is popularly known as the "Fall Classic". (Amateur baseball is usually finished by August.) Likewise, professional winter sports, such as ice hockey and basketball, and most leagues of association football in Europe, are in the early stages of their seasons during autumn; American college basketball and college ice hockey play teams outside their athletic conferences during the late autumn before their in-conference schedules begin in winter. The Christian religious holidays of All Saints Day and All Souls Day are observed in autumn in the Northern hemisphere. Easter falls in autumn in the southern hemisphere. The secular celebration of International Workers Day also falls in autumn in the southern hemisphere. Since 1997, Autumn has been one of the top 100 names for girls in the United States.In Indian mythology, autumn is considered to be the preferred season for the goddess of learning Saraswati, who is also known by the name of "goddess of autumn" (Sharada). In Asian mysticism, Autumn is associated with the element of metal, and subsequently with the colour white, the White Tiger of the West, and death and mourning. Tourism Although colour change in leaves occurs wherever deciduous trees are found, coloured autumn foliage is noted in various regions of the world: most of North America, Eastern Asia (including China, Korea, and Japan), Europe, southeast, south, and part of the midwest of Brazil, the forest of Patagonia, eastern Australia and New Zealands South Island. Eastern Canada and New England are famous for their autumnal foliage, and this attracts major tourism (worth billions of US dollars) for the regions. Views of autumn Allegories of autumn in art See also Autumn in New England Diwali References == External links ==

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

I'm looking for a concise explanation of the medical term 'Lidocaine/prilocaine.'

Lidocaine/prilocaine is a eutectic mixture of equal quantities (by weight) of lidocaine and prilocaine. A 5% emulsion preparation, containing 2.5% each of lidocaine/prilocaine, is marketed by APP Pharmaceuticals under the trade name EMLA (an abbreviation for Eutectic Mixture of Local Anesthetics). As a spray, it is marketed under the name Tempe (topical eutectic-like mixture for premature ejaculation) (PSD502) that can be used by men to help with premature ejaculation. The spray is manufactured by Plethora Solutions and branded as Fortacin in the UK and Recordati in the EU. Eutectic mixture Separately, lidocaine and prilocaine are solid bases. When mixed in equal quantities by weight, however, they form a eutectic mixture – that is the melting point of the mixture is lower than the melting points of the individual components. The lidocaine/prilocaine eutectic mixture is an oil with a melting point of 18 °C, and can be formulated into preparations without the use of a non-aqueous solvent. This allows higher concentrations of anaesthetic to be formulated into the preparation and maintained during application. Clinical use Indications The lidocaine/prilocaine combination is indicated for dermal anaesthesia. Specifically it is applied to prevent pain associated with intravenous catheter insertion, blood sampling, superficial surgical procedures, and topical anaesthesia of leg ulcers for cleansing or debridement. Also, it can be used to numb the skin before tattooing as well as electrolysis and laser hair removal. It is also sometimes used in advance of injected local anaesthetics for minor surgery and biopsies. A topical spray consisting of an aerosol formulation of lidocaine and prilocaine was evaluated under the name PSD502 for use in treating premature ejaculation. The spray is applied on the penile skin prior to intercourse. While this formulation was not approved by the FDA, a similar product, Promescent, is available over-the-counter in the U.S. Dosage forms Lidocaine/prilocaine eutectic mixture is marketed as a 5% oil-in-water emulsion incorporated in a cream base (EMLA cream) or a cellulose disk (EMLA patch). The cream is applied under an occlusive dressing, while the patch incorporates an occlusive dressing to facilitate absorption of lidocaine and prilocaine into the area where anaesthesia is required. Local dermal anaesthesia is achieved after approximately 60 minutes, whereupon the occlusive dressing (or patch) is removed. The duration of anaesthesia is approximately two hours following removal of the occlusive dressing. E. Fougera & Co., makers of the generic cream widely used in the United States as Lidocaine and Prilocaine Cream, 2.5%/2.5%, recommends different timing for application of the cream as well as length of anesthesia. They state the cream must be applied at least one hour before the start of a routine procedure and for two hours before the start of a painful procedure. Additionally, they state that the duration of effective skin anesthesia will be at least one hour after removal of the occlusive dressing. Circumcision Lidocaine/prilocaine eutectic mixture has been used during circumcision in newborn boys and has been considered efficacious and safe to lessen pain from circumcision.The European Medicines Agency concludes in its latest (2014) statement on Emla: "Safety and efficacy for the use of EMLA on genital skin and genital mucosa have not been established in children younger than 12 years. Available paediatric data do not demonstrate adequate efficacy for circumcision."The Patient Information Leaflet of EMLA in the UK states: "EMLA Cream should not be applied to the genital skin (e.g. penis) and genital mucosa (e.g. in the vagina) of children (below 12 years of age) owing to insufficient data on absorption of active substances." Tempe The spray is a combination of local anaesthetics lidocaine and prilocaine in a metered-dose aerosol that is sprayed directly on the penis to numb sensations. It was developed by the same group that invented the erectile dysfunction drug sildenafil. The drug was approved in Europe and was released in the UK market in November 2016 and within the EU will be marketed by, early in 2017 In the United States, the Food and Drug Administration (FDA) is expected to approve the drug in 2018. Compendial status United States Pharmacopeia 31 See also Dosage form Eutectic point Lidocaine Prilocaine References External links "Lidocaine mixture with Prilocaine". Drug Information Portal. U.S. National Library of Medicine.

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I'm encountering the term 'Trichomoniasis' in medical literature. What's its definition?

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

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

What is the significance of the term 'Transsexual' in the medical field?

Transsexual people experience a gender identity that is inconsistent with their assigned sex, and desire to permanently transition to the sex or gender with which they identify, usually seeking medical assistance (including sex reassignment therapies, such as hormone replacement therapy and sex reassignment surgery) to help them align their body with their identified sex or gender. The term transsexual is a subset of transgender, but some transsexual people reject the label of transgender. A medical diagnosis of gender dysphoria can be made if a person experiences marked and persistent incongruence between their experienced gender — their personal sense of their own gender — and their assigned sex. Understanding of transsexuality has changed very quickly in the 21st century. Many 20th century medical beliefs and practices around transsexuality are now considered deeply outdated. It was once classified as a mental disorder and subject to extensive gatekeeping by the medical establishment, and remains so in much of the world. Terminology Transsexual has had different meanings throughout time. In modern usage, it refers to "a person who desires to or who has modified their body to transition from one gender or sex to another through the use of medical technologies such as hormones or surgeries." It is considered an antiquated term, and is sometimes pejorative. The general shift is to instead use the term transgender or the abbreviated form trans, but due to its historical usage, transsexual remains in the modern vernacular.: 742–744  In understanding the subject, it is noted that there is a difference between gender and sex. Gender is defined as a "set of social, cultural, and linguistic norms that can be attributed to someone’s identity, expression, or role as masculine, feminine, androgynous, or nonbinary." Sex is defined as being "assigned at birth by medical professionals based on the appearance of genitalia, and related assumptions about chromosomal makeup, gender identity, expressions, and roles emerge over the life span, sometimes changing over time.": 277–278 Origins Norman Haire reported that in 1921 Dora R of Germany began a surgical transition, under the care of Magnus Hirschfeld, which ended in 1930 with a successful genital reassignment surgery (GRS). In 1930, Hirschfeld supervised the second genital reassignment surgery to be reported in detail in a peer-reviewed journal, that of Lili Elbe of Denmark. In 1923, Hirschfeld introduced the (German) term "Transsexualismus", after which David Oliver Cauldwell introduced "transsexualism" and "transsexual" to English in 1949 and 1950.Cauldwell appears to be the first to use the term to refer to those who desired a change of physiological sex. In 1969, Harry Benjamin claimed to have been the first to use the term "transsexual" in a public lecture, which he gave in December 1953. Benjamin went on to popularize the term in his 1966 book, The Transsexual Phenomenon, in which he described transsexual people on a scale (later called the "Benjamin scale") of three levels of intensity: "Transsexual (nonsurgical)", "Transsexual (moderate intensity)", and "Transsexual (high intensity)". In his book, Benjamin described "true" transsexualism as the following: True transsexuals feel that they belong to the other sex, they want to be and function as members of the opposite sex, not only to appear as such. For them, their sex organs, the primary (testes) as well as the secondary (penis and others) are disgusting deformities that must be changed by the surgeons knife. Relationship to transgender The term transgender was coined by John Oliven in 1965. By the 1990s, transsexual had come to be considered a subset of the umbrella term transgender. The term transgender is now more common, and many transgender people prefer the designation transgender and reject transsexual. Some people who pursue medical assistance (for example, sex reassignment surgery) to change their sexual characteristics to match their gender identity prefer the designation transsexual and reject transgender. One perspective offered by transsexual people who reject a transgender label for that of transsexed is that, for people who have gone through sexual reassignment surgery, their anatomical sex has been altered, whilst their gender remains constant.Historically, one reason some people preferred transsexual to transgender is that the medical community in the 1950s through the 1980s encouraged a distinction between the terms that would only allow the former access to medical treatment. Other self-identified transsexual people state that those who do not seek sex reassignment surgery (SRS) are fundamentally different from those who do, and that the two have different concerns, but this view is controversial, and others argue that merely having some medical procedures does not have such far-reaching consequences as to put those who have them and those who have not (e.g. because they cannot afford them) into such distinctive categories. Some have objected to the term transsexual on the basis that it describes a condition related to gender identity rather than sexuality. For example, Christine Jorgensen, the first person widely known to have sex reassignment surgery (in this case, male-to-female), rejected transsexual and instead identified herself in newsprint as trans-gender, on this basis.The trans community has generally taken issue with the term transsexual because it over-medicalizes the trans experience, and focuses too much on diagnosis.: 743  The term transgender emerged in part in an attempt to break the "medical monopoly" on transitioning that transsexual implied. GLAADs media reference guide offers the following distinction on the use of transsexual:An older term that originated in the medical and psychological communities. As the gay and lesbian community rejected homosexual and replaced it with gay and lesbian, the transgender community rejected transsexual and replaced it with transgender. Some people within the trans community may still call themselves transsexual. Do not use transsexual to describe a person unless it is a word they use to describe themself. If the subject of your news article uses the word transsexual to describe themself, use it as an adjective: transsexual woman or transsexual man. Terminological variance The word transsexual is most often used as an adjective rather than a noun – a "transsexual person" rather than simply "a transsexual". As of 2018, use of the noun form (e.g. referring to people as transsexuals) is often deprecated by those in the transsexual community. Like other trans people, transsexual people prefer to be referred to by the gender pronouns and terms associated with their gender identity. For example, a trans man is a person who was assigned the female sex at birth on the basis of his genitals, but despite that assignment, identifies as a man and is transitioning or has transitioned to a male gender role; in the case of a transsexual man, he furthermore has or will have a masculine body. Transsexual people are sometimes referred to with directional terms, such as "female-to-male" for a transsexual man, abbreviated to "F2M", "FTM", and "F to M", or "male-to-female" for a transsexual woman, abbreviated "M2F", "MTF" and "M to F". Individuals who have undergone and completed sex reassignment surgery are sometimes referred to as transsexed individuals; however, the term transsexed is not to be confused with the term transsexual, which can also refer to individuals who have not yet undergone SRS, and whose anatomical sex (still) does not match their psychological sense of personal gender identity. The terms gender dysphoria and gender identity disorder were not used until the 1970s, when Laub and Fisk published several works on transsexualism using these terms. "Transsexualism" was replaced in the DSM-IV by "gender identity disorder in adolescents and adults". Male-to-female transsexualism has sometimes been called "Harry Benjamins syndrome" after the endocrinologist who pioneered the study of dysphoria. As the present-day medical study of gender variance is much broader than Benjamins early description, there is greater understanding of its aspects, and use of the term Harry Benjamins syndrome has been criticized for delegitimizing gender-variant people with different experiences. Sexual orientation Since the middle of the 20th century, homosexual transsexual and related terms were used to label individuals sexual orientation based on their birth sex. Many sources criticize this choice of wording as confusing, "heterosexist", "archaic", and demeaning because it labels people by sex assigned at birth instead of their gender identity. Sexologist John Bancroft also recently expressed regret for having used this terminology, which was standard when he used it, to refer to transsexual women. He says that he now tries to choose his words more sensitively. Sexologist Charles Allen Moser is likewise critical of the terminology. Sociomedical scientist Rebecca Jordan-Young challenges researchers like Simon LeVay, J. Michael Bailey, and Martin Lalumiere, who she says "have completely failed to appreciate the implications of alternative ways of framing sexual orientation."The terms androphilia and gynephilia to describe a persons sexual orientation without reference to their gender identity were proposed and popularized by psychologist Ron Langevin in the 1980s. The similar specifiers attracted to men, attracted to women, attracted to both or attracted to neither were used in the DSM-IV.Many transsexual people choose the language of how they refer to their sexual orientation based on their gender identity, not their birth assigned sex. Surgical status Several terms are in common use, especially within the community itself relating to the surgical or operative status of someone who is transsexual, depending on whether they have already had sex reassignment surgery (SRS), have not had SRS but still intend to, or do not intend to have SRS. They are, post-op, pre-op, and non-op, respectively. Pre-operative A pre-operative transsexual person, or simply pre-op for short, is someone who intends to have SRS at some point, but has not yet had it. Post-operative A post-operative transsexual person, or post-op for short, is someone who has had SRS. Non-operative A non-operative transsexual person, or non-op, is someone who has not had SRS, and does not intend to have it in the future. There can be various reasons for this, from personal to financial. Having SRS is not a requirement of being transsexual. Evolutionary biologist and trans woman Julia Serano criticizes the societal preoccupation with SRS as phallocentric, objectifying of transsexuals, and an invasion of privacy.: 229–231 Historical understanding Transgender people are known to have existed since ancient times. A wide range of societies had traditional third gender roles, or otherwise accepted trans people in some form. However, a precise history is difficult because the modern concept of being transgender, and gender in general, did not develop until the mid-1900s. Historical understandings are thus inherently filtered through modern principles, and were largely viewed through a medical lens until the late 1900s.Ancient Greek Hippocrates (interpreting the writing of Herodotus) discusses transgender individuals briefly. He describes the "disease of the Scythians" (regarding the Enaree), which he attributes to impotency due to riding on a horse without stirrups. Hippocrates reference was well discussed by medical writings of the 1500s–1700s. Pierre Petit writing in 1596 viewed the "Scythian disease" as natural variation, but by the 1700s writers viewed it as a "melancholy", or "hysterical" psychiatric disease. By the early 1800s, being transgender separate from Hippocrates idea of it was claimed to be widely known, but remained poorly documented. Both MtF and FtM individuals were cited in European insane asylums of the early 1800s. The most complete account of the time came from the life of the Chevalier dÉon (1728–1810). As cross-dressing became more widespread in the late 1800s, discussion of transgender people increased greatly and writers attempted to explain the origins of being transgender. Much study came out of Germany, and was exported to other Western audiences. Cross-dressing was seen in a pragmatic light until the late 1800s; it had previously served a satirical or disguising purpose. But in the latter half of the 1800s, cross-dressing and being transgender became viewed as an increasing societal danger.William A. Hammond wrote an 1882 account of transgender Pueblo shamans (mujerados), comparing them to the Scythian disease. Other writers of the late 1700s and 1800s (including Hammonds associates in the American Neurological Association) had noted the widespread nature of transgender cultural practices among native peoples. Explanations varied, but authors generally did not ascribe native transgender practices to psychiatric causes, instead condemning the practices in a religious and moral sense. Native groups provided much study on the subject, and perhaps the majority of all study until after WWII.Critical studies first began to emerge in the late 1800s in Germany, with the works of Magnus Hirschfeld. Hirschfeld coined the term "transvestite" in 1910 as the scope of transgender study grew. His work would lead to the 1919 founding of the Institut für Sexualwissenschaft in Berlin. Though Hirschelds legacy is disputed, he revolutionized the field of study. The Institut was destroyed when the Nazis seized power in 1933, and its research was infamously burned in the May 1933 Nazi book burnings. Transgender issues went largely out of the public eye until after World War II. Even when they re-emerged, they reflected a forensic psychology approach, unlike the more sexological that had been employed in the lost German research. 20th century medical understanding Benjamin suggested that moderate intensity male to female transsexual people may benefit from estrogen medication as a "substitute for or preliminary to operation." Some people have had sex reassignment surgery (SRS) but do not meet the above definition of transsexual. Other people do not desire SRS although they meet the other elements of Benjamins definition of a "true transsexual". Transsexuality was included for the first time in the DSM-III in 1980 and again in the DSM-III-R in 1987, where it was located under Disorders Usually First Evident in Infancy, Childhood or Adolescence. Beyond Benjamins work, which focused on male-to-female (MTF) transsexual people, there are cases of the female to male transsexual, for whom genital surgery may not be practical. Benjamin gave certifying letters to his MTF transsexual patients that stated "Their anatomical sex, that is to say, the body, is male. Their psychological sex, that is to say, the mind, is female." Starting in 1968 Benjamin abandoned his early terminology and adopted that of "gender identity." Medical diagnosis Transsexualism no longer is classified as a mental disorder in the International Statistical Classification of Diseases and Related Health Problems (ICD). The World Professional Association for Transgender Health (WPATH) and many transsexual people had recommended this removal,: 743  arguing that at least some mental health professionals are being insensitive by labelling transsexualism as a "disease" rather than as an inborn trait, as many transsexuals believe it to be. Now, instead, it is classified as a sexual health condition; this classification continues to enable healthcare systems to provide healthcare needs related to gender. The eleventh edition was released in June 2018. The previous version, ICD-10, had incorporated transsexualism, dual role transvestism, and gender identity disorder of childhood into its gender identity disorder category. It defined transsexualism as "[a] desire to live and be accepted as a member of the opposite sex, usually accompanied by a sense of discomfort with, or inappropriateness of, ones anatomic sex, and a wish to have surgery and hormonal treatment to make ones body as congruent as possible with ones preferred sex." ICD-11 renamed Transexualism as Gender incongruence of adolescence or adulthood (HA60), and Gender identity disorder of childhood was renamed Gender incongruence of childhood (HA61). HA60 of the ICD-11 reads:Gender Incongruence of Adolescence and Adulthood is characterised by a marked and persistent incongruence between an individual´s experienced gender and the assigned sex, which often leads to a desire to ‘transition’, in order to live and be accepted as a person of the experienced gender, through hormonal treatment, surgery or other health care services to make the individual´s body align, as much as desired and to the extent possible, with the experienced gender. The diagnosis cannot be assigned prior the onset of puberty. [HA61 applies before puberty] Gender variant behaviour and preferences alone are not a basis for assigning the diagnosis.Historically, transsexualism has also been included in the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM). With the DSM-5, transsexualism was removed as a diagnosis, and a diagnosis of gender dysphoria was created in its place. This change was made to reflect the consensus view by members of the APA that transsexuality is not in and of itself a disorder and that transsexual people should not be stigmatized unnecessarily. By including a diagnosis for gender dysphoria, transsexual people are still able to access medical care through the process of transition. The current diagnosis for transsexual people who present themselves for medical treatment is gender dysphoria (leaving out those who have sexual identity disorders without gender concerns). According to the Standards of care formulated by WPATH, formerly the Harry Benjamin International Gender Dysphoria Association, this diagnostic label is often necessary to obtain sex reassignment therapy with health insurance coverage, and the designation of gender identity disorders as mental disorders is not a license for stigmatization or for the deprivation of gender patients civil rights. Causes, studies, and theories Causes Studies conducted on twins suggest that there are likely genetic causes of gender incongruence, although the precise genes involved are not known or fully understood. One study published in the International Journal of Transgender Health found that in 20% of identical twin pairs, if one twin was trans, the other was as well, compared to only 2.6% of non-identical twins where this was the case; researchers attribute this to their shared genetics.Sexologist Ray Blanchard created a taxonomy of male-to-female transsexualism that proposes two distinct etiologies for androphilic and gynephilic individuals; this taxonomy has become controversial, supported by J. Michael Bailey, Anne Lawrence, James Cantor and others, but opposed by Charles Allen Moser, Julia Serano, and the World Professional Association for Transgender Health. Focus on trans women over trans men Historically, formal efforts by the medical community to provide transsexual healthcare were extremely focused on transsexual women, with little thought for transsexual men. Julia Serano suggests that effemimania (the idea that male femininity is more psychopathological than female masculinity) was the driving factor. She sees this as a kind of transmisogyny (hatred of trans women as an extension of sexism).: 126–127  This effimimania conflates male homosexuality, MTF transsexuality, and feminine gender expression, while treating them all as a disease.: 129  She points to the medical communitys long love of now outdated theories such as autogynephilia.: 131 Medical assistance Individuals make different choices regarding sex reassignment therapy, which may include hormones, minor to extensive surgery, social changes, and psychological interventions. The extent of medical intervention is a highly personal decision: there is no one-size-fits-all solution. Hormone replacement therapy Transsexual individuals frequently opt for masculinizing or feminizing hormone replacement therapy (HRT) to modify secondary sex characteristics. Sex reassignment therapy Sex reassignment therapy (SRT) is an umbrella term for all medical treatments related to sex reassignment of both transgender and intersex people. Sex reassignment surgery (such as orchiectomy) alters primary sex characteristics, including chest surgery such as top surgery or breast augmentation, or, in the case of trans women, a trachea shave, facial feminization surgery or permanent hair removal. To obtain sex reassignment therapy, transsexual people are generally required to undergo a psychological evaluation and receive a diagnosis of gender identity disorder in accordance with the Standards of Care (SOC) as published by the World Professional Association for Transgender Health. This assessment is usually accompanied by counseling on issues of adjustment to the desired gender role, effects and risks of medical treatments, and sometimes also by psychological therapy. The SOC are intended as guidelines, not inflexible rules, and are intended to ensure that clients are properly informed and in sound psychological health, and to discourage people from transitioning based on unrealistic expectations. Gender roles and transitioning After an initial psychological evaluation, trans men and trans women may begin medical treatment, starting with hormone replacement therapy or hormone blockers. In these cases, people who change their gender are usually required to live as members of their target gender for at least one year prior to genital surgery, gaining real-life experience, which is sometimes called the "real-life test" (RLT). Transsexual individuals may undergo some, all, or none of the medical procedures available, depending on personal feelings, health, income, and other considerations. Some people posit that transsexualism is a physical condition, not a psychological issue, and assert that sex reassignment therapy should be given on request. (Brown 103) Like other trans people, transsexual people may refer to themselves as trans men or trans women. Transsexual people desire to establish a permanent gender role as a member of the gender with which they identify, and many transsexual people pursue medical interventions as part of the process of expressing their gender. The entire process of switching from one physical sex and social gender presentation to another is often referred to as transitioning, and usually takes several years. Transsexual people who transition usually change their social gender roles, legal names and legal sex designation.Not all transsexual people undergo a physical transition. Some have obstacles or concerns preventing them from doing so, such as the expense of surgery, the risk of medical complications, or medical conditions which make the use of hormones or surgery dangerous. Others may not identify strongly with another binary gender role. Still others may find balance at a midpoint during the process, regardless of whether or not they are binary-identified. Many transsexual people, including binary-identified transsexual people, do not undergo genital surgery, because they are comfortable with their own genitals, or because they are concerned about nerve damage and the potential loss of sexual pleasure, including orgasm. This is especially so in the case of trans men, many of whom are dissatisfied with the current state of phalloplasty, which is typically very expensive, not covered by health insurance, and commonly does not achieve desired results. For example, not only does phalloplasty not result in a completely natural erection, it may not allow for an erection at all, and its results commonly lack penile sexual sensitivity; in other cases, however, phalloplasty results are satisfying for trans men. By contrast, metoidioplasty, which is more popular, is significantly less expensive and has far better sexual results.Transsexual people can be heterosexual, gay, lesbian, or bisexual; many choose the language of how they refer to their sexual orientation based on their gender identity, not their birth assigned sex. Psychological treatment Psychological techniques that attempt to alter gender identity to one considered appropriate for the persons assigned sex, aka conversion therapy, are ineffective. The widely recognized Standards of Care note that sometimes the only reasonable and effective course of treatment for transsexual people is to go through sex reassignment therapy.The need for treatment of transsexual people is emphasized by the high rate of mental health problems, including depression, anxiety, and various addictions, as well as a higher suicide rate among untreated transsexual people than in the general population. These problems are alleviated by a change of gender role and/or physical characteristics.Many transgender and transsexual activists, and many caregivers, note that these problems are not usually related to the gender identity issues themselves, but the social and cultural responses to gender-variant individuals. Some transsexual people reject the counseling that is recommended by the Standards of Care because they do not consider their gender identity to be a cause of psychological problems. Brown and Rounsley noted that "some transsexual people acquiesce to legal and medical expectations in order to gain rights granted through the medical/psychological hierarchy." Legal needs, such as a change of sex on legal documents, and medical needs, such as sex reassignment surgery, are usually difficult to obtain without a doctor or therapists approval. Because of this, some transsexual people feel coerced into affirming outdated concepts of gender to overcome simple legal and medical hurdles. Regrets and detransitions People who undergo sex reassignment surgery can develop regret for the procedure later in life, largely predicted by a lack of support from family or peers, with data from the 1990s suggesting a rate of 3.8%. In a 2001 study of 232 MTF patients who underwent GRS, none of the patients reported complete regret and only 6% reported partial or occasional regrets. A 2009 review of Medline literature suggests the total rate of patients expressing feelings of doubt or regret is estimated to be as high as 8%.A 2010 meta-study, based on 28 previous long-term studies of transsexual men and women, found that the overall psychological functioning of transsexual people after transition was similar to that of the general population and significantly better than that of untreated transsexual people. Prevalence Estimates of the prevalence of transsexual people are highly dependent on the specific case definitions used in the studies, with prevalence rates varying by orders of magnitude. In the United States, the Diagnostic and Statistical Manual of Mental Disorders (DSM-V 2013) gives the following estimates: "For natal adult males [MTF], prevalence ranges from 0.005% to 0.014%, and for natal females [FTM], from 0.002% to 0.003%." It states, however, that these are likely underestimates since the figures are based on referrals to specialty clinics.The Amsterdam Gender Dysphoria Clinic over four decades has treated roughly 95% of Dutch transsexual clients, and it suggests (1997) a prevalence of 1:10,000 among assigned males and 1:30,000 among assigned females.Olyslager and Conway presented a paper at the WPATH 20th International Symposium (2007) arguing that the data from their own and other studies actually imply much higher prevalence, with minimum lower bounds of 1:4,500 male-to-female transsexual people and 1:8,000 female-to-male transsexual people for a number of countries worldwide. They estimate the number of post-op women in the US to be 32,000 and obtain a figure of 1:2500 male-to-female transsexual people. They further compare the annual instances of sex reassignment surgery (SRS) and male birth in the U.S. to obtain a figure of 1:1000 MTF transsexual people and suggest a prevalence of 1:500 extrapolated from the rising rates of SRS in the US and a "common sense" estimate of the number of undiagnosed transsexual people. Olyslager and Conway also argue that the US population of assigned males having already undergone reassignment surgery by the top three US SRS surgeons alone is enough to account for the entire transsexual population implied by the 1:10,000 prevalence number, yet this excludes all other US SRS surgeons, surgeons in countries such as Thailand, Canada, and others, and the high proportion of transsexual people who have not yet sought treatment, suggesting that a prevalence of 1:10,000 is too low. A 2008 study of the number of New Zealand passport holders who changed the sex on their passport estimated that 1:3,639 birth-assigned males and 1:22,714 birth-assigned females were transsexual.A 2008 presentation at the LGBT Health Summit in Bristol, UK, showed that the prevalence of transsexual people in the UK was increasing (14% per year) and that the mean age of transition was rising. Though no direct studies on the prevalence of gender identity disorder (GID) have been done, a variety of clinical papers published in the past 20 years provide estimates ranging from 1:7,400 to 1:42,000 in assigned males and 1:30,040 to 1:104,000 in assigned females.In 2015, the National Center for Transgender Equality conducted a National Transgender Discrimination Survey. Of the 27,715 transgender and genderqueer people who took the survey, 35% identified as "non-binary", 33% identified as transgender women, 29% identified as transgender men, and 3% said that "crossdresser" best described their gender identity.A 2016 systematic review and meta-analysis of "how various definitions of transgender affect prevalence estimates" in 27 studies found a meta-prevalence (mP) estimates per 100,000 population of 9.2 (95% CI = 4.9–13.6), equal to 1:11,000 for surgical or hormonal gender affirmation therapy and 6.8 (95% CI = 4.6–9.1), equal to 1:15,000 for transgender-related medical condition diagnoses. Of studies assessing self-reported transgender identity, prevalence was 355 (95% CI = 144–566), equal to 1 in 282. However, a single outlier study would have influenced the result to 871 (95% CI = 519–1,224), equal to 1 in 115; this study was removed. "Significant heterogeneity was observed in most analyses." Society and culture A number of Native American and First Nations cultures have traditional social and ceremonial roles for individuals who do not fit into the usual roles for males and females in that culture. These roles can vary widely between tribes, because gender roles, when they exist at all, also vary considerably among different Native cultures. However, a modern, pan-Indian status known as Two-Spirit has emerged among LGBT Natives in recent years. Legal and social aspects Laws regarding changes to the legal status of transsexual people are different from country to country. Some jurisdictions allow an individual to change their name, and sometimes, their legal gender, to reflect their gender identity. Within the US, some states allow amendments or complete replacement of the original birth certificates. Some states seal earlier records against all but court orders in order to protect the transsexual persons privacy. In many places, it is not possible to change birth records or other legal designations of sex, although changes are occurring. Estelle Asmodelle’s book documented her struggle to change the Australian birth certificate and passport laws, although there are other individuals who have been instrumental in changing laws and thus attaining more acceptance for transsexual people in general. Medical treatment for transsexual and transgender people is available in most Western countries. However, transsexual and transgender people challenge the "normative" gender roles of many cultures and often face considerable hatred and prejudice. The film Boys Dont Cry chronicles the case of Brandon Teena, a transsexual man who was raped and murdered after his status was discovered. In 1999 Brandon was memoralised in the first Transgender Day of Remembrance. The Transgeder Day of Rembrance is observed annually on November 20 by members of the transgender community and LGBT+ organisations across the world.Jurisdictions allowing changes to birth records generally allow trans people to marry members of the opposite sex to their gender identity and to adopt children. Jurisdictions which prohibit same sex marriage often require pre-transition marriages to be ended before they will issue an amended birth certificate.Health-practitioner manuals, professional journalistic style guides, and LGBT advocacy groups advise the adoption by others of the name and pronouns identified by the person in question, including present references to the transgender or transsexual persons past. Family members and friends who may be confused about pronoun usage or the definitions of sex are commonly instructed in proper pronoun usage, either by the transsexual person or by professionals or other persons familiar with pronoun usage as it relates to transsexual people. Sometimes transsexual people have to correct their friends and family members many times before they begin to use the transsexual persons desired pronouns consistently. According to Julia Serano, deliberate mis-gendering of transsexual people is "an arrogant attempt to belittle and humiliate trans people."Both "transsexualism" and "gender identity disorders not resulting from physical impairments" are specifically excluded from coverage under the Americans with Disabilities Act Section 12211. Gender dysphoria is not excluded. Employment issues Openly transsexual people can have difficulty maintaining employment. Most find it necessary to remain employed during transition in order to cover the costs of living and transition. However, employment discrimination against trans people is rampant and many of them are fired when they come out or are involuntarily outed at work. Transsexual people must decide whether to transition on-the-job, or to find a new job when they make their social transition. Other stresses that transsexual people face in the workplace are being fearful of coworkers negatively responding to their transition, and losing job experience under a previous name—even deciding which rest room to use can prove challenging. Finding employment can be especially challenging for those in mid-transition. Laws regarding name and gender changes in many countries make it difficult for transsexual people to conceal their trans status from their employers. Because the Harry Benjamin Standards of Care requires one-year of real life experience prior to SRS, some feel this creates a Catch-22 situation which makes it difficult for trans people to remain employed or obtain SRS. In many countries, laws provide protection from workplace discrimination based on gender identity or gender expression, including masculine women and feminine men. An increasing number of companies are including "gender identity and expression" in their non-discrimination policies. Often these laws and policies do not cover all situations and are not strictly enforced. Californias anti-discrimination laws protect transsexual persons in the workplace and specifically prohibit employers from terminating or refusing to hire a person based on their transsexuality. The European Union provides employment protection as part of gender discrimination protections following the European Court of Justice decisions in P v S and Cornwall County Council.In the United States National Transgender Discrimination Survey, 44% of respondents reported not getting a job they applied for because of being transgender. 36% of trans women reported losing a job due to discrimination compared to 19% of trans men. 54% of trans women and 50% of trans men report having been harassed in the workplace. Transgender people who have been fired due to bias are more than 34 times likely than members of the general population to attempt suicide. Stealth Many transsexual men and women choose to live completely as members of their gender without disclosing details of their birth-assigned sex. This approach is sometimes called stealth. Stealth transsexuals choose not to disclose their past for numerous reasons, including fear of discrimination and fear of physical violence.: 63  There are examples of people having been denied medical treatment upon discovery of their trans status, whether it was revealed by the patient or inadvertently discovered by the doctors. In the media Before transsexual people were depicted in popular movies and television shows, Aleshia Brevard—a transsexual woman whose surgery took place in 1962: 3 —was actively working as an actress: 141  and model: 200  in Hollywood and New York throughout the 1960s and 70s. Aleshia never portrayed a transsexual person, though she appeared in eight Hollywood-produced films, on most of the popular variety shows of the day, including The Dean Martin Show, and was a regular on The Red Skelton Show and One Life to Live before returning to university to teach drama and acting. In pageantry Since 2004, with the goal of crowning the top transsexual of the world, a beauty pageant by the name of The Worlds Most Beautiful Transsexual Contest was held in Las Vegas, Nevada. The pageant accepted pre-operation and post-operation trans women, but required proof of their gender at birth. The winner of the 2004 pageant was a woman named Mimi Marks.Jenna Talackova, the 23-year-old woman who forced Donald Trump and his Miss Universe Canada pageant to end its ban on transgender contestants, competed in the pageant on May 19, 2012, in Toronto. On January 12, 2013, Kylan Arianna Wenzel was the first transgender woman allowed to compete in a Miss Universe Organization pageant since Donald Trump changed the rules to allow women like Wenzel to enter officially. Wenzel was the first transgender woman to compete in a Miss Universe Organization pageant since officials disqualified 23-year-old Miss Canada Jenna Talackova the previous year after learning she was transgender. See also List of transgender-related topics List of transgender-rights organizations List of LGBT-related organizations List of transgender people Transgender References Bibliography Benjamin, Harry (1966). The Transsexual Phenomenon. Julian Press, Incorporated Publishers. OCLC 1138665289. Brown, Mildred L.; Chloe Ann Rounsley (1996). True Selves: Understanding Transsexualism – For Families, Friends, Coworkers, and Helping Professionals. Jossey-Bass. ISBN 978-0-7879-6702-4. OCLC 51437864. Feinberg, Leslie (1999). Trans Liberation : Beyond Pink or Blue. Beacon Press. ISBN 978-0-8070-7951-5. OCLC 38732343. Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People (PDF) (Report). 7. World Professional Association for Transgender Health. 2012. Archived (PDF) from the original on 11 May 2022. Kruijver, Frank P. M.; Zhou, Jiang-Ning; Pool, Chris W.; Hofman, Michel A.; Gooren, Louis J. G.; Swaab, Dick F. (1 May 2000). "Male-to-Female Transsexuals Have Female Neuron Numbers in a Limbic Nucleus". The Journal of Clinical Endocrinology and Metabolism. The Endocrine Society. 85 (5): 2034–41. doi:10.1210/jcem.85.5.6564. ISSN 0021-972X. PMID 10843193. Archived from the original on 6 February 2007. Retrieved 25 February 2007. Rathus, Spencer A.; Jeffery S. Nevid, Lois Fichner-Rathus (2002). Human Sexuality in a World of Diversity. Allyn & Bacon. ISBN 978-0-205-40615-9. OCLC 55502508. Schreiber, Gerhard (2016). Transsexuality in Theology and Neuroscience. Findings, Controversies, and Perspectives (in German). Walter de Gruyter. ISBN 978-3-11-044080-5. OCLC 962412457. Pepper, Shanti M.; Lorah, Peggy (2008). "Career Issues and Workplace Considerations for the Transsexual Community: Bridging a Gap of Knowledge for Career Counselors and Mental Health Care Providers". The Career Development Quarterly. Wiley. 56 (4): 330–343. doi:10.1002/j.2161-0045.2008.tb00098.x. ISSN 0889-4019. ProQuest 219546491. External links The International Journal of Transgenderism – The Official Journal of the World Professional Association for Transgender Health (formerly HBIGDA). An archive of IJT Volumes I through V is available, as are several books on transsexualism, including Harry Benjamins The Transsexual Phenomenon

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

Please help me grasp the concept behind the medical term 'Oculomotor apraxia.'

Oculomotor apraxia (OMA) is the absence or defect of controlled, voluntary, and purposeful eye movement. It was first described in 1952 by the American ophthalmologist David Glendenning Cogan. People with this condition have difficulty moving their eyes horizontally and moving them quickly. The main difficulty is in saccade initiation, but there is also impaired cancellation of the vestibulo-ocular reflex. Patients have to turn their head in order to compensate for the lack of eye movement initiation in order to follow an object or see objects in their peripheral vision, but they often exceed their target. There is controversy regarding whether OMA should be considered an apraxia, since apraxia is the inability to perform a learned or skilled motor action to command, and saccade initiation is neither a learned nor a skilled action. Symptoms Absence of fast phase nystagmus on horizontal optokinetic testing Problems in nerve function involved in eye movement control, called neuropathy Inability to visually follow objects Head thrusts to compensate for the inability to accomplish voluntary horizontal gaze. Related developmental problems Even though OMA is not always associated with developmental issues, children with this condition often have hypotonia, decreased muscle tone, and show developmental delays. Some common delays are seen in speech, reading and motor development Causes OMA is a neurological condition. Although some brain imaging studies of people with OMA reveal a normal brain, some MRI studies have revealed unusual appearance of some brain areas, in particular the corpus callosum, cerebellum, and/or fourth ventricle. Oculomotor apraxia can be acquired or congenital. Sometimes no cause is found, in which case it is described as idiopathicA person may be born with the parts of the brain for eye movement control not working, or may manifest poor eye movement control in childhood. If any part of the brain that controls eye movement becomes damaged, then OMA may develop. One of the potential causes is bifrontal hemorrhages. In this case, OMA is associated with bilateral lesions of the frontal eye fields (FEF), located in the caudal middle frontal gyrus. The FEF control voluntary eye movements, including saccades, smooth pursuit and vergence. OMA can also be associated with bilateral hemorrhages in the parietal eye fields (PEF). The PEF surround the posterior, medial segment of the intraparietal sulcus. They have a role in reflexive saccades, and send information to the FEF. Since the FEF and PEF have complementary roles in voluntary and reflexive production of saccades, respectively, and they get inputs from different areas of the brain, only bilateral lesions to both the FEF and PEF will cause persistent OMA. Patients with either bilateral FEF or bilateral PEF damage (but not both FEF and PEF) have been shown to regain at least some voluntary saccadic initiation some time after their hemorrhages. Other causes of OMA include brain tumors and cardiovascular problems,. Ataxia with oculomotor apraxia A subgroup of genetically recessive ataxias associated with OMA has been identified, with an onset during childhood. These are ataxia with oculomotor apraxia type 1 (AOA1), ataxia with oculomotor apraxia 2 (AOA2), and ataxia telangiectasia. These are autosomal recessive disorders and the associated gene products are involved in DNA repair. Both horizontal and vertical eye movements are affected in these disorders. Although people with either type may have some mild cognitive problems, such as difficulty with concentration or performing multi-step activities, intellectual function is usually not affected. Type 1 Ataxia-oculomotor apraxia type 1 (AOA1) usually has an onset of symptoms during childhood. It is an autosomal recessive cerebellar ataxia (ARCA) associated with hypoalbuminemia and hypercholesterolemia. Mutations in the gene APTX, which encodes for aprataxin, have been identified to be responsible for AOA1. Elevated creatine kinase is occasionally present, in addition to a sensorimotor axonal neuropathy, as shown by nerve conduction velocity studies. In addition, MRI studies have shown cerebellar atrophy, mild brainstem atrophy, and, in advanced cases, cortical atrophyThe aprataxin protein APTX can remove obstructive termini from DNA strand breaks that interfere with DNA repair. APTX is recruited to DNA single-strand breaks by XRCC1 protein, where it functions as a nick sensor to scan the single-strand breaks for 5’-AMP obstructive termini that are intermediates in failed DNA ligase reactions. The removal of these obstructions allows DNA repair of the break to be completed. It is not yet clear which specific single-strand breaks are the neurodegenerative agents in AOA1 patients that lack functional aprataxin protein. However single-strand breaks with 5’-AMP termini appear to be the most likely candidate lesion. Type 2 Ataxia-oculomotor apraxia type 2 (AOA2), also known as spinocerebellar ataxia with axonal neuropathy type 2, has its onset during adolescence. It is characterized by cerebellar atrophy and peripheral neuropathy. Sufferers of Type 2 have high amounts of another protein called alpha-fetoprotein (AFP), and may also have high amounts of the protein creatine phosphokinase (CPK). Mutations in the SETX gene are the cause of the disease. AOA2 shows cerebellar atrophy, loss of Purkinje cells, and demyelination. In particular, there is a failure of the cerebrocerebellar circuit in AOA2 that has been shown to be responsible for the weaker coordination of complex cognitive functions such as working memory, executive functions, speech, and sequence learning. Although there is no sign of mental retardation or severe dementia, even after long disease duration, research on families with possible AOA2 have shown mild cognitive impairment as indexed by the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale. These impairments appear to be mostly due to a deficit in initiation and concept subtests,. Ataxia telangiectasia Telangiectasias are widened blood vessels that can develop anywhere on the skin, mucous membranes, whites of the eyes, and even in the brain. Telangiectasias are associated with multiple systemic signs, the most serious of which are unusual sensitivity to ionizing radiation, excessive chromosomal breakage, and a deficiency in the immune system. Ataxia telangiectasia results from defects in the ataxia telangiectasia mutated gene, which can cause abnormal cell death in various places of the body, including brain areas related to coordinated movement of the eyes. Patients with ataxia telangiectasia have prolonged vertical and horizontal saccade latencies and hypometric saccades, and, although not all, some patients show head thrusts,. Diagnosis == References ==

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I've encountered the term 'Chondrocalcinosis' while reading about medical topics. What does it refer to exactly?

Chondrocalcinosis or cartilage calcification is calcification (accumulation of calcium salts) in hyaline cartilage and/or fibrocartilage. It can be seen on radiography. Causes Buildup of calcium phosphate in the ankle joints has been found in about 50% of the general population, and may be associated with osteoarthritis.Another common cause of chondrocalcinosis is calcium pyrophosphate dihydrate crystal deposition disease (CPPD). CPPD is estimated to affect 4% to 7% of the adult populations of Europe and the United States. Previous studies have overestimated the prevalence by simply estimating the prevalence of chondrocalcinosis regardless of cause.A magnesium deficiency may cause chondrocalcinosis, and magnesium supplementation may reduce or alleviate symptoms. In some cases, arthritis from injury can cause chondrocalcinosis. Other causes of chondrocalcinosis include: Hypercalcaemia, especially when caused by hyperparathyroidism Arthritis Pseudogout Wilson disease Hemochromatosis Ochronosis Hypophosphatasia Hypothyroidism Hyperoxalemia Acromegaly Gitelman syndrome Diagnosis Chondrocalcinosis can be visualized on projectional radiography, CT scan, MRI, US, and nuclear medicine. CT scans and MRIs show calcific masses (usually within the ligamentum flavum or joint capsule), however radiography is more successful. At ultrasound, chondrocalcinosis may be depicted as echogenic foci with no acoustic shadow within the hyaline cartilage. As with most conditions, chondrocalcinosis can present with similarity to other diseases such as ankylosing spondylitis and gout. == References ==

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

Can you break down the meaning of the medical term 'Rajani' for me?

Rajani may refer to: Rajani (name), people named Rajani Rajani (actress) (born 1965), Indian film actress Rajani (TV series), a 1980s Indian TV series Rajani (film), a 2009 Indian Kannada romantic comedy Rajani, an 1877 novel by Bankimchandra Chattopadhyay See also Rajini (disambiguation)

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

Please help me grasp the concept behind the medical term 'Classic autism.'

Kanner autism, or classic autism, is an outdated neurodevelopmental diagnosis which is now considered part of autism spectrum disorder. The term autism was historically used to refer specifically to classic autism, but it is now more commonly used for the spectrum at large.Parents often noticed signs of autism during the first three years of their childs life.Autism was hypothesized to be caused by a combination of genetic and environmental factors, with genetic factors thought to heavily predominate. Controversies surround other proposed environmental causes; for example, the vaccine hypothesis, which although disproven, continues to hold sway in certain communities. Contemporary diagnostic manuals include only one diagnosis - autism spectrum disorder (ASD) - which includes classic autism along with Asperger syndrome and pervasive developmental disorder not otherwise specified (PDD-NOS).Globally, classic autism was estimated to affect 24.8 million people as of 2015. Characteristics Classic autism is a highly variable neurodevelopmental disorder whose symptoms first appear during infancy or childhood, and generally follows a steady course without remission. Autistic people may be severely impaired in some respects but average, or even superior, in others. Overt symptoms gradually begin after the age of six months and become established by age two or three years. Some autistic children experience regression in their communication and social skills after reaching developmental milestones at a normal pace. It was said to be distinguished by a characteristic triad of symptoms: impairments in social interaction, impairments in communication, and repetitive behavior. Other aspects, such as atypical eating, are also common but are not essential for diagnosis. Individual symptoms of autism occur in the general population and appear not to associate highly, without a sharp line separating pathologically severe from common traits. Social development Autistic people have social impairments and often lack the intuition about others that many people take for granted. Unusual social development becomes apparent early in childhood. Autistic infants show less attention to social stimuli, smile and look at others less often, and respond less to their own name. Autistic toddlers differ more strikingly from social norms; for example, they have less eye contact and turn-taking, and do not have the ability to use simple movements to express themselves, such as pointing at things. Three- to five-year-old autistic children are less likely to exhibit social understanding, approach others spontaneously, imitate and respond to emotions, communicate nonverbally, and take turns with others. However, they do form attachments to their primary caregivers. Most autistic children displayed moderately less attachment security than neurotypical children, although this difference disappears in children with higher mental development or less pronounced autistic traits. Children with high-functioning autism have more intense and frequent loneliness compared to non-autistic peers, despite the common belief that autistic children prefer to be alone. Making and maintaining friendships often proves to be difficult for autistic people. For them, the quality of friendships, not the number of friends, predicts how lonely they feel. Functional friendships, such as those resulting in invitations to parties, may affect the quality of life more deeply. Communication Differences in communication may be present from the first year of life, and may include delayed onset of babbling, unusual gestures, diminished responsiveness, and vocal patterns that are not synchronized with the caregiver. In the second and third years, autistic children have less frequent and less diverse babbling, consonants, words, and word combinations; their gestures are less often integrated with words. Autistic children are less likely to make requests or share experiences, and are more likely to simply repeat others words (echolalia) or reverse pronouns. Deficits in joint attention may be present - for example, they may look at a pointing hand instead of the object to which the hand is pointing. Autistic children may have difficulty with imaginative play and with developing symbols into language. Repetitive behavior Autistic individuals can display many forms of repetitive or restricted behavior, which the Repetitive Behavior Scale-Revised (RBS-R) categorizes as follows. Stereotyped behaviors: Repetitive movements, such as hand flapping, head rolling, or body rocking. Compulsive behaviors: Time-consuming behaviors intended to reduce the anxiety that an individual feels compelled to perform repeatedly or according to rigid rules, such as placing objects in a specific order, checking things, or handwashing. Sameness: Resistance to change; for example, insisting that the furniture not be moved or refusing to be interrupted. Ritualistic behavior: Unvarying pattern of daily activities, such as an unchanging menu or a dressing ritual. Restricted interests: Interests or fixations that are abnormal in theme or intensity of focus, such as preoccupation with a single television program, toy, or game.No single repetitive or self-injurious behavior seems to be specific to autism, but autism appears to have an elevated pattern of occurrence and severity of these behaviors. Other symptoms Autistic individuals may have symptoms that are independent of the diagnosis. An estimated 0.5% to 10% of individuals with classic autism show unusual abilities, ranging from splinter skills such as the memorization of trivia to the extraordinarily rare talents of prodigious autistic savants. Sensory abnormalities are found in over 90% of autistic people, and are considered core features by some, although there was no good evidence that sensory symptoms differentiate autism from other developmental disorders. An estimated 60–80% of autistic people have motor signs that include poor muscle tone, poor motor planning, and toe walking. Causes It was presumed initially that there was a common cause at the genetic, cognitive, and neural levels for classic autisms characteristic triad of symptoms. However, over time, there was increasing evidence that autism was instead a complex and highly heritable disorder whose core aspects have distinct causes which often often co-occur. Although theories regarding vaccines lack convincing scientific evidence, are biologically implausible, and originated from a fraudulent study, parental concern about a potential vaccine link with autism (and subsequent concern about ASD) has led to lower rates of childhood immunizations, outbreaks of previously controlled childhood diseases in some countries, and the preventable deaths of several children. Diagnosis Diagnosis of classic autism was based on behavioral symptoms, not cause or mechanism. Classification Classic autism was listed as autistic disorder in the fourth edition of the American Psychiatric Associations diagnostic manual, as one of the five pervasive developmental disorders (PDDs). However, the PDDs were collapsed into the single diagnosis of Autism Spectrum Disorder in 2013, and the WHOs diagnostic manual ICD-11 (which had listed it as childhood autism in its previous edition) followed suit a few years later. Classic autism was said to be characterized by widespread abnormalities of social interactions and communication, severely restricted interests, and highly repetitive behavior.Of the PDDs, Asperger syndrome was closest to classic autism in signs and likely causes; Rett syndrome and childhood disintegrative disorder share several signs with it, but were understood to potentially have unrelated causes; PDD not otherwise specified (PDD-NOS; also called atypical autism) was diagnosed when the criteria are not met for one of the other four PDDs. People would usually attract a diagnosis of Asperger syndrome rather than classic autism if they showed no substantial delay in language development, but early language ability was found to be a poor predictor of outcomes in adulthood. Prognosis and management There is no known cure for autism, and very little research addressed long-term prognosis for classic autism. Many autistic children lack social support, future employment opportunities or self-determination.The main goals when treating autistic children are to lessen associated deficits and family distress, and to increase quality of life and functional independence. In general, higher IQs are correlated with greater responsiveness to treatment and improved treatment outcomes. Services should be carried out by behavior analysts, special education teachers, speech pathologists, and licensed psychologists. Intensive, sustained special education programs and behavior therapy early in life often improves functioning and decreases symptom severity and maladaptive behaviors; claims that intervention by around age three years is crucial are not substantiated.No known medication relieves autisms core symptoms of social and communication impairments. Education Early, intensive ABA therapy has demonstrated effectiveness in enhancing communication and adaptive functioning in preschool children; it is also well-established for improving the intellectual performance of that age group. It is not known whether treatment programs for children lead to significant improvements after the children grow up, and the limited research on the effectiveness of adult residential programs shows mixed results. Alternative medicine Although many alternative therapies and interventions were used, few are supported by scientific studies. Treatment approaches have little empirical support in quality-of-life contexts, and many programs focus on success measures that lack predictive validity and real-world relevance. Some alternative treatments placed autistic individuals at risk. For example, in 2005, a five-year-old child with autism was killed by botched chelation therapy (which is not recommended for autism as risks outweigh any potential benefits). Epidemiology Globally, classic autism was understood to affect an estimated 24.8 million people as of 2015. After it was recognised as a distinct disorder, reports of autism cases substantially increased, which was largely attributable to changes in diagnostic practices, referral patterns, availability of services, age at diagnosis, and public awareness (particularly among women).Several other conditions were commonly seen in children with autism. They include: Intellectual disability. The percentage of autistic individuals who also met criteria for intellectual disability has been reported as anywhere from 25% to 70%, a wide variation illustrating the difficulty of assessing intelligence of individuals on the autism spectrum. In comparison, for PDD-NOS the association with intellectual disability was much weaker, and by definition, the diagnosis of Aspergers excluded intellectual disability. Minor physical anomalies are significantly increased in the autistic population. Preempted diagnoses. Although the DSM-IV ruled out the concurrent diagnosis of many other conditions along with autism, the full criteria for Attention deficit hyperactivity disorder (ADHD), Tourette syndrome, and other of these conditions were often present. As a result, modern ASD allows for these diagnoses. History The New Latin word autismus (English translation autism) was coined by the Swiss psychiatrist Eugen Bleuler in 1910 as he was defining symptoms of schizophrenia. He derived it from the Greek word autós (αὐτός, meaning "self"), and used it to mean morbid self-admiration, referring to "autistic withdrawal of the patient to his fantasies, against which any influence from outside becomes an intolerable disturbance". The word autism first took its modern sense in 1938 when Hans Asperger of the Vienna University Hospital adopted Bleulers terminology autistic psychopaths in a lecture in German about child psychology. Asperger was investigating Asperger syndrome which, for various reasons, was not widely considered a separate diagnosis until 1981, although both are now considered part of ASD. Leo Kanner of the Johns Hopkins Hospital first used autism in English to refer to classic autism when he introduced the label early infantile autism in a 1943 report. Almost all the characteristics described in Kanners first paper on the subject, notably "autistic aloneness" and "insistence on sameness", are still regarded as typical of the autistic spectrum of disorders. Starting in the late 1960s, classic autism was established as a separate syndrome.It took until 1980 for the DSM-III to differentiate autism from childhood schizophrenia. In 1987, the DSM-III-R provided a checklist for diagnosing autism. In May 2013, the DSM-5 was released, updating the classification for pervasive developmental disorders. The grouping of disorders, including PDD-NOS, autism, Asperger syndrome, Rett syndrome, and CDD, has been removed and replaced with the general term of Autism Spectrum Disorder. References == External links ==

You act as a medical communicator. Your goal is to translate medical terms into comprehensive, yet straightforward language for all readers.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Bronchiectasis'?

Bronchiectasis is a disease in which there is permanent enlargement of parts of the airways of the lung. Symptoms typically include a chronic cough with mucus production. Other symptoms include shortness of breath, coughing up blood, and chest pain. Wheezing and nail clubbing may also occur. Those with the disease often get frequent lung infections.Bronchiectasis may result from a number of infectious and acquired causes, including measles, pneumonia, tuberculosis, immune system problems, as well as the genetic disorder cystic fibrosis. Cystic fibrosis eventually results in severe bronchiectasis in nearly all cases. The cause in 10–50% of those without cystic fibrosis is unknown. The mechanism of disease is breakdown of the airways due to an excessive inflammatory response. Involved airways (bronchi) become enlarged and thus less able to clear secretions. These secretions increase the amount of bacteria in the lungs, resulting in airway blockage and further breakdown of the airways. It is classified as an obstructive lung disease, along with chronic obstructive pulmonary disease and asthma. The diagnosis is suspected based on symptoms and confirmed using computed tomography. Cultures of the mucus produced may be useful to determine treatment in those who have acute worsening and at least once a year.Periods of worsening may occur due to infection. In these cases, antibiotics are recommended. Common antibiotics used include amoxicillin, erythromycin, or doxycycline. Antibiotics, such as erythromycin, may also be used to prevent worsening of disease. Airway clearance techniques, a type of physical therapy, are also recommended. Medications to dilate the airways and inhaled steroids may be used during sudden worsening, but there are no studies to determine effectiveness. There are also no studies on the use of inhaled steroids in children. Surgery, while commonly done, has not been well studied. Lung transplantation may be an option in those with very severe disease.The disease affects between 1 per 1000 and 1 per 250,000 adults. The disease is more common in women and increases as people age. It became less common since the 1950s with the introduction of antibiotics. It is more common among certain ethnic groups (such as indigenous people in the US). It was first described by René Laennec in 1819. The economic costs in the United States are estimated at $630 million per year. Signs and symptoms Symptoms of bronchiectasis commonly include a cough productive of frequent green or yellow sputum lasting months to years. Other common symptoms include difficulty breathing, wheezing (a whistling sound when you breathe), and chest pain. Exacerbations of symptoms may occur, these exacerbations occur more frequently in advanced or severe disease. Systemic symptoms, including fevers, chills, night sweats, fatigue and weight loss may be seen with bronchiectasis. Bronchiectasis may also present with coughing up blood in the absence of sputum, which has been called "dry bronchiectasis." Exacerbations in bronchiectasis present as a worsening of cough, increasing sputum volume or thickened consistency lasting at least 48 hours, worsening shortness of breath (breathlessness), worsening exercise intolerance, increased fatigue or malaise and the development of hemoptysis.People often report frequent bouts of "bronchitis" requiring therapy with repeated courses of antibiotics. People with bronchiectasis may have bad breath from active infection. On examination, crepitations and expiratory rhonchi may be heard with auscultation. Nail clubbing is a rare symptom.The complications of bronchiectasis include serious health conditions, such as respiratory failure and atelectasis: collapse or closure of a lung. Respiratory failure occurs when not enough oxygen passes from the lungs into the blood. Atelectasis occur when one or more segments of the lungs collapse or do not inflate properly. Other pulmonary complications include lung abscess and empyema. Cardiovascular complications include cor pulmonale, in which there is enlargement and failure of the right side of the heart as a result of disease of the lungs. Causes There are many causes that can induce or contribute to the development of bronchiectasis. The frequency of these different causes varies with geographic location. Cystic fibrosis is identified as a cause in up to half of cases. Bronchiectasis without CF is known as non-CF bronchiectasis. Historically, about half of all case of non-CF bronchiectasis were found to be idiopathic, or without a known cause. However, more recent studies with a more thorough diagnostic work-up have found an etiology in 60 to 90% of patients. Cystic fibrosis Cystic fibrosis is the most common life-threatening autosomal recessive disease in the United States and Europe. It is a genetic disorder that affects the lungs, but also the pancreas, liver, kidneys, and intestine. It is caused by mutations in the CFTR protein, a chloride channel expressed in epithelial cells. Lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation. In later stages, changes to the structure of the lung, such as bronchiectasis, occur. Around 5 to 10% of all patients with cystic fibrosis develop bronchiectasis. Airway obstruction An airway obstruction can be caused by either an intraluminal mass such as a tumor or a foreign body. The presence of an airway obstruction leads to a cycle of inflammation. It is important to identify the presence of an obstruction because surgical resection is often curative if obstruction is the cause. In adults, foreign body aspiration is often associated with an altered state of consciousness. The foreign body is often unchewed food, or part of a tooth or crown. Bronchiectasis that results from foreign body aspiration generally occurs in the right lung in the lower lobe or posterior segments of the upper lobe. Lung infections A range of bacterial, mycobacterial, and viral lung infections are associated with the development of bronchiectasis. Bacterial infections commonly associated with bronchiectasis include P. aeruginosa, H. influenzae, and S. pneumoniae. Gram-negative bacteria are more commonly implicated than gram-positive bacteria. A history of mycobacterial infections such as tuberculosis can lead to damage of the airways that predisposes to bacterial colonization. Severe viral infections in childhood can also lead to bronchiectasis through a similar mechanism. Nontuberculous mycobacteria infections such as Mycobacterium avium complex are found to be a cause in some patients. Recent studies have also shown Nocardia infections to been implicated in bronchiectasis. Impaired host defenses Impairments in host defenses that lead to bronchiectasis may be congenital, such as with primary ciliary dyskinesia, or acquired, such as with the prolonged use of immunosuppressive drugs. Additionally, these impairments may be localized to the lungs, or systemic throughout the body. In these states of immunodeficiency, there is a weakened or absent immune system response to severe infections that repeatedly affect the lung and eventually result in bronchial wall injury. HIV/AIDS is an example of an acquired immunodeficiency that can lead to the development of bronchiectasis. Aspergillosis Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory disease caused by hypersensitivity to the fungus Aspergillus fumigatus. It is suspected in patients with a long history of asthma and symptoms of bronchiectasis such as a productive, mucopurulent cough. Imaging often shows peripheral and central airway bronchiectasis, which is unusual in patients with bronchiectasis caused by other disorders. Autoimmune diseases Several autoimmune diseases have been associated with bronchiectasis. Specifically, individuals with rheumatoid arthritis and Sjögren syndrome have increased rates of bronchiectasis. In these diseases, the symptoms of bronchiectasis usually presents later in the disease course. Other autoimmune diseases such as ulcerative colitis and Crohns disease also have an association with bronchiectasis. Additionally, graft-versus-host disease in patients who have undergone stem cell transplantation can lead to bronchiectasis as well. Lung injury Bronchiectasis could be caused by: inhalation of ammonia and other toxic gases, chronic pulmonary aspiration of stomach acid from esophageal reflux, or a hiatal hernia. Congenital Bronchiectasis may result from congenital disorders that affect cilia motility or ion transport. A common genetic cause is cystic fibrosis, which affects chloride ion transport. Another genetic cause is primary ciliary dyskinesia, a rare disorder that leads to immotility of cilia and can lead to situs inversus. When situs inversus is accompanied by chronic sinusitis and bronchiectasis, this is known as Kartageners syndrome. Other rare genetic causes include Youngs syndrome and Williams-Campbell syndrome. Tracheobronchomegaly, or Mournier-Kuhn syndrome is a rare condition characterized by significant tracheobronchial dilation and recurrent lower respiratory tract infections. Individuals with alpha 1-antitrypsin deficiency have been found to be particularly susceptible to bronchiectasis, due to the loss of inhibition to enzyme elastase which cleaves elastin. This decreases the ability of the alveoli to return to normal shape during expiration. Cigarette smoking A causal role for tobacco smoke in bronchiectasis has not been demonstrated. Nonetheless, tobacco smoking can worsen pulmonary function and accelerate the progression of disease that is already present. Pathophysiology The development of bronchiectasis requires two factors: an initial injury to the lung (such as from infection, auto-immune destruction of lung tissue, or other destruction of lung tissue (as seen in gastroesophageal reflux disease or aspiration syndromes)) which leads to impaired mucociliary clearance, obstruction, or a defect in host defense. This triggers a host immune response from neutrophils (elastases), reactive oxygen species, and inflammatory cytokines that results in progressive destruction of normal lung architecture. In particular, the elastic fibers of bronchi are affected. The result is permanent abnormal dilation and destruction of the major bronchi and bronchiole walls.Disordered neutrophil function is believed to play a role in the pathogenesis of bronchiectasis. Neutrophil extracellular traps(NETs), which are extracellular fibers secreted by neutrophils that are used to trap and destroy pathogens, are hyperactive in bronchiectasis. Increased NET activity is associated with more severe bronchiectasis. Neutrophil elastase, which is an extracellular protein secreted by neutrophils to destroy pathogens as well as host tissue, is also hyperactive in many cases of bronchiectasis. An increased neutrophil elastase activity is also associated with worse outcomes and more severe disease in bronchiectasis. The initial lung injury in bronchiectasis leads to an impaired mucociliary clearance of the lung airways, which leads to mucous stasis. This mucous stasis leads to bacterial colonization in bronchiectasis which leads to neutrophil activation. This neutrophil activation leads to further further tissue destruction and airway distortion by neutrophils in addition to direct tissue destruction by the pathogenic bacteria. The distorted, damaged lung airways thus have impaired mucociliary clearance; leading to mucous stasis and bacterial colonization leading to further neutrophil activation and thus fueling a self-perpetuating "vicious cycle" of inflammation in bronchiectasis. This "vicious cycle" theory is the generally accepted explanation for the pathogenesis of bronchiectasis.Endobronchial tuberculosis commonly leads to bronchiectasis, either from bronchial stenosis or secondary traction from fibrosis. Traction bronchiectasis characteristically affects peripheral bronchi (which lack cartilage support) in areas of end-stage fibrosis. Diagnosis The goals of a diagnostic evaluation for bronchiectasis are radiographic confirmation of the diagnosis, identification of potential treatable causes, and functional assessment of the patient. A comprehensive evaluation consists of radiographic imaging, laboratory testing, and lung function testing.Laboratory tests that are commonly part of the initial evaluation include a complete blood count, sputum cultures for bacteria, mycobacteria, and fungi, testing for cystic fibrosis, and immunoglobulin levels. Additional tests that are sometimes indicated include testing for specific genetic disorders.Lung function testing is used for the assessment and monitoring of functional impairment due to bronchiectasis. These tests may include spirometry and walking tests. Obstructive lung impairment is the most common finding but restrictive lung impairment can be seen in advanced disease. Flexible bronchoscopy may be performed when sputum studies are negative and a focal obstructing lesion is suspected.A chest x-ray is abnormal in most patients with bronchiectasis. Computed tomography is recommended to confirm the diagnosis and is also used to describe the distribution and grade the severity of the disease. Radiographic findings include airway dilation, bronchial wall thickening, and atelectasis. There are three types bronchiectasis that can be seen on CT scan, namely cylindrical, varicose, and cystic bronchiectasis. Prevention In preventing bronchiectasis, it is necessary to prevent the lung infections and lung damage that can cause it. Children should be immunized against measles, pertussis, pneumonia, and other acute respiratory infections of childhood. Additionally, parents should stay alert to keep children from inhaling objects such as pieces of food or small toys that may get stuck in small airways. Smoking and other toxic fumes and gases should be avoided by all patients with bronchiectasis to decrease the development of infections (such as bronchitis) and further complications.Treatments to slow down the progression of this chronic disease include keeping bronchial airways clear and secretions weakened through various forms of airway clearance. Aggressively treating bronchial infections with antibiotics to prevent the destructive cycle of infection, damage to bronchi and bronchioles, and more infection is also standard treatment. Regular vaccination against pneumonia, influenza, and pertussis are generally advised. A healthy body mass index and regular doctor visits may have beneficial effects on the prevention of progressing bronchiectasis. The presence of hypoxemia, hypercapnia, dyspnea level and radiographic extent can greatly affect the mortality rate from this disease. Management A comprehensive approach to the management of bronchiectasis is recommended. It is important to establish whether an underlying modifiable cause, such as immunoglobulin deficiency or alpha-1 antitrypsin deficiency is present. The next steps include controlling infections and bronchial secretions, relieving airway obstructions, removing affected portions of lung by surgery, and preventing complications. Airway clearance The goal of airway clearance therapy is to loosen secretions and interrupt the cycle of inflammation and infection. Airway clearance techniques improve difficulty breathing, cough, and help patients cough up phlegm and mucus plugs. Airway clearance usually uses an inhaled agent (hypertonic saline) with chest physiotherapy, such as high-frequency chest wall oscillation. Many airway clearance techniques and devices exist. The choice of a technique or device is based on the frequency and tenacity of phlegm, patient comfort, cost, and the patients ability to use the technique or device with minimal interference to their lifestyle. The active cycle of breathing technique (ACBT), which can be employed with or without a flutter device, is beneficial in treating those with bronchiectasis. Mucolytic agents such as dornase alfa are not recommended for individuals with non-CF bronchiectasis. Mannitol is a hyperosmolar agent that is thought to hydrate airway secretions, however, clinical trials with it have not demonstrated efficacy. Anti-inflammatories The two most commonly used classes of anti-inflammatory therapies are macrolides and corticosteroids.Despite also being antibiotics, macrolides exert immunomodulatory effects on the host inflammatory response without systemic suppression of the immune system. These effects include modifying mucus production, inhibition of biofilm production, and suppression of inflammatory mediators. Three large multicenter, randomized trials have shown reduced rates of exacerbations and improved cough and dyspnea with use of macrolide therapy. The impact of adverse effects of macrolides such as gastrointestinal symptoms, hepatotoxicity, and increased antimicrobial resistance needs ongoing review and study.Inhaled corticosteroid therapy can reduce sputum production and decrease airway constriction over a period of time, helping prevent progression of bronchiectasis. Long term use of high-dose inhaled corticosteroids can lead to adverse consequences such as cataracts and osteoporosis. It is not recommended for routine use in children. One commonly used therapy is beclometasone dipropionate. Antibiotics Antibiotics are used in bronchiectasis to eradicate P. aeruginosa or MRSA, to suppress the burden of chronic bacterial colonization, and to treat exacerbations. The use of daily oral non-macrolide antibiotic treatment has been studied in small case series, but not in randomized trials. The role of inhaled antibiotics in non-CF bronchiectasis has recently evolved with two society guidelines and a systematic review suggesting a therapeutic trial of inhaled antibiotics in patients with three or more exacerbations per year and P. aeruginosa in their sputum. Options for inhaled antibiotics include aerosolized tobramycin, inhaled ciprofloxacin, aerosolized aztreonam, and aerosolized colistin. Bronchodilators Some clinical trials have shown a benefit with inhaled bronchodilators in certain people with bronchiectasis. In people with demonstrated bronchodilator reversibility on spirometry, the use of inhaled bronchodilators resulted in improved dyspnea, cough, and quality of life without any increase in adverse events. However, overall there is a lack of data to recommend use of bronchodilators in all patients with bronchiectasis. Surgery The primary role of surgery in the management of bronchiectasis is in localized disease to remove segments of the lung or to control massive hemoptysis. Additionally, surgery is used to remove an airway obstruction that is contributing to bronchiectasis. The goals are conservative, aiming to control specific disease manifestations rather than cure or eliminate all areas of bronchiectasis. Surgical case series have shown low operative mortality rate (less than 2%) and improvement of symptoms in the majority of patients selected to receive surgery. However, no randomized clinical trials have been performed evaluating the efficacy of surgery in bronchiectasis. Clinical trials Results from a phase 2 clinical trial were published in 2018. In a placebo-controlled, double-blind study conducted in 256 patients worldwide, patients who received Brensocatib reported prolonged time to the first exacerbation and also reduced rate of yearly exacerbation. Prognosis Two clinical scales have been used to predict disease severity and outcomes in bronchiectasis; the Bronchiectasis Severity Index and the FACED scale. The FACED scale uses the FEV-1 (forced expiratory volume in 1 second), age of the affected person, presence of chronic infection, extent of disease (number of lung lobes involved) and dyspnea scale rating (MRC dyspnea scale) to predict clinical outcomes in bronchiectasis. The Bronchiectasis Severity Index uses the same criteria as the FACED scale in addition to including criteria related to number of hospital admissions, annual exacerbations, colonization with other organisms and BMI (body mass index) less than 18.5. A decreased FEV-1, increasing age, presence of chronic infection (especially pseudomonas), a greater extent of lung involvement, high clinical dyspnea scale ratings, increased hospital admissions, a high number of annual exacerbations, and a BMI less than 18.5 lead to higher scores on both clinical scales and are associated with a poor prognosis in bronchiectasis; including increased mortality. Epidemiology The prevalence and incidence of bronchiectasis is unclear as the symptoms are variable. The disease affects between 1 per 1000 and 1 per 250,000 adults. The disease is more common in women and in the elderly. In a Medicare cohort study in the United States, consisting of adults 65 years and older, the prevalence of bronchiectasis was 701 per 100,000 persons. A similar prevalence rate of bronchiectasis has been reported in other countries including China, Germany, the United Kingdom, Spain and Singapore. Those with a dual COPD and bronchiectasis diagnosis are more likely to be cigarette smokers and more likely to be hospitalized as compared to those with bronchiectasis without COPD. It became less common since the 1950s, with the introduction of antibiotics. It is more common among certain ethnic groups such as indigenous people.An estimated 350,000 to 500,000 adults have bronchiectasis in the United States. Specifically, children of the indigenous populations of Australia, Alaska, Canada and New Zealand have significantly higher rates than other populations. Overall, a shortage of data exists concerning the epidemiology of bronchiectasis in Asia, Africa, and South America.The prevalence and incidence of bronchiectasis has increased greatly in the 21st century. In a Medicare cohort analysis, consisting of adults 65 years and older in the United States; the annual rates of diagnosis have increased by 8.7% every year between 2000 and 2007. This large increase in the diagnosis of bronchiectasis may be due to increased recognition of the disease (including more widespread use of CT scans) or it may be due to an increase in the underlying causes of bronchiectasis. History René Laennec, the man who invented the stethoscope, used his invention to first discover bronchiectasis in 1819.The disease was researched in greater detail by Sir William Osler, one of the four founding professors of Johns Hopkins Hospital, in the late 1800s. It is suspected that Osler himself died of complications from undiagnosed bronchiectasis. His biographies mention that he had frequent severe chest infections for many years.The term "bronchiectasis" comes from the Greek words bronkhia (meaning "airway") and ektasis (meaning "widening"). References == External links ==

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I'm seeking clarification on the medical term 'Norgestimate.' Could you explain it?

Norgestimate, sold under the brand names Ortho Tri-Cyclen and Previfem among others, is a progestin medication which is used in birth control pills for women and in menopausal hormone therapy. The medication is available in combination with an estrogen and is not available alone. It is taken by mouth.Side effects of the combination of an estrogen and norgestimate include menstrual irregularities, headaches, nausea, abdominal pain, breast tenderness, mood changes, and others. Norgestimate 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 very weak androgenic activity and no other important hormonal activity. The medication is a prodrug of norelgestromin and to a lesser extent of levonorgestrel in the body.Norgestimate was patented in 1965 and introduced for medical use, specifically in birth control pills, in 1986. It was introduced for use in menopausal hormone therapy in the United States in 1999. Norgestimate is sometimes referred to as a "third-generation" progestin. It is marketed in birth control pills widely throughout the world, whereas it is available for use in menopausal hormone therapy only in the United States and Brazil. Norgestimate is available as a generic medication. In 2019, the version with ethinylestradiol was the 70th most commonly prescribed medication in the United States, with more than 10 million prescriptions. Medical uses Norgestimate is used in hormonal contraception and in menopausal hormone therapy for the treatment of menopausal symptoms. It is used in combination with ethinylestradiol in birth control pills and in combination with estradiol in menopausal hormone therapy. Available forms Norgestimate is available only in combination with the estrogens ethinylestradiol and estradiol. These formulations are for use by mouth and are indicated specifically for hormonal contraception and menopausal hormone therapy. Norgestimate is not available on its own (i.e., as a standalone medication). Contraindications Side effects Norgestimate has mostly been studied in combination with an estrogen, so the side effects of norgestimate specifically or on its own have not been well-defined.Side effects associated with the combination of ethinylestradiol and norgestimate in premenopausal women, with greater than or equal to 2% incidence over up to 24 menstrual cycles, include headache/migraine (33%), abdominal/gastrointestinal pain (7.8%), vaginal infection (8.4%), vaginal discharge (6.8%), breast issues (including breast pain, discharge, and enlargement) (6.3%), mood disorders (including depression and mood alterations) (5.0%), flatulence (3.2%), nervousness (2.9%), and rash (2.6%).Side effects associated with the combination of estradiol and norgestimate in postmenopausal women, with greater than or equal to 5% incidence over one year, include headache (23%), upper respiratory tract infection (21%), breast pain (16%), back pain (12%), abdominal pain (12%), flu-like symptoms (11%), arthralgia (9%), vaginal bleeding (9%), dysmenorrhea (8%), sinusitis (8%), vaginitis (7%), pharyngitis (7%), fatigue (6%), pain (6%), nausea (6%), viral infection (6%), flatulence (5%), tooth disorder (5%), myalgia (5%), dizziness (5%), depression (5%), and coughing (5%). Overdose Interactions Pharmacology Pharmacodynamics Norgestimate is a rapidly and completely converted prodrug, mainly of norelgestromin (17β-deacetylnorgestimate or levonorgestrel 3-oxime), but also of levonorgestrel (3-keto-17β-deacetylnorgestimate) to a lesser extent (22 ± 6% of an administered dose or about 40–70 µg) and of levonorgestrel acetate (levonorgestrel 17β-acetate) in very small amounts. Via its active metabolites, norgestimate has progestogenic activity, antigonadotropic effects, very weak androgenic activity, and no other important hormonal activity. Progestogenic activity Norgestimate is a progestogen, or an agonist of the progesterone receptor. The relative binding affinities of norgestimate and its active metabolites for the progesterone receptor compared to promegestone (100%) are 15% for norgestimate, 10% for norelgestromin, 150% for levonorgestrel, and 135% for levonorgestrel acetate. Because of their low concentrations, norgestimate and levonorgestrel acetate are not thought to contribute significantly to the biological activity of norgestimate. In addition, although levonorgestrel binds to the progesterone receptor with much higher affinity than norelgestromin, levonorgestrel has high affinity for sex hormone-binding globulin (SHBG) (87% of that of testosterone), which may limit its activity, whereas norelgestromin does not bind to SHBG. The ovulation-inhibiting dosage of norgestimate is 200 µg/day. Androgenic activity In addition to its progestogenic activity, norgestimate has weak androgenic activity. However, the medication shows less androgenic activity than related 19-nortestosterone progestins like levonorgestrel and norethisterone. Norgestimate and norelgestromin have negligible affinity for the androgen receptor (both 0% of the affinity of metribolone), while levonorgestrel has considerable affinity for the androgen receptor (45% of that of metribolone). In addition to their lack of affinity for the androgen receptor, norgestimate and norelgestromin have virtually no affinity for SHBG, and therefore do not displace testosterone from this carrier protein (although levonorgestrel does still bind with high affinity to SHBG and hence could increase free testosterone levels via occupation of SHBG). In accordance, clinical trials of norgestimate have observed minimal androgenic side effects in women treated with the medication. As an example, clinical studies have found that norgestimate does not appreciably inhibit the increase in SHBG levels produced by ethinylestradiol. This is of interest because estrogens increase and androgens decrease liver production of SHBG and by extension circulating levels of SHBG.The relative binding affinity of norgestimate and its metabolite norelgestromin for the rat prostatic androgen receptor (AR) are 0.3% and 1.3% of those of dihydrotestosterone (DHT), respectively, whereas the respective values for levonorgestrel and gestodene are 22% and 15%. Based on these findings, the ratios of AR to PR binding are 219 for norgestimate and 48 for norelgestromin, whereas the ratios for progesterone, levonorgestrel, and gestodene are 93, 11, and 28, respectively. As such, norgestimate and norelgestromin would appear to have much lower androgenic potency than other 19-nortestosterone progestins. However, levonorgestrel is an important metabolite of both norgestimate and norelgestromin, and it may serve to increase their androgenic potency to some degree.When norgestimate is combined with ethinylestradiol, which is potently antiandrogenic, there are only antiandrogenic effects overall and the combination is suitable for treatment of hyperandrogenism. Other activities Norgestimate and its active metabolites do not bind to other steroid hormone receptors besides the progesterone and androgen receptors and hence have no other off-target hormonal activity. This includes estrogenic, glucocorticoid, antimineralocorticoid, and neurosteroid activity. However, levonorgestrel has been found to inhibit 5α-reductase and hepatic cytochrome P450 enzymes in vitro to some extent. Pharmacokinetics Norgestimate is rapidly and almost completely metabolized into its active metabolites, mainly norelgestromin (the primary active metabolite) and to a lesser extent levonorgestrel, upon oral ingestion. As a result, only very low concentrations (70 pg/mL) of norgestimate itself are detectable in the circulation, and only for about 6 hours after an oral dose. The oral bioavailability of norgestimate is unknown. This is due to the rapid and extensive metabolism of norgestimate, which makes determination of overall bioavailability difficult and necessitates methods other than area-under-the-curve (AUC) to do so. Peak levels of norelgestromin (3,500 pg/mL) are reached at approximately 2 hours following administration of norgestimate. Co-administration of norgestimate with a high-fat meal has been found to significantly decrease peak levels of norelgestromin, although the area-under-the-curve levels of norelgestromin are not significantly altered by food. Steady-state levels of norelgestromin and levonorgestrel are reached within 21 days of treatment with norgestimate. There is an approximate 2-fold accumulation in levels of norelgestromin and a non-linear approximate 8-fold accumulation in levels of levonorgestrel with continuous administration of norgestimate. The accumulation of levonorgestrel is thought to be a result of its high affinity for SHBG, which limits its biological activity. The plasma protein binding of norelgestromin is approximately 99% and it is bound to albumin but not to SHBG. Conversely, levonorgestrel is approximately 98% bound to plasma proteins and is bound to both albumin and SHBG.Norgestimate is extensively metabolized into its active metabolites during first-pass metabolism in the liver and intestines. The major metabolite of norgestimate is norelgestromin and is formed from norgestimate via deacetylation in the liver and intestines. A more minor metabolite of norgestimate is levonorgestrel, which accounts for 20 to 25% (22 ± 6%) of an administered dose or about 40 to 70 µg norgestimate, and a very minor metabolite of norgestimate is levonorgestrel 17β-acetate. Both of these metabolites are active similarly to norgelstromin. With a typical oral contraceptive dosage of norgestimate of 200 to 250 µg/day, an amount of 50 to 60 µg/day levonorgestrel may be produced. This is similar to the ovulation-inhibiting dosage of levonorgestrel, and suggests that norgestimate may act in considerable part as a prodrug specifically of levonorgestrel. Following their formation, the active metabolites of norgestimate are inactivated via reduction, hydroxylation, and conjugation into levonorgestrel metabolites. The terminal half-life of norelgestromin is between 17 and 37 hours and of levonorgestrel is between 24 and 32 hours. The metabolites of norgestimate are eliminated 47% in urine and 37% in feces. Unchanged norgestimate is undetectable in urine. Chemistry Norgestimate, also known as 17α-ethynyl-18-methyl-19-nortestosterone 3-oxime 17β-acetate or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one 3-oxime 17β-acetate, is a synthetic estrane steroid and a derivative of testosterone. It is a racemic mixture of E and Z isomers. Norgestimate is more specifically a derivative of norethisterone (17α-ethynyl-19-nortestosterone) and is a member of the gonane (18-methylestrane) subgroup of the 19-nortestosterone family of progestins. It is the C3 oxime and C17β acetate ester of levonorgestrel and is also known as levonorgestrel acetate oxime. A related compound is norethisterone acetate oxime (norethisterone-3-oxime 17β-acetate). History Norgestimate was introduced as a component of combined oral contraceptives in 1986. Based on its year of introduction, norgestimate is sometimes described as a "third-generation" progestin. Norgestimate was approved in combination with estradiol for use in menopausal hormone therapy in 1999 in the United States, and a generic version of this preparation became available in this country in 2005. Society and culture Generic names Norgestimate is the generic name of the drug and its INN, USAN, USP, BAN, and DCF. It is also known by its developmental code name ORF-10131. Brand names Norgestimate is marketed in combination with ethinylestradiol as a birth control pill under the brand names Amicette, Cilest, Cyclen, Edelsin, Effiprev, Estarylla, MonoNessa, Orlon, Ortho Tri-Cyclen, Ortho Tri-Cyclen Lo, Ortho-Cyclen, Pramino, Previfem, Sprintec, Triafemi, TriCilest, Tri-Cyclen, Tri-Cyclen LO, Tridette, Tri-Estarylla, Tri-Linyah, TriNessa, Tri-Previfem, and Tri-Sprintec. It is marketed in combination with estradiol for menopausal hormone therapy under the brand name Prefest only. Availability Norgestimate in combination with ethinylestradiol is marketed widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe, South Africa, Latin America, and Asia. It is not listed as being marketed in Australia, New Zealand, Japan, South Korea, China, India, or certain other countries. Unlike the combined birth control pills of norgestimate with ethinylestradiol, the combination of norgestimate with estradiol, sold under the brand name Prefest for menopausal hormone therapy, is reportedly only marketed currently in the United States and Brazil. Research A 2017 study found that norgestimate inhibits staphylococcal biofilm formation and resensitizes methicillin-resistant Staphylococcus aureus to β-lactam antibiotics. In contrast, norelgestromin showed much weaker activity, indicating that the acetyl group of norgestimate is important for the activity. It was suggested by the researchers that norgestimate may be a promising lead compound for the development of new antibiotics. References Further reading Henzl MR (July 2001). "Norgestimate. From the laboratory to three clinical indications". J Reprod Med. 46 (7): 647–61. PMID 11499185. Curran MP, Wagstaff AJ (2001). "Estradiol and norgestimate: a review of their combined use as hormone replacement therapy in postmenopausal women". Drugs Aging. 18 (11): 863–85. doi:10.2165/00002512-200118110-00007. PMID 11772126. S2CID 22720686. Curran MP, Wagstaff AJ (2002). "Spotlight on estradiol and norgestimate as hormone replacement therapy in postmenopausal women". Treat Endocrinol. 1 (2): 127–9. doi:10.2165/00024677-200201020-00006. PMID 15765628. S2CID 1936039. External links "Norgestimate". Drug Information Portal. U.S. National Library of Medicine. "Ethinyl estradiol mixture with norgestimate". Drug Information Portal. U.S. National Library of Medicine. "Estradiol mixture with norgestimate". Drug Information Portal. U.S. National Library of Medicine.

You serve as a medical tutor. Your objective is to demystify medical terms, providing thorough explanations that cater to various levels of medical knowledge.

Can you break down the meaning of the medical term 'Side' for me?

