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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 'Preterm birth.' Can you provide some details?

Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between 28 and 32 weeks, early preterm birth occurs between 32 and 36 weeks, late preterm birth is between 34 and 36 weeks gestation. These babies are also known as premature babies or colloquially preemies (American English) or premmies (Australian English). Symptoms of preterm labor include uterine contractions which occur more often than every ten minutes and/or the leaking of fluid from the vagina before 37 weeks. Premature infants are at greater risk for cerebral palsy, delays in development, hearing problems and problems with their vision. The earlier a baby is born, the greater these risks will be.The cause of spontaneous preterm birth is often not known. Risk factors include diabetes, high blood pressure, multiple gestation (being pregnant with more than one baby), being either obese or underweight, vaginal infections, air pollution exposure, tobacco smoking, and psychological stress. For a healthy pregnancy, medical induction of labor or cesarean section are not recommended before 39 weeks unless required for other medical reasons. There may be certain medical reasons for early delivery such as preeclampsia.Preterm birth may be prevented in those at risk if the hormone progesterone is taken during pregnancy. Evidence does not support the usefulness of bed rest. It is estimated that at least 75% of preterm infants would survive with appropriate treatment, and the survival rate is highest among the infants born the latest in gestation. In women who might deliver between 24 and 37 weeks, corticosteroid treatment may improve outcomes. A number of medications, including nifedipine, may delay delivery so that a mother can be moved to where more medical care is available and the corticosteroids have a greater chance to work. Once the baby is born, care includes keeping the baby warm through skin-to-skin contact or incubation, supporting breastfeeding and/or formula feeding, treating infections, and supporting breathing. Preterm babies sometimes require intubation.Preterm birth is the most common cause of death among infants worldwide. About 15 million babies are preterm each year (5% to 18% of all deliveries). Late preterm birth accounts for 75% of all preterm births. This rate is inconsistent across countries. In the United Kingdom 7.9% of babies are born pre-term and in the United States 12.3% of all births are before 37 weeks gestation. Approximately 0.5% of births are extremely early periviable births (20–25 weeks of gestation), and these account for most of the deaths. In many countries, rates of premature births have increased between the 1990s and 2010s. Complications from preterm births resulted in 0.81 million deaths in 2015, down from 1.57 million in 1990. The chance of survival at 22 weeks is about 6%, while at 23 weeks it is 26%, 24 weeks 55% and 25 weeks about 72%. The chances of survival without any long-term difficulties are lower. Signs and symptoms Signs and symptoms of preterm labor include four or more uterine contractions in one hour. In contrast to false labour, true labor is accompanied by cervical dilatation and effacement. Also, vaginal bleeding in the third trimester, heavy pressure in the pelvis, or abdominal or back pain could be indicators that a preterm birth is about to occur. A watery discharge from the vagina may indicate premature rupture of the membranes that surround the baby. While the rupture of the membranes may not be followed by labor, usually delivery is indicated as infection (chorioamnionitis) is a serious threat to both fetus and mother. In some cases, the cervix dilates prematurely without pain or perceived contractions, so that the mother may not have warning signs until very late in the birthing process. Causes The main categories of causes of preterm birth are preterm labor induction and spontaneous preterm labor. Risk factors The exact cause of spontaneous preterm birth is difficult to determine and it may be caused by many different factors at the same time as labor is a complex process. Four different pathways have been identified that can result in preterm birth and have considerable evidence: precocious fetal endocrine activation, uterine overdistension (placental abruption), decidual bleeding, and intrauterine inflammation or infection.Identifying women at high risk of giving birth early would enable the health services to provide specialized care for these women and their babies, for example a hospital with a special care baby unit such as a neonatal intensive care unit (NICU). In some instances, it may be possible to delay the birth. Risk scoring systems have been suggested as an approach to identify those at higher risk, however, there is no strong research in this area so it is unclear whether the use of risk scoring systems for identifying mothers would prolong pregnancy and reduce the numbers of preterm births or not. Maternal factors Risk factors in the mother have been identified that are linked to a higher risk of a preterm birth. These include age (either very young or older), high or low body mass index (BMI), length of time between pregnancies, previous spontaneous (i.e., miscarriage) or surgical abortions, unintended pregnancies, untreated or undiagnosed celiac disease, fertility difficulties, heat exposure, and genetic variables.Studies on type of work and physical activity have given conflicting results, but it is opined that stressful conditions, hard labor, and long hours are probably linked to preterm birth. Obesity does not directly lead to preterm birth; however, it is associated with diabetes and hypertension which are risk factors by themselves. To some degree those individuals may have underlying conditions (i.e., uterine malformation, hypertension, diabetes) that persist. Couples who have tried more than 1 year versus those who have tried less than 1 year before achieving a spontaneous conception have an adjusted odds ratio of 1.35 (95% confidence interval 1.22-1.50) of preterm birth. Pregnancies after IVF confers a greater risk of preterm birth than spontaneous conceptions after more than 1 year of trying, with an adjusted odds ratio of 1.55 (95% CI 1.30-1.85).Certain ethnicities may have a higher risk as well. For example, in the U.S. and the UK, Black women have preterm birth rates of 15–18%, more than double than that of the white population. Many Black women have higher preterm birth rates due to multiple factors but the most common is high amounts of chronic stress, which can eventually lead to premature birth. Adult chronic disease isnt always the case with premature birth in Black women, which makes the main factor of premature birth challenging to identify. Filipinos are also at high risk of premature birth, and it is believed that nearly 11–15% of Filipinos born in the U.S. (compared to other Asians at 7.6% and whites at 7.8%) are premature. Filipinos being a big risk factor is evidenced with the Philippines being the eighth-highest ranking in the world for preterm births, the only non-African country in the top 10. This discrepancy is not seen in comparison to other Asian groups or Hispanic immigrants and remains unexplained. Genetic make-up is a factor in the causality of preterm birth. Genetics has been a big factor into why Filipinos have a high risk of premature birth as the Filipinos have a large prevalence of mutations that help them be predisposed to premature births. An intra- and transgenerational increase in the risk of preterm delivery has been demonstrated. No single gene has been identified. Marital status is associated with risk for preterm birth. A study of 25,373 pregnancies in Finland revealed that unmarried mothers had more preterm deliveries than married mothers (P=0.001). Pregnancy outside of marriage was associated overall with a 20% increase in total adverse outcomes, even at a time when Finland provided free maternity care. A study in Quebec of 720,586 births from 1990 to 1997 revealed less risk of preterm birth for infants with legally married mothers compared with those with common-law wed or unwed parents. Factors during pregnancy Medications during pregnancy, living conditions, air pollution, smoking, illicit drugs or alcohol, infection, or physical trauma may also cause a preterm birth. Air pollution: Living in an area with a high concentration of air pollution is a major risk factor for preterm labor, including living near major roadways or highways where vehicle emissions are high from traffic congestion or are a route for diesel trucks that tend to emit more pollution.The use of fertility medication that stimulates the ovary to release multiple eggs and of IVF with embryo transfer of multiple embryos has been implicated as a risk factor for preterm birth. Often labor has to be induced for medical reasons; such conditions include high blood pressure, pre-eclampsia, maternal diabetes, asthma, thyroid disease, and heart disease. Certain medical conditions in the pregnant mother may also increase the risk of preterm birth. Some women have anatomical problems that prevent the baby from being carried to term. These include a weak or short cervix (the strongest predictor of premature birth). Women with vaginal bleeding during pregnancy are at higher risk for preterm birth. While bleeding in the third trimester may be a sign of placenta previa or placental abruption—conditions that occur frequently preterm—even earlier bleeding that is not caused by these conditions is linked to a higher preterm birth rate. Women with abnormal amounts of amniotic fluid, whether too much (polyhydramnios) or too little (oligohydramnios), are also at risk. Anxiety and depression have been linked as risk factors for preterm birth.The use of tobacco, cocaine, and excessive alcohol during pregnancy increases the chance of preterm delivery. Tobacco is the most commonly used drug during pregnancy and contributes significantly to low birth weight delivery. Babies with birth defects are at higher risk of being born preterm.Passive smoking and/or smoking before the pregnancy influences the probability of a preterm birth. The World Health Organization published an international study in March 2014.Presence of anti-thyroid antibodies is associated with an increased risk preterm birth with an odds ratio of 1.9 and 95% confidence interval of 1.1–3.5.Intimate violence against the mother is another risk factor for preterm birth.Physical trauma may case a preterm birth. The Nigerian cultural method of abdominal massage has been shown to result in 19% preterm birth among women in Nigeria, plus many other adverse outcomes for the mother and baby. This ought not be confused with massage therapy conducted by a fully trained and certified/licensed massage therapist or by significant others trained to provide massage during pregnancy, which—in a study involving pregnant females with prenatal depression—has been shown to have numerous positive results during pregnancy, including the reduction of preterm birth, less depression, lower cortisol, and reduced anxiety. In healthy women, however, no effects have been demonstrated in a controlled study. Infection The frequency of infection in preterm birth is inversely related to the gestational age. Mycoplasma genitalium infection is associated with increased risk of preterm birth, and spontaneous abortion.Infectious microorganisms can be ascending, hematogeneous, iatrogenic by a procedure, or retrograde through the Fallopian tubes. From the deciduas they may reach the space between the amnion and chorion, the amniotic fluid, and the fetus. A chorioamnionitis also may lead to sepsis of the mother. Fetal infection is linked to preterm birth and to significant long-term disability including cerebral palsy.It has been reported that asymptomatic colonization of the decidua occurs in up to 70% of women at term using a DNA probe suggesting that the presence of micro-organism alone may be insufficient to initiate the infectious response. As the condition is more prevalent in black women in the U.S. and the UK, it has been suggested to be an explanation for the higher rate of preterm birth in these populations. It is opined that bacterial vaginosis before or during pregnancy may affect the decidual inflammatory response that leads to preterm birth. The condition known as aerobic vaginitis can be a serious risk factor for preterm labor; several previous studies failed to acknowledge the difference between aerobic vaginitis and bacterial vaginosis, which may explain some of the contradiction in the results.Untreated yeast infections are associated with preterm birth.A review into prophylactic antibiotics (given to prevent infection) in the second and third trimester of pregnancy (13–42 weeks of pregnancy) found a reduction in the number of preterm births in women with bacterial vaginosis. These antibiotics also reduced the number of waters breaking before labor in full-term pregnancies, reduced the risk of infection of the lining of the womb after delivery (endometritis), and rates of gonococcal infection. However, the women without bacterial vaginosis did not have any reduction in preterm births or pre-labor preterm waters breaking. Much of the research included in this review lost participants during follow-up so did not report the long-term effects of the antibiotics on mothers or babies. More research in this area is needed to find the full effects of giving antibiotics throughout the second and third trimesters of pregnancy.A number of maternal bacterial infections are associated with preterm birth including pyelonephritis, asymptomatic bacteriuria, pneumonia, and appendicitis. A review into giving antibiotics in pregnancy for asymptomatic bacteriuria (urine infection with no symptoms) found the research was of very low quality but that it did suggest that taking antibiotics reduced the numbers of preterm births and babies with low birth weight. Another review found that one dose of antibiotics did not seem as effective as a course of antibiotics but fewer women reported side effects from one dose. This review recommended that more research is needed to discover the best way of treating asymptomatic bacteriuria.A different review found that preterm births happened less for pregnant women who had routine testing for low genital tract infections than for women who only had testing when they showed symptoms of low genital tract infections. The women being routinely tested also gave birth to fewer babies with a low birth weight. Even though these results look promising, the review was only based on one study so more research is needed into routine screening for low genital tract infections.Also periodontal disease has been shown repeatedly to be linked to preterm birth. In contrast, viral infections, unless accompanied by a significant febrile response, are considered not to be a major factor in relation to preterm birth. Genetics There is believed to be a maternal genetic component in preterm birth. Estimated heritability of timing-of-birth in women was 34%. However, the occurrence of preterm birth in families does not follow a clear inheritance pattern, thus supporting the idea that preterm birth is a non-Mendelian trait with a polygenic nature. Prenatal Care The absence of prenatal care has been associated with higher rates of preterm births. Analysis of 15,627,407 live births in the United States in 1995–1998 concluded that the absence of prenatal care carried a 2.9 (95%CI 2.8, 3.0) times higher risk of preterm births. This same study found statistically significant relative risks of maternal anemia, intrapartum fever, unknown bleeding, renal disease, placental previa, hydramnios, placenta abruption, and pregnancy-induced hypertension with the absence of prenatal care. All these prenatal risks were controlled for other high-risk conditions, maternal age, gravidity, marital status, and maternal education. The absence of prenatal care prior to and during the pregnancy is primarily a function of socioeconomic factors (low family income and education), access to medical consultations (large distance from the place of residence to the healthcare unit and transportation costs), quality of healthcare, and social support. Efforts to decrease rates of preterm birth should aim to increase the deficits posed by the aforementioned barriers and to increase access to prenatal care. Diagnosis Placental alpha microglobulin-1 Placental alpha microglobulin-1 (PAMG-1) has been the subject of several investigations evaluating its ability to predict imminent spontaneous preterm birth in women with signs, symptoms, or complaints suggestive of preterm labor. In one investigation comparing this test to fetal fibronectin testing and cervical length measurement via transvaginal ultrasound, the test for PAMG-1 (commercially known as the PartoSure test) has been reported to be the single best predictor of imminent spontaneous delivery within 7 days of a patient presenting with signs, symptoms, or complaints of preterm labor. Specifically, the PPV, or positive predictive value, of the tests were 76%, 29%, and 30% for PAMG-1, fFN and CL, respectively (P < 0.01). Fetal fibronectin Fetal fibronectin (fFN) has become an important biomarker—the presence of this glycoprotein in the cervical or vaginal secretions indicates that the border between the chorion and deciduas has been disrupted. A positive test indicates an increased risk of preterm birth, and a negative test has a high predictive value. It has been shown that only 1% of women in questionable cases of preterm labor delivered within the next week when the test was negative. Ultrasound Obstetric ultrasound has become useful in the assessment of the cervix in women at risk for premature delivery. A short cervix preterm is undesirable: A cervical length of less than 25 mm at or before 24 weeks of gestational age is the most common definition of cervical incompetence. Classification In humans, the usual definition of preterm birth is birth before a gestational age of 37 complete weeks. In the normal human fetus, several organ systems mature between 34 and 37 weeks, and the fetus reaches adequate maturity by the end of this period. One of the main organs greatly affected by premature birth is the lungs. The lungs are one of the last organs to mature in the womb; because of this, many premature babies spend the first days and weeks of their lives on ventilators. Therefore, a significant overlap exists between preterm birth and prematurity. Generally, preterm babies are premature and term babies are mature. Preterm babies born near 37 weeks often have no problems relating to prematurity if their lungs have developed adequate surfactant, which allows the lungs to remain expanded between breaths. Sequelae of prematurity can be reduced to a small extent by using drugs to accelerate maturation of the fetus, and to a greater extent by preventing preterm birth. Prevention Historically efforts have been primarily aimed to improve survival and health of preterm infants (tertiary intervention). Such efforts, however, have not reduced the incidence of preterm birth. Increasingly primary interventions that are directed at all women, and secondary intervention that reduce existing risks are looked upon as measures that need to be developed and implemented to prevent the health problems of premature infants and children. Smoking bans are effective in decreasing preterm births. Different strategies are used in the administration of prenatal care, and future studies need to determine if the focus can be on screening for high-risk women, or widened support for low-risk women, or to what degree these approaches can be merged. Before pregnancy Adoption of specific professional policies can immediately reduce risk of preterm birth as the experience in assisted reproduction has shown when the number of embryos during embryo transfer was limited. Many countries have established specific programs to protect pregnant women from hazardous or night-shift work and to provide them with time for prenatal visits and paid pregnancy-leave. The EUROPOP study showed that preterm birth is not related to type of employment, but to prolonged work (over 42 hours per week) or prolonged standing (over 6 hours per day). Also, night work has been linked to preterm birth. Health policies that take these findings into account can be expected to reduce the rate of preterm birth. Preconceptional intake of folic acid is recommended to reduce birth defects. There is also some evidence that folic acid supplement preconceptionally (before becoming pregnant) may reduce premature birth. Reducing smoking is expected to benefit pregnant women and their offspring. During pregnancy Self-care methods to reduce the risk of preterm birth include proper nutrition, avoiding stress, seeking appropriate medical care, avoiding infections, and the control of preterm birth risk factors (e.g. working long hours while standing on feet, carbon monoxide exposure, domestic abuse, and other factors). Reducing physical activity during pregnancy has not been shown to reduce the risk of a preterm birth. Healthy eating can be instituted at any stage of the pregnancy including nutritional adjustments and consuming suggested vitamin supplements. Calcium supplementation in women who have low dietary calcium may reduce the number of negative outcomes including preterm birth, pre-eclampsia, and maternal death. The World Health Organization (WHO) suggests 1.5–2 g of calcium supplements daily, for pregnant women who have low levels of calcium in their diet. Supplemental intake of C and E vitamins have not been found to reduce preterm birth rates.While periodontal infection has been linked with preterm birth, randomized trials have not shown that periodontal care during pregnancy reduces preterm birth rates. Smoking cessation has also been shown to reduce the risk. The use of personal at home uterine monitoring devices to detect contractions and possible preterm births in women at higher risk of having a preterm baby have been suggested. These home monitors may not reduce the number of preterm births, however, using these devices may increase the number of unplanned antenatal visits and may reduce the number of babies admitted to special care when compared with women receiving normal antenatal care. Support from medical professionals, friends, and family during pregnancy may be beneficial at reducing caesarean birth and may reduce prenatal hospital admissions, however, these social supports alone may not prevent preterm birth. Screening during pregnancy Screening for asymptomatic bacteriuria followed by appropriate treatment reduces pyelonephritis and reduces the risk of preterm birth. Extensive studies have been carried out to determine if other forms of screening in low-risk women followed by appropriate intervention are beneficial, including screening for and treatment of Ureaplasma urealyticum, group B streptococcus, Trichomonas vaginalis, and bacterial vaginosis did not reduce the rate of preterm birth. Routine ultrasound examination of the length of the cervix may identify women at risk of preterm labour and tentative evidence suggests ultrasound measurement of the length of the cervix in those with preterm labor can help adjust management and results in the extension of pregnancy by about 4 days. Screening for the presence of fibronectin in vaginal secretions is not recommended at this time in women at low risk of preterm birth. Reducing existing risks Women are identified to be at increased risk for preterm birth on the basis of their past obstetrical history or the presence of known risk factors. Preconception intervention can be helpful in selected patients in a number of ways. Patients with certain uterine anomalies may have a surgical correction (i.e. removal of a uterine septum), and those with certain medical problems can be helped by optimizing medical therapies prior to conception, be it for asthma, diabetes, hypertension, and others. Multiple pregnancies In multiple pregnancies, which often result from use of assisted reproductive technology, there is a high risk of preterm birth. Selective reduction is used to reduce the number of fetuses to two or three. Reducing indicated preterm birth A number of agents have been studied for the secondary prevention of indicated preterm birth. Trials using low-dose aspirin, fish oil, vitamin C and E, and calcium to reduce preeclampsia demonstrated some reduction in preterm birth only when low-dose aspirin was used. Even if agents such as calcium or antioxidants were able to reduce preeclampsia, a resulting decrease in preterm birth was not observed. Reducing spontaneous preterm birth Reduction in activity by the mother—pelvic rest, limited work, bed rest—may be recommended although there is no evidence it is useful with some concerns it is harmful. Increasing medical care by more frequent visits and more education has not been shown to reduce preterm birth rates. Use of nutritional supplements such as omega-3 polyunsaturated fatty acids is based on the observation that populations who have a high intake of such agents are at low risk for preterm birth, presumably as these agents inhibit production of proinflammatory cytokines. A randomized trial showed a significant decline in preterm birth rates, and further studies are in the making. Antibiotics While antibiotics can get rid of bacterial vaginosis in pregnancy, this does not appear to change the risk of preterm birth. It has been suggested that chronic chorioamnionitis is not sufficiently treated by antibiotics alone (and therefore they cannot ameliorate the need for preterm delivery in this condition). Progestogens Progestogens—often given in the form of vaginal progesterone or hydroxyprogesterone caproate—relax the uterine musculature, maintain cervical length, and possess anti-inflammatory properties; all of which invoke physiological and anatomical changes considered to be beneficial in reducing preterm birth. Two meta-analyses demonstrated a reduction in the risk of preterm birth in women with recurrent preterm birth by 40–55%.Progestogen supplementation also reduces the frequency of preterm birth in pregnancies where there is a short cervix. A short cervix is one that is less than 25mm, as detected during a transvaginal cervical length assessment in the midtrimester. However, progestogens are not effective in all populations, as a study involving twin gestations failed to see any benefit. Despite extensive research related to progestogen effectiveness, uncertainties remain concerning types of progesterone and routes of administration. Cervical cerclage In preparation for childbirth, the womans cervix shortens. Preterm cervical shortening is linked to preterm birth and can be detected by ultrasonography. Cervical cerclage is a surgical intervention that places a suture around the cervix to prevent its shortening and widening. Numerous studies have been performed to assess the value of cervical cerclage and the procedure appears helpful primarily for women with a short cervix and a history of preterm birth. Instead of a prophylactic cerclage, women at risk can be monitored during pregnancy by sonography, and when shortening of the cervix is observed, the cerclage can be performed. Management (Treatment) Tertiary interventions are aimed at women who are about to go into preterm labor, or rupture the membranes or bleed preterm. The use of the fibronectin test and ultrasonography improves the diagnostic accuracy and reduces false-positive diagnosis. While treatments to arrest early labor where there is progressive cervical dilatation and effacement will not be effective to gain sufficient time to allow the fetus to grow and mature further, it may defer delivery sufficiently to allow the mother to be brought to a specialized center that is equipped and staffed to handle preterm deliveries. In a hospital setting women are hydrated via intravenous infusion (as dehydration can lead to premature uterine contractions).If a baby has cardiac arrest at birth and is before 23 weeks or less than 400 g attempts at resuscitation are not indicated. Steroids Severely premature infants may have underdeveloped lungs because they are not yet producing their own surfactant. This can lead directly to respiratory distress syndrome, also called hyaline membrane disease, in the neonate. To try to reduce the risk of this outcome, pregnant mothers with threatened premature delivery prior to 34 weeks are often administered at least one course of glucocorticoids, an antenatal steroid that crosses the placental barrier and stimulates the production of surfactant in the lungs of the baby. Steroid use up to 37 weeks is also recommended by the American Congress of Obstetricians and Gynecologists. Typical glucocorticoids that would be administered in this context are betamethasone or dexamethasone, often when the pregnancy has reached viability at 23 weeks. In cases where premature birth is imminent, a second "rescue" course of steroids may be administered 12 to 24 hours before the anticipated birth. There are still some concerns about the efficacy and side effects of a second course of steroids, but the consequences of RDS are so severe that a second course is often viewed as worth the risk. A 2015 Cochrane review (updated in 2022) supports the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course.A Cochrane review from 2020 recommends the use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. Treatment with antenatal corticosteroids reduces the risk of perinatal death, neonatal death and respiratory distress syndrome and probably reduces the risk of IVH.Concerns about adverse effects of prenatal corticosteroids include increased risk for maternal infection, difficulty with diabetic control, and possible long-term effects on neurodevelopmental outcomes for the infants. There is ongoing discussion about when steroids should be given (i.e. only antenatally or postnatally too) and for how long (i.e. single course or repeated administration). Despite these unknowns, there is a consensus that the benefits of a single course of prenatal glucocorticosteroids vastly outweigh the potential risks. Antibiotics The routine administration of antibiotics to all women with threatened preterm labor reduces the risk of the baby to get infected with group B streptococcus and has been shown to reduce related mortality rates.When membranes rupture prematurely, obstetrical management looks for development of labor and signs of infection. Prophylactic antibiotic administration has been shown to prolong pregnancy and reduced neonatal morbidity with rupture of membranes at less than 34 weeks. Because of concern about necrotizing enterocolitis, amoxicillin or erythromycin has been recommended, but not amoxicillin + clavulanic acid (co-amoxiclav). Tocolysis A number of medications may be useful to delay delivery including: nonsteroidal anti-inflammatory drugs, calcium channel blockers, beta mimetics, and atosiban. Tocolysis rarely delays delivery beyond 24–48 hours. This delay, however, may be sufficient to allow the pregnant woman to be transferred to a center specialized for management of preterm deliveries and give administered corticosteroids to reduce neonatal organ immaturity. Meta-analyses indicate that calcium-channel blockers and an oxytocin antagonist can delay delivery by 2–7 days, and β2-agonist drugs delay by 48 hours but carry more side effects. Magnesium sulfate does not appear to be useful to prevent preterm birth. Its use before delivery, however, does appear to decrease the risk of cerebral palsy. Mode of delivery The routine use of caesarean section for early delivery of infants expected to have very low birth weight is controversial, and a decision concerning the route and time of delivery probably needs to be made on a case-by-case basis. Neonatal care In developed countries premature infants are usually cared for in a NICU. The physicians who specialize in the care of very sick or premature babies are known as neonatologists. In the NICU, premature babies are kept under radiant warmers or in incubators (also called isolettes), which are bassinets enclosed in plastic with climate control equipment designed to keep them warm and limit their exposure to germs. Modern neonatal intensive care involves sophisticated measurement of temperature, respiration, cardiac function, oxygenation, and brain activity. After delivery, plastic wraps or warm mattresses are useful to keep the infant warm on their way to the neonatal intensive care unit (NICU). Treatments may include fluids and nutrition through intravenous catheters, oxygen supplementation, mechanical ventilation support, and medications. In developing countries where advanced equipment and even electricity may not be available or reliable, simple measures such as kangaroo care (skin to skin warming), encouraging breastfeeding, and basic infection control measures can significantly reduce preterm morbidity and mortality. Kangaroo mother care (KMC) can decrease the risk of neonatal sepsis, hypothermia, hypoglycemia and increase exclusive breastfeeding Bili lights may also be used to treat newborn jaundice (hyperbilirubinemia). Water can be carefully provided to prevent dehydration but not so much to increase risks of side effects. Breathing support In terms of respiratory support, there may be little or no difference in the risk of death or chronic lung disease between high flow nasal cannulae (HFNC) and continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NPPV). For extremely preterm babies (born before 28 weeks gestation), targeting a higher versus a lower oxygen saturation range makes little or no difference overall to the risk of death or major disability. Babies born before 32 weeks probably have a lower risk of death from bronchopulmonary dysplasia if they have CPAP immediately after being born, compared to receiving either supportive care or assisted ventilation.There is insufficient evidence for or against placing preterm stable twins in the same cot or incubator (co-bedding). Nutrition Meeting the appropriate nutritional needs of preterm infants is important for long-term health. Optimal care may require a balance of meeting nutritional needs and preventing complications related to feeding. The ideal growth rate is not known, however, preterm infants usually require a higher energy intake compared to babies who are born at term. The recommended amount of milk is often prescribed based on approximated nutritional requirements of a similar aged fetus who is not compromised. An immature gastrointestinal tract (GI tract), medical conditions (or co-morbidities), risk of aspirating milk, and necrotizing enterocolitis may lead to difficulties in meeting this high nutritional demand and many preterm infants have nutritional deficits that may result in growth restrictions. In addition, very small preterm infants cannot coordinate sucking, swallowing, and breathing. Tolerating a full enteral feeding (the prescribed volume of milk or formula) is a priority in neonatal care as this reduces the risks associated with venous catheters including infection, and may reduce the length of time the infant requires specialized care in the hospital. Different strategies can be used to optimize feeding for preterm infants. The type of milk/formula and fortifiers, route of administration (by mouth, tube feeding, venous catheter), timing of feeding, quantity of milk, continuous or intermittent feeding, and managing gastric residuals are all considered by the neonatal care team when optimizing care. The evidence in the form of high quality randomized trials is generally fairly weak in this area, and for this reason different neonatal intensive care units may have different practices and this results in a fairly large variation in practice. The care of preterm infants also varies in different countries and depends on resources that are available. Human breast milk and formula The American Academy of Pediatrics recommended feeding preterm infants human milk, finding "significant short- and long-term beneficial effects," including lower rates of necrotizing enterocolitis (NEC). In the absence of evidence from randomised controlled trials about the effects of feeding preterm infants with formula compared with mothers own breast milk, data collected from other types of studies suggest that mothers own breast milk is likely to have advantages over formula in terms of the babys growth and development. When a mothers breast milk is not available, formula is probably better than donor breast milk for preterm babies in terms of weight gain, linear growth and head growth but there may be little or no difference in terms of neuro-developmental disability, death or necrotising enterocolitis. Fortified human breast milk and preterm/term formula Breast milk or formula alone may not be sufficient to meet the nutritional needs of some preterm infants. Fortification of breast milk or formula by adding extra nutrients is an approach often taken for feeding preterm infants, with the goal of meeting the high nutritional demand. High quality randomized controlled trials are needed in this field to determine the effectiveness of fortification. It is unclear if fortification of breast milk improves outcomes in preterm babies, though it may speed growth. Supplementing human milk with extra protein may increase short-term growth but the longer-term effects on body composition, growth and brain development are uncertain. Higher protein formula (between 3 and 4 grams of protein per kilo of body weight) may be more effective than low protein formula (less than 3 grams per kilo per day) for weight gain in formula-fed low-birth-weight infants. There is insufficient evidence about the effect on preterm babies growth of supplementing human milk with carbohydrate, fat, and branched-chain amino acids. Conversely, there is some indication that preterm babies who cannot breastfeed may do better if they are fed only with diluted formula compared to full strength formula but the clinical trial evidence remains uncertain.Individualizing the nutrients and quantities used to fortify enteral milk feeds in infants born with very low birth weight may lead to better short-term weight gain and growth but the evidence is uncertain for longer term outcomes and for the risk of serious illness and death. This includes targeted fortification (adjusting the level of nutrients in response to the results of a test on the breast milk) and adjustable fortification (adding nutrients based on testing the infant).Multi-nutrient fortifier used to fortify human milk and formula has traditionally been derived from bovine milk. Fortifier derived from humans is available, however, the evidence from clinical trials is uncertain and it is not clear if there are any differences between human-derived fortifier and bovine-derived fortifier in terms of neonatal weight gain, feeding intolerance, infections, or the risk of death. Timing of feeds For very preterm infants, most neonatal care centres start milk feeds gradually, rather than starting with a full enteral feeding right away, however, is not clear if starting full enteral feeding early effects the risk of necrotising enterocolitis. In these cases, the preterm infant would be receiving the majority of their nutrition and fluids intravenously. The milk volume is usually gradually increased over the following weeks. Research into the ideal timing of enteral feeding and whether delaying enteral feeding or gradually introducing enteral feeds is beneficial at improving growth for preterm infants or low birth weight infants is needed. In addition, the ideal timing of enteral feeds to prevent side effects such as necrotising enterocolitis or mortality in preterm infants who require a packed red blood cell transfusion is not clear. Potential disadvantages of a more gradual approach to feeding preterm infants associated with less milk in the gut and include slower GI tract secretion of hormones and gut motility and slower microbial colonization of the gut.Regarding the timing of starting fortified milk, preterm infants are often started on fortified milk/formula once they are fed 100 mL/kg of their body weight. Other some neonatal specialists feel that starting to feed a preterm infant fortified milk earlier is beneficial to improve intake of nutrients. The risks of feeding intolerance and necrotising enterocolitis related to early versus later fortification of human milk are not clear. Once the infant is able to go home from the hospital there is limited evidence to support prescribing a preterm (fortified) formula. Intermittent feeding versus continuous feeding For infants who weigh less than 1500 grams, tube feeding is usually necessary. Most often, neonatal specialists feed preterm babies intermittently with a prescribed amount of milk over a short period of time. For example, a feed could last 10–20 minutes and be given every 3 hours. This intermittent approach is meant to mimic conditions of normal bodily functions involved with feeding and allow for a cyclic pattern in the release of gastrointestinal tract hormones to promote development of the gastrointestinal system. In certain cases, continuous nasogastric feeding is sometimes preferred. There is low to very low certainty evidence to suggest that low birth weight babies who receive continuous nasogastic feeding may reach the benchmark of tolerating full enteral feeding later than babies fed intermittently and it is not clear if continuous feeding has any effect on weight gain or the number of interruptions in feedings. Continuous feeding may have little to no effect on length of body growth or head circumference and the effects of continuous feeding on the risk of developing necrotising enterocolitis is not clear.Since preterm infants with gastro-oesophageal reflux disease do not have a fully developed antireflux mechanism, deciding on the most effective approach for nutrition is important. It is not clear if continuous bolus intragastric tube feeding is more effective compared to intermittent bolus intragastric tube feeding for feeding preterm infants with gastro-oesophageal reflux disease.For infants who would benefit from intermittent bolus feeding, some infants may be fed using the "push feed" method using a syringe to gently push the milk or formula into the stomach of the infant. Others may be fed using a gravity feeding system where the syringe is attached directly to a tube and the milk or formula drips into the infants stomach. It is not clear from medical studies which approach to intermittent bolus feeding is more effective or reduces adverse effects such as apnoea, bradycardia, or oxygen desaturation episodes. High volume feeds High-volume (more than 180 mL per kilogram per day) enteral feeds of fortified or non-fortified human breast milk or formula may improve weight gain while the pre-term infant is hospitalized, however, there is insufficient evidence to determine if this approach improves growth of the neonate and other clinical outcomes including length of hospital stay. The risks or adverse effects associated with high-volume enteral feeding of preterm infants including aspiration pneumonia, reflux, apnoea, and sudden oxygen desaturation episodes have not been reported in the trials considered in a 2021 systematic review. Parenteral (intraveneous) nutrition For preterm infants who are born after 34 weeks of gestation ("late preterm infants") who are critically ill and cannot tolerate milk, there is some weak evidence that the infant may benefit from including amino acids and fats in the intravenous nutrition at a later time point (72 hours or longer from hospital admission) versus early (less than 72 hours from admission to hospital), however further research is required to understand the ideal timing of starting intravenous nutrition. Gastric residuals For preterm infants in neonatal intensive care on gavage feeds, monitoring the volume and colour of gastric residuals, the milk and gastrointestinal secretions that remain in the stomach after a set amount of time, is common standard of care practice. Gastric residual often contains gastric acid, hormones, enzymes, and other substances that may help improve digestion and mobility of the gastrointestinal tract. Analysis of gastric residuals may help guide timing of feeds. Increased gastric residual may indicate feeding intolerance or it may be an early sign of necrotizing enterocolitis. Increased gastric residual may be caused by an underdeveloped gastrointestinal system that leads to slower gastric emptying or movement of the milk in the intestinal tract, reduced hormone or enzyme secretions from the gastrointestinal tract, duodenogastric reflux, formula, medications, and/or illness. The clinical decision to discard the gastric residuals (versus re-feeding) is often individualized based on the quantity and quality of the residual. Some experts also suggest replacing the fresh milk or curded milk and bile-stained aspirates, but not replacing haemorrhagic residual. Evidence to support or refute the practice of re-feeding preterm infants with gastric residuals is lacking. Hearing assessment The Joint Committee on Infant Hearing (JCIH) state that for preterm infants who are in the neonatal intensive care unit (NICU) for a prolonged time should have a diagnostic audiologic evaluation before they are discharged from the hospital. Well babies follow a 1-2-3-month benchmark timeline where they are screened, diagnosed, and receiving intervention for a hearing loss. However, very premature babies it might not be possible to complete a hearing screen at one month of age due to several factors. Once the baby is stable an audiologic evaluation should be performed. For premature babies in the NICU, auditory brainstem response (ABR) testing is recommended. If the infant doesnt pass the screen, they should be referred for an audiologic evaluation by an audiologist. If the infant is on aminoglycosides such as gentamicin for less than five days they should be monitored and have a follow up 6–7 months of being discharged from the hospital to ensure there is no late onset hearing loss due to the medication. Outcomes and prognosis Preterm births can result in a range of problems including mortality and physical and mental delays. Mortality and morbidity In the U.S. where many neonatal infections and other causes of neonatal death have been markedly reduced, prematurity is the leading cause of neonatal mortality at 25%. Prematurely born infants are also at greater risk for having subsequent serious chronic health problems as discussed below. The earliest gestational age at which the infant has at least a 50% chance of survival is referred to as the limit of viability. As NICU care has improved over the last 40 years, the limit of viability has reduced to approximately 24 weeks. Most newborns who die, and 40% of older infants who die, were born between 20 and 25.9 weeks (gestational age), during the second trimester.As risk of brain damage and developmental delay is significant at that threshold even if the infant survives, there are ethical controversies over the aggressiveness of the care rendered to such infants. The limit of viability has also become a factor in the abortion debate. Specific risks for the preterm neonate Preterm infants usually show physical signs of prematurity in reverse proportion to the gestational age. As a result, they are at risk for numerous medical problems affecting different organ systems. Neurological problems include apnea of prematurity, hypoxic-ischemic encephalopathy (HIE), retinopathy of prematurity (ROP), developmental disability, transient hyperammonemia of the newborn, cerebral palsy and intraventricular hemorrhage, the latter affecting 25% of babies born preterm, usually before 32 weeks of pregnancy. Mild brain bleeds usually leave no or few lasting complications, but severe bleeds often result in brain damage or even death. Neurodevelopmental problems have been linked to lack of maternal thyroid hormones, at a time when their own thyroid is unable to meet postnatal needs. Cardiovascular complications may arise from the failure of the ductus arteriosus to close after birth: patent ductus arteriosus (PDA). Respiratory problems are common, specifically the respiratory distress syndrome (RDS or IRDS) (previously called hyaline membrane disease). Another problem can be chronic lung disease (previously called bronchopulmonary dysplasia or BPD). Gastrointestinal and metabolic issues can arise from neonatal hypoglycemia, feeding difficulties, rickets of prematurity, hypocalcemia, inguinal hernia, and necrotizing enterocolitis (NEC). Hematologic complications include anemia of prematurity, thrombocytopenia, and hyperbilirubinemia (jaundice) that can lead to kernicterus. Infection, including sepsis, pneumonia, and urinary tract infection [1] Survival The chance of survival at 22 weeks is about 6%, while at 23 weeks it is 26%, 24 weeks 55% and 25 weeks about 72% as of 2016. With extensive treatment up to 30% of those who survive birth at 22 weeks survive longer term as of 2019. The chances of survival without long-term difficulties is less. Of those who survive following birth at 22 weeks 33% have severe disabilities. In the developed world overall survival is about 90% while in low-income countries survival rates are about 10%.Some children will adjust well during childhood and adolescence, although disability is more likely nearer the limits of viability. A large study followed children born between 22 and 25 weeks until the age of 6 years old. Of these children, 46 percent had moderate to severe disabilities such as cerebral palsy, vision or hearing loss and learning disabilities, 34 percent had mild disabilities, and 20 percent had no disabilities. 12 percent had disabling cerebral palsy. Up to 15 out of 100 premature infants have significant hearing loss.As survival has improved, the focus of interventions directed at the newborn has shifted to reduce long-term disabilities, particularly those related to brain injury. Some of the complications related to prematurity may not be apparent until years after the birth. A long-term study demonstrated that the risks of medical and social disabilities extend into adulthood and are higher with decreasing gestational age at birth and include cerebral palsy, intellectual disability, disorders of psychological development, behavior, and emotion, disabilities of vision and hearing, and epilepsy. Standard intelligence tests showed that 41 percent of children born between 22 and 25 weeks had moderate or severe learning disabilities when compared to the test scores of a group of similar classmates who were born at full term. It is also shown that higher levels of education were less likely to be obtained with decreasing gestational age at birth. People born prematurely may be more susceptible to developing depression as teenagers. Some of these problems can be described as being within the executive domain and have been speculated to arise due to decreased myelinization of the frontal lobes. Studies of people born premature and investigated later with MRI brain imaging, demonstrate qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence. Throughout life they are more likely to require services provided by physical therapists, occupational therapists, or speech therapists.Despite the neurosensory, mental and educational problems studied in school age and adolescent children born extremely preterm, the majority of preterm survivors born during the early years of neonatal intensive care are found to do well and to live fairly normal lives in young adulthood. Young adults born preterm seem to acknowledge that they have more health problems than their peers, yet feel the same degree of satisfaction with their quality of life.Beyond the neurodevelopmental consequences of prematurity, infants born preterm have a greater risk for many other health problems. For instance, children born prematurely have an increased risk for developing chronic kidney disease. Epidemiology Preterm birth complicates the births of infants worldwide affecting 5% to 18% of births. In Europe and many developed countries the preterm birth rate is generally 5–9%, and in the U.S. it has even risen to 12–13% in the last decades.As weight is easier to determine than gestational age, the World Health Organization tracks rates of low birth weight (< 2,500 grams), which occurred in 16.5 percent of births in less developed regions in 2000. It is estimated that one third of these low birth weight deliveries are due to preterm delivery. Weight generally correlates to gestational age; however, infants may be underweight for other reasons than a preterm delivery. Neonates of low birth weight (LBW) have a birth weight of less than 2,500 g (5 lb 8 oz) and are mostly but not exclusively preterm babies as they also include small for gestational age (SGA) babies. Weight-based classification further recognizes Very Low Birth Weight (VLBW) which is less than 1,500 g, and Extremely Low Birth Weight (ELBW) which is less than 1,000 g. Almost all neonates in these latter two groups are born preterm. About 75% of nearly a million deaths due to preterm deliver would survive if provided warmth, breastfeeding, treatments for infection, and breathing support. Complications from preterm births resulted in 740,000 deaths in 2013, down from 1.57 million in 1990. Society and culture Economics Preterm birth is a significant cost factor in healthcare, not even considering the expenses of long-term care for individuals with disabilities due to preterm birth. A 2003 study in the U.S. determined neonatal costs to be $224,400 for a newborn at 500–700 g versus $1,000 at over 3,000 g. The costs increase exponentially with decreasing gestational age and weight. The 2007 Institute of Medicine report Preterm Birth found that the 550,000 premature babies born each year in the U.S. run up about $26 billion in annual costs, mostly related to care in neonatal intensive care units, but the real tab may top $50 billion. Notable cases James Elgin Gill (born on 20 May 1987 in Ottawa, Ontario, Canada) was the earliest premature baby in the world, until that record was broken in 2004. He was 128 days premature (21 weeks 5 days gestation) and weighed 624 g (1 lb 6 oz). He survived.In 2014, Lyla Stensrud, born in San Antonio, Texas, U.S. became the youngest premature baby in the world. She was born at 21 weeks 4 days and weighed 410 grams (less than a pound). Kaashif Ahmad resuscitated the baby after she was born. As of November 2018, Lyla was attending preschool. She had a slight delay in speech, but no other known medical issues or disabilities.Amillia Taylor is also often cited as the most premature baby. She was born on 24 October 2006 in Miami, Florida, U.S. at 21 weeks and 6 days gestation. This report has created some confusion as her gestation was measured from the date of conception (through in vitro fertilization) rather than the date of her mothers last menstrual period, making her appear 2 weeks younger than if gestation was calculated by the more common method. At birth, she was 23 cm (9 in) long and weighed 280 g (10 oz). She had digestive and respiratory problems, together with a brain hemorrhage. She was discharged from the Baptist Childrens Hospital on 20 February 2007.The record for the smallest premature baby to survive was held for a considerable amount of time by Madeline Mann, who was born in 1989 at 26 weeks, weighing 280 g (9+7⁄8 oz) and measuring 24 cm (9+1⁄2 in) long. This record was broken in September 2004 by Rumaisa Rahman, who was born in the same hospital, Loyola University Medical Center in Maywood, Illinois. at 25 weeks gestation. At birth, she was 20 cm (8 in) long and weighed 261 g (9+1⁄4 oz). Her twin sister was also a small baby, weighing 563 g (1 lb 3+7⁄8 oz) at birth. During pregnancy their mother had pre-eclampsia, requiring birth by caesarean section. The larger twin left the hospital at the end of December, while the smaller remained there until 10 February 2005 by which time her weight had increased to 1.18 kg (2 lb 9+5⁄8 oz). Generally healthy, the twins had to undergo laser eye surgery to correct vision problems, a common occurrence among premature babies. In May 2019, Sharp Mary Birch Hospital for Women & Newborns in San Diego announced that a baby nicknamed "Saybie" had been discharged almost five months after being born at 23 weeks gestation and weighing 244 g (8+5⁄8 oz). Saybie was confirmed by Dr. Edward Bell of the University of Iowa, which keeps the Tiniest Babies Registry, to be the new smallest surviving premature baby in that registry.The worlds smallest premature boy to survive was born in February 2009 at Childrens Hospitals and Clinics of Minnesota in Minneapolis, Minnesota, U.S. Jonathon Whitehill was born at 25 weeks gestation with a weight of 310 g (10+7⁄8 oz). He was hospitalized in a neonatal intensive care unit for five months, and then discharged.In 2020, at the height of the COVID-19 pandemic, the worlds most premature baby was born. The baby, named Richard Hutchinson, was born at Childrens Hospitals and Clinics of Minnesota in Minneapolis, Minnesota, on June 5, 2020, at 21 weeks 2 days gestation. At birth he weighed 340 g (12 oz). He remained hospitalized until November 2020, when he was then discharged.Historical figures who were born prematurely include Johannes Kepler (born in 1571 at seven months gestation), Isaac Newton (born in 1642, small enough to fit into a quart mug, according to his mother), Winston Churchill (born in 1874 at seven months gestation), and Anna Pavlova (born in 1885 at seven months gestation). Effect of the coronavirus pandemic During the COVID-19 pandemic, a drastic drop in the rate of premature births has been reported in many countries, ranging from a 20% reduction to a 90% drop in the starkest cases. Studies in Ireland and Denmark first noticed the phenomenon, and it has been confirmed elsewhere. There is no universally accepted explanation for this drop as of August 2020. Hypotheses include additional rest and support for expectant mothers staying at home, less air pollution due to shutdowns and reduced car fumes, and reduced likelihood of catching other diseases and viruses in general due to the lockdowns. Research Brain injury is common among preterms, ranging from white matter injury to intraventricular and cerebellar haemorrhages. The characteristic neuropathology of preterms has been described as the "encephalopathy of prematurity". The number of preterms that receive special education is doubled compared to the general population. School marks are lower and so are verbal learning, executive function, language skills, and memory performance scores, as well as IQ scores. Behaviourally, adolescents who were born very preterm and/or very low birth weight have similar self-reports of quality of life, health status and self-esteem as term controls.Various structural magnetic resonance studies found consistent reductions in whole brain volume. The extensive list of particular regions with smaller volumes compared to controls includes many cortical areas (temporal, frontal, parietal, occipital and cingulate), the hippocampal regions, thalamus, basal ganglia, amygdala, brain stem, internal capsule, corpus callosum and cerebellum. Brain volume reduction seems to be present throughout the whole brain. In contrast, larger volumes were found in some of the same areas including medial/anterior frontal, parietal and temporal cortex, cerebellum, middle temporal gyrus, parahippocampal gyrus, and fusiform gyrus, as well as larger lateral ventricles on average. The cause of these inconsistencies are unknown. Additionally, reductions in cortical surface area/cortical thickness were found in the temporal lobes bilaterally and in left frontal and parietal areas. Thicker cortex was found bilaterally in the medial inferior and anterior parts of the frontal lobes and in the occipital lobes. Gestational age was positively correlated with volumes of the temporal and fusiform gyri and sensorimotor cortex bilaterally, left inferior parietal lobule, brain stem, and various white matter tracts, as well as specific positive associations with the cerebellum and thalamus. Several structural brain alterations have been linked back to cognitive and behavioural outcome measures. For example, total brain tissue volume explained between 20 and 40% of the IQ and educational outcome differences between extremely preterm born adolescents and control adolescents. In another study, a 25% quartile decrease in white matter values in middle temporal gyrus was associated with a 60% increase in the risk of cognitive impairment. Nosarti and colleagues previously hypothesised that maturational patterns in preterm brains were consistent with the age-related stages typically observed in younger subjects. Their most recent study suggests, however, that their trajectory may not only be delayed but also fundamentally distinctive. Since both smaller and larger regional volumes were found in very preterm individuals compared to controls.The evidence to support the use of osteopathic manipulations to provide benefit in neonatal care is weak. See also Canadian Perinatal Network Preemie Parents: 26 Little Ways to Grow With Your Premature Baby (2011), by Tami Gaines World Prematurity Day References == External links ==

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

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

Tezepelumab, sold under the brand name Tezspire, is a human monoclonal antibody used for the treatment of asthma. Tezepelumab blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine that has been suggested to be critical in the initiation and persistence of airway inflammation.The most common side effects include arthralgia (joint pain) and pharyngitis (sore throat).Tezepelumab was approved for medical use in the United States in December 2021, and in the European Union in September 2022. Medical uses Tezepelumab is indicated for the add-on maintenance treatment of people aged twelve years and older with severe asthma. History Two main studies including over 1,500 adults and adolescents with inadequately controlled asthma showed that tezepelumab was effective in reducing the number of severe asthma flare‑ups. Society and culture Legal status On 21 July 2022, 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 the medicinal product Tezspire, intended as add-on treatment in adult and adolescent patients with severe asthma. The applicant for this medicinal product is AstraZeneca AB. Tezepelumab was approved for medical use in the European Union in September 2022. Research It is being studied for the treatment of chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, chronic spontaneous urticaria and eosinophilic esophagitis (EoE).In phase III trials, tezepelumab demonstrated efficacy compared to placebo for patients with severe, uncontrolled asthma.Structural studies by X-ray crystallography showed that tezepelumab competes against a critical part of the TSLPR binding site on TSLP. References External links "Tezepelumab". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT02054130 for "Study to Evaluate the Efficacy and Safety of MEDI9929 (AMG 157) in Adult Subjects With Inadequately Controlled, Severe Asthma" at ClinicalTrials.gov Clinical trial number NCT03347279 for "Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma (NAVIGATOR)" at ClinicalTrials.gov

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

What does the medical term 'Polycarbophil calcium' encompass?

Polycarbophil calcium (INN) is a drug used as a stool stabilizer. Chemically, it is a synthetic polymer of polyacrylic acid cross-linked with divinyl glycol, with calcium as a counter-ion. Clinical uses It is used as stool stabilizer to treat constipation, diarrhea and abdominal discomfort. Bulk laxatives absorb liquid in the intestines and swell to form a soft bulky stool. The bulky mass stimulates the intestinal muscles, speeding stool transit time through the colon. Results usually occur within 12 to 72 hours. Calcium polycarbophil will not work without increased fluid intake. Calcium polycarbophil has been marketed as an over-the-counter agent used for treating functional bowel disorder and as a bulk-producing agent. A study looked at the effects of calcium polycarbophil on general irritable bowel syndrome (IBS) symptoms. Fourteen patients with IBS-diarrhea and twelve with IBS-constipation were given calcium polycarbophil for eight weeks and their colon transit times were measured with radiopaque markers in the colon. The patients with diarrhea reported fewer bowel movements, more solid stools and reduced abdominal pain. Patients with constipation reported more frequent bowel movements, looser stools and less pain.The human stomach presents a mild acidic environment due to the presence of HCl. Polycarbophil absorbs about ten times its own weight of water under acidic conditions, but the swelling ratio markedly increases at above pH 4.0 and reaches 70 times the initial weight under pH-neutral conditions. The swelling of polycarbophil is not affected by non-ionic osmolarity, but by ionic strength, showing a decrease with increase of ionic strength. Monovalent metal ions such as sodium and potassium ions in gastrointestinal fluid do not reduce the equilibrium swelling of polycarbophil, but divalent ions such as calcium and magnesium ions do. However, calcium ions only slightly reduce the equilibrium swelling under sodium-rich conditions. Adverse effects Common side effects can include: Mild stomach painBloating GasSeek medical attention if: severe stomach cramps rectal bleeding no bowel movement within 3 days after using polycarbophil References == Further reading ==

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 provide a brief overview of 'Immunoglobulin therapy' in a medical context?

Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat a number of health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinating polyneuropathy, Kawasaki disease, certain cases of HIV/AIDS and measles, Guillain-Barré syndrome, and certain other infections when a more specific immunoglobulin is not available. Depending on the formulation it can be given by injection into muscle, a vein, or under the skin. The effects last a few weeks.Common side effects include pain at the site of injection, muscle pain, and allergic reactions. Other severe side effects include kidney problems, anaphylaxis, blood clots, and red blood cell breakdown. Use is not recommended in people with some types of IgA deficiency. Use appears to be relatively safe during pregnancy. Human immunoglobulin is made from human blood plasma. It contains antibodies against many viruses.Human immunoglobulin therapy first occurred in the 1930s and a formulation for injection into a vein was approved for medical use in the United States in 1981. It is on the World Health Organizations List of Essential Medicines. Each formulation of product is somewhat different. A number of specific immunoglobulin formulations are also available including for hepatitis B, rabies, tetanus, varicella infection, and Rh positive blood exposure. Medical uses Immunoglobulin therapy is used in a variety of conditions, many of which involve decreased or abolished antibody production capabilities, which range from a complete absence of multiple types of antibodies, to IgG subclass deficiencies (usually involving IgG2 or IgG3), to other disorders in which antibodies are within a normal quantitative range, but lacking in quality – unable to respond to antigens as they normally should – resulting in an increased rate or increased severity of infections. In these situations, immunoglobulin infusions confer passive resistance to infection on their recipients by increasing the quantity/quality of IgG they possess. Immunoglobulin therapy is also used for a number of other conditions, including in many autoimmune disorders such as dermatomyositis in an attempt to decrease the severity of symptoms. Immunoglobulin therapy is also used in some treatment protocols for secondary immunodeficiencies such as human immunodeficiency virus (HIV), some autoimmune disorders (such as immune thrombocytopenia and Kawasaki disease), some neurological diseases (multifocal motor neuropathy, stiff person syndrome, multiple sclerosis and myasthenia gravis) some acute infections and some complications of organ transplantation.Immunoglobulin therapy is especially useful in some acute infection cases such as pediatric HIV infection and is also considered the standard of treatment for some autoimmune disorders such as Guillain–Barré syndrome. The high demand which coupled with the difficulty of producing immunoglobulin in large quantities has resulted in increasing global shortages, usage limitations and rationing of immunoglobulin. United Kingdom The United Kingdoms National Health Service recommends the routine use of immunoglobulin for a variety of conditions including primary immunodeficiencies and a number of other conditions, but recommends against the use of immunoglobulin in sepsis (unless a specific toxin has been identified), multiple sclerosis, neonatal sepsis, and pediatric HIV/AIDS. United States The American Academy of Allergy, Asthma, and Immunology supports the use of immunoglobulin for primary immunodeficiencies, while noting that such usage actually accounts for a minority of usage and acknowledging that immunoglobulin supplementation can be appropriately used for a number of other conditions, including neonatal sepsis (citing a sixfold decrease in mortality), considered in cases of HIV (including pediatric HIV), considered as a second line treatment in relapsing-remitting multiple sclerosis, but recommending against its use in such conditions as chronic fatigue syndrome, PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) until further evidence to support its use is found (though noting that it may be useful in PANDAS patients with an autoimmune component), cystic fibrosis, and a number of other conditions.Brands include Asceniv (immune globulin intravenous, human – slra) Bivigam (immune globulin intravenous – human 10% liquid) Gamunex-C, (immune globulin injection human) Hizentra (immune globulin subcutaneous human) Hyqvia (immune globulin 10 percent – human with recombinant human hyaluronidase) Octagam (immune globulin intravenous, human) Panzyga (immune globulin intravenous, human – ifas) Xembify (immune globulin subcutaneous, human – klhw) Canada The National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services have also developed their own separate set of guidelines for the appropriate use of immunoglobulin therapy, which strongly support the use of immunoglobulin therapy in primary immunodeficiencies and some complications of HIV, while remaining silent on the issues of sepsis, multiple sclerosis, and chronic fatigue syndrome. Australia The Australian Red Cross Blood Service developed their own guidelines for the appropriate use of immunoglobulin therapy in 1997. Immunoglobulin is funded under the National Blood Supply and indications are classified as either an established or emerging therapeutic role or conditions for which immunoglobulin use is in exceptional circumstances only.Subcutaneous immunoglobulin access programs have been developed to facilitate hospital based programs.Human normal immunoglobulin (human immunoglobulin G) (Cutaquig) was approved for medical use in Australia in May 2021. European Union Brands include HyQvia (human normal immunoglobulin), Privigen (human normal immunoglobulin (IVIg)), Hizentra (human normal immunoglobulin (SCIg)), Kiovig (human normal immunoglobulin), and Flebogamma DIF (human normal immunoglobulin).In the EU human normal immunoglobulin (SCIg) (Hizentra) is used in people whose blood does not contain enough antibodies (proteins that help the body to fight infections and other diseases), also known as immunoglobulins. It is used to treat the following conditions: primary immunodeficiency syndromes (PID, when people are born with an inability to produce enough antibodies); low levels of antibodies in the blood in people with chronic lymphocytic leukaemia (a cancer of a type of white blood cell) or myeloma (a cancer of another type of white blood cell) and who have frequent infections; low levels of antibodies in the blood in people before or after allogeneic haematopoietic stem cell transplantation (a procedure where the patients bone marrow is cleared of cells and replaced by stem cells from a donor); chronic inflammatory demyelinating polyneuropathy (CIDP). In this rare disease, the immune system (the bodys defence system) works abnormally and destroys the protective covering over the nerves.It is indicated for replacement therapy in adults and children in primary immunodeficiency syndromes such as: congenital agammaglobulinaemia and hypogammaglobulinaemia (low levels of antibodies); common variable immunodeficiency; severe combined immunodeficiency; immunoglobulin-G-subclass deficiencies with recurrent infections; replacement therapy in myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections.Flebogamma DIF is indicated for the replacement therapy in adults, children and adolescents (0–18 years) in: primary immunodeficiency syndromes with impaired antibody production; hypogammaglobulinaemia (low levels of antibodies) and recurrent bacterial infections in patients with chronic lymphocytic leukaemia (a cancer of a type of white blood cell), in whom prophylactic antibiotics have failed; hypogammaglobulinaemia (low levels of antibodies) and recurrent bacterial infections in plateau-phase-multiple-myeloma (another cancer of a type of white blood cell) patients who failed to respond to pneumococcal immunisation; hypogammaglobulinaemia (low levels of antibodies) in patients after allogenic haematopoietic-stem-cell transplantation (HSCT) (when the patient receives stem cells from a matched donor to help restore the bone marrow); congenital acquired immune deficiency syndrome (AIDS) with recurrent bacterial infections.and for the immunomodulation in adults, children and adolescents (0–18 years) in: primary immune thrombocytopenia (ITP), in patients at high risk of bleeding or prior to surgery to correct the platelet count; Guillain–Barré syndrome, which causes multiple inflammations of the nerves in the body; Kawasaki disease, which causes multiple inflammation of several organs in the body. Side effects Although immunoglobulin is frequently used for long periods of time and is generally considered safe, immunoglobulin therapy can have severe adverse effects, both localized and systemic. Subcutaneous administration of immunoglobulin is associated with a lower risk of both systemic and localized risk when compared to intravenous administration (hyaluronidase-assisted subcutaneous administration is associated with a greater frequency of adverse effects than traditional subcutaneous administration but still a lower frequency of adverse effects when compared to intravenous administration). Patients who are receiving immunoglobulin and experience adverse events are sometimes recommended to take acetaminophen and diphenhydramine before their infusions to reduce the rate of adverse effects. Additional premedication may be required in some instances (especially when first getting accustomed to a new dosage), prednisone or another oral steroid.Local side effects of immunoglobulin infusions most frequently include an injection site reaction (reddening of the skin around the injection site), itching, rash, and hives. Less serious systemic side effects to immunoglobulin infusions include an increased heart rate, hyper or hypotension, an increased body temperature, diarrhea, nausea, abdominal pain, vomiting, arthralgia or myalgia, dizziness, headache, fatigue, fever, and pain.Serious side effects of immunoglobulin infusions include chest discomfort or pain, myocardial infarction, tachycardia, hyponatremia, hemolysis, hemolytic anemia, thrombosis, hepatitis, anaphylaxis, backache, aseptic meningitis, acute kidney injury, hypokalemic nephropathy, pulmonary embolism, and transfusion related acute lung injury. There is also a small chance that even given the precautions taken in preparing immunoglobulin preparations, an immunoglobulin infusion may pass a virus to its recipient. Some immunoglobulin solutions also contain isohemagglutinins, which in rare circumstances can cause hemolysis by the isohemagglutinins triggering phagocytosis.In the case of less serious side effects, a patients infusion rate can be adjusted downwards until the side effects become tolerable, while in the case of more serious side effects, emergency medical attention should be sought.Immunoglobulin therapy also interferes with the ability of the body to produce a normal immune response to an attenuated live virus vaccine for up to a year, can result in falsely elevated blood glucose levels, and can interfere with many of the IgG-based assays often used to diagnose a patient with a particular infection. Routes of administration 1950s – intramuscular After immunoglobulin therapys discovery and description in Pediatrics in 1952, weekly intramuscular injections of immunoglobulin (IMIg) were the norm until intravenous formulations (IVIg) began to be introduced in the 1980s. During the mid and late 1950s, one-time IMIg injections were a common public health response to outbreaks of polio before the widespread availability of vaccines. Intramuscular injections were extremely poorly tolerated due to their extreme pain and poor efficacy – rarely could intramuscular injections alone raise plasma immunoglobulin levels enough to make a clinically meaningful difference. 1980s – intravenous Intravenous formulations began to be approved in the 1980s, which represented a significant improvement over intramuscular injections, as they allowed for a sufficient amount of immunoglobulin to be injected to reach clinical efficacy, although they still had a fairly high rate of adverse effects (though the addition of stabilizing agents reduced this further). 1990s – subcutaneous The first description of a subcutaneous route of administration for immunoglobulin therapy dates back to 1980, but for many years subcutaneous administration was considered to be a secondary choice, only to be considered when peripheral venous access was no longer possible or tolerable.During the late 1980s and early 1990s, it became obvious that for at least a subset of patients the systemic adverse events associated with intravenous therapy were still not easily tolerable, and more doctors began to experiment with subcutaneous immunoglobulin administration, culminating in an ad hoc clinical trial in Sweden of 3000 subcutaneous injections administered to 25 adults (most of whom had previously experienced systemic adverse effects with IMIg or IVIg), where no infusion in the ad hoc trial resulted in a severe systemic adverse reaction, and most subcutaneous injections were able to be administered in non-hospital settings, allowing for considerably more freedom for the people involved.In the later 1990s, large-scale trials began in Europe to test the feasibility of subcutaneous immunoglobulin administration, although it was not until 2006 that the first subcutaneous-specific preparation of immunoglobulin was approved by a major regulatory agency (Vivaglobin, which was voluntarily discontinued in 2011). A number of other trade names of subcutaneous immunoglobulin have since been approved, although some small-scale studies have indicated that a particular cohort of patients with common variable immunodeficiency (CVID) may develop intolerable side effects with subcutaneous immunoglobulin (SCIg) that they do not with intravenous immunoglobulin (IVIg).Although intravenous was the preferred route for immunoglobulin therapy for many years, in 2006, the US Food and Drug Administration (FDA) approved the first preparation of immunoglobulin that was designed exclusively for subcutaneous use. Mechanism of action The precise mechanism by which immunoglobulin therapy suppresses harmful inflammation is likely multifactorial. For example, it has been reported that immunoglobulin therapy can block Fas-mediated cell death.Perhaps a more popular theory is that the immunosuppressive effects of immunoglobulin therapy are mediated through IgGs Fc glycosylation. By binding to receptors on antigen presenting cells, IVIG can increase the expression of the inhibitory Fc receptor, FcgRIIB, and shorten the half-life of auto-reactive antibodies. The ability of immunoglobulin therapy to suppress pathogenic immune responses by this mechanism is dependent on the presence of a sialylated glycan at position CH2-84.4 of IgG. Specifically, de-sialylated preparations of immunoglobulin lose their therapeutic activity and the anti-inflammatory effects of IVIG can be recapitulated by administration of recombinant sialylated IgG1 Fc.Sialylated-Fc-dependent mechanism was not reproduced in other experimental models suggesting that this mechanism is functional under a particular disease or experimental settings. On the other hand, several other mechanisms of action and the actual primary targets of immunoglobulin therapy have been reported. In particular, F(ab)2-dependent action of immunoglobulin to inhibit activation of human dendritic cells, induction of autophagy, induction of COX-2-dependent PGE-2 in human dendritic cells leading to expansion of regulatory T cells, inhibition of pathogenic Th17 responses, and induction of human basophil activation and IL-4 induction via anti-IgE autoantibodies. Some believe that immunoglobulin therapy may work via a multi-step model where the injected immunoglobulin first forms a type of immune complex in the patient. Once these immune complexes are formed, they can interact with Fc receptors on dendritic cells, which then mediate anti-inflammatory effects helping to reduce the severity of the autoimmune disease or inflammatory state. Other proposed mechanisms include the possibility that donor antibodies may bind directly with the abnormal host antibodies, stimulating their removal; the possibility that IgG stimulates the hosts complement system, leading to enhanced removal of all antibodies, including the harmful ones; and the ability of immunoglobulin to block the antibody receptors on immune cells (macrophages), leading to decreased damage by these cells, or regulation of macrophage phagocytosis. Indeed, it is becoming more clear that immunoglobulin can bind to a number of membrane receptors on T cells, B cells, and monocytes that are pertinent to autoreactivity and induction of tolerance to self.A recent report stated that immunoglobulin application to activated T cells leads to their decreased ability to engage microglia. As a result of immunoglobulin treatment of T cells, the findings showed reduced levels of tumor necrosis factor-alpha and interleukin-10 in T cell-microglia co-culture. The results add to the understanding of how immunoglobulin may affect inflammation of the central nervous system in autoimmune inflammatory diseases. Hyperimmune globulin Hyperimmune globulins are a class of immunoglobulins prepared in a similar way as for normal human immunoglobulin, except that the donor has high titers of antibody against a specific organism or antigen in their plasma. Some agents against which hyperimmune globulins are available include hepatitis B, rabies, tetanus toxin, varicella-zoster, etc. Administration of hyperimmune globulin provides "passive" immunity to the patient against an agent. This is in contrast to vaccines that provide "active" immunity. However, vaccines take much longer to achieve that purpose while hyperimmune globulin provides instant "passive" short-lived immunity. Hyperimmune globulin may have serious side effects, thus usage is taken very seriously.Hyperimmune serum is blood plasma containing high amounts of an antibody. It has been hypothesised that hyperimmune serum may be an effective therapy for persons infected with the Ebola virus. Society and culture Economics In the United Kingdom a dose cost the NHS between 11.20 and 1,200.00 pounds depending on the type and amount. Brand names As biologicals, various trade names of immunoglobulin products are not necessarily interchangeable, and care must be exercised when changing between them. Trade names of intravenous immunoglobulin formulations include Flebogamma, Gamunex, Privigen, Octagam and Gammagard, while trade names of subcutaneous formulations include Cutaquig, Cuvitru, HyQvia, Hizentra, Gamunex-C, and Gammaked. Supply issues The United States is one of a handful of countries that allow plasma donors to be paid, meaning that the US supplies much of the plasma-derived medicinal products (including immunoglobulin) used across the world, including more than 50% of the European Unions supply. The Council of Europe has officially endorsed the idea of not paying for plasma donations for both ethical reasons and reasons of safety, but studies have found that relying on entirely voluntary plasma donation leads to shortages of immunoglobulin and forces member countries to import immunoglobulin from countries that do compensate donors.In Australia, blood donation is voluntary and therefore to cope with increasing demand and to reduce the shortages of locally produced immunoglobulin, several programs have been undertaken including adopting plasma for first time blood donors, better processes for donation, plasma donor centres and encouraging current blood donors to consider plasma only donation. Research Experimental results from a small clinical trial in humans suggested protection against the progression of Alzheimers disease, but no such benefit was found in a subsequent phase III clinical trial. In May 2020, the US approved a phase three clinical trial on the efficacy and safety of high-concentration intravenous immune globulin therapy in severe COVID-19. References External links "Immune globulin". 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.

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

Hydroxycarbamide, also known as hydroxyurea, is a medication used in sickle-cell disease, essential thrombocythemia, chronic myelogenous leukemia and cervical cancer. In sickle-cell disease it increases fetal hemoglobin and decreases the number of attacks. It is taken by mouth.Common side effects include bone marrow suppression, fevers, loss of appetite, psychiatric problems, shortness of breath, and headaches. There is also concern that it increases the risk of later cancers. Use during pregnancy is typically harmful to the baby. Hydroxycarbamide is in the antineoplastic family of medications. It is believed to work by blocking the making of DNA.Hydroxycarbamide was approved for medical use in the United States in 1967. It is on the World Health Organizations List of Essential Medicines. Hydroxycarbamide is available as a generic medication. Medical uses Hydroxycarbamide is used for the following indications: Myeloproliferative disease (primarily essential thrombocythemia and polycythemia vera). It has been found to be superior to anagrelide for the control of ET. Sickle-cell disease (increases production of fetal hemoglobin that then interferes with the hemoglobin polymerisation as well as by reducing white blood cells that contribute to the general inflammatory state in sickle cell patients.) Second line treatment for psoriasis (slows down the rapid division of skin cells) Systemic mastocytosis Chronic myelogenous leukemia (largely replaced by imatinib, but still in use for its cost-effectiveness) Side effects Reported side effects are: neurological reactions (e.g., headache, dizziness, drowsiness, disorientation, hallucinations, and convulsions), nausea, vomiting, diarrhea, constipation, mucositis, anorexia, stomatitis, bone marrow toxicity (dose-limiting toxicity; may take 7–21 days to recover after the drug has been discontinued), megaloblastic anemia, thrombocytopenia, bleeding, hemorrhage, gastrointestinal ulceration and perforation, immunosuppression, leukopenia, alopecia (hair loss), skin rashes (e.g., maculopapular rash), erythema, pruritus, vesication or irritation of the skin and mucous membranes, pulmonary edema, abnormal liver enzymes, creatinine and blood urea nitrogen.Due to its negative effect on the bone marrow, regular monitoring of the full blood count is vital, as well as early response to possible infections. In addition, renal function, uric acid and electrolytes, as well as liver enzymes, are commonly checked. Moreover, because of this, its use in people with leukopenia, thrombocytopenia or severe anemia is contraindicated.Hydroxycarbamide has been used primarily for the treatment of myeloproliferative diseases, which has an inherent risk of transforming to acute myeloid leukemia. There has been a longstanding concern that hydroxycarbamide itself carries a leukemia risk, but large studies have shown that the risk is either absent or very small. Nevertheless, it has been a barrier for its wider use in patients with sickle-cell disease. Mechanism of action Hydroxycarbamide decreases the production of deoxyribonucleotides via inhibition of the enzyme ribonucleotide reductase by scavenging tyrosyl free radicals as they are involved in the reduction of nucleoside diphosphates (NDPs).In the treatment of sickle-cell disease, hydroxycarbamide increases the concentration of fetal hemoglobin. The precise mechanism of action is not yet clear, but it appears that hydroxycarbamide increases nitric oxide levels, causing soluble guanylyl cyclase activation with a resultant rise in cyclic GMP, and the activation of gamma globin gene expression and subsequent gamma chain synthesis necessary for fetal hemoglobin (HbF) production (which does not polymerize and deform red blood cells like the mutated HbS, responsible for sickle cell disease). Adult red cells containing more than 1% HbF are termed F cells. These cells are progeny of a small pool of immature committed erythroid precursors (BFU-e) that retain the ability to produce HbF. Hydroxyurea also suppresses the production of granulocytes in the bone marrow which has a mild immunosuppressive effect particularly at vascular sites where sickle cells have occluded blood flow. Natural occurrence Hydroxyurea has been reported as endogenous in human blood plasma at concentrations of approximately 30 to 200 ng/ml. Chemistry Hydroxyurea has been prepared in many different ways since its initial synthesis in 1869. Medical chemists, Dresler and Stein created Hydroxyurea from hydroxylamine, hydrochloric acid and potassium cyanide as a technical exercise in organic chemistry, as part of a series of experiments generating derivatives of urea. Hydroxyurea lay dormant for more than fifty years until it was studied as part of an investigation into the toxicity of protein metabolites. Due to its chemical properties hydroxyurea was explored as an antisickling agent in the treatment of hematological conditions. One common mechanism for synthesizing hydroxyurea is by the reaction of calcium cyanate with hydroxylamine nitrate in absolute ethanol and by the reaction of salt (i.e. sodium or potassium) cyanates and hydroxylamine hydrochloride in aqueous solution. Hydroxyurea has also been prepared by converting a quaternary ammonium anion exchange resin from the chloride form to the cyanate form with sodium cyanate and reacting the resin in the cyanate form with hydroxylamine hydrochloride. This method of hydroxyurea synthesis was patented by Hussain et al. (2015). Pharmacology Hydroxyurea is a monohydroxyl-substituted urea (hydroxycarbamate) antimetabolite. Similar to other antimetabolite anti-cancer drugs, it acts by disrupting the DNA replication process of dividing cancer cells in the body. Hydroxyurea selectively inhibits ribonucleoside diphosphate reductase, an enzyme required to convert ribonucleoside diphosphates into deoxyribonucleoside diphosphates, thereby preventing cells from leaving the G1/S phase of the cell cycle. This agent also exhibits radiosensitizing activity by maintaining cells in the radiation-sensitive G1 phase and interfering with DNA repair.Biochemical research has explored its role as a DNA replication inhibitor which causes deoxyribonucleotide depletion and results in DNA double strand breaks near replication forks (see DNA repair). Repair of DNA damaged by chemicals or irradiation is also inhibited by hydroxyurea, offering potential synergy between hydroxyurea and radiation or alkylating agents.Hydroxyurea has many pharmacological applications under the Medical Subject Headings classification system: Antineoplastic Agents – Substances that inhibit or prevent the proliferation of neoplasms. Antisickling Agents – Agents used to prevent or reverse the pathological events leading to sickling of erythrocytes in sickle cell conditions. Nucleic Acid Synthesis Inhibitors – Compounds that inhibit cell production of DNA or RNA. Enzyme Inhibitors – Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Cytochrome P-450 CYP2D6 Inhibitors – Acts as an inhibitor to one of the most important enzymes involved in the metabolism of xenobiotics in the body, CYP2D6 a member of the cytochrome P450 mixed oxidase system. Society and culture Brand names Brand names include: Hydrea, Litalir, Droxia, and Siklos. References External links "Hydroxyurea". Drug Information Portal. U.S. National Library of Medicine.

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Can you break down the meaning of the medical term 'Multiple chemical sensitivity' for me?

Multiple chemical sensitivity (MCS), also known as idiopathic environmental intolerances (IEI), is an unrecognized and controversial diagnosis characterized by chronic symptoms attributed to exposure to low levels of commonly used chemicals. Symptoms are typically vague and non-specific. They may include fatigue, headaches, nausea, and dizziness. Although these symptoms can be debilitating, MCS is not recognized as an organic, chemical-caused illness by the World Health Organization, American Medical Association, nor any of several other professional medical organizations. Blinded clinical trials show that people with MCS react as often and as strongly to placebos as they do to chemical stimuli; the existence and severity of symptoms is seemingly related to the perception that a chemical stimulus is present.Commonly attributed substances include scented products (e.g. perfumes), pesticides, plastics, synthetic fabrics, smoke, petroleum products, and paint fumes. Symptoms Symptoms are typically vague and non-specific, such as fatigue or headaches. These symptoms, although they can be disabling, are called non-specific because they are not associated with any single specific medical condition. A 2010 review of MCS literature said that the following symptoms, in this order, were the most reported in the condition: headache, fatigue, confusion, depression, shortness of breath, arthralgia, myalgia, nausea, dizziness, memory problems, gastrointestinal symptoms, respiratory symptoms.Symptoms mainly arise from the autonomic nervous system (such as nausea or dizziness) or have psychiatric or psychological aspects (such as difficulty concentrating). Possible causes Various different causes for MCS have been hypothesized.There is a general agreement among most MCS researchers that the cause is not specifically related to sensitivity to chemicals, but this does not preclude the possibility that symptoms are caused by other known or unknown factors. Various health care professionals and government agencies are working on giving those who report the symptoms proper care while searching for a cause.In 2017, a Canadian government Task Force on Environmental Health said that there had been very little rigorous peer-reviewed research into MCS and almost a complete lack of funding for such research in North America. "Most recently," it said, "some peer-reviewed clinical research has emerged from centres in Italy, Denmark and Japan suggesting that there are fundamental neurobiologic, metabolic, and genetic susceptibility factors that underlie ES/MCS."The US Occupational Safety and Health Administration (OSHA) says that MCS is highly controversial and that there is insufficient scientific evidence to explain the relationship between any of the suggested causes of MCS – it lists "allergy, dysfunction of the immune system, neurobiological sensitization, and various psychological theories" as the suggested causes – and its symptoms. Immunological Researchers have studied immunity biomarkers in people with MCS to determine whether MCS could be an autoimmune disorder or allergic response, but the results have been inconclusive. Some people with MCS appear to have excess production of inflammatory cytokines, but this phenomenon is not specific to MCS and overall there is no evidence that low-level chemical exposure causes an immune response. Genetic It has been hypothesized that there is a heritable genetic trait which pre-disposes people to be hypersensitive to low-level chemical exposure and so develop MCS. To investigate, researchers compared the genetic makeup of people with MCS, to people without. The results were generally inconclusive and contradictory, thus failing to support the hypothesis.Gaétan Carrier and colleagues write that the genetic hypothesis appears implausible when the evidence around it is judged by the Bradford Hill criteria. Psychological Several mechanisms for a psychological etiology of the condition have been proposed, including theories based on misdiagnoses of an underlying mental illness, stress, or classical conditioning. Many people with MCS also meet the criteria for major depressive disorder or anxiety disorder. Other proposed explanations include somatic symptom disorder, panic disorder, migraine, chronic fatigue syndrome, or fibromyalgia and brain fog. Through behavioral conditioning, it has been proposed that people with MCS may develop real, but unintentionally psychologically produced, symptoms, such as anticipatory nausea, when they encounter certain odors or other perceived triggers. It has also been proposed in one study that individuals may have a tendency to "catastrophically misinterpret benign physical symptoms" or simply have a disturbingly acute sense of smell. The personality trait absorption, in which individuals are predisposed to becoming deeply immersed in sensory experiences, may be stronger in individuals reporting symptoms of MCS. In the 1990s, behaviors exhibited by MCS sufferers were hypothesized by some to reflect broader sociological fears about industrial pollution and broader societal trends of technophobia and chemophobia.These theories have attracted criticism.In Canada, in 2017, following a three-year government inquiry into environmental illness, it was recommended that a public statement be made by the health department.A 2018 systematic review concluded that the evidence suggests that abnormalities in sensory processing pathways combined with peculiar personality traits best explains this condition. Diagnosis In practice, diagnosis relies entirely upon the self-reported claim that symptoms are triggered by exposure to various substances.Many other tests have been promoted by various people over the years, including testing of the immune system, porphyrin metabolism, provocation-neutralization testing, autoantibodies, the Epstein–Barr virus, testing for evidence of exposure to pesticides or heavy metals, and challenges involving exposure to chemicals, foods, or inhalants. None of these tests correlate with MCS symptoms, and none are useful for diagnosing MCS.The stress and anxiety experienced by people reporting MCS symptoms are significant. Neuropsychological assessments do not find differences between people reporting MCS symptoms and other people in areas such as verbal learning, memory functioning, or psychomotor performance. Neuropsychological tests are sensitive but not specific, and they identify differences that may be caused by unrelated medical, neurological, or neuropsychological conditions.Another major goal for diagnostic work is to identify and treat any other medical conditions the person may have. People reporting MCS-like symptoms may have other health issues, ranging from common conditions, such as depression or asthma, to less common circumstances, such a documented chemical exposure during a work accident. These other conditions may or may not have any relationship to MCS symptoms, but they should be diagnosed and treated appropriately, whenever the patient history, physical examination, or routine medical tests indicates their presence. The differential diagnosis list includes solvent exposure, occupational asthma, and allergies. Definitions Different researchers and proponents use different definitions, which complicates research and can affect diagnosis. For example, the 1987 definition that requires symptoms to begin suddenly after an identifiable, documented exposure to a chemical, but the 1996 definition by the WHO/ICPS says that the cause can be anything, including other medical conditions or psychological factors.In 1996, an expert panel at WHO/ICPS was set up to examine MCS. The panel accepted the existence of "a disease of unclear pathogenesis", rejected the claim that MCS was caused by chemical exposure, and proposed these three diagnostic requirements for what they re-named idiopathic environmental intolerances (IEI): the disease was acquired (not present from birth) and must produce multiple relapsing symptoms; the symptoms must be closely related to "multiple environmental influences, which are well tolerated by the majority of the population"; and it could not be explained by any other medical condition.In Japan, MCS is called chemical hypersensitivity or chemical intolerance (化学物質過敏症; kagaku bushitsu kabinsho), and the 1999 Japanese definition requires one or more of four major symptoms – headaches; malaise and fatigue; muscle pain; joint pain – combined with laboratory findings and/or some minor symptoms, such as mental effects or skin conditions. The defined lab findings are abnormalities in parasympathetic nerves, cerebral cortical dysfunction diagnosed by SPECT testing, visuospatial abnormalities, abnormalities of eye movement, or a positive provocation test. International Statistical Classification of Diseases The International Statistical Classification of Diseases and Related Health Problems (ICD), maintained by the World Health Organization, is a medical coding system used for medical billing and statistical purposes – not for deciding whether any person is sick, or whether any collection of symptoms constitutes a single disease. The ICD does not list MCS as a discrete disease. However, this does not mean that people with MCS-related symptoms cannot be treated or billed for medical services. For example, the public health service in Germany permits healthcare providers to bill for MCS-related medical services under the ICD-10 code T78.4, which is for idiosyncratic reactions, classified under the heading T78, Unerwünschte Nebenwirkungen, anderenorts nicht klassifiziert ("adverse reactions, not otherwise specified"). Being able to get paid for medical services and collect statistics about unspecified, idiosyncratic reactions does not mean that MCS is recognized as a specific disease or that any particular cause has been defined by the German government. Healthcare providers can also bill for MCS-related services under the ICD-10 codes of F45.0 for somatization disorder. MCS is named in evidence-based ("S3") guidelines for the management of patients with nonspecific, functional, and somatoform physical symptoms. Management There is no single proven treatment for MCS. The goal of treatment is to improve quality of life, with fewer distressing symptoms and the ability to maintain employment and social relationships, rather than to produce a permanent cure.A multidisciplinary treatment approach is recommended. It should take into account the uncommon personality traits often seen in affected individuals and physiological abnormalities in sensory pathways and the limbic system. There is also no scientific consensus on supportive therapies for MCS, "but the literature agrees on the need for patients with MCS to avoid the specific substances that trigger reactions for them and also on the avoidance of xenobiotics in general, to prevent further sensitization.": 17 Common self-care strategies include avoiding exposure to known triggers and emotional self-care. Healthcare providers can provide useful education on the bodys natural ability to eliminate and excrete toxins on its own and support positive self-care efforts. Avoiding triggers, such as by removing smelly cleaning products from the home, can reduce symptoms and increase the persons sense of being able to reclaim a reasonably normal life. However, for other people with MCS, their efforts to avoid suspected triggers will backfire, and instead produce harmful emotional side effects that interfere with the overall goal of reducing distress and disability. Treatments that have not been scientifically validated, such as detoxification, have been used by MCS patients. Unproven treatments can be expensive, may cause side effects, and may be counterproductive. Epidemiology Prevalence rates for MCS vary according to the diagnostic criteria used. The condition is reported across industrialized countries and it affects women more than men.: 37 In 2018, the same researchers reported that the prevalence rate of diagnosed MCS had increased by more than 300% and self-reported chemical sensitivity by more than 200% in the previous decade. They found that 12.8% of those surveyed reported medically diagnosed MCS and 25.9% reported having chemical sensitivities.A 2014 study by the Canadian Ministry of Health estimated, based on its survey, that 0.9% of Canadian males and 3.3% of Canadian females had a diagnosis of MCS by a health professional.: 37 While a 2018 study at the University of Melbourne found that 6.5% of Australian adults reported having a medical diagnosis of MCS and that 18.9 per cent reported having adverse reactions to multiple chemicals. The study also found that for 55.4% of those with MCS, the symptoms triggered by chemical exposures could be disabling. Gulf War syndrome Symptoms attributed to Gulf War syndrome are similar to those reported for MCS, including headache, fatigue, muscle stiffness, joint pain, inability to concentrate, sleep problems, and gastrointestinal issues.A population-based, cross-sectional epidemiological study involving American veterans of the Gulf War, non-Gulf War veterans, and non-deployed reservists enlisted both during Gulf War era and outside the Gulf War era concluded the prevalence of MCS-type symptoms in Gulf War veterans was somewhat higher than in non-Gulf War veterans. After adjusting for potentially confounding factors (age, sex, and military training), there was a robust association between individuals with MCS-type symptoms and psychiatric treatment (either therapy or medication) before deployment and, therefore, before any possible deployment-connected chemical exposures.The odds of reporting MCS or chronic multiple-symptom illness was 3.5 times greater for Gulf War veterans than non-Gulf veterans. Gulf War veterans have an increased rate of being diagnosed with multiple-symptom conditions compared to military personnel deployed to other conflicts. Prognosis About half of those who claim to be affected by MCS get better over the course of several years, while about half continue to experience distressing symptoms. History MCS was first proposed as a distinct disease by Theron G. Randolph in 1950. In 1965, Randolph founded the Society for Clinical Ecology as an organization to promote his ideas about symptoms reported by his patients. As a consequence of his insistence upon his own, non-standard definition of allergy and his unusual theories about how the immune system and toxins affect people, the ideas he promoted were widely rejected, and clinical ecology emerged as a non-recognized medical specialty.Since the 1950s, many hypotheses have been advanced for the science surrounding multiple chemical sensitivity.In the 1990s, an association was noted with chronic fatigue syndrome, fibromyalgia, and Gulf War syndrome.In 1994, the AMA, American Lung Association, US EPA and the US Consumer Product Safety Commission published a booklet on indoor air pollution that discusses MCS, among other issues. The booklet further states that a pathogenesis of MCS has not been definitively proven, and that symptoms that have been self-diagnosed by a patient as related to MCS could actually be related to allergies or have a psychological basis, and recommends that physicians should counsel patients seeking relief from their symptoms that they may benefit from consultation with specialists in these fields.In 1995, an Interagency Workgroup on Multiple Chemical Sensitivity was formed under the supervision of the Environmental Health Policy Committee within the United States Department of Health and Human Services to examine the body of research that had been conducted on MCS to that date. The work group included representatives from the Centers for Disease Control and Prevention, United States Environmental Protection Agency, United States Department of Energy, Agency for Toxic Substances and Disease Registry, and the National Institutes of Health. The Predecisional Draft document generated by the workgroup in 1998 recommended additional research in the basic epidemiology of MCS, the performance of case-comparison and challenge studies, and the development of a case definition for MCS. However, the workgroup also concluded that it was unlikely that MCS would receive extensive financial resources from federal agencies because of budgetary constraints and the allocation of funds to other, extensively overlapping syndromes with unknown cause, such as chronic fatigue syndrome, fibromyalgia, and Gulf War syndrome. The Environmental Health Policy Committee is currently inactive, and the workgroup document has not been finalized.The different understandings of MCS over the years have also resulted in different proposals for names. For example, in 1996 the International Programme on Chemical Safety proposed calling it idiopathic environmental illness, because of their belief that chemical exposure may not the sole cause, while another researcher, whose definition includes people with allergies and acute poisoning, calls it chemical sensitivity. See also Electromagnetic hypersensitivity Sick building syndrome Sensory processing disorder Sensory processing sensitivity List of questionable diseases Environmental health Environmental medicine Indoor air quality Sense of smell#Disorders References External links Multiple Chemical Sensitivity Syndrome at the Merck Manual Professional Edition

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What does the medical term 'Thrombocytopenia' encompass?

Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in 20% of medical patients and a third of surgical patients.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. Values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000 per microliter. Thrombocytopenia can be contrasted with the conditions associated with an abnormally high level of platelets in the blood: thrombocythemia (when the cause is unknown), and thrombocytosis (when the cause is known). Signs and symptoms Thrombocytopenia usually has no symptoms and is picked up on a routine complete blood count. Some individuals with thrombocytopenia may experience external bleeding such as nosebleeds, or bleeding gums. Some women may have heavier or longer periods or breakthrough bleeding. Bruising, particularly purpura in the forearms and petechiae in the feet, legs, and mucous membranes, may be caused by spontaneous bleeding under the skin.Eliciting a full medical history is vital to ensure the low platelet count is not secondary to another disorder. Ensuring that the other blood cell types, such as red blood cells and white blood cells are not also suppressed, is also important. Painless, round, and pinpoint (1 to 3 mm in diameter) petechiae usually appear and fade, and sometimes group to form ecchymoses. Larger than petechiae, ecchymoses are purple, blue, or yellow-green areas of skin that vary in size and shape. They can occur anywhere on the body.A person with this disease may also complain of malaise, fatigue, and general weakness (with or without accompanying blood loss). Acquired thrombocytopenia may be associated with the use of certain drugs. Inspection typically reveals evidence of bleeding (petechiae or ecchymoses), along with slow, continuous bleeding from any injuries or wounds. Adults may have large, blood-filled bullae in the mouth. If the persons platelet count is between 30,000 and 50,000/mm3, bruising with minor trauma may be expected; if it is between 15,000 and 30,000/mm3, spontaneous bruising will be seen (mostly on the arms and legs). Causes Thrombocytopenia can be inherited or acquired. Decreased production Abnormally low platelet production may be caused by: Dehydration, Vitamin B12 or folic acid deficiency Leukemia, myelodysplastic syndrome, or aplastic anemia Decreased production of thrombopoietin by the liver in liver failure Sepsis, systemic viral or bacterial infection Leptospirosis Hereditary syndromesACTN1-related thrombocytopenia Amegakaryocytic thrombocytopenia with radio-ulnar synostosis ANKRD26 related thrombocytopenia Autosomal dominant thrombocytopenia Bernard–Soulier syndrome (associated with giant platelet disorder) Congenital amegakaryocytic thrombocytopenia Congenital amegakaryocytic thrombocytopenia and radioulnar synostosis CYCS-related thrombocytopenia Epstein syndrome (associated with giant platelet disorder) ETV6 related thrombocytopenia Fanconi anemia Filaminopathies A FYB related thrombocytopenia Glanzmanns thrombasthenia GNE myopathy with congenital thrombocytopenia Gray platelet syndrome (associated with giant platelet disorder) Harris platelet syndrome (associated with giant platelet disorder) Macrothrombocytopenia and hearing loss May–Hegglin anomaly (associated with giant platelet disorder) MYH9-related disease (associated with giant platelet disorder) PRKACG-related thrombocytopenia Paris-Trousseau thrombocytopenia/Jacobsen syndrome Sebastian syndrome SLFN14-related thrombocytopenia Stormorken syndrome TRPM7-related thrombocytopenia Thrombocytopenia absent radius syndrome Tropomyosin 4-related thrombocytopenia TUBB1-related thrombocytopenia Upshaw–Schulman syndrome Wiskott–Aldrich syndrome X-linked thrombocytopenia X-linked thrombocytopenia with thalassemia Increased destruction Abnormally high rates of platelet destruction may be due to immune or nonimmune conditions, including: Immune thrombocytopenic purpura Thrombotic thrombocytopenic purpura Hemolytic–uremic syndrome Disseminated intravascular coagulation Paroxysmal nocturnal hemoglobinuria Antiphospholipid syndrome Systemic lupus erythematosus Post-transfusion purpura Neonatal alloimmune thrombocytopenia Hypersplenism Dengue fever Gauchers disease Zika virus Medication-induced These medications can induce thrombocytopenia through direct myelosuppression: Valproic acid Methotrexate Carboplatin Interferon Isotretinoin Panobinostat H2 blockers and proton-pump inhibitors Other causes Lab error, possibly due to the anticoagulant EDTA in CBC specimen tubes; a citrated platelet count is a useful follow-up study Snakebite Niacin toxicity Lyme disease Thrombocytapheresis (also called plateletpheresis) Niemann–Pick disease Diagnosis Laboratory tests for thrombocytopenia might include full blood count, liver enzymes, kidney function, vitamin B12 levels, folic acid levels, erythrocyte sedimentation rate, and peripheral blood smear. If the cause for the low platelet count remains unclear, a bone marrow biopsy is usually recommended to differentiate cases of decreased platelet production from cases of peripheral platelet destruction.Thrombocytopenia in hospitalized alcoholics may be caused by spleen enlargement, folate deficiency, and most frequently, the direct toxic effect of alcohol on production, survival time, and function of platelets. Platelet count begins to rise after 2 to 5 days abstinence from alcohol. The condition is generally benign, and clinically significant hemorrhage is rare.In severe thrombocytopenia, a bone marrow study can determine the number, size, and maturity of the megakaryocytes. This information may identify ineffective platelet production as the cause of thrombocytopenia and rule out a malignant disease process at the same time. Treatment Treatment is guided by the severity and specific cause of the disease. Treatment focuses on eliminating the underlying problem, whether that means discontinuing drugs suspected to cause it or treating underlying sepsis. Diagnosis and treatment of serious thrombocytopenia is usually directed by a hematologist. Corticosteroids may be used to increase platelet production. Lithium carbonate or folate may also be used to stimulate platelet production in the bone marrow. Platelet transfusions Platelet transfusions may be suggested for people who have a low platelet count due to thrombocytopenia. Thrombotic thrombocytopenic purpura Treatment of thrombotic thrombocytopenic purpura (TTP) is a medical emergency, since the associated hemolytic anemia and platelet activation can lead to kidney failure and changes in the level of consciousness. Treatment of TTP was revolutionized in the 1980s with the application of plasmapheresis. According to the Furlan-Tsai hypothesis, this treatment works by removing antibodies against the von Willebrand factor-cleaving protease ADAMTS-13. The plasmapheresis procedure also adds active ADAMTS-13 protease proteins to the patient, restoring a normal level of von Willebrand factor multimers. Patients with persistent antibodies against ADAMTS-13 do not always manifest TTP, and these antibodies alone are not sufficient to explain how plasmapheresis treats TTP. Immune thrombocytopenic purpura Many cases of immune thrombocytopenic purpura (ITP) also known as idiopathic thrombocytopenic purpura, can be left untreated, and spontaneous remission (especially in children) is not uncommon. However, counts under 50,000 are usually monitored with regular blood tests, and those with counts under 10,000 are usually treated, as the risk of serious spontaneous bleeding is high with such low platelet counts. Any patient experiencing severe bleeding symptoms is also usually treated. The threshold for treating ITP has decreased since the 1990s; hematologists recognize that patients rarely spontaneously bleed with platelet counts greater than 10,000, although exceptions to this observation have been documented.Thrombopoetin analogues have been tested extensively for the treatment of ITP. These agents had previously shown promise, but had been found to stimulate antibodies against endogenous thrombopoietin or lead to thrombosis. Romiplostim (trade name Nplate, formerly AMG 531) was found to be safe and effective for the treatment of ITP in refractory patients, especially those who relapsed following splenectomy. Heparin-induced thrombocytopenia Discontinuation of heparin is critical in a case of heparin-induced thrombocytopenia (HIT). Beyond that, however, clinicians generally treat to avoid thrombosis. Treatment may include a direct thrombin inhibitor, such as lepirudin or argatroban. Other blood thinners sometimes used in this setting include bivalirudin and fondaparinux. Platelet transfusions are not routinely used to treat HIT because thrombosis, not bleeding, is the primary problem. Warfarin is not recommended until platelets have normalized. Congenital amegakaryocytic thrombocytopenia Bone marrow/stem cell transplants are the only known cures for this genetic disease. Frequent platelet transfusions are required to keep the patient from bleeding to death before the transplant can be performed, although this is not always the case. Human induced pluripotent stem cell-derived platelets Human induced pluripotent stem cell-derived platelets is a technology currently being researched by the private sector, in association with the Biomedical Advanced Research and Development Authority and the U.S. Department of Health and Human Services, that would create platelets outside the human body. Neonatal thrombocytopenia Thrombocytopenia affects a few newborns, and its prevalence in neonatal intensive care units is high. Normally, it is mild and resolves without consequences. Most cases affect preterm birth infants and result from placental insufficiency and/or fetal hypoxia. Other causes, such as alloimmunity, genetics, autoimmunity, and infection, are less frequent.Thrombocytopenia that starts after the first 72 hours since birth is often the result of underlying sepsis or necrotizing enterocolitis. In the case of infection, PCR tests may be useful for rapid pathogen identification and detection of antibiotic resistance genes. Possible pathogens include viruses (e.g. cytomegalovirus, rubella virus, HIV), bacteria (e.g. Staphylococcus spp., Enterococcus spp., Streptococcus agalactiae, Listeria monocytogenes, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Yersinia enterocolitica), fungi (e.g. Candida spp.), and Toxoplasma gondii. The severity of thrombocytopenia may be correlated with pathogen type; some research indicates that the most severe cases are related to fungal or Gram-negative bacterial infection. The pathogen may be transmitted during or before birth, by breast feeding, or during transfusion. Interleukin-11 is being investigated as a drug for managing thrombocytopenia, especially in cases of sepsis or necrotizing enterocolitis. References == External links ==

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

Could you provide a brief overview of 'Cerebro-costo-mandibular syndrome' in a medical context?

Cerebro-costo-mandibular syndrome is a very rare genetic disorder which is characterized by jaw/chin, palate and rib abnormalities. Signs and symptoms The following list comprises the most common symptoms people with this disorder exhibit: Severe micrognathia Thorax in the shape of a bell Cleft palate Neonatal respiratory difficulties Rib gapsCommon (but not the most) symptoms include: External auditory canal atresia Hearing loss Failure to thrive Glossoptosis Intellectual disabilities Fetal growth delays Kyphosis Short height TracheomalaciaNot common but also not rare symptoms include: Fifth finger clinodactyly Cerebral calcification Hydranencephaly Meningocele Microcephaly Polycystic kidney dysplasia Myelomeningocele Porencephalic cyst Short, hard palate Spina bifida Ventricular septal defect Webbed neck Causes This disorder is caused by autosomal dominant mutations in the SNRPB gene, in chromosome 20. Epidemiology Only 110 cases have been described in medical literature. == 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.

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

Uterine perforation is a potential complication of any intrauterine procedure. It may be associated with injury to surrounding blood vessels or viscera such as the bladder or intestine. If not diagnosed at the time of the procedure it can occasionally result in massive hemorrhage or sepsis; however, the majority of uterine perforations are sub-clinical and safely resolve by themselves without treatment and do not cause any significant long-term damage. Risk factors include cervical stenosis during trans-cervical procedures or decreased strength of the myometrial wall as in pregnancy or menopause. See also Uterine rupture 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've encountered the term 'Pulmonary heart disease' while reading about medical topics. What does it refer to exactly?

Pulmonary heart disease, also known as cor pulmonale, is the enlargement and failure of the right ventricle of the heart as a response to increased vascular resistance (such as from pulmonic stenosis) or high blood pressure in the lungs.Chronic pulmonary heart disease usually results in right ventricular hypertrophy (RVH), whereas acute pulmonary heart disease usually results in dilatation. Hypertrophy is an adaptive response to a long-term increase in pressure. Individual muscle cells grow larger (in thickness) and change to drive the increased contractile force required to move the blood against greater resistance. Dilatation is a stretching (in length) of the ventricle in response to acute increased pressure.To be classified as pulmonary heart disease, the cause must originate in the pulmonary circulation system; RVH due to a systemic defect is not classified as pulmonary heart disease. Two causes are vascular changes as a result of tissue damage (e.g. disease, hypoxic injury), and chronic hypoxic pulmonary vasoconstriction. If left untreated, then death may result. The heart and lungs are intricately related; whenever the heart is affected by a disease, the lungs risk following and vice versa. Signs and symptoms The symptoms/signs of pulmonary heart disease (cor pulmonale) can be non-specific and depend on the stage of the disorder, and can include blood backing up into the systemic venous system, including the hepatic vein. As pulmonary heart disease progresses, most individuals will develop symptoms like: Shortness of breath Wheezing Cyanosis Ascites Jaundice Enlargement of the liver Raised jugular venous pressure (JVP) Third heart sound Intercostal recession Presence of abnormal heart sounds Causes The causes of pulmonary heart disease (cor pulmonale) are the following: Acute respiratory distress syndrome (ARDS) COPD Primary pulmonary hypertension Blood clots in lungs Kyphoscoliosis Interstitial lung disease Cystic fibrosis Sarcoidosis Obstructive sleep apnea (untreated) Sickle cell anemia Bronchopulmonary dysplasia (in infants) Pathophysiology The pathophysiology of pulmonary heart disease (cor pulmonale) has always indicated that an increase in right ventricular afterload causes RV failure (pulmonary vasoconstriction, anatomic disruption/pulmonary vascular bed and increased blood viscosity are usually involved), however most of the time, the right ventricle adjusts to an overload in chronic pressure. According to Voelkel, et al., pressure overload is the initial step for changes in RV, other factors include: Ischemia Inflammation Oxidative damage Epigenetics Abnormal cardiac energetics Diagnosis Investigations available to determine the cause of cor pulmonale include the following: Chest x-ray – right ventricular hypertrophy, right atrial dilatation, prominent pulmonary artery ECG – right ventricular hypertrophy, dysrhythmia, P pulmonale (characteristic peaked P wave) Thrombophilia screen- to detect chronic venous thromboembolism (proteins C and S, antithrombin III, homocysteine levels) Differential diagnosis The diagnosis of pulmonary heart disease is not easy as both lung and heart disease can produce similar symptoms. Therefore, the differential diagnosis (DDx) should assess: Atrial myxoma Congestive heart failure Constrictive pericarditis Infiltrative cardiomyopathies Right heart failure (right ventricular infarction) Ventricular septal defect Treatment The treatment for cor pulmonale can include the following: antibiotics, expectorants, oxygen therapy, diuretics, digitalis, vasodilators, and anticoagulants. Some studies have indicated that Shenmai injection with conventional treatment is safe and effective for cor pulmonale (chronic).Treatment requires diuretics (to decrease strain on the heart). Oxygen is often required to resolve the shortness of breath. Additionally, oxygen to the lungs also helps relax the blood vessels and eases right heart failure. When wheezing is present, the majority of individuals require a bronchodilator. A variety of medications have been developed to relax the blood vessels in the lung, calcium channel blockers are used but only work in few cases and according to NICE are not recommended for use at all.Anticoagulants are used when venous thromboembolism is present. Venesection is used in severe secondary polycythemia (because of hypoxia), which improves symptoms though survival rate has not been proven to increase. Finally, transplantation of single/double lung in extreme cases of cor pulmonale is also an option. Epidemiology The epidemiology of pulmonary heart disease (cor pulmonale) accounts for 7% of all heart disease in the U.S According to Weitzenblum, et al., the mortality that is related to cor pulmonale is not easy to ascertain, as it is a complication of COPD. See also Bilharzial cor pulmonale. References Further reading Forfia, Paul R.; Vaidya, Anjali; Wiegers, Susan E. (2013-01-01). "Pulmonary heart disease: The heart-lung interaction and its impact on patient phenotypes". Pulmonary Circulation. 3 (1): 5–19. doi:10.4103/2045-8932.109910. ISSN 2045-8932. PMC 3641739. PMID 23662171. Taussig, Lynn M.; Landau, Louis I. (2008-04-09). Pediatric Respiratory Medicine. Elsevier Health Sciences. ISBN 978-0323070720. Jamal, K.; Fleetham, J. A.; Thurlbeck, W. M. (1990-05-01). "Cor Pulmonale: Correlation with Central Airway Lesions, Peripheral Airway Lesions, Emphysema, and Control of Breathing". American Review of Respiratory Disease. 141 (5_pt_1): 1172–1177. doi:10.1164/ajrccm/141.5_Pt_1.1172. ISSN 0003-0805. PMID 2339840. == External links ==

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

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

Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. It is only recommended in those with significant abnormal heart rhythms due to potentially serious side effects. Evidence does not support a decreased risk of death with long term use. It is taken by mouth or injection into a vein.Common side effects include a slow heart rate, chest pain, low blood pressure, feeling tired, dizziness, shortness of breath, problems seeing, vomiting, and swelling. Other serious side effects may include QT prolongation, heart failure, or bronchospasm. Sotalol is a non-selective beta-adrenergic receptor blocker which has both class II and class III antiarrhythmic properties.Sotalol was first described in 1964 and came into medical use in 1974. It is available as a generic medication. In 2017, it was the 267th most commonly prescribed medication in the United States, with more than one million prescriptions. Medical uses According to the U.S. Food and Drug Administration (FDA), sotalol can be validly used to maintain a normal heart rhythm in people with life-threatening ventricular arrhythmias (e.g., ventricular tachycardia), or very symptomatic atrial fibrillation or flutter. Due to the risk of serious side effects, the FDA states that sotalol should generally be reserved for people whose ventricular arrhythmias are life-threatening, or whose fibrillation/flutter cannot be resolved using the Valsalva maneuver or another simple method. Contraindications According to the FDA, sotalol should not be used in people with a waking heart rate lower than 50 beats per minute. It should not be used in people with sick sinus syndrome, long QT syndrome, cardiogenic shock, uncontrolled heart failure, asthma or a related bronchospastic condition, or people with serum potassium below 4 meq/L. It should only be used in people with a second and third degree AV block if a functioning pacemaker is present.Since sotalol is removed from the body through the kidneys, it should not be used in people with a creatinine clearance rate below 40 mL/min. It is also excreted in breast milk, so mothers should not breastfeed while taking sotalol.Since sotalol prolongs the QT interval, the FDA recommends against using it in conjunction with other medications that prolong the QT interval. Studies have found serious side effects to be more common in individuals also taking digoxin, possibly because of pre-existing heart failure in those people. As with other beta blockers, it may interact with calcium channel blockers, catecholamine-depleting drugs, insulin or antidiabetic drugs, beta2-adrenergic agonists, and clonidine.Some evidence suggests that sotalol should be avoided in the setting of heart failure with a reduced ejection fraction (resulting in the heart squeezing little blood out into the circulation with each pump) due to an increased risk of death. Adverse effects Over 10% of oral sotalol users experience fatigue, dizziness, lightheadedness, headache, weakness, nausea, shortness of breath, bradycardia (slow heart rate), a sensation of the heart beating too hard, fast, or irregularly, or chest pain. Higher doses of sotalol increase the risk for all of these possible side effects.In rare cases, the QT prolongation caused by sotalol can lead to the development of life-threatening torsade de pointes (TdP) polymorphic ventricular tachycardia. Across several clinical trials, 0.6% of oral sotalol patients with supraventricular abnormal heart rhythms (such as atrial fibrillation) developed TdP. For patients who had a history of sustained ventricular tachycardia (abnormal rhythm lasting more than 30 seconds), 4% developed TdP. Risk increases with dosage, female sex, or having a history of an enlarged heart or congestive heart failure. The incidence of TdP for sustained ventricular tachycardia patients was 0% with an 80 mg daily dose, 0.5% at 160 mg, 1.6% at 320 mg, 4.4% at 480 mg, 3.7% at 640 mg, and 5.8% at doses greater than 640 mg. Due to this risk, the U.S. Food and Drug Administration requires affected individuals to be hospitalized for at least three days in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring upon starting or restarting sotalol. Mechanisms of action Beta-blocker action Sotalol non-selectively binds to both β1- and β2-adrenergic receptors preventing activation of the receptors by their stimulatory ligand (catecholamines). Without the binding of this ligand to the receptor, the G-protein complex associated with the receptor cannot activate production of cyclic AMP, which is responsible for turning on calcium inflow channels. A decrease in activation of calcium channels will therefore result in a decrease in intracellular calcium. In heart cells, calcium is important in generating electrical signals for heart muscle contraction, as well as generating force for this contraction. In consideration of these important properties of calcium, two conclusions can be drawn. First, with less calcium in the cell, there is a decrease in electrical signals for contraction, thus allowing time for the hearts natural pacemaker to rectify arrhythmic contractions. Secondly, lower calcium means a decrease in strength and rate of the contractions, which can be helpful in treatment of abnormally fast heart rates. Type III antiarrhythmic action Sotalol also acts on potassium channels and causes a delay in relaxation of the ventricles. By blocking these potassium channels, sotalol inhibits efflux of K+ ions, which results in an increase in the time before another electrical signal can be generated in ventricular myocytes. This increase in the period before a new signal for contraction is generated, helps to correct arrhythmias by reducing the potential for premature or abnormal contraction of the ventricles but also prolongs the frequency of ventricular contraction to help treat tachycardia. History Sotalol was first synthesized in 1960 by A. A. Larsen of Mead-Johnson Pharmaceutical. It was originally recognized for its blood pressure lowering effects and its ability to reduce the symptoms of angina. It was made available in the United Kingdom and France in 1974, Germany in 1975, and Sweden in 1979. It became widely used in the 1980s. In the 1980s, its antiarrhythmic properties were discovered. The United States approved the drug in 1992. Brand names Trade names for Sotalol include Betapace and Betapace AF (Berlex Laboratories), Sotalex and Sotacor (Bristol-Myers Squibb), and Sotylize (Arbor Pharmaceuticals). References External links "Sotalol". Drug Information Portal. U.S. National Library of Medicine.

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

I'm trying to expand my medical knowledge. Can you elucidate the term 'Glycogen storage disease type I'?

Glycogen storage disease type I (GSD I) is an inherited disease that results in the liver being unable to properly break down stored glycogen. This impairment disrupts the livers ability to break down stored glycogen that is necessary to maintain adequate blood sugar levels. GSD I is divided into two main types, GSD Ia and GSD Ib, which differ in cause, presentation, and treatment. GSD Ia is caused by a deficiency in the enzyme glucose-6-phosphatase, while GSD Ib is caused a deficiency in the enzyme glucose-6-phosphate translocase. Since glycogenolysis is the principal metabolic mechanism by which the liver supplies glucose to the body during periods of fasting, both deficiencies cause severe low blood sugar and, over time, excess glycogen storage in the liver and (in some cases) the kidneys. GSD I patients typically present with an enlarged liver from non-alcoholic fatty liver disease as the result of this glycogen buildup. Other functions of the liver and kidneys are initially intact in GSD I, but are susceptible to a variety of other problems. Without proper treatment, GSD I gives rise to chronic low blood sugar, which can result in derangements including excessive levels of lactic acid and abnormally high levels of lipids in the bloodstream. Frequent feedings of cornstarch or other carbohydrates are the principal treatment for all forms of GSD I. GSD Ib also features chronic neutropenia due to a dysfunction in the production of neutrophils in the bone marrow. This immunodeficiency, if untreated, makes GSD Ib patients susceptible to infection. The principal treatment for this feature of GSD Ib is filgrastim; however, patients often still require treatment for frequent infections, and a chronically enlarged spleen is a common side effect. GSD Ib patients often present with inflammatory bowel disease.It is the most common of the glycogen storage diseases. GSD I has an incidence of approximately 1 in 100,000 births in the American population, and approximately 1 in 20,000 births among Ashkenazi Jews. The disease was named after German doctor Edgar von Gierke, who first described it in 1929. Signs and symptoms Early research into GSD I identified numerous clinical manifestations falsely thought to be primary features of the genetic disorder. However, continuing research has revealed that these clinical features are the consequences of only one (in GSD Ia) or two (in GSD Ib) fundamental abnormalities: impairment in the livers ability to convert stored glycogen into glucose through glycogenolysis in GSD Ib, impairment of the neutrophils ability to take up glucose, resulting in neutrophil dysfunction and neutropeniaThese fundamental abnormalities give rise to a small number of primary clinical manifestations, which are the features considered in diagnosis of GSD I: Low blood sugar (hypoglycemia), due to impairment of glycogen breakdown (glycogenolysis) causing insufficient fasting blood glucose hepatomegaly of non-alcoholic fatty liver disease, due to impairment of glycogenolysis causing glycogen accumulation in the liver in GSD Ib, increased infection risk, due to neutropenia and neutrophil dysfunctionAffected people commonly present with secondary clinical manifestations, linked to one or more of the primary clinical manifestations: High levels of uric acid in the blood and attendant risk of gout or kidney damage, caused by low serum insulin levels in prolonged hypoglycemia High levels of lactic acid in the blood, in extreme cases leading to lactic acidosis, caused by prolonged hypoglycemia hepatic adenomas developing in adulthood and attendant risk of anemia, suspected to be caused by blood glucose dysregulation in the presence of non-alcoholic fatty liver disease in GSD Ib, inflammatory bowel disease and attendant risk of anemia, caused by neutrophil dysfunction and exacerbated by the increased carbohydrate intake required to prevent hypoglycemiaIn addition, there are several clinical manifestations that often result from the treatment of the primary clinical manifestations: pancreatic hypertrophy, due to increased carbohydrate intake causing frequent engagement of the insulin response in GSD Ib, splenomegaly, due to the long-term use of filgrastim to treat neutropenia causing sequestration of blood factors in the spleen in GSD Ib, an abnormally low number of platelets in the blood may occur, due to long-term use of filgrastim causing sequestration of platelets in the spleen in GSD Ib, anemia, due to long-term use of filgrastim causing sequestration of hemoglobin in the spleen, potentially exacerbated by uncontrolled inflammatory bowel disease Hypoglycemia Low blood sugar (hypoglycemia) is the primary clinical symptom common to both GSD Ia and GSD Ib and most often prompts initial diagnosis of the disease. During fetal development in utero, maternal glucose transferred across the placenta prevents hypoglycemia. However, after birth, the inability to maintain blood glucose from stored glycogen in the liver causes measurable hypoglycemia in no more than 1–2 hours after feedings. Without proper dietary treatment after birth, prolonged hypoglycemia often leads to sudden lactic acidosis that can induce primary respiratory distress in the newborn period, as well as ketoacidosis.Neurological manifestations of hypoglycemia are less severe in GSD I than in other instances. Rather than acute hypoglycemia, GSD I patients experience persistent mild hypoglycemia. The diminished likelihood of neurological manifestations is due to the habituation of the brain to mild hypoglycemia. Given the reduced blood glucose level, the brain adapts to using alternative fuels like lactate. These gradual metabolic adaptations during infancy make severe symptoms like unconsciousness or seizure uncommon before diagnosis.In the early weeks of life, undiagnosed infants with GSD I tolerate persistent hypoglycemia and compensated lactic acidosis between feedings without symptoms. Without consistent carbohydrate feeding, infant blood glucose levels typically measure between 25 and 50 mg/dL (1.4 to 2.8 mmol/L). After weeks to months without treatment with consistent oral carbohydrates, infants will progress to show clear symptoms of hypoglycemia and lactic acidosis. Infants may present with paleness, clamminess, irritability, respiratory distress, and an inability to sleep through the night even in the second year of life. Developmental delay is not an intrinsic effect of GSD I, but is common if the diagnosis is not made in early infancy. Genetics GSD I is inherited in an autosomal recessive manner. People with one copy of the faulty gene are carriers of the disease and have no symptoms. As with other autosomal recessive diseases, each child born to two carriers of the disease has a 25% chance of inheriting both copies of the faulty gene and manifesting the disease. Unaffected parents of a child with GSD I can be assumed to be carriers. Prenatal diagnosis has been made by fetal liver biopsy at 18–22 weeks of gestation, but no fetal treatment has been proposed. Prenatal diagnosis is possible with fetal DNA obtained by chorionic villus sampling when a fetus is known to be at risk.The most common forms of GSD I are designated GSD Ia and GSD Ib, the former accounting for over 80% of diagnosed cases and the latter for less than 20%. A few rarer forms have been described. GSD Ia results from mutations of G6PC, the gene for glucose-6-phosphatase, located on chromosome 17q21. GSD Ib results from mutations of the gene for SLC37A4 or "G6PT1", the glucose-6-phosphate transporter. GSD Ic results from mutations of SLC17A3 or SLC37A4.Glucose-6-phosphatase is an enzyme located on the inner membrane of the endoplasmic reticulum. The catalytic unit is associated with a calcium binding protein, and three transport proteins (T1, T2, T3) that facilitate movement of glucose-6-phosphate (G6P), phosphate, and glucose (respectively) into and out of the enzyme. Pathophysiology Normal carbohydrate balance and maintenance of blood glucose levels Glycogen in liver and (to a lesser degree) kidneys serves as a form of stored, rapidly accessible glucose, so that the blood glucose level can be maintained between meals. For about 3 hours after a carbohydrate-containing meal, high insulin levels direct liver cells to take glucose from the blood, to convert it to glucose-6-phosphate (G6P) with the enzyme glucokinase, and to add the G6P molecules to the ends of chains of glycogen (glycogen synthesis). Excess G6P is also shunted into production of triglycerides and exported for storage in adipose tissue as fat. When digestion of a meal is complete, insulin levels fall, and enzyme systems in the liver cells begin to remove glucose molecules from strands of glycogen in the form of G6P. This process is termed glycogenolysis. The G6P remains within the liver cell unless the phosphate is cleaved by glucose-6-phosphatase. This dephosphorylation reaction produces free glucose and free PO4 anions. The free glucose molecules can be transported out of the liver cells into the blood to maintain an adequate supply of glucose to the brain and other organs of the body. Glycogenolysis can supply the glucose needs of an adult body for 12–18 hours. When fasting continues for more than a few hours, falling insulin levels permit catabolism of muscle protein and triglycerides from adipose tissue. The products of these processes are amino acids (mainly alanine), free fatty acids, and lactic acid. Free fatty acids from triglycerides are converted to ketones, and to acetyl-CoA. Amino acids and lactic acid are used to synthesize new G6P in liver cells by the process of gluconeogenesis. The last step of normal gluconeogenesis, like the last step of glycogenolysis, is the dephosphorylation of G6P by glucose-6-phosphatase to free glucose and PO4. Thus glucose-6-phosphatase mediates the final, key, step in both of the two main processes of glucose production during fasting. The effect is amplified because the resulting high levels of glucose-6-phosphate inhibit earlier key steps in both glycogenolysis and gluconeogenesis. Pathophysiology The principal metabolic effects of deficiency of glucose-6-phosphatase are hypoglycemia, lactic acidosis, hypertriglyceridemia, and hyperuricemia. The hypoglycemia of GSD I is termed "fasting", or "post-absorptive", usually about 4 hours after the complete digestion of a meal. This inability to maintain adequate blood glucose levels during fasting results from the combined impairment of both glycogenolysis and gluconeogenesis. Fasting hypoglycemia is often the most significant problem in GSD I, and typically the problem that leads to the diagnosis. Chronic hypoglycemia produces secondary metabolic adaptations, including chronically low insulin levels and high levels of glucagon and cortisol. Lactic acidosis arises from impairment of gluconeogenesis. Lactic acid is generated both in the liver and muscle and is oxidized by NAD+ to pyruvic acid and then converted via the gluconeogenic pathway to G6P. Accumulation of G6P inhibits conversion of lactate to pyruvate. The lactic acid level rises during fasting as glucose falls. In people with GSD I, it may not fall entirely to normal even when normal glucose levels are restored. Hypertriglyceridemia resulting from amplified triglyceride production is another indirect effect of impaired gluconeogenesis, amplified by chronically low insulin levels. During fasting, the normal conversion of triglycerides to free fatty acids, ketones, and ultimately acetyl-CoA is impaired. Triglyceride levels in GSD I can reach several times normal and serve as a clinical index of "metabolic control". Hyperuricemia results from a combination of increased generation and decreased excretion of uric acid, which is generated when increased amounts of G6P are metabolized via the pentose phosphate pathway. It is also a byproduct of purine degradation. Uric acid competes with lactic acid and other organic acids for renal excretion in the urine. In GSD I increased availability of G6P for the pentose phosphate pathway, increased rates of catabolism, and diminished urinary excretion due to high levels of lactic acid all combine to produce uric acid levels several times normal. Although hyperuricemia is asymptomatic for years, kidney and joint damage gradually accrue. Elevated lactate and lactic acidosis High levels of lactic acid in the blood are observed in all people with GSD I, due to impaired gluconeogenesis. Baseline elevations generally range from 4 to 10 mol/mL, which will not cause any clinical impact. However, during and after an episode of low blood sugar, lactate levels will abruptly rise to exceed 15 mol/mL, the threshold for lactic acidosis. Symptoms of lactic acidosis include vomiting and hyperpnea, both of which can exacerbate hypoglycemia in the setting of GSD I. In cases of acute lactic acidosis, patients need emergency care to stabilize blood oxygen, and restore blood glucose. Proper identification of lactic acidosis in undiagnosed children presents a challenge, since the first symptoms are typically vomiting and dehydration, both of which mimic childhood infections like gastroenteritis or pneumonia. Moreover, both of these common infections can precipitate more severe hypoglycemia in undiagnosed children, making diagnosis of the underlying cause difficult. As elevated lactate persists, uric acid, ketoacids, and free fatty acids further increase the anion gap. In adults and children, the high concentrations of lactate cause significant discomfort in the muscles. This discomfort is an amplified form of the burning sensation a runner may feel in the quadriceps after sprinting, which is caused by a brief buildup of lactic acid. Proper control of hypoglycemia in GSD I eliminates the possibility for lactic acidosis. Elevated urate and complications High levels of uric acid often present as a consequence of elevated lactic acid in GSD I patients. When lactate levels are elevated, blood-borne lactic acid competes for the same kidney tubular transport mechanism as urate, limiting the rate that urate can be cleared by the kidneys into the urine. If present, increased purine catabolism is an additional contributing factor. Uric acid levels of 6 to 12 mg/dl (530 to 1060 umol/L) are common among GSD I patients, if the disease is not properly treated. In some affected people, the use of the medication allopurinol is necessary to lower blood urate levels. Consequences of hyperuricemia among GSD I patients include the development of kidney stones and the accumulation of uric acid crystals in joints, leading to kidney disease and gout, respectively. Hyperlipidemia and plasma effects Elevated triglycerides in GSD I result from low serum insulin in patients with frequent prolonged hypoglycemia. It may also be caused by intracellular accumulation of glucose-6-phosphate with secondary shunting to pyruvate, which is converted into Acetyl-CoA, which is transported to the cytosol where the synthesis of fatty acids and cholesterol occurs. Triglycerides above the 3.4 mmol/L (300 mg/dL) range may produce visible lipemia, and even a mild pseudohyponatremia due to a reduced aqueous fraction of the blood plasma. In GSD I, cholesterol is typically only mildly elevated compared to other lipids. Hepatomegaly Impairment in the livers ability to perform gluconeogenesis leads to clinically apparent hepatomegaly. Without this process, the body is unable to liberate glycogen from the liver and convert it into blood glucose, leading to an accumulation of stored glycogen in the liver. Hepatomegaly from the accumulation of stored glycogen in the liver is considered a form of non-alcoholic fatty liver disease. GSD I patients present with a degree of hepatomegaly throughout life, but severity often relates to the consumption of excess dietary carbohydrate. Reductions in the mass of the liver are possible, since most patients retain residual hepatic function that allows for the liberation of stored glycogen at a limited rate. GSD I patients often present with hepatomegaly from the time of birth. In fetal development, maternal glucose transferred to the fetus prevents hypoglycemia, but the storage of glucose as glycogen in the liver leads to hepatomegaly. There is no evidence that this hepatomegaly presents any risk to proper fetal development. Hepatomegaly in GSD type I generally occurs without sympathetic enlargement of the spleen. GSD Ib patients may present with splenomegaly, but this is connected to the use of filgrastim to treat neutropenia in this subtype, not comorbid hepatomegaly. Hepatomegaly will persist to some degree throughout life, often causing the abdomen to protrude, and in severe cases may be palpable at or below the navel. In GSD-related non-alcoholic fatty liver disease, hepatic function is usually spared, with liver enzymes and bilirubin remaining within the normal range. However, liver function may be affected by other hepatic complications in adulthood, including the development of hepatic adenomas. Hepatic adenomas The specific etiology of hepatic adenomas in GSD I remains unknown, despite ongoing research. The typical GSD I patient presenting with at least one adenoma is an adult, though lesions have been observed in patients as young as fourteen. Adenomas, composed of heterogeneous neoplasms, may occur individually or in multiples. Estimates on the rate of conversion of a hepatocellular adenoma into hepatocellular carcinoma in GSD I range from 0% to 11%, with the latter figure representing more recent research. One reason for the increasing estimate is the growing population of GSD I patients surviving into adulthood, when most adenomas develop. Treatment standards dictate regular observation of the liver by MRI or CT scan to monitor for structural abnormalities. Hepatic adenomas may be misidentified as focal nodular hyperplasia in diagnostic imaging, though this condition is rare. However, hepatic adenomas in GSD I uniquely involve diffuse Mallory hyaline deposition, which is otherwise commonly observed in focal nodular hyperplasia. Unlike common hepatic adenomas related to oral contraception, hemorrhaging in GSD I patients is rare. While the reason for the high prevalence of adenomas in GSD I is unclear, research since the 1970s has implicated serum glucagon as a potential driver. In studies, patients that have been put on a dietary regimen to keep blood sugar in a normal range spanning 72 to 108 mg/dL (4.0 to 6.0 mmol/L) have shown a decreased likelihood of developing adenomas. Moreover, patients with well controlled blood glucose have consistently seen a reduction in the size and number of hepatic adenomas, suggesting that adenomas may be caused by imbalances of hepatotropic agents like serum insulin and especially serum glucagon in the liver. Osteopenia Patients with GSD I will often develop osteopenia. The specific etiology of low bone mineral density in GSD is not known, though it is strongly associated with poor metabolic control. Osteopenia may be directly caused by hypoglycemia, or the resulting endocrine and metabolic sequelae. Improvements in metabolic control have consistently been shown to prevent or reverse clinically relevant osteopenia in GSD I patients. In cases where osteopenia progresses with age, bone mineral density in the ribs is typically more severe than in the vertebrae. In some cases bone mineral density T-score will drop below -2.5, indicating osteoporosis. There is some evidence that osteopenia may be connected with associated kidney abnormalities in GSD I, particularly glomular hyperfiltration. The condition also seems responsive to calcium supplementation. In many cases bone mineral density can increase and return to the normal range given proper metabolic control and calcium supplementation alone, reversing osteopenia. Kidney effects The kidneys are usually 10 to 20% enlarged with stored glycogen. In adults with GSD I, chronic glomerular damage similar to diabetic nephropathy may lead to kidney failure. GSD I may present with various kidney complications. Renal tubular abnormalities related to hyperlactatemia are seen early in life, likely because prolonged lactic acidosis is more likely to occur in childhood. This will often present as Fanconi syndrome with multiple derangements of renal tubular reabsorption, including tubular acidosis with bicarbonate and phosphate wasting. These tubular abnormalities in GSD I are typically detected and monitored by urinary calcium. Long term these derangements can exacerbate uric acid nephropathy, otherwise driven by hyperlactatemia. In adolescence and beyond, glomerular disease may independently develop, initially presenting as glomerular hyperfiltration indicated by elevated urinary eGFR. Splenomegaly Enlargement of the spleen (splenomegaly) is common in GSD I and has two primary causes. In GSD Ia, splenomegaly may be caused by a relation between the liver and the spleen which causes either to grow or shrink to match the relative size of the other, to a lessened degree. In GSD Ib, it is a side effect of the use of filgrastim to treat neutropenia. Bowel effects Intestinal involvement can cause mild malabsorption with greasy stools (steatorrhea), but usually requires no treatment. Infection risk Neutropenia is a distinguishing feature of GSD Ib, absent in GSD Ia. The microbiological cause of neutropenia in GSD Ib is not well understood. Broadly, the problem arises from compromised cellular metabolism in the neutrophil, resulting in accelerated neutrophil apoptosis. The neutropenia in GSD is characterized by both a decrease in absolute neutrophil count and diminished neutrophil function. Neutrophils use a specific G6P metabolic pathway which relies on the presence of G6Pase-β or G6PT to maintain energy homeostasis within the cell. The absence of G6PT in GSD Ib limits this pathway, leading to endoplasmic reticulum stress, oxidative stress within the neutrophil, triggering premature apoptosis. Granulocyte colony-stimulating factor (G-CSF), available as filgrastim, can reduce the risk of infection. In some cases, G-CSF formulated as pegfilgrastim, sold under the trade name Neulasta, may be used as a slow-acting alternative, requiring less frequent dosing. Thrombocytopenia and blood clotting problems Impaired platelet aggregation is an uncommon consequence of chronic hypoglycemia, seen in GSD I patients. Research has demonstrated decreased platelet function, characterized by decreased prothrombin consumption, abnormal aggregation reactions, prolonged bleeding time, and low platelet adhesiveness. Severity of platelet dysfunction typically correlates with clinical condition, with the most severe cases correlating with lactic acidosis and severely lipidemia. It may cause clinically significant bleeding, especially epistaxis. Additionally, GSD I patients may present with thrombocytopenia as a consequence of splenomegaly. In the setting of splenomegaly various hematologic factors may be sequestered in the tissues of the spleen as blood is filtered through the organ. This can diminish levels of platelets available in the bloodstream, leading to thrombocytopenia. Developmental effects Developmental delay is a potential secondary effect of chronic or recurrent hypoglycemia, but is at least theoretically preventable. Normal neuronal and muscle cells do not express glucose-6-phosphatase, and are thus not impacted by GSD I directly. However, without proper treatment of hypoglycemia, growth failure commonly results from chronically low insulin levels, persistent acidosis, chronic elevation of catabolic hormones, and calorie insufficiency (or malabsorption). The most dramatic developmental delays are often the cause of severe (not just persistent) episodes of hypoglycemia. Diagnosis Several different problems may lead to the diagnosis, usually by two years of age: seizures or other manifestations of severe fasting hypoglycemia hepatomegaly with abdominal protuberance hyperventilation and apparent respiratory distress due to metabolic acidosis episodes of vomiting due to metabolic acidosis, often precipitated by minor illness and accompanied by hypoglycemiaOnce the diagnosis is suspected, the multiplicity of clinical and laboratory features usually makes a strong circumstantial case. If hepatomegaly, fasting hypoglycemia, and poor growth are accompanied by lactic acidosis, hyperuricemia, hypertriglyceridemia, and enlarged kidneys by ultrasound, GSD I is the most likely diagnosis. The differential diagnosis list includes glycogenoses types III and VI, fructose 1,6-bisphosphatase deficiency, and a few other conditions (page 5), but none are likely to produce all of the features of GSD I. The next step is usually a carefully monitored fast. Hypoglycemia often occurs within six hours. A critical blood specimen obtained at the time of hypoglycemia typically reveals a mild metabolic acidosis, high free fatty acids and beta-hydroxybutyrate, very low insulin levels, and high levels of glucagon, cortisol, and growth hormone. Administration of intramuscular or intravenous glucagon (0.25 to 1 mg, depending on age) or epinephrine produces little rise of blood sugar. The diagnosis is definitively confirmed by liver biopsy with electron microscopy and assay of glucose-6-phosphatase activity in the tissue and/or specific gene testing, available in recent years. Treatment The primary treatment goal is prevention of hypoglycemia and the secondary metabolic derangements by frequent feedings of foods high in glucose or starch (which is readily digested to glucose). To compensate for the inability of the liver to provide sugar, the total amount of dietary carbohydrate should approximate the 24-hour glucose production rate. The diet should contain approximately 65–70% carbohydrate, 10–15% protein, and 20–25% fat. At least a third of the carbohydrates should be supplied through the night, so that a young child goes no more than 3–4 hours without carbohydrate intake. Once a diagnosis is made, the priority in GSD I treatment is to maintain an adequate blood glucose. Patients aim to maintain a blood glucose above the 72 mg/dL (4.0 mmol/L) cutoff for hypoglycemia. GSD Ib patients have an additional treatment priority relating to neutropenia. Proper management of blood glucose in GSD I is critical in avoiding the more severe effects of high leves of lactic acid and uric acid in the blood, and the development of hepatic adenomas. In the last 30 years, two methods have been used to achieve this goal in young children: (1) continuous nocturnal gastric infusion of glucose or starch; and (2) night-time feedings of uncooked cornstarch. An elemental formula, glucose polymer, and/or cornstarch can be infused continuously through the night at a rate supplying 0.5–0.6 g/kg/h of glucose for an infant, or 0.3–0.4 for an older child. This method requires a nasogastric or gastrostomy tube and pump. Sudden death from hypoglycemia has occurred due to malfunction or disconnection, and periodic cornstarch feedings are now preferred to continuous infusion. Cornstarch is an inexpensive way to provide gradually digested glucose. One tablespoon contains nearly 9 g carbohydrate (36 calories). Although it is safer, less expensive, and requires no equipment, this method does require that parents arise every 3–4 hours to administer the cornstarch. A typical requirement for a young child is 1.6 g/kg every 4 hours. Long-term management should eliminate hypoglycemic symptoms and maintain normal growth. Treatment should achieve normal glucose, lactic acid, and electrolyte levels, and only mild elevations of uric acid and triglycerides. Avoidance of other sugars Intake of carbohydrates which must be converted to G6P to be utilized (e.g., galactose and fructose) should be minimized. Although elemental formulas are available for infants, many foods contain fructose or galactose in the forms of sucrose or lactose. Adherence becomes a contentious treatment issue after infancy. Other therapeutic measures Persistent elevation of uric acid above 6.5 mg/dl warrants treatment with allopurinol to prevent uric acid deposition in kidneys and joints. Because of the potential for impaired platelet function, coagulation ability should be checked and the metabolic state normalized before surgery. Bleeding time may be normalized with 1–2 days of glucose loading, and improved with ddavp. During surgery, IV fluids should contain 10% dextrose and no lactate. A patient with GSD, type 1b was treated with a liver transplant at UCSF Medical Center in 1993 that resulted in the resolution of hypoglycemic episodes and the need for the patient to stay away from natural sources of sugar. Other patients have undergone this procedure as well with positive results. Although a liver transplant resulted in the resolution of hypoglycemia it did not however resolve the chronic neutropenia and the risk of infection among patients. Treatment of acute metabolic acidosis episodes The most significant acute problem in childhood is a vulnerability to episodes of metabolic acidosis precipitated by minor illnesses. If a vomiting illness persists longer than 2–4 hours, the child should be seen and assessed for dehydration, acidosis, and hypoglycemia. If these are developing, intravenous fluids should be provided at a rate above maintenance. For mild acidosis, an effective fluid is 10% dextrose in ½ normal saline with 20 mEq/L KCl, but if acidosis is severe, 75–100 mEq/L NaHCO3 and 20 mEq/L of K acetate can be substituted for the NaCl and KCl. Metabolic control Metabolic control often diminishes during and after puberty, as a result of a patient outgrowing their dietary treatment plan. Prognosis Without adequate metabolic treatment, patients with GSD I have died in infancy or childhood of overwhelming hypoglycemia and acidosis. Those who survived were stunted in physical growth and delayed in puberty because of chronically low insulin levels. Intellectual disability resulting from recurrent, severe hypoglycemia is considered preventable with appropriate treatment. Liver complications have been serious in some patients. Adenomas of the liver can develop in the second decade or later, with a small chance of later malignant transformation to hepatoma or hepatic carcinomas (detectable by alpha-fetoprotein screening). Several children with advanced hepatic complications have improved after liver transplantation. Additional problems reported in adolescents and adults with GSD I have included hyperuricemic gout, pancreatitis, and chronic kidney failure. Despite hyperlipidemia, atherosclerotic complications are uncommon. With diagnosis before serious harm occurs, prompt reversal of acidotic episodes, and appropriate long-term treatment, most children will be healthy. With exceptions and qualifications, adult health and life span may also be fairly good, although lack of effective treatment before the mid-1970s means information on long-term efficacy is limited. Epidemiology In the United States, GSD I has an incidence of approximately 1 in 50,000 to 100,000 births. None of the glycogenoses are currently detected by standard or extended newborn screening. The disease is more common in people of Ashkenazi Jewish, Mexican, Chinese, and Japanese descent. References Further reading GeneReview/NIH/UW entry on Glycogen Storage Disease Type I External links Media related to Glycogen storage disease type I at Wikimedia Commons

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.

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

Intussusception may refer to: Intussusception (medical disorder) Intussusception (blood vessel growth) Rectal prolapse#Internal rectal intussusception

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

Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brains cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side effects (EPSE). The symptoms can be acute (short-term) or chronic (long-term). They include movement dysfunction such as dystonia (continuous spasms and muscle contractions), akathisia (may manifest as motor restlessness), parkinsonism characteristic symptoms such as rigidity, bradykinesia (slowness of movement), tremor, and tardive dyskinesia (irregular, jerky movements). Extrapyramidal symptoms are a reason why subjects drop out of clinical trials of antipsychotics; of the 213 (14.6%) subjects that dropped out of one of the largest clinical trials of antipsychotics (the CATIE trial (Clinical Antipsychotic Trials for Intervention Effectiveness), which included 1460 randomized subjects), 58 (27.2%) of those discontinuations were due to EPS. Causes Medications Extrapyramidal symptoms are most commonly caused by typical antipsychotic drugs that antagonize dopamine D2 receptors. The most common typical antipsychotics associated with EPS are haloperidol and fluphenazine. Atypical antipsychotics have lower D2 receptor affinity or higher serotonin 5-HT2A receptor affinity which lead to lower rates of EPS.Other anti-dopaminergic drugs, like the antiemetic metoclopramide, can also result in extrapyramidal side effects. Short and long-term use of antidepressants such as selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), and norepinephrine-dopamine reuptake inhibitors (NDRI) have also resulted in EPS. Specifically, duloxetine, sertraline, escitalopram, fluoxetine, and bupropion have been linked to the induction of EPS. Non-medication-related Other causes of extrapyramidal symptoms can include brain damage and meningitis. However, the term "extrapyramidal symptoms" generally refers to medication-induced causes in the field of psychiatry. Diagnosis Since it is difficult to measure extrapyramidal symptoms, rating scales are commonly used to assess the severity of movement disorders. The Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), Abnormal Involuntary Movement Scale (AIMS), and Extrapyramidal Symptom Rating Scale (ESRS) are rating scales frequently used for such assessment and are not weighted for diagnostic purposes; these scales can help clinicians weigh the benefit/expected benefit of a medication against the degree of distress which the side effects are causing the patient, aiding in the decision to maintain, reduce, or discontinue the causative medication(s). Classification Acute dystonic reactions: painful, muscular spasms of neck, jaw, back, extremities, eyes, throat, and tongue; highest risk in young men.Oculogyric crisis is a kind of acute dystonic reaction that involves the prolonged involuntary upward deviation of the eyes. Akathisia: A feeling of internal motor restlessness that can present as tension, nervousness, or anxiety. Clinical manifestations include pacing and an inability to sit still. Pseudoparkinsonism: drug-induced parkinsonism (rigidity, bradykinesia, tremor, masked facies, shuffling gait, stooped posture, sialorrhoea, and seborrhoea; greater risk in the elderly). Although Parkinsons disease is primarily a disease of the nigrostriatal pathway and not the extrapyramidal system, loss of dopaminergic neurons in the substantia nigra leads to dysregulation of the extrapyramidal system. Since this system regulates posture and skeletal muscle tone, a result is the characteristic bradykinesia of Parkinsons. Tardive dyskinesia: involuntary muscle movements in the lower face and distal extremities; this can be a chronic condition associated with long-term use of antipsychotics. Treatment Medications are used to reverse the symptoms of extrapyramidal side effects caused by antipsychotics or other drugs, either by directly or indirectly inhibiting dopaminergic neurotransmission. The treatment varies by the type of the EPS, but may involve anticholinergic agents such as procyclidine, benztropine, diphenhydramine, and trihexyphenidyl, and (rarely) dopamine agonists like pramipexole.If the EPS are induced by an antipsychotic, EPS may be reduced by decreasing the dose of the antipsychotic or by switching from a typical antipsychotic to an (or to a different) atypical antipsychotic, such as aripiprazole, ziprasidone, quetiapine, olanzapine, risperidone, or clozapine. These medications possess an additional mode of action that is believed to mitigate their effect on the nigrostriatal pathway, which means they are associated with fewer extrapyramidal side-effects than "conventional" antipsychotics (chlorpromazine, haloperidol, etc.) Dystonia Anticholinergic medications are used to reverse acute dystonia. If the symptoms are particularly severe, the anticholinergic medication may be administered by injection into a muscle to rapidly reverse the dystonia. Akathisia Certain second-generation antipsychotics, such as lurasidone and the partial D2-agonist aripiprazole, are more likely to cause akathisia compared to other second-generation antipsychotics. If akathisia occurs, switching to an antipsychotic with a lower risk of akathisia may improve symptoms. Beta blockers (like propranolol) are frequently used to treat akathisia. Other medications that are sometimes used include clonidine, mirtazapine, or even benzodiazepines. Anticholinergic medications are not helpful for treating akathisia. Pseudoparkinsonism Medication interventions are generally reserved for cases in which withdrawing the medication that caused the pseudoparkinsonism is either ineffective or infeasible. Anticholinergic medications are sometimes used to treat pseudoparkinsonism, but they can be difficult to tolerate when given chronically. Amantadine is sometimes used as well. It is rare for dopamine agonists to be used for antipsychotic-induced EPS, as they may exacerbate psychosis. Tardive dyskinesia When other measures fail or are not feasible, medications are used to treat tardive dyskinesia. These include the vesicular monoamine transporter 2 inhibitors tetrabenazine and deutetrabenazine. History Extrapyramidal symptoms (also called extrapyramidal side effects) get their name because they are symptoms of disorders in the extrapyramidal system, which regulates posture and skeletal muscle tone. This is in contrast to symptoms originating from the pyramidal tracts. See also Neuroleptic malignant syndrome Rabbit syndrome References == External links ==

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I need a basic explanation for the medical term 'Osteoporotic bone marrow defect.'

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

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

A macular hole is a small break in the macula, located in the center of the eyes light-sensitive tissue called the retina. Symptoms If the vitreous is firmly attached to the retina when it pulls away, it can tear the retina and create a macular hole. Also, once the vitreous has pulled away from the surface of the retina, some of the fibers can remain on the retinal surface and can contract. This increases tension on the retina and can lead to a macular hole. In either case, the fluid that has replaced the shrunken vitreous can then seep through the hole onto the macula, blurring and distorting central vision. Causes The eye contains a jelly-like substance called the vitreous. Shrinking of the vitreous usually causes the hole. As a person ages, the vitreous becomes watery and begins to pull away from the retina. If the vitreous is firmly attached to the retina when it pulls away, a hole can result. Diagnosis Macular degeneration is a condition affecting the tissues lying under the retina, while a macular hole involves damage from within the eye, at the junction between the vitreous and the retina itself. There is no relationship between the two diseases. Depending upon the degree of attachment or traction between the vitreous and the retina, there may be risk of developing a macular hole in the other eye. In those cases where the vitreous has already become separated from the retinal surface, there is very little chance of developing a macular hole in the other eye. On the other hand, when the vitreous remains adherent and pulling on the macular region in both eyes, then there may be a greater risk of developing a hole in the second eye. In very rare instances, trauma or other conditions lead to the development of a macular hole. In the vast majority of cases, however, macular holes develop spontaneously. As a result, there is no known way to prevent their development through any nutritional or chemical means, nor is there any way to know who is at risk for developing a hole prior to its appearance in one or both eyes. Management Vitrectomy is the common way to treat a macular hole. It is done by placing a gas bubble in the vitreous of the eye which helps flatten the macular hole and holds it in place as the eye heals. The gas bubble slowly shrinks on its own. Treatment is also done using ocriplasmin. References 5. Saurabh K, Roy R, Mishra S, Garg B, Goel S. Multicolor imaging features of dissociated optic nerve fiber layer after internal limiting membrane peeling. Indian journal of ophthalmology. 2018 Dec 1;66(12):1853. External links Macular Hole Resource Guide from the National Eye Institute (NEI).

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

Keratomalacia is an eye disorder that results from vitamin A deficiency. Vitamin A is required to maintain specialized epithelia (such as in the cornea and conjunctiva). The precise mechanism is still not known, but vitamin A is necessary for the maintenance of the specialized epithelial surfaces of the body. A lack of vitamin A leads to atrophic changes in the normal mucosal surface, with loss of goblet cells, and replacement of the normal epithelium by an inappropriate keratinized stratified squamous epithelium. In addition, the substantia propria of the cornea breaks down and liquefies, resulting in keratomalacia.The resulting cornea becomes totally opaque, which is one of the most common reasons for blindness around the world, particularly in developing countries. See also Acute promyelocytic leukemia Keratoconjunctivitis sicca Xerophthalmia References External links patient.co.uk

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

Degarelix, sold under the brand name Firmagon among others, is a hormonal therapy used in the treatment of prostate cancer.Testosterone is a male hormone that promotes growth of many prostate tumours and therefore reducing circulating testosterone to very low (castration) levels is often the treatment goal in the management of advanced prostate cancer. Degarelix has an immediate onset of action, binding to gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland and blocking their interaction with GnRH. This induces a fast and profound reduction in luteinizing hormone (LH), follicle-stimulating hormone (FSH) and in turn, testosterone suppression. Medical uses The GnRH antagonist degarelix, through its ability to reduce serum testosterone, is used to treat hormone-sensitive prostate cancer. Side effects As with all hormonal therapies, degarelix is commonly associated with hormonal side effects such as hot flashes and weight gain. Due to its mode of administration (subcutaneous injection), degarelix is also associated with injection-site reactions such as injection-site pain, erythema or swelling. Injection-site reactions are usually mild or moderate in intensity and occur predominantly after the first dose, decreasing in frequency thereafter. Less common: Anemia. Diarrhea, nausea. Hyperhidrosis including night sweats, rash. Gynecomastia, testicular atrophy, erectile dysfunction. Increased transaminases. Musculoskeletal pain and discomfort. Dizziness, headache. Insomnia. Weight gain. Chills, fever, fatigue, flu-like illness. Pharmacology GnRH antagonists (receptor blockers) such as degarelix are synthetic peptide derivatives of the natural GnRH decapeptide – a hormone that is made by neurons in the hypothalamus. GnRH antagonists compete with natural GnRH for binding to GnRH receptors in the pituitary gland. This reversible binding blocks the release of LH and FSH from the pituitary. The reduction in LH subsequently leads to a rapid and sustained suppression of testosterone release from the testes and subsequently reduces the size and growth of the prostate cancer. This in turn results in a reduction in prostate-specific antigen (PSA) levels in the patients blood. Measuring PSA levels helps to monitor how patients with prostate cancer are responding to treatment.Unlike GnRH agonists, which cause an initial stimulation of the hypothalamic-pituitary-gonadal axis (HPGA), leading to a surge in testosterone levels, and under certain circumstances, a flare-up of the tumour, GnRH antagonists do not cause a surge in testosterone or clinical flare. Clinical flare is a phenomenon that occurs in patients with advanced disease, which can precipitate a range of clinical symptoms such as bone pain, urethral obstruction, and spinal cord compression. Drug agencies have issued boxed warnings regarding this phenomenon in the prescribing information for GnRH agonists. As testosterone surge does not occur with GnRH antagonists, there is no need for patients to receive an antiandrogen as flare protection during prostate cancer treatment. GnRH agonists also induce an increase in testosterone levels after each reinjection of the drug – a phenomenon that does not occur with GnRH antagonists such as degarelix.GnRH antagonists have an immediate onset of action leading to a fast and profound suppression of testosterone and are therefore especially valuable in the treatment of patients with prostate cancer where fast control of disease is needed. History In December 2008, the US Food and Drug Administration (FDA) approved degarelix for the treatment of patients with advanced prostate cancer in the United States. It was subsequently approved by the European Commission at the recommendation of the European Medicines Agency (EMA) in February 2009, for use in adult males with advanced, hormone-dependent prostate cancer. Ferring Pharmaceuticals markets the drug under the name Firmagon. Research Degarelix is studied for use as a chemical castration agent on sex offenders in Sweden. A study published on April 29, 2020, in JAMA Psychiatry demonstrated a reduced the risk score for committing child sexual abuse in men with pedophilic disorder two weeks after initial injection. See also Gonadotropin-releasing hormone receptor § Antagonists References External links "Degarelix". Drug Information Portal. U.S. National Library of Medicine.

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I'm trying to understand 'Lutetium (177Lu) oxodotreotide' within a medical context. Could you shed some light on it?

Lutetium (177Lu) oxodotreotide (INN) or 177Lu DOTA-TATE, trade name Lutathera, is a chelated complex of a radioisotope of the element lutetium with DOTA-TATE, used in peptide receptor radionuclide therapy (PRRT). Specifically, it is used in the treatment of cancers which express somatostatin receptors.Alternatives to 177Lu-DOTATE include yttrium-90 DOTATATE or DOTATOC. The longer range of the beta particles emitted by 90Y, which deliver the therapeutic effect, may make it more suitable for large tumors with 177Lu reserved for smaller volumesThe U.S. Food and Drug Administration (FDA) considers 177Lu dotatate to be a first-in-class medication. Clinical trials and drug approval The European Commission approved lutetium (177Lu) oxodotreotide (trade name Lutathera) "for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults" in September 2017.177Lu DOTA-TATE was approved in the United States for the treatment of SSTR positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors in adults, in January 2018. This was the first time a radiopharmaceutical had been approved for the treatment of GEP-NETs in the United States.The U.S. Food and Drug Administration (FDA) approved 177Lu dotatate based primarily on evidence from one clinical trial, NETTER-1 of 229 participants with somatostatin-receptor positive midgut GEP-NETs. Enrolled participants had tumors which could not be surgically removed and were worsening while receiving treatment with octreotide.Participants were randomly assigned to receive either 177Lu dotatate with long-acting octreotide or long-acting octreotide, at a higher dose, alone. 177Lu dotatate was injected through the vein and long-acting octreotide was injected in the muscle. Both, participants and health care providers knew which treatment was given. The benefit of 177Lu dotatate was evaluated by measuring the length of time that tumors did not grow after treatment and compared it to the control group (progression free survival).The FDA considered additional data from a second study based on data from 1,214 participants with somatostatin receptor-positive tumors, including GEP-NETS, who received 177Lu dotatate at a single site in the Netherlands, Erasmus MC. All participants received 177Lu dotatate with octreotide. Participants and health care providers knew which treatment was given. The benefit of 177Lu dotatate was evaluated by measuring if and how much the tumor size changed during treatment (the overall response rate). Complete or partial tumor shrinkage was reported in 16 percent of a subset of 360 participants with GEP-NETs who were evaluated for response by the FDA. Participants initially enrolled in the study received 177Lu dotatate as part of an expanded access program.The FDA granted the application for 177Lu dotatate priority review designation and orphan drug designation. The FDA granted the approval of Lutathera to Advanced Accelerator Applications. Adverse effects The therapeutic effect of 177Lu derives from the ionizing beta radiation it emits, however this can also be harmful to healthy tissue and organs. The kidneys are particularly at risk as they help to remove 177Lu DOTA-TATE from the body. To protect them, an amino acid solution (arginine/lysine) is administered by slow infusion, starting before the radioactive administration and normally continuing for several hours afterwards. References External links "Lutetium Lu 177 dotatate". Drug Information Portal. U.S. National Library of Medicine.

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

What does the medical term 'Paralysis' encompass?

Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 people have been diagnosed with some form of permanent or transient paralysis. The word "paralysis" derives from the Greek παράλυσις, meaning "disabling of the nerves" from παρά (para) meaning "beside, by" and λύσις (lysis) meaning "making loose". A paralysis accompanied by involuntary tremors is usually called "palsy". Causes Paralysis is most often caused by damage in the nervous system, especially the spinal cord. Other major causes are stroke, trauma with nerve injury, poliomyelitis, cerebral palsy, peripheral neuropathy, Parkinsons disease, ALS, botulism, spina bifida, multiple sclerosis, and Guillain–Barré syndrome. Temporary paralysis occurs during REM sleep, and dysregulation of this system can lead to episodes of waking paralysis. Drugs that interfere with nerve function, such as curare, can also cause paralysis. Pseudoparalysis (pseudo- meaning "false, not genuine", from Greek ψεῦδος) is voluntary restriction or inhibition of motion because of pain, incoordination, orgasm, or other cause, and is not due to actual muscular paralysis. In an infant, it may be a symptom of congenital syphilis. Pseudoparalysis can be caused by extreme mental stresses, and is a common feature of mental disorders such as panic anxiety disorder. Variations Paralysis can occur in localised or generalised forms, or it may follow a certain pattern. Most paralyses caused by nervous-system damage (e.g., spinal cord injuries) are constant in nature; however, some forms of periodic paralysis, including sleep paralysis, are caused by other factors.Paralysis can occur in newborns due to a congenital defect known as spina bifida. Spina bifida causes one or more of the vertebrae to fail to form vertebral arches within the infant, which allows the spinal cord to protrude from the rest of the spine. In extreme cases, this can cause spinal cord function inferior to the missing vertebral arches to cease. This cessation of spinal cord function can result in paralysis of lower extremities. Documented cases of paralysis of the anal sphincter in newborns have been observed when spina bifida has gone untreated. While life-threatening, many cases of spina bifida can be corrected surgically if operated on within 72 hours of birth. Ascending paralysis presents in the lower limbs before the upper limbs. It can be associated with: Guillain–Barré syndrome (another name for this condition is Landrys ascending paralysis) Tick paralysisAscending paralysis contrasts with descending paralysis, which occurs in conditions such as botulism. Other animals Many animal species use paralyzing toxins to capture prey, evade predation, or both. In stimulated muscles, the decrease in frequency of the miniature potentials runs parallel to the decrease in postsynaptic potential, and to the decrease in muscle contraction. In invertebrates, this clearly indicates that, e.g., Microbracon (wasp genus) venom causes paralysis of the neuromuscular system by acting at a presynaptic site. Philanthus venom inhibits both the fast and slow neuromuscular system at identical concentrations. It causes a decrease in the frequency of the miniature potentials without affecting their amplitude significantly. Invertebrates In some species of wasp, to complete the reproductive cycle, the female wasp paralyses a prey item such as a grasshopper and places it in her nest. In the species Philanthus gibbosus, the paralysed insect (most often a bee species) is coated in a thick layer of pollen. The adult P. gibbosus then lays eggs in the paralysed insect, which is devoured by the larvae when they hatch. Vertebrates A well-known example of a vertebrate-produced paralyzing toxin is the tetrodotoxin of fish species such as Takifugu rubripes, the famously lethal pufferfish of Japanese fugu. This toxin works by binding to sodium channels in nerve cells, inhibiting the cells proper function. A non-lethal dose of this toxin results in temporary paralysis. This toxin is also present in many other species ranging from toads to nemerteans. Paralysis can be seen in breeds of dogs that are chondrodysplastic. These dogs have short legs, and may also have short muzzles. Their intervertebral disc material can calcify and become more brittle. In such cases, the disc may rupture, with disc material ending up in the spinal canal, or rupturing more laterally to press on spinal nerves. A minor rupture may only result in paresis, but a major rupture can cause enough damage to cut off circulation. If no signs of pain can be elicited, surgery should be performed within 24 hours of the incident, to remove the disc material and relieve pressure on the spinal cord. After 24 hours, the chance of recovery declines rapidly, since with continued pressure, the spinal cord tissue deteriorates and dies. Another type of paralysis is caused by a fibrocartilaginous embolism. This is a microscopic piece of disc material that breaks off and becomes lodged in a spinal artery. Nerves served by the artery will die when deprived of blood. The German Shepherd Dog is especially prone to developing degenerative myelopathy. This is a deterioration of nerves in the spinal cord, starting in the posterior part of the cord. Affected dogs will become gradually weaker in the hind legs as nerves die off. Eventually, their hind legs become useless. They often also exhibit faecal and urinary incontinence. As the disease progresses, the paresis and paralysis gradually move forward. This disease also affects other large breeds of dogs. It is suspected to be an autoimmune problem. Cats with a heart murmur may develop blood clots that travel through arteries. If a clot is large enough to block one or both femoral arteries, there may be hind leg paralysis because the major source of blood flow to the hind leg is blocked. Many snakes exhibit powerful neurotoxins that can cause non-permanent paralysis or death. Also, many trees contain neurotoxins. See also References == External links ==

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

Caught is a method of dismissing a batsman in cricket. A batsman is out caught if the batsman hits the ball, from a legitimate delivery, with the bat, and the ball is caught by the bowler or a fielder before it hits the ground. If the ball hits the stumps after hitting the wicket-keeper, If the wicket-keeper fails to do this, the delivery is a "no ball", and the batsman cannot be stumped (nor run out, unless he attempts to run to the other wicket.) If the catch taken by the wicket-keeper,then informally it is known as caught behind or caught at the wicket. A catch by the bowler is known as caught and bowled. This has nothing to do with the dismissal bowled but is rather a shorthand for saying the catcher and bowler are the same player. (The scorecard annotation is usually c. and b. or c&b followed by the bowlers name.) Caught is the most common method of dismissal at higher levels of competition, accounting for 36,190 Test match dismissals between 1877 and 2012, which is 56.9% of all Test match dismissals in this period.South African wicket-keeper Mark Boucher holds the record for the most Test match catches, with 532, while Rahul Dravid holds the record for the most Test match catches by non-wicket-keepers, with 210. Laws This method of dismissal is covered by Law 33 of the Laws of cricket which reads: The striker is out Caught if a ball delivered by the bowler, not being a No ball, touches his/her bat without having previously been in contact with any fielder, and is subsequently held by a fielder as a fair catch,..., before it touches the wicket and ground.This means that the batsman cannot be out caught if: The ball is called a no-ball or dead ball. The batsman does not hit the ball with his bat or a gloved hand holding the bat. The ball, having been hit, makes contact with the field before a fielder catches the ball. The ball does not remain under the control of the fielder. The ball is hit and lands beyond or on the boundary; (six runs). A fielder taking the catch makes contact with the boundary rope or the area outside the boundary, with any part of his body, equipment, when touching the ball. An airborne fielder taking the catch, having not previously legally touched the ball, had his last contact with the ground not entirely within the boundary.Note that if a batsman could be given out both caught and by another method, caught takes precedence, unless the other method is bowled.If a batsman is out caught, any runs scored off that delivery are voided. If a batsman is caught, the bowler is credited with the batsmans wicket and the catching fielder is credited for the dismissal, there is no catch assists for a saving boundaries before catch, or deflecting the ball to a different fielder in the slips cordon. If the two batsmen cross each other, in attempting to take a run, before the catch was taken, the non-striking batsman at the time remains at the opposite end of the pitch as the new incoming batsman comes to the crease at his former end. This means, unless it is now a new over, he is now on strike and the incoming batsman is not. Adjudication If the catch taken is pronounced or obvious, the players need not appeal to the umpire; the batsman normally chooses to acknowledge the dismissal himself. However, if the ball brushes the edge of the bat, or the catch is taken very close to the ground, or the ball appears to have bounced off the batsmans foot (so it has not touched the ground), or the ball appearing to come off the bat very close to the pitch surface (bump ball), or if the batsman is reluctant to accept that he has been dismissed, then the fielding team has to appeal to the umpire for this decision. In international competition, if neither field umpire can clearly decide if a catch has been made or not, they may refer to the third (television) umpire for a review. The third umpire may also be used if the Umpire Decision Review System is available and a team wishes to dispute a call concerning a possible catch. Celebration Before 2000, the Laws of Cricket defined a catch as being completed when the player had "complete control over the further disposal of the ball". In the very strictest sense, this meant that the player did not finish catching the ball until he threw it away, though the player doesnt have to throw the ball to anyone in particular in so doing. For this reason, even today many cricketers celebrate a catch by lobbing the ball into the air. In a Super Sixes match in the 1999 Cricket World Cup, South African Herschelle Gibbs caught Australian captain Steve Waugh but Waugh was given not out when Gibbs was ruled to not have control of the ball when attempting to throw the ball in celebration. Waugh went on to score a match-winning 120 not out to qualify his team for the semi-finals; Australia went on to win the tournament. Records Test matches The wicket-keepers with the highest number of catches taken in Test matches are as follows. Note this excludes catches made while not fielding as a wicket-keeper. Source: Cricinfo Statsguru. Last updated: 19 April 2019. The non-wicket-keepers with the highest number of catches taken in Test matches are as follows. Note this excludes any catches made while fielding as a wicket-keeper. Source: Cricinfo Statsguru. Last updated: 19 April 2019. One Day Internationals T20 Internationals First Class cricket See also Other sports Catch (baseball) == References ==

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What does the medical term 'Otitis externa' encompass?

