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Neonatal alloimmune thrombocytopenia	Neonatal alloimmune thrombocytopenia (NAITP, NAIT, NATP or NAT) is a disease that affects babies in which the platelet count is decreased because the mothers immune system attacks her fetus or newborns platelets. A low platelet count increases the risk of bleeding in the fetus and newborn. If the bleeding occurs in the brain, there may be long-term effects. Platelet antigens are inherited from both mother and father. NAIT is caused by antibodies specific for platelet antigens inherited from the father but which are absent in the mother. Fetomaternal transfusions (or fetomaternal hemorrhage) results in the recognition of these antigens by the mothers immune system as non-self, with the subsequent generation of allo-reactive antibodies which cross the placenta. NAIT, hence, is caused by transplacental passage of maternal platelet-specific alloantibody and rarely human leukocyte antigen (HLA) allo-antibodies (which are expressed by platelets) to fetuses whose platelets express the corresponding antigens. NAIT occurs in somewhere between 1/800 and 1/5000 live births. More recent studies of NAIT seem to indicate that it occurs in around 1/600 live births in the Caucasian population. Signs and symptoms The diagnosis of NAIT is usually made after an incidental finding of a low platelet count on a blood test or because of bleeding complications ranging from bruising or petechiae to intracranial hemorrhage in the fetus or newborn.Frequently, the reduction in platelet count is mild and the affected neonates remain largely asymptomatic. NAIT is the commonest cause of a very low platelet count, and the commonest cause of intracranial haemorrhage in the term neonate.In case of severe thrombocytopenia, the neonates may exhibit bleeding complications at or a few hours after delivery. The most serious complication is intracranial hemorrhage, leading to death in approximately 10% of symptomatic babies or neurologic sequelae in 20% of cases. 80% of intracranial hemorrhages occur before birth. After birth the greatest risk of bleeding is in the first four days of life. Related conditions Immune thrombocytopenic purpura (ITP), sometimes called idiopathic thrombocytopenic purpura is a condition in which autoantibodies are directed against a patients own platelets, causing platelet destruction and thrombocytopenia. Anti-platelet autoantibodies in a pregnant woman with immune thrombocytopenic purpura will attack the patients own platelets and will also cross the placenta and react against fetal platelets. Therefore, ITP is a significant cause of fetal and neonatal immune thrombocytopenia. Approximately 10% of newborns affected by ITP will have platelet counts <50,000 μL−1 and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with NAIT.Mothers with thrombocytopenia or a previous diagnosis of ITP should be tested for serum anti-platelet antibodies. A woman with symptomatic thrombocytopenia and an identifiable anti-platelet antibody should be started on therapy for their ITP which may include steroids or IVIG. Fetal blood analysis to determine the platelet count is not generally performed as ITP-induced thrombocytopenia in the fetus is generally less severe than NAIT. Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia. Other conditions causing a low platelet count Other conditions that can cause a low platelet count in the neonate include bacterial and viral infection, disseminated intravascular coagulation and other rare congenital conditions associated with a low platelet count. Pathophysiology Platelets have many proteins on their surface. Each person has a different set of proteins, which are inherited from their parents. These different platelet proteins make different platelet groups, just like different proteins on red blood cells make different blood groups. These differences do not affect how the platelets work. However, if a baby inherits a protein that is found on the fathers platelets but is absent from the mothers platelets, the mother may respond to this foreign protein by developing an antibody that fights against it.This antibody may pass from the mothers blood into the babys blood and attach to the babys platelets. This antibody destroys the babys platelets and suppresses production of fetal platelets, they are also thought to weaken the blood vessel walls (vascular integrity) and affect production of new blood vessels (angiogenesis). This results in an increased risk of bleeding for the baby, and this can lead to the babys death. The mothers antibodies can remain in the babys bloodstream for weeks, and bleeding can occur in the baby before birth (fetal), during birth or after birth (neonatal).A number of different proteins can cause NAIT, about 80% of cases are caused by antibodies against platelet antigen HPA-1a, 15% by anti-HPA-5b, and 5% by other antibodies (e.g. HPA-1b, HPA-15, HPA-3 and HPA-9b). HPA-1a is present in 98% of the population of the United States, suggesting that approximately 2% of women who are HPA-1a negative may be at risk for NAIT during pregnancy. Of course, the antigen expression of the father must also be taken into account - in most cases the father is HPA-1a/1a or 1a/1b and the mother is HPA-1b/1b with anti-HPA-1a antibodies. In women of Asian descent, HPA-4 antigens are the most frequently implicated.Studies have shown a relationship between maternal HLA type DRw52a (DRB3* 0101) and the development of anti-HPA-1a.The offending antibodies are IgG subtype and therefore capable of crossing the placenta and entering the fetal circulation.Unlike hemolytic disease of the fetus and newborn, NAIT occurs during the first pregnancy in up to 50% of cases, and the affected fetuses may develop severe thrombocytopenia (<50,000 μL−1) very early during pregnancy (as early as 20 weeks gestation, consistent with the development of platelet antigens, and the majority of the time in utero). Usually, the thrombocytopenia increases as gestation progresses. During the first pregnancy, NAIT is often not detected until birth when the newborn presents with classic symptoms of thrombocytopenia including petechiae, bruising or intracranial hemorrhage. In utero intracranial hemorrhage occurs in about 10% to 30% of affected cases (and NAIT is thought to be the underlying cause in the majority of cases of intracranial hemorrhage due to thrombocytopenia- greater than all other causes of thrombocytopenia combined). The risk of hemorrhage is inversely related to the platelet count with the greatest risk when the platelet count is below 100,000 μL−1.The recurrence of NAIT has been estimated to be more than 80% in subsequent pregnancies in which the fetus also carries the target platelet antigen. Subsequent cases of NAIT may be equivalent or more severe.The fetal response to NAIT is variable and may include compensatory extramedullary hematopoiesis. Rarely, fetal hydrops may develop. Fetal anemia (in presence of red cell incompatibility) may also occur. Diagnosis Doctors may consider a diagnosis of NAIT if they notice bleeding or bruising in a baby, or low platelet counts on a blood test after birth, or neurologic symptoms. Some babies may have a specific pinpoint rash called “petechiae”. If a diagnosis of NAIT is suspected, then the baby should be treated as if it had NAIT until the diagnosis is confirmed.The diagnosis is confirmed by taking blood samples from the babys parents, and sometimes the baby. Maternal and paternal platelet antigen phenotyping and screening of the maternal serum for anti-platelet antibodies can be performed. Additionally, platelet antigen genotyping can be performed on the maternal and paternal blood to determine the exact nature of the incompatibility.Neonatal platelet counts on laboratory testing are typically under 20,000 μL−1. Higher counts may suggest a different diagnosis, such as maternal immune thrombocytopenic purpura.Even in mildly affected babies, it is important to fully investigate and diagnose the baby because the results can be critical for the effective management of any future pregnancies. Treatment During pregnancy Antenatal management only occurs if a mother has had a previously affected baby or a family member has had an affected baby.Interventions can be classified as invasive or non-invasive.A review of the evidence has shown that invasive management resulted in a relatively high complication rate (mainly preterm emergency cesarean section) of 11% per treated pregnancy. Noninvasive management was also shown to be effective, but without the relatively high rate of adverse outcomes seen with invasive management. They concluded that first-line antenatal management in NAIT should be non-invasive with weekly intravenous immunoglobulin administration, with or without the addition of corticosteroids.Recent international guidelines have now recommended non-invasive management of NAIT. Previously there had been no international consensus on the optimal antenatal management of NAIT, and numerous strategies had been used in different centers that specialized in antenatal treatment. Invasive management Fetal blood sampling from the umbilical cord and intrauterine platelet transfusion was the first antenatal treatment for NAIT to prevent intracerebral hemorrhage. However, this is no longer recommended routinely because of the serious risk of harms. Cordocentesis in the presence of a low platelet count may lead to serious complications, these included slowing of the babys heart (fetal bradycardia), tamponade of the cord, and bleeding complications in the baby, including exsanguination. Fetal blood sampling is estimated to cause death of the baby in 1.3% of procedures, however the incidence varies significantly from center to center. With an overall risk of death of the fetus due to the repeated procedures of about 3% (17 deaths out of 485 pregnancies).In addition, given the short life span of transfused platelets, transfusions are needed regularly, increasing the overall risk of death of the baby. If intrauterine platelet transfusions are performed, they are generally repeated weekly (platelet lifespan after transfusion is approximately 8 to 10 days). Platelets administered to the fetus must be negative for the culprit antigen (often HPA-1a, as stated above). Many blood suppliers (such as American Red Cross; NHS Blood and Transplant; United Blood Services) have identified HPA-1a and 5b negative donors. An alternative donor is a mother who is, of course, negative for the culprit antigen. However, she must meet general criteria for donation and platelets received from the mother must be washed to remove the offending alloantibody and irradiated to reduce the risk of graft-versus-host disease. If platelet transfusions are needed urgently, incompatible platelets may be used, with the understanding that they may be less effective and that the administration of any blood product carries risk.Any administered cellular blood products must be irradiated to reduce the risk of graft-versus-host disease in the fetus. Additionally, all administered blood products should be CMV reduced-risk (CMV seronegative and leukoreduced are considered essentially equivalent for the purposes of CMV risk reduction). Non-invasive management The use of Intravenous immunoglobulin (IVIG) during pregnancy and immediately after birth has been shown to help reduce or alleviate the effects of NAIT in infants and reduce the severity of thrombocytopenia. The most common treatment is weekly IVIG infusions at a dosage of 1 g/kg beginning at 12 to 16 weeks of pregnancy in women who have had a previously affected child with an intracranial hemorrhage. For all other pregnancies, use of IVIG should be discussed, and, if indicated, should be started before 24 weeks of pregnancy and continued until the birth of the child. In some cases this dosage is increased to 2 g/kg and/or combined with a course of prednisolone depending on the exact circumstances of the case.In a review they found that giving IVIG alone during pregnancy prevented intracranial hemorrhage in 98.7% of treated pregnancies (4 cases occurred in 315 pregnancies). This is a similar estimate to a previous review that only assessed the evidence within randomised controlled trials. They also found no consistent benefit of adding steroids to IVIG.The goal of both IVIG and platelet transfusion is to avoid hemorrhage. Ultrasound monitoring to detect hemorrhage in the fetus is not recommended as detection of intracranial hemorrhage generally indicates permanent brain damage (there is no intervention that can be performed to reverse the damage once it has occurred).Before delivery, the fetal platelet count may not be known, due to the high risks associated with cordocentesis (see above). If the platelet count is not known then assisted forms of delivery, for example forceps or ventouse, should be avoided to reduce the risk of harm. If the delivery has been planned then antigen negative platelets should be available in case the infants platelet count is low on a cord blood sample. After birth The most rapidly effective treatment in infants with severe hemorrhage and/or a very low platelet count (<30,000 μL−1) is the transfusion of compatible platelets (i.e. platelets from a donor who, like the mother, lacks the causative antigen). If antigen negative platelets are unavailable, then standard neonatal platelet transfusions should be given until antigen negative platelets become available. If a platelet transfusion is not available immediately then the infant can be given IVIG (1g/kg) however, this will have no effect on the platelet count before 24 to 72 hours.A platelet transfusion is required immediately if there is severe or life-threatening bleeding. If life-threatening bleeding occurs, for example an intracranial hemorrhage, then the platelet count needs to be increased to decrease the risk of further bleeding (> 100,000 μL−1).Any infant with suspected NAIT should have an ultrasound of the head within the first 24 hours after birth to make sure that there is no evidence of an intracranial hemorrhage.If the infant has a platelet count >30,000 μL−1 and no evidence of bleeding, then the baby can be monitored with blood counts until the blood counts return to normal, without the need for any additional treatment. In the past, infusions of IVIG (1 g/kg/day for two days) have been given to the infant and have been shown to rapidly increase the platelet count. However, IVIG and platelet transfusions are also associated with harm and therefore should be avoided if they are not necessary.After a first affected pregnancy, if a mother has plans for a subsequent pregnancy, then the mother and father should be typed for platelet antigens and the mother screened for alloantibodies. Testing is available through reference laboratories (such as ARUP). DNA testing of the father can be used to determine zygosity of the involved antigen and therefore risk to future pregnancies (if homozygous for the antigen, all subsequent pregnancies will be affected, if heterozygous, there is an approximate 50% risk to each subsequent pregnancy). During subsequent pregnancies, the genotype of the fetus can also be determined using amniotic fluid analysis or maternal blood as early as 18 weeks gestation to definitively determine the risk to the fetus. References External links [1]
Hereditary persistence of fetal hemoglobin	Hereditary persistence of fetal hemoglobin (HPFH) is a benign condition in which increased fetal hemoglobin (hemoglobin F, HbF) production continues well into adulthood, disregarding the normal shutoff point after which only adult-type hemoglobin should be produced. Presentation The condition is asymptomatic, and is only noticed when screening for other hemoglobin disorders. Sickle cell disease In persons with sickle cell disease, high levels of fetal hemoglobin as found in a newborn or as found abnormally in persons with hereditary persistence of fetal hemoglobin, the HbF causes the sickle cell disease to be less severe. In essence the HbF inhibits polymerization of HbS. A similar mechanism occurs with persons who have sickle cell trait. Approximately 40% of the hemoglobin is in the HbS form while the rest is in normal HbA form. The HbA form interferes with HbS polymerization. Causes HPFH can be caused by mutations in the β globin gene cluster, or the γ gene promoter region. In addition HbF levels are influenced by polymorphisms in the BCL11A gene and in the MYB gene enhancer. In HPFH the percentage of HbF varies from 0.8-1.0% to about 30% of the total hemoglobin, but levels as high as 100% can be seen in homozygotes for delta beta thalassemia. Diagnosis Epidemiology About 10% of the population has an HbF level >1.0%. HPFH may alleviate the severity of certain hemoglobinopathies and thalassemias, and is selected for in populations with a high prevalence of these conditions (which in turn are often selected for in areas where malaria is endemic). Thus, it has been found to affect people of African and Greek descent. References == External links ==
Cornea verticillata	Cornea verticillata, also called vortex keratopathy or whorl keratopathy, is a condition characterised by corneal deposits at the level of the basal epithelium forming a faint golden-brown whorl pattern. It is seen in Fabry disease or in case of prolonged amiodarone intake. Presentation No ocular complaints or visual difficulty is usually present. Pathophysiology This keratopathy is probably a type of drug-induced lipidosis. Diagnosis == References ==
Barbiturate	A barbiturate is a drug that acts as a central nervous system depressant. Barbiturates are effective as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as well as overdose potential among other possible adverse effects. They have largely been replaced by benzodiazepines and nonbenzodiazepines ("Z-drugs") in routine medical practice, particularly in the treatment of anxiety and insomnia, because of the significantly lower risk of addiction and overdose and the lack of an antidote for barbiturate overdose. Despite this, barbiturates are still in use for various purposes: in general anesthesia, epilepsy, treatment of acute migraines or cluster headaches, acute tension headaches, euthanasia, capital punishment, and assisted suicide.The name barbiturate originates from the fact that they are all chemical derivatives of barbituric acid. Uses Medicine Barbiturates, such as phenobarbital, were long used as anxiolytics and hypnotics. Intermediate-acting barbiturates reduce time to fall asleep, increase total sleep time, and reduce REM sleep time. Today they have been largely replaced by benzodiazepines for these purposes because the latter are less toxic in drug overdose. However, barbiturates are still used as anticonvulsants (e.g., phenobarbital and primidone) and general anesthetics (e.g., sodium thiopental). Barbiturates in high doses are used for medical aid in dying, and in combination with a muscle relaxant for euthanasia and for capital punishment by lethal injection. Barbiturates are frequently employed as euthanizing agents in small-animal veterinary medicine. Interrogation Sodium thiopental is an ultra-short-acting barbiturate that is marketed under the name Sodium Pentothal. It is often mistaken for "truth serum", or sodium amytal, an intermediate-acting barbiturate that is used for sedation and to treat insomnia, but was also used in so-called sodium amytal "interviews" where the person being questioned would be much more likely to provide the truth whilst under the influence of this drug. When dissolved in water, sodium amytal can be swallowed, or it can be administered by intravenous injection. The drug does not itself force people to tell the truth, but is thought to decrease inhibitions and slow creative thinking, making subjects more likely to be caught off guard when questioned, and increasing the possibility of the subject revealing information through emotional outbursts. Lying is somewhat more complex than telling the truth, especially under the influence of a sedative-hypnotic drug.The memory-impairing effects and cognitive impairments induced by sodium thiopental are thought to reduce a subjects ability to invent and remember lies. This practice is no longer considered legally admissible in court, owing to findings that subjects undergoing such interrogations may form false memories, putting the reliability of all information obtained through such methods into question. Nonetheless, it is still employed in certain circumstances by defense and law enforcement agencies as a "humane" alternative to torture interrogation when the subject is believed to have information critical to the security of the state or agency employing the tactic. Chemistry In 1988, the synthesis and binding studies of an artificial receptor binding barbiturates by six complementary hydrogen bonds was published. Since this first article, different kind of receptors were designed, as well as different barbiturates and cyanurates, not for their efficiencies as drugs but for applications in supramolecular chemistry, in the conception of materials and molecular devices. The preferred IUPAC name of the base compound, barbituric acid, is 1,3-diazinane-2,4,6-trione. Different barbiturates has different substituents in the basic structure, mainly in position 5 on the ring.Sodium barbital and barbital have also been used as pH buffers for biological research, e.g., in immuno-electrophoresis or in fixative solutions. Classification Barbiturates are classified based on the duration of action. Examples of each class include: Ultra short acting (30 minutes): thiopentone, methohexitone Short acting (2 hours): hexobarbitone, cyclobarbitone, pentobarbitone, secobarbitone Intermediate acting(3–6 hours): amobarbitone, butabarbitone Long acting (6 hours): phenobarbitone Indications Indications for the use of barbiturates include: Seizure Neonatal withdrawal syndrome Insomnia Anxiety Inducing anesthesia Side effects There are special risks to consider for older adults, and women who are pregnant. When a person ages, the body becomes less able to rid itself of barbiturates. As a result, people over the age of sixty-five are at higher risk of experiencing the harmful effects of barbiturates, including drug dependence and accidental overdose. When barbiturates are taken during pregnancy, the drug passes through the placenta to the fetus. After the baby is born, it may experience withdrawal symptoms and have trouble breathing. In addition, nursing mothers who take barbiturates may transmit the drug to their babies through breast milk. A rare adverse reaction to barbiturates is Stevens–Johnson syndrome, which primarily affects the mucous membranes. Common side effects Nausea Hypotension Headache Drowsiness Skin rash Serious side effects Confusion Coma Hallucination Fainting Slow breathing Rare side effects Agranulocytosis Stevens–Johnson syndrome Liver injury Megaloblastic anemia Tolerance and dependence With regular use, tolerance to the effects of barbiturates develops. Research shows tolerance can develop with even one administration of a barbiturate. As with all GABAergic drugs, barbiturate withdrawal produces potentially fatal effects such as seizures, in a manner reminiscent of delirium tremens and benzodiazepine withdrawal although its more direct mechanism of GABA agonism makes barbiturate withdrawal even more severe than that of alcohol or benzodiazepines. It is considered one of the most dangerous withdrawals of any known addictive substance. Similarly to benzodiazepines, the longer acting barbiturates produce a less severe withdrawal syndrome than short acting and ultra-short acting barbiturates. Withdrawal symptoms are dose-dependent with heavier users being more affected than lower-dose addicts. The pharmacological treatment of barbiturate withdrawal is an extended process often consisting of converting the patient to a long-acting benzodiazepine (i.e. Valium), followed by slowly tapering off the benzodiazepine. Mental cravings for barbiturates can last for months or years in some cases and counselling/support groups are highly encouraged by addiction specialists. Patients should never try to tackle the task of discontinuing barbiturates without consulting a doctor, owing to the high lethality and relatively sudden onset of the withdrawal. Attempting to quit "cold turkey" may result in neurological damage due to excitotoxicity, severe physical injuries received during convulsions, and even death resulting from arrhythmias during grande Mal seizures, paralleling death caused by delirium tremens. Overdose Some symptoms of an overdose typically include sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgement, drowsiness, shallow breathing, staggering, and, in severe cases, coma or death. The lethal dosage of barbiturates varies greatly with tolerance and from one individual to another. The lethal dose is highly variable among different members of the class, with superpotent barbiturates such as pentobarbital being potentially fatal in considerably lower doses than the low-potency barbiturates such as butalbital. Even in inpatient settings, the development of tolerance is still a problem, as dangerous and unpleasant withdrawal symptoms can result when the drug is stopped after dependence has developed. Tolerance to the anxiolytic and sedative effects of barbiturates tends to develop faster than tolerance to their effects on smooth muscle, respiration, and heart rate, making them generally unsuitable for a long time psychiatric use. Tolerance to the anticonvulsant effects tends to correlate more with tolerance to physiological effects, however, meaning that they are still a viable option for long-term epilepsy treatment. Barbiturates in overdose with other CNS (central nervous system) depressants (e.g. alcohol, opiates, benzodiazepines) are even more dangerous owing to additive CNS and respiratory depressant effects. In the case of benzodiazepines, not only do they have additive effects, barbiturates also increase the binding affinity of the benzodiazepine binding site, leading to exaggerated benzodiazepine effects. (ex. If a benzodiazepine increases the frequency of channel opening by 300%, and a barbiturate increases the duration of their opening by 300%, then the combined effects of the drugs increases the channels overall function by 900%, not 600%). The longest-acting barbiturates have half-lives of a day or more, and subsequently result in bioaccumulation of the drug in the system. The therapeutic and recreational effects of long-acting barbiturates wear off significantly faster than the drug can be eliminated, allowing the drug to reach toxic concentrations in the blood following repeated administration (even when taken at the therapeutic or prescribed dose) despite the user feeling little or no effects from the plasma-bound concentrations of the drug. Users who consume alcohol or other sedatives after the drugs effects have worn off, but before it has cleared the system, may experience a greatly exaggerated effect from the other sedatives which can be incapacitating or even fatal. Barbiturates induce a number of hepatic CYP enzymes (most notably CYP2C9, CYP2C19, and CYP3A4), leading to exaggerated effects from many prodrugs and decreased effects from drugs which are metabolized by these enzymes to inactive metabolites. This can result in fatal overdoses from drugs such as codeine, tramadol, and carisoprodol, which become considerably more potent after being metabolized by CYP enzymes. Although all known members of the class possess relevant enzyme induction capabilities, the degree of induction overall as well as the impact on each specific enzyme span a broad range, with phenobarbital and secobarbital being the most potent enzyme inducers and butalbital and talbutal being among the weakest enzyme inducers in the class. People who are known to have killed themselves by barbiturate overdose include Stefan Zweig, Charles Boyer, Ruan Lingyu, Dalida, Jeannine Deckers, Felix Hausdorff, Abbie Hoffman, Phyllis Hyman, C. P. Ramanujam, George Sanders, Jean Seberg, Lupe Vélez and the members of Heavens Gate cult. Others who have died as a result of barbiturate overdose include Pier Angeli, Brian Epstein, Judy Garland, Jimi Hendrix, Marilyn Monroe, Inger Stevens, Dinah Washington, Ellen Wilkinson, and Alan Wilson; in some cases these have been speculated to be suicides as well. Those who died of a combination of barbiturates and other drugs include Rainer Werner Fassbinder, Dorothy Kilgallen, Malcolm Lowry, Edie Sedgwick and Kenneth Williams. Dorothy Dandridge died of either an overdose or an unrelated embolism. Ingeborg Bachmann may have died of the consequences of barbiturate withdrawal (she was hospitalized with burns, the doctors treating her not being aware of her barbiturate addiction). Contraindications The use of Barbiturates is contraindicated in the following conditions: variegate porphyria (because of induction of enzymes needed for porphyria synthesis by barbiturates) Status asthmaticus (because of respiratory depression caused by the barbiturates) Mechanism of action Barbiturates act as positive allosteric modulators and, at higher doses, as agonists of GABAA receptors. GABA is the principal inhibitory neurotransmitter in the mammalian central nervous system (CNS). Barbiturates bind to the GABAA receptor at multiple homologous transmembrane pockets located at subunit interfaces, which are binding sites distinct from GABA itself and also distinct from the benzodiazepine binding site. Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. In addition to this GABAergic effect, barbiturates also block AMPA and kainate receptors, subtypes of ionotropic glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. Taken together, the findings that barbiturates potentiate inhibitory GABAA receptors and inhibit excitatory AMPA receptors can explain the superior CNS-depressant effects of these agents to alternative GABA potentiating agents such as benzodiazepines and quinazolinones. At higher concentration, they inhibit the Ca2+-dependent release of neurotransmitters such as glutamate via an effect on P/Q-type voltage-dependent calcium channels. Barbiturates produce their pharmacological effects by increasing the duration of chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the efficacy of GABA), whereas benzodiazepines increase the frequency of the chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the potency of GABA). The direct gating or opening of the chloride ion channel is the reason for the increased toxicity of barbiturates compared to benzodiazepines in overdose.Further, barbiturates are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA receptor channel is only one of several representatives. This Cys-loop receptor superfamily of ion channels includes the neuronal nACh receptor channel, the 5-HT3 receptor channel, and the glycine receptor channel. However, while GABAA receptor currents are increased by barbiturates (and other general anesthetics), ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nAChR channels are blocked by clinically relevant anesthetic concentrations of both thiopental and pentobarbital. Such findings implicate (non-GABA-ergic) ligand-gated ion channels, e.g. the neuronal nAChR channel, in mediating some of the (side) effects of barbiturates. This is the mechanism responsible for the (mild to moderate) anesthetic effect of barbiturates in high doses when used in anesthetic concentration. Interactions Drug interactions with barbiturates are: alcohol alprazolam anticoagulants antihistamines atazanavir birth-control pills boceprevir clonazepam Caution Medications such as opioids, Benzodiazepines alcohol asthma kidney or liver problems Heart disease Substance use disorder Depression History of suicidal thoughts History Barbituric acid was first synthesized 27 November 1864, by German chemist Adolf von Baeyer. This was done by condensing urea with diethyl malonate. There are several stories about how the substance got its name. The most likely story is that Baeyer and his colleagues went to celebrate their discovery in a tavern where the towns artillery garrison were also celebrating the feast of Saint Barbara – the patron saint of artillerymen. An artillery officer is said to have christened the new substance by amalgamating Barbara with urea. Another story was barbiturate was invented on the feast day of St. Barbara. Another story holds that Baeyer synthesized the substance from the collected urine of a Munich waitress named Barbara. No substance of medical value was discovered, however, until 1903 when two German scientists working at Bayer, Emil Fischer and Joseph von Mering, discovered that barbital was very effective in putting dogs to sleep. Barbital was then marketed by Bayer under the trade name Veronal. It is said that Mering proposed this name because the most peaceful place he knew was the Italian city of Verona.It was not until the 1950s that the behavioral disturbances and physical dependence potential of barbiturates became recognized.Barbituric acid itself does not have any direct effect on the central nervous system and chemists have derived over 2,500 compounds from it that possess pharmacologically active qualities. The broad class of barbiturates is further broken down and classified according to speed of onset and duration of action. Ultrashort-acting barbiturates are commonly used for anesthesia because their extremely short duration of action allows for greater control. These properties allow doctors to rapidly put a patient "under" in emergency surgery situations. Doctors can also bring a patient out of anesthesia just as quickly, should complications arise during surgery. The middle two classes of barbiturates are often combined under the title "short/intermediate-acting." These barbiturates are also employed for anesthetic purposes, and are also sometimes prescribed for anxiety or insomnia. This is not a common practice anymore, however, owing to the dangers of long-term use of barbiturates; they have been replaced by the benzodiazepines and Z-drugs such as zolpidem, zaleplon and eszopiclone for sleep. The final class of barbiturates are known as long-acting barbiturates (the most notable one being phenobarbital, which has a half-life of roughly 92 hours). This class of barbiturates is used almost exclusively as anticonvulsants, although on rare occasions they are prescribed for daytime sedation. Barbiturates in this class are not used for insomnia, because, owing to their extremely long half-life, patients would awake with a residual "hang-over" effect and feel groggy. Barbiturates can in most cases be used either as the free acid or as salts of sodium, calcium, potassium, magnesium, lithium, etc. Codeine- and Dionine-based salts of barbituric acid have been developed. In 1912, Bayer introduced another barbituric acid derivative, phenobarbital, under the trade name Luminal, as a sedative–hypnotic. Society and culture Legal status During World War II, military personnel in the Pacific region were given "goofballs" to allow them to tolerate the heat and humidity of daily working conditions. Goofballs were distributed to reduce the demand on the respiratory system, as well as maintaining blood pressure, to combat the extreme conditions. Many soldiers returned with addictions that required several months of rehabilitation before discharge. This led to growing dependency problems, often exacerbated by indifferent doctors prescribing high doses to unknowing patients through the 1950s and 1960s.In the late 1950s and 1960s, an increasing number of published reports of barbiturate overdoses and dependence problems led physicians to reduce their prescription, particularly for spurious requests. This eventually led to the scheduling of barbiturates as controlled drugs. In the Netherlands, the Opium Law classifies all barbiturates as List II drugs, with the exception of secobarbital, which is on List I. There is a small group of List II drugs for which doctors have to write the prescriptions according to the same, tougher guidelines as those for List I drugs (writing the prescription in full in letters, listing the patients name, and have to contain the name and initials, address, city and telephone number of the licensed prescriber issuing the prescriptions, as well as the name and initials, address and city of the person the prescription is issued to). Among that group of drugs are the barbiturates amobarbital, butalbital, cyclobarbital, and pentobarbital. In the United States, the Controlled Substances Act of 1970 classified most barbiturates as controlled substances—and they remain so as of September 2020. Barbital, methylphenobarbital (also known as mephobarbital), and phenobarbital are designated schedule IV drugs, and "Any substance which contains any quantity of a derivative of barbituric acid, or any salt of a derivative of barbituric acid" (all other barbiturates) were designated as being schedule III. Under the original CSA, no barbiturates were placed in schedule I, II, or V; however, amobarbital, pentobarbital, and secobarbital are schedule II controlled substances unless they are in a suppository dosage form.In 1971, the Convention on Psychotropic Substances was signed in Vienna. Designed to regulate amphetamines, barbiturates, and other synthetics, the 34th version of the treaty, as of 25 January 2014, regulates secobarbital as schedule II, amobarbital, butalbital, cyclobarbital, and pentobarbital as schedule III, and allobarbital, barbital, butobarbital, mephobarbital, phenobarbital, butabarbital, and vinylbital as schedule IV on its "Green List". The combination medication Fioricet, consisting of butalbital, caffeine, and paracetamol (acetaminophen), however, is specifically exempted from controlled substance status, while its sibling Fiorinal, which contains aspirin instead of paracetamol and may contain codeine phosphate, remains a schedule III drug. Recreational use Recreational users report that a barbiturate high gives them feelings of relaxed contentment and euphoria. Physical and psychological dependence may also develop with repeated use. Chronic misuse of barbiturates is associated with significant morbidity. One study found that 11% of males and 23% of females with a sedative-hypnotic misuse die by suicide. Other effects of barbiturate intoxication include drowsiness, lateral and vertical nystagmus, slurred speech and ataxia, decreased anxiety, and loss of inhibitions. Barbiturates are also used to alleviate the adverse or withdrawal effects of illicit drug use, in a manner similar to long-acting benzodiazepines such as diazepam and clonazepam. Often polysubstance use occurs and barbiturates are consumed with or substituted by other available substances, most commonly alcohol. People who use substances tend to prefer short-acting and intermediate-acting barbiturates. The most commonly used are amobarbital (Amytal), pentobarbital (Nembutal), and secobarbital (Seconal). A combination of amobarbital and secobarbital (called Tuinal) is also highly used. Short-acting and intermediate-acting barbiturates are usually prescribed as sedatives and sleeping pills. These pills begin acting fifteen to forty minutes after they are swallowed, and their effects last from five to six hours. Slang terms for barbiturates include barbs, barbies, bluebirds, dolls, wallbangers, yellows, downers, goofballs, sleepers, reds & blues, and tooties. Examples Thiopental is a barbiturate with one of the C=O double bonds (with the carbon being labelled 2 in the adjacent diagram) replaced with a C=S double bond, R1 being CH2CH3 and R2 being CH(CH3)CH2CH2CH3. Thiopental is no longer available in the United States. See also Benzodiazepine Psycholeptic Dille–Koppanyi reagent, Zwikker reagent, and others spot tests for barbiturates Notes References External links and further reading U.S. Drug Enforcement Administration Source for some public-domain text used on this page. López-Muñoz, F.; Ucha-Udabe, R.; Alamo, C. (2005). "The history of barbiturates a century after their clinical introduction". Neuropsychiatric Disease and Treatment. 1 (4): 329–343. PMC 2424120. PMID 18568113. National Institute on Drug Abuse: "NIDA for Teens: Prescription Depressant Medications".