Side or Sides may refer to: Geometry Edge (geometry) of a polygon (two-dimensional shape) Face (geometry) of a polyhedron (three-dimensional shape) Places Side (Ainis), a town of Ainis, ancient Thessaly, Greece Side (Caria), a town of ancient Caria, Anatolia Side (Laconia), a town of ancient Laconia, Greece Side (Pontus), a town of ancient Pontus, Anatolia Side, Turkey, a city in Turkey Side, Iran, a village in Iran Side, Gloucestershire, or Syde, a village in England Music Side (recording), the A-side or B-side of a record The Side, a Scottish rock band Sides (album), a 1979 album by Anthony Phillips Sides, a 2020 album by Emily King "Side" (song), a 2001 song by Travis "Sides", a song by Flobots from the album The Circle in the Square, 2012 "Sides", a song by Allday from the album Speeding, 2017 Teams Side (cue sports technique) Side, a team, in particular: Sports team Other uses Side (mythology), one of three mythological figures Side, a Morris dance team Sideboard (cards), known as a "side" in some collectible card games Sides (surname), a surname Side dish, a food item accompanying a main course School of Isolated and Distance Education, a public school in Perth, Western Australia Secretaría de Inteligencia, the premier intelligence agency of the Argentine Republic Social identity model of deindividuation effects, in social psychology Side (gay sex), a term describes gay men who are not interested in anal sex See also All pages with titles beginning with Side All pages with titles containing side Cide (disambiguation) Relative direction, left and right Sidle (disambiguation)

You function as a medical dictionary. Offer comprehensive and accurate descriptions of medical terms, ensuring clarity and depth in your explanations.

I'm looking for a concise explanation of the medical term 'Subacute lymphocytic thyroiditis.'

Subacute lymphocytic thyroiditis is a form of thyroiditis. Subacute lymphocytic thyroiditis may occur at any age and is more common in females. A variant of subacute lymphocytic thyroiditis occurs postpartum: postpartum thyroiditis. Both of these entities can be considered subtypes of Hashimotos thyroiditis and have an autoimmune basis. Anti-thyroid antibodies are common in all three and the underlying histology is similar. This disorder should not be confused with de Quervains thyroiditis which is another form of subacute thyroiditis. Symptoms and signs Subacute lymphocytic thyroiditis features a small goiter without tenderness. This condition tends to have a phase of hyperthyroidism followed by a return to a euthyroid state, and then a phase of hypothyroidism, followed again by a return to the euthyroid state. The time span of each phase can vary; however, each phase usually lasts 2–3 months. Diagnosis Subacute lymphocytic thyroiditis can only be diagnosed correctly by taking a radioactive iodine uptake test (RAIU) test. During both the hyperthyroid and hypothyroid phases, radioiodine uptake is decreased. This situation contrasts greatly with the elevated iodine uptake found in patients with Graves disease. Treatment Treatment is based on symptoms. Beta-blockers relieve rapid heart rate and excessive sweating during the hyperthyroid phase. == References ==

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I'm looking for a concise explanation of the medical term 'Lipoblastomatosis.'

Benign lipoblastomatosis is a tumor consisting of fetal-embryonal adipocytes, frequently confused with a liposarcoma, affecting exclusively infants and young children, with approximately 90% of cases occurring before 3 years of age.: 626  The term lipoblastomatosis was first used by Vellios et al. in 1958, at which point the tumor became generally accepted as a distinctive entity. Today Diffuse lipoblastoma is the preferred term for Lipoblastomatosis. The tumor is rare, accounting for less than 1% of all childhood neoplasm, and it has been found to be more common in males than females. It often presents as an asymptomatic rapidly enlarging mass, occurring more often in the soft tissues of the extremities. See also Myxoid lipoblastoma List of cutaneous conditions References == External links ==

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Could you provide a brief overview of 'Palonosetron' in a medical context?

Palonosetron, sold under the brand name Aloxi, is used for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is a 5-HT3 antagonist.Palonosetron is administered intravenously, or as a single oral capsule. It has a longer duration of action than other 5-HT3 antagonists. The oral formulation was approved on August 22, 2008, for prevention of acute CINV alone, as a large clinical trial did not show oral administration to be as effective as intravenous use against delayed CINV. It is on the World Health Organizations List of Essential Medicines.The oral combination netupitant/palonosetron is approved for both acute and delayed CINV. Adverse effects The most common adverse effects are headache, which occurs in 4–11% of patients, and constipation in up to 6% of patients. In less than 1% of patients, other gastrointestinal disorders occur, as well as sleeplessness, first- and second-degree atrioventricular block, muscle pain and shortness of breath. Palonosetron is similarly well tolerated as other 5-HT3 antagonists, and slightly less than placebo. Interactions Palonosetron does not relevantly inhibit or induce cytochrome P450 liver enzymes. There are case reports about serotonin syndrome when the drug is combined with serotonergic substances such as selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), two common types of antidepressants. Pharmacology Mechanism of action Palonosetron is a 5-HT3 antagonist, commonly known as a setron. These drugs act by blocking serotonin from binding to the 5-HT3 receptor. Pharmacokinetics Orally taken palonosetron is absorbed well from the gut and has a bioavailability of 97%. Highest blood plasma levels are reached after 5.1±1.7 hours, independently of food intake, and plasma protein binding is 62%. 40% of the substance are eliminated in the unchanged form, and a further 45–50% are metabolized by the liver enzyme CYP2D6 and to a lesser extent by CYP3A4 and CYP1A2. The two main metabolites, the N-oxide and a hydroxy derivative, have less than 1% of palonosetrons antagonistic effect and are thus practically inactive.Palonosetron and its metabolites are mainly (to 80–93%) eliminated via the kidney. Biological half-life in healthy persons was 37±12 hours in a study, and 48±19 hours in cancer patients. In 10% of patients, half-life is over 100 hours. Most other marketed setrons have half-lives in the range of about two to 15 hours. Chemistry The substance is solid at room temperature and melts at 87 to 88 °C (189 to 190 °F). The infusions and capsules contain palonosetron hydrochloride, which is also a solid. The hydrochloride is easily soluble in water, soluble in propylene glycol, and slightly soluble in ethanol and isopropyl alcohol.The molecule has two asymmetric carbon atoms. It is used in form of the pure (S,S)-stereoisomer. References External links "Palonosetron". Drug Information Portal. U.S. National Library of Medicine.

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

What is the significance of the term 'Perihepatitis' in the medical field?

Perihepatitis is inflammation of the serous or peritoneal coating of the liver. Perihepatitis is often caused by one of the inflammatory disorders of the female upper genital tract, known collectively as pelvic inflammatory disease. Some patients have sharp right upper abdominal quadrant pain. One of the complications of perihepatitis is Fitz-Hugh–Curtis syndrome.Common bacterial causes for this disease are Chlamydia trachomatis and Neisseria gonorrhoeae. == References ==

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I'm curious about the meaning of the medical term 'Nitrogen narcosis.' Can you give me some insights?

Narcosis while diving (also known as nitrogen narcosis, inert gas narcosis, raptures of the deep, Martini effect) is a reversible alteration in consciousness that occurs while diving at depth. It is caused by the anesthetic effect of certain gases at high pressure. The Greek word νάρκωσις (narkōsis), "the act of making numb", is derived from νάρκη (narkē), "numbness, torpor", a term used by Homer and Hippocrates. Narcosis produces a state similar to drunkenness (alcohol intoxication), or nitrous oxide inhalation. It can occur during shallow dives, but does not usually become noticeable at depths less than 30 meters (100 ft). Except for helium and probably neon, all gases that can be breathed have a narcotic effect, although widely varying in degree. The effect is consistently greater for gases with a higher lipid solubility, and although the mechanism of this phenomenon is still not fully clear, there is good evidence that the two properties are mechanistically related. As depth increases, the mental impairment may become hazardous. Divers can learn to cope with some of the effects of narcosis, but it is impossible to develop a tolerance. Narcosis can affect all divers, although susceptibility varies widely among individuals and from dive to dive. The main class of diving that deals with its prevention and treatment is scuba diving at substantial depth. Narcosis may be completely reversed in a few minutes by ascending to a shallower depth, with no long-term effects. Thus narcosis while diving in open water rarely develops into a serious problem as long as the divers are aware of its symptoms, and are able to ascend to manage it. Diving much beyond 40 m (130 ft) is generally considered outside the scope of recreational diving. In order to dive at greater depths, as narcosis and oxygen toxicity become critical risk factors, specialist training is required in the use of various helium-containing gas mixtures such as trimix or heliox. These mixtures prevent narcosis by replacing some or all of the inert fraction of the breathing gas with non-narcotic helium. Classification Narcosis results from breathing gases under elevated pressure, and may be classified by the principal gas involved. The noble gases, except helium and probably neon, as well as nitrogen, oxygen and hydrogen cause a decrement in mental function, but their effect on psychomotor function (processes affecting the coordination of sensory or cognitive processes and motor activity) varies widely. The effect of carbon dioxide is a consistent diminution of mental and psychomotor function. The noble gases argon, krypton, and xenon are more narcotic than nitrogen at a given pressure, and xenon has so much anesthetic activity that it is a usable anesthetic at 80% concentration and normal atmospheric pressure. Xenon has historically been too expensive to be used very much in practice, but it has been successfully used for surgical operations, and xenon anesthesia systems are still being proposed and designed. Signs and symptoms Due to its perception-altering effects, the onset of narcosis may be hard to recognize. At its most benign, narcosis results in relief of anxiety – a feeling of tranquillity and mastery of the environment. These effects are essentially identical to various concentrations of nitrous oxide. They also resemble (though not as closely) the effects of alcohol and the familiar benzodiazepine drugs such as diazepam and alprazolam. Such effects are not harmful unless they cause some immediate danger to go unrecognized and unaddressed. Once stabilized, the effects generally remain the same at a given depth, only worsening if the diver ventures deeper.The most dangerous aspects of narcosis are the impairment of judgement, multi-tasking and coordination, and the loss of decision-making ability and focus. Other effects include vertigo and visual or auditory disturbances. The syndrome may cause exhilaration, giddiness, extreme anxiety, depression, or paranoia, depending on the individual diver and the divers medical or personal history. When more serious, the diver may feel overconfident, disregarding normal safe diving practices. Slowed mental activity, as indicated by increased reaction time and increased errors in cognitive function, are effects which increase the risk of a diver mismanaging an incident. Narcosis reduces both the perception of cold discomfort and shivering and thereby affects the production of body heat and consequently allows a faster drop in the core temperature in cold water, with reduced awareness of the developing problem.The relation of depth to narcosis is sometimes informally known as "Martinis law", the idea that narcosis results in the feeling of one martini for every 10 m (33 ft) below 20 m (66 ft) depth. Professional divers use such a calculation only as a rough guide to give new divers a metaphor, comparing a situation they may be more familiar with.Reported signs and symptoms are summarized against typical depths in meters and feet of sea water in the following table, closely adapted from Deeper into Diving by Lippman and Mitchell: Causes The cause of narcosis is related to the increased solubility of gases in body tissues, as a result of the elevated pressures at depth (Henrys law). Modern theories have suggested that inert gases dissolving in the lipid bilayer of cell membranes cause narcosis. More recently, researchers have been looking at neurotransmitter receptor protein mechanisms as a possible cause of narcosis. The breathing gas mix entering the divers lungs will have the same pressure as the surrounding water, known as the ambient pressure. After any change of depth, the pressure of gases in the blood passing through the brain catches up with ambient pressure within a minute or two, which results in a delayed narcotic effect after descending to a new depth. Rapid compression potentiates narcosis owing to carbon dioxide retention.A divers cognition may be affected on dives as shallow as 10 m (33 ft), but the changes are not usually noticeable. There is no reliable method to predict the depth at which narcosis becomes noticeable, or the severity of the effect on an individual diver, as it may vary from dive to dive even on the same day.Significant impairment due to narcosis is an increasing risk below depths of about 30 m (100 ft), corresponding to an ambient pressure of about 4 bar (400 kPa). Most sport scuba training organizations recommend depths of no more than 40 m (130 ft) because of the risk of narcosis. When breathing air at depths of 90 m (300 ft) – an ambient pressure of about 10 bar (1,000 kPa) – narcosis in most divers leads to hallucinations, loss of memory, and unconsciousness. A number of divers have died in attempts to set air depth records below 120 m (400 ft). Because of these incidents, Guinness World Records no longer reports on this figure.Narcosis has been compared with altitude sickness regarding its variability of onset (though not its symptoms); its effects depend on many factors, with variations between individuals. Thermal cold, stress, heavy work, fatigue, and carbon dioxide retention all increase the risk and severity of narcosis. Carbon dioxide has a high narcotic potential and also causes increased blood flow to the brain, increasing the effects of other gases. Increased risk of narcosis results from increasing the amount of carbon dioxide retained through heavy exercise, shallow or skip breathing, or because of poor gas exchange in the lungs.Narcosis is known to be additive to even minimal alcohol intoxication. Other sedative and analgesic drugs, such as opiate narcotics and benzodiazepines, add to narcosis. Mechanism The precise mechanism is not well understood, but it appears to be the direct effect of gas dissolving into nerve membranes and causing temporary disruption in nerve transmissions. While the effect was first observed with air, other gases including argon, krypton and hydrogen cause very similar effects at higher than atmospheric pressure. Some of these effects may be due to antagonism at NMDA receptors and potentiation of GABAA receptors, similar to the mechanism of nonpolar anesthetics such diethyl ether or ethylene. However, their reproduction by the very chemically inactive gas argon makes them unlikely to be a strictly chemical bonding to receptors in the usual sense of a chemical bond. An indirect physical effect – such as a change in membrane volume – would therefore be needed to affect the ligand-gated ion channels of nerve cells. Trudell et al. have suggested non-chemical binding due to the attractive van der Waals force between proteins and inert gases.Similar to the mechanism of ethanols effect, the increase of gas dissolved in nerve cell membranes may cause altered ion permeability properties of the neural cells lipid bilayers. The partial pressure of a gas required to cause a measured degree of impairment correlates well with the lipid solubility of the gas: the greater the solubility, the less partial pressure is needed.An early theory, the Meyer-Overton hypothesis, suggested that narcosis happens when the gas penetrates the lipids of the brains nerve cells, causing direct mechanical interference with the transmission of signals from one nerve cell to another. More recently, specific types of chemically gated receptors in nerve cells have been identified as being involved with anesthesia and narcosis. However, the basic and most general underlying idea, that nerve transmission is altered in many diffuse areas of the brain as a result of gas molecules dissolved in the nerve cells fatty membranes, remains largely unchallenged. Management and diagnosis The management of narcosis is simply to ascend to shallower depths; the effects then disappear within minutes. In the event of complications or other conditions being present, ascending is always the correct initial response. Should problems remain, then it is necessary to abort the dive. The decompression schedule can still be followed unless other conditions require emergency assistance.The symptoms of narcosis may be caused by other factors during a dive: ear problems causing disorientation or nausea; early signs of oxygen toxicity causing visual disturbances; or hypothermia causing rapid breathing and shivering. Nevertheless, the presence of any of these symptoms should imply narcosis. Alleviation of the effects upon ascending to a shallower depth will confirm the diagnosis. Given the setting, other likely conditions do not produce reversible effects. In the rare event of misdiagnosis when another condition is causing the symptoms, the initial management – ascending closer to the surface – is still essential. Prevention The most straightforward way to avoid nitrogen narcosis is for a diver to limit the depth of dives. The other main preventive measure is properly informed selection/choice of which gas to use for the particular dive under consideration. Since narcosis becomes more severe as depth increases, a diver keeping to shallower depths can avoid serious narcosis. Most recreational dive schools will only certify entry level divers to depths of 18 to 20 m (60 to 70 ft), and at these depths narcosis does not present a significant risk. Further training is normally required for certification up to 30 m (100 ft) on air, and this training should include a discussion of narcosis, its effects, and management. Some diver training agencies offer specialized training to prepare recreational divers to go to depths of 40 m (130 ft), often consisting of further theory and some practice in deep dives under close supervision. Scuba organizations that train for diving beyond recreational depths, may forbid diving with gases that cause too much narcosis at depth in the average diver (such as the typical widely used nitrox mixtures suitable for most recreational diving), and strongly encourage the use of other breathing gas mixes containing helium in place of some or all of the nitrogen in air – such as trimix and heliox – because helium has no narcotic effect. The use of these gases forms part of technical diving and requires further training and certification.While the individual diver cannot predict exactly at what depth the onset of narcosis will occur on a given day, the first symptoms of narcosis for any given diver are often more predictable and personal. For example, one diver may have trouble with eye focus (close accommodation for middle-aged divers), another may experience feelings of euphoria, and another feelings of claustrophobia. Some divers report that they have hearing changes, and that the sound their exhaled bubbles make becomes different. Specialist training may help divers to identify these personal onset signs, which may then be used as a signal to ascend to avoid the narcosis, although severe narcosis may interfere with the judgement necessary to take preventive action.Deep dives should be made only after a gradual training to test the individual divers sensitivity to increasing depths, with careful supervision and logging of reactions. Scientific evidence does not show that a diver can train to overcome any measure of narcosis at a given depth or become tolerant of it.Equivalent narcotic depth (END) is a commonly used way of expressing the narcotic effect of different breathing gases. The National Oceanic and Atmospheric Administration (NOAA) Diving Manual now states that oxygen and nitrogen should be considered equally narcotic. Standard tables, based on relative lipid solubilities, list conversion factors for narcotic effect of other gases. For example, hydrogen at a given pressure has a narcotic effect equivalent to nitrogen at 0.55 times that pressure, so in principle it should be usable at more than twice the depth. Argon, however, has 2.33 times the narcotic effect of nitrogen, and is a poor choice as a breathing gas for diving (it is used as a drysuit inflation gas, owing to its low thermal conductivity). Some gases have other dangerous effects when breathed at pressure; for example, high-pressure oxygen can lead to oxygen toxicity. Although helium is the least intoxicating of the breathing gases, at greater depths it can cause high pressure nervous syndrome, a still mysterious but apparently unrelated phenomenon. Inert gas narcosis is only one factor influencing the choice of gas mixture; the risks of decompression sickness and oxygen toxicity, cost, and other factors are also important.Because of similar and additive effects, divers should avoid sedating medications and drugs, such as cannabis and alcohol before any dive. A hangover, combined with the reduced physical capacity that goes with it, makes nitrogen narcosis more likely. Experts recommend total abstinence from alcohol for at least 12 hours before diving, and longer for other drugs. Prognosis and epidemiology Narcosis is potentially one of the most dangerous conditions to affect the scuba diver below about 30 m (100 ft). Except for occasional amnesia of events at depth, the effects of narcosis are entirely removed on ascent and therefore pose no problem in themselves, even for repeated, chronic or acute exposure. Nevertheless, the severity of narcosis is unpredictable and it can be fatal while diving, as the result of illogical behavior in a dangerous environment.Tests have shown that all divers are affected by nitrogen narcosis, though some experience lesser effects than others. Even though it is possible that some divers can manage better than others because of learning to cope with the subjective impairment, the underlying behavioral effects remain. These effects are particularly dangerous because a diver may feel they are not experiencing narcosis, yet still be affected by it. History French researcher Victor T. Junod was the first to describe symptoms of narcosis in 1834, noting "the functions of the brain are activated, imagination is lively, thoughts have a peculiar charm and, in some persons, symptoms of intoxication are present." Junod suggested that narcosis resulted from pressure causing increased blood flow and hence stimulating nerve centers. Walter Moxon (1836–1886), a prominent Victorian physician, hypothesized in 1881 that pressure forced blood to inaccessible parts of the body and the stagnant blood then resulted in emotional changes. The first report of anesthetic potency being related to lipid solubility was published by Hans H. Meyer in 1899, entitled Zur Theorie der Alkoholnarkose. Two years later a similar theory was published independently by Charles Ernest Overton. What became known as the Meyer-Overton hypothesis may be illustrated by a graph comparing narcotic potency with solubility in oil. In 1939, Albert R. Behnke and O. D. Yarborough demonstrated that gases other than nitrogen also could cause narcosis. For an inert gas the narcotic potency was found to be proportional to its lipid solubility. As hydrogen has only 0.55 the solubility of nitrogen, deep diving experiments using hydrox were conducted by Arne Zetterström between 1943 and 1945. Jacques-Yves Cousteau in 1953 famously described it as "livresse des grandes profondeurs" or the "rapture of the deep".Further research into the possible mechanisms of narcosis by anesthetic action led to the "minimum alveolar concentration" concept in 1965. This measures the relative concentration of different gases required to prevent motor response in 50% of subjects in response to stimulus, and shows similar results for anesthetic potency as the measurements of lipid solubility. The (NOAA) Diving Manual was revised to recommend treating oxygen as if it were as narcotic as nitrogen, following research by Christian J. Lambertsen et al. in 1977 and 1978. See also Hydrogen narcosis – Psychotropic state induced by breathing hydrogen at high partial pressures Oxygen toxicity – Toxic effects of breathing oxygen at high concentrations Footnotes References Notes Sources Bennett, Peter; Rostain, Jean Claude (2003). "Inert Gas Narcosis". In Brubakk, Alf O; Neuman, Tom S (eds.). Bennett and Elliotts physiology and medicine of diving (5th ed.). United States: Saunders. ISBN 0-7020-2571-2. OCLC 51607923. Lippmann, John; Mitchell, Simon J. (2005). "Nitrogen narcosis". Deeper into Diving (2nd ed.). Victoria, Australia: J. L. Publications. pp. 103–8. ISBN 0-9752290-1-X. OCLC 66524750. U.S. Navy Supervisor of Diving (2008). U.S. Navy Diving Manual (PDF). SS521-AG-PRO-010, revision 6. U.S. Naval Sea Systems Command. Archived from the original (PDF) on 2014-12-10. Retrieved 2014-01-21. External links Undersea and Hyperbaric Medical Society Scientific body, publications about nitrogen narcosis. Rubicon Research Repository Searchable repository of Diving and Environmental Physiology Research. Diving Diseases Research Centre (DDRC) UK charity dedicated to treatment of diving diseases. Campbell, Ernest S. (2009-06-25). "Diving While Using Marijuana". Retrieved 2009-08-25. ScubaDocs overview of marijuana and diving. Campbell, Ernest S. (2009-05-03). "Alcohol and Diving". Archived from the original on 2007-04-30. Retrieved 2009-08-25. ScubaDocs overview of alcohol and diving. Campbell, George D. (2009-02-01). "Nitrogen Narcosis". Diving with Deep-Six. Retrieved 2009-08-25.

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

I'm trying to understand 'Chylothorax' within a medical context. Could you shed some light on it?

A chylothorax is an abnormal accumulation of chyle, a type of lipid-rich lymph, in the space surrounding the lung. The lymphatics of the digestive system normally returns lipids absorbed from the small bowel via the thoracic duct, which ascends behind the esophagus to drain into the left brachiocephalic vein. If normal thoracic duct drainage is disrupted, either due to obstruction or rupture, chyle can leak and accumulate within the negative-pressured pleural space. In people on a normal diet, this fluid collection can sometimes be identified by its turbid, milky white appearance, since chyle contains emulsified triglycerides. Chylothorax is a rare but serious condition, as it signals leakage of the thoracic duct or one of its tributaries. There are many treatments, both surgical and conservative. About 2–3% of all fluid collections surrounding the lungs (pleural effusions) are chylothoraces. It is important to distinguish a chylothorax from a pseudochylothorax (a pleural effusion that happens to be high in cholesterol), which has a similar appearance visually but is caused by more chronic inflammatory processes and requires a different treatment. Signs and symptoms The symptoms of a chylothorax depend its size and the underlying cause. A small chylothorax may not cause any symptoms and only be detected on a chest X-ray performed for another reason. A large chylothorax may lead to breathlessness or a feeling of pressure in the chest, caused by fluid restricting the expansion of the lungs, although large chylothoraces may remain asymptomatic if the chylothorax has accumulated slowly, as the lungs may have had time to become used to the pressure. Fever or chest pain are not usually associated with chylothorax, as chyle does not generate inflammation by itself.On examination, chylothorax may lead to reduced breath sounds on the affected side, associated with a dull sound when the chest is tapped or percussed. In cases of postoperative chylothorax, the first sign may be persistent drainage from intercostal drains. Large chylothoraces may cause signs related to the loss of nutrients, including features of malnutrition or decreased ability to fight infections. Rapidly accumulating chylothoraces can cause a sudden drop in blood volume, leading to low blood pressure. Causes There are three main types of chylothorax: traumatic, non-traumatic, and idiopathic. Historically the most common form of chylothorax was non-traumatic, but traumatic chylothoraces now represent the majority of cases, with most arising as postoperative complications of surgery. The most common cause of non-traumatic chylothoraces is cancer. Chylothoraces can also be classified as low- or high-output based on the rate of chyle accumulation: low-output chylothoraces accumulate <500 mL of chyle per 24 hours, while high-output chylothoraces accumulate >1000 mL per 24 hours. Non-traumatic Malignancies are the most frequent cause of non-traumatic chylothorax. Cancers like chronic lymphocytic leukemia, lung cancer, lymphoma, Kaposi sarcoma, metastatic carcinoma or esophageal cancer are potential causes of chylothorax. Infectious causes are also observed, most often in developing countries. The most common cause of an infectious chylothorax is a complication of tuberculous lymphadenitis. Other possible causative infections include aortitis, histoplasmosis, and filariasis. Chylothorax can also be congenital, and may co-occur with other lymphatic malformations like lymphangiectasis and lymphangiomatosis. Other conditions like tuberous sclerosis, congenital heart disease, trisomy 21 (Down syndrome), Noonan syndrome, or Turner syndrome (missing X chromosome) are also possible causes of congenital chylothorax. Other, more rare causes of congenital chylothorax include Castlemans disease, yellow nail syndrome, Waldenströms macroglobulinemia, sarcoidosis, venous thrombosis, thoracic radiation, macroglobulinemia, amyloidosis, and a goiter. These diseases cause chylothorax by obstructing or destroying the thoracic duct. Also, parenteral nutrition has been a possible cause; a quick dose of total parenteral nutrition can overwhelm the thoracic duct, causing the chyle to leak into the surrounding pleural space. Traumatic Iatrogenic chylothorax after surgery is the most common variety of chylothorax. It is a common and serious complication of a pneumonectomy. It is especially common in surgeries requiring mediastinal dissection. The probability of chylothorax depends on the type of surgery. The surgery with the highest risk of chylothorax is an esophagostomy, with a 5-10% risk of chylothorax. Lung resection and mediastinal node dissection have the second highest risk, with 3-7% risk. Other operations like mediastinal tumor resection, thoracic aneurysm repair, sympathectomy, and any other surgeries that take place in the lower neck or the mediastinum can lead to chylothorax. Chylotharax after trauma but not after surgery has also been described after central line placement, pacemaker implantation, and embolization of a pulmonary arteriovenous malformation. Blunt trauma to the chest region is another cause of chylothorax, which has occurred after blast injuries and even simple injuries from coughing or sneezing. Mechanism The main mechanism of chylothorax is the leaking of chyle from the thoracic duct, usually caused by a disturbance affecting the structural integrity of the thoracic duct. For example, placement of a central venous catheter can potentially disrupt drainage of lymph into the subclavian veins, followed by the thoracic duct, resulting in chylothorax. The disturbances cause the pressure in the thoracic duct to increase. Soon, collateral channels form, which eventually drain into the thorax. Trauma affecting the thoracic duct is the most common disturbing mechanism. Whether a chylothorax occurs in the left or right pleural space is a consequence of the thoracic ducts anatomic location in the body and depends on the level where the duct was injured. If the thoracic duct is injured above the fifth thoracic vertebra, then a left-sided chylothorax results. Conversely, a thoracic duct injury below that level will lead to the formation of a right-sided chylothorax. Chylothoraces most commonly occur in the right pleural space (50% of cases). Left-sided and bilateral chylothoraces are less common and occur in 33% and 17% of cases, respectively.In the case of cancer, invasion into the thoracic duct or collateral lymph channels can obstruct lymph. In the case of mediastinal lymphadenopathy, the enlarged lymph node causes compression of the lymphatic channels and thoracic duct. This impedes the centripetal drainage of the flow of lymph from the edges of the lung parenchyma and pleural surfaces. This causes the chyle to ooze extensively into the pleural cavity, leading to a chylothorax. In the case of yellow nail syndrome, or lymphedema, chylothorax is caused by hypoplasia or dilation of the lymph vessels. In rare cases, like in hepatic chylothorax, chylous ascites crosses the diaphragm into the pleural cavity. In idiopathic cases like genetic disorders, the mechanism is not known. Up to three liters of chyle can easily drain into the pleural space daily. Diagnosis Chest X-rays can detect a chylothorax. It appears as a dense, homogeneous area that obscures the costophrenic and cardiophrenic angles. Ultrasounds can also detect a chylothorax, which appears as an echoic region that is isodense with no septation or loculation. However, neither a normal chest x-ray nor an ultrasound can differentiate a chylothorax from any other type of pleural effusion. The cisterna chyli can be found in a thoracic MRI, making it possible to confirm chylothorax. However, MRI is not the ideal method to scan the thorax, and so it is rarely used. Another diagnostic technique is conventional lymphangiography. It is rarely used since there are equally sensitive yet less invasive techniques available to identify a chylothorax. Lymphangiography procedures use the contrast dye agent lipiodol, which is injected into the lymphatic vessels. The chylothorax shows up on the images and identifies the source any leak in the thoracic duct.Another, more commonly used type of lymphogram is nuclear lymphoscintigraphy; this procedure requires human pentetic acid labeled Tc99m to be injected into the subcutaneous lesions of both sides of the dorsum of the foot. Then two images, anterior and posterior, are obtained using gamma-ray cameras. This test can be used with an integrated low-dose CT-scan with photon emission to get images that are more precise. Once pleural effusion is detected, a thoracentesis is recommended.The fluid of a chylothorax may appear milky, serous or serosanguineous. If the appearance of the fluid is not milky, that does not exclude a chylothorax from consideration. Since chyle is rich in triglycerides, a pleural effusion that is rich in triglycerides (>110 mg/dL) confirms the presence of a chylothorax; a pleural effusion that is low in triglyceride content (<50 mg/dL) virtually excludes the diagnosis. If a pleural effusion contains triglycerides between 50 and 110 mg/dL, analysis of the lipoprotein content of the pleural effusion to evaluate for chylomicrons is recommended. If that procedure detects chylomicrons in the fluid, that confirms a chylothorax. Chylothoraces are typically exudative and often contain a high number of lymphocytes and have low levels of the enzyme lactate dehydrogenase (LDH). However, atypical chylothoraces can occur and are transudative in 14% of cases. A milky appearance of pleural fluid is insufficient to confirm the diagnosis of chylothorax as pseudochylothoraces and empyemas can mimic this appearance. Conversely, the absence of a milky appearance does not mean a chylothorax is not present as they may instead appear serous or bloody. Treatment The treatment for chylothorax depends on the underlying cause but may include dietary modification, medication to prevent chyle formation including somatostatin/octreotide, midodrine and sirolimus, pleurodesis, and surgical treatment including ligation of the thoracic duct, pleurovenous or pleuroperitoneal shunting or thoracic duct embolization. Initial The initial treatment of a chylothorax is usually drainage of the fluid from the pleural space. This may be necessary to restore lung function compromised by the pressure exerted by the chyle on the lungs. Those with large chylothoraces may need nutritional support due to the nutrients lost, primarily to correct protein and electrolyte losses. Once the affected person is hemodynamically and nutritionally stable, then specific treatment can begin. Conservative A conservative treatment is changing diet to include fewer long-chain fatty acids, in particular free fatty acids. Since chyle is formed from these acids, chyle formation will reduce, allowing the defects to heal spontaneously. However, this can lead to fat deficiency and malnutrition over time. A possible response to this drawback is a venous fat hemorrhage, in which small and medium-chain fatty acids are given by diet, and long-chain fatty acids are given intravenously. Thoracentesis and an indwelling catheter for use at home is generally used to drain the chylothorax. If a malignant neoplastic chylothorax is present, then treatment with radiotherapy and/or chemotherapy is warranted. Surgical Surgery is indicated if the case is post-traumatic, iatrogenic, or refractory to other treatments, in which cases surgery reduces mortality by 40%. One invasive surgical intervention called a thoracic duct ligation involves closing off the thoracic ducts. Surgical pleurodesis is another option and can be undertaken if the affected person fails to respond to conservative treatment and is not a candidate for surgical intervention.Another treatment option is pleuroperitoneal shunting (creating a communication channel between the pleural space and peritoneal cavity). Since surgery to close the leak is not reliable, talc pleurodesis is recommended; in a case study of 19 people with refractory malignant chylothorax due to lymphoma, it resulted in success for all affected individuals. Chemical pleurodesis is an option, since the leaking of lymphatic fluids is stopped by irritating the lungs and chest wall, resulting in a sterile inflammation. This causes the lung and the chest wall to fuse together, thus preventing lymphatic fluids from leaking into the pleural space. Prognosis The morbidity and mortality rates associated with chylothorax have declined as treatments have improved. Malignant, bilateral, and chronic chylothoraces have an inferior prognosis to other types. Currently, the mortality and morbidity rates are about 10% if treated surgically. If cases are post-operative and treated conservatively, mortality rates approach 50%. Complications Complications of chylothorax include malnutrition, immunosuppression, dehydration, and respiratory distress. The severity of the complications depends on how quickly the chylothorax accumulated, its size, and its chronicity. Epidemiology Chylothoraces are rare and usually occur as a complication of surgeries in the neck and mediastinum. It has no gender or age predisposition. A chylothorax occurs in 0.2-1% of cardiothoracic surgeries, 5-10% of esophagostomies, and 3-7% of lung resections. Other animals Horses Chylothorax is uncommon in horses. Clinical signs and symptoms in foals include difficulty breathing, fast breathing, cough, fever, and lethargy. The fluid generally appears opalescent and milky without any odor. A line of fluid is observed on percussion and there are reduced lung sounds. To differentiate between chyle is pseudochyle, which does not clear after centrifugation. There is not much information on the treatment of chylothorax in horses. Supportive care, antimicrobials, drainage of the thorax, and dietary management have been used with success. Surgery has been done in other animals with limited success, but has not yet been reported in horses. Although success has been reported, the prognosis is relatively unknown due to the lack of data. References == External links ==

You are a resource for medical understanding. Offer detailed explanations of medical terms, making complex concepts clear and comprehensible.

Can you break down the meaning of the medical term 'Xanthopsia' for me?

Xanthopsia is a color vision deficiency in which there is a predominance of blue in vision due to a yellowing of the optical media of the eye. The most common causes are digoxins inhibitory action on the sodium pump, and the development of cataracts which can cause a yellow filtering effect. It has been suggested that Van Gogh contracted Xanthopsia as a result of digoxin consumption. Digoxin is a medication derived from digitalis and used to treat various heart conditions. This theory claims Xanthopsia as the cause of the yellow tinting exhibited by many of his works.Xanthopsia is also a rare side-effect of jaundice, in which bilirubin may be deposited into the eye in sufficient quantity to produce a yellow tint to the vision. See also Cyanopsia References External links Acquired Colour Vision Deficiencies —University of Calgary, Vision & Aging Lab

You act as a medical communicator. Your goal is to translate medical terms into comprehensive, yet straightforward language for all readers.

I've encountered the term 'Tobi' while reading about medical topics. What does it refer to exactly?

Tobi may refer to: Tobi (given name), a unisex name Tobi (island), island in the Palauan state of Hatohobei Tobian language, the language of Tobi Hatohobei, an island and the southernmost of Palaus sixteen states Tobi (month), in the Coptic calendar Tobi!, a 2009 television series Tobramycin, an antibiotic drug that is sold under the brand name "Tobi" Tobi (Naruto), the alias of Obito Uchiha, one of the primary antagonists in the anime and manga series Naruto Shippuden ToBI, a standard for transcribing English intonation Tobi shokunin or tobi for short; construction workers in Japan Tobi trousers, the typical piece of clothing of tobi shokunin Texas Oilmans Bass Invitational (TOBI) Tobi (1978 film) See also Tobias Toby (disambiguation)

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

I've encountered the term 'Denasalization' while reading about medical topics. What does it refer to exactly?

In phonetics, denasalization is the loss of nasal airflow in a nasal sound, such as a nasal consonant or a nasal vowel. That may be due to speech pathology but also occurs when the sinuses are blocked from a common cold, when it is called a nasal voice, which is not a linguistic term. Acoustically, it is the "absence of the expected nasal resonance." The symbol in the Extended IPA is ⟨◌͊⟩. When one speaks with a cold, the nasal passages still function as a resonant cavity so a denasalized nasal [m͊] does not sound like a voiced oral stop [b], and a denasalized vowel [a͊] does not sound like an oral vowel [a]. However, there are cases of historical or allophonic denasalization that have produced oral stops. In some languages with nasal vowels, such as Paicĩ, nasal consonants may occur only before nasal vowels; before oral vowels, prenasalized stops are found. That allophonic variation is likely to be from a historical process of partial denasalization. Similarly, several languages around Puget Sound underwent a process of denasalization about 100 years ago. Except in special speech registers, such as baby talk, the nasals [m, n] became the voiced stops [b, d]. It appears from historical records that there was an intermediate stage in which the stops were prenasalized stops [ᵐb, ⁿd] or poststopped nasals [mᵇ, nᵈ]. Something similar has occurred with word-initial nasals in Korean; in some contexts, /m/, /n/ are denasalized to [b, d]. The process is sometimes represented with the IPA [m͊] and [n͊], which simply places the IPA ◌͊ denasalization diacritic on [m] and [n] to show the underlying phoneme.In speech pathology, practice varies in whether ⟨m͊⟩ is a partially denasalized /m/, with ⟨b⟩ for full denasalization, or is a target /m/ whether partially denasalized or a fully denasalized [b]. See also Nasalization Hypernasal speech == References ==

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

I'm not familiar with the medical term 'Amédée Galzin.' Could you provide some insights?

Amédée Galzin (1 May 1853, Parrinet, Aveyron – 14 February 1925, Parrinet) was a French veterinarian and mycologist. In 1878 he obtained his degree from the veterinary college in Toulouse. From 1879 to 1905, he served as a military veterinarian, becoming a knight of the Legion of Honour in 1899.With Abbé Hubert Bourdot, he was co-author of a series of publications (11 parts, 1909 to 1925) involving Hymenomycetes native to France; all parts being published in the Bulletin de la Société Mycologique de France. With Bourdot, he also wrote Heterobasidiae nondum descriptae (Descriptions of a few jelly fungi).With Bourdot, he was the taxonomic authority of the fungi genus Oxyporus, as well as of numerous mycological species. == References ==

You serve as an encyclopedia of medical terms. Deliver clear, detailed explanations, making medical language understandable to a diverse audience.

The term 'Phenazopyridine' keeps coming up in medical discussions. What does it stand for?

Phenazopyridine is a medication which, when excreted by the kidneys into the urine, has a local analgesic effect on the urinary tract. It is often used to help with the pain, irritation, or urgency caused by urinary tract infections, surgery, or injury to the urinary tract. Phenazopyridine was discovered by Bernhard Joos, the founder of Cilag. Medical uses Phenazopyridine is prescribed for its local analgesic effects on the urinary tract. It is sometimes used in conjunction with an antibiotic or other anti-infective medication at the beginning of treatment to help provide immediate symptomatic relief. Phenazopyridine does not treat infections or injury; it is only used for symptom relief. It is recommended that it be used for no longer than the first two days of antibacterial treatment as longer treatment may mask symptoms.Phenazopyridine is also prescribed for other cases requiring relief from irritation or discomfort during urination. For example, it is often prescribed after the use of an in-dwelling Foley catheter, endoscopic (cystoscopy) procedures, or after urethral, prostate, or urinary bladder surgery which may result in irritation of the epithelial lining of the urinary tract.This medication is not used to treat infection and may mask symptoms of inappropriately treated UTI. It provides symptom relief during a UTI, following surgery, or injury to the urinary tract. UTI therapy should be limited to 1–2 days. Long-term use of phenazopyridine can mask symptoms. Side effects Phenazopyridine produces a vivid color change in urine, typically to a dark orange to reddish color. This effect is common and harmless, and indeed a key indicator of the presence of the medication in the body. Users of phenazopyridine are warned not to wear contact lenses, as phenazopyridine has been known to permanently discolor contact lenses and fabrics. It also tends to leave an orange-yellow stain on surfaces it comes in contact with. Some may be mistakenly concerned that this indicated blood in the urine. Phenazopyridine can also cause headaches, upset stomach (especially when not taken with food), or dizziness. Less frequently it can cause a pigment change in the skin or eyes, to a noticeable yellowish color. This is due to a depressed excretion via the kidneys causing a buildup of the medication in the skin, and normally indicates a need to discontinue usage. Other such side effects include fever, confusion, shortness of breath, skin rash, and swelling of the face, fingers, feet, or legs. Long-term use may cause yellowing of nails.Phenazopyridine should be avoided by people with glucose-6-phosphate dehydrogenase deficiency, because it can cause hemolysis (destruction of red blood cells) due to oxidative stress. It has been reported to cause methemoglobinemia after overdose and even normal doses. In at least one case the patient had pre-existing low levels of methemoglobin reductase, which likely predisposed her to the condition. It has also been reported to cause sulfhemoglobinemia.Phenazopyridine is an azo dye. Other azo dyes, which were previously used in textiles, printing, and plastic manufacturing, have been implicated as carcinogens that can cause bladder cancer. While phenazopyridine has never been shown to cause cancer in humans, evidence from animal models suggests that it is potentially carcinogenic. Pregnancy This medication is pregnancy category B. This means that the medication has shown no adverse events in animal models, but no human trials have been conducted. It is not known if phenazopyridine is excreted in breast milk. Pharmacokinetics The full pharmacokinetic properties of phenazopyridine have not been determined. It has mostly been studied in animal models, but they may not be very representative of humans. Rat models have shown its half-life to be 7.35 hours, and 40% is metabolized hepatically (by the liver). Mechanism of action Phenazopyridines mechanism of action is not well known, and only basic information on its interaction with the body is available. It is known that the chemical has a direct topical analgesic effect on the mucosa lining of the urinary tract. It is rapidly excreted by the kidneys directly into the urine. Hydroxylation is the major form of metabolism in humans, and the azo bond is usually not cleaved. On the order of 65% of an oral dose will be secreted directly into the urine chemically unchanged. Brand names In addition to its generic form, phenazopyridine is distributed under the following brand names: References External links Information about phenazopyridine from the US National Library of Medicine Interstitial Cystitis Association American Urological Association

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

I'd like to learn more about the medical term 'Merkel-cell carcinoma.' Can you provide some details?

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer occurring in about 3 people per 1,000,000 members of the population. It is also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carcinoma of the skin, and trabecular carcinoma of the skin. Factors involved in the development of MCC include the Merkel cell polyomavirus (MCPyV or MCV), a weakened immune system, and exposure to ultraviolet radiation. Merkel-cell carcinoma usually arises on the head, neck, and extremities, as well as in the perianal region and on the eyelid. It is more common in people over 60 years old, Caucasian people, and males. MCC is less common in children. Signs and symptoms Merkel cell carcinoma (MCC) usually presents as a firm nodule (up to 2 cm diameter) or mass (>2 cm diameter). These flesh-colored, red, or blue tumors typically vary in size from 0.5 cm (less than one-quarter of an inch) to more than 5 cm (2 inches) in diameter and may enlarge rapidly. Tumors can present as painless, tender or itchy, and other MCC manifestations as papules or plaques have also been reported. Although MCC may arise almost anywhere on the body, it is most commonly found in sun-exposed areas such as the head, neck or extremities. Five key attributes of MCC were summarized in 2008 in the acronym AEIOU (Asymptomatic/lack of tenderness, Expanding rapidly, Immune suppression, Older than 50 years, and Ultraviolet-exposed site on a person with fair skin). Ninety percent of MCCs have three or more of those features. MCC is sometimes mistaken for other histological types of cancer, including basal cell carcinoma, squamous cell carcinoma, malignant melanoma, lymphoma, and small cell carcinoma, or as a benign cyst. Merkel cell carcinomas have been described in children, however pediatric cases are very rare.Merkel-cell cancers tend to invade locally, infiltrating the underlying subcutaneous fat, fascia, and muscle, and typically metastasize early in their natural history, most often to the regional lymph nodes. MCCs also spread aggressively through the blood vessels to many organs, particularly to liver, lung, brain, and bone. Pathophysiology Cell of origin Although MCC was initially named for the Merkel cell due to histologic and physiologic similarities between MCC and Merkel cells, the cellular progenitor of MCC has been a heavily debated question. Merkel cells are highly specialized cells that act as pressure receptors in the epidermis. The origin of Merkel cells themselves is debated and proposed to be derived from neural crest cells or epidermal progenitors. MCC is similar to Merkel cells in its histological appearance (see below: Diagnosis) and shares many immunohistochemical markers with Merkel cells, including epidermal marker cytokeratin 20 and neuroendocrine markers synaptophysin and chromogranin A. Furthermore, the ion channel Piezo2 and transcription factor Atoh1, both specific to Merkel cells, are also expressed by MCC. However, Merkel cells are post-mitotic cells with a low probability of cancerous transformation. Additionally, they have not been shown to support Merkel-cell polyoma virus infection, which is believed to drive oncogenesis in approximately 80% of MCC.Instead, it has been proposed the MCC may originate from a Merkel cell precursor, at which point it gains features similar to those of Merkel cells. One such precursor is the human fibroblast. Evidence for a fibroblast precursor includes its location in the dermis, which is thought to be the primary site of origin for MCC. Additionally, in vitro experiments have demonstrated that fibroblasts not only support Merkel cell polyomavirus (MCV) infection but can be induced into having a MCC phenotype by the expression of viral proteins.However, others have argued that MCC likely derives from an epithelial precursor cell due to its frequent presence in mixed tumors including epithelial neoplasms such as squamous cell carcinoma. While epithelial cells are not typically found in the dermis, hair follicles include epithelial cells that have been shown to have oncogenic potential, and have therefore been proposed as a possible site for a MCC precursor.Finally, the presence of B-cell surface markers on MCC in addition to the high correlation between MCC and B-cell lymphomatous cancers have also led to suggestions that MCC may share a progenitor with B-cells. Because of the differences in physiology and prognosis between MCV+ and MCV- MCC (see below), however, some have suggested that these two subtypes of MCC may actually derive from different progenitor cells.Several factors are involved in the pathophysiology of MCC, including MCV, ultraviolet radiation (UV) exposure, and weakened immune function. Merkel cell polyomavirus The MCV is a small double-stranded DNA virus that is believed to contribute to the development of the majority of MCC. About 80% of MCC tumors are infected with MCV, with the virus integrated into the host genome in a monoclonal pattern. However, the majority of people with MCV infection do not develop MCC: MCV is a ubiquitous virus and infection commonly occurs during childhood but remains asymptomatic throughout an individuals lifetime.MCC was first believed to be associated with MCV when it was observed to occur at a much higher rate in HIV patients during the 1980s. Since then, studies have demonstrated integration of the MCV genome into the genome of MCC tumor cells. Central to the our understanding of the pathogenicity of MCV are two viral proteins expressed in infected cells known as the large tumor antigen (LT) and small tumor antigen (sT). Normally, patients infected with MCV show low levels of antibodies to the LT protein, perhaps due to a nuclear localization domain in its C-terminal that limits its cellular dispersion. However, integration of the viral genome into the host genome can result in truncation of the LT protein proximal to this domain. This serves two oncogenic purposes: first, it prevents successful viral replication that would culminate in lysis of the infected cell. Second, it redistributes the LT protein to the cytoplasm, where it can interact with cytoplasmic signaling. The N-terminal LXCXE motif of the LT protein has been shown to interact with known oncogene Rb and is conserved in other cancer-causing viruses. Studies suggest that LT may also preserve cell proliferation signals such as c-Myc and cyclin E and cause DNA injury to the p53 tumor suppressor.Meanwhile, sT has been shown to induce cell proliferation through hyper-phosphorylation of the translation initiator 4EBP1 as well as inhibition of a ubiquitin ligase complex responsible for degradation of cellular proliferation signals. sT also contains a region known as the LT stabilization domain (LSD), which potentiates the LT proteins oncogenic function. Unlike LT, MCC samples have been identified that express sT alone, and sT expression in fibroblasts has been shown to cause MCC phenotype development. UV light About 20% of MCC tumors are MCV negative. In contrast to MCV-induced MCC, these tumors tend to have much higher mutational burdens with mutational signatures characteristic of UV damage. Genes frequently mutated in MCV-negative MCC include p53 and Rb, among others. The link between MCC and UV exposure has been demonstrated through various epidemiological studies indicating a higher incidence of MCC in fair-skinned people in areas of high UV exposure, as well as among those receiving UV phototherapy. The typical distribution of MCC in sun-exposed regions and its co-occurrence with other skin cancers also indicate that UV exposure is a contributing factor to MCC development. It is unclear whether this is through direct mutational impact, immune down-regulation, or some combination of the two. Immunosuppression The incidence of MCC is increased in conditions with defective immune functions such as malignancy, HIV infection, and organ transplant patients, etc. Conversely, patients with brisk immune response have been shown to have improved prognoses. This is suspected to be due to the inability of the body to defend itself from infection by or reactivation of MVC. The body of data indicating the importance of immune function in MCC pathogenesis has been exploited for the development of immunotherapies discussed below. Diagnosis Diagnosis of MCC begins with a clinical examination of the skin and lymph nodes. Following clinical exam, definitive diagnosis of Merkel cell carcinoma (MCC) requires examination of biopsy tissue to identify its histopathologic features. An ideal biopsy specimen is either a punch biopsy or a full-thickness incisional biopsy of the skin including full-thickness dermis and subcutaneous fat. On light microscopy, MCC shows basaloid tumor nests with neuroendocrine features ("salt and pepper" chromatin, scarce cytoplasm, and brisk mitotic activity). In addition to standard examination under light microscopy, immunohistochemistry (IHC) is also generally required to differentiate MCC from other morphologically similar tumors such as small cell lung cancer, the small cell variant of melanoma, various cutaneous leukemic/lymphoid neoplasms, and Ewings sarcoma. Neuroendocrine molecular markers such as synaptophysin or chromogranin A are characteristic of MCC and other neuroendocrine tumors, while other markers such as PAX5 or cytokeratin 20 can distinguish MCC from these tumors. Longitudinal imaging may also help in ruling out a diagnosis of metastatic small cell lung cancer. Once an MCC diagnosis is made, a sentinel lymph node biopsy as well as other imaging is recommended as a part of the staging work-up needed to determine prognosis and subsequent treatment options. Prevention Sunlight exposure is thought to be one of the causes of Merkel cell carcinoma (MCC). The World Health Organization, American Academy of Dermatology, and Skin Cancer Foundation recommend the following measures to prevent excessive UV exposure and skin cancer: Limiting sun exposure between the hours of 10am and 4pm, when UV rays are the strongest Seeking shade when UV rays are most intense Wearing sun-protective clothing including a wide brim hat, sunglasses, and tightly woven, loose-fitting clothing Using sunscreen Avoiding tanning beds and artificial UV exposure Treatment MCC is rare and expedient referral to radiation oncology is critical. MCC will quickly relapse following any attempted excisional biopsy. Surgery The first step and primary goal of surgical treatment is to obtain negative histologic margins with 1-cm to 2-cm margins. Retrospective analyses of data from the National Comprehensive Database (NCDB) suggest no difference in the overall and relative survival of patients with stage I to II MCC who were treated with wide local excision versus MMS. Radiation Radiation therapy is the primary management of Merkel cell carcinoma (MCC). The largest series we have are from Australia and have demonstrated that radiotherapy alone achieves equal outcomes with upfront or neoadjuvant surgery followed by radiation therapy. The role of surgery is largely historical and relegated to biopsy. There have been no head-to-head trials comparing the two treatment strategies, and in the absence of this, surgeons tend to most commonly perform excisional biopsy prior to referring for radiation therapy to eradicate MCC. MCC is exquisitely radiosensitive. The conclusion amongst published studies in the Radiation Oncology community is that MCC should be managed ideally with radiation therapy alone. Chemotherapy Because of its significant adverse effects, traditional chemotherapy has been saved for late-stage highly metastasized cases of MCC. While some chemotherapeutic regiments have been shown to have transient effects, studies have not found any significant long-term effect on recurrence rate or life expectancy. As of 2015, there were no FDA-approved standard chemotherapy regimens for MCC treatment. The most recent American guidelines do not recommend adjuvant chemotherapy, citing a lack of evidence to suggest improved outcomes. Instead, consideration of the need for chemotherapy on a case-by-case basis is recommended. Drug therapy Immunotherapies, namely inhibitors of the PD1-PDL1 checkpoint signaling pathway, are novel anticancer agents that have shown benefit in advanced-stage MCC or chemotherapy-resistant MCC. The PD-1 pathway is responsible for regulating the balance between T-cell activation and over-activation leading to T-cell exhaustion or autoimmunity. However, over-expression of PD-1 ligands (PDL1) have been observed in tumors as a method of evading immune attack. PD-1 inhibition therefore enhances the bodys immune response, enabling it to target cancer cells for destruction. Due to their side effects, however, National Comprehensive Cancer Network guidelines recommend PD-1 inhibitors for people with disseminated rather than early-stage MCC.PD1/PDL1 pathway inhibitors approved or in clinical trials for use in MCC treatment include: In March 2017, the U.S. Food and Drug Administration granted accelerated approval to avelumab, a PDL1 inhibitor, to treat adults and children above 12 years with metastatic MCC. In December 2018, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA, Merck & Co. Inc.) for all ages (adults and pediatrics) with recurrent locally advanced or metastatic Merkel cell carcinoma Nivolumab (brand name Opdivo, Bristol-Myers Squibb) is in phase III/IV clinical trials Ipilimumab (brand name Yervoy, Bristol-Myers Squibb) is in phase II clinical trials for use in adults with metastatic MCC.Studies to date have shown a clinical response rate between 50 and 65% for MCC treated with PD-1 pathway inhibitors. Suggestions for further immunotherapy research areas have included therapeutic vaccines or epigenetic modification of HLA-receptors. Prognosis According to the American Joint Committee on Cancer (AJCC), the natural course of MCC is "variable and depends heavily on the stage at diagnosis". Staging of MCC is classified according to the TNM staging system, a notation system that describes the stage of cancer according to the size of the primary tumor (T), the degree of spread to regional lymph nodes (N), and the presence of distant metastasis (M). A combination of T, N, and M stages dictate the final clinical stage group (0, I, IIA, IIB, IIIA, IIIB, IV). Advanced stage (i.e. increased size of the tumor, spreading of the tumor into surrounding and/or distant tissue, and involvement of lymph nodes) is associated with lower survival rates.The National Cancer Data Base has survival rates collected from nearly 3000 MCC patients from year 1996–2000 with 5-year survival rates listed as follows:Stage IA: 80%. Stage IB: 60%. Stage IIA: 60%. Stage IIB: 50%. Stage IIC: 50%. Stage IIIA: 45%. Stage IIIB: 25%. Stage IV: 20%. 5 yr survival may be 51% among people with localized disease, 35% for those with nodal disease, and 14% with metastases to a distant site.Several other features may also affect prognosis, independent of tumor stage. They include MCV viral status, histological features, and immune status. In viral status, MCV large tumor antigen (LT antigen) and retinoblastoma protein (RB protein) expression correlates with more favorable prognosis, while p63 expression correlates with a poorer prognosis. Histological features such as intratumoral CD8+ T lymphocyte infiltration may be associated with a favorable prognosis, while lymphovascular infiltrative pattern may be associated with a poorer prognosis. Immune status, especially T cell immunosuppression (e.g., organ transplant, HIV infection, certain malignancy) predicts poorer prognosis and higher mortality.The antibody titer in the blood to the Merkel cell polyomavirus oncoprotein can be used as a treatment response biomarker in people that have detectable antibodies at the time of diagnosis. Epidemiology Merkel cell carcinoma occurs most often in Caucasians between 60 and 80 years of age. Its incidence is about twice as high in males as in females. It is a rare type of skin cancer, with a 2013 incidence of only 0.7 per 100,000 persons in the U.S. As of 2005, roughly 2,500 new cases of MCC are diagnosed each year in the United States, as compared to around 60,000 new cases of malignant melanoma and over 1 million new cases of nonmelanoma skin cancer. Similar to melanoma, the incidence of MCC in the US is increasing rapidly. Worldwide, MCC is most commonly found in regions with increased sun exposure. Australia is the country with the highest incidence of MCC but has a lower incidence of MCV-positive MCC than observed in other countries.Since 2006, it has been known that other primary cancers increase the risk of MCC significantly, especially in those with the prior multiple myeloma, chronic lymphocytic leukemia, and malignant melanoma. Immunosuppression including HIV infection or immunosuppressant therapy following organ transplant or for autoimmune disease can also increase the odds of developing MCC. History Friedrich Sigmund Merkel (1845–1919) was a German anatomist and histopathologist who first described the Tastzellen (touch cells) in the skin in 1875. In 1878 the term Merkel cell was coined by the anatomist Robert Bonnet (1851–1921). Merkel-cell carcinoma was first described in 1972 by Cyril Toker. He reported five cases of trabecular carcinoma of the skin. Notable patients Avigdor Arikha – Paris-based painter and art historian David Brudnoy – Boston talk radio host Al Copeland – New Orleans entrepreneur, powerboat racer Al Davis – Principal owner of the Oakland Raiders of the National Football League Ed Derwinski – U.S. Representative from Illinois and 1st Secretary of Veterans Affairs Leonard Hirshan – Showbusiness agent and manager. Max Perutz – Nobel Prize–winning chemist Lindsay Thompson – Former Premier of Victoria, Australia Joe Zawinul – Jazz-fusion keyboardist and composer John Fitch – Race car driver and road safety pioneer Carl Mundy – 30th Commandant of the United States Marine Corps Geoffrey Penwill Parsons – Pianist Maria Bueno – Tennis player References External links Media related to Merkel cell carcinoma at Wikimedia Commons National Cancer Institute. "Merkel Cell Carcinoma". National Institutes of Health (US). Archived from the original on 2010-12-21. Retrieved 2011-01-20.

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

I'm curious about the meaning of the medical term 'Impulsivity.' Can you give me some insights?

In psychology, impulsivity (or impulsiveness) is a tendency to act on a whim, displaying behavior characterized by little or no forethought, reflection, or consideration of the consequences. Impulsive actions are typically "poorly conceived, prematurely expressed, unduly risky, or inappropriate to the situation that often result in undesirable consequences," which imperil long-term goals and strategies for success. Impulsivity can be classified as a multifactorial construct. A functional variety of impulsivity has also been suggested, which involves action without much forethought in appropriate situations that can and does result in desirable consequences. "When such actions have positive outcomes, they tend not to be seen as signs of impulsivity, but as indicators of boldness, quickness, spontaneity, courageousness, or unconventionality" Thus, the construct of impulsivity includes at least two independent components: first, acting without an appropriate amount of deliberation, which may or may not be functional; and second, choosing short-term gains over long-term ones.Impulsivity is both a facet of personality and a major component of various disorders, including FASD, ADHD, substance use disorders, bipolar disorder, antisocial personality disorder, and borderline personality disorder. Abnormal patterns of impulsivity have also been noted instances of acquired brain injury and neurodegenerative diseases. Neurobiological findings suggest that there are specific brain regions involved in impulsive behavior, although different brain networks may contribute to different manifestations of impulsivity, and that genetics may play a role.Many actions contain both impulsive and compulsive features, but impulsivity and compulsivity are functionally distinct. Impulsivity and compulsivity are interrelated in that each exhibits a tendency to act prematurely or without considered thought and often include negative outcomes. Compulsivity may be on a continuum with compulsivity on one end and impulsivity on the other, but research has been contradictory on this point. Compulsivity occurs in response to a perceived risk or threat, impulsivity occurs in response to a perceived immediate gain or benefit, and, whereas compulsivity involves repetitive actions, impulsivity involves unplanned reactions. Impulsivity is a common feature of the conditions of gambling and alcohol addiction. Research has shown that individuals with either of these addictions discount delayed money at higher rates than those without, and that the presence of gambling and alcohol abuse lead to additive effects on discounting. Impulse An impulse is a wish or urge, particularly a sudden one. It can be considered as a normal and fundamental part of human thought processes, but also one that can become problematic, as in a condition like obsessive-compulsive disorder, borderline personality disorder, attention deficit hyperactivity disorder, or in fetal alcohol spectrum disorders. The ability to control impulses, or more specifically control the desire to act on them, is an important factor in personality and socialization. Deferred gratification, also known as impulse control is an example of this, concerning impulses primarily relating to things that a person wants or desires. Delayed gratification comes when one avoids acting on initial impulses. Delayed gratification has been studied in relation to childhood obesity. Resisting the urge to act on impulses is important to teach children, because it teaches the value of delayed gratification. Many psychological problems are characterized by a loss of control or a lack of control in specific situations. Usually, this lack of control is part of a pattern of behavior that also involves other maladaptive thoughts and actions, such as substance abuse problems or sexual disorders like the paraphilias (e.g. pedophilia and exhibitionism). When loss of control is only a component of a disorder, it usually does not have to be a part of the behavior pattern, and other symptoms must also be present for the diagnosis to be made. (Franklin) The five traits that can lead to impulsive actions For many years it was understood that impulsivity is a trait but with further analysis it can be found that there were five traits that can lead to impulsive actions: positive urgency, negative urgency, sensation seeking, lack of planning, and lack of perseverance. Associated behavioral and societal problems Attention-deficit hyperactivity disorder Attention deficit-hyperactivity disorder (ADHD) is a multiple component disorder involving inattention, impulsivity, and hyperactivity. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) breaks ADHD into three subtypes according to the behavioral symptoms: Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Type, Attention-Deficit/Hyperactivity Disorder Predominantly Hyperactive-Impulsive Type, and Attention-Deficit/Hyperactivity Disorder Combined Type. Predominantly hyperactive-impulsive type symptoms may include fidgeting and squirming in seats, talking nonstop, dashing around and touching or playing with anything in sight, having trouble sitting still during dinner/school/story time, being constantly in motion, and having difficulty doing quiet tasks or activities. Other manifestations primarily of impulsivity include being very impatient, having difficulty waiting for things they want or waiting their turns in games, often interrupting conversations or others activities, or blurting out inappropriate comments, showing their emotions without restraint, and act without regard for consequences. Prevalence of the disorder worldwide is estimated to be between 4% and 10%, with reports as low as 2.2% and as high as 17.8%. Variation in rate of diagnoses may be attributed to differences between populations (i.e. culture), and differences in diagnostic methodologies. Prevalence of ADHD among females is less than half that of males, and females more commonly fall into the inattentive subtype.Despite an upward trend in diagnoses of the inattentive subtype of ADHD, impulsivity is commonly considered to be the central feature of ADHD, and the impulsive and combined subtypes are the major contributors to the societal costs associated with ADHD. The estimated cost of illness for a child with ADHD is $14,576 (in 2005 dollars) annually. Prevalence of ADHD among prison populations is significantly higher than that of the normal population.In both adults and children, ADHD has a high rate of comorbidity with other mental health disorders such as learning disability, conduct disorder, anxiety disorder, major depressive disorder, bipolar disorder, and substance use disorders. The precise genetic and environmental factors contributing to ADHD are relatively unknown, but endophenotypes offer a potential middle ground between genes and symptoms. ADHD is commonly linked to "core" deficits involving "executive function," "delay aversion," or "activation/arousal" theories that attempt to explain ADHD through its symptomology. Endophenotypes, on the other hand, purport to identify potential behavioral markers that correlate with specific genetic etiology. There is some evidence to support deficits in response inhibition as one such marker. Problems inhibiting prepotent responses are linked with deficits in pre-frontal cortex (PFC) functioning, which is a common dysfunction associated with ADHD and other impulse-control disorders.Evidence-based psychopharmacological and behavioral interventions exist for ADHD. Substance abuse Impulsivity appears to be linked to all stages of substance abuse.The acquisition phase of substance abuse involves the escalation from single use to regular use. Impulsivity may be related to the acquisition of substance abuse because of the potential role that instant gratification provided by the substance may offset the larger future benefits of abstaining from the substance, and because people with impaired inhibitory control may not be able to overcome motivating environmental cues, such as peer pressure. "Similarly, individuals that discount the value of delayed reinforcers begin to abuse alcohol, marijuana, and cigarettes early in life, while also abusing a wider array of illicit drugs compared to those who discounted delayed reinforcers less."Escalation or dysregulation is the next and more severe phase of substance abuse. In this phase individuals "lose control" of their addiction with large levels of drug consumption and binge drug use. Animal studies suggest that individuals with higher levels of impulsivity may be more prone to the escalation stage of substance abuse.Impulsivity is also related to the abstinence, relapse, and treatment stages of substance abuse. People who scored high on the Barratt Impulsivity Scale (BIS) were more likely to stop treatment for cocaine abuse. Additionally, they adhered to treatment for a shorter duration than people that scored low on impulsivity. Also, impulsive people had greater cravings for drugs during withdrawal periods and were more likely to relapse. This effect was shown in a study where smokers that test high on the BIS had increased craving in response to smoking cues, and gave into the cravings more quickly than less impulsive smokers. Taken as a whole the current research suggests that impulsive individuals are less likely to abstain from drugs and more likely to relapse earlier than less impulsive individuals.While it is important to note the effect of impulsivity on substance abuse, the reciprocating effect whereby substance abuse can increase impulsivity has also been researched and documented. The promoting effect of impulsivity on substance abuse and the effect of substance abuse on increased impulsivity creates a positive feedback loop that maintains substance seeking behaviors. It also makes conclusions about the direction of causality difficult. This phenomenon has been shown to be related to several substances, but not all. For example, alcohol has been shown to increase impulsivity while amphetamines have had mixed results.Substance use disorder treatments include prescription of medications such as acamprosate, buprenorphine, disulfiram, LAAM, methadone, and naltrexone, as well as effective psychotherapeutic treatment like behavioral couples therapy, CBT, contingency management, motivational enhancement therapy, and relapse prevention. Eating Impulsive overeating spans from an episode of indulgence by an otherwise healthy person to chronic binges by a person with an eating disorder.Consumption of a tempting food by non-clinical individuals increases when self-regulatory resources are previously depleted by another task, suggesting that it is caused by a breakdown in self control. Impulsive eating of unhealthy snack foods appears to be regulated by individual differences in impulsivity when self-control is weak and by attitudes towards the snack and towards healthy eating when self-control is strong. There is also evidence that greater food consumption occurs when people are in a sad mood, although it is possible that this is due more to emotional regulation than to a lack of self-control. In these cases, overeating will only take place if the food is palatable to the person, and if so individual differences in impulsivity can predict the amount of consumption.Chronic overeating is a behavioral component of binge eating disorder, compulsive overeating, and bulimia nervosa. These diseases are more common for women and may involve eating thousands of calories at a time. Depending on which of these disorders is the underlying cause, an episode of overeating can have a variety of different motivations. Characteristics common among these three disorders include low self-esteem, depression, eating when not physically hungry, preoccupation with food, eating alone due to embarrassment, and feelings of regret or disgust after an episode. In these cases, overeating is not limited to palatable foods.Impulsivity differentially affects disorders involving the overcontrol of food intake (such as anorexia nervosa) and disorders involving the lack of control of food intake (such as bulimia nervosa). Cognitive impulsivity, such as risk-taking, is a component of many eating disorders, including those that are restrictive. However, only people with disorders involving episodes of overeating have elevated levels of motoric impulsivity, such as reduced response inhibition capacity.One theory suggests that binging provides a short-term escape from feelings of sadness, anger, or boredom, although it may contribute to these negative emotions in the long-term. Another theory suggests that binge eating involves reward seeking, as evidenced by decreased serotonin binding receptors of binge-eating women compared to matched-weight controls and predictive value of heightened reward sensitivity/drive in dysfunctional eating.Treatments for clinical-grade overeating include cognitive behavioral therapy to teach people how to track and change their eating habits and actions, interpersonal psychotherapy to help people analyze the contribution of their friends and family in their disorder, and pharmacological therapies including antidepressants and SSRIs. Impulse buying Impulse buying consists of purchasing a product or service without any previous intent to make that purchase. It has been speculated to account for as much as eighty percent of all purchases in the United States.There are several theories pertaining to impulsive buying. One theory suggests that it is exposure combining with the speed that a reward can be obtained that influences an individual to choose lesser immediate rewards over greater rewards that can be obtained later. For example, a person might choose to buy a candy bar because they are in the candy aisle even though they had decided earlier that they would not buy candy while in the store. Another theory is one of self-regulation which suggests that the capacity to refrain from impulsive buying is a finite resource. As this capacity is depleted with repeated acts of restraint susceptibility to purchasing other items on impulse increases.Finally, a third theory suggests an emotional and behavioral tie between the purchaser and the product which drives both the likelihood of an impulsive purchase as well as the degree that a person will retroactively be satisfied with that purchase result. Some studies have shown a large number of individuals are happy with purchases made on impulse (41% in one study) which is explained as a preexisting emotional attachment which has a positive relationship both with the likelihood of initiating the purchase as well as mitigating post purchase satisfaction. As an example, when purchasing team-related college paraphernalia a large percentage of those purchases are made on impulse and are tied to the degree with which a person has positive ties to that team.Impulsive buying is seen both as an individual trait in which each person has a preconditioned or hereditary allotment, as well as a situational construct which is mitigated by such things as emotion in the moment of the purchase and the preconditioned ties an individual has with the product.Psychotherapy and pharmacological treatments have been shown to be helpful interventions for patients with impulsive-compulsive buying disorder. Psychotherapy interventions include the use of desensitization techniques, self-help books or attending a support group. Pharmacological interventions include the use of SSRIs, such as fluvoxamine, citalopram, escitalopram, and naltrexone. Impulse control disorders not elsewhere classified Impulse control disorder (ICDs) are a class of DSM diagnoses that do not fall into the other diagnostic categories of the manual (e.g. substance use disorders), and that are characterized by extreme difficulty controlling impulses or urges despite negative consequences. Individuals suffering from an impulse control disorder frequently experience five stages of symptoms: compelling urge or desire, failure to resist the urge, a heightened sense of arousal, succumbing to the urge (which usually yields relief from tension), and potential remorse or feelings of guilt after the behavior is completed. Specific disorders included within this category include intermittent explosive disorder, kleptomania, pathological gambling, pyromania, trichotillomania (hair-pulling disorder), and impulse control disorders not otherwise specified (ICD NOS). ICD NOS includes other significant difficulties that seem to be related to impulsivity but do not meet the criteria for a specific DSM diagnosis.There has been much debate over whether or not the ICDs deserve a diagnostic category of their own, or whether they are in fact phenomenologically and epidemiologically related to other major psychiatric conditions like obsessive-compulsive disorder (OCD), affective disorders, and addictive disorders. In fact, the ICD classification is likely to change with the release of the DSM-V in May 2013. In this new revision the ICD NOS will likely be reduced or removed; proposed revisions include reclassifying trichotillomania (to be renamed hair-pulling disorder) and skin-picking disorder as obsessive-compulsive and related disorders, moving intermittent explosive disorder under the diagnostic heading of disruptive, impulse control, and conduct disorders, and gambling disorder may be included in addiction and related disorders.The role of impulsivity in the ICDs varies. Research on kleptomania and pyromania is lacking, though there is some evidence that greater kleptomania severity is tied to poor executive functioning.Trichotillomania and skin-picking disorder seem to be disorders that primarily involve motor impulsivity, and will likely be classified in the DSM-V within the obsessive-compulsive and related disorders category.Pathological gambling, in contrast, seems to involve many diverse aspects of impulsivity and abnormal reward circuitry (similar to substance use disorders) that has led to it being increasingly conceptualized as a non-substance or behavioral addiction. Evidence elucidating the role of impulsivity in pathological gambling is accumulating, with pathological gambling samples demonstrating greater response impulsivity, choice impulsivity, and reflection impulsivity than comparison control samples. Additionally, pathological gamblers tend to demonstrate greater response perseveration (compulsivity) and risky decisionmaking in laboratory gambling tasks compared to controls, though there is no strong evidence suggesting that attention and working memory are impaired in pathological gamblers. These relations between impulsivity and pathological gambling are confirmed by brain function research: pathological gamblers demonstrate less activation in the frontal cortical regions (implicated in impulsivity) compared to controls during behavioral tasks tapping response impulsivity, compulsivity, and risk/reward. Preliminary, though variable, findings also suggest that striatal activation is different between gamblers and controls, and that neurotransmitter differences (e.g. dopamine, serotonin, opioids, glutamate, norepinephrine) may exist as well.Individuals with intermittent explosive disorder, also known as impulsive aggression, have exhibited serotonergic abnormalities and show differential activation in response to emotional stimuli and situations. Notably, intermittent explosive disorder is not associated with a higher likelihood of diagnosis with any of the other ICDs but is highly comorbid with disruptive behavior disorders in childhood. Intermittent explosive disorder is likely to be re-classified in the DSM-V under the heading of disruptive, impulse control, and conduct disorders.These sorts of impulse control disorders are most often treated using certain types of psychopharamcological interventions (e.g. antidepressants) and behavioral treatments like cognitive behavioral therapy. Theories of impulsivity Ego (cognitive) depletion According to the ego (or cognitive) depletion theory of impulsivity, self-control refers to the capacity for altering ones own responses, especially to bring them into line with standards such as ideals, values, morals, and social expectations, and to support the pursuit of long-term goals. Self-control enables a person to restrain or override one response, thereby making a different response possible. A major tenet of the theory is that engaging in acts of self-control draws from a limited "reservoir" of self-control that, when depleted, results in reduced capacity for further self-regulation. Self-control is viewed as analogous to a muscle: Just as a muscle requires strength and energy to exert force over a period of time, acts that have high self-control demands also require strength and energy to perform. Similarly, as muscles become fatigued after a period of sustained exertion and have reduced capacity to exert further force, self-control can also become depleted when demands are made of self-control resources over a period of time. Baumeister and colleagues termed the state of diminished self-control strength ego depletion (or cognitive depletion).The strength model of self-control asserts that: Just as exercise can make muscles stronger, there are signs that regular exertions of self-control can improve willpower strength. These improvements typically take the form of resistance to depletion, in the sense that performance at self-control tasks deteriorates at a slower rate. Targeted efforts to control behavior in one area, such as spending money or exercise, lead to improvements in unrelated areas, such as studying or household chores. And daily exercises in self-control, such as improving posture, altering verbal behavior, and using ones nondominant hand for simple tasks, gradually produce improvements in self-control as measured by laboratory tasks. The finding that these improvements carry over into tasks vastly different from the daily exercises shows that the improvements are not due to simply increasing skill or acquiring self-efficacy from practice. Just as athletes begin to conserve their remaining strength when their muscles begin to tire, so do self-controllers when some of their self-regulatory resources have been expended. The severity of behavioral impairment during depletion depends in part on whether the person expects further challenges and demands. When people expect to have to exert self-control later, they will curtail current performance more severely than if no such demands are anticipated. Consistent with the conservation hypothesis, people can exert self-control despite ego depletion if the stakes are high enough. Offering cash incentives or other motives for good performance counteracts the effects of ego depletion. This may seem surprising but in fact it may be highly adaptive. Given the value and importance of the capacity for self-control, it would be dangerous for a person to lose that capacity completely, and so ego depletion effects may occur because people start conserving their remaining strength. When people do exert themselves on the second task, they deplete the resource even more, as reflected in severe impairments on a third task that they have not anticipated.Empirical tests of the ego-depletion effect typically adopt dual-task paradigm. Participants assigned to an experimental ego-depletion group are required to engage in two consecutive tasks requiring self-control. Control participants are also required to engage in two consecutive tasks, but only the second task requires self-control. The strength model predicts that the performance of the experimental-group on the second self-control task will be impaired relative to that of the control group. This is because the finite self-control resources of the experimental participants will be diminished after the initial self-control task, leaving little to draw on for the second task.The effects of ego depletion do not appear to be a product of mood or arousal. In most studies, mood and arousal has not been found to differ between participants who exerted self-control and those who did not. Likewise, mood and arousal was not related to final self-control performance. The same is true for more specific mood items, such as frustration, irritation, annoyance, boredom, or interest as well. Feedback about success and failure of the self-control efforts does not appear to affect performance. In short, the decline in self-control performance after exerting self-control appears to be directly related to the amount of self-control exerted and cannot be easily explained by other, well-established psychological processes. Automatic vs. controlled processes/cognitive control Dual process theory states that mental processes operate in two separate classes: automatic and controlled. In general, automatic processes are those that are experiential in nature, occur without involving higher levels of cognition, and are based on prior experiences or informal heuristics. Controlled decisions are effortful and largely conscious processes in which an individual weighs alternatives and makes a more deliberate decision. Automatic Process: Automatic processes have four main features. They occur unintentionally or without a conscious decision, the cost of the decision is very low in mental resources, they cannot be easily stopped, and they occur without conscious thought on the part of the individual making them. Controlled Process: Controlled processes also have four main features that are very close to the opposite in spectrum from their automatic counterparts. Controlled processes occur intentionally, they require the expenditure of cognitive resources, the individual making the decision can stop the process voluntarily, and the mental process is a conscious one.Dual process theories at one time considered any single action/thought as either being automatic or controlled. However, currently they are seen as operating more along a continuum as most impulsive actions will have both controlled and automatic attributes. Automatic processes are classified according to whether they are meant to inhibit or to facilitate a thought process. For example, in one study researchers offered individuals a choice between a 1 in 10 chance of winning a prize and a 10 in 100 chance. Many participants chose one of the choices over the other without identifying that the chances inherent in each were the same as they saw either only 10 chances total as more beneficial, or of having 10 chances to win as more beneficial. In effect impulsive decisions can be made as prior information and experiences dictate one of the courses of action is more beneficial when in actuality careful consideration would better enable the individual to make a more informed and improved decision. Intertemporal choice Intertemporal choice is defined as "decisions with consequences that play out over time". This is often assessed using the relative value people assign to rewards at different points in time, either by asking experimental subjects to choose between alternatives or examining behavioral choices in a naturalistic setting.Intertemporal choice is commonly measured in the laboratory using a "delayed discounting" paradigm, which measures the process of devaluing rewards and punishments that happen in the future. In this paradigm, subjects must choose between a smaller reward delivered soon and a larger reward delivered at a delay in the future. Choosing the smaller-sooner reward is considered impulsive. By repeatedly making these choices, indifference points can be estimated. For example, if someone chose $70 now over $100 in a week, but chose the $100 in a week over $60 now, it can be inferred that they are indifferent between $100 in a week and an intermediate value between $60 and $70. A delay discounting curve can be obtained for each participant by plotting their indifference points with different reward amounts and time delays. Individual differences in discounting curves are affected by personality characteristics such as self-reports of impulsivity and locus of control; personal characteristics such as age, gender, IQ, race, and culture; socioeconomic characteristics such as income and education; and many other variables. to drug addiction. Lesions of the nucleus accumbens core subregion or basolateral amygdala produce shifts towards choosing the smaller-sooner reward, suggesting the involvement of these brain regions in the preference for delayed reinforcers. There is also evidence that the orbitofrontal cortex is involved in delay discounting, although there is currently debate on whether lesions in this region result in more or less impulsivity.Economic theory suggests that optimal discounting involves the exponential discounting of value over time. This model assumes that people and institutions should discount the value of rewards and punishments at a constant rate according to how delayed they are in time. While economically rational, recent evidence suggests that people and animals do not discount exponentially. Many studies suggest that humans and animals discount future values according to a hyperbolic discounting curve where the discount factor decreases with the length of the delay (for example, waiting from today to tomorrow involves more loss of value than waiting from twenty days to twenty-one days). Further evidence for non-constant delay discounting is suggested by the differential involvement of various brain regions in evaluating immediate versus delayed consequences. Specifically, the prefrontal cortex is activated when choosing between rewards at a short delay or a long delay, but regions associated with the dopamine system are additionally activated when the option of an immediate reinforcer is added. Additionally, intertemporal choices differ from economic models because they involve anticipation (which may involve a neurological "reward" even if the reinforcer is delayed), self-control (and the breakdown of it when faced with temptations), and representation (how the choice is framed may influence desirability of the reinforcer), none of which are accounted for by a model that assumes economic rationality.One facet of intertemporal choice is the possibility for preference reversal, when a tempting reward becomes more highly valued than abstaining only when immediately available. For example, when sitting home alone, a person may report that they value the health benefit of not smoking a cigarette over the effect of smoking one. However, later at night when the cigarette is immediately available, their subjective value of the cigarette may rise and they may choose to smoke it.A theory called the "primrose path" is intended to explain how preference reversal can lead to addiction in the long run. As an example, a lifetime of sobriety may be more highly valued than a lifetime of alcoholism, but, at the same time, one drink now may be more highly valued than not drinking now. Because it is always "now," the drink is always chosen, and a paradoxical effect occurs whereby the more-valued long-term alternative is not achieved because the more-valued short-term alternative is always chosen. This is an example of complex ambivalence, when a choice is made not between two concrete alternatives but between one immediate and tangible alternative (i.e. having a drink) and one delayed and abstract alternative (i.e. sobriety). Similarities between humans and non-human animals in intertemporal choice have been studied. Pigeons and rats also discount hyperbolically; tamarin monkeys do not wait more than eight seconds to triple the amount of a food reward. The question arises as to whether this is a difference of homology or analogy—that is, whether the same underlying process underlies human-animal similarities or whether different processes are manifesting in similar patterns of results. Inhibitory control Inhibitory control, often conceptualized as an executive function, is the ability to inhibit or hold back a prepotent response. It is theorized that impulsive behavior reflects a deficit in this ability to inhibit a response; impulsive people may find it more difficult to inhibit action whereas non-impulsive people may find it easier to do so. There is evidence that, in normal adults, commonly used behavioral measures of inhibitory control correlate with standard self-report measures of impulsivity.Inhibitory control may itself be multifaceted, evidenced by numerous distinct inhibition constructs that can be measured in different ways, and relate to specific types of psychopathology. Joel Nigg developed a useful working taxonomy of these different types of inhibition, drawing heavily from the fields of cognitive and personality psychology Niggs eight proposed types of inhibition include the following: Executive Inhibition Interference control Suppression of a stimulus that elicits an interfering response, enabling a person to complete the primary response. Interference control can also refer to suppressing distractors.Interference control has been measured using cognitive tasks like the stroop test, flanker tasks, dual task interference, and priming tasks. Personality researchers have used the Rothbart effortful control measures and the conscientiousness scale of the Big Five as inventory measures of interference control. Based on imaging and neural research it is theorized that the anterior cingulate, the dorsolateral prefrontal/premotor cortex, and the basal ganglia are related to interference control. Cognitive inhibition Cognitive inhibition is the suppression of unwanted or irrelevant thoughts to protect working memory and attention resources.Cognitive inhibition is most often measured through tests of directed ignoring, self-report on ones intrusive thoughts, and negative priming tasks. As with interference control, personality psychologists have measured cognitive inhibition using the Rothbart Effortful Control scale and the Big Five Conscientiousness scale. The anterior cingulate, the prefrontal regions, and the association cortex seem to be involved in cognitive inhibition. Behavioral inhibition Behavioral Inhibition is the suppression of prepotent response.Behavioral inhibition is usually measured using the Go/No Go task, Stop signal task, and reports of suppression of attentional orienting. Surveys that are theoretically relevant to behavioral inhibition include the Rothbart effortful control scale, and the Big Five Conscientiousness dimension. The rationale behind the use of behavioral measures like the Stop signal task is that "go" processes and "stop processes" are independent, and that, upon "go" and "stop" cues, they "race" against each other; if the go process wins the race, the prepotent response is executed, whereas if the stop processes wins the race, the response is withheld. In this context, impulsivity is conceptualized as a relatively slow stop process. The brain regions involved in behavioral inhibition appear to be the lateral and orbital prefrontal regions along with premotor processes. Oculomotor Inhibition Oculomotor Inhibition is the effortful suppression of reflexive saccade.Oculomotor inhibition is tested using antisaccade and oculomotor tasks. Also, the Rothbart effortful control measure and the Big Five Conscientiousness dimension are thought to tap some of the effortful processes underlying the ability to suppress saccade. The frontal eye fields and the dorsolateral prefrontal cortex are involved in oculomotor inhibition. Motivational inhibition In response to punishment Motivational inhibition and response in the face of punishment can be measured using tasks tapping inhibition of primary response, modified go/no go tasks, inhibition of competing response, and emotional Stroop tasks. Personality psychologists also use the Gray behavioral inhibition system measure, the Eysenck scale for neurotic introversion, and the Zuckerman Neuroticism-Anxiety scale. The Septal-hippocampal formation, cingulate, and motor systems seem to be the brain areas most involved in response to punishment. In response to novelty Response to novelty has been measured using the Kagan behavioral inhibition system measure and scales of neurotic introversion. The amygdaloid system is implicated in novelty response. Automatic inhibition of attention Recently inspected stimuli Suppression of recently inspected stimuli for both attention and oculomotor saccade is usually measured using attentional and oculomotor inhibition of return tests. The superior colliculus and the midbrain, oculomotor pathway are involved in suppression of stimuli. Neglected stimuli Information at locations that are not presently being attended to is suppressed, while attending elsewhere.This involves measures of covert attentional orienting and neglect, along with personality scales on neuroticism. The posterior association cortex and subcortical pathways are implicated in this sort of inhibition. Action/Inaction goals Recent psychology research also yields out the condition of impulsivity in relation to peoples general goal setting. It is possible these action and inaction goals are underlying peoples behavioral differences in their daily lives since they can demonstrate "patterns comparable to natural variation in overall activity levels". More specifically, the level of impulsivity and mania people have might positive correlated with favorable attitudes about and goals of general action while negatively respond to favorable attitudes about and goals of general inaction. Assessment of impulsivity Personality tests and reports Barratt Impulsiveness Scale The Barratt Impulsiveness Scale (BIS) is one of the oldest and most widely used measures of impulsive personality traits. The first BIS was developed in 1959 by Dr. Ernest Barratt. It has been revised extensively to achieve two major goals: (1) to identify a set of "impulsiveness" items that was orthogonal to a set of "anxiety" items as measured by the Taylor Manifest Anxiety Scale (MAS) or the Cattell Anxiety Scale, and (2) to define impulsiveness within the structure of related personality traits like Eysencks Extraversion dimension or Zuckermans Sensation-Seeking dimension, especially the disinhibition subfactor. The BIS-11 with 30 items was developed in 1995. According to Patton and colleagues, there are 3 subscales (Attentional Impulsiveness, Motor Impulsiveness, and Non-Planning Impulsiveness) with six factors: Attention: "focusing on a task at hand". Motor impulsiveness: "acting on the spur of the moment". Self-control: "planning and thinking carefully". Cognitive complexity: "enjoying challenging mental tasks". Perseverance: "a consistent life style". Cognitive instability: "thought insertion and racing thoughts". Eysenck Impulsiveness Scale The Eysenck Impulsiveness Scale (EIS) is a 54-item yes/no questionnaire designed to measure impulsiveness. Three subscales are computed from this measure: Impulsiveness, Venturesomeness, and Empathy. Impulsiveness is defined as "behaving without thinking and without realizing the risk involved in the behavior". Venturesomeness is conceptualized as "being conscious of the risk of the behavior but acting anyway" The questionnaire was constructed through factor analysis to contain items that most highly loaded on impulsiveness and venturesomeness. The EIS is a widely used and well-validated measure. Dickman Impulsivity Inventory The Dickman Impulsivity Inventory was first developed in 1990 by Scott J. Dickman. This scale is based on Dickmans proposal that there are two types of impulsivity that are significantly different from one another. This includes functional impulsivity which is characterized by quick decision making when it is optimal, a trait that is often considered to be a source of pride. The scale also includes dysfunctional impulsivity which is characterized by making quick decisions when it is not optimal. This type of impulsivity is most often associated with life difficulties including substance abuse problems and other negative outcomes.This scale includes 63 items of which 23 are related to dysfunctional impulsivity, 17 are related to functional impulsivity, and 23 are filler questions that relate to neither construct. This scale has been developed into a version for use with children as well as into several languages. Dickman showed there is no correlation between these two tendencies across individuals, and they also have different cognitive correlates. UPPS Impulsive Behavior Scale The UPPS Impulsive Behavior Scale is a 45-item self-report questionnaire that was designed to measure impulsivity across dimensions of the Five Factor Model of personality. The UPPS includes 4 sub-scales: lack of premeditation, urgency, lack of perseverance, and sensation-seeking. UPPS-P Impulsive Behavior Scale (UPPS-P) is a revised version of the UPPS, including 59 items. It assesses an additional personality pathway to impulsive behavior, Positive Urgency, in addition to the four pathways assessed in the original version of the scale: Urgency (now Negative Urgency), (lack of) Premeditation, (lack of) Perseverance, and Sensation Seeking UPPS-P short version (UPPS-Ps) is 20-item scale that evaluates five different impulsivity facets (4 items per dimension). UPPS-R Interview is a semi-structured interview that measures the degree to which individuals exhibit the various components of impulsivity assessed by the UPPS-P. Lifetime History of Impulsive Behaviors Lifetime History of Impulsive Behaviors (LHIB) is a 53-item questionnaire designed to assess lifetime history of impulsive behavior (as opposed to impulsive tendencies) as well as the level of distress and impairment associated with these behaviors. The assessment battery was designed to measure the following six dimensions: (a) impulsivity, (b) sensation seeking, (c) trait anxiety, (d) state depression, (e) empathy, and (f) social desirability. The LHIB consists of scales for clinically significant impulsivity, non-clinically significant impulsivity, and impulsivity related distress/impairment. Behavioral Inhibition System/Behavioral Activation System Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) was developed based on the Grays biopsychological theory of personality which suggests that there are two general motivational systems that underlie behavior and affect: BIS and BAS. This 20-item self-report questionnaire is designed to assess dispositional BIS and BAS sensitivities. Impulsive/Premeditated Aggression Scale Impulsive/Premeditated Aggression Scale (IPAS) is a 30-item self-report questionnaire. Half of the items describe impulsive aggression and half the items describe premeditated aggression. Aggressive behavior has traditionally been classified into two distinct subtypes, impulsive or premeditated. Impulsive aggression is defined as a hair-trigger aggressive response to provocation with loss of behavioral control. Premeditated aggression is defined as a planned or conscious aggressive act, not spontaneous or related to an agitated state. The IPAS is designed to characterize aggressive behavior as predominately impulsive or predominately premeditated in nature. Those subjects who clustered on the impulsive factor showed a broad range of emotional and cognitive impairments; those who clustered on the premeditated factor showed a greater inclination for aggression and anti-social behaviour. Padua Inventory The Padua Inventory (PI) consists of 60 items describing common obsessional and compulsive behavior and allows investigation of such problems in normal and clinical subjects. Behavioral paradigms A wide variety of behavioral tests have been devised for the assessment of impulsivity in both clinical and experimental settings. While no single test is a perfect predictor or a sufficient replacement for an actual clinical diagnosis, when used in conjunction with parent/teacher reports, behavioral surveys, and other diagnostic criteria, the utility of behavioral paradigms lies in their ability to narrow in on specific, discrete aspects of the impulsivity umbrella. Quantifying specific deficits is of use to the clinician and the experimenter, both of whom are generally concerned with obtaining objectively measurable treatment effects. Marshmallow test One widely recognizable test for impulsivity is the delay of gratification paradigm commonly known as the marshmallow test. Developed in the 1960s to assess willpower and self-control in preschoolers, the marshmallow test consists of placing a single marshmallow in front of a child and informing them that they will be left alone in the room for some duration. The child is told that if the marshmallow remains uneaten when the experimenter returns, they will be awarded a second marshmallow, both of which can then be eaten.Despite its simplicity and ease of administration, evidence from longitudinal studies suggests that the number of seconds preschoolers wait to obtain the second marshmallow is predictive of higher SAT scores, better social and emotional coping in adolescence, higher educational achievement, and less cocaine/crack use. Delay discounting Like the marshmallow test, delay discounting is also a delay of gratification paradigm. It is designed around the principle that the subjective value of a reinforcer decreases, or is discounted, as the delay to reinforcement increases. Subjects are given varying choices between smaller, immediate rewards and larger, delayed rewards. By manipulating reward magnitude and/or reward delay over multiple trials, indifference points can be estimated whereby choosing the small, immediate reward, or the large, delayed reward are about equally likely. Subjects are labeled impulsive when their indifference points decline more steeply as a function of delay compared to the normal population (i.e. greater preference for immediate reward). Unlike the marshmallow test, delay discounting does not require verbal instruction and can be implemented on non-human animals. Go/no-go and stop-signal reaction time tasks Two common tests of response inhibition used in humans are the go/no-go task, and a slight variant known as the stop-signal reaction time (SSRT) test. During a go/no-task, the participant is trained over multiple trials to make a particular response (e.g., a key-press) when presented with a go signal. On some trials, a stop signal is presented just prior to, or simultaneously with the go signal, and the subject must inhibit the impending response. The SSRT test is similar, except that the stop signal is presented after the go signal. This small modification increases the difficulty of inhibiting the go response, because the participant has typically already initiated the go response by the time the stop signal is presented. The participant is instructed to respond as fast as possible to the go signal while maintaining the highest possible inhibition accuracy (on no-go trials). During the task, the time at which the stop signal is presented (the stop signal delay or SSD) is dynamically adjusted to match the time after the go signal at which the participant is just able/unable to inhibit their go response. If the participant fails to inhibit their go response, the stop signal is moved slightly closer to the original go signal, and if the participant successfully inhibits their go response, the stop signal is moved slightly ahead in time. The SSRT is thus measured as the average go response time minus the average stop signal presentation time (SSD). Balloon Analogue Risk Task The balloon analogue risk task (BART) was designed to assess risk-taking behavior. Subjects are presented with a computer depiction of a balloon that can be incrementally inflated by pressing a response key. As the balloon inflates, the subject accumulates rewards with each new key-press. The balloon is programmed with a constant probability of popping. If the balloon pops, all rewards for that balloon are lost, or the subject may choose to stop inflating and bank the reward for that balloon at any time. Therefore, more key-presses equate to greater reward, but also greater probability of popping and cancelling rewards for that trial. The BART assumes that those with an affinity for risk-taking are more likely to pop the balloon, earning less reward overall than the typical population. Iowa Gambling Task The Iowa gambling task (IGT) is a test originally meant to measure decision making specifically within individuals who have ventromedial prefrontal cortex damage. The concept of impulsivity as relates to the IGT is one in which impulsive decisions are a function of an individuals lack of ability to make rational decisions over time due to an over amplification of emotional/somatic reward. In the IGT individuals are provided four decks of cards to choose from. Two of these decks provide much higher rewards but the deductions are also much higher while the second two decks have lower rewards per card but also much lower deductions. Over time anyone who chooses predominantly from the high rewards decks will lose money while those who choose from the smaller rewards decks will gain money. The IGT uses hot and cold processes in its concept of decision making. Hot decision making involves emotional responses to the material presented based on motivation related to reward and punishment. Cold processes occur when an individual uses rational cognitive determinations when making decisions. Combined an individual should gain a positive emotional reaction when choices have beneficial consequences and will have negative emotional responses tied to choices that have greater negative consequences. In general, healthy responders to the IGT will begin to drift to the lower gain decks as they realize that they are gaining more money than they lose both through an ability to recognize that one is more consistently providing rewards as well as through the emotions related to winning consistently. However, those who have emotional deficits will fail to recognize that they are losing money over time and will continue to be more influenced by the exhilaration of higher value rewards without being influenced by the negative emotions of the loses associated with them.For more information concerning these process refer to the Somatic marker hypothesis Differential Reinforcement of Low Response Rate Task Differential reinforcement of low response rate (DRL) described by Ferster and Skinner is used to encourage low rates of responding. It is derived from research in operant conditioning that provides an excellent opportunity to measure the hyperactive childs ability to inhibit behavioral responding. Hyperactive children were relatively unable to perform efficiently on the task, and this deficit endured regardless of age, IQ, or experimental condition. Therefore, it can be used to discriminate accurately between teacher rated and parent rated hyperactive and nonhyperactive children. In this procedure, responses that occur before a set time interval has passed are not reinforced and reset the time required between behaviors.In a study, a child was taken to the experimental room and told that they were going to play a game in which they had a chance to win a lot of M&Ms. Every time they made the light of the reward indicator by pressing a red button, they would earn an M&Ms. However, they had to wait a while (6 seconds) before they could press it to get another point. If they had pressed the button too soon, then they would have not gotten a point, and the light would not go on, and they had to wait a while before they could press it to get another point.Researchers have also observed that subjects in a time-based situation will often engage in a sequence or chain of behaviors between reinforceable responses. This is because this collateral behavior sequence helps the subject "wait out" the required temporal delay between responses. Other Other common impulsivity tasks include the Continuous performance task (CPT), 5-choice serial reaction time task (5-CSRTT), Stroop task, and Matching Familiar Figures Task. Pharmacology and neurobiology Neurobiological findings Although the precise neural mechanisms underlying disorders of impulse control are not fully known, the prefrontal cortex (PFC) is the brain region most ubiquitously implicated in impulsivity. Damage to the prefrontal cortex has been associated with difficulties preparing to act, switching between response alternatives, and inhibiting inappropriate responses. Recent research has uncovered additional regions of interest, as well as highlighted particular subregions of the PFC, that can be tied to performance in specific behavioral tasks. Delay discounting Excitotoxic lesions in the nucleus accumbens core have been shown to increase preference for the smaller, immediate reward, whereas lesions to the nucleus accumbens shell have had no observable effect. Additionally, lesions of the basolateral amygdala, a region tied closely to the PFC, negatively affect impulsive choice similarly to what is observed in the nucleus accumbens core lesions. Moreover, dorsal striatum may also be involved in impulsive choice in an intricate manner. Go/No-go and Stop-signal reaction time test The orbitofrontal cortex is now thought to play a role in disinhibiting, and injury to other brain structures, such as to the right inferior frontal gyrus, a specific subregion of the PFC, has been associated with deficits in stop-signal inhibition. 5-Choice Serial Reaction Time Task (5-CSRTT) and Differential Reinforcement of Low rates (DRL) As with delay discounting, lesion studies have implicated the core region of the nucleus accumbens in response inhibition for both DRL and 5-CSRTT. Premature responses in the 5-CSRTT may also be modulated by other systems within the ventral striatum. In the 5-CSRTT, lesions of the anterior cingulate cortex have been shown to increase impulsive responding, and lesions to the prelimbic cortex impair attentional performance. Iowa Gambling Task Patients with damage to the ventromedial frontal cortex exhibit poor decision-making and persist in making risky choices in the Iowa Gambling Task. Neurochemical and pharmacological findings The primary pharmacological treatments for ADHD are methylphenidate (Ritalin) and amphetamine. Both methylphenidate and amphetamines block re-uptake of dopamine and norepinephrine into the pre-synaptic neuron, acting to increase post-synaptic levels of dopamine and norepinephrine. Of these two monoamines, increased availability of dopamine is considered the primary cause for the ameliorative effects of ADHD medications, whereas increased levels of norepinephrine may be efficacious only to the extent that it has downstream, indirect effects on dopamine. The effectiveness of dopamine re-uptake inhibitors in treating the symptoms of ADHD has led to the hypothesis that ADHD may arise from low tonic levels of dopamine (particularly in the fronto-limbic circuitry), but evidence in support of this theory is mixed. Genetics There are several difficulties when it comes to trying to identify a gene for complex traits such as impulsivity, such as genetic heterogeneity. Another difficulty is that the genes in question might sometimes show incomplete penetrance, "where a given gene variant does not always cause the phenotype". Much of the research on the genetics of impulsivity-related disorders, such as ADHD, is based on family or linkage studies. There are several genes of interest that have been studied in an attempt to find the major genetic contributors to impulsivity. Some of these genes are: DAT1 is the dopamine transporter gene which is responsible for the active reuptake of dopamine from the neural synapse. DAT1 polymorphisms have been shown to be linked to hyperactivity and ADHD. DRD4 is the dopamine D4 receptor gene and is associated with ADHD and novelty seeking behaviors. It has been proposed that novelty seeking is associated with impulsivity. Mice deficient for DRD4 have shown less behavioral responses to novelty. 5HT2A is the serotonin receptor gene. The serotonin 2A receptor gene has been associated with both hyper locomotion, ADHD, as well as impulsivity. Subjects with a particular polymorphism of the 5HT2A gene made more commission errors during a punishment-reward condition in a go/no-go task. HTR2B a serotonin receptor gene. CTNNA2 encodes for a brain-expressed α-catenin that has been associated with Excitement-Seeking in a genome-wide association study (GWAS) of 7860 individuals. Intervention Interventions to impact impulsivity generally While impulsivity can take on pathological forms (e.g. substance use disorder, ADHD), there are less severe, non-clinical forms of problematic impulsivity in many peoples daily lives. Research on the different facets of impulsivity can inform small interventions to change decision making and reduce impulsive behavior For example, changing cognitive representations of rewards (e.g. making long term rewards seem more concrete) and/or creating situations of "precommitment" (eliminating the option of changing ones mind later) can reduce the preference for immediate reward seen in delay discounting. Brain training Brain training interventions include laboratory-based interventions (e.g. training using tasks like go/no go) as well as community, family, and school based interventions that are ecologically valid (e.g. teaching techniques for regulating emotions or behaviors) and can be used with individuals with non-clinical levels of impulsivity. Both sorts of interventions are aimed at improving executive functioning and self-control capacities, with different interventions specifically targeting different aspects of executive functioning like inhibitory control, working memory, or attention. Emerging evidence suggests that brain training interventions may succeed in impacting executive function, including inhibitory control. Inhibitory control training specifically is accumulating evidence that it can help individuals resist temptation to consume high calorie food and drinking behavior. Some have voiced concerns that the favorable results of studies testing working memory training should be interpreted with caution, claiming that conclusions regarding changes to abilities are measured using single tasks, inconsistent use of working memory tasks, no-contact control groups, and subjective measurements of change. Treatment of specific disorders of impulsivity Behavioral, psychosocial, and psychopharmacological treatments for disorders involving impulsivity are common. Psychopharmacological intervention Psychopharmacological intervention in disorders of impulsivity has shown evidence of positive effects; common pharmacological interventions include the use of stimulant medication, selective serotonin reuptake inhibitors (SSRIs) and other antidepressants. ADHD has a well-established evidence base supporting the use of stimulant medication for the reduction of ADHD symptoms. Pathological gambling has also been studied in drug trials, and there is evidence that gambling is responsive to SSRIs and other antidepressants. Evidence based pharmacological treatment for trichotillomania is not yet available, with mixed results of studies investigating the use of SSRIs, though cognitive behavioral therapy has shown positive effects. Intermittent explosive disorder is most often treated with mood stabilizers, SSRIs, beta blockers, alpha agonists, and anti-psychotics (all of which have shown positive effects). There is evidence that some pharmacological interventions are efficacious in treating substance-use disorders, though their use can depend on the type of substance that is abused. Pharmacological treatments for substance-use disorders include acamprosate, buprenorphine, disulfiram, LAAM, methadone, and naltrexone. Behavioral interventions Behavioral interventions also have a fairly strong evidence base in impulse-control disorders. In ADHD, the behavioral interventions of behavioral parent training, behavioral classroom management, and intensive peer-focused behavioral interventions in recreational settings meet stringent guidelines qualifying them for evidence based treatment status. In addition, a recent meta-analysis of evidence-based ADHD treatment found organization training to be a well-established treatment method. Empirically validated behavioral treatments for substance use disorder are fairly similar across substance use disorders, and include behavioral couples therapy, CBT, contingency management, motivational enhancement therapy, and relapse prevention. Pyromania and kleptomania are understudied (due in large part to the illegality of the behaviors), though there is some evidence that psychotherapeutic interventions (CBT, short term counseling, day treatment programs) are efficacious in treating pyromania, while kleptomania seems to be best addressed using SSRIs. Additionally, therapies including CBT, family therapy, and social skill training have shown positive effects on explosive aggressive behaviors. See also Affect ADHD Addiction Deferred gratification Drive theory Emotion Feeling Instinct Impulse control disorder Sensation seeking Novelty seeking Alternative five model of personality References Further reading Evenden, J. L. (21 October 1999). "Varieties of impulsivity". Psychopharmacology. 146 (4): 348–361. doi:10.1007/PL00005481. PMID 10550486. S2CID 5972342. Hollander, E.; Rosen, J. (March 2000). "Impulsivity". Journal of Psychopharmacology. 14 (2_suppl1): S39–S44. doi:10.1177/02698811000142S106. PMID 10888030. S2CID 243171966. Moeller, F. Gerard; Barratt, Ernest S.; Dougherty, Donald M.; Schmitz, Joy M.; Swann, Alan C. (November 2001). "Psychiatric Aspects of Impulsivity". American Journal of Psychiatry. 158 (11): 1783–1793. doi:10.1176/appi.ajp.158.11.1783. PMID 11691682. Chamberlain, Samuel R; Sahakian, Barbara J (May 2007). "The neuropsychiatry of impulsivity". Current Opinion in Psychiatry. 20 (3): 255–261. doi:10.1097/YCO.0b013e3280ba4989. PMID 17415079. S2CID 22198972. External links Media related to Impulsivity at Wikimedia Commons Impulsive Info