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

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

Angelman syndrome or Angelmans syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no functional speech, balance and movement problems, seizures, and sleep problems. Children usually have a happy personality and have a particular interest in water. The symptoms generally become noticeable by one year of age.Angelman syndrome is due to a lack of function of part of chromosome 15, typically due to a new mutation rather than one inherited from a persons parents. Most of the time, it is due to a deletion or mutation of the UBE3A gene on that chromosome. Occasionally, it is due to inheriting two copies of chromosome 15 from a persons father and none from their mother (paternal uniparental disomy). As the fathers versions are inactivated by a process known as genomic imprinting, no functional version of the gene remains. Diagnosis is based on symptoms and possibly genetic testing.No cure is available. Treatment is generally supportive in nature. Anti-seizure medications are used in those with seizures. Physical therapy and bracing may help with walking. Those affected have a nearly normal life expectancy.AS affects 1 in 12,000 to 20,000 people. Males and females are affected with equal frequency. It is named after British pediatrician Harry Angelman, who first described the syndrome in 1965. An older term, happy puppet syndrome, is generally considered pejorative. Prader–Willi syndrome is a separate condition, caused by a similar loss of the fathers chromosome 15. Signs and symptoms Signs and symptoms of Angelman syndrome and their relative frequency in affected individuals are: Consistent (100%) Developmental delay, functionally severe Speech impairment, no or minimal use of words; receptive and non-verbal communication skills higher than verbal ones Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs Behavioral characteristics of the following types: any combination of atypical frequent laughter/smiling; atypically happy demeanor; easily excitable personality, often with hand flapping movements; hypermotoric behavior; short attention span Frequent (more than 80%) Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (absolute or relative) by age 2 Seizures, onset usually less than 3 years of age Abnormal EEG, characteristic pattern with large amplitude slow-spike waves Associated (20–80%) Cause Angelman syndrome is caused by the lack of expression of a gene known as UBE3A during development. This gene is located within a region of chromosome 15 known as 15q11-q13 and is part of the ubiquitin pathway. In fact, UBE3A codes for a very selective E6-AP ubiquitin ligase for which MAPK1, PRMT5, CDK1, CDK4, β-catenin, and UBXD8 have been identified as ubiquitination targetsTypically, a fetus inherits a maternal copy of UBE3A and a paternal copy of UBE3A. In certain areas of the developing brain, the paternal copy of UBE3A is inactivated through a process known as imprinting and the fetus relies on the functioning maternal copy of UBE3A in order to develop normally. In an individual with AS, however, the maternal UBE3A gene is absent or not functioning normally. This can be due to genetic errors such as the deletion or mutation of a segment of chromosome 15, uniparental disomy, or translocation. While Angelman syndrome can be caused by a single mutation in the UBE3A gene, the most common genetic defect leading to Angelman syndrome is a 5- to 7-Mb (megabase) maternal deletion in chromosomal region 15q11.2-q13.Specifically, the paternal copy of UBE3A is known to be imprinted within the hippocampus, cortex, thalamus, olfactory bulb, and cerebellum. Therefore, in these areas of the brain, a functioning maternal copy of UBE3A is essential for proper development.Region 15q11-13 is implicated in both Angelman syndrome and Prader–Willi syndrome (PWS). While AS results from mutation, loss or abnormal imprinting involving the UBE3A gene within this region on the maternal chromosome, loss of a different cluster of genes within the same region on the paternal chromosome causes PWS.The methylation test that is performed for Angelman syndrome looks for methylation on the genes neighbor SNRPN, which is silenced by methylation on the maternal copy of the gene. Neurophysiology The electroencephalogram (EEG) in AS is usually abnormal, more so than clinically expected. This EEG facilitates the differential diagnosis of AS, but is not pathognomonic. Three distinct interictal patterns are seen in these patients. The most common pattern is a very large amplitude 2–3 Hz rhythm most prominent in prefrontal leads. Next most common is a symmetrical 4–6 Hz high voltage rhythm. The third pattern, 3–6 Hz activity punctuated by spikes and sharp waves in occipital leads, is associated with eye closure. Paroxysms of laughter have no relation to the EEG, ruling out this feature as a gelastic phenomenon.EEG anomalies may be used as a quantitative biomarkers to "chart progression of AS and as clinical outcome measures". Slow delta activity (~3 Hz) is greatly increased in AS relative to typically developing children, yet more pronounced in children with partial 15q deletions as opposed to those with etiologies principally affecting UBE3A. Theta activity (~5 Hz) is much greater in children with partial 15q deletions. Thus, delta activity appears to be chiefly reflective of UBE3A dysfunction with some modulation from other 15q genes, whereas theta activity may be an electrophysiological readout of genes beyond UBE3A such as GABRA5, GABRB3, and GABRG3. Future clinical trials in AS might exploit the foregoing by using EEG as a readout of drug target engagement.It appears that the neurons of people with Angelman syndrome are formed correctly, but they cannot function properly. Diagnosis The diagnosis of Angelman syndrome is based on: A history of delayed motor milestones and then later a delay in general development, especially of speech Unusual movements including fine tremors, jerky limb movements, hand flapping and a wide-based, stiff-legged gait. Characteristic facial appearance (but not in all cases). A history of epilepsy and an abnormal EEG tracing. A happy disposition with frequent laughter A deletion or inactivity on chromosome 15 by array comparative genomic hybridization (aCGH) or by BACs-on-Beads technology.Diagnostic criteria for the disorder were initially established in 1995 in collaboration with the Angelman syndrome Foundation (US); these criteria underwent revision in 2005.Seizures are a consequence, but so is excessive laughter, which is a major hindrance to early diagnosis. Differential diagnosis Other conditions that can appear similar include: Autism spectrum Cerebral palsy Rett syndrome Mowat–Wilson syndrome Adenylosuccinate lyase deficiency Pitt–Hopkins syndrome Phelan–McDermid syndrome Prader–Willi syndrome Treatment There is currently no cure available. The epilepsy can be controlled by the use of one or more types of anticonvulsant medications. However, there are difficulties in ascertaining the levels and types of anticonvulsant medications needed to establish control, because people with AS often have multiple types of seizures. Many families use melatonin to promote sleep in a condition which often affects sleep patterns. Many individuals with Angelman syndrome sleep for a maximum of five hours at any one time. Mild laxatives are also used frequently to encourage regular bowel movements. Early intervention with physiotherapy is sometimes used to encourage joint mobility and prevent stiffening of the joints. Speech and Language Therapy is commonly employed to assist individuals with Angelman syndrome and their communication issues.Occupational therapists can contribute to the development and augmentation of non-verbal communication skills by addressing the foundational skills such as finger isolation, motor planning, hand-eye coordination, spatial awareness, and refining gestures. This is important because individuals with Angelman Syndrome who already possess some form of non-verbal communication have a much harder time adapting to changes in a new or existing AAC device because they can communicate their needs much faster nonverbally.Occupational therapists can assist individuals with Angelman syndrome with many other skills as well. Many individuals with Angelman syndrome also have difficulty processing sensory information and responding appropriately to sensory stimuli. Occupational therapists can work together with these individuals to improve their visual perceptual skills and increase their sensory awareness.Those with the syndrome are generally happy and contented people who like human contact and play. People with AS exhibit a profound desire for personal interaction with others. Communication can be difficult at first, but as a child with AS develops, there is a definite character and ability to make themselves understood. People with AS tend to develop strong non-verbal skills to compensate for their limited use of speech. It is widely accepted that their understanding of communication directed to them is much larger than their ability to return conversation. Most affected people will not develop more than 5–10 words, if any at all. Prognosis The severity of the symptoms associated with Angelman syndrome varies significantly across the population of those affected. Some speech and a greater degree of self-care are possible among the least profoundly affected. Walking and the use of simple sign language may be beyond the reach of the more profoundly affected. Early and continued participation in physical, occupational (related to the development of fine-motor control skills), and communication (speech) therapies are believed to significantly improve the prognosis (in the areas of cognition and communication) of individuals affected by AS. Further, the specific genetic mechanism underlying the condition is thought to correlate to the general prognosis of the affected person. On one end of the spectrum, a mutation to the UBE3A gene is thought to correlate to the least affected, whereas larger deletions on chromosome 15 are thought to correspond to the most affected.The clinical features of Angelman syndrome alter with age. As adulthood approaches, hyperactivity and poor sleep patterns improve. The seizures decrease in frequency and often cease altogether and the EEG abnormalities are less obvious. Medication is typically advisable to those with seizure disorders. Often overlooked is the contribution of the poor sleep patterns to the frequency and/or severity of the seizures. Medication may be worthwhile to help deal with this issue and improve the prognosis with respect to seizures and sleep. Also noteworthy are the reports that the frequency and severity of seizures temporarily escalate in pubescent Angelman syndrome girls, but do not seem to affect long-term health.The facial features remain recognizable with age, but many adults with AS look remarkably youthful for their age.Puberty and menstruation begin at around the average age. Sexual development is thought to be unaffected, as evidenced by a single reported case of a woman with Angelman syndrome conceiving a female child who also had Angelman syndrome.The majority of those with AS achieve continence by day and some by night. Angelman syndrome is not a degenerative syndrome, and thus people with AS may improve their living skills with support.Dressing skills are variable and usually limited to items of clothing without buttons or zippers. Most adults can eat with a knife or spoon and fork, and can learn to perform simple household tasks. Particular problems which have arisen in adults are a tendency to obesity (more in females), and worsening of scoliosis if it is present. The affectionate nature may also persist into adult life where it can pose a problem socially, but this problem is not insurmountable. People with Angelman syndrome appear to have a reduced but near-normal life expectancy, dying on average 10 to 15 years earlier than the general population. Epidemiology Though the prevalence of Angelman syndrome is not precisely known, there are some estimates. The best data available are from studies of school age children, ages 6–13 years, living in Sweden and from Denmark where the diagnosis of AS children in medical clinics was compared to an 8-year period of about 45,000 births. The Swedish study showed an AS prevalence of about 1/20,000 and the Danish study showed a minimum AS prevalence of about 1/10,000. History Harry Angelman, a pediatrician working in Warrington, England, first reported three children with this condition in 1965. Angelman later described his choice of the title "Puppet Children" to describe these cases as being related to an oil painting he had seen while vacationing in Italy: The history of medicine is full of interesting stories about the discovery of illnesses. The saga of Angelmans syndrome is one such story. It was purely by chance that nearly thirty years ago (e.g. [sic], circa 1964) three handicapped children were admitted at various times to my childrens ward in England. They had a variety of disabilities and although at first sight they seemed to be suffering from different conditions I felt that there was a common cause for their illness. The diagnosis was purely a clinical one because in spite of technical investigations which today are more refined I was unable to establish scientific proof that the three children all had the same handicap. In view of this I hesitated to write about them in the medical journals. However, when on holiday in Italy I happened to see an oil painting in the Castelvecchio Museum in Verona called ... a Boy with a Puppet. The boys laughing face and the fact that my patients exhibited jerky movements gave me the idea of writing an article about the three children with a title of Puppet Children. It was not a name that pleased all parents but it served as a means of combining the three little patients into a single group. Later the name was changed to Angelman syndrome. This article was published in 1965 and after some initial interest lay almost forgotten until the early eighties. Case reports from the United States first began appearing in the medical literature in the early 1980s. In 1987, it was first noted that around half of the children with AS have a small piece of chromosome 15 missing (chromosome 15q partial deletion). Society and culture Many poems in Richard Prices poetry collections Hand Held (1997), Lucky Day (2005), and Small World (2012) reflect on the disability of the poets daughter, who has Angelman syndrome. In the 2011 Philippine drama series Budoy, the titular character and main protagonist Budoy Maniego (played by Filipino actor Gerald Anderson) is diagnosed with Angelman syndrome. References External links Angelman syndrome at Curlie GeneReviews/NCBI/NIH/UW entry on Angelman syndrome

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What does the medical term 'Pulmonary alveolar microlithiasis' encompass?

Pulmonary alveolar microlithiasis (PAM) is a rare, inherited disorder of lung phosphate balance that is associated with small stone formation in the airspaces of the lung. Mutations in the gene SLC34A2 result in loss of a key sodium, phosphate co-transporter (called Npt2b), known to be expressed in distal alveolar type II cells, as well as in the mammary gland, and to a lesser extent in intestine, kidney, skin, prostate and testes. As the disease progresses, the lung fields become progressively more dense (white) on the chest xray, and low oxygen level, lung inflammation and fibrosis, elevated pressures in the lung blood vessels, and respiratory failure ensue, usually in middle age. The clinical course of PAM can be highly variable, with some patients remaining asymptomatic for decades, and others progressing more rapidly. There is no effective treatment, and the mechanisms of stone formation, inflammation and scarring are not known. Signs and symptoms Patients typically have no symptoms until the third or fourth decade of life. In most cases, the disease is discovered incidentally on routine chest Xray. The most common symptoms include the following: dyspnea dry cough chest pain sporadic hemoptysis asthenia pneumothoraces Genetics PAM is hereditary and another involved family member can be identified in 36% to 61% of cases. Impaired activity of the SLC34A2 gene is responsible for PAM.The SLC34A2 gene encodes a membrane protein that is expressed primarily in the apical portions of alveolar type II cells and is the most abundant phosphate carrier in the lungs. Pathogenesis Type II alveolar cells have many important functions in the lung, including the production of pulmonary surfactant, maintenance of fluid balance and composition in the airspace. Phospholipids that make up pulmonary surfactant are broken down by macrophages, releasing phosphate into the alveolar lining fluid. The loss of the Npt2b phosphate transported eliminates the ability of alveolar type II cells to pump phosphorus ions from the alveolar space back into the bloodstream, and leads to microlith formation.Epithelial deletion of Npt2b in mice results in an authentic mimic of the human condition, including accumulation of calcium phosphate microliths in the lung tissue and progressive diffuse radiographic opacities. The mouse model provides a useful platform for preclinical studies, including therapeutic trials of EDTA lavage and low phosphate diet/phosphate binders. Pathology PAM may be confined to certain areas or show diffuse distribution through the lungs. Lung biopsy and autopsy specimens demonstrate characteristic intra-alveolar lamellar microliths. Calcium deposits in the alveoli begin in the lower lobes and spread over a period of years throughout the lungs. Diagnosis PAM is usually diagnosed on the basis of a typical radiological pattern, namely a very fine, sand-like micronodulation of calcific density diffusely involving both lungs, with basal predominance. Many authors argue that this pattern precludes the need for a lung biopsy in most cases. After PAM is diagnosed in a given patient, family members should be screened by chest radiography, and parents should be counseled that future children are also at risk of developing the disease. Radiology Chest radiographs of patients with PAM usually reveal bilateral diffuse micronodular calcifications, producing a "sandstorm” appearance that first involves the inferior portions and then the middle and upper portions of the lungs. High-resolution computed tomography The most common findings on HRCT are diffuse hyperdense ground-glass attenuation and subpleural linear calcifications, often most predominant in the inferior and posterior portions of the lungs. Additionally, the medial aspects of the lungs appear to be more heavily involved than the lateral aspects. Ground-glass opacities, probably due to small calculi in the air space, are the most common finding in children and in patients with early-stage PAM. Magnetic resonance imaging On magnetic resonance imaging (MRI), the calcific lesions usually show hypointensity or a signal void on T1- and T2-weighted images. Pulmonary function studies Pulmonary function tests, arterial blood gases, ventilation perfusion relationships, and O2 diffusing capacity are normal in the initial stages of PAM. As the disease progresses, pulmonary function tests reveal typical features of a restrictive defect with reduced forced vital capacity (FVC) and elevated forced expiratory volume in FEV1/FVC. Treatment To date, no treatment has been proven to effectively reverse or prevent the progression of PAM. Lung transplantation is an option for end stage disease, but is typically only recommended as a last resort when quality of life is significantly impaired.Etidronate is a bisphosphonate and can reduce the formation of calcium hydroxyapatite crystals. It has led to clinical and radiological improvements in few cases. Epidemiology Since the disease was first described in 1918, over 500 case reports have appeared in the literature. PAM is associated with consanguinity. The incidence is higher in Turkey, Japan, India and Italy. The disease affects both men and women equally, and it has been associated with intermarriage within families. The mean age at diagnosis is 35 years based on the cases reported in the literature. Society PAM is one of the rare lung diseases currently being studied by the Rare Lung Diseases Consortium (RLDC). Pulmonary Alveolar Microlithiasis patients, families, and caregivers are encouraged to join the NIH Rare Lung Diseases Consortium Contact Registry. This is a privacy protected site that provides up-to-date information for individuals interested in the latest scientific news, trials, and treatments related to rare lung diseases. References == External links ==

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

Oxiconazole (trade names Oxistat in the US, Oxizole in Canada) is an antifungal medication typically administered in a cream or lotion to treat skin infections, such as athletes foot, jock itch and ringworm. It can also be prescribed to treat the skin rash known as tinea versicolor, caused by systemic yeast overgrowth (Candida spp.). It was patented in 1975 and approved for medical use in 1983. See also Fluconazole References External links MedlinePlus - Oxiconazole

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

Pseudoxanthoma elasticum (PXE) is a genetic disease that causes mineralization of elastic fibers in some tissues. The most common problems arise in the skin and eyes, and later in blood vessels in the form of premature atherosclerosis. PXE is caused by autosomal recessive mutations in the ABCC6 gene on the short arm of chromosome 16 (16p13.1). Signs and symptoms Usually, pseudoxanthoma elasticum affects the skin first, often in childhood or early adolescence. Small, yellowish papular lesions form and cutaneous laxity mainly affect the neck, axillae (armpits), groin, and flexural creases (the inside parts of the elbows and knees). Skin may become lax and redundant. Many individuals have "oblique mental creases" (horizontal grooves of the chin)PXE first affects the retina through a dimpling of the Bruch membrane (a thin membrane separating the blood vessel-rich layer from the pigmented layer of the retina), that is only visible during ophthalmologic examinations. This is called peau dorange (a French term meaning "skin of the orange"). Eventually the mineralization of the elastic fibers in the Bruch membrane create cracks called angioid streaks that radiate out from the optic nerve. Angioid streaks themselves do not cause distortion of vision, even if they cross into the foveal area. This symptom is present in almost all PXE patients and is usually noticed a few years after the onset of cutaneous lesions. These cracks may allow small blood vessels that were originally held back by Bruchs membrane to penetrate the retina. These blood vessels sometimes leak, and these retinal hemorrhages may lead to the loss of central vision. Vision loss is a major issue in many PXE patients.PXE may affect the gastrointestinal and cardiovascular systems. Gastrointestinal bleeding is a rare symptom and usually involved bleeding from the stomach. In the circulatory system, intermittent claudication, a condition in which cramping pain in the leg is induced by exercise, is a prominent feature. At later stages, coronary artery disease may develop, leading to angina and myocardial infarction (heart attack). Cerebral ischemia in PXE is caused by small vessel occlusive disease. Other rare neurological complications may include intracranial aneurysms, subarachnoid and intracerebral hemorrhages. Genetics 80% of clinical cases of pseudoxanthoma elasticum have detectable mutations in the ABCC6 gene. Mutations in almost all parts of the gene have been described, of all types (missense, nonsense, splice alteration, insertion, small deletion or large deletion). Although there have been reports of autosomal dominant inheritance, the inheritance is typically autosomal recessive (both parents need to be carriers, and there is a 25% chance that a child will inherit both abnormal copies of the gene and therefore develop the condition).Strong genetic linkage was found with mutations in the ABCC6 gene, which codes for the ABCC6 protein, which is a membrane transporter from the large ATP-binding cassette transporter family. The protein is expressed in most organs, but mainly in the liver and kidney. ABCC6 mediates ATP release in the liver. This is the main source of circulating pyrophosphate (PPi), and individuals affected by PXE have strongly reduced plasma PPi levels, explaining their mineralization disorder. One study suggested that mutations causing total absence of an ABCC6 protein caused a more severe disease, but this could not be confirmed in a subsequent case series. Given the variations in age of onset and severity it is likely that other unknown risk factors (genetic, environmental, and lifestyle) may be involved.Premature atherosclerosis is also associated with mutations in the ABCC6 gene, even in those without PXE. A syndrome almost indistinguishable from hereditary PXE has been described in patients with hemoglobinopathies (sickle-cell disease and thalassemia) through a poorly understood mechanism. In addition, there appears to be another PXE-like syndrome with a similar phenotype but as a result of problems with another gene, gamma-glutamyl carboxylase. Mutations in ABCC6 can also cause generalized arterial calcification of infancy. In some cases of PXE, mutations in ABCC6 cannot be found, and other genes such as ENPP1 may be implicated Pathophysiology In PXE, there is mineralization (accumulation of calcium and other minerals) and fragmentation of the elastin-containing fibers in connective tissue, but primarily in the midlaminar layer of the dermis, Bruchs membrane and the midsized arteries. Recent studies have confirmed that PXE is a metabolic disease, and that its features arise because metabolites of vitamin K cannot reach peripheral tissues. Low levels of PPi cause mineralization in peripheral tissues. Diagnosis The diagnostic criteria for PXE are the typical skin biopsy appearance and the presence of angioid streaks in the retina. Criteria were established by consensus of clinicians and researchers at the 2010 biennial research meeting of the PXE Research Consortium. and confirmed at the 2014 meeting These consensus criteria state that definitive PXE is characterized by two pathogenic mutations in the ABCC6 or ocular findings – angioid streaks > 1 DD or peau d’orange in an individual <20 years of age together with skin findings: Characteristic pseudoxanthomatous papules and plaques on the neck or flexural creases. Diagnostic histopathological changes in lesional skin: Calcified elastic fibers in the mid and lower dermis, confirmed by positive calcium stain Differential diagnosis Treatment There is no confirmed treatment that directly interferes with the disease process.Cosmetic surgery to remove excessive skin has been used to improve aesthetic appearance in PXE patients but because of the non-life-threatening nature of these symptoms, should be used with caution.One of the most critical symptom of PXE is choroidal neovascularization which can lead to deterioration of central vision. Photodynamic therapy has been used as a treatment, but this has been replaced with endothelial growth factor (VEGF) inhibitors (such as bevacizumab, ranibizumab, and aflibercept) with efficacy similar to their use in treatment of age-related macular degeneration.To limit cardiovascular symptoms, reduction of cardiovascular risk factors through lifestyle changes is recommended. Generally clinicians recommend avoidance of non-steroidal anti-inflammatory drugs (NSAIDS) that increase bleeding risk, such as aspirin, and ibuprofen to prevent eye and gastrointestinal bleeding.Formerly, dietary restriction of calcium was tried with no benefit, and in fact accelerated mineralization in mice. There are a number of potential treatments that are currently being tested or have just undergone testing including magnesium, etidronate, PPi, and tissue-nonspecific alkaline phosphatase inhibitors.Given that ABCC6 heterozygous mutations result in few symptoms of PXE, this disease is a candidate for gene therapy. Some initial proof-of-principle experiments have been done in mice that have relieved some of symptoms of PXE, but as with all gene therapy treatments, there are many hurdles that must be over come including insuring that the treatment will be long-lasting and reducing the risk of insertional mutagenesis and severe immune reactions. Epidemiology The reported prevalence of pseudoxanthoma elasticum is about 1:25,000. Females are twice as likely to be affected as males. The disease occurs in all ethnicities, but Afrikaners are more likely to have PXE as a result of a founder effect (i.e., higher prevalence in the small group of people from whom Afrikaners descend). History The first description of PXE that distinguished it from other xanthoma conditions was by Dr Ferdinand-Jean Darrier in 1896. The eponym "Grönblad-Strandberg syndrome" is used in older literature, after two physicians who made further discoveries in the disease manifestations.PXE has the distinction of being the only disease for which a layperson is the discover of the mutated gene. The ABCC6 gene mutation was discovered simultaneously by four research teams, all of which published at the same time. The principal investigators were (in order of the date of publication): Jouni Uitto, Arthur Bergen, Charles Boyd, and Klaus Lindpainter. The gene was patented by Charles D. Boyd, Katalin Csiszar, Olivier LeSaux, Zsolt Urban, Sharon Terry, and assigned to PXE International by these co-inventors. Between the filing and 2013, when the Supreme Court of the United States declared that genes may not be patented. PXE International freely licensed the gene to any lab for clinical testing and research. PXE International continues to hold and maintain other patents (diagnosis and treatment patents).PXE International, a support organization, was founded in 1995, by Patrick and Sharon Terry, following the diagnosis of their two children. It has a registry of 4,600 affected individuals. Images See also List of cutaneous conditions References External links PXE international pxe at NIH/UW GeneTests Pseudoxanthoma elasticum at NLM Genetics Home Reference

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

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

Metirosine (INN and BAN; α-Methyltyrosine, Metyrosine USAN, AMPT) is an antihypertensive drug. It inhibits the enzyme tyrosine hydroxylase and, therefore, catecholamine synthesis, which, as a consequence, depletes the levels of the catecholamines dopamine, adrenaline and noradrenaline in the body. It is available as a generic medication. Clinical use Metirosine has been shown to suppress catecholamine synthesis and alleviate symptoms related to catecholamine excess, including hypertension, headache, tachycardia, constipation, and tremor. Metirosine is primarily used to reduce these symptoms in patients with pheochromocytoma. It is contraindicated for the treatment of essential hypertension. Metirosine is used as an off-label treatment for DiGeorge syndrome.Metirosine is used in scientific research to investigate the effects of catecholamine depletion on behavior. There is evidence that catecholamine depletion causes an increase in sleepiness that is more pronounced than sleep deprivation, and that the fatigue lingers after the drug is discontinued. Negative mood is also a reported side effect of catecholamine depletion, although this is reported less consistently than sleepiness. See also p-Chlorophenylalanine References External links "Metyrosine". Drug Information Portal. U.S. National Library of Medicine.

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 need a basic explanation for the medical term 'Pustular bacterid.'

Pustular bacterid is a skin condition characterized by a symmetric, grouped, vesicular or pustular eruption on the palms and soles marked by exacerbations and remissions over long periods of time.: 205 See also List of cutaneous conditions References == External links ==

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

Choriocarcinoma is a malignant, trophoblastic cancer, usually of the placenta. It is characterized by early hematogenous spread to the lungs. It belongs to the malignant end of the spectrum in gestational trophoblastic disease (GTD). It is also classified as a germ cell tumor and may arise in the testis or ovary. Signs and symptoms increased quantitative chorionic gonadotropin (the "pregnancy hormone") levels vaginal bleeding shortness of breath hemoptysis (coughing up blood) chest pain chest X-ray shows multiple infiltrates of various shapes in both lungs presents in males as a testicular cancer, sometimes with skin hyperpigmentation (from excess chorionic gonadotropin cross reacting with the alpha MSH receptor), gynecomastia, and weight loss (from excess chorionic gonadotropin cross reacting with the LH, FSH, and TSH receptor) in males can present with decreased thyroid-stimulating hormone (TSH) due to hyperthyroidism. Cause Choriocarcinoma of the placenta during pregnancy is preceded by: hydatidiform mole (50% of cases) spontaneous abortion (20% of cases) ectopic pregnancy (2% of cases) normal term pregnancy (20–30% of cases) hyperemesis gravidarumRarely, choriocarcinoma occurs in primary locations other than the placenta; very rarely, it occurs in testicles. Although trophoblastic components are common components of mixed germ cell tumors, pure choriocarcinoma of the adult testis is rare. Pure choriocarcinoma of the testis represents the most aggressive pathologic variant of germ cell tumors in adults, characteristically with early hematogenous and lymphatic metastatic spread. Because of early spread and inherent resistance to anticancer drugs, patients have poor prognosis. Elements of choriocarcinoma in a mixed testicular tumor have no prognostic importance.Choriocarcinomas can also occur in the ovaries and other organs. Pathology Characteristic feature is the identification of intimately related syncytiotrophoblasts and cytotrophoblasts without formation of definite placental type villi. Since choriocarcinomas include syncytiotrophoblasts (beta-HCG producing cells), they cause elevated blood levels of beta-human chorionic gonadotropin. Syncytiotrophoblasts are large multi-nucleated cells with eosinophilic cytoplasm. They often surround the cytotrophoblasts, reminiscent of their normal anatomical relationship in chorionic villi. Cytotrophoblasts are polyhedral, mononuclear cells with hyperchromatic nuclei and a clear or pale cytoplasm. Extensive hemorrhage is a common finding. Treatment Since gestational choriocarcinoma (which arises from a hydatidiform mole) contains paternal DNA (and thus paternal antigens), it is exquisitely sensitive to chemotherapy. The cure rates, even for metastatic gestational choriocarcinoma, more than 90% when using chemotherapy for invasive mole and choriocarcinoma.As of 2019, treatment with either single-agent methotrexate or actinomycin-D is recommended for low-risk disease, while intense combination regimens including EMACO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (Oncovin) are recommended for intermediate or high-risk disease.Hysterectomy (surgical removal of the uterus) can also be offered to patients >40 years of age or those for whom sterilisation is not an obstacle. It may be required for those with severe infection and uncontrolled bleeding. Choriocarcinoma arising in the testicle is rare, malignant and highly resistant to chemotherapy. The same is true of choriocarcinoma arising in the ovary. Testicular choriocarcinoma has the worst prognosis of all germ-cell cancers. References External links 00976 at CHORUS

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

Please help me grasp the concept behind the medical term 'Mineral deficiency.'

Mineral deficiency is a lack of the dietary minerals, the micronutrients that are needed for an organisms proper health. The cause may be a poor diet, impaired uptake of the minerals that are consumed, or a dysfunction in the organisms use of the mineral after it is absorbed. These deficiencies can result in many disorders including anemia and goitre. Examples of mineral deficiency include, zinc deficiency, iron deficiency, and magnesium deficiency. Individual Mineral Deficiency See also Mineral (nutrient) Micronutrient deficiency Vitamin deficiency References == External links ==

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

Please help me grasp the concept behind the medical term 'Chronic mountain sickness.'

Chronic mountain sickness (CMS) is a disease in which the proportion of blood volume that is occupied by red blood cells increases (polycythaemia) and there is an abnormally low level of oxygen in the blood (hypoxemia). CMS typically develops after extended time living at high altitude (over 2,500 metres (8,200 ft)). It is most common amongst native populations of high altitude nations. The most frequent symptoms of CMS are headache, dizziness, tinnitus, breathlessness, palpitations, sleep disturbance, fatigue, loss of appetite, confusion, cyanosis, and dilation of veins.CMS was first described in 1925 by Carlos Monge Medrano, a Peruvian doctor who specialised in diseases of high altitude. While acute mountain sickness is experienced shortly after ascent to high altitude, chronic mountain sickness may develop only after many years of living at high altitude. In medicine, high altitude is defined as over 2,500 metres (8,200 ft), but most cases of CMS occur at over 3,000 metres (9,800 ft). It has recently been correlated with increased expression of the genes ANP32D and SENP1. Diagnosis CMS is characterised by polycythaemia (with subsequent increased haematocrit) and hypoxaemia; raised blood pressure in the lungs (pulmonary hypertension) can develop over time and in some cases progress to heart failure (cor pulmonale). CMS is believed to arise because of an excessive production of red blood cells (erythrocytes) due to the low oxygen levels at altitude, which increases the oxygen carrying capacity of the blood[1]. The increased levels of erythrocytes causes increased blood viscosity and uneven blood flow through the lungs (V/Q mismatch). However, CMS is also considered an adaptation of pulmonary and heart disease to life under chronic hypoxia at altitude.Consensus for clinical diagnosis of CMS use laboratory values: haemoglobin in Males ≥ 21 g/dL; Females ≥ 19 g/dL, haematocrit > 65%, and arterial oxygen saturation (SaO2) < 85% in both genders. Treatment Migration to low altitude is curative, though not immediate, as the body adapts to the normal oxygen level near sea-level and the haematocrit normalises. Alternatively, bloodletting (phlebotomy) can be performed to lower the haematocrit temporarily; when combined with volume replacement with fluids this can have a longer effect.Medication with acetazolamide, a carbonic anhydrase inhibitor, has been shown to improve chronic mountain sickness by reducing erythropoietin and the resulting polycythaemia, which results in better arterial oxygenation and a lower heart rate.Oxygen therapy and training in slow breathing techniques has been shown to reduce symptoms through increasing blood oxygenation. Epidemiology Although CMS generally affects people native to altitudes higher than 3,000 metres (9,800 ft), it does not affect populations around the world equally. A 2013 study reviewed CMS prevalence rates around the world and found the highest rates were found in Andean countries of South America and the lowest rates in people native to the East African Mountains of Ethiopia. CMS prevalence rates reported from the study are summarised below: Ethiopia [3600–4100 m]: 0% Tibetan Plateau (Tibetans): 0.91–1.2% Indian Himalayas [3000–4200 m]: 4–7% Kyrgyzstan [3000–4200 m]: 4.6% Tibetan Plateau (Han Chinese): 5.6% La Paz, Bolivia [3600 m]: 6% to 8% Bolivia: 8–10% Cerro de Pasco, Peru [4300 m]: 14.8–18.2% References External links ^ Online calculator illustrating blood oxygen carrying capacity at altitude

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

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

Nasal congestion is the blockage of nasal breathing usually due to membranes lining the nose becoming swollen from inflamed blood vessels. Background In about 85% of cases, nasal congestion leads to mouth breathing rather than nasal breathing. According to Jason Turowski, MD of the Cleveland Clinic, "we are designed to breathe through our noses from birth—its the way humans have evolved." This is referred to as "obligate nasal breathing."Nasal congestion can interfere with hearing and speech. Significant congestion may interfere with sleep, cause snoring, and can be associated with sleep apnea or upper airway resistance syndrome. In children, nasal congestion from enlarged adenoids has caused chronic sleep apnea with insufficient oxygen levels and hypoxia, as well as right-sided heart failure. The problem usually resolves after surgery to remove the adenoids and tonsils, however the problem often relapses later in life due to craniofacial alterations from chronic nasal congestion. Causes Allergies, like hay fever, allergic reaction to pollen or grass Common cold or influenza Rhinitis medicamentosa, a condition of rebound nasal congestion brought on by extended use of topical decongestants (e.g., oxymetazoline, phenylephrine, xylometazoline, and naphazoline nasal sprays) Sinusitis or sinus infection Narrow or collapsing nasal valve Pregnancy may cause women to suffer from nasal congestion due to the increased amount of blood flowing through the body. Nasal polyps Gastroesophageal reflux disease (theorized to cause chronic rhinosinusitis- the "airway reflux paradigm") COVID-19 Nasal obstruction Nasal obstruction characterized by insufficient airflow through the nose can be a subjective sensation or the result of objective pathology. It is difficult to quantify by subjective complaints or clinical examinations alone, hence both clinicians and researchers depend both on concurrent subjective assessment and on objective measurement of the nasal airway.Prevalence of kyphosis has been linked to nasal obstruction in a study. Treatment According to WebMD, congestion can be addressed through the use of a humidifier, warm showers, drinking fluids, using a neti pot, using a nasal saline spray, and sleeping with ones head elevated. It also recommends a number of over the counter decongestants and antihistamines. A 2012 study concluded that combining nasal sprays with "nasal breathing exercises" (NBE) led to improvement of symptoms. Though it may seem weird, crying can also be helpful.The Cleveland Clinic also states that congestion may be a sign of a deviated septum, a condition that needs to be addressed by a doctor. See also Decongestant Honeymoon rhinitis Inhaler References Further reading Nestor, James (2020). Breath: The New Science of a Lost Art. Riverhead Books. ISBN 978-0735213616. == 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.

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

A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other health care provider. Etymology The word patient originally meant one who suffers. This English noun comes from the Latin word patienscode: lat promoted to code: la , the present participle of the deponent verb, patiorcode: lat promoted to code: la , meaning I am suffering, and akin to the Greek verb πάσχεινcode: ell promoted to code: el (paskhein, to suffer) and its cognate noun πάθοςcode: ell promoted to code: el (pathos). This language has been construed as meaning that the role of patients is to passively accept and tolerate the suffering and treatments prescribed by the healthcare providers, without engaging in shared decision-making about their care. Outpatients and inpatients An outpatient (or out-patient) is a patient who attends an outpatient clinic with no plan to stay beyond the duration of the visit. Even if the patient will not be formally admitted with a note as an outpatient, their attendance is still registered, and the provider will usually give a note explaining the reason for the visit, tests, or procedure/surgery, which should include the names and titles of the participating personnel, the patients name and date of birth, signature of informed consent, estimated pre-and post-service time for history and exam (before and after), any anesthesia, medications or future treatment plans needed, and estimated time of discharge absent any (further) complications. Treatment provided in this fashion is called ambulatory care. Sometimes surgery is performed without the need for a formal hospital admission or an overnight stay, and this is called outpatient surgery or day surgery, which has many benefits including lowered healthcare cost, reducing the amount of medication prescribed, and using the physicians or surgeons time more efficiently. Outpatient surgery is suited best for more healthy patients undergoing minor or intermediate procedures (limited urinary-tract, eye, or ear, nose, and throat procedures and procedures involving superficial skin and the extremities). More procedures are being performed in a surgeons office, termed office-based surgery, rather than in a hospital-based operating room. An inpatient (or in-patient), on the other hand, is "admitted" to stay in a hospital overnight or for an indeterminate time, usually, several days or weeks, though in some extreme cases, such as with coma or persistent vegetative state, patients can stay in hospitals for years, sometimes until death. Treatment provided in this fashion is called inpatient care. The admission to the hospital involves the production of an admission note. The leaving of the hospital is officially termed discharge, and involves a corresponding discharge note, and sometimes an assessment process to consider ongoing needs. In the English National Health Service this may take the form of "Discharge to Assess" - where the assessment takes place after the patient has gone home.Misdiagnosis is the leading cause of medical error in outpatient facilities. When the U.S. Institute of Medicine’s groundbreaking 1999 report, To Err Is Human, found up to 98,000 hospital patients die from preventable medical errors in the U.S. each year, early efforts focused on inpatient safety. While patient safety efforts have focused on inpatient hospital settings for more than a decade, medical errors are even more likely to happen in a doctor’s office or outpatient clinic or center. Day patient A day patient or (day-patient) is a patient who is using the full range of services of a hospital or clinic but is not expected to stay the night. The term was originally used by psychiatric hospital services using of this patient type to care for people needing support to make the transition from in-patient to out-patient care. However, the term is now also heavily used for people attending hospitals for day surgery. Alternative terminology Because of concerns such as dignity, human rights and political correctness, the term "patient" is not always used to refer to a person receiving health care. Other terms that are sometimes used include health consumer, healthcare consumer, customer or client. However, such terminology may be offensive to those receiving public health care, as it implies a business relationship. In veterinary medicine, the client is the owner or guardian of the patient. These may be used by governmental agencies, insurance companies, patient groups, or health care facilities. Individuals who use or have used psychiatric services may alternatively refer to themselves as consumers, users, or survivors. In nursing homes and assisted living facilities, the term resident is generally used in lieu of patient. Similarly, those receiving home health care are called clients. Patient-centered healthcare The doctor–patient relationship has sometimes been characterized as silencing the voice of patients. It is now widely agreed that putting patients at the centre of healthcare by trying to provide a consistent, informative and respectful service to patients will improve both outcomes and patient satisfaction.When patients are not at the centre of healthcare, when institutional procedures and targets eclipse local concerns, then patient neglect is possible. Incidents, such as the Stafford Hospital scandal, Winterbourne View hospital abuse scandal and the Veterans Health Administration controversy of 2014 have shown the dangers of prioritizing cost control over the patient experience. Investigations into these and other scandals have recommended that healthcare systems put patient experience at the center, and especially that patients themselves are heard loud and clear within health services.There are many reasons for why health services should listen more to patients. Patients spend more time in healthcare services than regulators or quality controllers, and can recognize problems such as service delays, poor hygiene, and poor conduct. Patients are particularly good at identifying soft problems, such as attitudes, communication, and caring neglect, that are difficult to capture with institutional monitoring.One important way in which patients can be placed at the centre of healthcare is for health services to be more open about patient complaints. Each year many hundreds of thousands of patients complain about the care they have received, and these complaints contain valuable information for any health services which want to learn about and improve patient experience. See also References External links Jadad AR, Rizo CA, Enkin MW (June 2003). "I am a good patient, believe it or not". BMJ. 326 (7402): 1293–5. doi:10.1136/bmj.326.7402.1293. PMC 1126181. PMID 12805157.a peer-reviewed article published in the British Medical Journals (BMJ) first issue dedicated to patients in its 160-year history Sokol DK (21 February 2004). "How (not) to be a good patient". BMJ. 328 (7437): 471. doi:10.1136/bmj.328.7437.471. PMC 344286.review article with views on the meaning of the words "good doctor" vs. "good patient" "Time Magazines Dr. Scott Haig Proves that Patients Need to Be Googlers!" – Mary Shomons response to the Time Magazine article "When the Patient is a Googler"

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'm not familiar with the medical term 'Ross syndrome.' Could you provide some insights?

Ross syndrome consists of Adies syndrome (myotonic pupils and absent deep tendon reflexes) plus segmental anhidrosis (typically associated with compensatory hyperhidrosis).It was characterized in 1958 by A.T. Ross.By 1992, eighteen cases had been documented.Signs and Symptoms Initial manifestations often include an abnormal segmental sweating response (described as hyperhidrosis or anhidrosis in some patients) and a tonic pupil. Other commonly reported symptoms included fatigue, chronic cough, and increased urinary frequency.Prognosis Ross syndrome is a non life-threatening benign condition but delay in diagnosis can result in slow progression of autonomic symptoms. Epidemiology Ross Syndrome is a progressive autonomic dysfunction that can occur in any age, ethnicity, or gender. The average age of diagnosis for Ross syndrome is 36 years and affects more females than males. See also Hypohidrosis List of cutaneous conditions 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'm encountering the term 'Pseudobulbar palsy' in medical literature. What's its definition?

Pseudobulbar palsy is a medical condition characterized by the inability to control facial movements (such as chewing and speaking) and caused by a variety of neurological disorders. Patients experience difficulty chewing and swallowing, have increased reflexes and spasticity in tongue and the bulbar region, and demonstrate slurred speech (which is often the initial presentation of the disorder), sometimes also demonstrating uncontrolled emotional outbursts.The condition is usually caused by the bilateral damage to corticobulbar pathways, which are upper motor neuron pathways that course from the cerebral cortex to nuclei of cranial nerves in the brain stem. Signs and symptoms Signs and symptoms of pseudobulbar palsy include: Slow and indistinct speech Dysphagia (difficulty in swallowing) Small, stiff and spastic tongue Brisk jaw jerk Dysarthria Labile affect Gag reflex may be normal, exaggerated or absent Examination may reveal upper motor neuron lesion of the limbs Causes Pseudobulbar palsy is the result of damage of motor fibers traveling from the cerebral cortex to the lower brain stem. This damage might arise in the course of a variety of neurological conditions that involve demyelination and bilateral corticobulbar lesions. Examples include: Vascular causes: bilateral hemisphere infarction, CADASIL syndrome, artery of percheron infarct Progressive supranuclear palsy Amyotrophic lateral sclerosis Parkinsons disease and related multiple system atrophy Various motor neuron diseases, especially those involving demyelination Multiple sclerosis and other inflammatory disorders High brain stem tumors Metabolic causes: osmotic demyelination syndrome Neurological involvement in Behçets disease Brain trauma Pathophysiology The proposed mechanism of pseudobulbar palsy points to the disinhibition of the motor neurons controlling laughter and crying, proposing that a reciprocal pathway exists between the cerebellum and the brain stem that adjusts laughter and crying responses, making them appropriate to context. The pseudobulbar crying could also be induced by stimulation in the region of the subthalamic nucleus of the brain. Diagnosis Diagnosis of pseudobulbar palsy is based on observation of the symptoms of the condition. Tests examining jaw jerk and gag reflex can also be performed. It has been suggested that the majority of patients with pathological laughter and crying have pseudobulbar palsy due to bilateral corticobulbar lesions and often a bipyramidal involvement of arms and legs. To further confirm the condition, MRI can be performed to define the areas of brain abnormality. Treatment Since pseudobulbar palsy is a syndrome associated with other diseases, treating the underlying disease may eventually reduce the symptoms of pseudobulbar palsy.Possible pharmacological interventions for pseudobulbar affect include the tricyclic antidepressants, serotonin reuptake inhibitors, and a novel approach utilizing dextromethorphan and quinidine sulfate. Nuedexta is an FDA approved medication for pseudobulbar affect. Dextromethorphan, an N-methyl-D-aspartate receptor antagonist, inhibits glutamatergic transmission in the regions of the brainstem and cerebellum, which are hypothesized to be involved in pseudobulbar symptoms, and acts as a sigma ligand, binding to the sigma-1 receptors that mediate the emotional motor expression. See also Corticobulbar tract Bulbar palsy, a similar syndrome caused by the damage of lower motor neurons. Motor neuron disease 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.

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

Midodrine is a vasopressor/antihypotensive agent (it raises the blood pressure). Midodrine was approved in the United States by the Food and Drug Administration (FDA) in 1996 for the treatment of dysautonomia and orthostatic hypotension. In August 2010, the FDA proposed withdrawing this approval because the manufacturer, Shire plc, failed to complete required studies after the medicine reached the market. In September 2010, the FDA reversed its decision to remove midodrine from the market and allowed it to remain available to patients while Shire plc collected further data regarding the efficacy and safety of the drug. Shire announced on September 22, 2011, that it was withdrawing completely from supplying midodrine and leaving it to several generics to supply the drug. Medical uses Midodrine is indicated for the treatment of symptomatic orthostatic hypotension. It can reduce dizziness and faints by about a third, but can be limited by troublesome goose bumps, skin itch, gastrointestinal discomfort, chills, elevated blood pressure while lying down, and urinary retention. A meta-analysis of clinical trials of midodrine or droxidopa in patients with low blood pressure when standing found that midodrine increased standing blood pressure more than droxidopa but that midodrine but not droxidopa increased the risk of high blood pressure when lying down. Small studies have also shown that midodrine can be used to prevent excessive drops in blood pressure in people requiring dialysis.Midodrine has been used in the complications of cirrhosis. It is also used with octreotide for hepatorenal syndrome; the proposed mechanism is constriction of splanchnic vessels and dilation of renal vasculature. Studies have not been sufficiently well conducted to show a clear place for midodrine. Contraindications Midodrine is contraindicated in patients with severe organic heart disease, acute kidney disease, urinary retention, pheochromocytoma or thyrotoxicosis. Midodrine should not be used in patients with persistent and excessive supine hypertension. Side effects Headache, feeling of pressure/fullness in the head, vasodilation/flushing face, scalp tingling, confusion/thinking abnormality, dry mouth, nervousness/anxiety and rash. Pharmacology Mechanism of action Midodrine is a prodrug which forms an active metabolite, desglymidodrine, which is an α1-receptor agonist and exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. Desglymidodrine does not stimulate cardiac beta-adrenergic receptors. Desglymidodrine diffuses poorly across the blood–brain barrier, and is therefore not associated with effects on the central nervous system. Pharmacokinetics After oral administration, midodrine is rapidly absorbed. The plasma levels of the prodrug peak after about half an hour, and decline with a half-life of approximately 25 minutes, while the metabolite reaches peak blood concentrations about 1 to 2 hours after a dose of midodrine and has a half-life of about 3 to 4 hours. The absolute bioavailability of midodrine (measured as desglymidodrine) is 93%. Chemistry Midodrine is an odorless, white, crystalline powder, soluble in water and sparingly soluble in methanol. Stereochemistry Midodrine contains a stereocenter and consists of two enantiomers, making it a racemate; i.e., a 1:1 mixture of (R)- and (S)-forms: Synthesis Acylation of 1,4-dimethoxybenzene with chloroacetyl chloride gives the chloroketone 2. The halogen is then converted to the amine 3 by any set of standard schemes, and the ketone reduced to an alcohol with borohydride (4). Acylation of the amino group in this last intermediate with chloroacetyl chloride affords the amide 5. The halogen is then displaced with azide and the resulting product 6 reduced catalytically to the glycinamide, midodrine (7). References External links Media related to Midodrine at Wikimedia Commons "Midodrine". 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'm curious about the meaning of the medical term 'Hemopericardium.' Can you give me some insights?

Hemopericardium refers to blood in the pericardial sac of the heart. It is clinically similar to a pericardial effusion, and, depending on the volume and rapidity with which it develops, may cause cardiac tamponade.The condition can be caused by full-thickness necrosis (death) of the myocardium (heart muscle) after myocardial infarction, chest trauma, and by over-prescription of anticoagulants. Other causes include ruptured aneurysm of sinus of Valsalva and other aneurysms of the aortic arch.Hemopericardium can be diagnosed with a chest X-ray or a chest ultrasound, and is most commonly treated with pericardiocentesis. While hemopericardium itself is not deadly, it can lead to cardiac tamponade, a condition that is fatal if left untreated. Symptoms and signs Symptoms of hemopericardium often include difficulty breathing, abnormally rapid breathing, and fatigue, each of which can be a sign of a serious medical condition not limited to hemopericardium. In many cases, patients also report feeling chest pressure and have an abnormally elevated heart rate. Cause Hemopericardium has been reported to result from various afflictions including chest trauma, free wall rupture after a myocardial infarction, bleeding into the pericardial sac following a type A aortic dissection, and as a complication of invasive cardiac procedures. Acute leukemia has also been reported as a cause of the condition. Several cases of hemopericardium have also been reported as a side-effect of anticoagulants. Patients should be made aware of this fact when prescribed these drugs. Mechanism Hemopericardium is a condition that affects the cardiovascular system. It typically begins with blood accumulating in the pericardial sac posterior to the heart, and eventually expands to surround the entire heart. The fluid build-up then causes pressure within the pericardial sac to increase. If the pressure becomes greater than the intracardiac pressure of the heart, compression of the adjacent cardiac chambers can occur. This compression, called cardiac tamponade, is often associated with hemopericardium and can be fatal if not diagnosed and treated promptly. Early signs of this compression include right atrial inversion during ventricular systole followed by diastolic compression of the right ventricular outflow tract.There have also been cases reported in which hemopericardium was noted as an initial manifestation of essential thrombocythemia. Diagnosis Hemopericardium can be diagnosed using echocardiography, a cardiac ultrasound. Chest X-rays are also often taken when hemopericardium is suspected and would reveal an enlarged heart. Other observable signs include rapid heart rate, jugular venous distension, low blood pressure, and pulsus paradoxus. Treatment When discovered, hemopericardium is usually treated by pericardiocentesis, a procedure wherein a needle is used to remove the fluid from the pericardial sac. This procedure typically utilizes an 8-cm, 18-gauge needle that is inserted between the xiphoid process and the left costal margin until it enters the pericardial sac, when it can then be used to drain the fluid from the sac. A catheter is often left in the pericardium to continue draining any remaining fluid after the initial procedure. The catheter can be removed when the hemopericardium no longer persists. The underlying causes of the condition, such as over-prescription of anticoagulants, must be addressed as well so that the hemopericardium does not return.While hemopericardium itself is not fatal, it may lead to cardiac tamponade, which can be deadly if not treated promptly. One study found that cardiac tamponade was fatal in 13.3% of cases in which it was not caused by a malignant disease. Research Studies have shown that hemopericardium can occur spontaneously in people with essential thrombocythemia, although this is relatively rare. It is a more common occurrence in patients who have been over-prescribed anticoagulants. Regardless of the underlying cause of the hemopericardium, pericardiocentesis has shown to be the best treatment method for the condition. 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'm seeking clarification on the medical term 'Hydrocodone.' Could you explain it?

Hydrocodone (dihydrocodeinone) is an opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe enough to require an opioid and in combination with homatropine methylbromide to relieve cough. It is also available by itself in a long-acting form under the brand name Zohydro ER, among others, to treat severe pain of a prolonged duration. Hydrocodone is a controlled drug, in the United States a Schedule II Controlled Substance. Common side effects include dizziness, sleepiness, nausea, and constipation. Serious side effects may include low blood pressure, seizures, QT prolongation, respiratory depression, and serotonin syndrome. Rapidly decreasing the dose may result in opioid withdrawal. Use during pregnancy or breastfeeding is generally not recommended. Hydrocodone is believed to work by activating opioid receptors, mainly in the brain and spinal cord. Hydrocodone 10 mg is equivalent to about 10 mg of morphine by mouth.Hydrocodone was patented in 1923, while the long-acting formulation was approved for medical use in the United States in 2013. It is most commonly prescribed in the United States, which consumed 99% of the worldwide supply as of 2010. In 2017, it was the 118th most commonly prescribed medication in the United States, with more than six million prescriptions. Hydrocodone is a semisynthetic opioid, converted from codeine or less often from thebaine. Production using genetically engineered yeasts have been developed but are not used commercially. Medical uses Hydrocodone is used to treat moderate to severe pain. In liquid formulations, it is used to treat cough. In one study comparing the potency of hydrocodone to that of oxycodone, it was found that it took 50% more hydrocodone to achieve the same degree of miosis (pupillary contraction). The investigators interpreted this to mean that oxycodone is about 50% more potent than hydrocodone. However, in a study of emergency department patients with fractures, it was found that an equal amount of either drug provided about the same degree of pain relief, indicating that there is little practical difference between them when used for that purpose. Some references state that the analgesic action of hydrocodone begins in 20–30 minutes and lasts about 4–8 hours. The manufacturers information says onset of action is about 10–30 minutes and duration is about 4–6 hours. Recommended dosing interval is 4–6 hours. Available forms Hydrocodone is available in a variety of formulations for oral administration: The original oral form of hydrocodone alone, Dicodid, as immediate-release 5- and 10-mg tablets is available for prescription in Continental Europe per national drug control and prescription laws and Title 76 of the Schengen Treaty, but dihydrocodeine has been more widely used for the same indications since the beginning in the early 1920s, with hydrocodone being regulated the same way as morphine in the German Betäubungsmittelgesetz, the similarly named law in Switzerland and the Austrian Suchtmittelgesetz, whereas dihydrocodeine is regulated like codeine. For a number of decades, the liquid hydrocodone products available have been cough medicines. Hydrocodone plus homatropine (Hycodan) in the form of small tablets for coughing and especially neuropathic moderate pain (the homatropine, an anticholinergic, is useful in both of those cases and is a deterrent to intentional overdose) was more widely used than Dicodid and was labelled as a cough medicine in the United States whilst Vicodin and similar drugs were the choices for analgesia. Extended-release hydrocodone in a time-release syrup also containing chlorphenamine/chlorpheniramine is a cough medicine called Tussionex in North America. In Europe, similar time-release syrups containing codeine (numerous), dihydrocodeine (Paracodin Retard Hustensaft), nicocodeine (Tusscodin), thebacon, acetyldihydrocodeine, dionine, and nicodicodeine are used instead. Immediate-release hydrocodone with paracetamol (acetaminophen) (Vicodin, Lortab, Lorcet, Maxidone, Norco, Zydone) Immediate-release hydrocodone with ibuprofen (Vicoprofen, Ibudone, Reprexain) Immediate-release hydrocodone with aspirin (Alor 5/500, Azdone, Damason-P, Lortab ASA, Panasal 5/500) Controlled-release hydrocodone (Hysingla ER by Purdue Pharma, Zohydro ER)Hydrocodone is not available in parenteral or any other non-oral forms. Side effects Common side effects of hydrocodone are nausea, vomiting, constipation, drowsiness, dizziness, lightheadedness, anxiety, abnormally happy or sad mood, dry throat, difficulty urinating, rash, itching, and contraction of the pupils. Serious side effects include slowed or irregular breathing and chest tightness.Several cases of progressive bilateral hearing loss unresponsive to steroid therapy have been described as an infrequent adverse reaction to hydrocodone/paracetamol misuse. This adverse effect has been considered by some to be due to the ototoxicity of hydrocodone. Other researchers have suggested that paracetamol is the primary agent responsible for the ototoxicity.Hydrocodone is in U.S. Food and Drug Administration (FDA) pregnancy category C. No adequate and well-controlled studies in humans have been conducted. A newborn of a mother taking opioid medications regularly prior to the birth will be physically dependent. The baby may also exhibit respiratory depression if the opioid dose was high. An epidemiological study indicated that opioid treatment during early pregnancy results in increased risk of various birth defects.Symptoms of hydrocodone overdose include narrowed or widened pupils; slow, shallow, or stopped breathing; slowed or stopped heartbeat; cold, clammy, or blue skin; excessive sleepiness; loss of consciousness; seizures; or death.Hydrocodone can be habit forming, causing physical and psychological dependence. Its abuse liability is similar to morphine and less than oxycodone. Interactions Patients consuming alcohol, other opioids, anticholinergic antihistamines, anti-psychotics, anti-anxiety agents, or other central nervous system (CNS) depressants together with hydrocodone may exhibit an additive CNS depression. Hydrocodone may interact with serotonergic medications. Pharmacology Pharmacodynamics Hydrocodone is a highly selective full agonist of the μ-opioid receptor (MOR). This is the main biological target of the endogenous opioid neuropeptide β-endorphin. Hydrocodone has low affinity for the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR), where it is an agonist similarly.Studies have shown hydrocodone is stronger than codeine but only one-tenth as potent as morphine at binding to receptors and reported to be only 59% as potent as morphine in analgesic properties. However, in tests conducted on rhesus monkeys, the analgesic potency of hydrocodone was actually higher than morphine. Oral hydrocodone has a mean equivalent daily dosage (MEDD) factor of 0.4, meaning that 1 mg of hydrocodone is equivalent to 0.4 mg of intravenous morphine. However, because of morphines low oral bioavailability, there is a 1:1 correspondence between orally administered morphine and orally administered hydrocodone. Pharmacokinetics Absorption Hydrocodone is only pharmaceutically available as an oral medication. It is well-absorbed, but the oral bioavailability of hydrocodone is only approximately 25%. The onset of action of hydrocodone via this route is 10 to 20 minutes, with a peak effect (Tmax) occurring at 30 to 60 minutes, and it has a duration of 4 to 8 hours. Distribution The volume of distribution of hydrocodone is 3.3 to 4.7 L/kg. The plasma protein binding of hydrocodone is 20 to 50%. Metabolism In the liver, hydrocodone is transformed into several metabolites, including norhydrocodone, hydromorphone, 6α-hydrocodol (dihydrocodeine), and 6β-hydrocodol. 6α- and 6β-hydromorphol are also formed, and the metabolites of hydrocodone are conjugated (via glucuronidation). Hydrocodone has a terminal half-life that averages 3.8 hours (range 3.3–4.4 hours). The hepatic cytochrome P450 enzyme CYP2D6 converts hydrocodone into hydromorphone, a more potent opioid (5-fold higher binding affinity to the MOR). However, extensive and poor cytochrome 450 CYP2D6 metabolizers had similar physiological and subjective responses to hydrocodone, and CYP2D6 inhibitor quinidine did not change the responses of extensive metabolizers, suggesting that inhibition of CYP2D6 metabolism of hydrocodone has no practical importance. Ultra-rapid CYP2D6 metabolizers (1–2% of the population) may have an increased response to hydrocodone; however, hydrocodone metabolism in this population has not been studied.Norhydrocodone, the major metabolite of hydrocodone, is predominantly formed by CYP3A4-catalyzed oxidation. In contrast to hydromorphone, it is described as inactive. However, norhydrocodone is actually a MOR agonist with similar potency to hydrocodone, but has been found to produce only minimal analgesia when administered peripherally to animals (likely due to poor blood–brain barrier and thus central nervous system penetration). Inhibition of CYP3A4 in a child who was, in addition, a poor CYP2D6 metabolizer, resulted in a fatal overdose of hydrocodone. Approximately 40% of hydrocodone metabolism is attributed to non-cytochrome P450-catalyzed reactions. Elimination Hydrocodone is excreted in urine, mainly in the form of conjugates. Chemistry Detection in body fluids Hydrocodone concentrations are measured in blood, plasma, and urine to seek evidence of misuse, to confirm diagnoses of poisoning, and to assist in investigations into deaths. Many commercial opiate screening tests react indiscriminately with hydrocodone, other opiates, and their metabolites, but chromatographic techniques can easily distinguish hydrocodone uniquely. Blood and plasma hydrocodone concentrations typically fall into the 5–30 µg/L range among people taking the drug therapeutically, 100–200 µg/L among recreational users, and 100–1,600 µg/L in cases of acute, fatal overdosage. Co-administration of the drug with food or alcohol can very significantly increase the resulting plasma hydrocodone concentrations that are subsequently achieved. Synthesis Hydrocodone is most commonly synthesized from Thebaine, a constituent of opium latex from the dried poppy plant. Once Thebaine is obtained, the reaction undergoes hydrogenation using a palladium catalyst. Structure There are three important structures in hydrocodone: the amine group, which binds to the tertiary nitrogen binding site in the central nervous systems opioid receptor, the hydroxy group that binds to the anionic binding side, and the phenyl group which binds to the phenolic binding site. This triggers a G protein activation and subsequent release of dopamine. History Hydrocodone was first synthesized in Germany in 1920 by Carl Mannich and Helene Löwenheim. It was approved by the Food and Drug Administration on 23 March 1943 for sale in the United States and approved by Health Canada for sale in Canada under the brand name Hycodan.Hydrocodone was first marketed by Knoll as Dicodid, starting in February 1924 in Germany. This name is analogous to other products the company introduced or otherwise marketed: Dilaudid (hydromorphone, 1926), Dinarkon (oxycodone, 1917), Dihydrin (dihydrocodeine, 1911), and Dimorphan (dihydromorphine). Paramorfan is the trade name of dihydromorphine from another manufacturer, as is Paracodin, for dihydrocodeine.The name Dicodid was registered in the United States and appears without a monograph as late as 1978 in the Physicians Desk Reference; Dicodid may have been marketed to one extent or another in North America in the 1920s and early 1930s. The drug was pure hydrocodone in small 5 and 10 mg tablets, physically similar to the Dilaudid tablets. It is no longer manufactured by Knoll in Germany, nor is a generic available. Hydrocodone was never as common in Europe as it is in North America—dihydrocodeine is used for its spectrum of indications. Germany was the number two consumer of hydrocodone until the manufacture of the drug was discontinued there. Now, the world outside the United States accounts for less than 1% of annual consumption. It was listed as a Suchtgift under the German Betäubungsmittelgesetz and regulated like morphine. It became available in the Schengen Area of the European Union as of 1 January 2002 under Title 76 of the Schengen Treaty. Society and culture Formulations Several common imprints for hydrocodone are M365, M366, M367. Combination products Most hydrocodone formulations include a second analgesic, such as paracetamol (acetaminophen) or ibuprofen. Examples of hydrocodone combinations include Norco, Vicodin, Vicoprofen and Riboxen. Legal status United States The US government imposed tougher prescribing rules for hydrocodone in 2014, changing the drug from Schedule III to Schedule II. In 2011, hydrocodone products were involved in around 100,000 abuse-related emergency department visits in the United States, more than double the number in 2004. References External links "Hydrocodone". Drug Information Portal. U.S. National Library of Medicine. "DEA Schedules of Controlled Substances: Rescheduling of Hydrocodone Combination Products From Schedule III to Schedule II". Federal Register. 6 October 2014.

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

Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a persons blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hypotension. The drop in blood pressure may be sudden (vasovagal orthostatic hypotension), within 3 minutes (classic orthostatic hypotension) or gradual (delayed orthostatic hypotension). It is defined as a fall in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg when a person assumes a standing position. It occurs predominantly by delayed (or absent) constriction of the lower body blood vessels, which is normally required to maintain adequate blood pressure when changing the position to standing. As a result, blood pools in the blood vessels of the legs for a longer period, and less is returned to the heart, thereby leading to a reduced cardiac output and inadequate blood flow to the brain. Very mild occasional orthostatic hypotension is common and can occur briefly in anyone, although it is prevalent in particular among the elderly and those with known low blood pressure. Severe drops in blood pressure can lead to fainting, with a possibility of injury. Moderate drops in blood pressure can cause confusion/inattention, delirium, and episodes of ataxia. Chronic orthostatic hypotension is associated with cerebral hypoperfusion that may accelerate the pathophysiology of dementia. Whether it is a causative factor in dementia is unclear.The numerous possible causes for orthostatic hypotension include certain medications (e.g. alpha blockers), autonomic neuropathy, decreased blood volume, multiple system atrophy, and age-related blood-vessel stiffness. Apart from addressing the underlying cause, orthostatic hypotension may be treated with a recommendation to increase salt and water intake (to increase the blood volume), wearing compression stockings, and sometimes medication (fludrocortisone, midodrine, or others). Salt loading (dramatic increases in salt intake) must be supervised by a doctor, as this can cause severe neurological problems if done too aggressively. Signs and symptoms Orthostatic hypotension is characterized by symptoms that occur after standing (from lying or sitting), particularly when done rapidly. Many report lightheadedness (a feeling that one might be about to faint), sometimes severe, or even actual fainting with associated fall risk. With chronic orthostatic hypotension, the condition and its effects may worsen even as fainting and many other symptoms become less frequent. Generalized weakness or tiredness may also occur. Some also report difficulty concentrating, blurred vision, tremulousness, vertigo, anxiety, palpitations (awareness of the heartbeat), unsteadiness, feeling sweaty or clammy, and sometimes nausea. A person may look pale. Some people may experience severe orthostatic hypotension with the only symptoms being confusion or extreme fatigue. Chronic severe orthostatic hypotension may present as fluctuating cognition/delirium. Women who are pregnant are also susceptible to orthostatic hypotension. Associated diseases The disorder may be associated with Addisons disease, atherosclerosis (build-up of fatty deposits in the arteries), diabetes, pheochromocytoma, porphyria, and certain neurological disorders, including autoimmune autonomic ganglionopathy, multiple system atrophy, and other forms of dysautonomia. It is also associated with Ehlers–Danlos syndrome and anorexia nervosa. It is also present in many patients with Parkinsons disease or Lewy body dementia resulting from sympathetic denervation of the heart or as a side effect of dopaminomimetic therapy. This rarely leads to fainting unless the person has developed true autonomic failure or has an unrelated heart problem.Another disease, dopamine beta hydroxylase deficiency, also thought to be underdiagnosed, causes loss of sympathetic noradrenergic function and is characterized by low or extremely low levels of norepinephrine, but an excess of dopamine.Quadriplegics and paraplegics also might experience these symptoms due to multiple systems inability to maintain normal blood pressure and blood flow to the upper part of the body. Causes Some causes of orthostatic hypotension include neurodegenerative disorders, low blood volume (e.g. caused by dehydration, bleeding, or the use of diuretics), drugs that cause vasodilation, other types of drugs (notably, narcotics and marijuana), discontinuation of vasoconstrictors, prolonged bed rest (immobility), significant recent weight loss, anemia, vitamin B12 deficiency, or recent bariatric surgery. Medication Orthostatic hypotension can be a side effect of certain antidepressants, such as tricyclics or monoamine oxidase inhibitors (MAOIs). Marijuana and tetrahydrocannabinol can on occasion produce marked orthostatic hypotension. Alcohol can potentiate orthostatic hypotension to the point of syncope. Orthostatic hypotension can also be a side effect of alpha-1 blockers (alpha1 adrenergic blocking agents). Alpha1 blockers inhibit vasoconstriction normally initiated by the baroreceptor reflex upon postural change and the subsequent drop in pressure. Other factors Patients prone to orthostatic hypotension are the elderly, post partum mothers, and those having been on bed rest. People with anorexia nervosa and bulimia nervosa often develop orthostatic hypotension as a common side effect. Consuming alcohol may also lead to orthostatic hypotension due to its dehydrating effects. Mechanism Orthostatic hypotension happens when gravity causes blood to pool in the lower extremities, which in turn compromises venous return, resulting in decreased cardiac output and subsequent lowering of arterial pressure. For example, changing from a lying position to standing loses about 700 ml of blood from the thorax, with a decrease in systolic and diastolic blood pressures. The overall effect is insufficient blood perfusion in the upper part of the body.Normally, a series of cardiac, vascular, neurologic, muscular, and neurohumoral responses occurs quickly so the blood pressure does not fall very much. One response is a vasoconstriction (baroreceptor reflex), pressing the blood up into the body again. (Often, this mechanism is exaggerated and is why diastolic blood pressure is a bit higher when a person is standing up, compared to a person in the horizontal position.) Therefore, some factor that inhibits one of these responses and causes a greater than normal fall in blood pressure is required. Such factors include low blood volume, diseases, and medications. Diagnosis Orthostatic hypotension can be confirmed by measuring a persons blood pressure after lying flat for 5 minutes, then 1 minute after standing, and 3 minutes after standing. Orthostatic hypotension is defined as a fall in systolic blood pressure of at least 20 mmHg or the diastolic blood pressure of at least 10 mmHg between the supine reading and the upright reading. Also, the heart rate should be measured for both positions. A significant increase in heart rate from supine to standing may indicate a compensatory effort by the heart to maintain cardiac output. A related syndrome, postural orthostatic tachycardia syndrome (POTS), is diagnosed when at least a 30 bpm increase in heart rate occurs with little or no change in blood pressure. A tilt table test may also be performed. Definition Orthostatic hypotension (or postural hypotension) is a drop in blood pressure upon standing. One definition (AAFP) calls for a systolic blood pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg within 3 minutes of standing. A common first symptom is lightheadedness upon standing, possibly followed by more severe symptoms: narrowing or loss of vision, dizziness, weakness, and even syncope (fainting). Subcategories Orthostatic hypotension can be subcategorized into three groups – initial, classic, and delayed.Initial orthostatic hypotension is frequently characterized by a systolic blood pressure decrease of ≥40 mmHg or diastolic blood pressure decrease of ≥20 mmHg within 15 seconds of standing. Blood pressure then spontaneously and rapidly returns to normal, so the period of hypotension and symptoms is short (<30 s). Only continuous beat-to-beat BP measurement during an active standing-up maneuver can document this condition.Classic orthostatic hypotension is frequently characterized by a systolic blood pressure decrease of ≥20 mmHg or diastolic blood pressure decrease of ≥10 mmHg between 30 seconds and 3 min of standing.Delayed orthostatic hypotension is frequently characterized by a sustained systolic blood pressure decrease of ≥20 mm Hg or a sustained diastolic blood pressure decrease ≥of 10 mm Hg beyond 3 minutes of standing or upright tilt table testing. Management Lifestyle changes Apart from treating underlying reversible causes (e.g., stopping or reducing certain medications, treating autoimmune causes), several measures can improve the symptoms of orthostatic hypotension and prevent episodes of syncope (fainting). Even small increases in the blood pressure may be sufficient to maintain blood flow to the brain on standing.In dysautonomic patients who do not have a diagnosis of high blood pressure, drinking 2–3 liters of fluid a day and taking 10 g of salt can improve symptoms, by maximizing the amount of fluid in the bloodstream. Another strategy is keeping the head of the bed slightly elevated. This reduces the return of fluid from the limbs to the kidneys at night, thereby reducing nighttime urine production and maintaining fluid in the circulation. Various measures can be used to improve the return of blood to the heart; the wearing of compression stockings and exercises ("physical counterpressure maneuvers" or PCMs) can be undertaken just before standing up (e.g., leg crossing and squatting). Medications The medication midodrine can benefit people with orthostatic hypotension, The main side effect is piloerection ("goose bumps"). Fludrocortisone is also used, although based on more limited evidence.Droxidopa has been shown to be effective as well, with few, mostly mild side effects reported.A number of other measures have slight evidence to support their use – indomethacin, fluoxetine, dopamine antagonists, metoclopramide, domperidone, monoamine oxidase inhibitors with tyramine (can produce severe hypertension), oxilofrine, potassium chloride, and yohimbine. Other Robotic devices, such as the ERIGO machine, has been proven to help orthostatic hypotension in some patients. These machines adjust a patients position from 0 degrees to 90 degrees in progressive increments, allowing the blood pressure to adjust more slowly. Prognosis Orthostatic hypotension may cause accidental falls. It is also linked to an increased risk of cardiovascular disease, heart failure, and stroke. Also, observational data suggest that orthostatic hypotension in middle age increases the risk of eventual dementia and reduced cognitive function. See also Orthostatic hypertension Orthostatic intolerance Vasovagal response References External links Orthostatic hypotension at Curlie Postural hypotension : what it is and how to manage it – Centers for Disease Control and Prevention

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

Primary juvenile glaucoma is glaucoma that develops due to ocular hypertension and is evident either at birth or within the first few years of life. It is caused due to abnormalities in the anterior chamber angle development that obstruct aqueous outflow in the absence of systemic anomalies or other ocular malformation. Presentation The typical infant who has congenital glaucoma usually is initially referred to an ophthalmologist because of apparent corneal edema. The commonly described triad of epiphora (excessive tearing), blepharospasm and photophobia may be missed until the corneal edema becomes apparent. Systemic associations Two of the more commonly encountered disorders that may be associated with congenital glaucoma are Aniridia and Sturge-Weber syndrome. Genetics JOAG is an autosomal dominant condition. The primary cause is the myocilin protein dysfunction. Myocilin gene mutations are identified in approximately 10% of patients affected by juvenile glaucoma. Diagnosis The diagnosis is clinical. The intraocular pressure (IOP) can be measured in the office in a conscious swaddled infant using a Tonopen or hand-held Goldmann tonometer. Usually, the IOP in normal infants is in the range of 11-14 mmHg. Buphthalmos and Haabs striae can often be seen in case of congenital glaucoma. Differential diagnosis Corneal cloudiness may have myriad of causes. Corneal opacity that results from hereditary dystrophies is usually symmetric. Corneal enlargement may result from megalocornea, a condition in which the diameter of the cornea is larger than usual and the eye is otherwise normal. Treatment The preferred treatment of congenital glaucoma is surgical, not medical. The initial procedures of choice are goniotomy or trabeculotomy if the cornea is clear, and trabeculectomy ab externo if the cornea is hazy. The success rates are similar for both procedures in patients with clear corneas. Trabeculectomy and shunt procedures should be reserved for those cases in which goniotomy or trabeculotomy has failed. Cyclophotocoagulation is necessary in some intractable cases but should be avoided whenever possible because of its potential adverse effects on the lens and the retina. Epidemiology In the United States, the incidence of primary congenital glaucoma is about one in 10,000 live births. Worldwide, the incidence ranges from a low of 1:22,000 in Northern Ireland to a high of 1:2,500 in Saudi Arabia and 1:1,250 in Romania. In about two-thirds of cases, it is bilateral. The distribution between males and females varies with geography. In North America and Europe, it is more common in boys, whereas in Japan it is more common in girls. Congenital glaucomaIncidence: one in every 10000-15000 live births. Bilateral in up to 80% of cases. Most cases are sporadic (90%). However, in the remaining 10% there appears to be a strong familial component. See also Axenfeld syndrome Peters-plus syndrome Weill–Marchesani syndrome References Further reading Lively GD, Alward, WL, Fingert JH. Juvenile open-angle glaucoma: 22-year-old Caucasian female referred in 1990 for evaluation of elevated intraocular pressure (IOP). EyeRounds.org. September 17, 2008. External links 231300 137750; MYOC 137750; CYP1B1 Juvenile Glaucoma at eMedicine on eMedicine Glaucoma for Children on AAPOS. Congenital Primary Glaucoma on patient.info GeneReview/NCBI/NIH/UW entry on Primary Congenital Glaucoma Glaucoma entry on PGCFA

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

Postpartum bleeding or postpartum hemorrhage (PPH) is often defined as the loss of more than 500 ml or 1,000 ml of blood following childbirth. Some have added the requirement that there also be signs or symptoms of low blood volume for the condition to exist. Signs and symptoms may initially include: an increased heart rate, feeling faint upon standing, and an increased breathing rate. As more blood is lost, the patient may feel cold, blood pressure may drop, and they may become restless or unconscious. The condition can occur up to six weeks following delivery.The most common cause is poor contraction of the uterus following childbirth. Not all of the placenta being delivered, a tear of the uterus, or poor blood clotting are other possible causes. It occurs more commonly in those who: already have a low amount of red blood, are Asian, with bigger or more than one baby, are obese or are older than 40 years of age. It also occurs more commonly following caesarean sections, those in whom medications are used to start labor, those requiring the use of a vacuum or forceps, and those who have an episiotomy.Prevention involves decreasing known risk factors including procedures associated with the condition, if possible, and giving the medication oxytocin to stimulate the uterus to contract shortly after the baby is born. Misoprostol may be used instead of oxytocin in resource-poor settings. Treatments may include: intravenous fluids, blood transfusions, and the medication ergotamine to cause further uterine contraction. Efforts to compress the uterus using the hands may be effective if other treatments do not work. The aorta may also be compressed by pressing on the abdomen. The World Health Organization has recommended the non-pneumatic anti-shock garment to help until other measures such as surgery can be carried out. Tranexamic acid has also been shown to reduce the risk of death, and has been recommended within three hours of delivery.In the developing world about 1.2% of deliveries are associated with PPH and when PPH occurred about 3% of women died. Globally it occurs about 8.7 million times and results in 44,000 to 86,000 deaths per year making it the leading cause of death during pregnancy. About 0.4 women per 100,000 deliveries die from PPH in the United Kingdom while about 150 women per 100,000 deliveries die in sub-Saharan Africa. Rates of death have decreased substantially since at least the late 1800s in the United Kingdom. Definition Depending on the source, primary postpartum bleeding is defined as blood loss in excess of 500 ml following vaginal delivery or 1000 ml following caesarean section in the first 24 hours following birth. Secondary postpartum bleeding is that which occurs after the first day and up to six weeks after childbirth. Signs and symptoms Symptoms generally include heavy bleeding from the vagina that doesnt slow or stop over time. Initially there may be an increased heart rate, feeling faint upon standing, and an increased respiratory rate. As more blood is lost, the patient may feel cold, blood pressure may drop, and they may become unconscious.Signs and symptoms of circulatory shock may also include blurry vision, cold and clammy skin, confusion, and feeling sleepy or weak. Causes Causes of postpartum hemorrhage are uterine atony, trauma, retained placenta or placental abnormalities, and coagulopathy, commonly referred to as the "four Ts": Tone: uterine atony is the inability of the uterus to contract and may lead to continuous bleeding. Retained placental tissue and infection may contribute to uterine atony. Uterine atony is the most common cause of postpartum hemorrhage. Trauma: Injury to the birth canal which includes the uterus, cervix, vagina and the perineum which can happen even if the delivery is monitored properly. The bleeding is substantial as all these organs become more vascular during pregnancy. Tissue: retention of tissue from the placenta or fetus as well as placental abnormalities such as placenta accreta and percreta may lead to bleeding. Thrombin: a bleeding disorder occurs when there is a failure of clotting, such as with diseases known as coagulopathies.Other risk factors include obesity, fever during pregnancy, bleeding before delivery, and heart disease. Prevention Oxytocin is typically used right after the delivery of the baby to prevent PPH. Misoprostol may be used in areas where oxytocin is not available. Early clamping of the umbilical cord does not decrease risks and may cause anemia in the baby, and thus is usually not recommended.Active management of the third stage is a method of shortening the stage between when the baby is born and when the placenta is delivered. This stage is when the mother is at risk of having a PPH. Active management involves giving a drug which helps the uterus contract before delivering the placenta by a gentle but sustained pull on the umbilical cord whilst exerting upward pressure on the lower abdomen to support the uterus (controlled cord traction).Another method of active management which is not recommended now is fundal pressure during the delivery of the placenta. A review into this method found no research and advises controlled cord traction because fundal pressure can cause the mother unnecessary pain. Allowing the cord to drain appears to shorten the third stage and reduce blood loss but evidence around this subject is not strong enough to draw solid conclusions.Nipple stimulation and breastfeeding triggers the release of natural oxytocin in the body, therefore it is thought that encouraging the baby to suckle soon after birth may reduce the risk of PPH for the mother. A review looking into this did not find enough good research to say whether or not nipple stimulation did reduce PPH. More research is needed to answer this question. Management Uterine massage is a simple first line treatment as it helps the uterus to contract to reduce bleeding. Although the evidence around the effectiveness of uterine massage is inconclusive, it is common practice after the delivery of the placenta. Medication Intravenous oxytocin is the drug of choice for postpartum hemorrhage. Ergotamine may also be used.Oxytocin helps the uterus to contract quickly and the contractions to last for longer. It is the first line treatment for PPH when its cause is the uterus not contracting well. A combination of syntocinon and ergometrine is commonly used as part of active management of the third stage of labour. This is called syntometrine. Syntocinon alone lowers the risk of PPH. Based on limited research available it is unclear whether syntocinon or syntometrine is most effective in preventing PPH but adverse effects are worse with syntometrine making syntocinon a more attractive option. Ergometrine also has to be kept cool and in a dark place so that it is safe to use. It may reduce the risk of PPH by improving the tone of the uterus when compared with no treatment, however it must be used with caution due to its effects of raising blood pressure and worsening pain. More research would be useful in determining the best doses of ergometrine and syntocinon.Oxytocin requires refrigeration, which may not always be available, particularly in low-resourced settings. When oxytocin is not available, misoprostol can be used. Misoprostol does not need to be kept at a certain temperature and research into its effectiveness in reducing blood loss appears promising when compared with a placebo in a setting where it is not appropriate to use oxytocin. Misoprostol can cause unpleasant side effects such as very high body temperatures and shivering. Lower doses of misoprostol appear to be safer and cause less side effects.Giving oxytocin in a solution of saline into the umbilical vein is a method of administering the drug directly to the placental bed and uterus. However quality of evidence around this technique is poor and it is not recommended for routine use in the management of the third stage. More research is needed to ascertain whether this is an effective way of administering uterotonic drugs. As a way of treating a retained placenta, this method is not harmful and has shown low certainty evidence of effectiveness.Carbetocin compared with oxytocin produced a reduction in women who needed uterine massage and further uterotonic drugs for women having caesarean sections. There was no difference in rates of PPH in women having caesarean sections or women having vaginal deliveries when given carbetocin. Carbetocin appears to cause less adverse effects. More research is needed to find the cost effectiveness of using carbetocin.Tranexamic acid, a clot stabilizing medication, may also be used to reduce bleeding and blood transfusions in low-risk patients, however evidence as of 2015 was not strong. A 2017 trial found that it decreased the risk of death from bleeding from 1.9% to 1.5% in women with postpartum bleeding. The benefit was greater when the medication was given within three hours.In some countries, such as Japan, methylergometrine and other herbal remedies are given following the delivery of the placenta to prevent severe bleeding more than a day after the birth. However, there is not enough evidence to suggest that these methods are effective. Surgery Surgery may be used if medical management fails or in case of cervical lacerations or tear or uterine rupture. Methods used may include uterine artery ligation, ovarian artery ligation, internal iliac artery ligation, selective arterial embolization, B-lynch suture, and hysterectomy. Bleeding caused by traumatic causes should be managed by surgical repair. When there is bleeding due to uterine rupture a repair can be performed but most of the time a hysterectomy is needed.There is currently no reliable evidence from randomised clinical trials about the effectiveness or risks of mechanical and surgical methods of treating postpartum bleeding. Medical devices The World Health Organization recommends the use of a device called the non-pneumatic anti-shock garment (NASG) for use in delivery activities outside of a hospital setting, the aim being to improve shock in a mother with obstetrical bleeding long enough to reach a hospital. External aortic compression devices (EACD) may also be used.Uterine balloon tamponade (UBT) can improve postpartum bleeding. Inflating a Sengstaken–Blakemore tube in the uterus successfully treats atonic postpartum hemorrhage refractory to medical management in approximately 80% of cases. Such procedure is relatively simple, inexpensive and has low surgical morbidity. A Bakri balloon is a balloon tamponade specifically constructed for uterine postpartum hemorrhage. While effective, commercially available devices may be expensive for settings in which postpartum hemorrhage is most common. Low-cost devices, such as the ESM-UBT, have been shown to be effective without the need for operative intervention. Protocol Protocols to manage postpartum bleeding are recommended to ensure the rapid giving of blood products when needed. A detailed stepwise management protocol has been introduced by the California Maternity Quality Care Collaborative. It describes four stages of obstetrical hemorrhage after childbirth and its application reduces maternal mortality. Stage 0: normal - treated with fundal massage and oxytocin. Stage 1: more than normal bleeding - establish large-bore intravenous access, assemble personnel, increase oxytocin, consider use of methergine, perform fundal massage, prepare 2 units of packed red blood cells. Stage 2: bleeding continues - check coagulation status, assemble response team, move to operating room, place intrauterine balloon, administer additional uterotonics (misoprostol, carboprost tromethamine), consider: uterine artery embolization, dilatation and curettage, and laparotomy with uterine compression stitches or hysterectomy. Stage 3: bleeding continues - activate massive transfusion protocol, mobilize additional personnel, recheck laboratory tests, perform laparotomy, consider hysterectomy.A Cochrane review suggests that active management (use of uterotonic drugs, cord clamping and controlled cord traction) during the third stage of labour may reduce severe bleeding and anemia. However, the review also found that active management increased the patients blood pressure, nausea, vomiting, and pain. In the active management group more patients returned to hospital with bleeding after discharge, and there was also a reduction in birthweight due to infants having a lower blood volume. The effects on the baby of early cord clamping was discussed in another review which found that delayed cord clamping improved iron stores longer term in the infants. Although they were more likely to need phototherapy (light therapy) to treat jaundice, the improved iron stores are expected to be worth increasing the practice of delayed cord clamping in healthy term babies.For preterm babies (babies born before 37 weeks) a review of the research found that delaying cord clamping may lead to fewer babies with bleeding in the brain, compared to early cord clamping.Another Cochrane review looking at the timing of the giving oxytocin as part of the active management found similar benefits with giving it before or after the expulsion of the placenta.There is no good quality evidence on how best to treat a secondary PPH (PPH occurring 24 hrs or more after the birth). Epidemiology Methods of measuring blood loss associated with childbirth vary, complicating comparison of prevalence rates. A systematic review reported the highest rates of PPH in Africa (27.5%), and the lowest in Oceania (7.2%), with an overall rate globally of 10.8%. The rate in both Europe and North America was around 13%. The rate is higher for multiple pregnancies (32.4% compared with 10.6% for singletons), and for first-time mothers (12.9% compared with 10.0% for women in subsequent pregnancies). The overall rate of severe PPH (>1000 ml) was much lower at an overall rate of 2.8%, again with the highest rate in Africa (5.1%). References External links WHO recommendations for the prevention and treatment of postpartum haemorrhage. Geneva: World Health Organization. 2012. ISBN 9789241548502. Postpartum hemorrhage and the B-Lynch technique

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

A brother is a man or boy who shares one or more parents with another; a male sibling. The female counterpart is a sister. Although the term typically refers to a familial relationship, it is sometimes used endearingly to refer to non-familial relationships. A full brother is a first degree relative. Overview The term brother comes from the Proto-Indo-European *bʰréh₂tēr, which becomes Latin frater, of the same meaning. Sibling warmth or affection between male siblings has been correlated to some more negative effects. In pairs of brothers, higher sibling warmth is related to more risk taking behaviour, although risk taking behaviour is not related to sibling warmth in any other type of sibling pair. The cause of this phenomenon in which sibling warmth is only correlated with risk taking behaviours in brother pairs still is unclear. This finding does, however, suggest that although sibling conflict is a risk factor for risk taking behaviour, sibling warmth does not serve as a protective factor. Some studies suggest that girls having an older brother delays the onset of menarche by roughly one year. Research also suggests that the likelihood of being gay increases with the more older brothers a man has. Some analyzers have suggested that a mans attractiveness to a heterosexual woman may increase with the more he resembles her brother, while his unattractiveness may increase the more his likeness diverges from her brother. Females with a twin or very close-in-age brother, sometimes view him as their male alter ego, or what they would have been like, if they had a Y chromosomes. Fraternal relationship The book Nicomachean Ethics, Book VIII written by Aristotle in 350 B.C.E., offers a way in which people should view the relationships between biological brothers. The relationship of brothers is laid out with the following quote: "The friendship of brothers has the characteristics found in that of comrades and in general between people who are like each other, is as much as they belong more to each other and start with a love for each other from their very birth, and in as much as those born to the same parents and brought up together and similarly educated are more akin in character; and the test of time has been applied most fully and convincingly in their case". For these reasons, it is the job of the older brother to influence the ethics of the younger brother by being a person of good action. Aristotle says "by imitating and reenacting the acts of good people, a child becomes habituated to good action". Over time the younger brother will develop the good actions of the older brother as well and be like him. Aristotle also adds this on the matter of retaining the action of doing good once imitated: "Once the habits of ethics or immorality become entrenched, they are difficult to break." The good habits that are created by the influence of the older brother become habit in the life of the younger brother and turn out to be seemingly permanent. It is the role of the older brother to be a positive influence on the development of the younger brothers upbringing when it comes to the education of ethics and good actions. When positive characteristics are properly displayed to the younger brother by the older brother, these habits and characteristics are imitated and foster an influential understanding of good ethics and positive actions. Famous brothers Gracchi, Ancient Roman reformers George Washington Adams, John Adams II, and Charles Francis Adams Sr., politicians Ben Affleck and Casey Affleck, actors The Alexander Brothers; musicians Alec Baldwin, William Baldwin, Stephen Baldwin, Daniel Baldwin, also known as the Baldwin brothers; actors John and Lionel Barrymore, actors Chang and Eng Bunker, the original Siamese twins George W. Bush, Jeb Bush, Neil Bush and Marvin Bush, sons of George H. W. Bush David Carradine, Keith Carradine, and Robert Carradine, American actors Bill Clinton, 42nd President of the United States, and Roger Clinton, Jr., his younger half-brother Joel and Ethan Coen; filmmakers Stephen Curry and Seth Curry; current NBA point guards in the Western Conference Dizzy and Daffy Dean, Major League Baseball pitchers Mark DeBarge, Randy DeBarge, El DeBarge, James DeBarge, and Bobby DeBarge, the male members of the singing group DeBarge Doud Eisenhower and John Eisenhower, sons of Dwight D. Eisenhower Emilio Estevez and Charlie Sheen, actors Isaac Everly and Phil Everly, The Everly Brothers, singers Liam Gallagher and Noel Gallagher, members of Oasis (band) Barry Gibb, Robin Gibb, and Maurice Gibb, members of the Brothers Gibb or "Bee Gees" singing group John Gotti, Eugene "Gene" Gotti, Peter Gotti and Richard V. Gotti, and Vincent Gotti, New York "made men" with the Gambino crime family Frederick Dent Grant, Ulysses S. Grant, and Jesse Root Grant Jacob Grimm and Wilhelm Grimm, known as the Brothers Grimm, German academics and folk tale collectors Matt Hardy and Jeff Hardy, professional wrestlers Herbert Hoover Jr. and Allan Hoover Pau and Marc Gasol, professional basketball players OKelly Isley, Jr., Rudolph Isley, and Ronald Isley, Ernie Isley, Marvin Isley, and Vernon Isley, members of The Isley Brothers singer-songwriting group and band, which also included their brother-in-law, Chris Jasper Jackie Jackson, Tito Jackson, Jermaine Jackson, Marlon Jackson, Michael Jackson and Randy Jackson, members of The Jackson 5 and later The Jacksons Jesse and Frank James, Old West outlaws John, Robert and Ted Kennedy, politicians Edward M. Kennedy Jr. and Patrick J. Kennedy, politicians Terry Labonte and Bobby Labonte, race car drivers Robert Todd Lincoln, Edward Baker Lincoln, William Wallace Lincoln and Tad Lincoln, sons of Abraham Lincoln Loud Brothers, piano designers and manufacturers Eli and Peyton Manning, National Football League quarterbacks Mario and Luigi, video game characters John McCain, U.S. Senator and two-time presidential candidate, and Joe McCain, American stage actor, newspaper reporter Justin, Travis, and Griffin McElroy, podcasters Billy Leon McCrary and Benny Loyd McCrary, wrestlers known as The McGuire Twins Harold Nixon, Richard Nixon, Donald Nixon, Arthur Nixon, and Edward Nixon Alan Osmond, Wayne Osmond, Merrill Osmond, Jay Osmond and Donny Osmond, members of The Osmonds Logan Paul and Jake Paul, YouTubers, internet personalities, and actors Neil and Ronald Reagan Ringling brothers, circus performers, owners, and show runners John D. Rockefeller and William Rockefeller, co-founders of Standard Oil and members of the Rockefeller family Cornelius Roosevelt and James I. Roosevelt Theodore Roosevelt Jr., Kermit Roosevelt, Archibald Bulloch Roosevelt, and Quentin Roosevelt James Roosevelt, Elliot Roosevelt, Franklin Delano Roosevelt Jr., and John Aspinwall Roosevelt Russo brothers, filmmakers, producers, and directors Daniel Sedin and Henrik Sedin, professional hockey players Wallace Shawn and Allen Shawn, writer and composer of The Fever Bobby Shriver, Timothy Shriver, Mark Shriver, and Anthony Shriver Thomas "Tommy" Smothers and Richard "Dick" Smothers, performing artists known as the Smothers Brothers Prabowo Subianto and Hashim Djojohadikusumo, politicians Fred Trump Jr., Donald Trump, and Robert Trump Vincent van Gogh, painter, and Theo van Gogh, art dealer J. J. Watt, T. J. Watt, Derek Watt, National Football League Players Damon Wayans, Dwayne Wayans, Keenan Ivory Wayans, Marlon Wayans, Shawn Wayans, performing artists, directors and producers Bob Weinstein and Harvey Weinstein, film producers Brian Wilson, Dennis Wilson, and Carl Wilson, members of The Beach Boys Marvin Winans, Carvin Winans, Michael Winans, and Ronald Winans, members of The Winans, singers and musicians Orville Wright and Wilbur Wright, known as the Wright brothers, pioneer aviators Agus Harimurti Yudhoyono and Edhie Baskoro Yudhoyono, politicians Other works about brothers In the Bible: Cain and Abel, the sons of Adam and Eve Jacob and Esau, the sons of Isaac and Rebecca Moses and Aaron, prophets Sts. Peter and Andrew, apostles Sts. James and John, apostles My Brother, My Brother, and Me, podcast Saving Private Ryan (1998), film Simon & Simon, television series Supernatural, American television series The Brothers Karamazov, novel The Wayans Bros., television series Bonanza (1959–1973), television series In the Ramayana: Rama, Lakshmana, Bharata, and Shatrughna In the Mahabharata: The Pandavas – Yudhishthira, Arjuna, Bhima, Sahadeva and Nakula The Kauravas – One hundred brothers including Duryodhana, Dushasana and Vikarna, among others See also Sister Brotherhood (disambiguation) Stepsibling References External links The dictionary definition of brother at Wiktionary

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

I need a basic explanation for the medical term 'Heat syncope.'