Osteitis fibrosa cystica	Osteitis fibrosa cystica ( OSS-tee-EYE-tis fy-BROH-sə SIS-tik-ə) is a skeletal disorder resulting in a loss of bone mass, a weakening of the bones as their calcified supporting structures are replaced with fibrous tissue (peritrabecular fibrosis), and the formation of cyst-like brown tumors in and around the bone. Osteitis fibrosis cystica (OFC), also known as osteitis fibrosa, osteodystrophia fibrosa, and von Recklinghausens disease of bone (not to be confused with von Recklinghausens disease, neurofibromatosis type I), is caused by hyperparathyroidism, which is a surplus of parathyroid hormone from over-active parathyroid glands. This surplus stimulates the activity of osteoclasts, cells that break down bone, in a process known as osteoclastic bone resorption. The hyperparathyroidism can be triggered by a parathyroid adenoma, hereditary factors, parathyroid carcinoma, or renal osteodystrophy. Osteoclastic bone resorption releases minerals, including calcium, from the bone into the bloodstream, causing both elevated blood calcium levels, and the structural changes which weaken the bone. The symptoms of the disease are the consequences of both the general softening of the bones and the excess calcium in the blood, and include bone fractures, kidney stones, nausea, moth-eaten appearance in the bones, appetite loss, and weight loss. First described in the nineteenth century, OFC is currently detected through a combination of blood testing, X-rays, and tissue sampling. Before 1950, around half of those diagnosed with hyperparathyroidism in the United States saw it progress to OFC, but with early identification techniques and improved treatment methods, instances of OFC in developed countries are increasingly rare. Where treatment is required, it normally involves addressing the underlying hyperparathyroidism before commencing long-term treatment for OFC—depending on its cause and severity, this can range from hydration and exercise to surgical intervention. Classification Osteitis fibrosa cystica is defined as the classic skeletal manifestation of advanced hyperparathyroidism. Under the ICD-10 classification system, established by the World Health Organization, OFC is listed under category E21.0, primary hyperparathyroidism. Signs and symptoms The major symptoms of OFC are bone pain or tenderness, bone fractures, and skeletal deformities such as bowing of the bones. The underlying hyperparathyroidism may cause kidney stones, nausea, constipation, fatigue and weakness. X-rays may indicate thin bones, fractures, bowing, and cysts. Fractures are most commonly localized in the arms, legs, or spine.The addition of weight loss, appetite loss, vomiting, polyuria, and polydipsia to the aforementioned symptoms may indicate that OFC is the result of parathyroid carcinoma. Parathyroid carcinoma, an uncommon cancer of the parathyroid glands, is generally indicated by serum calcium levels higher than usual, even in comparison to the high serum calcium levels that OFC generally presents with. Symptoms are also often more severe. Generally, the presence of a palpable neck mass is also indicative of the cancer, occurring in approximately 50% of patients, but virtually nonexistent in individuals with OFC with a different origin. Causes Osteitis fibrosa cystica is the result of unchecked hyperparathyroidism, or the overactivity of the parathyroid glands, which results in an overproduction of parathyroid hormone (PTH). PTH causes the release of calcium from the bones into the blood, and the reabsorption of calcium in the kidney. Thus, excess PTH in hyperparathyroidism causes elevated blood calcium levels, or hypercalcemia. There are four major causes of primary hyperparathyroidism that result in OFC: Parathyroid adenomaThe vast majority of cases of hyperparathyroidism are the result of the random formation of benign, but metabolically active, parathyroid adenoma swellings. These instances comprise approximately 80–85% of all documented cases of hyperparathyroidism. Hereditary factorsApproximately 1 in 10 documented cases of hyperparathyroidism are a result of hereditary factors. Disorders such as familial hyperparathyroidism, multiple endocrine neoplasia type 1 (MEN Type 1) and hyperparathyroidism-jaw tumor syndrome can, if left unchecked, result in OFC. MEN Type 1 is an autosomal dominant disorder and the most common hereditary form of hyperparathyroidism, affecting about 95% of genetic cases of OFC, and also tends to affect younger patients than other forms. Major mutations which can lead to hyperparathyroidism generally involve the parathyroid hormone receptor, G proteins, or adenylate cyclase. Certain genetic mutations have been linked to a higher rate of parathyroid carcinoma occurrence, specifically mutations to the gene HRPT2, which codes for the protein parafibromin. Parathyroid carcinomaParathyroid carcinoma (cancer of the parathyroid gland) is the rarest cause of OFC, accounting for about 0.5% of all cases of hyperparathyroidism. OFC onset by parathyroid carcinoma is difficult to diagnose. Renal complicationsOFC is a common presentation of renal osteodystrophy, which is a term used to refer to the skeletal complications of end stage renal disease (ESRD). OFC occurs in approximately 50% of patients with ESRD. ESRD occurs when the kidneys fail to produce calcitriol, a form of vitamin D, which assists in the absorption of calcium into the bones. When calcitriol levels decrease, parathyroid hormone levels increase, halting the storage of calcium, and instead triggering its removal from the bones. The concept of renal osteodystrophy is currently included into the broader term chronic kidney disease-mineral and bone disorder (CKD-MBD). Fluoride intoxicationOFC was noticed in the early years of community fluoridation to be at higher risk when water supplies were fluoridated. Indeed, death rates which in some cases were gruesomely dramatic during dialysis quickly brought attention to the fact that fluoride in water during dialysis was a health hazard. Modern dialysis takes pains to de-fluoridate water in order to minimize bone disease including OFC. The 2006 National Research Council confirmed kidney patients are a sub-population particularly susceptible to ill effects from fluoride exposure which manifest in bones.Fanconi syndrome: decrease amino acids, phosphate, glucose, bicarbonate and potassium salts. Pathophysiology The effects of OFC on bone are largely dependent on the duration of the disease and the level of parathyroid hormone (PTH) produced. PTH is responsible for maintaining a homeostatic calcium concentration in the blood. It activates the parathyroid-hormone related protein receptor located on osteoclasts and osteocytes, both of which are responsible for the breakdown and maintaining of bone. Abnormalities affecting the parathyroid glands cause a surplus of PTH, which, in turn, increases the activity and frequency of osteoclasts and osteocytes. Increased PTH levels trigger the release of stored calcium through the dissolution of old bone, as well as the conservation of serum calcium through a cessation in the production of new bone.Generally, the first bones to be affected are the fingers, facial bones, ribs, and pelvis. Long bones, which are longer than they are wide, are also among the first affected. As the disease progresses, any bone may be affected. Diagnosis OFC may be diagnosed using a variety of techniques. Muscles in patients with OFC can either appear unaffected or "bulked up." If muscular symptoms appear upon the onset of hyperparathyroidism, they are generally sluggish contraction and relaxation of the muscles. Deviation of the trachea (a condition in which the trachea shifts from its position at the midline of the neck), in conjunction with other known symptoms of OFC can point to a diagnosis of parathyroid carcinoma.Blood tests on patients with OFC generally show high levels of calcium (normal levels are considered to range between 8.5 and 10.2 mg/dL, parathyroid hormone (levels generally above 250 pg/mL, as opposed to the "normal" upper-range value of 65 pg/mL), and alkaline phosphatase (normal range is 20 to 140 IU/L). X-rays may also be used to diagnose the disease. Usually, these X-rays will show extremely thin bones, which are often bowed or fractured. However, such symptoms are also associated with other bone diseases, such as osteopenia or osteoporosis. Generally, the first bones to show symptoms via X-ray are the fingers. Furthermore, brown tumors, especially when manifested on facial bones, can be misdiagnosed as cancerous. Radiographs distinctly show bone resorption and X-rays of the skull may depict an image often described as "ground glass" or "salt and pepper". Dental X-rays may also be abnormal. Cysts may be lined by osteoclasts and sometimes blood pigments, which lend to the notion of "brown tumors." Such cysts can be identified with nuclear imaging combined with specific tracers, such as sestamibi. Identification of muscular degeneration or lack of reflex can occur through clinical testing of deep tendon reflexes, or via photomotogram (an achilles tendon reflex test).Fine needle aspiration (FNA) can be used to biopsy bone lesions, once found on an X-ray or other scan. Such tests can be vital in diagnosis and can also prevent unnecessary treatment and invasive surgery. Conversely, FNA biopsy of tumors of the parathyroid gland is not recommended for diagnosing parathyroid carcinoma and may in fact be harmful, as the needle can puncture the tumor, leading to dissemination and the possible spread of cancerous cells.The brown tumors commonly associated with OFC display many of the same characteristics of osteoclasts. These cells are characteristically benign, feature a dense, granular cytoplasm, and a nucleus that tends to be ovular in shape, enclosing comparatively fine chromatin. Nucleoli also tend to be smaller than average. Management Medical Medical management of OFC consists of vitamin D treatment, generally alfacalcidol or calcitriol, delivered intravenously. Studies have shown that in cases of OFC caused by either end-stage renal disease or primary hyperparathyroidism, this method is successful not only in treating underlying hyperparathyroidism, but also in causing the regression of brown tumors and other symptoms of OFC. Surgery In especially severe cases of OFC, parathyroidectomy, or the full removal of the parathyroid glands, is the chosen route of treatment. Parathyroidectomy has been shown to result in the reversal of bone resorption and the complete regression of brown tumors. In situations where parathyroid carcinoma is present, surgery to remove the tumors has also led to the regression of hyperparathyroidism as well as the symptoms of OFC.Bone transplants have proven successful in filling the lesions caused by OFC. A report showed that in 8 out of 11 instances where cavities caused by OFC were filled with transplanted bone, the lesion healed and the transplanted bone blended rapidly and seamlessly with the original bone. Prognosis Almost all who undergo parathyroidectomy experience increased bone density and repair of the skeleton within weeks. Additionally, patients with OFC who have undergone parathyroidectomy begin to show regression of brown tumors within six months. Following parathyroidectomy, hypocalcaemia is common. This results from a combination of suppressed parathyroid glands due to prolonged hypercalcaemia, as well as the need for calcium and phosphate in the mineralization of new bone.Thirty percent of patients with OFC-like tumors caused by metastatic parathyroid carcinoma who undergo surgery see a local recurrence of symptoms. The post-surgical survival rate hovers around seven years, while patients who do not undergo surgery have a survival rate of around five years. Epidemiology Osteitis fibrosa cystica has long been a rare disease. Today, it appears in only 2% of individuals diagnosed with primary hyperparathyroidism, which accounts for 90% of instances of the disease. Primary hyperparathyroidism is three times as common in individuals with diabetes mellitus.The hospitalization rate for hyperparathyroidism in the United States in 1999 was 8.0 out of 100,000. The disease has a definite tendency to affect younger individuals, typically appearing before the age of 40, with a study in 1922 reporting that 70% of cases display symptoms before the age of 20, and 85% before 35. Primary hyperparathyroidism, as well as OFC, is more common in Asiatic countries. Before treatment for hyperparathyroidism improved in the 1950s, half of those diagnosed with hyperparathyroidism saw it progress into OFC.Rates of OFC increase alongside cases of unchecked primary hyperparathyroidism. In developing countries, such as India, rates of disease as well as case reports often mirror those published in past decades in the developed world.The other 10% of cases are primarily caused by primary hyperplasia, or an increase of the number of cells. Parathyroid carcinoma accounts for less than 1% of all cases, occurring most frequently in individuals around 50 years of age (in stark contrast to OFC as a result of primary hyperparathyroidism) and showing no gender preference. Approximately 95% of hyperparathyroidism caused by genetic factors is attributed to MEN type 1. This mutation also tends to affect younger individuals. History The condition was first described by Gerhard Engel in 1864 and Friedrich Daniel von Recklinghausen in 1890, though William Hunter, who died in 1783, is credited with finding the first example of the disease. "von Recklinghausens disease" (without the qualification "of bone") is a completely unrelated disorder, nowadays termed neurofibromatosis. In 1884, Davies Colley delivered a presentation to the Pathological Society of London that detailed the manifestation of hyperparathyroidism into a brown tumor of the mandible, as well as the histological makeup of the tumor.The discovery and subsequent description of the parathyroid glands is credited to Ivar Sandstrom, though his publication, On a New Gland in Man and Several Mammals-Glandulae Parathyroideae, received little attention. Gustaf Retzius and Eugene Gley compounded his research, the latter credited with the discovery of the function of the parathyroid glands. This research cumulated in the first surgical removal of a parathyroid tumor by Felix Mandel in 1925. A 2.5 × 1.5-inch (64 × 38 mm) tumor was removed from the thyroid artery of a man with advanced OFC. The patients symptoms disappeared, only to return in approximately six years as a result of renal stones that were diagnosed only after the patient had died. In 1932, blood tests on a female patient with renal stone-based OFC revealed extremely high blood calcium levels. Fuller Albright diagnosed and treated the woman, who had a large tumor of the neck as well as renal stones.The first published literature to describe a brown tumor (which was linked to OFC) was published in 1953, though clinical reports from before 1953 do draw a correlation between the disease and tumors previous to the publication.The advent of the multichannel autoanalyzer in the 1960s and 70s led to an increase in early diagnosis of primary hyperparathyroidism. This increase led to a sharp decline in the prolonged manifestation of the disease, leading to a drop in the number of cases of OFC due to the early detection of hyperparathyroidism. Before this invention, the diagnosis of primary hyperparathyroidism was generally prolonged until the emergence of severe manifestations, such as OFC. References Bibliography Campbell, Neil (1987). Biology. Menlo Park, Calif: Benjamin/Cummings Pub. Co. ISBN 978-0-8053-1840-1. Eberstein, Arthur; Goodgold, Joseph (1983). Electrodiagnosis of Neuromuscular Diseases. Baltimore: Williams & Wilkins. ISBN 978-0-683-03686-2. Ellis, Harold (2002). A History of Surgery. London: Greenwich Medical Media. p. 210. ISBN 978-1-84110-181-1. Hricik, Donald; R. Tyler Miller; John R. Sedor (2003). Nephrology Secrets. Hanley & Belfus. p. 175. ISBN 978-1-56053-502-7. Levine, Michael W.; Bilezikian, John P.; Marcus, Robert (2001). The Parathyroids: Basic and Clinical Concepts. Boston: Academic Press. ISBN 978-0-12-098651-4. Stevens, Arthur (1922). "The Practice of Medicine". W. B. Saunders Co. {{cite journal}}: Cite journal requires \|journal= (help) Patton, Kevin T.; Thibodeau, Gary A. (1996). Anthonys Textbook of Anatomy & Physiology. St. Louis: Mosby. ISBN 978-0-8151-8861-2. == External links ==
Ulnar dimelia	Ulnar dimelia, also referred to simply as mirror hand, is a very rare congenital disorder characterized by the absence of the radial ray, duplication of the ulna, duplication of the carpal, metacarpal, and phalanx bones, and symmetric polydactyly. In some cases surgical amputation is performed to remove the duplicate carpals, metacarpals and phalanges. As of 2015, approximately 70 cases have been recorded in the medical literature. Bone deformity may also accompany nervous and arterial anomalies in some cases due to the duplication of the ulnar nerve, the presence of abnormal arterial arches, the duplication of the ulnar artery, the shortening of the radial nerve, and the absence of the radial artery. The diagnosis of ulnar dimelia is based on laboratory tests of frontal and sagittal planes in individuals suspected of the condition. There are two types of ulnar dimelia noted in medical journals: Type 1 ulnar dimelia entails one lunate and one trapezoid bone as well as one index finger, while type 2 ulnar dimelia has two lunate and two trapezoid bones as well as two index fingers. The American Society for Surgery of the Hand and the International Federation of Societies for Surgery of the Hand classified ulnar dimelia in the third group of congenital hand deformities in accordance with the characteristics proposed in the Swanson classification (1976). References Tomaszewski, Ryszard; Bulandra, Andrzej (2015). "Ulnar dimelia-diagnosis and management of a rare congenital anomaly of the upper limb". Journal of Orthopaedics. 12 (Suppl 1): S121–S124. doi:10.1016/j.jor.2015.01.027. PMC 4674541. PMID 26719621. Namdev, Rupesh. "Ulnar dimelia \| Radiology Reference Article \| Radiopaedia.org". radiopaedia.org. Chinegwundoh, J. O. M.; Gupta, M.; Scott, W. A. (1 February 1997). "Ulnar dimelia: Is it a true duplication of the ulna?". Journal of Hand Surgery. 22 (1): 77–79. doi:10.1016/S0266-7681(97)80024-1. PMID 9061533. S2CID 31636571. Jameel, Javed; Khan, Abdul Qayyum; Ahmad, Sohail; Abbas, Mazhar (2011). "Ulnar dimelia variant: a case report". Journal of Orthopaedics and Traumatology. 12 (3): 163–165. doi:10.1007/s10195-011-0146-y. PMC 3163772. PMID 21769660.
Kindler syndrome	Kindler syndrome (also known as "bullous acrokeratotic poikiloderma of Kindler and Weary",) is a rare congenital disease of the skin caused by a mutation in the KIND1 gene. Symptoms and signs Infants and young children with Kindler syndrome have a tendency to blister with minor trauma and are prone to sunburns. As individuals with Kindler syndrome age, they tend to have fewer problems with blistering and photosensitivity. However, pigment changes and thinning of the skin become more prominent. Kindler syndrome can affect various mucous tissues such as the mouth and eyes, which can lead to other health problems. Genetics Kindler syndrome is an autosomal recessive genodermatosis. The KIND1 gene mutated in Kindler syndrome codes for the protein kindlin-1, which is thought to be active in the interactions between actin and the extracellular matrix (focal adhesion plaques). Kindler syndrome was first described in 1954 by Theresa Kindler. Diagnosis Clinical and genetic tests are used to confirm diagnosis. Management Treatment may involve several different types of practitioner to address the various manifestations that may occur. This multidisciplinary team will also be involved in preventing secondary complications. See also Rothmund–Thomson syndrome Epidermolysis bullosa List of cutaneous conditions References == External links ==
Aspiration pneumonia	Aspiration pneumonia is a type of lung infection that is due to a relatively large amount of material from the stomach or mouth entering the lungs. Signs and symptoms often include fever and cough of relatively rapid onset. Complications may include lung abscess, Acute respiratory distress syndrome, empyema, and parapneumonic effusion. Some include chemical induced inflammation of the lungs as a subtype, which occurs from acidic but non-infectious stomach contents entering the lungs.Infection can be due to a variety of bacteria. Risk factors include decreased level of consciousness, problems with swallowing, alcoholism, tube feeding, and poor oral health. Diagnosis is typically based on the presenting history, symptoms, chest X-ray, and sputum culture. Differentiating from other types of pneumonia may be difficult.Treatment is typically with antibiotics such as clindamycin, meropenem, ampicillin/sulbactam, or moxifloxacin. For those with only chemical pneumonitis, antibiotics are not typically required. Among people hospitalized with pneumonia, about 10% are due to aspiration. It occurs more often in older people, especially those in nursing homes. Both sexes are equally affected. Signs and symptoms The person may have an insidious course with increased respiratory rate, foul-smelling sputum, hemoptysis, and fever. Complications may occur, such as exudative pleural effusion, empyema, and lung abscesses. If left untreated, aspiration pneumonia can progress to form a lung abscess. Another possible complication is an empyema, in which pus collects inside the lungs. If continual aspiration occurs, the chronic inflammation can cause compensatory thickening of the insides of the lungs, resulting in bronchiectasis. Causes Most aspiration events occur in patients with a defective swallowing mechanism, such as a neurological disease or as the result of an injury that directly impairs swallowing or interferes with consciousness. Impaired consciousness can be intentional, such as the use of general anesthesia for surgery. For many types of surgical operations, people preparing for surgery are therefore instructed to take nothing by mouth (nil per os, abbreviated as NPO) for at least four hours before surgery. These conditions enable the entry of bacteria into the lungs, thus allowing the development of an infection. Risk factors Impaired swallowing: Conditions that cause dysphagia worsen the ability of people to swallow, causing an increased risk of entry of particles from the stomach or mouth into the airways. While swallowing dysfunction is associated with aspiration pneumonia, dysphagia may not be sufficient unless other risk factors are present. Neurologic conditions that can directly impact the nerves involved in the swallow mechanism include stroke, neurodegenerative diseases (such as Parkinsons disease), and multiple sclerosis. Anatomical changes in the chest can also disrupt the swallow mechanism. For example, patients with advanced COPD tend to develop enlarged lungs, resulting in compression of the esophagus and thus regurgitation. Altered mental status: Changes in levels of consciousness affect the swallow mechanism by both disabling the bodys natural protective measures against aspiration as well as possibly causing nausea and vomiting. Altered mental status can be caused by medical conditions such as seizures. However, many other agents can be responsible as well, including general anesthesia and alcohol. Bacterial colonization: Poor oral hygiene can result in colonization of the mouth with excessive amounts of bacteria, which is linked to increased incidence of aspiration pneumonia. Ethnicity: Asians diagnosed with aspiration pneumonia have a lower risk of death compared to other ethnic groups while African Americans and whites share a relatively similar risk of death. Hispanics have a lower risk of death than non-Hispanics. Others: Age, male gender, diabetes mellitus, malnutrition, use of antipsychotic drugs, proton pump inhibitors, and angiotensin-converting enzyme inhibitors. Residence in an institutional setting, prolonged hospitalization or surgical procedures, gastric tube feeding, mechanical airway interventions, immunocompromised, history of smoking, antibiotic therapy, advanced age, reduced pulmonary clearance, diminished cough reflex, disrupted normal mucosal barrier, impaired mucociliary clearance, alter cellular and humoral immunity, obstruction of the airways, and damaged lung tissue. Bacteria Bacteria involved in aspiration pneumonia may be either aerobic or anaerobic. Common aerobic bacteria involved include: Streptococcus pneumoniae Staphylococcus aureus Haemophilus influenzae Pseudomonas aeruginosa Klebsiella: often seen in aspiration lobar pneumonia in alcoholicsAnaerobic bacteria also play a key role in the pathogenesis of aspiration pneumonia. They make up the majority of normal oral flora and the presence of putrid fluid in the lungs is highly suggestive of aspiration pneumonia secondary to an anaerobic organism. While it is difficult to confirm the presence of anaerobes through cultures, the treatment of aspiration pneumonia typically includes anaerobic coverage regardless. Potential anaerobic bacteria are as follows: Bacteroides Prevotella Fusobacterium Peptostreptococcus Pathophysiology Aspiration is defined as inhalation of oropharyngeal or gastric contents into the pulmonary tree. Depending on the composition of the aspirate, three complications have been described: Chemical pneumonitis may develop whose severity depends on the pH value and quantity of aspirate. The two lung changes after acid aspiration are: a) direct toxic damage to the respiratory epithelium resulting in interstitial pulmonary edema and b) a few hours later, inflammatory response with production of cytokines, neutrophil infiltration, and macrophage activation. Oxygen-free radicals are generated which, in turn, lead to further lung damage. Patients may remain asymptomatic after acid aspiration. Others may develop dyspnea, pleuritic chest pain, cough, fever, bloody or frothy sputum, and respiratory failure. Aspiration pneumonia may develop. The third complication occurs after inhalation of particulate matter that obstructs airways. The patients will have sudden arterial hypoxemia with development of lung atelectasis. Location The location is often gravity dependent, and depends on the persons position. Generally, the right middle and lower lung lobes are the most common sites affected, due to the larger caliber and more vertical orientation of the right mainstem bronchus. People who aspirate while standing can have bilateral lower lung lobe infiltrates. The right upper lobe is a common area of consolidation, where liquids accumulate in a particular region of the lung, in alcoholics who aspirate in the supine position. Diagnosis Evaluation of aspiration is generally performed with a video fluoroscopic swallowing study involving radiologic evaluation of the swallowing mechanism via challenges with liquid and solid food consistencies. These studies allow for evaluation of penetration to the vocal folds and below but are not a sensitive and specific marker for aspiration. Additionally, it is difficult to distinguish between aspiration pneumonia and aspiration pneumonitis.Aspiration pneumonia is typically diagnosed by a combination of clinical circumstances (people with risk factors for aspiration) and radiologic findings (an infiltrate in the proper location). A chest x-ray is typically performed in cases where any pneumonia is suspected, including aspiration pneumonia. Findings on chest x-ray supportive of aspiration pneumonia include localized consolidation depending on the patients position when the aspiration occurred. For example, people that are supine when they aspirate often develop consolidation in the right lower lobe of the lung. Sputum cultures are not used for diagnosing aspiration pneumonia because of the high risk of contamination. Clinical symptoms may also increase suspicion of aspiration pneumonia, including new difficulty breathing and fever after an aspiration event. Likewise, physical exam findings such as altered breath sounds heard in the affected lung fields may also be suggestive of aspiration pneumonia. Some cases of aspiration pneumonia are caused by aspiration of food particles or other particulate substances like pill fragments; these can be diagnosed by pathologists on lung biopsy specimens.While aspiration pneumonia and chemical pneumonitis may appear similar, it is important to differentiate between the two due to major differences in management of these conditions. Chemical pneumonitis is caused by damage to the inner layer of lung tissue, which triggers an influx of fluid. The inflammation caused by this reaction can rapidly cause similar findings seen in aspiration pneumonia, such as an elevated WBC (white blood cell) count, radiologic findings, and fever. However, it is important to note that the findings of chemical pneumonitis are triggered by inflammation not caused by infection, as seen in aspiration pneumonia. Inflammation is the bodys immune response to any perceived threat to the body. Thus, treatment of chemical pneumonitis typically involves removal of the inflammatory fluid and supportive measures, notably excluding antibiotics. The use of antimicrobials is reserved for chemical pneumonitis complicated by secondary bacterial infection. Prevention There have been several practices associated with decreased incidence and decreased severity of aspiration pneumonia as detailed below. Oral hygiene Studies showed that the net reduction of oral bacteria was associated with a decrease in both incidence of aspiration pneumonia as well as mortality from aspiration pneumonia. One broad method of decreasing the number of bacteria in the mouth involves the use of antimicrobials, ranging from topical antibiotics to intravenous antibiotic use. Whereas the use of antibiotics focuses on destroying and hindering the growth of bacteria, mechanical removal of oral bacteria by a dental professional also plays a key role in reducing the bacterial burden. By reducing the amount of bacteria in the mouth, the likelihood of infection when aspiration occurs is reduced as well. For people who are critically ill that require a feeding tube, there is evidence suggesting that the risk of aspiration pneumonia may be reduced by inserting the feeding tube into the duodenum or the jejunum (post-pyloric feeding), when compared to inserting the feeding tube into the stomach (gastric feeding). Enhanced swallow Many people at risk for aspiration pneumonia have an impaired swallowing mechanism, which may increase the chance of aspiration of food particles with meals. There is some evidence to indicate that training of various parts of the body involved in the act of swallowing, including the tongue and lips, may reduce episodes of aspiration and aspiration pneumonia; however, further research is required to confirm this benefit. Other simple actions during feeding can improve the swallowing capability of a person and thus reduce the risk of aspiration, including changes in position and feeding assistance. After surgery Many instances of aspiration occur during surgical operations, especially during anesthesia induction. The administration of anesthesia causes suppression of protective reflexes, most importantly the gag reflex. As a result, stomach particles can easily enter the lungs. Certain risk factors predispose individuals to aspiration, especially conditions causing dysfunction of the upper gastrointestinal system. Identifying these conditions before the operation begins is essential for proper preparation during the procedure. It is recommended that patients fast prior to procedures as well. Other practices that may be beneficial but have not been well-studied include medication that reduce the acidity of gastric contents and rapid sequence induction. On the other hand, regarding reducing acidity of the stomach, an acid environment is needed to kill the organisms that colonize the gastrointestinal tract; agents, such as proton pump inhibitors, that decrease the acidity of the stomach, may favor the growth of bacteria and increase the risk of pneumonia. Treatment Adjusting the patients posture should come first, then the oropharyngeal contents should be suctioned with the nasogastric tube in place. Humidified oxygen is given to patients who are not intubated, and the head end of the bed should be elevated by 45 degrees. Its crucial to keep a close eye on the patients oxygen saturation, and if hypoxia is detected, urgent intubation with mechanical breathing should be given. Flexible bronchoscopy is often used to gather samples of bronchoalveolar lavage for quantitative bacteriological tests as well as high volume aspiration to clear the secretion. In general practice The main treatment of aspiration pneumonia revolves around the use of antibiotics to remove the bacteria causing the infection. Broad antibiotic coverage is required to account for the diverse types of bacteria possibly causing the infection. Even though they are not necessary in cases with aspiration pneumonitis, antibiotics are typically started right away to stop the diseases development.Recommended antibiotics include clindamycin, meropenem, ertapenem, ampicillin/sulbactam, and moxifloxacin. Treatment with piperacillin/tazobactam, cefepime, levofloxacin, imipenem, or meropenem is recommended in cases of potential antibiotic resistance. The typical duration of antibiotic therapy is about 5 to 7 days. If there is a large accumulation of fluid within the lungs, drainage of the fluid may also aid in the healing process. Prognosis Dysphagia clinicians often recommend alteration of dietary regimens, altered head positioning, or removal of all oral intake. While studies have suggested that thickening liquids can decrease aspiration through slowed pharyngeal transit time, they have also demonstrated increased pharyngeal residues with risk for delayed aspiration. The ability of clinical interventions to reduce pneumonia incidence is relatively unknown. Dietary modifications or nothing-by-mouth status also have no effect on a patients ability to handle their own secretions. A patients individual vigor may impact the development of pulmonary infections more than aspiration. Also increased pneumonia risk exists in patients with esophageal dysphagia when compared to stroke patients because patients with stroke will improve as they recover from their acute injury, whereas esophageal dysphagia is likely to worsen with time. In one cohort of aspiration pneumonia patients, overall three-year mortality was 40%.Studies have shown that aspiration pneumonia has been associated with an overall increased in-hospital mortality as compared with other forms of pneumonia. Further studies investigating differing time spans including 30-day mortality, 90-day mortality, and 1-year mortality. Individuals diagnosed with aspiration pneumonia were also at increased risk of developing future episodes of pneumonia. In fact, these individuals were also found to be at higher risk for readmission after being discharged from the hospital. Lastly, one study found that individuals diagnosed with aspiration pneumonia were more likely to fail treatment compared to other types of pneumonia. Elderly Aging increases the risk of dysphagia. The prevalence of dysphagia in nursing homes is approximately 50%, and 30% of the elderly with dysphagia develop aspiration. For individuals older than 75, the risk of pneumonia due to dysphagia, is six times greater than those 65. Owing to multiple factors, such as frailty, impaired efficacy of swallowing, decreased cough reflex and neurological complications, dysphagia can be considered as a geriatric syndrome. Atypical presentation is common in the elderly. Older patients may have impaired T cell function and hence, they may be unable to mount a febrile response. The mucociliary clearance of older people is also impaired, resulting in diminished sputum production and cough. Therefore, they can present non-specifically with different geriatric syndromes. Microaspirations In the elderly, dysphagia is a significant risk factor for the development of aspiration pneumonia. Aspiration pneumonia most often develops due to micro-aspiration of saliva, or bacteria carried on food and liquids, in combination with impaired host immune function. Chronic inflammation of the lungs is a key feature in aspiration pneumonia in elderly nursing home residents and presents as a sporadic fever (one day per week for several months). Radiological review shows chronic inflammation in the consolidated lung tissue, linking chronic micro-aspiration and chronic lung inflammation. Choking After falls, choking on food presents as the second highest cause of preventable death in aged care. Although food choking risk is commonly associated with young children, data shows that individuals over 65 years of age have a choking incidence that is seven times higher than children aged 1–4 years. Parkinsons disease The reported prevalence of dysphagia in patients with Parkinsons disease ranges from 20% to 100% due to variations in the methods of assessing the swallowing function. Unlike some medical problems, such as stroke, dysphagia in Parkinsons Disease degenerates with disease progression. Aspiration pneumonia was the most common reason for the emergency admission of patients with Parkinsons Disease whose disease duration was >5 years and pneumonia was one of the main causes of death. Dementia The familiar model of care for people with advanced dementia and dysphagia is the revolving door of recurrent chest infections, frequently associated with aspiration and related readmissions. Many individuals with dementia resist or are indifferent to food and fail to manage the food bolus. There are also many contributory factors such as poor oral hygiene, high dependency levels for being positioned and fed, as well as the need for oral suctioning. While tube feeding might therefore be considered a safer option, tube feeding has not been shown to be beneficial in people with advanced dementia. The preferred option therefore is to continue eating and drinking orally despite the risk of developing chest infections. See also Dysphagia Meconium aspiration syndrome Nosocomial pneumonia Chemical pneumonitis References == External links ==