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

What does the medical term 'Persistent Müllerian duct syndrome' encompass?

Persistent Müllerian duct syndrome (PMDS) is the presence of Müllerian duct derivatives (fallopian tubes, uterus, and/or the upper part of the vagina) in what would be considered a genetically and otherwise physically normal male animal by typical human based standards. In humans, PMDS typically is due to an autosomal recessive congenital disorder and is considered by some to be a form of pseudohermaphroditism due to the presence of Müllerian derivatives.Typical features include undescended testes (cryptorchidism) and the presence of a small, underdeveloped uterus in an XY infant or adult. This condition is usually caused by deficiency of fetal anti-Müllerian hormone (AMH) effect due to mutations of the gene for AMH or the anti-Müllerian hormone receptor, but may also be as a result of insensitivity to AMH of the target organ.PMDS can also present in non-human animals. Presentation The first visible signs of PMDS after birth is cryptorchidism (undescended testes) either unilaterally or bilaterally. Along with cryptorchidism, is also inguinal hernias which may be presented unilaterally (affects one testicle) or bilaterally (affects both testicles). Adults who have been oblivious to this condition may be presented with haematuria, which is when blood appears in urine because of hormonal imbalances. PMDS Type I, is also referred to as hernia uteri inguinalis, which exhibits one descended testis that has also pulled the fallopian tube and sometimes uterus, through the inguinal canal. The descended testes, fallopian tube and uterus all fall in the same inguinal canal, causing an inguinal hernia. Altogether when the aforementioned conditions occur, it is called transverse testicular ectopia.Under the microscope, some samples taken for biopsies displayed results where testicular tissue was at a stage of immaturity, and showed dysplasia. Genetics Mutation in AMH gene (PMDS Type 1) or AMHR2 gene (PMDS Type 2) are the primary causes of PMDS. AMH, or sometimes referred to as Müllerian inhibiting substance (MIS), is secreted by Sertoli cells during an individuals whole life. It is essential during the foetal period as it functions to regress the Müllerian ducts. However, AMH also functions in the last trimester of pregnancy, after birth, and even during adulthood in minimal amounts. The Sertoli cells in males secrete AMH, through the presence of a Y chromosome.The role of the AMH gene in reproductive development, is the production of a protein that contributes to male sex differentiation. During development of male foetuses, the AMH protein is secreted by cells within the testes. AMHs bind to the AMH Type 2 Receptors, which are present on cells on the surface of the Müllerian duct. The binding of AMH to its receptors on the Müllerian duct induces the apoptosis of the Müllerian duct cells, thus the regression of the Müllerian duct within males. However, for females who originally do not produce AMH proteins during foetal development, the Müllerian duct eventually becomes the uterus and fallopian tubes as normal. With the AMH gene mutation (PMDS Type 1), the AMH is either not produced, produced in deficient amounts, defective, secreted at the wrong critical period for male differentiation or the Müllerian ducts manifested a resistance to AMH.AMHR2 contains the instructions for generating the receptors that AMH binds to. If there if a mutation in the AMHR2 gene, the response to AMH molecules binding to the receptor cannot be properly reciprocated. Other possibilities include an absence of the receptors, such that the AMH molecules cannot induce differentiation. Mutation in the AMHR2 is critical to proper male sex differentiation. The genetic mutational cause of PMDS, is a 27 base-pair deletion of the Anti-Müllerian Type 2 Receptor gene. The 27-base-pair deletion that occurs PMDS is in exon 10 on one allele.PMDS is inherited in an autosomal recessive manner. The male individuals inherit mutated copies of the X chromosomes from the maternal and paternal genes, implying the parents are carriers and do not show symptoms. Females inheriting two mutated genes do not display symptoms of PMDS, though remain as carriers. Males are affected genotypically with the karyotype (46, XY) and phenotypically. Mechanism AMH (anti Müllerian hormone) is produced by the primitive Sertoli cells as one of the earliest Sertoli cell products and induces regression of the Müllerian ducts. Fetal Müllerian ducts are only sensitive to AMH action around the 7th or 8th week of gestation, and Müllerian regression is completed by the end of the 9th week. The AMH induced regression of the Müllerian duct occurs in cranio-caudal direction via apoptosis. The AMH receptors are on the Müllerian duct mesenchyme and transfer the apoptotic signal to the Müllerian epithelial cell, presumably via paracrine actors. The Wolffian ducts differentiate into epididymides, vasa deferentia and seminal vesicles under the influence of testosterone, produced by the fetal Leydig cells. Diagnosis Persistent Müllerian duct syndrome (PMDS), also known as persistent oviduct syndrome, is a congenital disorder related to male sexual development. PMDS usually affects phenotypically normal male individuals with the karyotype (46, XY) and is a form of pseudohermaphroditism.The condition occurs in males and consists of normal-functioning reproductive organs and gonads, but also female reproductive organs such as the uterus and the fallopian tubes. The fetus has two sets of tubes which give rise to accessory reproductive organs - the (Wolffian) mesonephric ducts and the (Müllerian) paramesonephric ducts. Usually, the Wolffian duct gives rise to male reproductive organs (specifically the testicle, epididymis and vas deferens) while the Müllerian to female (the fallopian tubes, the uterus and the vagina), while the other duct regresses. In PMDS, an abnormality in the anti-Müllerian hormone signalling pathway causes the in-males-redundant Müllerian duct to persist and give rise to variously developed female reproductive organs.PMDS has various causes related to AMH or receptor abnormalities. For example, AMH has failed to synthesize, failed to release or was secreted at the wrong time. Normally, both the Müllerian and Wolffian ducts are present during the 7th week of gestation. At approximately the end of the 7th and the beginning of the 8th week of gestation, the Sertoli cells secretion of AMH occurs, causing male sex differentiation during fetal development. The AMH molecules bind to AMHRII (anti-Müllerian hormone receptor type II) regressing the Müllerian duct. The Leydig cells secrete testosterone to aid the male differentiation process by inducing structures such as the epididymis, vas deferens and seminal vesicles. However, with PMDS individuals, the Müllerian duct persists instead of regressing, either due to AMH secretion (PMDS Type I) or AMH receptors (PMDS Type II). PMDS is usually coincidentally found during surgery for inguinal hernia, or when searching for adult male infertility causes. Other diagnostic tests Genetic Another method for the confirmation of PMDS is genetic testing. It is not usually preferred because of its processing period and cost. With image screenings such as ultrasound and MRI, the condition can be efficiently confirmed. Genetic tests can identify those who hold the mutated gene, identify the family members chances and risks, and advise those who are trying to get pregnant. Genetic counseling and further genetic testing is offered to confirm the chances and risks of an individuals offspring obtaining the pair of mutated genes. Further research into the family tree and inheritance is possible as well. ELISA An ELISA test is a form of immunoassay, a technique which uses an antibody or antigen to identify the presence of particular substances. For PMDS, ELISA tests can be used to determine the levels of AMH within the male individuals serum, but this is only effective before the individual reaches puberty as it normally increases during this period. PMDS patients display low levels of AMH within the serum, and low levels of testosterone. Treatment The main form of treatment is laparotomy, a modern and minimally invasive type of surgery. Laparotomy properly positions the testes within the scrotum (orchidopexy) and remove Müllerian structures, the uterus and fallopian tubes. Occasionally they are unsalvageable if located high in the retroperitoneum. During this surgery, the uterus is usually removed and attempts made to dissect away Müllerian tissue from the vas deferens and epididymis to improve the chance of fertility. If the person has male gender identity and the testes cannot be retrieved, testosterone replacement will be usually necessary at puberty should the affected individual choose to pursue medical attention. Recently, laparoscopic hysterectomy is offered to patients as a solution to both improve the chances of fertility and to prevent the occurrence of neoplastic tissue formation. The surgery is recommended to be performed when the individual is between one and two years old, but usually done when less than one year old. Having a target age for surgery reduces the risks of damaging the vas deferens. The vas deferens is in close proximity to the Müllerian structures, and is sometimes lodged in the uterine wall. Overall, the purpose of the treatment improves self-identification of an individual, reduces the increased risk of cancer and reduces the possibility of infertility, if not already present. PMDS patients have a possibility of infertility in the future if not promptly operated on. When the affected males are adults, those who are not aware of the condition may find the presence of blood in their semen (hematospermia). The Müllerian structures and cryptorchidism can also develop into cancer if ignored, or if there are pieces of Müllerian structures left from past surgery. If PMDS is found during adulthood, or if Müllerian structures had to be left behind due to risks in surgery, biopsies of the remaining Müllerian structures can be performed. Upon pathohistological observation, the endometrial tissues appear atrophied, and the fallopian tubes have begun to congest showing signs of fibrosis. Epidemiology PMDS is a relatively rare congenital disease. From current data, approximately 45% of the known cases are caused by mutations in the AMH gene, being a mutation on chromosome 19 (Type I PMDS). Approximately, 40% are AMHR2 mutations, on the AMH receptor type 2 gene, which is on chromosome 12 (Type 2 PMDS). The remaining unknown 15% are referred to as idiopathic PMDS. Case studies Especially before the 21st century, these conditions were hard to diagnose due to the lack of modern imaging capabilities. For this reason, the older population, or those in poorer countries found out later. PMDS was usually overlooked because the external symptoms, such as the cryptorchidism and inguinal hernias, were assumed to be the only complication. A case reported in 2013, involves a 50-year-old male with a history of low testosterone levels, high cholesterol and the congenital absence of his right testis. Imaging revealed that the patient had three cystic masses, with structures similar to the uterus and ovaries, thus PMDS. During the operation, the surgeons found malignant degeneration of the Müllerian remnants which occurs if PMDS is unnoticed for a long period of time. The cause of the complications presented in the male patient was due to the unidentified bilateral cryptorchidism since birth, as doctors at that time assumed the complication was just the "congenital absence of his right testis". Overlooking the symptoms of PDMS can cause permanent negative effects such as infertility and future malignancies, as shown by this male patient. The malignant degeneration of the Müllerian structures is supportive evidence for the cause of the male patients infertility. See also Intersex Sexual differentiation Cryptorchidism Anti-Müllerian hormone References Further reading == External links ==

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

The term 'Tubo-ovarian abscess' keeps coming up in medical discussions. What does it stand for?

A tubo-ovarian abscess (TOA) is one of the late complications of pelvic inflammatory disease (PID) and can be life-threatening if the abscess ruptures and results in sepsis. It consists of an encapsulated or confined pocket of pus with defined boundaries that forms during an infection of a fallopian tube and ovary. These abscesses are found most commonly in reproductive age women and typically result from upper genital tract infection. It is an inflammatory mass involving the fallopian tube, ovary and, occasionally, other adjacent pelvic organs. A TOA can also develop as a complication of a hysterectomy.: 103 Symptoms typically include fever, an elevated white blood cell count, lower abdominal-pelvic pain, and/or vaginal discharge. Fever and leukocytosis may be absent. TOAs are often polymicrobial with a high percentage of anaerobic bacteria. The cost of treatment in the United States is approximately $2,000 per patient, which equals about $1.5 billion annually. Though rare, TOA can occur without a preceding episode of PID or sexual activity. Signs and symptoms The signs and symptoms of tubo-ovarian abscess (TOA) are the same as with pelvic inflammatory disease (PID) with the exception that the abscess can be found with magnetic resonance imaging (MRI), sonography and x-ray. It also differs from PID in that it can create symptoms of acute-onset pelvic pain. Typically this disease is found in sexually active women. Tubo-ovarian abscess can mimic abdominal tumours. Complications Complications of TOA are related to the possible removal of one or both ovaries and fallopian tubes. Without these reproductive structures, fertility can be affected. Surgical complications can develop and include: Allergic shock due to anesthetics A paradoxical reaction to a drug Infection Cause The development of TOA is thought to begin with the pathogens spreading from the cervix to the endometrium, through the salpinx, into the peritoneal cavity and forming the tubo-ovarian abscess with (in some cases) pelvic peritonitis. TOA can develop from the lymphatic system with infection of the parametrium from an intrauterine device (IUD). Bacteria recovered from TOAs are Escherichia coli, Bacteroides fragilis, other Bacteroides species, Peptostreptococcus, Peptococcus, and aerobic streptococci. Long term IUD use is associated with TOA. Actinomyces is also recovered from TOA. Diagnosis Laparoscopy and other imaging tools can visualize the abscess. Physicians are able to make the diagnosis if the abscess ruptures when the woman begins to have lower abdominal pain that then begins to spread. The symptoms then become the same as the symptoms for peritonitis. Sepsis occurs, if left untreated.: 103  Ultrasonography is a sensitive enough imaging tool that it can accurately differentiate between pregnancy, hemorrhagic ovarian cysts, endometriosis, ovarian torsion, and tubo-ovarian abscess. Its availability, the relative advancement in the training of its use, its low cost, and because it does not expose the woman (or fetus) to ionizing radiation, ultrasonography an ideal imaging procedure for women of reproductive age. Prevention Risk factors have been identified which indicate what women will be more likely to develop TOA. These are: increased age, IUD insertion, chlamydia infection, and increased levels of certain proteins (CRP and CA-125) and will alert clinicians to follow up on unresolved symptoms of PID. Treatment Treatment for TOA differs from PID in that some clinicians recommend patients with tubo-ovarian abscesses have at least 24 hours of inpatient parenteral treatment with antibiotics, and that they may require surgery. If surgery becomes necessary, pre-operative administration of broad-spectrum antibiotics is started and removal of the abscess, the affected ovary and fallopian tube is done. After discharge from the hospital, oral antibiotics are continued for the length of time prescribed by the physician.: 103 Treatment is different if the TOA is discovered before it ruptures and can be treated with IV antibiotics. During this treatment, IV antibiotics are usually replaced with oral antibiotics on an outpatient basis. Patients are usually seen three days after hospital discharge and then again one to two weeks later to confirm that the infection has cleared.: 103  Ampicillin/sulbactam plus doxycycline is effective against C. trachomatis, N. gonorrhoeae, and anaerobes in women with tubo-ovarian abscess. Parenteral Regimens described by the Centers for Disease Control and prevention are Ampicillin/Sulbactam 3 g IV every 6 hours and Doxycycline 200 mg orally or IV every 24 hours, though other regiments that are used for pelvic inflammatory disease have been effective. Epidemiology The epidemiology of TOA is closely related to that of pelvic inflammatory disease which is estimated to one million people yearly. References == External links ==

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Could you offer a clear explanation of the term 'Leydig cell hypoplasia' as used in the medical field?

Leydig cell hypoplasia (or aplasia) (LCH), also known as Leydig cell agenesis, is a rare autosomal recessive genetic and endocrine syndrome affecting an estimated 1 in 1,000,000 genetic males. It is characterized by an inability of the body to respond to luteinizing hormone (LH), a gonadotropin which is normally responsible for signaling Leydig cells of the testicles to produce testosterone and other androgen sex hormones. The condition manifests itself as pseudohermaphroditism (partially or fully underdeveloped genitalia), hypergonadotropic hypogonadism (decreased or lack of production of sex steroids by the gonads despite high circulating levels of gonadotropins), reduced or absent puberty (lack of development of secondary sexual characteristics, resulting in sexual infantilism if left untreated), and infertility.Leydig cell hypoplasia does not occur in biological females as they do not have either Leydig cells or testicles. However, the cause of the condition in males, luteinizing hormone insensitivity, does affect females, and because LH plays a role in the female reproductive system, it can result in primary amenorrhea or oligomenorrhea (absent or reduced menstruation), infertility due to anovulation, and ovarian cysts.A related condition is follicle-stimulating hormone (FSH) insensitivity, which presents with similar symptoms to those of Leydig cell hypoplasia but with the symptoms in the respective sexes reversed (i.e., hypogonadism and sexual infantilism in females and merely problems with fertility in males). Despite their similar causes, FSH insensitivity is considerably less common in comparison to LH insensitivity. Symptoms and signs The symptoms of Leydig cell hypoplasia include pseudohermaphroditism, i.e., feminized, ambiguous, or relatively mildly underdeveloped (e.g., micropenis, severe hypospadias, and/or cryptorchidism [undescended testes]) external genitalia, a female gender identity or gender variance, hypergonadotropic hypogonadism (hypogonadism despite high levels of gonadotropins), delayed, impaired, or fully absent puberty with an associated reduction in or complete lack of development of secondary sexual characteristics (sexual infantilism), impaired fertility or complete sterility, tall stature (due to delayed epiphyseal closure), eunuchoid skeletal proportions, delayed or absent bone maturation, and osteoporosis. Cause Leydig cell hypoplasia is caused by genetic mutations in LHCGR, a gene which encodes the LH/hCG receptor. LH normally acts through the LH/hCG receptor to stimulate the growth of Leydig cells in the testicles and the production of androgens such as testosterone and dihydrotestosterone (DHT) by these cells. In Leydig cell hypoplasia however, there is a reduced capacity for the LH/hCG receptor to respond to LH. This results in hypoplasia or absence of Leydig cells, testicular atrophy, and lower than normal androgen levels. In the most severe form of the condition in which there is a complete lack of response of the Leydig cells to LH, androgen production by the testicles is virtually negligible and secondary sexual characteristics entirely fail to develop at puberty. Diagnosis Since the Sertoli cells are not affected by Leydig cell hypoplasia, anti-Müllerian hormone is secreted normally and so there are no Müllerian structures. Wolffian structures, such as the prostate, vasa deferentia, and epidydimides are present. In type I, abdominal testes are revealed on ultrasound; in type II testes may be descended or undescended.People with Leydig cell hypoplasia type I display no response to the hCG stimulation test; there is no increase in serum levels of testosterone and dihydrotestosterone. Leydig cell hypoplasia type II can display either a pronounced rise of testosterone levels or no rise.In any case, the diagnosis is confirmed on biopsy of the testes, revealing either absent or hypoplastic Leydig cells. The inside of the testis will be grayish and mucous, displaying arrested spermatogenesis and the presence of Sertoli cells. The diagnosis can also be confirmed by looking for mutations in the gene for the LH receptor.A diagnosis of Leydig cell hypoplasia is usually made in the neonatal period, following the discovery of ambiguous genitalia, or at puberty, when secondary sex characteristics fail to develop. Puberty is the most common time for Leydig cell hypoplasia to be diagnosed. Treatment Patients with Leydig cell hypoplasia may be treated with hormone replacement therapy (i.e., with androgens), which will result in normal sexual development and the resolution of most symptoms. In the case of 46,XY (genetically "male") individuals who are phenotypically female and/or identify as the female gender, estrogens should be given instead. Surgical correction of the genitals in 46,XY males may be required, and, if necessary, an orchidopexy (relocation of the undescended testes to the scrotum) may be performed as well. See also Disorders of sex development Intersexuality, pseudohermaphroditism, and ambiguous genitalia Hypogonadism and hypogonadotropic hypogonadism Familial male-limited precocious puberty (or LH oversensitivity) Follicle-stimulating hormone insensitivity Gonadotropin-releasing hormone insensitivity Inborn errors of steroid metabolism Isolated 17,20-lyase deficiency Combined 17α-hydroxylase/17,20-lyase deficiency 17β-Hydroxysteroid dehydrogenase III deficiency Androgen insensitivity syndrome References == External links ==

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

Can you demystify the medical term 'Dupuytrens contracture' for me?

Dupuytrens contracture (also called Dupuytrens disease, Morbus Dupuytren, Viking disease, palmar fibromatosis and Celtic hand) is a condition in which one or more fingers become progressively bent in a flexed position. It is named after Guillaume Dupuytren, who first described the underlying mechanism of action, followed by the first successful operation in 1831 and publication of the results in The Lancet in 1834. It usually begins as small, hard nodules just under the skin of the palm, then worsens over time until the fingers can no longer be fully straightened. While typically not painful, some aching or itching may be present. The ring finger followed by the little and middle fingers are most commonly affected. It can affect one or both hands. The condition can interfere with activities such as preparing food, writing, putting your hand in a tight pocket, putting on gloves, or shaking hands.The cause is unknown but might have a genetic component. Risk factors include family history, alcoholism, smoking, thyroid problems, liver disease, diabetes, previous hand trauma, and epilepsy. The underlying mechanism involves the formation of abnormal connective tissue within the palmar fascia. Diagnosis is usually based on a physical exam. Blood tests or imaging studies are not usually necessary.Initial treatment is typically with a cortisone shot into the affected area, occupational therapy, and physical therapy. Among those who worsen, clostridial collagenase injections or surgery may be tried. While radiation therapy is used to treat this condition, the evidence for this use is scarce. The Royal College of Radiologists (RCR) Faculty of Clinical Oncology concluded that radiotherapy is effective in early stage disease which has progressed within the last 6 to 12 months. The condition may recur despite treatment. If it does return after treatment, it can be treated again with further improvement. It is easier to treat when the amount of finger bending is more mild.It was once believed that Dupuytrens most often occurs in white males over the age of 50 and is rare among Asians and Africans. It sometimes was erroneously called "Viking disease," since it was often recorded among those of Nordic descent. In Norway, about 30% of men over 60 years old have the condition, while in the United States about 5% of people are affected at some point in time. In the United Kingdom, about 20% of people over 65 have some form of the disease.More recent and wider studies show the highest prevalence in Africa (17 per cent), Asia (15 per cent). Signs and symptoms Typically, Dupuytrens contracture first presents as a thickening or nodule in the palm, which initially can be with or without pain. Later in the disease process, which can be years later, there is painless increasing loss of range of motion of the affected finger(s). The earliest sign of a contracture is a triangular "puckering" of the skin of the palm as it passes over the flexor tendon just before the flexor crease of the finger, at the metacarpophalangeal (MCP) joint.Generally, the cords or contractures are painless, but, rarely, tenosynovitis can occur and produce pain. The most common finger to be affected is the ring finger; the thumb and index finger are much less often affected. The disease begins in the palm and moves towards the fingers, with the metacarpophalangeal (MCP) joints affected before the proximal interphalangeal (PIP) joints. The MCP joints at the base of the finger responds much better to treatment and are usually able to fully extend after treatment. Due to anatomic differences in the ligaments and extensor tendons at the PIP joints, they may have some residual flexion. Proper patient education is necessary to set realistic treatment expectation. In Dupuytrens contracture, the palmar fascia within the hand becomes abnormally thick, which can cause the fingers to curl and can impair finger function. The main function of the palmar fascia is to increase grip strength; thus, over time, Dupuytrens contracture decreases a persons ability to hold objects and use the hand in many different activities. Dupuytrens contracture can also be experienced as embarrassing in social situations and can affect quality of life People may report pain, aching, and itching with the contractions. Normally, the palmar fascia consists of collagen type I, but in Dupuytren patients, the collagen changes to collagen type III, which is significantly thicker than collagen type I. Related conditions People with severe involvement often show lumps on the back of their finger joints (called "Garrods pads", "knuckle pads", or "dorsal Dupuytren nodules"), and lumps in the arch of the feet (plantar fibromatosis or Ledderhose disease). In severe cases, the area where the palm meets the wrist may develop lumps. It is thought the condition Peyronies disease is related to Dupuytrens contracture. Risk factors Dupuytrens contracture is a non-specific condition, but primarily affects: Non-modifiable People of Scandinavian or Northern European ancestry; it has been called the "Viking disease", though it is also widespread in some Mediterranean countries, e.g., Spain and Bosnia. Dupuytrens is unusual among groups such as Chinese and Africans. Men rather than women; men are more likely to develop the condition (80%) People over the age of 50 (5% to 15% of men in that group in the US); the likelihood of getting Dupuytrens disease increases with age People with a family history (60% to 70% of those affected have a genetic predisposition to Dupuytrens contracture) Modifiable Smokers, especially those who smoke 25 cigarettes or more a day Thinner people, i.e., those with a lower-than-average body mass index. Manual workers Alcoholics Other conditions People with a higher-than-average fasting blood glucose level People with previous hand injury People with Ledderhose disease (plantar fibromatosis) People with epilepsy (possibly due to anti-convulsive medication) People with diabetes mellitus People with HIV Previous myocardial infarctionIn one study, those with stage 2 of the disease were found to have a slightly increased risk of mortality, especially from cancer. Diagnosis Types According to the American Dupuytrens specialist Dr. Charles Eaton, there may be three types of Dupuytrens disease: Type 1: A very aggressive form of the disease found in only 3% of people with Dupuytrens, which can affect men under 50 with a family history of Dupuytrens. It is often associated with other symptoms such as knuckle pads and Ledderhose disease. This type is sometimes known as Dupuytrens diathesis. Type 2: The more normal type of Dupuytrens disease, usually found in the palm only, and which generally begins above the age of 50. According to Eaton, this type may be made more severe by other factors such as diabetes or heavy manual labor. Type 3: A mild form of Dupuytrens which is common among diabetics or which may also be caused by certain medications, such as the anti-convulsants taken by people with epilepsy. This type does not lead to full contracture of the fingers, and is probably not inherited. Treatment Treatment is indicated when the so-called table-top test is positive. With this test, the person places their hand on a table. If the hand lies completely flat on the table, the test is considered negative. If the hand cannot be placed completely flat on the table, leaving a space between the table and a part of the hand as big as the diameter of a ballpoint pen, the test is considered positive and surgery or other treatment may be indicated. Additionally, finger joints may become fixed and rigid. There are several types of treatment, with some hands needing repeated treatment.The main categories listed by the International Dupuytren Society in order of stage of disease are radiation therapy, needle aponeurotomy (NA), collagenase injection, and hand surgery. As of 2016 the evidence on the efficacy of radiation therapy was considered inadequate in quantity and quality, and difficult to interpret because of uncertainty about the natural history of Dupuytrens disease.Needle aponeurotomy is most effective for Stages I and II, covering 6–90 degrees of deformation of the finger. However, it is also used at other stages. Collagenase injection is likewise most effective for Stages I and II. However, it is also used at other stages.Hand surgery is effective at stage I to stage IV. Surgery On 12 June 1831, Dupuytren performed a surgical procedure on a person with contracture of the 4th and 5th digits who had been previously told by other surgeons that the only remedy was cutting the flexor tendons. He described the condition and the operation in The Lancet in 1834 after presenting it in 1833, and posthumously in 1836 in a French publication by Hôtel-Dieu de Paris. The procedure he described was a minimally invasive needle procedure. Because of high recurrence rates, new surgical techniques were introduced, such as fasciectomy and then dermofasciectomy. Most of the diseased tissue is removed with these procedures.Recurrence rates are low. For some individuals, the partial insertion of "K-wires" into either the DIP or PIP joint of the affected digit for a period of a least 21 days to fuse the joint is the only way to halt the diseases progress. After removal of the wires, the joint is fixed into flexion, which is considered preferable to fusion at extension. In extreme cases, amputation of fingers may be needed for severe or recurrent cases or after surgical complications. Limited fasciectomy Limited/selective fasciectomy removes the pathological tissue, and is a common approach. Low-quality evidence suggests that fasciectomy may be more effective for people with advanced Dupuytrens contractures.During the procedure, the person is under regional or general anesthesia. A surgical tourniquet prevents blood flow to the limb. The skin is often opened with a zig-zag incision but straight incisions with or without Z-plasty are also described and may reduce damage to neurovascular bundles. All diseased cords and fascia are excised. The excision has to be very precise to spare the neurovascular bundles. Because not all the diseased tissue is visible macroscopically, complete excision is uncertain.A 20-year review of surgical complications associated with fasciectomy showed that major complications occurred in 15.7% of cases, including digital nerve injury (3.4%), digital artery injury (2%), infection (2.4%), hematoma (2.1%), and complex regional pain syndrome (5.5%), in addition to minor complications including painful flare reactions in 9.9% of cases and wound healing complications in 22.9% of cases. After the tissue is removed the incision is closed. In the case of a shortage of skin, the transverse part of the zig-zag incision is left open. Stitches are removed 10 days after surgery.After surgery, the hand is wrapped in a light compressive bandage for one week. Flexion and extension of the fingers can start as soon as the anaesthesia has resolved. It is common to experience tingling within the first week after surgery. Hand therapy is often recommended. Approximately 6 weeks after surgery the patient is able completely to use the hand.The average recurrence rate is 39% after a fasciectomy after a median interval of about 4 years. Wide-awake fasciectomy Limited/selective fasciectomy under local anesthesia (LA) with epinephrine but no tourniquet is possible. In 2005, Denkler described the technique. Dermofasciectomy Dermofasciectomy is a surgical procedure that may be used when: The skin is clinically involved (pits, tethering, deficiency, etc.) The risk of recurrence is high and the skin appears uninvolved (subclinical skin involvement occurs in ~50% of cases) Recurrent disease. Similar to a limited fasciectomy, the dermofasciectomy removes diseased cords, fascia, and the overlying skin.Typically, the excised skin is replaced with a skin graft, usually full thickness, consisting of the epidermis and the entire dermis. In most cases the graft is taken from the antecubital fossa (the crease of skin at the elbow joint) or the inner side of the upper arm. This place is chosen because the skin color best matches the palms skin color. The skin on the inner side of the upper arm is thin and has enough skin to supply a full-thickness graft. The donor site can be closed with a direct suture.The graft is sutured to the skin surrounding the wound. For one week the hand is protected with a dressing. The hand and arm are elevated with a sling. The dressing is then removed and careful mobilization can be started, gradually increasing in intensity. After this procedure the risk of recurrence is minimised, but Dupuytrens can recur in the skin graft and complications from surgery may occur. Segmental fasciectomy with/without cellulose Segmental fasciectomy involves excising part(s) of the contracted cord so that it disappears or no longer contracts the finger. It is less invasive than the limited fasciectomy, because not all the diseased tissue is excised and the skin incisions are smaller.The person is placed under regional anesthesia and a surgical tourniquet is used. The skin is opened with small curved incisions over the diseased tissue. If necessary, incisions are made in the fingers. Pieces of cord and fascia of approximately one centimeter are excised. The cords are placed under maximum tension while they are cut. A scalpel is used to separate the tissues. The surgeon keeps removing small parts until the finger can fully extend. The person is encouraged to start moving his or her hand the day after surgery. They wear an extension splint for two to three weeks, except during physical therapy.The same procedure is used in the segmental fasciectomy with cellulose implant. After the excision and a careful hemostasis, the cellulose implant is placed in a single layer in between the remaining parts of the cord.After surgery people wear a light pressure dressing for four days, followed by an extension splint. The splint is worn continuously during nighttime for eight weeks. During the first weeks after surgery the splint may be worn during daytime. Less invasive treatments Studies have been conducted for percutaneous release, extensive percutaneous aponeurotomy with lipografting and collagenase. These treatments show promise. Percutaneous needle fasciotomy Needle aponeurotomy is a minimally-invasive technique where the cords are weakened through the insertion and manipulation of a small needle. The cord is sectioned at as many levels as possible in the palm and fingers, depending on the location and extent of the disease, using a 25-gauge needle mounted on a 10 ml syringe. Once weakened, the offending cords can be snapped by putting tension on the finger(s) and pulling the finger(s) straight. After the treatment a small dressing is applied for 24 hours, after which people are able to use their hands normally. No splints or physiotherapy are given.The advantage of needle aponeurotomy is the minimal intervention without incision (done in the office under local anesthesia) and the very rapid return to normal activities without need for rehabilitation, but the nodules may resume growing. A study reported postoperative gain is greater at the MCP-joint level than at the level of the IP-joint and found a reoperation rate of 24%; complications are scarce. Needle aponeurotomy may be performed on fingers that are severely bent (stage IV), and not just in early stages. A 2003 study showed 85% recurrence rate after 5 years.A comprehensive review of the results of needle aponeurotomy in 1,013 fingers was performed by Gary M. Pess, MD, Rebecca Pess, DPT, and Rachel Pess, PsyD, and published in the Journal of Hand Surgery April 2012. Minimal follow-up was 3 years. Metacarpophalangeal joint (MP) contractures were corrected at an average of 99% and proximal interphalangeal joint (PIP) contractures at an average of 89% immediately post procedure. At final follow-up, 72% of the correction was maintained for MP joints and 31% for PIP joints. The difference between the final corrections for MP versus PIP joints was statistically significant. When a comparison was performed between people aged 55 years and older versus under 55 years, there was a statistically significant difference at both MP and PIP joints, with greater correction maintained in the older group.Gender differences were not statistically significant. Needle aponeurotomy provided successful correction to 5° or less contracture immediately post procedure in 98% (791) of MP joints and 67% (350) of PIP joints. There was recurrence of 20° or less over the original post-procedure corrected level in 80% (646) of MP joints and 35% (183) of PIP joints. Complications were rare except for skin tears, which occurred in 3.4% (34) of digits. This study showed that NA is a safe procedure that can be performed in an outpatient setting. The complication rate was low, but recurrences were frequent in younger people and for PIP contractures. Extensive percutaneous aponeurotomy and lipografting A technique introduced in 2011 is extensive percutaneous aponeurotomy with lipografting. This procedure also uses a needle to cut the cords. The difference with the percutaneous needle fasciotomy is that the cord is cut at many places. The cord is also separated from the skin to make place for the lipograft that is taken from the abdomen or ipsilateral flank. This technique shortens the recovery time. The fat graft results in supple skin.Before the aponeurotomy, a liposuction is done to the abdomen and ipsilateral flank to collect the lipograft. The treatment can be performed under regional or general anesthesia. The digits are placed under maximal extension tension using a firm lead hand retractor. The surgeon makes multiple palmar puncture wounds with small nicks. The tension on the cords is crucial, because tight constricting bands are most susceptible to be cut and torn by the small nicks, whereas the relatively loose neurovascular structures are spared. After the cord is completely cut and separated from the skin the lipograft is injected under the skin. A total of about 5 to 10 ml is injected per ray.After the treatment the person wears an extension splint for 5 to 7 days. Thereafter the person returns to normal activities and is advised to use a night splint for up to 20 weeks. Collagenase Clostridial collagenase injections have been found to be more effective than placebo. The cords are weakened through the injection of small amounts of the enzyme collagenase, which breaks peptide bonds in collagen.The treatment with collagenase is different for the MCP joint and the PIP joint. In a MCP joint contracture the needle must be placed at the point of maximum bowstringing of the palpable cord.The needle is placed vertically on the bowstring. The collagenase is distributed across three injection points. For the PIP joint the needle must be placed not more than 4 mm distal to palmar digital crease at 2–3 mm depth. The injection for PIP consists of one injection filled with 0.58 mg CCH 0.20 ml. The needle must be placed horizontal to the cord and also uses a 3-point distribution. After the injection the persons hand is wrapped in bulky gauze dressing and must be elevated for the rest of the day. After 24 hours the person returns for passive digital extension to rupture the cord. Moderate pressure for 10–20 seconds ruptures the cord.After the treatment with collagenase the person should use a night splint and perform digital flexion/extension exercises several times per day for 4 months.In February 2010 the US Food and Drug Administration (FDA) approved injectable collagenase extracted from Clostridium histolyticum for the treatment of Dupuytrens contracture in adults with a palpable Dupuytrens cord. (Three years later, it was approved as well for the treatment of the sometimes related Peyronies disease.) In 2011 its use for the treatment of Dupuytrens contracture was approved as well by the European Medicines Agency, and it received similar approval in Australia in 2013. However, the Swedish manufacturer abruptly withdrew distribution of this drug in Europe and the UK in March 2020 for commercial reasons.(It now is promoted primarily as a dermatological treatment for cellulite aka "cottage cheese thighs"). Collagenase is no longer available on the National Health System except as part of a small clinical trial. Radiation therapy Radiation therapy has been used mostly for early-stage disease, but is unproven. Evidence to support its use as of 2017, however, was scarce —efforts to gather evidence are complicated due to a poor understanding of how the condition develops over time. It has only been looked at in early disease. The Royal College of Radiologists concluded that radiotherapy is effective in early stage disease which has progressed within the last 6 to 12 months. Alternative medicine Several alternate therapies such as vitamin E treatment have been studied, though without control groups. Most doctors do not value those treatments. None of these treatments stops or cures the condition permanently. A 1949 study of vitamin E therapy found that "In twelve of the thirteen patients there was no evidence whatever of any alteration. ... The treatment has been abandoned."Laser treatment (using red and infrared at low power) was informally discussed in 2013 at an International Dupuytren Society forum, as of which time little or no formal evaluation of the techniques had been completed. Postoperative care Postoperative care involves hand therapy and splinting. Hand therapy is prescribed to optimize post-surgical function and to prevent joint stiffness. The extent of hand therapy is depending on the patient and the corrective procedure.Besides hand therapy, many surgeons advise the use of static or dynamic splints after surgery to maintain finger mobility. The splint is used to provide prolonged stretch to the healing tissues and prevent flexion contractures. Although splinting is a widely used post-operative intervention, evidence of its effectiveness is limited, leading to variation in splinting approaches. Most surgeons use clinical experience to decide whether to splint. Cited advantages include maintenance of finger extension and prevention of new flexion contractures. Cited disadvantages include joint stiffness, prolonged pain, discomfort, subsequently reduced function and edema. A third approach emphasizes early self-exercise and stretching. Prognosis Dupuytrens disease has a high recurrence rate, especially when a person has so-called Dupuytrens diathesis. The term diathesis relates to certain features of Dupuytrens disease, and indicates an aggressive course of disease.The presence of all new Dupuytrens diathesis factors increases the risk of recurrent Dupuytrens disease by 71%, compared with a baseline risk of 23% in people lacking the factors. In another study the prognostic value of diathesis was evaluated. It was concluded that presence of diathesis can predict recurrence and extension. A scoring system was made to evaluate the risk of recurrence and extension, based on the following values: bilateral hand involvement, little-finger surgery, early onset of disease, plantar fibrosis, knuckle pads, and radial side involvement.Minimally invasive therapies may precede higher recurrence rates. Recurrence lacks a consensus definition. Furthermore, different standards and measurements follow from the various definitions. Notable cases == References ==

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I'm trying to expand my medical knowledge. Can you elucidate the term 'Iron(II) sulfate'?

Iron(II) sulfate (British English: iron(II) sulphate) or ferrous sulfate denotes a range of salts with the formula FeSO4·xH2O. These compounds exist most commonly as the heptahydrate (x = 7) but several values for x are known. The hydrated form is used medically to treat iron deficiency, and also for industrial applications. Known since ancient times as copperas and as green vitriol (vitriol is an archaic name for sulfate), the blue-green heptahydrate (hydrate with 7 molecules of water) is the most common form of this material. All the iron(II) sulfates dissolve in water to give the same aquo complex [Fe(H2O)6]2+, which has octahedral molecular geometry and is paramagnetic. The name copperas dates from times when the copper(II) sulfate was known as blue copperas, and perhaps in analogy, iron(II) and zinc sulfate were known respectively as green and white copperas.It is on the World Health Organizations List of Essential Medicines. In 2019, it was the 103rd most commonly prescribed medication in the United States, with more than 6 million prescriptions. Uses Industrially, ferrous sulfate is mainly used as a precursor to other iron compounds. It is a reducing agent, and as such is useful for the reduction of chromate in cement to less toxic Cr(III) compounds. Historically ferrous sulfate was used in the textile industry for centuries as a dye fixative. It is used historically to blacken leather and as a constituent of iron gall ink. The preparation of sulfuric acid (oil of vitriol) by the distillation of green vitriol (Iron(II) sulfate) has been known for at least 700 years. Medical use Plant growth Iron(II) sulfate is sold as ferrous sulfate, a soil amendment for lowering the pH of a high alkaline soil so that plants can access the soils nutrients.In horticulture it is used for treating iron chlorosis. Although not as rapid-acting as ferric EDTA, its effects are longer-lasting. It can be mixed with compost and dug into the soil to create a store which can last for years. Ferrous sulfate can be used as a lawn conditioner. It can also be used to eliminate silvery thread moss in golf course putting greens. Pigment and craft Ferrous sulfate can be used to stain concrete and some limestones and sandstones a yellowish rust color.Woodworkers use ferrous sulfate solutions to color maple wood a silvery hue. Green vitriol is also a useful reagent in the identification of mushrooms. Historical uses Ferrous sulfate was used in the manufacture of inks, most notably iron gall ink, which was used from the middle ages until the end of the 18th century. Chemical tests made on the Lachish letters (c. 588–586 BCE) showed the possible presence of iron. It is thought that oak galls and copperas may have been used in making the ink on those letters. It also finds use in wool dyeing as a mordant. Harewood, a material used in marquetry and parquetry since the 17th century, is also made using ferrous sulfate. Two different methods for the direct application of indigo dye were developed in England in the 18th century and remained in use well into the 19th century. One of these, known as china blue, involved iron(II) sulfate. After printing an insoluble form of indigo onto the fabric, the indigo was reduced to leuco-indigo in a sequence of baths of ferrous sulfate (with reoxidation to indigo in air between immersions). The china blue process could make sharp designs, but it could not produce the dark hues of other methods. In the second half of the 1850s ferrous sulfate was used as a photographic developer for collodion process images. Hydrates Iron(II) sulfate can be found in various states of hydration, and several of these forms exist in nature. FeSO4·H2O (mineral: szomolnokite, relatively rare) FeSO4·4H2O (mineral: rozenite, white, relatively common, may be dehydratation product of melanterite) FeSO4·5H2O (mineral: siderotil, relatively rare) FeSO4·6H2O (mineral: ferrohexahydrite, relatively rare) FeSO4·7H2O (mineral: melanterite, blue-green, relatively common) The tetrahydrate is stabilized when the temperature of aqueous solutions reaches 56.6 °C (133.9 °F). At 64.8 °C (148.6 °F) these solutions form both the tetrahydrate and monohydrate.Mineral forms are found in oxidation zones of iron-bearing ore beds, e.g. pyrite, marcasite, chalcopyrite, etc. They are also found in related environments, like coal fire sites. Many rapidly dehydrate and sometimes oxidize. Numerous other, more complex (either basic, hydrated, and/or containing additional cations) Fe(II)-bearing sulfates exist in such environments, with copiapite being a common example. Production and reactions In the finishing of steel prior to plating or coating, the steel sheet or rod is passed through pickling baths of sulfuric acid. This treatment produces large quantities of iron(II) sulfate as a by-product. Fe + H2SO4 → FeSO4 + H2Another source of large amounts results from the production of titanium dioxide from ilmenite via the sulfate process. Ferrous sulfate is also prepared commercially by oxidation of pyrite: 2 FeS2 + 7 O2 + 2 H2O → 2 FeSO4 + 2 H2SO4It can be produced by displacement of metals less reactive than Iron from solutions of their sulfate: CuSO4 + Fe → FeSO4 + Cu Reactions Upon dissolving in water, ferrous sulfates form the metal aquo complex [Fe(H2O)6]2+, which is an almost colorless, paramagnetic ion. On heating, iron(II) sulfate first loses its water of crystallization and the original green crystals are converted into a white anhydrous solid. When further heated, the anhydrous material decomposes into sulfur dioxide and sulfur trioxide, leaving a reddish-brown iron(III) oxide. Thermolysis of iron(II) sulfate begins at about 680 °C (1,256 °F). 2 FeSO 4 → Δ Fe 2 O 3 + SO 2 + SO 3 {\displaystyle {\ce {2FeSO_4->[\Delta]Fe_2O_3 + SO_2 + SO_3}}} Like other iron(II) salts, iron(II) sulfate is a reducing agent. For example, it reduces nitric acid to nitrogen monoxide and chlorine to chloride: 6 FeSO4 + 3 H2SO4 + 2 HNO3 → 3 Fe2(SO4)3 + 4 H2O + 2 NO 6 FeSO4 + 3 Cl2 → 2 Fe2(SO4)3 + 2 FeCl3Its mild reducing power is of value in organic synthesis. It is used as the iron catalyst component of Fentons reagent. Ferrous sulfate can be detected by the cerimetric method, which is the official method of the Indian Pharmacopoeia. This method includes the use of ferroin solution showing a red to light green colour change during titration. See also Iron(III) sulfate (ferric sulfate), the other common simple sulfate of iron. Copper(II) sulfate Ammonium iron(II) sulfate, also known as Mohrs salt, the common double salt of ammonium sulfate with iron(II) sulfate. Chalcanthum Ephraim Seehl known as an early manufacturer of Iron(II) sulfate, which he called green vitriol. References External links "Ferrous sulfate". Drug Information Portal. U.S. National Library of Medicine.

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I've encountered the term 'Identity disorder' while reading about medical topics. What does it refer to exactly?

Identity disorder in the DSM was first listed as a separate diagnosis in version III (1980). In the DSM-IV (1994), it was replaced by "Identity problem", which was not defined as a mental disorder per se, but was listed in a chapter containing problems that might be a focus of clinical attention. Identity disorder was downgraded to Identity problem as research indicated that distress over ones identity is so common that it might very well be considered part of the normality. In practice, if a persons distress persisted or worsened, an Identity problem would often be succeeded by a diagnosis of an actual disorder, such as a mood disorder or borderline personality disorder. In DSM-5 (2013), Identity problem was removed. See also Body integrity dysphoria, sometimes also called body integrity identity disorder Dissociative identity disorder Gender dysphoria, sometimes also called gender identity disorder Self-concept Self-image == References ==

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Please help me grasp the concept behind the medical term 'Trastuzumab/hyaluronidase.'

Trastuzumab/hyaluronidase, sold under the brand name Herceptin SC among others, is a fixed-dose combination medication for the treatment of HER2-overexpressing breast cancer in adults. It is a combination of trastuzumab and hyaluronidase.The most common adverse reactions include fatigue, arthralgia, diarrhea, injection site reaction, upper respiratory tract infection, rash, myalgia, nausea, headache, edema, flushing, pyrexia, cough, and pain in extremity.Trastuzumab/hyaluronidase was approved for medical use in the European Union in August 2013. Trastuzumab/hyaluronidase was approved for medical use in the United States in February 2019. Medical uses Trastuzumab/hyaluronidase is indicated for adjuvant treatment of adults with HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature; and it is indicated in combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer. History Trastuzumab/hyaluronidase (Herceptin SC) was approved for medical use in the European Union in August 2013.Trastuzumab/hyaluronidase (Herceptin Hylecta) was approved for medical use in the United States in February 2019.Approval of trastuzumab/hyaluronidase was based on two randomized trials, HannaH (NCT00950300) and SafeHER (NCT01566721). In HannaH, 596 participants with HER2-positive operable or locally advanced breast cancer, including inflammatory breast cancer, were randomized to receive 8 cycles of either trastuzumab/hyaluronidase or intravenous trastuzumab concurrently with chemotherapy, followed by surgery and continued therapy with either trastuzumab/hyaluronidase or intravenous trastuzumab, for an additional 10 cycles. HannaH demonstrated comparability between trastuzumab/hyaluronidase and intravenous trastuzumab based on co-primary endpoints of pathologic complete response and pharmacokinetics. Pathological complete response (pCR) was observed in 118 participants (45.4%) on the trastuzumab/hyaluronidase arm and in 107 participants (40.7%) receiving intravenous trastuzumab (95% CI for difference in pCR: -4.0; 13.4).SafeHER was a prospective, two-cohort, non-randomized, multinational, open-label trial assessing the overall safety and tolerability of trastuzumab/hyaluronidase with chemotherapy in 1,864 participants with HER2-positive breast cancer. Participants received a fixed dose of 600 mg trastuzumab/hyaluronidase every 3 weeks for 18 cycles. trastuzumab/hyaluronidase was initiated either sequentially with chemotherapy, concurrently with chemotherapy, or without adjuvant chemotherapy, or in combination with neoadjuvant chemotherapy followed by trastuzumab. References Further reading "Application for the addition of Herceptin (trastuzmab) on the WHO Model List of Essential Medicines" (PDF). F. Hoffmann-La Roche Ltd. 7 December 2018. External links "Trastuzumab". Drug Information Portal. U.S. National Library of Medicine. "Hyaluronidase". Drug Information Portal. U.S. National Library of Medicine. "Trastuzumab and Hyaluronidase-oysk". National Cancer Institute. 14 March 2019. "Trastuzumab and Hyaluronidase-oysk". NCI Drug Dictionary. National Cancer Institute. Clinical trial number NCT00950300 for "A Study to Compare Subcutaneous (SC) Versus Intravenous (IV) Administration of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer" at ClinicalTrials.gov Clinical trial number NCT01566721 for "A Safety and Tolerability Study of Assisted and Self-Administered Subcutaneous (SC) Herceptin (Trastuzumab) as Adjuvant Therapy in Early Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer (SafeHER)" at ClinicalTrials.gov

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I'm encountering the term 'Ketotifen' in medical literature. What's its definition?

Ketotifen, sold under the brand name Zaditor among others, is a second-generation noncompetitive H1-antihistamine and mast cell stabilizer. It is most commonly sold as a salt with fumaric acid, ketotifen fumarate, and is available in two forms. In its ophthalmic form, it is used to treat allergic conjunctivitis. In its oral form, it is used to prevent asthma attacks or anaphylaxis, as well as various mast cell, allergic-type disorders.It was patented in 1970 and came into medical use in 1976. Medical uses Ketotifen relieves and prevents eye itchiness and/or irritation associated with most seasonal allergies. It starts working within minutes after administering the drops. The drug has not been studied in children under three. The mean elimination half life is 12 hours. Besides its anti-histaminic activity, it is also a functional leukotriene antagonist and a phosphodiesterase inhibitor."[O]ral ketotifen has been used in patients with asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, chronic urticaria, cold-induced urticaria, cholinergic urticaria, exercise-induced urticaria, [systemic mast cell disease including mastocytosis, Mast Cell Activation Syndrome (MCAS), allergic and nonallergic anaphylaxis, angioedema], and food allergy in Canada, Europe, and Mexico." Now available via prescription at US compounding pharmacies: "For adults and older children with asthma or allergic disease, the recommended dose of ketotifen is 1 mg twice daily." "FDA staff did recommend more extensive evaluations for management of urticaria."The drug may also help relieve irritable bowel syndrome. Side effects Side effects of systemic (oral) use include drowsiness, weight gain (11-12lbs), dry mouth, irritability, and increased nosebleeds. Pharmacology Ketotifen is a selective antihistamine – that is, an inverse agonist of the histamine H1 receptor (Ki = 0.166 nM) – and mast cell stabilizer. In addition, ketotifen has weak anticholinergic (Ki = 204 nM for mACh) and antiserotonergic (Ki = 38.9 nM for 5-HT2A) activity. However, at the dosages in which it is typically used clinically, both the anticholinergic and antiserotonergic activity of ketotifen are said not to be appreciable. Society and culture Brand names Ketotifen is marketed under many brand names worldwide. References External links "Ketotifen". Drug Information Portal. U.S. National Library of Medicine.

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

Please help me grasp the concept behind the medical term 'Pulmonary-renal syndrome.'

Pulmonary-renal syndrome (PRS) is a rare medical syndrome in which respiratory failure involving bleeding in the lungs and kidney failure (glomerulonephritis) occur. PRS is associated with a high rate of morbidity and death. The term was first used by Goodpasture in 1919 to describe the association of respiratory and kidney failure. Causes Pulmonary-renal syndromes are most commonly caused by an underlying autoimmune disease. PRS is most commonly due to ANCA-associated vasculitides (e.g., granulomatosis with polyangiitis) or due to anti-basement membrane diseases (e.g., Goodpastures syndrome). Granulomatosis with polyangiitis usually presents with nasopharyngeal involvement as well, whereas Goodpastures will not. Microscopic polyangiitis is the most common cause of pulmonary-renal syndrome.Other causes include systemic lupus erythematosus, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, dermatomyositis, polymyositis, mixed connective tissue disease, poststreptococcal glomerulonephritis, rheumatoid arthritis, and systemic sclerosis. Less common causes also include IgA vasculitis and cryoglobulinemic vasculitis. Other etiologies include toxic injury such as paraquat poisoning, infection with hantavirus, leptospirosis, or legionella, or vascular, as seen in nephrotic syndrome when a renal vein thrombosis embolizes to the lungs. Diagnosis Differential diagnosis Cardiogenic shock can mimic a pulmonary renal syndrome and lead to coughing up blood due to pulmonary edema and kidney failure from inadequate blood flow. Treatment Treatment is primarily by corticosteroids and immunosuppressive medications like cyclophosphamide, methotrexate, and azathioprine. Plasmapheresis can be used in some circumstances. == References ==

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

I'd like to learn more about the medical term 'Dorzolamide.' Can you provide some details?

Dorzolamide, sold under the brand name Trusopt among others, is a medication used to treat high pressure inside the eye, including in cases of glaucoma. It is used as an eye drop. Effects begin within three hours and last for at least eight hours. It is also available as the combination dorzolamide/timolol.Common side effects include eye discomfort, eye redness, taste changes, and blurry vision. Serious side effects include Steven Johnson syndrome. Those allergic to sulfonamides may be allergic to dorzolamide. Use is not recommended in pregnancy or breastfeeding. It is a carbonic anhydrase inhibitor and works by decreasing the production of aqueous humour.Dorzolamide was approved for medical use in the United States in 1994. It is available as a generic medication. In 2017, it was the 281st most commonly prescribed medication in the United States, with more than one million prescriptions. It is a second-generation carbonic anhydrase inhibitor. Medical uses Dorzolamide hydrochloride is used to lower excessive intraocular pressure in open-angle glaucoma and ocular hypertension. This drug is able to cross the cornea, reach the ciliary body of the eye, and produce systemic effects on the carbonic anhydrase enzyme within the eye. Side effects Ocular stinging, burning, itching and bitter taste. It causes shallowing of the anterior chamber and leads to transient myopia. As a second generation carbonic anhydrase inhibitor, Dorzolamide avoids systemic effects associated with first generation carbonic anhydrase inhibitors such as Acetazolamide, Methazolamide, and Dichlorphenamide. Pharmacodynamics Dorzolamide lowers intraocular pressure by about 20%. Normally, carbonic anhydrase converts carbonic acid (H2CO3) into bicarbonate (HCO3), releasing a proton (H+) into solution. The H+ is then exchanged for sodium (Na+) ions, which facilitates the production of aqueous humor. By blocking the function of carbonic anhydrase, the Na+/H+ exchange is unable to occur, which leads to a decrease in Na+ in the cell and prevents aqueous humor production. History This drug, developed by Merck, was the first drug in human therapy (market introduction 1995) that resulted from structure-based drug design. It was developed to circumvent the systemic side effects of acetazolamide which has to be taken orally. References Further reading Kubinyi H (1999). "Chance favors the prepared mind--from serendipity to rational drug design". J Recept Signal Transduct Res. 19 (1–4): 15–39. doi:10.3109/10799899909036635. PMID 10071748. Plummer C, MacKay E, Gelatt K (2006). "Comparison of the effects of topical administration of a fixed combination of dorzolamide-timolol to monotherapy with timolol or dorzolamide on IOP, pupil size, and heart rate in glaucomatous dogs". Veterinary Ophthalmology. 9 (4): 245–9. doi:10.1111/j.1463-5224.2006.00469.x. PMID 16771760. Grover S, Apushkin M, Fishman G (2006). "Topical dorzolamide for the treatment of cystoid macular edema in patients with retinitis pigmentosa". Am J Ophthalmol. 141 (5): 850–8. doi:10.1016/j.ajo.2005.12.030. PMID 16546110. Almeida G, Faria e Souza S (2006). "Effect of topical dorzolamide on rabbit central corneal thickness". Braz J Med Biol Res. 39 (2): 277–81. doi:10.1590/S0100-879X2006000200015. PMID 16470316.

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

Can you demystify the medical term 'Relugolix' for me?

Relugolix, sold under the brand names Orgovyx and Relumina and as one component of Myfembree, is a gonadotropin-releasing hormone antagonist (GnRH receptor antagonist) medication which is used in the treatment of prostate cancer in men and uterine fibroids in women. It is also under development for use in the treatment of endometriosis. It is taken by mouth once per day.Side effects of relugolix include menstrual abnormalities, hot flashes, excessive sweating, headache, and decreased bone mineral density. Relugolix is a GnRH antagonist, or an antagonist of the gonadotropin-releasing hormone receptor. Unlike most other GnRH modulators, but similarly to elagolix (brand name Orilissa), relugolix is a non-peptide, small-molecule compound and is orally active. It suppresses sex hormone levels to the postmenopausal or castrate range in both women and men with administration once per day.As of February 2019, relugolix is in phase III clinical trials for endometriosis. It was approved for use for the treatment of uterine fibroids in Japan in January 2019, and for the treatment of prostate cancer in the United States in December 2020. Medical uses Relugolix is approved in the United States for the treatment of prostate cancer in men and in Japan for the treatment of uterine fibroids (uterine leiomyoma) in women. It is used at a dosage of 120 mg once daily by mouth in the treatment of prostate cancer (after a single 360 mg loading dose on the first day of therapy) and at a dosage of 40 mg once daily in the treatment of uterine fibroids. Available forms Relugolix is available in the form of 40 and 120 mg oral tablets. Side effects The main side effects of relugolix for uterine fibroids include abnormal uterine bleeding (24.6–48.6% vs. 6.3% for placebo), hot flashes (42.8–45.5% vs. 0% for placebo), heavy menstrual bleeding (12.1–49.3% vs. 9.4% for placebo), headache (12.3–15.2%), and excessive sweating (9.4–15.2% vs. 0% for placebo). In addition, decreased bone mineral density occurs with relugolix (21.7% decrease by week 12, 24.4% decrease by week 24). Pharmacology Pharmacodynamics Relugolix is a selective antagonist of the gonadotropin-releasing hormone receptor (GnRHR), with a half-maximal inhibitory concentration (IC50) of 0.12 nM.A dosage of relugolix of 40 mg once per day has been found to suppress estradiol levels to postmenopausal levels (<20 pg/mL) within 24 hours in premenopausal women. In the control group of women, estradiol levels fluctuated between 50 and 250 pg/mL. Estradiol levels have been found to return to normal concentrations within 4 weeks of discontinuation of relugolix in premenopausal women. The medication additionally suppresses levels of progesterone, luteinizing hormone, and follicle-stimulating hormone in premenopausal women. Relugolix at a dosage of 40 mg or more once per day has been found to reduce testosterone levels to sustained castrate levels (<20 ng/dL) in men. It additionally suppresses luteinizing hormone and follicle-stimulating hormone levels in men.Lower doses of relugolix (<40 mg/day) are under investigation for achieving partial sex hormone suppression in the treatment of endometriosis and uterine fibroids. This is intended to reduce the incidence and severity of menopausal symptoms such as hot flushes and decreased bone mineral density that are secondary to estrogen deficiency. Pharmacokinetics A single 40-mg oral dose of relugolix has been found to result in peak levels of relugolix of 29 ng/mL (47 nmol/L) after 1.5 hours. Steady-state levels are reached within 7 days with 40 mg/day relugolix administration. There is an approximate 2-fold accumulation of relugolix by 2 weeks of continuous administration. Food diminishes the oral bioavailability of relugolix by about 50%.Relugolix is a substrate for P-glycoprotein, which may have a limiting effect on its absorption and distribution. The plasma protein binding of relugolix is approximately 68 to 71% over a concentration range of 0.05 to 5 μg/mL.Relugolix is not a substrate for CYP3A4. The elimination half-life of relugolix is 36 to 65 hours across a dosage range of 20 to 180 mg/day. There is moderate to high interindividual variability in systemic exposure to relugolix.Relugolix is excreted mainly in feces (83%) and to a small degree in urine (4%). Only about 6% of a dose of relugolix is excreted unchanged. Chemistry Relugolix is a non-peptide, small-molecule compound, and is structurally distinct from GnRH analogues. It is an N-phenylurea derivative. History Relugolix was first described in 2004. It superseded sufugolix (developmental code name TAK-013), which was developed by the same researchers. Relugolix was approved for the treatment of uterine fibroids in Japan on 8 January 2019. It was the second orally active GnRH antagonist to be introduced for medical use, following elagolix (brand name Orilissa) in July 2018. Relugolix was approved for the treatment of prostate cancer in the United States on 18 December 2020.The FDA approved relugolix based on evidence from a clinical trial (NCT03085095) of 930 participants 48 to 97 years old with advanced prostate cancer. The trial was conducted at 155 sites in the United States, Canada, and countries in South America, Europe and the Asia Pacific region. All participants in the trial had advanced prostate cancer. Participants were randomly assigned to receive either one relugolix tablet daily (on the first day they received three tables) or an active control (leuprolide acetate) which was given as an injection under the skin every three months. The participants and healthcare providers were aware of which treatment was being given. The treatment lasted for 48 weeks. The efficacy of relugolix was assessed by the percentage of participants who achieved and maintained low testosterone level equal to castration. Society and culture Names Relugolix is the generic name of the drug and its INN, USAN, and JAN. It is also known by its former developmental code names RVT-601 and TAK-385.Relugolix is sold under the brand name Orgovyx for the treatment of prostate cancer and under the brand name Relumina for the treatment of uterine fibroids. Relugolix compounded with ethinyl estradiol and norethindrone is sold under the brand name Myfembree for the treatment of uterine fibroids. Availability Relugolix is available in the United States and in Japan. Legal status On 24 February 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Orgovyx, intended for the treatment of prostate cancer. The applicant for this medicinal product is Myovant Sciences Ireland Limited. Research Relugolix is under development by Myovant Sciences and Takeda for the treatment of uterine fibroids in countries besides Japan such as the United States. Relugolix is also under development for the treatment of endometriosis in the United States and other countries. References Further reading Markham, Anthony (April 2019). "Relugolix: First Global Approval". Drugs. 79 (6): 675–679. doi:10.1007/s40265-019-01105-0. ISSN 0012-6667. PMID 30937733. S2CID 89616869. Elsharoud, A.; Ali, M.; Al-Hendy, A. (2019). "Relugolix. GnRH (LHRH) receptor antagonist, Treatment of uterine fibroids, Treatment of endometriosis-related pain, Treatment of prostate cancer". Drugs of the Future. 44 (2): 131. doi:10.1358/dof.2019.44.2.2927590. ISSN 0377-8282. S2CID 87369995. Barra F, Seca M, Della Corte L, Giampaolino P, Ferrero S (August 2019). "Relugolix for the treatment of uterine fibroids". Drugs Today. 55 (8): 503–512. doi:10.1358/dot.2019.55.8.3020179. PMID 31461087. S2CID 201654739. External links "Relugolix". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03085095 for "A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer (HERO)" at ClinicalTrials.gov

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

I'm encountering the term 'Canine degenerative myelopathy' in medical literature. What's its definition?

Canine degenerative myelopathy, also known as chronic degenerative radiculomyelopathy, is an incurable, progressive disease of the canine spinal cord that is similar in many ways to amyotrophic lateral sclerosis (ALS). Onset is typically after the age of 7 years and it is seen most frequently in the German shepherd dog, Pembroke Welsh corgi, and boxer dog, though the disorder is strongly associated with a gene mutation in SOD1 that has been found in 43 breeds as of 2008, including the wire fox terrier, Chesapeake Bay retriever, Rhodesian ridgeback, and Cardigan Welsh corgi. Progressive weakness and incoordination of the rear limbs are often the first signs seen in affected dogs, with progression over time to complete paralysis. Myelin is an insulating sheath around neurons in the spinal cord. One proposed cause of degenerative myelopathy is that the immune system attacks this sheath, breaking it down. This results in a loss of communication between nerves in lower body of the animal and the brain. Testing The Orthopedic Foundation for Animals has a DNA saliva test to screen for the mutated gene that has been seen in dogs with degenerative myelopathy. Now that a test is available the disease can be bred out of breeds with a high preponderance. The test is only recommended for predisposed breeds, but can be performed on DNA from any dog on samples collected through swabbing the inside of the animals cheek with a sterile cotton swab or through venipuncture. The test determines whether the mutated copy of SOD1 is present in the DNA sample submitted. It must be interpreted with caution by a veterinary clinician in combination with the animals clinical signs and other lab test results. The results reported are: Normal / Normal (N/N, or clear): The dog does not have the mutation and is extremely unlikely to develop degenerative myelopathy. There have been cases, however, in which dogs that tested clear were found to have DM upon necropsy. Normal / Abnormal (N/A or carrier): The dog has one mutated copy of the gene (is heterozygous) and is a carrier but will not have degenerative myelopathy though there has now been some cases of heterozygous carriers developing DM. It will be possible for it to pass the mutation to offspring. A thorough examination of the dogs pedigree and DNA testing should be undertaken prior to breeding a dog with this result. Abnormal / Abnormal (A/A or At Risk): The dog has two copies (is homozygous) for the mutation and is at risk for degenerative myelopathy. Genetics Breeding risks for degenerative myelopathy can be calculated using the Punnett Square: If both parents are clear (N/N) then all of the puppies will be clear. If one parent is a carrier (N/A) and one is clear (N/N) each puppy has a 50% chance of being clear and a 50% chance of being a carrier. If both parents are carriers (N/A) each puppy has a 25% chance of being clear (N/N), 50% chance of being a carrier (N/A), and 25% chance of being affected and carrier (A/A) If one parent is clear (N/N) and one parent is affected (A/A) then all puppies will be carriers (N/A) If one parent is a carrier (N/A) and one is at risk (A/A) each puppy has a 50% chance of being a carrier(N/A) and 50% chance of being affected and carrier (A/A) If both parents are at risk (A/A) then all puppies will be affected and carrier (A/A) Symptoms Degenerative myelopathy initially affects the back legs and causes muscle weakness and loss, and lack of coordination. These cause a staggering affect that may appear to be arthritis. The dog may drag one or both rear paws when it walks. This dragging can cause the nails of one foot to be worn down. The condition may lead to extensive paralysis of the back legs. As the disease progresses, the animal may display symptoms such as incontinence and has considerable difficulties with both balance and walking. If allowed to progress, the animal will show front limb involvement and extensive muscle atrophy and paralysis. Eventually cranial nerve or respiratory muscle involvement necessitates euthanasia or long term palliative care.Progression of the disease is generally slow but highly variable. The animal could be crippled within a few months, or may survive as long as three years or more. Causes The etiology of this disease is unknown. Recent research has shown that a mutation in the SOD1 gene is a risk factor for developing degenerative myelopathy in several breeds. Mutations in SOD1 are also associated with familial amyotrophic lateral sclerosis (Lou Gehrigs disease) in people. More than 100 SOD1 gene mutations are involved in human familial amyotrophic lateral sclerosis (ALS), and the pathologic spinal lesions of ALS are similar to those of canine DM, making canine DM a potentially useful animal model of ALS. Known causes of spinal cord dysfunction should be excluded before accepting the diagnosis of degenerative myelopathy; disc disease (protrusions) or spinal cord tumors can cause compression of the spinal cord with similar signs to degenerative myelopathy. Treatment Degenerative myelopathy is an irreversible, progressive disease that cannot currently be cured. There are no treatments that have been clearly shown to stop or slow progression of DM. Exercise Exercise has been recommended to maintain the dogs ability to walk. Physiotherapy may prolong the length of time that the dog remains mobile and increase survival time. Canine hydrotherapy (swimming) may be more useful than walking. Use of a belly sling or hand-held harness allows the handler the ability to support the dogs hind legs for exercising or going up and down stairs. A 2-wheel dog cart, or "dog wheelchair" can allow the dog to remain active and maintain its quality of life once signs of weakness or paralysis of the hind limbs is detected. Prognosis The prognosis for the disease is generally poor. Aggressive therapy may be used to combat the disease, but even this puts the life expectancy at only around 14 months. It is recommended to put the dog to sleep at around 12 months, to prevent unnecessary suffering that comes from the disease. Some dogs have lived for many years with the disease, with one female boxer even living for 11 years. Without treatment, survival is around 3 months. The disease progresses rapidly without treatment, but this option arguably comes with less suffering. The dog begins to realize it is ill during the late stages. Some dogs have even appeared to be combating the disease on their own, walking on their own and doing exercise. The record survival without treatment is 14 years. Sources External links "How to Care for a Dog with Degenerative Myelopathy Video". Retrieved 2013-07-19. "Degenerative Myelopathy Symptoms, Diagnosis and Treatment Video". Retrieved 2011-06-18. "Degenerative myelopathy in Canis familiaris". Online Mendelian Inheritance in Animals (OMIA). Retrieved 2008-07-25. "Degenerative Myelopathy". Canine Genetic Diseases Network. University of Missouri College of Veterinary Medicine. Retrieved 2007-07-02. "DM of the German Shepherd Dog". Retrieved 2013-07-12.