Heat syncope is fainting or dizziness as a result of overheating (syncope is the medical term for fainting). It is a type of heat illness. The basic symptom of heat syncope is fainting, with or without mental confusion. Heat syncope is caused by peripheral vessel dilation, resulting in diminished blood flow to the brain and dehydration. Signs and symptoms Faintness, dizziness, headache, increased pulse, restlessness, nausea, vomiting, pale/clammy skin, and brief loss of consciousness. Causes Heat syncope occurs in a warm environment when blood pressure is lowered as the body dilates (widens) arterioles (small blood vessels) in the skin to radiate heat. This condition occurs within five days of heat acclimatization, before the blood volume expands. The result is less blood to the brain, causing light-headedness and fainting when a person stands up quickly or stands for a long period of time. Those who perform strenuous work outside in warm climates are at particular risk. Diagnosis The diagnosis of heat syncope is done during a physical examination. During the physical exam the practitioner will test the blood pressure of the patient, and the pulse. If the patient is experiencing heat syncope the blood pressure will be low, and the pulse will be elevated. Observation of excess sweating will also be a key sign. Finally, the practitioner will ask questions figuring out the history of the patients symptoms. If the patient developed symptoms while engaging in physical activity and high temperatures it will then be a true case of heat syncope. Prevention Physical activity in extremely hot weather should be avoided. If a person starts to experience over heating, and symptoms of heat syncope, they should move or be moved to a shaded or cool area. It is also recommended to avoid alcoholic beverages in hot weather, because they cause dehydration which may worsen symptoms. Finally, drinking plenty of water with electrolytes is imperative when engaging in physical activity in hot weather. Treatment The basic treatment for heat syncope is like that for other types of fainting: the patient is positioned in a seating or supine position with legs raised. Water containing salt, or another drink containing electrolytes, is administered slowly, and the patient is moved to a cooler area, such as the shade. The affected person should rest and recover, because heat syncope can lead to heat stroke or heat exhaustion. References == External links ==

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

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

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

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

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

Bexarotene, sold under the brand Targretin, is an antineoplastic (anti-cancer) agent used for the treatment of cutaneous T cell lymphoma (CTCL). It is a third-generation retinoid.It was approved by the U.S. Food and Drug Administration (FDA) in December 1999, and the European Medicines Agency (EMA) in March 2001. It is available as a generic medication. Medical uses Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in people who are refractory to at least one prior systemic therapy (oral) and for the topical treatment of cutaneous lesions in patients with CTCL who have refractory or persistent disease after other therapies or who have not tolerated other therapies (topical).It has been used off-label for non-small cell lung cancer and breast cancer. Contraindications Known contraindications include: Adverse effects Overall the most common adverse effects are skin reactions (mostly itchiness and rashes), leucopenia, headache, weakness, thyroid anomalies (which seem to be mediated by RXR-mediated downregulation of thyroid stimulating hormone) and blood lipid anomalies such as hypercholesterolaemia (high blood cholesterol) and hyperlipidaemia, hypothyroidism. Interactions Its plasma concentration may be increased by concomitant treatment with CYP3A4 inhibitors such as ketoconazole. It may also induce CYP3A4, and hence CYP3A4 substrates like cyclophosphamide may have their plasma concentrations reduced. Likewise consumption of grapefruit juice might increase bexarotenes plasma concentrations, hence potentially altering its therapeutic effects. Mechanism Bexarotene is a retinoid that selectively activates retinoid X receptors (RXRs), as opposed to the retinoic acid receptors, the other major target of retinoic acid (the acid form of vitamin A). By so doing it induces cell differentiation and apoptosis and prevents the development of drug resistance. It also has anti-angiogenic effects and inhibits cancer metastasis. The retinoic acid receptors (RARs) regulate cell differentiation and proliferation whereas RXRs regulate apoptosis. Physical properties Bexarotene is a solid, white powder. It is poorly soluble in water; the solubility is estimated to be about 10-50 μM. It is soluble in DMSO at 65 mg/mL and in ethanol at 10 mg/mL with warming. History SRI International and the La Jolla Cancer Research Foundation (now the Sanford-Burnham Medical Research Institute) collaborated on work that resulted in patent filings for the drug.The developer of bexarotene (brand name Targretin) was Ligand Pharmaceuticals, a San Diego biotech company which received FDA approval for the drug in 1999. The FDA approved bexarotene on 29 December 1999.Japanese pharmaceutical Eisai bought the rights to Targretin and three other anti-cancer products from Ligand in 2006. In the United States, patents on the drug expired in 2016.It received EMA approval on 29 March 2001.Early-stage preclinical studies suggested that bexarotene reduced amyloid plaques and improved mental functioning in a small sample of mice engineered to exhibit Alzheimers-like symptoms although subsequent studies have yielded mixed results.The results of CCMR-One, a clinical trial of the effects of bexarotene on patients with multiple sclerosis operated by the University of Cambridge, have shown that the drug can cause remyelination, but will not lead to the drug being used as a therapy, due to its risk profile. References External links "Bexarotene". Drug Information Portal. U.S. National Library of Medicine.

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

Trichofolliculoma is a cutaneous condition characterized by a benign, highly structured tumor of the pilosebaceous unit.: 671 See also Multiple familial trichoepithelioma Pilomatricoma Skin lesion List of cutaneous conditions References == External links ==

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

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

Desmopressin, sold under the trade name DDAVP among others, is a medication used to treat diabetes insipidus, bedwetting, hemophilia A, von Willebrand disease, and high blood urea levels. In hemophilia A and von Willebrand disease, it should only be used for mild to moderate cases. It may be given in the nose, by injection into a vein, by mouth, or under the tongue.Common side effects include headaches, diarrhea, and low blood sodium. The low blood sodium that results may cause seizures. It should not be used in people with significant kidney problems or low blood sodium. It appears to be safe to use during pregnancy. It is a synthetic analogue of vasopressin, the hormone that plays roles in the control of the body’s osmotic balance, blood pressure regulation, kidney function, and reduction of urine production.Desmopressin was approved for medical use in the United States in 1978. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. Medical uses Bed wetting Desmopressin is used to treat nocturnal enuresis (bedwetting). It is usually prescribed in the form of desmopressin acetate, by mouth. Children taking DDAVP have 2.2 fewer wet nights per week and are 4.5 times more likely to sleep without disruption compared with placebo. Nighttime urination In 2017, the FDA approved Desmopressin has some benefit for adults who have problems with night time urination (known as nocturia). Bleeding disorders Desmopressin (DDAVP) is usually the first line treatment for mild to moderate type 1 von Willebrand disease. It is not recommended in severe disease or in those with abnormal factor VIII. Usefulness in type 2A, 2M, or 2N von Willebrand disease is variable. Generally not recommended in 2B and type 3 von Willebrand disease.Desmopressin is only recommended in mild hemophilia A. It may be used both for bleeding due to trauma or to try to prevent bleeding due to surgery. It is not effective in the treatment of hemophilia B (factor IX deficiency) or severe hemophilia A. May also be used in uremia induced bleeding. Diabetes insipidus Desmopressin is used in the treatment of central diabetes insipidus (DI) as a replacement for endogenous antidiuretic hormone (ADH) that is in insufficient quantity due to decreased or non-existent secretion or production of ADH by the posterior pituitary or hypothalamus, respectively. It is also used in the diagnostic workup for diabetes insipidus, in order to distinguish central from DI due to the kidneys. Desmopressin is not effective at treating nephrogenic DI, thus a positive response is generally indicative of central DI. Side effects headaches facial flushing nausea hyponatremia seizuresUS drug regulators added warning to the nasal sprays after two people died and fifty-nine other people had seizures. This occurred due to hyponatremia, a deficit of the bodys sodium levels, and the nasal spray is no longer approved for use in children in the United States. However, US drug regulators have said that desmopressin tablets can still be considered safe for treatment of nocturnal enuresis in children as long as the person is otherwise healthy. Patients must stop taking desmopressin if they develop severe vomiting and diarrhea, fever, the flu, or severe cold. Patients should also be very cautious about taking desmopressin during hot weather conditions or following strenuous exercise, as these conditions can place stress on the bodys electrolyte and water balance. A body needs to maintain a balance of water and (sodium). If sodium levels become too low (hyponatremia) – either as a result of increased water take-up or reduced salt levels – a person may have seizures and, in extreme cases, may die. Mechanism of action Desmopressin works by limiting the amount of water that is eliminated in the urine; that is, it is an antidiuretic. It works at the level of the renal collecting duct by binding to V2 receptors, which signal for the translocation of aquaporin channels via cytosolic vesicles to the apical membrane of the collecting duct. The presence of these aquaporin channels in the distal nephron causes increasing water reabsorption from the urine, which becomes passively re-distributed from the nephron to systemic circulation by way of basolateral membrane channels. Desmopressin also stimulates release of von Willebrand factor from endothelial cells by acting on the V2 receptor. It also increases endogenous levels of factor VIII, making it useful in the treatment of hemophilia A.Desmopressin is degraded more slowly than recombinant vasopressin, and requires less frequent administration. In addition, it has little effect on blood pressure, while vasopressin may cause arterial hypertension. Vasopressin stimulates the release of ACTH, which indirectly increases responsiveness of alpha-1 receptor in blood vessel smooth muscle, increasing vessel tone and blood pressure. Several studies have shown that Desmopressin does not stimulate ACTH release (except in Cushings Disease), and therefore does not directly raise blood pressure, however, one study showed that it stimulates ACTH release in over 50% of healthy subjects. Additionally, desmopressin is able to enhance ACTH and cortisol release in normal subjects following oCRH administration, but not in patients with anorexia nervosa. Chemistry Desmopressin (1-deamino-8-D-arginine vasopressin) is a synthetic form of the normal human hormone arginine vasopressin (the antidiuretic hormone, or ADH), a peptide containing nine amino acids. Compared to vasopressin, desmopressins first amino acid has been deaminated, and the arginine at the eighth position is in the dextro rather than the levo form (see stereochemistry). References Further reading Leissinger, C; Becton, D; Cornell, C Jr; Cox Gill, J (2001). "High-dose DDAVP intranasal spray (Stimate) for the prevention and treatment of bleeding in patients with mild haemophilia A, mild or moderate type 1 von Willebrand disease and symptomatic carriers of haemophilia A.". Haemophilia. 7 (3): 258–66. doi:10.1046/j.1365-2516.2001.00500.x. PMID 11380629. S2CID 20472310. External links "Desmopressin". Drug Information Portal. U.S. National Library of Medicine.

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

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

Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and anemia may also occur. Often, symptoms come on slowly and can range from mild to severe. Symptoms typically occur intermittently with periods of no symptoms between flares. Complications may include abnormal dilation of the colon (megacolon), inflammation of the eye, joints, or liver, and colon cancer.The cause of UC is unknown. Theories involve immune system dysfunction, genetics, changes in the normal gut bacteria, and environmental factors. Rates tend to be higher in the developed world with some proposing this to be the result of less exposure to intestinal infections, or to a Western diet and lifestyle. The removal of the appendix at an early age may be protective. Diagnosis is typically by colonoscopy with tissue biopsies. It is a type of inflammatory bowel disease (IBD) along with Crohns disease and microscopic colitis.Dietary changes, such as maintaining a high-calorie diet or lactose-free diet, may improve symptoms. Several medications are used to treat symptoms and bring about and maintain remission, including aminosalicylates such as mesalazine or sulfasalazine, steroids, immunosuppressants such as azathioprine, and biologic therapy. Removal of the colon by surgery may be necessary if the disease is severe, does not respond to treatment, or if complications such as colon cancer develop. Removal of the colon and rectum generally cures the condition.Together with Crohns disease, about 11.2 million people were affected as of 2015. Each year it newly occurs in 1 to 20 per 100,000 people, and 5 to 500 per 100,000 individuals are affected. The disease is more common in North America and Europe than other regions. Often it begins in people aged 15 to 30 years, or among those over 60. Males and females appear to be affected in equal proportions. It has also become more common since the 1950s. Together, ulcerative colitis and Crohns disease affect about a million people in the United States. With appropriate treatment the risk of death appears the same as that of the general population. The first description of ulcerative colitis occurred around the 1850s. Signs and symptoms Gastrointestinal People with ulcerative colitis usually present with diarrhea mixed with blood, of gradual onset that persists for an extended period of time (weeks). Additional symptoms may include fecal incontinence, increased frequency of bowel movements, mucus discharge, and nocturnal defecations. With proctitis (inflammation of the rectum), people with UC may experience urgency or rectal tenesmus, which is the urgent desire to evacuate the bowels but with the passage of little stool. Tenesmus may be misinterpreted as constipation, due to the urge to defecate despite small volume of stool passage. Bloody diarrhea and abdominal pain may be more prominent features in severe disease. The severity of abdominal pain with UC varies from mild discomfort to very painful bowel movements and abdominal cramping. High frequency of bowel movements, weight loss, nausea, fatigue, and fever are also common during disease flares. Chronic bleeding from the GI tract, chronic inflammation, and iron deficiency often leads to anemia, which can affect quality of life.The clinical presentation of ulcerative colitis depends on the extent of the disease process. Up to 15% of individuals may have severe disease upon initial onset of symptoms. A substantial proportion (up to 45%) of people with a history of UC without any ongoing symptoms (clinical remission) have objective evidence of ongoing inflammation. Ulcerative colitis is associated with a generalized inflammatory process that can affect many parts of the body. Sometimes, these associated extra-intestinal symptoms are the initial signs of the disease. Extent of involvement In contrast to Crohns disease, which can affect areas of the gastrointestinal tract outside of the colon, ulcerative colitis is usually confined to the colon. Inflammation in ulcerative colitis is usually continuous, typically involving the rectum, with involvement extending proximally (to sigmoid colon, ascending colon, etc.). In contrast, inflammation with Crohns disease is often patchy, with so-called "skip lesions" (intermittent regions of inflamed bowel).The disease is classified by the extent of involvement, depending on how far the disease extends: proctitis (rectal inflammation), left sided colitis (inflammation extending to descending colon), and extensive colitis (inflammation proximal to the descending colon). Proctosigmoiditis describes inflammation of the rectum and sigmoid colon. Pancolitis describes involvement of the entire colon, extending from the rectum to the cecum. While usually associated with Crohns disease, ileitis (inflammation of the ileum) also occurs in UC. About 17% of individuals with UC have ileitis. Ileitis more commonly occurs in the setting of pancolitis (occurring in 20% of cases of pancolitis), and tends to correlate with the activity of colitis. This so-called "backwash ileitis" can occur in 10–20% of people with pancolitis and is believed to be of little clinical significance. Severity of disease In addition to the extent of involvement, UC is also characterized by severity of disease. Severity of disease is defined by symptoms, objective markers of inflammation (endoscopic findings, blood tests), disease course, and the impact of the disease on day-to-day life. Most patients are categorized through endoscopy and fecal calprotectin levels. Indicators of low risk for future complications in mild and moderate UC include the following parameters: exhibiting less than 6 stools daily and lack of fever/weight loss. Other indicators include lack of extraintestinal symptoms, none to little elevation in CRP, ESR, and calprotectin, and later age of diagnosis (over 40 years). Mild disease correlates with fewer than four stools daily; in addition, mild urgency and rectal bleeding may occur intermittently. Mild disease lacks systemic signs of toxicity (eg. fever, chills, weight changes) and exhibits normal levels of serum inflammatory markers (erythrocyte sedimentation rate and C-reactive protein).Moderate to severe disease correlates with more than six stools daily, frequent bloody stools and urgency. Moderate abdominal pain, low-grade fever, 38 to 39 °C (100 to 102 °F), and anemia may develop (75% of normal). Toxicity is present, as demonstrated by fever, tachycardia, anemia or an elevated ESR or CRP.Fulminant disease correlates with more than 10 bowel movements daily, continuous bleeding, toxicity, abdominal tenderness and distension, blood transfusion requirement, and colonic dilation (expansion). People with fulminant UC may have inflammation extending beyond just the mucosal layer, causing impaired colonic motility and leading to toxic megacolon. Toxic megacolon is defined by diameter of colon (>6 cm) or cecum (>9 cm) and represents a medical emergency, one often treated surgically. If the serous membrane is involved, a colonic perforation may ensue, which has a 50% mortality rate in patients afflicted with UC.Ulcerative colitis may improve and enter remission. Remission of disease is characterized by formed stools, the absence of bloody diarrhea, resolution of urgency, and normal levels of serum inflammatory markers. Extraintestinal manifestations and complications UC is characterized by immune dysregulation and systemic inflammation, which may result in symptoms and complications outside the colon. Commonly affected organs include: eyes, joints, skin, and liver. The frequency of such extraintestinal manifestations has been reported as between 6 and 47%.UC may affect the mouth. About 8% of individuals with UC develop oral manifestations. The two most common oral manifestations are aphthous stomatitis and angular cheilitis. Aphthous stomatitis is characterized by ulcers in the mouth, which are benign, noncontagious and often recurrent. Angular chelitis is characterized by redness at the corners of the mouth, which may include painful sores or breaks in the skin. Very rarely, benign pustules may occur in the mouth (pyostomatitis vegetans).UC may affect the eyes manifesting in scleritis, iritis, and conjunctivitis. Patients may be asymptomatic or experience redness, burning, or itching in eyes (CITE CMDP). Inflammation may occur in the interior portion of the eye, leading to uveitis and iritis. Uveitis can cause blurred vision and eye pain, especially when exposed to light (photophobia). Untreated, uveitis can lead to permanent vision loss. Inflammation may also involve the white part of the eye (sclera) or the overlying connective tissue (episclera), causing conditions called scleritis and episcleritis. Ulcerative colitis is most commonly associated with uveitis and episcleritis.UC may cause several joint manifestations, including a type of rheumatologic disease known as seronegative arthritis, which may affect few large joints (oligoarthritis), the vertebra (ankylosing spondylitis) or several small joints of the hands and feet (peripheral arthritis). Often the insertion site where muscle attaches to bone (entheses) becomes inflamed (enthesitis). Inflammation may affect the sacroiliac joint (sacroiliitis). It is estimated that round 50% of IBD patients suffer from migratory arthritis. Synovitis, or inflammation of the synovial fluid surrounding a joint, can occur for months and recur in later times but usually does not erode the joint. The symptoms of arthritis include joint pain, swelling, and effusion, and often leads to significant morbidity. The severity of joint symptoms often does not correspond with severity of IBD. Ulcerative colitis may affect the skin. The most common type of skin manifestation, erythema nodosum, presents in up to 3% of UC patients and almost 8% in patients afflicted with Crohns disease. It develops as raised, tender red nodules usually appearing on the outer areas of the arms or legs, especially in the anterior tibial area (shins). The nodules have diameters that measure approximately 1–5 cm. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue (panniculitis), and biopsy will display focal panniculitis (although is often unnecessary in diagnosis). In contrast to joint-related manifestations, erythema nodosum often occurs alongside intestinal disease. Thus, treatment of UC can often lead to resolution of skin nodules.A lesser common skin complication associated with UC, pyoderma gangrenosum, is typically more severe. One study discovered this skin manifestation in only 0.75% pf patients. Pyoderma gangrenosum is characterized by painful lesions or nodules that become ulcers which progressively grow. It often starts as many small raised red spots (papules) or pus-filled lesions (pustules) that are usually detected on lower extremities. The inner layer of the skin, or dermis, slowly undergoes necrosis (process of dying) causing the ulcerations that are typical of pyoderma gangrenosum. The ulcers are often filled with sterile pus-like material, so biopsy often displays an abscess that is sterile. Whereas erythema nodosum tends to correlate with the activity of the ulcerative colitis and often improves with treatment of the colonic inflammation, pyoderma gangrenosum may occur independently of UC disease activity. In some cases, pyoderma gangrenosum may require injection with corticosteroids. Treatment may also involve inhibitors of tumor necrosis factor (TNF), a cytokine that promotes cell survival.Other associations determined between the skin and ulcerative colitis include a skin condition known as hidradenitis suppurativa (HS). This condition represents a chronic process in which follicles become occluded leading to recurring inflammation of nodules and abscesses and even tunnels in the skin that drain fluid.Ulcerative colitis may affect the blood and endocrine system. UC increases the risk of blood clots in both arteries and veins; painful swelling of the lower legs can be a sign of deep venous thrombosis, while difficulty breathing may be a result of pulmonary embolism (blood clots in the lungs). The risk of blood clots is about threefold higher in individuals with IBD. The risk of venous thromboembolism is high in ulcerative colitis due to hypercoagulability from inflammation, especially with active or extensive disease. Additional risk factors may include surgery, hospitalization, pregnancy, the use of corticosteroids and tofacitinib, a JAK inhibitor.The immune system may also attack red blood cells, leading to autoimmune hemolytic anemia. In addition to autoimmune destruction, anemia may occur due to chronic blood loss from rectal bleeding and bone marrow suppression due to inflammation (anemia of chronic disease). Anemic patients can present asymptomatically. However, 75% of individuals exhibit symptoms such as shortness of breath, fatigue, and tachycardia (racing heart). About 1/3rd of patients show signs of jaundice (yellowing of the skin) or darkened urine from loss of bilirubin in urine. A smaller percentage may present with chest pain or a concurrent immune cytopenia, most commonly immune thrombocytopenia (ITP) (CITE WAHA). Osteoporosis may occur related to systemic inflammation, which increases the risk of bone fractures. Clubbing, a deformity of the ends of the fingers, may occur. Amyloidosis may occur, especially with severe and poorly controlled disease, which usually presents with protein in the urine (proteinuria) and nephritic syndrome. Primary sclerosing cholangitis Ulcerative colitis has a significant association with primary sclerosing cholangitis (PSC), a progressive inflammatory disorder of small and large bile ducts. Up to 70-90% of people with primary sclerosing cholangitis have ulcerative colitis. As many as 5% of people with ulcerative colitis may progress to develop primary sclerosing cholangitis. PSC is more common in men, and often begins between 30 and 40 years of age. It can present asymptomatically or exhibit symptoms of itchiness (pruritis) and fatigue. Other symptoms include systemic signs such as fever and night sweats. Such symptoms are often associated with a bacterial episodic version of PSC. Upon physical exam, one may discern enlarged liver contours (hepatomegaly) or enlarged spleen (splenomegaly) as well as areas of excoriation. Yellow coloring of the skin, or jaundice, may also be present due to excess of bile byproduct buildup (bilirubin) from the biliary tract. In diagnosis, lab results often reveal a pattern indicative of biliary disease (cholestatic pattern). This is often displayed by markedly elevated alkaline phosphatase levels and milder or no elevation in liver enzyme levels. Xray results often show bile ducts with thicker walls, areas of dilation or narrowing.In some cases, primary sclerosing cholangitis occurs several years before the bowel symptoms of ulcerative colitis develop. PSC does not parallel the onset, extent, duration, or activity of the colonic inflammation in ulcerative colitis. In addition, colectomy does not have an impact on the course of primary sclerosing cholangitis in individuals with UC. PSC is associated with an increased risk of colorectal cancer and cholangiocarcinoma (bile duct cancer). PSC is a progressive condition, and may result in cirrhosis of the liver. No specific therapy has been proven to affect the long term course of PSC.Other liver-related manifestations of UC include fatty liver disease and autoimmune liver disease. Causes Ulcerative colitis is an autoimmune disease characterized by T-cells infiltrating the colon. No direct causes for UC are known, but factors such as genetics, environment, and an overactive immune system play a role. UC is associated with comorbidities that produce symptoms in many areas of the body outside the digestive system. Genetic factors A genetic component to the cause of UC can be hypothesized based on aggregation of UC in families, variation of prevalence between different ethnicities, genetic markers and linkages. In addition, the identical twin concordance rate is 10%, whereas the dizygotic twin concordance rate is only 3%. Between 8 and 14% of people with ulcerative colitis have a family history of inflammatory bowel disease. In addition, people with a first degree relative with UC have a four-fold increase in their risk of developing the disease.Twelve regions of the genome may be linked to UC, including, in the order of their discovery, chromosomes 16, 12, 6, 14, 5, 19, 1, and 3, but none of these loci has been consistently shown to be at fault, suggesting that the disorder is influenced by multiple genes. For example, chromosome band 1p36 is one such region thought to be linked to inflammatory bowel disease. Some of the putative regions encode transporter proteins such as OCTN1 and OCTN2. Other potential regions involve cell scaffolding proteins such as the MAGUK family. Human leukocyte antigen associations may even be at work. In fact, this linkage on chromosome 6 may be the most convincing and consistent of the genetic candidates.Multiple autoimmune disorders are associated with ulcerative colitis, including celiac disease, psoriasis, lupus erythematosus, rheumatoid arthritis, episcleritis, and scleritis. Ulcerative colitis is also associated with acute intermittent porphyria. Environmental factors Many hypotheses have been raised for environmental factors contributing to the pathogenesis of ulcerative colitis, including diet, breastfeeding and medications. Breastfeeding may have a protective effect in the development of ulcerative colitis. One study of isotretinoin found a small increase in the rate of UC.As the colon is exposed to many dietary substances which may encourage inflammation, dietary factors have been hypothesized to play a role in the pathogenesis of both ulcerative colitis and Crohns disease. However, current research does not show a link between diet and the development of ulcerative colitis. Few studies have investigated such an association; one study showed no association of refined sugar on the number of people affected of ulcerative colitis. High intake of unsaturated fat and vitamin B6 may enhance the risk of developing ulcerative colitis. Other identified dietary factors that may influence the development and/or relapse of the disease include meat protein and alcoholic beverages. Specifically, sulfur has been investigated as being involved in the cause of ulcerative colitis, but this is controversial. Sulfur restricted diets have been investigated in people with UC and animal models of the disease. The theory of sulfur as an etiological factor is related to the gut microbiota and mucosal sulfide detoxification in addition to the diet.As a result of a class-action lawsuit and community settlement with DuPont, three epidemiologists conducted studies on the population surrounding a chemical plant that was exposed to PFOA at levels greater than in the general population. The studies concluded that there was an association between PFOA exposure and six health outcomes, one of which being ulcerative colitis. Alternative theories Levels of sulfate-reducing bacteria tend to be higher in persons with ulcerative colitis, which could indicate higher levels of hydrogen sulfide in the intestine. An alternative theory suggests that the symptoms of the disease may be caused by toxic effects of the hydrogen sulfide on the cells lining the intestine.Infection by mycobacterium avium, subspecies paratuberculosis, has been proposed as the ultimate cause of both ulcerative colitis and Crohns disease. Pathophysiology An increased amount of colonic sulfate-reducing bacteria has been observed in some people with ulcerative colitis, resulting in higher concentrations of the toxic gas hydrogen sulfide. Human colonic mucosa is maintained by the colonic epithelial barrier and immune cells in the lamina propria (see intestinal mucosal barrier). N-butyrate, a short-chain fatty acid, gets oxidized through the beta oxidation pathway into carbon dioxide and ketone bodies. It has been shown that N-butyrate helps supply nutrients to this epithelial barrier. Studies have proposed that hydrogen sulfide plays a role in impairing this beta-oxidation pathway by interrupting the short chain acetyl-CoA dehydrogenase, an enzyme within the pathway. Furthermore, it has been suggested that the protective benefit of smoking in ulcerative colitis is due to the hydrogen cyanide from cigarette smoke reacting with hydrogen sulfide to produce the non-toxic isothiocyanate, thereby inhibiting sulfides from interrupting the pathway. An unrelated study suggested that the sulfur contained in red meats and alcohol may lead to an increased risk of relapse for people in remission. Diagnosis The initial diagnostic workup for ulcerative colitis consists of a complete history and physical examination, assessment of signs and symptoms, laboratory tests and endoscopy. Severe UC can exhibit high erythrocyte sedimentation rate (ESR), decreased albumin (a protein produced by the liver), and various changes in electrolytes. As discussed previously, UC patients often also display elevated alkaline phosphatase. Inflammation in the intestine may also cause higher levels of fecal calprotectin or lactoferrin.Specific testing may include the following: A complete blood count is done to check for anemia; thrombocytosis, a high platelet count, is occasionally seen Electrolyte studies and kidney function tests are done, as chronic diarrhea may be associated with hypokalemia, hypomagnesemia and kidney injury. Liver function tests are performed to screen for bile duct involvement: primary sclerosing cholangitis. Imaging such as x-ray or CT scan to evaluate for possible perforation or toxic megacolon Stool culture and Clostridioides difficile stool assay to rule out infectious colitis Inflammatory markers, such as erythrocyte sedimentation rate or C-reactive protein Lower endoscopy to evaluate the rectum and distal large intestine (sigmoidoscopy) or entire colon and end of the small intestine (colonoscopy) for ulcers and inflammationAlthough ulcerative colitis is a disease of unknown causation, inquiry should be made as to unusual factors believed to trigger the disease.The simple clinical colitis activity index was created in 1998 and is used to assess the severity of symptoms. Endoscopic The best test for diagnosis of ulcerative colitis remains endoscopy, which is examination of the internal surface of the bowel using a flexible camera. Initially, a flexible sigmoidoscopy may be completed to establish the diagnosis. The physician may elect to limit the extent of the initial exam if severe colitis is encountered to minimize the risk of perforation of the colon. However, a complete colonoscopy with entry into the terminal ileum should be performed to rule out Crohns disease, and assess extent and severity of disease. Endoscopic findings in ulcerative colitis include: erythema (redness of the mucosa), friability of the mucosa, superficial ulceration, and loss of the vascular appearance of the colon. When present, ulcerations may be confluent. Pseudopolyps may be observed.Ulcerative colitis is usually continuous from the rectum, with the rectum almost universally being involved. Perianal disease is rare. The degree of involvement endoscopically ranges from proctitis (rectal inflammation) to left sided colitis (extending to descending colon), to extensive colitis (extending proximal to descending colon). Histologic Biopsies of the mucosa are taken during endoscopy to confirm the diagnosis of UC and differentiate it from Crohns disease, which is managed differently clinically. Histologic findings in ulcerative colitis includes: distortion of crypt architecture, crypt abscesses, and inflammatory cells in the mucosa (lymphocytes, plasma cells, and granulocytes). Unlike the transmural inflammation seen in Crohns disease, the inflammation of ulcerative colitis is limited to the mucosa. Laboratory tests Blood and stool tests serve primarily to assess disease severity, level of inflammation and rule out causes of infectious colitis. All individuals with suspected ulcerative colitis should have stool testing to rule out infection.A complete blood count may demonstrate anemia, leukocytosis, or thrombocytosis. Anemia may be caused by inflammation or bleeding. Chronic blood loss may lead to iron deficiency as a cause for anemia, particularly microcytic anemia (small red blood cells), which can be evaluated with a serum ferritin, iron, total iron-binding capacity and transferrin saturation. Anemia may be due to a complication of treatment from azathioprine, which can cause low blood counts, or sulfasalazine, which can result in folate deficiency. Thiopurine metabolites (from azathioprine) and a folate level can help.UC may cause high levels of inflammation throughout the body, which may be quantified with serum inflammatory markers, such as CRP and ESR. However, elevated inflammatory markers are not specific for UC and elevations are commonly seen in other conditions, including infection. In addition, inflammatory markers are not uniformly elevated in people with ulcerative colitis. Twenty five percent of individuals with confirmed inflammation on endoscopic evaluation have a normal CRP level. Serum albumin may also be low related to inflammation, in addition to loss of protein in the GI tract associated with bleeding and colitis. Low serum levels of vitamin D are associated with UC, although the significance of this finding is unclear.Specific antibody markers may be elevated in ulcerative colitis. Specifically, perinuclear antineutrophil cytoplasmic antibodies (pANCA) are found in 70 percent of cases of UC. Antibodies against Saccharomyces cerevisiae may be present, but are more often positive in Crohns disease compared with ulcerative colitis. However, due to poor accuracy of these serolologic tests, they are not helpful in the diagnostic evaluation of possible inflammatory bowel disease.Several stool tests may help quantify the extent of inflammation present in the colon and rectum. Fecal calprotectin is elevated in inflammatory conditions affecting the colon, and is useful in distinguishing irritable bowel syndrome (noninflammatory) from a flare in inflammatory bowel disease. Fecal calprotectin is 88% sensitive and 79% specific for the diagnosis of ulcerative colitis. If the fecal calprotectin is low, the likelihood of inflammatory bowel disease are less than 1 percent. Lactoferrin is an additional nonspecific marker of intestinal inflammation. Imaging Overall, imaging tests, such as x-ray or CT scan, may be helpful in assessing for complications of ulcerative colitis, such as perforation or toxic megacolon. Bowel ultrasound (US) is a cost-effective, well-tolerated, non-invasive and readily available tool for the management of patients with inflammatory bowel disease (IBD), including UC, in clinical practice. Some recent studies demonstrated that US is an accurate tool for assessing disease activity in patients with UC. Imaging is otherwise of limited use in diagnosing ulcerative colitis. Magnetic resonance imaging (MRI) is necessary to diagnose underlying PSC.Abdominal xray is often the test of choice and may display nonspecific findings in cases of mild or moderate ulcerative colitis. In circumstances of severe UC, radiographic findings may include thickening of the mucosa, often termed "thumbprinting," which indicates swelling due to fluid displacement (edema). Other findings may include colonic dilation and stool buildup evidencing constipation.Similar to xray, in mild ulcerative colitis, double contrast barium enema often shows nonspecific findings. Conversely, barium enema may display small buildups of barium in microulcerations. Severe UC can be characterized by various polyps, colonic shortening, loss of haustrae (the small bulging pouches in the colon),and narrowing of the colon. It is important to note that barium enema should not be conducted in patients exhibiting very severe symptoms as this may slow or stop stool passage through the colon causing ileus and toxic megacolon.Other methods of imaging include computed tomography (CT) and magnetic resonance imaging (MRI). Both may depict colonic wall thickening but have decreased ability to find early signs of wall changes when compared to barium enema. In cases of severe ulcerative colitis, however, they often exhibit equivalent ability to detect colonic changes.Doppler ultrasound is the last means of imaging that may be used. Similar to the imaging methods mentioned earlier, this may show some thickened bowel wall layers. In severe cases, this may show thickening in all bowel wall layers (transmural thickness). Differential diagnosis Several conditions may present in a similar manner as ulcerative colitis, and should be excluded. Such conditions include: Crohns disease, infectious colitis, nonsteroidal anti-inflammatory drug enteropathy, and irritable bowel syndrome. Alternative causes of colitis should be considered, such as ischemic colitis (inadequate blood flow to the colon), radiation colitis (if prior exposure to radiation therapy), or chemical colitis. Pseudomembranous colitis may occur due to Clostridioides difficile infection following administration of antibiotics. Entamoeba histolytica is a protozoan parasite that causes intestinal inflammation. A few cases have been misdiagnosed as UC with poor outcomes occurring due to the use of corticosteroids.The most common disease that mimics the symptoms of ulcerative colitis is Crohns disease, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. It is important to differentiate these diseases since their courses and treatments may differ. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis. Crohns disease can be distinguished from ulcerative colitis in several ways. Characteristics that indicate Crohns include evidence of disease around the anus (perianal disease). This includes anal fissures and abscesses as well as fistulas, which are abnormal connections between various bodily structures.Infectious colitis is another condition that may present in similar manner to ulcerative colitis. Endoscopic findings are also oftentimes similar. One can discern whether a patient has infectious colitis by employing tissue cultures and stool studies. Biopsy of the colon is another beneficial test but is more invasive. Other forms of colitis that may present similarly include radiation and diversion colitis. Radiation colitis occurs after irradiation and often affects the rectum or sigmoid colon, similar to ulcerative colitis. Upon histology radiation colitis may indicate eosinophilic infiltrates, abnormal epithelial cells, or fibrosis. Diversion colitis, on the other hand, occurs after portions of bowel loops have been removed. Histology in this condition often shows increased growth of lymphoid tissue. In patients who have undergone transplantation, graft versus host disease may also be a differential diagnosis. This response to transplantation often causes prolonged diarrhea if the colon is affected. Typical symptoms also include rash. Involvement of the upper gastrointestinal tract may lead to difficulty swallowing or ulceration. Upon histology, graft versus host disease may present with crypt cell necrosis and breakdown products within the crypts themselves. Management Standard treatment for ulcerative colitis depends on the extent of involvement and disease severity. The goal is to induce remission initially with medications, followed by the administration of maintenance medications to prevent a relapse. The concept of induction of remission and maintenance of remission is very important. The medications used to induce and maintain a remission somewhat overlap, but the treatments are different. Physicians first direct treatment to inducing remission, which involves relief of symptoms and mucosal healing of the colons lining, and then longer-term treatment to maintain remission and prevent complications. Acute severe ulcerative colitis requires hospitalisation, exclusion of infections, and corticosteroids.For acute stages of the disease, a low fiber diet may be recommended. Medication Ulcerative colitis can be treated with a number of medications, including 5-ASA drugs such as sulfasalazine and mesalazine. Corticosteroids such as prednisone can also be used due to their immunosuppressive and short-term healing properties, but because their risks outweigh their benefits, they are not used long-term in treatment. Immunosuppressive medications such as azathioprine and biological agents such as infliximab and adalimumab are given only if people cannot achieve remission with 5-ASA and corticosteroids. Infliximab, ustekinumab, or vedolizumab are recommended in those with moderate or severe disease.A formulation of budesonide was approved by the U.S. Food and Drug Administration (FDA) for treatment of active ulcerative colitis in January 2013. In 2018, tofacitinib was approved for treatment of moderately to severely active ulcerative colitis in the United States, the first oral medication indicated for long term use in this condition. The evidence on methotrexate does not show a benefit in producing remission in people with ulcerative colitis. Cyclosporine is effective for severe UC and tacrolimus has also shown benefits. Aminosalicylates Sulfasalazine has been a major agent in the therapy of mild to moderate ulcerative colitis for over 50 years. In 1977, it was shown that 5-aminosalicylic acid (5-ASA, mesalazine/mesalamine) was the therapeutically active component in sulfasalazine. Many 5-ASA drugs have been developed with the aim of delivering the active compound to the large intestine to maintain therapeutic efficacy but with reduction of the side effects associated with the sulfapyridine moiety in sulfasalazine. Oral 5-ASA drugs are particularly effective in inducing and in maintaining remission in mild to moderate ulcerative colitis. Rectal suppository, foam or liquid enema formulations of 5-ASA are used for colitis affecting the rectum, sigmoid or descending colon, and have been shown to be effective especially when combined with oral treatment. Biologics Biologic treatments such as the TNF inhibitors infliximab, adalimumab, and golimumab are commonly used to treat people with UC who are no longer responding to corticosteroids. Tofacitinib and vedolizumab can also produce good clinical remission and response rates in UC. Biologics may be used early in treatment (step down approach), or after other treatments have failed to induce remission (step up approach); the strategy should be individualized.Unlike aminosalicylates, biologics can cause serious side effects such as an increased risk of developing extra-intestinal cancers, heart failure; and weakening of the immune system, resulting in a decreased ability of the immune system to clear infections and reactivation of latent infections such as tuberculosis. For this reason, people on these treatments are closely monitored and are often tested for hepatitis and tuberculosis annually. Nicotine Unlike Crohns disease, ulcerative colitis has a lesser chance of affecting smokers than non-smokers. In select individuals with a history of previous tobacco use, resuming low dose smoking may improve signs and symptoms of active ulcerative colitis, but it is not recommended due to the overwhelmingly negative health effects of tobacco. Studies using a transdermal nicotine patch have shown clinical and histological improvement. In one double-blind, placebo-controlled study conducted in the United Kingdom, 48.6% of people with UC who used the nicotine patch, in conjunction with their standard treatment, showed complete resolution of symptoms. Another randomized, double-blind, placebo-controlled, single-center clinical trial conducted in the United States showed that 39% of people who used the patch showed significant improvement, versus 9% of those given a placebo. However, nicotine therapy is generally not recommended due to side effects and inconsistent results. Iron supplementation The gradual loss of blood from the gastrointestinal tract, as well as chronic inflammation, often leads to anemia, and professional guidelines suggest routinely monitoring for anemia with blood tests repeated every three months in active disease and annually in quiescent disease. Adequate disease control usually improves anemia of chronic disease, but iron deficiency anemia should be treated with iron supplements. The form in which treatment is administered depends both on the severity of the anemia and on the guidelines that are followed. Some advise that parenteral iron be used first because people respond to it more quickly, it is associated with fewer gastrointestinal side effects, and it is not associated with compliance issues. Others require oral iron to be used first, as people eventually respond and many will tolerate the side effects. Surgery Unlike in Crohns disease, the gastrointestinal aspects of ulcerative colitis can generally be cured by surgical removal of the large intestine, though extraintestinal symptoms may persist. This procedure is necessary in the event of: exsanguinating hemorrhage, frank perforation, or documented or strongly suspected carcinoma. Surgery is also indicated for people with severe colitis or toxic megacolon. People with symptoms that are disabling and do not respond to drugs may wish to consider whether surgery would improve the quality of life.The removal of the entire large intestine, known as a proctocolectomy, results in a permanent ileostomy – where a stoma is created by pulling the terminal ileum through the abdomen. Intestinal contents are emptied into a removable ostomy bag which is secured around the stoma using adhesive.Another surgical option for ulcerative colitis that is affecting most of the large bowel is called the ileal pouch-anal anastomosis (IPAA). This is a two- or three-step procedure. In a three-step procedure, the first surgery is a sub-total colectomy, in which the large bowel is removed, but the rectum remains in situ, and a temporary ileostomy is made. The second step is a proctectomy and formation of the ileal pouch (commonly known as a "j-pouch"). This involves removing the large majority of the remaining rectal stump and creating a new "rectum" by fashioning the end of the small intestine into a pouch and attaching it to the anus. After this procedure, a new type of ileostomy is created (known as a loop ileostomy) to allow the anastomoses to heal. The final surgery is a take-down procedure where the ileostomy is reversed and there is no longer the need for an ostomy bag. When done in two steps, a proctocolectomy – removing both the colon and rectum – is performed alongside the pouch formation and loop ileostomy. The final step is the same take-down surgery as in the three-step procedure. Time taken between each step can vary, but typically a six- to twelve-month interval is recommended between the first two steps, and a minimum of two to three months is required between the formation of the pouch and the ileostomy take-down.While the ileal pouch procedure removes the need for an ostomy bag, it does not restore normal bowel function. In the months following the final operation, patients typically experience 8–15 bowel movements a day. Over time this number decreases, with many patients reporting four-six bowel movements after one year post-op. While many patients have success with this procedure, there are a number of known complications. Pouchitis, inflammation of the ileal pouch resulting in symptoms similar to ulcerative colitis, is relatively common. Pouchitis can be acute, remitting, or chronic however treatment using antibiotics, steroids, or biologics can be highly effective. Other complications include fistulas, abscesses, and pouch failure. Depending on the severity of the condition, pouch revision surgery may need to be performed. In some cased the pouch may need to be de-functioned or removed and an ileostomy recreated.The risk of cancer arising from a ileal pouch anal anastomosis is low. However, annual surveillance with pouchoscopy may be considered in individuals with risk factors for dysplasia, such as a history of dysplasia or colorectal cancer, a history of PSC, refractory pouchitis, and severely inflamed atrophic pouch mucosa. Bacterial recolonization In a number of randomized clinical trials, probiotics have demonstrated the potential to be helpful in the treatment of ulcerative colitis. Specific types of probiotics such as Escherichia coli Nissle have been shown to induce remission in some people for up to a year. A probiotic named after its gastroenterologist medical doctor inventor, the De Simone Formulation, may be effective in inducing remission in active ulcerative colitis, and may be as effective as 5-ASAs in preventing relapse of quiescent UC. The De Simone Formulation was sold and researched under the brand name VSL#3 until 2016. Since, it has been sold and researched under various regional brand names including Visbiome in the United States and Vivomixx in Europe.Fecal microbiota transplant involves the infusion of human probiotics through fecal enemas. Ulcerative colitis typically requires a more prolonged bacteriotherapy treatment than Clostridium difficile infection to be successful, possibly due to the time needed to heal the ulcerated epithelium. The response of ulcerative colitis is potentially very favorable with one study reporting 67.7% of people experiencing complete remission. Other studies found a benefit from using fecal microbiota transplantation. Alternative medicine A variety of alternative medicine therapies have been used for ulcerative colitis, with inconsistent results. Curcumin (turmeric) therapy, in conjunction with taking the medications mesalamine or sulfasalazine, may be effective and safe for maintaining remission in people with quiescent ulcerative colitis. The effect of curcumin therapy alone on quiescent ulcerative colitis is unknown.Treatments using cannabis or cannabis oil are uncertain. So far, studies havent determined its effectiveness and safety. Abdominal pain management Many interventions have been considered to manage abdominal pain in people with ulcerative colitis, including FODMAPs diet, relaxation training, yoga, kefir diet and stellate ganglion block treatment. It is unclear whether any of these are safe or effective at improving pain or reducing anxiety and depression. Prognosis Poor prognostic factors include: age < 40 years upon diagnosis, extensive colitis, severe colitis on endoscopy, prior hospitalization, elevated CRP and low serum albumin. Progression or remission People with ulcerative colitis usually have an intermittent course, with periods of disease inactivity alternating with "flares" of disease. People with proctitis or left-sided colitis usually have a more benign course: only 15% progress proximally with their disease, and up to 20% can have sustained remission in the absence of any therapy. A subset of people experience a course of disease progress rapidly. In these cases, there is usually a failure to respond to medication and surgery often is performed within the first few years of disease onset. People with more extensive disease are less likely to sustain remission, but the rate of remission is independent of the severity of the disease. Several risk factors are associated with eventual need for colectomy, including: prior hospitalization for UC, extensive colitis, need for systemic steroids, young age at diagnosis, low serum albumin, elevated inflammatory markers (CRP & ESR), and severe inflammation seen during colonoscopy. Surgical removal of the large intestine is necessary in some cases. Colorectal cancer The risk of colorectal cancer is significantly increased in people with ulcerative colitis after ten years if involvement is beyond the splenic flexure. People with backwash ileitis might have an increased risk for colorectal carcinoma. Those people with only proctitis usually have no increased risk. It is recommended that people have screening colonoscopies with random biopsies to look for dysplasia after eight years of disease activity, at one to two year intervals. Mortality People with ulcerative colitis are at similar or perhaps slightly increased overall risk of death compared with the background population. However, the distribution of causes-of-death differs from the general population. Specific risk factors may predict worse outcomes and a higher risk of mortality in people with ulcerative colitis, including: C. difficile infection and cytomegalovirus infection (due to reactivation). Epidemiology Together with Crohns disease, about 11.2 million people were affected as of 2015. Each year, ulcerative colitis newly occurs in 1 to 20 per 100,000 people (incidence), and there are a total of 5-500 per 100,000 individuals with the disease (prevalence). In 2015, a worldwide total of 47,400 people died due to inflammatory bowel disease (UC and Crohns disease). The peak onset is between 30 and 40 years of age, with a second peak of onset occurring in the 6th decade of life. Ulcerative colitis is equally common among men and women. With appropriate treatment the risk of death appears similar to that of the general population. UC has become more common since the 1950s.The geographic distribution of UC and Crohns disease is similar worldwide, with the highest number of new cases a year of UC found in Canada, New Zealand and the United Kingdom. The disease is more common in North America and Europe than other regions. In general, higher rates are seen in northern locations compared to southern locations in Europe and the United States. UC is more common in western Europe compared with eastern Europe. Worldwide, the prevalence of UC varies from 2 - 299 per 100,000 people. Together, ulcerative colitis and Crohns disease affect about a million people in the United States.As with Crohns disease, the rates of UC are greater among Ashkenazi Jews and decreases progressively in other persons of Jewish descent, non-Jewish Caucasians, Africans, Hispanics, and Asians. Appendectomy prior to age 20 for appendicitis and current tobacco use are protective against development of UC. However, former tobacco use is associated with a higher risk of developing the disease. United States As of 2004, the number of new cases of UC in the United States was between 2.2 and 14.3 per 100,000 per year. The number of people affected in the United States in 2004 was between 37 and 246 per 100,000. Canada In Canada, between 1998 and 2000, the number of new cases per year was 12.9 per 100,000 population or 4,500 new cases. The number of people affected was estimated to be 211 per 100,000 or 104,000. United Kingdom In the United Kingdom 10 per 100,000 people newly develop the condition a year while the number of people affected is 243 per 100,000. Approximately 146,000 people in the United Kingdom have been diagnosed with UC. History The first description of ulcerative colitis occurred around the 1850s. Research Helminthic therapy using the whipworm Trichuris suis has been shown in a randomized control trial from Iowa to show benefit in people with ulcerative colitis. The therapy tests the hygiene hypothesis which argues that the absence of helminths in the colons of people in the developed world may lead to inflammation. Both helminthic therapy and fecal microbiota transplant induce a characteristic Th2 white cell response in the diseased areas, which was unexpected given that ulcerative colitis was thought to involve Th2 overproduction.Alicaforsen is a first generation antisense oligodeoxynucleotide designed to bind specifically to the human ICAM-1 messenger RNA through Watson-Crick base pair interactions in order to subdue expression of ICAM-1. ICAM-1 propagates an inflammatory response promoting the extravasation and activation of leukocytes (white blood cells) into inflamed tissue. Increased expression of ICAM-1 has been observed within the inflamed intestinal mucosa of ulcerative colitis patients, where ICAM-1 over production correlated with disease activity. This suggests that ICAM-1 is a potential therapeutic target in the treatment of ulcerative colitis.Gram positive bacteria present in the lumen could be associated with extending the time of relapse for ulcerative colitis.A series of drugs in development looks to disrupt the inflammation process by selectively targeting an ion channel in the inflammation signaling cascade known as KCa3.1. In a preclinical study in rats and mice, inhibition of KCa3.1 disrupted the production of Th1 cytokines IL-2 and TNF-∝ and decreased colon inflammation as effectively as sulfasalazine.Neutrophil extracellular traps and the resulting degradation of the extracellular matrix have been reported in the colon mucosa in ulcerative colitis patients in clinical remission, indicating the involvement of the innate immune system in the etiology.Fexofenadine, an antihistamine drug used in treatment of allergies, has shown promise in a combination therapy in some studies. Opportunely, low gastrointestinal absorption (or high absorbed drug gastrointestinal secretion) of fexofenadine results in higher concentration at the site of inflammation. Thus, the drug may locally decrease histamine secretion by involved gastrointestinal mast cells and alleviate the inflammation.There is evidence that etrolizumab is effective for ulcerative colitis, with phase 3 trials underway as of 2016. Etrolizumab is a humanized monoclonal antibody that targets he β7 subunit of integrins α4β7 and αEβ7. Etrolizumab decreases lymphocytes trafficking, similar to vedolizumab (another integrin antagonist). A type of leukocyte apheresis, known as granulocyte and monocyte adsorptive apheresis, still requires large-scale trials to determine whether or not it is effective. Results from small trials have been tentatively positive. Notable cases References Further reading External links MedlinePlus ulcerative colitis page

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I'm seeking clarification on the medical term 'Monosomy 9p.' Could you explain it?

Monosomy 9p (also known as Alfis Syndrome or simply 9P-) is a rare chromosomal disorder in which some DNA is missing or has been deleted on the short arm region, “p”, of one of the 9th Chromosomes (9p22.2-p23). This deletion either happens de novo or a result of a parent having the chromosome abnormality. This rare chromosome abnormality is often diagnosed after birth when development delay, irregular facial features, and structural irregularities within the heart, and genital defects are noticed. Treatments for this syndrome usually focus on fixing the common malformations associated with this syndrome. Chromosome 9p deletion syndrome was first discovered in 1973 when 3 infants with similar clinical features were observed to have a partial deletion of the short arm of Chromosome 9. Symptoms include microgenitalia, intellectual disability with microcephaly and dysmorphic features. Signs and Symptoms Psychomotor Development Delays Psychomotor development refers to the changes experienced directly after birth through adolescence. Development occurs in cognitive, emotional, motor, and social skills over the childs growth and a delay can result in lagging development of language, motor skills, cognition, or social skills, however these delays can vary in severity. Facial Dysmorphism Facial Dysmorphisms broadly describe any abnormalities in facial structure. Facial Dysmorphisms include slopping forehead, frontal bossing (prominent protruding forehead), hemifacial microsomia (one side of the face underdeveloped), and otocephaly (absence of mandible and fusion of ears under chin). Malformation of Limbs Congenital limb defects occur when a fetus limbs, either upper or lower, experience altered development. These developmental abnormalities include absence of the limb, failure of portions of the limb to separate (commonly fingers and toes), duplication of digits, or overgrowth or undergrowth of limbs. Genetics Inheritance Pattern The inheritance pattern for the Chromosome 9p deletion syndrome is inherited in an autosomal dominant inheritance pattern. This means that a single copy of the deletion is sufficient to cause the disease. Mutation The mutation, which occurs in the form of a deletion of the short arm of chromosome 9, causes the cell to not express the gene products normally controlled by the genes within the chromosome 9 deletion. Genes Involved The 9p deletion causes a loss of genes that would normally be there. Which genes are lost on the short arm of chromosome 9 dictates the symptoms that are present within the individual and the spectrum of disease severity. Most of the genes involved are associated with the development of tissues.There are many possible genes that can be deleted, but two particular genes that are proven to be involved in the emergence of the symptoms associated with Chromosome 9p deletion syndrome are DMRT1 and DMRT2. When DMRT1 and DMRT2 are deleted, genital malformations and mental retardation are evident although, the direct mechanisms as to how this occurs remains undefined. Location Geneticists originally had the syndrome narrowed down to the short arm region of Chromosome 9. Now, the location of the deletion has recently been narrowed to 9p22.2-p23. Diagnosis Diagnoses can occur at any age. Most of time chromosome 9p deletion syndrome is diagnosed after birth by the detection of symptoms via clinical evaluation. Common methods used to detect Monosomy 9p after birth include the use of a stethoscope, X-ray, and EKG. Monosomy 9p is also diagnosed before birth by ultrasound, amniocentesis, and chorionic villus sampling (CVS). Ultrasound can hint at the malformations of the face, limbs, and heart. While amniocentesis and CVS both use fluid and tissue to perform chromosomal studies to identify chromosomal abnormalities. Finally, karyotyping, a procedure used to examine a patients chromosomes, can be used to diagnose Monosomy 9p both before birth and after birth. Management Treatment of Monosomy 9p focuses mainly on fixing the malformations. For example, to fix facial malformations, physicians can perform facial surgery to repair the facial malformations. This can open airways for the infant or patient; especially the nose-to-throat pathway. Similarly, to fix heart malformations, physicians can recommend surgery or medication to improve the efficiency of the pumping of the heart. Lastly remedial education, speech therapy, and physical therapy can be used to improve the developmental delay associated with the syndrome. Epidemiology Chromosome 9p deletion syndrome occurs 1 in 50,000 births. Half of the cases occur sporadically, while the other half of cases result from parent translocations or the parent having deletion as well. References == External links ==

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

Aponeurotic fibroma (also known as "Calcifying aponeurotic fibroma," and "Juvenile aponeurotic fibroma") is characterized by a lesion that usually presents as a painless, solitary, deep fibrous nodule, often adherent to tendon, fascia, or periosteum, on the hands and feet. The World Health Organization, 2020, reclassified aponeurotic fibroma nodules as a specific benign type of the fibroblastic and myofibroblastic tumors. See also Skin lesion == References ==

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I'm seeking clarification on the medical term 'Dapagliflozin/metformin.' Could you explain it?

Dapagliflozin/metformin, sold under the brand name Xigduo XR among others, is a fixed-dose combination anti-diabetic medication used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. It is a combination of dapagliflozin and metformin. Dapagliflozin/metformin was approved for use in the European Union in January 2014, and for use in the United States in February 2014. It is taken by mouth. Adverse effects To lessen the risk of developing ketoacidosis (a serious condition in which the body produces high levels of blood acids called ketones) after surgery, the FDA has approved changes to the prescribing information for SGLT2 inhibitor diabetes medicines to recommend they be stopped temporarily before scheduled surgery. Canagliflozin, dapagliflozin, and empagliflozin should each be stopped at least three days before, and ertugliflozin should be stopped at least four days before scheduled surgery.Symptoms of ketoacidosis include nausea, vomiting, abdominal pain, tiredness, and trouble breathing. References External links "Dapagliflozin mixture with metformin hydrochloride". Drug Information Portal. U.S. National Library of Medicine. "Dapagliflozin". MedlinePlus. "Metformin". MedlinePlus.

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I'm trying to understand 'Ring chromosome 14 syndrome' within a medical context. Could you shed some light on it?

Ring chromosome 14 syndrome is a very rare human chromosome abnormality. It occurs when one or both of the telomeres that mark the ends of chromosome 14 are lost allowing the now uncapped ends to fuse together forming a ring chromosome. It causes a number of serious health issues. Symptoms and signs The most common symptoms are intellectual disability and recurrent seizures developing in infancy or early childhood. Typically the seizures are resistant to treatment with anti-epileptic drugs. Other symptoms may include: Microcephaly Lymphedema Facial abnormalities Immune deficiencies Abnormalities of retina Slow growth Short stature Cause The syndrome is caused by the loss of genetic material near the end of the long arm (q) of chromosome 14 . The break that causes the telomere(s) to be lost occurs near the end of the chromosome, and is called a constitutional ring. These rings arise spontaneously ( it is rarely inherited).The genetic abnormality occurs randomly in sperm or egg cells or it may occur in early embryonic growth, if it occurs during embryonic growth the ring chromosome may be present in only some of a persons cells. Diagnosis Diagnosis is achieved by examining the structure of the chromosomes through karyotyping; while once born, one can do the following to ascertain a diagnosis of the condition: MRI EEG Management In terms of the management of ring chromosome 14 syndrome, anticonvulsive medication for seizures, as well as, proper therapy to help prevent respiratory infections in the affected individual are management measures that can be taken. Epidemiology Ring chromosome 14 syndrome is extremely rare, the true rate of occurrence is unknown (as it is less than 1 per 1,000,000), but there are at least 50 documented cases in the literature. See also Ring chromosome 18 syndrome Ring chromosome 20 syndrome References Further reading Disorders, National Organization for Rare (2003-01-01). NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. ISBN 9780781730631. Zollino M.; Seminara L.; Orteschi D.; Gobbi G.; Giovannini S.; Della Giustina E.; Frattini D.; Scarano A.; Neri G. (2009). "The Ring14 Syndrome: Clinical and Molecular Definition" (PDF). American Journal of Medical Genetics. 149A (6): 1116–1124. doi:10.1002/ajmg.a.32831. PMID 19441122. S2CID 22919033. == External links ==

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

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

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I'm trying to understand 'Anterior spinal artery syndrome' within a medical context. Could you shed some light on it?

Anterior spinal artery syndrome (also known as "anterior spinal cord syndrome") is syndrome caused by ischemia of the anterior spinal artery, resulting in loss of function of the anterior two-thirds of the spinal cord. The region affected includes the descending corticospinal tract, ascending spinothalamic tract, and autonomic fibers. It is characterized by a corresponding loss of motor function, loss of pain and temperature sensation, and hypotension. Anterior spinal artery syndrome is the most common form of spinal cord infarction. The anterior spinal cord is at increased risk for infarction because it is supplied by the single anterior spinal artery and has little collateral circulation, unlike the posterior spinal cord which is supplied by two posterior spinal arteries. Signs and symptoms Complete motor paralysis below the level of the lesion due to interruption of the corticospinal tract Loss of pain and temperature sensation at and below the level of the lesion due to interruption of the spinothalamic tract Retained proprioception and vibratory sensation due to intact dorsal columns Autonomic dysfunction may be present and can manifest as hypotension (either orthostatic or frank hypotension), sexual dysfunction, and/or bowel and bladder dysfunction Areflexia, flaccid internal and external anal sphincter, urinary retention and intestinal obstruction may also be present in individuals with anterior cord syndrome.Symptoms usually occur very quickly and are often experienced within one hour of the initial damage. MRI can detect the magnitude and location of the damage 10–15 hours after the initiation of symptoms. Diffusion-weighted imaging may be used as it is able to identify the damage within a few minutes of symptomatic onset.Clinical features include paraparesis or quadriparesis (depending on the level of the injury) and impaired pain and temperature sensation. Complete motor paralysis below the level of the lesion due to interruption of the corticospinal tract, and loss of pain and temperature sensation at and below the level of the lesion. Proprioception and vibratory sensation is preserved, as it is in the dorsal side of the spinal cord. Causes Due to the branches of the aorta that supply the anterior spinal artery, the most common causes are insufficiencies within the aorta. These include aortic aneurysms, dissections, direct trauma to the aorta, surgeries, and atherosclerosis. Acute disc herniation, cervical spondylosis, kyphoscoliosis, damage to the spinal column and neoplasia all could result in ischemia from anterior spinal artery occlusion leading to anterior cord syndrome. Other causes include vasculitis, polycythemia, sickle cell disease, decompression sickness, and collagen and elastin disorders. A thrombus in the artery of Adamkiewicz can lead to an anterior spinal syndrome. This is the most feared, though rare complication of bronchial artery embolization done in massive hemoptysis. Anatomy The anterior portion of the spinal cord is supplied by the anterior spinal artery. It begins at the foramen magnum where branches of the two vertebral arteries exit, merge, and descend along the anterior spinal cord. As the anterior spinal artery proceeds inferiorly, it receives branches originating mostly from the aorta. The largest aortic branch is the artery of Adamkiewicz. Diagnosis An MRI is used in the process of making a diagnosis for this condition Treatment Treatment is determined based on the primary cause of anterior cord syndrome. When the diagnosis of anterior cord syndrome is determined, the prognosis is unfortunate. The mortality rate is approximately 20%, with 50% of individuals living with anterior cord syndrome having very little or no changes in symptoms. Eponym It is also known as "Becks syndrome". See also Spinal cord injury References == External links ==

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

Myotonic dystrophy (DM) is a type of muscular dystrophy, a group of genetic disorders that cause progressive muscle loss and weakness. In DM, muscles are often unable to relax after contraction. Other manifestations may include cataracts, intellectual disability and heart conduction problems. In men, there may be early balding and an inability to have children. While myotonic dystrophy can occur at any age, onset is typically in the 20s and 30s.Myotonic dystrophy is caused by a genetic mutation in one of two genes. Mutation of the DMPK gene causes myotonic dystrophy type 1 (DM1). Mutation of CNBP gene causes type 2 (DM2). DM is typically inherited from a persons parents, following an autosomal dominant inheritance pattern, and it generally worsens with each generation. A type of DM1 may be apparent at birth. DM2 is generally milder. Diagnosis is confirmed by genetic testing.There is no cure. Treatments may include braces or wheelchairs, pacemakers and non-invasive positive pressure ventilation. The medications mexiletine or carbamazepine can help relax muscles. Pain, if it occurs, may be treated with tricyclic antidepressants and nonsteroidal anti-inflammatory drugs (NSAIDs).Myotonic dystrophy affects more than 1 in 8,000 people worldwide. It is the most common form of muscular dystrophy that begins in adulthood. It was first described in 1909, with the underlying cause of type 1 determined in 1992. Signs and symptoms DM causes muscle weakness, early onset of cataracts, and myotonia, which is delayed relaxation of muscles after contraction. Cataracts can be either a cortical cataract with a blue dot appearance, or a posterior subcapsular cataract. Other organs affected include the heart, lungs, gastrointestinal tract, skin, and brain. Insulin resistance can also occur. Signs and symptoms vary considerably by severity, unusual phenotype, and form (DM1/DM2). DM1 and DM2 differ in regards to the muscles they affect, age of onset, severity of disease, and extramuscular manifestations. DM1 DM1 usually begins in the muscles of the hands, feet, neck, or face. One manifestation of facial weakness is drooping of the eyelid (ptosis). It slowly progresses to involve other muscle groups, including the heart. Myotonia tends to be more prominent in DM1 compared to DM2. Other DM1 manifestations include problems with executive function (e.g., organization, concentration, word-finding) and hypersomnia. Abnormalities in the electrical activity of the heart are common in DM1, manifesting as arrhythmias or conduction blocks. Sometimes, dilated cardiomyopathy occurs. Symptoms onset any time from birth to adulthood. The earlier the disease onset, the greater the variety of possible signs and symptoms. Thus, various diagnostic classifications based on the age of onset/severity of the disease have been proposed, although DM1 manifestations likely lie on a continuum. Congenital DM1 When DM1 onsets at birth, it is called congenital DM1. Manifestations that can be present at birth include hypotonia, respiratory failure, feeding difficulty, and club foot (talipes equinovarus), any of which tend to resolve over several years. During childhood, intellectual impairment, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorders (ASD) can result. Gastrointestinal issues can result, which can be severe, manifestations including diarrhea, constipation, and fecal incontinence. The symptoms of adult DM often manifest during adolescence. Infantile DM1 can be distinguished as another disease category, or it can be grouped with congenital DM1 or childhood-onset DM1. Childhood-onset DM1 Childhood-onset DM1 is defined as onset of symptoms between ages 1 and 10 years. Manifestations include the same intellectual and gastrointestinal symptoms seen in congenital DM1. DM2 DM2 is generally milder than DM1, with generally fewer DM2 people requiring assistive devices than DM1 people. DM2 preferentially affects muscles closer to or on the torso, including the neck flexors, hip flexors, and hip extensors. Muscle pain is prominent in DM2. Heart issues, while still potentially fatal, are less common and severe in DM2 than DM1. Symptoms onset in early to late adulthood. Severe congenital onset, which can occur in DM1, has not been observed in DM2. Genetics Myotonic dystrophy (DM) is a genetic condition that is inherited in an autosomal dominant pattern, meaning each child of an affected individual has a 50% chance of inheriting the disease. The mutation involves satellite DNA, which is tandemly repeated sequences of DNA that do not code for a protein. The repeats implicated in myotonic dystrophy are either 3 or 4 nucleotides in length, classified as microsatellites. Disease results from an abnormally increased number of these microsatellites, termed microsatellite expansion. DM1 The microsatellite expansion responsible for DM1 is of cytosine-thymine-guanine (CTG) triplet repeats, termed trinucleotide repeat expansion and classifying DM1 as a one of several trinucleotide repeat disorders. This expansion occurs at the end of the DMPK gene, in the 3 untranslated region. DMPK is located on the long arm of chromosome 19. DMPK codes for myotonic dystrophy protein kinase, a protein expressed predominantly in skeletal muscle.Between 5 and 37 repeats is considered normal; between 38 and 49 repeats is considered pre-mutation, and although not producing symptoms, children can have further repeat expansion and symptomatic disease; greater than 50 repeats almost invariably is symptomatic, with some noted exceptions. Longer repeats are usually associated with earlier onset and more severe disease.DMPK alleles with greater than 37 repeats are unstable and additional trinucleotide repeats may be inserted during cell division in mitosis and meiosis. Consequently, the children of individuals with premutations or mutations inherit DMPK alleles which are longer than their parents and therefore are more likely to be affected or display an earlier onset and greater severity of the condition, a phenomenon known as anticipation. Repeat expansion is generally considered to be a consequence of the incorporation of additional bases as a result of strand slippage during either DNA replication or DNA repair synthesis. Misalignments occurring during homologous recombinational repair, double-strand break repair or during other DNA repair processes likely contribute to trinucleotide repeat expansions in DM1. Paternal transmission of the congenital form is uncommon (13%), possibly due to selection pressures against sperm with expanded repeats, but juvenile or adult-onset is equally transmitted from either parent. Anticipation tends to be less severe than in cases of maternal inheritance.The RNA from the expanded trinucleotide repeat region forms intranucleoplasmic hairpin loops due to the extensive hydrogen bonding between C-G base pairs, and it has been demonstrated that these sequester the splicing regulator MBNL1 to form distinctive foci.A severe form of DM1, congenital myotonic dystrophy, may appear in newborns of mothers who have DM. Congenital myotonic dystrophy can also be inherited via the paternal gene, although it is said to be relatively rare. Congenital means that the condition is present from birth. DM2 The microsatellite expansion responsible for DM2 is of cytosine-cytosine-thymine-guanine (CCTG) repeats, classifying it as a tetranucleotide repeat disorder. This expansion occurs in the first intron CNBP gene on chromosome 3.The repeat expansion for DM2 is much larger than for DM1, ranging from 75 to over 11,000 repeats. Like DM1, the size of the microsatellite repeat array lengthens from generation to generation. Unlike DM1, anticipation does not result, as the degree of repeat expansion beyond 75 repeats does not affect the age of onset or disease severity.The repeat expansion produces an RNA transcript that binds to RNA-binding proteins such as MBNL1, as in DM1. Also, repeat expansion likely reduces expression of CNBP, loss of which causes muscle toxicity. Pathophysiology Molecular Mutations of DM1 and DM2 cause production of RNA that sequesters RNA-binding proteins, causing dysregulated RNA splicing. This dysregulated RNA splicing is particularly toxic to skeletal, cardiac, and smooth muscle. One example in DM1 involves the chloride channel ClC-1. Mutated DMPK RNA binds to MBNL1, causing ClC-1 pre-mRNA to be spliced into the fetal form instead of the adult form. Functional loss of the chloride channel causes myotonia. Histology In DM1, there can be increased central nuclei, angular fibers, fiber atrophy, and pyknotic clumps. There can be selective atrophy of type 1 muscle fibers. Muscle fibers show signs of degeneration and regeneration. There is modest fibrosis of the endomysium.In DM2, there can be variation in the sizes of muscle fibers, although often there are no abnormalities. There is selective atrophy of type 2 muscle fibers. Again, there are central nuclei and nuclear clumps. Diagnosis The diagnosis of DM1 and DM2 can be difficult due to the large number of neuromuscular disorders, most of which are very rare. One study found that diagnosis is made an average of seven years after symptom onset for DM1, and fourteen years for DM2.As a result, people with multiple symptoms that may be explained by a complex disorder such as DM1 or DM2 will generally be referred by their primary care physician to a neurologist for diagnosis. Depending on the presentation of symptoms, people may be referred to a number of medical specialists including cardiologists, ophthalmologists, endocrinologists, and rheumatologists. In addition, the clinical presentation is obscured by the degree of severity or the presence of unusual phenotypes. Though there is presently no cure for DM and management is currently symptom-based, a precise diagnosis is still necessary to anticipate multiple other problems that may develop over time (e.g. cataracts). An accurate diagnosis is important to assist with appropriate medical monitoring and management of symptoms. In addition, genetic counseling should be made available to all people because of the high risk of transmission. Potentially serious anesthetic risks are important to note, so the presence of this disorder should be brought to the attention of all medical providers. Classification There are two main types of myotonic dystrophy. Type 1 (DM1), also known as Steinert disease, has a severe congenital form and a milder childhood-onset form as well as an adult-onset form. This disease is most often in the facial muscles, levator palpebrae superioris, temporalis, sternocleidomastoids, distal muscles of the forearm, hand intrinsic muscles, and ankle dorsiflexors. Type 2 (DM2), also known as proximal myotonic myopathy (PROMM), is rarer and generally manifests with milder signs and symptoms than DM1.Other forms of myotonic dystrophy not associated with DM1 or DM2 genetic mutations have been described. One case which was proposed as a candidate for the "DM3" label, was later characterized as an unusual form of inclusion body myopathy associated with Pagets disease and frontotemporal dementia. Genetic testing Genetic tests, including prenatal testing, are available for both confirmed forms. Molecular testing is considered the gold standard of diagnosis. Prenatal testing Testing at pregnancy to determine whether an unborn child is affected is possible if genetic testing in a family has identified a DMPK mutation. This can be done at 10–12 weeks gestation by a procedure called chorionic villus sampling (CVS) that involves removing a tiny piece of the placenta and analyzing DNA from its cells. It can also be done by amniocentesis after 14 weeks gestation by removing a small amount of the amniotic fluid surrounding the baby and analyzing the cells in the fluid. Each of these procedures has a small risk of miscarriage associated with it and those who are interested in learning more should check with their doctor or genetic counselor. There is also another procedure called preimplantation diagnosis that allows a couple to have a child that is unaffected by the genetic condition in their family. This procedure is experimental and not widely available. Those interested in learning more about this procedure should check with their doctor or genetic counselor. Predictive testing It is possible to test someone who is at risk for developing DM1 before they are showing symptoms to see whether they inherited an expanded trinucleotide repeat. This is called predictive testing. Predictive testing cannot determine the age of onset that someone will begin to have symptoms or the course of the disease. If the child is not having symptoms, the testing is not possible with an exception of emancipated minors as a policy. Auxiliary testing Electrodiagnostic testing (EMG and NCS) can detect the electrical signs of myotonia before myotonia becomes noticeable to the affected individual.Muscle biopsy can reveal damage of the muscle, but findings are generally nonspecific and do not greatly aid in diagnosis. Management There is currently no cure for or treatment specific to myotonic dystrophy. Management is focused on the complications of the disease, particularly those related to the lungs and heart, which are life-threatening. Complications relating to the cardiopulmonary system account for 70% of deaths due to DM1. Compromised lung function can, in turn, contribute to life-threatening complications during anesthesia and pregnancy.Lung complications are the leading cause of death in DM1, warranting lung function monitoring with pulmonary function tests every 6 months. Central sleep apnea or obstructive sleep apnea may cause excessive daytime sleepiness, and these individuals should undergo a sleep study. Non-invasive ventilation may be offered if there is an abnormality. Otherwise, there is evidence for the use of modafinil as a central nervous system stimulant, although a Cochrane review has described the evidence thus far as inconclusive.Cardiac complications are the second leading cause of death in DM1, and commonly no symptoms are present prior to adverse events. All affected individuals are advised to have an annual or biennial ECG. Pacemaker insertion may be required for individuals with cardiac conduction abnormalities. Improving the quality of life which can be measured using specific questionnaires is also a main objective of the medical care. Physical activity There is a lack of high-quality evidence to determine the effectiveness and the safety of physical activities for people who have myotonic dystrophy. Further research is required to determine if combined strength and aerobic training at moderate intensity is safe for people who have neuromuscular diseases, however the combination of aerobic and strength exercises may increase muscle strength. Aerobic exercise via stationary bicycle with an ergometer may be safe and effective in improving fitness in people with DM1. Cardiovascular impairments and myotonic sensitivities to exercise and temperature necessitate close monitoring of people and educating people in self-monitoring during exercise via the Borg scale, heart rate monitors, and other physical exertion measurements. Orthotics Muscular weakness of dorsiflexors (dorsiflexion) hinders the ability to clear the floor during the swing phase of gait and people may adopt a steppage gait pattern or ankle-foot-orthotics may be indicated. Factors such as hand function, skin integrity, and comfort must be assessed prior to prescription. Neck braces can also be prescribed for neck muscle weakness. Mobility aids and adaptive equipment Upper and lower limb weakness, visual impairments and myotonia may lead to the need for mobility aids and functional adaptive equipment such as buttonhooks and handled sponges for optimal hand function. If assistive devices and home adaptations are needed, physical therapists may refer on to occupational therapist(s) for further assessment. Prognosis Life expectancy in non-congenital late-onset or adult onset DM1 is in the early 50s, with pulmonary complications being the leading cause of death, followed by cardiac complications. DM2 life expectancy has yet to be studied. Epidemiology The prevalence of DM1 ranges from 5 to 20 per 100,000 (1:20,000–1:5000). Up to 48 per 100,000 (1:2100) of individuals tested positive for the mutation of DM1 in New York, although not all of these individuals would have become symptomatic. Again in New York, premutations for DM1 were found in 191 per 100,000 (1:525). DM2 prevalence is not known, but genetic studies estimate it to be as high as 1:1830. DM affects males and females approximately equally. About 30,000 people in the United States are affected. In most populations, DM1 appears to be more common than DM2. However, recent studies suggest that type 2 may be as common as type 1 among people in Germany and Finland.DM1 is the most common form of myotonic muscular dystrophy diagnosed in children, with a prevalence ranging from 1 per 100,000 in Japan to 3–15 per 100,000 in Europe. The prevalence may be as high as 1 in 500 in regions such as Quebec, possibly due to the founder effect. The incidence of congenital myotonic dystrophy is thought to be about 1:20,000. History Myotonic dystrophy was first described by a German physician, Hans Gustav Wilhelm Steinert, who first published a series of 6 cases of the condition in 1909. Isolated case reports of myotonia had been published previously, including reports by Frederick Eustace Batten and Hans Curschmann, and type 1 myotonic dystrophy is therefore sometimes known as Curschmann-Batten-Steinert syndrome. The underlying cause of type 1 myotonic dystrophy was determined in 1992. Research directions Altered splicing of the muscle-specific chloride channel 1 (ClC-1) has been shown to cause the myotonic phenotype of DM1 and is reversible in mouse models using Morpholino antisense to modify splicing of ClC-1 mRNA.Some small studies have suggested that imipramine, clomipramine and taurine may be useful in the treatment of myotonia. However, due to the weak evidence and potential side effects such as cardiac arrhythmias, these treatments are rarely used. A recent study in December 2015 showed that a common FDA approved antibiotic, Erythromycin reduced myotonia in mice. Human studies are planned for erythromycin. Erythromycin has been used successfully in patients with gastric issues. References External links Myotonic dystrophy at Curlie

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

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

Taliglucerase alfa, sold under the brand name Elelyso among others, is a biopharmaceutical medication developed by Protalix and Pfizer. The drug, a recombinant glucocerebrosidase used to treat Gauchers disease, is the first plant-made pharmaceutical to win approval by the U.S. Food and Drug Administration (FDA). Each vial has 200 units of taliglucerase alfa. Approval history The U.S. FDA New Drug Application (NDA) was granted approval in May 2012, for use in adults. The U.S. FDA Supplemental New Drug Application (sNDA) for pediatric use was granted approved in August 2014. In Israel, the Israeli Ministry of Health granted approval in September 2012. In Brazil, the Brazilian Health Surveillance Agency (ANVISA) granted approval in March 2013. In Canada, Health Canada issued a Notice of Compliance in May 2014, for both adults and pediatric patients.Taliglucerase alfa is made by the Israeli biotherapeutics company Protalix and sold by the American pharmaceutical company Pfizer. Society and culture Economics For 2016, Elelyso was ranked third for pharmaceuticals with the highest cost-per-patient, with an average cost of $483,242 per year. References External links "Taliglucerase alfa". Drug Information Portal. U.S. National Library of Medicine.