Human height	Human height or stature is the distance from the bottom of the feet to the top of the head in a human body, standing erect. It is measured using a stadiometer, in centimetres when using the metric system, or feet and inches when using United States customary units or the imperial system.In the early phase of anthropometric research history, questions about height techniques for measuring nutritional status often concerned genetic differences.Height is also important because it is closely correlated with other health components, such as life expectancy. Studies show that there is a correlation between small stature and a longer life expectancy. Individuals of small stature are also more likely to have lower blood pressure and are less likely to acquire cancer. The University of Hawaii has found that the "longevity gene" FOXO3 that reduces the effects of aging is more commonly found in individuals of small body size. Short stature decreases the risk of venous insufficiency.When populations share genetic backgrounds and environmental factors, average height is frequently characteristic within the group. Exceptional height variation (around 20% deviation from average) within such a population is sometimes due to gigantism or dwarfism, which are medical conditions caused by specific genes or endocrine abnormalities.The development of human height can serve as an indicator of two key welfare components, namely nutritional quality and health. In regions of poverty or warfare, environmental factors like chronic malnutrition during childhood or adolescence may result in delayed growth and/or marked reductions in adult stature even without the presence of any of these medical conditions. A study of 20th-century British natality trends indicated that while tall men tended to reproduce more than short men, women of below-average height had more children than taller women. Determinants of growth and height The study of height is known as auxology. Growth has long been recognized as a measure of the health of individuals, hence part of the reasoning for the use of growth charts. For individuals, as indicators of health problems, growth trends are tracked for significant deviations, and growth is also monitored for significant deficiency from genetic expectations. Genetics is a major factor in determining the height of individuals, though it is far less influential regarding differences among populations. Average height is relevant to the measurement of the health and wellness (standard of living and quality of life) of populations.Attributed as a significant reason for the trend of increasing height in parts of Europe are the egalitarian populations where proper medical care and adequate nutrition are relatively equally distributed. The uneven distribution of nutritional resources makes it more plausible for individuals with better access to resources to grow taller, while the other population group who does not have so much of a nutritious food availability height growth is not as promising. Average height in a nation is correlated with protein quality. Nations that consume more protein in the form of meat, dairy, eggs, and fish tend to be taller, while those that obtain more protein from cereals tend to be shorter. Therefore, populations with high cattle per capita and high consumption of dairy live longer and are taller. Historically, this can be seen in the cases of the United States, Argentina, New Zealand and Australia in the beginning of the 19th century. Moreover, when the production and consumption of milk and beef is taken to consideration, it can be seen why the Germanic people who lived outside of the “imperium Romanum” were taller than those who lived at the heart of the Empire.Changes in diet (nutrition) and a general rise in quality of health care and standard of living are the cited factors in the Asian populations. Malnutrition including chronic undernutrition and acute malnutrition is known to have caused stunted growth in various populations. This has been seen in North Korea, parts of Africa, certain historical Europe, and other populations. Developing countries such as Guatemala have rates of stunting in children under 5 living as high as 82.2% in Totonicapán, and 49.8% nationwide.Height measurements are by nature subject to statistical sampling errors even for a single individual. In a clinical situation, height measurements are seldom taken more often than once per office visit, which may mean sampling taking place a week to several months apart. The smooth 50th percentile male and female growth curves illustrated above are aggregate values from thousands of individuals sampled at ages from birth to age 20. In reality, a single individuals growth curve shows large upward and downward spikes, partly due to actual differences in growth velocity, and partly due to small measurement errors. For example, a typical measurement error of plus or minus 0.5 cm (0.20 in) may completely nullify 0.5 cm of actual growth resulting in either a "negative" 0.5 cm growth (due to overestimation in the previous visit combined with underestimation in the latter), up to a 1.5 cm (0.6 in) growth (the first visit underestimating and the second visit overestimating) in the same elapsed period between measurements. Note there is a discontinuity in the growth curves at age 2, which reflects the difference in recumbent length (with the child on his or her back), used in measuring infants and toddlers, and standing height typically measured from age 2 onwards. Height, like other phenotypic traits, is determined by a combination of genetics and environmental factors. A childs height based on parental heights is subject to regression toward the mean, therefore extremely tall or short parents will likely have correspondingly taller or shorter offspring, but their offspring will also likely be closer to average height than the parents themselves. Genetic potential and several hormones, minus illness, is a basic determinant for height. Other factors include the genetic response to external factors such as diet, exercise, environment, and life circumstances. Humans grow fastest (other than in the womb) as infants and toddlers, rapidly declining from a maximum at birth to roughly age 2, tapering to a slowly declining rate, and then, during the pubertal growth spurt (with an average girl starting her puberty and pubertal growth spurt at 10 years and an average boy starting his puberty and pubertal growth spurt at 12 years), a rapid rise to a second maximum (at around 11–12 years for an average female, and 13–14 years for an average male), followed by a steady decline to zero. The average female growth speed trails off to zero at about 15 or 16 years, whereas the average male curve continues for approximately 3 more years, going to zero at about 18–19. These are also critical periods where stressors such as malnutrition (or even severe child neglect) have the greatest effect. Moreover, the health of a mother throughout her life, especially during her critical period and pregnancy, has a role. A healthier child and adult develops a body that is better able to provide optimal prenatal conditions. The pregnant mothers health is essential for herself but also the fetus as gestation is itself a critical period for an embryo/fetus, though some problems affecting height during this period are resolved by catch-up growth assuming childhood conditions are good. Thus, there is a cumulative generation effect such that nutrition and health over generations influence the height of descendants to vary degrees. The age of the mother also has some influence on her childs height. Studies in modern times have observed a gradual increase in height with maternal age, though these early studies suggest that trend is due to various socio-economic situations that select certain demographics as being more likely to have a first birth early in the mothers life. These same studies show that children born to a young mother are more likely to have below-average educational and behavioural development, again suggesting an ultimate cause of resources and family status rather than a purely biological explanation.It has been observed that first-born males are shorter than later-born males. However, more recently the reverse observation was made. The study authors suggest that the cause may be socio-economic in nature. Nature versus nurture The precise relationship between genetics and environment is complex and uncertain. Differences in human height is 60–80% heritable, according to several twin studies and has been considered polygenic since the Mendelian-biometrician debate a hundred years ago. A genome-wide association (GWA) study of more than 180,000 individuals has identified hundreds of genetic variants in at least 180 loci associated with adult human height. The number of individuals has since been expanded to 253,288 individuals and the number of genetic variants identified is 697 in 423 genetic loci. In a separate study of body proportion using sitting-height ratio, it reports that these 697 variants can be partitioned into 3 specific classes, (1) variants that primarily determine leg length, (2) variants that primarily determine spine and head length, or (3) variants that affect overall body size. This gives insights into the biological mechanisms underlying how these 697 genetic variants affect overall height. These loci do not only determine height, but other features or characteristics. As an example, 4 of the 7 loci identified for intracranial volume had previously been discovered for human height.The effect of environment on height is illustrated by studies performed by anthropologist Barry Bogin and coworkers of Guatemala Mayan children living in the United States. In the early 1970s, when Bogin first visited Guatemala, he observed that Mayan Indian men averaged 157.5 centimetres (5 ft 2 in) in height and the women averaged 142.2 centimetres (4 ft 8 in). Bogin took another series of measurements after the Guatemalan Civil War, during which up to a million Guatemalans fled to the United States. He discovered that Maya refugees, who ranged from six to twelve years old, were significantly taller than their Guatemalan counterparts. By 2000, the American Maya were 10.24 cm (4.03 in) taller than the Guatemalan Maya of the same age, largely due to better nutrition and health care. Bogin also noted that American Maya children had relatively longer legs, averaging 7.02 cm (2.76 in) longer than the Guatemalan Maya (a significantly lower sitting height ratio).The Nilotic peoples of Sudan such as the Shilluk and Dinka have been described as some of the tallest in the world. Dinka Ruweng males investigated by Roberts in 1953–54 were on average 181.3 centimetres (5 ft 11+1⁄2 in) tall, and Shilluk males averaged 182.6 centimetres (6 ft 0 in). The Nilotic people are characterized as having long legs, narrow bodies and short trunks, an adaptation to hot weather. However, male Dinka and Shilluk refugees measured in 1995 in Southwestern Ethiopia were on average only 176.4 cm (5 ft 9+1⁄2 in) and 172.6 cm (5 ft 8 in) tall, respectively. As the study points out, Nilotic people "may attain greater height if privileged with favourable environmental conditions during early childhood and adolescence, allowing full expression of the genetic material." Before fleeing, these refugees were subject to privation as a consequence of the succession of civil wars in their country from 1955 to the present. The tallest living married couple are ex-basketball players Yao Ming and Ye Li (both of China) who measure 228.6 cm (7 ft 6 in) and 190.5 cm (6 ft 3 in) respectively, giving a combined height of 419.1 cm (13 ft 9 in). They married in Shanghai, China, on 6 August 2007.In Tibet, the Khampas are known for their great height. Khampa males are on average 180 cm (5 ft 11 in). Role of an individuals height Height and health Studies show that there is a correlation between small stature and a longer life expectancy. Individuals of small stature are also more likely to have lower blood pressure and are less likely to acquire cancer. The University of Hawaii has found that the “longevity gene” FOXO3 that reduces the effects of aging is more commonly found in individuals of a small body size. Short stature decreases the risk of venous insufficiency. Certain studies have shown that height is a factor in overall health while some suggest tallness is associated with better cardiovascular health and shortness with longevity. Cancer risk has also been found to grow with height. Moreover, scientists have also observed a protective effect of height on risk for Alzheimers disease, although this fact could be a result of the genetic overlap between height and intracraneal volume and there are also genetic variants influencing height that could affect biological mechanisms involved in Alzheimers disease etiology, such as Insulin-like growth factor 1 (IGF-1).Nonetheless, modern westernized interpretations of the relationship between height and health fail to account for the observed height variations worldwide. Cavalli-Sforza and Cavalli-Sforza note that variations in height worldwide can be partly attributed to evolutionary pressures resulting from differing environments. These evolutionary pressures result in height-related health implications. While tallness is an adaptive benefit in colder climates such as those found in Europe, shortness helps dissipate body heat in warmer climatic regions. Consequently, the relationships between health and height cannot be easily generalized since tallness and shortness can both provide health benefits in different environmental settings. In the end, being excessively tall can cause various medical problems, including cardiovascular problems, because of the increased load on the heart to supply the body with blood, and problems resulting from the increased time it takes the brain to communicate with the extremities. For example, Robert Wadlow, the tallest man known to verifiable history, developed trouble walking as his height increased throughout his life. In many of the pictures of the latter portion of his life, Wadlow can be seen gripping something for support. Late in his life, although he died at age 22, he had to wear braces on his legs and walk with a cane; and he died after developing an infection in his legs because he was unable to feel the irritation and cutting caused by his leg braces. Sources are in disagreement about the overall relationship between height and longevity. Samaras and Elrick, in the Western Journal of Medicine, demonstrate an inverse correlation between height and longevity in several mammals including humans.Women whose height is under 150 cm (4 ft 11 in) may have a small pelvis, resulting in such complications during childbirth as shoulder dystocia.A study done in Sweden in 2005 has shown that there is a strong inverse correlation between height and suicide among Swedish men.A large body of human and animal evidence indicates that shorter, smaller bodies age more slowly, and have fewer chronic diseases and greater longevity. For example, a study found eight areas of support for the "smaller lives longer" thesis. These areas of evidence include studies involving longevity, life expectancy, centenarians, male vs. female longevity differences, mortality advantages of shorter people, survival findings, smaller body size due to calorie restriction, and within-species body size differences. They all support the conclusion that smaller individuals live longer in healthy environments and with good nutrition. However, the difference in longevity is modest. Several human studies have found a loss of 0.5 years/centimeter of increased height (1.2 yr/inch). But these findings do not mean that all tall people die young. Many live to advanced ages and some become centenarians.In medicine, height is measured to monitor child development, this is a better indicator of growth than weight in the long term. For older people, excessive height loss is a symptom of osteoporosis. Height is also used to compute indicators like body surface area or body mass index. Height and occupational success There is a large body of research in psychology, economics, and human biology that has assessed the relationship between several seemingly innocuous physical features (e.g., body height) and occupational success. The correlation between height and success was explored decades ago. Shorter people are considered to have an advantage in certain sports (e.g., gymnastics, race car driving, etc.), whereas in many other sports taller people have a major advantage. In most occupational fields, body height is not relevant to how well people are able to perform; nonetheless several studies found that success was positively correlated with body height, although there may be other factors such as gender or socioeconomic status that are correlated with height which may account for the difference in success.A demonstration of the height-success association can be found in the realm of politics. In the United States presidential elections, the taller candidate won 22 out of 25 times in the 20th century. Nevertheless, Ignatius Loyola, founder of the Jesuits, was 150 cm (4 ft 11 in) and several prominent world leaders of the 20th century, such as Vladimir Lenin, Benito Mussolini, Nicolae Ceaușescu and Joseph Stalin were of below-average height. These examples, however, were all before modern forms of multi-media, i.e., television, which may further height discrimination in modern society. Further, growing evidence suggests that height may be a proxy for confidence, which is likewise strongly correlated with occupational success. Sports History of human height In the 150 years since the mid-nineteenth century, the average human height in industrialised countries has increased by up to 10 centimetres (3.9 in). However, these increases appear to have largely levelled off. Before the mid-nineteenth century, there were cycles in height, with periods of increase and decrease; however, apart from the decline associated with the transition to agriculture, examinations of skeletons show no significant differences in height from the neolithic revolution through the early-1800s.In general, there were no significant differences in regional height levels throughout the nineteenth century. The only exceptions of this rather uniform height distribution were people in the Anglo-Saxon settlement regions who were taller than the average and people from Southeast Asia with below-average heights. However, at the end of the nineteenth century and in the middle of the first globalization period, heights between rich and poor countries began to diverge. These differences did not disappear in the deglobalization period of the two World wars. Baten and Blum (2014) find that in the nineteenth century, important determinants of height were the local availability of cattle, meat and milk as well as the local disease environment. In the late twentieth century, however, technologies and trade became more important, decreasing the impact of local availability of agricultural products. In the eighteenth and nineteenth centuries, people of European descent in North America were far taller than those in Europe and were the tallest in the world. The original indigenous population of Plains Native Americans was also among the tallest populations of the world at the time.Some studies also suggest that there existed the correlation between the height and the real wage, moreover, the correlation was higher among the less developed countries. The difference in height between children from different social classes was already observed by age two.In the late nineteenth century, the Netherlands was a land renowned for its short population, but today Dutch people are among the worlds tallest with young men averaging 183.8 cm (6 ft 0.4 in) tall.According to a study by economist John Komlos and Francesco Cinnirella, in the first half of the eighteenth century, the average height of an English male was 165 cm (5 ft 5 in), and the average height of an Irish male was 168 cm (5 ft 6 in). The estimated mean height of English, German, and Scottish soldiers was 163.6 cm (5 ft 4+1⁄2 in) – 165.9 cm (5 ft 5+1⁄2 in) for the period as a whole, while that of Irish was 167.9 cm (5 ft 6 in). The average height of male slaves and convicts in North America was 171 cm (5 ft 7+1⁄2 in).The average height of Americans and Europeans decreased during periods of rapid industrialization, possibly due to rapid population growth and broad decreases in economic status. This has become known as the early-industrial growth puzzle in the U.S. context the Antebellum Puzzle. In England during the early nineteenth century, the difference between the average height of English upper-class youth (students of Sandhurst Military Academy) and English working-class youth (Marine Society boys) reached 22 cm (8+1⁄2 in), the highest that has been observed.Data derived from burials show that before 1850, the mean stature of males and females in Leiden, The Netherlands was respectively 167.7 cm (5 ft 6 in) and 156.7 cm (5 ft 1+1⁄2 in). The average height of 19-year-old Dutch orphans in 1865 was 160 cm (5 ft 3 in).According to a study by J.W. Drukker and Vincent Tassenaar, the average height of a Dutch person decreased from 1830 to 1857, even while Dutch real GNP per capita was growing at an average rate of more than 0.5% per year. The worst decline was in urban areas that in 1847, the urban height penalty was 2.5 cm (0.98 in). Urban mortality was also much higher than in rural regions. In 1829, the average urban and rural Dutchman was 164 cm (5 ft 4+1⁄2 in). By 1856, the average rural Dutchman was 162 cm (5 ft 4 in) and urban Dutchman was 158.5 cm (5 ft 2+1⁄2 in).A 2004 report citing a 2003 UNICEF study on the effects of malnutrition in North Korea, due to "successive famines," found young adult males to be significantly shorter. In contrast South Koreans "feasting on an increasingly Western-influenced diet," without famine, were growing taller. The height difference is minimal for Koreans over forty years old, who grew up at a time when economic conditions in the North were roughly comparable to those in the South, while height disparities are most acute for Koreans who grew up in the mid-1990s – a demographic in which South Koreans are about 12 cm (4.7 in) taller than their North Korean counterparts – as this was a period during which the North was affected by a harsh famine where hundreds of thousands, if not millions, died of hunger. A study by South Korean anthropologists of North Korean children who had defected to China found that eighteen-year-old males were 13 centimetres (5 in) shorter than South Koreans their age due to malnutrition.The tallest living man is Sultan Kösen of Turkey, at 251 cm (8 ft 3 in). The tallest man in modern history was Robert Pershing Wadlow (1918–1940), from Illinois, United States, who was 272 cm (8 ft 11 in) at the time of his death. The tallest woman in medical history was Trijntje Keever of Edam, Netherlands, who stood 254 cm (8 ft 4 in) when she died at the age of seventeen. The shortest adult human on record was Chandra Bahadur Dangi of Nepal at 54.6 cm (1 ft 9+1⁄2 in). An anecdotal article titled "Ancient American Giants" from the 14 August 1880 edition of Scientific American notes a case from Brushcreek Township, Ohio, when Dr. J. F. Everhart supervised a team that discovered ancient clay coffins within a mound which were reported to contain skeletons of the following length: 8 ft 0 in (2.44 m) woman with a child 3.5 ft 0 in (1.07 m), a second coffin with a 9 ft 0 in (2.74 m) man and 8 ft 0 in (2.44 m) woman, a third coffin with a 9 ft 4 in (2.84 m) man and 8 ft 0 in (2.44 m) woman, and seven other independent skeletons measuring between 8 ft 0 in (2.44 m) and 10 ft 0 in (3.05 m). An image and stone tablet were found with the giants.Adult height between populations often differs significantly. For example, the average height of women from the Czech Republic is greater than that of men from Malawi. This may be caused by genetic differences, childhood lifestyle differences (nutrition, sleep patterns, physical labor), or both. Depending on sex, genetic and environmental factors, shrinkage of stature may begin in middle age in some individuals but tends to be universal in the extremely aged. This decrease in height is due to such factors as decreased height of inter-vertebral discs because of desiccation, atrophy of soft tissues, and postural changes secondary to degenerative disease. Working on data of Indonesia, the study by Baten, Stegl and van der Eng suggests a positive relationship of economic development and average height. In Indonesia, human height has decreased coincidentally with natural or political shocks. Average height around the world As with any statistical data, the accuracy of such data may be questionable for various reasons: Some studies may allow subjects to self-report values. Generally speaking, self-reported height tends to be taller than its measured height, although the overestimation of height depends on the reporting subjects height, age, gender and region. Test subjects may have been invited instead of chosen randomly, resulting in sampling bias. Some countries may have significant height gaps between different regions. For instance, one survey shows there is 10.8 cm (4+1⁄2 in) gap between the tallest state and the shortest state in Germany. Under such circumstances, the mean height may not represent the total population unless sample subjects are appropriately taken from all regions with using weighted average of the different regional groups. Different social groups can show different mean height. According to a study in France, executives and professionals are 2.6 cm (1 in) taller, and university students are 2.55 cm (1 in) taller than the national average. As this case shows, data taken from a particular social group may not represent a total population in some countries. A relatively small sample of the population may have been measured, which makes it uncertain whether this sample accurately represents the entire population. The height of persons can vary over a day, due to factors such as a height increase from exercise done directly before measurement (normally inversely correlated), or a height increase since lying down for a significant period (normally inversely correlated). For example, one study revealed a mean decrease of 1.54 centimetres (0.61 in) in the heights of 100 children from getting out of bed in the morning to between 4 and 5 p.m. that same day. Such factors may not have been controlled in some of the studies. Men from Bosnia and Herzegovina, the Netherlands, Croatia, Serbia and Montenegro have the tallest average height. Dinka people are sometimes noted for their height. With the Tutsi of Rwanda, they are believed to be the tallest people in Africa. Roberts and Bainbridge reported the average height of 182.6 cm (5 ft 11.9 in) in a sample of 52 Dinka Agaar and 181.3 cm (5 ft 11.4 in) in 227 Dinka Ruweng measured in 1953–1954. Other studies of comparative historical height data and nutrition place the Dinka as the tallest people in the world. Measurement Crown-rump length is the measurement of the length of human embryos and fetuses from the top of the head (crown) to the bottom of the buttocks (rump). It is typically determined from ultrasound imagery and can be used to estimate gestational age. Until two years old, recumbent length is used to measure infants. Length measures the same dimension as height, but height is measured standing up while the length is measured lying down. In developed nations, the average total body length of a newborn is about 50 cm (20 in), although premature newborns may be much smaller. Standing height is used to measure children over two years old and adults who can stand without assistance. Measure is done with a stadiometer. In general, standing height is about 0.7 cm (0.28 in) less than recumbent length.Surrogate height measurements are used when standing height and recumbent length are impractical. For sample Chumlea equation use knee height as indicator of stature. Other techniques include: arm span, sitting height, ulna length, etc. See also Anthropometry, the measurement of the human individual Body weight Economics and Human Biology (academic journal) History of anthropometry Human physical appearance Human variability Pygmy peoples Citations General bibliography Grandjean, Etienne (1987). Fitting the Task to the Man
Human height	: An Ergonomic Approach. London, UK: Taylor & Francis. ISBN 978-0-85066-192-7. (for heights in U.S. and Japan) Eurostat Statistical Yearbook 2004. Luxembourg: Eurostat. 2014. ISBN 978-92-79-38906-1. (for heights in Germany) Netherlands Central Bureau for Statistics, 1996 (for average heights) Ogden, Cynthia L.; Fryar, Cheryl D.; Carroll, Margaret D. & Flegal, Katherine M. (27 October 2004). "Mean Body Weight, Height, and Body Mass Index, United States 1960–2002" (PDF). Advance Data from Vital and Health Statistics (347): 1–17. PMID 15544194. "Health Survey for England – trend data". Department of Health and Social Care. Archived from the original on 10 October 2004. Bilger, Burkhard (29 March 2004). "The Height Gap". The New Yorker. Archived from the original on 2 April 2004. A collection of data on human height, referred to here as "karube" but originally collected from other sources, is archived here. A copy is available here (an English translation of this Japanese page would make it easier to evaluate the quality of the data...) "Americans Slightly Taller, Much Heavier Than Four Decades Ago". National Center for Health Statistics. 27 October 2004. Aminorroaya, A.; Amini, M.; Naghdi, H. & Zadeh, A. H. (2003). "Growth charts of heights and weights of male children and adolescents of Isfahan, Iran" (PDF). Journal of Health, Population, and Nutrition. 21 (4): 341–346. PMID 15038589. S2CID 21907084. Archived from the original (PDF) on 19 September 2018. 6. Celostátní antropologický výzkum dětí a mládeže 2001, Česká republika [6th Nationwide anthropological research of children and youth 2001, Czech Republic] (in Czech). Prague: State Health Institute (SZÚ). 2005. ISBN 978-8-07071-251-1. Bogin, Barry (2001). The Growth of Humanity. Hoboken, NJ: Wiley-Liss. ISBN 978-0-471-35448-2. Eveleth, P.B.; Tanner, J.M. (1990). Worldwide Variation in Human Growth (2nd ed.). Cambridge University Press. ISBN 978-0-521-35916-0. Miura, K.; Nakagawa, H. & Greenland, P. (2002). "Invited commentary: Height-cardiovascular disease relation: where to go from here?". American Journal of Epidemiology. 155 (8): 688–689. doi:10.1093/aje/155.8.688. PMID 11943684. Ruff, Christopher (October 2002). "Variation in human body size and shape". Annual Review of Anthropology. 31: 211–232. doi:10.1146/annurev.anthro.31.040402.085407. "Los españoles somos 3,5 cm más altos que hace 20 años" [Spaniards are 3.5 cm taller than 20 years ago]. 20 minutos (in Spanish). 31 July 2006. Krishan, K. & Sharma, J. C. (2002). "Intra-individual difference between recumbent length and stature among growing children". Indian Journal of Pediatrics. 69 (7): 565–569. doi:10.1007/BF02722678. PMID 12173694. S2CID 22427304. Case, A. & Paxson, C. (2008). "Stature and Status: Height, ability, and labor market outcomes". The Journal of Political Economy. 116 (3): 499–532. doi:10.1086/589524. PMC 2709415. PMID 19603086. Sakamaki, R.; Amamoto, R.; Mochida, Y.; Shinfuku, N. & Toyama, K. (2005). "A comparative study of food habits and body shape perception of university students in Japan and Korea". Nutrition Journal. 4: 31. doi:10.1186/1475-2891-4-31. PMC 1298329. PMID 16255785. Habicht, Michael E.; Henneberg, Maciej; Öhrström, Lena M.; Staub, Kaspar & Rühli, Frank J. (27 April 2015). "Body height of mummified pharaohs supports historical suggestions of sibling marriages". American Journal of Physical Anthropology. 157 (3): 519–525. doi:10.1002/ajpa.22728. PMID 25916977. Further reading Marouli, Eirini]; et al. (9 February 2017). "Rare and low-frequency coding variants alter human adult height". Nature. 542 (7640): 186–190. Bibcode:2017Natur.542..186M. doi:10.1038/nature21039. PMC 5302847. PMID 28146470. External links CDC National Center for Health Statistics: Growth Charts of American Percentiles fao.org, Body Weights and Heights by Countries (given in percentiles) The Height Gap, Article discussing differences in height around the world Tallest in the World: Native Americans of the Great Plains in the Nineteenth Century European Heights in the Early eighteenth Century Spatial Convergence in Height in East-Central Europe, 1890–1910 The Biological Standard of Living in Europe During the Last Two Millennia HEALTH AND NUTRITION IN THE PREINDUSTRIAL ERA: INSIGHTS FROM A MILLENNIUM OF AVERAGE HEIGHTS IN NORTHERN EUROPE Our World In Data – Human Height – Visualizations of how human height around the world has changed historically (by Max Roser). Charts for all countries, world maps, and links to more data sources. What Has Happened to the Quality of Life in the Advanced Industrialized Nations? A century of trends in adult human height, NCD Risk Factor Collaboration (NCD-RISC), DOI: 10.7554/eLife.13410, 25 July 2016
Bifid nose	A bifid nose (also known as cleft nose) is an uncommon congenital malformation which is characterized by the presence of a cleft between the two nostrils of the nose. It is the result of a disturbance during embryological nose development.It is part of the Tessier classification for craniofacial clefts. Signs and symptoms The visibility of this malformation varies from person to person; from a barely noticeable "line" in the middle of the nose to the complete clefting of the nose which results in two "half noses", the airway is usually adequate. Individuals with this birth anomaly dont have any symptoms related to their bifid nose. Complications This condition is merely comestic, and the severity of it doesnt affect a person with the disorder (health-wise) since usually there is a normal and adequate nasal airway. Diagnosis This condition can be diagnosed by physical examination. This difference can serve as a diagnostic method since it occurs alongside other malformations, such as frontonasal dysplasia, hypertelorbitism and cleft lips.Bifid noses can also be diagnosed prenatally via a coronal view of the face under ultrasonography, they typically have a broad appearance with "a cleavage between the nostrils resembling a double barrel gun". Causes This condition is caused due to incomplete fusion of both sides of the nose during embryonic life.This anomaly is highly hereditary: autosomal dominant and autosomal recessive inheritance patterns have been observed in multiple families.If the bifid nose is accompanied by abnormalities of the anorectal and renal systems, it may be part of a different separate genetic disorder (which is characterized by overlapping toes, renal adysplasia and variable anorectal anomalies) that is caused by autosomal recessive mutations in the FREM1 gene. Treatment Generally, sutures and rhinoplasty can be done in order to get rid of a bifid nose tip (though what surgery should be done depends on the severity of the cleft nose). Open W-shaped surgical incisions have also proven to be effective. Surgery is usually done before the age of 5. Prevalence This birth anomaly affects less than 0.0008% of people worldwide, making it the most common midline craniofacial cleft.8% of people with bifid nose also have hypertelorism. Bifid nose as a hereditary trait Two forms of inheritance pattern for bifid noses have been described: autosomal recessive and autosomal dominant. One case per inheritance pattern follows: Autosomal dominant: Anyane-Yeboa et al. (1984) describes 5 women from a 3-generation American family. Karyotypes and skull X-rays done on the younger sisters gave normal results. Autosomal recessive: Boo-Chai et al. (1965) describes 3 siblings from a continental Indian family. History This condition was first described in medical literature in 1939 by Esser et al. when they described 5 children (4 siblings and a male first-cousin of theirs) from a single family. Occurrence in animals This condition can also occur in animals, such as dogs. See also Cleft palate Cleft lip Cleft chin == References ==
Pellegrini–Stieda syndrome	Pellegrini–Stieda syndrome (also called Stieda disease and Köhler–Pellegrini–Stieda disease) refers to the ossification of the superior part of the medial collateral ligament of the knee. It is a common incidental finding on knee radiographs. It is named for the Italian surgeon A. Pellegrini (b. 1877) and the German surgeon A. Stieda (1869–1945). References Further reading Altschuler, Eric L.; Bryce, Thomas N. (December 2006). "Images in clinical medicine. Pellegrini-Stieda syndrome". The New England Journal of Medicine. 354 (1): e1. doi:10.1056/NEJMicm040406. PMID 16394294. Wang, JC; Shapiro, MS (1995). "Pellegrini-Stieda syndrome". American Journal of Orthopedics. 24 (6): 493–7. PMID 7670873. External links Whonamedit.com
Inferior vena cava syndrome	Inferior vena cava syndrome (IVCS) is a very rare constellation of symptoms resulting from either an obstruction, or stenosis of the inferior vena cava. It can be caused by physical invasion or compression by a pathological process or by thrombosis within the vein itself. It can also occur during pregnancy. Pregnancy leads to high venous pressure in the lower limbs, decreased blood return to the heart, decreased cardiac output due to obstruction of the inferior vena cava, sudden rise in venous pressure which can lead to placental separation, and a decrease in kidney function. All of these issues can arise from lying in the supine position during late pregnancy which can cause compression of the inferior vena cava by the uterus. Symptoms of late pregnancy inferior vena cava syndrome consist of intense pain in the right hand side, muscle twitching, hypotension, and fluid retention. Signs and symptoms IVCS presents with a wide variety of signs and symptoms, making it difficult to diagnose clinically. Edema of the lower extremities (peripheral edema), caused by an increase in the venous blood pressure. Tachycardia. This is caused by the decreased preload, decreased cardiac output, and leads to increased frequency. In pregnant women, signs of fetal hypoxia and distress may be seen in the cardiotocography. This is caused by decreased perfusion of the uterus, resulting in hypoxemia of the fetus. Supine hypotensive syndrome Causes the causes for this condition are the following: Obstruction by deep vein thrombosis or tumors (most commonly renal cell carcinoma) Compression through external pressure by neighbouring structures or tumors, either by significantly compressing the vein or by promoting thrombosis by causing turbulence by disturbing the blood flow. This is quite common during the third trimester of pregnancy when the uterus compresses the vein in the right side position. Iatrogenic causes may be suspected in patients with a medical history of liver transplantion, vascular catheters, dialysis and other invasive procedures in the vicinity Budd-Chiari syndrome Diagnosis The diagnosis can be made clinically by observing the patient when in the right sided position where you can see multiple dilated veins over abdomen due to collaterals. Ultrasound with Doppler flow measurement may be used to assess the IVC and circulatory system. Treatment Treatment will vary depending on the cause of the vena cava compression or interruption. Often, treatment includes positional changes, avoidance of supine positioning, especially on the right side. In pregnancy, definitive management of the IVCS is to deliver the baby. In other conditions, medical or surgical treatment to remove or relieve the offending structure will relieve symptoms. Frequency Epidemiological data is elusive owing to the wide variety of clinical presentation. In the U.S., incidence is estimated to be at 5–10 cases per 100,000 per year. Minor compression of the inferior vena cava during pregnancy is a relatively common occurrence. It is seen most commonly when women lie on their back or right side. 90% of women lying in the supine position during pregnancy experience some form of inferior vena cava syndrome; however, not all of the women display symptoms. References == External links ==
Vanishing bile duct syndrome	Vanishing bile duct syndrome is a loose collection of diseases which leads to the injury to hepatic bile ducts and eventual ductopenia. Signs and symptoms The presentation is dependent upon the underlying cause. The course can be rapid or chronic. Fatigue Anorexia Abdominal pain Weight loss Pruritus Hyperlipidemia Malabsorption Fat-soluble vitamin deficiencies Elevated alkaline phosphatase Elevated gamma-glutamyltransferase Elevated conjugated bilirubin Cause Congenital In fetal and neonatal life the ductal plates are remodeled. The malformations can be atretic or fibrocystic. Atretic causes Intrahepatic bile duct atresia (Alagille syndrome) (ALGS2 MIM:610205 and ALGS1 MIM:118450) Extrahepatic bile duct atresia Fibrocystic causes Autosomal recessive polycystic kidney disease Congential hepatic fibrosis Carolis disease Von Meyenburg complex Chromosomal associations Trisomy 17, 18 and 21 Genetic associations Cystic fibrosis Alpha 1 antitrypsin deficiency Trihydroxycoprostanic acidemia Bylers disease Immunologic associations Bile duct injury and loss can result from autoimmune destruction. T cells recognize biliary epithelial cell antigens causing injury and eventual atresia. Other causes Primary biliary cirrhosis Primary sclerosing cholangitis Hodgkins lymphoma Chronic graft-versus-host disease Drugs(chlorpromazine)/Toxins Ischemia Diagnosis Treatment Treatment is dependent upon the underlying cause. Treatment is supportive as it is not possible to induce regrowth of lost ducts. Medical therapies Ursodeoxycholic acid Immunosuppression General consensus is that more studies are needed before this can be considered Organ transplant References External links Uptodate:Hepatic ductopenia and vanishing bile duct syndrome
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
Desmoplastic trichoepithelioma	A desmoplastic trichoepithelioma is a cutaneous condition characterized by a solitary, firm skin lesion on the face.: 672 Treatment Desmoplastic trichoepithelioma is a benign tumour and can be managed safely with surgical removal, electrodesiccation and curettage. See also Trichoepithelioma Skin lesion == References ==
Meconium	Meconium is the earliest stool of a mammalian infant resulting from defecation. Unlike later feces, meconium is composed of materials ingested during the time the infant spends in the uterus: intestinal epithelial cells, lanugo, mucus, amniotic fluid, bile, and water. Meconium, unlike later feces, is viscous and sticky like tar – its color usually being a very dark olive green and it is almost odorless. When diluted in amniotic fluid, it may appear in various shades of green, brown, or yellow. It should be completely passed by the end of the first few days after birth, with the stools progressing toward yellow (digested milk). Clinical significance Meconium in amniotic fluid Meconium is normally retained in the infants bowel until after birth, but sometimes it is expelled into the amniotic fluid (also called "amniotic liquor") prior to birth or during labor and delivery. The stained amniotic fluid (called "meconium liquor" or "meconium-stained liquor") is recognized by medical staff as a possible sign of fetal distress. Some post-dates pregnancies (when they are more than 40 weeks pregnant) may also have meconium-stained liquor without fetal distress. Medical staff may aspirate the meconium from the nose and mouth of a newborn immediately after delivery in the event the baby shows signs of respiratory distress to decrease the risk of meconium aspiration syndrome, which can occur in meconium-stained amniotic fluid. Most of the time that the amniotic fluid is stained with meconium, it will be homogeneously distributed throughout the fluid, making it brown. This indicates that the fetus passed the meconium some time ago such that sufficient mixing occurred as to establish the homogeneous mixture. Terminal meconium occurs when the fetus passes the meconium a short enough time before birth/cesarean section that the amniotic fluid remains clear, but individual clumps of meconium are in the fluid. Failure to pass meconium The failure to pass meconium is a symptom of several diseases including Hirschsprungs disease and cystic fibrosis. The meconium sometimes becomes thickened and congested in the intestines, a condition known as meconium ileus. Meconium ileus is often the first sign of cystic fibrosis. In cystic fibrosis, the meconium can form a bituminous black-green mechanical obstruction in a segment of the ileum. Beyond this, there may be a few separate grey-white globular pellets. Below this level, the bowel is a narrow and empty micro-colon. Above the level of the obstruction, there are several loops of hypertrophied bowel distended with fluid. No meconium is passed, and abdominal distension and vomiting appear soon after birth. About 20% of cases of cystic fibrosis present with meconium ileus, while approximately 20% of one series of cases of meconium ileus did not have cystic fibrosis. The presence of meconium ileus is not related to the severity of the cystic fibrosis. The obstruction can be relieved in a number of different ways.Meconium ileus should be distinguished from meconium plug syndrome, in which a tenacious mass of mucus prevents the meconium from passing and there is no risk of intestinal perforation. Meconium ileus has a significant risk of intestinal perforation. In a barium enema, meconium plug syndrome shows a normal or dilated colon as compared to micro-colon in meconium ileus. Testing meconium for drugs Meconium can be tested for various drugs, to check for in utero exposure. Using meconium, a Canadian research group showed that by measuring a by-product of alcohol, fatty acid ethyl esters (FAEE) they could objectively detect excessive maternal drinking of alcohol during pregnancy. In the US, the results of meconium testing may be used by child protective services and other law enforcement agencies to determine the eligibility of the parents to keep the newborn. Meconium can also be analyzed to detect the tobacco use of mothers during their pregnancy, which is commonly under-reported. Sterility The issue of whether meconium is sterile remains debated and is an area of ongoing research. Although some researchers have reported evidence of bacteria in meconium, this has not been consistently confirmed. Other researchers have raised questions about whether these findings may be due to contamination after sample collection and that meconium is, in fact, sterile until after birth. Further researchers have hypothesized that there may be bacteria in the womb, but these are a normal part of pregnancy and could have an important role in shaping the developing immune system and are not harmful to the baby. Etymology The Latin term meconium derives from the Greek μηκώνιον, mēkōnion, a diminutive of μήκων, mēkōn, i.e. poppy, in reference either to its tar-like appearance that may resemble some raw opium preparations or to Aristotles belief that it induces sleep in the fetus. Other uses In biology, meconium describes the metabolic waste product from the pupal stage of an insect that is expelled through the anal opening of the adult upon eclosion from the pupa. Other insects, such as beetles and some Hymenoptera (Aculeata) expel the meconium at the end of the larval stage, before becoming a pupa. Gallery References External links Media related to Meconium at Wikimedia Commons