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

I've come across the term 'Thiamazole' in a medical context, but I'm not sure what it means. Can you clarify?

Thiamazole, also known as methimazole, is a medication used to treat hyperthyroidism. This includes Graves disease, toxic multinodular goiter, and thyrotoxic crisis. It is taken by mouth. Full effects may take a few weeks to occur.Common side effects include itchiness, hair loss, nausea, muscle pain, swelling, and abdominal pain. Severe side effects may include low blood cell counts, liver failure, and vasculitis. Use is not recommended during the first trimester of pregnancy due to the risk of congenital anomalies, but it may be used in the second trimester or third trimester. It may be used during breastfeeding. Those who developed significant side effects may also have problems with propylthiouracil. Thiamazole is a thioamide and works by decreasing the production of thyroid hormones.Thiamazole was approved for medical use in the United States in 1950. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. It is also available in Europe and Asia. In 2019, it was the 194th most commonly prescribed medication in the United States, with more than 2 million prescriptions. Medical uses Thiamazole is a drug used to treat hyperthyroidism such as in Graves disease, a condition that occurs when the thyroid gland begins to produce an excess of thyroid hormone. The drug may also be taken before thyroid surgery to lower thyroid hormone levels and minimize the effects of thyroid manipulation. Additionally, thiamazole is used in the veterinary setting to treat hyperthyroidism in cats. Adverse effects It is important to monitor any symptoms of fever or sore throat while taking thiamazole; this could indicate the development of agranulocytosis, an uncommon but severe side effect resulting from a drop in the white blood cell count (to be specific, neutropenia, a deficiency of neutrophils). A complete blood count (CBC) with differential is performed to confirm the suspicion, in which case the drug is discontinued. Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) may increase recovery. Other known side effects include: skin rash itching abnormal hair loss upset stomach vomiting loss of taste abnormal sensations (tingling, prickling, burning, tightness, and pulling) swelling joint and muscle pain drowsiness dizziness decreased platelet count (thrombocytopenia) aplasia cutis congenita (prenatal exposure) thyroid gland enlargement (prenatal exposure) choanal atresia (prenatal exposure during the first trimester of pregnancy) acute pancreatitis Interactions Adverse effects may occur for individuals who: Take anticoagulants (blood thinners) such as warfarin (Coumadin), diabetes medications, digoxin (Lanoxin), theophylline (Theobid, Theo-Dur), and vitamins Have ever had any blood disease, such as decreased white blood cells (leukopenia), decreased platelets (thrombocytopenia) or aplastic anemia, or liver disease (hepatitis, jaundice) Mechanism of action Thiamazole inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I−) to iodine (I2), hypoiodous acid (HOI), and enzyme linked hypoiodate (EOI), facilitating iodines addition to tyrosine residues on the hormone precursor thyroglobulin, a necessary step in the synthesis of triiodothyronine (T3) and thyroxine (T4). It does not inhibit the action of the sodium-dependent iodide transporter located on follicular cells basolateral membranes. Inhibition of this step requires competitive inhibitors such as perchlorate and thiocyanate. A study has shown that it modulates secretion of CXCL10. Chemical properties The imidazole derivative thiamazole is a white to matte brown crystalline powder with a characteristic odour. The boiling point is 280 °C (decomposition). Thiamazole is soluble in water, ethanol and chloroform, but hardly soluble in ether. Galenic preparations are injectable solutions and tablets. Thiamazole acts as a free radical scavenger for radicals such as the hydroxyl radical (•OH) radical. It is used as free radical scavenger in organic chemistry. Veterinary uses Thiamazole is also indicated in cats to treat hyperthyroidism. References External links "Methimazole". Drug Information Portal. U.S. National Library of Medicine.

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

I've come across the term 'Hypermobility spectrum disorder' in a medical context, but I'm not sure what it means. Can you clarify?

Hypermobility spectrum disorder (HSD), related to earlier diagnoses such as hypermobility syndrome (HMS), and joint hypermobility syndrome (JHS) is a heritable connective tissue disorder that affects joints and ligaments. Different forms and sub-types have been distinguished, but it does not include asymptomatic joint hypermobility, sometimes known as double-jointedness. Symptoms can include the inability to walk properly or for long distances, and pain in affected areas. Some people with HSD have hypersensitive nerves and a weaker immune system. It can also cause severe fatigue and some cases cause depressive episodes. It is somewhat similar to other genetic connective tissue disorders such as Ehlers–Danlos syndromes. There is a strong association between HSD and neurodevelopmental disorders such as ADHD (Attention deficit hyperactivity disorder) and ASD (autism spectrum disorder). Classification Hypermobility spectrum disorders are diagnosed when individuals have symptomatic joint hypermobility but do not meet the criteria for other connective tissue disorders, such as Ehlers-Danlos syndrome.The term "hypermobility spectrum disorder" was coined in 2017 after criteria for hypermobile Ehlers-Danlos syndrome were made more restrictive. In part, this classification change was designed to address the overlap between joint hypermobility syndrome and what was then known as Ehlers-Danlos syndrome, hypermobility type (EDS-HT), which some researchers believed were the same condition. While hypermobility spectrum disorders are most analogous to JHS, the 2017 diagnostic criteria for hypermobile Ehlers-Danlos syndrome excludes many people who fit the old criteria, who would instead be diagnosed with hypermobility spectrum disorders.Hypermobility syndrome and hypermobility spectrum disorders do not include people with asymptomatic hypermobility or people with double-jointedness but no other symptoms. Hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders may be equally severe. Signs and symptoms Some common symptoms of hypermobility spectrum disorder include: Joint pain (pain can arise in every joint) Exhaustion (typically when affected area is the legs); Swelling around the joint when joint is being exerted; Depression; Weaker immune system; Muscle pain Varying pain levels around the affected areas. Muscle spasms.Other symptoms can appear and not everyone affected experiences the same symptoms. Diagnosis Being diagnosed with hypermobility syndrome can be a difficult task. There is a lack of wide understanding of the condition and it can be considered a zebra condition. As hypermobility syndrome can be easily mistaken for being double-jointed or categorised as nothing more than perhaps an achy body from lack of exercise, medical professionals may diagnose those affected incorrectly and not adequately investigate the symptoms. Due to these circumstances many affected individuals can live not knowing they have it. As a result, those affected without a proper diagnosis can easily injure themselves and not take proper care to ensure they go about working safely. The Beighton Score can be used to determine generalised joint hypermobility (GJH) related to hypermobility syndrome. The newer term "generalised hypermobility spectrum disorder" includes people with generalised joint hypermobility, often determined using the Beighton Score, and other symptoms. Those who do not meet the Beighton Score criteria may be diagnosed with historical joint hypermobility spectrum disorder, peripheral hypermobility spectrum disorder, or localised hypermobility spectrum disorder.In comparison to the diagnostic criteria of hypermobile Ehlers-Danlos syndrome, the criteria for hypermobile spectrum disorder are less strict. However, these criteria are differentiated from criteria of other EDS types and therefore its less-strict criteria are only comparable to the criteria of hEDS. As those with HSD experience a considerable amount of discomfort, it is important to focus on the treatment, not the labels. The severity of each condition can be equivalent. In particular, musculoskeletal involvement is a requirement for diagnosis with any form of hypermobility spectrum disorder but not for hypermobile Ehlers-Danlos syndrome. Like hypermobile Ehlers-Danlos syndrome, hypermobility spectrum disorders are associated with orthostatic tachycardia, gastrointestinal disorders, and pelvic and bladder dysfunction. Treatment Treating hypermobility syndrome can be difficult. The condition has no direct cure, but its symptoms can be treated. Physiotherapy, particularly exercise, is the main treatment for the condition, although there is only limited evidence for its effectiveness.Treatments for pain include: Bandaging the affected area; Placing an ice pack on the affected area; Taking over the counter pain killers such as paracetamol or ibuprofen. Prevalence Prevalence of the condition is unknown, but can be high in those attending musculoskeletal services. == References ==

You act as a mediator between medical professionals and the public. Provide comprehensive explanations of medical terms, ensuring they are both precise and easily understood.

Please help me grasp the concept behind the medical term 'Postoperative cognitive dysfunction.'

Postoperative cognitive dysfunction (POCD) is a decline in cognitive function (especially in memory and executive functions) that may last from 1–12 months after surgery, or longer. In some cases, this disorder may persist for several years after major surgery. POCD is distinct from emergence delirium. Its causes are under investigation and occurs commonly in older patients and those with pre-existing cognitive impairment.The causes of POCD are not understood. It does not appear to be caused by lack of oxygen or impaired blood flow to the brain and is equally likely under regional and general anesthesia. It may be mediated by the bodys inflammatory response to surgery. Causes The bodys inflammatory response to surgery likely plays an important role, at least in elderly patients. Various research initiatives during recent years have evaluated whether actions taken before, during and after surgery can lessen the possible deleterious effects of inflammation. For example, anti-inflammatory agents can be given before surgery. During surgery, inflammation can be modulated by temperature control, use of regional rather than general anesthesia or the use of beta blockers. After surgery, optimal pain management and infection control is important. Several studies have shown variable-significance positive effects when a multidisciplinary, multifactorial approach to elderly patient is followed during pre, peri and post-operative care.A Cochrane review explored whether inhalation anaesthetics or intravenous anaesthetics were more likely to cause POCD when used in the elderly for non-cardiac surgery. Seven studies (869 participants) included in the review led to the conclusion that fewer people experienced POCD with total intravenous anaesthesia (TIVA) compared to inhalational anaesthesia. The conclusions, however, rated "low" on GRADE scoring (confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect). Assessment Cognitive tests are given prior to operations to establish a baseline. The same tests are again given post-operatively to determine the extent and duration of the decline for POCD. "A project examining adults 55 and older who have major non-cardiac surgeries is finding that upward of 30 percent of patients is testing significantly worse than their baseline 3 months later". Epidemiology POCD is common after cardiac surgery, and recent studies have now verified that POCD also exists after major non-cardiac surgery, although at a lower incidence. The risk of POCD increases with age, and the type of surgery is also important because there is a very low incidence associated with minor surgery. POCD is common in adult patients of all ages at hospital discharge after major noncardiac surgery, but only the elderly (aged 60 years or older) are at significant risk for long-term cognitive problems. Patients with POCD are at an increased risk of death in the first year after surgery. Research interest has increased since early 2000, especially as more elderly patients are able to undergo successful minor and major surgeries.POCD has been studied through various institutions since the inception of the IPOCDS-I study centred in Eindhoven, Netherlands and Copenhagen, Denmark. This study found no causal relationship between cerebral hypoxia and low blood pressure and POCD. Age, duration of anaesthesia, introperative complications, and postoperative infections were found to be associated with POCD. POCD is just as likely to occur after operations under regional anesthesia as under general anesthesia. More likely after major operations than minor operations. More likely after heart operations than other types of surgery. More likely in aged than in younger patients. More likely in older patients with high alcohol intake. People with higher preoperative ASA physical status scores are more likely to develop POCD. People with lower educational level are more likely to develop POCD than those with a higher educational level. People with prior history of a stroke, even though there is complete functional recovery, are more likely to develop POCD. More likely in the elderly with pre-existing declining mental functions, termed mild cognitive impairment (MCI). MCI is a transitional zone between normal mental function and evident Alzheimers disease or other forms of dementia. It is insidious, and seldom recognized, except in retrospect after affected persons are evidently demented. Delirium and severe worsening of mental function is very likely in those with clinically evident Alzheimers disease or other forms of dementia, as well as those with a history of delirium after previous operations. Footnotes Further reading "Postoperative cognitive dysfunction" (PDF). {{cite journal}}: Cite journal requires |journal= (help) Muñoz-Corsini L, Gómez-Arnau J, Porras MC, Galindo S, Jiménez R (May 1997). "Postoperative cognitive dysfunction". Rev Esp Anestesiol Reanim. 44 (5): 191–200. PMID 9280997. Crosby, Gregory; Culley, Deborah J. (2011). "Surgery and anesthesia: healing the body but harming the brain?". Anesthesia & Analgesia. 112 (5): 999–1001. doi:10.1213/ANE.0b013e3182160431. PMC 3092153. PMID 21515644. Rasmussen, L. S. (November 1998). "Defining postoperative cognitive dysfunction". European Journal of Anaesthesiology. 15 (6): 761–764. doi:10.1097/00003643-199811000-00026. PMID 9884870. Deiner, S.; Silverstein, J.H. (2009). "Postoperative delirium and cognitive dysfunction". British Journal of Anaesthesia. 103: i41–i46. doi:10.1093/bja/aep291. PMC 2791855. PMID 20007989. External links International Study of Post-Operative Cognitive Dysfunction (ISPOCD)

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

Could you offer a clear explanation of the term 'Carpal tunnel syndrome' as used in the medical field?

Carpal tunnel syndrome (CTS) is the collection of symptoms and signs associated with median neuropathy at the carpal tunnel. Most CTS is related to idiopathic compression of the median nerve as it travels through the wrist at the carpal tunnel (IMNCT). Idiopathic means that there is no other disease process contributing to pressure on the nerve. As with most structural issues, it occurs in both hands, and the strongest risk factor is genetics.Other conditions can cause CTS such as wrist fracture or rheumatoid arthritis. After fracture, swelling, bleeding, and deformity compress the median nerve. With rheumatoid arthritis, the enlarged synovial lining of the tendons causes compression. The main symptoms are numbness and tingling in the thumb, index finger, middle finger and the thumb side of the ring finger. People often report pain, but pain without tingling is not characteristic of IMNCT. Rather, the numbness can be so intense that it is described as painful. Symptoms are typically most troublesome at night. Untreated, and over years to decades, IMNCT causes loss of sensibility and weakness and shrinkage (atrophy) of the muscles at the base of the thumb. Work-related factors such as vibration, wrist extension or flexion, hand force, and repetition increase the risk of developing CTS. The only certain risk factor for IMNCT is genetics. All other risk factors are open to debate. It is important to consider IMNCT separately from CTS in diseases such as rheumatoid arthritis.Diagnosis of IMNCT can be made with a high probability based on characteristic symptoms and signs. IMNCT can be measured with electrodiagnostic tests.People wake less often at night if they wear a wrist splint. Injection of corticosteroids may or may not alleviate better than simulated (placebo) injections. There is no evidence that corticosteroid injection alters the natural history of the disease, which seems to be a gradual progression of neuropathy. Surgery to cut the transverse carpal ligament is the only known disease modifying treatment. Anatomy The carpal tunnel is an anatomical compartment located at the base of the palm. Nine flexor tendons and the median nerve pass through the carpal tunnel that is surrounded on three sides by the carpal bones that form an arch. The median nerve provides feeling or sensation to the thumb, index finger, long finger, and half of the ring finger. At the level of the wrist, the median nerve supplies the muscles at the base of the thumb that allow it to abduct, move away from the other four fingers, as well as move out of the plane of the palm. The carpal tunnel is located at the middle third of the base of the palm, bounded by the bony prominence of the scaphoid tubercle and trapezium at the base of the thumb, and the hamate hook that can be palpated along the axis of the ring finger. From the anatomical position, the carpal tunnel is bordered on the anterior surface by the transverse carpal ligament, also known as the flexor retinaculum. The flexor retinaculum is a strong, fibrous band that attaches to the pisiform and the hamulus of the hamate. The proximal boundary is the distal wrist skin crease, and the distal boundary is approximated by a line known as Kaplans cardinal line. This line uses surface landmarks, and is drawn between the apex of the skin fold between the thumb and index finger to the palpated hamate hook. Pathophysiology The median nerve can be compressed by a decrease in the size of the canal, an increase in the size of the contents (such as the swelling of tissue around the flexor tendons), or both. When the pressure builds up inside the tunnel, it damages the median nerve (median neuropathy). As the median neuropathy gets worse, there is loss of sensibility in the thumb, index, middle, and thumb side of the ring finger. As the neuropathy progresses, there may be first weakness, then to atrophy of the muscles of thenar eminence (the flexor pollicis brevis, opponens pollicis, and abductor pollicis brevis). The sensibility of the palm remains normal because the superficial sensory branch of the median nerve branches proximal to the TCL and travels superficial to it.The role of nerve adherence is speculative. Epidemiology IMNCT is estimated to affect one out of ten people during their lifetime and is the most common nerve compression syndrome. There is notable variation in such estimates based on how one defines the problem, in particular whether one studies people presenting with symptoms vs. measurable median neuropathy (IMNCT) whether or not people are seeking care. It accounts for about 90% of all nerve compression syndromes. The best data regarding IMNCT and CTS comes from population-based studies, which demonstrate no relationship to gender, and increasing prevalence (accumulation) with age. Symptoms The characteristic symptom of CTS is numbness, tingling, or burning sensations in the thumb, index, middle, and radial half of the ring finger. These areas process sensation through the median nerve. Numbness or tingling is usually worse with sleep. People tend to sleep with their wrists flexed, which increases pressure on the nerve. Ache and discomfort may be reported in the forearm or even the upper arm, but its relationship to IMNCT is uncertain. Symptoms that are not characteristic of CTS include pain in the wrists or hands, loss of grip strength, minor loss of sleep, and loss of manual dexterity.Median nerve symptoms may arise from compression at the level of the thoracic outlet or the area where the median nerve passes between the two heads of the pronator teres in the forearm, although this is debated. Signs Severe IMNCT is associated with measurable loss of sensibility. Diminished threshold sensibility (the ability to distinguish different amounts of pressure) can be measured using Semmes-Weinstein monofilament testing. Diminished discriminant sensibility can be measured by testing two-point discrimination: the number of millimeters two points of contact need to be separated before you can distinguish them.A person with idiopathic median neuropathy at the carpal tunnel will not have any sensory loss over the thenar eminence (bulge of muscles in the palm of hand and at the base of the thumb). This is because the palmar branch of the median nerve, which innervates that area of the palm, separates from the median nerve and passes over the carpal tunnel.Severe IMNCT is also associated with weakness and atrophy of the muscles at the base of the thumb. People may lose the ability to palmarly abduct the thumb. IMNCT can be detected on examination using one of several maneuvers to provoke paresthesia (a sensation of tingling or "pins and needles" in the median nerve distribution). These so-called provocative signs include: Phalens maneuver. Performed by fully flexing the wrist, then holding this position and awaiting symptoms. A positive test is one that results in paresthesia in the median nerve distribution within sixty seconds. Tinels sign is performed by lightly tapping the median nerve just proximal to flexor retinaculum to elicit paresthesia. Durkan test, carpal compression test, or applying firm pressure to the palm over the nerve for up to 30 seconds to elicit paresthesia. Hand elevation test The hand elevation test is performed by lifting both hands above the head. Paresthesia in the median nerve distribution within 2 minutes is considered positive.Diagnostic performance characteristics such as sensitivity and specificity are reported, but difficult to interpret because of the lack of a consensus reference standard for CTS or IMNCT. Causes Idiopathic Median Neuropathy at the Carpal Tunnel Genetic factors are believed to be the most important determinants of who develops carpal tunnel syndrome due to IMNCT. In other words, your wrist structure seems programmed at birth to develop IMNCT later in life. A genome-wide association study (GWAS) of carpal tunnel syndrome identified 16 genomic loci significantly associated with the disease, including several loci previously known to be associated with human height.Factors that may contribute to symptoms, but have not been experimentally associated with neuropathy include obesity, and Diabetes mellitus . One case-control study noted that individuals classified as obese (BMI > 29) are 2.5 times more likely than slender individuals (BMI < 20) to be diagnosed with CTS. Its not clear whether this association is due to an alteration of pathophysiology, a variation in symptoms, or a variation in care-seeking. Discrete Pathophysiology and Carpal Tunnel Syndrome Hereditary neuropathy with susceptibility to pressure palsies is a genetic condition that appears to increase the probability of developing MNCT. Heterozygous mutations in the gene SH3TC2, associated with Charcot-Marie-Tooth, may confer susceptibility to neuropathy, including CTS.Association between common benign tumors such as lipomas, ganglion, and vascular malformation should be handled with care. Such tumors are very common and overlap with IMNCT is more likely than pressure on the median nerve. Similarly, the degree to which transthyretin amyloidosis-associated polyneuropathy and carpal tunnel syndrome is under investigation. Prior carpal tunnel release is often noted in individuals who later present with transthyretin amyloid-associated cardiomyopathy. There is consideration that bilateral carpal tunnel syndrome could be a reason to consider amyloidosis, timely diagnosis of which could improve heart health. Amyloidosis is rare, even among people with carpal tunnel syndrome (0.55% incidence within 10 years of carpal tunnel release). In the absence of other factors associated with a notable probability of amyloidosis, its not clear that biopsy at the time of carpal tunnel release has a suitable balance between potential harms and potential benefits.Other specific pathophysiologies that can cause median neuropathy via pressure include: Rheumatoid arthritis and other diseases that cause inflammation of the flexor tendons. With severe untreated hypothyroidism, generalized myxedema causes deposition of mucopolysaccharides within both the perineurium of the median nerve, as well as the tendons passing through the carpal tunnel. Association of CTS and IMNCT with lesser degrees of hypothyroidism is questioned. Pregnancy may bring out symptoms in genetically predisposed individuals. Perhaps the changes in hormones and fluid increase pressure temporarily in the carpal tunnel. High progesterone levels and water retention may increase the size of the synovium. Bleeding and swelling from a fracture or dislocation. This is referred to as acute carpal tunnel syndrome. Acromegaly causes excessive secretion of growth hormones. This causes the soft tissues and bones around the carpal tunnel to grow and compress the median nerve.Other considerations Double-crush syndrome is a debated hypothesis that compression or irritation of nerve branches contributing to the median nerve in the neck, or anywhere above the wrist, increases sensitivity of the nerve to compression in the wrist. There is little evidence to support this theory and some concern that it may be used to justify more surgery. Median Neuropathy and Activity Work-related factors that increase risk of CTS include vibration (5.4 effect ratio), hand force (4.2), and repetition (2.3). Exposure to wrist extension or flexion at work increases the risk of CTS by two times. The balance of evidence suggests that keyboard and computer use does not cause CTS.The international debate regarding the relationship between CTS and repetitive hand use (at work in particular) is ongoing. The Occupational Safety and Health Administration (OSHA) has adopted rules and regulations regarding so-called "cumulative trauma disorders" based concerns regarding potential harm from exposure to repetitive tasks, force, posture, and vibration.A review of available scientific data by the National Institute for Occupational Safety and Health (NIOSH) indicated that job tasks that involve highly repetitive manual acts or specific wrist postures were associated with symptoms of CTS, but there was not a clear distinction of paresthesia (appropriate) from pain (inappropriate) and causation was not established. The distinction from work-related arm pains that are not carpal tunnel syndrome was unclear. It is proposed that repetitive use of the arm can affect the biomechanics of the upper limb or cause damage to tissues. It is proposed that postural and spinal assessment along with ergonomic assessments should be considered, based on observation that addressing these factors has been found to improve comfort in some studies although experimental data are lacking and the perceived benefits may not be specific to those interventions. A 2010 survey by NIOSH showed that 2/3 of the 5 million carpal tunnel diagnosed in the US that year were related to work. Women are more likely to be diagnosed with work-related carpal tunnel syndrome than men. Associated conditions A variety of patient factors can lead to CTS, including heredity, size of the carpal tunnel, associated local and systematic diseases, and certain habits. Non-traumatic causes generally happen over a period of time, and are not triggered by one certain event. Many of these factors are manifestations of physiologic aging. Diagnosis There is no consensus reference standard for the diagnosis of carpal tunnel syndrome. A combination of characteristic symptoms (how it feels) and signs (what the clinician finds on exam) are associated with a high probability of IMNCT without electrophysiological testing. Electrodiagnostic testing (electromyography and nerve conduction velocity) can objectively measure and verify median neuropathy.Ultrasound can image and measure the cross sectional diameter of the median nerve, which has some correlation with idiopathic median neuropathy at the carpal tunnel (IMNCT). The role of ultrasound in diagnosis--just as for electrodiagnostic testing--is a matter of debate. EDX cannot fully exclude the diagnosis of CTS due to the lack of sensitivity. A joint report published by the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), the American Academy of Physical Medicine and Rehabilitation (AAPM&R), and the American Academy of Neurology defines practice parameters, standards, and guidelines for EDX studies of CTS based on an extensive critical literature review. This joint review concluded median and sensory nerve conduction studies are valid and reproducible in a clinical laboratory setting and a clinical diagnosis of CTS can be made with a sensitivity greater than 85% and specificity greater than 95%. Given the key role of electrodiagnostic testing in the diagnosis of CTS, The AANEM has issued evidence-based practice guidelines, both for the diagnosis of carpal tunnel syndrome. Electrodiagnostic testing (electromyography and nerve conduction velocity) can objectively verify the median nerve dysfunction. Normal nerve conduction studies, however, do not exclude the diagnosis of CTS. Clinical assessment by history taking and physical examination can support a diagnosis of CTS. If clinical suspicion of CTS is high, treatment should be initiated despite normal electrodiagnostic testing. The role of confirmatory electrodiagnostic testing is debated. The goal of electrodiagnostic testing is to compare the speed of conduction in the median nerve with conduction in other nerves supplying the hand. When the median nerve is compressed, as in IMNCT, it will conduct more slowly than normal and more slowly than other nerves. Compression results in damage to the myelin sheath and manifests as delayed latencies and slowed conduction velocities. There are many electrodiagnostic tests used to make a diagnosis of CTS, but the most sensitive, specific, and reliable test is the Combined Sensory Index (also known as the Robinson index). Electrodiagnosis rests upon demonstrating impaired median nerve conduction across the carpal tunnel in context of normal conduction elsewhere. It is often stated that normal electrodiagnostic studies do not preclude the diagnosis of carpal tunnel syndrome. The rational for this is that a threshold of neuropathy must be reached before study results become abnormal and also that threshold values for abnormality vary. Others contend that idiopathic median neuropathy at the carpal tunnel with normal electrodiagnostic tests would represent very, very mild neuropathy that would be best managed as a normal median nerve. Even more important, notable symptoms with mild disease is strongly associated with unhelpful thoughts and symptoms of worry and despair. Notable CTS with unmeasurable IMNCT should remind clinicians to always consider the whole person, including their mindset and circumstances, in strategies to help people get and stay healthy. Imaging The role of MRI or ultrasound imaging in the diagnosis of idiopathic median neuropathy at the carpal tunnel (IMNCT) is unclear. Their routine use is not recommended. MRI has high sensitivity but low specificity for IMNCT. High signal intensity may suggest accumulation of axonal transportation, myelin sheath degeneration or oedema. Differential diagnosis There are few disorders on the differential diagnosis for carpal tunnel syndrome. Cervical radiculopathy can also cause paresthesia abnormal sensibility in the hands and wrist. The distribution usually follows the nerve root, and the paresthesia may be provoked by neck movement. Electromyography and imaging of the cervical spine can help to differentiate cervical radiculopathy from carpal tunnel syndrome if the diagnosis is unclear. Carpal tunnel syndrome is sometimes applied as a label to anyone with pain, numbness, swelling, or burning in the radial side of the hands or wrists. When pain is the primary symptom, carpal tunnel syndrome is unlikely to be the source of the symptoms.When the symptoms and signs point to atrophy and muscle weakness more than numbness, consider neurodegenerative disorders such as Amyotrophic Lateral Sclerosis or Charcot-Marie Tooth. Prevention There is little or no data to support the concept that activity adjustment prevents carpal tunnel syndrome. The evidence for wrist rest is debated. There is also little research supporting that ergonomics is related to carpal tunnel syndrome. Due to risk factors for hand and wrist dysfunction being multifactorial and very complex it is difficult to assess the true physical factors of carpal tunnel syndrome.Biological factors such as genetic predisposition and anthropometric features are more strongly associated with idiopathic carpal tunnel syndrome than occupational/environmental factors such as hand use. Treatment CTS related to another pathophysiology is addressed by treating that pathology. For instance, disease-modifying medications for rheumatoid arthritis or surgery for traumatic acute carpal tunnel syndrome.Generally accepted treatments include: physiotherapy, steroids either orally or injected locally, splinting, and surgical release of the transverse carpal ligament. Limited evidence suggests that gabapentin is no more effective than placebo for CTS treatment. There is insufficient evidence to recommend therapeutic ultrasound, yoga, acupuncture, low level laser therapy, vitamin B6, myofascial release, and any form of stretch or exercise. Change in activity may include avoiding activities that worsen symptoms.The American Academy of Orthopedic Surgeons recommends proceeding conservatively with a course of nonsurgical therapies tried before release surgery is considered. A different treatment should be tried if the current treatment fails to resolve the symptoms within 2 to 7 weeks. Early surgery with carpal tunnel release is indicated where there is evidence of median nerve denervation or a person elects to proceed directly to surgical treatment. Recommendations may differ when carpal tunnel syndrome is found in association with the following conditions: diabetes mellitus, coexistent cervical radiculopathy, hypothyroidism, polyneuropathy, pregnancy, rheumatoid arthritis, and carpal tunnel syndrome in the workplace. Splint Immobilizations The importance of wrist braces and splints in the carpal tunnel syndrome therapy is known, but many people are unwilling to use braces. In 1993, The American Academy of Neurology recommended a non-invasive treatment for the CTS at the beginning (except for sensitive or motor deficit or grave report at EMG/ENG): a therapy using splints was indicated for light and moderate pathology. Current recommendations generally dont suggest immobilizing braces, but instead activity modification and non-steroidal anti-inflammatory drugs as initial therapy, followed by more aggressive options or specialist referral if symptoms do not improve.Many health professionals suggest that, for the best results, one should wear braces at night. When possible, braces can be worn during the activity primarily causing stress on the wrists. The brace should not generally be used during the day as wrist activity is needed to keep the wrist from becoming stiff and to prevent muscles from weakening. Corticosteroids Corticosteroid injections may provide temporary alleviation of symptoms although they are not clearly better than placebo. This form of treatment is thought to reduce discomfort in those with CTS due to its ability to decrease median nerve swelling. The use of ultrasound while performing the injection is more expensive but leads to faster resolution of CTS symptoms. The injections are done under local anesthesia. This treatment is not appropriate for extended periods, however. In general, local steroid injections are only used until more definitive treatment options can be used. Corticosteroid injections do not appear to slow disease progression. Surgery Release of the transverse carpal ligament is known as "carpal tunnel release" surgery. It is recommended when there is static (constant, not just intermittent) numbness, muscle weakness, or atrophy, and when night-splinting or other palliative interventions no longer alleviate intermittent symptoms. The surgery may be done with local or regional anesthesia with or without sedation, or under general anesthesia. In general, milder cases can be controlled for months to years, but severe cases are unrelenting symptomatically and are likely to result in surgical treatment.Surgery is more beneficial in the short term to alleviate symptoms (up to six months) than wearing an orthosis for a minimum of six weeks. However, surgery and wearing a brace resulted in similar symptom relief in the long term (12–18 month outcomes). Physical therapy An evidence-based guideline produced by the American Academy of Orthopedic Surgeons assigned various grades of recommendation to physical therapy and other nonsurgical treatments. One of the primary issues with physiotherapy is that it attempts to reverse (often) years of pathology inside the carpal tunnel. Self-myofascial ligament stretching can be an easy, do-at-home, treatment to help alleviate symptoms. Self-myofascial stretching involves stretching the carpal ligament for 30 seconds, 6 times a day for about 6 weeks. Many patients report improvements in symptoms such as pain, function, and nerve conduction. Practitioners caution that any physiotherapy such as myofascial release may take weeks of persistent application to effectively manage carpal tunnel syndrome.Again, some claim that pro-active ways to reduce stress on the wrists, which alleviates wrist pain and strain, involve adopting a more ergonomic work and life environment. For example, some have claimed that switching from a QWERTY computer keyboard layout to a more optimised ergonomic layout such as Dvorak was commonly cited as beneficial in early CTS studies; however, some meta-analyses of these studies claim that the evidence that they present is limited.Tendon and nerve gliding exercises appear to be useful in carpal tunnel syndrome.A randomized control trial published in 2017 sought to examine the efficacy of manual therapy techniques for the treatment of carpal tunnel syndrome. The study included a total of 140 individuals diagnosed with carpal tunnel syndrome and the patients were divided into two groups. One group received treatment that consisted of manual therapy. Manual therapy included the incorporation of specified neurodynamic techniques, functional massage, and carpal bone mobilizations. Another group only received treatment through electrophysical modalities. The duration of the study was over the course of 20 physical therapy sessions for both groups. Results of this study showed that the group being treated through manual techniques and mobilizations yielded a 290% reduction in overall pain when compared to reports of pain prior to conducting the study. Total function improved by 47%. Conversely, the group being treated with electrophysical modalities reported a 47% reduction in overall pain with a 9% increase in function. Alternative medicine A 2018 Cochrane review on acupuncture and related interventions for the treatment of carpal tunnel syndrome concluded that, "Acupuncture and laser acupuncture may have little or no effect in the short term on symptoms of carpal tunnel syndrome (CTS) in comparison with placebo or sham acupuncture." It was also noted that all studies had an unclear or high overall risk of bias and that all evidence was of low or very low quality. Prognosis Most people relieved of their carpal tunnel symptoms with conservative or surgical management find minimal residual or "nerve damage". Long-term chronic carpal tunnel syndrome (typically seen in the elderly) can result in permanent "nerve damage", i.e. irreversible numbness, muscle wasting, and weakness. Those that undergo a carpal tunnel release are nearly twice as likely as those not having surgery to develop trigger thumb in the months following the procedure.While outcomes are generally good, certain factors can contribute to poorer results that have little to do with nerves, anatomy, or surgery type. One study showed that mental status parameters or alcohol use yields much poorer overall results of treatment.Recurrence of carpal tunnel syndrome after successful surgery is rare. History The condition known as carpal tunnel syndrome had major appearances throughout the years but it was most commonly heard of in the years following World War II. Individuals who had had this condition have been depicted in surgical literature for the mid-19th century. In 1854, Sir James Paget was the first to report median nerve compression at the wrist in two cases.The first to notice the association between the carpal ligament pathology and median nerve compression appear to have been Pierre Marie and Charles Foix in 1913. They described the results of a postmortem of an 80-year-old man with bilateral carpal tunnel syndrome. They suggested that division of the carpal ligament would be curative in such cases. Putman had previously described a series of 37 patients and suggested a vasomotor origin. The association between the thenar muscle atrophy and compression was noted in 1914. The name "carpal tunnel syndrome" appears to have been coined by Moersch in 1938.In the early 20th century there were various cases of median nerve compression underneath the transverse carpal ligament. Physician George S. Phalen of the Cleveland Clinic identified the pathology after working with a group of patients in the 1950s and 1960s. TreatmentPaget described two cases of carpal tunnel syndrome. The first was due to an injury where a cord had been wrapped around a mans wrist. The second was due to a distal radial fracture. For the first case, Paget performed an amputation of the hand. For the second case Paget recommended a wrist splint – a treatment that is still in use today. Surgery for this condition initially involved the removal of cervical ribs despite Marie and Foixs suggested treatment. In 1933 Sir James Learmonth outlined a method of decompression of the nerve at the wrist. This procedure appears to have been pioneered by the Canadian surgeons Herbert Galloway and Andrew MacKinnon in 1924 in Winnipeg but was not published. Endoscopic release was described in 1988. See also Repetitive strain injury Tarsal tunnel syndrome Ulnar nerve entrapment References External links Carpal Tunnel Syndrome Fact Sheet (National Institute of Neurological Disorders and Stroke) Archived 2016-03-03 at the Wayback Machine NHS website carpal-tunnel.net provides a free to use, validated, online self diagnosis questionnaire for CTS "Carpal Tunnel Syndrome". MedlinePlus. U.S. National Library of Medicine.

You are a facilitator of medical knowledge. Provide thorough and accessible explanations of medical terms, catering to both specialists and non-specialists.

I'd like to learn more about the medical term 'Peripheral T-cell lymphoma.' Can you provide some details?

Peripheral T-cell lymphoma refers to a group of T-cell lymphomas that develop away from the thymus or bone marrow.Examples include: Cutaneous T-cell lymphomas Angioimmunoblastic T-cell lymphoma Extranodal natural killer/T-cell lymphoma, nasal type Enteropathy type T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Anaplastic large cell lymphoma Peripheral T-cell lymphoma-Not-Otherwise-SpecifiedIn ICD-10, cutaneous T-cell lymphomas are classified separately. References == External links ==

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

I'd like to learn more about the medical term 'Bicipital tenosynovitis.' Can you provide some details?

Bicipital tenosynovitis is tendinitis or inflammation of the tendon and sheath lining of the biceps muscle. It is often the result of many years of small tears or other degenerative changes in the tendon first manifesting in middle age, but can be due to a sudden injury. Calcification of the tendon, and osteophytes ("bone spurs") in the intertubercular groove can be apparent on x-rays. The condition (which can also occur in dogs) is commonly treated with physical therapy and cortisone == References ==

You act as a mediator between medical professionals and the public. Provide comprehensive explanations of medical terms, ensuring they are both precise and easily understood.

Could you provide a brief overview of 'Altered level of consciousness' in a medical context?

An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a persons arousability and responsiveness to stimuli from the environment. A mildly depressed level of consciousness or alertness may be classed as lethargy; someone in this state can be aroused with little difficulty. People who are obtunded have a more depressed level of consciousness and cannot be fully aroused. Those who are not able to be aroused from a sleep-like state are said to be stuporous. Coma is the inability to make any purposeful response. Scales such as the Glasgow coma scale have been designed to measure the level of consciousness. An altered level of consciousness can result from a variety of factors, including alterations in the chemical environment of the brain (e.g. exposure to poisons or intoxicants), insufficient oxygen or blood flow in the brain, and excessive pressure within the skull. Prolonged unconsciousness is understood to be a sign of a medical emergency. A deficit in the level of consciousness suggests that both of the cerebral hemispheres or the reticular activating system have been injured. A decreased level of consciousness correlates to increased morbidity (sickness) and mortality (death). Thus it is a valuable measure of a patients medical and neurological status. In fact, some sources consider level of consciousness to be one of the vital signs. Definition Scales and terms to classify the levels of consciousness differ, but in general, reduction in response to stimuli indicates an altered level of consciousness: Altered level of consciousness is sometimes described as altered sensorium. Glasgow Coma Scale The most commonly used tool for measuring LOC objectively is the Glasgow Coma Scale (GCS). It has come into almost universal use for assessing people with brain injury, or an altered level of consciousness. Verbal, motor, and eye-opening responses to stimuli are measured, scored, and added into a final score on a scale of 3–15, with a lower score being a more decreased level of consciousness. Others The AVPU scale is another means of measuring LOC: people are assessed to determine whether they are alert, responsive to verbal stimuli, responsive to painful stimuli, or unresponsive. To determine responsiveness to voice, a caregiver speaks to, or, failing that, yells at the person. Responsiveness to pain is determined with a mild painful stimulus such as a pinch; moaning or withdrawal from the stimulus is considered a response to pain. The ACDU scale, like AVPU, is easier to use than the GCS and produces similarly accurate results. Using ACDU, a patient is assessed for alertness, confusion, drowsiness, and unresponsiveness.The Grady Coma Scale classes people on a scale of I to V along a scale of confusion, stupor, deep stupor, abnormal posturing, and coma. Pathophysiology Although the neural science behind alertness, wakefulness, and arousal are not fully known, the reticular formation is known to play a role in these. The ascending reticular activating system is a postulated group of neural connections that receives sensory input and projects to the cerebral cortex through the midbrain and thalamus from the reticular formation. Since this system is thought to modulate wakefulness and sleep, interference with it, such as injury, illness, or metabolic disturbances, could alter the level of consciousness.Normally, stupor and coma are produced by interference with the brain stem, such as can be caused by a lesion or indirect effects, such as brain herniation. Mass lesions in the brain stem normally cause coma due to their effects on the reticular formation. Mass lesions that occur above the tentorium cerebelli normally do not significantly alter the level of consciousness unless they are very large or affect both cerebral hemispheres. Diagnosis Assessing LOC involves determining an individuals response to external stimuli. Speed and accuracy of responses to questions and reactions to stimuli such as touch and pain are noted. Reflexes, such as the cough and gag reflexes, are also means of judging LOC. Once the level of consciousness is determined, clinicians seek clues for the cause of any alteration. Usually the first tests in the ER are pulse oximetry to determine if there is hypoxia, serum glucose levels to rule out hypoglycemia. A urine drug screen may be sent. A CT head is very important to obtain to rule out bleed. In cases where meningitis is suspected, a lumbar puncture must be performed. A serum TSH is an important test to order. In select groups consider vitamin B12 levels. Checking serum ammonia is particularly advised in neonatal coma to discern inborn errors of metabolism. Differential diagnosis A lowered level of consciousness indicate a deficit in brain function. Level of consciousness can be lowered when the brain receives insufficient oxygen (as occurs in hypoxia); insufficient blood (as occurs in shock, in children for example due to intussusception); or has an alteration in the brains chemistry. Metabolic disorders such as diabetes mellitus and uremia can alter consciousness. Hypo- or hypernatremia (decreased and elevated levels of sodium, respectively) as well as dehydration can also produce an altered LOC. A pH outside of the range the brain can tolerate will also alter LOC. Exposure to drugs (e.g. alcohol) or toxins may also lower LOC, as may a core temperature that is too high or too low (hyperthermia or hypothermia). Increases in intracranial pressure (the pressure within the skull) can also cause altered LOC. It can result from traumatic brain injury such as concussion. Stroke and intracranial hemorrhage are other causes. Infections of the central nervous system may also be associated with decreased LOC; for example, an altered LOC is the most common symptom of encephalitis. Neoplasms within the intracranial cavity can also affect consciousness, as can epilepsy and post-seizure states. A decreased LOC can also result from a combination of factors. A concussion, which is a mild traumatic brain injury (MTBI) may result in decreased LOC. Treatment Treatment depends on the degree of decrease in consciousness and its underlying cause. Initial treatment often involves the administration of dextrose if the blood sugar is low as well as the administration of oxygen, naloxone and thiamine. See also Altered state of consciousness Disorders of consciousness Level of consciousness (esotericism) Cognitive deficit References == External links ==

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I've come across the term 'Butalbital' in a medical context, but I'm not sure what it means. Can you clarify?

Butalbital is a barbiturate with an intermediate duration of action. Butalbital is often combined with other medications, such as paracetamol (acetaminophen) or aspirin, for the treatment of pain and headache. The various formulations combined with codeine are FDA-approved for the treatment of tension headaches. Butalbital has the same chemical formula as talbutal but a different structure—one that presents as 5-allyl-5-isobutylbarbituric acid. Preparations Combinations include: Butalbital and acetaminophen (paracetamol) (trade names: Axocet, Bucet, Bupap, Cephadyn, Dolgic, Phrenilin, Forte, Sedapap) Butalbital, paracetamol (acetaminophen), and caffeine (trade names: Fioricet, Esgic, Esgic-Plus, Orbivan, Fiorinal, Fiormor, Fiortal, Fortabs, Laniroif) Butalbital, paracetamol (acetaminophen), caffeine, and codeine phosphate (trade name: Fioricet#3 with Codeine) Butalbital and aspirin (trade name: Axotal) Butalbital, aspirin, caffeine, and codeine phosphate (trade name: Fiorinal#3 with Codeine) Ergotamine tartrate, caffeine, butalbital, belladonna alkaloids (trade name: Cafergot-PB) Contraindications There are specific treatments which are appropriate for targeting migraines and headaches. Butalbital is not recommended as a first-line treatment because it impairs alertness, brings risk of dependence and addiction, and increases the risk that episodic headaches will become chronic. When other treatments are unavailable or ineffective, butalbital may be appropriate if the patient can be monitored to prevent the development of chronic headache. Side effects Side effects for any psychoactive drug are difficult to predict, though butalbital is usually well tolerated. Commonly reported side effects for butalbital, some of which tend to subside with continued use, include: Rare side-effects include Stevens–Johnson syndrome, an adverse reaction to barbiturates, and anaphylaxis. The risk and severity of all side effects is greatly increased when butalbital (or butalbital-containing medications) are combined with other sedatives (ex. ethanol, opiates, benzodiazepines, antihistamines). In particular, butalbital, especially when combined with other sedatives (e.g. opioids), can cause life-threatening respiratory depression and death. Inhibitors of the hepatic enzyme CYP3A4 may also increase the risk, severity, and duration of side effects, many drugs inhibit this enzyme as do some foods such as grapefruit and the blood orange. Taking butalbital-based medications with some other drugs may also increase the side effects of the other medication. Dangers and risks Butalbital can cause dependence or addiction. Mixing with alcohol, benzodiazepines, and other CNS-depressants increases the risk of intoxication, increases respiratory depression, and increases liver toxicity when in combination with paracetamol (acetaminophen). Use of butalbital and alcohol, benzodiazepines, and other CNS-depressants can contribute to coma, and in extreme cases, fatality. References External links Butalbital, Online Medical Dictionary Butalbital and Acetaminophen (Systemic) (archive), MedicinePlus Drug Information Controlled Substances in Schedule III, (archive), U.S. Drug Enforcement Administration

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I'm trying to understand 'Amiodarone' within a medical context. Could you shed some light on it?

Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibrillation and paroxysmal supraventricular tachycardia. Evidence in cardiac arrest, however, is poor. It can be given by mouth, intravenously, or intraosseously. When used by mouth, it can take a few weeks for effects to begin.Common side effects include feeling tired, tremor, nausea, and constipation. As amiodarone can have serious side effects, it is mainly recommended only for significant ventricular arrhythmias. Serious side effects include lung toxicity such as interstitial pneumonitis, liver problems, heart arrhythmias, vision problems, thyroid problems, and death. If taken during pregnancy or breastfeeding it can cause problems in the fetus. It is a class III antiarrhythmic medication. It works partly by increasing the time before a heart cell can contract again.Amiodarone was first made in 1961 and came into medical use in 1962 for chest pain believed to be related to the heart. It was pulled from the market in 1967 due to side effects. In 1974 it was found to be useful for arrhythmias and reintroduced. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. In 2019, it was the 183rd most commonly prescribed medication in the United States, with more than 3 million prescriptions. Medical uses Amiodarone has been used both in the treatment of acute life-threatening arrhythmias as well as the long term suppression of arrhythmias. It is used both in supraventricular arrhythmias and ventricular arrhythmias. Cardiac arrest Defibrillation is the treatment of choice for ventricular fibrillation and pulseless ventricular tachycardia resulting in cardiac arrest. While amiodarone has been used in shock-refractory cases, evidence of benefit is poor. Amiodarone does not appear to improve survival or positive outcomes in those who had a cardiac arrest. Ventricular tachycardia Amiodarone may be used in the treatment of ventricular tachycardia in certain instances. Individuals with hemodynamically unstable ventricular tachycardia should not initially receive amiodarone. These individuals should be cardioverted. Amiodarone can be used in individuals with hemodynamically stable ventricular tachycardia. In these cases, amiodarone can be used regardless of the individuals underlying heart function and the type of ventricular tachycardia; it can be used in individuals with monomorphic ventricular tachycardia, but is contraindicated in individuals with polymorphic ventricular tachycardia as it is associated with a prolonged QT interval which will be made worse with anti-arrhythmic drugs. Atrial fibrillation Individuals who have undergone open heart surgery are at an increased risk of developing atrial fibrillation (or AF) in the first few days post-procedure. In the ARCH trial, intravenous amiodarone (2 g administered over 2 d) has been shown to reduce the incidence of atrial fibrillation after open heart surgery when compared to placebo. However, clinical studies have failed to demonstrate long-term efficacy and have shown potentially fatal side effects such as pulmonary toxicities. While amiodarone is not approved for AF by the FDA, it is a commonly prescribed off-label treatment due to the lack of equally effective treatment alternatives.So-called acute onset atrial fibrillation, defined by the North American Society of Pacing and Electrophysiology (NASPE) in 2003, responds well to short duration treatment with amiodarone. This has been demonstrated in seventeen randomized controlled trials, of which five included a placebo arm. The incidence of severe side effects in this group is low.The benefit of amiodarone in the treatment of atrial fibrillation in the critical care population has yet to be determined but it may prove to be the agent of choice where the patient is hemodynamically unstable and unsuitable for DC cardioversion. It is recommended in such a role by the UK governments National Institute for Health and Clinical Excellence (NICE). Contraindications Women who are pregnant or may become pregnant are strongly advised to not take amiodarone. Since amiodarone can be expressed in breast milk, women taking amiodarone are advised to stop nursing. It is contraindicated in individuals with sinus nodal bradycardia, atrioventricular block, and second or third degree heart block who do not have an artificial pacemaker. Individuals with baseline depressed lung function should be monitored closely if amiodarone therapy is to be initiated. Formulations of amiodarone that contain benzyl alcohol should not be given to neonates, because the benzyl alcohol may cause the potentially fatal "gasping syndrome".Amiodarone can worsen the cardiac arrhythmia brought on by digitalis toxicity. Side effects At oral doses of 400 mg per day or higher, amiodarone can have serious, varied side effects, including toxicity to thyroid, liver, lung, and retinal functions, requiring clinical surveillance and regular laboratory testing. Allergic reactions to amiodarone may occur. Most individuals administered amiodarone on a chronic basis will experience at least one side effect. In some people, daily use of amiodarone at 100 mg oral doses can be effective for arrhythmia control with no or minimal side effects. Lung Side effects of oral amiodarone at doses of 400 mg or higher include various pulmonary effects. The most serious reaction is interstitial lung disease. Risk factors include high cumulative dose, more than 400 milligrams per day, duration over two months, increased age, and preexisting pulmonary disease. Some individuals were noted to develop pulmonary fibrosis after a week of treatment, while others did not develop it after years of continuous use. Common practice is to avoid the agent if possible in individuals with decreased lung function. The most specific test of pulmonary toxicity due to amiodarone is a dramatically decreased DLCO noted on pulmonary function testing. Thyroid Induced abnormalities in thyroid function are common. Both under- and overactivity of the thyroid may occur. Amiodarone is structurally similar to thyroxine and also contains iodine. Both of these contribute to the effects of amiodarone on thyroid function. Amiodarone also causes an anti-thyroid action, via Plummer and Wolff–Chaikoff effects, due its large amount of iodine in its molecule, which causes a particular "cardiac hypothyroidism" with bradycardia and arrhythmia.Thyroid function should be checked at least every six months. Hypothyroidism (slowing of the thyroid) occurs frequently; in the SAFE trial, which compared amiodarone with other medications for the treatment of atrial fibrillation, biochemical hypothyroidism (as defined by a TSH level of 4.5–10 mU/L) occurred in 25.8% of the amiodarone-treated group as opposed to 6.6% of the control group (taking placebo or sotalol). Overt hypothyroidism (defined as TSH >10 mU/L) occurred at 5.0% compared to 0.3%; most of these (>90%) were detected within the first six months of amiodarone treatment. Amiodarone induced thyrotoxicosis (AIT), can be caused due to the high iodine contebt in the drug via the Jod-Basedow effect. This is known as Type 1 AIT, and usually occurs in patients with an underlying predisposition to hyperthyroidism such as Graves disease, within weeks to months after starting amiodarone. Type 1 AIT is usually treated with anti-thyroid drugs or thyroidectomy. Type 2 AIT is caused by a destructive thyroiditis due to a direct toxic effect of amiodarone on thyroid follicular epithelial cells. Type 2 AIT can occur even years after starting amiodarone, is usually self-limited and responds to anti-inflammatory treatment such as corticosteroids. In practice, often the type of AIT is undetermined or presumed as mixed with both treatments combined. Thyroid uptake measurements (I-123 or I-131), which are used to differentiate causes of hyperthyroidism, are generally unreliable in patients who have been taking amiodarone. Because of the high iodine content of amiodarone, the thyroid gland is effectively saturated, thus preventing further uptake of isotopes of iodine. However, a positive radioactive iodine can be used to rule in type 1AIT . Eye Corneal micro-deposits (cornea verticillata, also called vortex or whorl keratopathy) are almost universally present (over 90%) in individuals taking amiodarone longer than 6 months, especially doses greater than 400 mg/day. These deposits typically do not cause any symptoms. About 1 in 10 individuals may complain of a bluish halo. Anterior subcapsular lens deposits are relatively common (50%) in higher doses (greater than 600 mg/day) after 6 months of treatment. Optic neuropathy, nonarteritic anterior ischemic optic neuropathy (N-AION), occurs in 1–2% of people and is not dosage dependent. Bilateral optic disc swelling and mild and reversible visual field defects can also occur. Loss of eyelashes has been linked to amiodarone use. Liver Abnormal liver enzyme results are common in people taking amiodarone. Much rarer are jaundice, hepatomegaly (liver enlargement), and hepatitis (inflammation of the liver).Low-dose amiodarone has been reported to cause pseudo-alcoholic cirrhosis. Skin Long-term administration of amiodarone (usually more than eighteen months) is associated with a light-sensitive blue-grey discoloration of the skin, sometimes called ceruloderma; such patients should avoid exposure to the sun and use sunscreen that protects against ultraviolet-A and -B. The discoloration will slowly improve upon cessation of the medication, however, the skin color may not return completely. Pregnancy and breastfeeding Use during pregnancy may result in a number of problems in the infant including thyroid problems, heart problems, neurological problems, and preterm birth. Use during breastfeeding is generally not recommended though one dose may be okay. Other Long-term use of amiodarone has been associated with peripheral neuropathies.Amiodarone is sometimes responsible for epididymitis. Amiodarone accumulates in the head of the organ and can cause unilateral or bilateral inflammation. It tends to resolve if amiodarone is stopped.Some cases of gynecomastia have been reported with men on amiodarone.A study published in 2013 showed a possible association between amiodarone and an increased risk of cancer, especially in males, with a dose-dependent effect. Interactions The pharmacokinetics of numerous drugs, including many that are commonly administered to individuals with heart disease, are affected by amiodarone. Particularly, doses of digoxin should be halved in individuals taking amiodarone. Amiodarone may also interact with sotalol.Amiodarone potentiates the action of warfarin by inhibiting the clearance of both (S) and (R) warfarin. Individuals taking both of these medications should have their warfarin doses adjusted based on their dosing of amiodarone, and have their anticoagulation status (measured as prothrombin time (PT) and international normalized ratio (INR)) measured more frequently. Dose reduction of warfarin is as follows: 40% reduction if amiodarone dose is 400 mg daily, 35% reduction if amiodarone dose is 300 mg daily, 30% reduction if amiodarone dose is 200 mg daily, and 25% reduction if amiodarone dose is 100 mg daily. The effect of amiodarone on the warfarin concentrations can be as early as a few days after initiation of treatment; however, the interaction may not peak for up to seven weeks. Amiodarone inhibits the action of the cytochrome P450 isozyme family. This reduces the clearance of many drugs, including the following: Ciclosporin Digoxin Flecainide Procainamide Quinidine Sildenafil Simvastatin Theophylline WarfarinIn 2015, Gilead Sciences warned health care providers about people that began taking the hepatitis C drugs ledipasvir/sofosbuvir or sofosbuvir along with amiodarone, who developed abnormally slow heartbeats or died of cardiac arrest. Metabolism Amiodarone is extensively metabolized in the liver by cytochrome P450 3A4 and can affect the metabolism of numerous other drugs. It interacts with digoxin, warfarin, phenytoin, and others. The major metabolite of amiodarone is desethylamiodarone (DEA), which also has antiarrhythmic properties. The metabolism of amiodarone is inhibited by grapefruit juice, leading to elevated serum levels of amiodarone. On 8 August 2008, the FDA issued a warning of the risk of rhabdomyolysis, which can lead to kidney failure or death, when simvastatin is used with amiodarone. This interaction is dose-dependent with simvastatin doses exceeding 20 mg. This drug combination especially with higher doses of simvastatin should be avoided. Excretion Excretion is primarily via the liver and the bile duct with almost no elimination via the kidney and it is not dialyzable. Elimination half-life average of 58 days (ranging from 25 to 100 days [Remington: The Science and Practice of Pharmacy 21st edition]) for amiodarone and 36 days for the active metabolite, desethylamiodarone (DEA). There is 10-50% transfer of amiodarone and DEA in the placenta as well as a presence in breast milk. Accumulation of amiodarone and DEA occurs in adipose tissue and highly perfused organs (i.e. liver, lungs), therefore, if an individual was taking amiodarone on a chronic basis, if it is stopped it will remain in the system for weeks to months. Pharmacology Amiodarone is categorized as a class III antiarrhythmic agent, and prolongs phase 3 of the cardiac action potential, the repolarization phase where there is normally decreased calcium permeability and increased potassium permeability. It has numerous other effects, however, including actions that are similar to those of antiarrhythmic classes Ia, II, and IV. Amiodarone is a blocker of voltage gated potassium (KCNH2) and voltage gated calcium channels (CACNA2D2).Amiodarone slows conduction rate and prolongs the refractory period of the SA and AV nodes. It also prolongs the refractory periods of the ventricles, bundles of His, and the Purkinje fibres without exhibiting any effects on the conduction rate. Amiodarone has been shown to prolong the myocardial cell action potential duration and refractory period and is a non-competitive β-adrenergic inhibitor.It also shows beta blocker-like and calcium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects. It is suggested that amiodarone may also exacerbate the phenotype associated with Long QT-3 syndrome causing mutations such as ∆KPQ. This effect is due to a combination of blocking the peak sodium current, but also contributing to an increased persistent sodium current.Amiodarone chemically resembles thyroxine (thyroid hormone), and its binding to the nuclear thyroid receptor might contribute to some of its pharmacologic and toxic actions. History The original observation that amiodarones progenitor molecule, khellin, had cardioactive properties, was made by the Russian physiologist Gleb von Anrep while working in Cairo in 1946. Khellin is obtained from a plant extract of Khella or Ammi visnaga, a common plant in north Africa. Anrep noticed that one of his technicians had been cured of anginal symptoms after taking khellin, then used for various, non-cardiac ailments. This led to efforts by European pharmaceutical industries to isolate an active compound. Amiodarone was initially developed in 1961 at the Labaz company, Belgium, by chemists Tondeur and Binon, who were working on preparations derived from khellin. It became popular in Europe as a treatment for angina pectoris.As a doctoral candidate at Oxford University, Bramah Singh determined that amiodarone and sotalol had antiarrhythmic properties and belonged to a new class of antiarrhythmic agents (what would become the class III antiarrhythmic agents). Today the mechanisms of action of amiodarone and sotalol have been investigated in more detail. Both drugs have been demonstrated to prolong the duration of the action potential, prolonging the refractory period, by interacting among other cellular function with K+ channels. Based on Singhs work, the Argentinian physician Mauricio Rosenbaum began using amiodarone to treat his patients who have supraventricular and ventricular arrhythmias, with impressive results. Based on papers written by Rosenbaum developing Singhs theories, physicians in the United States began prescribing amiodarone to their patients with potentially life-threatening arrhythmias in the late 1970s. By 1980, amiodarone was commonly prescribed throughout Europe for the treatment of arrhythmias, but in the U.S. amiodarone remained unapproved by the Food and Drug Administration, and physicians were forced to directly obtain amiodarone from pharmaceutical companies in Canada and Europe.The FDA was reluctant to officially approve the use of amiodarone since initial reports had shown increased incidence of serious pulmonary side-effects of the drug. In the mid-1980s, the European pharmaceutical companies began putting pressure on the FDA to approve amiodarone by threatening to cut the supply to American physicians if it was not approved. In December 1985, amiodarone was approved by the FDA for the treatment of arrhythmias. This makes amiodarone one of the few drugs approved by the FDA without rigorous randomized clinical trials. Name Amiodarone may be an acronym for its IUPAC name (2-butyl-1-benzofuran-3-yl)-[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]methanone, where ar is a placeholder for phenyl. This is partially supported by dronedarone which is noniodinated benzofuran derivative of amiodarone, where the arylmethanone is conserved. Dosing Amiodarone is available in oral and intravenous formulations. Orally, it is available under the brand names Pacerone (produced by Upsher-Smith Laboratories, Inc.) and Cordarone (produced by Wyeth-Ayerst Laboratories). It is also available under the brand name Aratac (produced by Alphapharm Pty Ltd) in Australia and New Zealand, and further in Australia under the brands Cardinorm and Rithmik as well as a number of generic brands. Also Arycor in South Africa (Produced by Winthrop Pharmaceuticals.). In South America, it is known as Atlansil and is produced by Roemmers. In India, amiodarone is marketed (produced by Cipla Pharmaceutical) under the brand name Tachyra. It is also available in intravenous ampules and vials. The dose of amiodarone administered is tailored to the individual and the dysrhythmia that is being treated. When administered orally, the bioavailability of amiodarone is quite variable. Absorption ranges from 22 to 95%, with better absorption when it is given with food. Administration Amiodarone IV should be administered via a central venous catheter. It has a pH of 4.08. If administered outside of the standard concentration of 900 mg/500mL it should be administered using a 0.22 micron filter to prevent precipitate from reaching the patient. Amiodarone IV is a known vesicant. For infusions of longer than 1 hour, concentrations of 2 mg/mL should not be exceeded unless a central venous catheter is used. References Further reading Siddoway LA (December 2003). "Amiodarone: guidelines for use and monitoring". Am Fam Physician. 68 (11): 2189–2196. PMID 14677664. Archived from the original on 15 May 2008. Retrieved 16 May 2004. External links "Amiodarone". Drug Information Portal. U.S. National Library of Medicine.

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What does the medical term 'Indometacin' encompass?

Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of prostaglandins, endogenous signaling molecules known to cause these symptoms. It does this by inhibiting cyclooxygenase, an enzyme that catalyzes the production of prostaglandins.It was patented in 1961 and approved for medical use in 1963. It is on the World Health Organizations List of Essential Medicines. It is marketed under more than twelve different trade names. In 2017, it was the 291st most commonly prescribed medication in the United States, with more than one million prescriptions. Medical uses As an NSAID, indometacin is an analgesic, anti-inflammatory, and antipyretic. Clinical indications for indometacin include:Joint diseases rheumatoid arthritis ankylosing spondylitis osteoarthritis gouty arthritis acute painful shoulder bursitis or tendinitisHeadaches Trigeminal autonomic cephalgias Paroxysmal hemicranias Chronic paroxysmal hemicrania Episodic paroxysmal hemicrania Hemicrania continua Valsalva-induced headaches Primary cough headache Primary exertional headache Primary headache associated with sexual activity (preorgasmic and orgasmic) Primary stabbing headache (jabs and jolts syndrome) Hypnic headacheOthers Patent ductus arteriosus Contraindications Concurrent peptic ulcer, or history of ulcer disease Allergy to indometacin, aspirin, or other NSAIDs Roux-en-Y gastric bypass and gastric sleeve patients Patients with nasal polyps reacting with an angioedema to other NSAIDs Children under 2 years of age (with the exception of neonates with patent ductus arteriosus) Severe pre-existing renal and liver damage Caution: pre-existing bone marrow damage (frequent blood cell counts are indicated) Caution: bleeding tendencies of unknown origin (indometacin inhibits platelet aggregation) Caution: Parkinsons disease, epilepsy, psychotic disorders (indometacin may worsen these conditions) Concurrent with potassium sparing diuretics Patients who have a patent ductus arteriosus dependent heart defect (such as transposition of the great vessels) Significant hypertension (high blood pressure) Concomitant administration of lithium salts (such as lithium carbonate) Adverse effects In general, adverse effects seen with indometacin are similar to all other NSAIDs. For instance, indometacin inhibits both cyclooxygenase-1 and cyclooxygenase-2, which then inhibits the production of prostaglandins in the stomach and intestines responsible for maintaining the mucous lining of the gastrointestinal tract. Indometacin, therefore, like other non-selective COX inhibitors, can cause peptic ulcers. These ulcers can result in serious bleeding or perforation, requiring hospitalization of the patient. To reduce the possibility of peptic ulcers, indometacin should be prescribed at the lowest dosage needed to achieve a therapeutic effect, usually between 50 and 200 mg/day. It should always be taken with food. Nearly all patients benefit from an ulcer protective drug (e.g. highly dosed antacids, ranitidine 150 mg at bedtime, or omeprazole 20 mg at bedtime). Other common gastrointestinal complaints, including dyspepsia, heartburn and mild diarrhea are less serious and rarely require discontinuation of indometacin. Many NSAIDs, but particularly indometacin, cause lithium retention by reducing its excretion by the kidneys. Thus indometacin users have an elevated risk of lithium toxicity. For patients taking lithium (e.g. for treatment of depression or bipolar disorder), less toxic NSAIDs such as sulindac or aspirin are preferred. All NSAIDs, including indometacin, also increase plasma renin activity and aldosterone levels, and increase sodium and potassium retention. Vasopressin activity is also enhanced. Together these may lead to: Edema (swelling due to fluid retention) Hyperkalemia (high potassium levels) Hypernatremia (high sodium levels) HypertensionElevations of serum creatinine and more serious renal damage such as acute kidney failure, chronic nephritis and nephrotic syndrome, are also possible. These conditions also often begin with edema and high potassium levels in the blood. Paradoxically yet uncommonly, indometacin can cause headache (10 to 20%), sometimes with vertigo and dizziness, hearing loss, tinnitus, blurred vision (with or without retinal damage). There are unsubstantiated reports of worsening Parkinsons disease, epilepsy, and psychiatric disorders. Cases of life-threatening shock (including angioedema, sweating, severe hypotension and tachycardia as well as acute bronchospasm), severe or lethal hepatitis and severe bone marrow damage have all been reported. Skin reactions and photosensitivity are also possible side effects. The frequency and severity of side effects and the availability of better tolerated alternatives make indometacin today a drug of second choice. Its use in acute gout attacks and in dysmenorrhea is well-established because in these indications the duration of treatment is limited to a few days only, therefore serious side effects are not likely to occur. People should undergo regular physical examination to detect edema and signs of central nervous side effects. Blood pressure checks will reveal development of hypertension. Periodic serum electrolyte (sodium, potassium, chloride) measurements, complete blood cell counts and assessment of liver enzymes as well as of creatinine (renal function) should be performed. This is particularly important if Indometacin is given together with an ACE inhibitor or with potassium-sparing diuretics, because these combinations can lead to hyperkalemia and/or serious kidney failure. No examinations are necessary if only the topical preparations (spray or gel) are applied. Rare cases have shown that use of this medication by pregnant women can have an effect on the fetal heart, possibly resulting in fetal death via premature closing of the Ductus arteriosus.In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy. Mechanism of action Indometacin, a non-steroidal anti-inflammatory drug (NSAID), has similar mode of action when compared to other drugs in this group. It is a nonselective inhibitor of cyclooxygenase (COX) 1 and 2, the enzymes that participate in prostaglandin synthesis from arachidonic acid. Prostaglandins are hormone-like molecules normally found in the body, where they have a wide variety of effects, some of which lead to pain, fever, and inflammation. By inhibiting the synthesis of prostaglandins, indometacin can reduce pain, fever, and inflammation. Indometacin mechanism of action, along with several other NSAIDs that inhibit COX, was described in 1971.Additionally, indometacin has recently been found to be a positive allosteric modulator (PAM) of the CB1 cannabinoid receptor. By enhancing the binding and signalling of endogenous cannabinoids such as anandamide, PAMs may elicit increased cannabinergic signalling in a tissue specific manner, reducing the incidence of problematic side effects such as psychoactivity while maintaining some antinociceptive activity.Besides, indometacin has logarithmic acid dissociation constant pKa of 3 to 4.5. Since the physiologic body pH is well above the pKa range of indometacin, most of the indometacin molecules will be dissociated into ionized form, leaving very little un-ionized form of indometacin to cross a cell membrane. If the pH gradient across a cell membrane is high, most of the indometacin molecules will be trapped in one side of the membrane with higher pH. This phenomenon is called "ion trapping". The phenomenon of ion trapping is particularly prominent in the stomach as pH at the stomach mucosa layer is extremely acidic, while the parietal cells are more alkaline. Therefore, indometacin are trapped inside the parietal cells in ionized form, damaging the stomach cells, causing stomach irritation. This stomach irritation can reduce if the stomach acid pH is reduced.Indometacins role in treating certain headaches is unique compared to other NSAIDs. In addition to the class effect of COX inhibition, there is evidence that indometacin has the ability to reduce cerebral blood flow not only through modulation of nitric oxide pathways but also via intracranial precapillary vasoconstriction. Indometacin property of reducing cerebral blood flow is useful in treating raised intracranial pressure. A case report has shown that an intravenous bolus dose of indometacin given with 2 hours of continuous infusion is able to reduce intracranial pressure by 37% in 10 to 15 minutes and increases cerebral perfusion pressure by 30% at the same time. This reduction in cerebral pressure may be responsible for the remarkable efficacy in a group of headaches that is referred to as "indometacin-responsive headaches", such as idiopathic stabbing headache, chronic paroxysmal hemicranial, and exertional headaches. On the other hand, the activation of superior salivary nucleus in the brainstem is used to stimulate the trigeminal autonomic reflex arc, causing a type of headache called trigeminal autonomic cephalgia. Indometacin inhibits the superior salivatory nucleus, thus relieving this type of headache.Prostaglandins also cause uterine contractions in pregnant women. Indometacin is an effective tocolytic agent, able to delay premature labor by reducing uterine contractions through inhibition of prostaglandin synthesis in the uterus and possibly through calcium channel blockade. Indometacin readily crosses the placenta and can reduce fetal urine production to treat polyhydramnios. It does so by reducing renal blood flow and increasing renal vascular resistance, possibly by enhancing the effects of vasopressin on the fetal kidneys. Other modes of action for indometacin are: it inhibits motility of polymorphonuclear leukocytes, similar to colchicine it uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, like salicylates it has been found to specifically inhibit MRP (multidrug resistance proteins) in murine and human cells Nomenclature Indometacin is the INN, BAN, and JAN of the drug while indomethacin is the USAN, and former AAN and BAN. See also Indometacin farnesil Indometacin morpholinylamide Pravadoline GW-405,833 References External links Effects of Perinatal Indomethacin Treatment on Preterm Infants, academic dissertation (PDF) Indomethacin, from MedicineNet Indomethacin, from Drugs.com Indocin: Description, chemistry, ingredients, from RxList.com

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I need a basic explanation for the medical term 'Adult polyglucosan body disease.'

Adult polyglucosan body disease (APBD) is a rare genetic glycogen storage disorder caused by an inborn error of metabolism. Symptoms can emerge any time after the age of 30; early symptoms include trouble controlling urination, trouble walking, and lack of sensation in the legs. People eventually develop dementia. A person inherits loss-of-function mutations in the GBE1 gene from each parent, and the lack of glycogen branching enzyme (the protein encoded by GBE1) leads to buildup of unbranched glycogen in cells, which harms neurons more than other kinds of cells. Most people first go to the doctor due to trouble with urination. The condition is diagnosed by gathering symptoms, a neurological examination, laboratory tests including genetic testing, and medical imaging. As of 2015 there was no cure or treatment, but the symptoms could be managed. People diagnosed with APBD can live a long time after diagnosis, but will probably die earlier than people without the condition. Signs and symptoms Adult polyglucosan body disease is a condition that affects the nervous system. People with this condition have problems walking due to reduced sensation in their legs (peripheral neuropathy) and progressive muscle weakness and stiffness (spasticity). Damage to the nerves that control bladder function (neurogenic bladder) causes progressive difficulty in controlling the flow of urine. About half of people with adult polyglucosan body disease experience dementia. Most people with the condition first complain of bladder issues.People with adult polyglucosan body disease typically first experience signs and symptoms related to the condition between ages 30 and 60. Causes APBD is an autosomal recessive disorder that is caused when a person inherits genes from both parents containing one or more loss-of-function mutations in the gene GBE1 which encodes for glycogen branching enzyme, also called 1,4-alpha-glucan-branching enzyme. Mechanism The GBE1 gene provides instructions for making the glycogen branching enzyme. This enzyme is involved in the production of a complex sugar called glycogen, which is a major source of stored energy in the body. Most GBE1 gene mutations result in a shortage (deficiency) of the glycogen branching enzyme, which leads to the production of abnormal glycogen molecules. These abnormal glycogen molecules, called polyglucosan bodies, accumulate within cells and cause damage. Neurons appear to be particularly vulnerable to the accumulation of polyglucosan bodies in people with this disorder, leading to impaired neuronal function.Some mutations in the GBE1 gene that cause adult polyglucosan body disease do not result in a shortage of glycogen branching enzyme. In people with these mutations, the activity of this enzyme is normal. How mutations cause the disease in these individuals is unclear. Other people with adult polyglucosan body disease do not have identified mutations in the GBE1 gene. In these individuals, the cause of the disease is unknown. Diagnosis Along with evaluation of the symptoms and a neurological examination, a diagnosis can be made based on genetic testing. Whether or not a person is making sufficient amounts of functional glycogen branching enzyme can be determined by taking a skin biopsy and testing for activity of the enzyme. Examination of tissue biopsied from the sural nerve under a microscope can reveal the presence of polyglucosan bodies. There will also be white matter changes visible in a magnetic resonance imaging scans. Classification Adult polyglucosan body disease is an orphan disease and a glycogen storage disorder that is caused by an inborn error of metabolism, that affects the central and peripheral nervous systems.The condition in newborns caused by the same mutations is called glycogen storage disease type IV. Prevention APBD can only be prevented if parents undergo genetic screening to understand their risk of producing a child with the condition; if in vitro fertilization is used, then preimplantation genetic diagnosis can be done to identify fertilized eggs that do not carry two copies of mutated GBE1. Management As of 2015 there was no cure for APDB, instead symptoms are managed. There are various approaches to managing neurogenic bladder dysfunction, physical therapy and mobility aids to help with walking, and dementia can be managed with occupational therapy, counseling and drugs. Presently a number of promising research initiatives are underway in universities and hospitals in the United States, Canada, and Israel. These studies are in need of funding but due to the small number of known cases both research funding and participation is small. It is estimated that there are upwards of 12,000 cases in the United States, most of which are undiagnosed. Outcomes The rate of progression varies significantly from person to person.There is not good data on outcomes; it appears that APBD likely leads to earlier death, but people with APBD can live many years after diagnosis with relatively good quality of life. Epidemiology The prevalence is unknown; about 70 cases had been reported in the medical literature as of 2016. As of 2016 the largest set of case studies included 50 people; about 70% of them were of Ashkenazic Jewish descent. Society and culture A person with APBD named Gregory Weiss created a foundation, the Adult Polyglucosan Body Disease Research Foundation, to fund research into the disease and its management. Research directions In 2015 the first transgenic mouse that appeared to be a useful model organism for studying APBD was published. References This article incorporates public domain material from Adult polyglucosan body disease. United States Department of Health and Human Services. == External links ==

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The term 'Influenza vaccine' keeps coming up in medical discussions. What does it stand for?