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

The term 'Testosterone (medication)' keeps coming up in medical discussions. What does it stand for?

Testosterone (T) is a medication and naturally occurring steroid hormone. It is used to treat male hypogonadism, gender dysphoria, and certain types of breast cancer. It may also be used to increase athletic ability in the form of doping. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. Testosterone can be used as a gel or patch that is applied to the skin, injection into a muscle, tablet that is placed in the cheek, or tablet that is taken by mouth.Common side effects of testosterone include acne, swelling, and breast enlargement in men. Serious side effects may include liver toxicity, heart disease, and behavioral changes. Women and children who are exposed may develop masculinization. It is recommended that individuals with prostate cancer not use the medication. It can cause harm to the baby if used during pregnancy or breastfeeding. Testosterone is in the androgen family of medications.Testosterone was first isolated in 1935, and approved for medical use in 1939. Rates of use have increased three times in the United States between 2001 and 2011. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. In 2019, it was the 126th most commonly prescribed medication in the United States, with more than 5 million prescriptions. Medical uses The primary use of testosterone is the treatment of males with too little or no natural testosterone production, also termed hypogonadism or hypoandrogenism (androgen deficiency). This treatment is referred to as hormone replacement therapy (HRT), or alternatively, and more specifically, as testosterone replacement therapy (TRT) or androgen replacement therapy (ART). It is used to maintain serum testosterone levels in the normal male range. Decline of testosterone production with age has led to interest in testosterone supplementation.A 2020 guidelines from the American College of Physicians support the discussion of testosterone in adult men with age-related low levels of testosterone who have sexual dysfunction. They recommend yearly evaluation regarding possible improvement and, if none, to discontinue testosterone; physicians should consider intramuscular treatments, rather than transdermal treatments, due to costs and since the effectiveness and harm of either method is similar. Testosterone treatment for reasons other than possible improvement of sexual dysfunction may not be recommended. Deficiency Testosterone deficiency (also termed hypotestosteronism or hypotestosteronemia) is an abnormally low testosterone production. It may occur because of testicular dysfunction (primary hypogonadism) or hypothalamic–pituitary dysfunction (secondary hypogonadism) and may be congenital or acquired. Low levels due to aging Testosterone levels may decline gradually with age. The United States Food and Drug Administration (FDA) stated in 2015 that neither the benefits nor the safety of testosterone supplement have been established for low testosterone levels due to aging. The FDA has required that labels on testosterone include warnings about increased risk of heart attacks and stroke. Transgender men To take advantage of its virilizing effects, testosterone is administered to transgender men and other transmasculine individuals as part of masculinizing hormone therapy, titrated to clinical effect with a "target level" of the average males testosterone level. Women Testosterone therapy is effective in the short-term for the treatment of hypoactive sexual desire disorder (HSDD) in women. However, its long-term safety is unclear. Because of a lack data to support its efficacy and safety, the Endocrine Society recommends against the routine use of testosterone in women to treat low androgen levels due to hypopituitarism, adrenal insufficiency, surgical removal of the ovaries, high-dose corticosteroid therapy, or other causes. Similarly, because of a lack of data to support its efficacy and safety, the Endocrine Society recommends against the use of testosterone in women to improve general well-being, to treat infertility, sexual dysfunction due to causes other than HSDD, or to improve cognitive, cardiovascular, metabolic, and/or bone health.A 2014 systematic review and meta-analysis of 35 studies consisting of over 5,000 postmenopausal women with normal adrenal gland function found that testosterone therapy was associated with significant improvement in a variety of domains of sexual function. These domains included frequency of sexual activity, orgasm, arousal, and sexual satisfaction, among others. Women who were menopausal due to ovariectomy showed significantly greater improvement in sexual function with testosterone relative to those who had normal menopause. In addition to beneficial effects on sexual function, testosterone was associated with unfavorable changes in blood lipids. These included decreased levels of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol, and increased levels of low-density lipoprotein (LDL) cholesterol. However, the changes were small in magnitude, and the long-term significance in relation to cardiovascular outcomes is uncertain. The changes were more pronounced with oral testosterone undecanoate than with parenteral routes, such as transdermal testosterone. Testosterone showed no significant effect on depressed mood anxiety, bone mineral density (BMD), or anthropomorphic measures like body weight or body mass index. Conversely, it was associated with a significant incidence of androgenic side effects, including acne and hirsutism (excessive facial/body hair growth). Other androgenic side effects, such as weight gain, pattern hair loss, and voice deepening, were also reported in some trials, but were excluded from analyses due to insufficient data. The overall quality of the evidence was rated as low and was considered to be inconclusive in certain areas, for instance on long-term safety.A subsequent 2017 systematic review and meta-analysis of studies including over 3,000 postmenopausal women with HSDD similarly found that short-term transdermal testosterone therapy was effective in improving multiple domains of sexual function. Androgenic adverse effects such as acne and hirsutism were significantly greater in incidence with testosterone therapy, whereas no significant differences in "increase in facial hair, alopecia, voice deepening, urinary symptoms, breast pain, headache, site reaction to the patch, total adverse events, serious adverse events, reasons for withdrawal from the study, and the number of women who completed the study" were seen relative to controls.Although testosterone has been found to be effective at improving sexual function in postmenopausal women, the doses employed have been supraphysiological. In contrast to these high doses, there is little support for the notion that testosterone is a critical hormone for sexual desire and function in women under normal physiological circumstances. Low doses of testosterone resulting in physiological levels of testosterone (<50 ng/dL) have not been found to significantly increase sexual desire or function in women in most studies. Similarly, there appears to be little or no relationship between total or free testosterone levels in the normal physiological range and sexual desire in premenopausal women. Only high doses of testosterone resulting in supraphysiological levels of testosterone (>50 ng/dL) significantly increase sexual desire in women, with levels of testosterone of 80 to 150 ng/dL "slightly" increasing sex drive. In accordance, men experience sexual dysfunction at testosterone levels of below 300 ng/dL, and men that have levels of testosterone of approximately 200 ng/dL frequently experience such problems. The high doses of testosterone required to increase sexual desire in women may have a significant risk of masculinization with long-term therapy. For this reason, and due to the unknown health effects and safety of testosterone therapy, its use may be inappropriate. In 2003, the FDA rejected Intrinsa, a 300 µg/day testosterone patch for the treatment of sexual dysfunction in postmenopausal women. The reasons cited were limited efficacy (about one additional sexually satisfying event per month), concerns about safety and potential adverse effects with long-term therapy, and concerns about inappropriate off-label use. It appears that in women, rather than testosterone, estradiol may be the most important hormone involved in sexual desire, although data on the clinical use of estradiol to increase sexual desire in women is limited.There are no testosterone products approved for use in women in the United States and many other countries. There are approved testosterone products for women in Australia (where it is considered a drug of dependence, medicines that are subject to misuse and trafficking.) and some European countries. Testosterone pellet implants are approved for use in postmenopausal women in the United Kingdom. Testosterone products for men can be used off-label in women in the United States. Alternatively, testosterone products for women are available from compounding pharmacies in the United States, although such products are unregulated and manufacturing quality is not ensured. Available forms Testosterone has been marketed for use by oral, sublingual, buccal, intranasal, transdermal (patches), topical (gels), intramuscular (injection), and subcutaneous (implant administration. It is provided unmodified and as a testosterone ester such as testosterone cypionate, testosterone enanthate, testosterone propionate, or testosterone undecanoate, which act as prodrugs of testosterone. The most common route of administration for testosterone is by intramuscular injection. However, it has been reported that AndroGel, a transdermal gel formulation of testosterone, has become the most popular form of testosterone in androgen replacement therapy for hypogonadism in the United States. Non-medical use Athletics Testosterone is used as a form of doping among athletes in order to improve performance. Testosterone is classified as an anabolic agent and is on the World Anti-Doping Agency (WADA) List of Prohibited Substances and Methods. Hormone supplements cause the endocrine system to adjust its production and lower the natural production of the hormone, so when supplements are discontinued, natural hormone production is lower than it was originally.Anabolic–androgenic steroids (AAS), including testosterone and its esters, have also been taken to enhance muscle development, strength, or endurance. They do so directly by increasing the muscles protein synthesis. As a result, muscle fibers become larger and repair faster than the average persons.After a series of scandals and publicity in the 1980s (such as Ben Johnsons improved performance at the 1988 Summer Olympics), prohibitions of AAS use were renewed or strengthened by many sports organizations. Testosterone and other AAS were designated a "controlled substance" by the United States Congress in 1990, with the Anabolic Steroid Control Act. Their use is seen as an issue in modern sport, particularly given the lengths to which athletes and professional laboratories go to in trying to conceal such use from sports regulators. Steroid use once again came into the spotlight as a result of Canadian professional wrestler Chris Benoits double murder-suicide in 2007; however, there is no evidence implicating steroid use as a factor in the incident.Some female athletes may have naturally higher levels of testosterone than others, and may be asked to consent to sex verification and either surgery or drugs to decrease testosterone levels. This has proven contentious, with the Court of Arbitration for Sport suspending the IAAF policy due to insufficient evidence of a link between high androgen levels and improved athletic performance. Detection of abuse A number of methods for detecting testosterone use by athletes have been employed, most based on a urine test. These include the testosterone/epitestosterone ratio (normally less than 6), the testosterone/luteinizing hormone ratio and the carbon-13/carbon-12 ratio (pharmaceutical testosterone contains less carbon-13 than endogenous testosterone). In some testing programs, an individuals own historical results may serve as a reference interval for interpretation of a suspicious finding. Another approach being investigated is the detection of the administered form of testosterone, usually an ester, in hair. Contraindications Absolute contraindications of testosterone include prostate cancer, elevated hematocrit (>54%), uncontrolled congestive heart failure, various other cardiovascular diseases, and uncontrolled obstructive sleep apnea. Breast cancer is said by some sources to be an absolute contraindication of testosterone therapy, but androgens including testosterone have also actually been used to treat breast cancer. Relative contraindications of testosterone include elevated prostate-specific antigen (PSA) in men with a high risk of prostate cancer due to ethnicity or family history, severe lower urinary tract symptoms, and elevated hematocrit (>50%). Side effects Adverse effects may also include minor side effects such as oily skin, acne, and seborrhea, as well as loss of scalp hair, which may be prevented or reduced with 5α-reductase inhibitors. In women, testosterone can produce hirsutism (excessive facial/body hair growth), deepening of the voice, and other signs of virilization. Exogenous testosterone may cause suppression of spermatogenesis in men, leading to, in some cases, reversible infertility. Gynecomastia and breast tenderness may occur with high dosages of testosterone due to peripheral conversion of testosterone by aromatase into excessive amounts of the estrogen estradiol. Testosterone treatment, particularly in high dosages, can also be associated with mood changes, increased aggression, increased sex drive, spontaneous erections, and nocturnal emissions.Other side effects include increased hematocrit, which can require venipuncture in order to treat, and exacerbation of sleep apnea.The FDA stated in 2015 that neither the benefits nor the safety of testosterone have been established for low testosterone levels due to aging. The FDA has required that testosterone pharmaceutical labels include warning information about the possibility of an increased risk of heart attacks and stroke. They have also required the label include concerns about abuse and dependence.Injectable forms of testosterone can cause a lung problem called pulmonary oil microembolism (POME). Symptoms of POME include cough, shortness of breath, tightening of the throat, chest pain, sweating, dizziness, and fainting. A postmarketing analysis by the manufacturer of Aveed (testosterone undeconate injection) found that POME occurred at a rate of less than 1% per injection per year for Aveed. Long-term adverse effects Cardiovascular disease Adverse effects of testosterone supplementation may include increased cardiovascular events (including strokes and heart attacks) and deaths based on three peer-reviewed studies involving men taking testosterone replacement. In addition, an increase of 30% in deaths and heart attacks in older men has been reported. Due to an increased incidence of adverse cardiovascular events compared to a placebo group, a Testosterone in Older Men with Mobility Limitations (TOM) trial (a National Institute of Aging randomized trial) was halted early by the Data Safety and Monitoring Committee. On January 31, 2014, reports of strokes, heart attacks, and deaths in men taking FDA-approved testosterone-replacement led the FDA to announce that it would be investigating the issue. Later, in September 2014, the FDA announced, as a result of the "potential for adverse cardiovascular outcomes", a review of the appropriateness and safety of Testosterone Replacement Therapy (TRT). The FDA now requires warnings in the drug labeling of all approved testosterone products regarding deep vein thrombosis and pulmonary embolism.Up to the year 2010, studies had not shown any effect on the risk of death, prostate cancer or cardiovascular disease; more recent studies, however, do raise concerns. A 2013 study, published in the Journal of the American Medical Association, reported "the use of testosterone therapy was significantly associated with increased risk of adverse outcomes." The study began after a previous, randomized, clinical trial of testosterone therapy in men was stopped prematurely "due to adverse cardiovascular events raising concerns about testosterone therapy safety." Prostate cancer Testosterone in the presence of a slow-growing prostate cancer is assumed to increase its growth rate. However, the association between testosterone supplementation and the development of prostate cancer is unproven. Nevertheless, physicians are cautioned about the cancer risk associated with testosterone supplementation.Testosterone may accelerate pre-existing prostate cancer growth in individuals who have undergone androgen deprivation. It is recommended that physicians screen for prostate cancer with a digital rectal exam and prostate-specific antigen (PSA) level before starting therapy, and monitor PSA and hematocrit levels closely during therapy.Ethnic groups have different rates of prostate cancer. Differences in sex hormones, including testosterone, have been suggested as an explanation for these differences. This apparent paradox can be resolved by noting that prostate cancer is very common. In autopsies, 80% of 80-year-old men have prostate cancer. Pregnancy and breastfeeding Testosterone is contraindicated in pregnancy and not recommended during breastfeeding. Androgens like testosterone are teratogens and are known to cause fetal harm, such as producing virilization and ambiguous genitalia. Interactions 5α-Reductase inhibitors 5α-Reductase inhibitors like finasteride and dutasteride can slightly increase circulating levels of testosterone by inhibiting its metabolism. However, these drugs do this via prevention of the conversion of testosterone into its more potent metabolite dihydrotestosterone (DHT), and this results in dramatically reduced circulating levels of DHT (which circulates at much lower relative concentrations). In addition, local levels of DHT in so-called androgenic (5α-reductase-expressing) tissues are also markedly reduced, and this can have a strong impact on certain effects of testosterone. For instance, growth of body and facial hair and penile growth induced by testosterone may be inhibited by 5α-reductase inhibitors, and this could be considered undesirable in the context of, for instance, puberty induction. On the other hand, 5α-reductase inhibitors may prevent or reduce adverse androgenic side effects of testosterone like scalp hair loss, oily skin, acne, and seborrhea. In addition to the prevention of testosterone conversion into DHT, 5α-reductase inhibitors also prevent the formation of neurosteroids like 3α-androstanediol from testosterone, and this may have neuropsychiatric consequences in some men. Aromatase inhibitors Aromatase inhibitors like anastrozole prevent the conversion of testosterone into estradiol by aromatase. As only a very small fraction of testosterone is converted into estradiol, this does not affect testosterone levels, but it can prevent estrogenic side effects like gynecomastia that can occur when testosterone is administered at relatively high dosages. However, estradiol exerts negative feedback on the hypothalamic–pituitary–gonadal axis and, for this reason, prevention of its formation can reduce this feedback and disinhibit gonadal production of testosterone, which in turn can increase levels of endogenous testosterone. Testosterone therapy is sometimes combined with an aromatase inhibitor for men with secondary hypogonadism who wish to conceive children with their partners. Cytochrome P450 inhibitors Inhibitors and inducers of cytochrome P450 enzymes like CYP3A4 have been associated with little or no effect on circulating testosterone levels. Antiandrogens and estrogens Antiandrogens like cyproterone acetate, spironolactone, and bicalutamide can block the androgenic and anabolic effects of testosterone. Estrogens can reduce the effects of testosterone by increasing the hepatic production and in turn circulating levels of sex hormone-binding globulin (SHBG), a carrier protein that binds to and occupies androgens like testosterone and DHT, and thereby reducing free concentrations of these androgens. Pharmacology Pharmacodynamics Testosterone is a high affinity ligand for and agonist of the nuclear androgen receptor (AR). In addition, testosterone binds to and activates membrane androgen receptors (mARs) such as GPRC6A and ZIP9. Testosterone is also potentiated via transformation by 5α-reductase into the more potent androgen DHT in so-called androgenic tissues such as the prostate gland, seminal vesicles, skin, and hair follicles. In contrast to the case of testosterone, such potentiation occurs to a reduced extent or not at all with most synthetic AAS (as well as with DHT), and this is primarily responsible for the dissociation of anabolic and androgenic effects with these agents. In addition to DHT, testosterone is converted at a rate of approximately 0.3% into the estrogen estradiol via aromatase. This occurs in many tissues, especially adipose tissue, the liver, and the brain, but primarily in adipose tissue. Testosterone, after conversion into DHT, is also metabolized into 3α-androstanediol, a neurosteroid and potent positive allosteric modulator of the GABAA receptor, and 3β-androstanediol, a potent and preferential agonist of the ERβ. These metabolites, along with estradiol, may be involved in a number of the effects of testosterone in the brain, including its antidepressant, anxiolytic, stress-relieving, rewarding, and pro-sexual effects. Effects in the body and brain The ARs are expressed widely throughout the body, including in the penis, testicles, epididymides, prostate gland, seminal vesicles, fat, skin, bone, bone marrow, muscle, larynx, heart, liver, kidneys, pituitary gland, hypothalamus, and elsewhere throughout the brain. Through activation of the ARs (as well as the mARs), testosterone has many effects, including the following: Promotes growth, function, and maintenance of the prostate gland, seminal vesicles, and penis during puberty and thereafter Promotes growth and maintenance of muscles, particularly of the upper body Causes subcutaneous fat to be deposited in a masculine pattern and decreases overall body fat Suppresses breast development induced by estrogens, but can also still produce gynecomastia via excessive conversion into estradiol if levels are too high Maintains skin health, integrity, appearance, and hydration and slows the rate of aging of the skin, but can also cause oily skin, acne, and seborrhea Promotes the growth of facial and body hair, but can also cause scalp hair loss and hirsutism Contributes to bone growth and causes broadening of the shoulders at puberty Modulates liver protein synthesis, such as the production of sex hormone-binding globulin and many other proteins Increases production of erythropoietin in the kidneys and thereby stimulates red blood cell production in bone marrow and elevates hematocrit Exerts negative feedback on the hypothalamic–pituitary–gonadal axis by suppressing the secretion of the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland, thereby inhibiting gonadal sex hormone production as well as spermatogenesis and fertility Regulates the vasomotor system and body temperature via the hypothalamus, thereby preventing hot flashes Modulates brain function, with effects on mood, emotionality, aggression, and sexuality, as well as cognition and memory Increases sex drive and erectile capacity and causes spontaneous erections and nocturnal emissions Increases the risk of benign prostatic hyperplasia and prostate cancer and accelerates the progression of prostate cancer Decreases breast proliferation and the risk of breast cancer Pharmacokinetics Testosterone can be taken by a variety of different routes of administration. These include oral, buccal, sublingual, intranasal, transdermal (gels, creams, patches), rectal suppositories), by intramuscular or subcutaneous injection (in oil or aqueous), and as a subcutaneous implant. The pharmacokinetics of testosterone, including its bioavailability, circulating testosterone levels, metabolism, biological half-life, and other parameters, differ by route of administration. Chemistry Testosterone is a naturally occurring androstane steroid and is also known by the chemical name androst-4-en-17β-ol-3-one. It has a double bond between the C4 and C5 positions (making it an androstene), a ketone group at the C3 position, and a hydroxyl (alcohol) group at the C17β position. Derivatives Testosterone esters are substituted at the C17β position with a lipophilic fatty acid ester moiety of varying chain length. Major testosterone esters include testosterone cypionate, testosterone enanthate, testosterone propionate, and testosterone undecanoate. A C17β ether prodrug of testosterone, cloxotestosterone acetate, has also been marketed, although it is little known and is used very rarely or no longer. Another C17β ether prodrug of testosterone, silandrone, also exists but was never marketed, and is notable in that it is orally active. In addition to ester and ether prodrugs, androgen prohormones or precursors of testosterone, such as dehydroepiandrosterone (DHEA), androstenediol, and androstenedione, exist as well, and convert into testosterone to variable extents upon oral ingestion. Unlike testosterone ester and ether prodrugs however, these prohormones are only weakly androgenic/anabolic.All synthetic AAS are derivatives of testosterone. Prominent examples include nandrolone (19-nortestosterone), metandienone (17α-methyl-δ1-testosterone), and stanozolol (a 17α-alkylated derivative of DHT). Unlike testosterone, AAS that are 17α-alkylated, like metandienone and stanozolol, are orally active. This is due to steric hindrance of C17β-position metabolism during the first-pass through the liver. In contrast, most AAS that are not 17α-alkylated, like nandrolone, are not active orally, and must instead be administered via intramuscular injection. This is almost always in ester form; for instance, in the case of nandrolone, as nandrolone decanoate or nandrolone phenylpropionate. History Testosterone was first isolated and synthesized in 1935. Shortly thereafter, in 1937, testosterone first became commercially available as a pharmaceutical drug in the form of pellets and then in ester form for intramuscular injection as the relatively short-acting testosterone propionate. Methyltestosterone, one of the first synthetic AAS and orally active androgens, was introduced in 1935, but was associated with hepatotoxicity and eventually became largely medically obsolete. In the mid-1950s, the longer-acting testosterone esters testosterone enanthate and testosterone cypionate were introduced. They largely superseded testosterone propionate and became the major testosterone esters used medically for over half a century. In the 1970s, testosterone undecanoate was introduced for oral use in Europe, although intramuscular testosterone undecanoate had already been in use in China for several years. Intramuscular testosterone undecanoate was not introduced in Europe and the United States until much later (in the early to mid 2000s and 2014, respectively).The history of testosterone as a medication has been reviewed. Society and culture Usage In the US in the 2000s, companies and figures in the popular media have heavily marketed notions of "andropause" as something parallel to menopause; these notions have been rejected by the medical community. Additionally, advertising from drug companies selling testosterone and human growth hormone, as well as dietary supplement companies selling all kinds of "boosters" for aging men, have emphasized the "need" of middle-aged or ageing men for testosterone. There is a medical condition called late-onset hypogonadism; according to Thomas Perls and David J. Handelsman, writing in a 2015 editorial in the Journal of the American Geriatrics Society, it appears that this condition is overdiagnosed and overtreated. Perls and Handelsman note that in the US, "sales of testosterone increased from $324 million in 2002 to $2 billion in 2012, and the number of testosterone doses prescribed climbed from 100 million in 2007 to half a billion in 2012, not including the additional contributions from compounding pharmacies, Internet, and direct-to-patient clinic sales." Generic names Testosterone is the generic name of testosterone in English and Italian and the INN, USAN, USP, BAN, and DCIT of the drug, while testostérone is its French name and the DCF. It is also referred to in Latin as testosteronum, in Spanish and Portuguese as testosterona, and in German, Dutch, and Russian and other Slavic languages as testosteron. The Cyrillic script of testosterone is тестостерон. Brand names Testosterone is marketed under a large number of brand names throughout the world. Major brand names of testosterone and/or its esters include Andriol, Androderm, AndroGel, Axiron, Delatestryl, Depo-Testosterone, Intrinsa, Nebido, Omnadren, Primoteston, Sustanon, Testim, TestoGel, TestoPatch, Testoviron, and Tostran. Availability United States As of November 2016, unmodified (non-esterified) testosterone is available in the United States in the following formulations: Topical gels: AndroGel, Fortesta, Testim, Testosterone (generic) Topical solutions: Axiron, Testosterone (generic) Transdermal patches: Androderm, Testoderm (discontinued), Testoderm TTS (discontinued), Testosterone (generic) Intranasal gels: Natesto Buccal tablets: Striant Pellet implants: TestopelAnd the following ester prodrugs of testosterone are available in the United States in oil solutions for intramuscular injection: Testosterone cypionate: Depo-Testosterone, Testosterone Cypionate (generic) Testosterone enanthate: Delatestryl, Xyosted (auto-injector), Testosterone Enanthate (generic) Testosterone propionate: Testosterone Propionate (generic) Testosterone undecanoate: AveedUnmodified testosterone was also formerly available for intramuscular injection but was discontinued.Testosterone cypionate and testosterone enanthate were formerly available in combination with estradiol cypionate and estradiol valerate, respectively, under the brand names Depo-Testadiol and Ditate-DS, respectively, as oil solutions for intramuscular injection, but these formulations have been discontinued.Unlike in Europe, Canada, and much of the rest of the world, oral testosterone undecanoate is not available in the United States. Canada As of November 2016, testosterone is available in Canada in the form of topical gels (AndroGel, Testim), topical solutions (Axiron), transdermal patches (Androderm), and intranasal gels (Natesto). Testosterone cypionate (Depo-Testosterone, Testosterone Cypionate (generic)), testosterone enanthate (Delatestryl, PMS-Testosterone Enanthate), and testosterone propionate (Testosterone Propionate (generic)) are available as oil solutions for intramuscular injection and testosterone undecanoate (Andriol, PMS-Testosterone, Taro-Testosterone) is available in the form of oral capsules. Testosterone buccal tablets and pellet implants do not appear to be available in Canada. Other countries Testosterone and/or its esters are widely available in countries throughout the world in a variety of formulations. Legal status Testosterone and its esters, along with other AAS, are prescription-only controlled substances in many countries throughout the world. In the United States, they are Schedule III drugs under the Controlled Substances Act, in Canada, they are Schedule IV drugs under the Controlled Drugs and Substances Act, and in the United Kingdom, they are Class C drugs under the Misuse of Drugs Act. Litigation As of 2014, a number of lawsuits are underway against manufacturers of testosterone, alleging a significantly increased rate of stroke and heart attack in elderly men who use testosterone supplementation. Doping in sports There are many known cases of doping in sports with testosterone and its esters by professional athletes. Research Depression Testosterone has been used to treat depression in men who are of middle age with low testosterone. However, a 2014 review showed no benefit on the mood of the men with normal levels of testosterone or on the mood of the older men with low testosterone. Conversely, a 2009 review found that testosterone had an antidepressant effect in men with depression, especially those with hypogonadism, HIV/AIDS, and in the elderly. Heart failure Testosterone replacement can significantly improve exercise capacity, muscle strength and reduce QT intervals in men with chronic heart failure (CHF). Over the 3 to 6-month course of the studies reviewed, testosterone therapy appeared safe and generally effective, and (ruling out prostate cancer) the authors found no justification to absolutely restrict its use in men with CHF. A similar 2012 review also found increased exercise capacity and reasoned the benefits generlizable to women. However, both reviews advocate larger, longer term, randomized controlled trials. Male contraception Testosterone, as esters such as testosterone undecanoate or testosterone buciclate, has been studied and promoted as a male contraceptive analogous to estrogen-based contraceptives in women. Otherwise considered an adverse effect of testosterone, reduced spermatogenesis can be further suppressed with the addition of a progestin such as norethisterone enanthate or levonorgestrel butanoate, improving the contraceptive effect. Anorgasmia Testosterone is under development in a low-dose intranasal formulation for the treatment of anorgasmia in women. Miscellaneous Testosterone therapy may improve the management of type 2 diabetes. Low testosterone has been associated with the development of Alzheimers disease.Topical androgens like testosterone have been used and studied in the treatment of cellulite in women. References Further reading External links "Testosterone". Drug Information Portal. U.S. National Library of Medicine. "Testosterone Transdermal Patch". MedlinePlus. "Testosterone Buccal". MedlinePlus. "Testosterone Topical". MedlinePlus. "Testosterone Injection". MedlinePlus. "Testosterone Nasal Gel". MedlinePlus.

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.

Can you demystify the medical term 'Primordial cyst' for me?

A primordial cyst is a developmental odontogenic cyst. It is found in an area where a tooth should have formed but is missing. Primordial cysts most commonly arise in the area of mandibular third molars. Under microscopes, the cyst looks like an odontogenic keratocyst (also called a Keratocyst odontogenic tumor) whereby the lesions displays a parakeratinized epithelium with palisading basal epithelial cells. The term "Primordial cyst" is considered an outdated term and should be avoided. Most "primordial cysts" are actually Keratocyst odontogenic tumors (KOTs). References Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001.

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 understand 'H5N1 vaccine' within a medical context. Could you shed some light on it?

A H5N1 vaccine is an influenza vaccine intended to provide immunization to influenza A virus subtype H5N1. Vaccines have been formulated against several of the avian H5N1 influenza varieties. Vaccination of poultry against the H5N1 epizootic is widespread in certain countries. Some vaccines also exist for use in humans, and others are in testing, but none have been made available to civilian populations, nor produced in quantities sufficient to protect more than a tiny fraction of the Earths population in the event of an H5N1 pandemic. In January 2020, the U.S. Food and Drug Administration (FDA) approved Audenz, an adjuvanted influenza A (H5N1) monovalent vaccine. 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.Some older, egg-based H5N1 vaccines for humans that have been licensed are: Sanofi Pasteurs vaccine approved by the United States in April 2007, GlaxoSmithKlines vaccine Prepandrix approved by the European Union in May 2008, with reactive AS03 (containing squalene) adjuvant. and CSL Limiteds vaccine Panvax approved by Australia in June 2008.Other licensed H5N1 vaccines include: Adjupanrix, approved for medical use in the European Union in October 2009. Adjupanrix contains the flu strain A/VietNam/1194/2004 NIBRG 14 (H5N1). Foclivia, approved for medical use in the European Union in October 2009. Foclivia contains the flu strain A/Vietnam/1194/2004 (H5N1). Aflunov, approved for medical use in the European Union in November 2010. Aflunov contains the flu strain A/turkey/Turkey/1/2005 (H5N1)-like strain (NIBRG-23) (clade 2.2.1). Pumarix, approved for medical use in the European Union in March 2011.In November 2013, the U.S. Food and Drug Administration (FDA) approved an experimental H5N1 bird flu vaccine to be held in stockpiles. In a clinical trial including 3,400 adults, 91% of people age 18-64 and 74% of people age 65 or older formed an immune response sufficient to provide protection. Reported adverse effects were generally mild, with pain at the injection site being the most common adverse effect.H5N1 continually mutates, meaning vaccines based on current samples of avian H5N1 cannot be depended upon to work in the case of a future pandemic of H5N1. While there can be some cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Daniel R. Lucey, co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University, has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine." However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic. Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain.Problems with H5N1 vaccine production include: lack of overall production capacity lack of surge production capacity (it is impractical to develop a system that depends on hundreds of millions of 11-day-old specialized eggs on a standby basis) the pandemic H5N1 might be lethal to chickensCell culture (cell-based) manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines and thereby solve the problems associated with creating flu vaccines using chicken eggs. Vaccine production capacity: The protective immune response generated by influenza vaccines is largely based on viral hemagglutinin (HA) and neuraminidase (NA) antigens in the vaccine. As a consequence, the basis of influenza vaccine manufacturing is growing massive quantities of virus in order to have sufficient amounts of these protein antigens to stimulate immune responses. Influenza vaccines used in the United States and around world are manufactured by growing virus in fertilized hens eggs, a commercial process that has been in place for decades. To achieve vaccine production targets millions of 11-day-old fertilized eggs must be available every day of production.In the near term, further expansion of these systems will provide additional capacity for the U.S.-based production of both seasonal and pandemic vaccines, however, the surge capacity that will be needed for a pandemic response cannot be met by egg-based vaccine production alone, as it is impractical to develop a system that depends on hundreds of millions of 11-day-old specialized eggs on a standby basis. In addition, because a pandemic could result from an avian influenza strain that is lethal to chickens, it is impossible to ensure that eggs will be available to produce vaccine when needed.In contrast, cell culture manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines (e.g., polio vaccine, measles-mumps-rubella vaccine, chickenpox vaccine). In this system, viruses are grown in closed systems such as bioreactors containing large numbers of cells in growth media rather than eggs. The surge capacity afforded by cell-based technology is insensitive to seasons and can be adjusted to vaccine demand, as capacity can be increased or decreased by the number of bioreactors or the volume used within a bioreactor. In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States. The US government has purchased from Sanofi Pasteur and Chiron Corporation several million doses of vaccine meant to be used in case of an influenza pandemic of H5N1 avian influenza and is conducting clinical trials with these vaccines. Researchers at the University of Pittsburgh have had success with a genetically engineered vaccine that took only a month to make and completely protected chickens from the highly pathogenic H5N1 virus.According to the United States Department of Health & Human Services: In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States. Dose-sparing technologies. Current U.S.-licensed vaccines stimulate an immune response based on the quantity of HA (hemagglutinin) antigen included in the dose. Methods to stimulate a strong immune response using less HA antigen are being studied in H5N1 and H9N2 vaccine trials. These include changing the mode of delivery from intramuscular to intradermal and the addition of immune-enhancing adjuvant to the vaccine formulation. Additionally, HHS is soliciting contract proposals from manufacturers of vaccines, adjuvants, and medical devices for the development and licensure of influenza vaccines that will provide dose-sparing alternative strategies.Chiron Corporation is now recertified and under contract with the National Institutes of Health to produce 8,000–10,000 investigational doses of Avian Flu (H5N1) vaccine. MedImmune and Aventis Pasteur are under similar contracts. The United States government hopes to obtain enough vaccine in 2006 to treat 4 million people. However, it is unclear whether this vaccine would be effective against a hypothetical mutated strain that would be easily transmitted through human populations, and the shelf life of stockpiled doses has yet to be determined.The New England Journal of Medicine reported on March 30, 2006, on one of dozens of vaccine studies being conducted. The Treanor et al. study was on vaccine produced from the human isolate (A/Vietnam/1203/2004 H5N1) of a virulent clade 1 influenza A (H5N1) virus with the use of a plasmid rescue system, with only the hemagglutinin and neuraminidase genes expressed and administered without adjuvant. "The rest of the genes were derived from an avirulent egg-adapted influenza A/PR/8/34 strain. The hemagglutinin gene was further modified to replace six basic amino acids associated with high pathogenicity in birds at the cleavage site between hemagglutinin 1 and hemagglutinin 2. Immunogenicity was assessed by microneutralization and hemagglutination-inhibition assays with the use of the vaccine virus, although a subgroup of samples were tested with the use of the wild-type influenza A/Vietnam/1203/2004 (H5N1) virus." The results of this study combined with others scheduled to be completed by spring 2007 is hoped will provide a highly immunogenic vaccine that is cross-protective against heterologous influenza strains.On August 18, 2006. the World Health Organization (WHO) changed the H5N1 strains recommended for candidate vaccines for the first time since 2004. "The WHOs new prototype strains, prepared by reverse genetics, include three new H5N1 subclades. The hemagglutinin sequences of most of the H5N1 avian influenza viruses circulating in the past few years fall into two genetic groups, or clades. Clade 1 includes human and bird isolates from Vietnam, Thailand, and Cambodia and bird isolates from Laos and Malaysia. Clade 2 viruses were first identified in bird isolates from China, Indonesia, Japan, and South Korea before spreading westward to the Middle East, Europe, and Africa. The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections: Subclade 1, Indonesia Subclade 2, Middle East, Europe, and Africa Subclade 3, ChinaOn the basis of the three subclades, the WHO is offering companies and other groups that are interested in pandemic vaccine development these three new prototype strains: An A/Indonesia/2/2005-like virus An A/Bar headed goose/Quinghai/1A/2005-like virus An A/Anhui/1/2005-like virus[...] Until now, researchers have been working on prepandemic vaccines for H5N1 viruses in clade 1. In March, the first clinical trial of a U.S. vaccine for H5N1 showed modest results. In May, French researchers showed somewhat better results in a clinical trial of an H5N1 vaccine that included an adjuvant. Vaccine experts arent sure if a vaccine effective against known H5N1 viral strains would be effective against future strains. Although the new viruses will now be available for vaccine research, WHO said clinical trials using the clade 1 viruses should continue as an essential step in pandemic preparedness, because the trials yield useful information on priming, cross-reactivity, and cross-protection by vaccine viruses from different clades and subclades."</ref>As of November 2006, the United States Department of Health and Human Services (HHS) had enough H5N1 pre-pandemic vaccine to treat about 3 million people (5.9 million full-potency doses) in spite of 0.2 million doses used for research and 1.4 million doses that have begun to lose potency (from the original 7.5 million full-potency doses purchased from Sanofi Pasteur and Chiron Corp.). The expected shelf life of seasonal flu vaccine is about a year so the fact that most of the H5N1 pre-pandemic stockpile is still good after about two years is considered encouraging. Clinical trials H5N1 clinical trials are clinical trials concerning H5N1 vaccines. They are intended to discover pharmacological effects and identify any adverse reactions the vaccines may achieve in humans. References Further reading Khurana S, Suguitan AL, Rivera Y, Simmons CP, Lanzavecchia A, Sallusto F, Manischewitz J, King LR, Subbarao K, Golding H (April 2009). "Antigenic fingerprinting of H5N1 avian influenza using convalescent sera and monoclonal antibodies reveals potential vaccine and diagnostic targets". PLOS Med. 6 (4): e1000049. doi:10.1371/journal.pmed.1000049. PMC 2661249. PMID 19381279. External links "Diagnostic Targets and Potential Vaccine Against H5n1 Avian Influenza". U.S. Food and Drug Administration (FDA). 2019-10-21. US patent 8778847, "Immunogenic peptides of influenza virus", published 2010-11-11, issued 2014-06-25 "Pandemic Influenza". HHS.gov. 2016-07-14.

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

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

Melioidosis is an infectious disease caused by a gram-negative bacterium called Burkholderia pseudomallei. Most people exposed to B. pseudomallei experience no symptoms; however, those who do experience symptoms have signs and symptoms that range from mild such as fever and skin changes, to severe with pneumonia, abscesses, and septic shock that could cause death. Approximately 10% of people with melioidosis develop symptoms that last longer than two months, termed "chronic melioidosis".Humans are infected with B. pseudomallei by contact with contaminated soil or water. The bacteria enter the body through wounds, inhalation, or ingestion. Person-to-person or animal-to-human transmission is extremely rare. The infection is constantly present in Southeast Asia particularly in northeast Thailand and northern Australia. In temperate countries such as Europe and the United States, melioidosis cases are usually imported from countries where melioidosis is endemic. The signs and symptoms of melioidosis resemble tuberculosis and misdiagnosis is common. Diagnosis is usually confirmed by the growth of B. pseudomallei from an infected persons blood or other bodily fluid such as pus, sputum, and urine. Those with melioidosis are treated first with an "intensive phase" course of intravenous antibiotics (most commonly ceftazidime) followed by a several-months treatment course of co-trimoxazole. In countries with the advanced healthcare system, approximately 10% of people with melioidosis die from the disease. In less developed countries, the death rate could reach 40%.Efforts to prevent melioidosis include: wearing protective gear while handling contaminated water or soil, practising hand hygiene, drinking boiled water, and avoiding direct contact with soil, water, or heavy rain. There is little evidence in supporting the use of melioidosis prophylaxis in humans. The antibiotic co-trimoxazole is used as a preventative only for individuals at high risk for getting the disease after being exposed to the bacteria in laboratory settings. One study conducted in 2018 determined that the drug could be useful in preventing melioidosis in high-risk renal failure patients undergoing haemodylysis. There is no approved vaccine for melioidosis.Approximately 165,000 people are infected by melioidosis per year, resulting in about 89,000 deaths, based on a mathematical model published in 2016. Diabetes is a major risk factor for melioidosis; over half of melioidosis cases are in people with diabetes. Increased rainfall and severe weather events such as thunderstorm are associated with an increased number of melioidosis cases in endemic areas. Signs and symptoms Acute Most people exposed to B. pseudomallei experience no symptoms. The mean incubation period of acute melioidosis is 9 days (range 1–21 days). Nevertheless, symptoms of melioidosis can appear in 24 hours for those who experienced near drowning in water. Those affected present with symptoms of sepsis (predominantly fever) with or without pneumonia, or localised abscess or other focus of infection. The presence of non-specific signs and symptoms has caused melioidosis to be nicknamed "the great mimicker".Diabetes mellitus is one of the most important risk factors in developing melioidosis. The disease should be considered in anyone who has spent time in endemic areas who develops a fever, pneumonia, or abscesses in their liver, spleen, prostate, or parotid gland. The clinical manifestation of the disease can range from simple skin changes such as abscesses or ulcerations to severe organ problems. The commonest organs affected are liver, spleen, lungs, prostate, and kidneys. Among the most common features are bacteremia (in 40 to 60% of cases), pneumonia (50%), and septic shock (20%). People with only pneumonia may have a prominent cough with sputum and shortness of breath. However, those with septic shock together with pneumonia may have minimal coughing. Results of a chest X-ray can range from diffuse nodular infiltrates in those with septic shock to progressive consolidation located most commonly in the upper lobes for those with pneumonia only. Pleural effusion and empyema are more common for melioidosis affecting lower lobes of the lungs. In 10% of cases, people develop secondary pneumonia caused by other bacteria after the primary infection. In northern Australia, 60% of the infected children presented with only skin lesions, while 20% presented with pneumonia.Depending on the course of infection, other severe manifestations develop. Approximately 1 to 5% of those infected develop inflammation of the brain and brain covering or brain abscess; 14 to 28% develop pyelonephritis, kidney abscess or prostatic abscesses; 0 to 30% develop neck or salivary gland abscesses; 10 to 33% develop liver, spleen, or paraintestinal abscesses; and 4 to 14% develop septic arthritis and osteomyelitis. Rare manifestations include lymph node disease resembling tuberculosis, mediastinal masses, pericardial effusion, mycotic aneurysm, and inflammation of the pancreas. In Australia, up to 20% of infected males develop prostatic abscess which may manifests clinically as pain during urination, difficulty in passing urine, and urinary retention requiring catheterisation. Rectal examination may find enlarged prostate. In Thailand, 30% of the infected children develop parotid abscesses. Encephalomyelitis not only happens in those with risk factors, but can also occur in healthy people without risk factors. Those with melioidosis encephomyelitis tend to have normal computed tomography (CT) scans but increased T2 signal by magnetic resonance imaging (MRI), extending to the brain stem and spinal cord. Clinical signs include: unilateral upper motor neuron limb weakness, cerebellar signs, and cranial nerve palsies (VI, VII nerve palsies and bulbar palsy). Some cases presented with flaccid paralysis alone. In northern Australia, all melioidosis with encephalomyelitis cases had elevated white cells in the cerebrospinal fluid (CSF), mostly mononuclear cells with elevated CSF protein. Chronic Chronic melioidosis is usually defined by symptoms lasting greater than two months and occurs in about 10% of patients. Clinical presentations include fever, weight loss, productive cough with or without bloody sputum which may mimic tuberculosis. Additionally, long-standing abscesses at multiple body sites may also present. Tuberculosis should be considered for lymph nodes enlargement at the root of the lung. Additionally, pneumonia caused by melioidosis rarely causes scarring and calcification of the lungs, unlike tuberculosis. Latent The potential for prolonged incubation was recognized in US servicemen involved in the Vietnam War, and was referred to as the "Vietnam time-bomb". Initially, it was thought that the longest period between presumed exposure and clinical presentation is 62 years in a prisoner of war in Burma-Thailand-Malaysia. However, subsequent genotyping of the bacteria isolate from the Vietnam veteran showed that the isolate may not come from Southeast Asia, but from South America. This reinstates another report that put the longest latency period for melioidosis as 29 years. Patients with latent melioidosis may be symptom-free for decades. Less than 5% of all melioidosis cases have activation after a period of latency. Various comorbidities such as diabetes, renal failure, and alcoholism can predispose to reactivation of melioidosis. Cause Bacteria Melioidosis is caused by gram-negative, motile, saprophytic bacteria named Burkholderia pseudomallei. The bacteria are usually opportunistic, facultative intracellular pathogens. It is also aerobic and oxidase test positive. A granule at the centre of the bacterium makes it resemble a "safety pin" when Gram stained. The bacteria emit a strong soil smell after 24 to 48 hours of growth in culture, however smelling for the identification of the bacteria is not recommended for routine laboratory practice. One of the factors causing B. pseudomalleis resistance to various kinds of antibiotics is because of its production of a glycocalyx polysaccharide capsule. It is generally resistant to gentamicin and colistin but sensitive to co-amoxiclav. B. pseudomallei is a biosafety level 3 pathogen which requires specialized laboratory handling. In humans and animals, another similar organism named Burkholderia mallei is the causative agent of the disease glanders. B. pseudomallei can be differentiated from another closely related, but less pathogenic species B. thailandensis by its ability to assimilate arabinose. B. pseudomallei is highly adaptable to various host environments ranging from inside mycorrhizal fungi spores to amoeba. Its adaptability may give it a survival advantage in the human body.The genome of B. pseudomallei consists of two replicons: chromosome 1 encodes housekeeping functions of the bacteria such as cell wall synthesis, mobility, and metabolism; chromosome 2 encodes functions that allow the bacteria to adapt to various environments. Horizontal gene transfer has resulted in highly variable genomes in B. pseudomallei. Australia has been suggested as the origin for B. pseudomallei because of the high genetic variability of the bacteria found in this region. Bacteria that was introduced to Central and South America in the 17th to 19th centuries seem to have a common ancestor from Africa. B. mallei is a clone of B. pseudomallei that has lost substantial portions of its genome as it adapted to live exclusively in mammals. This makes the B. mallei genome much smaller than B. pseudomallei. Transmission B. pseudomallei is normally found in soil and surface water, and is most abundant at soil depths of 10 to 90 cm. It has been found in soils, ponds, streams, pools, stagnant water, and rice paddy fields. B. pseudomallei can survive in nutrient-poor conditions such as distilled water, desert soil, and nutrient-depleted soil for more than 16 years. It can also survive in antiseptic and detergent solutions, acidic environments (pH 4.5 for 70 days), and in environments at temperatures ranging from 24 °C (75.2 °F) to 32 °C (89.6 °F). However, the bacteria may be killed by the presence of ultraviolet light.Bacteria can enter the body through wounds, inhalation, and ingestion of contaminated soil or water. Person-to-person transmission is extremely rare. Melioidosis is a recognised disease in animals including pigs, cats, dogs, goats, sheep, horses and others. Cattle, water buffalo, and crocodiles are considered to be relatively resistant to melioidosis despite their constant exposure to mud. Birds are also considered resistant to melioidosis although several cases had been reported in Australia and aquatic birds. Transmission from animals to humans is rare.Inadequate chlorination of water supply has been associated with B. pseudomallei outbreak in Northern and Western Australia. The were also several cases of where bacteria have also been found in unchlorinated water supply in rural Thailand. Based on the whole genome sequencing of the bacteria, the variety of the bacteria B. pseudomallei in Papua New Guinea is narrow due to limited movements of the indigenous people. This findings supports the hypothesis that humans play an important role in bacterial transmission. Pathogenesis B. pseudomallei has the ability to infect various types of cells and to evade human immune responses. Bacteria first enter at a break in the skin or mucous membrane and replicate in the epithelial cells. From there, they use flagellar motility to spread and infect various cell types. In the bloodstream, the bacteria can infect both phagocytes and non-phagocytes. B. pseudomallei use their flagella to move near host cells, then attach to the cells using various adhesion proteins, including the type IV pilus protein PilA as well as adhesion proteins BoaA and BoaB. Additionally, adhesion of the bacteria partially depends on the presence of the host protein Protease-activated receptor-1 which is present on the surface of endothelial cells, platelets, and monocytes. Once bound, the bacteria enter host cells through endocytosis, ending up inside an endocytic vesicle. As the vesicle acidifies, B. pseudomallei uses its Type 3 secretion system (T3SS) to inject effector proteins into the host cell, disrupting the vesicle and allowing the bacteria to escape into the host cytoplasm. Within the host cytoplasm, the bacteria evade being killed by the host autophagy using various T3SS effector proteins. The bacteria replicate in the host cytoplasm.Inside the host cell, the bacteria move by inducing the polymerization of the host actin behind them, propelling the bacteria forward. This actin-mediated motility is accomplished with the autotransporter BimA which interacts with actin at the tail-end of the bacterium. The bacteria that has BimABm allele has higher possibility of causing neurological melioidosis, thus higher chance of death and residual disability to the host when compared to the bacteria that has BimABp variant. Propelled by actin, the bacteria push against the host membrane, creating protrusions that extend into neighbouring cells. These protrusions cause neighboring cells to fuse, leading to the formation of multinucleated giant cells (MNGCs). When MNGCs lyse, they form plaques (a central clear area with a ring of fused cells) that provide shelter for the bacteria for further replication or latent infection. This same process in infected neurons can allow bacteria to travel through nerve roots in the spinal cord and brain, leading to inflammation of the brain and spinal cord. In addition to spreading from cell to cell, the bacteria can also spread through the bloodstream, causing sepsis. The bacteria can survive in antigen-presenting cells and dendritic cells. Thus, these cells act as vehicles that transport the bacteria into the lymphatic system, causing widespread dissemination of the bacteria in the human body.While B. pseudomallei can survive in phagocytic cells, these cells can kill B. pseudomallei by several mechanisms. Macrophages activated by interferon gamma (IFN) have improved the killing of B. pseudomallei via the production of inducible nitric oxide synthase. Acidification of the endosome and degradation of the bacteria is also possible, however, the bacterial capsule and LPS makes B. pseudomallei resistant to lysosomal degradation. Once B. pseudomallei escapes into the host cytosol it can be recognized by pattern recognition receptors such as NOD-like receptors, triggering the formation of the inflammasome and activation of caspase 1, which induces death of the host cell by pyroptosis and further activation of the immune system. Several systemic host defenses also contribute to the immune response. B. pseudomallei triggers both the complement system and coagulation cascade, however the thick bacterial capsule prevent the action of the complement membrane attack complex.Additional elements of the immune system are activated by the host toll-like receptors such as TLR2, TLR4, and TLR5 that recognize the conserved pieces of the bacteria such as LPS and flagella. This activation results in the production of cytokines such as Interleukin 1 beta (IL-1β) and Interleukin 18 (IL-18). IL-18 increases IFN production through natural killer cells while IL-1beta reduces the IFN production. These immune molecules drive the recruitment of other immune cells such as neutrophils, dendritic cells, B cells, and T cells to the site of infection. T cells seem to be particularly important for controlling B. pseudomallei; T cell numbers are increased in survivors, and low T cell numbers are associated with a high risk of death from melioidosis. Despite this, HIV infection is not a risk factor for melioidosis. Although macrophages show deregulated cytokine responses in individuals with HIV infection, bacterial internalization and intracellular killing are still effective. People infected with B. pseudomallei may develop antibodies against the bacteria, and people that live in endemic areas tend to have antibodies in their blood that recognize B. pseudomallei. However, the effectiveness of these antibodies at preventing melioidosis is unclear.B. pseudomallei can remain latent in the human body for up to 29 years until it is reactivated during human immunosuppression or stress response. However, the site of bacteria during latent infection and the mechanism by which they avoid immune recognition for years are both unclear. Amongst mechanisms suggested are: residing in the nucleus of the cell to prevent being digested, entering a stage of slower growth, antibiotic resistance, and genetic adaption to the host environment. Granulomas (containing neutrophils, macrophages, lymphocytes, and multinucleated giant cells) formed at the infection site in melioidosis have been associated with latent infection in humans. Diagnosis Culture Bacterial culture has 60% sensitivity in diagnosing melioidosis. B. pseudomallei is never part of human flora. Therefore, any growth of the bacteria is diagnostic of melioidosis. Other samples such as throat, rectal swabs, pus from abscesses, and sputum can also be used for culture. However, culture from CSF is difficult because in one case series, only 29% of the neuromelioidosis cases are culture positive. When bacteria do not grow from people strongly suspected of having melioidosis, repeated cultures should be taken as subsequent cultures can become positive. B. pseudomallei can be grown on any blood agar, MacConkey agar, and agar containing antibiotics such as Ashdowns medium (containing gentamicin), and Ashdowns broth (containing colistin) for better isolation of B. pseudomallei from other types of bacteria. Agar plates for melioidosis should be incubated at 37 °C (98.6 °F) in air and inspected daily for four days. On the agar plates, B. pseudomallei forms creamy, non-haemolytic, colonies after 2 days of incubation. After 4 days of incubation, colonies appear dry and wrinkled. Colonies of B. pseudomallei that are grown on Francis medium (a modification of Ashdown medium with gentamicin concentration increased to 8 mg/L and neutral red indicator replaced with 0.2% bromocresol purple) are yellow. For laboratories located outside endemic areas, Burkholderia cepacia selective agar can be used if Ashdowns medium is not available. It is important not misinterpret the bacterial growth as Pseudomonas or Bacillus spp. Other biochemical screening tools can also be used for detecting B. pseudomallei, including the API 20NE or 20E biochemical kit combined with Gram stain, oxidase test, typical growth characteristics, and resistance to certain antibiotics of the bacteria. API 20NE biochemical kit is 99% sensitive in identifying B. pseudomallei.Molecular methods such as 16S rDNA sequencing, multiplex polymerase chain reaction (PCR), and real-time PCR can also be used to identify B. pseudomallei in culture. Other bacterial genes such as fliC genes encoding flagellin, rpsU gene encoding for ribosomal protein, and TTS genes encoding Type III secretion systems has also been employed for detection. Another method of gene detection namely multiple cross displacement amplification for the bacterial TTS1 gene detection produces results within an hour. Hematological and biochemical tests General blood tests in people with melioidosis show low white blood cell counts (indicates infection), raised liver enzymes, increased bilirubin levels (indicates liver dysfunction), and raised urea and creatinine levels (indicates kidney dysfunction). Low blood glucose and acidosis predicts a poorer prognosis in those with melioidosis. However, other tests such as C-reactive protein and procalcitonin levels are not reliable in predicting the severity of melioidosis infection. Serological tests Serological tests such as indirect haemagglutination assay (IHA) have been used to detect the presence of antibodies against B. pseudomallei. However, different groups of people have widely different levels of antibodies, so interpretation of these tests depends on location. In Australia, less than 5% of people have B. pseudomallei antibodies, so the presence of even relatively low amounts of antibody is unusual and could suggest melioidosis. In Thailand, many people have antibodies against B. pseudomallei so the diagnosis of melioidosis should not be reliant entirely on the serological tests done in endemic areas. Indirect immunofluorescent test (IFAT) uses either B. pseudomallei or B. thailandensis antigens to look for the total number of antibodies in human serum. Using IFAT is labour intensive and is not used in large scale investigations.Antigen detect tests allow rapid detection of melioidosis. Examples of antigen detection tests are: latex agglutination test and ELISA. Latex agglutination uses antibodies coated on latex beads to detect B. pseudomallei antigens in solid or liquid media, although not all the assays can detect different species of Burkholderia. Latex agglutination is useful in screening for suspected B. pseudomallei colonies. IgG and IgM ELISAs has been used to detect lipopolysaccharide (LPS) antigens of B. pseudomallei, but plagued with low sensitivity. Commercial ELISA kits for melioidosis no longer available in the market due to low sensitivity to human antibodies detection. Nevertheless, antigen detection tests may be useful in severely ill patients because the bacterial load is high enough for detection. Other methods of antigen detection such as direct immunofluorescence, antibody-sandwich ELISAs, and lateral flow immunoassays using monoclonal antibody. Microscopy By microscopy, B. pseudomallei is seen as gram-negative and rod-shaped, with a bipolar staining similar in appearance to a safety pin. Bacteria can sometimes be seen directly in clinical samples from infected people; however, identification by light microscopy is neither specific nor sensitive. Immunofluorescence microscopy is highly specific for detecting bacteria directly from clinical specimens, but has less than 50% sensitivity. Imaging Various imaging modalities can also help with the diagnosis of melioidosis. In acute melioidosis with the spreading of the bacteria through the bloodstream, the chest X-ray shows multifocal nodular lesions. It may also show merging nodules or cavitations. For those with acute melioidosis without the spread to the bloodstream, chest x-ray most commonly shows upper lobe consolidation or cavitations. In chronic melioidosis, the slowly progressing of upper lobe consolidation of the lungs resembles tuberculosis. For abscesses located in other parts of the body apart from the lungs, especially in the liver and spleen, CT scan has higher sensitivity when compared with an ultrasound scan. In liver and splenic abscesses, an ultrasound scan shows "target-like" lesions while CT scan shows "honeycomb sign" (abscess with loculations separated by thin septa) in liver abscesses. For melioidosis involving the brain, MRI have higher sensitivity than a CT scan in diagnosing the lesion. MRI shows ring-enhancing lesions for brain melioidosis. Prevention Melioidosis is a notifiable disease in Australia which enables the country to monitor disease burden and contain outbreaks. On the other hand, melioidosis is only a notifiable condition in Thailand since June 2016. However, until recently, the official notification system in Thailand has significantly underestimated the incidence of culture-positive melioidosis and its mortality. Nevertheless, Australia also embarked on awareness campaigns to increase the communitys understanding of the disease. In the United Kingdom, where reporting by laboratories is mandatory, 41.3% of cases imported since 2010 were not notified. In the United States, lab workers can handle clinical specimens of B. pseudomallei under BSL-2 conditions, while mass production of such organisms requires BSL-3 precautions. On the other hand, in other endemic areas where the B. pseudomallei samples were handled less stringently, there has been no confirmed laboratory-acquired infection reported. This phenomenon may show that the risk of infection with B. pseudomallei is less than a typical biohazard type 3 agent. There are also several cases of hospital-acquired infection of melioidosis. Therefore, healthcare providers are recommended to practice hand hygiene and universal precautions.Large-scale water chlorination has been successful at reducing B. pseudomallei in the water in Australia. In middle to low-income countries, water should be boiled before consumption. In high income countries, water could be treated with ultraviolet light for those at risk of contracting melioidosis. Those who are at high risk of contact with the bacteria should wear protective gear (such as boots and gloves) during work. Those staying in endemic areas should avoid direct contact with soil, and outdoor exposure to heavy rain or dust clouds. Bottled water or boiled water are preferred as drinking water. A study conducted from 2014 to 2018, however showed no significant differences on whether behavioural changes can reduce the risk of contracting melioidosis. Modification of behavioural changes or more frequent interventions may be needed to ensure a definite reduction in risk of getting melioidosis. Antibiotic prophylaxis Administering cotrimoxazole three times a week throughout a wet season for dialysis patients has no obvious benefit of preventing melioidosis. Besides, high cost and side effects of this drug limits its use to only those with high risk of getting melioidosis. After exposure to B. pseudomallei (particularly following a laboratory accident, penetrating injuries, exposure of mouth and eyes to contaminated materials or aerosols), treatment with antibiotics is only given when in highly selected individuals after weighing the risk of adverse effects of the drugs against the benefits from contracting melioidosis. Cotrimoxazole can be used in this context. Alternatively, co-amoxiclav and doxycycline can be used for those who are intolerant to co-trimoxazole. Low-risk individuals would receive frequent monitoring instead. Vaccination Several vaccine candidates have been tested in animal models. Nevertheless, no vaccine candidates have been tried in humans. Major hurdles of the vaccines are limited efficacy in animal models, establishing the best method of vaccine administration in humans and logistical and financial issues in establishing human trials in endemic areas. Treatment The treatment of melioidosis is divided into two stages: an intravenous intensive phase and an eradication phase to prevent recurrence. The choice of antibiotics depends upon the susceptibility of the bacteria to various antibiotics. B. pesudomallei are generally susceptible to ceftazidime, meropenem, imipenem, and co-amoxiclav. These drugs generally kill bacteria. B. pseudomallei is also susceptible to doyxcycline, chloramphenicol, and co-trimoxazole. These drugs generally inhibit the growth of the bacteria. However, the bacteria are resistant to penicillin, ampicillin, 1st and 2nd generation cephalosporin, gentamicin, streptomycin, tobramycin, macrolides, and polymyxins. On the other hand, 86% of the B. pseudomallei isolates from the region of Sarawak, Malaysia are susceptible to gentamicin and this has not been found elsewhere in other parts of the world.Prior to 1989, the standard treatment for acute melioidosis was a three-drug combination of chloramphenicol, co-trimoxazole and doxycycline; this regimen is associated with a mortality rate of 80% and is no longer used unless no other alternatives are available. All three drugs are bacteriostatic (they stop the bacterium from growing, but do not kill it) and the action of co-trimoxazole antagonizes both chloramphenicol and doxycycline. Intensive phase Intravenous ceftazidime is the current drug of choice for treatment of acute melioidosis and should be administered for at least 10 to 14 days. Meropenem, imipenem and the cefoperazone-sulbactam combination (Sulperazone) are also effective. Intravenous amoxicillin-clavulanate (co-amoxiclav) may be used if none of the above four drugs is available; co-amoxiclav prevents death from melioidosis as well as ceftazidime. Co-amoxiclav is also used if patient has allergy towards sulfonamide, unable to tolerate co-trimaxazole, in pregnant patients or in children. High dose of co-amoxiclav (20 mg/kg for amoxicillin and 5 mg/kg for clavulanate) is recommended to prevent treatment failures. Intravenous antibiotics are given for a minimum of 10 to 14 days. The median fever clearance time in melioidosis is 9 days. The treatment duration is in accordance with Darwin melioidosis treatment guidelines where there is low rate of recrudescence and relapse.Meropenem is the preferred antibiotic therapy for neurological melioidosis and those with septic shock admitted into intensive care units. Co-trimoxazole is recommended in addition to ceftazidime for neurological melioidosis, osteomyelitis, septic arthritis, skin and gastrointestinal infection, and deeply seated abscess. For deep-seated infections such as abscesses of internal organs, osteomyelitis, septic arthritis, and neurological melioidosis, the duration of antibiotics given should be longer (up to 4 to 8 weeks). The time taken for the fever to be resolved can be more than 10 days in those with deep-seated infection. According to the 2020 Revised Royal Darwin Hospital Guideline, the dosage for intravenous ceftazidime is 2g 6-hourly in adults (50 mg/kg up to 2g in children less than 15 years old). The dosage for meropenem is 1g 8-hourly in adults (25 mg/kg up to 1g in children). Acquired resistance to ceftazidime, carbapenems, and co-amoxiclav is rare in the intensive phase but resistance to cotrimoxazole during eradication therapy is technically difficult to assess. There are no differences between using cefoperazone/sulbactam or ceftazidime to treat melioidosis as both shows similar death rates and disease progression following treatment. However, data are lacking to recommend cefoperazone/sulbactam usage. For those with kidney impairment, the dosage of ceftazidime, meropenem, and co-trimoxazole should be lowered. Once the clinical condition improved, meropenem can be switched back to ceftazidime. Eradication phase Following the treatment of the acute disease, eradication treatment with co-trimoxazole is the drug of choice and should be used for 3 months (12 weeks) as all-cause mortality was lower in 12 weeks group when compared to those receiving treatment for 20 weeks. For those with neurological melioidosis and osteomyelitis, drugs should be given for more than 6 months. Co-amoxiclav and doxycycline are drugs of second choice. Co-trimoxazole should not be used in those with glucose-6-phosphate dehydrogenase deficiency as it can cause haemolytic anemia. However, in Thailand, usage of co-trimoxazole does not accompany G6PD screening. Other side effects such as rash, hyperkalemia, renal dysfunction, and gastrointestinal symptoms should prompt the reduction of co-trimoxazole doses. Chloramphenicol is no longer routinely recommended for this purpose. Co-amoxiclav is an alternative for patients unable to take co-trimoxazole and doxycycline (e.g. pregnant women and children under the age of 12), but is not as effective and has a higher relapse rate. Single-agent treatment with fluoroquinolone (e.g., ciprofloxacin) or doxycycline for the oral eradication phase is ineffective.In Australia, co-trimoxazole is used with children and pregnant mothers after the first 12 weeks of pregnancy. Meanwhile, in Thailand, co-amoxiclav is the drug of choice for children and pregnant women. B. pseudomallei rarely acquires resistance when co-amoxiclav is used. The dosing regimen for co-trimoxazole (trimethoprim/sulfamethoxazole) in eradication phase is 6/30 mg/kg, up to maximum 240/1200 mg in children, 240/1200 mg in adults weighing 40 to 60 kg, and 320/1600 mg in adults weighing more than 60 kg, taken orally every 12 hours. In both Thailand and Australia, co-trimoxazole is taken together with folic acid (0.1 mg/kg up to 5 mg in children). There are also cases where melioidosis is successfully treated with co-trimoxazole for 3 months without going through intensive therapy provided that there is only skin manifestations without the involvement of internal organs or sepsis. Resistance to cotrimoxazole is rare in Asia. Besides that, it is difficult to determine the resistance reliably because resistance to cotrimoxazole is defined when minimum inhibitory concentration (MIC) of more than 4 mg/L is required to completely inhibit the growth of 80% of the bacteria (80% inhibition point). Interpretation of 80% inhibition point is subjective and prone to human error. In 2021, European Committee on Antimicrobial Susceptibility Testing (EUCAST) released a new guideline on interpreting the susceptibility of B pseudomallei towards various antibiotics on disc susceptibility testing. The new guideline includes "S" for susceptible organism, "I" for susceptible organism only after increased exposure (when dosage or concentration of the drug increases) and "R" for resistant organism. Surgery Surgical drainage is indicated for single, large abscesses in the liver, muscle, and prostate. However, for multiple abscesses in the liver, spleen, and kidney, surgical drainage may not be possible or necessary. For septic arthritis, arthrotomy washout and drainage are required. Surgical debridement may be necessary. For those with mycotic aneurysm, urgent surgery is required for prosthetic vascular grafts. Lifelong therapy with co-trimoxazole may be needed for those with prosthetic vascular grafts according to a review of case reports in 2005. Other abscesses rarely need to be drained because most resolve with antibiotic treatment. Prostate abscess may require routine imaging. Antibiotics treatment for prostatic abscess may be enough except for abscesses more than 10 to 15 mm where surgical drainage is required. Others Several immunomodulating therapies are suggested to boost the human body immune function against the bacteria because the pathogenesis of melioidosis is thought to be contributed by defects in neutrophils. The Royal Darwin Hospital 2014 guidelines recommended granulocyte colony-stimulating factor (G-CSF) as immunomodulating therapy for those with septic shock at 300 ug daily as soon as the bacteriological laboratory flag the culture as possibly Burkholderia pseudomallei. The main contraindication of starting (G-CSF) is a heart event. The G-CSF is continued for ten days depends on clinical response or a contraindication develops such as white cell count greater than >50,000 X106/litre.Anti-PDI (programmed cell death) agents could be useful in melioidosis treatment especially for those with septic shock. This is because Burkholderia pseudomallei bacteria increases the expression of PDI-1 that regulates and inhibits the formation of T-cells that are essential for fighting against melioidosis. Prognosis In well-resourced settings, where the disease can be detected and treated early, the risk of death is 10%. In resource-poor settings, the risk of death from the disease is more than 40%.Recurrent melioidosis can occur either due to re-infection or relapse after the completion of eradication therapy. Re-infection is due to a new strain of B. pseudomallei bacteria. Meanwhile, relapse is due to failure to clear infections after the eradication therapy. Recurrent melioidosis is rare since 2014 due to improved antibiotic therapy and prolongation of the intensive phase of therapy as evident in Darwin Prospective Melioidosis Study. On the other hand, recrudescence are those who present with symptoms during the eradication therapy. Recrudescence rates may be improved by ensuring adherence to a full course of eradication therapy e.g. by reducing self-discharge against medical advice.Underlying medical conditions such as diabetes mellitus, chronic kidney disease, and cancer can worsen the long-term survival and disability of those who recover from infection. One of the complications of melioidosis is encephalomyelitis. It can cause quadriparesis (muscle weakness in all the limbs), partial flaccid paraparesis (muscle weakness of both legs), or foot drop. For those with previous melioidosis-associated bone and joint infections, complications such as sinus tract infection, bone and joint deformities with limited range of motion can occur. Epidemiology Melioidosis is an understudied disease that remains endemic in developing countries. In 2015, the International Melioidosis Society was formed to raise awareness of the disease. In 2016, a statistical model was developed which predicted that the number is 165,000 cases per year with 138,000 of those occurring in East and South Asia and the Pacific. In approximately half of those cases (54% or 89,000), people will die. Under-reporting is a common problem as only 1,300 cases were reported worldwide since 2010, which is less than 1% of the projected incidence based on the modelling. Lack of laboratory diagnostic capabilities and lack of disease awareness amongst health care providers also causes under diagnosis. Even if bacterial cultures show positive result for B. pesudomallei, they can be discarded as contaminants especially in laboratories in non-endemic areas. In 2015, it was estimated that the yearly disability-adjusted life year (DALY) was 84.3 per 100,000 people. As of 2022, melioidosis is not included in the WHO list of neglected tropical diseases. Geography Melioidosis is endemic in parts of southeast Asia (including Thailand, Laos, Singapore, Brunei, Malaysia, Myanmar and Vietnam), southern China, Taiwan northern Australia. India, and South America. Since 1991, a total of 583 cases were reported in India. Most Indian cases are located in Karnataka and Tamil Nadu. Fifty-one cases of melioidosis were reported in Bangladesh from 1961–2017. Nonetheless, lack of awareness and resources gives rise to under diagnosis of the disease in the country. The true burden of melioidosis in Africa and Middle East remain unknown due to low amount of data. Several melioidosis cases were reported over the years. Although 24 African countries and three Middle Eastern countries predicted to be endemic with melioidosis, however not a single case was reported from these specific countries. In the United States, two historical cases (1950 and 1971) and four recent cases (2010, 2011, 2013, 2020) have been reported amongst people that did not travel overseas. Despite extensive investigations, the source of melioidosis was never confirmed. One possible explanation is that importation of medicinal plant products or exotic reptiles could have resulted in the introduction of melioidosis in the United States. In 2021, there was a melioidosis outbreak in several states in the United States due to usage of contaminated aromatherapy spray imported from India. There are also cases of infection through imported tropical fishes in home aquariums. In Europe, more than half of the melioidosis cases are imported from Thailand. Age, risk factors Melioidosis is found in all age groups. For Australia and Thailand, the median age of infection is at 50 years; 5 to 10% of the patients are under 15 years. The single most important risk factor for developing melioidosis is diabetes mellitus, followed by hazardous alcohol use, chronic kidney disease, and chronic lung disease. More than 50% of people with melioidosis have diabetes; diabetics have a 12-fold increased risk of contracting melioidosis. Diabetes decreases the ability of macrophages to fight the bacteria and reduced the T helper cell production. Excessive release of Tumor necrosis factor alpha and Interleukin 12 by mononuclear cells increases the risk of septic shock. Other risk factors include thalassaemia, occupational exposure (e.g. rice paddy farmers), recreational exposure to soil, water, being male, age greater than 45 years, and prolonged steroid use/immunosuppression. However, 8% of children and 20% of adults with melioidosis have no risk factors. HIV infection does not appear to predispose to melioidosis, although several other co-infections have been reported. Infant cases have been reported possibly due to mother-to-child transmission, community-acquired infection, or healthcare-associated infection. Those who are well may also be infected with B. pseudomallei. For example, 25% of children started producing antibodies against B. pseudomallei between 6 months to 4 years of staying in endemic areas although they did not experience any melioidosis symptoms; suggesting they were exposed to it over this time. This means that many people without symptoms will test positive in serology tests in endemic areas. In Thailand, the seropositivity rate exceeds 50%, while in Australia the seropositivity rate is only 5%. The disease is clearly associated with increased rainfall, with the number of cases rising following increased precipitation. Severe rainfall increases the concentration of the bacteria in the topsoil, thus increasing thus of transmitting the bacteria through the air. A recent CDC Advisory indicated that the recent detection of the organism in the environment in Mississippi following the occurrence of two indigenous cases of melioidosis, confirms that parts of the southern USA should now be regarded as melioidosis-endemic. History Pathologist Alfred Whitmore and his assistant Krishnaswami first reported melioidosis among beggars and morphine addicts at autopsy in Rangoon, present-day Myanmar, in a report published in 1912. Whitmore was able to grow the organism in culture and its showed similarity with B. mallei, another bacteria that was known causing glanders in animals. Therefore, he named the new organism Bacillus pseudomallei. He did no further work on the organism. Arthur Conan Doyle may have read Whitmores report before writing a short story that involved the fictitious tropical disease "Tapanuli fever" in a Sherlock Holmes story titled "The Adventure of the Dying Detective" published in 1913. In the same year, melioidosis outbreak occurred inside the Institute for Medical Research (IMR), Kuala Lumpur, Malaya after its laboratory animals such as guinea pigs and rabbits were infected. William Fletcher and Ambrose Thomas Stanton, doctors who worked at the IMR, were the next ones to study the organism. They were unable identify the organism that caused the outbreak. It was only in 1917, when Fletcher isolated an organism similar to Whitmores bacillus from a Tamil rubber estate worker, the presence of the new species of bacteria was confirmed. The term "melioidosis" was first coined in 1921. The name melioidosis is derived from the Greek melis (μηλις) meaning "a distemper of asses" with the suffixes -oid meaning "similar to" and -osis meaning "a condition", that is, a condition similar to glanders. B pseudomallei is similar in clinical presentation and genome make-up with B. mallei but is distinguished from it due to epidemiological and zoonotic characteristics.The first human case of melioidosis in South Asia was reported in Sri Lanka in 1927. In 1932, Thomas and Fletcher collected 83 cases of melioidosis from literature. In this case series, there were only two survivals. Since then, more case series of melioidosis were reported. Thomas and Fletcher also pioneered the use of serological methods in diagnosing the disease. Thomas and Fletcher incorrectly believed that melioidosis infection came from human contact with rodents. However, observations on the disease noted that humans usually got it after exposure to mud or contaminated water. Besides, the organism was never grown from rats. This led to a search of the bacteria in the environment. In 1936, the first animal (pig) case of melioidosis in Africa was reported in Madagascar. In 1937, water was first identified as the habitat of B. pseudomallei. The first case of Australian melioidosis was described in an outbreak in sheep in 1949 at North Queensland. This was followed by the first case of human melioidosis at Townsville in 1950. Initially, the discovery of melioidosis in Australia had led to a debate on when and how the disease spread from Southeast Asia to a new distant environment. However, this hypothesis was later disproved in 2017 when whole genome sequencing of B. pseudomallei over 30 countries collected over 79 years suggested Australia as the early reservoir for melioidosis. In 1955, first case of local human melioidosis was reported in Thailand. During the Vietnam War from 1967 to 1973, 343 American soldiers were reported with melioidosis, with about 50 cases transmitted through inhalation. An outbreak of melioidosis at the Paris Zoo in the 1970s (known as Laffaire du jardin des plantes) was thought to have originated from an imported panda or horses from Iran. It is unclear how imported melioidosis is able to persist in a completely new environment. Eventually, the outbreak terminated by itself after a period of time. It was only during the 1980s, Infectious Disease Association of Thailand started took notice of this disease. First conference on melioidosis was held in 1985 in Thailand. It was during this meeting that collaboration between Sappasitprasong Hospital, Thailand, and Wellcome-Mahido-Oxford Tropical Medicine Research Programme was established. Such collaboration made Thailand a world leader in clinical and epidemiology research on melioidosis.In 1989, several studies conducted in Thailand demonstrated ceftazidime as an effective antibiotic against melioidosis. Ceftazidime had been shown to reduce the risk of death of melioidosis from 74% to 37%. In 1990, a non-virulent arabinose-positive B. pseudomallei was found by Vanaporn Wuthiekanun. The organism was later reclassified into a new species called B. thailandensis. This species has become a useful tool in the laboratory for the studies of the pathogenesis of B. pseudomallei. B. pseudomallei was previously classified as part of the genus Pseudomonas. In 1992, the pathogen was formally named B. pseudomallei. In 1994, First International Symposium on melioidosis was held in Kuala Lumpur where 80 delegates attended. Papers were presented and later published as a book. Subsequent congresses were held in Thailand, Australia, and Singapore once every three years. In 2002, B. pseudomallei was classified as a "Category B agent". In 2004, the complete genome of B. pseudomallei was published. In 2012, B pseudomallei was classified as a "Tier 1 select agent" by the U.S. Centers for Disease Control. In 2014, co-trimoxazole was established as the only oral eradication therapy rather than combination therapy of co-trimoxazole with doxycycline. In 2016, a statistical model was developed to predict the occurrence of global melioidosis per year. Synonyms Pseudoglanders Whitmores disease (after Captain Alfred Whitmore, who first described the disease) Nightcliff gardeners disease (Nightcliff is a suburb of Darwin, Australia where melioidosis is endemic) Paddy-field disease Morphia injectors septicaemia Biological warfare Interest in melioidosis has been expressed because it has the potential to be developed as a biological weapon. Another similar bacterium, Burkholderia mallei was used by the Germans in World War I to infect livestock shipped to Allied countries. Deliberate infection of human prisoners of war and animals using B. mallei were carried out in Chinas Pingfang District by the Japanese during World War II. The Soviet Union reportedly used B. mallei during the Soviet–Afghan War in 1982 and 1984. B. pseudomallei, like B. mallei, was studied by both the US and Soviet Union as a potential biological warfare agent, but never weaponized. Other countries such as Iran, Iraq, North Korea, and Syria may have investigated the properties of B. pseudomallei for biological weapons. The bacterium is readily available in the environment. It can also be aerosolized and transmitted via inhalation. However, the B. pseudomallei has never been used in biological warfare. The actual risk of the deliberate release of B. pseudomallei or B. mallei is unknown. References This article was adapted from the following source under a [ ] license (2022) (reviewer reports): Siang Ching Raymond Chieng (14 August 2022). "Melioidosis" (PDF). WikiJournal of Medicine. 9 (1): 4. doi:10.15347/WJM/2022.004. ISSN 2002-4436. Wikidata Q100400594. External links Resource Center for melioidosis CDC Disease Info melioidosisBurkholderia pseudomallei genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID

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

Thrombophlebitis is a phlebitis (inflammation of a vein) related to a thrombus (blood clot). When it occurs repeatedly in different locations, it is known as thrombophlebitis migrans (migratory thrombophlebitis). Signs and symptoms The following symptoms or signs are often associated with thrombophlebitis, although thrombophlebitis is not restricted to the veins of the legs. Pain (area affected) Skin redness/inflammation Edema Veins hard and cord-like Tenderness Complications In terms of complications, one of the most serious occurs when the superficial blood clot is associated with a deep vein thrombosis; this can then dislodge, traveling through the heart and occluding the dense capillary network of the lungs This is a pulmonary embolism which can be life-threatening. Causes Thrombophlebitis causes include disorders related to increased tendency for blood clotting and reduced speed of blood in the veins such as prolonged immobility; prolonged traveling (sitting) may promote a blood clot leading to thrombophlebitis but this occurs relatively less. High estrogen states such as pregnancy, estrogen replacement therapy, or oral contraceptives are associated with an increased risk of thrombophlebitis.Specific disorders associated with thrombophlebitis include superficial thrombophlebitis which affects veins near the skin surface, deep vein thrombosis which affects deeper veins, and pulmonary embolism.Those with familial clotting disorders such as protein S deficiency, protein C deficiency, or factor V Leiden are also at increased risk of thrombophlebitis. Thrombophlebitis can be found in people with vasculitis including Behçets disease. Thrombophlebitis migrans can be a sign of malignancy – Trousseau sign of malignancy. Diagnosis The diagnosis for thrombophlebitis is primarily based on the appearance of the affected area. Frequent checks of the pulse, blood pressure, and temperature may be required. If the cause is not readily identifiable, tests may be performed to determine the cause, including the following: Doppler ultrasound Extremity arteriography Blood coagulation studies (Blood clotting tests) Prevention Prevention consists of walking, drinking fluids and if currently hospitalized, changing of IV lines. Walking is especially suggested after a long period seated, particularly when one travels. Treatment In terms of treatment for this condition the individual may be advised to do the following: raise the affected area to decrease swelling, and relieve pressure off of the affected area so it will encounter less pain. In certain circumstances drainage of the clot might be an option. In general, treatment may include the following: Epidemiology Thrombophlebitis occurs almost equally between women and men, though males do have a slightly higher possibility. The average age of developing thrombophlebitis, based on analyzed incidents, is 54 for men and 58 for women. See also Mondors disease Phlebothrombosis References Further reading Sadick, Neil S.; Khilnani, Neil; Morrison, Nick (2012). Practical Approach to the Management and Treatment of Venous Disorders. Springer Science & Business Media. ISBN 9781447128915. Retrieved 23 October 2016. Mulholland, Michael W.; Lillemoe, Keith D.; Doherty, Gerard M.; Maier, Ronald V.; Simeone, Diane M.; Upchurch, Gilbert R. (2012). Greenfields Surgery: Scientific Principles & Practice. Lippincott Williams & Wilkins. ISBN 9781451152920. Retrieved 23 October 2016. == External links ==

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I need a basic explanation for the medical term 'Generalized epilepsy with febrile seizures plus.'