Danon disease	Danon disease (or glycogen storage disease Type IIb) is a metabolic disorder. Danon disease is an X-linked lysosomal and glycogen storage disorder associated with hypertrophic cardiomyopathy, skeletal muscle weakness, and intellectual disability. It is inherited in an X-linked dominant pattern. Symptoms and signs Males In males the symptoms of Danon Disease are more severe. Features of Danon Disease in males are: An early age of onset of muscle weakness and heart disease (onset in childhood or adolescence) Some learning problems or intellectual disability can be present Muscle weakness can be severe and can affect endurance and the ability to walk Heart disease (cardiomyopathy) can be severe and can lead to a need for medications. It usually progress to heart failure, commonly complicated by atrial fibrillation and embolic strokes with severe neurological disability, leading to death unless heart transplant is performed. Cardiac conduction abnormalities can occur. Wolff-Parkinson-White syndrome is a common conduction pattern in Danon disease. Symptoms are usually gradually progressive Some individuals may have visual disturbances, and/or retinal pigment abnormalities Danon Disease is rare and unfamiliar to most physicians. It can be mistaken for other forms of heart disease and/or muscular dystrophies, including Pompe disease.Females In females the symptoms of Danon Disease are less severe. Common symptoms of Danon Disease in females are: A later age of onset of symptoms. Many females will not have obvious symptoms until late adolescence or even adulthood. Learning problems and intellectual disability are usually absent. Muscle weakness is often absent or subtle. Some females will tire easily with exercise Cardiomyopathy is often absent in childhood. Some women will develop this in adulthood. Cardiomyopathy can be associated with atrial fibrillation and embolic strokes. Cardiac conduction abnormalities can occur. Wolff-Parkinson-White syndrome is a common conduction pattern in Danon disease. Symptoms in females progress more slowly than in males. Some females may have visual disturbances, and/or retinal pigment abnormalities Danon Disease is rare and unfamiliar to most physicians. The milder and more subtle symptoms in females can make it more difficult to diagnose females with Danon Disease Causes Although the genetic cause of Danon Disease is known, the mechanism of disease is not well understood. Danon disease involves a genetic defect (mutation) in a gene called LAMP2, which results in a change to the normal protein structure. While the function of the LAMP2 gene is not well understood, it is known that LAMP2 protein is primarily located in small structures within cells called lysosomes. Genetics It is associated with LAMP2. The status of this condition as a GSD has been disputed. Diagnosis Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a persons medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional. Testing Resources The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional. Orphanet lists international laboratories offering diagnostic testing for this condition. Treatment RP-A501 is an AAV-based gene therapy aimed to restore the LAMP-2 gene which is defective in male patients with Danon Disease and how to cure it. Cardiac transplantation has been performed as a treatment; however, most patients die early in life. History Danon disease was characterized by Moris Danon in 1981. Dr. Danon first described the disease in 2 boys with heart and skeletal muscle disease (muscle weakness), and intellectual disability. The first case of Danon disease reported in the Middle East was a family diagnosed in the eastern region of United Arab Emirates with a new LAMP2 mutation; discovered by the Egyptian cardiologist Dr. Mahmoud Ramadan the associate professor of Cardiology in Mansoura University (Egypt) after doing genetic analysis for all the family members in Bergamo, Italy where 6 males were diagnosed as Danon disease patients and 5 female were diagnosed as carriers; as published in Al-Bayan newspaper on 20 February 2016 making this family the largest one with patients and carriers of Danon disease. Danon Disease has overlapping symptoms with another rare genetic condition called Pompe disease. Microscopically, muscles from Danon Disease patients appear similar to muscles from Pompe disease patients. However, intellectual disability is rarely, if ever, a symptom of Pompe disease. Negative enzymatic or molecular genetic testing for Pompe disease can help rule out this disorder as a differential diagnosis. References == External links ==
Granulomatous prostatitis	Granulomatous prostatitis is an uncommon disease of the prostate, an exocrine gland of the male reproductive system. It is a form of prostatitis (prostate inflammation), resulting from infection (bacterial, viral, or fungal), BCG vaccine, malacoplakia or systemic granulomatous diseases which involve the prostate. Pathogenesis Prostatic secretions escape into the stroma and elicit an inflammatory response. Histopathology Noticeable destruction of Acini, surrounded by epitheloid cells, giant cells, lymphocytes, plasma cells and dense fibrosis. References == External links ==
Restrictive lung disease	Restrictive lung diseases are a category of extrapulmonary, pleural, or parenchymal respiratory diseases that restrict lung expansion, resulting in a decreased lung volume, an increased work of breathing, and inadequate ventilation and/or oxygenation. Pulmonary function test demonstrates a decrease in the forced vital capacity. Presentation Due to the chronic nature of this disease, the leading symptom of restrictive lung disease is progressive exertional dyspnea. For acute on chronic cases, shortness of breath, cough, and respiratory failure are some of the more common signs. Causes Restrictive lung diseases may be due to specific causes which can be intrinsic to the parenchyma of the lung, or extrinsic to it. Intrinsic Pneumoconiosis caused by long-term exposure to dusts, especially in mining. For example, Asbestosis. Radiation fibrosis, usually from the radiation given for cancer treatment. Certain drugs such as amiodarone, bleomycin and methotrexate. As a consequence of another disease such as rheumatoid arthritis. Hypersensitivity pneumonitis due to an allergic reaction to inhaled particles. Acute respiratory distress syndrome (ARDS), a severe lung condition occurring in response to a critical illness or injury. Infant respiratory distress syndrome due to a deficiency of surfactant in the lungs of a baby born prematurely. TuberculosisMany cases of restrictive lung disease are idiopathic (have no known cause). Still, there is generally pulmonary fibrosis. Examples are: Idiopathic pulmonary fibrosis Idiopathic interstitial pneumonia, of which there are several types Sarcoidosis Eosinophilic pneumonia Lymphangioleiomyomatosis Pulmonary Langerhans cell histiocytosis Pulmonary alveolar proteinosisConditions specifically affecting the interstitium are called interstitial lung diseases. Extrinsic Nonmuscular diseases of the upper thorax such as kyphosis, pectus carinatum and pectus excavatum. Diseases restricting lower thoracic/abdominal volume (e.g. obesity, diaphragmatic hernia, or the presence of ascites). Pleural thickening. Pathophysiology In normal respiratory function, the air flows in through the upper airway, down through the bronchi and into the lung parenchyma (the bronchioles down to the alveoli) where gas exchange of carbon dioxide and oxygen occurs. During inspiration, the lungs expand to allow airflow into the lungs and thereby increasing total volume. After inspiration follows expiration during which the lungs recoil and push air back out of the pulmonary pathway. Lung compliance is the difference of volume during inspiration and expiration.Restrictive lung disease is characterized by reduced lung volumes, and therefore reduced lung compliance, either due to an intrinsic reason, for example a change in the lung parenchyma, or due to an extrinsic reason, for example diseases of the chest wall, pleura, or respiratory muscles. Generally, intrinsic causes are from lung parenchyma diseases that cause inflammation or scarring of the lung tissue, such as interstitial lung disease or pulmonary fibrosis, or from having the alveoli air spaces filled with external material such as debris or exudate in pneumonitis. As some diseases of the lung parenchyma progress, the normal lung tissue can be gradually replaced with scar tissue that is interspersed with pockets of air. This can lead to parts of the lung having a honeycomb-like appearance. The extrinsic causes result in lung restriction, impaired ventilatory function, and even respiratory failure due to the diseases that effect the lungs ability to create a change in lung volumes during respiration due to the diseases of the systems stated above. Diagnosis In restrictive lung disease, both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) are reduced, however, the decline in FVC is more than that of FEV1, resulting in a higher than 80% FEV1/FVC ratio. In obstructive lung disease however, the FEV1/FVC is less than 0.7, indicating that FEV1 is significantly reduced when compared to the total expired volume. This indicates that the FVC is also reduced, but not by the same ratio as FEV1.One definition requires a total lung capacity which is 80% or less of the expected value. Management Medical treatment for restrictive lung disease is normally limited to supportive care since both the intrinsic and extrinsic causes can have irreversible effects on lung compliance. The supportive therapies focus on maximizing pulmonary function and preserving activity tolerance through oxygen therapy, bronchodilators, inhaled beta-adrenergic agonists, and diuretics. Because there is no effective treatment for restrictive lung disease, prevention is key. See also Chronic obstructive pulmonary disease Extrapulmonary restriction Obstructive lung disease References == External links ==
Urolagnia	Urolagnia (also urophilia, and, more colloquially, a golden shower or watersports) associates sexual excitement with the sight or thought of urine or urination, and may also refer to such behaviours or acts. It is a paraphilia.The term has origins in the Greek language (from ouron, "urine", and lagneia, "lust").Golden shower is slang for the practice of urinating on another person for sexual pleasure. Overview Urolagnia is an inclination to derive sexual satisfaction from the vision or idea of urination. It is a paraphilia. During the activity, urine may be consumed or the person may bathe in it. Other variations include arousal from wetting or seeing someone else urinate in their pants or underclothes, or wetting the bed. Other forms of urolagnia may involve a tendency to be sexually aroused by smelling urine-soaked clothing or body parts. In many cases, a strong correlation or conditioning arises between urine smell or sight, and the sexual act. For some individuals the phenomenon may include a diaper fetish and/or arousal from infantilism. Urolagnia is sometimes associated with, or confused with the Japanese practice of omorashi, arousal from having a full bladder or a sexual attraction to someone else experiencing the discomfort or pain of a full bladder, possibly a sadomasochistic inclination. Common variations Golden shower: A shower or stream of urine is directed onto another person or persons. Clothes wetting: The person is sexually aroused by wetting ones clothing or observing another person doing so. Usually that person prefers to stage the wetting so that his/her legs (or other body parts) become soaked with urine. The warm sensation felt when urine trickles on the body seems to give very relaxing and pleasurable feelings to the person. In many cases, that person is also aroused by smelling body parts that have a urine scent. Others get aroused by telling some people about when they lost control and wet themselves. Some prefer a particular type of clothing to urinate. Exhibitionism: Becoming noticeably desperate or wetting oneself with the express purpose of being seen by strangers. Practitioners have described going to public places such as a mall or a park. Some intend to create situations where others can see their wet clothing. Human urinal: Within the BDSM community, some individuals desire to be used as a human urinal and some desire to use a human urinal. The submissive is usually strictly forbidden from placing their lips directly on the body of the dominant so the practice routinely involves them receiving much of the spray all over their face, hair and body; however, another way of doing this that applies mostly to male dominants, is to place the mouth on the head of the penis and drink the urine as it is released. One other, less common variation of this kink involves the dominant partner urinating inside the submissive partners vagina or anus, which is usually followed up by the submissive partner ejecting the urine from their orifice(s). Omorashi: The act of holding ones own urine until the need to urinate is urgent, making another hold in their urine, or watching another person with an urgent need to urinate. This fetish sometimes originates from childhood memories of needing, or of seeing another needing, to urinate. Arousal may be triggered by seeing the body movements or facial expressions of that person. It can also be heightened by the person saying that they have to urinate. The arousal from being desperate comes from the sensation of having a full bladder. Voyeurism: Seeing another urinate without the persons knowledge either through video taping by a hidden camera, or by lurking in locations where people are urinating or are likely to have an urge to urinate. Frequency Jennifer Eve Rehor of San Francisco State University points out that such data as exists on what she calls "unconventional" or "kink" sexual behavior is generally problematic because of the way that it has been collected, through criminal and clinical case studies. Behavior that appears neither in criminal trials nor in clinical studies (for example, because the individuals concerned do not commonly seek professional help) is therefore under-reported. Rehor therefore surveyed 1,764 female participants in "kink" behavior (mostly association with BDSM) in 2010–11, receiving 1,580 valid responses. What Rehor calls "urine play" is relatively infrequent, with only 36.52% of her sample reporting having done it or having had it done to them. In contrast, 93.99% of her sample reported having done spanking or having had it done to them, and 61.96% reported having used or been exposed to feathers/fur. It is impossible to extrapolate Rehors data onto the general population, but her study does give a guide to prevalence in the North American BDSM community. In Channel 4s 2017 nationwide Great British Sex survey, watersports (or urolagnia) was ranked ninth in popularity among sexual fetishes in the UK. Notable cases Chuck Berry: American musician who was featured urinating on a woman in a sex tape, and was sued for videotaping dozens of women in the restroom of a restaurant he owned. Havelock Ellis: British sexologist who was impotent until at age sixty he discovered that he was aroused by the sight of a woman urinating. Albert Fish: an American serial killer, also known as The Grayman, The Boogeyman. He wrote several letters to widows with want-ads in The New York Times and described in detail women urinating on him, inside of him, and in cups so that he could drink it. He later forced children to drink urine. Ashley MacIsaac: Nova Scotian fiddler and singer. In 1996 he spoke with a Macleans interviewer mentioning his sexual life, including his boyfriend and his taste for urolagnia. In 2003 he told an interviewer for the Montreal Mirror that he loves to have men urinate on him. Ricky Martin: a Puerto Rican singer. He gave an interview with Blender magazine in which he stated that he enjoyed "giving the golden shower". Patrice ONeal: American standup comedian who had on several occasions mentioned his appreciation for golden showers, even stating that his girlfriend noticing that his urine tasted like "birthday cake" is how he came to find out that he suffered from diabetes. Annie Sprinkle: an American porn actress, later turned sex educator and advocate for female sexual enjoyment. Her stage name is derived from her obsession with fluids. Troughman: an Australian noted in the Sydney media for lying down in urinal troughs at Sydney Mardi Gras parties and other events. Ian Watkins: the former lead singer for the Welsh rock band Lostprophets. Convicted in December 2013 of numerous child sex abuse charges, which include urolagnia. See also Urination and sexual activity Urophagia References External links Media related to Urolagnia at Wikimedia Commons
Uterine hypoplasia	Uterine hypoplasia, also known as naive uterus or infantile uterus, is a reproductive disorder characterized by hypoplasia of the uterus. It is usually due to pubertal failure/hypogonadism and may be treated with puberty induction using estrogens and/or progestogens. See also Uterine hyperplasia Uterine malformation == References ==
Nasal concha	In anatomy, a nasal concha (), plural conchae (), also called a nasal turbinate or turbinal, is a long, narrow, curled shelf of bone that protrudes into the breathing passage of the nose in humans and various animals. The conchae are shaped like an elongated seashell, which gave them their name (Latin concha from Greek κόγχη). A concha is any of the scrolled spongy bones of the nasal passages in vertebrates.In humans, the conchae divide the nasal airway into four groove-like air passages, and are responsible for forcing inhaled air to flow in a steady, regular pattern around the largest possible surface area of nasal mucosa. As a ciliated mucous membrane with shallow blood supply, the nasal mucosa cleans and warms the inhaled air in preparation for the lungs. A rapidly dilating arteriolar circulation to these bones may lead to a sharp increase in the pressure within, in response to acute cooling of the body core. The pain from this pressure is often referred to as "brain freeze", and is frequently associated with the rapid consumption of ice cream. The shallowness of the venous blood supply of the mucosa contributes to the ease with which nosebleed can occur. Structure Conchae are composed of pseudostratified columnar, ciliated respiratory epithelium with a thick, vascular, and erectile glandular tissue layer. The conchae are located laterally in the nasal cavities, curling medially and downward into the nasal airway. Each pair is composed of one concha in either side of the nasal cavity, divided by the septum.The superior conchae are smaller structures, connected to the middle conchae by nerve-endings, and serve to protect the olfactory bulb. The openings to the posterior ethmoidal sinuses exist under the superior meatus.The middle conchae are smaller. In humans, they are usually as long as the little finger. They project downwards over the openings of the maxillary and anterior and middle ethmoid sinuses, and act as buffers to protect the sinuses from coming in direct contact with pressurized nasal airflow. Most inhaled airflow travels between the inferior concha and the middle meatus.The inferior conchae are the largest, and can be as long as the index finger in humans, and are responsible for the majority of airflow direction, humidification, heating, and filtering of air inhaled through the nose.The inferior conchae are graded 1–4 based on the inferior concha classification system (known as the inferior turbinate classification system) in which the total amount of the airway space that the inferior concha takes up is estimated. Grade 1 is 0–25% of the airway, grade 2 is 26–50% of the airway, grade 3 is 51–75% of the airway and grade 4 is 76–100% of the airway.There is sometimes a pair of supreme conchae superior to the superior conchae. When present, these usually take the form of a small crest. Function The conchae comprise most of the mucosal tissue of the nose and are required for functional respiration. They are enriched with airflow pressure and temperature-sensing nerve receptors (linked to the trigeminal nerve route, the fifth cranial nerve), allowing for tremendous erectile capabilities of nasal congestion and decongestion, in response to the weather conditions and changing needs of the body. In addition, the erectile tissue undergoes an often unnoticed cycle of partial congestion and decongestion called the nasal cycle. The flow of blood to the nasal mucosa in particular the venous plexus of the conchae is regulated by the pterygopalatine ganglion and heats or cools the air in the nose. The nasopulmonary and nasothoracic reflexes regulate the mechanism of breathing through deepening of inhalation. Triggered by the flow of the air, the pressure of the air in the nose, and the quality of the air, impulses from the nasal mucosa are transmitted by the trigeminal nerve to the breathing centres in the brainstem, and the generated response is transmitted to the bronchi, the intercostal muscles, and the diaphragm. The conchae are also responsible for filtration, heating, and humidification of air inhaled through the nose. Of these three, filtration is achieved mostly by other more effective means such as mucous and cilia. As air passes over the conchae, it is heated to 32–34 °C (89–93 °F), humidified (up to 98% water saturation) and filtered. Immunological role The respiratory epithelium that covers the erectile tissue (or lamina propria) of the conchae plays a major role in the bodys first line of immunological defense. The respiratory epithelium is partially composed of mucus-producing goblet cells. This secreted mucus covers the nasal cavities, and serves as a filter, by trapping air-borne particles larger than 2 to 3 micrometers. The respiratory epithelium also serves as a means of access for the lymphatic system, which protects the body from being infected by viruses or bacteria. Smell The conchae provide, first and foremost, the humidity needed to preserve the delicate olfactory epithelium, which in turn is needed to keep the olfactory receptors healthy and alert. If the epithelial layer gets dry or irritated, it may cease to function. This is usually a temporary condition but, over time, may lead to chronic anosmia. The turbinates also increase the surface area of the inside of the nose, and, by directing and deflecting airflow across the maximum mucosal surface of the inner nose, they are able to propel the inspired air. This, coupled with the humidity and filtration provided by the conchae, helps to carry more scent molecules towards the higher, and very narrow regions of the nasal airways, where olfaction nerve receptors are located.The superior conchae completely cover and protect the nerve axons piercing through the cribriform plate (a porous bone plate that separates the nose from the brain) into the nose. Some areas of the middle conchae are also innervated by the olfactory bulb. All three pairs of conchae are innervated by pain and temperature receptors, via the trigeminal nerve (or, the fifth cranial nerve). Research has shown that there is a strong connection between these nerve endings and activation of the olfactory receptors, but science has yet to fully explain this interaction. Clinical significance Dysfunction Large, swollen conchae, often referred to clinically as turbinates, may lead to blockage of nasal breathing. Allergies, exposure to environmental irritants, or a persistent inflammation within the sinuses can lead to turbinate swelling. Deformity of the nasal septum can also result in enlarged turbinates.Treatment of the underlying allergy or irritant may reduce turbinate swelling. In cases that do not resolve, or for treatment of deviated septum, turbinate surgery may be required. Surgery Turbinectomy is a surgery for the reduction or removal of the turbinates. There are different techniques, including bipolar radiofrequency ablation, also known as somnoplasty; reduction by the use of pure heat; and turbinate sectioning. In the case of sectioning, only small amounts of turbinate tissue are removed because the turbinates are essential for respiration. Risks of reduction of the inferior or middle turbinates include empty nose syndrome. Dr. Houser: "this is especially true in cases of anterior inferior turbinate (IT) resection because of its important role in the internal nasal valve."Concha bullosa is an abnormal pneumatization of the middle turbinate, which may interfere with normal ventilation of the sinus ostia and can result in recurrent sinusitis. Other animals Generally, in animals, nasal conchae are convoluted structures of thin bone or cartilage located in the nasal cavity. These are lined with mucous membranes that can perform two functions. They can improve the sense of smell by increasing the area available to absorb airborne chemicals, and they can warm and moisten inhaled air, and extract heat and moisture from exhaled air to prevent desiccation of the lungs. Olfactory turbinates are found in all living tetrapods, and respiratory turbinates are found in most mammals and birds. Animals with respiratory turbinates can breathe faster without drying out their lungs, and consequently can have a faster metabolism. For example, when the emu exhales, its nasal turbinates condense moisture from the air and absorbs it for reuse. Dogs and other canids possess well-developed nasal turbinates. These turbinates allow for heat exchange between small arteries and veins on their maxilloturbinate (turbinates positioned on maxilla bone) surfaces in a counter-current heat-exchange system. Dogs are capable of prolonged chases, in contrast to the ambush predation of cats, and these complex turbinates play an important role in enabling this (cats only possess a much smaller and less-developed set of nasal turbinates). This same complex turbinate structure help conserve water in arid environments. The water conservation and thermoregulatory capabilities of these well-developed turbinates in dogs may have been crucial adaptations that allowed dogs (including both domestic dogs and their wild prehistoric gray wolf ancestors) to survive in the harsh Arctic environment and other cold areas of northern Eurasia and North America, which are both very dry and very cold.Reptiles and more primitive synapsids have olfactory turbinates that are involved in sensing smell rather than preventing desiccation. While the maxilloturbinates of mammals are located in the path of airflow to collect moisture, sensory turbinates in both mammals and reptiles are positioned farther back and above the nasal passage, away from the flow of air. Glanosuchus has ridges positioned low in the nasal cavity, indicating that it had maxilloturbinates that were in the direct path of airflow. The maxilloturbinates may not have been preserved because they were either very thin or cartilaginous. The possibility has also been raised that these ridges are associated with an olfactory epithelium rather than turbinates. Nonetheless, the possible presence of maxilloturbinates suggests that Glanosuchus may have been able to rapidly breathe without drying out the nasal passage, and therefore could have been an endotherm.The bones of nasal turbinates are very fragile and seldom survive as fossils. In particular none have been found in fossil birds. But there is indirect evidence for their presence in some fossils. Rudimentary ridges like those that support respiratory turbinates have been found in advanced Triassic cynodonts, such as Thrinaxodon and Diademodon. This suggests that they may have had fairly high metabolic rates. The paleontologist John Ruben and others have argued that no evidence of nasal turbinates has been found in dinosaurs. All the dinosaurs they examined had nasal passages that they claimed were too narrow and too short to accommodate nasal turbinates, so dinosaurs could not have sustained the breathing rate required for a mammal-like or bird-like metabolic rate while at rest, because their lungs would have dried out. However, objections have been raised against this argument. Nasal turbinates are absent or very small in some birds, such as ratites, Procellariiformes and Falconiformes. They are also absent or very small in some mammals, such as anteaters, bats, elephants, whales and most primates, although these animals are fully endothermic and in some cases very active. Furthermore, ossified turbinate bones have been identified in the ankylosaurid dinosaur Saichania. See also Additional images Notes References Wang, Xiaoming (2008) Dogs: Their Fossil Relatives and Evolutionary History Columbia University Press. ISBN 9780231509435.
Left anterior fascicular block	Left anterior fascicular block (LAFB) is an abnormal condition of the left ventricle of the heart, related to, but distinguished from, left bundle branch block (LBBB). It is caused by only the left anterior fascicle – one half of the left bundle branch being defective. It is manifested on the ECG by left axis deviation. It is much more common than left posterior fascicular block. Mechanism Normal activation of the left ventricle (LV) proceeds down the left bundle branch, which consist of three fascicles, the left anterior fascicle, the left posterior fascicle, and the septal fascicle. The posterior fascicle supplies the posterior and inferoposterior walls of the LV, the anterior fascicle supplies the upper and anterior parts of the LV and the septal fascicle supplies the septal wall with innervation. LAFB — which is also known as left anterior hemiblock (LAHB) — occurs when a cardiac impulse spreads first through the left posterior fascicle, causing a delay in activation of the anterior and upper parts of the LV. Although there is a delay or block in activation of the left anterior fascicle there is still preservation of initial left to right septal activation as well as preservation of the inferior activation of the LV (preservation, on the EKG, of septal Q waves in I and aVL and predominantly negative QRS complex in leads II, III, and aVF). The delayed and unopposed activation of the remainder of the LV now results in a shift in the QRS axis leftward and superiorly, causing marked left axis deviation. This delayed activation also results in a widening of the QRS complex, although not to the extent of a complete LBBB. Diagnosis Abnormal left axis deviation (usually between –45° and –60°) qR pattern (small q, tall R) in the lateral limb leads I and aVL rS pattern (small r, deep S) in the inferior leads II, III, and aVF Delayed intrinsicoid deflection in lead aVL (> 0.045 s)LAFB cannot be diagnosed when a prior inferior wall myocardial infarction (IMI) is evident on the ECG. IMI can also cause extreme left-axis deviation, but will manifest with Q-waves in the inferior leads II, III, and aVF. By contrast, QRS complexes in the inferior leads should begin with r-waves in LAFB. Effects of LAFB on Diagnosing Infarctions and Left Ventricular Hypertrophy LAHB may be a cause of poor R wave progression across the precordium causing a pseudoinfarction pattern mimicking an anteroseptal infarction. It also makes the electrocardiographic diagnosis of LVH more complicated, because both may cause a large R wave in lead aVL. Therefore, to call LVH on an EKG in the setting of an LAHB you should see the presence of a “strain pattern” when you are relying on limb lead criteria to diagnose LVH Clinical significance It can be seen in approximately 4% of cases of acute myocardial infarctionIt is the most common type of intraventricular conduction defect seen in acute anterior myocardial infarction, and the left anterior descending artery is usually the culprit vessel. It can be seen with acute inferior wall myocardial infarction. It is also associated with hypertensive heart disease, aortic valvular disease, cardiomyopathies, and degenerative fibrotic disease of the cardiac skeleton. See also Bundle branch block References == External links ==
Sudden arrhythmic death syndrome	Sudden arrhythmic death syndrome (SADS) is a sudden unexpected death of adolescents and adults, mainly during sleep. One relatively common type is known as Brugada syndrome.The syndrome is rare in most areas around the world but occurs in populations that are culturally and genetically distinct. It was first noted in 1977 among southeast Asian Hmong refugees in the United States and Canada. The syndrome was again noted in Singapore when a retrospective survey of records showed that 230 otherwise healthy Thai foreign workers living in Singapore died suddenly of unexplained causes between 1982 and 1990. Causes A sudden death in a young person can be caused by heart disease (including cardiomyopathy, congenital heart disease, myocarditis, genetic connective tissue disorders) or conduction disease (WPW syndrome, etc.), medication-related causes or other causes. Rare diseases called ion channelopathies may play a role such as long QT syndrome (LQTS), Brugada syndrome (BrS), CPVT (catecholaminergic polymorphic ventricular tachycardia), PCCD (progressive cardiac conduction defect), early repolarization syndrome, mixed sodium channel disease, and short QT syndrome. In 20% of cases, no cause of death can be found, even after extensive examination.In young people with type 1 diabetes, unexplained deaths could be attributed to night time hypoglycemia triggering abnormal heart rhythms or cardiac autonomic neuropathy, a damage to nerves that control the function of the heart.Medical examiners have taken into account various factors, such as nutrition, toxicology, heart disease, metabolism, and genetics. Although there is no real known definite cause, extensive research showed people 18 years or older were found to have had a hypertrophic cardiomyopathy, a condition in which the heart muscle becomes oddly thickened without any obvious cause. This was the most commonly identified abnormality in sudden death of young adults. In the instances where people experience sudden death, it is most commonly found that they had had CAD (coronary artery disease) or ASCAD (atherosclerotic coronary artery disease), or any level of stress. However, studies reveal that people experienced early symptoms within the week before the terminal event such as chest pain at ~52% of patients, dyspnea at ~22%, syncope at ~7% and ~19% who experienced no symptoms. Scientists have also associated this syndrome with the gene SCN5A that is mutated and affects the function of the heart. However, all autopsies done on those who had this syndrome came back negative.In the Philippines, bangungot (or in their term, sudden adult death syndrome) is mainly caused by the Brugada syndrome. Diagnosis Diagnosis occurs post-mortem. Treatment The only proven way to prevent SADS is with an implantable cardioverter-defibrillator. Oral beta-blockers such as propranolol are ineffective. Epidemiology In 1980, a reported pattern of sudden deaths was brought to the attention of the Centers for Disease Control. The first reported sudden death occurred in 1948 when there were 81 similar deaths of Filipino men in Oahu County, Hawaii. However, it did not become relevant because there was no associated pattern. This syndrome continued to become more significant as years went on. By 1981–1982, the annual rate in the United States was high with 92/100,000 among Laotians-Hmong, 82/100,000 among other Laotian ethnic groups, and 59/100,000 among Cambodians.In a 2008 study it was found that over half of SADS deaths could be attributed to inherited heart disease: unexplained premature sudden deaths in family, long QT syndrome, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy and others.A national SADS study in England, funded by the British Heart Foundation, reported results in a 2007 journal article published in Health. The study surveyed 117 coroners jurisdictions in England. Researchers found that deaths from SADS reported by these coroners occurred "predominantly in young males". There were 500 cases a year in England, which is 8 times more than was previously estimated. Families are more at risk of SADS if they have a genetic cardiac disease. The study recommended that affected families should undergo "specialised cardiological evaluation". Asia Southeast Asian immigrants, who were mostly fleeing the Vietnam War, most often had this syndrome, marking Southeast Asia as the area containing the most people with this fatal syndrome. There are other Asian populations that were affected, such as Filipinos and Chinese Filipinos, Japanese in Japan, and natives of Guam in the United States and Guam. The immigrants with this syndrome were about 33 years old and seemingly healthy, and all but one of the Laotian Hmong refugees were men. The condition appears to primarily affect young Hmong men from Laos (median age 33) and Northeastern Thailand (where the population is mainly of Laotian descent). History Laotian Hmongs were chosen for the study because they had one of the highest sudden death rates in the United States while sleeping. They were originally from Southern China and the highlands of North Vietnam, Laos, and Thailand. The location that was picked for this study was in Ban Vinai in the Loei Province, which is approximately 15 kilometers from the Lao border. This study took place between October 1982 and June 1983 as this syndrome became more of a pressing issue. Ban Vinai was the location chosen because it had 33,000 refugees in 1982, and the largest number of recorded SADS deaths. Because this syndrome was occurring most commonly in those particular men, researchers found it most beneficial and effective to study the populations they migrated from instead of studying victims and populations in the U.S. Because of local religious practices, the Hmong men in Ban Vinai did not receive autopsies. Therefore, the only results and research obtained were relating to deaths outside of the local religion or geographical area.An interview was arranged with the next of kin who lived with them, witnessed the death, or found the body. The interviews were open ended and allowed the person who was next of kin to describe what they witnessed and what preceding events they thought were relevant to the victims death. The interviewers also collected information such as illness history, the circumstances of the death, demographic background, and history of any sleep disturbances. A genealogy was then created which included all the relatives and their vital status and/or circumstances of death. Society and culture During the 1970s and 1980s, when an outbreak of this syndrome began, many Southeast Asians were not able to worship properly due to the Laotian Civil War. Hmong people believe that when they do not worship properly, do not perform religious rituals properly or forget to sacrifice, the ancestor spirits or the village spirits do not protect them, thus allowing evil spirit to reach them. These attacks induce a nightmare that leads to sleep paralysis, in which the victim is conscious and experiencing pressure on the chest. It is also common to have a REM state that is out of sequence, where there is a mix of brain states that are normally held separate. After the war, the United States government scattered the Hmong refugees across the U.S. in 53 different cities. Once these nightmare visitations began, a shaman was recommended for psychic protection from the spirits of their sleep. However, scattered across 53 different cities, these victims had no access to a shaman who could protect them. Hmong people believed that rejecting the role of becoming a shaman, they are taken into the spirit world.The study author suggested that the Hmong who died were killed by their own beliefs in the spiritual world, otherwise known as Nocturnal pressing spirit attacks. In Indonesia it is called digeuton, which translates to "pressed on" in English. In China it is called bèi guǐ yā (traditional Chinese: 被鬼壓; simplified Chinese: 被鬼压) which translates to "crushed by a ghost" in English. The Dutch call the presence a nachtmerrie, the night-mare. The "merrie" comes from the Middle Dutch mare, an incubus who "lies on peoples chests, suffocating them". This phenomenon is known among the Hmong people of Laos, who ascribe these deaths to a malign spirit, dab tsuam (pronounced "dah chua"), said to take the form of a jealous woman. Bangungot is depicted in the Philippines as a mythological creature called batibat or bangungot. This hag-like creature sits on the victims face or chest so as to immobilize and suffocate him. When this occurs, the victim is usually experiencing sleep paralysis. English names Names in other languages See also Brugada syndrome Night hag Sleep paralysis Sudden infant death syndrome Sudden unexpected death in epilepsy Sudden unexplained death in childhood Yunnan sudden death syndrome References Further reading Agence France Presse (8 April 2002). "Sleeping death syndrome terrorises young men". The Borneo Post. Center for Disease Control (23 September 1988). "Sudden Unexplained Death Syndrome Among Southeast Asian Refugees". MMWR. == External links ==
Median raphe cyst	Median raphe cysts are a cutaneous condition of the penis due to developmental defects near the glans.: 682 See also Cutaneous columnar cyst List of cutaneous conditions == References ==