Influenza vaccines, also known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies from year to year, most provide modest to high protection against influenza. The United States Centers for Disease Control and Prevention (CDC) estimates that vaccination against influenza reduces sickness, medical visits, hospitalizations, and deaths. Immunized workers who do catch the flu return to work half a day sooner on average. Vaccine effectiveness in those over 65 years old remains uncertain due to a lack of high-quality research. Vaccinating children may protect those around them.Vaccination against influenza began in the 1930s, with large-scale availability in the United States beginning in 1945. It is on the World Health Organizations List of Essential Medicines.The World Health Organization (WHO) and the CDC recommend yearly vaccination for nearly all people over the age of six months, especially those at high risk. The European Centre for Disease Prevention and Control (ECDC) also recommends yearly vaccination of high risk groups. These groups include pregnant women, the elderly, children between six months and five years of age, and those with certain health problems.The vaccines are generally safe; fever occurs in five to ten percent of children vaccinated, and temporary muscle pains or feelings of tiredness may occur. In certain years, the vaccine was linked to an increase in Guillain–Barré syndrome among older people at a rate of about one case per million doses. Although most influenza vaccines are produced using egg proteins, they are still recommended as safe for people who have severe egg allergies, as no increased risk of allergic reaction to the egg-based vaccines has been shown for people with egg allergies. Vaccines produced using other technologies, notably recombinant vaccines and those based on cell culture rather than egg protein, started to become available from 2012 in the US, and later in Europe and Australia. Influenza vaccines are not recommended in those who have had a severe allergy to previous versions of the vaccine itself. The vaccine comes in inactive and weakened viral forms. The live, weakened vaccine is generally not recommended in pregnant women, children less than two years old, adults older than 50, or people with a weakened immune system. Depending on the type they can be injected into a muscle, sprayed into the nose, or injected into the middle layer of the skin (intradermal). The intradermal vaccine was not available during the 2018–2019 and 2019–2020 influenza seasons. History Vaccines are used in both humans and nonhumans. Human vaccine is meant unless specifically identified as a veterinary, poultry or livestock vaccine. Origins and development In the worldwide Spanish flu pandemic of 1918, "Pharmacists tried everything they knew, everything they had ever heard of, from the ancient art of bleeding patients, to administering oxygen, to developing new vaccines and serums (chiefly against what we now call Hemophilus influenzae – a name derived from the fact that it was originally considered the etiological agent – and several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success."In 1931, viral growth in embryonated hens eggs was reported by Ernest William Goodpasture and colleagues at Vanderbilt University. The work was extended to growth of influenza virus by several workers, including Thomas Francis, Jonas Salk, Wilson Smith and Macfarlane Burnet, leading to the first experimental influenza vaccines. In the 1940s, the US military developed the first approved inactivated vaccines for influenza, which were used in the Second World War. Hens eggs continued to be used to produce virus used in influenza vaccines, but manufacturers made improvements in the purity of the virus by developing improved processes to remove egg proteins and to reduce systemic reactivity of the vaccine. In 2012, the US Food and Drug Administration (FDA) approved influenza vaccines made by growing virus in cell cultures and influenza vaccines made from recombinant proteins have been approved, with plant-based influenza vaccines being tested in clinical trials. Acceptance The egg-based technology for producing influenza vaccine was created in the 1950s. In the US swine flu scare of 1976, President Gerald Ford was confronted with a potential swine flu pandemic. The vaccination program was rushed, yet plagued by delays and public relations problems. Meanwhile, maximum military containment efforts succeeded unexpectedly in confining the new strain to the single army base where it had originated. On that base, a number of soldiers fell severely ill, but only one died. The program was canceled after about 24% of the population had received vaccinations. An excess in deaths of 25 over normal annual levels as well as 400 excess hospitalizations, both from Guillain–Barré syndrome, were estimated to have occurred from the vaccination program itself, demonstrating that the vaccine itself is not free of risks. The result can be cited to support lingering doubts about vaccination as well as to counter ungrounded claims about the safety of vaccination. In the end, however, even the maligned 1976 vaccine may have saved lives. A 2010 study found a significantly enhanced immune response against the 2009 pandemic H1N1 in study participants who had received vaccination against the swine flu in 1976. Quadrivalent vaccines for seasonal flu A quadrivalent flu vaccine administered by nasal mist was approved by the FDA in March 2012. Fluarix Quadrivalent was approved by the FDA in December 2012.In 2014, the Canadian National Advisory Committee on Immunization (NACI) published a review of quadrivalent influenza vaccines.Starting with the 2018–2019 influenza season most of the regular-dose egg-based flu shots and all the recombinant and cell-grown flu vaccines in the United States are quadrivalent. In the 2019–2020 influenza season all regular-dose flu shots and all recombinant influenza vaccine in the United States are quadrivalent.In November 2019, the FDA approved Fluzone High-Dose Quadrivalent for use in the United States starting with the 2020–2021 influenza season.In February 2020, the FDA approved Fluad Quadrivalent for use in the United States. In July 2020, the FDA approved both Fluad and Fluad Quadrivalent for use in the United States for the 2020–2021 influenza season. Medical uses The U.S Centers for Disease Control and Prevention (CDC) recommends the flu vaccine as the best way to protect people against the flu and prevent its spread. The flu vaccine can also reduce the severity of the flu if a person contracts a strain that the vaccine did not contain. It takes about two weeks following vaccination for protective antibodies to form.A 2012 meta-analysis found that flu vaccination was effective 67 percent of the time; the populations that benefited the most were HIV-positive adults aged 18 to 55 (76 percent), healthy adults aged 18 to 46 (approximately 70 percent), and healthy children aged six months to 24 months (66 percent). The influenza vaccine also appears to protect against myocardial infarction with a benefit of 15–45%. Effectiveness A vaccine is assessed by its efficacy – the extent to which it reduces risk of disease under controlled conditions – and its effectiveness – the observed reduction in risk after the vaccine is put into use. In the case of influenza, effectiveness is expected to be lower than the efficacy because it is measured using the rates of influenza-like illness, which is not always caused by influenza. Studies on the effectiveness of flu vaccines in the real world are difficult; vaccines may be imperfectly matched, virus prevalence varies widely between years, and influenza is often confused with other influenza-like illnesses. However, in most years (16 of the 19 years before 2007), the flu vaccine strains have been a good match for the circulating strains, and even a mismatched vaccine can often provide cross-protection. The virus rapidly changes due to antigenic drift, a slight mutation in the virus that causes a new strain to arise.The effectiveness of seasonal flu vaccines varies significantly, with an estimated average efficacy of 50–60% against symptomatic disease, depending on vaccine strain, age, prior immunity, and immune function, so vaccinated people can still contract influenza. The effectiveness of flu vaccines is considered to be suboptimal, particularly among the elderly, but vaccination is still beneficial in reducing the mortality rate and hospitalization rate due to influenza as well as duration of hospitalization. Vaccination of school-age children has shown to provide indirect protection for other age groups. LAIVs are recommended for children based on superior efficacy, especially for children under 6, and greater immunity against non-vaccine strains when compared to inactivated vaccines.From 2012 to 2015 in New Zealand, vaccine effectiveness against admission to an intensive care unit was 82%. Effectiveness against hospitalized influenza illness in the 2019–2020 United States flu season was 41% overall and 54% in people aged 65 years or older. One review found 31% effectiveness against death among adults.Repeated annual influenza vaccination generally offer consistent year-on-year protection against influenza. There is, however, suggestive evidence that repeated vaccinations may cause a reduction in vaccine effectiveness for certain influenza subtypes; this has no relevance to current recommendations for yearly vaccinations but might influence future vaccination policy. As of 2019, the CDC recommends a yearly vaccine as most studies demonstrate overall effectiveness of annual influenza vaccination.There is not enough evidence to establish significant differences in the effectiveness of different influenza vaccine types, but there are high-dose or adjuvanted products that induce a stronger immune response in the elderly. Children In April 2002, the Advisory Committee on Immunization Practices (ACIP) encouraged that children 6 to 23 months of age be vaccinated annually against influenza. In 2010, ACIP recommended annual influenza vaccination for those 6 months of age and older. Currently the CDC recommends that everyone except infants under the age of six months should receive the seasonal influenza vaccine. Vaccination campaigns usually focus special attention on people who are at high risk of serious complications if they catch the flu, such as pregnant women, children under 59 months, the elderly, and people with chronic illnesses or weakened immune systems, as well as those to whom they are exposed, such as health care workers.As the death rate is also high among infants who catch influenza, the CDC and the WHO recommend that household contacts and caregivers of infants be vaccinated to reduce the risk of passing an influenza infection to the infant.In children, the vaccine appears to decrease the risk of influenza and possibly influenza-like illness. In children under the age of two data are limited. During the 2017–18 flu season, the CDC director indicated that 85 percent of the children who died "likely will not have been vaccinated".In the United States, as of January 2019, the CDC recommend that children aged six through 35 months may receive either 0.25 milliliters or 0.5 milliliters per dose of Fluzone Quadrivalent. There is no preference for one or the other dose volume of Fluzone Quadrivalent for that age group. All persons 36 months of age and older should receive 0.5 milliliters per dose of Fluzone Quadrivalent. As of October 2018, Afluria Quadrivalent is licensed for children six months of age and older in the United States. Children six months through 35 months of age should receive 0.25 milliliters for each dose of Afluria Quadrivalent. All persons 36 months of age and older should receive 0.5 milliliters per dose of Afluria Quadrivalent. As of February 2018, Afluria Tetra is licensed for adults and children five years of age and older in Canada.In 2014, the Canadian National Advisory Committee on Immunization (NACI) published a review of influenza vaccination in healthy 5–18-year-olds, and in 2015, published a review of the use of pediatric Fluad in children 6–72 months of age. In one study, conducted in a tertiary referral center, the rate of influenza vaccination in children was only 31%. Higher rates were found among immuno-suppressed pediatric patients (46%), and in patients with inflammatory bowel disease (50%). Adults In unvaccinated adults, 16% get symptoms similar to the flu, while about 10% of vaccinated adults do. Vaccination decreased confirmed cases of influenza from about 2.4% to 1.1%. No effect on hospitalization was found.In working adults, a review by the Cochrane Collaboration found that vaccination resulted in a modest decrease in both influenza symptoms and working days lost, without affecting transmission or influenza-related complications. In healthy working adults, influenza vaccines can provide moderate protection against virologically confirmed influenza, though such protection is greatly reduced or absent in some seasons.In health care workers, a 2006 review found a net benefit. Of the eighteen studies in this review, only two also assessed the relationship of patient mortality relative to staff influenza vaccine uptake; both found that higher rates of health care worker vaccination correlated with reduced patient deaths. A 2014 review found benefits to patients when health care workers were immunized, as supported by moderate evidence based in part on the observed reduction in all-cause deaths in patients whose health care workers were given immunization compared with comparison patients where the workers were not offered vaccine. Elderly Evidence for an effect in adults over 65 is unclear. Systematic reviews examining both randomized controlled and case–control studies found a lack of high-quality evidence. Reviews of case–control studies found effects against laboratory-confirmed influenza, pneumonia, and death among the community-dwelling elderly.The group most vulnerable to non-pandemic flu, the elderly, benefits least from the vaccine. There are multiple reasons behind this steep decline in vaccine efficacy, the most common of which are the declining immunological function and frailty associated with advanced age. In a non-pandemic year, a person in the United States aged 50–64 is nearly ten times more likely to die an influenza-associated death than a younger person, and a person over 65 is more than ten times more likely to die an influenza-associated death than the 50–64 age group.There is a high-dose flu vaccine specifically formulated to provide a stronger immune response. Available evidence indicates that vaccinating the elderly with the high-dose vaccine leads to a stronger immune response against influenza than the regular-dose vaccine.A flu vaccine containing an adjuvant was approved by the US Food and Drug Administration (FDA) in November 2015, for use by adults aged 65 years of age and older. The vaccine is marketed as Fluad in the US and was first available in the 2016–2017 flu season. The vaccine contains the MF59C.1 adjuvant which is an oil-in-water emulsion of squalene oil. It is the first adjuvanted seasonal flu vaccine marketed in the United States. It is not clear if there is a significant benefit for the elderly to use a flu vaccine containing the MF59C.1 adjuvant. Per Advisory Committee on Immunization Practices guidelines, Fluad can be used as an alternative to other influenza vaccines approved for people 65 years and older.Vaccinating health care workers who work with elderly people is recommended in many countries, with the goal of reducing influenza outbreaks in this vulnerable population. While there is no conclusive evidence from randomized clinical trials that vaccinating health care workers helps protect elderly people from influenza, there is tentative evidence of benefit.Fluad Quad was approved for use in Australia in September 2019, Fluad Quadrivalent was approved for use in the United States in February 2020, and Fluad Tetra was approved for use in the European Union in May 2020. Pregnancy As well as protecting mother and child from the effects of an influenza infection, the immunization of pregnant women tends to increase their chances of experiencing a successful full-term pregnancy.The trivalent inactivated influenza vaccine is protective in pregnant women infected with HIV. Safety Side effects Common side effects of vaccination include local injection-site reactions and cold-like symptoms. Fever, malaise, and myalgia are less common. Flu vaccines are contraindicated for people who have experienced a severe allergic reaction in response to a flu vaccine or to any component of the vaccine. LAIVs are not given to children or adolescents with severe immunodeficiency or to those who are using salicylate treatments because of the risk of developing Reye syndrome. LAIVs are also not recommended for children under the age of 2, pregnant women, and adults with immunosuppression. Inactivated flu vaccines cannot cause influenza and are regarded as safe during pregnancy.While side effects of the flu vaccine may occur, they are usually minor, including soreness, redness, and swelling around the point of injection, headache, fever, nausea or fatigue. Side effects of a nasal spray vaccine may include runny nose, wheezing, sore throat, cough, or vomiting.In some people, a flu vaccine may cause serious side effects, including an allergic reaction, but this is rare. Furthermore, the common side effects and risks are mild and temporary when compared to the risks and severe health effects of the annual influenza epidemic. Guillain–Barré syndrome Although Guillain–Barré syndrome had been feared as a complication of vaccination, the CDC states that most studies on modern influenza vaccines have seen no link with Guillain–Barré. Infection with influenza virus itself increases both the risk of death (up to one in ten thousand) and the risk of developing Guillain–Barré syndrome to a far higher level than the highest level of suspected vaccine involvement (approximately ten times higher by 2009 estimates).Although one review gives an incidence of about one case of Guillain–Barré per million vaccinations, a large study in China, covering close to a hundred million doses of vaccine against the 2009 H1N1 "swine" flu found only eleven cases of Guillain–Barré syndrome, (0.1 per million doses) total incidence in persons vaccinated, actually lower than the normal rate of the disease in China, and no other notable side effects. Egg allergy Although most influenza vaccines are produced using egg-based techniques, influenza vaccines are nonetheless still recommended for people with egg allergies, even if severe. Studies examining the safety of influenza vaccines in people with severe egg allergies found that anaphylaxis was very rare, occurring in 1.3 cases per million doses given.Monitoring for symptoms from vaccination is recommended in those with more severe symptoms. A study of nearly 800 children with egg allergy, including over 250 with previous anaphylactic reactions, had zero systemic allergic reactions when given the live attenuated flu vaccine. Other Several studies have identified an increased incidence of narcolepsy among recipients of the pandemic H1N1 influenza AS03-adjuvanted vaccine; efforts to identify a mechanism for this suggest that narcolepsy is autoimmune, and that the AS03-adjuvanted H1N1 vaccine may mimic hypocretin, serving as a trigger.Some injection-based flu vaccines intended for adults in the United States contain thiomersal (also known as thimerosal), a mercury-based preservative. Despite some controversy in the media, the World Health Organizations Global Advisory Committee on Vaccine Safety has concluded that there is no evidence of toxicity from thiomersal in vaccines and no reason on grounds of safety to change to more-expensive single-dose administration. Types Flu vaccines are available either as: a trivalent or quadrivalent intramuscular injection (IIV3, IIV4, or RIV4, that is, TIV or QIV), which contains the inactivated form of the virus a nasal spray of live attenuated influenza vaccine (LAIV, Q/LAIV), which contains the live but attenuated (weakened) form of the virus.TIV or QIV induce protection after injection (typically intramuscular, though subcutaneous and intradermal routes can also be protective) based on an immune response to the antigens present on the inactivated virus, while cold-adapted LAIV works by establishing infection in the nasal passages. Recommendations Various public health organizations, including the World Health Organization (WHO), recommend that yearly influenza vaccination be routinely offered, particularly to people at risk of complications of influenza and those individuals who live with or care for high-risk individuals, including: people aged 50 years of age or older people with chronic lung diseases, including asthma people with chronic heart diseases people with chronic liver diseases people with chronic kidney diseases people who have had their spleen removed or whose spleen is not working properly people who are immunocompromised residents of nursing homes and other long-term care facilities health care workers (both to prevent sickness and to prevent spread to their patients) women who are or will be pregnant during the influenza season children and adolescents (aged 6 months through 18 years) who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection American Indians/Alaska Natives people who are extremely obese (body mass index ≥40 for adults)The flu vaccine is contraindicated for those under six months of age and those with severe, life-threatening allergies to flu vaccine or any ingredient in the vaccine. World Health Organization As of 2016, the World Health Organization (WHO) recommends seasonal influenza vaccination for:First priority: Pregnant womenSecond priority (in no particular order): Children aged 6–59 months Elderly Individuals with specific chronic medical conditions Health-care workers Canada The National Advisory Committee on Immunization (NACI), the group that advises the Public Health Agency of Canada, recommends that everyone over six months of age be encouraged to receive annual influenza vaccination, and that children between the age of six months and 24 months, and their household contacts, should be considered a high priority for the flu vaccine. Particularly: People at high risk of influenza-related complications or hospitalization, including people who are morbidly obese, healthy pregnant women, children aged 6–59 months, the elderly, aboriginals, and people with one of an itemized list of chronic health conditions People capable of transmitting influenza to those at high risk, including household contacts and health care workers People who provide essential community services Certain poultry workersLive attenuated influenza vaccine (LAIV) was not available in Canada for the 2019–2020 season. European Union The European Centre for Disease Prevention and Control (ECDC) recommends vaccinating the elderly as a priority, with a secondary priority people with chronic medical conditions and health care workers.The influenza vaccination strategy is generally that of protecting vulnerable people, rather than limiting influenza circulation or eliminating human influenza sickness. This is in contrast with the high herd immunity strategies for other infectious diseases such as polio and measles. This is also due in part to the financial and logistics burden associated with the need of an annual injection. United States In the United States routine influenza vaccination is recommended for all persons aged six months and over. It takes up to two weeks after vaccination for sufficient antibodies to develop in the body. The CDC recommends vaccination before the end of October, although it considers getting a vaccine in December or even later to be still beneficial.According to the CDC, the live attenuated virus (LAIV4) (which comes in the form of the nasal spray in the US) should be avoided by some groups.Within its blanket recommendation for general vaccination in the United States, the CDC, which began recommending the influenza vaccine to health care workers in 1981, emphasizes to clinicians the special urgency of vaccination for members of certain vulnerable groups, and their caregivers: Vaccination is especially important for people at higher risk of serious influenza complications or people who live with or care for people at higher risk for serious complications. In 2009, a new high-dose formulation of the standard influenza vaccine was approved. The Fluzone High Dose is specifically for people 65 and older; the difference is that it has four times the antigen dose of the standard Fluzone.The US government requires hospitals to report worker vaccination rates. Some US states and hundreds of US hospitals require health care workers to either get vaccinations or wear masks during flu season. These requirements occasionally engender union lawsuits on narrow collective bargaining grounds, but proponents note that courts have generally endorsed forced vaccination laws affecting the general population during disease outbreaks.Vaccination against influenza is especially considered important for members of high-risk groups who would be likely to have complications from influenza, for example pregnant women and children and teenagers from six months to 18 years of age who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection; In raising the upper age limit to 18 years, the aim is to reduce both the time children and parents lose from visits to pediatricians and missing school and the need for antibiotics for complications An added benefit expected from the vaccination of children is a reduction in the number of influenza cases among parents and other household members, and of possible spread to the general community.The CDC indicated that live attenuated influenza vaccine (LAIV), also called the nasal spray vaccine, was not recommended for the 2016–2017 flu season in the United States.Furthermore, the CDC recommends that health care personnel who care for severely immunocompromised persons receive injections (TIV or QIV) rather than LAIV. United Kingdom Dr Jenny Harries maintained winter 2021–2022 in the UK will be "uncertain" since flu and COVID-19 will be circulating together for the first time. She urged eligible people to get COVID-19 and flu vaccines. She maintains flu vaccination is important every year. People need to know that flu can be fatal as many people do not know this. Australia The Australian Government recommends seasonal flu vaccination for everyone over the age of six months. Australia uses inactivated vaccines. Until 2021, the egg-based vaccine has been the only one available (and continues to be the only free one), but from March 2021 a new cell-based vaccine is available for those who wish to pay for it, and it is expected that this one will become the standard by 2026. The standard flu vaccine is free for the following people: children aged six months to five years; people aged 65 years and over; Aboriginal and Torres Strait Islander people aged six months and over; pregnant women; and anyone over six months of age with medical conditions such as severe asthma, lung disease or heart disease, low immunity or diabetes that can lead to complications from influenza. Uptake At risk groups Uptake of flu vaccination, both seasonally and during pandemics, is often low. Systematic reviews of pandemic flu vaccination uptake have identified several personal factors that may influence uptake, including gender (higher uptake in men), ethnicity (higher in people from ethnic minorities) and having a chronic illness. Beliefs in the safety and effectiveness of the vaccine are also important.A number of measures have been found to be useful to increase rates of vaccination in those over sixty including: patient reminders using leaflets and letters, postcard reminders, client outreach programs, vaccine home visits, group vaccinations, free vaccinations, physician payment, physician reminders and encouraging physician competition. Health care workers Frontline health care workers are often recommended to get seasonal and any pandemic flu vaccination. For example, in the UK all health care workers involved in patient care are recommended to receive the seasonal flu vaccine, and were also recommended to be vaccinated against the H1N1/09 (later renamed A(H1N1)pdm09) swine flu virus during the 2009 pandemic. However, uptake is often low. During the 2009 pandemic, low uptake by healthcare workers was seen in countries including the UK, Italy, Greece, and Hong Kong.In a 2010 survey of United States health care workers, 63.5% reported that they received the flu vaccine during the 2010–11 season, an increase from 61.9% reported the previous season. US Health professionals with direct patient contact had higher vaccination uptake, such as physicians and dentists (84.2%) and nurse practitioners (82.6%).The main reason to vaccinate health care workers is to prevent staff from spreading flu to their patients and to reduce staff absence at a time of high service demand, but the reasons health care workers state for their decisions to accept or decline vaccination may more often be to do with perceived personal benefits.In Victoria (Australia) public hospitals, rates of health care worker vaccination in 2005 ranged from 34% for non-clinical staff to 42% for laboratory staff. One of the reasons for rejecting vaccines was concern over adverse reactions; in one study, 31% of resident physicians at a teaching hospital incorrectly believed Australian vaccines could cause influenza. Manufacturing Research continues into the idea of a "universal" influenza vaccine that would not require tailoring to a particular strain, but would be effective against a broad variety of influenza viruses. No vaccine candidates had been announced by November 2007, but as of 2021, there are several universal vaccines candidates, in pre-clinical development and in clinical trials.In a 2007 report, the global capacity of approximately 826 million seasonal influenza vaccine doses (inactivated and live) was double the production of 413 million doses. In an aggressive scenario of producing pandemic influenza vaccines by 2013, only 2.8 billion courses could be produced in a six-month time frame. If all high- and upper-middle-income countries sought vaccines for their entire populations in a pandemic, nearly two billion courses would be required. If China pursued this goal as well, more than three billion courses would be required to serve these populations. Vaccine research and development is ongoing to identify novel vaccine approaches that could produce much greater quantities of vaccine at a price that is affordable to the global population. Egg-based Most flu vaccines are grown by vaccine manufacturers in fertilized chicken eggs. In the Northern hemisphere, the manufacturing process begins following the announcement (typically in February) of the WHO recommended strains for the winter flu season. Three strains (representing an H1N1, an H3N2, and a B strain) of flu are selected and chicken eggs are inoculated separately. These monovalent harvests are then combined to make the trivalent vaccine. As of November 2007, both the conventional injection and the nasal spray are manufactured using chicken eggs. The European Union also approved Optaflu, a vaccine produced by Novartis using vats of animal cells. This technique is expected to be more scalable and avoid problems with eggs, such as allergic reactions and incompatibility with strains that affect avians like chickens.Influenza vaccines are produced in pathogen-free eggs that are eleven or twelve days old. The top of the egg is disinfected by wiping it with alcohol and then the egg is candled to identify a non-veinous area in the allantoic cavity where a small hole is poked to serve as a pressure release. A second hole is made at the top of the egg, where the influenza virus is injected in the allantoic cavity, past the chorioallantoic membrane. The two holes are then sealed with melted paraffin and the inoculated eggs are incubated for 48 hours at 37 degrees Celsius. During incubation time, the virus replicates and newly replicated viruses are released into the allantoic fluidAfter the 48-hour incubation period, the top of the egg is cracked and the ten milliliters of allantoic fluid is removed, from which about fifteen micrograms of the flu vaccine can be obtained. At this point, the viruses have been weakened or killed and the viral antigen is purified and placed inside vials, syringes, or nasal sprayers. Done on a large-scale, this method is used to produce the flu vaccine for the human population. Other methods of manufacture Methods of vaccine generation that bypass the need for eggs include the construction of influenza virus-like particles (VLP). VLP resemble viruses, but there is no need for inactivation, as they do not include viral coding elements, but merely present antigens in a similar manner to a virion. Some methods of producing VLP include cultures of Spodoptera frugiperda Sf9 insect cells and plant-based vaccine production (e.g., production in Nicotiana benthamiana). There is evidence that some VLPs elicit antibodies that recognize a broader panel of antigenically distinct viral isolates compared to other vaccines in the hemagglutination-inhibition assay (HIA).A gene-based DNA vaccine, used to prime the immune system after boosting with an inactivated H5N1 vaccine, underwent clinical trials in 2011.On November 20, 2012, Novartis received FDA approval for the first cell-culture vaccine. In 2013, the recombinant influenza vaccine, Flublok, was approved for use in the United States.On September 17, 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for Supemtek, a quadrivalent influenza vaccine (recombinant, prepared in cell culture). The applicant for this medicinal product is Sanofi Pasteur. Supemtek was approved for medical use in the European Union in November 2020.Australia authorised its first and cell-based vaccine in March 2021, based on an "eternal cell line" of a dog kidney. Because of the way it is produced, it produces better-matched vaccine (to the flu strains). Vaccine manufacturing countries According to the WHO, as of 2019, countries where influenza vaccine is produced include: In addition, Kazakhstan, Serbia and Thailand had facilities in final stages of establishing production. Cost-effectiveness The cost-effectiveness of seasonal influenza vaccination has been widely evaluated for different groups and in different settings. In the elderly (over 65), the majority of published studies have found that vaccination is cost saving, with the cost savings associated with influenza vaccination (e.g. prevented health care visits) outweighing the cost of vaccination. In older adults (aged 50–64 years), several published studies have found that influenza vaccination is likely to be cost-effective, however the results of these studies were often found to be dependent on key assumptions used in the economic evaluations. The uncertainty in influenza cost-effectiveness models can partially be explained by the complexities involved in estimating the disease burden, as well as the seasonal variability in the circulating strains and the match of the vaccine. In healthy working adults (aged 18–49 years), a 2012 review found that vaccination was generally not cost-saving, with the suitability for funding being dependent on the willingness to pay to obtain the associated health benefits. In children, the majority of studies have found that influenza vaccination was cost-effective, however many of the studies included (indirect) productivity gains, which may not be given the same weight in all settings. Several studies have attempted to predict the cost-effectiveness of interventions (including prepandemic vaccination) to help protect against a future pandemic, however estimating the cost-effectiveness has been complicated by uncertainty as to the severity of a potential future pandemic and the efficacy of measures against it. Research Influenza research includes molecular virology, molecular evolution, pathogenesis, host immune responses, genomics, and epidemiology. These help in developing influenza countermeasures such as vaccines, therapies and diagnostic tools. Improved influenza countermeasures require basic research on how viruses enter cells, replicate, mutate, evolve into new strains and induce an immune response. The Influenza Genome Sequencing Project is creating a library of influenza sequences that will help researchers understanding of what makes one strain more lethal than another, what genetic determinants most affect immunogenicity, and how the virus evolves over time. Solutions to limitations in current vaccine methods are being researched. A different approach uses Internet content to estimate the impact of an influenza vaccination campaign. More specifically, researchers have used data from Twitter and Microsofts Bing search engine, and proposed a statistical framework which, after a series of operations, maps this information to estimates of the influenza-like illness reduction percentage in areas where vaccinations have been performed. The method has been used to quantify the impact of two flu vaccination programmes in England (2013/14 and 2014/15), where school-age children were administered a live attenuated influenza vaccine (LAIV). Notably, the impact estimates were in accordance with estimations from Public Health England based on traditional syndromic surveillance endpoints. Rapid response to pandemic flu The rapid development, production, and distribution of pandemic influenza vaccines could potentially save millions of lives during an influenza pandemic. Due to the short time frame between identification of a pandemic strain and need for vaccination, researchers are looking at novel technologies for vaccine production that could provide better "real-time" access and be produced more affordably, thereby increasing access for people living in low- and moderate-income countries, where an influenza pandemic may likely originate, such as live attenuated (egg-based or cell-based) technology and recombinant technologies (proteins and virus-like particles). As of July 2009, more than seventy known clinical trials have been completed or are ongoing for pandemic influenza vaccines. In September 2009, the FDA approved four vaccines against the 2009 H1N1 influenza virus (the 2009 pandemic strain), and expected the initial vaccine lots to be available within the following month.In January 2020, the US Food and Drug Administration (FDA) approved Audenz as a vaccine for the H5N1 flu virus. Audenz is a vaccine indicated for active immunization for the prevention of disease caused by the influenza A virus H5N1 subtype contained in the vaccine. Audenz is approved for use in persons six months of age and older at increased risk of exposure to the influenza A virus H5N1 subtype contained in the vaccine. Universal flu vaccines A "universal vaccine" that would not have to be designed and made for each flu season in each hemisphere would stabilize the supply, avoid error in predicting the seasons variants, and protect against escape of the circulating strains by mutation. Such a vaccine has been the subject of research for decades.One approach is to use broadly neutralizing antibodies that, unlike the annual seasonal vaccines used over the first decades of the 21st century that provoke the body to generate an immune response, instead provide a component of the immune response itself. The first neutralizing antibodies were identified in 1993, via experimentation. It was found that the flu neutralizing antibodies bound to the stalk of the Hemagglutinin protein. Antibodies that could bind to the head of those proteins were identified. The highly conserved M2 proton channel was proposed as a potential target for broadly neutralizing antibodies.The challenges for researchers are to identify single antibodies that could neutralize many subtypes of the virus, so that they could be useful in any season, and that target conserved domains that are resistant to antigenic drift.Another approach is to take the conserved domains identified from these projects, and to deliver groups of these antigens to provoke an immune response; various approaches with different antigens, presented different ways (as fusion proteins, mounted on virus-like particles, on non-pathogenic viruses, as DNA, and others), are under development.Efforts have also been undertaken to develop universal vaccines that specifically activate a T-cell response, based on clinical data showing that people with a strong, early T-cell response have better outcomes when infected with influenza and because T-cells respond to conserved epitopes. The challenge for developers is that these epitopes are on internal protein domains that are only mildly immunogenic.Along with the rest of the vaccine field, people working on universal vaccines have experimented with vaccine adjuvants to improve the ability of their vaccines to create a sufficiently powerful and enduring immune response. Oral influenza vaccine As of 2019, an oral flu vaccine was in clinical research. The oral vaccine candidate is based on an adenovirus type 5 vector modified to remove genes needed for replication, with an added gene that expresses a small double-stranded RNA hairpin molecule as an adjuvant. In 2020, a Phase II human trial of the pill form of the vaccine showed that it was well tolerated and provided similar immunity to a licensed injectable vaccine. COVID-19 An influenza vaccine and a COVID-19 vaccine may be given safely at the same time. Preliminary research indicates that influenza vaccination does not prevent COVID-19, but may reduce the incidence and severity of COVID-19 infection. Criticism Tom Jefferson, who has led Cochrane Collaboration reviews of flu vaccines, has called clinical evidence concerning flu vaccines "rubbish" and has therefore declared them to be ineffective; he has called for placebo-controlled randomized clinical trials, which most in the field hold as unethical. His views on the efficacy of flu vaccines are rejected by medical institutions including the CDC and the National Institutes of Health, and by key figures in the field like Anthony Fauci.Michael Osterholm, who led the Center for Infectious Disease Research and Policy 2012 review on flu vaccines, recommended getting the vaccine but criticized its promotion, saying, "We have overpromoted and overhyped this vaccine ... it does not protect as promoted. Its all a sales job: its all public relations." Veterinary use Veterinary influenza vaccination aims to achieve the following four objectives: Protection from clinical disease Protection from infection with virulent virus Protection from virus excretion Serological differentiation of infected from vaccinated animals (so-called DIVA principle). Horses Horses with horse flu can run a fever, have a dry hacking cough, have a runny nose, and become depressed and reluctant to eat or drink for several days but usually recover in two to three weeks. "Vaccination schedules generally require a primary course of two doses, 3–6 weeks apart, followed by boosters at 6–12 month intervals. It is generally recognized that in many cases such schedules may not maintain protective levels of antibody and more frequent administration is advised in high-risk situations."It is a common requirement at shows in the United Kingdom that horses be vaccinated against equine flu and a vaccination card must be produced; the International Federation for Equestrian Sports (FEI) requires vaccination every six months. Poultry Poultry vaccines for bird flu are made inexpensively and are not filtered and purified like human vaccines to remove bits of bacteria or other viruses. They usually contain whole virus, not just hemagglutinin as in most human flu vaccines. Another difference between human and poultry vaccines is that poultry vaccines are adjuvated with mineral oil, which induces a strong immune reaction but can cause inflammation and abscesses. "Chicken vaccinators who have accidentally jabbed themselves have developed painful swollen fingers or even lost thumbs, doctors said. Effectiveness may also be limited. Chicken vaccines are often only vaguely similar to circulating flu strains – some contain an H5N2 strain isolated in Mexico years ago. With a chicken, if you use a vaccine thats only 85 percent related, youll get protection, Dr. Cardona said. In humans, you can get a single point mutation, and a vaccine thats 99.99 percent related wont protect you. And they are weaker [than human vaccines]. Chickens are smaller and you only need to protect them for six weeks, because thats how long they live till you eat them, said Dr. John J. Treanor, a vaccine expert at the University of Rochester. Human seasonal flu vaccines contain about 45 micrograms of antigen, while an experimental A(H5N1) vaccine contains 180. Chicken vaccines may contain less than one microgram. You have to be careful about extrapolating data from poultry to humans, warned Dr. David E. Swayne, director of the agriculture departments Southeast Poultry Research Laboratory. Birds are more closely related to dinosaurs."Researchers, led by Nicholas Savill of the University of Edinburgh in Scotland, used mathematical models to simulate the spread of H5N1 and concluded that "at least 95 percent of birds need to be protected to prevent the virus spreading silently. In practice, it is difficult to protect more than 90 percent of a flock; protection levels achieved by a vaccine are usually much lower than this." The Food and Agriculture Organization of the United Nations has issued recommendations on the prevention and control of avian influenza in poultry, including the use of vaccination.A filtered and purified Influenza A vaccine for humans is being developed and many countries have recommended it be stockpiled so if an Avian influenza pandemic starts jumping to humans, the vaccine can quickly be administered to avoid loss of life. Avian influenza is sometimes called avian flu, and commonly bird flu. Pigs Swine influenza vaccines are extensively used in pig farming in Europe and North America. Most swine flu vaccines include an H1N1 and an H3N2 strain. Swine influenza has been recognized as a major problem since the outbreak in 1976. Evolution of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine flu vaccines are effective in controlling the problem when the virus strains match enough to have significant cross-protection. Customised (autogenous) vaccines made from the specific viruses isolated, are made and used in the more difficult cases. The vaccine manufacturer Novartis claims that the H3N2 strain (first identified in 1998) has brought major losses to pig farmers. Abortion storms are a common sign and sows stop eating for a few days and run a high fever. The mortality rate can be as high as fifteen percent. Dogs In 2004, influenza A virus subtype H3N8 was discovered to cause canine influenza. Because of the lack of previous exposure to this virus, dogs have no natural immunity to this virus. However, a vaccine was found in 2004. Annual reformulation Each year, three strains are chosen for selection in that years flu vaccination by the WHO Global Influenza Surveillance and Response System. The chosen strains are the H1N1, H3N2, and Type-B strains thought most likely to cause significant human suffering in the coming season. Starting with the 2012–2013 Northern Hemisphere influenza season (coincident with the approval of quadrivalent influenza vaccines), the WHO has also recommended a 2nd B-strain for use in quadrivalent vaccines. The World Health Organization (WHO) coordinates the contents of the vaccine each year to contain the most likely strains of the virus to attack the next year. "The WHO Global Influenza Surveillance Network was established in 1952 [renamed "Global Influenza Surveillance and Response System" in 2011]. The network comprises four WHO Collaborating Centres (WHO CCs) and 112 institutions in 83 countries, which are recognized by WHO as WHO National Influenza Centres (NICs). These NICs collect specimens in their country, perform primary virus isolation and preliminary antigenic characterization. They ship newly isolated strains to WHO CCs for high level antigenic and genetic analysis, the result of which forms the basis for WHO recommendations on the composition of influenza vaccine for the Northern and Southern Hemisphere each year."The Global Influenza Surveillance and Response Systems selection of viruses for the vaccine manufacturing process is based on its best estimate of which strains will predominate the next year, amounting in the end to well-informed but fallible guesswork.Formal WHO recommendations were first issued in 1973. Beginning in 1999 there have been two recommendations per year: one for the northern hemisphere and the other for the southern hemisphere.Historical annual reformulations of the influenza vaccine are listed in a separate article. Recent WHO seasonal influenza vaccine composition recommendations: 2020–2021 northern hemisphere The composition of virus vaccines for use in the 2020–2021 Northern Hemisphere influenza season recommended by the World Health Organization on February 28, 2020, is:for egg-based: an A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus an A/Hong Kong/2671/2019 (H3N2)-like virus a B/Washington/02/2019 (B/Victoria lineage)-like virus a B/Phuket/3073/2013 (B/Yamagata lineage)-like virusfor cell- or recombinant-based: an A/Hawaii/70/2019 (H1N1)pdm09-like virus an A/Hong Kong/45/2019 (H3N2)-like virus a B/Washington/02/2019 (B/Victoria lineage)-like virus a B/Phuket/3073/2013 (B/Yamagata lineage)-like virusThe WHO recommends that trivalent vaccines use as their influenza B virus a B/Washington/02/2019 (B/Victoria lineage)-like virus. United StatesThe Vaccines and Related Biological Products Advisory Committee (VRBPAC) of the Food and Drug Administration (FDA) recommended that the quadrivalent formulation of egg-based influenza vaccines for the US 2020–2021 influenza season contain the following: an A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus; an A/HongKong/2671/2019 (H3N2)-like virus; a B/Washington/02/2019-like virus (B/Victoria lineage); a B/Phuket/3073/2013-like virus (B/Yamagata lineage).The committee recommended that the quadrivalent formulation of cell- or recombinant-based influenza vaccines for the US 2020–2021 influenza season contain the following: an A/Hawaii/70/2019 (H1N1)pdm09-like virus; an A/HongKong/45/2019 (H3N2)-like virus; a B/Washington/02/2019-like virus (B/Victoria lineage); a B/Phuket/3073/2013-like virus (B/Yamagata lineage)For trivalent influenza vaccines for use in the US for the 2020–2021 influenza season, depending on the manufacturing method of the vaccine, the committee recommended that the A(H1N1)pdm09, A(H3N2) and B/Victoria lineage viruses recommended above for the quadrivalent vaccines be used. European UnionThe composition of virus vaccines for use in the European Union for the 2020–2021 Northern Hemisphere influenza season recommended by the European Medicines Agency on April 1, 2020, was:Egg-based or live attenuated trivalent vaccines should contain: an A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus; an A/Hong Kong/2671/2019 (H3N2)-like virus; a B/Washington/02/2019 (B/Victoria lineage)-like virus.Cell-based trivalent vaccines should contain: an A/Hawaii/70/2019 (H1N1)pdm09-like virus; an A/Hong Kong/45/2019 (H3N2)-like virus; a B/Washington/02/2019 (B/Victoria lineage)-like virus.A B/Phuket/3073/2013-like virus is recommended in addition to the strains mentioned above for the quadrivalent vaccines. 2021 southern hemisphere The composition of vaccines for use in the 2021 Southern Hemisphere influenza season influenza season recommended by the World Health Organization in September 2020:For egg-based (trivalent): an A/Victoria/2570/2019 (H1N1)pdm09-like virus; an A/Hong Kong/2671/2019 (H3N2)-like virus; and a B/Washington/02/2019 (B/Victoria lineage)-like virus.For cell- or recombinant-based (trivalent): an A/Wisconsin/588/2019 (H1N1)pdm09-like virus; an A/Hong Kong/45/2019 (H3N2)-like virus; and a B/Washington/02/2019 (B/Victoria lineage)-like virus.The quadrivalent version should contain, in addition to the above: a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.In Australia, the standard vaccine under the National Immunisation Program for 2021 is the quadrivalent one. 2021–2022 northern hemisphere The composition of virus vaccines for use in the 2021–2022 Northern Hemisphere influenza season is European UnionThe composition of virus vaccines for use in the European Union for the 2021–2022 Northern Hemisphere influenza season recommended by the European Medicines Agency on March 30, 2021, is:Egg-based or live attenuated trivalent vaccines should contain: an A/Victoria/2570/2019 (H1N1)pdm09-like virus; an A/Cambodia/e0826360/2020 (H3N2)-like virus; a B/Washington/02/2019 (B/Victoria lineage)-like virus.Cell-based trivalent vaccines should contain: an A/Wisconsin/588/2019 (H1N1)pdm09-like virus; an A/Cambodia/e0826360/2020 (H3N2)-like virus; a B/Washington/02/2019 (B/Victoria lineage)-like virus.A B/Phuket/3073/2013-like virus is recommended in addition to the strains mentioned above for the quadrivalent vaccines. United StatesThe FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended that the quadrivalent formulation of egg-based influenza vaccines for the US 2021-2022 influenza season contain the following: an A/Victoria/2570/2019 (H1N1) pdm09-like virus; an A/Cambodia/e0826360/2020 (H3N2)-like virus; a B/Washington/02/2019- like virus (B/Victoria lineage); a B/Phuket/3073/2013-like virus (B/Yamagata lineage).The committee recommended that the quadrivalent formulation of cell- or recombinant based influenza vaccines for the US 2021-2022 influenza season contain the following: an A/Wisconsin/588/2019 (H1N1) pdm09-like virus; an A/Cambodia/e0826360/2020 (H3N2)-like virus; a B/Washington/02/2019- like virus (B/Victoria lineage); a B/Phuket/3073/2013-like virus (B/Yamagata lineage).For trivalent influenza vaccines for use in the US for the 2021-2022 influenza season, depending on the manufacturing method of the vaccine, the committee recommended that the A(H1N1) pdm09, A(H3N2) and B/Washington/02/2019-like virus (B/Victoria lineage) viruses recommended above for the quadrivalent vaccines be used. 2022 southern hemisphere The composition of vaccines for use in the 2022 Southern Hemisphere influenza season influenza season recommended by the World Health Organization in September 2021:Egg-based vaccines: A/Victoria/2570/2019 (H1N1)pdm09-like virus; A/Darwin/9/2021 (H3N2)-like virus; B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.Cell- or recombinant-based vaccines: A/Wisconsin/588/2019 (H1N1)pdm09-like virus; A/Darwin/6/2021 (H3N2)-like virus; B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.It is recommended that trivalent influenza vaccines for use in the 2022 southern hemisphere influenza season contain the following: Egg-based vaccines: A/Victoria/2570/2019 (H1N1)pdm09-like virus; A/Darwin/9/2021 (H3N2)-like virus; and B/Austria/1359417/2021 (B/Victoria lineage)-like virus.Cell- or Recombinant-based vaccines: A/Wisconsin/588/2019 (H1N1)pdm09-like virus; A/Darwin/6/2021 (H3N2)-like virus; and B/Austria/1359417/2021 (B/Victoria lineage)-like virus 2022–2023 northern hemisphere The composition of virus vaccines for use in the 2022–2023 Northern Hemisphere influenza season is European UnionThe composition of virus vaccines for use in the European Union for the 2022–2023 Northern Hemisphere influenza season recommended by the European Medicines Agency on March 29, 2022, is:Quadrivalent egg-based or live attenuated vaccines should contain: an A/Victoria/2570/2019 (H1N1)pdm09-like virus; an A/Darwin/9/2021 (H3N2)-like virus; a B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.Quadrivalent cell-culture or recombinant-based vaccines should contain: an A/Wisconsin/588/2019 (H1N1)pdm09-like virus; an A/Darwin/6/2021 (H3N2)-like virus; a B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.United StatesThe FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended that the quadrivalent formulation of egg-based influenza vaccines for the U.S. 2022-2023 influenza season contain the following: an A/Victoria/2570/2019 (H1N1)pdm09-like virus; an A/Darwin/9/2021 (H3N2)-like virus; a B/Austria/1359417/2021-like virus (B/Victoria lineage); and a B/Phuket/3073/2013-like virus (B/Yamagata lineage).The committee recommended that the quadrivalent formulation of cell- or recombinant-based influenza vaccines for the US 2022–2023 influenza season contain the following: an A/Wisconsin/588/2019 (H1N1)pdm09-like virus; an A/Darwin/6/2021 (H3N2)-like virus; a B/Austria/1359417/2021-like virus (B/Victoria lineage); and a B/Phuket/3073/2013-like virus (B/Yamagata lineage).For trivalent influenza vaccines for use in the US for the 2022–2023 influenza season, depending on the manufacturing method of the vaccine, the committee recommended that the A(H1N1)pdm09, A(H3N2) and B/Austria/1359417/2021-like virus (B/Victoria lineage) viruses recommended above for the quadrivalent vaccines be used. Notes See also H5N1 vaccine Seasonal influenza vaccine brands Universal influenza vaccine References Further reading World Health Organization (October 2017). The immunological basis for immunization series: module 23: influenza vaccines. World Health Organization (WHO). hdl:10665/259211. ISBN 978-9241513050. Ramsay M (ed.). "Chapter 19: Influenza". Immunisation against infectious disease. Public Health England. Hamborsky J, Kroger A, Wolfe S, eds. (2015). "Chapter 12: Influenza". Epidemiology and Prevention of Vaccine-Preventable Diseases (13th ed.). Washington D.C.: U.S. Centers for Disease Control and Prevention (CDC). ISBN 978-0990449119. Budd A, Blanton L, Grohskopf L, Campbell A, Dugan V, Wentworth DE, et al. (March 29, 2019). "Chapter 6: Influenza". In Roush SW, Baldy LM, Hall MA (eds.). Manual for the surveillance of vaccine-preventable diseases. Atlanta GA: U.S. Centers for Disease Control and Prevention (CDC). National Advisory Committee on Immunization (May 2020). "Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine for 2020–2021" (PDF). Public Health Agency of Canada. Cat.: HP37-25F-PDF; Pub.: 200003. Lay summary. {{cite web}}: Cite uses deprecated parameter |lay-url= (help) National Advisory Committee on Immunization (NACI) (May 2018). NACI literature review on the comparative effectiveness and immunogenicity of subunit and split virus inactivated influenza vaccines in adults 65 years of age and older (PDF). Government of Canada. ISBN 9780660264387. Cat.: HP40-213/2018E-PDF; Pub.: 180039. Lay summary. {{cite book}}: Cite uses deprecated parameter |lay-url= (help) Rajaram S, Wojcik R, Moore C, Ortiz de Lejarazu R, de Lusignan S, Montomoli E, et al. (August 2020). "The impact of candidate influenza virus and egg-based manufacture on vaccine effectiveness: Literature review and expert consensus". Vaccine. 38 (38): 6047–6056. doi:10.1016/j.vaccine.2020.06.021. PMID 32600916. External links Inactivated Influenza Vaccine Information Statement, US Centers for Disease Control and Prevention (CDC) Live, Intranasal Influenza Vaccine Information Statement, US Centers for Disease Control and Prevention (CDC) Seasonal Influenza (Flu) Vaccination and Preventable Disease, US Centers for Disease Control and Prevention (CDC) Misconceptions about Seasonal Flu and Flu Vaccines, US Centers for Disease Control and Prevention (CDC) "Influenza Vaccine". Drug Information Portal. U.S. National Library of Medicine. Influenza Vaccines at the US National Library of Medicine Medical Subject Headings (MeSH)

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I'm encountering the term 'Nail–patella syndrome' in medical literature. What's its definition?

Nail–patella syndrome is a genetic disorder that results in small, poorly developed nails and kneecaps, but can also affect many other areas of the body, such as the elbows, chest, and hips. The name "nail–patella" can be very misleading because the syndrome often affects many other areas of the body, including even the production of certain proteins.: 666  Those affected by NPS may have one or more affected areas of the body, and its severity varies depending on the individual. It is also referred to as iliac horn syndrome, hereditary onychoosteodysplasia (HOOD syndrome), Fong disease or Turner–Kieser syndrome.Diagnosis of NPS can be made at birth but is common for it to remain undiagnosed for several generations. While there is no cure available for NPS, treatment is available and recommended. Signs and symptoms The skeletal structures of individuals who have this disorder may have pronounced deformities. As reported by several medical doctors, the following features are commonly found in people who with nail–patella syndrome:Bones and joints Patellar involvement is present in approximately 90% of patients; however, patellar aplasia occurs in only 20%. In instances in which the patellae are smaller or luxated, the knees may be unstable. The elbows may have limited motion (e.g., limited pronation, supination, extension). Subluxation of the radial head may occur. Arthrodysplasia of the elbows is reported in approximately 90% of patients. General hyperextension of the joints can be present. Exostoses arising from the posterior aspect of the iliac bones ("iliac horns") are present in as many as 80% of patients; this finding is considered pathognomonic for the syndrome. Other reported bone changes include scoliosis, scapular hypoplasia, and the presence of cervical ribs. Glaucoma is also closely associated with nail-patella, specifically open-angled glaucoma (OAG). Side affects may include frequent headaches, blurred vision, or total vision loss. This occurs gradually over time and symptoms may not be evident in children.Kidney issues may arise such as deposition of protein in the urine and nephritis. Proteinuria is usually the first sign of kidney involvement. It can reveal itself either rapidly or years after having asymptomatic deposition of protein in the urine, kidney failure occurs in around 5% of NPS patients. Hypothyroidism, irritable bowel syndrome, attention deficit hyperactivity disorder (ADHD), and thin tooth enamel are associated with NPS, but whether these are related or simply coincidences are unclear. Genetics Nail–patella syndrome is inherited via autosomal dominancy linked to aberrancy on human chromosome 9s q arm (the longer arm), 9q34. This autosomal dominancy means that only a single copy, instead of both, is sufficient for the disorder to be expressed in the offspring, meaning the chance of getting the disorder from an affected heterozygous parent is 50%. The frequency of the occurrence is 1/50,000. The disorder is linked to the ABO blood group locus.It is associated with random mutations in the LMX1B gene. Studies have been conducted and 83 mutations of this gene have been identified. Diagnosis The hallmark features of this syndrome are poorly developed fingernails, toenails, and patellae (kneecaps). Sometimes, this disease causes the affected person to have either no thumbnails or a small piece of a thumbnail on the edge of the thumb. The lack of development or complete absence of fingernails results from the loss of function mutations in the LMX1B gene. This mutation may cause a reduction in dorsalising signals, which then results in the failure to normally develop dorsal specific structures such as nails and patellae. Other common abnormalities include elbow deformities, abnormally shaped pelvic (hip) bones, and kidney disease. Treatment Treatment for NPS varies depending on the symptoms observed. Perform screening for kidney disease and glaucoma, surgery, intensive physiotherapy, or genetic counseling. ACE inhibitors are taken to treat proteinuria and hypertension in NPS patients. Dialysis and kidney transplant. Physical therapy, bracing and analgesics for joint pain. See also List of cutaneous conditions List of radiographic findings associated with cutaneous conditions References External links GeneReview/NCBI/NIH/UW entry on nail–patella syndrome

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I'm curious about the meaning of the medical term 'Hawkinsinuria.' Can you give me some insights?

Hawkinsinuria is an autosomal dominant metabolic disorder affecting the metabolism of tyrosine.Normally, the breakdown of the amino acid tyrosine involves the conversion of 4-hydroxyphenylpyruvate to homogentisate by 4-hydroxyphenylpyruvate dioxygenase. Complete deficiency of this enzyme would lead to tyrosinemia III. In rare cases, however, the enzyme is still able to produce the reactive intermediate 1,2-epoxyphenyl acetic acid, but is unable to convert this intermediate to homogentisate. The intermediate then spontaneously reacts with glutathione to form 2-L-cystein-S-yl-1,4-dihydroxy-cyclohex-5-en-1-yl acetic acid (hawkinsin).Patients present with metabolic acidosis during the first year of life, and growth arrest around the time of weaning off breast milk. Treatment involves a diet containing a low amount of phenylalanine and tyrosine. Tolerance toward these amino acids normalizes as the patients get older. Then only a chlorine-like smell of the urine indicates the presence of the condition. Patients have a normal life and do not require treatment or a special diet.The production of hawkinsin is the result of a gain-of-function mutation. Inheritance of hawkinsinuria is therefore autosomal dominant (presence of a single mutated copy of the gene causes the condition). The gene affected is the HPD gene encoding 4-hydroxyphenylpyruvic acid dioxygenase, on chromosome 12q24. It is unusual in that most other inborn errors of metabolism are caused by loss-of-function mutations, and hence have recessive inheritance (condition occurs only if both copies are mutated). See also 4-Hydroxyphenylpyruvate dioxygenase References == External links ==

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I'm trying to understand 'Boomerang dysplasia' within a medical context. Could you shed some light on it?

Boomerang dysplasia is a lethal form of osteochondrodysplasia known for a characteristic congenital feature in which bones of the arms and legs are malformed into the shape of a boomerang. Death usually occurs in early infancy due to complications arising from overwhelming systemic bone malformations.Osteochondrodysplasias are skeletal disorders that cause malformations of both bone and cartilage. Presentation Prenatal and neonatal diagnosis of boomerang dysplasia includes several prominent features found in other osteochondrodysplasias, though the "boomerang" malformation seen in the long bones is the delineating factor.Featured symptoms of boomerang dysplasia include: dwarfism (a lethal type of infantile dwarfism caused by systemic bone deformities), underossification (lack of bone formation) in the limbs, spine and ilium (pelvis); proliferation of multinucleated giant-cell chondrocytes (cells that produce cartilage and play a role in skeletal development - chondrocytes of this type are rarely found in osteochondrodysplasias), brachydactyly (shortened fingers) and micromelia (undersized, shortened bones).The characteristic "boomerang" malformation presents intermittently among random absences of long bones throughout the skeleton, in affected individuals. For example, one individual may have an absent radius and fibula, with the "boomerang" formation found in both ulnas and tibias. Another patient may present "boomerang" femora, and an absent tibia. Cause Mutations in the Filamin B (FLNB) gene cause boomerang dysplasia. FLNB is a cytoplasmic protein that regulates intracellular communication and signalling by cross-linking the protein actin to allow direct communication between the cell membrane and cytoskeletal network, to control and guide proper skeletal development. Disruptions in this pathway, caused by FLNB mutations, result in the bone and cartilage abnormalities associated with boomerang dysplasia.Chondrocytes, which also have a role in bone development, are susceptible to these disruptions and either fail to undergo ossification, or ossify incorrectly.FLNB mutations are involved in a spectrum of lethal bone dysplasias. One such disorder, atelosteogenesis type I, is very similar to boomerang dysplasia, and several symptoms of both often overlap. Genetics Early journal reports of boomerang dysplasia suggested X-linked recessive inheritance, based on observation and family history. It was later discovered, however, that the disorder is actually caused by a sporadic genetic mutation fitting an autosomal dominant genetic profile.Autosomal dominant inheritance indicates that the defective gene responsible for a disorder is located on an autosome, and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.Boomerang dysplasia, although an autosomal dominant disorder, is not inherited because those afflicted do not live beyond infancy. They cannot pass the gene to the next generation. Diagnosis Treatment See also Larsen syndrome References == External links ==

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I'm not familiar with the medical term 'Macular degeneration.' Could you provide some insights?

Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, some people experience a gradual worsening of vision that may affect one or both eyes. While it does not result in complete blindness, loss of central vision can make it hard to recognize faces, drive, read, or perform other activities of daily life. Visual hallucinations may also occur but these do not represent a mental illness.Macular degeneration typically occurs in older people. Genetic factors and smoking also play a role. It is due to damage to the macula of the retina. Diagnosis is by a complete eye exam. The severity is divided into early, intermediate, and late types. The late type is additionally divided into "dry" and "wet" forms with the dry form making up 90% of cases.The difference between the two forms is the change of macula. Those with dry form AMD have drusen, cellular debris in their macula that gradually damages light-sensitive cells and leads to vision loss. In wet form AMD, blood vessels grow under the macula, causing blood and fluid to leak into the retina.Preventive efforts include exercising, eating well, and not smoking. There is no cure or treatment that returns vision already lost. In the wet form, anti-VEGF medication injected into the eye or less commonly laser coagulation or photodynamic therapy may slow worsening. Antioxidant vitamins and minerals do not appear to be useful for prevention. However, dietary supplements may slow the progression in those who already have the disease.Age-related macular degeneration is a main cause of central blindness among the working-aged population worldwide. As of 2020, it affects more than 190 million people globally with the prevalence expected to increase to 288 million people by 2040 as the proportion of elderly persons in the population increases. It is equally seen in males and females and it is more common in those of European or North American ancestry. In 2013, it was the fourth most common cause of blindness after cataracts, preterm birth, and glaucoma. It most commonly occurs in people over the age of fifty and in the United States is the most common cause of vision loss in this age group. About 0.4% of people between 50 and 60 have the disease, while it occurs in 0.7% of people 60 to 70, 2.3% of those 70 to 80, and nearly 12% of people over 80 years old. Signs and symptoms Early or intermediate AMD may be asymptomatic, or it may present with blurred or decreased vision in one or both eyes. This may manifest initially as difficulty with reading or driving (especially in poorly lit areas). Other symptoms of AMD include distortion of vision and blind spots (especially in and around the central visual field).Other signs and symptoms of macular degeneration include: Distorted vision in the form of metamorphopsia, in which a grid of straight lines appears wavy and parts of the grid may appear blank: Patients often first notice this when looking at things like miniblinds in their home or telephone poles while driving. There may also be central scotomas, shadows or missing areas of vision Slow recovery of visual function after exposure to bright light (photostress test) Visual acuity drastically decreasing (two levels or more), e.g.: 20/20 to 20/80 Blurred vision: Those with nonexudative (wet) macular degeneration may be asymptomatic or notice a gradual loss of central vision, whereas those with exudative (dry) macular degeneration often notice a rapid onset of vision loss (often caused by leakage and bleeding of abnormal blood vessels). Trouble discerning colors, specifically dark ones from dark ones and light ones from light ones A loss in contrast sensitivity Formed visual hallucinations and flashing lights have also been associated with severe visual loss secondary to wet AMD Macular degeneration by itself will not lead to total blindness. For that matter, only a small number of people with visual impairment are totally blind. In almost all cases, some vision remains, mainly peripheral. Other complicating conditions may lead to such an acute condition (severe stroke or trauma, untreated glaucoma, etc.), but few macular degeneration patients experience total visual loss.The area of the macula constitutes only about 2.1% of the retina, and the remaining 97.9% (the peripheral field) remains unaffected by the disease. Even though the macula provides such a small fraction of the visual field, almost half of the visual cortex is devoted to processing macular information.In addition, people with dry macular degeneration often do not experience any symptoms but can experience gradual onset of blurry vision in one or both eyes. People with wet macular degeneration may experience acute onset of visual symptoms. Risk factors Key risk factors are age, race/ethnicity, smoking, and family history. Advanced age is the strongest predictor of AMD, particularly over 50. Race/Ethnicity As illustrated by the Figure in this section, derived from data presented by the National Eye Institute of the United States (https://www.nei.nih.gov/learn-about-eye-health/eye-health-data-and-statistics/age-related-macular-degeneration-amd-data-and-statistics/age-related-macular-degeneration-amd-tables), among those over 80 years of age, White individuals are more than 6-fold more likely to develop AMD than Black or Hispanic individuals. Thus, white background is a major risk factor for AMD. In Caucasian (White) skin, there is a specific group of polymorphic genes (with single nucleotide alterations) that encode for enzymes and transcription factors responsible for the early steps (including the first step, formation of L-DOPA from the amino acid tyrosine) of the melanin synthesis pathway. Many of these enzymes and transcription factors are reviewed by Markiewicz and Idowu. Also, as reviewed by Sturm et al. “increasing intracellular concentrations of either tyrosine or L-DOPA both result in an increase in melanogenesis” or formation of the black pigment melanin. Thus there appears to be an association between reduced L-DOPA production and white skin. As suggested by the Figure and information in this section, reduced L-DOPA, resulting in white skin, appears to be associated with an increased risk of macular degeneration for white individuals over the age of 80. Environment and lifestyle Smoking: Smoking tobacco increases the risk of AMD by two to three times that of someone who has never smoked, and may be the most important modifiable factor in its prevention. A review of previous studies found "a strong association between current smoking and AMD. ... Cigarette smoking is likely to have toxic effects on the retina." Hypertension (high blood pressure): In the ALIENOR study 2013, early and late AMD were not significantly associated with systolic or diastolic blood pressure (BP), hypertension, or use of antihypertensive medications, but elevated pulse pressure [(PP) systolic BP minus diastolic BP] was significantly associated with an increased risk of late AMD. Atherosclerosis High cholesterol: Elevated cholesterol may increase the risk of AMD Obesity: Abdominal obesity is a risk factor, especially among men Fat intake: Consuming high amounts of certain fats, including saturated fats, trans fats, and omega-6 fatty acids, likely contributes to AMD, while monounsaturated fats are potentially protective. In particular, omega-3 fatty acids may decrease the risk of AMD. Exposure to UV light from sunlight is maybe associated with an increased risk of developing AMD, although evidence is weaker than other causes. A digital screen does not radiate harmful energy against human eyes, but staring at the screen for a long time without pauses does increase eye strain. There is no evidence to support the claim that exposure to digital screens contributes to the risk of macular degeneration. Genetics AMD is a highly heritable condition. Recurrence ratios for siblings of an affected individual are three- to six-fold higher than in the general population. Genetic linkage analysis has identified 5 sets of gene variants at three locations on different chromosomes (1, 6 and 10) as explaining at least 50% of the risk. These genes have roles regulating the immune response, inflammatory processes and homeostasis of the retina. Variants of these genes give rise to different kinds of dysfunction in these processes. Over time, this results in accumulation of intracellular and extracellular metabolic debris. This can cause scarring of the retina or breakdown of its vascularization. The list of genetic variations association with AMD include complement factors, apolipoprotein E, fibroblast growth factor 2, DNA excision repair protein, and age-related maculopathy susceptibility protein 2.Although genetic testing can lead to the identification of genetic variation which can predispose to AMD, the complex pathogenesis of the condition prevents the use of these tests in routine practice. Nevertheless, they can be useful in selecting patients for clinical trials and analysing their response to treatment. The three loci where identified gene variants are found are designated: Complement Factor H (CFH) on chromosome 1 at location 1q31.3 HTRA serine peptidase 1/Age Related Maculopathy Susceptibility 2 (HTRA1/ARMS2) on chromosome 10 at location 10q26 Complement Factor B/Complement Component 2 (CFB/CC2) on chromosome 6 at 6p21.3 Specific genes Polymorphisms in genes for complement system proteins: Variation in the genes for the complement system proteins factor H (CFH), factor B (CFB) and factor 3 (C3), among others, are strongly associated with a persons risk for developing AMD. CFH is involved in inhibiting the inflammatory response. The mutation in CFH (Y402H) results in reduced ability of the protein to localise to and protect tissues such as the retina from complement overactivation. Absence of the complement factor H-related genes R3 and R1 protects against AMD. Two independent studies in 2007 showed a certain common mutation Arg80Gly in the C3 gene, which is a central protein of the complement system, is strongly associated with the occurrence of AMD. The authors of both papers consider their study to underscore the influence of the complement pathway in the pathogenesis of this disease. In two 2006 studies, another gene that has implications for the disease, called HTRA1 (encoding a secreted serine protease), was identified. Six mutations of the gene SERPING1 (Serpin Peptidase Inhibitor, Clade G (C1 Inhibitor), Member 1) are associated with AMD. Mutations in this gene can also cause hereditary angioedema. Fibulin-5 mutation: Rare forms of the disease are caused by genetic defects in fibulin-5, in an autosomal dominant manner. In 2004, Stone et al. performed a screen on 402 AMD patients and revealed a statistically significant correlation between mutations in fibulin-5 and incidence of the disease. Mitochondrial-related gene polymorphisms such as that in the MT-ND2 molecule, predicts wet AMD. Pathophysiology The pathogenesis of age-related macular degeneration is not well known, although some theories have been put forward, including oxidative stress, mitochondrial dysfunction, and inflammatory processes. The imbalance between the production of damaged cellular components and degradation leads to the accumulation of harmful products, for example, intracellular lipofuscin and extracellular drusen. Incipient atrophy is demarcated by areas of retinal pigment epithelium (RPE) thinning or depigmentation that precede geographic atrophy in the early stages of AMD. In advanced stages of AMD, atrophy of the RPE (geographic atrophy) and/or development of new blood vessels (neovascularization) result in the death of photoreceptors and central vision loss. In the dry (nonexudative) form, drusen accumulates between the retina and the choroid, causing atrophy and scarring to the retina. In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid (neovascularization) behind the retina which can leak exudate and fluid and also cause hemorrhaging. Early work demonstrated a family of immune mediators was plentiful in drusen. Complement factor H (CFH) is an important inhibitor of this inflammatory cascade, and a disease-associated polymorphism in the CFH gene strongly associates with AMD. Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced. Lending credibility to this has been the discovery of disease-associated genetic polymorphisms in other elements of the complement cascade including complement component 3 (C3).A powerful predictor of AMD is found on chromosome 10q26 at LOC 387715. An insertion/deletion polymorphism at this site reduces expression of the ARMS2 gene though destabilization of its mRNA through deletion of the polyadenylation signal. ARMS2 protein may localize to the mitochondria and participate in energy metabolism, though much remains to be discovered about its function. Other gene markers of progression risk includes tissue inhibitor of metalloproteinase 3 (TIMP3), suggesting a role for extracellular matrix metabolism in AMD progression. Variations in cholesterol metabolising genes such as the hepatic lipase, cholesterol ester transferase, lipoprotein lipase and the ATP-binding cassette A1 correlate with disease progression. The early stigmata of disease, drusen, are rich in cholesterol, offering face validity to the results of genome-wide association studies. Stages In AMD there is a progressive accumulation of characteristic yellow deposits, called drusen (buildup of extracellular proteins and lipids), in the macula (a part of the retina), between the retinal pigment epithelium and the underlying choroid. This accumulation is believed to damage the retina over time. Amyloid beta, which builds up in Alzheimers disease brains, is one of the proteins that accumulate in AMD, which is a reason why AMD is sometimes called "Alzheimers of the eye" or "Alzheimers of the retina". AMD can be divided into 3 stages: early, intermediate, and late, based partially on the extent (size and number) of drusen.AMD-like pathology begins with small yellow deposits (drusen) in the macula, between the retinal pigment epithelium and the underlying choroid. Most people with these early changes (referred to as age-related maculopathy) still have good vision. People with drusen may or may not develop AMD. In fact, the majority of people over age 60 have drusen with no adverse effects. The risk of developing symptoms is higher when the drusen are large and numerous, and associated with the disturbance in the pigmented cell layer under the macula. Large and soft drusen are thought to be related to elevated cholesterol deposits. Early AMD Early AMD is diagnosed based on the presence of medium-sized drusen, about the width of an average human hair. Early AMD is usually asymptomatic. Intermediate AMD Intermediate AMD is diagnosed by large drusen and/or any retinal pigment abnormalities. Intermediate AMD may cause some vision loss, but, like early AMD, it is usually asymptomatic.Recently, subgroups of intermediate AMD have been identified, which have a very high risk of progression toward late AMD. This subgroup (depending on the precise definitions) is termed nascent GA and/or iRORA (incomplete retinal pigment epithelium and outer retinal atrophy). These high-risk subgroups of intermediate AMD can be used to inform patients of theirs prognosis. In addition, these can be applied in clinical trials as endpoints. Late AMD In late AMD, enough retinal damage occurs that, in addition to drusen, people will also begin to experience symptomatic central vision loss. The damage can either be the development of atrophy or the onset of neovascular disease. Late AMD is further divided into two subtypes based on the types of damage: Geographic atrophy and Wet AMD (also called Neovascular AMD). Dry AMD Dry AMD (also called nonexudative AMD) is a broad designation, encompassing all forms of AMD that are not neovascular (wet AMD). This includes early and intermediate forms of AMD, as well as the advanced form of dry AMD known as geographic atrophy. Dry AMD patients tend to have minimal symptoms in the earlier stages; visual function loss occurs more often if the condition advances to geographic atrophy. Dry AMD accounts for 80–90% of cases and tends to progress slowly. In 10–20% of people, dry AMD progresses to the wet type. Geographic atrophy Geographic atrophy (also called atrophic AMD) is an advanced form of AMD in which progressive and irreversible loss of retinal cells leads to a loss of visual function. There are multiple layers that make up the retina, and in geographic atrophy, there are three specific layers that undergo atrophy: the choriocapillaris, retinal pigment epithelium, and the overlying photoreceptors. The three layers that undergo atrophy in geographic atrophy are all adjacent to each other. The photoreceptors are the most superficial and they are the cells that are responsible for converting energy from the light from the outside world, into an electrical signal to be sent to the brain. There are several functions of the retinal pigment epithelium. One of the main functions of the retinal pigment epithelium is to minimize oxidative stress. It does so by absorbing light, and thus preventing it from getting to the underlying layers. The layers underlying the retinal pigment epithelium are very vascularlized so they have very high oxygen tension. Thus, if light was to get to those layers, many free radicals would form and cause damage to nearby tissues. The deepest layer that undergoes atrophy in geographic atrophy is called the choriocappilaris. It is a capillary network that provides nutrients to the retinal pigment epithelium. The pathophysiology of geographic atrophy is still uncertain. Some studies questioned whether it was due to a deficient retinal pigment epithelium, leading to increased oxidative stress. Other studies have looked for inflammatory causes of damage. Thus far, the medical community is still not certain. Recent studies have begun to look at each layer individually. They found that decrease blood flow in the choriocapillaris precedes atrophy of the retinal pigment epithelium and the overlying photoreceptors. Since the choriocapillaris is a vascular layer, this may be used as an argument for why geographic atrophy could be a disease due to decreased blood flow. Wet AMD Neovascular or exudative AMD, the "wet" form of advanced AMD, causes vision loss due to abnormal blood vessel growth (choroidal neovascularization) in the choriocapillaris, through Bruchs membrane. It is usually, but not always, preceded by the dry form of AMD. The proliferation of abnormal blood vessels in the retina is stimulated by vascular endothelial growth factor (VEGF). Because these blood vessels are abnormal, these are also more fragile than typical blood vessels, which ultimately leads to blood and protein leakage below the macula. Bleeding, leaking, and scarring from these blood vessels eventually cause irreversible damage to the photoreceptors and rapid vision loss if left untreated. Oxidative stress Age-related accumulation of low-molecular-weight, phototoxic, pro-oxidant melanin oligomers within lysosomes in the retinal pigment epithelium (RPE) may be partly responsible for decreasing the digestive rate of photoreceptor outer rod segments (POS) by the RPE – autophagy. A decrease in the digestive rate of POS has been shown to be associated with lipofuscin formation – a classic sign associated with AMD.The role of retinal oxidative stress in the cause of AMD by resulting in further inflammation of the macula is suggested by the enhanced rate of disease in smokers and those exposed to UV irradiation.Mitochondrial dysfunction may play a role. Evidence was recently reviewed that damage to mitochondrial DNA may be an essential element of AMD pathogenesis and that overproduction of reactive oxygen species may play a role in this process. Diagnosis Diagnosis of age-related macular degeneration depends on signs in the macula, not necessarily vision. Early diagnosis of AMD can prevent further visual deterioration and potentially improve vision.Diagnosis of dry (or early stage) AMD may include the following clinical examinations as well as procedures and tests: The transition from dry to wet AMD can happen rapidly, and if it is left untreated can lead to legal blindness in as little as six months. To prevent this from occurring and to initiate preventive strategies earlier in the disease process, dark adaptation testing may be performed. A dark adaptometer can detect subclinical AMD at least three years earlier than it is clinically evident. There is a loss of contrast sensitivity, so that contours, shadows, and color vision are less vivid. The loss in contrast sensitivity can be quickly and easily measured by a contrast sensitivity test like Pelli Robson performed either at home or by an eye specialist. When viewing an Amsler grid, some straight lines appear wavy and some patches appear blank When viewing a Snellen chart, at least 2 lines decline In dry macular degeneration, which occurs in 85–90 percent of AMD cases, drusen spots can be seen in Fundus photography Using an electroretinogram, points in the macula with a weak or absent response compared to a normal eye may be found Farnsworth-Munsell 100 hue test and Maximum Color Contrast Sensitivity test (MCCS) for assessing color acuity and color contrast sensitivity Optical coherence tomography is now used by most ophthalmologists in the diagnosis and the follow-up evaluation of the response to treatment with antiangiogenic drugs.Diagnosis of wet (or late stage) AMD may include the following in addition to the above tests: Preferential hyperacuity perimetry changes (for wet AMD). Preferential hyperacuity perimetry is a test that detects drastic changes in vision and involves the macula being stimulated with distorted patterns of dots and the patient identification of where in the visual field this occurs. In wet macular degeneration, angiography can visualize the leakage of bloodstream behind the macula. Fluorescein angiography allows for the identification and localization of abnormal vascular processes. Histology Pigmentary changes in the retina – In addition to the pigmented cells in the iris (the colored part of the eye), there are pigmented cells beneath the retina. As these cells break down and release their pigment, dark clumps of released pigment and later, areas that are less pigmented may appear Exudative changes: hemorrhages in the eye, hard exudates, subretinal/sub-RPE/intraretinal fluid Drusen, tiny accumulations of extracellular material that build up on the retina. While there is a tendency for drusen to be blamed for the progressive loss of vision, drusen deposits can be present in the retina without vision loss. Some patients with large deposits of drusen have normal visual acuity. If normal retinal reception and image transmission are sometimes possible in a retina when high concentrations of drusen are present, then, even if drusen can be implicated in the loss of visual function, there must be at least one other factor that accounts for the loss of vision. Prevention A 2017 Cochrane review found the use of vitamin and mineral supplements, alone or in combination, by the general population did not affect whether or not AMD started.Refraining from smoking, including fish in the diet and maintaining a healthy weight can prevent AMDThere appears to be a preventive effect of oral L-DOPA against AMD. Several reviews refer to a 2016 retrospective medical records study of 87,000,000 unique individuals by Brilliant et al. In this study those who were on, or had been on, L-DOPA oral medicine for movement disorders (Parkinson’s Disease, etc.) were significantly less likely to develop AMD compared to those not on L-DOPA. If the individuals on L-DOPA did develop AMD, the age of occurrence of the disease was about eight years later than for those without L-DOPA treatment, and for wet AMD, it was about five years later. At least two further reviews summarize a small “proof of concept” clinical research study by Figueroa et al. in 2021 that evaluated whether individuals who already had wet AMD could receive improvement if they took oral L-DOPA. The summary given by both reviews indicates that oral L-DOPA could cause retinal fluid to decrease by almost 30% even without standard anti-VEGF treatment, and this was accompanied by improvement in visual acuity. In addition, there was about a 50% reduction in the need for anti-VEGF injections. RPE and L-DOPA in amelioration of wet AMD The retinal pigment epithelium (RPE) (see diagram) has an essential role in the eye. It secretes a large variety of factors including at least 22 proteins important in maintaining the structure, function and micro-environments on the two sides of the RPE. (The two sides of the RPE include the choroid side, where blood vessels form and bring nourishment to the eye, and the photoreceptor side, with rods and cones that receive light signals.) In particular, the RPE secretes vascular endothelial growth factor (VEGF) at its basement membrane, with the VEGF reaching the choriocapillaris to maintain proper blood vessel formation in the choroid region. Many factors, including genetic factors, hypoxia, oxidative stress and inflammatory stressors, may cause pathologic over-production of VEGF by the RPE. This over-production causes excess blood vessel formation in the choroid region (the choriocapillaris), which is a major cause of wet AMD. However, the RPE has a G-protein coupled receptor, GPR143, that is activated by its ligand, extracellular L-DOPA. Activation of GPR143 reduces RPE secretion of VEGF. Activation of GPR143, with the reduction in VEGF, may be the main protective role of L-DOPA against wet AMD. Management Treatment of AMD varies depending on the category of the disease at the time of diagnosis. In general, treatment is aimed at slowing down the progression of AMD. As of 2018, there are no treatments to reverse the effects of AMD. Early-stage and intermediate-stage AMD is managed by modifying known risk factors such as smoking cessation, management of hypertension and atherosclerosis and making dietary modifications. For intermediate-stage AMD, management also includes antioxidant and mineral supplementation. Advanced-stage AMD is managed based on the presence of choroidal neovascularization (CNV): dry AMD (no CNV present) or wet AMD (CNV present). No effective treatments exist for dry AMD. The CNV present in wet AMD is managed with vascular endothelial growth factor (VEGF) inhibitors. Daily use of an Amsler grid or other home visual monitoring tools can be used to monitor for development of distorted vision, which may be a sign of disease progression. Vitamin and mineral supplementation The age related eye disease studies 1 and 2 (AREDS) showed that those with bilateral early or intermediate AMD, or intermediate AMD in one eye and advanced AMD in the other eye may benefit from specific vitamin and mineral supplementation. The specific vitamins and minerals in AREDS-1 are vitamin C (500 mg), zinc (80 mg), vitamin E (400 IU), copper (2 mg) and beta-carotene (15 mg). In the AREDS-2 formulation, lutein (10 mg) and zeaxanthin (2 mg) replaced beta-carotene due to the risk of lung cancer in smokers taking beta-carotene. These specific micronutrient supplementations were associated with a lower risk of progression to more severe forms of AMD and greater visual acuity at 5 years. There is no evidence that micronutrient supplementation prevents AMD progression in those with severe disease or prevents disease onset in those without AMD. Dry AMD There is no cure for dry AMD. While there is increasing academic and pharmaceutical interest in developing complement inhibitors to treat ophthalmic inflammation, with several clinical trials underway for dry AMD, the first such agent to complete Phase 3 trials in AMD (the anti-factor D agent, lampalizumab) did not significantly improve the rate of disease progression. Nevertheless, strategies targeting different aspects of the complement system are ongoing. Wet AMD Ranibizumab, aflibercept, brolucizumab and faricimab are approved VEGF inhibitors for the treatment of CNV in wet AMD. All three drugs are administered via intravitreal injection, meaning they are injected directly into the eye. Bevacizumab is another VEGF inhibitor that has been shown to have similar efficacy and safety as the previous two drugs, however, is not currently indicated for AMD. AMD can also be treated with laser coagulation therapy.A randomized control trial found that bevacizumab and ranibizumab had similar efficacy, and reported no significant increase in adverse events with bevacizumab. A 2014 Cochrane review found that the systemic safety of bevacizumab and ranibizumab are similar when used to treat neovascular AMD, except for gastrointestinal disorders. Bevacizumab however is not FDA approved for treatment of macular degeneration. A controversy in the UK involved the off-label use of cheaper bevacizumab over the approved, but expensive, ranibizumab. Ranibizumab is a smaller fragment, Fab fragment, of the parent bevacizumab molecule specifically designed for eye injections. Other approved antiangiogenic drugs for the treatment of neo-vascular AMD include pegaptanib and aflibercept.These anti-VEGF agents may be administered monthly or adaptively. For adaptive anti-VEGF treatment, two approaches are conventionally applied. In the case of pro re nata, the patient comes at fixed intervals, but treatment is only administered if an activity is detected (i.e., presence of fluid). In the case of treat-and-extend, the patients always receive treatment, but the interval to the next visit is extended if the lesion was inactive. Recently, researchers have started to apply AI algorithms to predict the future need for treatment. But these approaches have not been validated for clinical use as of today. The American Academy of Ophthalmology practice guidelines do not recommend laser coagulation therapy for macular degeneration, but state that it may be useful in people with new blood vessels in the choroid outside of the fovea who dont respond to drug treatment. There is strong evidence that laser coagulation will result in the disappearance of drusen but does not affect choroidal neovascularisation. A 2007 Cochrane review on found that laser photocoagulation of new blood vessels in the choroid outside of the fovea is effective and economical method, but that the benefits are limited for vessels next to or below the fovea.Photodynamic therapy has also been used to treat wet AMD. The drug verteporfin is administered intravenously; light of a certain wavelength is then applied to the abnormal blood vessels. This activates the verteporfin destroying the vessels. Cataract surgery could improve visual outcomes for people with AMD, though there have been concerns about surgery increasing the progression of AMD. A randomized controlled trial found that people who underwent immediate cataract surgery (within two weeks) had improved visual acuity and better quality of life outcomes than those who underwent delayed cataract surgery (6 months).Radiotherapy has been proposed as a treatment for wet AMD but the evidence to support the use of modern stereotactic radiotherapy combined with anti-VEGF is currently uncertain and is awaiting the results of ongoing studies.Nucleoside reverse transcription inhibitors like they are used in anti-HIV therapy was associated with a reduced risk of developing atrophic macular degeneration. This is because Alu elements undergo L1 (protein)-mediated reverse transcription in the cytoplasm resulting in DNA synthesis. First clinical trials are being prepared as of January 2021. Adaptive devices Because peripheral vision is not affected, people with macular degeneration can learn to use their remaining vision to partially compensate. Assistance and resources are available in many countries and every state in the U.S. Classes for "independent living" are given and some technology can be obtained from a state department of rehabilitation. Adaptive devices can help people read. These include magnifying glasses, special eyeglass lenses, computer screen readers, electronic glasses, and TV systems that enlarge the reading material. Computer screen readers such as JAWS or Thunder work with standard Windows computers. Also, Apple devices provide a wide range of features (voice-over, screen readers, Braille etc.). Video cameras can be fed into standard or special-purpose computer monitors, and the image can be zoomed in and magnified. These systems often include a movable table to move the written material. Accessible publishing provides larger fonts for printed books, patterns to make tracking easier, audiobooks and DAISY books with both text and audio. Epidemiology The prevalence of any age-related macular degeneration is higher in Europeans than in Asians and Africans. There is no difference in prevalence between Asians and Africans. The incidence of age-related macular degeneration and its associated features increases with age and is low in people <55 years of age. Smoking is the strongest modifiable risk factor. As of 2008, age-related macular degeneration accounts for more than 54% of all vision loss in the white population in the US. An estimated 8 million Americans are affected with early age-related macular degeneration, of whom over 1 million will develop advanced age-related macular degeneration within the next 5 years. In the UK, age-related macular degeneration is the cause of blindness in almost 42% of those who go blind aged 65–74 years, almost two-thirds of those aged 75–84 years, and almost three-quarters of those aged 85 years or older. Research directions Association with other age-related diseases Studies indicate drusen associated with AMD are similar in molecular composition to amyloid beta (Aβ) plaques and deposits in other age-related diseases such as Alzheimers disease and atherosclerosis. This suggests that similar pathways may be involved in the etiologies of AMD and other age-related diseases. AMD also shares several genetic and environmental risk factors with the kidneys, which have a similar structure to the eye. Genetic testing Genetic testing can help identify whether a patient with AMD is at a greater risk of developing the condition and can inform disease progression. Genetic testing can also allow researchers to identify whether patients are more or less likely to respond to treatments, such anti-VEGF medication or complement inhibitors. However, there remain several challenges to using predictive tools which incorporate genetic variation in clinical practice. As well as our limited understanding of the way that different genetic variants and environmental factors interact to influence AMD risk, the single nucleotide polymorphisms which are common in the population have small effects on individual patients with AMD. Therefore, there is increasing interest in understanding the functional consequences of rare mutations, which often have more pronounced effects. Genetic testing to guide clinical management is not currently recommended. Stem cell transplant Cell based therapies using bone marrow stem cells as well as retinal pigment epithelial transplantation are being studied. A number of trials have occurred in humans with encouraging results. Genome editing CRISPR-Cas9 genome editing may be used to treat wet age-related macular degeneration caused by VEGFA. Scientists described an approach in which engineered lentiviruses are injected into the affected anatomical regions for transient editing that could reduce the area of choroidal neovascularization by 63% without inducing undesired off-target edits or anti-Cas9 immune responses. Artificial intelligence for prediction Research is exploring if artificial intelligence can help in predicting wet AMD early enough to make prevention possible. A study tested an AI model for predicting whether people with wet AMD in one eye would develop it in the other within six months. Compared to doctors and optometrists the AI model predicted the development more accurately. Other types There are a few other (rare) kinds of macular degeneration with similar symptoms but unrelated in etiology to Wet or Dry age-related macular degeneration. They are all genetic disorders that may occur in childhood or middle age. Vitelliform macular dystrophy Sorsbys fundus dystrophy is an autosomal dominant, retinal disease characterized by sudden acuity loss resulting from untreatable submacular neovascularisation Stargardts disease (juvenile macular degeneration, STGD) is an autosomal recessive retinal disorder characterized by juvenile-onset macular dystrophy, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material.Similar symptoms with a very different etiology and different treatment can be caused by epiretinal membrane or macular pucker or any other condition affecting the macula, such as central serous retinopathy. Notable cases Judi Dench Joan Plowright Peter Sallis June Brown S. Robert Morgan See also Ophthalmology Macula of retina Visual impairment Gene therapy for color blindness Gene therapy of the human retina Stem cell therapy for macular degeneration References External links Macular degeneration at Curlie

You are a conduit for medical education. Your task is to offer detailed explanations of medical terms, ensuring they are understandable and precise.

I need a basic explanation for the medical term 'Variably protease-sensitive prionopathy.'

Variably protease-sensitive prionopathy (VPSPr) (formerly known as Protease Sensitive Prionopathy) is a sporadic prion protein disease first described in an abstract for a conference on prions in 2006, and this study was published in a 2008 report on 11 cases. The study was conducted by Gambetti P., Zou W.Q., and coworkers from the United States National Prion Disease Pathology Surveillance Center. It was first identified as a distinct disease in 2010 by Zou W.Q. and coworkers from the United States National Prion Disease Pathology Surveillance Center.VPSPr is very rare, occurring in just 2 or 3 out of every 100 million people. As of 2018, fourteen cases have been reported in the UK. It has similarities to Creutzfeldt–Jakob disease, but clinical manifestations differ somewhat, and the abnormal prion protein (PrP) is less resistant to digestion by proteases; some variants are more sensitive to proteases than others, hence the name: variably protease-sensitive. Patients present with behavioral and psychiatric symptoms, speech deficits (aphasia and/or dysarthria) and progressive cognitive and motor decline (dementia, ataxia, parkinsonism, psychosis, aphasia and mood disorder). Average age at onset is 70 years, and duration of survival is 24 months. About 40% of patients have a family history of dementia. Like CJD, it can be mistaken for Alzheimers dementia. Diagnosis is difficult, as pathognomonic signs on MRI such as cortical ribboning or hockey stick sign, periodic sharp wave complexes on EEG, and tests for 14-3-3 protein and tau protein are usually not helpful, and no mutations have been observed in the coding region of the PrP gene, unlike CJD and Variant CJD. The diagnosis can be made on pathological examination. There are unique microscopic and immunohistochemical features, and the prions cannot be digested using proteases. Because 8 out of 10 patients had a positive family history of dementia in the original study, a genetic cause was suspected. Some have suggested the disease may be a sporadic form of Gerstmann–Sträussler–Scheinker syndrome (GSS).In 2013, Zou W.Q. and coworkers revealed that the peculiar protease-resistant PrP (PrPres) originally found in VPSPr is also detectable in the brain of patients with a genetic CJD linked to PrP Valine (V) to isoleucine (I) mutation at residue 180 (PrPV180I); moreover, they found that the pathological PrP from both VPSPr and gCJDPrPV180I shares a similar glycoform-selective prion formation mechanism.[8,9] Interestingly, the authors further demonstrated that the protease-resistant PrPres from both VPSPr and gCJDV180I lacks the PrP species glycosylated at the first N-linked glycosylation site at residue 181 and they proposed that the deficiency in PrP glycosylation may be involved in the pathogenesis of the two conditions. In 2014, Gambetti P., Zou W.Q., and coworkers found that approximately 54% of mice inoculated with VPSPr brain homogenates exhibited histopathologic lesions and 34% harbored abnormal PrP similar to that of VPSPr on the first passage but no prion disease was detected on the second passage,[10] suggesting that the infectivity of the pathological PrP from VPSPr is lower compared to that from the most common sporadic CJD. See also Creutzfeldt–Jakob disease References 8. Xiao X, Yuan J, Haïk S, Cali I, Zhan YA, Moudjou M, Li B, Laplanche JL, Laude H, Langeveld J, Gambetti P, Kitamoto T, Kong Q, Brandel JP, Cobb BA, Petersen RB & Zou WQ. Glycoform-selective prion formation in sporadic and familial forms of prion disease. PLoS ONE, 2013; 8:e58786. 9. Zou, WQ, Gambetti P, Xiao X, Yuan J, Langeveld J & Pirisinu L. Prions in variably protease-sensitive prionopathy: An update. Pathogens 2013; 2(3): 457-471. 10. Notari S, Xiao X, Espinosa JC, Cohen Y, Qing L, Aguilar-Calvo P, Kofskey D, Cali I, Cracco L, Kong Q, Torres JM, Zou W & Gambetti P. Transmission characteristics of variably protease-sensitive prionopathy. Emerg Infect Dis 2014, 20:2006-14. External links Caroline Parkinson (13 August 2010). "Brain disease could affect more people, research finds". BBC News.

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

Can you demystify the medical term 'Nutcracker esophagus' for me?

Nutcracker esophagus, Jackhammer esophagus, or hypercontractile peristalsis, is a disorder of the movement of the esophagus characterized by contractions in the smooth muscle of the esophagus in a normal sequence but at an excessive amplitude or duration. Nutcracker esophagus is one of several motility disorders of the esophagus, including achalasia and diffuse esophageal spasm. It causes difficulty swallowing, or dysphagia, to both solid and liquid foods, and can cause significant chest pain; it may also be asymptomatic. Nutcracker esophagus can affect people of any age but is more common in the sixth and seventh decades of life. The diagnosis is made by an esophageal motility study (esophageal manometry), which evaluates the pressure of the esophagus at various points along its length. The term "nutcracker esophagus" comes from the finding of increased pressures during peristalsis, with a diagnosis made when pressures exceed 180 mmHg; this has been likened to the pressure of a mechanical nutcracker. The disorder does not progress, and is not associated with any complications; as a result, treatment of nutcracker esophagus targets control of symptoms only. Signs and symptoms Nutcracker esophagus is characterized as a motility disorder of the esophagus, meaning that it is caused by abnormal movement, or peristalsis of the esophagus. People with motility disorders present with two main symptoms: chest pain or difficulty with swallowing. Chest pain is the more common. The chest pain is very severe and intense, and mimics cardiac chest pain. It may spread into the arm and back. The symptoms of nutcracker esophagus are intermittent, and may occur with or without food. Rarely, patients can present with a sudden obstruction of the esophagus after eating food (termed a food bolus obstruction, or the steakhouse syndrome) requiring urgent treatment. The disorder does not progress to produce worsening symptoms or complications, unlike other motility disorders (such as achalasia) or anatomical abnormalities of the esophagus (such as peptic strictures or esophageal cancer). Many patients with nutcracker esophagus do not have any symptoms at all, as esophageal manometry studies done on patients without symptoms may show the same motility findings as nutcracker esophagus. Nutcracker esophagus may also be associated with metabolic syndrome. The incidence of nutcracker esophagus in all patients is uncertain. Pathophysiology Pathology specimens of the esophagus in patients with nutcracker esophagus show no significant abnormality, unlike patients with achalasia, where destruction of the Auerbachs plexus is seen. The pathophysiology of nutcracker esophagus may be related to abnormalities in neurotransmitters or other mediators in the distal esophagus. Abnormalities in nitric oxide levels, which have been seen in achalasia, are postulated as the primary abnormality. As GERD is associated with nutcracker esophagus, the alterations in nitric oxide and other released chemicals may be in response to reflux. Diagnosis In patients who have dysphagia, testing may first be done to exclude an anatomical cause of dysphagia, such as distortion of the anatomy of the esophagus. This usually includes visualization of the esophagus with an endoscope, and can also include barium swallow X-rays of the esophagus. Endoscopy is typically normal in patients with nutcracker esophagus; however, abnormalities associated with gastroesophageal reflux disease, or GERD, which associates with nutcracker esophagus, may be seen. Barium swallow in nutcracker esophagus is also typically normal, but may provide a definitive diagnosis if contrast is given in tablet or granule form. Studies on endoscopic ultrasound show slight trends toward thickening of the muscularis propria of the esophagus in nutcracker esophagus, but this is not useful in making the diagnosis. Esophageal motility studies The diagnosis of nutcracker esophagus is typically made with an esophageal motility study, which shows characteristic features of the disorder. Esophageal motility studies involve pressure measurements of the esophagus after a patient takes a wet (fluid-containing) or dry (solid-containing) swallow. Measurements are usually taken at various points in the esophagus.Nutcracker esophagus is characterized by a number of criteria described in the literature. The most commonly used criteria are the Castell criteria, named after American gastroenterologist D.O. Castell. The Castell criteria include one major criterion: a mean peristaltic amplitude in the distal esophagus of more than 180 mm Hg. The minor criterion is the presence of repetitive contractions (meaning two or more) that are greater than six seconds in duration. Castell also noted that the lower esophageal sphincter relaxes normally in nutcracker esophagus, but has an elevated pressure of greater than 40 mm Hg at baseline.Three other criteria for the definition of the nutcracker esophagus have been defined. The Gothenburg criterion consists of the presence of peristaltic contractions, with an amplitude of 180 mm Hg at any place in the esophagus. The Richter criterion involves the presence of peristaltic contractions with an amplitude of greater than 180 mm Hg from an average of measurements taken 3 and 8 cm above the lower esophageal sphincter. It has been incorporated into a number of clinical guidelines for the evaluation of dysphagia. The Achem criteria are more stringent, and are an extension of the study of 93 patients used by Richter and Castell in the development of their criteria, and require amplitudes of greater than 199 mm Hg at 3 cm above the lower esophageal sphincter (LES), greater than 172 mm Hg at 8 cm above the LES, or greater than 102 mm Hg at 13 cm above the LES. Treatment People are usually reassured that the disease is unlikely to worsen. However, the symptoms of chest pain and trouble swallowing may be severe enough to require treatment with medications, and rarely, surgery. The initial step of treatment focuses on reducing risk factors. While weight reduction may be useful in reducing symptoms, the role of acid suppression therapy to reduce esophageal reflux is still uncertain. Very cold and very hot beverages may trigger esophageal spasms. Medications Medications for nutcracker esophagus includes the use of calcium-channel blockers, which relax the lower esophageal sphincter (LES) and palliate the dysphagia symptoms. Diltiazem, a calcium-channel blocker, has been used in randomized control studies with good effect. Nitrate medications, including isosorbide dinitrate, given before meals, may also help relax the LES and improve symptoms. The inexpensive generic combination of belladonna and phenobarbital (Donnatal and other brands) may be taken three times daily as a tablet to prevent attacks or, for patients with only occasional episodes, as an elixir at the onset of symptoms. Phosphodiesterase inhibitors, such as sildenafil, can be given to reduce symptoms, particularly pain, but small trials have not been able to demonstrate clinical improvement. Procedures Endoscopic therapy with botulinum toxin can also be used to improve dysphagia which stabilizes unintentional weight loss, but the effect has limited effect on other symptoms, including pain, while also being a temporary treatment lasting a few weeks. Finally, pneumatic dilatation of the esophagus, which is an endoscopic technique where a high-pressure balloon is used to stretch the muscles of the LES, can be performed to improve symptoms, but again no clinical improvement is seen in regards to motility.In people who have no response to medical or endoscopic therapy, surgery can be performed. A Heller myotomy involves an incision to disrupt the LES and the myenteric plexus that innervates it. The Heller myotomy is used as a final treatment option in patients who do not respond to other therapies. Prognosis Nutcracker esophagus is a benign, nonprogressive condition, meaning it is not associated with significant complications. See also Esophageal spasm References == External links ==

You serve as a medical tutor. Your objective is to demystify medical terms, providing thorough explanations that cater to various levels of medical knowledge.