Generalized epilepsy with febrile seizures plus (GEFS+) is a syndromic autosomal dominant disorder where affected individuals can exhibit numerous epilepsy phenotypes. GEFS+ can persist beyond early childhood (i.e., 6 years of age). GEFS+ is also now believed to encompass three other epilepsy disorders: severe myoclonic epilepsy of infancy (SMEI), which is also known as Dravets syndrome, borderline SMEI (SMEB), and intractable epilepsy of childhood (IEC). There are at least six types of GEFS+, delineated by their causative gene. Known causative gene mutations are in the sodium channel α subunit genes SCN1A, an associated β subunit SCN1B, and in a GABAA receptor γ subunit gene, in GABRG2 and there is another gene related with calcium channel the PCDH19 which is also known as Epilepsy Female with Mental Retardation. Penetrance for this disorder is estimated at 60%. Signs and symptoms Individuals with GEFS+ present with a range of epilepsy phenotypes. These include febrile seizures that end by age 6 (FS), such seizures extending beyond age 6 that may include afebrile tonic-clonic, myoclonic, absence, atonic seizures and myoclonic-astatic epilepsy. Individuals may also present with SMEI, characterized by generally tonic-clonic seizures, impaired psychomotor development, myoclonic seizures, ataxia, and poor response to many anticonvulsants. Pathophysiology Type 1 GEFS+ type 1 is a subtype of GEFS+ in which there are mutations in SCN1B, a gene encoding a sodium channel β subunit. The β subunit is required for proper channel inactivation. There are two known mutations in SCN1B that lead to GEFS+ (Figure 1). The first and best characterized of these mutations is C121W. This mutation alters a cysteine involved in a disulfide bond in the extracellular N-terminus of the protein. This extracellular region is similar to the cell adhesion molecule contactin and other cell adhesion molecules. It is believed that the disulfide bond disrupted by the C121W mutation is required for the proper folding of this N-terminus motif. Coexpression of SCN1B with sodium channel α subunits in oocytes and other cells results in channels that inactivate more slowly. Expression of C121W mutant along with wild-type α subunits produces current indistinguishable from that through α subunits alone. Further investigation of this mutation has indicated that it results in decreased frequency dependent rundown and, thus, likely hyperexcitability when compared to cells expressing the wild-type subunit. This mutation also disrupts the subunits ability to induce cellular aggregation. The importance of this last fact is unclear, though it is presumed that proper channel aggregation within cells and cell-cell contact are required for normal neuronal function.A second mutation has been found in one kindred with GEFS+ type 1. This mutation is in a splice acceptor site of exon 3. The loss of this acceptor site reveals a downstream cryptic acceptor site and a protein missing 5 amino acids in the N-terminus (I70_E74del). This mutation has not been further characterized. Type 2 A second subtype of GEFS+, type 2, is the result of mutations in SCN1A, a gene encoding a sodium channel α subunit. There are currently almost 90 known mutations in the SCN1A gene throughout the entirety of the channel (see table 1). These mutations result in almost any imaginable mutation type in the gene, short of duplications. The results of these mutations are highly variable, some producing functional channels while others result in non-functional channels. Some functional channels result in membrane hyperexcitability while others result in hypoexcitability. Most of the functional mutant channels result in hyperexcitability due to decreased frequency dependent rundown. An example of this is the D188V mutation. A 10 Hz stimulation of wild-type channels causes current to decrease to approximately 70% of maximum whereas the same stimulation of mutant channels results in rundown to 90% of maximum. This is caused by an expedited recovery from inactivation for mutant channels versus wild-type. The D188V mutant, for example, recovers to 90% maximal current in 200ms while wild-type channels are unable to recover to this degree in >1000ms. Some other functional mutations that lead to hyperexcitability do so by other means, such as decreasing the rate of entrance into the slow inactivated state.Some of the other functional mutations are believed to result in hypoexcitability. The R859C mutation, for example, has a more depolarized voltage dependence of activation, meaning that the membrane must be more depolarized for the channel to open. This mutant also recovers more slowly from inactivation. The nonfunctional channels are believed to produce similar changes in cell excitability. Likewise, many of the nonsense mutations likely result in nonfunctional channels and hypoexcitability, though this has yet to be tested. It is also unclear how this membrane hypoexcitability leads to the GEFS+ phenotype. Type 3 Patients with GEFS+ type 3 have mutations in the GABRG2 gene, which encodes the GABAA γ2 subunit (figure 2). The first mutation discovered in GABRG2 was K289M, in the extracellular region linking membrane-spanning domains M2 and M3. Oocytes injected with α1, β2, and γ2 subunits produce large GABA inducible currents whereas those injected with K289M mutant instead of wild-type subunits produce currents much smaller (about 10% of wild-type). This abnormal current is not the result of non-incorporation of mutant subunits since mutant containing receptors are still sensitive to benzodiazepines, a property for which functional γ subunits are required. Because of these results, it is believed that the GEFS+ phenotype in these individuals is a result of hyperexcitability.Concurrent with the previous mutation, a second group found a second mutation in GABRG2 associated with GEFS+. This mutation, R43Q, is located in the one of two benzodiazepine binding-sites located in the extracellular N-terminus. Benzodiazepines, such as Diazepam, potentiate GABA induced current. This potentiation is abolished in cells expressing the R43Q mutant subunit instead of the wild-type γ subunit. This mutation does not affect the subunits ability to coassemble into function receptors as it still confers resistance to GABA current blockade by zinc. As with the previous mutation, this mutation is expected to result in neuronal hyperexcitability.The final known GEFS+ type 3 mutation is a nonsense mutation, Q351X, located in the intracellular region linking the third and fourth membrane spanning segments. When this mutant subunit is expressed in cells with wild-type α and β subunits it produces non-functional receptors. Since wild-type α and β subunits expressed alone are able to produce GABA inducible current this indicates that the mutation either prevents both coassembly of the mutant and wild-type subunits but also coassembly of the wild-type α and β subunits or prevents proper trafficking of the formed receptor to the membrane. Fusion of GFP onto this mutated subunit has indicated that it is localized to the endoplasmic reticulum instead of the cell membrane. As with other known GEFS+ type 3 mutation, Q351X likely results in neuronal hyperexcitability. SCN2A mutations The final type of GEFS+ is caused by mutations in the SCN2A gene, which encodes a sodium channel α subunit. The first associated mutation in this gene is R187W, located on the intracellular region linking membrane spanning units two and three in the first domain (D1S2-S3, figure 3). Patients with this mutation have both febrile and afebrile seizures. Electrophysiological examination of this mutant revealed that it increases the time constant for inactivation, presumably increasing sodium current and leading to hyperexcitability. However, this mutation also yields channels that inactivate at more hyperpolarized potentials relative to wild-type channels, indicative of hypoexcitability. Whether the result on membrane excitability of this mutation is hyperexcitability or hypoexcitability is, as yet, unclear.The second known mutation in SCN2A associated with GEFS+ is R102X. This mutation is located in the intracellular N-terminus (figure 3) and results in SMEI in patients. The result of this mutation is completely non-functional channels and membrane hypoexcitability. The truncated mutant protein also seems to cause wild-type channels to inactivate at more hyperpolarized potentials, indicating that it also acts in a dominant negative manner. Management Long term management is by use of anticonvulsant medication, principally valproate, stiripentol, topiramate or clobazam. Ketogenic diet has also been found useful in certain cases Management of breakthrough seizures is by benzodiazepine such as midazolam. See also Febrile seizures Idiopathic generalized epilepsy Dravet Syndrome Foundation International Dravet Epilepsy Action League References == External links ==

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

Cefotetan is an injectable antibiotic of the cephamycin type for prophylaxis and treatment of bacterial infections. It is often grouped together with second-generation cephalosporins and has a similar antibacterial spectrum, but with additional anti-anaerobe coverage. Cefotetan was developed by Yamanouchi. It is marketed outside Japan by AstraZeneca with the brand names Apatef and Cefotan. Adverse effects The chemical structure of cefotetan, like that of several other cephalosporins, contains an N-methylthiotetrazole (NMTT or 1-MTT) side chain. As the antibiotic is broken down in the body, it releases free NMTT, which can cause hypoprothrombinemia (likely due to inhibition of the enzyme vitamin K epoxide reductase) and a reaction with ethanol similar to that produced by disulfiram (Antabuse), due to inhibition of aldehyde dehydrogenase. Spectrum of bacterial susceptibility Cefotetan has a broad spectrum of activity and has been used to treat bacterial infections of the bone, skin, urinary tract, and lower respiratory tract. Notable species include Bacteroides, Streptococcus, and Escherichia. The following represents MIC susceptibility data for a few medically significant bacteria. Escherichia coli: 0.06 µg/mL Bacteroides fragilis: ≤0.06 µg/mL - 512 µg/mL Clostridium perfringens: 1 µg/mL - 4 µg/mL References External links Cefotan official web site run by AstraZeneca US Cefotetan entry in RxList

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What is the significance of the term 'Blastomycosis-like pyoderma' in the medical field?

Blastomycosis-like pyoderma is a cutaneous condition characterized by large verrucous plaques with elevated borders and multiple pustules.: 255, 272 See also List of cutaneous conditions pyoderma blastomycosis 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've come across the term 'Permethrin' in a medical context, but I'm not sure what it means. Can you clarify?

Permethrin is a medication and an insecticide. As a medication, it is used to treat scabies and lice. It is applied to the skin as a cream or lotion. As an insecticide, it can be sprayed onto clothing or mosquito nets to kill the insects that touch them.Side effects include rash and irritation at the area of use. Use during pregnancy appears to be safe. It is approved for use on and around people over the age of two months. Permethrin is in the pyrethroid family of medications. It works by disrupting the function of the neurons of lice and scabies mites.Permethrin was discovered in 1973. It is on the World Health Organizations List of Essential Medicines. In 2017, it was the 410th most commonly prescribed medication in the United States, with more than 150 thousand prescriptions. Uses Insecticide In agriculture, to protect crops (a drawback is that it is lethal to bees) In agriculture, to kill livestock parasites For industrial and domestic insect control In the textile industry, to prevent insect attack of woollen products In aviation, the WHO, IHR and ICAO require arriving aircraft be disinsected prior to embarkation, departure, descent, or deplaning in certain countries. Aircraft disinsection with permethrin-based products is recommended only prior to embarkation. Prior to departure (after boarding), at the top of descent or on arrival, d-phenothrin-based (1R-trans phenothrin) aircraft insecticides are recommended. Insect repellent As a personal protective measure, permethrin is applied to clothing. It is a cloth impregnant, notably in mosquito nets and field wear. While permethrin may be marketed as an insect repellent, it does not prevent insects from landing. Instead it works by incapacitating or killing insects before they can bite. In pet flea preventive collars or treatment (safe for use on dogs but not cats) In timber treatment Medical use Permethrin is available for topical use as a cream or lotion. It is indicated for the treatment and prevention in exposed individuals of head lice and treatment of scabies.For treatment of scabies: Adults and children older than 2 months are instructed to apply the cream to the entire body from head to the soles of the feet. Wash off the cream after 8–14 hours. In general, one treatment is curative.For treatment of head lice: Apply to hair, scalp, and neck after shampooing. Leave in for 10 minutes and rinse. Avoid contact with eyes. Pest control / effectiveness and persistence In agriculture, permethrin is mainly used on cotton, wheat, maize, and alfalfa crops. Its use is controversial because, as a broad-spectrum chemical, it kills indiscriminately; as well as the intended pests, it can harm beneficial insects, including honey bees, as well as cats and aquatic life.Permethrin kills ticks and mosquitoes on contact with treated clothing. A method of reducing deer tick populations by treating rodent vectors involves stuffing biodegradable cardboard tubes with permethrin-treated cotton. Mice collect the cotton for lining their nests. Permethrin on the cotton kills any immature ticks feeding on the mice. Permethrin is used in tropical areas to prevent mosquito-borne disease such as dengue fever and malaria. Mosquito nets used to cover beds may be treated with a solution of permethrin. This increases the effectiveness of the bed net by killing parasitic insects before they are able to find gaps or holes in the net. Personnel working in malaria-endemic areas may be instructed to treat their clothing with permethrin as well. Permethrin is the most commonly used insecticide worldwide for the protection of wool from keratinophagous insects such as Tineola bisselliella.To better protect soldiers from the risk and annoyance of biting insects, the British and US armies are treating all new uniforms with permethrin.Permethrin (as well as other long-term pyrethroids) is effective over several months, in particular when used indoors. International studies report that permethrin can be detected in house dust, in fine dust, and on indoor surfaces even years after the application. Its degradation rate under indoor conditions is approximately 10% after 3 months. Resistance Contrary to the most common mechanism of insecticide resistance evolution – selection for preexisting, low-frequency alleles – in Aedes aegypti permethrin resistance has arisen through the mechanism common to pyrethroids and DDT known as "knockdown resistance" (kdr) mutations. García et al 2009 found that a kdr allele has rapidly spread throughout Mexico and recently become dominant there. Side effects Permethrin application can cause mild skin irritation and burning. Permethrin has little systemic absorption, and is considered safe for topical use in adults and children over the age of two months. The FDA has assigned it as pregnancy category B. Animal studies have shown no effects on fertility or teratogenicity, but studies in humans have not been performed. The excretion of permethrin in breastmilk is unknown, and it is recommended that breastfeeding be temporarily discontinued during treatment. Skin reactions are uncommon. Excessive exposure to permethrin can cause nausea, headache, muscle weakness, excessive salivation, shortness of breath, and seizures. Worker exposure to the chemical can be monitored by measurement of the urinary metabolites, while severe overdose may be confirmed by measurement of permethrin in serum or blood plasma.Permethrin does not present any notable genotoxicity or immunotoxicity in humans and farm animals, but is classified by the EPA as a likely human carcinogen when ingested, based on reproducible studies in which mice fed permethrin developed liver and lung tumors. Pharmacokinetics Permethrin is a chemical categorized in the pyrethroid insecticide group. The chemicals in the pyrethroid family are created to emulate the chemicals found in the chrysanthemum flower. Absorption Absorption of topical permethrin is minimal. One in vivo study demonstrated 0.5% absorption in the first 48 hours based upon excretion of urinary metabolites. Distribution Distribution of permethrin has been studied in rat models, with highest amounts accumulating in fat and the brain. This can be explained by the lipophilic nature of the permethrin molecule. Metabolism Metabolism of permethrin occurs mainly in the liver, where the molecule undergoes oxidation by the cytochrome P450 system, as well as hydrolysis, into metabolites. Elimination of these metabolites occurs via urinary excretion. Stereochemistry Permethrin has four stereoisomers (two enantiomeric pairs), arising from the two stereocenters in the cyclopropane ring. The trans enantiomeric pair is known as transpermethrin. (1R,3S)-trans and (1R,3R)-cis enantiomers are responsible for the insecticidal properties of permethrin. History Permethrin was first made in 1973.Numerous synthetic routes exist for the production of the DV-acid ester precursor. The pathway known as the Kuraray Process uses four steps. In general, the final step in the total synthesis of any of the synthetic pyrethroids is a coupling of a DV-acid ester and an alcohol. In the case of permethrin synthesis, the DV-acid cyclopropanecarboxylic acid, 3-(2,2-dichloroethenyl)-2,2-dimethyl-, ethyl ester, is coupled with the alcohol, m-phenoxybenzyl alcohol, through a transesterification reaction with base. Tetraisopropyl titanate or sodium ethylate may be used as the base.The alcohol precursor may be prepared in three steps. First, m-cresol, chlorobenzene, sodium hydroxide, potassium hydroxide, and copper chloride react to yield m-phenoxytoluene. Second, oxidation of m-phenoxytoluene over selenium dioxide provides m-phenoxybenzaldehyde. Third, a Cannizzaro reaction of the benzaldehyde in formaldehyde and potassium hydroxide affords the m-phenoxybenzyl alcohol. Brand names In Nordic countries and North America, a permethrin formulation for lice treatment is marketed under trade name Nix, available over the counter. Johnson & Johnsons UK brand Lyclear covers an assortment of different products, mostly non-insecticidal, but a few of which are based on permethrin.Stronger concentrations of permethrin are used to treat scabies (which embed inside the skin), compared to lice (which remain outside the skin). In the U.S. the more concentrated products such as Elimite are available by prescription only. Other animals It is known to be highly toxic to cats, fish and aquatic species with long-lasting effects. Cats Permethrin is toxic to cats; however, it has little effect on dogs. Pesticide-grade permethrin is toxic to cats. Many cats die after being given flea treatments intended for dogs, or by contact with dogs having recently been treated with permethrin. In cats it may induce hyperexcitability, tremors, seizures, and death.Toxic exposure of permethrin can cause several symptoms, including convulsion, hyperaesthesia, hyperthermia, hypersalivation, and loss of balance and coordination. Exposure to pyrethroid-derived drugs such as permethrin requires treatment by a veterinarian, otherwise the poisoning is often fatal. This intolerance is due to a defect in glucuronosyltransferase, a common detoxification enzyme in other mammals, that also makes the cat intolerant to paracetamol (acetaminophen). The use of any external parasiticides based on permethrin is contraindicated for cats. Aquatic organisms Permethrin is listed as a "restricted use" substance by the US Environmental Protection Agency (EPA) due to its high toxicity to aquatic organisms, so permethrin and permethrin-contaminated water should be properly disposed of. Permethrin is quite stable, having a half life of 51–71 days in an aqueous environment exposed to light. It is also highly persistent in soil. See also Benzyl benzoate DEET Methoprene Pyrethrin Pyrethrum References External links Permethrin in the Pesticide Properties DataBase (PPDB) Permethrin General Fact Sheet – National Pesticide Information Center Permethrin Technical Fact Sheet – National Pesticide Information Center Permethrin-treated Clothing Hot Topic – National Pesticide Information Center "Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms", National Research Council (1994, US) Permethrin Pesticide Information Profile – Extension Toxicology Network "Permethrin". Drug Information Portal. U.S. National Library of Medicine.

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

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

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

I'm not familiar with the medical term 'Benign paroxysmal vertigo of childhood.' Could you provide some insights?

Benign paroxysmal vertigo of childhood is an uncommon neurological disorder which presents with recurrent episodes of dizziness. The presentation is usually between the ages of 2 years and 7 years of age and is characterised by short episodes of vertigo of sudden onset when the child appears distressed and unwell. The child may cling to something or someone for support. The episode lasts only minutes and resolves suddenly and completely. It is a self-limiting condition and usually resolves after about eighteen months, although many go on to experience migrainous vertigo (or vestibular migraine) when older.Benign paroxysmal vertigo of childhood is a migrainous phenomenon with more than 50% of those affected having a family history of migraines affecting a first-degree relative. It has no relationship to benign paroxysmal positional vertigo which is a different condition entirely. == References ==

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

Carbamate poisoning is poisoning due to exposure to carbamates. Carbamates are typically used as pesticides; however, some also have medical uses. Symptoms may be similar to organophosphate poisoning. == References ==

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

Balanitis is inflammation of the glans penis. When the foreskin is also affected, the proper term is balanoposthitis. Balanitis on boys still in diapers must be distinguished from redness caused by ammoniacal dermatitis. The word balanitis is from the Greek βάλανος balanos, literally meaning acorn, used because of the similarity in shape to the glans penis. Signs and symptoms Small red erosions on the glans (first sign) Redness of the foreskin Redness of the penis Other rashes on the head of the penis Foul smelling discharge Painful foreskin and penis Complications Recurrent bouts of balanitis may cause scarring of the preputial orifice; the reduced elasticity may lead to pathologic phimosis. Further complications may include: Stricture of urethral meatus Phimosis Paraphimosis Cause Inflammation has many possible causes, including irritation by environmental substances, physical trauma, and infection such as bacterial, viral, or fungal. Some of these infections are sexually transmitted diseases. It is less common among people who are circumcised, as in many cases, a dysfunction of the foreskin is a causal or contributing factor. Both not enough cleaning and too much cleaning can cause problems. Diabetes can make balanitis more likely, especially if the blood sugar is poorly controlled.It is important to exclude other causes of similar symptoms such as penile cancer. Diagnosis Diagnosis may include careful identification of the cause with the aid of a good patient history, swabs and cultures, and pathological examination of a biopsy. Types Zoons balanitis, also known as Balanitis Circumscripta Plasmacellularis or plasma cell balanitis (PCB), is an idiopathic, rare, benign penile dermatosis for which circumcision is often the preferred treatment. Zoons balanitis has been successfully treated with the carbon dioxide laser; and more recently, Albertini and colleagues report the avoidance of circumcision and successful treatment of Zoons balanitis with an Er:YAG laser. Another study, by Retamar and colleagues, found that 40 percent of those treated with CO2 laser relapsed. Circinate balanitis, also known as balanitis circinata, is a serpiginous annular dermatitis associated with reactive arthritis. Pseudoepitheliomatous keratotic and micaceous balanitis Treatment Initial treatment in adults often involves simply pulling back the foreskin and cleaning the penis. However, some topical antibiotic and fungal ointments may be used for treatment for mild cases. Depending upon severity, hydrocortisone and other steroidal creams may be used upon consultation. Epidemiology Balanitis "is a common condition affecting 11% of adult men seen in urology clinics and 3% of children" in the United States; globally, balanitis "may occur in up to 3% of uncircumcised males". Other animals In dogs, balanoposthitis is caused by a disruption in the integumentary system, such as a wound or intrusion of a foreign body. A dog with this condition behaves normally, with the exception of excessive licking at the prepuce, and a yellow green, pus-like discharge is usually present. In sheep (rams/wethers), ulcerative enzootic balanoposthitis is caused by the Corynebacterium renale group (C. renale, C. pilosum & C. cystidis). For the condition in bulls, caused by a virus see Bovine herpesvirus 1. Balanoposthitis is believed to have contributed to the decline to near-extinction of Gilberts potoroo. References Further reading Edwards S. (for the Clinical Effectiveness Group) National guideline on the management of balanitis. Association for Genitourinary Medicine (UK) and the Medical Society for the Study of Venereal Diseases (UK), 2001. External links Zoons Balanitis at eMedicine Dermatological atlas

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Please help me grasp the concept behind the medical term 'Thoracic aortic aneurysm.'

A thoracic aortic aneurysm is an aortic aneurysm that presents primarily in the thorax. A thoracic aortic aneurysm is the "ballooning" of the upper aspect of the aorta, above the diaphragm. Untreated or unrecognized they can be fatal due to dissection or "popping" of the aneurysm leading to nearly instant death. Thoracic aneurysms are less common than an abdominal aortic aneurysm. However, a syphilitic aneurysm is more likely to be a thoracic aortic aneurysm than an abdominal aortic aneurysm. This condition is commonly treated via a specialized multidisciplinary approach with both vascular surgeons and cardiac surgeons. Presentation Complications The principal causes of death due to thoracic aneurysmal disease are dissection and rupture. Once rupture occurs, the mortality rate is 50–80%. Most deaths in patients with Marfan syndrome are the result of aortic disease. Causes There are a number of causes, Aneurysms in patients younger than 40 usually involve the ascending aorta due to a weakening of the aortic wall associated with connective tissue disorders like the Marfan and Ehler-Danlos syndromes or congenital bicuspid aortic valve. Younger patients may develop aortic aneurysms of the thoracoabdominal aorta after an aortic dissection. It can also be caused by blunt injury. Atherosclerosis is the principal cause of descending aortic aneurysms, while aneurysms of the aortic arch may be due to dissection, atherosclerosis, or inflammation. Age The diagnosis of thoracic aortic aneurysm usually involves patients in their 60s and 70s. Risk factors Hypertension and cigarette smoking are the most important risk factors, though the importance of genetic factors has been increasingly recognized. Approximately 10 percent of patients may have other family members who have aortic aneurysms. It is also important to note that individuals with a history of aneurysms in other parts of the body have a higher chance of developing a thoracic aortic aneurysm. Diagnosis Thoracic aortic aneurysm is defined as a cross-sectional diameter exceeding the following cutoff: 4.5 cm in the United States 4.0 cm in South KoreaA diameter of 3.5 cm is generally considered dilated. However, average values vary with age and size of the reference population, as well as different segments of the aorta. Screening Guidelines were issued in March 2010 for early detection of thoracic aortic disease, by the American College of Cardiology, the American Heart Association, and other groups. Among the recommendations: First-degree relatives of people with thoracic aortic aneurysm or dissection should have aortic imaging to identify asymptomatic disease. People with symptoms suggestive of thoracic aortic dissection should be routinely evaluated "to establish a pretest risk of disease that can then be used to guide diagnostic decisions." People diagnosed with Marfan syndrome should immediately have an echocardiogram to measure the aorta and followed up six months later to check for aortic enlargement. Treatment The size cut off for aortic aneurysm is crucial to its treatment. A thoracic aorta greater than 4.5 cm is generally defined as aneurysmal, while a size greater than 6 cm is the distinction for treatment, which can be either endovascular or surgical, with the former reserved for pathology at the descending aorta.Indication for surgery may depend upon the size of the aneurysm. Aneurysms in the ascending aorta may require surgery at a smaller size than aneurysms in the descending aorta.Treatment may be via open or via endovascular means. Epidemiology Each year in the United States, some 45,000 people die from diseases of the aorta and its branches. Acute aortic dissection, a life-threatening event due to a tear in the aortic wall, affects 5 to 10 patients per million population each year, most often men between the ages of 50 and 70; of those that occur in women younger than 40, nearly half arise during pregnancy. The majority of these deaths occur as a result of complications of thoracic aneurysmal disease References == External links ==

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I'm seeking clarification on the medical term 'Traumatic brain injury.' Could you explain it?

A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury [mTBI/concussion] to severe traumatic brain injury), mechanism (closed or penetrating head injury), or other features (e.g., occurring in a specific location or over a widespread area). Head injury is a broader category that may involve damage to other structures such as the scalp and skull. TBI can result in physical, cognitive, social, emotional and behavioral symptoms, and outcomes can range from complete recovery to permanent disability or death. Causes include falls, vehicle collisions and violence. Brain trauma occurs as a consequence of a sudden acceleration or deceleration within the cranium or by a complex combination of both movement and sudden impact. In addition to the damage caused at the moment of injury, a variety of events following the injury may result in further injury. These processes include alterations in cerebral blood flow and pressure within the skull. Some of the imaging techniques used for diagnosis include computed tomography (CT) and magnetic resonance imaging (MRIs). Prevention measures include use of seat belts and helmets, not drinking and driving, fall prevention efforts in older adults and safety measures for children. Depending on the injury, treatment required may be minimal or may include interventions such as medications, emergency surgery or surgery years later. Physical therapy, speech therapy, recreation therapy, occupational therapy and vision therapy may be employed for rehabilitation. Counseling, supported employment and community support services may also be useful. TBI is a major cause of death and disability worldwide, especially in children and young adults. Males sustain traumatic brain injuries around twice as often as females. The 20th century saw developments in diagnosis and treatment that decreased death rates and improved outcomes. Classification Traumatic brain injury is defined as damage to the brain resulting from external mechanical force, such as rapid acceleration or deceleration, impact, blast waves, or penetration by a projectile. Brain function is temporarily or permanently impaired and structural damage may or may not be detectable with current technology.TBI is one of two subsets of acquired brain injury (brain damage that occur after birth); the other subset is non-traumatic brain injury, which does not involve external mechanical force (examples include stroke and infection). All traumatic brain injuries are head injuries, but the latter term may also refer to injury to other parts of the head. However, the terms head injury and brain injury are often used interchangeably. Similarly, brain injuries fall under the classification of central nervous system injuries and neurotrauma. In neuropsychology research literature, in general the term "traumatic brain injury" is used to refer to non-penetrating traumatic brain injuries. TBI is usually classified based on severity, anatomical features of the injury, and the mechanism (the causative forces). Mechanism-related classification divides TBI into closed and penetrating head injury. A closed (also called nonpenetrating, or blunt) injury occurs when the brain is not exposed. A penetrating, or open, head injury occurs when an object pierces the skull and breaches the dura mater, the outermost membrane surrounding the brain. Severity Brain injuries can be classified into mild, moderate, and severe categories. The Glasgow Coma Scale (GCS), the most commonly used system for classifying TBI severity, grades a persons level of consciousness on a scale of 3–15 based on verbal, motor, and eye-opening reactions to stimuli. In general, it is agreed that a TBI with a GCS of 13 or above is mild, 9–12 is moderate, and 8 or below is severe. Similar systems exist for young children. However, the GCS grading system has limited ability to predict outcomes. Because of this, other classification systems such as the one shown in the table are also used to help determine severity. A current model developed by the Department of Defense and Department of Veterans Affairs uses all three criteria of GCS after resuscitation, duration of post-traumatic amnesia (PTA), and loss of consciousness (LOC). It also has been proposed to use changes that are visible on neuroimaging, such as swelling, focal lesions, or diffuse injury as method of classification. Grading scales also exist to classify the severity of mild TBI, commonly called concussion; these use duration of LOC, PTA, and other concussion symptoms. Pathological features Systems also exist to classify TBI by its pathological features. Lesions can be extra-axial, (occurring within the skull but outside of the brain) or intra-axial (occurring within the brain tissue). Damage from TBI can be focal or diffuse, confined to specific areas or distributed in a more general manner, respectively. However, it is common for both types of injury to exist in a given case.Diffuse injury manifests with little apparent damage in neuroimaging studies, but lesions can be seen with microscopy techniques post-mortem, and in the early 2000s, researchers discovered that diffusion tensor imaging (DTI), a way of processing MRI images that shows white matter tracts, was an effective tool for displaying the extent of diffuse axonal injury. Types of injuries considered diffuse include edema (swelling), concussion and diffuse axonal injury, which is widespread damage to axons including white matter tracts and projections to the cortex.Focal injuries often produce symptoms related to the functions of the damaged area. Research shows that the most common areas to have focal lesions in non-penetrating traumatic brain injury are the orbitofrontal cortex (the lower surface of the frontal lobes) and the anterior temporal lobes, areas that are involved in social behavior, emotion regulation, olfaction, and decision-making, hence the common social/emotional and judgment deficits following moderate-severe TBI. Symptoms such as hemiparesis or aphasia can also occur when less commonly affected areas such as motor or language areas are, respectively, damaged.One type of focal injury, cerebral laceration, occurs when the tissue is cut or torn. Such tearing is common in orbitofrontal cortex in particular, because of bony protrusions on the interior skull ridge above the eyes. In a similar injury, cerebral contusion (bruising of brain tissue), blood is mixed among tissue. In contrast, intracranial hemorrhage involves bleeding that is not mixed with tissue.Hematomas, also focal lesions, are collections of blood in or around the brain that can result from hemorrhage. Intracerebral hemorrhage, with bleeding in the brain tissue itself, is an intra-axial lesion. Extra-axial lesions include epidural hematoma, subdural hematoma, subarachnoid hemorrhage, and intraventricular hemorrhage. Epidural hematoma involves bleeding into the area between the skull and the dura mater, the outermost of the three membranes surrounding the brain. In subdural hematoma, bleeding occurs between the dura and the arachnoid mater. Subarachnoid hemorrhage involves bleeding into the space between the arachnoid membrane and the pia mater. Intraventricular hemorrhage occurs when there is bleeding in the ventricles. Signs and symptoms Symptoms are dependent on the type of TBI (diffuse or focal) and the part of the brain that is affected. Unconsciousness tends to last longer for people with injuries on the left side of the brain than for those with injuries on the right. Symptoms are also dependent on the injurys severity. With mild TBI, the patient may remain conscious or may lose consciousness for a few seconds or minutes. Other symptoms of mild TBI include headache, vomiting, nausea, lack of motor coordination, dizziness, difficulty balancing, lightheadedness, blurred vision or tired eyes, ringing in the ears, bad taste in the mouth, fatigue or lethargy, and changes in sleep patterns. Cognitive and emotional symptoms include behavioral or mood changes, confusion, and trouble with memory, concentration, attention, or thinking. Mild TBI symptoms may also be present in moderate and severe injuries.A person with a moderate or severe TBI may have a headache that does not go away, repeated vomiting or nausea, convulsions, an inability to awaken, dilation of one or both pupils, slurred speech, aphasia (word-finding difficulties), dysarthria (muscle weakness that causes disordered speech), weakness or numbness in the limbs, loss of coordination, confusion, restlessness, or agitation. Common long-term symptoms of moderate to severe TBI are changes in appropriate social behavior, deficits in social judgment, and cognitive changes, especially problems with sustained attention, processing speed, and executive functioning. Alexithymia, a deficiency in identifying, understanding, processing, and describing emotions occurs in 60.9% of individuals with TBI. Cognitive and social deficits have long-term consequences for the daily lives of people with moderate to severe TBI, but can be improved with appropriate rehabilitation.When the pressure within the skull (intracranial pressure, abbreviated ICP) rises too high, it can be deadly. Signs of increased ICP include decreasing level of consciousness, paralysis or weakness on one side of the body, and a blown pupil, one that fails to constrict in response to light or is slow to do so. Cushings triad, a slow heart rate with high blood pressure and respiratory depression is a classic manifestation of significantly raised ICP. Anisocoria, unequal pupil size, is another sign of serious TBI. Abnormal posturing, a characteristic positioning of the limbs caused by severe diffuse injury or high ICP, is an ominous sign.Small children with moderate to severe TBI may have some of these symptoms but have difficulty communicating them. Other signs seen in young children include persistent crying, inability to be consoled, listlessness, refusal to nurse or eat, and irritability. Causes The most common causes of TBI in the U.S. include violence, transportation accidents, construction site mishaps, and sports. Motor bikes are major causes, increasing in significance in developing countries as other causes reduce. The estimates that between 1.6 and 3.8 million traumatic brain injuries each year are a result of sports and recreation activities in the US. In children aged two to four, falls are the most common cause of TBI, while in older children traffic accidents compete with falls for this position. TBI is the third most common injury to result from child abuse. Abuse causes 19% of cases of pediatric brain trauma, and the death rate is higher among these cases. Although men are twice as likely to have a TBI. Domestic violence is another cause of TBI, as are work-related and industrial accidents. Firearms and blast injuries from explosions are other causes of TBI, which is the leading cause of death and disability in war zones. According to Representative Bill Pascrell (Democrat, NJ), TBI is "the signature injury of the wars in Iraq and Afghanistan." There is a promising technology called activation database-guided EEG biofeedback, which has been documented to return a TBIs auditory memory ability to above the control groups performance Mechanism Physical forces The type, direction, intensity, and duration of forces all contribute to the characteristics and severity TBI. Forces that may contribute to TBI include angular, rotational, shear, and translational forces.Even in the absence of an impact, significant acceleration or deceleration of the head can cause TBI; however in most cases, a combination of impact and acceleration is probably to blame. Forces involving the head striking or being struck by something, termed contact or impact loading, are the cause of most focal injuries, and movement of the brain within the skull, termed noncontact or inertial loading, usually causes diffuse injuries. The violent shaking of an infant that causes shaken baby syndrome commonly manifests as diffuse injury. In impact loading, the force sends shock waves through the skull and brain, resulting in tissue damage. Shock waves caused by penetrating injuries can also destroy tissue along the path of a projectile, compounding the damage caused by the missile itself.Damage may occur directly under the site of impact, or it may occur on the side opposite the impact (coup and contrecoup injury, respectively). When a moving object impacts the stationary head, coup injuries are typical, while contrecoup injuries are usually produced when the moving head strikes a stationary object. Primary and secondary injury A large percentage of the people killed by brain trauma do not die right away but rather days to weeks after the event; rather than improving after being hospitalized, some 40% of TBI patients deteriorate. Primary brain injury (the damage that occurs at the moment of trauma when tissues and blood vessels are stretched, compressed, and torn) is not adequate to explain this deterioration; rather, it is caused by secondary injury, a complex set of cellular processes and biochemical cascades that occur in the minutes to days following the trauma. These secondary processes can dramatically worsen the damage caused by primary injury and account for the greatest number of TBI deaths occurring in hospitals.Secondary injury events include damage to the blood–brain barrier, release of factors that cause inflammation, free radical overload, excessive release of the neurotransmitter glutamate (excitotoxicity), influx of calcium and sodium ions into neurons, and dysfunction of mitochondria. Injured axons in the brains white matter may separate from their cell bodies as a result of secondary injury, potentially killing those neurons. Other factors in secondary injury are changes in the blood flow to the brain; ischemia (insufficient blood flow); cerebral hypoxia (insufficient oxygen in the brain); cerebral edema (swelling of the brain); and raised intracranial pressure (the pressure within the skull). Intracranial pressure may rise due to swelling or a mass effect from a lesion, such as a hemorrhage. As a result, cerebral perfusion pressure (the pressure of blood flow in the brain) is reduced; ischemia results. When the pressure within the skull rises too high, it can cause brain death or brain herniation, in which parts of the brain are squeezed by structures in the skull. Diagnosis Diagnosis is suspected based on lesion circumstances and clinical evidence, most prominently a neurological examination, for example checking whether the pupils constrict normally in response to light and assigning a Glasgow Coma Score. Neuroimaging helps in determining the diagnosis and prognosis and in deciding what treatments to give. DSM-5 can be utilized to diagnose TBI and its psychiatric sequelae.The preferred radiologic test in the emergency setting is computed tomography (CT): it is quick, accurate, and widely available. Follow-up CT scans may be performed later to determine whether the injury has progressed.Magnetic resonance imaging (MRI) can show more detail than CT, and can add information about expected outcome in the long term. It is more useful than CT for detecting injury characteristics such as diffuse axonal injury in the longer term. However, MRI is not used in the emergency setting for reasons including its relative inefficacy in detecting bleeds and fractures, its lengthy acquisition of images, the inaccessibility of the patient in the machine, and its incompatibility with metal items used in emergency care. A variant of MRI since 2012 is High definition fiber tracking (HDFT).Other techniques may be used to confirm a particular diagnosis. X-rays are still used for head trauma, but evidence suggests they are not useful; head injuries are either so mild that they do not need imaging or severe enough to merit the more accurate CT. Angiography may be used to detect blood vessel pathology when risk factors such as penetrating head trauma are involved. Functional imaging can measure cerebral blood flow or metabolism, inferring neuronal activity in specific regions and potentially helping to predict outcome.Neuropsychological assessment can be performed to evaluate the long-term cognitive sequelae and to aid in the planning of the rehabilitation. Instruments range from short measures of general mental functioning to complete batteries formed of different domain-specific tests. Prevention Since a major cause of TBI are vehicle accidents, their prevention or the amelioration of their consequences can both reduce the incidence and gravity of TBI. In accidents, damage can be reduced by use of seat belts, child safety seats and motorcycle helmets, and presence of roll bars and airbags. Education programs exist to lower the number of crashes. In addition, changes to public policy and safety laws can be made; these include speed limits, seat belt and helmet laws, and road engineering practices.Changes to common practices in sports have also been discussed. An increase in use of helmets could reduce the incidence of TBI. Due to the possibility that repeatedly "heading" a ball practicing soccer could cause cumulative brain injury, the idea of introducing protective headgear for players has been proposed. Improved equipment design can enhance safety; softer baseballs reduce head injury risk. Rules against dangerous types of contact, such as "spear tackling" in American football, when one player tackles another head first, may also reduce head injury rates.Falls can be avoided by installing grab bars in bathrooms and handrails on stairways; removing tripping hazards such as throw rugs; or installing window guards and safety gates at the top and bottom of stairs around young children. Playgrounds with shock-absorbing surfaces such as mulch or sand also prevent head injuries. Child abuse prevention is another tactic; programs exist to prevent shaken baby syndrome by educating about the dangers of shaking children. Gun safety, including keeping guns unloaded and locked, is another preventative measure. Studies on the effect of laws that aim to control access to guns in the United States have been insufficient to determine their effectiveness preventing number of deaths or injuries. Treatment It is important to begin emergency treatment within the so-called "golden hour" following the injury. People with moderate to severe injuries are likely to receive treatment in an intensive care unit followed by a neurosurgical ward. Treatment depends on the recovery stage of the patient. In the acute stage, the primary aim is to stabilize the patient and focus on preventing further injury. This is done because the initial damage caused by trauma cannot be reversed. Rehabilitation is the main treatment for the subacute and chronic stages of recovery. International clinical guidelines have been proposed with the aim of guiding decisions in TBI treatment, as defined by an authoritative examination of current evidence. Acute stage Tranexamic acid within three hours of a head injury decreases the risk of death. Certain facilities are equipped to handle TBI better than others; initial measures include transporting patients to an appropriate treatment center. Both during transport and in hospital the primary concerns are ensuring proper oxygen supply, maintaining adequate blood flow to the brain, and controlling raised intracranial pressure (ICP), since high ICP deprives the brain of badly needed blood flow and can cause deadly brain herniation. Other methods to prevent damage include management of other injuries and prevention of seizures. Some data supports the use of hyperbaric oxygen therapy to improve outcomes. Further research is required to determine the effectiveness and clinical importance of positioning the head at different angles (degrees of head-of-bed elevation) while the person is being treated in intensive care.Neuroimaging is helpful but not flawless in detecting raised ICP. A more accurate way to measure ICP is to place a catheter into a ventricle of the brain, which has the added benefit of allowing cerebrospinal fluid to drain, releasing pressure in the skull. Treatment of raised ICP may be as simple as tilting the persons bed and straightening the head to promote blood flow through the veins of the neck. Sedatives, analgesics and paralytic agents are often used. Propofol and midazolam are equally effective as sedatives.Hypertonic saline can improve ICP by reducing the amount of cerebral water (swelling), though it is used with caution to avoid electrolyte imbalances or heart failure. Mannitol, an osmotic diuretic, appears to be as effective as hypertonic saline at reducing ICP. Some concerns, however, have been raised regarding some of the studies performed. Diuretics, drugs that increase urine output to reduce excessive fluid in the system, may be used to treat high intracranial pressures, but may cause hypovolemia (insufficient blood volume). Hyperventilation (larger and/or faster breaths) reduces carbon dioxide levels and causes blood vessels to constrict; this decreases blood flow to the brain and reduces ICP, but it potentially causes ischemia and is, therefore, used only in the short term.Giving corticosteroids is associated with an increased risk of death, and so their routine use is not recommended. There is no strong evidence that the following pharmaceutical interventions should be recommended to routinely treat TBI: magnesium, monoaminergic and dopamine agonists, progesterone, aminosteroids, excitatory amino acid reuptake inhibitors, beta-2 antagonists (bronchodilators), haemostatic and antifibrinolytic drugs.Endotracheal intubation and mechanical ventilation may be used to ensure proper oxygen supply and provide a secure airway. Hypotension (low blood pressure), which has a devastating outcome in TBI, can be prevented by giving intravenous fluids to maintain a normal blood pressure. Failing to maintain blood pressure can result in inadequate blood flow to the brain. Blood pressure may be kept at an artificially high level under controlled conditions by infusion of norepinephrine or similar drugs; this helps maintain cerebral perfusion. Body temperature is carefully regulated because increased temperature raises the brains metabolic needs, potentially depriving it of nutrients. Seizures are common. While they can be treated with benzodiazepines, these drugs are used carefully because they can depress breathing and lower blood pressure. Anti-convulsant medications have only been found to be useful for reducing the risk of an early seizure. Phenytoin and leviteracetam appear to have similar levels of effectiveness for preventing early seizures. People with TBI are more susceptible to side effects and may react adversely to some medications. During treatment monitoring continues for signs of deterioration such as a decreasing level of consciousness.Traumatic brain injury may cause a range of serious coincidental complications that include cardiac arrhythmias and neurogenic pulmonary edema. These conditions must be adequately treated and stabilised as part of the core care. Surgery can be performed on mass lesions or to eliminate objects that have penetrated the brain. Mass lesions such as contusions or hematomas causing a significant mass effect (shift of intracranial structures) are considered emergencies and are removed surgically. For intracranial hematomas, the collected blood may be removed using suction or forceps or it may be floated off with water. Surgeons look for hemorrhaging blood vessels and seek to control bleeding. In penetrating brain injury, damaged tissue is surgically debrided, and craniotomy may be needed. Craniotomy, in which part of the skull is removed, may be needed to remove pieces of fractured skull or objects embedded in the brain. Decompressive craniectomy (DC) is performed routinely in the very short period following TBI during operations to treat hematomas; part of the skull is removed temporarily (primary DC). DC performed hours or days after TBI in order to control persistently high intracranial pressures (secondary DC), although can reduce intracranial pressure and length of stay in ICU, but have worse Glasgow Coma Scale (GCS) scores, and high chances of death, vegetative state, or severe disability when compared to those receiving standard medical therapies. Chronic stage Once medically stable, people may be transferred to a subacute rehabilitation unit of the medical center or to an independent rehabilitation hospital. Rehabilitation aims to improve independent functioning at home and in society, and to help adapt to disabilities. Rehabilitation has demonstrated its general effectiveness when conducted by a team of health professionals who specialize in head trauma. As for any person with neurologic deficits, a multidisciplinary approach is key to optimizing outcome. Physiatrists or neurologists are likely to be the key medical staff involved, but depending on the person, doctors of other medical specialties may also be helpful. Allied health professions such as physiotherapy, speech and language therapy, cognitive rehabilitation therapy, and occupational therapy will be essential to assess function and design the rehabilitation activities for each person. Treatment of neuropsychiatric symptoms such as emotional distress and clinical depression may involve mental health professionals such as therapists, psychologists, and psychiatrists, while neuropsychologists can help to evaluate and manage cognitive deficits. Social workers, rehabilitation support personnel, nutritionists, therapeutic recreationists, and pharmacists are also important members of the TBI rehabilitation team. After discharge from the inpatient rehabilitation treatment unit, care may be given on an outpatient basis. Community-based rehabilitation will be required for a high proportion of people, including vocational rehabilitation; this supportive employment matches job demands to the workers abilities. People with TBI who cannot live independently or with family may require care in supported living facilities such as group homes. Respite care, including day centers and leisure facilities for disabled people, offers time off for caregivers, and activities for people with TBI.Pharmacological treatment can help to manage psychiatric or behavioral problems. Medication is also used to control post-traumatic epilepsy; however the preventive use of anti-epileptics is not recommended. In those cases where the person is bedridden due to a reduction of consciousness, has to remain in a wheelchair because of mobility problems, or has any other problem heavily impacting self-caring capacities, caregiving and nursing are critical. The most effective research documented intervention approach is the activation database guided EEG biofeedback approach, which has shown significant improvements in memory abilities of the TBI subject that are far superior than traditional approaches (strategies, computers, medication intervention). Gains of 2.61 standard deviations have been documented. The TBIs auditory memory ability was superior to the control group after the treatment. Effect on the gait pattern In patients who have developed paralysis of the legs in the form of spastic hemiplegia or diplegia as a result of the traumatic brain injury, various gait patterns can be observed, the exact extent of which can only be described with the help of complex gait analysis systems. In order to facilitate interdisciplinary communication in the interdisciplinary team between those affected, doctors, physiotherapists and orthotists, a simple description of the gait pattern is useful. J. Rodda and H. K. Graham already described in 2001 how gait patterns of CP patients can be more easily recognized and defined gait types which they compared in a classification. They also described that gait patterns can vary with age. Building on this, the Amsterdam Gait Classification was developed at the free university in Amsterdam, the VU medisch centrum. A special feature of this classification is that it makes different gait patterns very recognizable and can be used in patients in whom only one leg and both legs are affected. The Amsterdam Gait Classification was developed for viewing patients with cerebral palsy. However, it can be used just as well in patients with traumatic brain injuries. According to the Amsterdam Gait Classification, five gait types are described. To assess the gait pattern, the patient is viewed visually or via a video recording from the side of the leg to be assessed. At the point in time at which the leg to be viewed is in mid stance and the leg not to be viewed is in mid swing, the knee angle and the contact of the foot with the ground are assessed on the one hand.Classification of the gait pattern according to the Amsterdam Gait Classification: In gait type 1, the knee angle is normal and the foot contact is complete. In gait type 2, the knee angle is hyperextended and the foot contact is complete. In gait type 3, the knee angle is hyperextended and foot contact is incomplete (only on the forefoot). In gait type 4, the knee angle is bent and foot contact is incomplete (only on the forefoot). With gait type 5, the knee angle is bent and the foot contact is complete.Gait types 5 is also known as crouch gait. Orthotics To improve the gait pattern, orthotics can be included in the therapy concept. An Orthosis can support physiotherapeutic treatment in setting the right motor impulses in order to create new cerebral connections. The orthosis must meet the requirements of the medical prescription. In addition, the orthosis must be designed by the orthotist in such a way that it achieves the effectiveness of the necessary levers, matching the gait pattern, in order to support the proprioceptive approaches of physiotherapy. The orthotic concepts of the treatment are based on the concepts for the patients with cerebral palsy. The characteristics of the stiffness of the orthosis shells and the adjustable dynamics in the ankle joint are important elements of the orthosis to be considered. The orthotic concepts of the treatment are based on the concepts for the patients with cerebral palsy. Due to these requirements, the development of orthoses has changed significantly in recent years, especially since around 2010. At about the same time, care concepts were developed that deal intensively with the orthotic treatment of the lower extremities in cerebral palsy. Modern materials and new functional elements enable the rigidity to be specifically adapted to the requirements that fits to the gait pattern of the patient. The adjustment of the stiffness has a decisive influence on the gait pattern and on the energy cost of walking. It is of great advantage if the stiffness of the orthosis can be adjusted separately from one another via resistances of the two functional elements in the two directions of movement, dorsiflexion and plantar flexion. Prognosis Prognosis worsens with the severity of injury. Most TBIs are mild and do not cause permanent or long-term disability; however, all severity levels of TBI have the potential to cause significant, long-lasting disability. Permanent disability is thought to occur in 10% of mild injuries, 66% of moderate injuries, and 100% of severe injuries. Most mild TBI is completely resolved within three weeks. Almost all people with mild TBI are able to live independently and return to the jobs they had before the injury, although a small portion have mild cognitive and social impairments. Over 90% of people with moderate TBI are able to live independently, although some require assistance in areas such as physical abilities, employment, and financial managing. Most people with severe closed head injury either die or recover enough to live independently; middle ground is less common. Coma, as it is closely related to severity, is a strong predictor of poor outcome.Prognosis differs depending on the severity and location of the lesion, and access to immediate, specialised acute management. Subarachnoid hemorrhage approximately doubles mortality. Subdural hematoma is associated with worse outcome and increased mortality, while people with epidural hematoma are expected to have a good outcome if they receive surgery quickly. Diffuse axonal injury may be associated with coma when severe, and poor outcome. Following the acute stage, prognosis is strongly influenced by the patients involvement in activity that promote recovery, which for most patients requires access to a specialised, intensive rehabilitation service. The Functional Independence Measure is a way to track progress and degree of independence throughout rehabilitation.Medical complications are associated with a bad prognosis. Examples of such complications include: hypotension (low blood pressure), hypoxia (low blood oxygen saturation), lower cerebral perfusion pressures, and longer times spent with high intracranial pressures. Patient characteristics also influence prognosis. Examples of factors thought to worsen it include: abuse of substances such as illicit drugs and alcohol and age over sixty or under two years (in children, younger age at time of injury may be associated with a slower recovery of some abilities). Other influences that may affect recovery include pre-injury intellectual ability, coping strategies, personality traits, family environment, social support systems and financial circumstances.Life satisfaction has been known to decrease for individuals with TBI immediately following the trauma, but evidence has shown that life roles, age, and depressive symptoms influence the trajectory of life satisfaction as time passes. Many people with traumatic brain injuries have poor physical fitness following their acute injury and this may result with difficulties in day-to-day activities and increased levels of fatigue. Complications Improvement of neurological function usually occurs for two or more years after the trauma. For many years it was believed that recovery was fastest during the first six months, but there is no evidence to support this. It may be related to services commonly being withdrawn after this period, rather than any physiological limitation to further progress. Children recover better in the immediate time frame and improve for longer periods.Complications are distinct medical problems that may arise as a result of the TBI. The results of traumatic brain injury vary widely in type and duration; they include physical, cognitive, emotional, and behavioral complications. TBI can cause prolonged or permanent effects on consciousness, such as coma, brain death, persistent vegetative state (in which patients are unable to achieve a state of alertness to interact with their surroundings), and minimally conscious state (in which patients show minimal signs of being aware of self or environment). Lying still for long periods can cause complications including pressure sores, pneumonia or other infections, progressive multiple organ failure, and deep venous thrombosis, which can cause pulmonary embolism. Infections that can follow skull fractures and penetrating injuries include meningitis and abscesses. Complications involving the blood vessels include vasospasm, in which vessels constrict and restrict blood flow, the formation of aneurysms, in which the side of a vessel weakens and balloons out, and stroke.Movement disorders that may develop after TBI include tremor, ataxia (uncoordinated muscle movements), spasticity (muscle contractions are overactive), myoclonus (shock-like contractions of muscles), and loss of movement range and control (in particular with a loss of movement repertoire). The risk of post-traumatic seizures increases with severity of trauma (image at right) and is particularly elevated with certain types of brain trauma such as cerebral contusions or hematomas. People with early seizures, those occurring within a week of injury, have an increased risk of post-traumatic epilepsy (recurrent seizures occurring more than a week after the initial trauma). People may lose or experience altered vision, hearing, or smell.Hormonal disturbances may occur secondary to hypopituitarism, occurring immediately or years after injury in 10 to 15% of TBI patients. Development of diabetes insipidus or an electrolyte abnormality acutely after injury indicate need for endocrinologic work up. Signs and symptoms of hypopituitarism may develop and be screened for in adults with moderate TBI and in mild TBI with imaging abnormalities. Children with moderate to severe head injury may also develop hypopituitarism. Screening should take place 3 to 6 months, and 12 months after injury, but problems may occur more remotely.Cognitive deficits that can follow TBI include impaired attention; disrupted insight, judgement, and thought; reduced processing speed; distractibility; and deficits in executive functions such as abstract reasoning, planning, problem-solving, and multitasking. Memory loss, the most common cognitive impairment among head-injured people, occurs in 20–79% of people with closed head trauma, depending on severity. People who have had TBI may also have difficulty with understanding or producing spoken or written language, or with more subtle aspects of communication such as body language. Post-concussion syndrome, a set of lasting symptoms experienced after mild TBI, can include physical, cognitive, emotional and behavioral problems such as headaches, dizziness, difficulty concentrating, and depression. Multiple TBIs may have a cumulative effect. A young person who receives a second concussion before symptoms from another one have healed may be at risk for developing a very rare but deadly condition called second-impact syndrome, in which the brain swells catastrophically after even a mild blow, with debilitating or deadly results. About one in five career boxers is affected by chronic traumatic brain injury (CTBI), which causes cognitive, behavioral, and physical impairments. Dementia pugilistica, the severe form of CTBI, affects primarily career boxers years after a boxing career. It commonly manifests as dementia, memory problems, and parkinsonism (tremors and lack of coordination).TBI may cause emotional, social, or behavioral problems and changes in personality. These may include emotional instability, depression, anxiety, hypomania, mania, apathy, irritability, problems with social judgment, and impaired conversational skills. TBI appears to predispose survivors to psychiatric disorders including obsessive compulsive disorder, substance abuse, dysthymia, clinical depression, bipolar disorder, and anxiety disorders. In patients who have depression after TBI, suicidal ideation is not uncommon; the suicide rate among these persons is increased 2- to 3-fold. Social and behavioral symptoms that can follow TBI include disinhibition, inability to control anger, impulsiveness, lack of initiative, inappropriate sexual activity, asociality and social withdrawal, and changes in personality.TBI also has a substantial impact on the functioning of family systems Caregiving family members and TBI survivors often significantly alter their familial roles and responsibilities following injury, creating significant change and strain on a family system. Typical challenges identified by families recovering from TBI include: frustration and impatience with one another, loss of former lives and relationships, difficulty setting reasonable goals, inability to effectively solve problems as a family, increased level of stress and household tension, changes in emotional dynamics, and overwhelming desire to return to pre-injury status. In addition, families may exhibit less effective functioning in areas including coping, problem solving and communication. Psychoeducation and counseling models have been demonstrated to be effective in minimizing family disruption. Epidemiology TBI is a leading cause of death and disability around the globe and presents a major worldwide social, economic, and health problem. It is the number one cause of coma, it plays the leading role in disability due to trauma, and is the leading cause of brain damage in children and young adults. In Europe it is responsible for more years of disability than any other cause. It also plays a significant role in half of trauma deaths.Findings on the frequency of each level of severity vary based on the definitions and methods used in studies. A World Health Organization study estimated that between 70 and 90% of head injuries that receive treatment are mild, and a US study found that moderate and severe injuries each account for 10% of TBIs, with the rest mild.The incidence of TBI varies by age, gender, region and other factors. Findings of incidence and prevalence in epidemiological studies vary based on such factors as which grades of severity are included, whether deaths are included, whether the study is restricted to hospitalized people, and the studys location. The annual incidence of mild TBI is difficult to determine but may be 100–600 people per 100,000. Mortality In the US, the case fatality rate is estimated to be 21% by 30 days after TBI. A study on Iraq War soldiers found that severe TBI carries a mortality of 30–50%. Deaths have declined due to improved treatments and systems for managing trauma in societies wealthy enough to provide modern emergency and neurosurgical services. The fraction of those who die after being hospitalized with TBI fell from almost half in the 1970s to about a quarter at the beginning of the 21st century. This decline in mortality has led to a concomitant increase in the number of people living with disabilities that result from TBI.Biological, clinical, and demographic factors contribute to the likelihood that an injury will be fatal. In addition, outcome depends heavily on the cause of head injury. In the US, patients with fall-related TBIs have an 89% survival rate, while only 9% of patients with firearm-related TBIs survive. In the US, firearms are the most common cause of fatal TBI, followed by vehicle accidents and then falls. Of deaths from firearms, 75% are considered to be suicides.The incidence of TBI is increasing globally, due largely to an increase in motor vehicle use in low- and middle-income countries. In developing countries, automobile use has increased faster than safety infrastructure could be introduced. In contrast, vehicle safety laws have decreased rates of TBI in high-income countries, which have seen decreases in traffic-related TBI since the 1970s. Each year in the United States, about two million people have a TBI, approximately 675,000 injuries are seen in the emergency department, and about 500,000 patients are hospitalized. The yearly incidence of TBI is estimated at 180–250 per 100,000 people in the US, 281 per 100,000 in France, 361 per 100,000 in South Africa, 322 per 100,000 in Australia, and 430 per 100,000 in England. In the European Union the yearly aggregate incidence of TBI hospitalizations and fatalities is estimated at 235 per 100,000. Demographics TBI is present in 85% of traumatically injured children, either alone or with other injuries. The greatest number of TBIs occur in people aged 15–24. Because TBI is more common in young people, its costs to society are high due to the loss of productive years to death and disability. The age groups most at risk for TBI are children ages five to nine and adults over age 80, and the highest rates of death and hospitalization due to TBI are in people over age 65. The incidence of fall-related TBI in First-World countries is increasing as the population ages; thus the median age of people with head injuries has increased.Regardless of age, TBI rates are higher in males. Men have twice as many TBIs as women do and have a fourfold risk of fatal head injury, and males account for two thirds of childhood and adolescent head trauma. However, when matched for severity of injury, women appear to fare more poorly than men.Socioeconomic status also appears to affect TBI rates; people with lower levels of education and employment and lower socioeconomic status are at greater risk. Approximately half of those incarcerated in prisons and jails in the United States have had TBIs. History Head injury is present in ancient myths that may date back before recorded history. Skulls found in battleground graves with holes drilled over fracture lines suggest that trepanation may have been used to treat TBI in ancient times. Ancient Mesopotamians knew of head injury and some of its effects, including seizures, paralysis, and loss of sight, hearing or speech. The Edwin Smith Papyrus, written around 1650–1550 BC, describes various head injuries and symptoms and classifies them based on their presentation and tractability. Ancient Greek physicians including Hippocrates understood the brain to be the center of thought, probably due to their experience observing the effects of head trauma.Medieval and Renaissance surgeons continued the practice of trepanation for head injury. In the Middle Ages, physicians further described head injury symptoms and the term concussion became more widespread. Concussion symptoms were first described systematically in the 16th century by Berengario da Carpi.It was first suggested in the 18th century that intracranial pressure rather than skull damage was the cause of pathology after TBI. This hypothesis was confirmed around the end of the 19th century, and opening the skull to relieve pressure was then proposed as a treatment.In the 19th century it was noted that TBI is related to the development of psychosis. At that time a debate arose around whether post-concussion syndrome was due to a disturbance of the brain tissue or psychological factors. The debate continues today. Perhaps the first reported case of personality change after brain injury is that of Phineas Gage, who survived an accident in which a large iron rod was driven through his head, destroying one or both of his frontal lobes; numerous cases of personality change after brain injury have been reported since.The 20th century saw the advancement of technologies that improved treatment and diagnosis such as the development of imaging tools including CT and MRI, and, in the 21st century, diffusion tensor imaging (DTI). The introduction of intracranial pressure monitoring in the 1950s has been credited with beginning the "modern era" of head injury. Until the 20th century, the mortality rate of TBI was high and rehabilitation was uncommon; improvements in care made during World War I reduced the death rate and made rehabilitation possible. Facilities dedicated to TBI rehabilitation were probably first established during World War I. Explosives used in World War I caused many blast injuries; the large number of TBIs that resulted allowed researchers to learn about localization of brain functions. Blast-related injuries are now common problems in returning veterans from Iraq & Afghanistan; research shows that the symptoms of such TBIs are largely the same as those of TBIs involving a physical blow to the head.In the 1970s, awareness of TBI as a public health problem grew, and a great deal of progress has been made since then in brain trauma research, such as the discovery of primary and secondary brain injury. The 1990s saw the development and dissemination of standardized guidelines for treatment of TBI, with protocols for a range of issues such as drugs and management of intracranial pressure. Research since the early 1990s has improved TBI survival; that decade was known as the "Decade of the Brain" for advances made in brain research. Research directions Diagnosis Quantitative EEG and EEG, which has no specific patterns in TBI is used in research settings to differentiate between mild TBI and no TBI. Medications No medication is approved to halt the progression of the initial injury to secondary injury. The variety of pathological events presents opportunities to find treatments that interfere with the damage processes. Neuroprotection methods to decrease secondary injury, have been the subject of interest follows TBI. However, trials to test agents that could halt these cellular mechanisms have met largely with failure. For example, interest existed in cooling the injured brain; however, a 2020 Cochrane review did not find enough evidence to see if it was useful or not. Maintaining a normal temperature in the immediate period after a TBI appeared useful. One review found a lower than normal temperature was useful in adults but not children. While two other reviews found it did not appear to be useful.Further research is necessary to determine if the vasoconstrictor indomethacin (indometacin) can be used to treat increased pressure in the skull following a TBI.In addition, drugs such as NMDA receptor antagonists to halt neurochemical cascades such as excitotoxicity showed promise in animal trials but failed in clinical trials. These failures could be due to factors including faults in the trials design or in the insufficiency of a single agent to prevent the array of injury processes involved in secondary injury.Other topics of research have included investigations into mannitol, dexamethasone, progesterone, xenon, barbiturates, magnesium (no strong evidence), calcium channel blockers, PPAR-γ agonists, curcuminoids, ethanol, NMDA antagonists, caffeine. Procedures In addition to traditional imaging modalities, there are several devices that help to monitor brain injury and facilitate research. Microdialysis allows ongoing sampling of extracellular fluid for analysis of metabolites that might indicate ischemia or brain metabolism, such as glucose, glycerol, and glutamate. Intraparenchymal brain tissue oxygen monitoring systems (either Licox or Neurovent-PTO) are used routinely in neurointensive care in the US. A non invasive model called CerOx is in development.Research is also planned to clarify factors correlated to outcome in TBI and to determine in which cases it is best to perform CT scans and surgical procedures.Hyperbaric oxygen therapy (HBO) has been evaluated as an add on treatment following TBI. The findings of a 2012 Cochrane systematic review does not justify the routine use of hyperbaric oxygen therapy to treat people recovering from a traumatic brain injury. This review also reported that only a small number of randomized controlled trials had been conducted at the time of the review, many of which had methodological problems and poor reporting. HBO for TBI is controversial with further evidence required to determine if it has a role. Psychological Further research is required to determine the effectiveness of non-pharmacological treatment approaches for treating depression in children/adolescents and adults with TBI.As of 2010, the use of predictive visual tracking measurement to identify mild traumatic brain injury was being studied. In visual tracking tests, a head-mounted display unit with eye-tracking capability shows an object moving in a regular pattern. People without brain injury are able to track the moving object with smooth pursuit eye movements and correct trajectory. The test requires both attention and working memory which are difficult functions for people with mild traumatic brain injury. The question being studied, is whether results for people with brain injury will show visual-tracking gaze errors relative to the moving target. Monitoring pressure Pressure reactivity index is used to correlate intracranial pressure with arterial blood pressure to give information about the state of cerebral perfusion, thus guiding treatment and prevent excessively high or low blood flow to the brain. However, such method of monitoring intracranial pressure of equal or less than 20 mmHg is no better than imaging and clinical examination that monitor the neurological status of the brain in prolonging the survival, preserving the mental or functional status of the subject. Sensory processing In animal models of TBI, sensory processing has been widely studied to show systematic defects arise and are slowly but likely only partially recovered. It is especially characterised by an initial period of decreased activity in upper cortical layers. This period of decreased activity has also been characterised as by specific timing effects in the patterns of cortical activity in these upper layers in response to regular sensory stimuli. References Cited texts The original version of this article contained text from the NINDS public domain pages on TBI Archived December 18, 2016, at the Wayback Machine External links Brain injury at Curlie The Brain Injury Hub – information and practical advice to parents and family members of children with acquired brain injury Archived October 5, 2020, at the Wayback Machine Defense and Veterans Brain Injury Center – U.S. Department of Defense Military Health System center for traumatic brain injury Archived October 12, 2019, at the Wayback Machine

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

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

Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia and procedural sedation, and to treat severe agitation. It works by inducing sleepiness, decreasing anxiety, and causing a loss of ability to create new memories. The drug does not cause an individual to become unconscious, merely to be sedated. It is also useful for the treatment of prolonged (lasting over 5 minutes) seizures. Midazolam can be given by mouth, intravenously, by injection into a muscle, by spraying into the nose, or through the cheek. When given intravenously, it typically begins working within five minutes; when injected into a muscle, it can take fifteen minutes to begin working. Effects last between one and six hours. Side effects can include a decrease in efforts to breathe, low blood pressure, and sleepiness. Tolerance to its effects and withdrawal syndrome may occur following long-term use. Paradoxical effects, such as increased activity, can occur especially in children and older people. There is evidence of risk when used during pregnancy but no evidence of harm with a single dose during breastfeeding. It belongs to the benzodiazepine class of drugs and works by increasing the activity of the GABA neurotransmitter in the brain.Midazolam was patented in 1974 and came into medical use in 1982. It is on the World Health Organizations List of Essential Medicines. Midazolam is available as a generic medication. In many countries, it is a controlled substance. Medical uses Seizures Midazolam is sometimes used for the acute management of prolonged seizures. Long-term use for the management of epilepsy is not recommended due to the significant risk of tolerance (which renders midazolam and other benzodiazepines ineffective) and the significant side effect of sedation. A benefit of midazolam is that in children it can be given in the cheek or in the nose for acute seizures, including status epilepticus. Midazolam is effective for status epilepticus or when intravenous access cannot be obtained, and has advantages of being water-soluble, having a rapid onset of action and not causing metabolic acidosis from the propylene glycol vehicle (which is not required due to its solubility in water), which occurs with other benzodiazepines.Drawbacks include a high degree of breakthrough seizures—due to the short half-life of midazolam—in over 50% of people treated, as well as treatment failure in 14–18% of people with refractory status epilepticus. Tolerance develops rapidly to the anticonvulsant effect, and the dose may need to be increased by several times to maintain anticonvulsant therapeutic effects. With prolonged use, tolerance and tachyphylaxis can occur and the elimination half-life may increase, up to days. Buccal and intranasal midazolam may be both easier to administer and more effective than rectally administered diazepam in the emergency control of seizures. Procedural sedation Intravenous midazolam is indicated for procedural sedation (often in combination with an opioid, such as fentanyl), preoperative sedation, for the induction of general anesthesia, and for sedation of people who are ventilated in critical care units. Midazolam is superior to diazepam in impairing memory of endoscopy procedures, but propofol has a quicker recovery time and a better memory-impairing effect. It is the most popular benzodiazepine in the intensive care unit (ICU) because of its short elimination half-life, combined with its water solubility and its suitability for continuous infusion. However, for long-term sedation, lorazepam is preferred due to its long duration of action, and propofol has advantages over midazolam when used in the ICU for sedation, such as shorter weaning time and earlier tracheal extubation.Midazolam is sometimes used in neonatal intensive care units. When used, additional caution is required in newborns; midazolam should not be used for longer than 72 hours due to risks of tachyphylaxis, and the possibility of development of a benzodiazepine withdrawal syndrome, as well as neurological complications. Bolus injections should be avoided due to the increased risk of cardiovascular depression, as well as neurological complications. Midazolam is also sometimes used in newborns who are receiving mechanical ventilation, although morphine is preferred, owing to its better safety profile for this indication.Sedation using midazolam can be used to relieve anxiety and manage behaviour in children undergoing dental treatment. Agitation Midazolam, in combination with an antipsychotic drug, is indicated for the acute management of schizophrenia when it is associated with aggressive or out-of-control behaviour. End of life care In the final stages of end-of-life care, midazolam is routinely used at low doses via subcutaneous injection to help with agitation, restlessness or anxiety in the last hours or days of life. At higher doses during the last weeks of life, midazolam is considered a first line agent in palliative continuous deep sedation therapy when it is necessary to alleviate intolerable suffering not responsive to other treatments, but the need for this is rare. Administration Routes of administration of midazolam can be oral, intranasal, buccal, intravenous, and intramuscular. Contraindications Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, in alcohol- or other drug-dependent individuals or those with comorbid psychiatric disorders. Additional caution is required in critically ill patients, as accumulation of midazolam and its active metabolites may occur. Kidney or liver impairments may slow down the elimination of midazolam leading to prolonged and enhanced effects. Contraindications include hypersensitivity, acute narrow-angle glaucoma, shock, hypotension, or head injury. Most are relative contraindications. Side effects Side effects of midazolam in the elderly are listed above. People experiencing amnesia as a side effect of midazolam are generally unaware their memory is impaired, unless they had previously known it as a side effect.Long-term use of benzodiazepines has been associated with long-lasting deficits in memory, and show only partial recovery six months after stopping benzodiazepines. It is unclear whether full recovery occurs after longer periods of abstinence. Benzodiazepines can cause or worsen depression. Paradoxical excitement occasionally occurs with benzodiazepines, including a worsening of seizures. Children and elderly individuals or those with a history of excessive alcohol use and individuals with a history of aggressive behavior or anger are at increased risk of paradoxical effects. Paradoxical reactions are particularly associated with intravenous administration. After nighttime administration of midazolam, residual hangover effects, such as sleepiness and impaired psychomotor and cognitive functions, may persist into the next day. This may impair the ability of users to drive safely and may increase the risk of falls and hip fractures. Sedation, respiratory depression and hypotension due to a reduction in systematic vascular resistance, and an increase in heart rate can occur. If intravenous midazolam is given too quickly, hypotension may occur. A "midazolam infusion syndrome" may result from high doses, is characterised by delayed arousal hours to days after discontinuation of midazolam, and may lead to an increase in the length of ventilatory support needed.In rare susceptible individuals, midazolam has been known to cause a paradoxical reaction, a well-documented complication with benzodiazepines. When this occurs, the individual may experience anxiety, involuntary movements, aggressive or violent behavior, uncontrollable crying or verbalization, and other similar effects. This seems to be related to the altered state of consciousness or disinhibition produced by the drug. Paradoxical behavior is often not recalled by the patient due to the amnesia-producing properties of the drug. In extreme situations, flumazenil can be administered to inhibit or reverse the effects of midazolam. Antipsychotic medications, such as haloperidol, have also been used for this purpose.Midazolam is known to cause respiratory depression. In healthy humans, 0.15 mg/kg of midazolam may cause respiratory depression, which is postulated to be a central nervous system (CNS) effect. When midazolam is administered in combination with fentanyl, the incidence of hypoxemia or apnea becomes more likely.Although the incidence of respiratory depression/arrest is low (0.1–0.5%) when midazolam is administered alone at normal doses, the concomitant use with CNS acting drugs, mainly analgesic opiates, may increase the possibility of hypotension, respiratory depression, respiratory arrest, and death, even at therapeutic doses. Potential drug interactions involving at least one CNS depressant were observed for 84% of midazolam users who were subsequently required to receive the benzodiazepine antagonist flumazenil. Therefore, efforts directed toward monitoring drug interactions and preventing injuries from midazolam administration are expected to have a substantial impact on the safe use of this drug. Pregnancy and breastfeeding Midazolam, when taken during the third trimester of pregnancy, may cause risk to the neonate, including benzodiazepine withdrawal syndrome, with possible symptoms including hypotonia, apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Symptoms of hypotonia and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth. Other neonatal withdrawal symptoms include hyperexcitability, tremor, and gastrointestinal upset (diarrhea or vomiting). Breastfeeding by mothers using midazolam is not recommended. Elderly Additional caution is required in the elderly, as they are more sensitive to the pharmacological effects of benzodiazepines, metabolise them more slowly, and are more prone to adverse effects, including drowsiness, amnesia (especially anterograde amnesia), ataxia, hangover effects, confusion, and falls. Tolerance, dependence, and withdrawal A benzodiazepine dependence occurs in about one-third of individuals who are treated with benzodiazepines for longer than 4 weeks, which typically results in tolerance and benzodiazepine withdrawal syndrome when the dose is reduced too rapidly. Midazolam infusions may induce tolerance and a withdrawal syndrome in a matter of days. The risk factors for dependence include dependent personality, use of a benzodiazepine that is short-acting, high potency and long-term use of benzodiazepines. Withdrawal symptoms from midazolam can range from insomnia and anxiety to seizures and psychosis. Withdrawal symptoms can sometimes resemble a persons underlying condition. Gradual reduction of midazolam after regular use can minimise withdrawal and rebound effects. Tolerance and the resultant withdrawal syndrome may be due to receptor down-regulation and GABAA receptor alterations in gene expression, which causes long-term changes in the function of the GABAergic neuronal system.Chronic users of benzodiazepine medication who are given midazolam experience reduced therapeutic effects of midazolam, due to tolerance to benzodiazepines. Prolonged infusions with midazolam results in the development of tolerance; if midazolam is given for a few days or more a withdrawal syndrome can occur. Therefore, preventing a withdrawal syndrome requires that a prolonged infusion be gradually withdrawn, and sometimes, continued tapering of dose with an oral long-acting benzodiazepine such as clorazepate dipotassium. When signs of tolerance to midazolam occur during intensive care unit sedation the addition of an opioid or propofol is recommended. Withdrawal symptoms can include irritability, abnormal reflexes, tremors, clonus, hypertonicity, delirium and seizures, nausea, vomiting, diarrhea, tachycardia, hypertension, and tachypnea. In those with significant dependence, sudden discontinuation may result in withdrawal symptoms such as status epilepticus. Overdose A midazolam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. Benzodiazepine overdose in healthy individuals is rarely life-threatening with proper medical support; however, the toxicity of benzodiazepines increases when they are combined with other CNS depressants such as alcohol, opioids, or tricyclic antidepressants. The toxicity of benzodiazepine overdose and the risk of death are also increased in the elderly and those with obstructive pulmonary disease or when used intravenously. Treatment is supportive; activated charcoal can be used within an hour of the overdose. The antidote for an overdose of midazolam (or any other benzodiazepine) is flumazenil. While effective in reversing the effects of benzodiazepines it is not used in most cases as it may trigger seizures in mixed overdoses and benzodiazepine dependent individuals.Symptoms of midazolam overdose can include: Detection in body fluids Concentrations of midazolam or its major metabolite, 1-hydroxymidazolam glucuronide, may be measured in plasma, serum, or whole blood to monitor for safety in those receiving the drug therapeutically, to confirm a diagnosis of poisoning in hospitalized patients, or to assist in a forensic investigation of a case of fatal overdosage. Patients with renal dysfunction may exhibit prolongation of elimination half-life for both the parent drug and its active metabolite, with accumulation of these two substances in the bloodstream and the appearance of adverse depressant effects. Interactions Protease inhibitors, nefazodone, sertraline, grapefruit, fluoxetine, erythromycin, diltiazem, clarithromycin inhibit the metabolism of midazolam, leading to a prolonged action. St Johns wort, rifapentine, rifampin, rifabutin, phenytoin enhance the metabolism of midazolam leading to a reduced action. Sedating antidepressants, antiepileptic drugs such as phenobarbital, phenytoin and carbamazepine, sedative antihistamines, opioids, antipsychotics and alcohol enhance the sedative effects of midazolam. Midazolam is metabolized almost completely by cytochrome P450-3A4. Atorvastatin administration along with midazolam results in a reduced elimination rate of midazolam. St Johns wort decreases the blood levels of midazolam. Grapefruit juice reduces intestinal 3A4 and results in less metabolism and higher plasma concentrations. Pharmacology Midazolam is a short-acting benzodiazepine in adults with an elimination half-life of 1.5–2.5 hours. In the elderly, as well as young children and adolescents, the elimination half-life is longer. Midazolam is metabolised into an active metabolite alpha1-hydroxymidazolam. Age-related deficits, renal and liver status affect the pharmacokinetic factors of midazolam as well as its active metabolite. However, the active metabolite of midazolam is minor and contributes to only 10 percent of biological activity of midazolam. Midazolam is poorly absorbed orally, with only 50 percent of the drug reaching the bloodstream. Midazolam is metabolised by cytochrome P450 (CYP) enzymes and by glucuronide conjugation. The therapeutic as well as adverse effects of midazolam are due to its effects on the GABAA receptors; midazolam does not activate GABAA receptors directly but, as with other benzodiazepines, it enhances the effect of the neurotransmitter GABA on the GABAA receptors (↑ frequency of Cl− channel opening) resulting in neural inhibition. Almost all of the properties can be explained by the actions of benzodiazepines on GABAA receptors. This results in the following pharmacological properties being produced: sedation, induction of sleep, reduction in anxiety, anterograde amnesia, muscle relaxation and anticonvulsant effects. History Midazolam is among about 35 benzodiazepines currently used medically, and was synthesized in 1975 by Walser and Fryer at Hoffmann-LaRoche, Inc in the United States. Owing to its water solubility, it was found to be less likely to cause thrombophlebitis than similar drugs. The anticonvulsant properties of midazolam were studied in the late 1970s, but not until the 1990s did it emerge as an effective treatment for convulsive status epilepticus. As of 2010, it is the most commonly used benzodiazepine in anesthetic medicine. In acute medicine, midazolam has become more popular than other benzodiazepines, such as lorazepam and diazepam, because it is shorter lasting, is more potent, and causes less pain at the injection site. Midazolam is also becoming increasingly popular in veterinary medicine due to its water solubility. In 2018 it was revealed the CIA considered using Midazolam as a "truth serum" on terrorist suspects in project "Medication". Society and culture Cost Midazolam is available as a generic medication. Availability Midazolam is available in the United States as a syrup or as an injectable solution.Dormicum brand midazolam is marketed by Roche as white, oval, 7.5-mg tablets in boxes of two or three blister strips of 10 tablets, and as blue, oval, 15-mg tablets in boxes of two (Dormonid 3x) blister strips of 10 tablets. The tablets are imprinted with "Roche" on one side and the dose of the tablet on the other side. Dormicum is also available as 1-, 3-, and 10-ml ampoules at a concentration of 5 mg/ml. Another manufacturer, Novell Pharmaceutical Laboratories, makes it available as Miloz in 3- and 5-ml ampoules. Midazolam is the only water-soluble benzodiazepine available. Another maker is Roxane Laboratories; the product in an oral solution, Midazolam HCl Syrup, 2 mg/ml clear, in a red to purplish-red syrup, cherry in flavor. It becomes soluble when the injectable solution is buffered to a pH of 2.9–3.7. Midazolam is also available in liquid form. It can be administered intramuscularly, intravenously, intrathecally, intranasally, buccally, or orally. Legal status In the Netherlands, midazolam is a List II drug of the Opium Law. Midazolam is a Schedule IV drug under the Convention on Psychotropic Substances. In the United Kingdom, midazolam is a Schedule 3/Class C controlled drug. In the United States, midazolam (DEA number 2884) is on the Schedule IV list of the Controlled Substances Act as a non-narcotic agent with low potential for abuse. Marketing authorization In 2011, the European Medicines Agency (EMA) granted a marketing authorisation for a buccal application form of midazolam, sold under the brand name Buccolam. Buccolam was initially approved for the treatment of prolonged, acute, convulsive seizures in people from three months to less than 18 years of age. This was the first application of a paediatric-use marketing authorisation. Use in executions The drug has been introduced for use in executions by lethal injection in certain jurisdictions in the United States in combination with other drugs. It was introduced to replace pentobarbital after the latters manufacturer disallowed that drugs use for executions. Midazolam acts as a sedative but will fail to render the condemned prisoner unconscious, at which time vecuronium bromide and potassium chloride are administered, stopping the prisoners breathing and heart, respectively. Since the condemned prisoner is not unconscious but merely sedated, two very different things, those following two drugs can cause extreme pain and panic in the soon to die prisoner.Midazolam has been used as part of a three-drug cocktail, with vecuronium bromide and potassium chloride in Florida and Oklahoma prisons. Midazolam has also been used along with hydromorphone in a two-drug protocol in Ohio and Arizona.The usage of midazolam in executions became controversial after condemned inmate Clayton Lockett apparently regained consciousness and started speaking midway through his 2014 execution when the state of Oklahoma attempted to execute him with an untested three-drug lethal injection combination using 100 mg of midazolam. Prison officials reportedly discussed taking him to a hospital before he was pronounced dead of a heart attack 40 minutes after the execution began. An observing doctor stated that Locketts vein had ruptured. It is not clear whether his death was caused by one or more of the drugs or by a problem in the administration procedure, nor is it clear what quantities of vecuronium bromide and potassium chloride were released to his system before the execution was cancelled. Notable incidents The state of Florida used midazolam to execute William Frederick Happ in October 2013.The state of Ohio used midazolam in the execution of Dennis McGuire in January 2014; it took McGuire 24 minutes to die after the procedure started, and he gasped and appeared to be choking during that time, leading to questions about the dosing and timing of the drug administration, as well as the choice of drugs.The execution of Ronald Bert Smith in the state of Alabama on 8 December 2016, "went awry soon after (midazolam) was administered" again putting the effectiveness of the drug in question.In October 2016, the state of Ohio announced that it would resume executions in January 2017, using a formulation of midazolam, vecuronium bromide, and potassium chloride, but this was blocked by a Federal judge. On 26 July 2017, Ronald Phillips was executed with a three-drug cocktail including midazolam after the Supreme Court refused to grant a stay. Prior to this, the last execution in Ohio had been that of Dennis McGuire. Murderer Gary Ottes lawyers unsuccessfully challenged his Ohio execution, arguing that midazolam might not protect him from serious pain when the other drugs are administered. He died without incident in about 14 minutes on 13 September 2017.On 24 April 2017, the state of Arkansas carried out a double-execution of Jack Harold Jones, 52, and Marcel Williams, 46. The state of Arkansas attempted to execute eight people before its supply of midazolam expired on 30 April 2017. Two of them were granted a stay of execution, and another, Ledell T. Lee, 51, was executed on 20 April 2017.On 28 October 2021, the state of Oklahoma executed inmate John Marion Grant, 60, using midazolam as part of its three-drug cocktail hours after the U.S. Supreme Court ruled to lift a stay of execution for Oklahoma death row inmates. The execution was the states first since 2015. Witnesses to the execution said that when the first drug, midazolam, began to flow at 4:09 p.m., Grant started convulsing about two dozen times and vomited. Grant continued breathing, and a member of the execution team wiped the vomit off his face. At 4:15 p.m., officials said Grant was unconscious, and he was pronounced dead at 4:21 p.m. Legal challenges In Glossip v. Gross, attorneys for three Oklahoma inmates argued that midazolam could not achieve the level of unconsciousness required for surgery, meaning severe pain and suffering was likely. They argued that midazolam was cruel and unusual punishment and thus contrary to the Eighth Amendment to the United States Constitution. In June 2015, the U.S. Supreme Court ruled that they had failed to prove that midazolam was cruel and unusual when compared to known, available alternatives.The state of Nevada is also known to use midazolam in execution procedures. In July 2018, one of the manufacturers accused state officials of obtaining the medication under pretences. This incident was the first time a drug company successfully, though temporarily, halted an execution. A previous attempt in 2017, to halt an execution in the state of Arizona by another drug manufacturer was not successful. References External links "Midazolam". Drug Information Portal. U.S. National Library of Medicine. "Midazolam hydrochloride". Drug Information Portal. U.S. National Library of Medicine. Inchem - Midazolam

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'm trying to expand my medical knowledge. Can you elucidate the term 'Urticaria pigmentosa'?