Neurofibromatosis type II	Neurofibromatosis type II (also known as MISME syndrome – multiple inherited schwannomas, meningiomas, and ependymomas) is a genetic condition that may be inherited or may arise spontaneously, and causes benign tumors of the brain, spinal cord, and peripheral nerves. The types of tumors frequently associated with NF2 include vestibular schwannomas, meningiomas, and ependymomas. The main manifestation of the condition is the development of bilateral benign brain tumors in the nerve sheath of the cranial nerve VIII, which is the "auditory-vestibular nerve" that transmits sensory information from the inner ear to the brain. Besides, other benign brain and spinal tumors occur. Symptoms depend on the presence, localisation and growth of the tumor(s), in which multiple cranial nerves can be involved. Many people with this condition also experience vision problems. Neurofibromatosis type II (NF2 or NF II) is caused by mutations of the "Merlin" gene, which seems to influence the form and movement of cells. The principal treatments consist of neurosurgical removal of the tumors and surgical treatment of the eye lesions. Historically the underlying disorder has not had any therapy due to the cell function caused by the genetic mutation. Classification NF2 is an inheritable disorder with an autosomal dominant mode of transmission.There are two forms of the NF2: The Wishart-phenotype form is characterized by multiple cerebral and spinal lesions in people younger than 20 years and with rapid progression of the tumours. People with NF2 who develop single central tumours with slow progression after the age of 20 are thought to have the Feiling–Gardner phenotype. Symptoms and signs Symptoms can occur at any age, typically in adolescence and early adulthood, and rarely seen in children, and severity depend on the location of the tumors. Symptoms include but are not limited to: Tinnitus Loss/problems of balance Glaucoma Seizures Hearing loss Vision impairment Numbness or weakness in arms and legs Hearing loss Because hearing loss in those with NF2 almost always occurs after acquisition of verbal language skills, people with NF2 do not always integrate well into Deaf culture and are more likely to resort to auditory assistive technology. One of these devices is the cochlear implant, which can sometimes restore a high level of auditory function even when natural hearing is totally lost. However, the amount of destruction to the cochlear nerve caused by the typical NF2 schwannoma often precludes the use of such an implant. In these cases, an auditory brainstem implant (ABI) can restore some level of hearing, supplemented by lip reading. Cause NF2 is caused by inactivating mutations in the NF2 gene located at 22q12.2 of chromosome 22, type of mutations vary and include protein-truncating alterations (frameshift deletions/insertions and nonsense mutations), splice-site mutations, missense mutations and others. Deletions, too, in the NH2-terminal domain of merlin proteins have been associated with early tumor onset and poor prognosis in people with NF2. Protein truncating mutations correlate with more severe phenotype. There is a broad clinical spectrum known, but all people with the condition who have been checked have been found to have some mutation of the same gene on chromosome 22. Through statistics, it is suspected that one-half of cases are inherited, and one-half are the result of new, de novo mutations. Cause loss of hearing The hearing loss caused by NF2 is gradual and results from the presences of bilateral cochleovestibular schwannomas, also known as acoustic neuromas, which damage to cochlear nerve causing hearing loss. Hearing loss may also result from benign tumors that grow on the vestibular and auditory nerves, which lead to the inner ear. Pathogenesis NF2 is caused by a defect in the gene that normally gives rise to a product called Merlin or Schwannomin, located on chromosome 22 band q11-13.1. Merlin was first discovered as a structural protein functioning as an actin cytoskeleton regulator. Later merlins tumour suppressant role was described. Merlin regulates multiple proliferative signalling cascades such as receptor tyrosine kinase signalling, p21-activated kinase signalling, Ras signalling, MEK-ERK cascade, MST-YAP cascade. In a normal cell, the concentrations of active (dephosphorylated) merlin are controlled by processes such as cell adhesion (which would indicate the need to restrain cell division). It has been shown that Merlin inhibits Rac1 which is crucial for cell motility and tumour invasion. Also, merlins interaction with cyclin D was described. It is known that Merlins deficiency can result in unmediated progression through the cell cycle due to the lack of contact-mediated tumour suppression, mainly because of the cell:cell junction disruption, sufficient to result in the tumors characteristic of Neurofibromatosis type II. Recent studies showed that besides its cytoskeletal and cytoplasmic functions Merlin also translocates to the nucleus and suppresses proliferation by inhibiting E3 ubiquitin ligase CRL4(DCAF1). Finally, most recent studies indicated that Merlin also plays important role in energy metabolism regulation. Mutations of NF2 is presumed to result in either a failure to synthesize Merlin or the production of a defective peptide that lacks the normal tumor-suppressive effect. The Schwannomin-peptide consists of 595 amino acids. Comparison of Schwannomin with other proteins shows similarities to proteins that connect the cytoskeleton to the cell membrane. Mutations in the Schwannomin-gene are thought to alter the movement and shape of affected cells with loss of contact inhibition. Ependymomas are tumors arising from the ependyma, an epithelium-like tissue of the central nervous system. In people with NF2 and ependymomas, the tumor suppressant function of Merlin may be compromised. Loss of function mutations occurring in chromosome 22q, where Merlin proteins are coded, can promote tumorigenesis, or the creation of new tumorous cells. Deletions, too, in the NH2-terminal domain of merlin proteins have been associated with early tumor onset and poor prognosis in affected people. Pathology The so-called acoustic neuroma of NF2 is in fact a schwannoma of the nervus vestibularis, or vestibular schwannoma. The misnomer of acoustic neuroma is still often used. The vestibular schwannomas grow slowly at the inner entrance of the internal auditory meatus (meatus acousticus internus). They derive from the nerve sheaths of the upper part of the nervus vestibularis in the region between the central and peripheral myelin (Obersteiner-Redlich-Zone) within the area of the porus acousticus, 1 cm from the brainstem. Genotype–phenotype correlation Many people with NF2 were included in studies that were designed to compare disease type and progression with exact determination of the associated mutation. The goal of such comparisons of genotype and phenotype is to determine whether specific mutations cause respective combinations of symptoms. This would be extremely valuable for the prediction of disease progression and the planning of therapy starting at a young age. The results of such studies are the following: In most cases the mutation in the NF2 gene causes shortened peptides. There are no mutational hot spots. People with frameshift mutations or nonsense mutations have poor prognosis. People with missense mutations have a better prognosis. In cases with mutations in the splice-acceptor-region, there is no good correlation to determine. Point mutations may have only minor effects. Cases are published in which exactly the same mutation is associated with clearly different outcomes.These results suggest that other factors (environment, other mutations) will probably determine the clinical outcome. Diagnosis NF2 is a genetically transmitted condition. Diagnosis is most common in early adulthood (20–30 years); however, it can be diagnosed earlier. NF2 can be diagnosed due to the presence of a bilateral vestibular schwannoma, or an acoustic neuroma, which causes a hearing loss that may begin unilaterally. If a patient does not meet this criterion of diagnosis, they must have a family history of NF2, and present with a unilateral vestibular schwannoma and other associated tumors (cranial meningioma, cranial nerve schwannoma, spinal meningioma, spinal ependymomas, peripheral nerve tumor, spinal schwannoma, subcutaneous tumor, skin plaque). This being said, more than half of all patients diagnosed with NF2 do not have a family history of the condition. Although it has yet to be included into clinical classification, peripheral neuropathy, or damage to the peripheral nerves, which often causes weakness, numbness and pain in the hands and feet, may also lead to a diagnosis of NF2. In children, NF2 can present with similar symptoms, but generally causes "visual disturbances (cataracts, hamartomas), skin tumors, mononeuropathhy (facial paresis, drop foot), symptomatic spinal cord tumors, or non-vestibular intracranial tumors". Prenatal Bilateral vestibular schwannomas are diagnostic of NF2. Postnatal Ferner et al. give three sets of diagnostic criteria for NF2: Bilateral vestibular schwannoma (VS) or family history of NF2 plus Unilateral VS or any two of: meningioma, glioma, neurofibroma, schwannoma, posterior subcapsular lenticular opacities Unilateral VS plus any two of meningioma, glioma, neurofibroma, schwannoma, posterior subcapsular lenticular opacities Two or more meningioma plus unilateral VS or any two of glioma, schwannoma and cataract.Another set of diagnostic criteria is the following: Detection of bilateral acoustic neuroma by imaging-procedures First degree relative with NF2 and the occurrence of neurofibroma, meningiomas, glioma, or Schwannoma First degree relative with NF2 and the occurrence of juvenile posterior subcapsular cataract.The criteria have varied over time. The last revision of the NF2 criteria was done by M.J. Smith in 2017. This included the consideration of a LZTR1 mutation (schwannomatosis) instead of NF2 and excluded bilateral vestibular schwannomas that occur after 70 years of age. Treatment Surgery There are several different surgical techniques for the removal of acoustic neuroma. The choice of approach is determined by size of the tumour, hearing capability, and general clinical condition of the person. The retrosigmoid approach offers some opportunity for the retention of hearing. The translabyrinthine approach will sacrifice hearing on that side, but will usually spare the facial nerve. Post-operative cerebrospinal fluid leaks are more common. The middle fossa approach is preferred for small tumors and offers the highest probability of retention of hearing and vestibular function. Less invasive endoscopic techniques have been done outside of the United States for some time. Recovery times are reported to be faster. However, this technique is not yet mainstream among surgeons in the US.Larger tumors can be treated by either the translabyrinthine approach or the retrosigmoid approach, depending upon the experience of the surgical team. With large tumors, the chance of hearing preservation is small with any approach. When hearing is already poor, the translabyrinthine approach may be used for even small tumors. Small, lateralized tumours in people with NF2 with good hearing should have the middle fossa approach. When the location of the tumour is more medial a retrosigmoid approach may be better. Auditory canal decompression is another surgical technique that can prolong usable hearing when a vestibular schwannoma has grown too large to remove without damage to the cochlear nerve. In the IAC (internal auditory canal) decompression, a middle fossa approach is employed to expose the bony roof of the IAC without any attempt to remove the tumor. The bone overlying the acoustic nerve is removed, allowing the tumour to expand upward into the middle cranial fossa. In this way, pressure on the cochlear nerve is relieved, reducing the risk of further hearing loss from direct compression or obstruction of vascular supply to the nerve. Radiosurgery is a conservative alternative to cranial base or other intracranial surgery. With conformal radiosurgical techniques, therapeutic radiation focused on the tumour, sparing exposure to surrounding normal tissues. Although radiosurgery can seldom completely destroy a tumor, it can often arrest its growth or reduce its size. While radiation is less immediately damaging than conventional surgery, it incurs a higher risk of subsequent malignant change in the irradiated tissues, and this risk is higher in NF2 than in sporadic (non-NF2) lesions. Medications There are no prescription medicines currently indicated for reduction in tumor burden for NF2 patients, although in patient studies Bevacizumab has resulted in reduction in tumor growth rates and hearing improvements in some patients. Treatment hearing loss As hearing loss in individuals with NF2 is generally gradual, eventually profound and sensorineural, the best options for treatment for hearing loss are cochlear implants and auditory brainstem implants (ABIs), as well as supplementing hearing with lip-reading, cued speech or sign language. Cochlear Implants A cochlear implant is an electronic device that is surgically implants to stimulate the cochlear nerve. Cochlear implants will work only when the cochleovestibular nerve (8th nerve) and the cochlea are still functioning. In a study done with open-set speech perception testing and closed-set speech perception testing by Neff et al., they discovered that the use of cochlear implants with NF2 patients allowed significant improvement of hearing abilities. In testing of recognition of sentences of everyday speech, five out of six patients scored within the 90–100% range, and in testing of hearing in noise setting, four of six of the patients scored within the 83–96%. Additionally, all testing was done without lip-reading. Auditory Brainstem Implants (ABIs) Auditory Brainsteam Implants, or ABIs, are used when the cochlea or any portion of the cochleovestibular nerve are not functioning due to damage to those areas or anatomic abnormalities. The procedure is done by implanting a device that send an electrical signal directly to the cochlear nucleus, allowing sound to bypass the peripheral auditory system and straight into the brain stem. Prognosis NF2 is a life limiting condition. It is a rare genetic disorder that involves noncancerous tumors of the nerves that transmit balance and sound impulses from the inner ear to the brain. The prognosis is affected by early age onset, a higher number of meningiomas and schwannomas and having a decrease in mutation.An early diagnosis is the best way to ensure improvement in management. Although, even with an early diagnosis, some patients still die very young.Meningiomas and schwannomas occur in around half of patients with NF2. Meningiomas are tumors that are both intracranial and intraspinal. Schwannomas are tumors that are often centered on the internal auditory canal. Patients with NF2 who have meningiomas have a higher risk of mortality, and the treatment can be very challenging. Individuals who develop schwannomas frequently develop hearing loss and deafness. These individuals may also develop tinnitus after being presented with unilateral hearing loss. The first symptom that individuals may encounter is dizziness or imbalance.Truncating mutations lead to smaller and non-functional protein products. Studies have shown that missense mutations and large deletions can both cause predominantly mild phenotypes. Phenotype is more variable in patients with splice-site mutations, and a milder disease in patients with mutations in exons 9–15. Patients with a missense mutation have a greater survival rate than nonsense and frameshift mutations. Prevalence Incidence of the condition is about 1 in 60,000. References Further reading Evans, D. Gareth (1993). "Neurofibromatosis 2". GeneReviews. University of Washington, Seattle. PMID 20301380. Retrieved 30 May 2017. == External links ==
Somatization disorder	Somatization disorder is a mental and behavioral disorder characterized by recurring, multiple, and current, clinically significant complaints about somatic symptoms. It was recognized in the DSM-IV-TR classification system, but in the latest version DSM-5, it was combined with undifferentiated somatoform disorder to become somatic symptom disorder, a diagnosis which no longer requires a specific number of somatic symptoms. ICD-10, the latest version of the International Statistical Classification of Diseases and Related Health Problems, still includes somatization syndrome. Criteria DSM-5 In the DSM-5 the disorder has been renamed somatic symptom disorder (SSD), and includes SSD with predominantly somatic complaints (previously referred to as somatization disorder), and SSD with pain features (previously known as pain disorder). DSM-IV-TR The DSM-IV-TR diagnostic criteria are: A history of somatic complaints over several years, starting prior to the age of 30. Such symptoms cannot be fully explained by a general medical condition or substance use or, when there is an associated medical condition, the impairments due to the somatic symptoms are more severe than generally expected. Complaints are not feigned as in malingering or factitious disorder.The symptoms do not all have to occur at the same time, but may occur over the course of the disorder. A somatization disorder itself is chronic but fluctuating that rarely remits completely. A thorough physical examination of the specified areas of complaint is critical for somatization disorder diagnosis. Medical examination would provide object evidence of subjective complaints of the individual.Diagnosis of somatization disorder is difficult because it is hard to determine to what degree psychological factors are exacerbating subjective feelings of pain. For instance, chronic pain is common in 30% of the U.S. population, making it difficult to determine whether or not the pain is due to predominantly psychological factors. ICD-10 In ICD-10, the latest version of the International Statistical Classification of Diseases and Related Health Problems, somatization syndrome is described as: "The main features are multiple, recurrent and frequently changing physical symptoms of at least two years duration. Most patients have a long and complicated history of contact with both primary and specialist medical care services, during which many negative investigations or fruitless exploratory operations may have been carried out. Symptoms may be referred to any part or system of the body. The course of the disorder is chronic and fluctuating, and is often associated with disruption of social, interpersonal, and family behaviour." ICD-10 also includes the following subgroups of somatization syndrome: Undifferentiated somatoform disorder. Hypochondriasis. Somatoform autonomic dysfunction. Persistent somatoform pain disorder. Other somatoform disorders, such ones predominated by dysmenorrhoea, dysphagia, pruritus and torticollis. Somatoform disorder, unspecified. Cause Although somatization disorder has been studied and diagnosed for more than a century, there is debate and uncertainty regarding its pathophysiology. Most current explanations focus on the concept of a misconnection between the mind and the body. Genetics probably contributes a very small amount to development of the disorder.One of the oldest explanations for somatization disorder advances the theory that it is a result of the bodys attempt to cope with emotional and psychological stress. The theory states that the body has a finite capacity to cope with psychological, emotional, and social distress, and that beyond a certain point symptoms are experienced as physical, principally affecting the digestive, nervous, and reproductive systems. There are many different feedback systems where the mind affects the body; for instance, headaches are known to be associated with psychological factors, and stress and the hormone cortisol are known to have a negative impact on immune functions. This might explain why somatization disorders are more likely in people with irritable bowel syndrome, and why patients with SSD are more likely to have a mood or anxiety disorder. There is also a much increased incidence of SSD in people with a history of physical, emotional or sexual abuse.Another hypothesis for the cause of somatization disorder is that people with the disorder have heightened sensitivity to internal physical sensations and pain. A biological sensitivity to somatic feelings could predispose a person to developing SSD. It is also possible that a persons body might develop increased sensitivity of nerves associated with pain and those responsible for pain perception, as a result of chronic exposure to stressors.Cognitive theories explain somatization disorder as arising from negative, distorted, and catastrophic thoughts and reinforcement of these cognitions. Catastrophic thinking could lead a person to believe that slight ailments, such as mild muscle pain or shortness of breath, are evidence of a serious illness such as cancer or a tumor. These thoughts can then be reinforced by supportive social connections. A spouse who responds more to his or her partners pain cues makes it more likely that he or she will express greater pain. Children of parents who are preoccupied or overly attentive to the somatic complaints of their children are more likely to develop somatic symptoms. Severe cognitive distortions can make a person with SSD limit the behaviors he or she engages in, and cause increased disability and impaired functioning. Neuroimaging evidence A recent review of the cognitive–affective neuroscience of somatization disorder suggested that catastrophization in patients with somatization disorders tends to present a greater vulnerability to pain. The relevant brain regions include the dorsolateral prefrontal, insular, rostral anterior cingulate, premotor, and parietal cortices. Treatments To date, cognitive behavioral therapy (CBT) is the best established treatment for a variety of somatoform disorders including somatization disorder. CBT aims to help patients realize their ailments are not catastrophic and to enable them to gradually return to activities they previously engaged in, without fear of "worsening their symptoms". Consultation and collaboration with the primary care physician also demonstrated some effectiveness. The use of antidepressants is preliminary but does not yet show conclusive evidence. Electroconvulsive shock therapy (ECT) has been used in treating somatization disorder among the elderly; however, the results were still debatable with some concerns around the side effects of using ECT. Overall, psychologists recommend addressing a common difficulty in patients with somatization disorder in the reading of their own emotions. This may be a central feature of treatment; as well as developing a close collaboration between the GP, the patient and the mental health practitioner. Epidemiology Somatization disorder is estimated to occur in 0.2% to 2% of females, and 0.2% of males. There are cultural differences in the prevalence of somatization disorder. For example, somatization disorder and symptoms were found to be significantly more common in Puerto Rico. In addition the diagnosis is also more prevalent among African Americans and those with less than a high school education or lower socioeconomic status.There is usually co-morbidity with other psychological disorders, particularly mood disorders or anxiety disorders. Research also showed comorbidity between somatization disorder and personality disorders, especially antisocial, borderline, narcissistic, histrionic, avoidant, and dependent personality disorder.About 10-20 percent of female first degree relatives also have somatization disorder and male relatives have increased rates of alcoholism and sociopathy. See also Body-centred countertransference Culture-bound syndrome Hypochondriasis Medically unexplained symptoms Psychosomatic illness Munchausen syndrome References == External links ==
Body dysmorphic disorder	Body dysmorphic disorder (BDD), occasionally still called dysmorphophobia, is a mental disorder characterized by the obsessive idea that some aspect of ones own body part or appearance is severely flawed and therefore warrants exceptional measures to hide or fix it. In BDDs delusional variant, the flaw is imagined. If the flaw is actual, its importance is severely exaggerated. Either way, thoughts about it are pervasive and intrusive, and may occupy several hours a day, causing severe distress and impairing ones otherwise normal activities. BDD is classified as a somatoform disorder, and the DSM-5 categorizes BDD in the obsessive–compulsive spectrum, and distinguishes it from anorexia nervosa. BDD is estimated to affect from 0.7% to 2.4% of the population. It usually starts during adolescence and affects both men and women. The BDD subtype muscle dysmorphia, perceiving the body as too small, affects mostly males. Besides thinking about it, one repetitively checks and compares the perceived flaw, and can adopt unusual routines to avoid social contact that exposes it. Fearing the stigma of vanity, one usually hides the preoccupation. Commonly unsuspected even by psychiatrists, BDD has been underdiagnosed. Severely impairing quality of life via educational and occupational dysfunction and social isolation, BDD has high rates of suicidal thoughts and attempts at suicide. History In 1886, Enrico Morselli reported a disorder that he termed dysmorphophobia, which described the disorder as a feeling of being ugly even though there does not appear to be anything wrong with the persons appearance. In 1980, the American Psychiatric Association recognized the disorder, while categorizing it as an atypical somatoform disorder, in the third edition of its Diagnostic and Statistical Manual of Mental Disorders (DSM). Classifying it as a distinct somatoform disorder, the DSM-IIIs 1987 revision switched the term to body dysmorphic disorder.Published in 1994, DSM-IV defines BDD as a preoccupation with an imagined or trivial defect in appearance, a preoccupation causing social or occupational dysfunction, and not better explained as another disorder, such as anorexia nervosa. Published in 2013, the DSM-5 shifts BDD to a new category (obsessive–compulsive spectrum), adds operational criteria (such as repetitive behaviors or intrusive thoughts), and notes the subtype muscle dysmorphia (preoccupation that ones body is too small or insufficiently muscular or lean).The term "dysmorphic" is derived from the Greek word, dismorfia - meaning abnormal or apart, and morpho meaning shape. Morselli described people who felt a subjective feeling of ugliness as people who were tormented by a physical deficit. Sigmund Freud (1856-1939), the Austrian founder of psychoanalysis, once described his patients as a "Wolf Man," as he was experiencing classical symptoms of BDD. The person he was referring to was a wealthy Russian aristocrat named Sergei Pankejeff (1886-1979). Signs and symptoms Dislike of ones appearance is common, but individuals with BDD have extreme misperceptions about their physical appearance. Whereas vanity involves a quest to aggrandize the appearance, BDD is experienced as a quest to normalize the appearance merely. Although delusional in about one of three cases, the appearance concern is usually non-delusional, an overvalued idea.The bodily area of focus can be nearly any and is commonly face, hair, and skin. In addition, multiple areas can be focused on simultaneously. A subtype of body dysmorphic disorder is bigorexia (anorexia reverse or muscle dysphoria). In muscular dysphoria, patients perceive their body as excessively thin despite being muscular and trained. Many seek dermatological treatment or cosmetic surgery, which typically does not resolve the distress. On the other hand, attempts at self-treatment, as by skin picking, can create lesions where none previously existed.BDD is an obsessive-compulsive disorder but involves more depression and social avoidance despite DOC. BDD often associates with social anxiety disorder. Some experience delusions that others are covertly pointing out their flaws. Cognitive testing and neuroimaging suggest both a bias toward detailed visual analysis and a tendency toward emotional hyper-arousal.Most generally, one experiencing BDD ruminates over the perceived bodily defect several hours daily or longer, uses either social avoidance or camouflaging with cosmetics or apparel, repetitively checks the appearance, compares it to that of other people, and might often seek verbal reassurances. One might sometimes avoid mirrors, repetitively change outfits, groom excessively, or restrict eating.BDDs severity can wax and wane, and flareups tend to yield absences from school, work, or socializing, sometimes leading to protracted social isolation, with some becoming housebound for extended periods. Social impairment is usually greatest, sometimes approaching avoidance of all social activities. Poor concentration and motivation impair academic and occupational performance. The distress of BDD tends to exceed that of either major depressive disorder or diabetes, and rates of suicidal ideation and attempts are especially high. Causal factors As with most mental disorders, BDDs cause is likely intricate, altogether biopsychosocial, through an interaction of multiple factors, including genetic, developmental, psychological, social, and cultural. BDD usually develops during early adolescence, although many patients note earlier trauma, abuse, neglect, teasing, or bullying. In many cases, social anxiety earlier in life precedes BDD. Though twin studies on BDD are few, one estimated its heritability at 43%. Yet other factors may be introversion, negative body image, perfectionism, heightened aesthetic sensitivity, and childhood abuse and neglect. Social media Constant use of social media and "selfie taking" may translate into low self-esteem and body dysmorphic tendencies. The sociocultural theory of self-esteem states that the messages given by media and peers about the importance of appearance are internalized by individuals who adopt others standards of beauty as their own. Due to excessive social media use and selfie taking, individuals may become preoccupied about presenting an ideal photograph for the public. Specifically, females mental health has been the most affected by persistent exposure to social media. Girls with BDD present symptoms of low self-esteem and negative self-evaluation. Researchers in Istanbul Bilgi University and Bogazici University in Turkey found that individuals who have low self-esteem participate more often in trends of taking selfies along with using social media to mediate their interpersonal interaction in order to fulfill their self-esteem needs. The self-verification theory, explains how individuals use selfies to gain verification from others through likes and comments. Social media may therefore trigger ones misconception about their physical look. Similar to those with body dysmorphic tendencies, such behavior may lead to constant seeking of approval, self-evaluation and even depression.In 2019 systematic review using Web of Science, PsycINFO, and PubMed databases was used to identify social networking site patterns. In particular appearance focused social media use was found to be significantly associated with greater body image dissatisfaction. It is highlighted that comparisons appear between body image dissatisfaction and BDD symptomatology. They concluded that heavy social media use may mediate the onset of sub-threshold BDD.Individuals with BDD tend to engage in heavy plastic surgery use. In 2018, the term "Snapchat Dysmorphia" was brought to life after several plastic surgeons reported that some of their patients were seeking plastic surgeries to mimic "filtered" pictures. Filtered photos, such as those on Instagram and Snapchat, often present unrealistic and unattainable looks that may be a causal factor in triggering BDD. A Socio-Cultural Perspective Historically, Body Dysmorphic Disorder (BDD) was originally coined “Dysmorphophobia”, a term which was widely applied in research literature among the Japanese, Russians, and Europeans. However, in American literature, the appearance of BDD was still overlooked in the 1980’s. It was introduced in the DSM-III by the APA, and the diagnostic criteria was not properly defined, as the non-delusional and delusional factors were not separated. This was later resolved with the revision of the DSM-III, which aided many by providing appropriate treatment for patients. BDD was initially considered non-delusional in European research, and was grouped with ‘monosymptomatic hypochondriacal psychoses’ – delusional paranoia disorders, before being introduced in the DSM-III. In 1991, the demographics of individuals who experience BDD were primarily single women aged 19 or older. This statistic has not changed over the decades, women are still considered the predominant gender to experience BDD. With the rise of social media platforms, individuals are easily able to seek validation and openly compare their physical appearance to online influences, finding more flaws and defects in their own appearance. This leads to attempts to conceal the defect such as seeking out surgeons to resolve the issue of ugliness.Universally, it is evident that different cultures place much emphasis on correcting the human body aesthetic, and that this preoccupation with body image is not exclusive to just one society; one example is the binding of women’s feet in Chinese culture.Whilst physically editing the body is not unique to any one culture, research suggests that it is more common throughout Western society and is on the rise. On close observation of contemporary Western societies, there has been an increase in disorders such as Body dysmorphic disorder, arising from ideals around the aesthetic of the human body. Scholars such as Nancy Scheper-Hughes have suggested such demand placed upon Western bodies has been around since the beginning of the 19th century, and that it has been driven by sexuality. Research also shows that BDD is linked to high comorbidity and suicidality rates. Furthermore, it appears that Caucasian women show higher rates of body dissatisfaction than women of different ethnic backgrounds and societies.Socio-cultural models depict and emphasise the way thinness is valued, and beauty is obsessed over in Western culture, where advertising, marketing and social media play a large role in manicuring the ‘perfect’ body shape, size and look. The billions of dollars spent to sell products become causal factors of image conscious societies. Advertising also supports a specific ideal body image and creates a social capital in how individuals can acquire this ideal.However, personal attitudes towards the body do vary cross-culturally. Some of this variability can be accounted for due to factors such as food insecurity, poverty, climate, and fertility management. Cultural groups who experience food insecurity generally prefer larger-bodied women, however, many societies that have abundant access to food also value moderate to larger bodies. This is evident in a comparative study of body image, body perception, body satisfaction, body-related self-esteem and overall self-esteem of German, Guatemalan Q’eqchi’ and Colombian women. Unlike the German and Colombian women, the Q’eqchi’ women in this study live in the jungles of Guatemala and remain relatively removed from modern technology and secure food resources. The study found that the Q’eqchi’ women did not have notably higher body satisfaction when compared to the German or Colombian women. Nevertheless, the Q’eqchi’ women also showed the greatest distortion in their own body perception, estimating their physique to be slimmer than it actually was. It is thought this could be due to a lack of access to body monitoring tools such as mirrors, scales, technology, and clothing choices, but in this instance, body distortion does not seem to influence body satisfaction. This has also been shown in groups of lower-income African American women, where the acceptance of larger bodies is not necessarily equivalent to positive body image.Similar studies have noted a high prevalence of BDD in East Asian societies, where facial dissatisfaction is especially common, indicating that this is not just a Western phenomenon. Diagnosis Estimates of prevalence and gender distribution have varied widely via discrepancies in diagnosis and reporting. In American psychiatry, BDD gained diagnostic criteria in the DSM-IV, having been historically unrecognized, only making its first appearance in the DSM in 1987, but clinicians knowledge of it, especially among general practitioners, is constricted. Meanwhile, shame about having the bodily concern, and fear of the stigma of vanity, makes many hide even having the concern.Via shared symptoms, BDD is commonly misdiagnosed as social anxiety disorder, obsessive-compulsive disorder, major depressive disorder, or social phobia. Social anxiety disorder and BDD are highly comorbid (within those with BDD, 12–68.8% also have SAD; within those with SAD, 4.8-12% also have BDD), developing similarly in patients -BDD is even classified as a subset of SAD by some researchers. Correct diagnosis can depend on specialized questioning and correlation with emotional distress or social dysfunction. Estimates place the Body Dysmorphic Disorder Questionnaires sensitivity at 100% (0% false negatives) and specificity at 92.5% (7.5% false positives). BDD is also comorbid with eating disorders, up to 12% comorbidity in one study. Both eating and body dysmorphic disorders are concerned with physical appearance, but eating disorders tend to focus more on weight rather than ones general appearance.BDD is classified as an obsessive-compulsive disorder in DSM-5. It is important to treat people with BDD as soon as possible because the person may have already been suffering for an extended period of time and as BDD has a high suicide rate, at 2-12 times higher than the national average. Treatment Medication and psychotherapy Anti-depressant medication, such as selective serotonin reuptake inhibitors (SSRIs), and cognitive-behavioral therapy (CBT) are considered effective. SSRIs can help relieve obsessive-compulsive and delusional traits, while cognitive-behavioral therapy can help patients recognize faulty thought patterns. Before treatment, it can help to provide psychoeducation, as with self-help books and support websites. Self-improvement For many people with BDD cosmetic surgery does not work to alleviate the symptoms of BDD as their opinion of their appearance is not grounded in reality. It is recommended that cosmetic surgeons and psychiatrists work together in order to screen surgery patients to see if they have BDD, as the results of the surgery could be harmful for them. References == External links ==
Guttate psoriasis	Guttate psoriasis (also known as eruptive psoriasis) is a type of psoriasis that presents as small (0.5–1.5 cm in diameter) lesions over the upper trunk and proximal extremities; it is found frequently in young adults.: 410 : 194 The term "guttate" is used to describe the drop-like appearance of skin lesions. Guttate psoriasis is classically triggered by a bacterial infection, usually an upper respiratory tract infection.: 726 Signs and symptoms Typically, guttate psoriasis erupts after a throat infection, or strep throat. Initially, when the throat infection has cleared up, the person can feel fine for several weeks before noticing the appearance of red spots. They appear small at first, like a dry red spot which is slightly itchy. When scratched or picked, the top layer of dry skin is removed, leaving dry, red skin beneath with white, dry areas marking where flakes of dry skin stop and start. In the weeks that follow, the spots can grow to as much as an inch in diameter. Some of the larger ones may form a pale area in the center which is slightly yellow. Guttate psoriasis can occur on any part of the body, particularly the legs, arms, torso, eyelids, back, bottom, bikini line, and neck. The number of lesions can range from 5 to over 100. Generally the parts of the body most affected are seen on the arms, legs, back and torso. Causes Genetic and environmental factors can influence the predilection for guttate psoriasis. Human leukocyte antigens, especially those in the HLA-C group are associated with the skin disorder. Beta-hemolytic streptococci infection is the major contributing environmental factor. The typical route of infection is the upper respiratory system. Rarely it is also caused by a skin infection surrounding the anus (perianal streptococcal dermatitis). Diagnosis Guttate psoriasis can typically be diagnosed by clinical examination alone. Management The treatments used for plaque psoriasis can also be used for guttate psoriasis. Few studies have specifically focused on guttate psoriasis management, so there are currently no firm guidelines for managing guttate psoriasis differently from plaque psoriasis. Immunosuppressive drugs that inhibit T cell activation have been effective in treating severe cases of chronic guttate psoriasis. Due to the role streptococcal infection plays in the development of guttate psoriasis, systemic antibiotics have been considered as a potential treatment option. There is uncertain evidence whether systemic antibiotics or tonsillectomy are effective and safe in treating the disease. The condition often clears up on its own within weeks to months, and only about one third of patients will develop chronic plaques. Epidemiology Guttate psoriasis accounts for approximately 2% of psoriasis cases. References == External links ==
Calcium deficiency	Calcium deficiency may refer to: Calcium deficiency, a plant disorder that can be caused by insufficient calcium in the growing medium, but is more frequently a product of low transpiration of the whole plant or more commonly the affected tissue Hypocalcaemia, the presence of low serum calcium levels in the blood
Andermann syndrome	Andermann syndrome, also known as agenesis of corpus callosum with neuronopathy (ACCPN) and Charlevoix disease, among other names, is a very rare neurodegenerative genetic disorder that damages the nerves used to control muscles and related to sensation and is often associated with agenesis of the corpus collosum.It was first described by Eva Andermann et al. in 1972. Symptoms and signs Symptoms begin in infancy and include: hypotonia areflexia amyotrophy variable degrees of dysgenesis of the corpus callosum mild to severe intellectual and developmental delay psychiatric problems including paranoid delusions, depression, hallucinations and autistic-like behavior Genetics The inheritance pattern is autosomal recessive. Several genes have been associated with the disorder, including SLC12A6. Neuropathology Autopsy examination of 8 cases has shown both developmental and degenerative neuropathologic features in this disease, consistent with clinical duality as both a neurodevelopmental and neurodegenerative disorder.In the central nervous system, accompanying the hypotonia at birth is hypoplasia of the corticospinal tracts. Another developmental feature is seen in the corpus callosum, which varies from absent to hypoplastic. The anterior commissure is almost always absent, but occasionally hypoplastic. A bundle of Probst can be found running antero-posterior rather than crossing the midline. The axonal damage due to the channel deficiency can cause a reactive axonal overgrowth leading to small tumor-like growths, or tumorlets, called axonomas, or balls of aberrant axons. Damaged axons can also show a sign of inhibition of axonal transport, forming axonal spheroids. These spheroids can be throughout the cerebral hemispheres, explaining the psychotic symptoms by disconnection of the brain from itself by axonal functional disruption.In the Peripheral nervous system, the disease is more severe. While most nervous system diseases affect either CNS or PNS, this disease affects both, but it is the changes in the peripheral nervous system that lead to death. This occurs by axonal disease paralyzing the skeletal muscles, including the respiratory muscles as a result of axonal damage in peripheral nerves. Changes in the axons are more severe in the PNS than CNS and under the electron microscope, some axons look necrotic, by virtue of containing mitochondrial flocculent densities and other irreversible changes. The lack of innervation of the body musculature during development gives rise to small body weights, often below 40 kilograms, remarkable in view of the preserved brain weights. Diagnosis Typical diagnostic workup includes clinical features electrophysiologic testing molecular genetic testing (SLC12A6) magnetic resonance imaging (MRI) of the brain (revealing in 60% of the patients callosal agenesis and in 10% partial callosal agenesis) Treatment There is currently no cure, but some symptoms may be treated such as neuroleptics for the psychiatric problems. Prognosis The prognosis is poor. Patients are usually wheelchair bound by their 20s and die by their 30s. Prevalence The prevalence rate has been estimated to be less than 1/1,000,000 worldwide. However, it is much more common in the French-Canadian population of the Saguenay and Lac-St-Jean regions of Quebec, Canada, where it has a frequency of about 1 in 2100 in live births, and a carrier rate of 1 in 23. References External links Andermann syndrome at OMIM Andermann syndrome at Orpha.net Andermann syndrome at GARD