Can you break down the meaning of the medical term 'Miosis' for me?

Miosis, or myosis (from Ancient Greek μύειν (múein) to close the eyes), is excessive constriction of the pupil. The opposite condition, mydriasis, is the dilation of the pupil. Anisocoria is the condition of one pupil being more dilated than the other. Causes Age Senile miosis (a reduction in the size of a persons pupil in old age) Diseases Horners syndrome Hemorrhage into pons (intracranial hemorrhage) Hereditary disorders Cluster headaches with ptosis Iridocyclitis Fatal familial insomnia Aphakia Drugs Opioids such as fentanyl, morphine, heroin and methadone (the notable exception being pethidine) Products containing nicotine such as cigarettes, chewing tobacco or gum. Imidazolines such as clonidine, naphazoline, oxymetazoline and tetrahydrozoline Antipsychotics, including risperidone, haloperidol, chlorpromazine, olanzapine, quetiapine Cholinergic agents such as acetylcholine Acetylcholinesterase inhibitors Serotonin antagonists, such as Ondansetron (an anti-emetic) known by its brand name Zofran Some cancer chemotherapy drugs, including camptothecin derivatives Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA) Some MAO Inhibitors. Pilocarpine eye drops and all other parasympathomimetics In some rare cases, when exposed to mustard gas Organophosphates Physiology of the photomotor reflex Light entering the eye strikes three different photoreceptors in the retina: the familiar rods and cones used in image forming and the more newly discovered photosensitive ganglion cells. The ganglion cells give information about ambient light levels, and react sluggishly compared to the rods and cones. Signals from photosensitive ganglion cells have multiple functions including acute suppression of the hormone melatonin, entrainment of the bodys circadian rhythms and regulation of the size of the pupil. The retinal photoceptors convert light stimuli into electric impulses. Nerves involved in the resizing of the pupil connect to the pretectal nucleus of the high midbrain, bypassing the lateral geniculate nucleus and the primary visual cortex. From the pretectal nucleus neurons send axons to neurons of the Edinger-Westphal nucleus whose visceromotor axons run along both the left and right oculomotor nerves. Visceromotor nerve axons (which constitute a portion of cranial nerve III, along with the somatomotor portion derived from the Edinger-Westphal nucleus) synapse on ciliary ganglion neurons, whose parasympathetic axons innervate the iris sphincter muscle, producing miosis. See also References External links FP Notebook

You are a medical knowledge base. Your task is to elucidate medical terminology, offering insights into their meanings, origins, and applications.

I'm seeking clarification on the medical term 'Night terror.' Could you explain it?

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

You serve as a medical tutor. Your objective is to demystify medical terms, providing thorough explanations that cater to various levels of medical knowledge.

The term 'Desiccated thyroid extract' keeps coming up in medical discussions. What does it stand for?

Desiccated thyroid, also known as thyroid extract, is thyroid gland that has been dried and powdered for medical use. It is used to treat hypothyroidism. It is less preferred than levothyroxine. It is taken by mouth. Maximal effects may take up to 3 weeks to occur.Side effects may occur from excessive doses. This may include weight loss, fever, headache, anxiety, trouble sleeping, arrythmias, and heart failure. Other side effects may include allergic reactions. Use in pregnancy and breastfeeding is generally safe. Regular blood tests are recommended to verify the appropriateness of the dose. They contain a mixture of thyroxine (T4) and triiodothyronine (T3).Desiccated thyroid has been used since the late 1800s. It is usually made from pigs, sheep, or cows. It is available as a generic medication. In 2017, it was the 130th most commonly prescribed medication in the United States, with more than five million prescriptions. Usage has decreased since the 1960s. Medical uses The American Association of Clinical Endocrinologists and the Royal College of Physicians recommend against the use of thyroid extract for the treatment of hypothyroidism. Concerns include the potential for adverse effects from superphysiological levels of T3 and the absence of long-term safety data from randomized clinical trials. They recommend levothyroxine as the preferred treatment. Some practitioners refuse to use desiccated thyroid.About 65 mg of thyroid extract is equivalent to 100 μg of levothyroxine.Arguments against desiccated thyroid include: Desiccated thyroid preparations have a greater variability from batch to batch than synthetic ones. Desiccated thyroid has roughly a 4:1 ratio of thyroxine (T4) to triiodothyronine (T3). In humans, the ratio is 11:1. A combination of various ratios of T4 and T3 might not provide benefits over T4 alone. Some controlled trials have shown inconsistent benefits of various ratios of T4 and T3. The use of desiccated thyroid is usually accompanied with the practice of dosing according to symptoms instead of dosing to achieve "ideal" lab results (e.g. serum levels of TSH). While there is debate as to what the ideal serum levels are, dosing according to symptoms often results in higher dosages. Most endocrinologists are opposed to these higher dosages as there may be risks of hyperthyroidism and osteoporosis. The preference for "natural" treatment seems to stem from philosophical belief as opposed to science.Arguments for desiccated thyroid include: Desiccated thyroid contains all the natural thyroid hormones produced exclusively by the thyroid gland, including calcitonin which plays a crucial but still quite unclear role in promoting and sustaining bone density, however it is already used in therapy for osteoporosis when other treatments fail. Desiccated thyroid therapy can be combined with synthetic thyroxine (T4) to balance out the T4/T3 correctly. Chemistry Desiccated thyroid has been described in the United States Pharmacopoeia for a century as the cleaned, dried, and powdered thyroid gland previously deprived of connective tissue and fat... obtained from domesticated animals that are used for food by man (USP XVI). In the last few decades, pork alone is the usual source. Before modern assays, the potency was specified only by iodine content ("not less than 0.17% and not more than 0.23%"), rather than hormonal content or activity. History The earliest oral treatment for hypothyroidism consisted of thyroid extract. George Redmayne Murray of the United Kingdom first described treatment of myxedema with thyroid extract in 1891, and published a description of long-term successful treatment (28 years) of a patient with myxedema (severe hypothyroidism) in 1920 His treatment was quickly adopted in North America and Europe. The first recorded American use dates to 1891 by a woman who was still taking it 52 years later at 84 years of age Desiccated thyroid extract is prepared from pig thyroid glands. The glands are dried (desiccated), ground to powder, combined with binder chemicals, and pressed into pills. This was a new use for parts that were previously unwanted slaughterhouse offal, and Armour and Company, the dominant American meatpacker in the 20th century, supplied the best-known brand of thyroid extract.Replacement by thyroid extract in hypothyroidism was one of the most effective treatments of any disease available to physicians before the middle of the 20th century, and in severe cases afforded dramatic relief of the myriad symptoms. The decision to treat was usually based on the presence of signs and symptoms of hypothyroidism because there were no accurate, readily available laboratory tests of thyroid function. Many less severe cases of hypothyroidism went untreated. Dosage was regulated by improvement of symptoms. Desiccated Thyroid became a commercial treatment option in 1934 with Westhroid,. In the early 1960s, desiccated thyroid hormones (thyroid extract) began to be replaced by levothyroxine (synthetic T4), or by combinations of T4 and T3. Replacement occurred faster in the United Kingdom than in North America, but by the 1980s more patients were being prescribed synthetic T4 (levothyroxine) or synthetic T4/T3 combinations than desiccated thyroid extract.Several reasons have been identified as to why prescriptions changed from desiccated thyroid treatment. Although thyroid extract was useful and usually effective, some patients continued to complain of fatigue, weight gain, or other symptoms. Dosing until the 1960s was often a matter of prolonged adjustment trials. It was known that not all of the iodine content of thyroid extract was in the form of effective T4 and T3 and that actual content of available preparations varied more than the permitted 15%. It was hoped that better dosing precision with levothyroxine (synthetic) alone would increase the proportion of patients effectively treated. In 1980, a widely publicized investigation published in JAMA revealed continued large ranges of hormone content and potency in all of the available thyroid extracts on the American market. By the 1960s, it was known that thyroxine was the essential hormone produced by the thyroid gland, and that most T3 was manufactured in other parts of the body by deiodination of thyroxine. It was demonstrated in hypothyroid animals and people that replacement of thyroxine alone corrected the measurable manifestations (laboratory test results) of hypothyroidism. By the 1970s doctors could measure T4, T3, and TSH in human blood with approximate accuracy and confirmed that treatment with thyroxine alone could produce normal blood levels of both T4 and T3, but desiccated thyroid caused supraphysiologic levels of T3. In the majority of patients normalization of these levels eliminated all signs and symptoms of hypothyroidism. It was discovered that a healthy person varied the amount of T3 produced from T4 in response to changing needs and conditions and it seemed wiser not to bypass this control system by providing larger amounts of T3 than were naturally produced each day. Furthermore, when T3 could be measured, it was discovered that thyroid extract and synthetic combinations of T4 and T3 produced significantly greater fluctuations of T3 throughout the day than occurred in healthy people or hypothyroid people treated with thyroxine alone. Endocrinologists found that treatment with thyroxine alone worked as well or better than thyroid extract for the majority of patients, although even thyroxine did not reverse all the symptoms of a minority.Thyroid care changed in other ways as well. Accurate T4 and T3 measurements became widely used in the 1970s, and by the late 1980s, TSH measurement had become sensitive enough to detect mild degrees of hyperthyroidism and overtreatment. Blood levels of thyroid hormones and TSH were found to be the best predictors of objective benefits from thyroid replacement: those with the most severe measurable deficiency enjoyed the most dramatic and sustained benefits. It was also discovered that even mild hyperthyroidism as defined by a suppressed TSH level, whether due to disease or overtreatment, was associated with poorer bone density in women, and with higher rates of atrial fibrillation in elderly patients. Names This product is sometimes referred to as thyroid USP, thyroid BP. Brands differing only in binders and fillers. References External links "Thyroid tablets". Drug Information Portal. U.S. National Library of Medicine.

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

Please help me grasp the concept behind the medical term 'Membranoproliferative glomerulonephritis.'

Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening, activating complement and damaging the glomeruli. MPGN accounts for approximately 4% of primary renal causes of nephrotic syndrome in children and 7% in adults.It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not. Type There are three types of MPGN, but this classification is becoming obsolete as the causes of this pattern are becoming understood. Type I Type I, the most common by far, is caused by immune complexes depositing in the kidney. It is characterised by subendothelial and mesangial immune deposits. It is believed to be associated with the classical complement pathway. Type II Also called recently as ‘C3 nephropathy’ The preferred name is "dense deposit disease." Most cases of dense deposit disease do not show a membranoproliferative pattern. A 2012 review considers DDD to be in a continuum with C3 glomerulonephritis, one reason the use of the type I to type III classification system is falling out of favour.Most cases are associated with the dysregulation of the alternative complement pathway.DDD is associated with deposition of complement C3 within the glomeruli with little or no staining for immunoglobulin. The presence of C3 without significant immunoglobulin suggested to early investigators that DDD was due to abnormal activation of the complement alternative pathway (AP). There is now strong evidence that DDD is caused by uncontrolled AP activation.Spontaneous remissions of MPGN II are rare; approximately half of those affected with MPGN II will progress to end stage renal disease within ten years.In many cases, people with MPGN II can develop drusen caused by deposits within Bruchs membrane beneath the retinal pigment epithelium of the eye. Over time, vision can deteriorate, and subretinal neovascular membranes, macular detachment, and central serous retinopathy can develop. Type III Type III is very rare, it is characterized by a mixture of subepithelial and subendothelial immune and/or complement deposits. These deposits elicit an immune response, causing damage to cells and structures within their vicinity. Has similar pathological findings of Type I disease.A candidate gene has been identified on chromosome 1.Complement component 3 is seen under immunofluorescence. it is associated with complement receptor 6 deficiency. Pathology Membranoproliferative glomerulonephritis involves deposits at the intraglomerular mesangium. It is also the main hepatitis C associated nephropathy. It also is related to a number of autoimmune diseases, prominently systemic lupus erythematosus (SLE), Class IV. Also found with Sjögren syndrome, rheumatoid arthritis, inherited complement deficiencies (esp C3 deficiency), scleroderma, Celiac disease.The histomorphologic differential diagnosis includes transplant glomerulopathy and thrombotic microangiopathies. Diagnosis The GBM is rebuilt on top of the deposits, causing a "tram tracking" appearance under the microscope. Mesangial cellularity is increased. Treatment Primary MPGN is treated with steroids, plasma exchange and other immunosuppressive drugs. Secondary MPGN is treated by treating the associated infection, autoimmune disease or neoplasms. Pegylated interferon and ribavirin are useful in reducing viral load. See also Diffuse proliferative nephritis References External links Glomerulonephritis, Membranoproliferative Types I, II, III at eMedicine Corchado, Johnny Cruz, Smith, Richard JH (July 2007). "Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II". In Pagon RA, Bird TD, Dolan CR, et al. (eds.). GeneReviews. Seattle WA: University of Washington. PMID 20301598. Membranoproliferative_GN at Nephropathology tutorial MP GN Pathophysiology discusses the nephritic auto-antibodies/factors

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

What does the medical term 'DTaP-IPV vaccine' encompass?

DTaP-IPV vaccine is a combination vaccine whose full generic name is diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine (IPV).It is also known as DTaP/IPV, dTaP/IPV, DTPa-IPV, or DPT-IPV. It protects against the infectious diseases diphtheria, tetanus, pertussis, and poliomyelitis.Branded formulations marketed in the USA are Kinrix from GlaxoSmithKline and Quadracel from Sanofi Pasteur.Repevax is available in the UK.Within Japan, the formulation is called 四種混合（shishukongou - "mixture of 4"). Astellas markets it under the クアトロバック (Quattro-back) formulation, while another is available from Mitsubishi Tanabe Pharma named テトラビック (Tetrabic). A previous product by Takeda Pharmaceutical Company has been withdrawn by the company. == References ==

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

Could you please explain the term 'Vesicovaginal fistula' in simple language?

Vesicovaginal fistula (VVF) is a subtype of female urogenital fistula (UGF). Presentation Vesicovaginal fistula, or VVF, is an abnormal fistulous tract extending between the bladder (vesica) and the vagina that allows the continuous involuntary discharge of urine into the vaginal vault.In addition to the medical sequela from these fistulas, they often have a profound effect on the patients emotional well-being. Causes It may be the result of a congenital birth condition such as VACTERL association. It is often caused by childbirth (in which case it is known as an obstetric fistula), when a prolonged labor presses the unborn child tightly against the pelvis, cutting off blood flow to the vesicovaginal wall. The affected tissue may necrotize (die), leaving a hole.Vaginal fistulas can also result from particularly violent cases of rape, especially those involving multiple rapists and/or foreign objects. Some health centers in countries such as the Democratic Republic of Congo have begun to specialize in the surgical repair of vaginal fistulas. It can also be associated with hysterectomy, cancer operations, radiation therapy and cone biopsy. Treatment Vesicovaginal fistulae are typically repaired either transvaginally or laparoscopically, although patients who have had multiple transvaginal procedures sometimes attempt a final repair through a large abdominal incision, or laparotomy.The laparoscopic (minimally invasive) approach to VVF repair has become more prevalent due to its greater visualization, higher success rate, and lower rate of complications. Possible complications of surgical treatment Recurrent formation of the fistula Injury to ureter, bowel, or intestines Vaginal shortening History Before the 19th century, women who suffered from VVF were judged harshly and rejected by society. Throughout the 19th century, treatment for VVF was limited because the practice of gynecology was perceived as taboo. Doctors were almost entirely male at this time and looking at a nude female, even for medical purposes, was seen as divergent from 19th-century values.One of the most famous gynecological surgeons of this time was Dr. J. Marion Sims, who developed a successful technique for treating VVF in the mid-1800s, for which he is hailed as a pioneer of gynecology.Black enslaved women in the American South were particularly prone to VVF because they were denied proper nutrients and medical care. Sims performed on these women without anesthesia, which had not been introduced until after he started his experiments, and which in its infancy Dr. Sims hesitated to use. (Ether anesthesia was publicly demonstrated in Boston in 1846, a year after Sims began his experimentation.) Sims did not have a white female patient until he made ether available to them, although he publicly noted that he never resorted to using anesthetics because he believed that the pain did not justify the risks. A detailed case study of Dr. Sims even discusses the case of a white woman who underwent three operations, all without anesthesia. It was considered acceptable to operate on them without anesthetic because, Sims claimed, African-American women have a naturally higher pain tolerance.The healing process of the VVF procedure is still arduous. To have a successful recovery from the surgery, it must be successful on the first attempt. Dr. J. Marion Sims operations on African-American enslaved women showcase the dangerous nature of the procedure. There still have not been clear instructions on how to properly recover from the procedure other than taking prescribed antibiotics. See also Colposcopy Double dye test Rectovaginal fistula Urinary incontinence References == External links ==

You are an expert in medical terminology. Explain medical terms in a way that is both precise and easy to understand for non-medical audiences.

I'm trying to understand 'Myoclonic dystonia' within a medical context. Could you shed some light on it?

Myoclonic dystonia or Myoclonus dystonia syndrome is a rare movement disorder that induces spontaneous muscle contraction causing abnormal posture. The prevalence of myoclonus dystonia has not been reported, however, this disorder falls under the umbrella of movement disorders which affect thousands worldwide. Myoclonus dystonia results from mutations in the SGCE gene coding for an integral membrane protein found in both neurons and muscle fibers. Those suffering from this disease exhibit symptoms of rapid, jerky movements of the upper limbs (myoclonus), as well as distortion of the bodys orientation due to simultaneous activation of agonist and antagonist muscles (dystonia). Myoclonus dystonia is caused by loss-of-function-mutations in the epsilon sarcoglycan gene (SGCE). The disease is dominantly inherited, however SGCE is an imprinted gene, so only the paternal allele is expressed. Therefore, children suffering from this disease inherit the mutation from the father. If the mutated allele is inherited from the mother, the child is not likely to exhibit symptoms. While no cure has been found for myoclonus dystonia, treatment options are available to those suffering from the disease. Ethanol often ameliorates the symptoms well, and so the syndrome is also called "Alcohol-responsive dystonia". Alcohol may be substituted by benzodiazepines, such as clonazepam, which work through the same mechanism. Deep brain stimulation (DBS) is another viable option that can alleviate symptoms without the unwanted side effects of medications, and has been successful in treating other movement disorders. Signs and symptoms Myoclonus dystonia is characterized by two primary features: myoclonus and dystonia. For the majority of individuals with myoclonus dystonia, the myoclonus component of the disorder is often the primary and most disabling feature in comparison to the dystonia component. The symptoms of myoclonus dystonia vary substantially in severity. Myoclonus Myoclonus is characterized by rapid contractions that affect the upper body including the neck, torso and arms, but may also affect the legs. These movements are stimulated by various factors including stress, noise, caffeine, and physical stimuli. Myoclonus can be characterized in multiple ways including neurological basis, muscular activity, and by stimuli. Myoclonus can be positive or negative; positive myoclonus results from brief spurts of muscle activity and negative myoclonus occurs when there is a lack of any muscular activity. Myoclonus is usually classified physiologically to optimize treatment. Myoclonus is a precursor effect to myoclonus dystonia and most commonly begins in childhood or adolescence.Myoclonus is classified as cortical, subcortical, peripheral or spinal. Cortical myoclonus is the most common of these four and affects the upper limbs and face. Myoclonus dystonia has been characterized under subcortical origin, specifically under nonsegmented myoclonus or brainstem myoclonus. Symptoms within this classification include the startle response and reticular reflex myoclonus. Sudden stimuli like noise or touch to areas around the head or chest cause the startle response which will go up the brain stem and down the spinal cord causing jerk-like movements. Hyperekplexia is a heightened brainstem response where an affected person will continue to elicit the same response to a repeated stimuli. In contrast, reticular reflex myoclonus occurs spontaneously to stimuli applied to distal limbs. Spinal myoclonus is caused by defects in spinal organization or connections, and peripheral myoclonus has symptoms of rhythmic jerks due to a neuron-the most common being the hemifacial spasm. Dystonia Dystonia is a response to simultaneous contraction of agonist and antagonist muscles seen as twisting and contorting that affect posture and stance. Other symptoms can include tremors and muscle spasms due to various interactions of muscle, contractions and movement. Dystonia can be either primary or secondary with the latter being more common. Primary dystonia or "pure" dystonia is only physiological in origin. Secondary dystonia has multiple origins that are physiological, pathological or neurological. Myoclonus dystonia Myoclonus dystonia includes the rapid contractions of myoclonus alongside the abnormal postures classified under dystonia, as well as neurological and psychiatric issues. This disease typically begins during childhood with symptoms of myoclonus and slight dystonia, most commonly cervical dystonia or writers cramp. Dystonia symptoms tend to not get exaggerated over the course of the disease and is rarely the only associated symptom, while the myoclonus symptoms can become more severe. Psychiatric issues are clinically diagnosed with the aforementioned symptoms and include depression, anxiety, personality disorders and addiction. Obsessive-compulsive disorder is associated with myoclonus dystonia as both have been found to have a commonality on chromosome 7 in various studies.Neurological symptoms are relatively common in those with myoclonus dystonia. Any neurological abnormalities will not normally be present in those affected at a young age. Neurological testing has been performed to determine the origins of these symptoms and multiple parts of the brain have been pinpointed including the brainstem, neocortex, pallidum, and thalamus. These cause various effects in those diagnosed with myoclonus dystonia including changes in posture and tremors, and very rarely dementia and ataxia. Cause The majority of myoclonus dystonia cases are the result of a mutation in the epsilon sarcoglycan gene (SGCE). This gene is found on chromosome 7, with its specific cytogenic location being 7q21.3. The 70,985 bp SGCE gene encodes the protein epsilon (ε)-sarcoglycan. The five proteins that make up the sarcoglycan family function as integral membrane proteins that anchor the cytoskeleton of cells to the extracellular matrix. Epsilon sarcoglycan is a membrane protein that can be found in the liver, lungs, kidney, and spleen, but is most prevalent in muscle and neuronal cells. Its prevalence in both muscle fibers and the synapses of neurons suggest why symptoms of both myoclonus and dystonia appear from the improperly functioning protein. Recessive mutations in the other sarcoglycans also result in muscular disorders, further supporting that mutations in the SGCE gene cause myoclonus dystonia.Epsilon sarcoglycan itself is part of the dystrophin-associated protein (DAP) complex that binds the sarcolemma of muscle cells to the extracellular connective tissue. The purpose is to reduce the mechanical force on the sarcolemma as a result of muscle contraction. In addition to myoclonus dystonia, problems associated with a dysfunctional DAP complex include Duchenne muscular dystrophy.Upwards of 65 mutations of the SGCE gene are thought to cause myoclonus dystonia. The majority of the mutations lead to a truncated protein product that results in the loss-of-function of the epsilon sarcoglycan protein. The dysfunctional protein is ultimately recycled by the cell by degradation mediated by the proteasome, resulting in significant shortages of the integral membrane protein in both neurons and muscle fibers. The mutant allele is inherited in a dominant fashion—that is the mutation can be inherited if one parent has that allele. However, genomic imprinting occurs on the mothers allele, so only the fathers allele is expressed. Therefore, inheriting a mutated, paternal allele of the SGCE gene will result in the expression of the dysfunctional epsilon sarcoglycan protein. Offspring will not produce a mutant protein product in 95% of cases where the mother passes on a mutation in the SGCE gene.While SGCE gene mutations are the central cause of myoclonus dystonia, there have been separate cases where individuals and families present symptoms akin to myoclonus dystonia but lack the mutations at this locus. Base-pair deletions of the DYT1 gene, missense mutations in the DRD2 gene, maternal uniparental disomy, and chromosome 18 linkage have all been associated in rare cases myoclonus dystonia where the SGCE gene is unaffected. Treatment To date, there is no single, universal treatment that has been found to cure myoclonus dystonia. However, there are several treatment methods that have been found to be effective for helping to reduce the symptoms associated with the syndrome. Medications Many drugs used to treat myoclonus dystonia do not have a significant impact individually, but when combined, can work on different brain mechanisms to best alleviate symptoms. The method of treatment used depends on the severity of the symptoms presented in the individual, and whether the underlying cause of the syndrome is known. Benzodiazepines Benzodiazepines such as clonazepam improve tremors caused by the myoclonus aspect of this syndrome by binding allosterically to GABAA ionotropic receptors, causing an influx of chloride ions that produce an inhibitory effect that can calm myoclonic jerks. Antiepileptics Antiepileptics like valproate must act upon GABA receptors and manipulate ionic conductance to reduce tremors and spasms in myoclonus dystonia. GABA neurons that fire rapidly and affect the motor cortex are blocked by antiepileptics in addition to changes in sodium and calcium concentrations that can excite the neuron. Different antiepileptics vary in sufficiency to control ionic conductance and can also produce seizures or myoclonus symptoms in some patients. Another agent that has been used is zonisamide. Anticholinergics Anticholinergics like benzatropine alleviate dystonia symptoms by blocking the activity of acetylcholine. Acetylcholine is involved in the pathophysiology of dystonia within the basal ganglia, although its exact role has not been determined. Acetylcholine is involved with dopamine and glutamate pathways in the basal ganglia, in addition to presynaptic muscarinic receptors which are involved in motor control. Acetylcholine is usually overactive in dystonia patients and blocking of this neurotransmitter would reduce contortion of the upper body, but can produce side effects of drowsiness, confusion and memory issues in adults. Botulinum toxin Botulinum toxin injections also act upon acetylcholine to reduce dystonia symptoms. The neurotoxin is active in presynaptic terminals and blocks exocytosis of acetylcholine into the synaptic cleft which reduces muscle activity. Botulinum may also have a role in inhibiting glutamate and changing muscle movement. Studies have also shown possible axon transport of this neurotoxin as well as its function as a pain reliever without effect on overactive muscle movement in myoclonus dystonia patients. Alcohol Consumption of alcohol has also been found to be an effective agent for temporarily easing the severity of the tremors associated with myoclonus dystonia. Alcohol causes an increase in GABA transmission between interneurons and Purkinje cells. This then reduces the transmission of glutamate at granule cell-Purkinje cell synapses, which decreases muscle movements. This treatment only alleviates the strength of the tremors for a short duration and does not change how often tremors will occur. Doctors inform patients of risks associated with the use of alcohol for myoclonus dystonia due to the high susceptibility for excessive alcohol use and dependency. Alcohol use disorder itself causes tremors in the hands and degeneration of the Purkinje cells and other parts of the cerebral cortex, counteracting alcohols original corrective effects. Deep brain stimulation Deep brain stimulation (DBS) has been found to be an effective and safe treatment for myoclonus dystonia patients, whose severe and debilitating symptoms are resistant to drug treatments. Electrical stimulation within the brain is a common treatment for many movement disorders because of the ability to excite or inhibit neurons within the brain. Deep brain stimulation patients have electrodes inserted into the brain and then an electrical signal is sent from an external source to elicit a response. The frequency and intensity of this signal can be changed to monitor the effects on neuronal activity using voltage recordings or neuroimaging, like functional MRIs. By re-positioning the electrodes in different areas or changing the size or timing of the stimulus, varying effects can be seen on the patient depending on the origin of the disorder.In one study, five patients with genetically determined epsilon sarcoglycan protein deficiency underwent deep brain stimulation of the internal pallidum. Each patients movement and disability symptoms were assessed before and after treatment using the Burke-Fahn-Marsden Dystonia Rating Scale and the Unified Myoclonus Rating Scale. Upon completion of the surgery, both the myoclonus and dystonia symptoms of the disorder had decreased by 70%, with no report of unfavorable side effects. Therefore, deep brain stimulation has been shown to effectively improve both myoclonus and dystonia, unlike many drug treatments which may improve one or the other.Other studies examined the effects of DBS to both the ventrointermediate nucleus of the thalamus, Vim, and the globus pallidus interna, GPi. Following deep brain stimulation of GPi and Vim, the Unified Myoclonus Rating Scale disability score improved 61-66%. In addition, the Dystomia Rating Scale score improved by 45-48%. While there was no significant difference in improvement between GPi-Vim stimulation and GPi stimulation, GPi-Vim stimulation was significantly more effective than Vim deep brain stimulation alone. Overall, Deep brain stimulation shows promise as a viable treatment for myoclonus dystonia.Although myoclonus and dystonia are present in myoclonus dystonia patients, optimum treatment for myoclonus dystonia differs from the treatment for myoclonus or dystonia alone. Myoclonus improved significantly more than dystonia when Deep brain stimulation was applied. In addition, myoclonus improved regardless of whether Deep brain stimulation was applied to GPi or Vim. However, GPi stimulation was more effective at reducing the symptoms of dystonia than Vim stimulation. References == External links ==

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

What is the significance of the term 'Reactive airway disease' in the medical field?

Reactive airway disease (RAD) is an informal label that physicians apply to patients with symptoms similar to those of asthma. An exact definition of the condition does not exist. Individuals who are typically labeled as having RAD generally have a history of wheezing, coughing, dyspnea, and production of sputum that may or may not be caused by asthma. Symptoms may also include, but are not limited to, coughing, shortness of breath, excess mucus in the bronchial tube, swollen mucous membrane in the bronchial tube, and/or hypersensitive bronchial tubes. Physicians most commonly label patients with RAD when they are hesitant about formally diagnosing a patient with asthma, which is most prevalent in the pediatric setting. While some physicians may use RAD and asthma synonymously, there is controversy over this usage. More generally, there is controversy over the use of RAD as a label in the healthcare setting, largely due to the ambiguous definition that the term has. Since RAD is not recognized as a real clinical diagnosis, its meaning is highly inconsistent and may cause confusion and misdiagnosis within the medical community. There are also concerns with overtreatment and undertreatment with RAD amongst physicians, since there is little formality with the label. Other problems that healthcare workers have with the use of the RAD label include its exclusion in the International Statistical Classification of Diseases and Related Health Problems, which can lead to billing issues in hospitals and other health care facilities, and the creation of a fabricated sense of security when using it has a diagnosis.RAD can be confused with reactive airways dysfunction syndrome, an asthma-like disorder that results from high exposure to vapors, fumes, and/or smoke. Unlike RAD, reactive airways dysfunction syndrome is recognized by multiple societies as a real clinical syndrome, including the American Thoracic Society and the American College of Chest Physicians. Terminology The term reactive airway disease originally began to appear in medical literature in the 1980s in reference to asthmatic patients with hyperactive airways, which is a common feature of asthma. This feature is characterized by increased bronchoconstriction reactions in response to stimuli that should not elicit so strong of response. These stimuli can include methacholine, histamine, and distilled water. However, while this was how the term initially was introduced, RAD soon began to be used interchangeably with the term asthma itself, which has led to the current controversy over its place in medical diagnoses.More commonly, RAD is now mostly used by physicians when they are hesitant to diagnose a patient with asthma. This is most prominent in pediatric settings for a variety of reasons. While infants tend to wheeze more often than adults, only one third of them eventually go on to actually have asthma. Asthma and viral bronchiolitis can also be nearly identical to each other when presented in very young children, since they both consist of wheezing, coughing, and nasal congestion. In addition, typical tests used to accurately diagnose children with asthma, such as the bronchial challenge test, are not considered to be accurate for children under the age of five. This can be due to failure of very young children to cooperate. Diagnosing a child with asthma also carries a certain negative connotation, causing hesitancy from some physicians to do so. All of these factors lead physicians to label young children with RAD instead of asthma, since the disease is often only suspected and unable to be confirmed with pediatric patients.Physicians will generally label an adult with RAD if they have no prior diagnosis or history of asthma while exhibiting symptoms of wheezing, production of sputum, and/or the use of an inhaler. Symptoms may also include, but are not limited to, coughing, shortness of breath, excess mucus in the bronchial tube, swollen mucous membrane in the bronchial tube, and/or hypersensitive bronchial tubes. In order to make a formal asthma diagnosis in adult patients, there is requirement to have documentation of either airway hyperreactivity or some sort of reversible airway obstruction. If none of these symptoms are present in an adult patients medical history or documentation, the physician may label the patient with RAD instead of asthma in order to still indicate there is an airway issue without formal diagnosis. Reactive airways dysfunction syndrome While the acronyms are similar, reactive airway disease (RAD) and reactive airways dysfunction syndrome (RADS) are not the same.Reactive airways dysfunction syndrome was first identified by Stuart M. Brooks and colleagues in 1985 as an asthma-like syndrome developing after a single exposure to high levels of an irritating vapor, fume, or smoke. It can manifest in adults with exposure to high levels of chlorine, ammonia, acetic acid, or sulphur dioxide, creating symptoms like asthma. These symptoms can vary from mild to fatal and can even create long-term airway damage, depending on the amount of exposure and the concentration of chlorine. Patients that have been diagnosed with RADS will likely have methacholine airway hyperreactivity, yet other tests that also measure pulmonary functions may appear normal. Some experts classify RADS as occupational asthma. Those with exposure to highly irritating substances should receive treatment to mitigate harmful effects. Treatment for RADS is similar to treatment for other disorders that result from acute inhalation. Preexisting allergies can be a risk factor for developing RADS.The main difference between RAD and RADS is that RADS can occur after just one exposure to the inhalants and without any prior sensitization. In addition, although the symptoms of RADS are very similar to those of asthma, they may be resolved. While some physicians argue that RADS is also not a real clinical syndrome, it is more commonly recognized in legitimate associations than RAD. These associations include the American Thoracic Society and the American College of Chest Physicians. Controversy over use There remains controversy over the use of RAD as an unofficial diagnosis. With its use not only being limited to clinical lexicon, but also transitioning to clinical literature now, more physicians are now increasingly disapproving its use in the healthcare setting.One of the largest problems with the using RAD as a diagnostic label lies in the ambiguity of its meaning, as RAD has no true clinical definition. It is either not listed or redirects to "asthma" in all major medical journal or website. In addition to that, it is also not recognized in the American Academy of Pediatrics; the American Thoracic Society; or the National Heart Lung and Blood Institute. In addition, treatments for asthma, chronic bronchitis, emphysema, or pneumonia may not be prescribed under a label of reactive airway disease. In contrast, some physicians also fear overtreatment for RAD, as patients can be prescribed inhaled beta-agonists or inhaled corticosteroids, which are medications used for asthma. If an individual with RAD doesnt have asthma, there is no evidence these treatments are beneficial. As a result of its ambiguous place in the medical field, the symptoms used to characterize it are often inconsistent and can lead to confusion in a healthcare setting. This is a troubling issue for many physicians, as care can be made more complicated; many patients labeled with RAD do not ultimately have asthma and most RAD patients have never formally had their airway reactivity measured.In addition to the inconsistencies of its labeling, there is also no billing designation for RAD in the International Statistical Classification of Diseases and Related Health Problems, or the ICD, which can lead to problems for healthcare facilities. Searches in the ICD, point to content relating to asthma. Some medical professionals argue that using RAD as a diagnosis will only complicate research on asthma in the context of clinical research and epidemiology. There is also dispute that by giving physicians the ability to label a patient with RAD, it gives them a fabricated sense of security that they have made a diagnosis, when no real recognizable diagnosis has been concluded. See also Bronchiolitis References == External links ==

You serve as a medical tutor. Your objective is to demystify medical terms, providing thorough explanations that cater to various levels of medical knowledge.

I've come across the term 'Osteomalacia' in a medical context, but I'm not sure what it means. Can you clarify?

Osteomalacia is a disease characterized by the softening of the bones caused by impaired bone metabolism primarily due to inadequate levels of available phosphate, calcium, and vitamin D, or because of resorption of calcium. The impairment of bone metabolism causes inadequate bone mineralization. Osteomalacia in children is known as rickets, and because of this, use of the term "osteomalacia" is often restricted to the milder, adult form of the disease. Signs and symptoms can include diffuse body pains, muscle weakness, and fragility of the bones. In addition to low systemic levels of circulating mineral ions (for example, caused by vitamin D deficiency or renal phosphate wasting) that result in decreased bone and tooth mineralization, accumulation of mineralization-inhibiting proteins and peptides (such as osteopontin and ASARM peptides), and small inhibitory molecules (such as pyrophosphate), can occur in the extracellular matrix of bones and teeth, contributing locally to cause matrix hypomineralization (osteomalacia/odontomalacia). A relationship describing local, physiologic double-negative (inhibiting inhibitors) regulation of mineralization has been termed the Stenciling Principle of mineralization, whereby enzyme-substrate pairs imprint mineralization patterns into the extracellular matrix (most notably described for bone) by degrading mineralization inhibitors (e.g. TNAP/TNSALP/ALPL enzyme degrading the pyrophosphate inhibition, and PHEX enzyme degrading the osteopontin inhibition). The Stenciling Principle for mineralization is particularly relevant to the osteomalacia and odontomalacia observed in hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH). The most common cause of osteomalacia is a deficiency of vitamin D, which is normally derived from sunlight exposure and, to a lesser extent, from the diet. The most specific screening test for vitamin D deficiency in otherwise healthy individuals is a serum 25(OH)D level. Less common causes of osteomalacia can include hereditary deficiencies of vitamin D or phosphate (which would typically be identified in childhood) or malignancy. Vitamin D and calcium supplements are measures that can be used to prevent and treat osteomalacia. Vitamin D should always be administered in conjunction with calcium supplementation (as the pair work together in the body) since most of the consequences of vitamin D deficiency are a result of impaired mineral ion homeostasis.Nursing home residents and the homebound elderly population are at particular risk for vitamin D deficiency, as these populations typically receive little sun exposure. In addition, both the efficiency of vitamin D synthesis in the skin and the absorption of vitamin D from the intestine decline with age, thus further increasing the risk in these populations. Other groups at risk include individuals with malabsorption secondary to gastrointestinal bypass surgery or celiac disease, and individuals who immigrate from warm climates to cold climates, especially women who wear traditional veils or dresses that prevent sun exposure. Signs and symptoms Osteomalacia is a generalized bone condition in which there is inadequate mineralization of the bone. Many of the effects of the disease overlap with the more common osteoporosis, but the two diseases are significantly different. There are two main causes of osteomalacia: insufficient calcium absorption from the intestine because of lack of dietary calcium or a deficiency of, or resistance to, the action of vitamin D, or due to undiagnosed celiac disease. phosphate deficiency caused by increased renal losses.Symptoms: Osteomalacia in adults starts insidiously as aches and pains in the lumbar (lower back) region and thighs before spreading to the arms and ribs. The pain is symmetrical, non-radiating and accompanied by sensitivity in the involved bones. Proximal muscles are weak, and there is difficulty in climbing upstairs and getting up from a squatting position. As a result of demineralization, the bones become less rigid. Physical signs include deformities like triradiate pelvis and lordosis. The patient has a typical "waddling" gait. However, these physical signs may derive from a previous osteomalacial state, since bones do not regain their original shape after they become deformed. Pathologic fractures due to weight bearing may develop. Most of the time, the only alleged symptom is chronic fatigue, while bone aches are not spontaneous but only revealed by pressure or shocks. It differs from renal osteodystrophy, where the latter shows hyperphosphatemia. Causes The causes of adult osteomalacia are varied, but ultimately result in a vitamin D deficiency: Diagnosis Biochemical findings Biochemical features are similar to those of rickets. The major factor is an abnormally low vitamin D concentration in blood serum. Major typical biochemical findings include: Low serum and urinary calcium Low serum phosphate, except in cases of renal osteodystrophy Elevated serum alkaline phosphatase (due to an increase in compensatory osteoblast activity) Elevated parathyroid hormone (due to low calcium)Furthermore, a technetium bone scan will show increased activity (also due to increased osteoblasts). Radiographic characteristics Radiological appearances include: Pseudofractures, also called Loosers zones. Protrusio acetabuli, a hip joint disorder Prevention Prevention of osteomalacia rests on having an adequate intake of vitamin D and calcium, or other treatments if the osteomalacia hereditary (genetic). Vitamin D3 Supplementation is often needed due to the scarcity of Vitamin D sources in the modern diet. Treatment Nutritional osteomalacia responds well to administration of 2,000-10,000 IU of vitamin D3 by mouth daily. Vitamin D3 (cholecalciferol) is typically absorbed more readily than vitamin D2 (ergocalciferol). Osteomalacia due to malabsorption may require treatment by injection or daily oral dosing of significant amounts of vitamin D3. Etymology Osteomalacia is derived from Greek: osteo- which means "bone", and malacia which means "softness". In the past, the disease was also known as malacosteon and its Latin-derived equivalent, mollities ossium. Osteomalacia is associated with increase in osteoid maturation time. See also Osteopetrosis References == External links ==

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What is the significance of the term 'Erythropoietic porphyria' in the medical field?

Erythropoietic porphyria is a type of porphyria associated with erythropoietic cells. In erythropoietic porphyrias, the enzyme deficiency occurs in the red blood cells. Types There are three types: Presentation X-linked dominant erythropoietic protoporphyria is a relatively mild version of porphyria with the predominant symptom being extreme photosensitivity causing severe itching and burning sensation of the skin due to the buildup of protoporphyrin IX. One possible treatment was discovered when treating an individual with supplemental iron for a gastric ulcer. Levels of free protoporphyrin decreased significantly as there was iron available for the FECH to produce heme. Levels of zinc-protoporphyrin, however did not decrease. Cause X-linked sideroblastic anemia or "X-linked dominant erythropoietic protoporphyria", associated with ALAS2 (aminolevulinic acid synthase), has also been described. X-linked dominant erythropoietic protoporphyria (XDEPP) is caused by a gain of function mutation in the ALAS2 (5-aminolevulinate synthase) gene; that gene encodes the very first enzyme in the heme biosynthetic pathway. The mutation is caused by a frameshift mutation caused by one of two deletions in the ALAS2 exon 11, either c. 1706-1709 delAGTG or c. 1699-1700 delAT. This alters the 19th and 20th residues of the C-terminal domain thereby altering the secondary structure of the enzyme. The delAT mutation only occurred in one family studied whereas the delAGTG mutation occurred in several genetically distinct families. The delAGTG causes a loss of an α-helix which is replaced by a β-sheet. Previously known mutations in the ALAS2 resulted in a loss-of-function mutation causing X-linked sideroblastic anemia. Erythropoietic protoporphyria (EPP) has similar symptoms as X-linked dominant erythropoietic protoporphyria but the mutation occurs as a loss-of-function in the FECH (ferrochelatase) enzyme; the very last enzyme in the pathway. All individuals studied presented symptoms without mutations in the FECH enzyme. The patterns of inheritance led the researchers to conclude the mutation must come from an enzyme on the X-chromosome with ALAS2 being the most likely candidate. X-linked dominant erythropoietic protoporphyria is distinct from EPP in that there is no overload of Fe2+ ions. Additionally, unlike the other condition the arises out of a mutation of the ALAS2 gene, there is no anaemia. XDEPP is characterized by a buildup of protoporphyrin IX caused by in increased level of function in the ALAS2 enzyme. Because there is a buildup of protoporphyrin IX with no malfunction of the FECH enzyme, all the available Fe2+ is used in the production of heme, causing the FECH enzyme to use Zn2+ in its place, causing a buildup of zinc-protoporphyrin IX. Diagnosis See also Hepatic porphyria References == External links ==

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I'm seeking clarification on the medical term 'Cisatracurium besilate.' Could you explain it?

Cisatracurium besilate (INN; cisatracurium besylate (USAN); formerly recognized as 51W89; trade name Nimbex) is a bisbenzyltetrahydroisoquinolinium that has effect as a neuromuscular-blocking drug non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. It shows intermediate duration of action. Cisatracurium is one of the ten isomers of the parent molecule, atracurium. Moreover, cisatracurium represents approximately 15% of the atracurium mixture. History The generic name cisatracurium was conceived by scientists at Burroughs Wellcome Co. (now part of GlaxoSmithKline) by combining the name "atracurium" with "cis" [hence cisatracurium] because the molecule is one of the three cis-cis isomers comprising the ten isomers of the parent, atracurium. Atracurium itself was invented at Strathclyde University and licensed to Burroughs Wellcome Co., Research Triangle Park, NC, for further development and subsequent marketing as Tracrium. As the secondary pharmacology of atracurium was being developed, it became clear that the primary clinical disadvantage of atracurium was likely to be its propensity to elicit histamine release. To address this issue, a program was initiated to investigate the individual isomer constituents of atracurium to identify and isolate the isomer(s) associated with the undesirable histamine effects as well as identify the isomer that might possibly retain the desirable properties without the histamine release. Thus, in 1989, D A Hill and G L Turner, PhD (both chemists at Burroughs Wellcome Co., Dartford, UK) first synthesized cisatracurium as an individual isomer molecule. The pharmacological research of cisatracurium and the other individual isomers was then developed further primarily by R. Brandt Maehr and William B. Wastila, PhD (both of whom were pharmacologists within the Division of Pharmacology at Burroughs Wellcome Co.) in collaboration with John J. Savarese MD (who at the time was an anesthesiologist in the Dept. of Anesthesia, Harvard Medical School at the Massachusetts General Hospital, Boston, MA). Thereafter, the entire clinical development of cisatracurium was completed in a record short period from 1992 to 1994: the team of scientists was led by J. Neal Weakly PhD, Martha M. Abou-Donia PhD, and Steve Quessy PhD, in the Division of Clinical Neurosciences at Burroughs Wellcome Co., Research Triangle Park, NC. By the time of its approval for human use, in 1995, by the US Food and Drug Administration, Burroughs Wellcome Co. had merged with Glaxo Inc., and cisatracurium was approved to be marketed as Nimbex by GlaxoWellcome Inc. The trade name "Nimbex" was derived from inserting an "i" to the original proposal "Nmbex," which stood for excellent Neuromuscular blocker. Preclinical pharmacology In vitro studies using human plasma indicated that cisatracurium spontaneously degrades at physiological pH via Hofmann elimination to yield laudanosine and the quaternary monoacrylate. Subsequent ester hydrolysis of the monoacrylate generates the monoquaternary alcohol, although the rate-limiting step is Hofmann elimination. In rat plasma, cisatracurium is also metabolized by non-specific carboxylesterases (a rate-limiting step) to the monoquaternary alcohol and the monoquaternary acid. Clinical pharmacology As is evident with the parent molecule, atracurium, cisatracurium is also susceptible to degradation by Hofmann elimination and ester hydrolysis as components of the in vivo metabolic processes. See the atracurium page for information on Hofmann elimination in vivo versus the Hofmann degradation chemical reaction. Because Hofmann elimination is a temperature- and plasma pH-dependent process, cisatracuriums rate of degradation in vivo is highly influenced by body pH and temperature just as it is with the parent molecule, atracurium: thus, an increase in body pH favors the elimination process, whereas a decrease in temperature slows down the process. One of the metabolites of cisatracurium via Hofmann elimination is laudanosine – see the atracurium page for further discussion of the issue regarding this metabolite. 80% of cisatracurium is metabolized eventually to laudanosine and 20% is metabolized hepatically or excreted renally. 10-15% of the dose is excreted unchanged in the urine.Since Hofmann elimination is an organ-independent chemodegradative mechanism, there is little or no risk to the use of cisatracurium in patients with liver or renal disease when compared with other neuromuscular-blocking agents.The two reverse ester linkages in the bridge between the two isoquinolinium groups make atracurium and cisatracurium poor targets for plasma cholinesterase, unlike mivacurium which has two conventional ester linkages. Adverse effects Histamine release – hypotension, reflex tachycardia and cutaneous flush Bronchospasm – Pulmonary compliance To date, cisatracurium has not been reported to elicit bronchospasm at doses that are clinically prescribed. Laudanosine – Epileptic foci Cisatracurium undergoes Hofmann elimination as a primary route of chemodegradation: consequently one of the metabolites from this process is laudanosine, a tertiary amino alkaloid reported to be a modest CNS stimulant with epileptogenic activity and cardiovascular effects such as low blood pressure and a slowed heart rate. As a tertiary amine, Laudanosine is unionised and readily crosses the blood–brain barrier. Presently, there is little evidence that laudanosine accumulation and related toxicity will likely ever be seen with the doses of cisatracurium that are administered in clinical practice especially given that the plasma concentrations of laudanosine generated are lower with cisatracurium than those seen with atracurium. Research A recent study showed that cisatracurium pretreatment effectively decreases the incidence and severity of pain induced by propofol general anaesthesia. Another study showed that hiccups accompanied by vomiting, insomnia, shortness of breath can also be relieved by the nondepolarizing muscle relaxant, cisatracurium, during total intravenous anesthesia. Synthesis Treatment of 1,5-Pentanediol with 3-bromopropionyl chloride gives the corresponding ester; dehydrohalogenation of the ester with triethylamine then gives the bis-acrylate (2). Reaction of that unsaturated ester with tetrahydropapaverine (3) leads to conjugate addition of the secondary amine and formation of the intermediate (4). Alkylation with methyl benzenesulfonate forms the bis-quaternary salt, affording cisatracuronium (5). References Further reading Caldwell JE (1995). "New skeletal muscle relaxants". Int Anesthesiol Clin. 33 (1): 39–60. doi:10.1097/00004311-199500000-00003. PMID 7635557. Hull CJ (1995). "Pharmacokinetics and pharmacodynamics of the benzylisoquinolinium muscle relaxants". Acta Anaesthesiol Scand. 106 Suppl: 13–17. doi:10.1111/j.1399-6576.1995.tb04302.x. PMID 8533537. S2CID 43784865. Savarese JJ, Wastila WB (1995). "The future of the benzylisoquinolinium relaxants". Acta Anaesthesiol Scand. 106 Suppl: 91–93. doi:10.1111/j.1399-6576.1995.tb04317.x. PMID 8533554. S2CID 39461057. Esmaoglu A, Akin A, Mizrak A, Turk Y, Boyaci A (2006). "Addition of cisatracurium to lidocaine for intravenous regional anesthesia". J Clin Anesth. 18 (3): 194–7. doi:10.1016/j.jclinane.2005.08.003. PMID 16731321. Melloni C, De Vivo P, Launo C, Mastronardi P, Novelli G, Romano E (2006). "Cisatracurium versus vecuronium: a comparative, double blind, randomized, multicenter study in adult patients under propofol/fentanyl/N2O anesthesia". Minerva Anestesiol. 72 (5): 299–308. PMID 16675938. Serra C, Oliveira A (2006). "Cisatracurium: myographical and electrophysiological studies in the isolated rat muscle". Fundam Clin Pharmacol. 20 (3): 291–8. doi:10.1111/j.1472-8206.2006.00395.x. PMID 16671964. S2CID 11980810. Katzung, Bertram G. (2011). Basic and clinical pharmacology (12th ed.). New York: Mcgraw-Hill. ISBN 978-0-07-176401-8. External links "Cisatracurium besylate". Drug Information Portal. U.S. National Library of Medicine. "Cisatracurium". Drug Information Portal. U.S. National Library of Medicine.

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Could you offer a clear explanation of the term 'Huntingtons disease' as used in the medical field?

Huntingtons disease (HD), also known as Huntingtons chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unsteady gait often follow. It is also a basal ganglia disease causing a hyperkinetic movement disorder known as chorea. As the disease advances, uncoordinated, involuntary body movements of chorea become more apparent. Physical abilities gradually worsen until coordinated movement becomes difficult and the person is unable to talk. Mental abilities generally decline into dementia. The specific symptoms vary somewhat between people. Symptoms usually begin between 30 and 50 years of age but can start at any age. The disease may develop earlier in each successive generation. About eight percent of cases start before the age of 20 years, and are known as juvenile HD, which typically present with the slow movement symptoms of Parkinsons disease rather than those of chorea.HD is typically inherited from an affected parent, who carries a mutation in the huntingtin gene (HTT). However, up to 10% of cases are due to a new mutation. The huntingtin gene provides the genetic information for huntingtin protein (Htt). Expansion of CAG repeats of cytosine-adenine-guanine (known as a trinucleotide repeat expansion) in the gene coding for the huntingtin protein results in an abnormal mutant protein (mHtt), which gradually damages brain cells through a number of possible mechanisms. Diagnosis is by genetic testing, which can be carried out at any time, regardless of whether or not symptoms are present. This fact raises several ethical debates: the age at which an individual is considered mature enough to choose testing; whether parents have the right to have their children tested; and managing confidentiality and disclosure of test results.No cure for HD is known, and full-time care is required in the later stages. Treatments can relieve some symptoms, and in some, improve quality of life. The best evidence for treatment of the movement problems is with tetrabenazine. HD affects about 4 to 15 in 100,000 people of European descent. It is rare among Japanese, while the occurrence rate in Africa is unknown. The disease affects men and women equally. Complications such as pneumonia, heart disease, and physical injury from falls reduce life expectancy. Suicide is the cause of death in about 9% of cases. Death typically occurs 15–20 years from when the disease was first detected.The earliest known description of the disease was in 1841 by American physician Charles Oscar Waters. The condition was described in further detail in 1872 by American physician George Huntington. The genetic basis was discovered in 1993 by an international collaborative effort led by the Hereditary Disease Foundation. Research and support organizations began forming in the late 1960s to increase public awareness, provide support for individuals and their families and promote research. 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. These are signs that the system in the brain that is responsible for movement has been affected. Psychomotor functions become increasingly impaired, such that any action that requires muscle control is affected. Common consequences are physical instability, abnormal facial expression, and difficulties chewing, swallowing, and speaking. Sleep disturbances and weight loss are also associated symptoms. Eating difficulties commonly cause weight loss and may lead to malnutrition. Juvenile HD generally progresses at a faster rate with greater cognitive decline, and chorea is exhibited briefly, if at all; the Westphal variant of slowness of movement, rigidity, and tremors is more typical in juvenile HD, as are seizures.Cognitive abilities are progressively impaired and tend to generally decline into dementia. Especially affected are executive functions, which include planning, cognitive flexibility, abstract thinking, rule acquisition, initiation of appropriate actions, and inhibition of inappropriate actions. As the disease progresses, memory deficits tend to appear. Reported impairments range from short-term memory deficits to long-term memory difficulties, including deficits in episodic (memory of ones life), procedural (memory of the body of how to perform an activity), and working memory.Reported neuropsychiatric signs are anxiety, depression, a reduced display of emotions, egocentrism, aggression, and compulsive behavior, the latter of which can cause or worsen addictions, including alcoholism, gambling, and hypersexuality. Difficulties in recognizing other peoples negative expressions have also been observed. The prevalence of these symptoms is highly variable between studies, with estimated rates for lifetime prevalence of psychiatric disorders between 33 and 76%. For many with the disease and their families, these symptoms are among the most distressing aspects of the disease, often affecting daily functioning and constituting reason for institutionalization. Early behavioral changes in HD result in an increased risk of suicide. Often, individuals have reduced awareness of chorea, cognitive, and emotional impairments.Mutant huntingtin is expressed throughout the body and associated with abnormalities in peripheral tissues that are directly caused by such expression outside the brain. These abnormalities include muscle atrophy, cardiac failure, impaired glucose tolerance, weight loss, osteoporosis, and testicular atrophy. Genetics Everyone has two copies of the huntingtin gene (HTT), which codes for the huntingtin protein (Htt). HTT is also called the HD gene, and the IT15 gene, (interesting transcript 15). Part of this gene is a repeated section called a trinucleotide repeat expansion – a short repeat, which varies in length between individuals, and may change length between generations. If the repeat is present in a healthy gene, a dynamic mutation may increase the repeat count and result in a defective gene. When the length of this repeated section reaches a certain threshold, it produces an altered form of the protein, called mutant huntingtin protein (mHtt). The differing functions of these proteins are the cause of pathological changes, which in turn cause the disease symptoms. The Huntingtons disease mutation is genetically dominant and almost fully penetrant; mutation of either of a persons HTT alleles causes the disease. It is not inherited according to sex, but by the length of the repeated section of the gene, hence its severity can be influenced by the sex of the affected parent. Genetic mutation HD is one of several trinucleotide repeat disorders that are caused by the length of a repeated section of a gene exceeding a normal range. The HTT gene is located on the short arm of chromosome 4 at 4p16.3. HTT contains a sequence of three DNA bases—cytosine-adenine-guanine (CAG)—repeated multiple times (i.e. ... CAGCAGCAG ...), known as a trinucleotide repeat. CAG is the three-letter genetic code (codon) for the amino acid glutamine, so a series of them results in the production of a chain of glutamine known as a polyglutamine tract (or polyQ tract), and the repeated part of the gene, the polyQ region. Generally, people have fewer than 36 repeated glutamines in the polyQ region, which results in the production of the cytoplasmic protein huntingtin. However, a sequence of 36 or more glutamines results in the production of a protein with different characteristics. This altered form, called mutant huntingtin (mHtt), increases the decay rate of certain types of neurons. Regions of the brain have differing amounts and reliance on these types of neurons and are affected accordingly. Generally, the number of CAG repeats is related to how much this process is affected, and accounts for about 60% of the variation of the age of the onset of symptoms. The remaining variation is attributed to the environment and other genes that modify the mechanism of HD. About 36 to 39 repeats result in a reduced-penetrance form of the disease, with a much later onset and slower progression of symptoms. In some cases, the onset may be so late that symptoms are never noticed. With very large repeat counts (more than 60), HD onset can occur below the age of 20, known as juvenile HD. Juvenile HD is typically of the Westphal variant that is characterised by slowness of movement, rigidity, and tremors. This accounts for about 7% of HD carriers. Inheritance Huntingtons disease has autosomal dominant inheritance, meaning that an affected individual typically inherits one copy of the gene with an expanded trinucleotide repeat (the mutant allele) from an affected parent. Since the penetrance of the mutation is very high, those who have a mutated copy of the gene will have the disease. In this type of inheritance pattern, each offspring of an affected individual has a 50% risk of inheriting the mutant allele, so are affected with the disorder (see figure). This probability is sex-independent.Trinucleotide CAG repeats numbering over 28 are unstable during replication, and this instability increases with the number of repeats present. This usually leads to new expansions as generations pass (dynamic mutations) instead of reproducing an exact copy of the trinucleotide repeat. This causes the number of repeats to change in successive generations, such that an unaffected parent with an "intermediate" number of repeats (28–35), or "reduced penetrance" (36–40), may pass on a copy of the gene with an increase in the number of repeats that produces fully penetrant HD. The earlier age of onset and greater severity of disease in successive generations due to increases in the number of repeats is known as genetic anticipation. Instability is greater in spermatogenesis than oogenesis; maternally inherited alleles are usually of a similar repeat length, whereas paternally inherited ones have a higher chance of increasing in length. Rarely is Huntingtons disease caused by a new mutation, where neither parent has over 36 CAG repeats.In the rare situations where both parents have an expanded HD gene, the risk increases to 75%, and when either parent has two expanded copies, the risk is 100% (all children will be affected). Individuals with both genes affected are rare. For some time, HD was thought to be the only disease for which possession of a second mutated gene did not affect symptoms and progression, but it has since been found that it can affect the phenotype and the rate of progression. Mechanisms Huntingtin protein interacts with over 100 other proteins, and appears to have multiple functions. The behavior of the mutated protein (mHtt) is not completely understood, but it is toxic to certain cell types, particularly brain cells. Early damage is most evident in the subcortical basal ganglia, initially in the striatum, but as the disease progresses, other areas of the brain are also affected, including regions of the cerebral cortex. Early symptoms are attributable to functions of the striatum and its cortical connections—namely control over movement, mood, and higher cognitive function. DNA methylation also appears to be changed in HD. Huntingtin function Htt is expressed in all cells, with the highest concentrations found in the brain and testes, and moderate amounts in the liver, heart, and lungs. Its functions are unclear, but it does interact with proteins involved in transcription, cell signaling, and intracellular transporting. In animals genetically modified to exhibit HD, several functions of Htt have been identified. In these animals, Htt is important for embryonic development, as its absence is related to embryonic death. Caspase, an enzyme which plays a role in catalyzing apoptosis, is thought to be activated by the mutated gene through damaging the ubiquitin-protease system. It also acts as an antiapoptotic agent preventing programmed cell death and controls the production of brain-derived neurotrophic factor, a protein that protects neurons and regulates their creation during neurogenesis. Htt also facilitates synaptic vesicular transport and synaptic transmission, and controls neuronal gene transcription. If the expression of Htt is increased, brain cell survival is improved and the effects of mHtt are reduced, whereas when the expression of Htt is reduced, the resulting characteristics are more as seen in the presence of mHtt. Accordingly, the disease is thought not to be caused by inadequate production of Htt, but by a toxic gain-of-function of mHtt in the body. Cellular changes The toxic action of mHtt may manifest and produce the HD pathology through multiple cellular changes. In its mutant (polyglutamine expanded) form, the protein is more prone to cleavage that creates shorter fragments containing the polyglutamine expansion. These protein fragments have a propensity to undergo misfolding and aggregation, yielding fibrillar aggregates in which non-native polyglutamine β-strands from multiple proteins are bonded together by hydrogen bonds. These aggregates share the same fundamental cross-beta amyloid architecture seen in other protein deposition diseases. Over time, the aggregates accumulate to form inclusion bodies within cells, ultimately interfering with neuronal function. Inclusion bodies have been found in both the cell nucleus and cytoplasm. Inclusion bodies in cells of the brain are one of the earliest pathological changes, and some experiments have found that they can be toxic for the cell, but other experiments have shown that they may form as part of the bodys defense mechanism and help protect cells.Several pathways by which mHtt may cause cell death have been identified. These include effects on chaperone proteins, which help fold proteins and remove misfolded ones; interactions with caspases, which play a role in the process of removing cells; the toxic effects of glutamine on nerve cells; impairment of energy production within cells; and effects on the expression of genes.Mutant huntingtin protein has been found to play a key role in mitochondrial dysfunction. The impairment of mitochondrial electron transport can result in higher levels of oxidative stress and release of reactive oxygen species.Glutamine is known to be excitotoxic when present in large amounts, that can cause damage to numerous cellular structures. Excessive glutamine is not found in HD, but the interactions of the altered huntingtin protein with numerous proteins in neurons lead to an increased vulnerability to glutamine. The increased vulnerability is thought to result in excitotoxic effects from normal glutamine levels. Macroscopic changes Initially, damage to the brain is regionally specific with the dorsal striatum in the subcortical basal ganglia being primarily affected, followed later by cortical involvement in all areas. Other areas of the basal ganglia affected include the substantia nigra; cortical involvement includes cortical layers 3, 5, and 6; also evident is involvement of the hippocampus, Purkinje cells in the cerebellum, lateral tuberal nuclei of the hypothalamus and parts of the thalamus. These areas are affected according to their structure and the types of neurons they contain, reducing in size as they lose cells. Striatal medium spiny neurons are the most vulnerable, particularly ones with projections towards the external globus pallidus, with interneurons and spiny cells projecting to the internal globus pallidus being less affected. HD also causes an abnormal increase in astrocytes and activation of the brains immune cells, microglia.The basal ganglia play a key role in movement and behavior control. Their functions are not fully understood, but theories propose that they are part of the cognitive executive system and the motor circuit. The basal ganglia ordinarily inhibit a large number of circuits that generate specific movements. To initiate a particular movement, the cerebral cortex sends a signal to the basal ganglia that causes the inhibition to be released. Damage to the basal ganglia can cause the release or reinstatement of the inhibitions to be erratic and uncontrolled, which results in an awkward start to motion or motions to be unintentionally initiated, or a motion to be halted before, or beyond, its intended completion. The accumulating damage to this area causes the characteristic erratic movements associated with HD known as chorea, a dyskinesia. Because of the basal ganglias inability to inhibit movements, individuals affected by it inevitably experience a reduced ability to produce speech and swallow foods and liquids (dysphagia). Transcriptional dysregulation CREB-binding protein (CBP), a transcriptional coregulator, is essential for cell function because as a coactivator at a significant number of promoters, it activates the transcription of genes for survival pathways. Furthermore, the amino acids that form CBP include a strip of 18 glutamines. Thus, the glutamines on CBP interact directly with the increased numbers of glutamine on the HTT chain and CBP gets pulled away from its typical location next to the nucleus. Specifically, CBP contains an acetyltransferase domain to which HTT binds through its polyglutamine-containing domain. Autopsied brains of those who had Huntingtons disease also have been found to have incredibly reduced amounts of CBP. In addition, when CBP is overexpressed, polyglutamine-induced death is diminished, further demonstrating that CBP plays an important role in Huntingtons disease and neurons in general. Diagnosis Diagnosis of the onset of HD can be made following the appearance of physical symptoms specific to the disease. Genetic testing can be used to confirm a physical diagnosis if no family history of HD exists. Even before the onset of symptoms, genetic testing can confirm if an individual or embryo carries an expanded copy of the trinucleotide repeat (CAG) in the HTT gene that causes the disease. Genetic counseling is available to provide advice and guidance throughout the testing procedure and on the implications of a confirmed diagnosis. These implications include the impact on an individuals psychology, career, family-planning decisions, relatives, and relationships. Despite the availability of presymptomatic testing, only 5% of those at risk of inheriting HD choose to do so. Clinical A physical examination, sometimes combined with a psychological examination, can determine whether the onset of the disease has begun. Excessive unintentional movements of any part of the body are often the reason for seeking medical consultation. If these are abrupt and have random timing and distribution, they suggest a diagnosis of HD. Cognitive or behavioral symptoms are rarely the first symptoms diagnosed; they are usually only recognized in hindsight or when they develop further. How far the disease has progressed can be measured using the unified Huntingtons disease rating scale, which provides an overall rating system based on motor, behavioral, cognitive, and functional assessments. Medical imaging, such as a CT scan or MRI scan, can show atrophy of the caudate nuclei early in the disease, as seen in the illustration to the right, but these changes are not, by themselves, diagnostic of HD. Cerebral atrophy can be seen in the advanced stages of the disease. Functional neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), can show changes in brain activity before the onset of physical symptoms, but they are experimental tools and are not used clinically. Predictive genetic testing Because HD follows an autosomal dominant pattern of inheritance, a strong motivation exists for individuals who are at risk of inheriting it to seek a diagnosis. The genetic test for HD consists of a blood test, which counts the numbers of CAG repeats in each of the HTT alleles. Cutoffs are given as follows: At 40 or more CAG repeats, full penetrance allele (FPA) exists. A "positive test" or "positive result" generally refers to this case. A positive result is not considered a diagnosis, since it may be obtained decades before the symptoms begin. However, a negative test means that the individual does not carry the expanded copy of the gene and will not develop HD. The test will tell a person who originally had a 50% chance of inheriting the disease if their risk goes up to 100% or is eliminated. Persons who test positive for the disease will develop HD sometime within their lifetimes, provided they live long enough for the disease to appear. At 36 to 39 repeats, incomplete or reduced penetrance allele (RPA) may cause symptoms, usually later in the adult life. The maximum risk is 60% that a person with an RPA will be symptomatic at age 65, and 70% at 75. At 27 to 35 repeats, intermediate allele (IA), or large normal allele, is not associated with symptomatic disease in the tested individual, but may expand upon further inheritance to give symptoms in offspring. With 26 or fewer repeats, the result is not associated with HD.Testing before the onset of symptoms is a life-changing event and a very personal decision. The main reason given for choosing to test for HD is to aid in career and family decisions. Predictive testing for Huntingtons disease has been available via linkage analysis (which requires testing multiple family members) since 1986 and via direct mutation analysis since 1993. At that time, surveys indicated that 50–70% of at-risk individuals would have been interested in receiving testing, but since predictive testing has been offered far fewer choose to be tested. Over 95% of individuals at risk of inheriting HD do not proceed with testing, mostly because it has no treatment. A key issue is the anxiety an individual experiences about not knowing whether they will eventually develop HD, compared to the impact of a positive result. Irrespective of the result, stress levels are lower two years after being tested, but the risk of suicide is increased after a positive test result. Individuals found to have not inherited the disorder may experience survivor guilt about family members who are affected. Other factors taken into account when considering testing include the possibility of discrimination and the implications of a positive result, which usually means a parent has an affected gene and that the individuals siblings will be at risk of inheriting it. In one study, genetic discrimination was found in 46% of individuals at risk for Huntingtons disease. It occurred at higher rates within personal relationships than health insurance or employment relations. Genetic counseling in HD can provide information, advice and support for initial decision-making, and then, if chosen, throughout all stages of the testing process. Because of the implications of this test, patients who wish to undergo testing must complete three counseling sessions which provide information about Huntingtons.Counseling and guidelines on the use of genetic testing for HD have become models for other genetic disorders, such as autosomal dominant cerebellar ataxia. Presymptomatic testing for HD has also influenced testing for other illnesses with genetic variants such as polycystic kidney disease, familial Alzheimers disease and breast cancer. The European Molecular Genetics Quality Network have published yearly external quality assessment scheme for molecular genetic testing for this disease and have developed best practice guidelines for genetic testing for HD to assist in testing and reporting of results. Preimplantation genetic diagnosis Embryos produced using in vitro fertilization may be genetically tested for HD using preimplantation genetic diagnosis. This technique, where one or two cells are extracted from a typically 4- to 8-cell embryo and then tested for the genetic abnormality, can then be used to ensure embryos affected with HD genes are not implanted, so any offspring will not inherit the disease. Some forms of preimplantation genetic diagnosis—non-disclosure or exclusion testing—allow at-risk people to have HD-free offspring without revealing their own parental genotype, giving no information about whether they themselves are destined to develop HD. In exclusion testing, the embryos DNA is compared with that of the parents and grandparents to avoid inheritance of the chromosomal region containing the HD gene from the affected grandparent. In nondisclosure testing, only disease-free embryos are replaced in the uterus while the parental genotype and hence parental risk for HD are never disclosed. Prenatal testing Obtaining a prenatal diagnosis for an embryo or fetus in the womb is also possible, using fetal genetic material acquired through chorionic villus sampling. An amniocentesis can be performed if the pregnancy is further along, within 14–18 weeks. This procedure looks at the amniotic fluid surrounding the baby for indicators of the HD mutation. This, too, can be paired with exclusion testing to avoid disclosure of parental genotype. Prenatal testing can be done when parents have been diagnosed with HD, when they have had genetic testing showing the expansion of the HTTgene, or when they have a 50% chance of inheriting the disease. The parents can be counseled on their options, which include termination of pregnancy, and on the difficulties of a child with the identified gene.In addition, in at-risk pregnancies due to an affected male partner, noninvasive prenatal diagnosis can be performed by analyzing cell-free fetal DNA in a blood sample taken from the mother (via venipuncture) between six and 12 weeks of pregnancy. It has no procedure-related risk of miscarriage. Differential diagnosis About 99% of HD diagnoses based on the typical symptoms and a family history of the disease are confirmed by genetic testing to have the expanded trinucleotide repeat that causes HD. Most of the remaining are called HD-like (HDL) syndromes. The cause of most HDL diseases is unknown, but those with known causes are due to mutations in the prion protein gene (HDL1), the junctophilin 3 gene (HDL2), a recessively inherited unknown gene (HDL3—only found in two families and poorly understood), and the gene encoding the TATA box-binding protein (SCA17, sometimes called HDL4). Other autosomal dominant diseases that can be misdiagnosed as HD are dentatorubral-pallidoluysian atrophy and neuroferritinopathy. Also, some autosomal recessive disorders resemble sporadic cases of HD. These include chorea acanthocytosis and pantothenate kinase-associated neurodegeneration. One X-linked disorder of this type is McLeod syndrome. Management Treatments are available to reduce the severity of some of HD symptoms. For many of these treatments, evidence to confirm their effectiveness in treating symptoms of HD specifically are incomplete. As the disease progresses, the ability to care for oneself declines, and carefully managed multidisciplinary caregiving becomes increasingly necessary. Although relatively few studies of exercises and therapies have shown to be helpful to rehabilitate cognitive symptoms of HD, some evidence shows the usefulness of physical therapy, occupational therapy, and speech therapy. Therapy Weight loss and problems in eating due to dysphagia and other muscle discoordination are common, making nutrition management increasingly important as the disease advances. Thickening agents can be added to liquids, as thicker fluids are easier and safer to swallow. Reminding the affected person to eat slowly and to take smaller pieces of food into the mouth may also be of use to prevent choking. If eating becomes too hazardous or uncomfortable, the option of using a percutaneous endoscopic gastrostomy is available. This feeding tube, permanently attached through the abdomen into the stomach, reduces the risk of aspirating food and provides better nutritional management. Assessment and management by speech-language pathologists with experience in Huntingtons disease is recommended.People with Huntingtons disease may see a physical therapist for noninvasive and nonmedication-based ways of managing the physical symptoms. Physical therapists may implement fall risk assessment and prevention, as well as strengthening, stretching, and cardiovascular exercises. Walking aids may be prescribed as appropriate. Physical therapists also prescribe breathing exercises and airway clearance techniques with the development of respiratory problems. Consensus guidelines on physiotherapy in Huntingtons disease have been produced by the European HD Network. Goals of early rehabilitation interventions are prevention of loss of function. Participation in rehabilitation programs during the early to middle stage of the disease may be beneficial as it translates into long-term maintenance of motor and functional performance. Rehabilitation during the late stage aims to compensate for motor and functional losses. For long-term independent management, the therapist may develop home exercise programs for appropriate people.Additionally, an increasing number of people with HD are turning to palliative care, which aims to improve quality of life through the treatment of the symptoms and stress of serious illness, in addition to their other treatments. Medications Tetrabenazine was approved in 2000 for treatment of chorea in Huntingtons disease in the EU, and in 2008 in the US. Although other drugs had been used "off label," tetrabenazine was the first approved treatment for Huntingtons disease in the U.S. The compound has been known since the 1950s. An alternative to tetrabenazine is amantadine but there is limited evidence for its safety and efficacy.Other drugs that help to reduce chorea include antipsychotics and benzodiazepines. Hypokinesia and rigidity, especially in juvenile cases, can be treated with antiparkinsonian drugs, and myoclonic hyperkinesia can be treated with valproic acid. Tentative evidence has found ethyl eicosapentaenoic acid to improve motor symptoms at one year. In 2017 Deutetrabenazine a heavier form of tetrabenazine medication for the treatment of chorea in HD was approved by the FDA. This is marketed as Austedo, and is the first small-molecule drug to receive U.S. FDA approval.Psychiatric symptoms can be treated with medications similar to those used in the general population. Selective serotonin reuptake inhibitors and mirtazapine have been recommended for depression, while atypical antipsychotics are recommended for psychosis and behavioral problems. Specialist neuropsychiatric input is recommended as people may require long-term treatment with multiple medications in combination. Education The families of individuals, and society at large, who have inherited or are at risk of inheriting HD have generations of experience of HD but may be unaware of recent breakthroughs in understanding the disease, and of the availability of genetic testing. Genetic counseling benefits these individuals by updating their knowledge, seeking to dispel any unfounded beliefs that they may have, and helping them consider their future options and plans. The Patient Education Program for Huntingtons Disease has been created to help educate family members, caretakers, and those diagnosed with Huntingtons disease. Also covered is information concerning family planning choices, care management, and other considerations. Prognosis The length of the trinucleotide repeat accounts for 60% of the variation of the age of symptoms onset and their rate of progress. A longer repeat results in an earlier age of onset and a faster progression of symptoms. Individuals with more than sixty repeats often develop the disease before age 20, while those with fewer than 40 repeats may remain asymptomatic. The remaining variation is due to environmental factors and other genes that influence the mechanism of the disease.Life expectancy in HD is generally around 20 years following the onset of visible symptoms. Most life-threatening complications result from muscle coordination, and to a lesser extent, behavioral changes induced by declining cognitive function. The largest risk is pneumonia, which causes death in one third of those with HD. As the ability to synchronize movements deteriorates, difficulty clearing the lungs, and an increased risk of aspirating food or drink both increase the risk of contracting pneumonia. The second-greatest risk is heart disease, which causes almost a quarter of fatalities of those with HD. Suicide is the third greatest cause of fatalities, with 7.3% of those with HD taking their own lives and up to 27% attempting to do so. To what extent suicidal thoughts are influenced by behavioral symptoms is unclear, as they signify a desire to avoid the later stages of the disease. Other associated risks include choking, physical injury from falls, and malnutrition. Epidemiology The late onset of Huntingtons disease means it does not usually affect reproduction. The worldwide prevalence of HD is 5–10 cases per 100,000 persons, but varies greatly geographically as a result of ethnicity, local migration and past immigration patterns. Prevalence is similar for men and women. The rate of occurrence is highest in peoples of Western European descent, averaging around seven per 100,000 people, and is lower in the rest of the world; e.g., one per million people of Asian and African descent. A 2013 epidemiological study of the prevalence of Huntingtons disease in the UK between 1990 and 2010 found that the average prevalence for the UK was 12.3 per 100,000. Additionally, some localized areas have a much higher prevalence than their regional average. One of the highest incidences is in the isolated populations of the Lake Maracaibo region of Venezuela, where HD affects up to 700 per 100,000 persons. Other areas of high localization have been found in Tasmania and specific regions of Scotland, Wales and Sweden. Increased prevalence in some cases occurs due to a local founder effect, a historical migration of carriers into an area of geographic isolation. Some of these carriers have been traced back hundreds of years using genealogical studies. Genetic haplotypes can also give clues for the geographic variations of prevalence. Iceland, on the contrary, has a rather low prevalence of 1 per 100,000, despite the fact that Icelanders as a people are descended of the early Germanic tribes of Scandinavia which also gave rise to the Swedes; all cases with the exception of one going back nearly two centuries having derived from the offspring of a couple living early in the 19th century. Finland, as well, has a low incidence of only 2.2 per 100,000 people.Until the discovery of a genetic test, statistics could only include clinical diagnosis based on physical symptoms and a family history of HD, excluding those who died of other causes before diagnosis. These cases can now be included in statistics; and, as the test becomes more widely available, estimates of the prevalence and incidence of the disorder are likely to increase. History The first definite mention of HD was in a letter by Charles Oscar Waters (1816–1892), published in the first edition of Robley Dunglisons Practice of Medicine in 1842. Waters described "a form of chorea, vulgarly called magrums", including accurate descriptions of the chorea, its progression, and the strong heredity of the disease. In 1846 Charles Rollin Gorman (1817–1879) observed how higher prevalence seemed to occur in localized regions. Independently of Gorman and Waters, both students of Dunglison at Jefferson Medical College in Philadelphia, Johan Christian Lund (1830–1906) also produced an early description in 1860. He specifically noted that in Setesdalen, a secluded mountain valley in Norway, the high prevalence of dementia was associated with a pattern of jerking movement disorders that ran in families.The first thorough description of the disease was by George Huntington in 1872. Examining the combined medical history of several generations of a family exhibiting similar symptoms, he realized their conditions must be linked; he presented his detailed and accurate definition of the disease as his first paper. Huntington described the exact pattern of inheritance of autosomal dominant disease years before the rediscovery by scientists of Mendelian inheritance. Of its hereditary nature. When either or both the parents have shown manifestations of the disease ... one or more of the offspring almost invariably suffer from the disease ... But if by any chance these children go through life without it, the thread is broken and the grandchildren and great-grandchildren of the original shakers may rest assured that they are free from the disease. Sir William Osler was interested in the disorder and chorea in general, and was impressed with Huntingtons paper, stating, "In the history of medicine, there are few instances in which a disease has been more accurately, more graphically or more briefly described." Oslers continued interest in HD, combined with his influence in the field of medicine, helped to rapidly spread awareness and knowledge of the disorder throughout the medical community. Great interest was shown by scientists in Europe, including Louis Théophile Joseph Landouzy, Désiré-Magloire Bourneville, Camillo Golgi, and Joseph Jules Dejerine, and until the end of the century, much of the research into HD was European in origin. By the end of the 19th century, research and reports on HD had been published in many countries and the disease was recognized as a worldwide condition.During the rediscovery of Mendelian inheritance at the turn of the 20th century, HD was used tentatively as an example of autosomal dominant inheritance. English biologist William Bateson used the pedigrees of affected families to establish that HD had an autosomal dominant inheritance pattern. The strong inheritance pattern prompted several researchers, including Smith Ely Jelliffe, to attempt to trace and connect family members of previous studies. Jelliffe collected information from across New York and published several articles regarding the genealogy of HD in New England. Jelliffes research roused the interest of his college friend, Charles Davenport, who commissioned Elizabeth Muncey to produce the first field study on the East Coast of the United States of families with HD and to construct their pedigrees. Davenport used this information to document the variable age of onset and range of symptoms of HD; he claimed that most cases of HD in the US could be traced back to a handful of individuals. This research was further embellished in 1932 by P. R. Vessie, who popularized the idea that three brothers who left England in 1630 bound for Boston were the progenitors of HD in the US. The claim that the earliest progenitors had been established and eugenic bias of Munceys, Davenports, and Vessies work contributed to misunderstandings and prejudice about HD. Muncey and Davenport also popularized the idea that in the past, some with HD may have been thought to be possessed by spirits or victims of witchcraft, and were sometimes shunned or exiled by society. This idea has not been proven. Researchers have found contrary evidence; for instance, the community of the family studied by George Huntington openly accommodated those who exhibited symptoms of HD.The search for the cause of this condition was enhanced considerably in 1968, when the Hereditary Disease Foundation (HDF) was created by Milton Wexler, a psychoanalyst based in Los Angeles, California, whose wife Leonore Sabin had been diagnosed earlier that year with Huntingtons disease. The three brothers of Wexlers wife also had this disease. The foundation was involved in the recruitment of more than 100 scientists in the US-Venezuela Huntingtons Disease Collaborative Project, which over a 10-year period from 1979, worked to locate the genetic cause. This was achieved in 1983 when a causal gene was approximately located, and in 1993, the gene was precisely located at chromosome 4 (4p16.3). The study had focused on the populations of two isolated Venezuelan villages, Barranquitas and Lagunetas, where there was an unusually high prevalence of HD, and involved over 18,000 people, mostly from a single extended family, and resulted in making HD the first autosomal disease locus found using genetic linkage analysis. Among other innovations, the project developed DNA-marking methods which were an important step in making the Human Genome Project possible.In the same time, key discoveries concerning the mechanisms of the disorder were being made, including the findings by Anita Hardings research group on the effects of the genes length.Modelling the disease in various types of animals, such as the transgenic mouse developed in 1996, enabled larger-scale experiments. As these animals have faster metabolisms and much shorter lifespans than humans results from experiments are received sooner, speeding research. The 1997 discovery that mHtt fragments misfold led to the discovery of the nuclear inclusions they cause. These advances have led to increasingly extensive research into the proteins involved with the disease, potential drug treatments, care methods, and the gene itself.The condition was formerly called Huntingtons chorea, but this term has been replaced by Huntingtons disease because not all patients develop chorea and due to the importance of cognitive and behavioral problems. Society and culture Ethics Genetic testing for Huntingtons disease has raised several ethical issues. The issues for genetic testing include defining how mature an individual should be before being considered eligible for testing, ensuring the confidentiality of results, and whether companies should be allowed to use test results for decisions on employment, life insurance or other financial matters. There was controversy when Charles Davenport proposed in 1910 that compulsory sterilization and immigration control be used for people with certain diseases, including HD, as part of the eugenics movement. In vitro fertilization has some issues regarding its use of embryos. Some HD research has ethical issues due to its use of animal testing and embryonic stem cells.The development of an accurate diagnostic test for Huntingtons disease has caused social, legal, and ethical concerns over access to and use of a persons results. Many guidelines and testing procedures have strict procedures for disclosure and confidentiality to allow individuals to decide when and how to receive their results and also to whom the results are made available. Insurance companies and businesses are faced with the question of whether to use genetic test results when assessing an individual, such as for life insurance or employment. The United Kingdoms insurance companies agreed with the Department of Health and Social Care that until 2017 customers would not need to disclose predictive genetics tests to them, but this agreement explicitly excluded the government-approved test for Huntingtons when writing policies with a value over £500,000. As with other untreatable genetic conditions with a later onset, it is ethically questionable to perform pre-symptomatic testing on a child or adolescent, as there would be no medical benefit for that individual. There is consensus for testing only individuals who are considered cognitively mature, although there is a counter-argument that parents have a right to make the decision on their childs behalf. With the lack of an effective treatment, testing a person under legal age who is not judged to be competent is considered unethical in most cases.There are ethical concerns related to prenatal genetic testing or preimplantation genetic diagnosis to ensure a child is not born with a given disease. For example, prenatal testing raises the issue of selective abortion, a choice considered unacceptable by some. As it is a dominant disease, there are difficulties in situations in which a parent does not want to know his or her own diagnosis. This would require parts of the process to be kept secret from the parent. Support organizations In 1968, after experiencing HD in his wifes family, Dr. Milton Wexler was inspired to start the Hereditary Disease Foundation (HDF), with the aim of curing genetic illnesses by coordinating and supporting research. The foundation and Wexlers daughter, Nancy Wexler, were key parts of the research team in Venezuela which discovered the HD gene.At roughly the same time as the HDF formed, Marjorie Guthrie helped to found the committee to Combat Huntingtons Disease (now the Huntingtons Disease Society of America), after her husband, folk singer-songwriter Woody Guthrie died from complications of HD.Since then, support and research organizations have formed in many countries around the world and have helped to increase public awareness of HD. A number of these collaborate in umbrella organizations, like the International Huntington Association and the European HD network. Many support organizations hold an annual HD awareness event, some of which have been endorsed by their respective governments. For example, 6 June is designated "National Huntingtons Disease Awareness Day" by the US Senate. Many organizations exist to support and inform those affected by HD, including the Huntingtons Disease Association in the UK. The largest funder of research is provided by the Cure Huntingtons Disease Initiative Foundation (CHDI). Research directions Research into the mechanism of HD is focused on identifying the functioning of Htt, how mHtt differs or interferes with it, and the brain pathology that the disease produces. Research is conducted using in vitro methods, genetically modified animals, (also called transgenic animal models), and human volunteers. Animal models are critical for understanding the fundamental mechanisms causing the disease, and for supporting the early stages of drug development. The identification of the causative gene has enabled the development of many genetically modified organisms including nematodes (roundworms), Drosophila fruit flies, and genetically modified mammals including mice, rats, sheep, pigs and monkeys that express mutant huntingtin and develop progressive neurodegeneration and HD-like symptoms.Research is being conducted using many approaches to either prevent Huntingtons disease or slow its progression. Disease-modifying strategies can be broadly grouped into three categories: reducing the level of the mutant huntingtin protein (including gene splicing and gene silencing); approaches aimed at improving neuronal survival by reducing the harm caused by the protein to specific cellular pathways and mechanisms (including protein homeostasis and histone deacetylase inhibition); and strategies to replace lost neurons. In addition, novel therapies to improve brain functioning are under development; these seek to produce symptomatic rather than disease-modifying therapies, and include phosphodiesterase inhibitors.The CHDI Foundation funds a great many research initiatives providing many publications. The CHDI foundation is the largest funder of Huntingtons disease research globally and aims to find and develop drugs that will slow the progression of HD. CHDI was formerly known as the High Q Foundation. In 2006, it spent $50 million on Huntingtons disease research. CHDI collaborates with many academic and commercial laboratories globally and engages in oversight and management of research projects as well as funding. Reducing huntingtin production Gene silencing aims to reduce the production of the mutant protein, since HD is caused by a single dominant gene encoding a toxic protein. Gene silencing experiments in mouse models have shown that when the expression of mHtt is reduced, symptoms improve. The safety of RNA interference, and allele-specific oligonucleotide (ASO) methods of gene silencing has been demonstrated in mice and the larger primate macaque brain. Allele-specific silencing attempts to silence mutant htt while leaving wild-type Htt untouched. One way of accomplishing this is to identify polymorphisms present on only one allele and produce gene silencing drugs that target polymorphisms in only the mutant allele. The first gene silencing trial involving humans with HD began in 2015, testing the safety of IONIS-HTTRx, produced by Ionis Pharmaceuticals and led by UCL Institute of Neurology. Mutant huntingtin was detected and quantified for the first time in cerebrospinal fluid from Huntingtons disease mutation-carriers in 2015 using a novel "single-molecule counting" immunoassay, providing a direct way to assess whether huntingtin-lowering treatments are achieving the desired effect. A phase 3 trial of this compound, renamed tominersen and sponsored by Roche Pharmaceuticals, began in 2019 but was halted in 2021 after the safety monitoring board concluded that the risk-benefit balance was unfavourable. A huntingtin-lowering gene therapy trial run by Uniqure began in 2019, and several trials of orally administered huntingtin-lowering splicing modulator compounds have been announced. Gene splicing techniques are being looked at to try to repair a genome with the erroneous gene that causes HD, using tools such as CRISPR/Cas9. Increasing huntingtin clearance Another strategy to reduce the level of mutant huntingtin is to increase the rate at which cells are able to clear it. As mHtt (and many other protein aggregates) are degraded by autophagy, increasing the rate of autophagy has the potential to reduce levels of mHtt and thereby ameliorate disease. Pharmacological and genetic inducers of autophagy have been tested in a variety of Huntingtons disease models; many have been shown to reduce mHtt levels and decrease toxicity. Improving cell survival Among the approaches aimed at improving cell survival in the presence of mutant huntingtin are correction of transcriptional regulation using histone deacetylase inhibitors, modulating aggregation of huntingtin, improving metabolism and mitochondrial function and restoring function of synapses. Neuronal replacement Stem-cell therapy is used to replace damaged neurons by transplantation of stem cells into affected regions of the brain. Experiments in animal models (rats and mice only) have yielded positive results.Whatever their future therapeutic potential, stem cells are already a valuable tool for studying Huntingtons disease in the laboratory. Clinical trials In 2020 there were 197 clinical trials related to varied therapies and biomarkers for Huntingtons disease listed as either underway, recruiting or newly completed. Compounds trialled, that have failed to prevent or slow the progression of Huntingtons disease include remacemide, coenzyme Q10, riluzole, creatine, minocycline, ethyl-EPA, phenylbutyrate and dimebon. See also Medicine portal References External links Huntingtons disease at Curlie HOPES project – Stanford Universitys HD information project HDBuzz – HD research news written by scientists in plain language HD Drug Works – news about current treatments and planned trials

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I'm seeking clarification on the medical term 'Venezuelan hemorrhagic fever.' Could you explain it?