Urticaria pigmentosa (also known as generalized eruption of cutaneous mastocytosis (childhood type): 616  ) is the most common form of cutaneous mastocytosis. It is a rare disease caused by excessive numbers of mast cells in the skin that produce hives or lesions on the skin when irritated. Signs and symptoms Urticaria pigmentosa is characterized by excessive amounts of mast cells in the skin. Red or brown spots are often seen on the skin, typically around the chest, forehead, and back. These mast cells, when irritated (e.g. by rubbing the skin, heat exposure), produce too much histamine, triggering an allergic reaction that leads to hives localized to the area of irritation, sometimes referred to as Dariers sign. Severe itching usually follows, and scratching the area only serves to further symptoms. Symptoms can be mild (flushing and hives that require no treatment), moderate (diarrhea, tachycardia, nausea/vomiting, headache, and fainting), or life-threatening (vascular collapse requiring emergency treatment and hospitalization). Cause The majority of urticaria pigmentosa cases are caused by a point mutation at amino acid 816 of the proto-oncogene c-kit. c-kit is a transmembrane protein which, when bound to Mast Cell Growth Factor (MCGF), signals the cell to divide. Mutations in position 816 of c-kit can result in a constant division signal being sent to the mast cells, resulting in abnormal proliferation. Different mutations have been linked to different onset times of the disease. For example, the Asp816Phe and Asp816Val mutations (the aspartate normally at position 816 in the c-kit protein has been replaced with phenylalanine or valine respectively) have been associated with early manifestation of the disease (mean age of onset: 1.3 and 5.9 months respectively). The c-kit gene is encoded on the q12 locus of chromosome 4. Irritants Several factors can worsen the symptoms of urticaria pigmentosa: Emotional stress Physical stimuli such as heat, friction, and excessive exercise Bacterial toxins Venom Eye drops containing dextran NSAIDs Alcohol MorphineThe classification of NSAIDs can be disputed. Aspirin, for example, causes the mast cells to degranulate, releasing histamines and causing symptoms to flare. However, daily intake of 81 mg aspirin may keep the mast cells degranulated. Thus, while symptoms may be worsened at first, they can get better as the mast cells are unable to recharge with histamine. Diagnosis The disease is most often diagnosed as an infant, when parents take their baby in for what appears to be bug bites. The bug bites are actually the clumps of mast cells. Doctors can confirm the presence of mast cells by rubbing the babys skin. If hives appear, it most likely signifies the presence of urticaria pigmentosa. Treatments There are no permanent cures for urticaria pigmentosa. However, treatments are possible. Most treatments for mastocytosis can be used to treat urticaria pigmentosa. Many common anti-allergy medications are useful because they reduce the mast cells ability to react to histamine.At least one clinical study suggested that nifedipine, a calcium channel blocker used to treat high blood pressure, may reduce mast cell degranulation in patients with urticaria pigmentosa. A 1984 study by Fairly et al. included a patient with symptomatic urticaria pigmentosa who responded to nifedipine at dose of 10 mg po tid. However, nifedipine has never been approved by the FDA for treatment of urticaria pigmentosa. Another mast cell stabilizer Gastrocrom, a form of cromoglicic acid has also been used to reduce mast cell degranulation. Epidemiology Urticaria pigmentosa is a rare disease, affecting fewer than 200,000 people in the United States. See also Urticaria Dermatographic urticaria Generalized eruption of cutaneous mastocytosis (adult type) References Further reading Alto WA, Clarcq L (June 1999). "Cutaneous and systemic manifestations of mastocytosis". Am Fam Physician. 59 (11): 3047–54, 3059–60. PMID 10392589. == External links ==

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.

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

In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. Myopathy means muscle disease (Greek : myo- muscle + patheia -pathy : suffering). This meaning implies that the primary defect is within the muscle, as opposed to the nerves ("neuropathies" or "neurogenic" disorders) or elsewhere (e.g., the brain). Muscle cramps, stiffness, and spasm can also be associated with myopathy. Capture myopathy can occur in wild or captive animals, such as deer and kangaroos, and leads to morbidity and mortality. It usually occurs as a result of stress and physical exertion during capture and restraint. Muscular disease can be classified as neuromuscular or musculoskeletal in nature. Some conditions, such as myositis, can be considered both neuromuscular and musculoskeletal. Signs and symptoms Common symptoms include muscle weakness, cramps, stiffness, and tetany. Systemic diseases Myopathies in systemic disease results from several different disease processes including endocrine, inflammatory, paraneoplastic, infectious, drug- and toxin-induced, critical illness myopathy, metabolic, collagen related, and myopathies with other systemic disorders. Patients with systemic myopathies often present acutely or sub acutely. On the other hand, familial myopathies or dystrophies generally present in a chronic fashion with exceptions of metabolic myopathies where symptoms on occasion can be precipitated acutely. Most of the inflammatory myopathies can have a chance association with malignant lesion; the incidence appears to be specifically increased only in patients with dermatomyositis.There are many types of myopathy. ICD-10 codes are provided here where available. Inherited forms (G71.0) Dystrophies (or muscular dystrophies) are a subgroup of myopathies characterized by muscle degeneration and regeneration. Clinically, muscular dystrophies are typically progressive, because the muscles ability to regenerate is eventually lost, leading to progressive weakness, often leading to use of a wheelchair, and eventually death, usually related to respiratory weakness. (G71.1) Myotonia Neuromyotonia (G71.2) The congenital myopathies do not show evidence for either a progressive dystrophic process (i.e., muscle death) or inflammation, but instead characteristic microscopic changes are seen in association with reduced contractile ability of the muscles. Congenital myopathies include, but are not limited to: (G71.2) nemaline myopathy (characterized by presence of "nemaline rods" in the muscle), (G71.2) multi/minicore myopathy (characterized by multiple small "cores" or areas of disruption in the muscle fibers), (G71.2) centronuclear myopathy (or myotubular myopathy) (in which the nuclei are abnormally found in the center of the muscle fibers), a rare muscle wasting disorder (G71.3) Mitochondrial myopathies, which are due to defects in mitochondria, which provide a critical source of energy for muscle (G72.3) Familial periodic paralysis (G72.4) Inflammatory myopathies, which are caused by problems with the immune system attacking components of the muscle, leading to signs of inflammation in the muscle (G73.6) Metabolic myopathies, which result from defects in biochemical metabolism that primarily affect muscle (G73.6/E74.0) Glycogen storage diseases, which may affect muscle (G73.6/E75) Lipid storage disorder (G72.89) Other myopathies Brody myopathy Congenital myopathy with abnormal subcellular organelles Fingerprint body myopathy Inclusion body myopathy 2 Megaconial myopathy Myofibrillar myopathy Rimmed vacuolar myopathy Acquired (G72.0 - G72.2) External substance induced myopathy (G72.0) Drug-induced myopathy Glucocorticoid myopathy is caused by this class of steroids increasing the breakdown of the muscle proteins leading to muscle atrophy. (G72.1) Alcoholic myopathy (G72.2) Myopathy due to other toxic agents - including atypical myopathy in horses caused by toxins in sycamore seeds and seedlings. (M33.0-M33.1) Dermatomyositis produces muscle weakness and skin changes. The skin rash is reddish and most commonly occurs on the face, especially around the eyes, and over the knuckles and elbows. Ragged nail folds with visible capillaries can be present. It can often be treated by drugs like corticosteroids or immunosuppressants. (M33.2) Polymyositis produces muscle weakness. It can often be treated by drugs like corticosteroids or immunosuppressants. Inclusion body myositis is a slowly progressive disease that produces weakness of hand grip and straightening of the knees. No effective treatment is known. (M61) Myositis ossificans (M62.89) Rhabdomyolysis and (R82.1) myoglobinuriasThe Food and Drug Administration is recommending that physicians restrict prescribing high-dose Simvastatin (Zocor, Merck) to patients, given an increased risk of muscle damage. The FDA drug safety communication stated that physicians should limit using the 80-mg dose unless the patient has already been taking the drug for 12 months and there is no evidence of myopathy. "Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug," the agency states. Statin-associated autoimmune myopathy Myocardium / cardio-myopathy (I40) Acute myocarditis (I41) Myocarditis in diseases classified elsewhere (I42) Cardiomyopathy (I42.0) Dilated cardiomyopathy (I42.1) Obstructive hypertrophy cardiomyopathy (I42.2) Other hypertrophic cardiomyopathy (I42.3) Endomyocardial (eosinophilic) disease Eosinophilic myocarditis Endomyocardial (tropical) fibrosis Löfflers endocarditis (I42.4) Endocardial fibroelastosis (I42.5) Other restrictive cardiomyopathy (I42.6) Alcoholic cardiomyopathy (I42.8) Other cardiomyopathies Arrhythmogenic right ventricular dysplasia (I43) Cardiomyopathy in diseases classified elsewhere Differential diagnosis At birth None as systemic causes; mainly hereditaryOnset in childhood Inflammatory myopathies – dermatomyositis, polymyositis (rarely) Infectious myopathies Endocrine and metabolic disorders – hypokalemia, hypocalcemia, hypercalcemiaOnset in adulthood Inflammatory myopathies – polymyositis, dermatomyositis, inclusion body myositis, viral (HIV) Infectious myopathies Endocrine myopathies – thyroid, parathyroid, adrenal, pituitary disorders Toxic myopathies – alcohol, corticosteroids, narcotics, colchicines, chloroquine Critical illness myopathy Metabolic myopathies Paraneoplastic myopathy Treatments Because different types of myopathies are caused by many different pathways, there is no single treatment for myopathy. Treatments range from treatment of the symptoms to very specific cause-targeting treatments. Drug therapy, physical therapy, bracing for support, surgery, and massage are all current treatments for a variety of myopathies. References External links GeneReviews/NCBI/NIH/UW entry on Myopathy with Deficiency of ISCU See http://neuromuscular.wustl.edu/ for medical descriptions.

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 'Azilsartan' as used in the medical field?

Azilsartan is an angiotensin II receptor antagonist used in the treatment of hypertension, developed by Takeda. It is marketed in tablet form under the brand name Edarbi as the prodrug azilsartan medoxomil.The most common adverse reaction in adults is diarrhea.It is also sold as a combination drug with chlortalidone under the brand name Edarbyclor. Structure activity relationship Like other ARBs, the Azilsartan group has an extended diphenyl group within the structure. An interesting aspect of the molecule is that unlike other ARBs which have a tetrazole attached to the molecule, Azilsartan has an oxadiazole, which has an acidic proton at the nitrogen. The tetraziole represents a non-classical bio-isostere. The carboxylate seen in the molecule is the active moiety after the molecule has been metabolized. Azilsartan is a pro-drug. Medical uses Azilsartan is used for the treatment of hypertension in adults. One of the benefits of the medication is that Azilsartan does not need dose adjustments for patients with renal or hepatic dysfunction. Contraindications Azilsartan must not be used with aliskiren, a renin inhibitor, in patients with diabetes as this increases the risk of serious adverse effects. Like other antihypertensive drugs acting on the renin–angiotensin system, it is contraindicated during the second and third trimesters of pregnancy. It should not be used during pregnancy in the United States. Interactions No relevant drug interactions have been found in studies. Based on experiences with other drugs acting on the renin–angiotensin system, it is theorized that azilsartan could increase the toxicity of lithium and of other drugs increasing potassium levels, such as potassium sparing diuretics. Pharmacology Mechanism of action Azilsartan medoxomil lowers blood pressure by blocking the action of angiotensin II at the AT1 receptor, a hormone that contracts blood vessels and reduces water excretion through the kidneys. Pharmacokinetics Azilsartan medoxomil is quickly absorbed from the gut, independently of food intake. Maximal blood plasma concentrations are reached after one to three hours. The liver enzyme CYP2C9 is involved in the formation of the two main metabolites, which are pharmacologically inactive; they are the O-deethylation and decarboxylation products of azilsartan. Elimination half life is about 11 hours. 55% are excreted via the feces, and 42% via the urine, of which 15% are present as azilsartan and the rest in form of the metabolites. Chemistry The drug formulation contains the potassium salt of azilsartan medoxomil (codenamed TAK-491), an ester of azilsartans carboxyl group with the alcohol (5-methyl-2-oxo-1,3-dioxol-4-yl)methanol. This ester is more lipophilic than azilsartan itself. History In February 2011, the U.S. Food and Drug Administration (FDA) approved azilsartan medoxomil for the treatment of high blood pressure in adults. In July 2011, azilsartan medoxomil was approved in the European Union for the treatment of essential hypertension. In March 2012, Health Canada approved the drug for mild to moderate essential hypertension.In December 2014, Valeant Canada acquired the marketing rights to Edarbi and Edarbyclor from Takeda Pharmaceutical. References External links "Azilsartan". Drug Information Portal. U.S. National Library of Medicine. "Azilsartan medoxomil". Drug Information Portal. 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.

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

Endemic goiter is a type of goitre that is associated with dietary iodine deficiency. Cause Some inland areas where soil and water lacks in iodine compounds and consumption of marine foods is low are known for higher incidence of goitre. In such areas goitre is said to be "endemic". Prevention This type of goiter is easily preventable. In most developed countries regulations have been put into force by health policy institutions requiring salt, flour or water to be fortified with iodine. Treatment Treatment of endemic goiter is medical with iodine and thyroxine preparations. Surgery is only necessary in cases where complicated by significant compression of nearby structures. 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 expand my medical knowledge. Can you elucidate the term 'Neorickettsia helminthoeca'?

Neorickettsia helminthoeca is a bacterium in the Neorickettsia genus that causes Salmon poisoning disease. Salmon poisoning disease Salmon poisoning disease (SPD) is a fatal disease of dogs and other canids caused by a rickettsial bacterium, Neorickettsia helminthoeca. It results from eating raw salmon, trout, or salamander and is common in the Pacific Northwest. These fish and amphibians are infected with the larvae of a fluke, Nanophyetus salmincola through an intermediate host, the snail Oxytrema plicifer. The larvae attaches to the intestine of the dog and the rickettsial bacteria are released, causing severe gastrointestinal disease and systemic infection. Neorickettsia elokominica, carried by the same fluke, causes a similar disease known as Elokomin fluke fever (EFF) in canids, bears, raccoons, and ferrets. Symptoms Symptoms of SPD begin about one week after eating the salmon and include vomiting, diarrhea, loss of appetite, depression, high fever, and enlarged lymph nodes. Untreated, mortality reaches 90 percent. Death occurs seven to ten days after symptoms begin.EFF has less severe symptoms than SPD, with less gastrointestinal signs and more lymph node involvement. The mortality in untreated cases is about 10 percent.A similar disease has been identified in Brazil. Diagnosis Diagnosis is through finding the fluke eggs microscopically in a stool sample. A needle aspiration biopsy of an enlarged lymph node will reveal rickettsial organisms within macrophages in many cases. The rickettsial infection can be successfully treated with tetracycline, and the fluke infection can be treated with fenbendazole. == References ==

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

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

An avalanche is a rapid flow of snow down a slope, such as a hill or mountain.Avalanches can be set off spontaneously, by such factors as increased precipitation or snowpack weakening, or by external means such as humans, animals, and earthquakes. Primarily composed of flowing snow and air, large avalanches have the capability to capture and move ice, rocks, and trees. Avalanches occur in two general forms, or combinations thereof: slab avalanches made of tightly packed snow, triggered by a collapse of an underlying weak snow layer, and loose snow avalanches made of looser snow. After being set off, avalanches usually accelerate rapidly and grow in mass and volume as they capture more snow. If an avalanche moves fast enough, some of the snow may mix with the air, forming a powder snow avalanche. Though they appear to share similarities, avalanches are distinct from slush flows, mudslides, rock slides, and serac collapses. They are also different from large scale movements of ice. Avalanches can happen in any mountain range that has an enduring snowpack. They are most frequent in winter or spring, but may occur at any time of year. In mountainous areas, avalanches are among the most serious natural hazards to life and property, so great efforts are made in avalanche control. There are many classification systems for the different forms of avalanches, which vary according to their users needs. Avalanches can be described by their size, destructive potential, initiation mechanism, composition, and dynamics. Formation Most avalanches occur spontaneously during storms under increased load due to snowfall and/or erosion. The second largest cause of natural avalanches is metamorphic changes in the snowpack such as melting due to solar radiation. Other natural causes include rain, earthquakes, rockfall and icefall. Artificial triggers of avalanches include skiers, snowmobiles, and controlled explosive work. Contrary to popular belief, avalanches are not triggered by loud sound; the pressure from sound is orders of magnitude too small to trigger an avalanche.Avalanche initiation can start at a point with only a small amount of snow moving initially; this is typical of wet snow avalanches or avalanches in dry unconsolidated snow. However, if the snow has sintered into a stiff slab overlying a weak layer then fractures can propagate very rapidly, so that a large volume of snow, that may be thousands of cubic metres, can start moving almost simultaneously. A snowpack will fail when the load exceeds the strength. The load is straightforward; it is the weight of the snow. However, the strength of the snowpack is much more difficult to determine and is extremely heterogeneous. It varies in detail with properties of the snow grains, size, density, morphology, temperature, water content; and the properties of the bonds between the grains. These properties may all metamorphose in time according to the local humidity, water vapour flux, temperature and heat flux. The top of the snowpack is also extensively influenced by incoming radiation and the local air flow. One of the aims of avalanche research is to develop and validate computer models that can describe the evolution of the seasonal snowpack over time. A complicating factor is the complex interaction of terrain and weather, which causes significant spatial and temporal variability of the depths, crystal forms, and layering of the seasonal snowpack. Slab avalanches Slab avalanches form frequently in snow that has been deposited, or redeposited by wind. They have the characteristic appearance of a block (slab) of snow cut out from its surroundings by fractures. Elements of slab avalanches include the following: a crown fracture at the top of the start zone, flank fractures on the sides of the start zones, and a fracture at the bottom called the stauchwall. The crown and flank fractures are vertical walls in the snow delineating the snow that was entrained in the avalanche from the snow that remained on the slope. Slabs can vary in thickness from a few centimetres to three metres. Slab avalanches account for around 90% of avalanche-related fatalities in backcountry users. Powder snow avalanches The largest avalanches form turbulent suspension currents known as powder snow avalanches or mixed avalanches, a kind of gravity current. These consist of a powder cloud, which overlies a dense avalanche. They can form from any type of snow or initiation mechanism, but usually occur with fresh dry powder. They can exceed speeds of 300 km/h (190 mph), and masses of 10,000,000 tonnes; their flows can travel long distances along flat valley bottoms and even uphill for short distances. Wet snow avalanches In contrast to powder snow avalanches, wet snow avalanches are a low velocity suspension of snow and water, with the flow confined to the track surface (McClung, first edition 1999, page 108). The low speed of travel is due to the friction between the sliding surface of the track and the water saturated flow. Despite the low speed of travel (≈10–40 km/h), wet snow avalanches are capable of generating powerful destructive forces, due to the large mass and density. The body of the flow of a wet snow avalanche can plough through soft snow, and can scour boulders, earth, trees, and other vegetation; leaving exposed and often scored ground in the avalanche track. Wet snow avalanches can be initiated from either loose snow releases, or slab releases, and only occur in snowpacks that are water saturated and isothermally equilibrated to the melting point of water. The isothermal characteristic of wet snow avalanches has led to the secondary term of isothermal slides found in the literature (for example in Daffern, 1999, page 93). At temperate latitudes wet snow avalanches are frequently associated with climatic avalanche cycles at the end of the winter season, when there is significant daytime warming. Ice avalanche An ice avalanche occurs when a large piece of ice, such as from a serac or calving glacier, falls onto ice (such as the Khumbu Icefall), triggering a movement of broken ice chunks. The resulting movement is more analogous to a rockfall or a landslide than a snow avalanche. They are typically very difficult to predict and almost impossible to mitigate. Avalanche pathway As an avalanche moves down a slope it follows a certain pathway that is dependent on the slopes degree of steepness and the volume of snow/ice involved in the mass movement. The origin of an avalanche is called the Starting Point and typically occurs on a 30–45 degree slope. The body of the pathway is called the Track of the avalanche and usually occurs on a 20–30 degree slope. When the avalanche loses its momentum and eventually stops it reaches the Runout Zone. This usually occurs when the slope has reached a steepness that is less than 20 degrees. These degrees are not consistently true due to the fact that each avalanche is unique depending on the stability of the snowpack that it was derived from as well as the environmental or human influences that triggered the mass movement. Injuries and deaths People caught in avalanches can die from suffocation, trauma, or hypothermia. From "1950 - 1951 to 2020 - 2021" there were 1,169 people who died in avalanches in the United states. For the 11-year period ending April 2006 445 people died in avalanches throughout North America. On average, 28 people die in avalanches every winter in the United States.In 2001 it was reported that globally an average of 150 people die each year from avalanches. Three of the deadliest recorded avalanches have killed over a thousand people each. Terrain, snowpack, weather Doug Fesler and Jill Fredston developed a conceptual model of the three primary elements of avalanches: terrain, weather, and snowpack. Terrain describes the places where avalanches occur, weather describes the meteorological conditions that create the snowpack, and snowpack describes the structural characteristics of snow that make avalanche formation possible. Terrain Avalanche formation requires a slope shallow enough for snow to accumulate but steep enough for the snow to accelerate once set in motion by the combination of mechanical failure (of the snowpack) and gravity. The angle of the slope that can hold snow, called the angle of repose, depends on a variety of factors such as crystal form and moisture content. Some forms of drier and colder snow will only stick to shallower slopes, while wet and warm snow can bond to very steep surfaces. In particular, in coastal mountains, such as the Cordillera del Paine region of Patagonia, deep snowpacks collect on vertical and even overhanging rock faces. The slope angle that can allow moving snow to accelerate depends on a variety of factors such as the snows shear strength (which is itself dependent upon crystal form) and the configuration of layers and inter-layer interfaces. The snowpack on slopes with sunny exposures is strongly influenced by sunshine. Diurnal cycles of thawing and refreezing can stabilize the snowpack by promoting settlement. Strong freeze-thaw cycles result in the formation of surface crusts during the night and of unstable surface snow during the day. Slopes in the lee of a ridge or of another wind obstacle accumulate more snow and are more likely to include pockets of deep snow, wind slabs, and cornices, all of which, when disturbed, may result in avalanche formation. Conversely, the snowpack on a windward slope is often much shallower than on a lee slope. Avalanches and avalanche paths share common elements: a start zone where the avalanche originates, a track along which the avalanche flows, and a runout zone where the avalanche comes to rest. The debris deposit is the accumulated mass of the avalanched snow once it has come to rest in the run-out zone. For the image at left, many small avalanches form in this avalanche path every year, but most of these avalanches do not run the full vertical or horizontal length of the path. The frequency with which avalanches form in a given area is known as the return period. The start zone of an avalanche must be steep enough to allow snow to accelerate once set in motion, additionally convex slopes are less stable than concave slopes, because of the disparity between the tensile strength of snow layers and their compressive strength. The composition and structure of the ground surface beneath the snowpack influences the stability of the snowpack, either being a source of strength or weakness. Avalanches are unlikely to form in very thick forests, but boulders and sparsely distributed vegetation can create weak areas deep within the snowpack through the formation of strong temperature gradients. Full-depth avalanches (avalanches that sweep a slope virtually clean of snow cover) are more common on slopes with smooth ground, such as grass or rock slabs. Generally speaking, avalanches follow drainages down-slope, frequently sharing drainage features with summertime watersheds. At and below tree line, avalanche paths through drainages are well defined by vegetation boundaries called trim lines, which occur where avalanches have removed trees and prevented regrowth of large vegetation. Engineered drainages, such as the avalanche dam on Mount Stephen in Kicking Horse Pass, have been constructed to protect people and property by redirecting the flow of avalanches. Deep debris deposits from avalanches will collect in catchments at the terminus of a run out, such as gullies and river beds. Slopes flatter than 25 degrees or steeper than 60 degrees typically have a lower incidence of avalanches. Human-triggered avalanches have the greatest incidence when the snows angle of repose is between 35 and 45 degrees; the critical angle, the angle at which human-triggered avalanches are most frequent, is 38 degrees. When the incidence of human triggered avalanches is normalized by the rates of recreational use, however, hazard increases uniformly with slope angle, and no significant difference in hazard for a given exposure direction can be found. The rule of thumb is: A slope that is flat enough to hold snow but steep enough to ski has the potential to generate an avalanche, regardless of the angle. Snowpack structure and characteristics The snowpack is composed of ground-parallel layers that accumulate over the winter. Each layer contains ice grains that are representative of the distinct meteorological conditions during which the snow formed and was deposited. Once deposited, a snow layer continues to evolve under the influence of the meteorological conditions that prevail after deposition. For an avalanche to occur, it is necessary that a snowpack have a weak layer (or instability) below a slab of cohesive snow. In practice the formal mechanical and structural factors related to snowpack instability are not directly observable outside of laboratories, thus the more easily observed properties of the snow layers (e.g. penetration resistance, grain size, grain type, temperature) are used as index measurements of the mechanical properties of the snow (e.g. tensile strength, friction coefficients, shear strength, and ductile strength). This results in two principal sources of uncertainty in determining snowpack stability based on snow structure: First, both the factors influencing snow stability and the specific characteristics of the snowpack vary widely within small areas and time scales, resulting in significant difficulty extrapolating point observations of snow layers across different scales of space and time. Second, the relationship between readily observable snowpack characteristics and the snowpacks critical mechanical properties has not been completely developed. While the deterministic relationship between snowpack characteristics and snowpack stability is still a matter of ongoing scientific study, there is a growing empirical understanding of the snow composition and deposition characteristics that influence the likelihood of an avalanche. Observation and experience has shown that newly fallen snow requires time to bond with the snow layers beneath it, especially if the new snow falls during very cold and dry conditions. If ambient air temperatures are cold enough, shallow snow above or around boulders, plants, and other discontinuities in the slope, weakens from rapid crystal growth that occurs in the presence of a critical temperature gradient. Large, angular snow crystals are indicators of weak snow, because such crystals have fewer bonds per unit volume than small, rounded crystals that pack tightly together. Consolidated snow is less likely to slough than loose powdery layers or wet isothermal snow; however, consolidated snow is a necessary condition for the occurrence of slab avalanches, and persistent instabilities within the snowpack can hide below well-consolidated surface layers. Uncertainty associated with the empirical understanding of the factors influencing snow stability leads most professional avalanche workers to recommend conservative use of avalanche terrain relative to current snowpack instability. Weather Avalanches only occur in a standing diksnowpack. Typically winter seasons at high latitudes, high altitudes, or both have weather that is sufficiently unsettled and cold enough for precipitated snow to accumulate into a seasonal snowpack. Continentality, through its potentiating influence on the meteorological extremes experienced by snowpacks, is an important factor in the evolution of instabilities, and consequential occurrence of avalanches faster stabilization of the snowpack after storm cycles. The evolution of the snowpack is critically sensitive to small variations within the narrow range of meteorological conditions that allow for the accumulation of snow into a snowpack. Among the critical factors controlling snowpack evolution are: heating by the sun, radiational cooling, vertical temperature gradients in standing snow, snowfall amounts, and snow types. Generally, mild winter weather will promote the settlement and stabilization of the snowpack; conversely, very cold, windy, or hot weather will weaken the snowpack. At temperatures close to the freezing point of water, or during times of moderate solar radiation, a gentle freeze-thaw cycle will take place. The melting and refreezing of water in the snow strengthens the snowpack during the freezing phase and weakens it during the thawing phase. A rapid rise in temperature, to a point significantly above the freezing point of water, may cause avalanche formation at any time of year. Persistent cold temperatures can either prevent new snow from stabilizing or destabilize the existing snowpack. Cold air temperatures on the snow surface produce a temperature gradient in the snow, because the ground temperature at the base of the snowpack is usually around 0 °C, and the ambient air temperature can be much colder. When a temperature gradient greater than 10 °C change per vertical meter of snow is sustained for more than a day, angular crystals called depth hoar or facets begin forming in the snowpack because of rapid moisture transport along the temperature gradient. These angular crystals, which bond poorly to one another and the surrounding snow, often become a persistent weakness in the snowpack. When a slab lying on top of a persistent weakness is loaded by a force greater than the strength of the slab and persistent weak layer, the persistent weak layer can fail and generate an avalanche. Any wind stronger than a light breeze can contribute to a rapid accumulation of snow on sheltered slopes downwind. Wind slabs form quickly and, if present, weaker snow below the slab may not have time to adjust to the new load. Even on a clear day, wind can quickly load a slope with snow by blowing snow from one place to another. Top-loading occurs when wind deposits snow from the top of a slope; cross-loading occurs when wind deposits snow parallel to the slope. When a wind blows over the top of a mountain, the leeward, or downwind, side of the mountain experiences top-loading, from the top to the bottom of that lee slope. When the wind blows across a ridge that leads up the mountain, the leeward side of the ridge is subject to cross-loading. Cross-loaded wind-slabs are usually difficult to identify visually. Snowstorms and rainstorms are important contributors to avalanche danger. Heavy snowfall will cause instability in the existing snowpack, both because of the additional weight and because the new snow has insufficient time to bond to underlying snow layers. Rain has a similar effect. In the short-term, rain causes instability because, like a heavy snowfall, it imposes an additional load on the snowpack; and, once rainwater seeps down through the snow, it acts as a lubricant, reducing the natural friction between snow layers that holds the snowpack together. Most avalanches happen during or soon after a storm. Daytime exposure to sunlight will rapidly destabilize the upper layers of the snowpack if the sunlight is strong enough to melt the snow, thereby reducing its hardness. During clear nights, the snowpack can re-freeze when ambient air temperatures fall below freezing, through the process of long-wave radiative cooling, or both. Radiative heat loss occurs when the night air is significantly cooler than the snowpack, and the heat stored in the snow is re-radiated into the atmosphere. Dynamics When a slab avalanche forms, the slab disintegrates into increasingly smaller fragments as the snow travels downhill. If the fragments become small enough the outer layer of the avalanche, called a saltation layer, takes on the characteristics of a fluid. When sufficiently fine particles are present they can become airborne and, given a sufficient quantity of airborne snow, this portion of the avalanche can become separated from the bulk of the avalanche and travel a greater distance as a powder snow avalanche. Scientific studies using radar, following the 1999 Galtür avalanche disaster, confirmed the hypothesis that a saltation layer forms between the surface and the airborne components of an avalanche, which can also separate from the bulk of the avalanche.Driving an avalanche is the component of the avalanches weight parallel to the slope; as the avalanche progresses any unstable snow in its path will tend to become incorporated, so increasing the overall weight. This force will increase as the steepness of the slope increases, and diminish as the slope flattens. Resisting this are a number of components that are thought to interact with each other: the friction between the avalanche and the surface beneath; friction between the air and snow within the fluid; fluid-dynamic drag at the leading edge of the avalanche; shear resistance between the avalanche and the air through which it is passing, and shear resistance between the fragments within the avalanche itself. An avalanche will continue to accelerate until the resistance exceeds the forward force. Modelling Attempts to model avalanche behaviour date from the early 20th century, notably the work of Professor Lagotala in preparation for the 1924 Winter Olympics in Chamonix. His method was developed by A. Voellmy and popularised following the publication in 1955 of his Ueber die Zerstoerungskraft von Lawinen (On the Destructive Force of Avalanches).Voellmy used a simple empirical formula, treating an avalanche as a sliding block of snow moving with a drag force that was proportional to the square of the speed of its flow: Pref = 1 2 ρ v 2 {\displaystyle {\textrm {Pref}}={\frac {1}{2}}\,{\rho }\,{v^{2}}\,\!} He and others subsequently derived other formulae that take other factors into account, with the Voellmy-Salm-Gubler and the Perla-Cheng-McClung models becoming most widely used as simple tools to model flowing (as opposed to powder snow) avalanches.Since the 1990s many more sophisticated models have been developed. In Europe much of the recent work was carried out as part of the SATSIE (Avalanche Studies and Model Validation in Europe) research project supported by the European Commission which produced the leading-edge MN2L model, now in use with the Service Restauration des Terrains en Montagne (Mountain Rescue Service) in France, and D2FRAM (Dynamical Two-Flow-Regime Avalanche Model), which was still undergoing validation as of 2007. Other known models are the SAMOS-AT avalanche simulation software and the RAMMS software. Human involvement Prevention Preventative measures are employed in areas where avalanches pose a significant threat to people, such as ski resorts, mountain towns, roads, and railways. There are several ways to prevent avalanches and lessen their power and develop preventative measures to reduce the likelihood and size of avalanches by disrupting the structure of the snowpack, while passive measures reinforce and stabilize the snowpack in situ. The simplest active measure is repeatedly traveling on a snowpack as snow accumulates; this can be by means of boot-packing, ski-cutting, or machine grooming. Explosives are used extensively to prevent avalanches, by triggering smaller avalanches that break down instabilities in the snowpack, and removing overburden that can result in larger avalanches. Explosive charges are delivered by a number of methods including hand-tossed charges, helicopter-dropped bombs, Gazex concussion lines, and ballistic projectiles launched by air cannons and artillery. Passive preventive systems such as snow fences and light walls can be used to direct the placement of snow. Snow builds up around the fence, especially the side that faces the prevailing winds. Downwind of the fence, snow build-up is lessened. This is caused by the loss of snow at the fence that would have been deposited and the pickup of the snow that is already there by the wind, which was depleted of snow at the fence. When there is a sufficient density of trees, they can greatly reduce the strength of avalanches. They hold snow in place and when there is an avalanche, the impact of the snow against the trees slows it down. Trees can either be planted or they can be conserved, such as in the building of a ski resort, to reduce the strength of avalanches. In turn, socio-environmental changes can influence the occurrence of damaging avalanches: some studies linking changes in land-use/land-cover patterns and the evolution of snow avalanche damage in mid latitude mountains show the importance of the role played by vegetation cover, that is at the root of the increase of damage when the protective forest is deforested (because of demographic growth, intensive grazing and industrial or legal causes), and at the root of the decrease of damage because of the transformation of a traditional land-management system based on overexploitation into a system based on land marginalization and reforestation, something that has happened mainly since the mid-20th century in mountain environments of developed countries Mitigation In many areas, regular avalanche tracks can be identified and precautions can be taken to minimize damage, such as the prevention of development in these areas. To mitigate the effect of avalanches the construction of artificial barriers can be very effective in reducing avalanche damage. There are several types: One kind of barrier (snow net) uses a net strung between poles that are anchored by guy wires in addition to their foundations. These barriers are similar to those used for rockslides. Another type of barrier is a rigid fence-like structure (snow fence) and may be constructed of steel, wood or pre-stressed concrete. They usually have gaps between the beams and are built perpendicular to the slope, with reinforcing beams on the downhill side. Rigid barriers are often considered unsightly, especially when many rows must be built. They are also expensive and vulnerable to damage from falling rocks in the warmer months. In addition to industrially manufactured barriers, landscaped barriers, called avalanche dams stop or deflect avalanches with their weight and strength. These barriers are made out of concrete, rocks, or earth. They are usually placed right above the structure, road, or railway that they are trying to protect, although they can also be used to channel avalanches into other barriers. Occasionally, earth mounds are placed in the avalanches path to slow it down. Finally, along transportation corridors, large shelters, called snow sheds, can be built directly in the slide path of an avalanche to protect traffic from avalanches. Early warning systems Warning systems can detect avalanches which develop slowly, such as ice avalanches caused by icefalls from glaciers. Interferometric radars, high-resolution cameras, or motion sensors can monitor instable areas over a long term, lasting from days to years. Experts interpret the recorded data and are able to recognize upcoming ruptures in order to initiate appropriate measures. Such systems (e.g. the monitoring of the Weissmies glacier in Switzerland) can recognize events several days in advance. Alarm systems Modern radar technology enables the monitoring of large areas and the localization of avalanches at any weather condition, by day and by night. Complex alarm systems are able to detect avalanches within a short time in order to close (e.g. roads and rails) or evacuate (e.g. construction sites) endangered areas. An example of such a system is installed on the only access road of Zermatt in Switzerland. Two radars monitor the slope of a mountain above the road. The system automatically closes the road by activating several barriers and traffic lights within seconds such that no people are harmed. Survival, rescue, and recovery Avalanche accidents are broadly differentiated into 2 categories: accidents in recreational settings, and accidents in residential, industrial, and transportation settings. This distinction is motivated by the observed difference in the causes of avalanche accidents in the two settings. In the recreational setting most accidents are caused by the people involved in the avalanche. In a 1996 study, Jamieson et al. (pages 7–20) found that 83% of all avalanches in the recreational setting were caused by those who were involved in the accident. In contrast, all of the accidents in the residential, industrial, and transportation settings were due to spontaneous natural avalanches. Because of the difference in the causes of avalanche accidents, and the activities pursued in the two settings, avalanche and disaster management professionals have developed two related preparedness, rescue, and recovery strategies for each of the settings. Notable avalanches Two avalanches occurred in March 1910 in the Cascade and Selkirk Mountain ranges; On 1 March the Wellington avalanche killed 96 in Washington state, United States. Three days later 62 railroad workers were killed in the Rogers Pass avalanche in British Columbia, Canada. During World War I, an estimated 40,000 to 80,000 soldiers died as a result of avalanches during the mountain campaign in the Alps at the Austrian-Italian front, many of which were caused by artillery fire. Some 10,000 men, from both sides, lost their lives in avalanches in December 1916.In the northern hemisphere winter of 1950–1951 approximately 649 avalanches were recorded in a three-month period throughout the Alps in Austria, France, Switzerland, Italy and Germany. This series of avalanches killed around 265 people and was termed the Winter of Terror. A mountain climbing camp on Lenin Peak, in what is now Kyrgyzstan, was wiped out in 1990 when an earthquake triggered a large avalanche that overran the camp. Forty-three climbers were killed.In 1993, the Bayburt Üzengili avalanche killed 60 individuals in Üzengili in the province of Bayburt, Turkey. A large avalanche in Montroc, France, in 1999, 300,000 cubic metres of snow slid on a 30° slope, achieving a speed in the region of 100 km/h (62 mph). It killed 12 people in their chalets under 100,000 tons of snow, 5 meters (16 feet) deep. The mayor of Chamonix was convicted of second-degree murder for not evacuating the area, but received a suspended sentence.The small Austrian village of Galtür was hit by the Galtür avalanche in 1999. The village was thought to be in a safe zone but the avalanche was exceptionally large and flowed into the village. Thirty-one people died. On 1 December 2000, the Glory Bowl Avalanche formed on Mt. Glory which is located within the Teton Mountain Range in Wyoming, United States. Joel Roof was snowboarding recreationally in this backcountry, bowl-shaped run and triggered the avalanche. He was carried nearly 2,000 feet to the base of the mountain and was not successfully rescued. Classification European avalanche risk In Europe, the avalanche risk is widely rated on the following scale, which was adopted in April 1993 to replace the earlier non-standard national schemes. Descriptions were last updated in May 2003 to enhance uniformity.In France, most avalanche deaths occur at risk levels 3 and 4. In Switzerland most occur at levels 2 and 3. It is thought that this may be due to national differences of interpretation when assessing the risks. [1] Stability: Generally described in more detail in the avalanche bulletin (regarding the altitude, aspect, type of terrain etc.)[2] additional load: heavy: two or more skiers or boarders without spacing between them, a single hiker or climber, a grooming machine, avalanche blasting light: a single skier or snowboarder smoothly linking turns and without falling, a group of skiers or snowboarders with a minimum 10 m gap between each person, a single person on snowshoesGradient: gentle slopes: with an incline below about 30° steep slopes: with an incline over 30° very steep slopes: with an incline over 35° extremely steep slopes: extreme in terms of the incline (over 40°), the terrain profile, proximity of the ridge, smoothness of underlying ground European avalanche size table Avalanche size: North American Avalanche Danger Scale In the United States and Canada, the following avalanche danger scale is used. Descriptors vary depending on country. Avalanche Problems There are nine different types of avalanche problems: Storm slab Wind slab Wet slab avalanches Persistent slab Deep persistent slab Loose dry avalanches Loose wet avalanches Glide avalanches Cornice fall Canadian classification for avalanche size The Canadian classification for avalanche size is based upon the consequences of the avalanche. Half sizes are commonly used. United States classification for avalanche size The size of avalanches are classified using two scales; size relative to destructive force or D-scale and size relative to the avalanche path or R-scale. Both size scales range from 1 to 5 with the D size scale half sizes can be used. Rutschblock Test Slab avalanche hazard analysis can be done using the Rutschblock Test. A 2 m wide block of snow is isolated from the rest of the slope and progressively loaded. The result is a rating of slope stability on a seven step scale. (Rutsch means slide in German). Avalanches and climate change Avalanche formation and frequency is highly affected by weather patterns and the local climate. Snowpack layers will form differently depending on whether snow is falling in very cold or very warm conditions, and very dry or very humid conditions. Thus, climate change may affect when, where, and how often avalanches occur, and may also change the type of avalanches that are occurring. Impacts on avalanche type and frequency Overall, a rising seasonal snow line and a decrease in the number of days with snow cover are predicted. Climate change-caused temperature increases and changes in precipitation patterns will likely differ between the different mountain regions, and the impacts of these changes on avalanches will change at different elevations. In the long term, avalanche frequency at lower elevations is expected to decline corresponding to a decrease in snow cover and depth, and a short-term increase in the number of wet avalanches are predicted.Precipitation is expected to increase, meaning more snow or rain depending on the elevation. Higher elevations predicted to remain above the seasonal snow line will likely see an increase in avalanche activity due to the increases in precipitation during the winter season. Storm precipitation intensity is also expected to increase, which is likely to lead to more days with enough snowfall to cause the snowpack to become unstable. Moderate and high elevations may see an increase in volatile swings from one weather extreme to the other. Predictions also show an increase in the number of rain on snow events, and wet avalanche cycles occurring earlier in the spring during the remainder of this century. Impacts on burial survival rate The warm, wet snowpacks that are likely to increase in frequency due to climate change may also make avalanche burials more deadly. Warm snow has a higher moisture content and is therefore denser than colder snow. Denser avalanche debris decreases the ability for a buried person to breath and the amount of time they have before they run out of oxygen. This increases the likelihood of death by asphyxia in the event of a burial. Additionally, the predicted thinner snowpacks may increase the frequency of injuries due to trauma, such as a buried skier striking a rock or tree. Avalanches on the planet Mars See also Related flows Avalanche disasters 1999 Galtür avalanche Montroc 2012 Gayari Sector avalanche References Bibliography McClung, David. Snow Avalanches as a Non-critical, Punctuated Equilibrium System: Chapter 24 in Nonlinear Dynamics in Geosciences, A.A. Tsonsis and J.B. Elsner (Eds.), Springer, 2007 Daffern, Tony: Avalanche Safety for Skiers, Climbers and Snowboarders, Rocky Mountain Books, 1999, ISBN 0-921102-72-0 Billman, John: Mike Elggren on Surviving an Avalanche. Skiing magazine February 2007: 26. McClung, David and Shaerer, Peter: The Avalanche Handbook, The Mountaineers: 2006. 978-0-89886-809-8 Tremper, Bruce: Staying Alive in Avalanche Terrain, The Mountaineers: 2001. ISBN 0-89886-834-3 Munter, Werner: Drei mal drei (3x3) Lawinen. Risikomanagement im Wintersport, Bergverlag Rother, 2002. ISBN 3-7633-2060-1 (in German) (partial English translation included in PowderGuide: Managing Avalanche Risk ISBN 0-9724827-3-3) Michael Falser: Historische Lawinenschutzlandschaften: eine Aufgabe für die Kulturlandschafts- und Denkmalpflege In: kunsttexte 3/2010, unter: Historische Lawinenschutzlandschaften: eine Aufgabe für die Kulturlandschafts- und Denkmalpflege Notes External links Media related to Avalanche chute at Wikimedia Commons The Avalanche Education Project Surviving an Avalanche – A guide for children and youth Avalanche Defense Photographs Avalanche Canada Canadian Avalanche Association Archived 21 October 2020 at the Wayback Machine Colorado Avalanche Information Center Center for Snow and Avalanche Studies EAWS – European Avalanche Warning Services Directory of European avalanche services Avalanches collected news and commentary at The New York Times Swiss Federal Institute for Snow and Avalanche Research Scottish Avalanche Information Service Chisholm, Hugh, ed. (1911). "Avalanche" . Encyclopædia Britannica (11th ed.). Cambridge University Press. But note the myths cited above Utah Avalanche Center New Zealand Avalanche Advisory Gulmarg Avalanche Center US Avalanche.org Sierra Avalanche Center (Tahoe National Forest)

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

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

Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a congenital, often hereditary neuromuscular disorder with many symptoms that can occur such as muscle weakness, hypoventilation, swallowing dysfunction, and impaired speech ability. The severity of these symptoms varies and can change throughout ones life to some extent. The prevalence is estimated at 1 in 50,000 live births. It is the most common non-dystrophic myopathy."Myopathy" means muscle disease. Muscle fibers from a person with nemaline myopathy contains thread-like rods, sometimes called nemaline bodies. While the rods are diagnostic of the disorder, they are more likely a byproduct of the disease process rather than causing any dysfunction on their own. People with nemaline myopathy (NM) usually experience delayed motor development, or no motor development in severe cases, and weakness may occur in all of the skeletal muscles, such as muscles in the arms, legs, torso, neck flexors, throat, and face. The weakness tends to be more severe in the proximal muscles rather than the distal muscles. The ocular muscles are normally spared. The disorder is often clinically categorized into groups with wide ranges of overlapping severity, from the most severe neonatal form which is incompatible with life, to a form so mild that it may not be diagnosed since the person appears to function at the lowest end of normal strength and breathing adequacy. Sporadic late onset nemaline myopathy (SLONM) is not a congenital disorder and is considered a different muscle disease from NM, which has its onset at birth or early childhood. Respiratory problems are usually a primary concern for people with all forms of NM, and respiratory infections are quite common. NM shortens life expectancy, particularly in the more severe forms, but aggressive and proactive care allows most individuals to survive and even lead active lives. Nemaline myopathy is one of the neuromuscular diseases covered by the Muscular Dystrophy Association in the United States. Signs and symptoms Signs vary from person to person. Young children and babies lack movement and have a difficult time eating and breathing. For young children not diagnosed immediately at birth, these are usually the first visible symptoms. One sign is a swollen face in disproportional areas. Other examples in newborns include swaying and a difficulty in moving. Other symptoms include feeble muscles in the neck and upper rib cage area. In adults, the most common symptom is respiratory problems. Other symptoms in adults could range from mild to severe speech impediments. It is common to be diagnosed with scoliosis in relations to nemaline myopathy. As babies that have NM develop and become of age when they should start walking, many take longer than average due to the lack of muscle, or just muscle fatigue.Since facial muscles are involved in NM takeover, elongated faces and a lower mandible are often observed in people with NM. People affected by NM usually will begin to feel muscle exhaustion between ages 20–50. NM is usually not progressive. Gastroesophageal reflux, although not common, is associated with NM. Heart abnormalities can occur as a result of NM, but the likelihood of that happening are not high. Mobility and orthopedics Most children with mild NM eventually walk independently, although often at a later age than their peers. Some use wheelchairs or other devices, such as walkers or braces, to enhance their mobility. Individuals with severe NM generally have limited limb movement and use wheelchairs full-time. Due to weakness in the trunk muscles, people with NM are prone to scoliosis, which usually develops in childhood and worsens during puberty. Many individuals with NM undergo spinal fusion surgery to straighten and stabilize their backs.Although patients early on often have mobility in their joints that is past the normal range, as they age, joint deformities and scoliosis usually occur. If the person with nemaline myopathy keeps an eye on his or her joints early on, the problems with them can be detected when they begin and their progression can be delayed. Treatment of joint problems ranges from stretching exercises with physical therapy to surgical introduction of braces. The benefits of exercise in people with nemaline myopathy are still being studied, however, researchers have seen improvements in muscle function from low-intensity exercise. Vigorous exercise and the use of heavy weights should be avoided. Respiratory involvement Attention to respiratory issues is critical to the health of many people with NM. Infants with severe NM frequently experience respiratory distress at or soon after birth, although this is only found in the rarest forms. Though respiratory compromise may not be immediately apparent in people with intermediate or mild NM, it often, but not always, exists to some extent. As in many neuromuscular disorders, hypoventilation can begin insidiously, and it may cause serious health problems if not remedied by the use of noninvasive mechanical devices to assist breathing, particularly at night. Communication and eating Bulbar (throat) muscle weakness is a main feature of nemaline myopathy. Individuals with the most severe forms of NM are unable to swallow and receive their nutrition through feeding tubes. Most people with intermediate and mild NM take some or all of their nutrition orally. Bulbar muscle impairment may also lead to difficulty with communication. People with NM often have hypernasal speech as a result of poor closure of the velopharyngeal port (between the soft palate and the back of the throat). This may be able to be surgically corrected. Communicative skills may be enhanced through speech therapy, oral prosthetic devices, surgery, and augmentative communication devices. NM does not have any impact on cognition or intelligence. Physical characteristics and effects Physical expression of nemaline myopathy varies greatly, but weakness is usually concentrated in the proximal muscles, particularly respiratory, bulbar and trunk muscles. People with severe NM show obvious symptoms at birth, while those with intermediate or mild NM may initially appear unaffected. Babies with NM are frequently observed to be "floppy" and hypotonic. Children born with NM often gain strength as they grow, though the effect of muscle weakness on body features may become more evident with time. Adults with NM typically have a very slender physique. Causes Nemaline myopathy is caused by mutations in one of at least 11 different genes. Nemaline myopathy is a clinically and genetically heterogeneous disorder and both autosomal dominant and autosomal recessive forms can occur. Diagnosis is made based upon clinical signs such as muscle weakness, absent or low deep tendon reflexes (hyporeflexia), and a high-arched palate, along with electron-dense aggregates, called nemaline rods, being observed at the microscopic level within muscle fibers. Genetic confirmation through identification of a known genetic mutation in the patient is also an important component of diagnosis.The two most common gene mutations causing nemaline myopathy are found on NEB or ACTA1. Mutations of the NEB gene usually result in symptoms present at birth or beginning in early childhood. This mutation results in about 50% of affected nemaline myopathy patients. The most common inheritance pathway for those with mutations in NEB is autosomal recessive in which each parent carries one mutated copy along with one normal functioning copy of the gene, and they pass the mutated copy to their offspring. In some cases, occasionally with ACTA1 mutations, NM can be caused by an inheritance pattern of autosomal dominance. This mutation results in about 15 to 25 percent of NM cases. One reason why this is lower is because NM is associated with de novo mutations in ACTA1, occurring spontaneously in the egg or sperm. When the condition is heritable, each pregnancy with the same partners has the same risk of passing the mutated genes to offspring. New mutations (de novo) can also occur causing NM and de novo mutations have been most often found to occur in the ACTA1 gene. MYPN is the last found gene related to NM The risk of all cases of nemaline myopathy is the same in males and females. The physical capabilities of a given person with NM do not correlate well either with genotype or with muscle pathology as observed in the biopsy. Mechanism Muscle cells contract in complex mechanical and chemical processes. If any part of the process or structure is disrupted, dysfunction will likely result, as in the case of those with genetic variations. In those with nemaline myopathy, muscle contraction is adversely affected. At the electron microscopic level, rod-shaped components can often be seen in some of the muscle cells, and when seen, are diagnostic for the condition called nemaline rod myopathy. The presence of these rods is not itself causing muscle weakness; rather they appear as a result of something going wrong within the muscle fiber. There is no connection between the number of rods found in the muscle cells and the amount of weakness a person has. All of the different gene mutations leading to the condition called nemaline myopathy that have been found so far are in genes that encode different components of the sarcomere. In normal muscle cells, the various parts of the muscle fibers that make up the sarcomere are distributed evenly in a pattern for effective muscle contraction. Evidence suggests that some kinds of NM affect the arrangement of these muscle fibers, causing the muscles to be unable to contract as efficiently or effectively. Nemaline myopathy is usually genetic and shows traits in the affected individual from birth or an early age. However, there are some cases of symptoms of nemaline myopathy not showing up until adulthood. These cases are usually not genetic. Of the genes that have been linked to nemaline myopathy, most are also involved in encoding proteins in the sarcomeres in the muscle cells. Respiratory muscles are often more affected than other skeletal muscle groups. Cardiac muscle is usually not affected in nemaline myopathy; however, in cases where it does, patients often present with dilated cardiomyopathy. The ocular muscles are usually spared.The different genes whose mutations lead to the different kinds of nemaline myopathies affect the cells and the persons body differently. The first kind of nemaline myopathy identified is due to the Slow α-Tropomyosin Gene TPM3 and varies from case to case with its severity. In this kind of nemaline myopathy, affected people are weaker and more affected in their lower limbs than their upper limbs.As stated above, the most common genetic form of NM is caused by a mutation in the nebulin gene, called Nebulin, and has a range of severity levels. All published cases up to this point where NM is thought to be caused by a mutation in the NEB gene have been autosomal recessive and are the most common cause of nemaline myopathy. Patients with this kind of NM are more affected in the muscles in their head, rather than their proximal muscles at the core of their body. Consequently, patients with this genetic mutation often cannot lift their heads and speak with a nasal voice. There have been cases that suggest this kind of NM may lead to patients having higher intellect.A third kind of nemaline myopathy in the Skeletal Muscle α-Actin Gene ACTA1 is due to a recessive null mutation. These patients do not always show the typical nemaline bodies in their muscle cells. The only abnormality they show is an abnormal distribution of muscle fibers. There are several other identified kinds of mutations that lead to Nemaline Myopathies. One affects slow skeletal muscles, one leads to the formation of both nemaline bodies and other abnormal, core-like, structures forming in the patients muscles. Diagnosis Electromyography or (EMG). This procedure determines if nerve or muscle cells are damaged. Since a common symptom of Nemaline Myopathy is muscle weakness this allows doctors to determine where and why the weakness is occurring. MRI of the Musculoskeletal System. MRI uses a magnetic field to take pictures of body structures and allows physicians to determine if a patient has a certain disease. Needle biopsy A needle biopsy allows a physician to test specific cells in the body. These cells are sent to a laboratory to undergo testing and can further determine why muscle weakness throughout the body could be occurring. This testing can confirm that muscle cells contain rod like structures. Treatment At present, Nemaline myopathy does not have a cure. Nemaline myopathy is a very rare disease that only affects 1 out of 50,000 on average, although recent studies show that this number is even smaller. There are a number of treatments to minimize the symptoms of the disease. The treatments and procedures to help patients with nemaline myopathy vary depending on the severity of the disease. A possible accommodation could be the use of a stabilizer, such as a brace. Other means include moderate stretching and moderate exercise to help target muscles maintain maximum health. As people with NM grow and develop throughout their lives, it is important for them to see a variety of health professionals regularly, including a neurologist, physical therapist, and others, such as speech therapists and psychologists, to help both the patient and family adjust to everyday life. Outcome Although there is no cure for NM, it is possible, and common for many people live healthy active lives even with moderate to severe cases. Research continues to seek ways to ameliorate debilitating symptoms and lengthen the life-span in quality ways for those affected. Some people have seen mild improvements in secretion handling, energy level, and physical functioning with supplemental L-tyrosine, an amino acid that is available through health centers. Some symptoms may worsen as the patient ages. Muscle loss increases with age naturally, but it is even more significant with nemaline myopathy. Current research New research resources have become available for the NM community, such as the CMDIR (registry) and the CMD-TR (biorepository). These two resources connect families and individuals interested in participating in research with the scientists that aim to treat or cure NM. Some research on NM seeks to better understand the molecular effects the gene mutations have on muscle cells and the rest of the body and to observe any connections NM may have to other diseases and health complications. History "Rod myopathy" was first identified by Douglas Reye, an Australian physician, in 1958. However, Reyes results were never published because another doctor dismissed his finding of rods in the muscle tissue as an artifact of the biopsy. Forty years later, Reyes "rod myopathy" patient was confirmed to have nemaline myopathy. Another group of Australian researchers has since published an article recognizing Reye for his work."Nemaline myopathy" was first named in a published paper in 1963 by North American researchers P.E. Cohen and G. M. Shy. Shy and his team discovered rod- like structures in muscle fibers of patients with muscle weakness by performing muscle biopsies on multiple patients. Laboratories performing research on NM are located around the world, notably in the United States, Canada, England, Finland, and Australia. Society and culture In 1999, the first website on nemaline myopathy was launched, and in October 2004, the first Nemaline Myopathy Convention was held in Toronto, Canada. Many more conferences and social events have been held since, and all events organized since 2008 have been co-sponsored by A Foundation Building Strength for Nemaline Myopathy (AFBS), the only foundation focused on supporting treatment development and social events for the NM community. In March 2006, Niki Shisler released a book, Fragile, in which she recounted her experiences surrounding the birth of twin sons with severe NM. In 2014, a team of experts collaborated with affected individuals and families caring for someone with a congenital myopathy to develop the first guidebook on managing life with a congenital myopathy References External links GeneReview/NCBI/NIH/UW entry on Nemaline Myo\

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What does the medical term 'Phytomenadione' encompass?

Phytomenadione, also known as vitamin K1 or phylloquinone, is a vitamin found in food and used as a dietary supplement. It is on the World Health Organizations List of Essential Medicines.As a supplement it is used to treat certain bleeding disorders. This includes warfarin overdose, vitamin K deficiency, and obstructive jaundice. It is also recommended to prevent and treat vitamin K deficiency bleeding in infants. Use is typically recommended by mouth, intramuscular injection or injection under the skin. When given by injection benefits are seen within two hours. Many countries in the world choose intramuscular injections in newborn to keep them safe from severe bleeding (VKDB). It is considered a safe treatment and saves many children from death and severe neurologic deficit every year.Side effects when given by injection may include pain at the site of injection. Severe allergic reactions may occur when it is injected into a vein or muscle, but this has mainly happened when large doses of a certain type of supplement containing castor oil were given intravenously. Use during pregnancy is considered safe, use is also likely okay during breastfeeding. It works by supplying a required component for making a number of blood clotting factors. Found sources include green vegetables, vegetable oil, and some fruit.Phytomenadione was first isolated in 1939. In 1943 Edward Doisy and Henrik Dam were given a Nobel Prize for its discovery. Terminology Phytomenadione is often also called phylloquinone, vitamin K, or phytonadione. A stereoisomer of phylloquinone is called vitamin k1 (note the difference in capitalization). Chemistry Vitamin K is a fat-soluble vitamin that is stable in air and moisture but decomposes in sunlight. It is a polycyclic aromatic ketone, based on 2-methyl-1,4-naphthoquinone, with a 3-phytyl substituent. It is found naturally in a wide variety of green plants, particularly in leaves, since it functions as an electron acceptor during photosynthesis, forming part of the electron transport chain of photosystem I. Biological function The best-known function of vitamin K in animals is as a cofactor in the formation of coagulation factors II (prothrombin), VII, IX, and X by the liver. It is also required for the formation of anticoagulant factors protein C and S. It is commonly used to treat warfarin toxicity, and as an antidote for coumatetralyl. Vitamin K is required for bone protein formation. Biosynthesis Vitamin K1 is synthesized from chorismate, a compound produced from shikimate via the shikimate pathway. The conversion of chorismate to vitamin K1 comprises a series of nine steps: Chorismate is isomerized to isochorismate by isochorismate synthase, or MenF (menaquinone enzyme). Addition of 2-oxoglutarate to isochorismate by PHYLLO, a multifunctional protein comprising three different enzymatic activities (MenD, H, and C). Elimination of pyruvate by PHYLLO. Aromatization to yield o-succinyl benzoate by PHYLLO. O-succinylbenzoate activation to corresponding CoA ester by MenE. Naphthoate ring formation by naphthoate synthase (MenB/NS). Thiolytic release of CoA by a thioesterase (MenH). Attachment of phytol chain to the naphthoate ring (MenA/ABC4). Methylation of the precursor at position 3 (MenG). Vitamin K1 is required for plant photosynthesis, where it participates in the Photosystem I electron transport chain. As a result, it is rich in leaves. See also Menatetrenone Vitamin K Vitamin K2 References External links "Phytomenadione". Drug Information Portal. U.S. National Library of Medicine.

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

Salsalate is a medication that belongs to the salicylate and nonsteroidal anti-inflammatory drug (NSAID) classes. Salsalate is the generic name of a prescription drug marketed under the brandnames Mono-Gesic, Salflex, Disalcid, and Salsitab. Other generic and brand name formulations may be available. Mechanism of action Relative to other NSAIDs, salsalate has a weak inhibitory effect on the cyclooxygenase enzyme and decreases the production of several proinflammatory chemical signals such as interleukin-6, TNF-alpha, and C-reactive protein.The mechanism through which salsalate is thought to reduce the production of these inflammatory chemical signals is through the inhibition of IκB kinase resulting in decreased action of NF-κB genes. This mechanism is thought to be responsible for salsalates insulin-sensitizing and blood sugar lowering properties. Medical uses Salsalate may be used for inflammatory disorders such as rheumatoid arthritis or noninflammatory disorders such as osteoarthritis. Safety The risk of bleeding is a common concern with use of the NSAID class of medications. However, the bleeding risk associated with salsalate is lower than that associated with aspirin use. Research Salsalate has been proposed for the prevention and treatment of type 2 diabetes mellitus due to its ability to lower insulin resistance associated with inflammation and may be useful in prediabetes. However, the use of salsalate to prevent the progression from prediabetes to type 2 diabetes mellitus has received limited study. History Salsalate had been suggested as possible treatment for diabetes as early as 1876. Synthesis == References ==

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

Quinupristin/dalfopristin, or quinupristin-dalfopristin, (pronunciation: kwi NYOO pris tin / dal FOE pris tin) (trade name Synercid) is a combination of two antibiotics used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium. Quinupristin and dalfopristin are both streptogramin antibiotics, derived from pristinamycin. Quinupristin is derived from pristinamycin IA; dalfopristin from pristinamycin IIA. They are combined in a weight-to-weight ratio of 30% quinupristin to 70% dalfopristin. Administration Intravenous, usually 7.5 mg/kg every 8 hours (infections/life threatening VRSA); every 12 hours (skin infections). No renal dosing adjustments, hepatic dosing adjustments are not defined, consider reducing dose. Mechanism of action Quinupristin and dalfopristin are protein synthesis inhibitors in a synergistic manner. While each of the two is only a bacteriostatic agent, the combination shows bactericidal activity. Dalfopristin binds to the 23S portion of the 50S ribosomal subunit, and changes the conformation of it, enhancing the binding of quinupristin by a factor of about 100. In addition, it inhibits peptidyl transfer. Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide, as well as causing incomplete chains to be released. Pharmacokinetics Clearance by the liver CYP450:3A4 inhibitor, half-life quinupristin 0.8 hours, dalfopristin 0.7 hours (with persistence of effects for 9–10 hours). Excretion: Quinupristin: 85% feces, 15% urine; Dalfopristin: 81% feces, 19% urine Side effects Serious: C.diff-associated diarrhea superinfection anaphylactoid reactions angioedemaCommon: Joint aches (arthralgia) or muscle aches (myalgia) Nausea, diarrhea (C. diff associated) or vomiting Rash or itching Headache Hyperbilirubinemia Anemia Thrombophlebitis Drug interactions The drug inhibits P450 and enhances the effects of terfenadine, astemizole, indinavir, midazolam, calcium channel blockers, warfarin, cisapride and ciclosporin. References == Further reading ==

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Could you provide a brief overview of 'Astasia-abasia' in a medical context?

Astasia-abasia refers to the inability to either stand or walk in a normal manner. Astasia refers to the inability to stand upright unassisted. Abasia refers to lack of motor coordination in walking. The term abasia literally means that the base of gait (the lateral distance between the two feet) is inconstant or unmeasurable. When seen in conversion disorder, the gait is bizarre and is not suggestive of a specific organic lesion: often the patient sways wildly and nearly falls, recovering at the last moment. An acquired total inability to stand and walk can be seen in organic neurological diseases, including stroke, Parkinsons disease, damage to the cerebellum, Guillain–Barré syndrome, normal pressure hydrocephalus and many others. In normal pressure hydrocephalus, for example, when the condition remains untreated, the patients gait becomes shortened, with frequent shuffling and falls; eventually standing, sitting, and even rolling over in bed become impossible. This advanced state is referred to as "hydrocephalic astasia-abasia". Phobias Astasia and/or abasia are associated with the corresponding fears of walking and/or standing, variously called stasophobia, basophobia, stasiphobia, basiphobia, stasobasophobia, stasibasiphobia, etc., sometimes turning into pathological forms, i.e., phobias. See also Blocqs disease, an illness named after Paul Oscar Blocq References == External links ==

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

A bunion, also known as hallux valgus, is a deformity of the joint connecting the big toe to the foot. The big toe often bends towards the other toes and the joint becomes red and painful. The onset of bunions is typically gradual. Complications may include bursitis or arthritis.The exact cause is unclear. Proposed factors include wearing overly tight shoes, high-heeled shoes, family history, and rheumatoid arthritis. Diagnosis is generally based on symptoms and supported by X-rays. A similar condition of the little toe is referred to as a bunionette.Treatment may include proper shoes, orthotics, or NSAIDs. If this is not effective for improving symptoms, surgery may be performed. It affects about 23% of adults. Females are affected more often than males. Usual age of onset is between 20 and 50 years old. The condition also becomes more common with age. It was first clearly described in 1870. Archaeologists have found a high incidence of bunions in skeletons from 14th- and 15th-century England, coinciding with a fashion for pointy shoes. Signs and symptoms Symptoms may include irritation of the skin around the bunion, and blisters may form more easily at the site. Pain may be worse when walking. Bunions can lead to difficulties finding properly fitting footwear and may force a person to buy a larger size shoe to accommodate the width of the bunion. If the bunion deformity becomes severe enough, the foot can hurt in different places even without the constriction of shoes. It is then considered as being a mechanical function problem of the forefoot. Cause The exact cause is unclear. It may be due to a combination of internal and external causes. Proposed factors include wearing overly tight shoes, high-heeled shoes, family history and rheumatoid arthritis. The American College of Foot and Ankle Surgeons states that footwear only worsens a problem caused by genetics.Excessive pronation of the foot causes increased pressure on the inside of the big toe that can result in a deformation of the medial capsular structures of the joint, subsequently increasing the risk of developing bunions. Pathophysiology The bump itself is partly due to the swollen bursal sac or an osseous (bony) anomaly on the metatarsophalangeal joint. The larger part of the bump is a normal part of the head of the first metatarsal bone that has tilted sideways to stick out at its distal (far) end (metatarsus primus varus). Bunions are commonly associated with a deviated position of the big toe toward the second toe, and the deviation in the angle between the first and second metatarsal bones of the foot. The small sesamoid bones found beneath the first metatarsal (which help the flexor tendon bend the big toe downwards) may also become deviated over time as the first metatarsal bone drifts away from its normal position. Osteoarthritis of the first metatarsophalangeal joint, diminished and/or altered range of motion, and discomfort with pressure applied to the bump or with motion of the joint, may all accompany bunion development. Atop of the first metatarsal head either medially or dorso-medially, there can also arise a bursa that when inflamed (bursitis), can be the most painful aspect of the process. Diagnosis Bunion can be diagnosed and analyzed with a simple x-ray, which should be taken with the weight on the foot. The hallux valgus angle (HVA) is the angle between the long axes of the proximal phalanx and the first metatarsal bone of the big toe. It is considered abnormal if greater than 15–18°. The following HV angles can also be used to grade the severity of hallux valgus: Mild: 15–20° Moderate: 21–39° Severe: ≥ 40°The intermetatarsal angle (IMA) is the angle between the longitudinal axes of the first and second metatarsal bones, and is normally less than 9°. The IM angle can also grade the severity of hallux valgus as: Mild: 9–11° Moderate: 12–17° Severe: ≥ 18° Treatment Conservative treatment for bunions include changes in footwear, the use of orthotics (accommodative padding and shielding), rest, ice, and pain medications such as acetaminophen or nonsteroidal anti-inflammatory drugs. These treatments address symptoms but do not correct the actual deformity. If the discomfort persists and is severe or when aesthetic correction of the deformity is desired, surgical correction by an orthopedic surgeon or a podiatric surgeon may be necessary. Orthotics Orthotics are splints or regulators while conservative measures include various footwear like toe spacers, valgus splints, and bunion shields. Toe spacers seem to be effective in reducing pain, but there is not evidence that any of these techniques reduces the physical deformity. There are a variety of available orthotics including off-the-shelf commercial products and custom-molded orthotics, which may be prescribed medical devices. Surgery Procedures are designed and chosen to correct a variety of pathologies that may be associated with the bunion. For instance, procedures may address some combination of: removing the abnormal bony enlargement of the first metatarsal, realigning the first metatarsal bone relative to the adjacent metatarsal bone, straightening the great toe relative to the first metatarsal and adjacent toes, realigning the cartilaginous surfaces of the great toe joint, addressing arthritic changes associated with the great toe joint, repositioning the sesamoid bones beneath the first metatarsal bone, shortening, lengthening, raising, or lowering the first metatarsal bone, correcting any abnormal bowing or misalignment within the great toe, connecting two parallel long bones side by side by syndesmosis procedureAt present there are many different bunion surgeries for different effects. The age, health, lifestyle and activity level of the patient may also play a role in the choice of procedure. Traditional bunion surgery can be performed under local, spinal or general anesthetic. A person who has undergone bunion surgery can expect a 6- to 8-week recovery period during which crutches are usually required to aid mobility. An orthopedic cast is much less common today as newer, more stable procedures and better forms of fixation (stabilizing the bone with screws and other hardware) are used. Hardware may even include absorbable pins that perform their function and are then broken down by the body over the course of months. After recovery long term stiffness or limited range of motion may occur in some patients. Visible or limited scarring may also occur for patients. References External links Textbook of Hallux Valgus and Forefoot Surgery, links to complete text in PDF files

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

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

Deflazacort (trade name Calcort among others) is a glucocorticoid used as an anti-inflammatory and immunomodulatory agent. It was patented in 1965 and approved for medical use in 1985. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication for Duchenne Muscular Dystrophy. Medical uses The manufacturer lists the following uses for deflazacort: In the United States, deflazacort is approved for the treatment of duchenne muscular dystrophy in people over the age of two. Adverse effects Deflazacort carries the risks common to all corticosteroids, including immune suppression, decreased bone density, and endocrine insufficiency. In clinical trials, the most common side effects (>10% above placebo) were Cushings-like appearance, weight gain, and increased appetite. Pharmacology Mechanism of action Deflazacort is an inactive prodrug which is metabolized rapidly to the active drug 21-desacetyldeflazacort. Relative potency Deflazacorts potency is around 70–90% that of prednisone. A 2017 review found its activity of 7.5 mg of deflazacort is approximately equivalent to 25 mg cortisone, 20 mg hydrocortisone, 5 mg of prednisolone or prednisone, 4 mg of methylprednisolone or triamcinolone, or 0.75 mg of betamethasone or dexamethasone. The review noted that the drug has a high therapeutic index, being used at initial oral doses ranging from 6 to 90 mg, and probably requires a 50% higher dose to induce the same demineralizing effect as prednisolone. Thus it has "a smaller impact on calcium metabolism than any other synthetic corticosteroid, and therefore shows a lower risk of growth rate retardation in children and of osteoporosis" in the elderly, and comparatively small effects on carbohydrate metabolism, sodium retention, and hypokalemia. History In January 2015, the FDA granted fast track status to Marathon Pharmaceuticals to pursue approval of deflazacort as a potential treatment for Duchenne muscular dystrophy, a rare, "progressive and fatal disease" that affects boys. Although deflazacort was approved by the FDA for use in treatment of Duchenne muscular dystrophy on February 9, 2017, Marathon CEO announced on February 13, 2017, that the launch of deflazacort (Emflaza) would be delayed amidst controversy over the steep price Marathon was asking for the drug in the United States - $89,000 per year, which is "roughly 70 times" more than it would cost overseas. Because deflazacort is an older drug which has been long-approved in some other countries, it is now available in many places as an inexpensive generic. For example, in Canada deflazacort can be purchased for around $1 per tablet.Deflazacort is sold in the United States under the brand name Emflaza after PTC Therapeutics, Inc. acquired all rights to Emflaza on March 16, 2017. Deflazacort is sold in the United Kingdom under the trade name Calcort; in Brazil as Cortax, Decortil, Defcort and Deflanil; in India as Moaid, Zenflav, Defolet, DFZ, Decotaz, and DefZot; in Bangladesh as Xalcort; in Panama as Zamen; Spain as Zamene; and in Honduras as Flezacor.The U.S. Food and Drug Administration approved deflazacort to treat people age five years and older with Duchenne muscular dystrophy (DMD), a rare genetic disorder that causes progressive muscle deterioration and weakness. Emflaza is a corticosteroid that works by decreasing inflammation and reducing the activity of the immune system. NDA 208684 was approved on February 9, 2017, as a Type 1- new molecular entity with orphan status. References External links "Deflazacort". Drug Information Portal. U.S. National Library of Medicine.

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

A Brodie abscess is a subacute osteomyelitis, which may persist for years before progressing to a chronic, frank osteomyelitis. Classically, this may present after progression to a draining abscess extending from the tibia out through the skin. Occasionally acute osteomyelitis may be contained to a localized area and walled off by fibrous and granulation tissue. The most frequent causative organism is Staphylococcus aureus. Presentation Localized pain, often nocturnal, alleviated by aspirin. Often mimics the symptoms of osteoid osteoma, which is typically less than 1 cm in diameter. Location Usually occurs at the metaphysis of long bones. Distal tibia, proximal tibia, distal femur, proximal or distal fibula, and distal radius. Diagnosis Radiographic features Oval, elliptical, or serpentine radiolucency usually greater than 1 cm surrounded by a heavily reactive sclerosis, granulation tissue, and a nidus often less than 1 cm. The margins often appear scalloped on radiograph. Brodies abscess is best visualized using computed tomography (CT) scan. Associated atrophy of soft tissue near the site of infection and shortening of the affected bone. Osteoblastoma may be a classic sign for Brodies abscess. Treatment In the majority of cases, surgery has to be performed. If the cavity is small then surgical evacuation and curettage is performed under antibiotic cover. If the cavity is large then the abscess space may need packing with cancellous bone chips after evacuation. History Brodie abscess is named after Sir Benjamin Collins Brodie, 1st Baronet. In the 1830s, he initially described a chronic inflammatory condition affecting the tibia without obvious acute etiology. It was later discovered that this was caused by infection. References == External links ==

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Could you please explain the term 'Cabotegravir/rilpivirine' in simple language?

Cabotegravir/rilpivirine, sold under the brand name Cabenuva, is a co-packaged antiretroviral medication for the treatment of HIV/AIDS. It contains cabotegravir and rilpivirine in a package with two separate injection vials.The most common adverse reactions include injection site reactions, fever or feeling hot (pyrexia), fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness and rash.The co-packaged medication was approved for medical use in the United States in January 2021. It is the first FDA-approved injectable, complete regimen for HIV-infected adults that is administered once a month. It is also approved for use in Canada. In the European Union, the two medications are approved separately. Medical uses Cabotegravir/rilpivirine is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace a current antiretroviral regimen in those who are virologically suppressed on a stable antiretroviral regimen with no history of treatment failure. In the European Union, the combination is indicated for maintenance treatment of adults who have undetectable HIV levels in the blood (viral load less than 50 copies/mL) with their current antiretroviral treatment, and when the virus has not developed resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors. Contraindications and interactions Cabotegravir/rilpivirine must not be combined with drugs that induce the liver enzyme CYP3A4, because they accelerate the inactivation of rilpivirine, and/or the enzyme UGT1A1, because they accelerate the inactivation of cabotegravir. These mechanisms potentially result in loss of effectiveness. Examples for such drugs are rifampicin, rifapentine, carbamazepine, oxcarbazepine, phenytoin and phenobarbital. Adverse effects The most common side effects include reactions at the injection site (in up to 84% of patients) such as pain and swelling, as well as headache (up to 12%) and fever or feeling hot (in 10%). Less common side effects (under 10%) are depressive disorders, insomnia, rashes, fatigue, musculoskeletal pain, nausea, sleep disorders, and dizziness. Pharmacology Cabotegravir is an integrase strand transfer inhibitor. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). History The safety and efficacy of cabotegravir/rilpivirine were established through two randomized, open-label, controlled clinical trials (Trial 1/NCT02938520 and Trial 2/NCT02951052) in 1,182 HIV-infected adults who were virologically suppressed (HIV-1 RNA less than 50 copies/milliliter) before initiation of treatment with cabotegravir/rilpivirine. Participants in both trials continued to show virologic suppression at the conclusion of each study, and no clinically relevant change from baseline in CD4+ cell counts was observed. Trials were conducted at 223 sites in 24 countries including the United States.In Trial 1, participants who were never treated for the infection before, received an approved therapy for 20 weeks. Those who did well after this treatment (who had HIV-1 RNA less than 50 copies/milliliter) were then randomized to receive either cabotegravir/rilpivirine (for the first four weeks they received tablets) or to remain on the same therapy for additional 44 weeks. Participants and the health providers knew which treatments have been given.In Trial 2, participants who were previously successfully treated for the infection (who had HIV-1 RNA less than 50 copies/milliliter), were randomized to receive either cabotegravir/rilpivirine (for the first four weeks they received tablets) or to remain on the same therapy for additional 44 weeks. Participants and the health providers knew which treatments have been given.In October 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the granting of a marketing authorization for rilpivirine and cabotegravir, to be used together for the treatment of people with human immunodeficiency virus type 1 (HIV-1) infection. The two medicines are the first antiretrovirals that come in a long-acting injectable formulation. This means that instead of daily pills, people receive intramuscular injections monthly or every two months. Rilpivirine and cabotegravir were approved for medical use in the European Union in December 2020, as two separate medications.In January 2021, the U.S. Food and Drug Administration (FDA) granted the approval of Cabenuva to ViiV Healthcare.The combination was approved for medical use in Australia in February 2021. References External links "Cabotegravir". Drug Information Portal. U.S. National Library of Medicine. "Rilpivirine". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT02938520 for "Study to Evaluate the Efficacy, Safety, and Tolerability of Long-acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor in HIV-1 Infected Therapy Naive Participants" at ClinicalTrials.gov Clinical trial number NCT02951052 for "Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current Antiretroviral Regimen in Virologically Suppressed HIV-1-infected Adults" at ClinicalTrials.gov

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.

Can you demystify the medical term 'Compensatory hyperhidrosis' for me?