Multiple endocrine neoplasia type 1	Multiple endocrine neoplasia type 1 (MEN-1) is one of a group of disorders, the multiple endocrine neoplasias, that affect the endocrine system through development of neoplastic lesions in pituitary, parathyroid gland and pancreas. It was first described by Paul Wermer in 1954. Signs and symptoms Parathyroid Hyperparathyroidism is present in ≥ 90% of patients. Asymptomatic hypercalcemia is the most common manifestation: about 25% of patients have evidence of nephrolithiasis or nephrocalcinosis. In contrast to sporadic cases of hyperparathyroidism, diffuse hyperplasia or multiple adenomas are more common than solitary adenomas. Pancreas Pancreatic islet cell tumors are today the major cause of death in persons with MEN-1. Tumors occur in 60-80% of persons with MEN-1 and they are usually multicentric. Multiple adenomas or diffuse islet cell hyperplasia commonly occurs. About 30% of tumors are malignant and have local or distant metastases. About 10-15% of islet cell tumors originate from a β-cell, secrete insulin (insulinoma), and can cause fasting hypoglycemia. β-cell tumors are more common in patients < 40 years of age. Most islet cell tumors secrete pancreatic polypeptide, the clinical significance of which is unknown. Gastrin is secreted by many non–β-cell tumors (increased gastrin secretion in MEN 1 also often originates from the duodenum). Increased gastrin secretion increases gastric acid, which may inactivate pancreatic lipase, leading to diarrhea and steatorrhea. Increased gastrin secretion also leads to peptic ulcers in > 50% of MEN 1 patients. Usually the ulcers are multiple or atypical in location, and often bleed, perforate, or become obstructed. Peptic ulcer disease may be intractable and complicated. Among patients presenting with Zollinger-Ellison syndrome, 20 to 60% have MEN 1. A severe secretory diarrhea can develop and cause fluid and electrolyte depletion with non–β-cell tumors. This complex, referred to as the watery diarrhea, hypokalemia and achlorhydria syndrome (VIPoma) has been ascribed to vasoactive intestinal polypeptide, although other intestinal hormones or secretagogues (including prostaglandins) may contribute. Hypersecretion of glucagon, somatostatin, chromogranin, or calcitonin, ectopic secretion of ACTH resulting in Cushings syndrome, and hypersecretion of somatotropin–releasing hormone (causing acromegaly) sometimes occur in non–β-cell tumors. All of these are rare in MEN 1.Nonfunctioning pancreatic tumors also occur in patients with MEN 1 and may be the most common type of pancreatoduodenal tumor in MEN 1. The size of the nonfunctioning tumor correlates with risk of metastasis and death. Pituitary Pituitary tumors occur in 15 to 42% of MEN 1 patients. From 25 to 90% are prolactinomas. About 25% of pituitary tumors secrete growth hormone or growth hormone and prolactin. Excess prolactin may cause galactorrhea, and excess growth hormone causes acromegaly clinically indistinguishable from sporadically occurring acromegaly. About 3% of tumors secrete ACTH, producing Cushings disease. Most of the remainder are nonfunctional. Local tumor expansion may cause visual disturbance, headache, and hypopituitarism. Pituitary tumors in MEN 1 patients appear to be larger and behave more aggressively than sporadic pituitary tumors. Other manifestations Adenomas of adrenal glands occurs occasionally in MEN 1 patients. Hormone secretion is rarely altered as a result, and the significance of these abnormalities is uncertain. Carcinoid tumors, particularly those derived from the embryologic foregut (lungs, thymus), occur in isolated cases. Multiple subcutaneous and visceral lipomas, angiofibromas, and collagenomas may also occur. Genetic People with multiple endocrine neoplasia type 1 are born with one mutated copy of the MEN1 gene in each cell. Then, during their lifetime, the other copy of the gene is mutated in a small number of cells. These genetic changes result in no functional copies of the MEN1 gene in selected cells, allowing the cells to divide with little control and form tumors. This is known as Knudsons two-hit hypothesis and is a common feature seen with inherited defects in tumor suppressor genes. Oncogenes can become neoplastic with only one activating mutation, but tumor suppressors inherited from both mother and father must be damaged before they lose their effectiveness. The exception to the "two-hit hypothesis" occurs when suppressor genes exhibit dose-response, such as ATR. The exact function of MEN1 and the protein, menin, produced by this gene is not known, but following the inheritance rules of the "two-hit hypothesis" indicates that it acts as a tumor suppressor. Diagnosis In a diagnostic workup individuals with a combination of endocrine neoplasias suggestive of the MEN1 syndrome are recommended to have a mutational analysis of the MEN1 gene if additional diagnostic criteria are sufficiently met, mainly including: age <40 years positive family history multifocal or recurrent neoplasia two or more organ systems affected Types Multiple endocrine neoplasia or MEN is part of a group of disorders that affect the bodys network of hormone-producing glands (the endocrine system). Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia involves tumors in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, some cases can be life-threatening. The two major forms of multiple endocrine neoplasia are called type 1 and type 2. These two types are often confused because of their similar names. However, type 1 and type 2 are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms. These disorders greatly increase the risk of developing multiple cancerous and noncancerous tumors in glands such as the parathyroid, pituitary, and pancreas. Multiple endocrine neoplasia occurs when tumors are found in at least two of the three main endocrine glands (parathyroid, pituitary, and pancreatico-duodenum). Tumors can also develop in organs and tissues other than endocrine glands. If the tumors become cancerous, some cases can be life-threatening. The disorder affects 1 in 30,000 people. Although many different types of hormone-producing tumors are associated with multiple endocrine neoplasia, tumors of the parathyroid gland, pituitary gland, and pancreas are most frequent in multiple endocrine neoplasia type 1. MEN1-associated overactivity of these three endocrine organs are briefly described here: Overactivity of the parathyroid gland (hyperparathyroidism) is the most common sign of this disorder. Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of the bones (osteoporosis), high blood pressure (hypertension), loss of appetite, nausea, weakness, fatigue, and depression. Neoplasia in the pituitary gland can manifest as prolactinomas whereby too much prolactin is secreted, suppressing the release of gonadotropins, causing a decrease in sex hormones such as testosterone. Pituitary tumor in MEN1 can be large and cause signs by compressing adjacent tissues. Pancreatic tumors associated with MEN-1 usually form in the beta cells of the islets of Langerhans, causing over-secretion of insulin, resulting in low blood glucose levels (hypoglycemia). However, many other tumors of the pancreatic Islets of Langerhans can occur in MEN-1. One of these, involving the alpha cells, causes over-secretion of glucagon, resulting in a classic triad of high blood glucose levels (hyperglycemia), a rash called necrolytic migratory erythema, and weight loss. Gastrinoma causes the over-secretion of the hormone gastrin, resulting in the over-production of acid by the acid-producing cells of the stomach (parietal cells) and a constellation of sequelae known as Zollinger-Ellison syndrome. Zollinger-Ellison syndrome may include severe gastric ulcers, abdominal pain, loss of appetite, chronic diarrhea, malnutrition, and subsequent weight loss. Other non-beta islet cell tumors associated with MEN1 are discussed below. Treatment The treatment of choice of parathyroid tumors is open bilateral exploration with subtotal (3/4) or total parathyroidectomy. Autoimplantation may be considered in case of a total parathyroidectomy. Optimal timing for this operation has not yet been established but it should be performed by an experienced endocrine surgeon.Endocrine pancreatic tumor are treated with surgery and cytotoxic drugs in case of malignant disease. Pituitary tumors are treated with surgery (acromegaly and Mb. Cushing) or medicine (prolactinomas). Culture and society In the video game Trauma Team, Gabriel Cunninghams son, Joshua Cunningham, is diagnosed with Wermers syndrome. It is also mentioned in the South Korean drama "Medical Top Team", as Dr. Choi Ah Jin (Oh Yeon-seo) is diagnosed with MEN-1. See also Acromegaly Multiple endocrine neoplasia Multiple endocrine neoplasia type 2a Multiple endocrine neoplasia type 2b Prolactinoma References This article incorporates public domain text from The U.S. National Library of Medicine Further reading GeneReview/NIH/UW entry on Multiple Endocrine Neoplasia Type 1 == External links ==
Congenital hypoplastic anemia	Congenital hypoplastic anemia is a type of aplastic anemia which is primarily due to a congenital disorder. Associated genes include TERC, TERT, IFNG, NBS1, PRF1, and SBDS.Examples include: Fanconi anemia Diamond–Blackfan anemia References == External links ==
Alternobaric vertigo	In aviation and underwater diving, alternobaric vertigo is dizziness resulting from unequal pressures being exerted between the ears due to one Eustachian tube being less patent than the other. Signs and symptoms Causes This might have occurred due to barotrauma of descent, and/or the effects of nasal decongestants. It is due to unequal increase in middle ear pressures on ascent, is usually mild, and most often cleared by further ascent. When the pressures in both ears reach ambient levels, the stimulus for the dizziness stops. Although most often mild, the vertigo can persist until the diver reaches the surface continuing the unequal pressures, which can damage the inner ear or ear drum. Alternobaric vertigo is most pronounced when the diver is in the vertical position; the spinning is towards the ear with the higher pressure and tends to develop when the pressures differ by 60 cm of water or more. Ear clearing may be a remedy. A similar vertigo can also occur as a result of unequal heating stimulation of one inner ear labyrinth over the other due to diving in a prone position in cold water - the undermost ear being stimulated. Diagnosis In terms of diagnosis for alternobaric vertigo the medical history and physical examination, are important. Furthermore, Eustachian tube function testing is also performed Management See also Vertigo – Type of dizziness where a person has the sensation of moving or surrounding objects moving Inner ear barotrauma – Pressure injury to the inner ear Inner ear decompression sickness – Medical condition caused by inert gas bubbles forming out of solution == References ==
Xeroderma	Xeroderma, xerosis or xerosis cutis, or simply dry skin, is a skin condition characterized by excessively dry skin.The medical term xeroderma, meaning "dry skin", derives from modern Latin, xero- dry + Greek derma skin. In most cases, dry skin can safely be treated with emollients or moisturizers. Xeroderma occurs most commonly on the scalp, lower legs, arms, hands, the knuckles, the sides of the abdomen, and thighs. Symptoms most associated with xeroderma are such skin conditions as scaling (the visible peeling of the outer skin layer), itching, and skin fissures (cracked skin). Causes Xeroderma is a very common condition. It happens more often in the winter when the cold air outside and the hot air inside creates a low relative humidity. This causes the skin to lose moisture and it may crack and peel. Bathing or hand washing too frequently, especially if one is using harsh soaps, can contribute to xeroderma. Xeroderma can be caused by a deficiency of vitamin A, vitamin D, zinc, systemic illness, severe sunburn, or some medication. Xeroderma can be caused by choline inhibitors. Detergents such as washing powder and dishwashing liquid can cause xeroderma. Prevention Today, many creams and lotions, commonly based on vegetable oils/butters, petroleum oils/jellies, and lanolin are widely available. As a preventive measure, such products may be rubbed onto the affected area as needed (often every other day) to prevent dry skin. The skin is then patted dry to prevent removal of natural lipids from the skin. Taking a shower or washing hands with special moisturizing soaps or body washes can protect skin from drying out further. Treatment Repeated application (typically over a few days) of emollients or skin lotions/creams to the affected area will likely result in quick alleviation of xeroderma. In particular, application of highly occlusive barriers to moisture, such as petrolatum, vegetable oils/butters, and mineral oil have been shown to provide excellent results. Many individuals find specific commercial skin creams and lotions (often comprising oils, butters, and or waxes emulsified in water) quite effective (although individual preferences and results vary among the wide array of commercially available creams).Lanolin, a natural mixture of lipids derived from sheeps wool, helps replace natural lipids in human skin and has been used since ancient times (and in modern medicine) as among the most powerful treatments for xeroderma. Some people may, however, have allergies to lanolin, producing the opposite of the desired effect. Also, pure lanolin is a thick waxy substance which, for many individuals, proves difficult and inconvenient for general use on dry skin (especially over large areas of the body). As a result, many formulated lanolin products, having a softer consistency than pure lanolin, are available. Safety Many skin creams include common allergens such as fragrances, parabens, and lanolin. See also Eczema Ichthyosis Xeroderma pigmentosum References == External links ==
De Quervain syndrome	De Quervain syndrome is mucoid degeneration of two tendons that control movement of the thumb and their tendon sheath. This results in pain and tenderness on the thumb side of the wrist. Radial abduction of the thumb is painful. On occasion, there is uneven movement or triggering the thumb with radial abduction. Symptoms can come on gradually or be noted suddenly.There is speculation that the problem is related to use of the hand, but this is not supported by experimental evidence. Humans tend to misinterpret painful activities as causing the problem to get worse and this misinterpretation is associated with greater pain intensity. For this reason, its better not to blame activity without strong scientific support. The diagnosis is generally based on symptoms and physical examination. Diagnosis is supported if pain increases when the wrist is bent inwards while a person is grabbing their thumb within a fist.There is some evidence that the natural history of de Quervain tendinopathy is resolution over a period of about 1 year. Symptomatic alleviation (palliative treatment) is provided mainly by splinting the thumb and wrist. Pain medications such as NSAIDs can also be considered. Steroid injections are commonly used, but are not proved to alter the natural history of the condition. Surgery to release the first dorsal component is an option. It may be most common in middle age. Signs and symptoms Symptoms are pain and tenderness at the radial side of the wrist, fullness or thickening over the thumb side of the wrist, and difficulty gripping with the affected side of the hand. The onset is often gradual. Pain is made worse by movement of the thumb and wrist, and may radiate to the thumb or the forearm. Causes The cause of de Quervains disease is not established. Evidence regarding a possible relation with activity and occupation is debated. A systematic review of potential risk factors discussed in the literature did not find any evidence of a causal relationship with activity or occupation. However, researchers in France found personal and work-related factors were associated with de Quervains disease in the working population; wrist bending and movements associated with the twisting or driving of screws were the most significant of the work-related factors. Proponents of the view that De Quervain syndrome is a repetitive strain injury consider postures where the thumb is held in abduction and extension to be predisposing factors. Workers who perform rapid repetitive activities involving pinching, grasping, pulling or pushing have been considered at increased risk. These movements are associated with many types of repetitive housework such as chopping vegetables, stirring and scrubbing pots, vacuuming, cleaning surfaces, drying dishes, pegging out washing, mending clothes, gardening, harvesting and weeding. Specific activities that have been postulated as potential risk factors include intensive computer mouse use, trackball use, and typing, as well as some pastimes, including bowling, golf, fly-fishing, piano-playing, sewing, and knitting.Women are diagnosed more often than men. The syndrome commonly occurs during and, even more so, after pregnancy. Contributory factors may include hormonal changes, fluid retention and—again, more debatably and potentially harmfully—increased housework and lifting. Pathophysiology De Quervain syndrome involves noninflammatory thickening of the tendons and the synovial sheaths that the tendons run through. The two tendons concerned are those of the extensor pollicis brevis and abductor pollicis longus muscles. These two muscles run side by side and function to bring the thumb away from the hand; the extensor pollicis brevis brings the thumb outwards radially, and the abductor pollicis longus brings the thumb forward away from the palm. De Quervain tendinopathy affects the tendons of these muscles as they pass from the forearm into the hand via a fibro-osseous tunnel (the first dorsal compartment). Evaluation of histopathological specimens shows a thickening and myxoid degeneration consistent with a chronic degenerative process, as opposed to inflammation. The pathology is identical in de Quervain seen in new mothers. Diagnosis De Quervain syndrome is diagnosed clinically, based on history and physical examination, though diagnostic imaging such as X-ray may be used to rule out fracture, arthritis, or other causes, based on the persons history and presentation. The modified Eichoff maneuver, commonly called the Finkelsteins test, is a physical exam maneuver used to diagnose de Quervain syndrome. To perform the test, the examiner grasps and ulnar deviates the hand when the person has their thumb held within their fist. If sharp pain occurs along the distal radius (top of forearm, about an inch below the wrist), de Quervains syndrome is likely. While a positive Finkelsteins test is often considered pathognomonic for de Quervain syndrome, the maneuver can also cause pain in those with osteoarthritis at the base of the thumb. Differential diagnosis Differential diagnoses include: Osteoarthritis of the trapezio-metacarpal joint Intersection syndrome—pain will be more towards the middle of the back of the forearm and about 2–3 inches below the wrist, usually with associated crepitus. Wartenbergs syndrome: The primary symptom is paresthesia (numbness/tingling). Treatment As with many musculoskeletal conditions, the management of de Quervains disease is determined more by convention than scientific data. A systematic review and meta-analysis published in 2013 found that corticosteroid injection seems to be an effective form of conservative management of de Quervains syndrome in approximately 50% of patients, although more research is needed regarding the extent of any clinical benefits. Efficacy data are relatively sparse and it is not clear whether benefits affect the overall natural history of the illness. One of the most common causes of corticosteroid injection failure are subcompartments of the extensor pollicis brevis tendon.Most tendinoses are self-limiting and the same is likely to be true of de Quervains although further study is needed.Palliative treatments include a splint that immobilized the wrist and the thumb to the interphalangeal joint and anti-inflammatory medication or acetaminophen. Systematic review and meta-analysis do not support the use of splinting over steroid injections.Surgery (in which the sheath of the first dorsal compartment is opened longitudinally) is documented to provide relief in most patients. The most important risk is to the radial sensory nerve. A small incision is made and the dorsal extensor retinaculum is identified. Once it has been identified the release is performed longitudinally along the tendon. This is done to prevent potential subluxation of the 1st compartment tendons. Next the abductor pollicis longus (APL) and extensor pollicis brevis (EPB) are identified and the compartments are released.Some occupational and physical therapists suggest alternative lifting mechanics based on the theory that the condition is due to repetitive use of the thumbs during lifting. Physical/Occupational therapy can suggest activities to avoid based on the theory that certain activities might exacerbate ones condition, as well as instruct on strengthening exercises based on the theory that this will contribute to better form and use of other muscle groups, which might limit irritation of the tendons.Some occupational and physical therapists use other treatments, in conjunction with Therapeutic Exercises, based on the rationale that they reduce inflammation and pain and promote healing: UST, SWD, or other deep heat treatments, as well as TENS, acupuncture, or infrared light therapy, and cold laser treatments. However, the pathology of the condition is not inflammatory changes to the synovial sheath and inflammation is secondary to the condition from friction. Teaching patients to reduce their secondary inflammation does not treat the underlying condition but may reduce their pain; which is helpful when trying to perform the prescribed exercise interventions. Getting Physical Therapy before surgery has shown to reduce overall cost of therapy. History From the original description of the illness in 1895 until the first description of corticosteroid injection by Jarrod Ismond in 1955, it appears that the only treatment offered was surgery. Since approximately 1972, the prevailing opinion has been that of McKenzie (1972) who suggested that corticosteroid injection was the first line of treatment and surgery should be reserved for unsuccessful injections. Eponym It is named after the Swiss surgeon Fritz de Quervain who first identified it in 1895. It should not be confused with de Quervains thyroiditis, another condition named after the same person. Society and culture BlackBerry thumb is a neologism that refers to a form of repetitive strain injury (RSI) caused by the frequent use of the thumbs to press buttons on PDAs, smartphones, or other mobile devices. The name of the condition comes from the BlackBerry, a brand of smartphone that debuted in 1999, although there are numerous other similar eponymous conditions that exist such as "Wiiitis", "Nintendinitis", "Playstation thumb", "texting thumb", "cellphone thumb", "smartphone thumb", "Android thumb", and "iPhone thumb". The medical name for the condition is De Quervain syndrome and is associated with the tendons connected to the thumb through the wrist. Causes for the condition extend beyond smartphones and gaming consoles to include activities like golf, racket sports, and lifting.Symptoms of BlackBerry thumb include aching and throbbing pain in the thumb and wrist. In severe cases, it can lead to temporary disability of the affected hand, particularly the ability to grip objects.One hypothesis is that the thumb does not have the dexterity the other four fingers have and is therefore not well-suited to high speed touch typing. See also Mobile phone overuse Nomophobia References == External links ==
Multiple system atrophy	Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by autonomic dysfunction, tremors, slow movement, muscle rigidity, and postural instability (collectively known as parkinsonism) and ataxia. This is caused by progressive degeneration of neurons in several parts of the brain including the basal ganglia, inferior olivary nucleus, and cerebellum. Many people affected by MSA experience dysfunction of the autonomic nervous system, which commonly manifests as orthostatic hypotension, impotence, loss of sweating, dry mouth and urinary retention and incontinence. Palsy of the vocal cords is an important and sometimes initial clinical manifestation of the disorder. A modified form of the alpha-synuclein protein within affected neurons may cause MSA. About 55% of MSA cases occur in men, with those affected first showing symptoms at the age of 50–60 years. MSA often presents with some of the same symptoms as Parkinsons disease. However, those with MSA generally show little response to the dopamine medications used to treat Parkinsons disease and only about 9% of MSA patients with tremor exhibit a true parkinsonian pill-rolling tremor.MSA is distinct from multisystem proteinopathy, a more common muscle-wasting syndrome. MSA is also different from multiple organ dysfunction syndrome, sometimes referred to as multiple organ failure, and from multiple organ system failures, an often-fatal complication of septic shock and other severe illnesses or injuries. Signs and symptoms MSA is characterized by the following, which can be present in any combination: autonomic dysfunction parkinsonism (muscle rigidity +/ tremor and slow movement) cerebellar ataxia (Poor coordination/unsteady walking, double vision)A variant with combined features of MSA and dementia with Lewy bodies may also exist. There have also been occasional instances of frontotemporal lobar degeneration associated with MSA. Initial presentation The most common first sign of MSA is the appearance of an "akinetic-rigid syndrome" (i.e. slowness of initiation of movement resembling Parkinsons disease) found in 62% at first presentation. Other common signs at onset include problems with balance (cerebellar ataxia) found in 22% at first presentation, followed by genito-urinary symptoms (9%): both men and women often experience urgency, frequency, incomplete bladder emptying, or an inability to pass urine (retention). About 1 in 5 MSA patients experience a fall in their first year of disease.For men, the first sign can be erectile dysfunction. Women have also reported reduced genital sensitivity. Progression As the disease progresses one of three groups of symptoms predominates. These are: Parkinsonism - slow, stiff movement, writing becomes small and spidery Cerebellar dysfunction - difficulty coordinating movement and balance Autonomic nervous system dysfunction - impaired automatic body functions, including one, some, or all of the following:postural or orthostatic hypotension, resulting in dizziness or fainting upon standing up urinary incontinence or urinary retention impotence constipation vocal cord paralysis dry mouth and skin trouble regulating body temperature due to sweating deficiency in all parts of the body loud snoring, abnormal breathing or inspiratory stridor during sleep other sleep disorders including sleep apnea, REM behavior disorder double vision muscle twitches Cognitive impairment Genetics One study found a correlation between the deletion of genes in a specific genetic region and the development of MSA in a group of Japanese patients. The region in question includes the SHC2 gene which, in mice and rats, appears to have some function in the nervous system. The authors of this study hypothesized that there may be a link between the deletion of the SHC2 and the development of MSA.A follow-up study was unable to replicate this finding in American MSA patients. The authors of the U.S. study concluded that "Our results indicate that SHC2 gene deletions underlie few, if any, cases of well-characterized MSA in the US population. This is in contrast to the Japanese experience reported by Sasaki et al., likely reflecting heterogeneity of the disease in different genetic backgrounds."Another study investigated the frequency of RFC1 intronic repeat expansions, a phenomenon implicated in CANVAS; a disease with a diagnostic overlap with MSA. The study concluded that these repeats were absent in pathologically confirmed MSA, suggesting an alternative genetic cause. Pathophysiology Multiple system atrophy can be explained as cell loss and gliosis or a proliferation of astrocytes in damaged areas of the central nervous system. This damage forms a scar which is then termed a glial scar. The presence of inclusion bodies known as Papp–Lantos bodies, in the movement, balance, and autonomic-control centres of the brain are the defining histopathologic hallmark of MSA.The major filamentous component of Papp-Lantos bodies, glial and neuronal cytoplasmic inclusions, is alpha-synuclein. Mutations in this substance may play a role in the disease. The conformation of the alpha-synuclein is different from that of alpha-synuclein in Lewy bodies. The disease probably starts with an oligodendrogliopathy.Tau proteins have been found in some glial cytoplasmic inclusion bodies. Diagnosis Clinical Clinical diagnostic criteria were defined in 1998 and updated in 2007. Certain signs and symptoms of MSA also occur with other disorders, such as Parkinsons disease, making the diagnosis more difficult. Radiologic Both MRI and CT scanning may show a decrease in the size of the cerebellum and pons in those with cerebellar features (MSA-C). The putamen is hypointense on T2-weighted MRI and may show an increased deposition of iron in the Parkinsonian (MSA-P) form. In MSA-C, a "hot cross bun" sign is sometimes found; it reflects atrophy of the pontocerebellar tracts that give T2 hyper intense signal intensity in the atrophic pons.MRI changes are not required to diagnose the disease as these features are often absent, especially early in the course of the disease. Additionally, the changes can be quite subtle and are usually missed by examiners who are not experienced with MSA. Pathologic Pathological diagnosis can only be made at autopsy by finding abundant GCIs on histological specimens of the central nervous system.Contrary to most other synucleinopathies, which develop α-synuclein inclusions primarily in neuronal cell populations, MSA presents with extensive pathological α-synuclein inclusions in the cytosol of oligodendrocytes (glial cytoplasmic inclusions), with limited pathology in neurons. MSA also differs from other synucleinopathies in its regional pathological presentation, with α-synuclein positive inclusions detected predominantly in the striatum, midbrain, pons, medulla and cerebellum, rather than the brainstem, limbic and cortical regions typically effected in Lewy inclusion diseases. However, recent studies using novel, monoclonal antibodies specific for C-terminally truncated α-synuclein (αSynΔC) have now shown that neuronal α-synuclein pathology is more abundant than previously thought. One group revealed robust α-synuclein pathology in the pontine nuclei and medullary inferior olivary nucleus upon histological analysis of neurological tissue from MSA patients. Histopathological investigation on six cases of pathologically confirmed MSA, using antibodies directed at a variety of α-synuclein epitopes, revealed substantial variation in α-synuclein protein deposition across both cases and brain regions within cases, providing evidence for strains of aggregated conformers that may differentially promote pathological prion-like spread.In 2020, researchers at The University of Texas Health Science Center at Houston concluded that protein misfolding cyclic amplification could be used to distinguish between two progressive neurodegenerative diseases, Parkinson’s disease and multiple system atrophy, being the first process to give an objective diagnosis of Multiple System Atrophy instead of just a differential diagnosis. Classification MSA is one of several neurodegenerative diseases known as synucleinopathies: they have in common an abnormal accumulation of alpha-synuclein protein in various parts of the brain. Other synucleinopathies include Parkinsons disease, the Lewy body dementias, and other more rare conditions. Old terminology Historically, many terms were used to refer to this disorder, based on the predominant systems presented. These terms were discontinued by consensus in 1996 and replaced with MSA and its subtypes, but awareness of these older terms and their definitions is helpful to understanding the relevant literature prior to 1996. These include striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA), and Shy–Drager syndrome. A table describing the characteristics and modern names of these conditions follows: Current terminology The current terminology and diagnostic criteria for the disease were established at a 2007 conference of experts and set forth in a position paper. This Second Consensus Statement defines two categories of MSA, based on the predominant symptoms of the disease at the time of evaluation. These are: MSA with predominant parkinsonism (MSA-P) - defined as MSA where extrapyramidal features predominate. It is sometimes termed striatonigral degeneration, a parkinsonian variant. MSA with cerebellar features (MSA-C) - defined as MSA in which cerebellar ataxia predominates. It is sometimes termed sporadic olivopontocerebellar atrophy. Management Supervision Ongoing care from a neurologist specializing in movement disorders is recommended, because the complex symptoms of MSA are often not familiar to less-specialized neurologists. Hospice/homecare services can be very useful as disability progresses. Drug therapy Levodopa (L-Dopa), a drug used in the treatment of Parkinsons disease, improves parkinsonian symptoms in a small percentage of MSA patients. A recent trial reported that only 1.5% of MSA patients experienced any improvement at all when taking levodopa, their improvement was less than 50%, and even that improvement was a transient effect lasting less than one year. Poor response to L-Dopa has been suggested as a possible element in the differential diagnosis of MSA from Parkinsons disease.The drug riluzole is ineffective in treating MSA or PSP. Rehabilitation Management by rehabilitation professionals including physiatrists, physiotherapists, occupational therapists, speech therapists, and others for difficulties with walking/movement, daily tasks, and speech problems is essential.Physiotherapists can help to maintain the patients mobility and will help to prevent contractures. Instructing patients in gait training will help to improve their mobility and decrease their risk of falls. A physiotherapist may also prescribe mobility aids such as a cane or a walker to increase the patients safety.Speech therapists may assist in assessing, treating and supporting speech (dysarthria) and swallowing difficulties (dysphagia). Speech changes mean that alternative communication may be needed, for example, communication aids or word charts.Early intervention of swallowing difficulties is particularly useful to allow for discussion around tube feeding further in the disease progression. At some point in the progression of the disease, fluid and food modification may be implemented. Avoidance of postural hypotension One particularly serious problem, the drop in blood pressure upon standing up (with risk of fainting and thus injury from falling), often responds to fludrocortisone, a synthetic mineralocorticoid. Another common drug treatment is the alpha-agonist midodrine.Non-drug treatments include "head-up tilt" (elevating the head of the whole bed by about 10 degrees), salt tablets or increasing salt in the diet, generous intake of fluids, and pressure (elastic) stockings. Avoidance of triggers of low blood pressure, such as hot weather, alcohol, and dehydration, are crucial. The patient can be taught to move and transfer from sitting to standing slowly to decrease risk of falls and limit the effect of postural hypotension. Instruction in ankle pumping helps to return blood in the legs to the systemic circulation. Other preventative measures are raising the head of the bed by 8 in (20.3 cm), and the use of compression stockings and abdominal binders. Support Social workers and occupational therapists can also help with coping with disability through the provision of equipment and home adaptations, services for caregivers and access to healthcare services, both for the person with MSA as well as family caregivers. Prognosis The average lifespan after the onset of symptoms in patients with MSA is 6–10 years. Approximately 60% of patients require a wheelchair within five years of onset of the motor symptoms, and few patients survive beyond 12 years. The disease progresses without remission at a variable rate. Those who present at an older age, those with parkinsonian features, and those with severe autonomic dysfunction have a poorer prognosis. Those with predominantly cerebellar features and those who display autonomic dysfunction later have a better prognosis. Causes of death The most common causes of death are sudden death and death caused by infections, which include urinary catheterization infections, feeding tube infections, and aspiration pneumonia. Some deaths are caused by cachexia, also known as wasting syndrome. Epidemiology Multiple system atrophy is estimated to affect approximately 5 per 100,000 people. At autopsy, many patients diagnosed during life with Parkinson’s disease are found actually to have MSA, suggesting that the actual incidence of MSA is higher than that estimate. While some suggest that MSA affects slightly more men than women (1.3:1), others suggest that the two sexes are equally likely to be affected. The condition most commonly presents in persons aged 50–60. Research Mesenchymal stem cell therapy may delay the progression of neurological deficits in patients with MSA-cerebellar type. Notable cases Ronald Green (1944–2012), American-Israeli basketball player Chef Kerry Simon died from complications of MSA. Nikolai Andrianov was a Soviet/Russian gymnast who held the record for men for the most Olympic medals at 15 (7 gold medals, 5 silver medals, 3 bronze medals) until Michael Phelps surpassed him at the 2008 Beijing Summer Olympics. Joseph C. Howard Sr. was the first African American to serve as a United States district judge of the United States District Court for the District of Maryland. Singer and songwriter Johnny Cash wrote in his autobiography that he was diagnosed with Shy–Drager in 1997. Kenneth More British actor, originally diagnosed with Parkinsons disease. Todd J. Campbell (1956–2021), United States district judge and counsel to former Vice President Al Gore. References External links Medical Textbook: "Multiple System Atrophy" edited by Gregor Wenning and Alessandra Fanciulli
17q12 microdeletion syndrome	17q12 microdeletion syndrome, also known as 17q12 deletion syndrome, is a rare chromosomal anomaly caused by the deletion of a small amount of material from a region in the long arm of chromosome 17. It is typified by deletion of the HNF1B gene, resulting in kidney abnormalities and renal cysts and diabetes syndrome. It also has neurocognitive effects, and has been implicated as a genetic factor for autism and schizophrenia. 17q12 microdeletion syndrome is not to be confused with 17q12 microduplication syndrome, caused by the addition of genetic material in the same region from which it is removed in the microdeletion, or 17q21.31 microdeletion syndrome, another name for Koolen–De Vries syndrome. Presentation 17q12 microdeletions have a variable phenotype, ranging from few or no symptoms to severe disability. The condition is thought to be underdiagnosed, and cases with milder phenotypes may not reach clinical attention unless they have an affected child themselves. The most characteristic symptom is renal cysts and diabetes syndrome (RCAD), also known as "type 5 diabetes", which is caused by deletion of the associated HNF1B gene in the region. RCAD is associated with kidney abnormalities and a characteristic form of diabetes that causes atrophy of the pancreas. However, some people with 17q12 microdeletions have normal renal function. RCAD is diagnosed in approximately 40% of people with 17q12 microdeletions, usually prior to age 25, while kidney abnormalities more broadly occur in approximately 85-90%.People with 17q12 microdeletions have a characteristic facial phenotype, albeit a subtle one not usually obvious in daily life. Macrocephaly is common, along with high arched eyebrows, flattening of the malar region, and epicanthic folds. Pathological short stature is possible, and a characteristic "short and stocky" body shape occurs in many cases.17q12 microdeletions are associated with neurocognitive and developmental involvement of variable severity. Some have mild to moderate intellectual disability; however, such impairment is not universal. Average intelligence is in the average to low average range. Speech delay is common, regardless of intellectual functioning. The most striking association between 17q12 microdeletions and neurodevelopment is the raised prevalence of autism spectrum disorder, with significant increases in both diagnosis and subclinical autistic traits. 17q12 microdeletions have been implicated as one of the major genetic causes of high-functioning autistic spectrum disorders. Schizophrenia is also a significant psychiatric complication of 17q12 microdeletion syndrome. 17q12 microdeletions are estimated to occur in approximately 1 in 1,600 people with schizophrenia, compared to an estimation of below 1 in 50,000 in the general population. Epilepsy, usually mild, occurs in approximately one-third of cases.Reproductive system anomalies are associated with 17q12 microdeletions, particularly in females. 17q12 microdeletions have been linked to uterine malformations, most frequently Müllerian agenesis, where the uterus and part of the vaginal canal are absent. Causes 17q12 microdeletion syndrome is an autosomal dominant disorder, where one copy of the relevant mutation is enough to cause the condition. Most cases are de novo, or spontaneous mutations that do not occur in the probands parents; approximately 75% are de novo, while 25% are inherited. People with 17q12 microdeletions who have normal fertility have a 50% chance of passing the deletion down to their offspring. Environmental factors have not been implicated in the syndrome. Diagnosis Like other chromosomal microdeletions, 17q12 microdeletion syndrome is diagnosed via fluorescence in situ hybridization. Traditional karyotyping, used to diagnose major chromosomal disorders such as aneuploidy, is rarely sensitive enough to detect microdeletions. Treatment As the underlying 17q12 microdeletion is an innate genetic disorder, it cannot by itself be treated. Rather, treatment is symptomatic and supportive. The high prevalence of kidney disease indicates routine monitoring of renal function, particularly in people taking potentially nephrotoxic medications such as lithium. The comorbities involved in 17q12 microdeletion syndrome require caution in medical treatment; for instance, the increased risk of diabetes requires strict monitoring for post-transplantation diabetes mellitus in kidney transplant patients, as does the risk of weight gain and diabetes from neuroleptic drugs in those with a mental health diagnosis. Epidemiology The prevalence of 17q12 microdeletion syndrome is unknown, and it is likely to be underdiagnosed. 17q12 microdeletions are estimated to occur in approximately 1 in 600 people on the autism spectrum and 1 in 1,600 with schizophrenia, but are far rarer in the general population. General prevalence is estimated to be between 1 in 14,000 and 1 in 62,500.In addition to the increased prevalence in autism and schizophrenia, some other clinical populations have increased prevalence of 17q12 microdeletion syndrome. The condition occurs in approximately 2% of those with congenital kidney abnormalities and 3-6% of women with Müllerian agenesis. It is one of the ten most common microdeletions amongst children with idiopathic developmental delay. Microduplication 17q12 microduplication syndrome is far rarer than the corresponding microdeletion, estimated to occur roughly one-fifth as frequently as 17q12 microdeletion syndrome. Due to its rarity and the overlap between their phenotypes, 17q12 microduplications are usually discussed as an adjunct to microdeletions. Like the microdeletion syndrome, the microduplication syndrome has a broad phenotypic range, ranging from asymptomatic to profound disability; intellectual disability is frequently but not always more severe than the microdeletion, while physical health is often better. Epilepsy is a frequent finding. A case of sex reversal has been reported. While autism comorbid with 17q12 microduplication has been reported, it appears far rarer than in the microdeletion. Physical anomalies associated with 17q12 microduplication syndrome include syndactyly, microcephaly, epicanthic folds, and thick eyebrows or a unibrow. The 17q12 microduplication appears to have a low penetrance, as many cases are inherited from asymptomatic parents. See also Causes of autism Risk factors of schizophrenia References == External links ==
Traumatic neuroma	A traumatic neuroma is a type of neuroma which results from trauma to a nerve, usually during a surgical procedure. The most common oral locations are on the tongue and near the mental foramen of the mouth. They are relatively rare on the head and neck. See also List of cutaneous conditions References == External links ==