Venezuelan hemorrhagic fever (VHF) is a zoonotic human illness first identified in 1989. The disease is most prevalent in several rural areas of central Venezuela and is caused by Guanarito mammarenavirus (GTOV) which belongs to the Arenaviridae family. The short-tailed cane mouse (Zygodontomys brevicauda) is the main host for GTOV which is spread mostly by inhalation of aerosolized droplets of saliva, respiratory secretions, urine, or blood from infected rodents. Person-to-person spread is possible, but uncommon. Presentation VHF has many similarities to Lassa fever and to the arenavirus hemorrhagic fevers that occur in Argentina and Bolivia. It causes fever and malaise followed by hemorrhagic manifestations and convulsions. Some presentations of the virus are also characterized by vascular damage, bleeding diathesis, fever, and multiple organ involvement. Clinical diagnosis of VHF has proven to be difficult based on the nonspecific symptoms. The disease is fatal in 30% of cases and is endemic to Portuguesa state and Barinas state in Venezuela. Treatment and prevention for the VHF virus are limited and there are currently no licensed vaccines available that can act to prevent the disease. However, once infected, ribavirin, an anti-viral drug given intravenously, is one way to treat VHF. Virus Arenaviruses are enveloped, single-stranded, bisegmented RNA viruses with antisense genomes. Based on their antigenic properties, arenaviruses have been classified into two major groups: the Old World arenaviruses, and the New World arenaviruses. Old World arenaviruses include lymphocytic choriomeningitis virus and Lassa virus. New world arena viruses are further broken down into three clades, A, B, and C. The Guanarito arena virus belongs to clade B and is the cause of VHF. On the biosafety level scale of one to four, with four causing the most risk, the viruses causing hemorrhagic fevers have been assigned a four by the CDC. Host The short-tailed cane mouse, the main host of GTOV, is native to western Venezuela and resides in large numbers in tall grass, cultivated agricultural fields, human homes, and outbuildings. It is speculated that demographic and ecological changes in the rural areas increased the frequency of contact between humans and infected rodents such that VHF emerged. History From September 1989 through December 2006, the State of Portuguesa recorded 618 cases of VHF. Nearly all of the cases were individuals who worked or lived in Guanarito during the time they became infected. The case fatality rate was 23.1%.Because the virus is contracted by aerosol dissemination, concern arose shortly after the first cases emerged in 1989 due to fear of biological warfare. Potential biological terrorism agents were identified and categorized in 1999 by the Centers for Disease Control and Prevention (CDC) as part of the Congressional initiative to further response capabilities to biological weapons. Arenaviruses causing hemorrhagic fevers, along with a genus of virus called filoviruses, were categorized in Category A; these are pathogens with the highest potential impact on public health safety. A notable event in the timeline of this virus scientific knowledge was the unexplained disappearance of a vial of the virus at the University of Texas Medical Branch Galveston National Laboratory, announced 2013 March 24. References == External links ==

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I'm encountering the term 'Peripheral artery disease' in medical literature. What's its definition?

Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular disease. Peripheral artery disease most commonly affects the legs, but other arteries may also be involved – such as those of the arms, neck, or kidneys. The classic symptom is leg pain when walking which resolves with rest, known as intermittent claudication. Other symptoms include skin ulcers, bluish skin, cold skin, or abnormal nail and hair growth in the affected leg. Complications may include an infection or tissue death which may require amputation; coronary artery disease, or stroke. Up to 50% of people with PAD do not have symptoms.The greatest risk factor for PAD is cigarette smoking. Other risk factors include diabetes, high blood pressure, kidney problems, and high blood cholesterol. The most common underlying mechanism of peripheral artery disease is atherosclerosis, especially in individuals over 40 years old. Other mechanisms include artery spasm, blood clots, trauma, fibromuscular dysplasia, and vasculitis. PAD is typically diagnosed by finding an ankle-brachial index (ABI) less than 0.90, which is the systolic blood pressure at the ankle divided by the systolic blood pressure of the arm. Duplex ultrasonography and angiography may also be used. Angiography is more accurate and allows for treatment at the same time; however, it is associated with greater risks.It is unclear if screening for peripheral artery disease in people without symptoms is useful as it has not been properly studied. In those with intermittent claudication from PAD, stopping smoking and supervised exercise therapy improve outcomes. Medications, including statins, ACE inhibitors, and cilostazol may also help. Aspirin does not appear to help those with mild disease but is usually recommended in those with more significant disease due to the increased risk of heart attacks. Anticoagulants such as warfarin are not typically of benefit. Procedures used to treat the disease include bypass grafting, angioplasty, and atherectomy.In 2015, about 155 million people had PAD worldwide. It becomes more common with age. In the developed world, it affects about 5.3% of 45- to 50-year-olds and 18.6% of 85- to 90-year-olds. In the developing world, it affects 4.6% of people between the ages of 45 and 50 and 15% of people between the ages of 85 and 90. PAD in the developed world is equally common among men and women, though in the developing world, women are more commonly affected. In 2015 PAD resulted in about 52,500 deaths, which is an increase from the 16,000 deaths in 1990. Signs and symptoms The signs and symptoms of peripheral artery disease are based on the part of the body that is affected. About 66% of patients affected by PAD either do not have symptoms or have atypical symptoms. The most common presenting symptom is intermittent claudication, which causes pain and severe cramping when walking or exercising. The pain is usually located in the calf muscles of the affected leg and relieved by rest. This occurs because during exercise the muscles of the leg need more oxygen. Normally, the arteries would be able to increase the amount of blood flow and therefore increase the amount of oxygen going to the exercised leg. However, in PAD, the artery is unable to respond appropriately to the increased demand for oxygen by the muscles, as a result, the leg muscles are overly saturated with lactic acid, resulting in pain of the muscle that only goes away with rest.Other symptoms may include Pain, aches, and/or cramps in the buttocks, hip, or thigh Muscle atrophy (muscle loss) of the affected limb Hair loss of the affected limb Skin that is smooth, shiny, or cool to the touch in the affected area Decreased or absent pulse in feet Cold and/or numbness in the toes Sores/ulcers on the affected limb that do not healIn individuals with severe PAD, complications may arise, including critical limb ischemia and gangrene. Critical limb ischemia occurs when the obstruction to blood flow in the artery is compromised to the point where the blood is unable to maintain oxygenation of tissue at rest. This can lead to pain at rest, feeling of cold, or numbness in the affected foot and toes. Other complications of severe PAD include lower limb tissue loss, arterial insufficiency ulcers, erectile dysfunction, and gangrene. People with diabetes are affected by gangrene of the feet at a rate that is 30 times higher than the unaffected population. Many of these severe complications are irreversible. Causes Risk factor Factors contributing to increased risk of PAD are the same as those for atherosclerosis. These include age, sex, and ethnicity. PAD is two times as common in males as females. In terms of ethnicity, PAD is more common in people of color compared to the white population in a 2:1 ratio. The factors with the greatest risk association are hyperlipidemia, hypertension, diabetes mellitus, chronic kidney disease, and smoking. Presenting three of these factors or more increases the risk of developing PAD ten-fold. Smoking – tobacco use in any form is the single greatest risk factor of peripheral artery disease internationally. Smokers have up to a 10-fold increase in risk of PAD in a dose-response relationship. Exposure to second-hand smoke has also been shown to promote changes in the lining of blood vessels (endothelium), which can lead to atherosclerosis. Smokers are 2–3 times more likely to have lower extremity PAD than coronary artery disease. Greater than 80%-90% of patients with lower extremity peripheral arterial disease are current or former smokers. The risk of PAD increases with the number of cigarettes smoked per day and the number of years smoked. High blood sugar – Diabetes mellitus is shown to increase risk of PAD by 2–4 fold. It does this by causing endothelial and smooth-muscle cell dysfunction in peripheral arteries. The risk of developing lower extremity peripheral arterial disease is proportional to the severity and duration of diabetes. High blood cholesterol – Dyslipidemia, which is an abnormally high level of cholesterol or fat in the blood. Dyslipidemia is caused by a high level of a protein called low-density lipoprotein (LDL cholesterol), low levels of high-density lipoprotein (HDL cholesterol), elevation of total cholesterol, and/or high triglyceride levels. This abnormality in blood cholesterol levels have been correlated with accelerated peripheral artery disease. Management of Dyslipidemia by diet, exercise, and/or medication is associated with a major reduction in rates of heart attack and stroke. High blood pressure – Hypertension or elevated blood pressure can increase a persons risk of developing PAD. Similarly to PAD, there is a known association between high blood pressure and heart attacks, strokes and abdominal aortic aneurysms. High blood pressure increases the risk of intermittent claudication, the most common symptom of PAD, by 2.5- to 4-fold in men and women, respectively. Other risk factors which are being studied include levels of various inflammatory mediators such as C-reactive protein, fibrinogen, homocysteine, and lipoprotein A. Individuals with increased levels of homocysteine in their blood have a 2-fold risk of peripheral artery disease. While there are genetics leading to risk factors for peripheral artery disease, including diabetes and high blood pressure; there have been no specific genes or gene mutations directly associated with the development of peripheral artery disease. High risk populations Peripheral arterial disease is more common in these populations: All people who have leg symptoms with exertion (suggestive of claudication) or ischemic rest pain All people aged 65 years and over regardless of risk factor status All people between 50 and 69 and who have a cardiovascular risk factor (particularly diabetes or smoking) Age less than 50 years, with diabetes and one other atherosclerosis risk factor (smoking, dyslipidemia, hypertension, or hyperhomocysteinemia) Individuals with an abnormal lower extremity pulse examination Those with known atherosclerotic coronary, carotid, or renal artery disease All people with a Framingham risk score of 10%–20% All people who have previously experienced chest pain Mechanism As previously mentioned, the most common cause of peripheral artery disease, especially in patients over 40 years old, is atherosclerosis. Atherosclerosis is a narrowing of the arteries caused by lipid or fat build up and calcium deposition in the wall of the affected arteries. The most commonly affected site occurs at arterial branch points, because there is an increase in turbulence and stress on the artery at these areas where the artery branches to supply distant structures. Disease of distant structures, including feet and toes, are usually caused by diabetes and seen in the elderly population.Additional mechanisms of peripheral artery disease including arterial spasm, thrombosis, and fibromuscular dysplasia. The mechanism of arterial spasm is still being studied, but it can occur secondary to trauma. The symptoms of claudication ensue when the artery spasms, or clamps down on itself, creating an obstruction. Similar to atherosclerosis, this leads to decreased blood flow to the tissue downstream of the obstruction. Thrombosis, or the formation of a blood clot, occurs usually due stasis or trauma. Damage to the lining of the blood vessel begins the process of clot formation. The blood clot ultimately creates a narrowing in the artery preventing adequate blood flow and oxygen to the tissue further down. Diagnosis Diagnosing or identifying peripheral artery disease requires history of symptoms and a physical exam followed by confirmatory testing. These tests could include CT scans (Computed Tomagraphic Angiography), MRA scans (Magnetic Resonance Angiography), or ultrasounds for imaging.In the setting of symptoms consistent with peripheral artery disease a physician will then examine an individual for specific exam findings. Abnormal physical exam findings can lead a health care provider to consider a specific diagnosis. However, in order to confirm a diagnosis, confirmatory testing is required.These findings are associated with peripheral artery disease: Decreased or absent pulses Muscle atrophy or wasting Noticeable blueness of the affected limb Decreased temperature (coolness) in affected limb when compared to the other Thickened nails Smooth or shiny skin and hair loss Buergers test can check for pallor when the affected limb is in an elevated position. The limb is then moved from elevated to sitting position and is checked for redness, which is called reactive hyperemia. Buergers test is an assessment of arterial sufficiency, which is the ability of the artery to supply oxygenated blood to the tissue that it goes to. Nonhealing lower extremity woundIf peripheral artery disease is suspected, the initial study is the ankle–brachial index (ABI). The ABI is a simple, non-invasive test, which measures the ratio of systolic blood pressure in the ankle to the systolic blood pressure in the upper arm. This is based on the idea that if blood pressure readings in the ankle are lower than those in the arm, a blockage in the arteries that provide blood from the heart to the ankle is suspected.An ABI range of 0.90 to 1.40 is considered normal. A person is considered to have PAD when the ABI is ≤ 0.90. However, PAD can be further graded as mild to moderate if the ABI is between 0.41 and 0.90, and severe if an ABI is less than 0.40. These categories can provide insight into the disease course. Furthermore, ABI values of 0.91 to 0.99 are considered borderline and values >1.40 indicate noncompressible arteries. If an ABI >1.40 is calculated, this could indicate vessel wall stiffness caused by calcification, which can occur in people with uncontrolled diabetes. Abnormally high ABIs (>1.40) are usually considered false negatives and thus, such results merit further investigation and higher-level studies. Individuals with noncompressible arteries have an increased risk of cardiovascular mortality within a two-year period.In individuals with suspected PAD with normal ABIs can undergo exercise testing of ABI. A baseline ABI is obtained prior to exercise. The patient is then asked to exercise (usually patients are made to walk on a treadmill at a constant speed) until claudication pain occurs (for a maximum of 5 minutes), after which the ankle pressure is again measured. A decrease in ABI of 15%–20% would be diagnostic of PAD.If ABIs are abnormal, the next step is generally a lower limb Doppler ultrasound to look at the site of obstruction and extent of atherosclerosis. Other imaging can be performed by angiography, where a catheter is inserted into the common femoral artery and selectively guided to the artery in question. While injecting a radio-dense contrast agent, an X-ray is taken. Any blood flow-limiting blockage found in the X-ray can be identified and treated by procedures including atherectomy, angioplasty, or stenting. Contrast angiography is the most readily available and widely used imaging technique. Modern computerized tomography (CT) scanners provide direct imaging of the arterial system as an alternative to angiography.Magnetic resonance angiography (MRA) is a noninvasive diagnostic procedure that uses a combination of a large magnet, radio frequencies, and a computer to produce detailed images of blood vessels inside the body. The advantages of MRA include its safety and ability to provide high-resolution, three-dimensional imaging of the entire abdomen, pelvis and lower extremities in one sitting. Classification The two most commonly used methods to classify peripheral artery disease are the Fontaine and the Rutherford systems of classification. The Fontaine stages, were introduced by René Fontaine in 1954 to define severity of chronic limb ischemia: Stage I: asymptomatic Stage IIa: intermittent claudication after walking a distance of more than 200 meters Stage IIb: intermittent claudication after walking a distance of less than 200 meters Stage III: rest pain Stage IV: ulcers or gangrene of the limbThe Rutherford classification was created by the Society for Vascular Surgery and International Society of Cardiovascular Surgery, introduced in 1986 and revised in 1997 (and known as the Rutherford classification after the lead author, Robert B. Rutherford). This classification system consists of four grades and seven categories (categories 0–6): Grade 0, Category 0: asymptomatic Grade I, Category 1: mild claudication Grade I, Category 2: moderate claudication Grade I, Category 3: severe claudication Grade II, Category 4: rest pain Grade III, Category 5: minor tissue loss; ischemic ulceration not exceeding ulcer of the digits of the foot Grade IV, Category 6: major tissue loss; severe ischemic ulcers or frank gangreneModerate to severe PAD classified by Fontaines stages III to IV or Rutherfords categories 4 to 5, presents limb threat (risk of limb loss) in the form of critical limb ischemia.Recently, the Society for Vascular Surgery came out with a classification system based on "wound, ischemia and foot Infection" (WIfI). This classification system, published in 2013 was created to account for the demographic changes that have occurred over the past forty years including increased incidence of high blood sugar and evolving techniques and ability for revascularization. This system was created on the basis of ischemia and angiographic disease patterns not being the sole determinants of amputation risk. The WIfI classification system is broken up into two parts: wounds and ischemia. Wounds are graded 0 through 3 on the presence of ulceration and/or gangrene and ischemia. Grade 0: no ulcer, no gangrene Grade 1: small, shallow ulcer; no gangrene Grade 2: deep ulcer with exposed tendon or bone, gangrene limited to toes Grade 3: extensive, full-thickness ulcer; gangrene extending to forefoot or midfootIschemia is graded 0 through 3 based on ABI, ankle systolic pressure, and toe pressure. Grade 0: ABI 0.8 or higher, ankle Grade 1: arterial brachial index 0.6 to 0.79, ankle pressure 70 to 100 mm Hg, toe pressure 40 to 59 mm Hg Grade 2: ABI 0.4–0.59, ankle pressure 50 to 70 mm Hg, toe pressure 30 to 39 mm HgThe TASC (and TASC II) classification suggested PAD treatment is based on the severity of disease seen on angiogram. Screening It is not clear if screening for disease in the general population is useful as it has not been properly studied. This includes screening with the ankle-brachial index.Testing for coronary artery disease or carotid artery disease is of unclear benefit. While PAD is a risk factor for abdominal aortic aneurysms (AAA), there is no data on screening individuals with asymptomatic PAD for abdominal aortic aneurysms. In people with symptomatic PAD screening by ultrasound for AAA is not unreasonable. Treatment Depending on the severity of the disease, these steps can be taken, according to these guidelines: Lifestyle Stopping smoking (cigarettes promote PAD and are a risk factor for cardiovascular disease) Regular exercise for those with claudication helps open up alternative small vessels (collateral flow) and the limitation in walking often improves. Treadmill exercise (35 to 50 minutes, three or four times per week) has been reviewed as another treatment with a number of positive outcomes, including reduction in cardiovascular events and improved quality of life. Supervised exercise programs increase pain-free walking time and the maximum walking distance in people with PAD. Medication Management of diabetes Management of hypertension Management of high cholesterol, and antiplatelet drugs such as aspirin and clopidogrel. Statins reduce clot formation and cholesterol levels, respectively, can help with disease progression, and address the other cardiovascular risks that the affected person is likely to have.According to guidelines, taking aspirin or clopidogrel is recommended to reduce AMI ("heart attack"), stroke, and other causes of vascular death in people with symptomatic peripheral artery disease. It is recommended that aspirin and clopidogrel be taken alone and not in conjunction with one another (i.e., not as dual antiplatelet therapy). The recommended daily dosage of aspirin for treating PAD is between 75 and 325 mg, while the recommended daily dosage for clopidogrel is 75 mg. The effectiveness of both aspirin and clopidogrel to reduce risk of cardiovascular ischemic events in people with symptomatic PAD is not well established. Research also suggests that low-dose rivaroxaban plus aspirin is effective as a new anti-thrombotic regimen for PAD.Cilostazol can improve symptoms in some. Pentoxifylline is of unclear benefit. Cilostazol may improve walking distance for people who experience claudication due to peripheral artery disease, but no strong evidence suggests that it improves the quality of life, decreases mortality, or decreases the risk of cardiovascular events.Treatment with other drugs or vitamins are unsupported by clinical evidence, "but trials evaluating the effect of folate and vitamin B12 on hyperhomocysteinemia, a putative vascular risk factor, are near completion". Revascularization After a trial of the best medical treatment outline above, if symptoms persist, patients may be referred to a vascular or endovascular surgeon. The benefit of revascularization is thought to correspond to the severity of ischemia and the presence of other risk factors for limb loss such as wound and infection severity. Angioplasty (or percutaneous transluminal angioplasty) can be done on solitary lesions in large arteries, such as the femoral artery, but may not have sustained benefits. Patency rates following angioplasty are highest for iliac arteries, and decrease with arteries towards the toes. Other criteria that affect outcome following revascularization are length of lesion and number of lesions. There does not appear to be long term advantages or sustained benefit to placing a stent following angioplasty in order to hold the narrowing of the subsartorial artery open. Atherectomy, in which the plaque is scraped off of the inside of the vessel wall (albeit with no better results than angioplasty). Vascular bypass grafting can be performed to circumvent a diseased area of the arterial vasculature. The great saphenous vein is used as a conduit if available, although artificial (Gore-Tex or PTFE) material is often used for long grafts when adequate venous conduit is unavailable. When gangrene has set in, amputation may be required to prevent infected tissues from causing sepsis, a life-threatening illness. Thrombolysis and thrombectomy are used in cases of arterial thrombosis or embolism. Guidelines A guideline from the American College of Cardiology and American Heart Association for the diagnosis and treatment of lower extremity, renal, mesenteric, and abdominal aortic PAD was compiled in 2013, combining the 2005 and 2011 guidelines. For chronic limb threatening ischemia the ACCF/AHA guidelines recommend balloon angioplasty only for people with a life expectancy of 2 years or less or those who do not have an autogenous vein available. For those with a life expectancy greater than 2 years, or who have an autogenous vein, bypass surgery is recommended. Prognosis Individuals with PAD have an "exceptionally elevated risk for cardiovascular events and the majority will eventually die of a cardiac or cerebrovascular etiology"; prognosis is correlated with the severity of the PAD as measured by an ABI. Large-vessel PAD increases mortality from cardiovascular disease significantly. PAD carries a greater than "20% risk of a coronary event in 10 years".The risk is low that an individual with claudication will develop severe ischemia and require amputation, but the risk of death from coronary events is three to four times higher than matched controls without claudication. Of patients with intermittent claudication, only "7% will undergo lower-extremity bypass surgery, 4% major amputations, and 16% worsening claudication", but stroke and heart attack events are elevated, and the "5-year mortality rate is estimated to be 30% (versus 10% in controls)". Epidemiology The prevalence of PAD in the general population is 3–7%, affecting up to 20% of those over 70; 70%–80% of affected individuals are asymptomatic; only a minority ever require revascularisation or amputation. Peripheral artery disease affects one in three diabetics over the age of 50. In the US, it affects 12–20 percent of Americans age 65 and older. Around 10 million Americans have PAD. Despite its prevalence and cardiovascular risk implications, only 25% of PAD patients are undergoing treatment.In people aged 40 years and older in the United States in 2000, rates of PAD was 4.3%. Rates were 14.5% people aged 70 years or over. Within age groups, rates were generally higher in women than men. Non-Hispanic blacks had a rates of 7.9% compared to 4.4% in Non-Hispanic whites and 3.0% (1.4%–4.6%) in Mexican Americans.The incidence of symptomatic PAD increases with age, from about 0.3% per year for men aged 40–55 years to about 1% per year for men aged over 75 years. The prevalence of PAD varies considerably depending on how PAD is defined, and the age of the population being studied. Diagnosis is critical, as people with PAD have a four- to five-fold higher risk of heart attack or stroke.The Diabetes Control and Complications Trial, and the U.K. Prospective Diabetes Study trials, in people with type 1 and type 2 diabetes, respectively, demonstrated that glycemic control is more strongly associated with microvascular disease than macrovascular disease. Pathologic changes occurring in small vessels may be more sensitive to chronically elevated glucose levels than is atherosclerosis occurring in larger arteries. Research Research is being done on therapies to prevent progression of PAD. In those who have developed critically poor blood flow to the legs, the benefit of autotransplantation of autologous mononuclear cells is unclear.Only one randomized controlled trial has been conducted comparing vascular bypass to angioplasty for the treatment of severe PAD. The trial found no difference in amputation-free survival between vascular bypass and angioplasty at the planned clinical endpoint, but the trial has been criticized as being underpowered, limiting endovascular options, and comparing inappropriate endpoints. As of 2017, two randomized clinical trials are being conducted to better understand the optimal revascularization technique for severe PAD and critical limb ischemia (CLI), the BEST-CLI (Best Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia) Trial, and the BASIL-2 (Bypass Versus Angioplasty in Severe Ischaemia of the Leg – 2 )Trial.In 2011, pCMV-vegf165 was registered in Russia as the first-in-class gene therapy drug for treatment of PAD, including the advanced stage of critical limb ischemia. References External links "Peripheral Arterial Disease" at the National Heart, Lung and Blood Institute Peripheral Arterial Disease (P.A.D.) at the American College of Foot and Ankle Surgeons Gerhard-Herman, Marie D.; Gornik, Heather L.; Barrett, Coletta; Barshes, Neal R.; Corriere, Matthew A.; et al. (November 13, 2016). "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary". Circulation. 135 (12): e686–e725. doi:10.1161/CIR.0000000000000470. PMC 5479414. PMID 27840332.

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What is the significance of the term 'Mucormycosis' in the medical field?

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

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Please help me grasp the concept behind the medical term 'Chapare mammarenavirus.'

Chapare mammarenavirus or Chapare virus is a virus from the family Arenaviridae which causes a hemorrhagic fever in humans known as Chapare hemorrhagic fever. It was first described after an outbreak of a novel zoonotic mammarenavirus infection occurred in the village of Samuzabeti, Chapare Province, Bolivia, in January 2003. A small number of people were infected and one person died.In 2019, nine people became infected with the virus in the La Paz regional area, four of whom died. Nosocomial and human-to-human transmission of the virus occurred in at least three of the cases which resulted in the death of a medical intern and a gastroenterologist. Like other members of the Arenavirus family, the specific zoonotic reservoir and primary transmission vector is suspected to be a rodent, probably the small-eared pygmy rice rat. Virology The Chapare virus is an enveloped virus with a bi-segmented single-stranded ambisense RNA genome. The two RNA segments are denoted Small (S) and Large (L). It belongs to the New World Clade B lineage of mammarenaviruses and is most closely related to the Sabia virus. Symptoms After an incubation period of around 9–19 days, initial symptoms include fever, malaise, headache, myalgia, back pain, dizziness, nausea, vomiting and diarrhoea. The disease often progresses to include hemorrhagic and neurological symptoms, such as gingival hemorrhage, anaemia, leukopaenia, confusion, seizures, echymoses, bleeding from mucous membranes, hemorrhagic shock and multi-organ failure.Chapare virus RNA was detected in the blood, urine, conjunctiva, semen and in broncho-alveolar and nasopharyngeal samples of the infected patients. Those who survived often had prolonged residual neurological symptoms. Viral RNA was detected in survivors up to 170 days after infection and infectious Chapare virus was obtained in a semen sample of one patient 86 days after symptom onset. Treatment Treatment relies mostly on supportive care and early diagnosis. Specific antiviral therapy for Chapare virus infection has yet to be properly investigated. References == External links ==

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What is the significance of the term 'Single umbilical artery' in the medical field?

Occasionally, there is only the one single umbilical artery (SUA) present in the umbilical cord. This is sometimes also called a two-vessel umbilical cord, or two-vessel cord. Approximately, this affects between 1 in 100 and 1 in 500 pregnancies, making it the most common umbilical abnormality. Its cause is not known. Most cords have one vein and two arteries. The vein carries oxygenated blood from the placenta to the baby and the arteries carry deoxygenated blood from the baby to the placenta. In approximately 1% of pregnancies there are only two vessels —usually a single vein and single artery. In about 75% of those cases, the baby is entirely normal and healthy. One artery can support a pregnancy and does not necessarily indicate problems. For the other 25%, a 2-vessel cord is a sign that the baby has other abnormalities—sometimes life-threatening and sometimes not.Doctors and midwives often suggest parents take the added precaution of having regular growth scans near term to rule out intrauterine growth restriction, which can happen on occasion and warrant intervention. Yet the majority of growth restricted infants with the abnormality also have other defects. Finally, neonates with the finding may also have a higher occurrence of renal problems, therefore close examination of the infant may be warranted shortly after birth. Among SUA infants, there is a slightly elevated risk for post-natal urinary infections. Presentation Associations SUA does increase the risk of the baby having cardiac, skeletal, intestinal or renal problems. Babies with SUA may have a higher likelihood of having other congenital abnormalities, especially of the heart. However, additional testing (high level ultrasound scans) can rule out many of these abnormalities prior to birth and alleviate parental anxiety.It may be associated with Trisomy 18, also known as Edwards syndrome. Intrauterine growth restriction has been found to be associated. Diagnosis It can be detected in the first trimester of pregnancy with the use of 2D ultrasound. The sonographer is able to identify a 2 vessel cord in an image with the bladder and color Doppler, which will show only one artery going around one side of the bladder. In a normal fetus, there would be 2 arteries (one on each side of the bladder). Echocardiograms of the fetus may be advised to ensure the heart is functioning properly. Genetic counseling may be useful, too, especially when weighing the pros and cons of more invasive procedures such as chorionic villus sampling and amniocentesis. These invasive procedures are usually performed when there is a suspected chromosomal abnormality or genetic defect and will confirm a diagnosis. Prognosis Although the presence of an SUA is a risk factor for additional complications, most fetuses with the condition will not experience other problems, either in utero or after birth. Especially encouraging are cases in which no other soft markers for congenital abnormalities are visible via ultrasound. Given that, the vast majority of expectant mothers do not receive the kind of advanced ultrasound scanning required to confirm SUA in utero. Epidemiology It is slightly more common in multiple births, in infants with chromosome anomalies, and in girls than in boys. References == External links ==

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Could you provide a brief overview of 'Semaglutide' in a medical context?

Semaglutide, sold under the brand names Wegovy and Ozempic among others, is an antidiabetic medication used for the treatment of type 2 diabetes and long-term weight management.Semaglutide is a GLP-1 receptor agonist, meaning that it mimics the action of the human incretin glucagon-like peptide-1 (GLP-1), thereby increasing insulin secretion and increasing blood sugar disposal and improving glycemic control. An injectable version (Ozempic) was approved for medical use in the United States in December 2017, and in the European Union, Canada, and Japan in 2018. A version which is taken by mouth (Rybelsus) was approved for medical use in the United States in September 2019, and in the European Union in April 2020. It is the first glucagon-like peptide receptor protein treatment approved for use in the United States that does not need to be injected. It was developed by Novo Nordisk. Side effects include nausea, vomiting, diarrhea, abdominal pain, and constipation.In June 2021, the US Food and Drug Administration (FDA) approved semaglutide injection sold under the brand name Wegovy for long-term weight management in adults. It was approved for medical use in the European Union in January 2022. Medical uses Semaglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.Semaglutide is also indicated as an adjunct to diet and exercise for long-term weight management in adults with obesity (initial body mass index (BMI) ≥ 30 kg/m2) or overweight (initial BMI ≥ 27 kg/m2) with at least one weight-related comorbidity. A 2022 review of anti-obesity treatments found that semaglutide as well as tirzepatide (which has an overlapping mechanism of action) were more promising than previous anti-obesity drugs, although less effective than bariatric surgery. Adverse effects Side effects include nausea, vomiting, diarrhea, abdominal pain, and constipation. In people with heart problems, it can cause damage to the retina of the eye (retinopathy). Other, less common side effects include kidney problems, allergic reactions, low blood sugar, and pancreatitis. Contraindications Due to data from rodents studies of GLP1 mediated thyroid C-cell hyperplasia, their use is contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients with multiple endocrine neoplasia syndrome type 2. Mechanism of action Semaglutide is a glucagon-like peptide-1 receptor agonist. By mimicking the action of the incretin GLP-1, it increases the production of insulin, a hormone that lowers the blood sugar level. It appears to enhance growth of pancreatic beta cells, which are responsible for insulin production and release. It also inhibits the production of glucagon, which is a hormone that increases glycogenolysis (release of stored carbohydrate from the liver) and gluconeogenesis (synthesis of new glucose). It reduces food intake by lowering appetite and slowing down digestion in the stomach, helping to reduce body fat. Its half-life in the blood is about seven days (165–184 hours). Structure Semaglutide is chemically similar to human GLP-1, with 94% similarity. The only differences are two amino-acid substitutions at positions 8 and 34, where alanine and lysine are replaced by 2-aminoisobutyric acid and arginine, respectively. Amino-acid substitution at position 8 prevents chemical breakdown by dipeptidyl peptidase-4. In addition, the lysine at position 26 is in its derivative form (acylated with stearic diacid). Acylation with a spacer and C-18 fatty diacid chain increases the drugs binding to blood protein (albumin), which enables longer presence in the blood circulation. History Semaglutide was developed in 2012, by a team of researchers at Novo Nordisk as a longer-acting alternative to liraglutide as a once-weekly diabetes therapy. It was given the brand name Ozempic. Clinical trials were started on 6 January 2016, and completed on 19 May 2017.Researchers at the University of Leeds and Novo Nordisk reported in 2017, that it can also be used for the treatment of obesity. It reduces hunger, food craving and body fat. A phase 3 randomized controlled trial found that once-weekly injection of 2.4 mg of the drug resulted in an average change of −14.9% body weight at 68 weeks compared to −2.4% for the placebo.The US FDA New Drug Application (NDA) was filed in December 2016, and in October 2017, the FDA Advisory Committee approved it unanimously. It can be administered by injection or orally. Authorization was granted in February 2018 for the European Union, in March 2018 in Japan, on 4 January 2018 in Canada, and in August 2019 in Australia.In November 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion on Wegovy, the formulation intended for the treatment of people with obesity or who are overweight in the presence of other related conditions, recommending the granting of a marketing authorization. The applicant for this medicinal product is Novo Nordisk A/S. Wegovy was approved for medical use in the European Union in January 2022. 2022 shortages As a result of an increase in prescriptions for weight loss in non-diabetic patients, a shortage of Semaglutide/Ozempic was reported in Australia in 2022. This shortage resulted in many people with type 2 diabetes being unable to access the drug. In May 2022, the Australian Therapeutic Goods Administration, along with Novo Nordisk, sent out guidelines to all health professionals, reminding them that people with type 2 diabetes need to be prioritised in terms of supply. An update to the guidelines was released in August 2022.Shortages were also reported contemporaneously in the United States In the same month, rival Eli Lilly stated in its quarterly investors call that it was working "around the clock" to ensure adequate supply of its rival GLP-1 agonist tirzepatide (Mounjaro). Research Semaglutide was found to be inferior to tirzepatide in a 2021 study of tirzepatide (LY3298176) vs semaglutide once weekly as add-on therapy to metformin in participants with type 2 diabetes (SURPASS-2), in both endpoints of reduction in A1C and body weight, with a roughly similar safety profile.A meta-analysis including a small number of patients found that semaglutide may be effective in lowering liver enzymes (transaminitis) and improving certain radiologically observed features of metabolic-dysfunction–associated fatty-liver disease (MAFLD). References External links "Semaglutide". Drug Information Portal. U.S. National Library of Medicine. "Semaglutide". MedlinePlus.

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

Could you offer a clear explanation of the term 'Alexander disease' as used in the medical field?

Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions caused by anomalies in the myelin which protects nerve fibers in the brain. The most common type is the infantile form that usually begins during the first 2 years of life. Symptoms include mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size and seizures. The juvenile form of Alexander disease has an onset between the ages of 2 and 13 years. These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control. Adult-onset forms of Alexander disease are less common. The symptoms sometimes mimic those of Parkinson’s disease or multiple sclerosis, or may present primarily as a psychiatric disorder. According to the National Institute of Neurological Disorders and Stroke, the destruction of white matter is accompanied by the formation of Rosenthal fibers—abnormal clumps of protein that accumulate in astrocytes in the brain. The disease occurs in both males and females, and no ethnic, racial, geographic or cultural/economic differences are seen in its distribution. Alexander disease is a progressive and often fatal disease. Presentation Delays in development of some physical, psychological and behavioral skills; progressive enlargement of the head (macrocephaly), seizures, spasticity, and in some cases also hydrocephalus, idiopathic intracranial hypertension, and dementia. Cause Alexander disease is a genetic disorder affecting the midbrain and cerebellum of the central nervous system. It is caused by mutations in the gene for glial fibrillary acidic protein (GFAP) that maps to chromosome 17q21. It is inherited in an autosomal dominant manner, such that the child of a parent with the disease has a 50% chance of inheriting the condition, if the parent is heterozygotic. However, most cases arise de novo as the result of sporadic mutations.Alexander disease belongs to leukodystrophies, a group of diseases that affect the growth or development of the myelin sheath. The destruction of white matter in the brain is accompanied by the formation of fibrous, eosinophilic deposits known as Rosenthal fibers. Rosenthal fibers appear not to be present in healthy people, but occur in specific diseases, like some forms of cancer, Alzheimer’s, Parkinson’s, Huntington’s, and ALS. The Rosenthal fibers found in Alexander disease do not share the distribution or concentration of other diseases and disorders. Pathology Alexander disease causes the gradual loss of bodily functions and the ability to talk. It also causes an overload of long-chain fatty acids in the brain, which destroy the myelin sheath. The cause of Alexander disease is a mutation in the gene encoding GFAP.A CT scan shows: Decreased density of white matter Frontal lobe predominance Dilated lateral ventricles may present Diagnosis Detecting the signs of Alexander disease is possible with magnetic resonance imaging (MRI), which looks for specific changes in the brain that may be tell-tale signs for the disease. It is even possible to detect adult-onset Alexander disease with MRI. Alexander disease may also be revealed by genetic testing for its known cause. A rough diagnosis may also be made through revealing of clinical symptoms, including enlarged head size, along with radiological studies, and negative tests for other leukodystrophies. Treatment No cure or standard procedure for treatment is known, although a University of Wisconsin study shows promise with gene editing of the astrocytes. A phase III clinical trial of an antisense therapy, sponsored by Ionis Pharmaceuticals, began in 2021. A bone marrow transplant has been attempted on a child, but it made no improvement. Hydrocephalus may be seen in younger patients and can be relieved with surgery or by implanting a shunt to relieve pressure. Prognosis The prognosis is generally poor. With early onset, death usually occurs within 10 years from the onset of symptoms. Individuals with the infantile form usually die before the age of seven. Usually, the later the disease occurs, the slower its course. Prevalence Its occurrence is very rare. The infantile form occurs from birth to 2 years of age. The average duration of the infantile form is usually about 3 years. Onset of the juvenile form presents between 2 and 12 years of age. Duration of this form is in most cases about 6 years. The adult form occurs after 12 years. In younger patients, seizures, megalencephaly, developmental delay, and spasticity are usually present. Neonatal onset is also reported. Onset in adults is least frequent. In older patients, bulbar or pseudobulbar symptoms and spasticity predominate. Symptoms of the adult form may also resemble multiple sclerosis. No more than 500 cases have been reported. See also The Myelin Project The Stennis Foundation References External links OMIM entries on Alexander disease Infantile-onset Alexander disease in a child with long-term follow-up by serial magnetic resonance imaging: a case report Alexander Disease: New Insights From Genetics

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

I need a basic explanation for the medical term 'Precordium.'

In anatomy, the precordium or praecordium is the portion of the body over the heart and lower chest.Defined anatomically, it is the area of the anterior chest wall over the heart. It is therefore usually on the left side, except in conditions like dextrocardia, where the individuals heart is on the right side. In such a case, the precordium is on the right side as well. The precordium is naturally a cardiac area of dullness. During examination of the chest, the percussion note will therefore be dull. In fact, this area only gives a resonant percussion note in hyperinflation, emphysema or tension pneumothorax. Precordial chest pain can be an indication of a variety of illnesses, including costochondritis and viral pericarditis. See also Precordial thump Precordial examination Commotio cordis Hyperdynamic precordium Precordial catch syndrome == References ==

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Could you please explain the term 'Copra itch' in simple language?

Copra itch is a skin condition that occurs on persons handling copra who are subject to Tyrophagus longior mite bites.: 454 See also Coolie itch Skin lesion == References ==

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I'm encountering the term 'Hypoglycemia' in medical literature. What's its definition?

Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipples triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly.The most common cause of hypoglycemia is medications used to treat diabetes such as insulin, sulfonylureas, and biguanides. Risk is greater in diabetics who have eaten less than usual, recently exercised, or consumed alcohol. Other causes of hypoglycemia include severe illness, sepsis, kidney failure, liver disease, hormone deficiency, tumors such as insulinomas or non-B cell tumors, inborn errors of metabolism, several medications, and alcohol. Low blood sugar may occur in otherwise healthy newborns who have not eaten for a few hours.Hypoglycemia is treated by eating a sugary food or drink, for example glucose tabs or gel, apple juice, soda, or candy. The person must be conscious and able to swallow. The goal is to consume 10-20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L). If a person is not able to take food by mouth, glucagon by injection or in the nose may help. The treatment of hypoglycemia unrelated to diabetes includes treating the underlying problem.Among people with diabetes, prevention starts with learning the signs and symptoms of hypoglycemia. Diabetes medications, like insulin, sulfonylureas, and biguanides can also be adjusted or stopped to prevent hypoglycemia. Frequent and routine blood glucose testing is recommended. Some may find continuous glucose monitors with insulin pumps to be helpful in the management of diabetes and prevention of hypoglycemia. Definition Blood sugar levels naturally fluctuate throughout the day, however hypoglycemia, also called low blood sugar or low blood glucose, is when blood sugar levels drop below 70 mg/dL (3.9 mmol/L).Blood sugar levels are generally maintained between 70 and 110 mg/dL (3.9-6.1 mmol/L). Although 70 mg/dL (3.9 mmol/L) is the lower limit of normal glucose, symptoms of hypoglycemia usually do not occur until 55 mg/dL (3.0 mmol/L) or lower. The blood glucose level at which symptoms of hypoglycemia develop in someone with several prior episodes of hypoglycemia may be even lower. Whipples triad The symptoms of low blood sugar alone are not specific enough to characterize a hypoglycemic episode. A single blood sugar reading below 70 mg/dL is also not specific enough characterize a hypoglycemic episode. Whipples triad is a set of three conditions that need to be met in order to accurately characterize a hypoglycemic episode.The three conditions are the following: The signs and symptoms of hypoglycemia are present (see section below on Signs and Symptoms) A low blood glucose measurement is present, typically less than 70 mg/dL (3.9 mmol/L) The signs and symptoms of hypoglycemia resolve after blood glucose levels have returned to normal Age The biggest difference in blood glucose levels between the adult and pediatric population occurs in newborns during the first 48 hours of life. After the first 48 hours of life, the Pediatric Endocrine Society cites that there is little difference in blood glucose level and the use of glucose between adults and children. During the 48 hour neonatal period, the neonate adjusts glucagon and epinephrine levels following birth, which may cause temporary hypoglycemia. As a result, there has been difficulty in developing guidelines on interpretation and treatment of low blood glucose in neonates aged less than 48 hours. Following a data review, the Pediatric Endocrine Society concluded that neonates aged less than 48 hours begin to respond to hypoglycemia at serum glucose levels of 55–65 mg/dL (3.0-3.6 mmol/L). This is contrasted by the value in adults, children, and older infants, which is approximately 80–85 mg/dL (4.4-4.7 mmol/L).In children who are aged greater than 48 hours, serum glucose on average ranges from 70 to 100 mg/dL (3.9-5.5 mmol/L), similar to adults. Whipples triad is used to identify hypoglycemia in children who can communicate their symptoms. Differential diagnosis Other conditions that may present similarly to hypoglycemia include the following: Alcohol or drug intoxication Cardiac arrhythmia Valvular heart disease Postprandial syndrome Hyperthyroidism Pheochromocytoma Post-gastric bypass hypoglycemia Generalized anxiety disorder Surreptitious insulin use Lab or blood draw error (lack of antiglycolytic agent in collection tube or during processing) Signs and symptoms Hypoglycemic symptoms are divided into two main categories. The first category is symptoms caused by low glucose in the brain, called neuroglycopenic symptoms. The second category of symptoms is caused by the bodys reaction to low glucose in the brain, called adrenergic symptoms. Everyone experiences different symptoms of hypoglycemia, so someone with hypoglycemia may not have all of the symptoms listed above. Symptoms also tend to have quick onset. It is important to quickly obtain a blood glucose measurement in someone presenting with symptoms of hypoglycemia to properly identify the hypoglycemic episode. Pathophysiology Glucose is the main source of energy for the brain, and a number of mechanisms are in place to prevent hypoglycemia and protect energy supply to the brain. The body can adjust insulin production and release, adjust glucose production by the liver, and adjust glucose use by the body. The body naturally produces the hormone insulin, in an organ called the pancreas. Insulin helps to regulate the amount of glucose in the body, especially after meals. Glucagon is another hormone involved in regulating blood glucose levels, and can be thought of as the opposite of insulin. Glucagon helps to increase blood glucose levels, especially in states of hunger.When blood sugar levels fall to the low-normal range, the first line of defense against hypoglycemia is decreasing insulin release by the pancreas. This drop in insulin allows the liver to increase glycogenolysis. Glycogenolysis is the process of glycogen breakdown that results in the production of glucose. Glycogen can be thought of as the inactive, storage form of glucose. Decreased insulin also allows for increased gluconeogenesis in the liver and kidneys. Gluconeogenesis is the process of glucose production from non-carbohydrate sources, supplied from muscles and fat.Once blood glucose levels fall out of the normal range, additional protective mechanisms work to prevent hypoglycemia. The pancreas is signaled to release glucagon, a hormone that increases glucose production by the liver and kidneys, and increases muscle and fat breakdown to supply gluconeogenesis. If increased glucagon does not raise blood sugar levels to normal, the adrenal glands release epinephrine. Epinephrine works to also increase gluconeogenesis and glycogenolysis, while also decreasing the use of glucose by organs, protecting the brains glucose supply.After hypoglycemia has been prolonged, cortisol and growth hormone are released to continue gluconeogenesis and glycogenolysis, while also preventing the use of glucose by other organs. The effects of cortisol and growth hormone are far less effective than epinephrine. In a state of hypoglycemia, the brain also signals a sense of hunger and drives the person to eat, in an attempt to increase glucose. Causes Hypoglycemia is most common in those with diabetes treated by insulin, glinides, and sulfonylureas. Hypoglycemia is rare in those without diabetes, because there are many regulatory mechanisms in place to appropriately balance glucose, insulin, and glucagon. Please refer to Pathophysiology section (above) for more information on glucose, insulin, and glucagon. Diabetics Medications The most common cause of hypoglycemia in diabetics is medications used to treat diabetes such as insulin, sulfonylureas, and biguanides. This is often due to excessive doses or poorly timed doses. Sometimes diabetics may take insulin in anticipation of a meal or snack, and missing or forgetting that meal will lead to hypoglycemia. This is due to increased insulin without the presence of glucose from the planned meal. Hypoglycemic unawareness Recurrent episodes of hypoglycemia can lead to hypoglycemic unawareness, or the decreased ability to recognize hypoglycemia. As diabetics experience more episodes of hypoglycemia, the blood glucose level which triggers symptoms of hypoglycemia decreases. In other words, people without hypoglycemic unawareness experience symptoms of hypoglycemia at a blood glucose of about 55 mg/dL (3.0 mmol/L). Those with hypoglycemic unawareness experience the symptoms of hypoglycemia at far lower levels of blood glucose. This is dangerous for a number of reasons. The hypoglycemic person not only gains awareness of hypoglycemia at very low blood glucose levels, but they also require high levels of carbohydrates or glucagon to recover their blood glucose to normal levels. These individuals are also at far greater risk of severe hypoglycemia.While the exact cause of hypoglycemic unawarenss is still under research, it is thought that these individuals progressively begin to develop fewer adrenergic-type symptoms, resulting in the loss of neuroglycopenic-type symptoms. Neuroglycopenic symptoms are caused by low glucose in the brain, and can result in tiredness, confusion, difficulty with speech, seizures, and loss of consciousness. Adrenergic symptoms are caused by the bodys reaction to low glucose in the brain, and can result in fast heart rate, sweating, nervousness, and hunger. See section above on Signs and Symptoms for further explanation of neuroglycopenic symptoms and adrenergic symptoms. In terms of epidemiology, hypoglycemic unawarenss occurs in 20-40% of type 1 diabetics. Other causes Other causes of hypoglycemia in diabetics include the following: Fasting, whether it be a planned fast or overnight fast, as there is a long period of time without glucose intake Exercising more than usual as it leads to more use of glucose, especially by the muscles Drinking alcohol, especially when combined with diabetic medications, as alcohol inhibits glucose production Kidney disease, as insulin cannot be cleared out of circulation well Non-diabetics Serious illness Serious illness may result in low blood sugar. Severe disease of many organ systems can cause hypoglycemia as a secondary problem. Hypoglycemia is especially common in those in the intensive care unit or those in whom food and drink is withheld as a part of their treatment plan.Sepsis, a common cause of hypoglycemia in serious illness, can lead to hypoglycemia through many ways. In a state of sepsis, the body uses large amounts of glucose for energy. Glucose use is further increased by cytokine production. Cytokines are a protein produced by the body in a state of stress, particularly when fighting an infection. Cytokines may inhibit glucose production, further decreasing the bodys energy stores. Finally, the liver and kidneys are sites of glucose production, and in a state of sepsis those organs may not receive enough oxygen, leading to decreased glucose production due to organ damage.Other causes of serious illness that may cause hypoglycemia include liver failure and kidney failure. The liver is the main site of glucose production in the body, and any liver failure or damage will lead to decreased glucose production. While the kidneys are also sites of glucose production, their failure of glucose production is not significant enough to cause hypoglycemia . Instead, the kidneys are responsible for removing insulin from the body, and when this function is impaired in kidney failure, the insulin stays in circulation longer, leading to hypoglycemia. Drugs A number of medications have been identified which may cause hypoglycemia, through a variety of ways. Moderate quality evidence implicates the non-steroidal anti-inflammatory drug indomethacin and the anti-malarial quinine. Low quality evidence implicates lithium, used for bipolar disorder. Finally, very low quality evidence implicates a number of hypertension medications including angiotensin converting enzyme inhibitors (also called ACE-inhibitors), angiotensin receptor blockers (also called ARBs), and β-adrenergic blockers (also called beta blockers). Other medications with very low quality evidence include the antibiotics levofloxacin and trimethoprim-sulfamethoxazole, progesterone blocker mifepristone, anti-arrhythmic disopyramide, anti-coagulant heparin, and chemotherapeutic mercaptopurine.If a person without diabetes accidentally takes medications that are traditionally used to treat diabetes, this may also cause hypoglycemia. These medications include insulin, glinides, and sulfonylureas. This may occur through medical errors in a healthcare setting or through pharmacy errors, also called iatrogenic hypoglycemia. Surreptitious insulin use When individuals take insulin without needing it, to purposefully induce hypoglycemia, this is referred to as surreptitious insulin use or factitious hypoglycemia. Some people may use insulin to induce weight loss, whereas for others this may be due to malingering or factitious disorder, which is a psychiatric disorder. Demographics affected by factitious hypoglycemia include women aged 30–40, particularly those with diabetes, relatives with diabetes, healthcare workers, or those with history of a psychiatric disorder. The classic way to identify surreptitious insulin use is through blood work revealing high insulin levels with low C-peptide and proinsulin. Alcohol misuse The production of glucose is blocked by alcohol. In those who misuse alcohol, hypoglycemia may be brought on by a several-day alcohol binge associated with little to no food intake. The cause of hypoglycemia is multifactorial, where glycogen becomes depleted in a state of starvation. Glycogen stores are then unable to be repleted due to the lack of food intake, all compounded the inhibition of glucose production by alcohol. Hormone deficiency Children with primary adrenal failure, also called Addisons disease, may experience hypoglycemia after long periods of fasting. Addisons disease is associated with chronically low levels of the stress hormone cortisol, which leads to decreased glucose production.Hypopituitarism, leading to decreased growth hormone, is another cause of hypoglycemia in children, particularly with long periods of fasting or increased exercise. Inborn errors of metabolism Briefly, inborn errors of metabolism are a group rare of genetic disorders that are associated with the improper breakdown or storage of proteins, carbohydrates, or fatty acids. Inborn errors of metabolism may cause infant hypoglycemia, and much less commonly adult hypoglycemia. Disorders that are related to the breakdown of glycogen, called glycogen storage diseases, may cause hypoglycemia. Normally, breakdown of glycogen leads to increased glucose levels, particularly in a fasting state. In glycogen storage diseases however, glycogen cannot be properly broken-down, leading to inappropriately decreased glucose levels in a fasting state, and thus hypoglycemia. The glycogen storage diseases associated with hypoglycemia include type 0, type I, type III, and type IV, as well as Fanconi syndrome. Insulinomas A primary B-cell tumor, such as an insulinoma, is associated with hypoglycemia. This is a tumor located in the pancreas. An insulinoma produces insulin, which in turn decreases glucose levels, causing hypoglycemia. Normal regulatory mechanisms are not in place, which prevent insulin levels from falling during states of low blood glucose. During an episode of hypoglycemia, plasma insulin, C-peptide, and proinsulin will be inappropriately high. Non-B cell tumors Hypoglycemia may occur in people with non-B cell tumors such as hepatomas, adrenocorticoid carcinomas, and carcinoid tumors. These tumors lead to a state of increased insulin, specifically increased insulin-like growth factor II, which decreases glucose levels. Post-gastric bypass postprandial hypoglycemia The Roux-en-Y gastric bypass, is a weight-loss surgery performed on the stomach, and has been associated with hypoglycemia, called post-gastric bypass postprandial hypoglycemia. Although the entire mechanism of hypoglycemia following this surgery is not fully understood, it is thought that meals cause very high levels of glucagon-like peptide-1 (also called GLP-1), a hormone that increases insulin, causing glucose levels to drop. Autoimmune hypoglycemia Antibodies can be formed against insulin, leading to autoimmune hypoglycemia. Antibodies are immune cells produced by the body, that normally attack bacteria and viruses, but sometimes can attack normal human cells, leading to an autoimmune disorder. In autoimmune hypoglycemia, there are two possible mechanisms. In one instance, antibodies bind to insulin following its release associated with a meal, resulting in insulin being non-functional. At a later time, the antibodies fall off insulin, causing insulin to be functional again leading late hypoglycemia after a meal, called late postprandial hypoglycemia. Another mechanism causing hypoglycemia is due to antibodies formed against insulin receptors, called insulin receptor antibodies. The antibodies attach to insulin receptors and prevent insulin breakdown, or degradation, leading to inappropriately high insulin levels and low glucose levels. Neonatal hypoglycemia Low blood sugar may occur in healthy neonates aged less than 48 hours who have not eaten for a few hours. During the 48 hour neonatal period, the neonate adjusts glucagon and epinephrine levels following birth, which may trigger transient hypoglycemia. In children who are aged greater than 48 hours, serum glucose on average ranges from 70 to 100 mg/dL (3.9-5.5 mmol/L), similar to adults, with hypoglycemia being far less common. Diagnostic approach The most reliable method of identifying hypoglycemia is through identifying Whipples triad. The components of Whipples triad are a blood sugar level below 70 mg/dL (3.9 mmol/L), symptoms related to low blood sugar, and improvement of symptoms when blood sugar is restored to normal. Identifying Whipples triad in a patient helps to avoid unnecessary diagnostic testing and decreases healthcare costs.In those with a history of diabetes treated with insulin, glinides, or sulfonylurea, who demonstrate Whipples triad, it is reasonable to assume the cause of hypoglycemia is due to insulin, glinides, or sulfonylurea use. In those without a history of diabetes with hypoglycemia, further diagnostic testing is necessary to identify the cause. Testing, during an episode of hypoglycemia, should include the following: Plasma glucose level, not point-of-care measurement Insulin level C-peptide level Proinsulin level Beta-hydroxybutyrate level Oral hypoglycemic agent screen Response of blood glucose level to glucagon Insulin antibodiesIf necessary, a diagnostic hypoglycemic episode can be produced in an inpatient or outpatient setting. This is called a diagnostic fast, in which a patient undergoes an observed fast to cause a hypoglyemic episode, allowing for appropriate blood work to be drawn. In some, the hypoglycemic episode may be reproduced simply after a mixed meal, whereas in others a fast may last up to 72 hours.In those with a suspected insulinoma, imaging is the most reliable diagnostic technique, including ultrasound, computed tomography imaging (also called CT imaging), and magnetic resonsance imaging (also called MRI). Treatment After hypoglycemia in a person is identified, rapid treatment is necessary and can be life-saving. The main goal of treatment is to raise blood glucose back to normal levels, which is done through various ways of administering glucose, depending on the severity of the hypoglycemia, what is on-hand to treat, and who is administering the treatment. A general rule used by the American Diabetes Association is the "15-15 Rule," which suggests consuming or administering 15 grams of a carbohydrate, followed by a 15-minute wait and re-measurement of blood glucose level to assess if blood glucose has returned to normal levels. Self-treatment If an individual recognizes the symptoms of hypoglycemia coming on, blood sugar should promptly be measured, and a sugary food or drink should be consumed. The person must be conscious and able to swallow. The goal is to consume 10-20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L).Examples of products to consume are: Glucose tabs or gel (refer to instructions on packet) Juice containing sugar like apple, grape, or cranberry juice, 4 ounces or 1/2 cup Soda or a soft-drink, 4 ounces or 1/2 cup (not diet soda) Candy Table sugar or honey, 1 tablespoonImprovement in blood sugar levels and symptoms are expected to occur in 15–20 minutes, at which point blood sugar should be measured again. If the repeat blood sugar level is not above 70 mg/dL (3.9 mmol/L), consume another 10-20 grams of a carbohydrate and remeasure blood sugar levels after 15–20 minutes. Repeat until blood glucose levels have returned to normal levels. The greatest improvements in blood glucose will be seen if the carbohydrate chewed or drunk, and then swallowed. This results in the greatest bioavaliablity of glucose, meaning the greatest amount of glucose enters the body producing the best possible improvements in blood glucose levels. The second best way to consume a carbohydrate it to allow it to dissolve under the tongue, also referred to as sublingual administration. For example, a hard candy can be dissolved under the tongue, however the best improvements in blood glucose will occur if the hard candy is chewed and crushed, then swallowed.After correcting blood glucose levels, people may consume a full meal within one hour in order to replenish glycogen stores. Education Family, friends, and co-workers of a person with diabetes may provide life-saving treatment in the case of a hypoglycemic episode It is important for these people to receive training on how to recognize hypoglycemia, what foods to help the hypoglycemic eat, how to administer injectable or intra-nasal glucagon, and how use a glucose meter. Treatment by family, friends, or co-workers Family, friends, and co-workers of those with hypoglycemia are often first to identify hypoglycemic episodes, and may offer help. Upon recognizing the signs and symptoms of hypoglycemia in a diabetic, a blood sugar level should first be measured using a glucose meter. If blood glucose is below 70 mg/dL (3.9 mmol/L), treatment will depend on whether the person is conscious and can swallow safely. If the person is conscious and able to swallow, the family, friend, or co-worker can help the hypoglycemic consume 10-20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L). Improvement in blood sugar level and symptoms is expected to occur in 15–20 minutes, at which point blood sugar is measured again. If the repeat blood sugar level is not above 70 mg/dL (3.9 mmol/L), the hypoglycemic should consume another 10-20 grams of a carbohydrate and with remeasurement of blood sugar levels after 15–20 minutes. Repeat until blood glucose levels have returned to normal levels, or call emergency services for further assistance.If the person is unconscious, a glucagon kit may be used to treat severe hypoglycemia, which delivers glucagon either by injection into a muscle or through nasal inhalation. In the United States, glucacon kits are available by prescription for diabetic patients to carry in case of an episode of severe hypoglycemia. Emergency services should be called for further assistance. Treatment by medical professionals In a healthcare setting, treatment depends on the severity of symptoms and intravenous access. If a patient is conscious and able to swallow safely, food or drink may be administered, as well as glucose tabs or gel. In those with intravenous access, 25 grams of 50% dextrose is commonly administered. When there is no intravenous access, intramuscular or intra-nasal glucagon may be administered. Other treatments While the treatment of hypoglycemia is typically managed with carbohydrate consumption, glucagon injection, or dextrose administration, there are some other treatments available. Medications like diazoxide and octreotide decrease insulin levels, increasing blood glucose levels. Dasiglucagon was approved for medical use in the United States in March 2021, to treat severe hypoglycemia. Dasiglucagon (brand name Zegalogue) is unique because it is glucagon in a prefilled syringe or auto-injector pen, as opposed to traditional glucagon kits that require mixing powdered glucagon with a liquid.The soft drink Lucozade has been used for hypoglycemia in the United Kingdom, but it has recently replaced much of its glucose with artificial sweeteners, which do not treat hypoglycemia. Prevention Diabetics The prevention of hypoglycemia depends on the cause. In those with diabetes treated by insulin, glinides, or sulfonylurea, the prevention of hypoglycemia has a large focus on patient education and medication adjustments. The foundation of diabetes education is learning how to recognize the signs and symptoms of hypoglycemia, as well as learning how to act quickly to prevent worsening of an episode. Another cornerstone of prevention is strong self-monitoring of blood glucose, with consistent and frequent measurements. Research has shown that patients with type 1 diabetes who use continuous glucose monitoring systems with insulin pumps significantly improve blood glucose control. Insulin pumps help to prevent high glucose spikes, and help prevent inappropriate insulin dosing. Continuous glucose monitors can sound alarms when blood glucose is too low or too high, especially helping those with nocturnal hypoglycemia or hypoglycemic unawareness. In terms of medication adjustments, medication doses and timing can be adjusted in order to prevent hypoglycemia, or a medication can be stopped altogether. Non-diabetics In those with hypoglycemia who do not have diabetes, there are a number of preventative measures dependent on the cause. Hypoglycemia caused by hormonal dysfunction like lack of cortisol in Addisons disease or lack of growth hormone in hypopituitarism can be prevented with appropriate hormone replacement. The hypoglycemic episodes associated with non-B cell tumors can be decreased following surgical removal of the tumor, as well as following radiotherapy or chemotherapy to reduce the size of the tumor. In some cases, those with non-B cell tumors may have hormone therapy with growth hormone, glucocorticoid, or octreotide to also lessen hypoglycemic episodes. Post-gastric bypass hypoglycemia can be prevented by eating smaller, more frequent meals, avoiding sugar-filled foods, as well as medical treatment with an alpha-glucosidase inhibitor, diazoxide, or octreotide.Some causes of hypoglycemia require treatment of the underlying cause to best prevent hypoglycemia. This is the case for insulinomas which often require surgical removal of the tumor in order for hypoglycemia to remit. In patients who cannot undergo surgery for removal of the insulinoma, diazoxide or octreotide may be used. Epidemiology Hypoglycemia is common in people with type 1 diabetes, and in people with type 2 diabetes taking insulin, glinides, or sulfonylurea. It is estimated that type 1 diabetics experience two mild, symptomatic episodes of hypoglycemia per week. Additionally, people with type 1 diabetes have at least one severe hypoglyemic episode per year, requiring treatment assistance. In terms of mortality, hypoglycemia causes death in 6-10% of type 1 diabetics.In those with type 2 diabetes, hypoglycemia is less common compared to type 1 diabetics, because medications that treat type 2 diabetes like metformin, glitazones, alpha-glucosidase inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase IV inhibitors, do not cause hypoglycemia. Hypoglycemia is common in type 2 diabetics who take insulin, glinides, or sulfonylurea. Insulin use remains a key risk factor in developing hypoglycemia, regardless of diabetes type. History Hypoglycemia was first discovered by James Collip when he was working with Frederick Banting on purifying insulin in 1922. Collip was asked to develop an assay to measure the activity of insulin. He first injected insulin into a rabbit, and then measured the reduction in blood-glucose levels. Measuring blood glucose was a time-consuming step. Collip observed that if he injected rabbits with a too large a dose of insulin, the rabbits began convulsing, went into a coma, and then died. This observation simplified his assay. He defined one unit of insulin as the amount necessary to induce this convulsing hypoglycemic reaction in a rabbit. Collip later found he could save money, and rabbits, by injecting them with glucose once they were convulsing. Etymology The word hypoglycemia is also spelled hypoglycaemia or hypoglycæmia. The term means low blood sugar from Greek ὑπογλυκαιμία, from ὑπο- hypo- under + γλυκύς glykys sweet + αἷμᾰ haima blood. References External links Hypoglycemia at the Mayo Clinic American Diabetes Association "Hypoglycemia". MedlinePlus. U.S. National Library of Medicine.

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

Please help me grasp the concept behind the medical term 'Nipple adenoma.'

A nipple adenoma is a rare benign tumour of the breast. The condition may also be known as : Florid papillomatosis of the nipple Florid adenomatosis Subareolar duct papillomatosis Erosive adenomatosis Signs and symptoms Nipple adenomas may be felt as a lump under the nipple or areola. They may come to attention because of nipple pain, ulceration, swelling or discharge. Diagnosis Definition A nipple adenoma is a type of intraductal papilloma that arises within the lactiferous ducts that are located within the nipple. Differential diagnosis The microscopic appearance of a nipple adenoma can be mistaken for carcinoma. Other conditions that have similar symptoms and signs as nipple adenoma include Pagets disease of the breast, other intraductal papillomas, ductal carcinoma in situ (DCIS), syringomatous adenoma of the nipple and subareolar sclerosing duct hyperplasia. Imaging Lesions of the nipple and areola, such as nipple adenoma, may be difficult to image clearly on routine mammogram or ultrasonography. Nipple adenomas can be imaged using magnetic resonance imaging (MRI) and conventional or MR ductogram. Biopsy Once excised, the macroscopic appearance of nipple adenomas is of a poorly defined nodular mass. The microscopic appearance can be quite bizarre, and may be misinterpreted as a carcinoma. Nipple adenomas usually have a rounded outline at low magnification, and at higher magnification can be seen to consist of a haphazardly arranged mass of proliferating tubular structures composed of epithelial and myoepithelial cells within varying amounts of fibrous stroma. The epithelial cells are usually columnar, but the columnar epithelial cells can undergo apocrine or squamous metaplasia. Mitotic figures and necrosis are not commonly seen. Treatment The appropriate treatment in contemporary western medicine is complete surgical excision of the abnormal growth with a small amount of normal surrounding breast tissue. Prognosis Nipple adenomas are non-cancerous growths, which can recur if not completely surgically removed. There are reported cases of cancers arising within nipple adenomas, and following excision of nipple adenomas, but these are rare occurrences. Epidemiology Nipple adenomas most commonly occur in 30- to 40-year-old women, but can also occur in men. They can also occur at any age, including in the elderly, in adolescence, and in infants. References == External links ==

You serve as a guide in the medical field. Explain medical terms thoroughly, ensuring the information is both insightful and comprehensible.

I've encountered the term 'Urachal diverticulum' while reading about medical topics. What does it refer to exactly?

A urachal diverticulum (also vesicourachal diverticulum) is a congenital disorder caused by the partial persistence of the allantois. The allantois, which later becomes the urachus, connects an embryos bladder to the yolk sac. Normally, the urachus closes off to become the median umbilical ligament; however, if it does not seal close to the bladder, a blind pouch connected to the bladder remains. This is usually asymptomatic but can lead to recurrent urinary tract infections. If the urachus is wholly patent, urine can drain from the bladder to an opening by the umbilicus, a condition known as urachal fistula. == References ==

You serve as a guide in the medical field. Explain medical terms thoroughly, ensuring the information is both insightful and comprehensible.

Could you please explain the term 'Tinnitus' in simple language?

Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone will experience a faint "normal tinnitus" in a completely quiet room but it is only of concern if it is bothersome or interferes with normal hearing or correlated with other problems. While often described as a ringing, it may also sound like a clicking, buzzing, hiss, or roaring. The sound may be soft or loud, low or high pitched, and often appears to be coming from one or both ears or from the head itself. In some people, the sound may interfere with concentration and in some cases it is associated with anxiety and depression. Tinnitus is usually associated with a degree of hearing loss and with decreased comprehension of speech in noisy environments. It is common, affecting about 10–15% of people. Most, however, tolerate it well, and it is a significant problem in only 1–2% of all people. It can trigger a fight-or-flight response, as the brain may perceive it as dangerous and important. The word tinnitus comes from the Latin tinnire which means "to ring".Rather than a disease, tinnitus is a symptom that may result from various underlying causes and may be generated at any level of the auditory system and structures beyond that system. The most common causes are hearing damage, noise-induced hearing loss or age-related hearing loss, known as presbycusis. Other causes include ear infections, disease of the heart or blood vessels, Ménières disease, brain tumors, acoustic neuromas (tumors on the auditory nerves of the ear), migraines, temporomandibular joint disorders, exposure to certain medications, a previous head injury, earwax; and tinnitus can suddenly emerge during a period of emotional stress. It is more common in those with depression.The diagnosis of tinnitus is usually based on the persons description. It is commonly supported by an audiogram, an otolaryngological and a neurological examination. The degree of interference with a persons life may be quantified with questionnaires. If certain problems are found, medical imaging, such as magnetic resonance imaging (MRI), may be performed. Other tests are suitable when tinnitus occurs with the same rhythm as the heartbeat. Rarely, the sound may be heard by someone else using a stethoscope, in which case it is known as objective tinnitus. Occasionally, spontaneous otoacoustic emissions, sounds produced normally by the inner ear, may result in tinnitus.Prevention involves avoiding exposure to loud noise for longer periods or chronically. If there is an underlying cause, treating it may lead to improvements. Otherwise, typically, management involves psychoeducation or counseling, such as talk therapy. Sound generators or hearing aids may help. No medication directly targets tinnitus. Signs and symptoms Tinnitus may be perceived in one or both ears, or more centrally in the head. The noise commonly occurs inside a persons head or ear(s) in the absence of auditory stimulation, similar to ringing, although in some people, it is a high-pitched whining or electric buzzing, among numerous other sounds. Tinnitus may be intermittent or continuous. In some individuals, the intensity may be changed by shoulder, neck, head, tongue, jaw, or eye movements.The specific type of tinnitus called objective tinnitus is characterized by hearing the sounds of ones own muscle contractions or pulse, which is typically a result of sounds that have been created by the movement of jaw muscles or sounds related to blood flow in the neck or face. Course Due to variations in study designs, data on the course of tinnitus showed few consistent results. Generally, the prevalence increased with age in adults, whereas the ratings of annoyance decreased with duration. Psychological effects Although an annoying condition to which most people adapt, persistent tinnitus may cause anxiety and depression in some people. Tinnitus annoyance is more strongly associated with the psychological condition of the person than the loudness or frequency range. Psychological problems such as depression, anxiety, sleep disturbances, and concentration difficulties are common in those with strongly annoying tinnitus. 45% of people with tinnitus have an anxiety disorder at some time in their life.Psychological research has focused on the tinnitus distress reaction to account for differences in tinnitus severity. The research indicates that conditioning at the initial perception of tinnitus linked it with negative emotions, such as fear and anxiety. Types A common tinnitus classification is into "subjective and objective tinnitus". Tinnitus is usually subjective, meaning that the sounds the person hears are not detectable by means currently available to physicians and hearing technicians. Subjective tinnitus has also been called "tinnitus aurium", "non-auditory" or "non-vibratory" tinnitus. In rare cases, tinnitus can be heard by someone else using a stethoscope. Even more rarely, in some cases it can be measured as a spontaneous otoacoustic emission (SOAE) in the ear canal. This is classified as objective tinnitus, also called "pseudo-tinnitus" or "vibratory" tinnitus. Subjective tinnitus Subjective tinnitus is the most frequent type of tinnitus. It may have many possible causes, but most commonly it results from hearing loss. When the tinnitus is caused by disorders of the inner ear or auditory nerve it can be called otic (from the Greek word for ear). These otological or neurological conditions include those triggered by infections, drugs, or trauma. A frequent cause is traumatic noise exposure that damages hair cells in the inner ear.When there does not seem to be a connection with a disorder of the inner ear or auditory nerve, the tinnitus can be called non-otic (i.e. not otic). In some 30% of tinnitus cases, the tinnitus is influenced by the somatosensory system, for instance, people can increase or decrease their tinnitus by moving their face, head, or neck. This type is called somatic or craniocervical tinnitus, since it is only head or neck movements that have an effect.There is a growing body of evidence suggesting that some tinnitus is a consequence of neuroplastic alterations in the central auditory pathway. These alterations are assumed to result from a disturbed sensory input, caused by hearing loss. Hearing loss could indeed cause a homeostatic response of neurons in the central auditory system, and therefore cause tinnitus. Hearing loss The most common cause of tinnitus is hearing loss. Hearing loss may have many different causes, but among those with tinnitus, the major cause is cochlear injury.Ototoxic drugs also may cause subjective tinnitus, as they may cause hearing loss, or increase the damage done by exposure to loud noise. Those damages may occur even at doses that are not considered ototoxic. More than 260 medications have been reported to cause tinnitus as a side effect. In many cases, however, no underlying cause could be identified.Tinnitus can also occur due to the discontinuation of therapeutic doses of benzodiazepines. It can sometimes be a protracted symptom of benzodiazepine withdrawal and may persist for many months. Medications such as bupropion may also result in tinnitus. In many cases, however, no underlying cause can be identified. Associated factors Factors associated with tinnitus include: ear problems and hearing loss: conductive hearing loss acoustic shock loud noise or music middle ear effusion otitis otosclerosis Eustachian tube dysfunction sensorineural hearing loss excessive or loud noise; e.g. acoustic trauma presbycusis (age-associated hearing loss) Ménières disease endolymphatic hydrops superior canal dehiscence acoustic neuroma mercury or lead poisoning ototoxic medications neurologic disorders: Arnold–Chiari malformation multiple sclerosis head injury giant cell arteritis temporomandibular joint dysfunction metabolic disorders: vitamin B12 deficiency iron deficiency anemia psychiatric disorders depression anxiety disorders other factors: vasculitis Some psychedelic drugs can produce temporary tinnitus-like symptoms as a side effect 5-MeO-DET diisopropyltryptamine (DiPT) benzodiazepine withdrawal intracranial hyper or hypotension caused by, for example, encephalitis or a cerebrospinal fluid leak Objective tinnitus Objective tinnitus can be detected by other people and is sometimes caused by an involuntary twitching of a muscle or a group of muscles (myoclonus) or by a vascular condition. In some cases, tinnitus is generated by muscle spasms around the middle ear.Spontaneous otoacoustic emissions (SOAEs), which are faint high-frequency tones that are produced in the inner ear and can be measured in the ear canal with a sensitive microphone, may also cause tinnitus. About 8% of those with SOAEs and tinnitus have SOAE-linked tinnitus, while the percentage of all cases of tinnitus caused by SOAEs is estimated at 4%. Pediatric tinnitus Children may be subject to pulsatile or continuous tinnitus. With pulsatile tinnitus involving anomalies and variants of the vascular parts. While continuous affecting the middle/inner ear structures. CT scans are able to check for integrity of the structures, and MR scans can evaluate the nerves and potential masses or malformations. Early diagnosis can prevent long term impairments to development, imaging and categorizing whether it nonpulsatile or pulsatile tinnitus help create an efficient diagnosis. Pulsatile tinnitus Some people experience a sound that beats in time with their pulse, known as pulsatile tinnitus or vascular tinnitus. Pulsatile tinnitus is usually objective in nature, resulting from altered blood flow, increased blood turbulence near the ear, such as from atherosclerosis or venous hum, but it can also arise as a subjective phenomenon from an increased awareness of blood flow in the ear. Rarely, pulsatile tinnitus may be a symptom of potentially life-threatening conditions such as carotid artery aneurysm or carotid artery dissection. Pulsatile tinnitus may also indicate vasculitis, or more specifically, giant cell arteritis. Pulsatile tinnitus may also be an indication of idiopathic intracranial hypertension. Pulsatile tinnitus can be a symptom of intracranial vascular abnormalities and should be evaluated for irregular noises of blood flow (bruits). Pathophysiology It may be caused by increased neural activity in the auditory brainstem, where the brain processes sounds, causing some auditory nerve cells to become over-excited. The basis of this theory is that many with tinnitus also have hearing loss.Three reviews of 2016 emphasized the large range and possible combinations of pathologies involved in tinnitus, which in turn result in a great variety of symptoms demanding specifically adapted therapies. Diagnosis The diagnostic approach is based on a history of the condition and an examination of the head, neck, and neurological system. Typically an audiogram is done, and occasionally medical imaging or electronystagmography. Treatable conditions may include middle ear infection, acoustic neuroma, concussion, and otosclerosis.Evaluation of tinnitus can include a hearing test (audiogram), measurement of acoustic parameters of the tinnitus like pitch and loudness, and psychological assessment of comorbid conditions like depression, anxiety, and stress that are associated with severity of the tinnitus.One definition of tinnitus, as compared to normal ear noise experience, is lasting five minutes at least twice a week. However, people with tinnitus often experience the noise more frequently than this. Tinnitus can be present constantly or intermittently. Some people with constant tinnitus might not be aware of it all the time, but only for example during the night when there is less environmental noise to mask it. Chronic tinnitus can be defined as tinnitus with duration of six months or more. Audiology Since most persons with tinnitus also have hearing loss, a pure tone hearing test resulting in an audiogram may help diagnose a cause, though some persons with tinnitus do not have hearing loss. An audiogram may also facilitate fitting of a hearing aid in those cases where hearing loss is significant. The pitch of tinnitus is often in the range of the hearing loss. Psychoacoustics Acoustic qualification of tinnitus will include measurement of several acoustic parameters like frequency in cases of monotone tinnitus or frequency range and bandwidth in cases of narrow band noise tinnitus, loudness in dB above hearing threshold at the indicated frequency, mixing-point, and minimum masking level. In most cases, tinnitus pitch or frequency range is between 5 kHz and 10 kHz, and loudness between 5 and 15 dB above the hearing threshold.Another relevant parameter of tinnitus is residual inhibition, the temporary suppression or disappearance of tinnitus following a period of masking. The degree of residual inhibition may indicate how effective tinnitus maskers would be as a treatment modality.An assessment of hyperacusis, a frequent accompaniment of tinnitus, may also be made. Hyperacusis is related to negative reactions to sound and can take many forms. One associated parameter that can be measured is Loudness Discomfort Level (LDL) in dB, the subjective level of acute discomfort at specified frequencies over the frequency range of hearing. This defines a dynamic range between the hearing threshold at that frequency and the loudness discomfort level. A compressed dynamic range over a particular frequency range can be associated with hyperacusis. Normal hearing threshold is generally defined as 0–20 decibels (dB). Normal loudness discomfort levels are 85–90+ dB, with some authorities citing 100 dB. A dynamic range of 55 dB or less is indicative of hyperacusis. Severity The condition is often rated on a scale from "slight" to "severe" according to the effects it has, such as interference with sleep, quiet activities and normal daily activities.Assessment of psychological processes related to tinnitus involves measurement of tinnitus severity and distress (i.e., nature and extent of tinnitus-related problems), measured subjectively by validated self-report tinnitus questionnaires. These questionnaires measure the degree of psychological distress and handicap associated with tinnitus, including effects on hearing, lifestyle, health and emotional functioning. A broader assessment of general functioning, such as levels of anxiety, depression, stress, life stressors and sleep difficulties, is also important in the assessment of tinnitus due to higher risk of negative well-being across these areas, which may be affected by or exacerbate the tinnitus symptoms for the individual. Overall, current assessment measures are aimed to identify individual levels of distress and interference, coping responses and perceptions of tinnitus to inform treatment and monitor progress. However, wide variability, inconsistencies and lack of consensus regarding assessment methodology are evidenced in the literature, limiting comparison of treatment effectiveness. Developed to guide diagnosis or classify severity, most tinnitus questionnaires have been shown to be treatment-sensitive outcome measures. Pulsatile tinnitus If the examination reveals a bruit (sound due to turbulent blood flow), imaging studies such as transcranial doppler (TCD) or magnetic resonance angiography (MRA) should be performed. Differential diagnosis Other potential sources of the sounds normally associated with tinnitus should be ruled out. For instance, two recognized sources of high-pitched sounds might be electromagnetic fields common in modern wiring and various sound signal transmissions. A common and often misdiagnosed condition that mimics tinnitus is radio frequency (RF) hearing, in which subjects have been tested and found to hear high-pitched transmission frequencies that sound similar to tinnitus. Prevention Prolonged exposure to loud sound or noise levels can lead to tinnitus. Custom made ear plugs or other measures can help with prevention. Employers may use hearing loss prevention programs to help educate and prevent dangerous levels of exposure to noise. Government organizations set regulations to ensure employees, if following the protocol, should have minimal risk to permanent damage to their hearing.Certain groups are advised to wear ear plugs when working or riding to avoid the risk of tinnitus, caused by overexposure to loud noises such as wind noise for motorcycle riders. Occupationally this includes musicians, DJs, agricultural, and construction workers as they are at a greater risk compared to the general population. Several medicines have ototoxic effects, and can have a cumulative effect that can increase the damage done by noise. If ototoxic medications must be administered, close attention by the physician to prescription details, such as dose and dosage interval, can reduce the damage done. Management If a specific underlying cause is determined, treating it may lead to improvements. Otherwise, the primary treatment for tinnitus is talk therapy, sound therapy, or hearing aids. There are no effective drugs that treat tinnitus. Psychological The best supported treatment for tinnitus is a type of counseling called cognitive behavioral therapy (CBT) which can be delivered via the internet or in person. It decreases the amount of stress those with tinnitus feel. These benefits appear to be independent of any effect on depression or anxiety in an individual. Acceptance and commitment therapy (ACT) also shows promise in the treatment of tinnitus. Relaxation techniques may also be useful. A clinical protocol called Progressive Tinnitus Management for treatment of tinnitus has been developed by the United States Department of Veterans Affairs. Sound-based interventions The use of sound therapy by either hearing aids or tinnitus maskers may help the brain ignore the specific tinnitus frequency. Whilst these methods are poorly supported by evidence, there are no negative effects. There are several approaches for tinnitus sound therapy. The first is sound modification to compensate for the individuals hearing loss. The second is a signal spectrum notching to eliminate energy close to the tinnitus frequency. There is some tentative evidence supporting tinnitus retraining therapy, which is aimed at reducing tinnitus-related neuronal activity. There are preliminary data on an alternative tinnitus treatment using mobile applications, including various methods: masking, sound therapy, relaxing exercises and other. These applications can work as a separate device or as a hearing aid control system. Medications As of 2018 there were no medications effective for idiopathic tinnitus. There is not enough evidence to determine if antidepressants or acamprosate are useful. There is no high-quality evidence to support the use of benzodiazepines for tinnitus. Usefulness of melatonin, as of 2015, is unclear. It is unclear if anticonvulsants are useful for treating tinnitus. Steroid injections into the middle ear also do not seem to be effective. There is no evidence to suggest that the use of betahistine to treat tinnitus is effective.Botulinum toxin injection has been tried with some success in some of the rare cases of objective tinnitus from a palatal tremor.Caroverine is used in a few countries to treat tinnitus. The evidence for its usefulness is very weak. Neuromodulation In 2020, information about recent clinical trials has indicated that bimodal neuromodulation may be a promising treatment for reducing the symptoms of tinnitus. It is a noninvasive technique that involves applying an electrical stimulus to the tongue while also administering sounds. Equipment associated with the treatments is available through physicians. Studies with it and similar devices continue in several research centers.There is some evidence supporting neuromodulation techniques such as transcranial magnetic stimulation; transcranial direct current stimulation and neurofeedback. However, the effects in terms of tinnitus relief are still under debate. Alternative medicine Ginkgo biloba does not appear to be effective. The American Academy of Otolaryngology recommends against taking melatonin or zinc supplements to relieve symptoms of tinnitus, and reported that evidence for the efficacy of many dietary supplements—lipoflavonoids, garlic, traditional Chinese/Korean herbal medicine, honeybee larvae and various other vitamins and minerals, as well as homeopathic preparations—did not exist. A 2016 Cochrane Review also concluded that evidence was not sufficient to support taking zinc supplements to reduce symptoms associated with tinnitus. Prognosis While there is no cure, most people with tinnitus get used to it over time; for a minority, it remains a significant problem. Epidemiology Adults Tinnitus affects 10–15% of people. About a third of North Americans over 55 experience tinnitus. Tinnitus affects one third of adults at some time in their lives, whereas ten to fifteen percent are disturbed enough to seek medical evaluation. 70 million people in Europe are estimated to have tinnitus. Children Tinnitus is commonly thought of as a symptom of adulthood, and is often overlooked in children. Children with hearing loss have a high incidence of pediatric tinnitus, even though they do not express the condition or its effect on their lives. Children do not generally report tinnitus spontaneously and their complaints may not be taken seriously. Among those children who do complain of tinnitus, there is an increased likelihood of associated otological or neurological pathology such as migraine, juvenile Menieres disease or chronic suppurative otitis media. Its reported prevalence varies from 12% to 36% in children with normal hearing thresholds and up to 66% in children with a hearing loss and approximately 3–10% of children have been reported to be troubled by tinnitus. See also References External links Tinnitus at Curlie Baguley, David; Andersson, Gerhard; McFerran, Don; McKenna, Laurence (2013) [2004]. Tinnitus: A Multidisciplinary Approach (2nd ed.). Indianapolis, IN: Wiley-Blackwell. ISBN 978-1-4051-9989-6. LCCN 2012032714. OCLC 712915603. Langguth, B; Hajak, G; Kleinjung, T; Cacace, A; Møller, AR, eds. (2007). Tinnitus: pathophysiology and treatment. Progress in brain research no. 166 (1st ed.). Amsterdam; Boston: Elsevier. ISBN 978-0-444-53167-4. LCCN 2012471552. OCLC 648331153. Retrieved 5 November 2012. Alt URL Møller, Aage R; Langguth, Berthold; Ridder, Dirk; et al., eds. (2011). Textbook of Tinnitus. New York: Springer. doi:10.1007/978-1-60761-145-5. ISBN 978-1-60761-144-8. LCCN 2010934377. OCLC 695388693, 771366370, 724696022. (subscription required)

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

Could you please explain the term 'Juvenile xanthogranuloma' in simple language?