Compensatory hyperhidrosis is a form of neuropathy. It is encountered in patients with myelopathy, thoracic disease, cerebrovascular disease, nerve trauma or after surgeries. The exact mechanism of the phenomenon is poorly understood. It is attributed to the perception in the hypothalamus (brain) that the body temperature is too high. The sweating is induced to reduce body heat. Excessive sweating due to nervousness, anger, previous trauma or fear is called hyperhidrosis. Compensatory hyperhidrosis is the most common side effect of endoscopic thoracic sympathectomy, a surgery to treat severe focal hyperhidrosis, often affecting just one part of the body. It may also be called rebound or reflex hyperhidrosis. In a small number of individuals, compensatory hyperhidrosis following sympathectomy is disruptive, because affected individuals may have to change sweat-soaked clothing two or three times a day. According to Dr. Hooshmand, sympathectomy permanently damages the temperature regulatory system. The permanent destruction of thermoregulatory function of the sympathetic nervous system causes latent complications, e.g., RSD in contralateral extremity.Following surgery for axillary (armpit), palmar (palm) hyperhidrosis (see focal hyperhidrosis) and blushing, the body may sweat excessively at untreated areas, most commonly the lower back and trunk, but can be spread over the total body surface below the level of the cut. The upper part of the body, above the sympathetic chain transection, the body becomes anhidriotic, where the patient is unable to sweat or cool down, which further compromises the bodys thermoregulation and can lead to elevated core temperature, overheating and hyperthermia. Below the level of the sympathetic chain interruption, body temperature is significantly lower, creating a stark contrast that can be observed on thermal images. The difference in temperatures between the sympathetically under- and overactive regions can be as high as 10 Celsius. Variations Gustatory sweating or Freys syndrome is another presentation of autonomic neuropathy. Gustatory sweating is brought on while eating, thinking or talking about food that produces a strong salivary stimulus. It is thought that ANS fibres to salivary glands have become connected in error with the sweat glands after nerve regeneration. Apart from sweating in the anhidriotic area of the body, it can produce flushing, goosebumps, drop of body temperature - vasoconstriction and paresthesia. Aberrant gustatory sweating follows up to 73% of surgical sympathectomies and is particularly common after bilateral procedures. Facial sweating during salivation has also been described in diabetes mellitus, cluster headache, following chorda tympani injury, and following facial herpes zoster.Phantom sweating is another form of autonomic neuropathy. It can be observed in patients with nerve damage (following accidents), diabetes mellitus and as a result of sympathectomy. Phantom sweating is a sensation that one is sweating, while the skin remains dry. Affected people can not distinguish whether it is real sweating or just a sensation. The phenomena is experienced in the anhidriotic, denervated area of the body, presenting an abnormal sympathetic nervous system function. Mechanism The term compensatory is largely misleading, as it indicates that there is a compensatory mechanism that takes effect after sympathectomy, in which the body redirects the sweating from the palms or face to other areas of the body. Sweating after sympathetic surgery is a reflex cycle between the sympathetic system and the anterior portion of the hypothalamus. Reflex sweating will not happen if hand sweating can be stopped without interrupting sympathetic tone to the human brain.Compensatory hyperhidrosis is aberrant sympathetic nervous system functioning. The only study evaluating the total body sweat prior and shortly after sympathectomy concluded that patients produce more sweat after the surgery, just not so much in the areas treated by the surgery. Epidemiology Of people that have a sympathectomy, it is impossible to predict who will end up with a more severe version of this disorder, as there is no link to gender, age or weight. There is no test or screening process that would enable doctors to predict who is more susceptible. == References ==

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

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

Pasireotide, sold under the brand name Signifor, is an orphan drug approved in the United States and the European Union for the treatment of Cushings disease in patients who fail or are ineligible for surgical therapy. It was developed by Novartis. Pasireotide is a somatostatin analog with a 40-fold increased affinity to somatostatin receptor 5 compared to other somatostatin analogs. The most common side effects include hyperglycaemia (high blood sugar levels), diabetes, diarrhoea, abdominal pain (stomach ache), nausea (feeling sick), cholelithiasis (gallstones), injection site reactions, and tiredness.Pasireotide was approved for Cushings disease by the European Medicines Agency (EMA) in April 2012 and by the U.S. Food and Drug Administration (FDA) in December 2012.Pasireotide LAR (the long-acting-release formulation) was approved by the FDA for treatment of acromegaly in December 2014, and had been approved for this indication by the EMA in September 2014. References External links "Pasireotide". Drug Information Portal. U.S. National Library of Medicine.

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 understand 'Anidulafungin' within a medical context. Could you shed some light on it?

Anidulafungin (INN): 42  (trade names Eraxis, Ecalta) is a semisynthetic echinocandin used as an antifungal drug. It was previously known as LY303366. It may also have application in treating invasive Aspergillus infection when used in combination with voriconazole. It is a member of the class of antifungal drugs known as the echinocandins; its mechanism of action is by inhibition of (1→3)-β-D-glucan synthase, an enzyme important to the synthesis of the fungal cell wall.It is on the World Health Organizations List of Essential Medicines. Indications Candidemia and other forms of invasive Candida infections (intra-abdominal abscess and peritonitis) Esophageal candidiasisAnidulafungin has not been studied in endocarditis, osteomyelitis, and meningitis due to Candida, and has not been studied in sufficient numbers of neutropenic patients to determine efficacy in this group. Pharmacodynamics and pharmacokinetics Anidulafungin significantly differs from other antifungals in that it undergoes chemical degradation to inactive forms at body pH and temperature. Because it does not rely on enzymatic degradation or hepatic or renal excretion, the drug is safe to use in patients with any degree of hepatic or renal impairment.Volume of distribution: 30–50 L. Anidulafungin is not evidently metabolized by the liver. This specific drug undergoes slow chemical hydrolysis to an open-ring peptide which lacks antifungal activity. The half-life of the drug is 27 hours. About 30% is excreted in the feces (10% as unchanged drug). Less than 1% is excreted in the urine. Mechanism of action Anidulafungin inhibits glucan synthase, an enzyme important in the formation of (1→3)-β-D-glucan, a major fungal cell wall component. Glucan synthase is not present in mammalian cells, so it is an attractive target for antifungal activity. Semisynthesis Anidulafungin is manufactured via semi-synthesis. The starting material is echinocandin B (a lipopeptide fermentation product of Aspergillus nidulans or the closely related species, A. rugulosus), which undergoes deacylation (cleavage of the linoleoyl side chain) by the action of a deacylase enzyme from the bacterium Actinoplanes utahensis; in three subsequent synthetic steps, including a chemical reacylation, the antifungal drug anidulafungin is synthesized. History Anidulafungin was originally discovered at Lilly laboratories by Turner and Debono and licensed to Vicuron Pharmaceuticals who submitted it to the FDA. Pfizer acquired the drug upon its acquisition of Vicuron in the fall of 2005. Pfizer gained approval by the Food and Drug Administration (FDA) on February 21, 2006. == References ==

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 'Clomifene' in simple language?

Clomifene, also known as clomiphene, is a medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome. Use results in a greater chance of twins. It is taken by mouth once a day, with a course of treatment that usually lasts for 5 days.Common side effects include pelvic pain and hot flashes. Other side effects can include changes in vision, vomiting, trouble sleeping, ovarian cancer, and seizures. It is not recommended in people with liver disease or abnormal vaginal bleeding of unknown cause or who are pregnant. Clomifene is in the selective estrogen receptor modulator (SERM) family of medication and is a nonsteroidal medication. It works by causing the release of GnRH by the hypothalamus, and subsequently gonadotropin from the anterior pituitary.Clomifene was approved for medical use in the United States in 1967. It is on the World Health Organizations List of Essential Medicines, under the category "Ovulation inducers" (Complementary List). Its introduction began the era of assisted reproductive technology.Clomifene (particularly the purified enclomiphene isomer) has also been found to have a powerful ability to boost or restore testosterone levels in hypogonadal men. Medical uses Ovulation induction Clomifene is one of several alternatives for ovulation induction in those who are infertile due to anovulation or oligoovulation. Evidence is lacking for the use of clomifene in those who are infertile without a known reason. In such cases, studies have observed a clinical pregnancy rate 5.6% per cycle with clomifene treatment vs. 1.3%–4.2% per cycle without treatment.Proper timing of the drug is important; it should be taken starting on about the fifth day of the cycle, and there should be frequent intercourse.The following procedures may be used to monitor induced cycles: Follicular monitoring with vaginal ultrasound, starting 4–6 days after the last pill. Serial transvaginal ultrasound can reveal the size and number of developing follicles. It can also provide presumptive evidence of ovulation such as the sudden collapse of the preovulatory follicle, and an increase in fluid volume in the rectouterine pouch. After ovulation, it may reveal signs of luteinization such as loss of clearly defined follicular margins and appearance of internal echoes. Serum estradiol levels, starting 4–6 days after the last pill Adequacy of LH surge by urine LH surge tests 3 to 4 days after last clomifene pill Post-coital test 1–3 days before ovulation to check whether there are at least 5 progressive sperm per HPF Mid-luteal progesterone, with at least 10 ng/ml 7–9 days after ovulation being regarded as adequate.Repeat dosing: This 5-day treatment course can be repeated every 30 days. The dosage may be increased by 50-mg increments in subsequent cycles until ovulation is achieved. It is not recommended by the manufacturer to use clomifene for more than 6 cycles.It is no longer recommended to perform an ultrasound examination to exclude any significant residual ovarian enlargement before each new treatment cycle. Other uses Clomifene has also been used with other assisted reproductive technology to increase success rates of these other modalities.Clomifene is sometimes used in the treatment of male hypogonadism as an alternative to testosterone replacement therapy. The medication has been used at a dosage of 20 to 50 mg three times per week to once day for this indication. It has been found to increase testosterone levels by 2- to 2.5-times in hypogonadal men at such dosages. Despite the use of questionnaires in testosterone replacement comparator trials being called into question, clomifenes lower cost, therapeutic benefits, and greater value towards hypogonadism improvement have been noted.Clomifene consists of two stereoisomers in equal proportion: enclomifene and zuclomifene. Zuclomifene has pro-estrogenic properties, whereas enclomifene is pro-androgenic, i.e. it promotes testosterone production through stimulation of the HPG axis. For this reason, purified enclomifene isomer has been found to be twice as effective in boosting testosterone compared to the standard mix of both isomers. Additionally, enclomifene has a half-life of just 10 hours, but zuclomifene has a half-life of 30 days—therefore if the goal is to boost testosterone, taking regular clomifene may produce far longer-lasting pro-estrogenic effects than pro-androgenic effects. Clomifene has been used in the treatment of gynecomastia. It has been found to be useful in the treatment of some cases of gynecomastia but it is not as effective as tamoxifen or raloxifene for this indication. It has shown variable results for gynecomastia (probably because the zuclomifene isomer is estrogenic), and hence is not recommended for treatment of the condition. Pure enclomifene isomer is likely to be more effective than clomifene at treating gynecomastia, because of the lack of the zuclomifene isomer (as noted above). Due to its long half-life, zuclomifene can be detected in urine for at least 261 days after discontinuation (261 days after discontinuation with a half-life of 30 days, there is still 0.24% of the peak level of zuclomifene being excreted, whereas with a half-life of 10 hours, enclomifene reaches the same 0.24% level in less than 4 days). Because of its potential for boosting testosterone, clomifene is listed as banned for use by competitive sportsmen, both in and out of competition, by the World Anti-Doping Agency, absent an organic etiology of primary hypogonadism. Contraindications Contraindications include an allergy to the medication, pregnancy, prior liver problems, abnormal vaginal bleeding of unclear cause, ovarian cysts other than those due to polycystic ovarian syndrome, unmanaged adrenal or thyroid problems, and pituitary tumors. Side effects The most common adverse drug reaction associated with the use of clomifene (>10% of people) is reversible ovarian enlargement.Less common effects (1–10% of people) include visual symptoms (blurred vision, double vision, floaters, eye sensitivity to light, scotomata), headaches, vasomotor flushes (or hot flashes), light sensitivity and pupil constriction, abnormal uterine bleeding and/or abdominal discomfort.Rare adverse events (<1% of people) include: high blood level of triglycerides, liver inflammation, reversible baldness and/or ovarian hyperstimulation syndrome.Clomifene can lead to multiple ovulation, hence increasing the chance of twins (10% of births instead of ~1% in the general population) and triplets. Rates of birth defects and miscarriages do not appear to change with the use of clomifene for fertility. Clomifene has been associated with liver abnormalities and a couple of cases of hepatotoxicity. Cancer risk Some studies have suggested that clomifene if used for more than a year may increase the risk of ovarian cancer. This may only be the case in those who have never been and do not become pregnant. Subsequent studies have failed to support those findings.Clomifene has been shown to be associated with an increased risk of malignant melanomas and thyroid cancer. Thyroid cancer risk was not associated with the number of pregnancies carried to viability. Pharmacology Pharmacodynamics Selective estrogen receptor modulator activity Clomifene is a nonsteroidal triphenylethylene derivative that acts as a selective estrogen receptor modulator (SERM). It consists of a racemic mixture of zuclomifene (~38%) and enclomifene (~62%), each of which has unique pharmacologic properties. It is a mixed agonist and antagonist of the estrogen receptor (ER). Clomifene activates the ERα in the setting of low baseline estrogen levels and partially blocks the receptor in the context of high baseline estrogen levels. Conversely, it is an antagonist of the ERβ. Clomifene has antiestrogenic effects in the uterus. There is little clinical research on the influence of clomifene in many target tissues, such as lipids, the cardiovascular system, and the breasts. Positive effects of clomifene on bone have been observed. Clomifene has been found to decrease insulin-like growth factor 1 (IGF-1) levels in women.Clomifene is a long-acting ER ligand, with a nuclear retention of greater than 48 hours. Clomifene is a prodrug being activated via similar metabolic pathways as the related triphenylethylene SERMs tamoxifen and toremifene. The affinity of clomifene for the ER relative to estradiol ranges from 0.1 to 12% in different studies, which is similar to the range for tamoxifen (0.06–16%). 4-Hydroxyclomifene, a major active metabolite of clomifene, and afimoxifene (4-hydroxytamoxifen), a major active metabolite of tamoxifen, show 89–251% and 41–246% of the affinity of estradiol for the ER in human MCF-7 breast cancer cells, respectively. The ER affinities of the isomers of 4-hydroxyclomifene were 285% for (E)-4-hydroxyclomifene and 16% for (Z)-4-hydroxyclomifene relative to estradiol. 4-Hydroxy-N-desmethylclomifene has similar affinity to 4-hydroxyclomifene for the ER. In one study, the affinities of clomifene and its metabolites for the ERα were ~100 nM for clomifene, ~2.4 nM for 4-hydroxyclomifene, ~125 nM for N-desmethylclomifene, and ~1.4 nM for 4-hydroxy-N-desmethylclomifene.Even though clomifene has some estrogenic effect, the antiestrogenic property is believed to be the primary source for stimulating ovulation. Clomifene appears to act mostly in the hypothalamus where it depletes hypothalamic ERs and blocks the negative feedback effect of circulating endogenous estradiol, which in turn results in an increase in hypothalamic gonadotropin-releasing hormone (GnRH) pulse frequency and circulating concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In normal physiologic female hormonal cycling, at 7 days past ovulation, high levels of estrogen and progesterone produced from the corpus luteum inhibit GnRH, FSH, and LH at the hypothalamus and anterior pituitary. If fertilization does not occur in the post-ovulation period the corpus luteum disintegrates due to a lack of human chorionic gonadotropin (hCG). This would normally be produced by the embryo in the effort of maintaining progesterone and estrogen levels during pregnancy. Therapeutically, clomifene is given early in the menstrual cycle. It is typically prescribed beginning on day 3 and continuing for 5 days. By that time, FSH levels are rising steadily, causing the development of a few follicles. Follicles, in turn, produce the estrogen, which circulates in serum. In the presence of clomifene, the body perceives a low level of estrogen, similar to day 22 in the previous cycle. Since estrogen can no longer effectively exert negative feedback on the hypothalamus, GnRH secretion becomes more rapidly pulsatile, which results in increased pituitary gonadotropin release. (More rapid, lower amplitude pulses of GnRH lead to increased LH and FSH secretion, while more irregular, larger amplitude pulses of GnRH leads to a decrease in the ratio of LH to FSH.) Increased FSH levels cause the growth of more ovarian follicles, and subsequently rupture of follicles resulting in ovulation. Ovulation occurs most often 6 to 7 days after a course of clomifene. In normal men, 50 mg/day clomifene for 8 months has been found to increase testosterone levels by around 870 ng/dL in younger men and by around 490 ng/dL in elderly men. Estradiol levels increased by 62 pg/mL in younger men and by 40 pg/mL in elderly men. These findings suggest that the progonadotropic effects of clomifene are stronger in younger men than in older men. In men with hypogonadism, clomifene has been found to increase testosterone levels by 293 to 362 ng/dL and estradiol levels by 5.5 to 13 pg/mL. In a large clinical study of men with low testosterone levels (<400 ng/dL), 25 mg/day clomifene increased testosterone levels from 309 ng/dL to 642 ng/dL after 3 months of therapy. No significant changes in HDL cholesterol, triglycerides, fasting glucose, or prolactin levels were observed, although total cholesterol levels decreased significantly. Other activities Clomifene is an inhibitor of the conversion of desmosterol into cholesterol by the enzyme 24-dehydrocholesterol reductase. Concerns about possible induction of desmosterolosis and associated symptoms such as cataracts and ichthyosis with extended exposure precluded the use of clomifene in the treatment of breast cancer. Continuous use of clomifene has been found to increase desmosterol levels by 10% and continuous high doses of clomifene (200 mg/day) have been reported to produce visual disturbances. Pharmacokinetics Clomifene produces N-desmethylclomifene, clomifenoxide (clomifene N-oxide), 4-hydroxyclomifene, and 4-hydroxy-N-desmethylclomifene as metabolites. Clomifene is a prodrug most importantly of 4-hydroxyclomifene and 4-hydroxy-N-desmethylclomifene, which are the most active of its metabolites. In one study, the peak levels after a single 50 mg dose of clomifene were 20.37 nmol/L for clomifene, 0.95 nmol/L for 4-hydroxyclomifene, and 1.15 nmol/L for 4-hydroxy-N-desmethylclomifene.Clomifene has an onset of action of 5 to 10 days following course of treatment and an elimination half-life about 5 days. In one study, after a single 50 mg dose of clomifene, the half-life of clomifene was 128 hours (5.3 days), of 4-hydroxyclomifene was 13 hours, and of 4-hydroxy-N-desmethylclomifene was 15 hours. Individuals with the CYP2D6*10 allele showed longer half-lives for 4-hydroxyclomifene and 4-hydroxy-N-desmethylclomifene.Most clomifene metabolism occurs in the liver, where it undergoes enterohepatic recirculation. Clomifene and its metabolites are excreted primarily through feces (42%), and excretion can occur up to 6 weeks after discontinuation. Chemistry Clomifene is a triphenylethylene derivative. It is a mixture of two geometric isomers, enclomifene ((E)-clomifene) and zuclomifene ((Z)-clomifene). These two isomers have been found to contribute to the mixed estrogenic and antiestrogenic properties of clomifene. History A team at William S. Merrell Chemical Company led by Frank Palopoli synthesized clomifene in 1956; after its biological activity was confirmed a patent was filed and issued in November 1959. Scientists at Merrell had previously synthesized chlorotrianisene and ethamoxytriphetol. Clomifene was studied in the treatment of advanced breast cancer during the period of 1964 to 1974 and was found to be effective but was abandoned due to concerns about desmosterolosis with extended use. Short-term use (e.g. days to months) did not raise the same concerns however and clomifene continued to be studied for other indications. Clinical studies were conducted under an Investigational New Drug Application; clomifene was third drug for which an IND had been filed under the 1962 Kefauver Harris Amendment to the Federal Food, Drug, and Cosmetic Act that had been passed in response to the thalidomide tragedy. It was approved for marketing in 1967 under the brand name Clomid. It was first used to treat cases of oligomenorrhea but was expanded to include treatment of anovulation when women undergoing treatment had higher than expected rates of pregnancy.The drug is widely considered to have been a revolution in the treatment of female infertility, the beginning of the modern era of assisted reproductive technology, and the beginning of what in the words of Eli Y. Adashi, was "the onset of the US multiple births epidemic".The company was acquired by Dow Chemical in 1980, and in 1989 Dow Chemical acquired 67 percent interest of Marion Laboratories, which was renamed Marion Merrell Dow. In 1995 Hoechst AG acquired the pharmaceutical business of Marion Merrell Dow. Hoechst in turn became part of Aventis in 1999,: 9–11  and subsequently a part of Sanofi. It became the most widely prescribed drug for ovulation induction to reverse anovulation or oligoovulation. Society and culture Brand names Clomifene is marketed under many brand names worldwide, including Beclom, Bemot, Biogen, Blesifen, Chloramiphene, Clofert, Clomene, ClomHEXAL, Clomi, Clomid, Clomidac, Clomifen, Clomifencitrat, Clomifene, Clomifène, Clomifene citrate, Clomifeni citras, Clomifeno, Clomifert, Clomihexal, Clomiphen, Clomiphene, Clomiphene Citrate, Cloninn, Clostil, Clostilbegyt, Clovertil, Clovul, Dipthen, Dufine, Duinum, Fensipros, Fertab, Fertec, Fertex, Ferticlo, Fertil, Fertilan, Fertilphen, Fertin, Fertomid, Ferton, Fertotab, Fertyl, Fetrop, Folistim, Genoclom, Genozym, Hete, I-Clom, Ikaclomin, Klofit, Klomen, Klomifen, Lomifen, MER 41, Milophene, Ofertil, Omifin, Ova-mit, Ovamit, Ovinum, Ovipreg, Ovofar, Ovuclon, Ovulet, Pergotime, Pinfetil, Profertil, Prolifen, Provula, Reomen, Serofene, Serophene, Serpafar, Serpafar, Surole, Tocofeno, and Zimaquin. Regulation Clomifene is included on the World Anti-Doping Agency list of illegal doping agents in sport. It is listed because it is an "anti-estrogenic substance". Research Clomifene has been used almost exclusively for ovulation induction in premenopausal women, and has been studied very limitedly in postmenopausal women.Clomifene was studied for treatment and prevention of breast cancer, but issues with toxicity led to abandonment of this indication, as did the discovery of tamoxifen. Like the structurally related drug triparanol, clomifene is known to inhibit the enzyme 24-dehydrocholesterol reductase and increase circulating desmosterol levels, making it unfavorable for extended use in breast cancer due to risk of side effects like irreversible cataracts. References External links "Clomifene". Drug Information Portal. U.S. National Library of Medicine.

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

Could you please explain the term 'Kidney disease' in simple language?

Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can be diagnosed by blood tests. Nephrosis is non-inflammatory kidney disease. Nephritis and nephrosis can give rise to nephritic syndrome and nephrotic syndrome respectively. Kidney disease usually causes a loss of kidney function to some degree and can result in kidney failure, the complete loss of kidney function. Kidney failure is known as the end-stage of kidney disease, where dialysis or a kidney transplant is the only treatment option. Chronic kidney disease is defined as prolonged kidney abnormalities (functional and/or structural in nature) that last for more than three months. Acute kidney disease is now termed acute kidney injury and is marked by the sudden reduction in kidney function over seven days. In 2007, about one in eight Americans had chronic kidney disease. This rate is increasing over time to where about 1 in 7 Americans are estimated to have CKD as of 2021.With the increasing prevalence of chronic kidney disease, there are many treatment plans available. Individuals can get blood or urine tests to access the health and function of the kidneys. For severe kidney disease, dialysis and kidney transplants are the most popular options. Dialysis is a treatment where it acts as an artificial kidney and removes waste products and fluid from an individuals blood. This is accomplished via a machine. Kidney transplants are the surgical procedure of transporting a healthy kidney from a donor into an individual with kidney disease. Both of these options have their pros and con, the success varies by individual. Causes Causes of kidney disease include deposition of the Immunoglobulin A antibodies in the glomerulus, administration of analgesics, xanthine oxidase deficiency, toxicity of chemotherapy agents, and long-term exposure to lead or its salts. Chronic conditions that can produce nephropathy include systemic lupus erythematosus, diabetes mellitus and high blood pressure (hypertension), which lead to diabetic nephropathy and hypertensive nephropathy, respectively. Analgesics One cause of nephropathy is the long term usage of pain medications known as analgesics. The pain medicines which can cause kidney problems include aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs). This form of nephropathy is "chronic analgesic nephritis," a chronic inflammatory change characterized by loss and atrophy of tubules and interstitial fibrosis and inflammation (BRS Pathology, 2nd edition). Specifically, long-term use of the analgesic phenacetin has been linked to renal papillary necrosis (necrotizing papillitis). Diabetes Diabetic nephropathy is a progressive kidney disease caused by angiopathy of the capillaries in the glomeruli. It is characterized by nephrotic syndrome and diffuse scarring of the glomeruli. It is particularly associated with poorly managed diabetes mellitus and is a primary reason for dialysis in many developed countries. It is classified as a small blood vessel complication of diabetes. Autosomal dominant polycystic kidney disease Gabow 1990 talks about Autosomal Dominant Polycystic Kidney disease and how this disease is genetic. They go on to say "Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease, affecting a half million Americans. The clinical phenotype can result from at least two different gene defects. One gene that can cause ADPKD has been located on the short arm of chromosome 16." The same article also goes on to say that millions of Americans are effected by this disease and is very common. Long COVID and Kidney Disease Yende & Parikh 2021 talk about the effects that COVID can have on a person that has a pre-existing health issue regarding kidney diseases. "frailty, chronic diseases, disability and immunodeficiency are at increased risk of kidney disease and progression to kidney failure, and infection with SARS-CoV-2 can further increase this risk” (Long COVID and Kidney Disease, 2021). Diet Higher dietary intake of animal protein, animal fat, and cholesterol may increase risk for microalbuminuria, a sign of kidney function decline, and generally, diets higher in fruits, vegetables, and whole grains but lower in meat and sweets may be protective against kidney function decline. This may be because sources of animal protein, animal fat, and cholesterol, and sweets are more acid-producing, while fruits, vegetables, legumes, and whole grains are more base-producing. IgA nephropathy IgA nephropathy is the most common glomerulonephritis throughout the world Primary IgA nephropathy is characterized by deposition of the IgA antibody in the glomerulus. The classic presentation (in 40-50% of the cases) is episodic frank hematuria which usually starts within a day or two of a non-specific upper respiratory tract infection (hence synpharyngitic) as opposed to post-streptococcal glomerulonephritis which occurs some time (weeks) after initial infection. Less commonly gastrointestinal or urinary infection can be the inciting agent. All of these infections have in common the activation of mucosal defenses and hence IgA antibody production. Iodinated contrast media Kidney disease induced by iodinated contrast media (ICM) is called CIN (= contrast induced nephropathy) or contrast-induced AKI (= acute kidney injury). Currently, the underlying mechanisms are unclear. But there is a body of evidence that several factors including apoptosis-induction seem to play a role. Lithium Lithium, a medication commonly used to treat bipolar disorder and schizoaffective disorders, can cause nephrogenic diabetes insipidus; its long-term use can lead to nephropathy. Lupus Despite expensive treatments, lupus nephritis remains a major cause of morbidity and mortality in people with relapsing or refractory lupus nephritis. Xanthine oxidase deficiency Another possible cause of Kidney disease is due to decreased function of xanthine oxidase in the purine degradation pathway. Xanthine oxidase will degrade hypoxanthine to xanthine and then to uric acid. Xanthine is not very soluble in water; therefore, an increase in xanthine forms crystals (which can lead to kidney stones) and result in damage to the kidney. Xanthine oxidase inhibitors, like allopurinol, can cause nephropathy. Polycystic disease of the kidneys Additional possible cause of nephropathy is due to the formation of cysts or pockets containing fluid within the kidneys. These cysts become enlarged with the progression of aging causing renal failure. Cysts may also form in other organs including the liver, brain, and ovaries. Polycystic Kidney Disease is a genetic disease caused by mutations in the PKD1, PKD2, and PKHD1 genes. This disease affects about half a million people in the US. Polycystic kidneys are susceptible to infections and cancer. Toxicity of chemotherapy agents Nephropathy can be associated with some therapies used to treat cancer. The most common form of kidney disease in cancer patients is Acute Kidney Injury (AKI) which can usually be due to volume depletion from vomiting and diarrhea that occur following chemotherapy or occasionally due to kidney toxicities of chemotherapeutic agents. Kidney failure from break down of cancer cells, usually after chemotherapy, is unique to onconephrology. Several chemotherapeutic agents, for example Cisplatin, are associated with acute and chronic kidney injuries. Newer agents such as anti Vascular Endothelial Growth Factor (anti VEGF) are also associated with similar injuries, as well as proteinuria, hypertension and thrombotic microangiopathy. Diagnosis The standard diagnostic workup of suspected kidney disease includes a medical history, physical examination, a urine test, and an ultrasound of the kidneys (renal ultrasonography). An ultrasound is essential in the diagnosis and management of kidney disease. Treatment Treatment approaches for kidney disease focus on managing the symptoms, controlling the progression, and also treating co-morbidities that a person may have. Dialysis Transplantation Millions of people across the world have kidney disease. Of those millions, several thousand will need dialysis or a kidney transplant at its end-stage. In the United States, as of 2008, 16,500 people needed a kidney transplant. Of those, 5,000 died while waiting for a transplant. Currently, there is a shortage of donors, and in 2007 there were only 64,606 kidney transplants in the world. This shortage of donors is causing countries to place monetary value on kidneys. Countries such as Iran and Singapore are eliminating their lists by paying their citizens to donate. Also, the black market accounts for 5-10 percent of transplants that occur worldwide. The act of buying an organ through the black market is illegal in the United States. To be put on the waiting list for a kidney transplant, patients must first be referred by a physician, then they must choose and contact a donor hospital. Once they choose a donor hospital, patients must then receive an evaluation to make sure they are sustainable to receive a transplant. In order to be a match for a kidney transplant, patients must match blood type and human leukocyte antigen factors with their donors. They must also have no reactions to the antibodies from the donors kidneys. Prognosis Kidney disease can have serious consequences if it cannot be controlled effectively. Generally, the progression of kidney disease is from mild to serious. Some kidney diseases can cause kidney failure. Notable people Nathan W. Levin, American physician, organization founder and author See also Hematologic Diseases Information Service Mesoamerican nephropathy, an enigmatic chronic kidney disease of Central America Protein toxicity References https://www.mayoclinic.org/diseases-conditions/chronic-kidney-disease/diagnosis-treatment/drc-20354527 == External links ==

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

Spindle cell rhabdomyosarcoma is a subtype of embryonal rhabdomyosarcoma first described by Cavazzana, Schmidt and Ninfo in 1992. This subtype has a more favorable clinical course and prognosis than usual embryonal rhabdomyosarcoma. Spindle cell rhabdomyosarcoma typically occurs in young males and most commonly occurs in paratesticular soft tissue, followed by the head and neck. == References ==

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

A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the persons mood is the main underlying feature. The classification is in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Mood disorders fall into seven groups, including; abnormally elevated mood, such as mania or hypomania; depressed mood, of which the best-known and most researched is major depressive disorder (MDD) (alternatively known as clinical depression, unipolar depression, or major depression); and moods which cycle between mania and depression, known as bipolar disorder (BD) (formerly known as manic depression). There are several sub-types of depressive disorders or psychiatric syndromes featuring less severe symptoms such as dysthymic disorder (similar to MDD, but longer lasting and more persistent, though often milder) and cyclothymic disorder (similar to but milder than BD).In some cases, more than one mood disorder can be present in an individual, like bipolar disorder and depressive disorder. If a mood disorder and schizophrenia are both present in an individual, this is known as schizoaffective disorder. Mood disorders may also be substance induced, or occur in response to a medical condition. English psychiatrist Henry Maudsley proposed an overarching category of affective disorder. The term was then replaced by mood disorder, as the latter term refers to the underlying or longitudinal emotional state, whereas the former refers to the external expression observed by others. Classification Depressive disorders Major depressive disorder (MDD), commonly called major depression, unipolar depression, or clinical depression, wherein a person has one or more major depressive episodes. After a single episode, Major Depressive Disorder (single episode) would be diagnosed. After more than one episode, the diagnosis becomes Major Depressive Disorder (Recurrent). Depression without periods of mania is sometimes referred to as unipolar depression because the mood remains at the bottom "pole" and does not climb to the higher, manic "pole" as in bipolar disorder.Individuals with a major depressive episode or major depressive disorder are at increased risk for suicide. Seeking help and treatment from a health professional dramatically reduces the individuals risk for suicide. Studies have demonstrated that asking if a depressed friend or family member has thought of committing suicide is an effective way of identifying those at risk, and it does not "plant" the idea or increase an individuals risk for suicide in any way. Epidemiological studies carried out in Europe suggest that, at this moment, roughly 8.5 percent of the worlds population have a depressive disorder. No age group seems to be exempt from depression, and studies have found that depression appears in infants as young as 6 months old who have been separated from their mothers.Depressive disorder is frequent in primary care and general hospital practice but is often undetected. Unrecognized depressive disorder may slow recovery and worsen prognosis in physical illness, therefore it is important that all doctors be able to recognize the condition, treat the less severe cases, and identify those requiring specialist care.Diagnosticians recognize several subtypes or course specifiers:Atypical depression (AD) is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain or increased appetite ("comfort eating"), excessive sleep or somnolence (hypersomnia), a sensation of heaviness in limbs known as leaden paralysis, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection. Difficulties in measuring this subtype have led to questions of its validity and prevalence.Melancholic depression is characterized by a loss of pleasure (anhedonia) in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of grief or loss, a worsening of symptoms in the morning hours, early-morning waking, psychomotor retardation, excessive weight loss (not to be confused with anorexia nervosa), or excessive guilt.Psychotic major depression (PMD), or simply psychotic depression, is the term for a major depressive episode, in particular of melancholic nature, wherein the patient experiences psychotic symptoms such as delusions or, less commonly, hallucinations. These are most commonly mood-congruent (content coincident with depressive themes).Catatonic depression is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here, the person is mute and almost stuporose, and either is immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms can also occur in schizophrenia or a manic episode, or can be due to neuroleptic malignant syndrome.Postpartum depression (PPD) is listed as a course specifier in DSM-IV-TR; it refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth. Postpartum depression, which affects 10–15% of women, typically sets in within three months of labor, and lasts as long as three months. It is quite common for women to experience a short-term feeling of tiredness and sadness in the first few weeks after giving birth; however, postpartum depression is different because it can cause significant hardship and impaired functioning at home, work, or school as well as, possibly, difficulty in relationships with family members, spouses, or friends, or even problems bonding with the newborn. In the treatment of postpartum major depressive disorders and other unipolar depressions in women who are breastfeeding, nortriptyline, paroxetine (Paxil), and sertraline (Zoloft) are in general considered to be the preferred medications. Women with personal or family histories of mood disorders are at particularly high risk of developing postpartum depression.Premenstrual dysphoric disorder (PMDD) is a severe and disabling form of premenstrual syndrome affecting 3–8% of menstruating women. The disorder consists of a "cluster of affective, behavioral and somatic symptoms" that recur monthly during the luteal phase of the menstrual cycle. PMDD was added to the list of depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders in 2013. The exact pathogenesis of the disorder is still unclear and is an active research topic. Treatment of PMDD relies largely on antidepressants that modulate serotonin levels in the brain via serotonin reuptake inhibitors as well as ovulation suppression using contraception.Seasonal affective disorder (SAD), also known as "winter depression" or "winter blues", is a specifier. Some people have a seasonal pattern, with depressive episodes coming on in the autumn or winter, and resolving in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times over a two-year period or longer. It is commonly hypothesised that people who live at higher latitudes tend to have less sunlight exposure in the winter and therefore experience higher rates of SAD, but the epidemiological support for this proposition is not strong (and latitude is not the only determinant of the amount of sunlight reaching the eyes in winter). It is said that this disorder can be treated by light therapy. SAD is also more prevalent in people who are younger and typically affects more females than males.Dysthymia is a condition related to unipolar depression, where the same physical and cognitive problems are evident, but they are not as severe and tend to last longer (usually at least 2 years). The treatment of dysthymia is largely the same as for major depression, including antidepressant medications and psychotherapy.Double depression can be defined as a fairly depressed mood (dysthymia) that lasts for at least two years and is punctuated by periods of major depression.Unspecified Depressive Disorder is designated by the code 311 for depressive disorders. In the DSM-5, Unspecified Depressive Disorder encompasses symptoms that are characteristic of depressive disorders and cause significant impairment in functioning, but do not meet the criteria for the diagnosis of any specified depressive disorders. In the DSM-IV, this was called Depressive Disorder Not Otherwise Specified.Depressive personality disorder (DPD) is a controversial psychiatric diagnosis that denotes a personality disorder with depressive features. Originally included in the DSM-II, depressive personality disorder was removed from the DSM-III and DSM-III-R. Recently, it has been reconsidered for reinstatement as a diagnosis. Depressive personality disorder is currently described in Appendix B in the DSM-IV-TR as worthy of further study.Recurrent brief depression (RBD), distinguished from major depressive disorder primarily by differences in duration. People with RBD have depressive episodes about once per month, with individual episodes lasting less than two weeks and typically less than 2–3 days. Diagnosis of RBD requires that the episodes occur over the span of at least one year and, in female patients, independently of the menstrual cycle. People with clinical depression can develop RBD, and vice versa, and both illnesses have similar risks.Minor depressive disorder, or simply minor depression, which refers to a depression that does not meet full criteria for major depression but in which at least two symptoms are present for two weeks. Bipolar disorders Bipolar disorder (BD) (also called "manic depression" or "manic-depressive disorder"), an unstable emotional condition characterized by cycles of abnormal, persistent high mood (mania) and low mood (depression), which was formerly known as "manic depression" (and in some cases rapid cycling, mixed states, and psychotic symptoms). Subtypes include:Bipolar I is distinguished by the presence or history of one or more manic episodes or mixed episodes with or without major depressive episodes. A depressive episode is not required for the diagnosis of Bipolar I Disorder, but depressive episodes are usually part of the course of the illness. Bipolar II consisting of recurrent intermittent hypomanic and depressive episodes or mixed episodes. Cyclothymia is a form of bipolar disorder, consisting of recurrent hypomanic and dysthymic episodes, but no full manic episodes or full major depressive episodes. Bipolar disorder not otherwise specified (BD-NOS), sometimes called "sub-threshold" bipolar, indicates that the patient has some symptoms in the bipolar spectrum (e.g., manic and depressive symptoms) but does not fully qualify for any of the three formal bipolar DSM-IV diagnoses mentioned above. It is estimated that roughly 1% of the adult population has bipolar I, a further 1% has bipolar II or cyclothymia, and somewhere between 2% and 5% percent have "sub-threshold" forms of bipolar disorder. Furthermore, the possibility of getting bipolar disorder when one parent is diagnosed with it is 15–30%. Risk, when both parents have it, is 50–75%. Also, while with bipolar siblings the risk is 15–25%, with identical twins it is about 70%.A minority of people with bipolar disorder have high creativity, artistry or a particular gifted talent. Before the mania phase becomes too extreme, its energy, ambition, enthusiasm and grandiosity often bring people with this type of mood disorder lifes masterpieces. Substance-induced A mood disorder can be classified as substance-induced if its etiology can be traced to the direct physiologic effects of a psychoactive drug or other chemical substance, or if the development of the mood disorder occurred contemporaneously with substance intoxication or withdrawal. Also, an individual may have a mood disorder coexisting with a substance abuse disorder. Substance-induced mood disorders can have features of a manic, hypomanic, mixed, or depressive episode. Most substances can induce a variety of mood disorders. For example, stimulants such as amphetamine, methamphetamine, and cocaine can cause manic, hypomanic, mixed, and depressive episodes. Alcohol-induced High rates of major depressive disorder occur in heavy drinkers and those with alcoholism. Controversy has previously surrounded whether those who abused alcohol and developed depression were self-medicating their pre-existing depression. Recent research has concluded that, while this may be true in some cases, alcohol misuse directly causes the development of depression in a significant number of heavy drinkers. Participants studied were also assessed during stressful events in their lives and measured on a Feeling Bad Scale. Likewise, they were also assessed on their affiliation with deviant peers, unemployment, and their partners substance use and criminal offending. High rates of suicide also occur in those who have alcohol-related problems. It is usually possible to differentiate between alcohol-related depression and depression that is not related to alcohol intake by taking a careful history of the patient. Depression and other mental health problems associated with alcohol misuse may be due to distortion of brain chemistry, as they tend to improve on their own after a period of abstinence. Benzodiazepine-induced Benzodiazepines, such as alprazolam, clonazepam, lorazepam and diazepam, can cause both depression and mania.Benzodiazepines are a class of medication commonly used to treat anxiety, panic attacks and insomnia, and are also commonly misused and abused. Those with anxiety, panic and sleep problems commonly have negative emotions and thoughts, depression, suicidal ideations, and often have comorbid depressive disorders. While the anxiolytic and hypnotic effects of benzodiazepines disappear as tolerance develops, depression and impulsivity with high suicidal risk commonly persist. These symptoms are "often interpreted as an exacerbation or as a natural evolution of previous disorders and the chronic use of sedatives is overlooked". Benzodiazepines do not prevent the development of depression, can exacerbate preexisting depression, can cause depression in those with no history of it, and can lead to suicide attempts. Risk factors for suicide and suicide attempts while using benzodiazepines include high dose prescriptions (even in those not misusing the medications), benzodiazepine intoxication, and underlying depression.The long-term use of benzodiazepines may have a similar effect on the brain as alcohol, and are also implicated in depression. As with alcohol, the effects of benzodiazepine on neurochemistry, such as decreased levels of serotonin and norepinephrine, are believed to be responsible for the increased depression. Additionally, benzodiazepines can indirectly worsen mood by worsening sleep (i.e., benzodiazepine-induced sleep disorder). Like alcohol, benzodiazepines can put people to sleep but, while asleep, they disrupt sleep architecture: decreasing sleep time, delaying time to REM sleep, and decreasing deep sleep (the most restorative part of sleep for both energy and mood). Just as some antidepressants can cause or worsen anxiety in some patients due to being activating, benzodiazepines can cause or worsen depression due to being a central nervous system depressant—worsening thinking, concentration and problem solving (i.e., benzodiazepine-induced neurocognitive disorder). However, unlike antidepressants, in which the activating effects usually improve with continued treatment, benzodiazepine-induced depression is unlikely to improve until after stopping the medication.In a long-term follow-up study of patients dependent on benzodiazepines, it was found that 10 people (20%) had taken drug overdoses while on chronic benzodiazepine medication despite only two people ever having had any pre-existing depressive disorder. A year after a gradual withdrawal program, no patients had taken any further overdoses.Just as with intoxication and chronic use, benzodiazepine withdrawal can also cause depression. While benzodiazepine-induced depressive disorder may be exacerbated immediately after discontinuation of benzodiazepines, evidence suggests that mood significantly improves after the acute withdrawal period to levels better than during use. Depression resulting from withdrawal from benzodiazepines usually subsides after a few months but in some cases may persist for 6–12 months. Due to another medical condition "Mood disorder due to a general medical condition" is used to describe manic or depressive episodes which occur secondary to a medical condition. There are many medical conditions that can trigger mood episodes, including neurological disorders (e.g. dementias), metabolic disorders (e.g. electrolyte disturbances), gastrointestinal diseases (e.g. cirrhosis), endocrine disease (e.g. thyroid abnormalities), cardiovascular disease (e.g. heart attack), pulmonary disease (e.g. chronic obstructive pulmonary disease), cancer, and autoimmune diseases (e.g. multiple sclerosis). Not otherwise specified Mood disorder not otherwise specified (MD-NOS) is a mood disorder that is impairing but does not fit in with any of the other officially specified diagnoses. In the DSM-IV MD-NOS is described as "any mood disorder that does not meet the criteria for a specific disorder." MD-NOS is not used as a clinical description but as a statistical concept for filing purposes. The diagnosis of MD-NOS does not exist in the DSM-5, however the diagnoses of unspecified depressive disorder and unspecified bipolar disorder are in the DSM-5.Most cases of MD-NOS represent hybrids between mood and anxiety disorders, such as mixed anxiety-depressive disorder or atypical depression. An example of an instance of MD-NOS is being in minor depression frequently during various intervals, such as once every month or once in three days. There is a risk for MD-NOS not to get noticed, and for that reason not to get treated. Causes Meta-analyses show that high scores on the personality domain neuroticism are a strong predictor for the development of mood disorders. A number of authors have also suggested that mood disorders are an evolutionary adaptation (see also evolutionary psychiatry). A low or depressed mood can increase an individuals ability to cope with situations in which the effort to pursue a major goal could result in danger, loss, or wasted effort. In such situations, low motivation may give an advantage by inhibiting certain actions. This theory helps to explain why negative life incidents precede depression in around 80 percent of cases, and why they so often strike people during their peak reproductive years. These characteristics would be difficult to understand if depression were a dysfunction.A depressed mood is a predictable response to certain types of life occurrences, such as loss of status, divorce, or death of a child or spouse. These are events that signal a loss of reproductive ability or potential, or that did so in humans ancestral environment. A depressed mood can be seen as an adaptive response, in the sense that it causes an individual to turn away from the earlier (and reproductively unsuccessful) modes of behavior.A depressed mood is common during illnesses, such as influenza. It has been argued that this is an evolved mechanism that assists the individual in recovering by limiting their physical activity. The occurrence of low-level depression during the winter months, or seasonal affective disorder, may have been adaptive in the past, by limiting physical activity at times when food was scarce. It is argued that humans have retained the instinct to experience low mood during the winter months, even if the availability of food is no longer determined by the weather.Much of what is known about the genetic influence of clinical depression is based upon research that has been done with identical twins. Identical twins have exactly the same genetic code. It has been found that when one identical twin becomes depressed the other will also develop clinical depression approximately 76% of the time. When identical twins are raised apart from each other, they will both become depressed about 67% of the time. Because both twins become depressed at such a high rate, the implication is that there is a strong genetic influence. If it happened that when one twin becomes clinically depressed the other always develops depression, then clinical depression would likely be entirely genetic.Bipolar disorder is also considered a mood disorder and it is hypothesized that it might be caused by mitochondrial dysfunction. Sex differences Mood disorders, specifically stress-related mood disorders such as anxiety and depression, have been shown to have differing rates of diagnosis based on sex. In the United States, women are two times more likely than men to be diagnosed with a stress-related mood disorder. Underlying these sex differences, studies have shown a dysregulation of stress-responsive neuroendocrine function causing an increase in the likelihood of developing these affective disorders. Overactivation of the hypothalamic-pituitary-adrenal (HPA) axis could provide potential insight into how these sex differences arise. Neuropeptide corticotropin-releasing factor (CRF) is released from the paraventricular nucleus (PVN) of the hypothalamus, stimulating adrenocorticotropic hormone (ACTH) release into the blood stream. From here ACTH triggers the release of glucocorticoids such as cortisol from the adrenal cortex. Cortisol, known as the main stress hormone, creates a negative feedback loop back to the hypothalamus to deactivate the stress response. When a constant stressor is present, the HPA axis remains overactivated and cortisol is constantly produced. This chronic stress is associated with sustained CRF release, resulting in the increased production of anxiety- and depressive-like behaviors and serving as a potential mechanism for differences in prevalence between men and women. Diagnosis DSM-5 The DSM-5, released in May 2013, separates the mood disorder chapter from the DSM-TR-IV into two sections: Depressive and related disorders and bipolar and related disorders. Bipolar disorders fall in between depressive disorders and schizophrenia spectrum and related disorders "in recognition of their place as a bridge between the two diagnostic classes in terms of symptomatology, family history and genetics" (Ref. 1, p 123). Bipolar disorders underwent a few changes in the DSM-5, most notably the addition of more specific symptomology related to hypomanic and mixed manic states. Depressive disorders underwent the most changes, the addition of three new disorders: disruptive mood dysregulation disorder, persistent depressive disorder (previously dysthymia), and premenstrual dysphoric disorder (previously in appendix B, the section for disorders needing further research). Disruptive mood dysregulation disorder is meant as a diagnosis for children and adolescents who would normally be diagnosed with bipolar disorder as a way to limit the bipolar diagnosis in this age cohort. Major depressive disorder (MDD) also underwent a notable change, in that the bereavement clause has been removed. Those previously exempt from a diagnosis of MDD due to bereavement are now candidates for the MDD diagnosis. Treatment There are different types of treatments available for mood disorders, such as therapy and medications. Behaviour therapy, cognitive behaviour therapy and interpersonal therapy have all shown to be potentially beneficial in depression. Major depressive disorder medications usually include antidepressants; a combination of antidepressants and cognitive behavioral therapy has shown to be more effective than one treatment alone. Bipolar disorder medications can consist of antipsychotics, mood stabilizers, anticonvulsants and/or lithium. Lithium specifically has been proven to reduce suicide and all causes of mortality in people with mood disorders. If mitochondrial dysfunction or mitochondrial diseases are the cause of mood disorders like bipolar disorder, then it has been hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options. In determining treatment, there are many types of depression scales that are used. One of the depression scales is a self-report scale called Beck Depression Inventory (BDI). Another scale is the Hamilton Depression Rating Scale (HAMD). HAMD is a clinical rating scale in which the patient is rated based on clinician observation. The Center for Epidemiologic Studies Depression Scale (CES-D) is a scale for depression symptoms that applies to the general population. This scale is typically used in research and not for self-reports. The PHQ-9 which stands for Patient-Health Questionnaire-9 questions, is a self-report as well. Finally, the Mood Disorder Questionnaire (MDQ) evaluates bipolar disorder. Epidemiology According to a substantial number of epidemiology studies conducted, women are twice as likely to develop certain mood disorders, such as major depression. Although there is an equal number of men and women diagnosed with bipolar II disorder, women have a slightly higher frequency of the disorder.The prevalence of depressive symptoms has increased over the years with recent generations reporting a 6% increase in symptoms of depression compared to individuals from older generations.In 2011, mood disorders were the most common reason for hospitalization among children aged 1–17 years in the United States, with approximately 112,000 stays. Mood disorders were top principal diagnosis for Medicaid super-utilizers in the United States in 2012. Further, a study of 18 States found that mood disorders accounted for the highest number of hospital readmissions among Medicaid patients and the uninsured, with 41,600 Medicaid patients and 12,200 uninsured patients being readmitted within 30 days of their index stay—a readmission rate of 19.8 per 100 admissions and 12.7 per 100 admissions, respectively. In 2012, mood and other behavioral health disorders were the most common diagnoses for Medicaid-covered and uninsured hospital stays in the United States (6.1% of Medicaid stays and 5.2% of uninsured stays).A study conducted in 1988 to 1994 amongst young American adults involved a selection of demographic and health characteristics. A population-based sample of 8,602 men and women ages 17–39 years participated. Lifetime prevalence were estimated based on six mood measures: major depressive episode (MDE) 8.6%, major depressive disorder with severity (MDE-s) 7.7%, dysthymia 6.2%, MDE-s with dysthymia 3.4%, any bipolar disorder 1.6%, and any mood disorder 11.5%. Research Kay Redfield Jamison and others have explored the possible links between mood disorders – especially bipolar disorder – and creativity. It has been proposed that a "ruminating personality type may contribute to both [mood disorders] and art."Jane Collingwood notes an Oregon State University study that "looked at the occupational status of a large group of typical patients and found that those with bipolar illness appear to be disproportionately concentrated in the most creative occupational category. They also found that the likelihood of engaging in creative activities on the job is significantly higher for bipolar than nonbipolar workers".In Liz Patereks article "Bipolar Disorder and the Creative Mind" she wrote "Memory and creativity are related to mania. Clinical studies have shown that those in a manic state will rhyme, find synonyms, and use alliteration more than controls. This mental fluidity could contribute to an increase in creativity. Moreover, mania creates increases in productivity and energy. Those in a manic state are more emotionally sensitive and show less inhibition about attitudes, which could create greater expression. Studies performed at Harvard looked into the amount of original thinking in solving creative tasks. Bipolar individuals, whose disorder was not severe, tended to show greater degrees of creativity".The relationship between depression and creativity appears to be especially strong among poets. See also Personality disorder References Cited textsAmerican Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders, Fourth Edition, Text Revision: DSM-IV-TR. Washington, DC: American Psychiatric Publishing, Inc. ISBN 978-0-89042-025-6. American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders, Fifth Edition, Text Revision: DSM-5. Washington, DC: American Psychiatric Association, Inc. ISBN 978-0-89042-554-1. Carlson, Neil R.; Heth, C. Donald (2007). Psychology the science of behaviour (4th ed.). Pearson Education Inc. ISBN 978-0-205-64524-4. Collier, Judith; Longmore, Murray (2003). "4". In Scally, Peter (ed.). Oxford Handbook of Clinical Specialties (6th ed.). Oxford University Press. ISBN 978-0-19-852518-9. Nesse, Randolphe M.; Williams, George C. (1994). Why We Get Sick: The New Science of Darwinian Medicine. Vintage Books. ISBN 0-8129-2224-7. Nolen-Hoeksema, S (2013). Abnormal Psychology (6th ed.). McGraw-Hill Higher Education. ISBN 9780077499693. Retrieved 5 December 2014. Parker, Gordon; Hadzi-Pavlovic, Dusan; Eyers, Kerrie (1996). Melancholia: A disorder of movement and mood: a phenomenological and neurobiological review. Cambridge: Cambridge University Press. ISBN 978-0-521-47275-3. Sadock, Benjamin J.; Sadock, Virginia A. (2002). Kaplan and Sadocks Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry (9th ed.). Lippincott Williams & Wilkins. ISBN 978-0-7817-3183-6. Semple, David; Smyth, Roger; Burns, Jonathan; Darjee, Rajan; McIntosh, Andrew (2007) [2005]. "13". Oxford Handbook of Psychiatry. Oxford University Press. ISBN 978-0-19-852783-1. Sartorius, Norman (1993). "The ICD-10 Classification of Mental and Behavioural Disorders – Clinical descriptions and diagnostic guidelines" (PDF). www.who.int. World Health Organization. Retrieved 3 July 2021.{{cite web}}: CS1 maint: url-status (link) Schacter, Daniel L.; Gilbert, Daniel T.; Wegner, Daniel M. (2011). "Chapter 14: Psychological Disorders". Psychology (2nd ed.). Worth Publishers. ISBN 9781429237192. External links Media related to Mood disorders at Wikimedia Commons

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

Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary muscle contraction), and several other symptoms. It is a very rare disease. The condition can be inherited, but it is also encountered after thyroid or parathyroid gland surgery, and it can be caused by immune system-related damage as well as a number of rarer causes. The diagnosis is made with blood tests, and other investigations such as genetic testing depending on the results. The primary treatment of hypoparathyroidism is calcium and vitamin D supplementation. Calcium replacement or vitamin D can ameliorate the symptoms but can increase the risk of kidney stones and chronic kidney disease. Additionally, injectable medications such as recombinant human parathyroid hormone or teriparatide may be given by injection to replace the missing hormone. Signs and symptoms The main symptoms of hypoparathyroidism are the result of the low blood calcium level, which interferes with normal muscle contraction and nerve conduction. As a result, people with hypoparathyroidism can experience paresthesia, an unpleasant tingling sensation around the mouth and in the hands and feet, as well as muscle cramps and severe spasms known as "tetany" that affect the hands and feet. Many also report a number of subjective symptoms such as fatigue, headaches, bone pain and insomnia. Crampy abdominal pain may occur. Physical examination of someone with hypocalcemia may show tetany, but it is also possible to provoke tetany of the facial muscles by tapping on the facial nerve (a phenomenon known as Chvosteks sign) or by using the cuff of a sphygmomanometer to temporarily obstruct the blood flow to the arm (a phenomenon known as Trousseaus sign of latent tetany).A number of medical emergencies can arise in people with low calcium levels. These are seizures, severe irregularities in the normal heart beat, as well as spasm of the upper part of the airways or the smaller airways known as the bronchi (both potentially causing respiratory failure). Related conditions Causes Hypoparathyroidism can have the following causes: Removal of, or trauma to, the parathyroid glands due to thyroid surgery (thyroidectomy), parathyroid surgery (parathyroidectomy) or other surgical interventions in the central part of the neck (such as operations on the larynx and/or pharynx) is a recognized cause. It is the most common cause of hypoparathyroidism. Although surgeons generally make attempts to spare normal parathyroid glands at surgery, inadvertent injury to the glands or their blood supply is still common. When this happens, the parathyroids may cease functioning. This is usually temporary but occasionally long term (permanent). Kenny-Caffey Syndrome Autoimmune invasion and destruction is the most common non-surgical cause. It can occur as part of autoimmune polyendocrine syndromes. Hemochromatosis can lead to iron accumulation and consequent dysfunction of a number of endocrine organs, including the parathyroids. Absence or dysfunction of the parathyroid glands is one of the components of chromosome 22q11 microdeletion syndrome (other names: DiGeorge syndrome, Schprintzen syndrome, velocardiofacial syndrome). Magnesium deficiency A defect in the calcium receptor leads to a rare congenital form of the disease Idiopathic (of unknown cause) Occasionally due to other hereditary causes (e.g. Barakat syndrome (HDR syndrome) a genetic development disorder resulting in hypoparathyroidism, sensorineural deafness, and kidney disease) Mechanism The parathyroid glands are so named because they are usually located behind the thyroid gland in the neck. They arise during fetal development from structures known as the third and fourth pharyngeal pouch. The glands, usually four in number, contain the parathyroid chief cells that sense the level of calcium in the blood through the calcium-sensing receptor and secrete parathyroid hormone. Magnesium is required for PTH secretion. Under normal circumstances, the parathyroids secrete PTH to maintain a calcium level within normal limits, as calcium is required for adequate muscle and nerve function (including the autonomic nervous system). PTH acts on several organs to increase calcium levels. It increases calcium absorption in the bowel, while in the kidney it prevents calcium excretion and increases phosphate release and in bone it increases calcium through bone resorption. Diagnosis Diagnosis is by measurement of calcium, serum albumin (for correction) and PTH in blood. If necessary, measuring cAMP (cyclic AMP) in the urine after an intravenous dose of PTH can help in the distinction between hypoparathyroidism and other causes.Differential diagnoses are: Pseudohypoparathyroidism (normal PTH levels but tissue insensitivity to the hormone, associated with intellectual disability and skeletal deformities) and pseudopseudohypoparathyroidism. Vitamin D deficiency or hereditary insensitivity to this vitamin (X-linked dominant). Malabsorption Kidney disease Medication: steroids, diuretics, some antiepileptics.Other tests include ECG for abnormal heart rhythms, and measurement of blood magnesium levels. Treatment Severe hypocalcaemia, a potentially life-threatening condition, is treated as soon as possible with intravenous calcium (e.g. as calcium gluconate). Generally, a central venous catheter is recommended, as the calcium can irritate peripheral veins and cause phlebitis. In the event of a life-threatening attack of low calcium levels or tetany (prolonged muscle contractions), calcium is administered by intravenous (IV) infusion. Precautions are taken to prevent seizures or larynx spasms. The heart is monitored for abnormal rhythms until the person is stable. When the life-threatening attack has been controlled, treatment continues with medicine taken by mouth as often as four times a day.Long-term treatment of hypoparathyroidism is with vitamin D analogs and calcium supplementation, but may be ineffective in some due to potential renal damage. The N-terminal fragment of parathyroid hormone (PTH 1-34) has full biological activity. The use of pump delivery of synthetic PTH 1-34 provides the closest approach to physiologic PTH replacement therapy. Injections of recombinant human parathyroid hormone are available as treatment in those with low blood calcium levels. See also Hyperparathyroidism References == External links ==

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

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

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

What is the significance of the term 'Breastfeeding difficulties' in the medical field?

Breastfeeding difficulties refers to problems that arise from breastfeeding, the feeding of an infant or young child with milk from a womans breasts. Although babies have a sucking reflex that enables them to suck and swallow milk, and human breast milk is usually the best source of nourishment for human infants, there are circumstances under which breastfeeding can be problematic, or even in rare instances, contraindicated. Difficulties can arise both in connection with the act of breastfeeding and with the health of the nursing infant. Breastfeeding problems While breastfeeding difficulties are not uncommon, putting the baby to the breast as soon as possible after birth helps to avoid many problems. The policy of the American Academy of Pediatrics on breastfeeding instructs to, "delay weighing, measuring, bathing, needle-sticks, and eye prophylaxis until after the first feeding is completed." Many breastfeeding difficulties can be resolved with research based hospital procedures, properly trained nurses and hospital staff, speech pathologists and lactation consultants. Another source of information is the volunteer-based breastfeeding promotion organization, La Leche League. A variety of factors and conditions can interfere with successful breastfeeding: Ankyloglossia (tongue tie) Formula feeding Distractions or interruptions during feeds Long separations from the mother Tachypnea (rapid breathing) such as in transient tachypnea of the newborn, surfactant deficiency, respiratory distress syndrome or other infant medical conditions Presence of an actual physical barrier between mother and infant Swallowing difficulties such as with prematurity and coordination of sucking, swallowing and breathing, or gastro-intestinal tract abnormalities like tracheo-oesophageal fistula. Pain resulting from surgical procedures like circumcision, blood tests, or vaccinations. Latching onto the breast Hypoplastic breasts/insufficient glandular tissue Galactorrhea Lactation failure Polycystic ovarian syndrome Diabetes Maternal stress Insufficient rest/support of the mother during the first 6 weeks post-partum Early return to work due to lack of financial support/maternity leave of mother Cleft palate Thrush Hypoglycemia or hyperglycemia Hypotonia, or "low-tone" infant disorder Hyperlactation syndrome Overactive let-down Premature babies can have difficulties coordinating their sucking reflex with breathing. They may need to be fed more frequently because their stomachs tend to be smaller, and they may get sleepier during feedings. Premature infants unable to take enough calories by mouth may need enteral or gavage feeding - inserting a feeding tube into the stomach to provide enough breast milk or a substitute. This is often done together with Kangaroo care (prolonged skin-to-skin contact with the mother) which makes later breastfeeding easier. For some suckling difficulties, such as may happen with cleft lip/palate, the baby can be fed with a Haberman Feeder. Dysphoric milk ejection reflex (D-MER) is a newly recognized condition affecting lactating women that is characterized by an abrupt dysphoria, or negative emotions that occur just before milk release and continuing not more than a few minutes. Preliminary testing tells us that D-MER is treatable and preliminary research tells us that inappropriate dopamine activity at the time of the milk ejection reflex is the cause of D-MER. Low milk supply Primary lactation failure: occurs when the mother has a condition incompatible with full milk production, for example breast hypoplasia, breast reduction surgery, or bilateral mastectomy. Secondary lactation failure: milk production that is low due to preventable factors, such as formula supplementation, poor milk transfer by the baby, or unrelieved breast engorgement. Chronic low milk supply is estimated to be experienced by 10-15% of women. Breast pain Pain often interferes with successful breastfeeding. It is cited as the second most common cause for the abandonment of exclusive breastfeeding after perceived low milk supply. Inverted nipples Inverted or retracted nipples sometimes make attachment to the breast difficult. These mothers need additional support to feed their babies. Treatment is started after the birth of the baby. The nipple is manually stretched out several times a day. A pump or a plastic syringe is used to draw out the nipple and the baby is then put to the breast. Engorgement Breast engorgement is the sense of breast fullness experienced by most women within 36 hours of delivery. Normally, this is a painless sensation of "heaviness". Breastfeeding on demand is the primary way of preventing painful engorgement. When the breast overfills with milk it becomes painful. Engorgement comes from not getting enough milk from the breast. It happens about 3 to 7 days after delivery and occurs more often in first time mothers. The increased blood supply, the accumulated milk and the swelling all contribute to the painful engorgement. Engorgement may affect the areola, the periphery of the breast or the entire breast, and may interfere with breastfeeding both from the pain and also from the distortion of the normal shape of the areola/nipple. This makes it harder for the baby to latch on properly for feeding. Latching may occur over only part of the areola. This can irritate the nipple more, and may lead to ineffective drainage of breast milk and more pain. Reverse pressure softening (RPS) is a technique that can soften the areola enabling deeper latching and more milk transfer; RPS involves gentle positive pressure in the direction of the chest wall from the fingertips around the areola. Engorgement may begin as a result of several factors such as nipple pain, improper feeding technique, infrequent feeding or infant-mother separation. To prevent or treat engorgement, remove the milk from the breast, by breastfeeding, expressing or pumping. Gentle massage can help start the milk flow and so reduce the pressure. The reduced pressure softens the areola, perhaps even allowing the infant to feed. Warm water or warm compresses and expressing some milk before feeding can also help make breastfeeding more effective. Some researchers have suggested that after breastfeeding, mothers should pump and/or apply cold compresses to reduce swelling pain and vascularity even more. One published study suggested the use of "chilled cabbage leaves" applied to the breasts. Attempts to reproduce this technique met with mixed results. Nonsteroidal anti-inflammatory drugs or paracetamol (acetaminophen) may relieve the pain. A warm shower and using cold compresses to help ease the discomfort. Nipple pain Sore nipples (nipple pain, or thelalgia) are probably the most common complaint after the birth. They are generally reported by the second day after delivery but improve within 5 days. Pain beyond the first week, severe pain, cracking, fissures or localized swelling is not normal. The mother should see a doctor for further evaluation. Sore nipples, a common cause of pain, often come from the baby not latching on properly. Factors include too much pressure on the nipple when not enough of the areola is latched onto and an improper release of suction at the end of the feeding. Improper use of breast pumps or topical remedies can also contribute. Nipple pain can also be a sign of infection. Candidiasis Symptoms of candidiasis of the breast include pain, itching, burning and redness, or a shiny or white patchy appearance. The baby could have a white tongue that does not wipe clean. Candidiasis is common and may be associated with infant thrush. Both mother and baby must be treated to get rid of this infection. First-line therapies include nystatin, ketaconazole or miconazole applied to the nipple and given by mouth to the baby. Strict cleaning of clothing and breast pumps is also required to eradicate the infection.Another non-prescription treatment of candidia is gentian violet. It usually works, and relief is rapid. It is messy, and will stain clothing. The babys lips will turn purple, but the purple will disappear after a few days. Milk stasis Milk stasis is when the milk ducts are blocked and cannot drain properly, usually due to swelling and insufficient breast emptying during the engorgement phase. This may affect only a part of the breast and is not associated with any infection. It can be treated by varying the babys feeding position and applying heat before feeding. If it happens more than once, further evaluation is needed. Milk stasis is an urgent matter for mothers who wish to breastfeed, as failure to remove milk from the breasts causes milk production to decrease and eventually stop. Mastitis Mastitis is an inflammation of the breast. It causes local pain (dolor), redness (rubor), swelling (tumor), and warmth (calor). Later stages of mastitis cause symptoms of systemic infection like fever and nausea. It mostly occurs 2–3 weeks after delivery but can happen at any time. Typically results from milk stasis with primary or secondary local, later systemic infection. Infectious organisms include Staphylococcus sp., Streptococcus sp. and E. coli. Continued breastfeeding, plenty of rest and adequate fluid supply is the best treatment for light cases. Overactive let-down Overactive let-down (OALD) is the forceful ejection of milk from the breast during breastfeeding. The forceful spray of milk can cause the baby to consume too much milk too quickly as well as to swallow air during the period of rapid swallowing following the let-down. Raynauds of the nipple Nipple pain can be caused by vasospasm of the nipple. In essence, blood does not flow properly to the nipple which causes the nipple to blanch. This can be caused by trauma to the nipple through early breastfeeding or candidal infection of the nipple. The pain is intense during the latch stage and in between breastfeeding sessions there is a throbbing pain when the nipple is blanched. The nipple can be massaged to help blood flow return to reduce pain, as well as avoiding cold. In some instances, heart medication, nifedipine, is used to help the blood flow return to the nipple. Infant health problems Infants with classic galactosemia cannot digest lactose and therefore cannot benefit from breast milk. Breastfeeding might harm the baby also if the mother has untreated pulmonary tuberculosis, is taking certain medications that suppress the immune system. has HIV, or uses potentially harmful substances such as cocaine, heroin, and amphetamines. Other than cases of acute poisoning, no environmental contaminant has been found to cause more harm to infants than lack of breastfeeding. Although heavy metals such as mercury are dispersed throughout the environment and are of concern to the nursing infant, the neurodevelopmental benefits of human milk tend to override the potential adverse effects of neurotoxicants. Weak sucking reflex Artificial teats (nipples) or dummies (pacifiers) can suppress the sucking reflex in infants. In addition, when a baby is put to the breast for shorter periods of time, milk production decreases. The time spent sucking by the infant on the pacifier or artificial teat reduces the time on the breast. The CDC also currently (2022) reports that early use of pacifiers can have a negative outcome on the success of breastfeeding and they suggest that it should be delayed until breastfeeding is firmly established. Transmission of infection Tuberculosis It is not safe for mothers with active, untreated tuberculosis to breastfeed until they are no longer contagious. According to the American Academy of Pediatrics 2006 Redbook: Women with tuberculosis who have been treated appropriately for 2 or more weeks and who are not considered contagious may breastfeed. Women with tuberculosis disease suspected of being contagious should refrain from breastfeeding or any other close contact with the infant because of potential transmission through respiratory tract droplets (see Tuberculosis, p 678). Mycobacterium tuberculosis rarely causes mastitis or a breast abscess, but if a breast abscess caused by M. tuberculosis is present, breastfeeding should be discontinued until the mother no longer is contagious. In areas where BCG vaccination is the standard of care, the WHO provides treatment recommendations and advises mothers to continue breastfeeding. TBC may be congenital, or perinatally acquired through airborne droplet spread. HIV Research published in the Lancet has highlighted a lower risk of HIV transmission with exclusive breastfeeding by HIV positive mothers (4% risk), compared to mixed feeding (10-40% risk). Research on the timing of HIV transmission in 2000 revealed that a "substantial transmission occurs early during breastfeeding," concluding that 75% of all breast milk transmission had occurred within the first 6 months during a randomized control trial in Kenya. This research is of particular importance in developing countries where infant formula is not widely available or safe to prepare. In fact, the World Health Organization recommended breastfeeding in 1987 and 1992 for seropositive and seronegative women in areas where malnutrition and infectious diseases are the major cause of infant mortality. In 1996 UNAIDS issued a recommendation that women in developing countries consider the risks and benefits of each feeding practice on an individual level; they recommended women make an informed choice about infant feeding. In the days before the AIDS epidemic was clearly understood, some researchers pointed to the need to increase breastfeeding rates and pointed to the risks of formula feeding, citing increased rates of marasmus and diarrhea. D Jelliffe and E Jelliffe also criticized the marketing of infant formulas by US companies to resource-poor countries, something they termed "comerciogenic malnutrition." A more recent article from 1992 describes how the health of an infant can be compromised by water, which in many resource-poor countries holds the risk of environmental pathogens that are not present in breastmilk. Transmission of drugs and toxins Medications The vast majority of over the counter and prescription medicines are compatible with breastfeeding, but there are some that might be passed onto the child through the milk. Tobacco smoke If one does continue tobacco smoking after giving birth, however, it is still more beneficial to breastfeed than to completely avoid this practice altogether. There is evidence that breastfeeding offers protection against many infectious diseases, especially diarrhea. Even in babies exposed to the harmful effects of nicotine through breast milk, the likelihood of acute respiratory illness is significantly diminished when compared to infants whose mothers smoked but were formula fed. Regardless, the benefits of breastfeeding outweigh the risks of nicotine exposure. The main concern about smoking and breastfeeding is that infants may have smoking-induced reductions to the milk iodine content. Smoking can adversely affect the lactation process by decreasing milk production and altering the milk composition. Smoking reduces daily milk output by roughly 250–300 mL. Not only will this be problematic on a daily basis for not producing enough milk, it will also cause the mother to wean her baby early. The altered milk composition also caused infants to exhibit daily behaviors such as colic and crying which can promote early weaning, again something that is not beneficial to the infant.Also, the nicotine obtained from smoking travels through a woman into her breast milk, thus giving nicotine to her child.Heavy use of cigarettes by the mother (more than 20 per day) has been shown to reduce the mothers milk supply and cause vomiting, diarrhoea, rapid heart rate, and restlessness in breastfed infants. Sudden Infant Death Syndrome (SIDS) is more common in babies exposed to a smoky environment. Breastfeeding mothers who smoke are counseled not to do so during or immediately before feeding their child, and are encouraged to seek advice to help them reduce their nicotine intake or quit. Other substance abuse With respect to alcohol, the American Academy of Pediatrics states that when breastfeeding, "moderation is definitely advised" and recommends waiting for 2 hours after drinking before nursing or pumping. A 2014 review found that "even in a theoretical case of binge drinking, the children would not be subjected to clinically relevant amounts of alcohol [through breastmilk]", and would have no adverse effects on children as long as drinking is "occasional".If the mother consumes too much caffeine, it can cause irritability, sleeplessness, nervousness and increased feeding in the breastfed infant. Moderate use (one to two cups per day of coffee, tea, or cola) usually produces no effect. Breastfeeding mothers are advised to restrict or avoid caffeine if her baby reacts negatively to it. Cigarette smoking is thought to increase the effects of caffeine in the baby. Cannabis Cannabis is listed by the American Association of Pediatrics as a compound that transfers into human breast milk. Research demonstrated that certain compounds in marijuana have a very long half-life. Diet An exclusively breastfed baby depends on breast milk completely so it is important for the mother to maintain a healthy lifestyle, and especially a good diet. Consumption of 1500–1800 calories per day could coincide with a weight loss of 450 grams (one pound) per week. While mothers in famine conditions can produce milk with highly nutritional content, a malnourished mother may produce milk with decreased levels of several micronutrients such as iron, zinc, and vitamin B12. She may also have a lower supply than well-fed mothers. There are no foods that are absolutely contraindicated during breastfeeding, but a baby may show sensitivity to particular foods that the mother eats. Workplaces Many mothers have to return to work soon after their babies have been born. If their employers and fellow employees do not support mothers in breastfeeding (for example, providing a private breastfeeding room containing a fridge where mothers can express and safely store breast milk), mothers might stop breastfeeding. This is not ideal for their infants. A Cochrane review assessed the effects of workplace interventions to support and promote breastfeeding among mothers returning to work after the birth of their babies. The review authors comprehensively searched in 2012 for studies addressing this question but found no eligible studies. References == External links ==

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

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

Pramlintide (trade name Symlin) is an injectable amylin analogue drug for diabetes (both type 1 and 2), developed by Amylin Pharmaceuticals (now a wholly owned subsidiary of AstraZeneca). Pramlintide is sold as an acetate salt. Pharmacology Pramlintide is an analogue of amylin, a small peptide hormone that is released into the bloodstream by the β cells of the pancreas along with insulin after a meal. Like insulin, amylin is completely absent in individuals with Type I diabetes.In synergy with endogenous amylin, pramlintide aids in the regulation of blood glucose by slowing gastric emptying, promoting satiety via hypothalamic receptors (different receptors than for GLP-1), and inhibiting inappropriate secretion of glucagon, a catabolic hormone that opposes the effects of insulin and amylin. Pramlintide also has effects in raising the acute first-phase insulin response threshold following a meal. Both a reduction in glycated hemoglobin and weight loss have been shown in insulin-treated patients with type 2 diabetes taking pramlintide as an adjunctive therapy. Research Applications In the research field, pramlintide has been experimented with and used as a potential treatment drug. Pramlintide has demonstrated its ability to decrease amyloid beta plaques in Alzheimers disease mouse models. Approval Pramlintide has been approved by the FDA, for use by type 1 and type 2 diabetic patients who use insulin. Pramlintide allows patients to use less insulin, lowers average blood sugar levels, and substantially reduces what otherwise would be a large unhealthy rise in blood sugar that occurs in diabetics right after eating. Apart from insulin analogs, pramlintide is the only drug approved by the FDA to lower blood sugar in type 1 diabetics since insulin in the early 1920s. Design and structure Since native human amylin is highly amyloidogenic and potentially toxic, the strategy for designing pramlintide was to substitute residues from rat amylin, which is less amyloidogenic although not completely (but would presumably retain clinical activity). Proline residues are known to be structure-breaking residues, so these were directly grafted into the human sequence. Despite its enhanced stability compared to human amylin, pramlintide is still able to organize into amyloid material.Amino acid sequences: Pramlintide as protein is (positively charged). References External links www.symlin.com - product website www.amylin.com - Symlin page on the Amylin Pharmaceuticals website

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

Tralokinumab sold under the brand names Adtralza (EU/UK) and Adbry (US) among others, is a human monoclonal antibody used for the treatment of atopic dermatitis. Tralokinumab targets the cytokine interleukin 13.The most common side effects include upper respiratory tract infections (colds and other infections of the nose and throat), reactions at the injection site, and redness and discomfort in the eye.Tralokinumab was approved for medical use in the European Union and in the United Kingdom in June 2021. It was approved for medical use in the United States in December 2021. Medical uses Tralokinumab is indicated for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy.In the United States, tralokinumab is indicated for the treatment of moderate-to-severe atopic dermatitis in adults whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Discovery and development Tralokinumab was discovered by Cambridge Antibody Technology scientists using protein optimization based on Ribosome Display. They used the extensive data sets from ribosome display to patent protect CAT-354 in a world-first of sequence-activity-relationship claims. In 2004, clinical development of CAT-354 was initiated with this first study completing in 2005. On 21 July 2011, MedImmune LLC initiated a Phase IIb, randomized, double-blind study to evaluate the efficacy of tralokinumab in adults with asthma.In 2016, MedImmune and AstraZeneca started developing tralokinumab for asthma (Phase III) and atopic dermatitis (Phase IIb) while clinical development for moderate-to-severe ulcerative colitis and idiopathic pulmonary fibrosis (IPF) have been discontinued. In July of that year AstraZeneca licensed tralokinumab to Leo Pharma for skin diseases.A phase IIb study of tralokinumab found that treatment was associated with early and sustained improvements in atopic dermatitis symptoms and tralokinumab had an acceptable safety and tolerability profile, thereby providing evidence for targeting IL-13 in patients with atopic dermatitis.On 15 June 2017, Leo Pharma announced that they were starting phase III clinical trials with tralokinumab in atopic dermatitis. Society and culture Legal status On 22 April 2021, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Adtralza, intended for the treatment of moderate‑to‑severe atopic dermatitis. The applicant for this medicinal product is LEO Pharma A/S. Tralokinumab was approved for medical use in the European Union in June 2021. Names Tralokinumab is the international nonproprietary name (INN) and the United States Adopted Name (USAN). References External links "Tralokinumab". 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.

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

Vascular myelopathy (vascular disease of the spinal cord) refers to an abnormality of the spinal cord in regard to its blood supply. The blood supply is complicated and supplied by two major vessel groups: the posterior spinal arteries and the anterior spinal arteries—of which the Artery of Adamkiewicz is the largest. Both the posterior and anterior spinal arteries run the entire length of the spinal cord and receive anastomotic (conjoined) vessels in many places. The anterior spinal artery has a less efficient supply of blood and is therefore more susceptible to vascular disease. Whilst atherosclerosis of spinal arteries is rare, necrosis (death of tissue) in the anterior artery can be caused by disease in vessels originating from the segmental arteries such as atheroma (arterial wall swelling) or aortic dissection (a tear in the aorta). Spinal cord infarction Anterior spinal artery syndrome Anterior spinal artery syndrome is necrosis of tissue in the anterior spinal artery or its branches. It is characterised by pain which radiates at onset and sudden quadraplegia (paralysis of all four limbs) or paraplegia (paralysis of the lower body). Within days, flaccid limbs become spastic and hyporeflexia (underactive nerve responses) turns into hyperreflexia (overactive nerve responses) and extensor plantar nerve responses. Sensory loss to pain and temperature also occurs up to the level of damage on the spinal cord, as damage to different areas will affect different parts of the body.In diagnosis, other causes of abrupt paralysis should be excluded such as cord compression, transverse myelitis (inflammation of the spinal cord) and Guillain–Barré syndrome. A specific cause of the infarction should be looked for, such as diabetes, polyarteritis nodosa (inflammatory damage of vessels) or systemic lupus erythematosus. Neurosyphilis is also a known cause. Other causes include: Treatment is supportive and aims to relieve symptoms. The prognosis is dependent upon individual circumstances and factors. Posterior spinal artery syndrome Posterior spinal artery syndrome is much rarer than its anterior counterpart as the white matter structures that are present are much less vulnerable to ischemia since they have a better blood supply. When posterior spinal artery syndrome does occur, dorsal columns are damaged and ischemia may spread into the posterior horns. Clinically the syndrome presents as a loss of tendon reflexes and loss of joint position sense Transient ischemic attack Transient ischemic attacks (TIAs) rarely affect the spinal cord and usually affect the brain; however, cases have been documented in these areas. Spinal arteriovenous malformations are the main cause and are represented later in this article. However, TIAs can result from emboli in calcific aortic disease and aortic coarctation. Spinal arteriovenous malformations Spinal arteriovenous malformations (AVMs, or angiomatous malformations) are congenital (from birth) abnormalities of blood vessels. Arteries that directly communicate with veins bypass the capillary network (which has not yet developed) and thus creates a shunt. AVMs appear as a mass of convoluted, dilated vessels. In regards to the spinal cord, they are usually located in the thoracolumbar region (between the thoracic and lumbar regions, 60% of the time), as opposed to the upper thoracic (20%) and cervical regions (approximately 15%). Cervical malformations arise from the anterior spinal artery and lie within the cord, whereas thoracolumbar malformations can be internal, external or encompass both areas of the cord.Malformations can be recognised as part of an acute illness or gradual onset disease. In diseases such as subarachnoid hemorrhage, signs and symptoms include headache, neck stiffness and back and leg pain. Extradural, subdural and intramedullary hematomas are all signs of acute cord compression. Gradual onset diseases are more common (85-90% of all diseases leading to a diagnosis of malformation) and are usually due to an increased venous pressure. Other factors such as thrombosis or arachnoiditis can be involved. A bruit (unusual blood sounds) may be heard overlying the spinal arteriovenous malformation. Very occasionally, nevus (moles) or angiolipomas are found.Myelography is used to confirm the diagnosis of AVMs and it shows snake-like vessels on the cords surface. If the myelogram is positive, angiography is required to show the extent of malformation and the exact site of the shunt. Magnetic resonance imaging (MRI) may show the appropriate area. If AVMs are left untreated, 50% of patients with gradual symptoms will be unable to walk within 3 years of onset. Surgical occlusion has been shown to halt the progression and may improve any gait or incontinence. See also Foix–Alajouanine syndrome Chronic cerebrospinal venous insufficiency Peripheral vascular disease References == External links ==