Brain fag syndrome	Brain fag syndrome (BFS) describes a set of symptoms; somatic, sleep-related and cognitive complaints, difficulty in concentrating and retaining information, head and or neck pains, and eye pain. Brain Fag is very common in adolescents and young adults. It is believed to be the most common in these age ranges due to the immense amount of pressure occurring in life during these years. The condition was arguably first described in Nigerian high school and university students in the 1960s. It is considered a culture-bound syndrome caused by excessive pressure to be successful among the young. Etymology The term brain fag presumably stems from the verb meaning of the word, "To cause (a person, animal, or part of the body) to become tired; to fatigue, wear out" chiefly found in British English. Classification BFS is classified in the fourth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a culture-bound syndrome. Individuals with symptoms of brain fag must be differentiated from those with the syndrome according to the Brain Fag Syndrome Scale (BFSS); Ola et al said it would not be "surpris[ing] if BFS was called an equivalent of either depression or anxiety". Causes Brain Fag is typically driven in people with high anxiety and people with high stress levels. Morakinyo found in 20 people with BFS an achievement drive that was anxiety-related that led to the use of psychostimulants and consequent sleep deprivation which contributed to cognitive disruption. Omoluabi related BFS to test anxiety. Treatment Anumonye reported treatment success with lorazepam; others found benefit with antidepressants and relaxation exercises. Epidemiology BFS has been reported in other African cultures, and also in Brazil, Argentina, and Ethiopian Jews. Historic higher reported prevalence among males may be due to more males being present in higher education in African countries. Studies since the 1990s have not verified gender differences. Other studies found a possible association with low socioeconomic status, an association with average or higher intelligence, and a high association with neuroticism. Individuals with BFS have been found to have problems with isolation, poor study habits, and the use of psychostimulants as well as physical changes including in muscle tension and heart rate. History The condition was first described by R. H. Prince who named the condition based on the term brain fag used by students who believed their symptoms were attributed to "brain fatigue". However, this term was used in the United States and Europe dating back to 1839. Furthermore, in a detailed historical account, Ayonrinde (2020) illustrates that contrary to widely held and published belief in diagnostic manuals, psychiatric, social science and educational text, the term "Brain Fag" and associated syndromes of anxiety, affective and somatoform symptoms in student and "brain worker" populations were first described in nineteenth century Britain (Tunstall, 1850) with dissemination across the British Empire. Ayonrinde concludes that, the time has come for the decolonization of brain fag and its African syndromization in the true spirit of ethical scientific rigor in the twenty-first century. See also Burnout Exhaustion == References ==
Persistent cloaca	A persistent cloaca is a symptom of a complex anorectal congenital disorder, in which the rectum, vagina, and urinary tract meet and fuse, creating a cloaca, a single common channel. Signs and symptoms Cloacas appear in a wide spectrum of variation in females born with the malformation. The single orifice, called a common channel, may occur varying in length from 1 to 10 cm. The length of the common channel can be used to judge prognostic outcomes and technical challenges during surgical repair. A common channel less than 3 cm in length usually has good sphincter muscles and a well-developed sacrum. Diagnosis Diagnosis of a female with cloaca should be suspected in a female born with an imperforate anus and small looking genitalia. The diagnosis can be made clinically. Failure to identify a cloaca as being present in a newborn may be dangerous, as more than 90% have associated urological problems. The goal for treatment of a female born with cloaca is to achieve bowel control, urinary control, and sexual function, which includes menstruation, sexual intercourse, and possibly pregnancy. Cloacas probably occur in 1 in 20,000 live births. Treatment The prognostic outcomes for this type of cloaca are good for bowel control and urinary function. The surgical repair for this type of cloaca can usually be done by performing posterior sagittal approach without opening of the abdomen. A common channel longer than 3 cm in length usually has poor sphincter muscles and a poor sacrum, suggesting a prognostic outcome for bowel control and urinary function to be less likely. Common channels longer than 3 cm are generally considered more complex and more technically challenging in surgical repair. See also Cloaca (embryology) Cloaca References == External links ==
Patella fracture	A patella fracture is a break of the kneecap. Symptoms include pain, swelling, and bruising to the front of the knee. A person may also be unable to walk. Complications may include injury to the tibia, femur, or knee ligaments.It typically results from a hard blow to the front of the knee or falling on the knee. Occasionally it may occur from a strong contraction of the thigh muscles. Diagnosis is based on symptoms and confirmed with X-rays. In children an MRI may be required.Treatment may be with or without surgery, depending on the type of fracture. Undisplaced fracture can usually be treated by casting. Even some displaced fractures can be treated with casting as long as a person can straighten their leg without help. Typically the leg is immobilized in a straight position for the first three weeks and then increasing degrees of bending are allowed. Other types of fractures generally require surgery.Patella fractures make up about 1% of all broken bones. Males are affected more often than females. Those of middle age are most often affected. Outcomes with treatment are generally good. Signs and symptoms Also known as a broken kneecap, a patella fracture usually follows a history of trauma and commonly presents with swelling, pain, bruising and inability to both bend and straighten the knee. The pain is worse when trying to stand and the person may be unable to walk. The pain can also be aggravated by prolonged periods of sitting. A painful defect may be felt in the knee and there may be blood in the joint. Complications Complications may include injury to the tibia, femur, or knee ligaments. In the longer term, the knee may not regain full movement, pain may persist and there is an increased likelihood of osteoarthritis of the knee. If there is an associated open wound as in an open fracture, complications also include risk of infection, inability of the broken bones to reunite and osteonecrosis. Diagnosis Diagnosis is based on symptoms and confirmed with X-rays. In children an MRI may be required. Differential diagnosis Some people have a normal bipartite patella or two-part patella which can appear as a fracture. The fragment is usually seen in the top outer corner of the patella and can be distinguished from a fracture by being present in both knees. Types The patella can break in various ways depending on the way it is injured, and into two or more pieces. Types include transverse, with one fracture line and is the most common type, marginal, osteochondral and the rare vertical type, or stellate, where a direct compression force gives rise to a comminuted pattern. Patella fractures can be further classified as displaced, where the broken ends of bone do not line up correctly and separate by more than 2mm, or undisplaced and stable where pieces of bone remain in contact with each other. If fragments of patella bone stick out from the skin it is known as an open patella fracture, and closed if the overlying skin is intact. Treatment Treatment may be with or without surgery, depending on the type of fracture and whether the overlying skin is intact or broken. Conservative Undisplaced fractures can usually be treated by casting. Even some displaced fractures can be treated with casting as long as the person can straighten their leg without help, thus confirming that the quadriceps mechanism of the leg is intact. In this case the leg is immobilized in a straight position for the first three weeks and then increasing degrees of bending are allowed as healing occurs. Surgery Most patella fractures are transverse or comminuted, hence the quadriceps mechanism is disrupted and they are treated by a combination of wires in a tension band construct. This unites the fractured bones, reconstructing the straightening mechanism of the leg.If the patella is broken in several places, that is comminuted, then traditionally a patellectomy (removal of the whole patella) is performed in order to reconstruct the extensor mechanism and prevent the onset of an extension lag at the knee joint, resulting in instability. Some surgeons however would rather opt for internal fixation. A partial patellectomy is removal of only a portion of the patella, and may be carried out if at least 60% of the patella can be maintained.Open fractures of the patella require emergency treatment with irrigation, debridement and fixation. Rehabilitation Irrespective of surgical or non-surgical resolution to the fracture, a physical therapist can advise on progressive weight-bearing exercises and help with strengthening muscles of the leg, improving range of motion of the knee and in reducing stiffness. Prognosis Outcomes with treatment are generally good, unless there is involvement of the articular surface or the quadriceps mechanism. There is an increased risk of developing osteoarthritis in people who have broken their patella.There is limited evidence supporting the different surgical interventions for treating fractures of the patella in adults. There is also no evidence of trials that could evaluate the effects of surgical treatment compared with the conservative treatment or other different types of conservative interventions. Epidemiology Patella fractures make up about 1% of all broken bones. Males are affected more often than females. Those of middle age are most often affected. 6% to 9% of patellar fractures are of the open type. An ageing population and global increase in the number of TKAs has led to an increasing number of periprosthetic fractures of which a patella fracture is one type. History Prior to the 19th century most patella fractures were treated non-surgically with extension splinting, frequently resulting in poorly joined fragments of bone and long-term pain and disability. Incomplete understanding of the importance of the patella led to the trend of removing the whole patella, also resulting in pain, disability and dissatisfaction. The first open reduction and internal fixation for a patella fracture was performed in 1877 by Scottish surgeon Sir Hector Cameron. Several techniques followed and materials used included metal loops, pins, kangaroo tendons and screws. Significant advances in surgery occurred in the 1950s with the development of banding after Herbert A. Haxton and others demonstrated that the patella was not just to protect the knee but important for straightening the leg. Subsequently, the three surgical treatments for displaced patella fractures became tension banding, partial patellectomy and total patellectomy, the decision of which to use tailored to the individual. References == External links ==
Bowel-associated dermatosis–arthritis syndrome	Bowel-associated dermatosis–arthritis syndrome (BADAS), is a complication of jejunoileal bypass surgery consisting of flu-like symptoms (fever, malaise), multiple painful joints (polyarthralgia), muscle aches (myalgia) and skin changes. It has been reported to occur in up to 20% of patients who had jejunoileal bypass surgery, a form of obesity surgery that is rarely performed today.An excessive immune response to gut bacteria is thought to cause BADAS. Antibiotics have been used successfully to treat the condition (including tetracyclines, macrolides, metronidazole and fluoroquinolones). Corticosteroids are an alternative. Surgical repair of the normal bowel transit, where possible, can be effective. BADAS has later been reported in patients with inflammatory bowel disease, diverticulitis and following resection of the stomach (gastrectomy). BADAS has also been reported following biliopancreatic diversion (a form of bariatric surgery, also known as Scopinaro procedure), and in one case, BADAS occurred in a patient with acute appendicitis. Since "bowel bypass syndrome" is not applicable to these cases, the term BADAS was coined by Jorizzo and co-authors in 1984. Symptoms and signs The most typical skin changes are a red patch (erythematous macula) with a central vesicle or pustule that heals without scarring. This maculopapular rash can recur every 4–6 weeks and predominantly affect the upper chest and arms. Erythema nodosum-like skin lesions can affect the legs. When a skin biopsy is examined under the microscope, there can be signs of a neutrophilic dermatosis. The joint pains in BADAS are typically episodic, migratory and affecting multiple joints. They can affect the small joints (e.g. interphalangeal joints of the fingers) and there can be associated tenosynovitis, but there is no erosion or deformation in the long term. Diarrhea may also occur. Mechanism Immune complexes are thought to cause blood vessel damage, attracting neutrophils into the skin and synovium in BADAS. These antigen-antibody complexes are thought to be caused by excessive exposure to bacterial antigens (especially peptidoglycans). Bacterial overgrowth appears to be a frequent underlying condition. These antibodies possibly stimulate migration of neutrophils into the affected joints and skin. The effect of antibacterial therapy supports a role for bacteria in the disease mechanism (pathogenesis). Diagnosis A diagnosis of this syndrome is made when an individual has the constellation of the characteristic recurrent neutrophilic dermatosis, flu-like symptoms, arthralgias or arthritis, and myalgias in the setting of a pathology of the bowels that is not best explained by another diagnosis. See also Sweets syndrome-like dermatosis List of cutaneous conditions == References ==
Autoimmune thyroiditis	Autoimmune thyroiditis, is a chronic disease in which the body interprets the thyroid glands and its hormone products T3, T4 and TSH as threats, therefore producing special antibodies that target the thyroids cells, thereby destroying it. It may present with hypothyroidism or hyperthyroidism and with or without a goiter. Signs and symptoms The symptoms may vary depending on the thyroid function, i.e. hyperthyroidism or hypothyroidism. Hyperthyroidism can cause sweating, rapid heart rate, anxiety, tremors, fatigue, difficulty sleeping, sudden weight loss, and protruding eyes. Hypothyroidism can cause weight gain, fatigue, dry skin, hair loss, intolerance to cold, and constipation. The effects of this disease may be permanent but can sometimes be transient. Symptoms may come and go depending on whether the person receives treatment, and whether the treatment takes effect. Causes Thyroid autoimmunity is familial. The disease is said to be inherited as a dominant trait since it has been reported that as many as fifty percent of the first degree relatives of patients with some type of autoimmune thyroiditis present with thyroid antibodies in serum.Few studies have even related it to chromosome 21 because of its high correlation with patients with Down syndrome and familial Alzheimer disease. This theory is controversial, since patients with Turner syndrome also present a high prevalence of autoimmune thyroiditis (up to fifty percent). High iodine consumption Autoimmune thyroiditis has a higher prevalence in societies that have a higher intake of iodine in their diet, such as the United States and Japan. Also, the rate of lymphocytic infiltration increased in areas where the iodine intake was once low, but increased due to iodine supplementation. "The prevalence of positive serum tests in such areas rises to over 40 percent within 0.5 to 5 years." Age It has been shown that "the prevalence of positive tests for thyroid antibodies increases with age, with a frequency as high as 33 percent in women 70 years old or older." The mean age of prevalence in women is higher than in men by one year, (58 and 59 years old respectively).Autoimmune thyroiditis can affect children. It is very rare in children under the age of five, but can occur; it accounts for around 40 percent of cases in adolescents with goiters.People with hypothyroidism over the age of 40 have an increased chance of developing autoimmune thyroiditis. Mechanism Thyroid autoantibodies appear mostly with the presence of lymphocytes in the targeted organ. Lymphocytes produce antibodies targeting three different thyroid proteins: Thyroid peroxidase Antibodies (TPOAb), Thyroglobulin Antibodies (TgAb), and Thyroid stimulating hormone receptor Antibodies (TRAb). The antibody attacks ultimately lead to hypothyroidism, which is caused by replacement of follicular cells with parenchymatous tissue.Some patients who are healthy may be positive for more than one of these antibodies. Doctors who attend to such patients will most likely do routine follow-ups on the patients health since, even though it is highly unlikely that they will present any thyroid problems, there is still a chance that they will develop some type of dysfunction with time. Categories Specialists separate autoimmune thyroiditis into two clinical categories. If goiters are present, it is understood as Hashimotos thyroiditis. If the thyroid is atrophic, and does not present goiters, it is called atrophic thyroiditis.Autoimmune thyroiditis can also refer to Graves disease, and various other forms of thyroid illnesses. If the symptoms of thyroiditis appear in women after giving birth, it is called postpartum thyroiditis. Diagnosis Various tests can be chosen depending on the presenting symptoms. Doctors may search for Thyroid peroxidase Antibodies (TPOAb) when a person has symptoms of hypothyroidism, or when a person will be started on a drug therapy associated with risks of developing hypothyroidism, such as lithium or Interferon alfa. This antibody is related to Hashimotos thyroiditis and Graves disease. If the person presents symptoms of hyperthyroidism, doctors are more likely to test for Thyroid stimulating hormone receptor Antibodies (TRAb), and monitor the effects of anti-thyroid therapy, also associated with Graves disease.Doctors may check Thyroglobulin Antibodies (TgAb) also, whenever a thyroglobulin test is performed to see if the antibody is interfering. TgAb may also be ordered in regular intervals after a person has been diagnosed with thyroid cancer, and just like TPOAb, it can be associated with Hashimotos thyroiditis. Treatment The usual therapy is Levothyroxine. References == External links ==
Alternariosis	Alternariosis is an infection by Alternaria, presenting cutaneously as focal, ulcerated papules and plaques.: 330 Treatment with itraconazole has been reported. See also Skin lesion References == External links ==
Irlen syndrome	Irlen syndrome, occasionally referred to as scotopic sensitivity syndrome (SSS) or Meares–Irlen syndrome, is a postulated disorder of vision or image-processing in the brain. Irlen syndrome is also sometimes referred to as asfedia or visual stress. Many mainstream professionals are skeptical of the concept. Research on Irlen syndrome has produced mixed results, finding a possible neurological basis for the condition but little or no evidence supporting the most commonly proposed treatment using tinted eyeglasses or overlays to aid reading. History In 1980, New Zealand teacher Olive Meares described the visual distortions some individuals reported when reading from white paper. In 1983, American psychologist Helen Irlen wrote a paper about the use of coloured overlays aiding the reading abilities of some people. Similar symptoms were separately described by Meares and Irlen, each unaware of the others work. Irlen, who was the first to systematically define the condition, named her findings "scotopic sensitivity", though in the discussions and debates over the following years, some referred to it as Meares-Irlen syndrome. The Irlen Institute, founded by Helen Irlen, describes scotopic sensitivity as "a perceptual processing disorder" related to brain interpretations of colours and light.It remains controversial whether non-Irlen-certified Meares-Irlen syndrome and the original Irlen syndrome are the same condition. Irlen syndrome, for example, seems to include a broader array of symptoms, including severe variants of the core condition. Basic testing for scotopic sensitivity was tried by optometrists, opticians and orthoptists in UK hospitals, and by optometrists and opticians in private practice employing a technique that used the Intuitive Colorimeter, developed under Medical Research Council licence. An alternative approach to correct Irlen syndrome was tried by Orthoscopics franchise in the UK, with wide colour coverage and tints manufactured by Hoyato match. Other commercial organisations have produced sets of therapeutic tints, although most have not received scientific evaluation.Studies investigating Irlens syndrome as a treatable condition have been criticised for having a biased and subjective approach to their research.Treatments offered by Irlens practitioners have not been found to be effective in improving reading ability. Classifications Irlen divides Irlen syndromes into six types: photophobia, distortion of the fundus, graphical distortions during reading, decreased visual field, difficulty in ocular fixation during reading and change in depth perception. Research The disorders have been studied in several institutions, including the Psychology Department at Essex University, the former Applied Psychology Unit, Cambridge University in England, and in the case of Meares-Irlen syndrome, Visual Unit at Glasgow Caledonian University in Scotland. As of 2012 the Visual Stress Unit offered non-commercial diagnostic and therapeutic services to individuals, and provided advice to the Scottish National Health Service. In Australia, Irlen syndrome was researched by Paul Whiting at the University of Sydney. Whiting set up the first Irlen Dyslexia Centre in Australia, which operated in the Childrens Centre at Sydney University for more than 15 years. Irlen syndrome was also studied in Australia by Greg Robinson (1944–2008) at the University of Newcastle. He was director of the Special Education Centre at the School of Education.In the US, peer-reviewed literature on the topic suggests that much is unknown about the cause of these disorders, ranging from the 2011 study in a journal of the American Academy of Pediatrics, "Irlen Colored Overlays Do not Alleviate Reading Difficulties" and the 2012 study in the journal Brain Topography, "A Functional Neuroimaging Case Study of Meares–Irlen Syndrome". The first, purely in relation to Meares-Irlen syndrome, finds that there is no evidence for one of the fundamental claims of therapeutic benefit. The second, which focused primarily on Irlen syndrome, found compelling evidence of unique brain function linked to the syndrome. Treatment The College of Optometrists (UK) has specified guidelines for optometrists who use the colorimeter system. A society for coloured lens prescribers has been established to provide a list of eye-care practitioners with expertise in the provision of coloured lenses for the treatment of visual stress. Irlen Method The Irlen Method uses coloured overlays and tinted lenses in the form of glass or contact lenses. The method is intended to reduce or eliminate perceptual processing errors; it is claimed the resultant retiming of visual signals in the brain improves the reading difficulties associated with scotopic sensitivity syndrome. Scientific repudiation Skepticism relating to scotopic sensitivity syndromes exact pathology has evolved on several fronts: Whether it exists as a distinct, predictably identifiable disease with a reasonable pathophysiological mechanism, or whether a range of symptoms from other conditions are being placed under this convenient heading; Whether it is causally or incidentally related to dyslexia, autism, or other conditions; and Whether existing methods of scotopic sensitivity syndrome treatment are appropriate and effective.A 2009 report by the American Academy of Pediatrics (AAP) does not find that there is conclusive scientific evidence for the use of coloured lenses (one treatment used to relieve symptoms of scotopic sensitivity syndrome) although it acknowledges anecdotal evidence in support of customized colored lenses. When discussing its scientific basis, the AAP mentions that "[t]he method used to select the lens or filter color has been highly variable, the color selection has also shown considerable variability, and the test-retest consistency has been poor" (p. 843). The association of scotopic sensitivity syndrome and dyslexia has been challenged by many authors in the optometric and ophthalmologic communities. Furthermore, many special education departments at universities challenge the validity of coloured lenses as an effective treatment for the condition as outlined by the Macquarie University Special Education Centre. In a joint statement, The American Academy of Ophthalmology, American Academy of Pediatrics, American Association for Pediatric Ophthalmology and Strabismus and American Association of Certified Orthoptists firmly repudiated the use of lenses, stating that there was no scientific evidence supporting their use. The expense of such treatment is unwarranted and may divert resources from evidence-based treatment. Critics claim that the symptoms of those with Scotopic Sensitivity Syndrome are related to already known visual perceptual and neurological disorders. According to a statement released by the American Optometric Association in 2004: There is evidence that the underlying symptoms associated with specifically Meares Irlen Syndrome, are related to identifiable vision anomalies, e.g., accommodative, binocular, and ocular motor dysfunctions, in many patients seeking help from coloured lenses. Furthermore, such conditions return to normal function when appropriately treated with lenses, prisms, or vision therapy. When patients exhibiting Meares Irlen Syndrome were treated with vision therapy, their symptoms were relieved. These patients were no longer classified as exhibiting this syndrome, and therefore did not demonstrate a need for the coloured overlays or tinted lenses. As outlined by Hyatt, Stephenson and Carter (2009): In 1990, the Journal of Learning Disabilities published a special issue that provided intensive coverage of Irlen lenses. In the preface to the issue, the editor in chief, Wiederholt, noted that each of the studies had serious theoretical, medical/physical, and methodological flaws, but were published along with articles critiquing the studies to provide readers with an overview of the Irlen procedures as well as guidance for conducting quality research studies. He, along with Hoyt (1990), Parker (1990), and Solan (1990), noted that these initial studies by Blaskey et al. (1990), OConnor, Sofo, Kendall, and Olsen (1990), and Robinson and Conway (1990) failed to support the treatment validity of colored overlays. See also References Further reading Hyatt, Keith J (February 2010). "Irlen Tinted Lenses and Overlay" (PDF). MUSEC Briefings. Macquarie University Special Education Centre (22). Archived from the original (PDF) on 29 August 2017. Retrieved 22 April 2017. Wilkins, Arnold J. (2003). Reading through color: how colored filters can reduce reading difficulty, eye strain, and headaches. Chichester: John Wiley & Sons. ISBN 0-470-85116-3. OCLC 78883050.
Neurotoxic shellfish poisoning	Neurotoxic shellfish poisoning (NSP) is caused by the consumption of brevetoxins, which are marine toxins produced by the dinoflagellate Karenia brevis (among several others). These toxins can produce a series of gastrointestinal and neurological effects. Outbreaks of NSP commonly take place following harmful algal bloom (HAB) events, commonly referred to as "Florida red tide" (given that blooms are more commonplace along the coasts of Florida and Texas, especially during late summer and early fall). Algal blooms are a naturally-occurring phenomenon, however their frequency has been increasing in recent decades at least in-part due to human activities, climate changes, and the eutrophication (over-abundance of plant nutrients as a result of agricultural runoff, deforestation, river bed erosion, etc.) of marine waters. HABs have been occurring for all of documented history, evidenced by the Native Americans understanding of the dangers of shellfish consumption during periods of marine bioluminescence (a phenomenon observed during algal blooms). Blooms have been noted to occur as far north as North Carolina and are commonly seen alongside the widespread death of fish and sea birds. In addition to the effects on human health, the economic impact of HAB-associated shellfish toxin outbreaks can have significant economic implications as well due to not only the associated healthcare costs, but the adverse impact on the commercial shellfish industry. Causes Humans are typically exposed to these potent natural toxins via filter-feeding mollusks (i.e., shellfish), because shellfish accumulate biotoxins in their flesh due to the way that they feed. Human exposure seems to be most common via consumption of commonly harvested shellfish such as clams, oysters, and mussels, although it has been proposed that exposure to lower levels of brevetoxins can take place following the consumption of certain planktivorous fish. Toxins will typically be found in the flesh of shellfish for up to 2–8 weeks following a HAB event, however there have been reports of toxin retention for nearly one year post-bloom. Notably, brevetoxins are tasteless and odorless and cannot be eradicated by rinsing, cleaning, cooking, freezing, or application of acid. To date, there is no reasonable means of preventing the uptake of toxins by shellfish, nor of removing the toxins from shellfish after harvest. Biochemistry/Toxicology Brevetoxins are a group of greater than ten lipid-soluble cyclic polyethers that bind to a specific site on the voltage-gated sodium channel (VGSC), leading to an influx of sodium ions into the cell. This results in activation of nerves and spontaneous nerve cell membrane depolarization and firing. Due to their lipid-solubility, brevetoxins are able to pass through cell membranes and cross the blood-brain barrier. They are metabolized primarily by the liver and are excreted in the bile, although it is thought that urinary excretion plays a role in toxin clearance as well. Additionally, brevetoxins can bind a separate site on VGSCs, causing release of neurotransmitters (such as acetylcholine), resulting in tracheal smooth muscle contraction and widespread mast cell degranulation. Presentation and Diagnosis Diagnosis of NSP is made based on clinical presentation as well as history findings including recent consumption of shellfish. On average, symptoms begin 3-4 hours after consumption, but can begin anywhere from several minutes to 18 hours afterward. Symptoms typically include neurologic and gastrointestinal issues including: nauseavomiting diarrhea numbness and tingling in the lips, mouth, face, and extremitiesThe latter has been described as “nerves being on fire” or “ants crawling and biting all over”.Other less common symptoms can include: ataxia loss of coordination limb paralysis reversal of hot and cold sensations slurred speech headache pupil dilation generalized fatiguePatients may be thought to be disoriented or intoxicated. Rarely, patients may experience respiratory distress requiring ventilatory support. Despite this seemingly severe constellation of symptoms, there have been no documented deaths due to NSP. NSP can present similar to other disorders such as: common food poisoning seafood allergy paralytic shellfish poisoning ciguatera fish poisoning pesticide poisoning alcohol intoxication certain psychiatric disorders.Due to the extensive list of disorders with similar symptoms, a detailed food history is necessary to make the diagnosis. Management and treatment Treatment for NSP is mostly supportive with monitoring and symptom management. Intravenous fluids and observation of respiratory function are the mainstay of treatment along with pain control. Activated charcoal can be given if the patient presents within four hours of consumption to decontaminate the gastrointestinal tract. Currently, there is no specific antidote for brevetoxins, however there may be a role for mannitol (the primary treatment for ciguatoxin, a dinoflagellate-produced toxin found in some species of fish) or brevatal, a natural antagonist of brevetoxin produced by K. brevis. Though public health policy differs by state, measures are taken to prevent shellfish poisoning outbreaks. The Florida Department of Health has added NSP to their list of reportable diseases. Additionally, since the mid-1970s the Florida Department of Environmental Protection has conducted monitoring of dinoflagellate levels and restricted the harvest of shellfish from nearby shellfish beds when levels are dangerously elevated. Shellfish beds are subsequently opened after two weeks with confirmation of safety by mouse bioassay testing (mouse bioassay testing involves the injection of mice with shellfish extract with subsequent observation for mouse death). See also Amnesic shellfish poisoning Diarrheal shellfish poisoning Paralytic shellfish poisoning Ciguatera fish poisoning == References ==
Thyroid hormone resistance	Thyroid hormone resistance (also resistance to thyroid hormone (RTH), and sometimes Refetoff syndrome) describes a rare syndrome in which the thyroid hormone levels are elevated but the thyroid stimulating hormone (TSH) level is not suppressed, or not completely suppressed as would be expected. The first report of the condition appeared in 1967. Essentially this is decreased end organ responsiveness to thyroid hormones. A new term "impaired sensitivity to thyroid hormone" has been suggested in March 2014 by Refetoff et al. Presentation The syndrome can present with variable symptoms, even between members of the same family harboring the same mutation. Typically most or all tissues are resistant to thyroid hormone, so despite raised measures of serum thyroid hormone the individual may appear euthyroid (have no symptoms of over- or underactivity of the thyroid gland). The most common symptoms are goiter and tachycardia. It has also been linked to some cases of attention deficit hyperactivity disorder (ADHD), although the majority of people with that diagnosis have no thyroid problems. An association with depression has been proposed. Causes Normal thyroid hormone function requires normal thyroid hormone transport across cell membrane, appropriate deiodination, thyroid hormone nuclear receptor, thyroid hormone response elements, co-activators, co-repressors, and normal histone acetylation. Any abnormalities in this chain can result in thyroid hormone resistance and it has not been as well studied as the various forms of insulin resistance.The most well known cause of the syndrome are mutations of the β (beta) form (THRB gene) of the thyroid hormone receptor, of which over 100 different mutations have been documented. Mutations in MCT8 and SECISBP2 have also been associated with this condition. Regulation of thyroid hormone secretion Hypothalamus secretes a hormone called thyrotropin releasing hormone (TRH) which in turn release thyroid stimulating hormone (TSH). TSH signals thyroid to secrete thyroid hormones thyroxine (T4) and triiodothyronine (T3). T4 gets converted to active T3 in peripheral tissues with the help of deiodinase enzymes. T3 negatively feedback on the pituitary and decreases TSH secretion. Diagnosis The characteristic blood test results for this disorder can also be found in other disorders (for example TSH-oma (pituitary adenoma), or other pituitary disorders). The diagnosis may involve identifying a mutation of the thyroid receptor, which is present in approximately 85% of cases. Management Beta blockers, like metoprolol, are sometimes used to help suppress symptoms. Incidence Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births. More than 1000 individuals have been identified with thyroid hormone resistance, of which 85% had thyroid hormone beta receptor mutation. References == External links ==
Monoarthritis	Monoarthritis is inflammation (arthritis) of one joint at a time. It is usually caused by trauma, infection, or crystalline arthritis. Causes Septic arthritis Septic arthritis is due to a bacterial infection to the joint. It requires urgent joint washout in the operating room followed by intravenous antibiotic therapy for large joints. Small joints or children can be treated with repeated aspirations and intravenous antibiotics. Gout In gout, the acute inflammatory arthritis is caused by excess uric acid caused by either overproduction or under-excretion. Before the age of menopause, women have a lower incidence than males, but the rates are equal above this age. Gout can cause mono- or polyarthritis, but usually results in monoarthritis first. Pseudogout When monoarthritis is caused by pseudogout (calcium pyrophosphate deposition disease, CPPD), the inflammation usually lasts days to weeks, and involves the knees in half of all attacks. Like gout, attacks can occur spontaneously or with physical trauma or metabolic stress. Patients may feel well in between pseudogout attacks, and 5% present with pseudo-rheumatoid symptoms. Osteoarthritis Osteoarthritis is a degenerative disease commonly involving the knees and hips. It results from erosion of the cartilage protecting the bones from rubbing together. Osteoarthritis is, in fact, a polyarthritis, but it starts initially in one joint before the involvement of other joints, hence, mimicking monoarthritis. Psoriatic arthritis Occurs in 5-10% of patients who have psoriasis. Classic presentation involves the DIP(distal interphalangeal joints). Morning stiffness is present. Deformity of involved joints, dactylitis and nail involvement are common. Well demarcated red plaques with silvery scaling - the classic lesions of psoriasis are seen on the dorsum of the hand. Diagnosis When faced with monoarthritis, one of the main decisions to make is whether to perform a joint aspirate by inserting a needle into the affected joint and removing some fluid for microscopic analysis. This decision is largely taken on inflammatory markers in blood tests (e.g. CRP), fever and the clinical picture. The main use of aspiration is to detect bacteria and neutrophil granulocytes (in septic arthritis) and crystals (crystal arthropathies). Treatment See also Gout Pseudogout Septic arthritis Osteoarthritis References == External links ==