Juvenile xanthogranuloma is a form of histiocytosis, classified as "non-Langerhans cell histiocytosis", or more specifically, "type 2".It is a rare skin disorder that primarily affects children under one year of age but can also be found in older children and adults. It was first described in 1905 by Adamson. In 5% to 17% of people, the disorder is present at birth, but the median age of onset is two years. JXG is a benign idiopathic cutaneous granulomatous tumor and the most common form of non-Langerhans cell histiocytosis (non-LHC). The lesions appear as orange-red macules or papules and are usually located on the face, neck, and upper trunk. They may also appear at the groin, scrotum, penis, clitoris, toenail, palms, soles, lips, lungs, bone, heart, and gastrointestinal tract more rarely. JXG usually manifests with multiple lesions on the head and neck in cases with children under six months of age. The condition usually resolves spontaneously over one to five years. A biopsy of the lesion is critical to confirm the diagnosis. Ocular JXG manifests in up to 10% of people with JXG and may affect their vision. The presence of JXG in the eye can cause spontaneous hyphema, secondary glaucoma or even blindness. It is most often seen in the iris but may be found on the eyelid, corneoscleral limbus, conjunctiva, orbit, retina, choroid, disc, or optic nerve. Of patients with ocular JXG, 92% are younger than the age of two. Although cutaneous JXG usually disappear spontaneously, ocular lesions rarely improve spontaneously and require treatment. Treatments that have been used include surgical excision, intralesional steroid injection, cryotherapy, and low dose radiotherapy. In the case of a resistant or reoccurring lesion, chemotherapy has been used as a treatment. Ocular JXG is usually unilateral and presents with a tumor, a red eye with signs of uveitis, unilateral glaucoma, spontaneous hyphema or heterochromia iridis. Diagnosing and treating the patient as early as possible contributes to the most positive visual outcome. Histiocytic disorders like JXG are identified by the cells that make them up. Immunohistochemical analysis is used to discern the immunoreactivity to certain antibodies in these analyses. JXG is a non-LHC disorder which is a varied group of disorders defined by the accumulation of histiocytes that do not meet criteria to be diagnosed as Langerhans cells. JXG is not metastatic and may be present with lipid deposits. JXG is often accompanied with other disorders such as neurofibromatosis type one and juvenile chronic myelogenous leukemia. Juvenile variety xanthogranuloma can be distinguished from xanthoma by the spread of the lesion and the lack of lipid abnormalities. Other similar diagnoses include molluscum contagiosum, hemangioma and neurofibroma. See also Non-X histiocytoses List of cutaneous conditions References == External links ==

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

I'd like to learn more about the medical term 'Acquired idiopathic generalized anhidrosis.' Can you provide some details?

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 ==

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

I've encountered the term 'Circumvallate placenta' while reading about medical topics. What does it refer to exactly?

Circumvallate placenta is a rare condition affecting about 1-2% of pregnancies, in which the amnion and chorion fetal membranes essentially "double back" on the fetal side around the edges of the placenta. After delivery, a circumvallate placenta has a thick ring of membranes on its fetal surface. Circumvallate placenta is a placental morphological abnormality associated with increased fetal morbidity and mortality due to the restricted availability of nutrients and oxygen to the developing fetus. Physicians may be able to detect a circumvallate placenta during pregnancy by using an ultrasound. However, in other cases, a circumvallate placenta is not identified until delivery of the baby. Circumvallate placenta can increase the risk of associated complications such as preterm delivery and placental abruption. Occasionally, a circumvallate placenta can also increase the risk of neonatal death and emergency caesarean section. Although there is no existing treatment for circumvallate placenta, physicians can attempt to minimize the effects of complications, if they occur, through frequent fetal monitoring and, if necessary, emergency cesarean section.In a circumvallate placenta, the chorionic plate, which forms the fetal surface of the placenta, tends to be smaller than the basal plate, which forms the maternal surface of the placenta. This results in the elevation of the placental margin and the appearance of an annular shape. The fetal surface is divided into a central depressed zone surrounded by a thickened white ring which is incomplete. The ring is situated at varying distances from the margin, or edges, of the placenta. This thick ring of membranes is composed of a double fold of amnion and chorion with degenerated decidua vera and fibrin in between. Blood vessels, supplying nutrients and carrying waste products to and from the developing fetus, radiate from the umbilical cord insertion to as far as the ring of membranes, and then disappears from view. Signs & Symptoms A circumvallate placenta does not always induce associated symptoms during pregnancy, making it extremely difficult to diagnose a circumvallate placenta in asymptomatic mothers. In symptomatic mothers, physicians may be able to detect a circumvallate placenta based on the presentation of the following signs. Vaginal bleeding: A circumvallate placenta can increase the risk of frequent vaginal bleeding during the first trimester of pregnancy. In a study conducted with 92 women with a circumvallate placenta, it was concluded that incidences of vaginal bleeding were significantly higher in women with a circumvallate placenta during all three trimesters when compared to the control group. However, a noted limitation of the study considered by the researchers was that because the study included such a small number of women, the obtained results may not be fully representative of the general population. Because the chorionic plate is much smaller than the basal plate in a circumvallate placenta, vaginal bleeding tends to occur at this site where the placenta is exposed and uncovered. In mothers presenting with vaginal bleeding, circumvallate placenta should be suspected as a possible cause of the vaginal bleeding. Inhibited fetal growth: Fetuses tend to develop more slowly when associated with a circumvallate placenta, largely due to the reduced supply of blood and nutrients from mother to fetus. Physicians will order tests to determine the cause of inhibited fetal growth when a developing fetus does not meet growth expectations during the course of the pregnancy. Premature rupture of membranes (PROM): PROM happens when the protective covering of the amniotic sac ruptures before the onset of labor and delivery. If PROM occurs within the first 37 weeks of pregnancy, it is termed preterm premature rupture of membranes (PPROM). PROM itself has many causes and risk factors. When PROM occurs along with vaginal bleeding in the second trimester of pregnancy, it is suspected that a mother likely has a circumvallate placenta. Complications Circumvallate placenta has also been associated with a higher incidence of complications including placental abruption, low birth weight, premature delivery, perinatal death, and fetal abnormalities. Low birth weight: Lack of proper nutrition and blood flow to the fetus during pregnancy often results in decreased weight of the baby at birth. Placenta abruption: Placenta abruption, in which the placenta divides from the wall of the uterus prior to birth, can have severe outcomes for a mother and her baby. Such consequences include vaginal bleeding, decreased birth weight, preterm delivery, and stillbirth. Significant vaginal bleeding can induce maternal anemia and dangerously low blood pressure. Oligohydramnios: Insufficiency of proper volumes of amniotic fluid, a condition called oligohydramnios, can also occur as a result of a circumvallate placenta. Amniotic fluid is essential to normal fetal movement, fetal organ development, and cushioning of the fetus within the mothers uterus. It is also imperative in preventing umbilical cord compression so that the fetus is able to obtain nourishment and oxygenation from its mother. Premature delivery: Premature birth of the fetus occurs at less than 37 weeks of gestation, compared to full-term delivery at about 40 weeks. Miscarriage: Loss of a fetus prior to birth via miscarriage can transpire if any of the above complications occur without prompt intervention and treatment. Cause Unfortunately, there is no known cause of circumvallate placenta and no major preventative measures that can be taken to minimize the risk of developing a circumvallate placenta. Circumvallate placenta is not a genetic disorder. Some potential causes of circumvallate placenta include reduced amniotic fluid pressure, circumferential hemorrhage, and superficial or deep implantation of the embryo within the uterine wall, although these potential causes are still not well-understood in terms of their relation to circumvallate placenta.High-risk pregnancies are described as pregnancies in which a mother, the fetus, or both are put at a higher risk for developing pregnancy complications before, during, or after birth. Risk factors such as hypertensive medical conditions, maternal age, and substance use are just some of the things that can put a woman at an increased risk for developing circumvallate placenta and/or any other complications. Risk factors Hypertensive disorders Women entering a pregnancy with hypertension are considered to be put at a higher risk for preeclampsia or eclampsia during the course of their pregnancy. Hypertensive disorders, like hypertension, have been found to affect about 10% of pregnancies in the United States and have resulted in about 6.8% of maternal deaths from 2011 to 2015. High blood pressure during pregnancy can potentially damage maternal organ systems such as the liver or the kidneys, which can be life-threatening. To prevent preeclampsia or eclampsia from developing in pregnancy, women with hypertension can be prescribed anti-hypertensive medications during pregnancy and are advised to monitor their blood pressure throughout the course of pregnancy. Maternal age Another risk factor for developing any pregnancy complications is maternal age. Advanced maternal age, considered to be when a woman enters pregnancy at age 35 or above, has also been linked to increased risk of maternal mortality, preeclampsia, restricted fetal growth, fetal distress, and a variety of other pregnancy complications. Conversely, teenage pregnancy is also associated with increased risk of endometriosis, postpartum hemorrhage, and mild preeclampsia, when compared with pregnant mothers in their 20s. Genetically, the long period of time between meiotic arrest of the egg gamete as a fetus and each ovulation cycle occurring after the onset of female puberty in teenage years can potentially contribute to the increased risk for pregnancy complications in mothers who are age 35 or older at time of pregnancy. Substance use Further, yet another factor inducing adverse complications in pregnancy is substance use status. Nicotine, alcohol, and marijuana are the most common substances used during pregnancies. Substance use in pregnancy is concerning because of its alarming association with other risk factors, such as mental illness. Depression alone has been associated within increased risk for preeclampsia, gestational diabetes, hypertension, premature birth, and low birth weight. Women with substance use disorders tend to live in areas that are unable to provide quality prenatal care or proper management of their psychiatric conditions. As a result of improper management of psychiatric illnesses, substances are abused during pregnancy, potentially causing harm to both the mother and the fetus. Some pregnancy complications that can occur as a result of substance use in pregnancy are fetal alcohol syndrome and neonatal abstinence disorder.Women with these risk factors are recommended additional surveillance during pregnancy to monitor fetal development and to be able to detect fetal, placental, or umbilical cord abnormalities as early as possible. Pathophysiology/Mechanism The placenta is a transient organ developed during pregnancy that facilitates nutrient, gas, and waste exchange between a mother and a developing fetus. Placental abnormalities, such as circumvallate placenta, can harm a developing fetus, as normal exchange of materials between a mother and a developing fetus is impaired. With placental abnormalities, a developing fetus is unable to receive the vital materials that it needs for proper development, resulting in the possibility of pregnancy complications, birth defects, and/or death of the fetus. In a normal placenta, there is a smooth transition from the parenchymal villous chorion to the membranous chorion at the border of the placental plate. Fetal blood vessels subdivide from the umbilical cord and spread diagonally throughout the parenchyma towards the edge of the placental plate.In a circumvallate placenta, the membranes often become restrained due to marginal infarct, hemorrhage, or fibrin depositing. This results in the reduction in size of the chorionic plate of the placenta, further causing the membranes on the fetal side to fold backward on themselves. The parenchymal villous chorion continues to proliferate beyond the tethered membranes and appears to protrude outward. The fetal blood vessels are directed downward and then horizontally in order to provide blood flow to the most peripheral parts of the placental plate extending beyond the tethered membranes.Since a portion of the placenta tends to become exposed in a circumvallate placenta, due to the reduced size of the chorionic plate, vaginal bleeding is more likely to occur at this site of exposure. Likewise, inhibited fetal growth can also ensue due to the decreased exchange of nutrients and waste between mother and fetus, since the fetus is unable to sustain necessary nutritional demands for proper fetal development. Premature rupture of membranes often occurs as a result of infection in the uterus, which can be caused by the occurrence vaginal bleeding. Therefore, placental abnormalities such as circumvallate placenta can be extremely detrimental in causing the onset of associated conditions. Diagnosis In some cases, a physician may be able to diagnose a circumvallate placenta via ultrasound during one of many routine ultrasound screenings. In most cases, a circumvallate placenta is not discovered until physical examination of the placenta after delivery of the fetus. For this reason, circumvallate placenta is very difficult to diagnose during pregnancy. On ultrasound, a normal placenta should appear complete and uniform, with the fetal surface of the placenta appearing slightly shiny and translucent. The appearance of a circumvallate placenta on ultrasound may present with irregular edges, uplifted margins, or placental sheets. In a study conducted in 1994, 62 healthy pregnant women were examined with placental sonography for detection of circumvallate placenta. Of the five experienced sonologists who interpreted the placental ultrasounds, all were unable to properly detect and diagnose circumvallate placenta, revealing the difficult nature of circumvallate placenta recognition. Further, these findings indicate that prenatal sonographic criteria used for detection of circumvallate placenta are not reliable enough for screening purposes. Complete circumvallate placenta involves morphological abnormality of the entire dimension of the placenta, while partial circumvallate placenta does not involve the entire placenta but rather a portion of the placenta. Complete circumvallate placenta is very rare, occurring within about 1% of pregnancies, and has been noted to increase the risks of associated complications such as placental abruption, premature childbirth, premature rupture of membranes, perinatal death, and congenital abnormalities. Partial circumvallate placenta is more common but is not found to be as clinically significant as complete circumvallate placenta.The accurate diagnosis of circumvallate placenta during pregnancy can have significant implications in the recognition of patients who are at risk of complications. Although the ability of sonography to accurately diagnosis circumvallate placenta during pregnancy is quite limited, research studies continue to emerge at the possibility of doing so. Treatment/Management Although there is no cure or specific treatment for restoration of the circumvallate placenta, there are ways to decrease the risks of possible complications prior to birth or attempt to manage complications if they develop. If circumvallate placenta is diagnosed during pregnancy, physicians may offer recommendations to reduce the risks of associated complications such as lower birth weight and placental abruption.Decreased birth weight is a major concern associated with circumvallate placenta. Infants born with birth weights that are lower than expected per their gestational age oftentimes end up requiring extra support in the neonatal intensive care unit (NICU). To assist in the monitoring of appropriate fetal growth, a physician may recommend more frequent growth checks during pregnancy if circumvallate placenta is suspected. If a fetus is not growing satisfactorily, premature delivery, via vaginal delivery or caesarean section, may be recommended, with C-section being more favorable compared to vaginal delivery.In women experiencing a placental abruption associated with circumvallate placenta, physicians will normally advocate for frequent growth checks, hospital bed rest, early delivery, and, if necessary, emergency C-section. Likewise, IV fluids and blood transfusions can also be given to patients with a placental abruption in attempts to increase blood pressure and minimize the effects of severe blood loss.If oligohydramnios occurs as a result of a circumvallate placenta, a treatment called amnioinfusion may be considered to replenish the amount of lost amniotic fluid within the amniotic sac. Amnioinfusion may help in preventing underdevelopment of the lungs.If diagnosed with a circumvallate placenta, consistent fetal monitoring by a licensed physician can help to prevent and/or reduce the effects of associated complications that may occur. Additionally, healthy lifestyle choices, a well-balanced and nutritious diet, adequate rest, and cessation of alcohol and tobacco products can also help to prevent the incidence of a circumvallate placenta and its associated complications. If diagnosed with a circumvallate placenta, in association with other threatening pregnancies complications, emergency cesarean section will most likely be suggested by a physician. Prognosis Unfortunately, there is currently not a cure available for circumvallate placenta. While some evidence suggests that a circumvallate placenta can increase the risk of complication during pregnancy, other research suggests this increased risk is marginal. Sadly, circumvallate placenta can occasionally result in infant death depending on the severity of the complications encountered. In other cases, circumvallate placenta can result in premature birth of infants who are otherwise healthy after being monitored in the neonatal intensive care unit for a period of time after birth. Therefore, proper medical care and monitoring are crucial in attempting to minimize the likelihood of complications. In other cases, patients diagnosed with circumvallate placenta are able to carry their babies until term or near-term. Epidemiology Circumvallate placenta is a very rare condition affecting pregnant women. This condition is a placental morphological abnormality, with the placenta being formed during the early periods of pregnancy. Women are able to become pregnant with the onset of ovulation and menstruation in early adolescence, with most women becoming pregnant during adulthood. Circumvallate placenta is currently known to affect about 1-2% of pregnancies. It is not virally transmissible to other individuals, nor can it be transferred through contact or respiration.There are no specific racial or ethnic groups that are more predisposed to acquiring a circumvallate placenta during pregnancy, however, as with all pregnancies, there are general risks factors that can put a pregnant woman at risk for complications, including circumvallate placenta. Notably, certain pregnancy complications, such as preeclampsia, tend to be almost three times as fatal in African American women compared to non-Hispanic white women, even though both groups tend to experience preeclampsia at almost the same rates. This is partially thought to be due to inequalities in accessing quality prenatal care in lower socioeconomic neighborhoods and the effect of structural racism within healthcare systems. Any woman residing in an area with a lower socioeconomic status, regardless of race or age, is predisposed to developing pregnancy complications like circumvallate placenta if quality prenatal care is not available. Women with significant obstetric histories can also be at higher risk for developing any type of pregnancy complication, including circumvallate placenta, and are recommended to be screened for placental abnormalities within their second trimester of pregnancy. Research Directions The placenta plays a dominant role in being responsible for a variety of complications within pregnancy and labor. Placental pathological studies have significantly contributed to recent obstetric literature. Many studies have examined the clinical significance of patients with circumvallate placenta compared to patients with a normal placenta. They have revealed that incidences of preterm birth, oligohydramnios, placental abruption, low birth weight, and fetal death were present in significantly higher rates than when compared to control patients with normal placentas. Because circumvallate placenta is such a rare condition, it is difficult to gain significant evidence and data.A case study reported in 2020 observed the correlation between circumvallate placenta and the occurrence of obstetric complications such as battledore insertion. Battledore insertion, abnormal insertion of the umbilical cord into the placenta, occurs in about 7% of pregnancies and can also result in many of the same pregnancy complications as circumvallate placenta; intrauterine growth restriction, fetal distress, and fetal death. This abnormal insertion of the umbilical cord into the placenta can result in a loss of adequate blood flow to the developing fetus due to restriction. The fetus is unable to obtain normal amounts of required oxygen and nutrition through the placenta, and this can further cause other severe complications. In the study, a 22-year-old woman at 28 weeks and 2 days of gestation, presented for a routine third trimester screening. She was noted to have had 2 prior miscarriages at 17 and 20 weeks. A previous normal second trimester routine screening at 21 weeks of gestation did not identify any structural abnormalities within the placenta, decreased fetal size, or abnormally-appearing umbilical cord insertion. The patient also did not have any episodes of vaginal bleeding during the current pregnancy.Upon presenting for routine screening at 28 weeks and 2 days of gestation, the patient was not exhibiting any signs of active contractions and a cardiotocography was performed as part of routine screening. Cardiotocography is a diagnostic tool used during the third trimester of pregnancy to observe fetal heart rates and presence of uterine contractions. It can also be used to detect signs of any sort of fetal distress. In interpreting the cardiotocography that the 22-year-old pregnant woman had completed, it was noted that the fetus appeared to be much smaller than expected and was exhibiting concerns of decreased amniotic fluid volume, oligohydramnios, and restricted blood flow through the umbilical cord. Cardiotocographic monitoring also noted decreases in fetal heart rate every 25 minutes without contractions. Fetal motion was present, with the placenta appearing enlarged and spherical.Decreases in the fetus heart rate, in addition to the other findings of the cardiotocography, ultimately prompted physicians to deliver the baby via emergency cesarean section without major complications. The newborn, with normal APGAR scores and umbilical cord arterial pH levels, was admitted to the neonatal intensive care unit. Upon examining the placenta after delivery, it was noted that the placenta demonstrated the appearance of a circumvallate placenta, and also showed evidence of abnormal umbilical cord insertion into the placenta. Postpartum, the mother had a good recovery and the newborn was discharged from the neonatal intensive care unit 105 days post-birth.This case study discussed the association of circumvallate placenta and abnormal battledore cord insertion in producing pregnancy complications. Restriction of umbilical cord blood flow from the placenta to the fetus and placental abnormalities like circumvallate placenta may work in conjunction to generate fetal distress. Decreased levels of oxygenation and nutrient absorption resulted in decelerations of fetal heart rate and the decision to deliver the fetus via cesarean section to prevent fetal death by hypoxia. Routine monitoring of fetal growth and development, placental structure, and placental function are recommended with high-risk pregnancies. In patients diagnosed with circumvallate placenta during pregnancy, monthly fetal growth assessments are also recommended. Patients found to have blood flow restrictions to or from the placenta are recommended to undergo weekly ultrasounds with consistent monitoring of fetal heart rate.In a separate case study reported in 2017, a woman at about 35 weeks of gestation presented with preeclampsia and intrauterine fetal demise, or more commonly known as stillbirth. After delivery of the stillborn fetus, examination of the placenta revealed a circumvallate placenta with battledore insertion of the umbilical cord. It was speculated that the combination of circumvallate placenta and battledore insertion had led to the loss of the fetus prior to delivery, as there was no other discernible cause for the stillbirth. While circumvallate placenta and battledore insertion are individually very rare conditions that can result in multiple pregnancy complications, the coexistence of these abnormalities likely resulted in the loss of the fetus. The diminished blood flow and circulation from the placenta to the fetus, as caused by battledore insertion, in combination with the impaired exchange of nutrients and wastes between mother and fetus, as caused by circumvallate placenta, likely contributed to the preeclampsia and this loss of fetal life. Thus, it is highly recommended that if placental or umbilical cord abnormalities, such as circumvallate placental and battledore insertion, are suspected or detected prior to birth, that the pregnancy should be considered high-risk. High-risk pregnancies significantly benefit from frequent follow-ups using ultransonography to monitor fetal developmental and placental and umbilical cord structure and function.Research directions continue to investigate methods in which circumvallate placenta may be more commonly diagnosed during pregnancy before complications can transpire. Biomarkers such as Sflt/PlGF can be used to predict severe pregnancy complications in high-risk pregnancies. Circumvallate placenta appears to be correlated with reduced placental efficacy due to increased placental thickness and abnormal villi function, affecting the Sflt/PlGF ratio. It is thought that obtaining Sflt/PlGF ratios can be used to determine deficiencies in placental function in cases of placental abnormalities. Future research analyzing the contribution of biomarkers like Sflt/PlGF to predict placental abnormalities would be influential to our understanding of many placental deformities, including circumvallate placenta.Due to the rare occurrences of circumvallate placenta, more extensive research trials are unavailable, resulting in data limitations. Therefore, the clinical importance of circumvallate placenta remains uncertain. See also circummarginate placenta References == External links ==

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

Can you break down the meaning of the medical term 'Minimal change disease' for me?

Minimal change disease (also known as MCD, minimal change glomerulopathy, and nil disease, among others) is a disease affecting the kidneys which causes a nephrotic syndrome. Nephrotic syndrome leads to the loss of significant amounts of protein in the urine, which causes the widespread edema (soft tissue swelling) and impaired kidney function commonly experienced by those affected by the disease. It is most common in children and has a peak incidence at 2 to 6 years of age. MCD is responsible for 10–25% of nephrotic syndrome cases in adults. It is also the most common cause of nephrotic syndrome of unclear cause (idiopathic) in children. Signs and symptoms The clinical signs of minimal change disease are proteinuria (abnormal excretion of proteins, mainly albumin, into the urine), edema (swelling of soft tissues as a consequence of water retention), weight gain, and hypoalbuminaemia (low serum albumin). These signs are referred to collectively as nephrotic syndrome. The first clinical sign of minimal change disease is usually edema with an associated increase in weight. The swelling may be mild but patients can present with edema in the lower half of the body, periorbital edema, swelling in the scrotal/labial area and anasarca in more severe cases. In older adults, patients may also present with acute kidney injury (20–25% of affected adults) and high blood pressure. Due to the disease process, patients with minimal change disease are also at risk of blood clots and infections. Pathology For years, pathologists found no changes when viewing kidney biopsy specimens under light microscopy, hence the name "minimal change disease." Sometimes, the mesangium may have expanded, but otherwise there is no injury to kidney tissue itself.Under immunofluorescence, there are no immunoglobulins or complement deposits bound to kidney tissue.With the advent of electron microscopy, the changes now known as the hallmarks of the disease were discovered. These are diffuse loss of visceral epithelial cells foot processes (i.e., podocyte effacement), vacuolation, and growth of microvilli on the visceral epithelial cells, allowing for excess protein loss in the urine. Pathophysiology Proteinuria The cause and pathogenesis of the pathology is unclear and it is currently considered idiopathic. However, it does not appear to involve complement or immune complex deposition. Rather, an altered T cell-mediated immunologic response with abnormal secretion of lymphokines by T cells is thought to modify the glomerular basement membrane, specifically the podocytes, increasing permeability. This allows the leakage of albumin and other serum proteins into the urine. Also, the exact cytokine responsible has yet to be elucidated, with IL-12, IL-18 and IL-13 having been most studied in this regard, yet never conclusively implicated. Data from a longitudinal study (Nephrotic Syndrome Study Network – NEPTUNE) published in 2022 suggested that up to 29% of biopsy-confirmed, mixed pediatric and adult minimal change disease cases exhibited serum autoantibodies against nephrin, a structural protein located in the podocyte slit diaphragm.There has been discussion of B cell involvement in nephrotic syndrome, especially minimal change disease due to the success of immunotherapy that target both B and T cells, increased markers for B cell activation during a relapse of minimal change disease, and alterations in B cell sub-classes during minimal change disease remission. This hypothesis is supported by recent findings of anti-nephrin antibodies isolated in minimal change disease. Edema When albumin is excreted in the urine, its serum (blood) concentration decreases. Consequently, the plasma oncotic pressure reduces relative to the interstitial tissue. The subsequent movement of fluid from the vascular compartment to the interstitial compartment manifests as the soft tissue swelling referred to as edema. This fluid collects most commonly in the feet and legs, in response to gravity, particularly in those with poorly functioning valves. In severe cases, fluid can shift into the peritoneal cavity (abdomen) and cause ascites. As a result of the excess fluid, individuals with minimal change disease often gain weight, as they are excreting less water in the urine, and experience fatigue. Diagnosis As minimal change disease is a subset of nephrotic syndrome, diagnosis involves looking for a combination of edema, high amounts of protein in urine, low albumin and high serum cholesterol. Initial workup can include a urinalysis, kidney function tests, serum albumin level and a lipid panel. Microscopic amounts of blood are present in the urine of 10-30% adults with MCD.As MCD is the most common type of nephrotic syndrome in children, renal biopsy is not usually done in children under the age of 10 unless there are concerning features that are unusual for the disease (high blood pressure, bloody urine, renal dysfunction) and if they fail to respond to corticosteroid therapy. These would suggest that it may not be minimal change disease. In adults, a renal biopsy is required as there is a much wider differential for nephrotic syndrome. As the name suggests, the renal biopsy of a patient with minimal change disease would show minimal or no evidence of disease in light microscopy, which is unique among the causes of nephrotic syndrome. Treatment Children The first line therapy to minimal change disease is corticosteroids T.Prednisolone 60mg/sq.m/day or 2mg/kg/day. For those are who are unable to tolerate corticosteroid treatment, cyclosporine is an alternative; other immunosuppressants have also been used such as calcineurin inhibitor, mycophenolate mofetil, rituximab though studies on their effectiveness is fairly limited. There is no common consensus on how long the corticosteroid therapy should be, with treatment length ranging from 4–12 weeks. Along with corticosteroid therapy, acute symptomatic management involves salt and fluid restriction to control the swelling.For children who do not respond to corticosteroids (usually after a trial of 8 weeks), cyclosporine can be tried. Adults Treatment guidelines for adults are fairly limited, and are largely based on studies done on children. The mainline therapy is also corticosteroid therapy T.Prednisolone 1mg/kg/day with other immunosuppressants as possible alternatives, though there is very little data on these alternatives efficacy. Other medications such as ACE inhibitors to reduce the amount of protein in the urine or statins to decrease high levels of cholesterol seen with nephrotic syndrome are generally unnecessary. ACE inhibitors may be considered in people with MCD who also have high blood pressure. Prognosis Children Minimal change disease usually responds well to initial treatment with the first-line therapy: corticosteroids, with 95% responding. Younger children, who are more likely to develop minimal change disease, usually respond faster than adults with 50% of children having complete remission with 8 days of corticosteroid therapy and most other patients responding by the 4th week. Few do not respond to corticosteroids and have to rely on an alternative therapy. However, despite positive response to corticosteroids, relapses are common, requiring repeat treatment with corticosteroids. About 25% never relapse, another 25% relapse infrequently (one relapse within 6 months of initial response or 1–3 relapses in 12 months), and 50% relapse frequently (>2 relapses within 6 months of initial response or >4 relapses in 12 months). The relapse rate is the reason behind a discussion on continuing prednisone treatment to even beyond 12 weeks to possibly decrease relapse rate; several studies trying this have failed to show significant improvement. A majority of relapses seem to be triggered by respiratory infections. Long term, children can relapse several years after having no symptoms; though after 2 years, the risk is significantly lower.In most children with minimal change disease, particularly among those who respond typically, there is minimal to no permanent damage observed in their kidneys. Complications primarily arise from the side effects of therapy. Prolonged use of corticosteroids can lead to immunosuppression (leading to infection), growth complications, weight gain. Adults While most adults diagnosed with minimal change disease respond to corticosteroids, 25% fail to respond after 3–4 months of corticosteroid therapy; it is possible that these patients were incorrectly diagnosed, and do not have minimal change disease. Adults with MCD tend to respond more slowly to corticosteroid treatment, taking up to 3 or 4 months, than children do. Data in adults is less complete than for children, but relapses are fairly frequent with 56–76% of patients relapsing and needing further treatment with immunosuppressants such as ciclosporin, tacrolimus, mycophenolate, and rituximab. There is little evidence to support the use of azathioprine for MCD.As in children, complications primarily arise from the side effects of therapy. Prolonged use of corticosteroids can lead to immunosuppression (leading to infection), growth complications, weight gain. Epidemiology Minimal change disease is most common in very young children but can occur in older children and adults.It is by far the most common cause of nephrotic syndrome in children, accounting for 70–90% of children >1 year of age. After puberty, it is caused by minimal change disease about half the time. Among young children, boys seem to be more likely to develop minimal change disease than girls (about 2:1). Minimal change disease is seen in about 16 in every 100,000 children, being more common in South Asians and Native Americans, but rarer in African Americans.In adults, it accounts for less than 15% of adults diagnosed with nephrotic syndrome. Etymology Minimal change disease has been called by many other names in the medical literature, including minimal change nephropathy, minimal change nephrosis, minimal change nephrotic syndrome, minimal change glomerulopathy, foot process disease (referring to the foot processes of the podocytes), nil disease (referring to the lack of pathologic findings on light microscopy), nil lesions, lipid nephrosis, and lipoid nephrosis. References == External links ==

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Please help me grasp the concept behind the medical term 'Hereditary spastic paraplegia.'

Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (spasticity) and contraction in the lower limbs. HSP is also known as hereditary spastic paraparesis, familial spastic paraplegia, French settlement disease, Strumpell disease, or Strumpell-Lorrain disease. The symptoms are a result of dysfunction of long axons in the spinal cord. The affected cells are the primary motor neurons; therefore, the disease is an upper motor neuron disease. HSP is not a form of cerebral palsy even though it physically may appear and behave much the same as spastic diplegia. The origin of HSP is different from cerebral palsy. Despite this, some of the same anti-spasticity medications used in spastic cerebral palsy are sometimes used to treat HSP symptoms. HSP is caused by defects in transport of proteins, structural proteins, cell-maintaining proteins, lipids, and other substances through the cell. Long nerve fibers (axons) are affected because long distances make nerve cells particularly sensitive to defects in these mentioned mechanisms.The disease was first described in 1880 by the German neurologist Adolph Strümpell. It was described more extensively in 1888 by Maurice Lorrain, a French physician. Due to their contribution in describing the disease, it is still called Strümpell-Lorrain disease in French-speaking countries. The term hereditary spastic paraplegia was coined by Anita Harding in 1983. Signs and symptoms Symptoms depend on the type of HSP inherited. The main feature of the disease is progressive spasticity in the lower limbs due to pyramidal tract dysfunction. This also results in brisk reflexes, extensor plantar reflexes, muscle weakness, and variable bladder disturbances. Furthermore, among the core symptoms of HSP are also included abnormal gait and difficulty in walking, decreased vibratory sense at the ankles, and paresthesia. Individuals with HSP can experience extreme fatigue associated with central nervous system and neuromuscular disorders, which can be disabling. Initial symptoms are typically difficulty with balance, stubbing the toe or stumbling. Symptoms of HSP may begin at any age, from infancy to older than 60 years. If symptoms begin during the teenage years or later, then spastic gait disturbance usually progresses over many years. Canes, walkers, and wheelchairs may eventually be required, although some people never require assistance devices. Disability has been described as progressing more rapidly in adult onset forms.More specifically, patients with the autosomal dominant pure form of HSP reveal normal facial and extraocular movement. Although jaw jerk may be brisk in older subjects, there is no speech disturbance or difficulty of swallowing. Upper extremity muscle tone and strength are normal. In the lower extremities, muscle tone is increased at the hamstrings, quadriceps and ankles. Weakness is most notable at the iliopsoas, tibialis anterior, and to a lesser extent, hamstring muscles. In the complex form of the disorder, additional symptoms are present. These include: peripheral neuropathy, amyotrophy, ataxia, intellectual disability, ichthyosis, epilepsy, optic neuropathy, dementia, deafness, or problems with speech, swallowing or breathing.Anita Harding classified the HSP in a pure and complicated form. Pure HSP presents with spasticity in the lower limbs, associated with neurogenic bladder disturbance as well as lack of vibration sensitivity (pallhypesthesia). On the other hand, HSP is classified as complex when lower limb spasticity is combined with any additional neurological symptom.This classification is subjective and patients with complex HSPs are sometimes diagnosed as having cerebellar ataxia with spasticity, intellectual disability (with spasticity), or leukodystrophy. Some of the genes listed below have been described in other diseases than HSP before. Therefore, some key genes overlap with other disease groups. Age of onset In the past, HSP has been classified as early onset beginning in early childhood or later onset in adulthood. The age of onsets has two points of maximum at age 2 and around age 40. New findings propose that an earlier onset leads to a longer disease duration without loss of ambulation or the need for the use of a wheelchair. This was also described earlier, that later onset forms evolve more rapidly. Cause HSP is a group of genetic disorders. It follows general inheritance rules and can be inherited in an autosomal dominant, autosomal recessive or X-linked recessive manner. The mode of inheritance involved has a direct impact on the chances of inheriting the disorder. Over 70 genotypes had been described, and over 50 genetic loci have been linked to this condition. Ten genes have been identified with autosomal dominant inheritance. One of these, SPG4, accounts for ~50% of all genetically solved cases, or approximately 25% of all HSP cases. Twelve genes are known to be inherited in an autosomal recessive fashion. Collectively this latter group account for ~1/3 cases.Most altered genes have known function, but for some the function havent been identified yet. All of them are listed in the gene list below, including their mode of inheritance. Some examples are spastin (SPG4) and paraplegin (SPG7) are both AAA ATPases. Genotypes The genes are designated SPG (Spastic gait gene). The gene locations are in the format: chromosome - arm (short or p: long or q) - band number. These designations are for the human genes only. The locations may (and probably will) vary in other organisms. Despite the number of genes known to be involved in this condition ~40% of cases have yet to have their cause identified. In the table below SPG? is used to indicate a gene that has been associated with HSP but has not yet received an official HSP gene designation. Pathophysiology The major feature of HSP is a length-dependent axonal degeneration. These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis. The spinocerebellar tract is involved to a lesser extent. Neuronal cell bodies of degenerating axons are preserved and there is no evidence of primary demyelination. Loss of anterior horn cells of the spinal cord are observed in some cases. Dorsal root ganglia, posterior roots and peripheral nerves are not directly affected.HSP affects several pathways in motor neurons. Many genes were identified and linked to HSP. It remains a challenge to accurately define the key players in each of the affected pathways, mainly because many genes have multiple functions and are involved in more than one pathway. Axon pathfinding Pathfinding is important for axon growth to the right destination (e.g. another nerve cell or a muscle). Significant for this mechanism is the L1CAM gene, a cell surface glycoprotein of the immunoglobulin superfamily. Mutations leading to a loss-of-function in L1CAM are also found in other X-linked syndromes. All of these disorders display corticospinal tract impairment (a hallmark feature of HSP). L1CAM participates in a set of interactions, binding other L1CAM molecules as well as extracellular cell adhesion molecules, integrins, and proteoglycans or intracellular proteins like ankyrins.The pathfinding defect occurs via the association of L1CAM with neuropilin-1. Neuropilin-1 interacts with Plexin-A proteins to form the Semaphorin-3A receptor complex. Semaphorin-a3A is then released in the ventral spinal cord to steer corticospinal neurons away from the midline spinal cord / medullary junction. If L1CAM does not work correctly due to a mutation, the cortiocospinal neurons are not directed to the correct position and the impairment occurs. Lipid metabolism Axons in the central and peripheral nervous system are coated with an insulation, the myelin layer, to increase the speed of action potential propagation. Abnormal myelination in the CNS is detected in some forms of hsp HSP. Several genes were linked to myelin malformation, namely PLP1, GFC2 and FA2H. The mutations alter myelin composition, thickness and integrity.Endoplasmic reticulum (ER) is the main organelle for lipid synthesis. Mutations in genes encoding proteins that have a role in shaping ER morphology and lipid metabolism were linked to HSP. Mutations in ATL1, BSCL2 and ERLIN2 alter ER structure, specifically the tubular network and the formation of three-way junctions in ER tubules. Many mutated genes are linked to abnormal lipid metabolism. The most prevalent effect is on arachidonic acid (CYP2U1) and cholesterol (CYP7B1) metabolism, phospholipase activity (DDHD1 and DDHD2), ganglioside formation (B4GALNT-1) and the balance between carbohydrate and fat metabolism (SLV33A1). Endosomal trafficking Neurons take in substances from their surrounding by endocytosis. Endocytic vesicles fuse to endosomes in order to release their content. There are three main compartments that have endosome trafficking: Golgi to/from endosomes; plasma membrane to/from early endosomes (via recycling endosomes) and late endosomes to lysosomes. Dysfunction of endosomal trafficking can have severe consequences in motor neurons with long axons, as reported in HSP. Mutations in AP4B1 and KIAA0415 are linked to disturbance in vesicle formation and membrane trafficking including selective uptake of proteins into vesicles. Both genes encode proteins that interact with several other proteins and disrupt the secretory and endocytic pathways. Mitochondrial function Mitochondrial dysfunctions have been connected with developmental and degenerative neurological disorders. Only a few HSP genes encode mitochondrial proteins. Two mitochondrial resident proteins are mutated in HSP: paraplegin and chaperonin 60. Paraplegin is a m-AAA metalloprotease of the inner mitochondrial membrane. It functions in ribosomal assembly and protein quality control. The impaired chaperonin 60 activity leads to impaired mitochondrial quality control. Two genes DDHD1 and CYP2U1 have shown alteration of mitochondrial architecture in patient fibroblasts. These genes encode enzymes involved in fatty-acid metabolism. Diagnosis Initial diagnosis of HSPs relies upon family history, the presence or absence of additional signs and the exclusion of other nongenetic causes of spasticity, the latter being particular important in sporadic cases.Cerebral and spinal MRI is an important procedure performed in order to rule out other frequent neurological conditions, such as multiple sclerosis, but also to detect associated abnormalities such as cerebellar or corpus callosum atrophy as well as white matter abnormalities. Differential diagnosis of HSP should also exclude spastic diplegia which presents with nearly identical day-to-day effects and even is treatable with similar medicines such as baclofen and orthopedic surgery; at times, these two conditions may look and feel so similar that the only perceived difference may be HSPs hereditary nature versus the explicitly non-hereditary nature of spastic diplegia (however, unlike spastic diplegia and other forms of spastic cerebral palsy, HSP cannot be reliably treated with selective dorsal rhizotomy).Ultimate confirmation of HSP diagnosis can only be provided by carrying out genetic tests targeted towards known genetic mutations. Classification Hereditary spastic paraplegias can be classified based on the symptoms; mode of inheritance; the patients age at onset; the affected genes; and biochemical pathways involved. Treatment No specific treatment is known that would prevent, slow, or reverse HSP. Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being. Therapeutics offered to HSP patients include: Baclofen – a voluntary muscle relaxant to relax muscles and reduce tone. This can be administered orally or intrathecally. (Studies in HSP ) Tizanidine – to treat nocturnal or intermittent spasms (studies available ) Diazepam and clonazepam – to decrease intensity of spasms Oxybutynin chloride – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems Tolterodine tartrate – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems Cro System – to reduce muscle overactivity (existing studies for spasticity ) Botulinum toxin – to reduce muscle overactivity (existing studies for HSP patients) Antidepressants (such as selective serotonin re-uptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors) – for patients experiencing clinical depression Physical therapy – to restore and maintain the ability to move; to reduce muscle tone; to maintain or improve range of motion and mobility; to increase strength and coordination; to prevent complications, such as frozen joints, contractures, or bedsores. Prognosis Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals. Some cases are seriously disabling while others are less disabling and are compatible with a productive and full life. The majority of individuals with HSP have a normal life expectancy. Epidemiology Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people. A Norwegian study of more than 2.5 million people published in March 2009 has found an HSP prevalence rate of 7.4/100,000 of population – a higher rate, but in the same range as previous studies. No differences in rate relating to gender were found, and average age at onset was 24 years. In the United States, Hereditary Spastic Paraplegia is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health which means that the disorder affects less than 200,000 people in the US population. References Further reading GeneReviews/NCBI/NIH/UW entry on Spastic Paraplegia 3A GeneReviews/NCBI/NIH/UW entry on Hereditary Spastic Paraplegia Overview Warner, Tom (January–February 2007). "Hereditary Spastic Paraplegia" (PDF). Advances in Clinical Neuroscience and Rehabilitation. 6 (6): 16–17. External links Spastic Paraplegia Foundation

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Could you provide a brief overview of 'Dyskeratosis congenita' in a medical context?

Dyskeratosis congenita (DKC), also known as Zinsser-Engman-Cole syndrome, is a rare progressive congenital disorder with a highly variable phenotype. The entity was classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, but these components do not always occur. DKC is characterized by short telomeres. Some of the manifestations resemble premature ageing (similar to progeria). The disease initially mainly affects the skin, but a major consequence is progressive bone marrow failure which occurs in over 80%, causing early mortality. Presentation DKC can be characterized by cutaneous pigmentation, premature graying, dystrophy of the nails, leukoplakia of the oral mucosa, continuous lacrimation due to atresia of the lacrimal ducts, often thrombocytopenia, anemia, testicular atrophy in the male carriers, and predisposition to cancer. Many of these symptoms are characteristic of geriatrics, and those carrying the more serious forms of the disease often have significantly shortened lifespans. Also, liver abnormalities are associated with this syndrome, Nodular Regenerative Hypoplasia of the liver, although rare, it is one of many manifestations of liver disorders short telomeres can cause. Predisposition to cancer Susceptibility to cancer seems counterintuitive because in many known cancers reactivation of telomerase is actually a required step for malignancy to evolve (see telomere). In a disease where telomerase is affected, it does not seem to follow that cancer would be a complication to result. The authors note the paradoxical nature of cancer predisposition in individuals who seem to lack one of the required components for cancer to form. It is thought that without functional telomerase, chromosomes will likely be attached together at their ends through the non-homologous end joining pathway. If this proves to be a common enough occurrence, malignancy even without telomerase present is possible. Myelodysplastic Syndrome is associated with this syndrome usually presenting as a Hypoplastic Bone Marrow that can resemble Aplastic Anemia, but can be differentiated with >10% dysplasia in affected cell lines, sometimes not possible though because of the Hypoplastic marrow reducing blood cells to be observed, genetic clones are usually not present more often than not with Hypoplastic Myelodysplastic Disorder associated with Dyskeratosis Congenita. Genetics Of the components of the telomerase RNA component (TERC), one of key importance is the box H/ACA domain. This H/ACA domain is responsible for maturation and stability of TERC and therefore of telomerase as a whole. The mammalian H/ACA ribonucleoprotein contains four protein subunits: dyskerin, Gar1, Nop10, and Nhp2. Mutations in Nop10, Nhp2 and dyskerin1 have all been shown to lead to DKC-like symptoms. X-linked The best characterized form of dyskeratosis congenita is a result of one or more mutations in the long arm of the X chromosome in the gene DKC1. This results in the X-linked recessive form of the disease wherein the major protein affected is dyskerin. Of the five mutations described by Heiss and colleagues in Nature Genetics, four were single nucleotide polymorphisms all resulting in the change of highly conserved amino acids. One case was an in-frame deletion resulting in the loss of a leucine residue, also conserved in mammals. In three of the cases, the specific amino acids affected (phenylalanine, proline, glycine) are found in the same locus in humans as they are in yeast (S. Cerevisiae) and the brown rat (R. Norvegicus). This establishes the sequence conservation and importance of dyskerin within the eukaryotes. The relevant nature of dyskerin throughout most species is to catalyze the post-transcriptional pseudouridylation of specific uridines found in non-coding RNAs, such as ribosomal RNA (rRNA). Cbf5, the yeast analog of human dyskerin, is indeed known to be associated with the processing and maturation of rRNA. In humans, this role can be attributed to dyskerin. Thus, the X-linked form of this disease may result in specific issues related to dysfunctional RNA and perhaps a graver phenotype. Within the vertebrates, as opposed to single celled eukaryotes, dyskerin is a key component of the telomerase RNA component (TERC) in the form of the H/ACA motif. This X-linked variety, like the Nop10 and Nhp2 mutations, demonstrates shortened telomeres as a result of lower TERC concentrations. Autosomal dominant 3 genes: TERC, TERT, TINF2 The evidence supporting the importance of the H/ACA domain in human telomerase is abundant. At least one study has shown that these mutations affect telomerase activity by negatively affecting pre-RNP assembly and maturation of human telomerase RNA. Nonetheless, mutations that directly affect the telomerase RNA components would presumably exist and should also cause premature aging or DKC-like symptoms. Indeed, three families with mutations in the human TERC gene have been studied with intriguing results. In two of these families, two family-specific single nucleotide polymorphisms were present while in the other there persisted a large-scale deletion (821 base pairs of DNA) on chromosome 3 which includes 74 bases coding for a section of the H/ACA domain. These three different mutations result in a mild form of dyskeratosis congenita which uniquely follows an autosomal dominant pattern of inheritance. Premature graying, early dental loss, predisposition to skin cancer, as well as shortening of telomere length continue to be characteristic of this disease. Autosomal recessive 6 genes: The true phenotype of DKC individuals may depend upon which protein has incurred a mutation. One documented autosomal recessive mutation in a family that carries DKC has been found in NOP10. Specifically, the mutation is a change of base from cytosine to thymine in a highly conserved region of the NOP10 sequence. This mutation, on chromosome 15, results in an amino acid change from arginine to tryptophan. Homozygous recessive individuals show the symptoms of dyskeratosis congenita in full. As compared to age-matched normal individuals, those suffering from DKC have telomeres of a much shorter length. Furthermore, heterozygotes, those who have one normal allele and one coding for the disease, also show relatively shortened telomeres. The cause of this was determined to be a reduction in TERC levels in those with the Nop10 mutation. With TERC levels down, telomere maintenance, especially in development, would be presumed to suffer accordingly. This would lead to the telomere shortening described.NHP2 mutations are similar in characterization to NOP10. These mutations are also autosomal recessive with three specific single-nucleotide polymorphisms being recognized which result in dyskeratosis congenita. Also, like NOP10, individuals with these NHP2 mutations have a reduction in the amount of telomerase RNA component (TERC) present in the cell. Again, it can be presumed that a reduction in TERC results in aberrant telomere maintenance and thus shortened telomeres. Those homozygous recessive for mutations in NHP2 do show shorter telomeres when compared with age-matched normal individuals. Pathophysiology Dyskeratosis congenita is a disorder of poor telomere maintenance mainly due to a number of gene mutations that give rise to abnormal ribosome function, termed ribosomopathy. Specifically, the disease is related to one or more mutations which directly or indirectly affect the vertebrate telomerase RNA component (TERC). Telomerase is a reverse transcriptase which maintains a specific repeat sequence of DNA, the telomere, during development. Telomeres are placed by telomerase on both ends of linear chromosomes as a way to protect linear DNA from general forms of chemical damage and to correct for the chromosomal end-shortening that occurs during normal DNA replication. This end-shortening is the result of the eukaryotic DNA polymerases having no mechanism for synthesizing the final nucleotides present on the end of the "lagging strand" of double stranded DNA. DNA polymerase can only synthesize new DNA from an old DNA strand in the 5→3 direction. Given that DNA has two strands that are complementary, one strand must be 5→3 while the other is 3→5. This inability to synthesize in the 3→5 directionality is compensated with the use of Okazaki fragments, short pieces of DNA that are synthesized 5→3 from the 3→5 as the replication fork moves. As DNA polymerase requires RNA primers for DNA binding in order to commence replication, each Okazaki fragment is thus preceded by an RNA primer on the strand being synthesized. When the end of the chromosome is reached, the final RNA primer is placed upon this nucleotide region, and it is inevitably removed. Unfortunately once the primer is removed, DNA polymerase is unable to synthesize the remaining bases.Sufferers of DKC have been shown to have a reduction in TERC levels invariably affecting the normal function of telomerase which maintains these telomeres. With TERC levels down, telomere maintenance during development suffers accordingly. In humans, telomerase is inactive in most cell types after early development (except in extreme cases such as cancer). Thus, if telomerase is not able to efficiently affect the DNA in the beginning of life, chromosomal instability becomes a grave possibility in individuals much earlier than would be expected. A study shows that proliferative defects in DC skin keratinocytes are corrected by expression of the telomerase reverse transcriptase, TERT, or by activation of endogenous telomerase through expression of papillomavirus E6/E7 of the telomerase RNA component, TERC. Diagnosis Since the disease has a wide variety of symptoms due to involvement of multiple systems of the body, diagnostic testing depends on the clinical findings in each individual patient. Commonly used tests include a complete blood count (CBC), bone marrow examination, leukocyte telomere length test (e.g. Flow FISH), pulmonary function test, and genetic testing. Management The mainstay of treatment in dyskeratosis congenita is hematopoietic stem cell transplantation, best outcome with sibling donor. Short term therapy in initial stages is with anabolic steroids [oxymetholone, danazol] or with erythropoietin-like hormones or with granulocyte-colony stimulating factor [filgrastim) all these therapies are directed to cope with effects of bone marrow failure which manifests as low red and white blood cell counts. These medications help to increase the blood components and make up for the deficiencies caused due to bone marrow failure. Dyskeratosis Congenita in regards to stem cell transplantation have to be very carefully treated with low intensity radiation/chemo to avoid potentially catastrophic effects of Host versus graft disease and toxicity to other organs affected by short telomeres which makes them very sensitive to any radiation especially the lungs, and liver. Prognosis DC is associated with shorter life expectancy, but many live to at least age 60. Main cause of mortality in these patients are related to bone marrow failure. Nearly 80% of the patients of dyskeratosis congenita develop bone marrow failure. Research Recent research has used induced pluripotent stem cells to study disease mechanisms in humans, and discovered that the reprogramming of somatic cells restores telomere elongation in dyskeratosis congenita (DKC) cells despite the genetic lesions that affect telomerase. The reprogrammed DKC cells were able to overcome a critical limitation in TERC levels and restored function (telomere maintenance and self-renewal). Therapeutically, methods aimed at increasing TERC expression could prove beneficial in DKC. See also Cutaneous conditions List of cutaneous conditions References External links GeneReviews/NCBI/NIH/UW entry on Dyskeratosis Congenita Dyskeratosis Congenita research study of Inherited Bone Marrow Failure Syndromes (IBMFS)

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I've encountered the term 'Sodium calcium edetate' while reading about medical topics. What does it refer to exactly?

Sodium calcium edetate (sodium calcium EDTA), also known as edetate calcium disodium among other names, is a medication primarily used to treat lead poisoning, including both short-term and long-term lead poisoning. Sodium calcium edetate came into medical use in the United States in 1953. Chelation agent Sodium calcium edetate is in the chelating agent family of medication. It is a salt of edetate with two sodium and one calcium atoms. It works by binding to a number of heavy metals, which renders them almost inert and allows them to leave the body in the urine.Edetate disodium is a different formulation which does not have the same effects. Medical use Sodium calcium edetates primary use is to treat lead poisoning, for which it is an alternative to succimer. It is given by slow injection into a vein or into a muscle.For lead encephalopathy sodium calcium edetate is typically used together with dimercaprol. It may also be used to treat plutonium poisoning. It does not appear to be useful for poisoning by tetra-ethyl lead. Side effects Common side effects include pain at the site of injection. Other side effects may include kidney problems, diarrhea, fever, muscle pains, and low blood pressure. Benefits when needed in pregnancy are likely greater than the risks. History Sodium calcium edetate came into medical use in the United States in 1953. It is on the World Health Organizations List of Essential Medicines. References External links "Sodium calcium edetate". U.S. National Library of Medicine. Drug Information Portal. U.S. National Institutes of Health.

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Could you please explain the term 'Morvans syndrome' in simple language?

Morvans syndrome is a rare, life-threatening autoimmune disease named after the nineteenth century French physician Augustin Marie Morvan. "La chorée fibrillaire" was first coined by Morvan in 1890 when describing patients with multiple, irregular contractions of the long muscles, cramping, weakness, pruritus, hyperhidrosis, insomnia, and delirium. It normally presents with a slow insidious onset over months to years. Approximately 90% of cases spontaneously go into remission, while the other 10% of cases lead to death.In 1890, Morvan described a patient with myokymia (muscle twitching) associated with muscle pain, excessive sweating, and disordered sleep. This rare disorder is characterized by severe insomnia, amounting to no less than complete lack of sleep (agrypnia) for weeks or months in a row, and associated with autonomic alterations consisting of profuse perspiration with characteristic skin miliaria (also known as sweat rash), tachycardia, increased body temperature, and hypertension. Patients display a remarkable hallucinatory behavior, and peculiar motor disturbances, which Morvan reported under the term “fibrillary chorea” but which are best described in modern terms as neuromyotonic discharges.The association of the disease with thymoma, tumour, autoimmune diseases, and autoantibodies suggests an autoimmune or paraneoplastic aetiology. Besides an immune-mediated etiology, it is also believed to occur in gold, mercury, or manganese poisoning. Signs and symptoms In one of the few reported cases, the subject presented with muscle weakness and fatigue, muscle twitching, excessive sweating and salivation, small joint pain, itching and weight loss. The subject also developed confusional episodes with spatial and temporal disorientation, visual and auditory hallucinations, complex behavior during sleep and progressive nocturnal insomnia associated with diurnal drowsiness. There was also severe constipation, urinary incontinence, and excessive lacrimation. When left alone, the subject would slowly lapse into a stuporous state with dreamlike episodes characterized by complex and quasi-purposeful gestures and movements (enacted dreams). Marked hyperhidrosis and excessive salivation were evident. Neurological examination disclosed diffuse muscle twitching and spontaneous and reflex myoclonus, slight muscle atrophy in the limbs, absence of tendon reflexes in the lower limbs and diffuse erythema especially on the trunk with scratching lesions of the skin. Compulsive behaviours, stereotypies and reduplicative paramnesias can be part of the CNS spectrum. Insomnia In all of the reported cases, the need for sleep was severely reduced and in some cases not necessary. The duration of sleep in one case decreased to about 2–4 hours per 24-hour period. Clinical features pertaining to insomnia include daytime drowsiness associated with a loss of ability to sleep, intermingled with confusional oneiric status, and the emergence of atypical REM sleep from wakefulness. The polysomnogram (PSG) picture of this disease is characterized by an inability to generate physiological sleep (key features are the suppression of the hallmarks of stage 2 non-REM sleep: spindles and K complexes) and by the emergence of REM sleep without atonia. The involvement of the thalamus and connected limbic structures in the pathology indicate the prominent role that the limbic thalamus plays in the pathophysiology of sleep. In a case documented in 1974, PSG findings documented the sustained absence of all sleep rhythms for up to a period of 4 months.Electroencephalography (EEG) in one case was dominated by "wakefulness" and “subwakefulness” states alternating or intermingled with short (< 1 min) atypical REM sleep phases, characterized by a loss of muscle atonia. The “subwakefulness” state was characterized by 4–6 Hz theta activity intermingled with fast activity and desynchronized lower voltage theta activity, behaviourally associated with sleep-like somatic and autonomic behavior. The subject was said to have “agrypnia excitata”, which consists of severe total insomnia of long duration associated with decreased vigilance, mental confusion, hallucinations, motor agitation, and complex motor behavior mimicking dreams, and autonomic activation. CNS and autonomic symptoms were caused by impaired corticolimbic control of the subcortical structures regulating the sleep-wake and autonomic functions. Neuromyotonia Neuromyotonia refers to muscle twitching and cramping at rest that is exacerbated with exercise. It is caused by sustained or repetitive spontaneous muscle activity of peripheral nerve origin. Myokymia, or spontaneous rippling and twitching movements of muscles, is a visible component of neuromyotonia. Electromyography (EMG) discloses spontaneous, repetitive motor unit or single fiber discharges firing in irregular rhythmic bursts at high intraburst frequencies. Some of the muscles exhibiting twitching include the bilateral gastrocnemii, quadriceps femoris, biceps brachii, and right masseter. In vivo electrophysiological studies suggest at least some dysfunction of the muscle cell membrane. In the examined muscles, no abnormal insertional activity or fibrillation potentials were noted. Nerve conduction studies were normal. Other symptoms Breathing difficulties can occur, resulting from neuromyotonic activity of the laryngeal muscles. Laryngeal spasm possibly resulting from neuromyotonia has been described previously, and this highlights that, in patients with unexplained laryngospasm, neuromytonia should be added to the list of differential diagnoses.Studies have shown subtly decreased metabolism on positron emission tomography (PET) and single photon emission computed tomography (SPECT) in the left inferior frontal and left temporal lobes. and or basal ganglia hypermetabolism. Ancillary laboratory tests including MRI and brain biopsy have confirmed temporal lobe involvement. Cranial MRI shows increased signal in the hippocampus.Cerebral spinal fluid (CSF) shows normal protein, glucose, white blood cell, and immunoglobulin G (IgG) levels, but there are weak oligoclonal bands, which are absent in the blood serum. Marked changes in circadian serum levels of neurohormones and increased levels of peripheral neurotransmitters were also observed. The absence of morphological alterations of the brain pathology, the suggestion of diffusion of IgG into the thalamus and striatum, more marked than in the cortex (consistent with effects on the thalamolimbic system) the oligoclonal bands in the CSF and the amelioration after PE all strongly support an antibody-mediated basis for the condition. Raised CSF IgG concentrations and oligoclonal bands have been reported in patients with psychosis. Anti-acetylcholine receptors (anti-AChR) antibodies have also been detected in patients with thymoma, but without clinical manifestations of myasthenia gravis. There have also been reports of non-paraneoplastic limbic encephalitis associated with raised serum VGKC suggesting that these antibodies may give rise to a spectrum of neurological disease presenting with symptoms arising peripherally, centrally, or both. Yet, in two cases, oligoclonal bands were absent in the CSF and serum, and CSF immunoglobulin profiles were unremarkable. Comorbid conditions In one case, a patient was diagnosed with both Morvans syndrome and pulmonary hyalinizing granulomas (PHG). PHG are rare fibrosing lesions of the lung, which have central whorled deposits of lamellar collagen. How these two diseases relate to one another is still unclear.Thymoma, prostate adenoma, and in situ carcinoma of the sigmoid colon have also been found in patients with Morvans Syndrome. Mechanism Antibodies against voltage-gated potassium channels (VGKC), which are detectable in about 40% of patients with acquired neuromytonia, have been implicated in Morvans pathophysiology. Raised serum levels of antibodies to VGKCs have been reported in three patients with Morvans Syndrome. Binding of serum from a patient with Morvans Syndrome to the hippocampus in a similar pattern of antibodies to known VGKC suggest that these antibodies can also cause CNS dysfunction. Additional antibodies against neuromuscular junction channels and receptors have also been described. Experimental evidence exists that these anti-VGKC antibodies cause nerve hyperexcitability by suppression of voltage gated K+ outward currents, whereas other, yet undefined humoral factors have been implicated in anti-VGKC antibody negative neuromyotonia. It is believed that antibodies to the Shaker-type K+ channels (the Kv1 family) are the type of potassium channel most strongly associated with acquired neuromyotonia and Morvans Syndrome.Whether VGKC antibodies play a pathogenic role in the encephalopathy as they do in the peripheral nervous system is as yet unclear. It has been suggested that the VGKC antibodies may cross the blood–brain barrier and act centrally, binding predominantly to thalamic and striatal neurons causing encephalopathic and autonomic features. Diagnosis Differential diagnosis The symptoms of Morvans Syndrome have been noted to bear a striking similarity to limbic encephalitis (LE). These include the CNS symptoms consisting of insomnia, hallucinations, and disorientation, as well as dementia and psychosis. Both entities can be paraneoplastic and associated with thymoma. Recently, VGKC antibodies were found in patients with LE, strengthening the hypothesis that LE and Morvans Syndrome may be closely connected. Varying symptoms may be used to determine which of the two diseases the subject has. Amnesia, seizures, and mesial temporal lobe structural abnormalities are features of LE, whereas myokymia, hyperhydrosis, and insomnia favor Morvans Syndrome. Treatment In most of the reported cases, the treatment options were very similar. Plasmapheresis alone or in combination with steroids, sometimes also with thymectomy and azathioprine, have been the most frequently used therapeutic approach in treating Morvans Syndrome. However, this does not always work, as failed response to steroids and to subsequently added plasmapheresis have been reported. Intravenous immunoglobulin was effective in one case.In one case, the dramatic response to high-dose oral prednisolone together with pulse methylprednisolone with almost complete disappearance of the symptoms within a short period should induce consideration of corticosteroids.In another case, the subject was treated with haloperidol (6 mg/day) with some improvement in the psychomotor agitation and hallucinations, but even high doses of carbamazepine given to the subject failed to improve the spontaneous muscle activity. Plasma Exchange (PE) was initiated, and after the third such session, the itching, sweating, mental disturbances, and complex nocturnal behavior improved and these symptoms completely disappeared after the sixth session, with improvement in insomnia and reduced muscle twitching. However, one month after the sixth PE session, there was a progressive worsening of insomnia and diurnal drowsiness, which promptly disappeared after another two PE sessions.In one case, high dose steroid treatment resulted in a transient improvement, but aggressive immuno-suppressive therapy with cyclophosphamide was necessary to control the disease and result in a dramatic clinical improvement.In another case, the subject was treated with prednisolone (1 mg/kg body weight) with carbamazepine, propranolol, and amitriptyline. After two weeks, improvement with decreased stiffness and spontaneous muscle activity and improved sleep was observed. After another 7–10 days, the abnormal sleep behavior disappeared completely.In another case, symptomatic improvement with plasmapheresis, thymectomy, and chronic immunosuppression provide further support for an autoimmune or paraneoplastic basis.Although thymectomy is believed to be a key element in the proposed treatment, there is a reported case of Morvans Syndrome presenting itself post-thymectomy. Epidemiology There are only about 14 reported cases of Morvans syndrome in the English literature. With only a limited number of reported cases, the complete spectrum of the central nervous system (CNS) symptomatology has not been well established. The natural history of Morvans is highly variable. Two cases have been reported to remit spontaneously. Others have required a combination of plasmapheresis and long term immunosuppression, although in one of these cases the patient died shortly after receiving plasma exchange (PE). Other fatalities without remission have been described by, amongst others, Morvan himself. References == External links ==

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Could you provide a brief overview of 'Etoposide' in a medical context?

Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is also used for hemophagocytic lymphohistiocytosis. It is used by mouth or injection into a vein.Side effects are very common. They can include low blood cell counts, vomiting, loss of appetite, diarrhea, hair loss, and fever. Other severe side effects include allergic reactions and low blood pressure. Use during pregnancy will likely harm the fetus. Etoposide is in the topoisomerase inhibitor family of medication. It is believed to work by damaging DNA.Etoposide was approved for medical use in the United States in 1983. It is on the World Health Organizations List of Essential Medicines. Medical uses Etoposide is used as a form of chemotherapy for cancers such as Kaposi’s sarcoma, Ewings sarcoma, lung cancer, testicular cancer, lymphoma, nonlymphocytic leukemia, and glioblastoma multiforme. It is often given in combination with other drugs (such as bleomycin in treating testicular cancer). It is also sometimes used in a conditioning regimen prior to a bone marrow or blood stem cell transplant. Administration It is given intravenously (IV) or orally in capsule or tablet form. If the drug is given IV, it must be done slowly over a 30- to 60-minute period because it can lower blood pressure as it is being administered. Blood pressure is checked often during infusing, with the speed of administration adjusted accordingly. Side effects Common are: infusion site reactions low blood pressure hair loss pain and or burning at the IV site constipation or diarrhea metallic food taste bone marrow suppression, leading to: decreased white blood cell counts (leading to increased susceptibility to infections) low red blood cell counts (anemia) low platelet counts (leading to easy bruising and bleeding)Less common are: nausea and vomiting allergic-type reactions rash fever, often occurring shortly after IV administration and not due to infection mouth sores acute myeloid leukemia (which can be treated with etoposide itself)When given with warfarin, it may cause bleeding. Pharmacology Mechanism of action Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme, which is an enzyme that aids in relaxing negative or positive supercoils in DNA. Topoisomerase II normally will form a double-stranded break in one DNA double-strand, allow another to pass through, and re-ligate the broken strands. Etoposides binding prevents topoisomerase II from re-ligating the broken DNA strands, which causes the DNA breaks made by topoisomerase II to stay broken, and also prevents the topoisomerase II molecule from leaving the site and relieving tension elsewhere. This results in a double-strand break in the DNA that can have various deleterious effects on the cell, and depletion of topoisomerase II available to relieve further tension. Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. Therefore, this causes errors in DNA synthesis and promotes apoptosis of the cancer cell. Chemistry Etoposide is a semisynthetic derivative of podophyllotoxin from the rhizome of the wild mandrake (Podophyllum peltatum). More specifically, it is a glycoside of podophyllotoxin with a D-glucose derivative. It is chemically similar to the anti-cancer drug teniposide, being distinguished only by a methyl group where teniposide has a thienyl. Both these compounds have been developed with the aim of creating less toxic derivatives of podophyllotoxin.The substance is a white to yellow-brown, crystalline powder. It is soluble in organic solvents.It is used in form of its salt etoposide phosphate. History Etoposide was first synthesized in 1966 and U.S. Food and Drug Administration approval was granted in 1983.The nickname VP-16 likely comes from a compounding of the last name of one of the chemists who performed early work on the drug (von Wartburg) and podophyllotoxin. Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologist Hartmann F. Stähelin. References External links "Etoposide". Drug Information Portal. U.S. National Library of Medicine. "Etoposide phosphate". Drug Information Portal. U.S. National Library of Medicine. "Etoposide". National Cancer Institute. 12 August 2008. "Etoposide". NCI Drug Dictionary. National Cancer Institute.

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Could you please explain the term 'Cushing ulcer' in simple language?

A Cushing ulcer, named after Harvey Cushing, is a gastric ulcer associated with elevated intracranial pressure. It is also called von Rokitansky–Cushing syndrome. Apart from the stomach, ulcers may also develop in the proximal duodenum and distal esophagus. Causes The mechanism of development of Cushing ulcers is thought to be due to direct stimulation of vagal nuclei as a result of increased intracranial pressure. Brain tumors, traumatic head injury, and other intracranial processes including infections, can cause increased intracranial pressure and lead to overstimulation of the vagus nerve. Efferent fibers of the vagus nerve then release acetylcholine onto gastric parietal cell M3 receptors, causing insertion of hydrogen potassium ATPase vesicles into the apical plasma membrane. The end result is increased secretion of gastric acid with eventual ulceration of the gastric mucosa. Diagnosis As Cushing ulcers have a higher incidence of developing after shock, sepsis or trauma, diagnosis should include recent medical history evaluation. Both endoscopy and angiography can be used to locate the lesion or ulcer, though endoscopy is more commonly used as a first-line diagnosis procedure. Treatment Most episodes of Cushing ulceration resolve on medical intervention, consisting primarily of rinsing the area with saline and the administration of antacids.Patients should also be put on proton pump inhibitors during the course of treatment until their intracranial pressure lowers to a normal level. As it is caused due to vagal stimulation, vagotomy is considered as last treatment resort.. See also Curling ulcer References == External links ==

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I've come across the term 'Hypochondrogenesis' in a medical context, but I'm not sure what it means. Can you clarify?

Hypochondrogenesis is a severe genetic disorder causing malformations of bone growth. The condition is characterized by a short body and limbs and abnormal bone formation in the spine and pelvis. Hypochondrogenesis is a subtype of collagenopathy, types II and XI, and is similar to another skeletal disorder, achondrogenesis type 2, although the spinal changes seen in hypochondrogenesis tend to be somewhat milder. Signs and symptoms Symptoms of hypochondrogenesis include: edema, limb undergrowth, spondyloepiphyseal dysplasia, short ribs, respiratory failure, short chin, upper limb undergrowth, thoracic hypoplasia, hypertelorism, hydrops fetalis, pulmonary hypoplasia, and a cleft palate. Pathophysiology Hypochondrogenesis is one of the most severe conditions in a spectrum of disorders caused by mutations in the COL2A1 gene. The protein made by this gene forms type II collagen, a molecule found mostly in cartilage and in the clear gel that fills the eyeball (the vitreous). Type II collagen is essential for the normal development of bones and other connective tissues (tissues that form the bodys supportive framework). Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones from developing properly. This condition is caused by new mutations in the COL2A1 gene. Hypochondrogenesis is considered an autosomal dominant disorder because the affected gene is located on an autosome, and only one copy of the altered gene is necessary to cause the condition. The disorder is not passed on to the next generation, however, because affected individuals do not live long enough to have children. Diagnosis Affected infants have short arms and legs, a small chest with short ribs, and underdeveloped lungs. The spinal bones (vertebrae) in the neck and part of the pelvis (the sacrum) do not harden, or ossify, properly. The face appears flat and oval-shaped, with widely spaced eyes, a small chin, and, in some cases, an opening in the roof of the mouth called a cleft palate. The abdomen is enlarged, and excess fluid may build up in the body before birth (a condition called hydrops fetalis). As a result of these serious health problems, infants are usually premature and stillborn or die shortly after birth from respiratory failure. Some infants have lived for a time, however, with intensive medical support. Babies who live past the newborn period are usually reclassified as having spondyloepiphyseal dysplasia congenita, a related disorder on the spectrum of abnormal bone growth. Treatment There is no cure or treatment for hypochondrogenesis. References External links This article incorporates public domain text from The U.S. National Library of Medicine

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I'm trying to understand 'Periapical cyst' within a medical context. Could you shed some light on it?

Commonly known as a dental cyst, the periapical cyst is the most common odontogenic cyst. It may develop rapidly from a periapical granuloma, as a consequence of untreated chronic periapical periodontitis.Periapical is defined as "the tissues surrounding the apex of the root of a tooth" and a cyst is "a pathological cavity lined by epithelium, having fluid or gaseous content that is not created by the accumulation of pus."Most frequently located in the maxillary anterior region, the cyst is caused by pulpal necrosis secondary to dental caries or trauma. Its lining is derived from the epithelial cell rests of Malassez which proliferate to form the cyst. Such cysts are very common. Although initially asymptomatic, they are clinically significant because secondary infection can cause pain and damage. In radiographs, the cyst appears as a radiolucency (dark area) around the apex of a tooths root. Signs and symptoms Periapical cysts begin as asymptomatic and progress slowly. Subsequent infection of the cyst causes swelling and pain. Initially, the cyst swells to a round hard protrusion, but later on the body resorbs some of the cyst wall, leaving a softer accumulation of fluid underneath the mucous membrane.Secondary symptoms of periapical cysts include inflammation and infection of the pulp causing dental caries. This infection is what causes necrosis of the pulp.Larger cysts may cause bone expansion or displace roots. Discoloration of the affected tooth may also occur. Patient will present negative results to electric and ice test of the affected tooth but will be sensitive to percussion. Surrounding gingival tissue may experience lymphadenopathy. The alveolar plate may exhibit crepitus when palpated. Complications Expansion of the cyst causes erosion of the floor of the maxillary sinus. As soon as it enters the maxillary antrum, the expansion rate increases due to available space for expansion. Performing a percussion test by tapping the affected teeth will cause shooting pain. This is often clinically diagnostic of pulpal infection. Causes Dental cysts are usually caused due to root infection involving tooth decay. Untreated dental caries then allow bacteria to reach the level of the pulp, causing infection. The bacteria gains access to the periapical region of the tooth through deeper infection of the pulp, traveling through the roots. The resulting pulpal necrosis causes proliferation of epithelial rests of Malassez which release toxins at the apex of the tooth. The bodys inflammatory response will attack the source of the toxins, leading to periapical inflammation. The many cells and proteins that rush to an area of infection create osmotic tension in the periapex which is the source of internal pressure increase at the cyst site. These lesions can grow large because they apply pressure over the bone, causing resorption. The toxins released by the breakdown of granulation tissue are one of the common causes of bone resorption. There are two schools of thought regarding cyst expansion. Complementary response to inflammation Chemical reaction with Interleukin and Prostaglandin Mechanisms Periapical cysts develop due to an inflammatory stimulus in 3 stages: Initial stage: Epithelial cells from the rests of Malassez at the apex of the roots of a non-vital tooth (one where the nerve and blood supply in the tooth have degenerated and no longer exist) become stimulated due to the bodys inflammatory response to bacterial endotoxins infecting the pulp or as a direct response to necrotic pulp tissue, therefore re-entering the growth phase. Bacterial byproducts then are able to seep into the periapical region through the infected pulp. Cyst development stage: Epithelial cells form strands and are attracted to the area which contains exposed connective tissue and foreign substances. Several strands from each rest converge and surround the abscess or foreign body. Cyst growth stage: Fluid flows into the cavity where the forming cyst is growing due to the increased osmolality of the cavity in relation to surrounding serum in capillaries. Pressure and size increase.The definitive mechanism by which cysts grow is under debate; several theories exist. Biomechanical theory Pressure and concentration differences between the cystic cavity and the growth surroundings influence fluid movement into the cyst, causing size increase. Biochemical theories a. Collagenase (breakdown of collagen) in the jaw bone leads to bone degeneration, providing room for cysts to develop. Substances released by the bodys immune system as a result of the connective tissue breakdown, such as cytokines and growth factors, contribute to the mobilization and proliferation of epithelial cells in the area. b. Bone resorption caused by metabolism of acidic substances produced by cysts contributes to cyst growth. Such substances include Prostaglandin-2 and Interleukin-1 which are both produced by the cyst itself. Nutritional deficiency theory Epithelial cells will form a mass inside the cavity and the innermost cells become deprived of nutrients because they are far from the source of nutrients (the blood vessels). The innermost cells die and form an aggregate of dead tissue. The inner cells undergo ischemic liquefactive necrosis which creates the cavity space surrounded by growing epithelial cells. This theory is unlikely in the absence of malignant transformation of epithelial cells as it does not follow the existing relationship between connective tissue and epithelium. Abscess theory Epithelial cells have an inherent quality to reproduce and cover any connective tissue that is not already lined with epithelia. Formation of an abscess must precede the epithelial proliferation in order for the cells to carry out this tendency. This theory explains why cysts are lined in epithelia but not why the initial cysts itself forms. Diagnosis A non-vital tooth is necessary for the diagnosis of a periapical cyst, meaning the nerve has been removed by root canal therapy. Oral examination The surrounding intraoral anatomical structures should be palpated to identify the presence of bone expansion or displacement of tooth roots as well as crepitus noises during examination, indicating extensive bone damage. Bulging of the buccal or lingual cortical plates may be present. Age of occurrence in the patient, the location of the cyst, the edges of cystic contours, and the impact that the cyst has on adjacent structures must all be considered for proper diagnosis. Radiology Several lesions can appear similarly in radiographic appearance. Intraoral X-rays or a 3-D cone beam scan of the affected area can be used to obtain radiological images and confirm diagnosis of cysts in the periapical area. Circular or ovoid radiolucency surrounding the root tip of approximately 1-1.5 cm in diameter is indicative of the presence of a periapical cyst. The border of the cyst is seen as a narrow opaque margin contiguous with the lamina dura. In cysts that are actively enlarging, peripheral areas of the margin may not be present. Periapical cysts have a characteristic unilocular shape on radiographs. There is also a severe border of cortication between the cyst and surrounding bone. Pseudocysts, on the other hand, have a fluid filled cavity but are not lined by epithelium, therefore they have a less severe and more blurred border between the fluid and bony surroundings. Histopathology In light microscopy, periapical cysts show: Stratified squamous epithelium of variable thickness, except when originating in a maxillary sinus where there is respiratory epithelium (pseudostratified ciliated columnar epithelium). A fibrous capsule of varying thickness, with chronic inflammatory cells, wherein a plasma cells may be abundantThey sometimes have the following features: Rushton hyaline bodies, which are amorphic, eosinophilic, linear to crescent-shaped bodies in the cyst epithelium, present in 10% of periapical cysts. Scattered ciliated cells Cholesterol clefts in the cyst lining. Classification Periapical cysts exist in two structurally distinct classes: Periapical true cysts - cysts containing cavities entirely surrounded in epithelial lining. Resolution of this type of cyst requires surgical treatment such as a cystectomy. Periapical pocket cysts - epithelium lined cavities that have an opening to the root canal of the affected tooth. Resolution may occur after traditional root canal therapy. Differentiation Radiographically, it is virtually impossible to differentiate granuloma from a cyst. If the lesion is large it is more likely to be a cyst. Radiographically, both granulomas and cysts appear radiolucent. Many lesions of the mandible in particular appear cystlike in appearance. It is often necessary to obtain a biopsy and evaluate the tissue under a microscope to accurately identify the lesion. Treatment The infected tissue of the periapical cyst must be entirely removed, including the epithelium of the cyst wall; otherwise, a relapse is likely to occur. Root canal treatment should be performed on the tooth if it is determined that previous therapy was unsuccessful. Removal of the necrotic pulp and the inflamed tissue as well as proper sealing of the canals and an appropriately fitting crown will allow the tooth to heal under uninfected conditions.Surgical options for previously treated teeth that would not benefit from root canal therapy include cystectomy and cystostomy. This route of treatment is recommended upon discovery of the cyst after inadequate root canal treatment. A cystectomy is the removal of a cyst followed by mucosa and wound closure to reduce chances of cyst regeneration. This type of treatment is more ideal for small cysts. A cystostomy is recommended for larger cysts that compromise important adjacent anatomy. The cyst is tamponaded to allow for the cyst contents to escape the bone. Over time, the cyst decreases in size and bone regenerates in the cavity space. Marsupialization could also be performed, which involves suturing the edges of the gingiva surrounding the cyst to remain open. The cyst then drains its contents and heal without being prematurely closed. The end result is the same as the cystostomy, bone regeneration. For both a cystostomy and marsupialization, root resectioning may also be required in cases where root resorption has occurred. Epidemiology Periapical cysts comprise approximately 75% of the types of cysts found in the oral region. The ratio of individuals diagnosed with periapical cysts is 3:2 male to female, as well as individuals between 20 and 60 years old. Periapical cysts occur worldwide. Types of Periapical cysts: Apical: 70% Lateral: 20% Residual: 10% References == External links ==