Cryofibrinogenemia	Cryofibrinogenemia refers to a condition classified as a fibrinogen disorder in which a persons blood plasma is allowed to cool substantially (i.e. from its normal temperature of 37 °C to the near-freezing temperature of 4 °C), causing the (reversible) precipitation of a complex containing fibrinogen, fibrin, fibronectin, and, occasionally, small amounts of fibrin split products, albumin, immunoglobulins and other plasma proteins. Return of plasma to more normal temperature resolubilizes the precipitate. Cryofibrinogenemia may occur in individuals that have no obvious evidence of precipitate-induced tissue damage (asymptomatic cryofibrinogenemia), or in consequence of cryofibrinogen precipitation resulting in blood clots in small and medium size arteries and veins. When occurring in association with another causual disease, cryofibrinogenemic disease is referred as secondary cryofibrinogenemia; in the absence of such an association, it is referred to as primary cryofibrinogenemia. Cryofibrinogen precipitation The reasons for the cold temperature-induced in vitro as well as the in vivo precipitation of the fibrinogen-containing complex is unknown. The fibrinogen involved in precipitate formation appears to have a normal structure. This separates cryofibrinogenemia from two pathological blood-clotting/bleeding diseases that can mimic cryofibrinogenemia but are due to structurally abnormal fibrinogen viz., dysfibrinogenemia and hypodysfibrinogenemia. Based on in vitro studies, three causes have been hypothesized for the precipitate formed in cryofibrinogenemia. 1) The blood and plasma of individuals with cryofibrinogenemia lack the fibrinolysis activity that normally degrades and thereby resolubilizes the precipitate. This hypothesis is based on the findings that some but not all individuals with the disorder have abnormally high levels of one or two of the agents, alpha-1 antitrypsin and alpha-2-Macroglobulin, which inhibit the naturally occurring fibrinolytic agent, plasmin. 2) The blood of individuals has an increased ability of the pro-coagulant thrombin to bind fibrinogen and thereby promote coagulation. 3) The blood of individuals, particularly those with cryofibriognemic disease associated with other severe disorders, has high levels of immunological elements such as immunoglobulins or immune complexes that interact with fibronectin to promote blood clotting. This hypothesis is base on findings that some patients with cyrofibrinogenemic disease improve when treated with immunosuppressive drugs. Further basic research into this area is required. Asymptomatic cryofibrinogenemia The occurrence of cryofibrinogenemia as defined by a 4 °C-induced formation of fibrinogen-based precipitation in plasma occurs in 2% to 9% of asymptomatic individuals and 8% to 13% of hospitalized patients without symptoms attributable to this precipitation. Most of these cases have relatively low levels of cold temperature-induced fibrinogen precipitate levels (<50 milligram/liter of fibrinogen) and do not have a disorder associated with the development of cryofibrinogenmia. Associated disorders Cryoglobulinemia may occur without evidence of an underlying associated disorders, i.e. primary cryoglobulinemia (also termed essential cryoglobulinemia) or, far more commonly, with evidence of an underlying disease, i.e. secondary cryoglobulinemia. Secondary cryofibrinogenemia can develop in individuals with infection (~12% of cases), malignant or premalignant disorders (21%), vasculitis (25%), and autoimmune diseases (42%). In these cases of the secondary disorder, cryofibrinogenemia may or may not cause tissue injury and/or other symptoms and the actual cause-effect relationship between these diseases and the development of cryofibrinogenemia is unclear. Cryofibrinogenemia can also occur in association with the intake of certain drugs. Infection-associated cryofibrinogenemia Acute bacterial and mycobacterium infections are sometimes associated with cryofibriongenemia. In these cases, cryofibrinogenemia is usually transient and rapidly resolves after appropriate anti-bacterial treatment. In HIV/AIDS virus, Epstein–Barr virus, cytomegalovirus, varicella zoster virus, herpes simplex virus, and hepatitis virus infections any rise in circulating cryofibrinogen is more sustained and potentially symptomatic. For example, one large study of the most thoroughly study example of viral infection-associated cryofibrinogenmia, Hepatitis C infection, found that cryofibrinogenemia occurred in 37% of cases, was associated with concurrent cryoglobulinemia in 89% of cases, and led to significantly increased vascular disruption. Antiviral therapy resulted in complete resolution of the cryofibrinogenemia in only ~50% of these cases. Malignancy-associated cryofibrinogenemia Lymphoproliferative disorders such as B-cell lymphomas, T-cell lymphomas, chronic lymphocytic leukemia, and various plasma cell dyscrasias (e.g. multiple myeloma, Waldenströms macroglobulinemia, and the premalignant precursors to these two diseases, MGUS, smoldering multiple myeloma, IgM MGUS, and smoldering Waldenströms macroglobulinemia as well as adenocarcinomas of the stomach, liver, lung, colon, and other solid tumor cancers have been reported to be associated with symptomatic or asymptomatic cryfibrinogenemia. Vasculitis-associated cryofibrinogenemia Cryofibrinogenemia is often associated with inflammatory disease of the arteries and/or veins. These vasculitis-associated diseases include ANCA-associated vasculitides, giant cell arteritis, Behcet disease, polyarteritis nodosa, and Henoch–Schonlein purpura. Cryofibrinogenemia is also often associated with the inflammatory vasculitis that accompanies mixed Cryoglobulinemia#Classification, i.e. cryoglobulinemic vasculitis, particularly but not exclusively in instances where hepatitis C virus is an underlining disease. Autoimmune disease-associated cryofibrinogenemia A broad range of autoimmune diseases have been reported to be associated with cryofibrinogenemia. These diseases include systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, mixed connective tissue disease, polymyositis, dermatomyositis, systemic sclerosis, antiphospholipid antibody syndrome, Hashimoto disease, Graves disease, sarcoidosis, pyoderma gangrenosum, spondyloarthropathy, Crohns disease, and ulcerative colitis. Cryofibrinogenemic disease Symptoms and signs Cryofibrinogenemic disease commonly begins in adults aged 40–50 years old with symptoms of the diseases occurring in the almost always affected organ, skin. Cutaneous symptoms include one or more of the following: cold contact-induced urticarial (which may be the first sign of the disease); painful episodes of finger and/or toe arterial spasms termed Raynaud phenomena; cyanosis, a palpable purpura termed cryofibrinogenemic purpura), and a lace-like purplish discoloration termed livedo reticularis all of which occur primarily in the lower extremities but some of which may occur in the nose, ears, and buttocks; non-healing painful ulcerations and gangrene of the areas impacted by the cited symptoms. Patients also have a history of cold sensitivity (~25% of cases), arthralgia (14–58%), neuritis (7–19%), myalgia (0–14%); and overt thrombosis of arteries and veins (25–40%) which may on rare occasions involve major arteries such of those of the brain and kidney. Signs of renal involvement (proteinuria, hematuria, decreased glomerular filtration rate, and/or, rarely, renal failure) occur in 4 to 25% of cases. Compared to secondary cryofibrinogemia, primary crygofibrinogenemia has a higher incidence of cutaneous lesions, arthralgia, and cold sensitivity while having a far lower incidence of renal involvement. Patients with secondary cryofibrinogenemia also exhibit signs and symptoms specific to the infectious, malignant, premalignant vasculitis, and autoimmune disorders associated with their disease. While rare, individuals with cryofibrinogenemic disease may experience pathological bleeding due to the consumption of blood clotting factors consequential to the formation of cryofibrinogen precipitates. Diagnosis Suggested diagnostic criteria for cryoglobulinemic disease fall into the following obligatory and additional categories: Obligatory criteria: 1) cold sensitivity; 2) cutaneous symptoms (i.e. urticaria, purpura, Raynaud phenomenon, ulceration/necrosis/gangrene, and/or livedo reticularis); 3) arterial and/or venous thrombotic events; fever; 4) arthralgia/myalgia; 5) neuritis in >1 site; and 6) renal disorder. Additional criteria: 1) typical biopsy findings at site(s) of involvement and 2) angiogram evidence of occlusion in one or more small to medium-sized arteries.The diagnosis of secondary cryofibrinogenemia also requires evidence for the cited infectious, malignant, premalignant vasculitis, and autoimmune disorders while the diagnosis of primary cryofibriongenemia requires a lack of evidence for 1) the cited associated disorders, 2) other vascular occlusive diseases, and 3) cryoglobulinemia. Treatment Studies on the treatment of cryofibrinoginemic disease have involved relatively few patients, are limited primarily to case reports, and differ based on whether the disease is primary or secondary. In all cases of cryofibrinogenemic disease, however, patients should avoid the exposure of affected body parts to cold weather or other environmental triggers of symptoms and avoid using cigarettes or other tobacco products. In severe cases, these individuals also risk developing serious thrombotic events which lead to tissue necrosis that may result in secondary bacterial infections and require intensive antimicrobial therapy and/or amputations. Careful treatment of these developments is required. Primary cryofibrinogenemic disease Success in treating the primary disease has been reported using blood clot lysing agents such as anabolic steroids (e.g. danazol or stanozolol which is no longer available in the United States), streptokinase, and streptodornase; anticoagulants such as heparin and warfarin, and immunosuppressive drug regimens such as a corticosteroid (e.g. prednisone) combined with either azathioprine of chlorambucil. Very moderate cases may do well by simply avoiding cold exposure. Treatment with a corticosteroid plus low-dose aspirin followed by maintenance therapy with an anabolic steroid where necessary are recommended for moderately severe cases. Very severe cases generally require an immunosuppressive drug regimen and if extreme or life-threatening require resorting to plasmaphoresis or plasma exchange. Cryofiltration apheresis, a method to remove plasma agents by removing cold-induced precipitated material, may be an effective alternative to plasmaphoresis and plasma exchange but is still regarded as second-line therapy for cryofibirnogenemic disease treatment.During the several years following its initial diagnosis, some 27 to 47% of primary cryofibrinoginemic diseases are complicated by the development of a B-cell or T-cell lymphoma. That is, the cryofibrinoginemic disease may appear to precede by years the malignant disorder to which it is associated. Accordingly, patients require careful follow-up not only to treat their primary cryofibrinoginemic disease but also to monitor them for movement to the diagnosis of secondary cryofibrinoginemic disease caused by the development of one of these hematological malignancies. Secondary cryofibrinogenemic disease Treatment of secondary cryofibrinoginemic disease may use the same methods used for treating the primary disease wherever necessary but focus on treating the associated infectious, malignant, premalignant, vasculitis, or autoimmune disorder with the methods prescribed for the associated disorder. Case report studies suggest that: corticosteroids and immunosuppressive drug regimens, antimicrobial therapy, and anti-neoplastic regimens can be effective treatments for controlling the cryfibrinoginemic disease in cases associated respectively with autoimmune, infectious, and premalignant/malignant disorders. Prognosis While the prognosis of cryofibrinoginemic disease varies greatly depending on its severity as well as the severity of its associated disorders, satisfactory clinical outcomes are reported in 50 to 80% of patients with primary or secondary disease treated with corticosteroid and/or immunosuppressive regimens. However, relapses occur within the first 6 months after stopping or decreasing therapy in 40 to 76% of cases. Sepsis resulting from infection of necrotic tissue is the most common threat to life in primary disease whereas the associated disorder is a critical determinant of prognosis in secondary disease. See also Cryofibrinogenemic purpura Cryoglobulinemia Dysfibrinogenemia Hypodysfibrinogenemia References Further reading Amdo, TD; Welker, JA (Mar 1, 2004). "An approach to the diagnosis and treatment of cryofibrinogenemia" (PDF). The American Journal of Medicine. 116 (5): 332–7. doi:10.1016/j.amjmed.2003.09.033. PMID 14984819. Archived from the original (PDF) on February 2, 2014. Retrieved January 25, 2014. Michaud, M; Pourrat, J (Apr 2013). "Cryofibrinogenemia". Journal of Clinical Rheumatology. 19 (3): 142–8. doi:10.1097/RHU.0b013e318289e06e. PMID 23519183. Kalbfleisch, John M.; Bird, Robert M. (3 November 1960). "Cryofibrinogenemia". New England Journal of Medicine. 263 (18): 881–886. doi:10.1056/NEJM196011032631803. PMID 13750865. Begin, Philippe; Leclerc, Georgette (22 August 2013). "Familial Primary Cryofibrinogenemia". New England Journal of Medicine. 369 (8): e10. doi:10.1056/NEJMicm1300987. PMID 23964955. van Geest, AJ; van Dooren-Greebe, RJ; Andriessen, MP; Blomjous, CE; Go, IH (Jan 1999). "Familial primary cryofibrinogenemia". Journal of the European Academy of Dermatology and Venereology. 12 (1): 47–50. doi:10.1111/j.1468-3083.1999.tb00808.x. PMID 10188150. S2CID 23748363. Soyfoo, MS; Goubella, A; Cogan, E; Wautrecht, JC; Ocmant, A; Stordeur, P (15 November 2011). "Clinical Significance of Cryofibrinogenemia: Possible Pathophysiological Link with Raynauds Phenomenon". The Journal of Rheumatology. 39 (1): 119–124. doi:10.3899/jrheum.110793. PMID 22089468. S2CID 29987316. == External links ==
Neonatal lupus erythematosus	Neonatal lupus erythematosus is an autoimmune disease in an infant born to a mother with anti-Ro/SSA and with or without anti-La/SSB antibodies. The disease most commonly presents with a rash resembling subacute cutaneous lupus erythematosus and can have systemic abnormalities such as complete heart block or hepatosplenomegaly. Neonatal lupus is usually benign and self-limited. Many of the clinical manifestations are transient, but certain heart problems can be permanent. Diagnosis is based on maternal antibodies and clinical manifestations. Treatment and management is mainly supportive and focused on preventing complete heart block if possible. Pathogenesis Ro/SSA and La/SSB are proteins found inside cells. Anti-Ro/SSA and anti-La/SSB are antibodies that form against these proteins. These antibodies can be seen in autoimmune diseases, the most common being Lupus and Sjögrens. Mothers can have these antibodies circulating in their blood without having any signs or symptoms of an autoimmune disease. Babies born to mothers with these antibodies have a chance of developing neonatal lupus erythematosus. This occurs when maternal anti-Ro/SSA and anti-La/SSB antibodies enter fetal circulation and affect neonatal organs by crossing the placenta using FcRn receptors. The mechanism in which the antibodies affect organs is not yet completely understood. For the heart, it is thought that these antibodies bind to cells in the heart that go through physiologic cell death during embryogenesis. This leads to heart cell injury which causes secondary fibrosis in the conduction system, ultimately causing heart block. These antibodies can also affect calcium channels which are needed to initiate action potentials. Disruption to action potential propagation can affect the AV and SA nodes which are part of the conduction system of the heart.Fetal susceptibility and environmental factors could also play a role in pathogenesis since not all infants develop congenital heart block even when exposed to antibodies. Clinical manifestations Neonatal lupus can present with several signs and symptoms. The most common manifestations involve the heart and skin. Problems involving the liver, gallbladder, brain, and blood can be seen but are usually transient. Heart Cardiac manifestations present more commonly in utero, but can also present after birth. The most common complications are varying degrees of heart block and endocardial fibroelastosis. A large percentage of infants diagnosed with isolated congenital heart block are associated to neonatal lupus. Heart block occurs when there is dysfunction in the conduction system, preventing impulses from traveling from the atria to the ventricles. Heart block can initially present with bradycardia in the prenatal period, usually around the second trimester. Infants with lower grades of heart block can progress to higher grades, but they can also present with rapid onset of complete heart block. Endocardial fibroelastosis is considered a type of cardiomyopathy that occurs in response to heart cell injury and can be seen with or without conduction system dysfunction.Common complications First degree heart block Second degree heart block Third degree heart block (Complete heart block) Endocardial fibroelastosisOther complications seen with neonatal lupus Patent ductus arteriosus Patent foramen ovale Pulmonic stenosis Pulmonary valvular dysplasia Fusion of chordae tendineae of the tricuspid valve Ostium secundum type atrial septal defects Skin A rash can be seen upon delivery. It is commonly found on the head and face, but can also be found on other parts of the body. It is most commonly seen around the eyes. The rash can be described as raised, red, and ring-shaped. The rash is not always visible at birth and can become more prominent after UV light exposure. Antibodies coming from the mother have a certain life span. Because of this, the rash usually lasts 6–8 months, resolving after the maternal antibodies are no longer in circulation. Telangiectasia has also been seen and can occur with or without the ring-shaped rash. Red, ring-shaped rash of face and head Telangiectasia Liver and gallbladder Severity in which the liver is affected can range from mildly elevated liver enzymes to liver failure. Elevated transaminases Hyperbilirubinemia Cholestasis Hepatitis Blood The conditions listed below have been reported with no issues of bleeding or sepsis. Anemia Neutropenia Thrombocytopenia Aplastic anemia Brain Although the conditions below have been reported, it is still uncertain that these manifestations are related to anti-Ro/SSA and anti-La/SSB antibodies. Majority of the neurologic conditions were found incidentally with no neurological signs or symptoms present and did not lead to physical disability or need for surgery. Hydrocephalus Macrocephaly Vasculopathy Hypocalcemic seizures Spastic diplegia Diagnosis An infant is diagnosed with neonatal lupus if maternal antibodies, anti-Ro/SSA, anti-La/SSB, or less commonly anti-ribonucleoprotein, are present and if any of the clinical manifestations are present without any other explanation. Screening Screening includes testing for maternal antibodies and evaluating for heart block in utero. Universal screening is not recommended. Screening is usually performed when there is a higher likelihood for neonatal lupus such as individuals who are more likely to have antibodies due to autoimmune diseases or individuals who have had prior pregnancies complicated with neonatal lupus. If a fetus develops heart block, screening for maternal antibodies can be considered. Monitoring for heart block can be done using a fetal echocardiogram. Management Infants with neonatal lupus are managed with supportive care. This means treating or monitoring the symptoms that can occur from this disease. For example, avoiding sunlight so that the infants rash wont worsen. Many of the manifestations are transient, but once complete heart block occurs, it is irreversible. Heart block can be managed in utero if diagnosed during pregnancy. Infants born to mothers with anti-Ro/SSA and anti-La/SSB should have an ECG performed to check for heart abnormalities if none were seen while in the uterus. In utero Fetal heart block treatment varies based on the degree. First degree heart block is usually treated with glucocorticoids, but it can also reverse on its own. As of right now, treatment guidelines for first-degree heart block is controversial due to lack of evidence. Second degree heart block commonly progresses to complete heart block. Second degree heart block can also reverse on its own. Treatment includes fluorinated glucocorticoids and immunoglobulin therapy. Third degree heart block is irreversible, and many treatments have been attempted without success. Management is mainly expectant. Early delivery should be avoided unless other complications arise. In third degree heart block, if the ventricular heart rate drops below 50-55 beats per minute, maternal beta-antagonists can be given. Glucocorticoids and immunoglobulin therapy can be used for endocardial fibroelastosis, but effectiveness is still unclear. See also Congenital heart block Lupus erythematosus References == External links ==
Palmoplantar hyperhidrosis	A palmoplantar hyperhidrosis is excessive sweating localized to the palms of the hands and soles of the feet. It is a form of focal hyperhidrosis in that the excessive sweating is limited to a specific region of the body. As with other types of focal hyperhidrosis (e.g. axillary and craniofacial) the sweating tends to worsen during warm weather. See also Hyperhidrosis == References ==
Enterocutaneous fistula	An enterocutaneous fistula (ECF) is an abnormal communication between the small or large bowel and the skin that allows the contents of the stomach or intestines to leak through an opening in the skin. Causes The mnemonic HIS FRIENDS can be used to memorize characteristics which impede the closure of ECF.H: high output I: IBD S:short tract F Foreign body R Radiation I Infection or Inflammatory bowel disease E Epithelialization N Neoplasm D Distal obstruction S Short tract (<2 cm) Diagnosis Classification Congenital types: tracheoesophageal, vitellointestinal duct, patent urachus, rectovaginal Acquired: trauma (postoperative), radiation, malignancy, infection Two categories Low-output fistula: < 500 mL/day High-output fistula: > 500 mL/day Three categories Low-output fistula: < 200 mL/day Moderate-output fistula: 200–500 mL/day High-output fistula: > 500 mL/day Treatment The majority will close spontaneously within approximately 6 weeks. If it has not closed by 12 weeks, it is unlikely to do so and definitive surgery should be planned. The median time to definitive repair from fistula onset was 6 months (range 1 day to 28 months). The 6-month time course is commonly utilized by groups with significant experience treating fistulas, owing to the trend in encountering a less hostile abdomen than in the early phases. Some evidence also suggests that somatostatin can be an effective treatment with respect to reducing closure time and improving the spontaneous closure rate of enterocutaneous fistulas. References Metcalf C (1999). "Enterocutaneous fistulae". Journal of Wound Care. 8 (3): 141–142. doi:10.12968/jowc.1999.8.3.25854.
Granuloma multiforme	Granuloma multiforme is a cutaneous condition most commonly seen in central Africa, and rarely elsewhere, characterized by skin lesions that are on the upper trunk and arms in sun-exposed areas.: 707 It may be confused with tuberculoid leprosy, with which it has clinical similarities. The condition was first noted by Gosset in the 1940s, but it was not until 1964 that Leiker coined the term to describe "a disease resembling leprosy" in his study in Nigeria. See also Skin lesion References == External links ==
Pancreatic cancer	Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass. These cancerous cells have the ability to invade other parts of the body. A number of types of pancreatic cancer are known.The most common, pancreatic adenocarcinoma, accounts for about 90% of cases, and the term "pancreatic cancer" is sometimes used to refer only to that type. These adenocarcinomas start within the part of the pancreas that makes digestive enzymes. Several other types of cancer, which collectively represent the majority of the non-adenocarcinomas, can also arise from these cells. About 1–2% of cases of pancreatic cancer are neuroendocrine tumors, which arise from the hormone-producing cells of the pancreas. These are generally less aggressive than pancreatic adenocarcinoma.Signs and symptoms of the most-common form of pancreatic cancer may include yellow skin, abdominal or back pain, unexplained weight loss, light-colored stools, dark urine, and loss of appetite. Usually, no symptoms are seen in the diseases early stages, and symptoms that are specific enough to suggest pancreatic cancer typically do not develop until the disease has reached an advanced stage. By the time of diagnosis, pancreatic cancer has often spread to other parts of the body.Pancreatic cancer rarely occurs before the age of 40, and more than half of cases of pancreatic adenocarcinoma occur in those over 70. Risk factors for pancreatic cancer include tobacco smoking, obesity, diabetes, and certain rare genetic conditions. About 25% of cases are linked to smoking, and 5–10% are linked to inherited genes. Pancreatic cancer is usually diagnosed by a combination of medical imaging techniques such as ultrasound or computed tomography, blood tests, and examination of tissue samples (biopsy). The disease is divided into stages, from early (stage I) to late (stage IV). Screening the general population has not been found to be effective.The risk of developing pancreatic cancer is lower among nonsmokers, and people who maintain a healthy weight and limit their consumption of red or processed meat; however, the risk is greater for men, especially at very high levels of red meat consumption. Smokers chances of developing the disease decrease if they stop smoking and almost return to that of the rest of the population after 20 years. Pancreatic cancer can be treated with surgery, radiotherapy, chemotherapy, palliative care, or a combination of these. Treatment options are partly based on the cancer stage. Surgery is the only treatment that can cure pancreatic adenocarcinoma, and may also be done to improve quality of life without the potential for cure. Pain management and medications to improve digestion are sometimes needed. Early palliative care is recommended even for those receiving treatment that aims for a cure.In 2015, pancreatic cancers of all types resulted in 411,600 deaths globally. Pancreatic cancer is the fifth-most-common cause of death from cancer in the United Kingdom, and the third most-common in the United States. The disease occurs most often in the developed world, where about 70% of the new cases in 2012 originated. Pancreatic adenocarcinoma typically has a very poor prognosis; after diagnosis, 25% of people survive one year and 5% live for five years. For cancers diagnosed early, the five-year survival rate rises to about 20%. Neuroendocrine cancers have better outcomes; at five years from diagnosis, 65% of those diagnosed are living, though survival considerably varies depending on the type of tumor. Types The many types of pancreatic cancer can be divided into two general groups. The vast majority of cases (about 95%) occur in the part of the pancreas that produces digestive enzymes, known as the exocrine component. Several subtypes of exocrine pancreatic cancers are described, but their diagnosis and treatment have much in common. The small minority of cancers that arise in the hormone-producing (endocrine) tissue of the pancreas have different clinical characteristics and are called pancreatic neuroendocrine tumors, sometimes abbreviated as "PanNETs". Both groups occur mainly (but not exclusively) in people over 40, and are slightly more common in men, but some rare subtypes mainly occur in women or children. Exocrine cancers The exocrine group is dominated by pancreatic adenocarcinoma (variations of this name may add "invasive" and "ductal"), which is by far the most common type, representing about 85% of all pancreatic cancers. Nearly all these start in the ducts of the pancreas, as pancreatic ductal adenocarcinoma (PDAC). This is despite the fact that the tissue from which it arises – the pancreatic ductal epithelium – represents less than 10% of the pancreas by cell volume, because it constitutes only the ducts (an extensive but capillary-like duct-system fanning out) within the pancreas. This cancer originates in the ducts that carry secretions (such as enzymes and bicarbonate) away from the pancreas. About 60–70% of adenocarcinomas occur in the head of the pancreas.The next-most common type, acinar cell carcinoma of the pancreas, arises in the clusters of cells that produce these enzymes, and represents 5% of exocrine pancreas cancers. Like the functioning endocrine cancers described below, acinar cell carcinomas may cause over-production of certain molecules, in this case digestive enzymes, which may cause symptoms such as skin rashes and joint pain. Cystadenocarcinomas account for 1% of pancreatic cancers, and they have a better prognosis than the other exocrine types.Pancreatoblastoma is a rare form, mostly occurring in childhood, and with a relatively good prognosis. Other exocrine cancers include adenosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells. Solid pseudopapillary tumor is a rare low-grade neoplasm that mainly affects younger women, and generally has a very good prognosis.Pancreatic mucinous cystic neoplasms are a broad group of pancreas tumors that have varying malignant potential. They are being detected at a greatly increased rate as CT scans become more powerful and common, and discussion continues as how best to assess and treat them, given that many are benign. Neuroendocrine The small minority of tumors that arise elsewhere in the pancreas are mainly pancreatic neuroendocrine tumors (PanNETs). Neuroendocrine tumors (NETs) are a diverse group of benign or malignant tumors that arise from the bodys neuroendocrine cells, which are responsible for integrating the nervous and endocrine systems. NETs can start in most organs of the body, including the pancreas, where the various malignant types are all considered to be rare. PanNETs are grouped into functioning and nonfunctioning types, depending on the degree to which they produce hormones. The functioning types secrete hormones such as insulin, gastrin, and glucagon into the bloodstream, often in large quantities, giving rise to serious symptoms such as low blood sugar, but also favoring relatively early detection. The most common functioning PanNETs are insulinomas and gastrinomas, named after the hormones they secrete. The nonfunctioning types do not secrete hormones in a sufficient quantity to give rise to overt clinical symptoms, so nonfunctioning PanNETs are often diagnosed only after the cancer has spread to other parts of the body.As with other neuroendocrine tumors, the history of the terminology and classification of PanNETs is complex. PanNETs are sometimes called "islet cell cancers", though they are now known to not actually arise from islet cells as previously thought. Signs and symptoms Since pancreatic cancer usually does not cause recognizable symptoms in its early stages, the disease is typically not diagnosed until it has spread beyond the pancreas itself. This is one of the main reasons for the generally poor survival rates. Exceptions to this are the functioning PanNETs, where over-production of various active hormones can give rise to symptoms (which depend on the type of hormone).Bearing in mind that the disease is rarely diagnosed before the age of 40, common symptoms of pancreatic adenocarcinoma occurring before diagnosis include: Pain in the upper abdomen or back, often spreading from around the stomach to the back. The location of the pain can indicate the part of the pancreas where a tumor is located. The pain may be worse at night and may increase over time to become severe and unremitting. It may be slightly relieved by bending forward. In the UK, about half of new cases of pancreatic cancer are diagnosed following a visit to a hospital emergency department for pain or jaundice. In up to two-thirds of people, abdominal pain is the main symptom, for 46% of the total accompanied by jaundice, with 13% having jaundice without pain. Jaundice, a yellow tint to the whites of the eyes or skin, with or without pain, and possibly in combination with darkened urine, results when a cancer in the head of the pancreas obstructs the common bile duct as it runs through the pancreas. Unexplained weight loss, either from loss of appetite, or loss of exocrine function resulting in poor digestion. The tumor may compress neighboring organs, disrupting digestive processes and making it difficult for the stomach to empty, which may cause nausea and a feeling of fullness. The undigested fat leads to foul-smelling, fatty feces that are difficult to flush away. Constipation is also common. At least 50% of people with pancreatic adenocarcinoma have diabetes at the time of diagnosis. While long-standing diabetes is a known risk factor for pancreatic cancer (see Risk factors), the cancer can itself cause diabetes, in which case recent onset of diabetes could be considered an early sign of the disease. People over 50 who develop diabetes have eight times the usual risk of developing pancreatic adenocarcinoma within three years, after which the relative risk declines. Other findings Trousseaus syndrome – in which blood clots form spontaneously in the portal blood vessels (portal vein thrombosis), the deep veins of the extremities (deep vein thrombosis), or the superficial veins (superficial vein thrombosis) anywhere on the body – may be associated with pancreatic cancer, and is found in about 10% of cases. Clinical depression has been reported in association with pancreatic cancer in some 10–20% of cases, and can be a hindrance to optimal management. The depression sometimes appears before the diagnosis of cancer, suggesting that it may be brought on by the biology of the disease.Other common manifestations of the disease include weakness and tiring easily, dry mouth, sleep problems, and a palpable abdominal mass. Symptoms of spread The spread of pancreatic cancer to other organs (metastasis) may also cause symptoms. Typically, pancreatic adenocarcinoma first spreads to nearby lymph nodes, and later to the liver or to the peritoneal cavity, large intestine, or lungs. Uncommonly, it spreads to the bones or brain.Cancers in the pancreas may also be secondary cancers that have spread from other parts of the body. This is uncommon, found in only about 2% of cases of pancreatic cancer. Kidney cancer is by far the most common cancer to spread to the pancreas, followed by colorectal cancer, and then cancers of the skin, breast, and lung. Surgery may be performed on the pancreas in such cases, whether in hope of a cure or to alleviate symptoms. Risk factors Risk factors for pancreatic adenocarcinoma include: Age, sex, and ethnicity – the risk of developing pancreatic cancer increases with age. Most cases occur after age 65, while cases before age 40 are uncommon. The disease is slightly more common in men than in women. In the United States, it is over 1.5 times more common in African Americans, though incidence in Africa is low. Cigarette smoking is the best-established avoidable risk factor for pancreatic cancer, approximately doubling risk among long-term smokers, the risk increasing with the number of cigarettes smoked and the years of smoking. The risk declines slowly after smoking cessation, taking some 20 years to return to almost that of nonsmokers. Obesity – a body mass index greater than 35 increases relative risk by about half. Family history – 5–10% of pancreatic cancer cases have an inherited component, where people have a family history of pancreatic cancer. The risk escalates greatly if more than one first-degree relative had the disease, and more modestly if they developed it before the age of 50. Most of the genes involved have not been identified. Hereditary pancreatitis gives a greatly increased lifetime risk of pancreatic cancer of 30–40% to the age of 70. Screening for early pancreatic cancer may be offered to individuals with hereditary pancreatitis on a research basis. Some people may choose to have their pancreas surgically removed to prevent cancer from developing in the future.Pancreatic cancer has been associated with these other rare hereditary syndromes: Peutz–Jeghers syndrome due to mutations in the STK11 tumor suppressor gene (very rare, but a very strong risk factor); dysplastic nevus syndrome (or familial atypical multiple mole and melanoma syndrome, FAMMM-PC) due to mutations in the CDKN2A tumor suppressor gene; autosomal recessive ataxia-telangiectasia and autosomal dominantly inherited mutations in the BRCA2 and PALB2 genes; hereditary non-polyposis colon cancer (Lynch syndrome); and familial adenomatous polyposis. PanNETs have been associated with multiple endocrine neoplasia type 1 (MEN1) and von Hippel Lindau syndromes.Chronic pancreatitis appears to almost triple risk, and as with diabetes, new-onset pancreatitis may be a symptom of a tumor. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high. Diabetes mellitus is a risk factor for pancreatic cancer and (as noted in the Signs and symptoms section) new-onset diabetes may also be an early sign of the disease. People who have been diagnosed with type 2 diabetes for longer than 10 years may have a 50% increased risk, as compared with individuals without diabetes. In 2021, Venturi reported that pancreas is able to absorb in great quantity radioactive cesium (Cs-134 and Cs-137) causing chronic pancreatitis and probably pancreatic cancer with damage of pancreatic islands, causing type 3c (pancreatogenic) diabetes. Chronic pancreatitis, pancreatic cancer and diabetes mellitus increased in contaminated population, particularly children and adolescents, after Fukushima and Chernobyl nuclear incidents. At the same time, worldwide pancreatic diseases, diabetes and environmental radiocesium are increasing. Specific types of food (as distinct from obesity) have not been clearly shown to increase the risk of pancreatic cancer. Dietary factors for which some evidence shows slightly increased risk include processed meat, red meat, and meat cooked at very high temperatures (e.g. by frying, broiling, or grilling). Alcohol Drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer, but considerable research has failed to firmly establish alcohol consumption as a direct risk factor for pancreatic cancer. Overall, the association is consistently weak and the majority of studies have found no association, with smoking a strong confounding factor. The evidence is stronger for a link with heavy drinking, of at least six drinks per day. Pathophysiology Precancer Exocrine cancers are thought to arise from several types of precancerous lesions within the pancreas, but these lesions do not always progress to cancer, and the increased numbers detected as a byproduct of the increasing use of CT scans for other reasons are not all treated. Apart from pancreatic serous cystadenomas, which are almost always benign, four types of precancerous lesion are recognized. The first is pancreatic intraepithelial neoplasia (PanIN). These lesions are microscopic abnormalities in the pancreas and are often found in autopsies of people with no diagnosed cancer. These lesions may progress from low to high grade and then to a tumor. More than 90% of cases at all grades carry a faulty KRAS gene, while in grades 2 and 3, damage to three further genes – CDKN2A (p16), p53, and SMAD4 – are increasingly often found.A second type is the intraductal papillary mucinous neoplasm (IPMN). These are macroscopic lesions, which are found in about 2% of all adults. This rate rises to about 10% by age 70. These lesions have about a 25% risk of developing into invasive cancer. They may have KRAS gene mutations (40–65% of cases) and in the GNAS Gs alpha subunit and RNF43, affecting the Wnt signaling pathway. Even if removed surgically, a considerably increased risk remains of pancreatic cancer developing subsequently.The third type, pancreatic mucinous cystic neoplasm (MCN), mainly occurs in women, and may remain benign or progress to cancer. If these lesions become large, cause symptoms, or have suspicious features, they can usually be successfully removed by surgery.A fourth type of cancer that arises in the pancreas is the intraductal tubulopapillary neoplasm. This type was recognised by the WHO in 2010 and constitutes about 1–3% of all pancreatic neoplasms. Mean age at diagnosis is 61 years (range 35–78 years). About 50% of these lesions become invasive. Diagnosis depends on histology, as these lesions are very difficult to differentiate from other lesions on either clinical or radiological grounds. Invasive cancer The genetic events found in ductal adenocarcinoma have been well characterized, and complete exome sequencing has been done for the common types of tumor. Four genes have each been found to be mutated in the majority of adenocarcinomas: KRAS (in 95% of cases), CDKN2A (also in 95%), TP53 (75%), and SMAD4 (55%). The last of these is especially associated with a poor prognosis. SWI/SNF mutations/deletions occur in about 10–15% of the adenocarcinomas. The genetic alterations in several other types of pancreatic cancer and precancerous lesions have also been researched. Transcriptomics analyses and mRNA sequencing for the common forms of pancreatic cancer have found that 75% of human genes are expressed in the tumors, with some 200 genes more specifically expressed in pancreatic cancer as compared to other tumor types. PanNETs The genes often found mutated in PanNETs are different from those in exocrine pancreatic cancer. For example, KRAS mutation is normally absent. Instead, hereditary MEN1 gene mutations give risk to MEN1 syndrome, in which primary tumors occur in two or more endocrine glands. About 40–70% of people born with a MEN1 mutation eventually develop a PanNet. Other genes that are frequently mutated include DAXX, mTOR, and ATRX. Diagnosis The symptoms of pancreatic adenocarcinoma do not usually appear in the diseases early stages, and they are not individually distinctive to the disease. The symptoms at diagnosis vary according to the location of the cancer in the pancreas, which anatomists divide (from left to right on most diagrams) into the thick head, the neck, and the tapering body, ending in the tail. Regardless of a tumors location, the most common symptom is unexplained weight loss, which may be considerable. A large minority (between 35% and 47%) of people diagnosed with the disease will have had nausea, vomiting, or a feeling of weakness. Tumors in the head of the pancreas typically also cause jaundice, pain, loss of appetite, dark urine, and light-colored stools. Tumors in the body and tail typically also cause pain.People sometimes have recent onset of atypical type 2 diabetes that is difficult to control, a history of recent but unexplained blood vessel inflammation caused by blood clots (thrombophlebitis) known as Trousseau sign, or a previous attack of pancreatitis. A doctor may suspect pancreatic cancer when the onset of diabetes in someone over 50 years old is accompanied by typical symptoms such as unexplained weight loss, persistent abdominal or back pain, indigestion, vomiting, or fatty feces. Jaundice accompanied by a painlessly swollen gallbladder (known as Courvoisiers sign) may also raise suspicion, and can help differentiate pancreatic cancer from gallstones.Medical imaging techniques, such as computed tomography (CT scan) and endoscopic ultrasound (EUS) are used both to confirm the diagnosis and to help decide whether the tumor can be surgically removed (its "resectability"). On contrast CT scan, pancreatic cancer typically shows a gradually increasing radiocontrast uptake, rather than a fast washout as seen in a normal pancreas or a delayed washout as seen in chronic pancreatitis. Magnetic resonance imaging and positron emission tomography may also be used, and magnetic resonance cholangiopancreatography may be useful in some cases. Abdominal ultrasound is less sensitive and will miss small tumors, but can identify cancers that have spread to the liver and build-up of fluid in the peritoneal cavity (ascites). It may be used for a quick and cheap first examination before other techniques. A biopsy by fine needle aspiration, often guided by endoscopic ultrasound, may be used where there is uncertainty over the diagnosis, but a histologic diagnosis is not usually required for removal of the tumor by surgery to go ahead.Liver function tests can show a combination of results indicative of bile duct obstruction (raised conjugated bilirubin, γ-glutamyl transpeptidase and alkaline phosphatase levels). CA19-9 (carbohydrate antigen 19.9) is a tumor marker that is frequently elevated in pancreatic cancer. However, it lacks sensitivity and specificity, not least because 5% of people lack the Lewis (a) antigen and cannot produce CA19-9. It has a sensitivity of 80% and specificity of 73% in detecting pancreatic adenocarcinoma, and is used for following known cases rather than diagnosis. Histopathology The most common form of pancreatic cancer (adenocarcinoma) is typically characterized by moderately to poorly differentiated glandular structures on microscopic examination. There is typically considerable desmoplasia or formation of a dense fibrous stroma or structural tissue consisting of a range of cell types (including myofibroblasts, macrophages, lymphocytes and mast cells) and deposited material (such as type I collagen and hyaluronic acid). This creates a tumor microenvironment that is short of blood vessels (hypovascular) and so of oxygen (tumor hypoxia). It is thought that this prevents many chemotherapy drugs from reaching the tumor, as one factor making the cancer especially hard to treat. Staging Exocrine cancers Pancreatic cancer is usually staged following a CT scan. The most widely used cancer staging system for pancreatic cancer is the one formulated by the American Joint Committee on Cancer (AJCC) together with the Union for International Cancer Control (UICC). The AJCC-UICC staging system designates four main overall stages, ranging from early to advanced disease, based on TNM classification of Tumor size, spread to lymph Nodes, and Metastasis.To help decide treatment, the tumors are also divided into three broader categories based on whether surgical removal seems possible: in this way, tumors are judged to be "resectable", "borderline resectable", or "unresectable". When the disease is still in an early stage (AJCC-UICC stages I and II), without spread to large blood vessels or distant organs such as the liver or lungs, surgical resection of the tumor can normally be performed, if the patient is willing to undergo this major operation and is thought to be sufficiently fit.The AJCC-UICC staging system allows distinction between stage III tumors that are judged to be "borderline resectable" (where surgery is technically feasible because the celiac axis and superior mesenteric artery are still free) and those that are "unresectable" (due to more locally advanced disease); in terms of the more detailed TNM classification, these two groups correspond to T3 and T4 respectively. Pancreatic cancer staging (TNM classification) Locally advanced adenocarcinomas have spread into neighboring organs, which may be any of the following (in roughly decreasing order of frequency): the duodenum, stomach, transverse colon, spleen, adrenal gland, or kidney. Very often they also spread to the important blood or lymphatic vessels and nerves that run close to the pancreas, making surgery far more difficult. Typical sites for metastatic spread (stage IV disease) are the liver, peritoneal cavity and lungs, all of which occur in 50% or more of fully advanced cases. PanNETs The 2010 WHO classification of tumors of the digestive system grades all the pancreatic neuroendocrine tumors (PanNETs) into three categories, based on their degree of cellular differentiation (from "NET G1" through to the poorly differentiated "NET G3"). The U.S. National Comprehensive Cancer Network recommends use of the same AJCC-UICC staging system as pancreatic adenocarcinoma.: 52 Using this scheme, the stage-by-stage outcomes for PanNETs are dissimilar to those of the exocrine cancers. A different TNM system for PanNETs has been proposed by the European Neuroendocrine Tumor Society. Prevention and screening Apart from not smoking, the American Cancer Society recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains, while decreasing consumption of red and processed meat, although there is no consistent evidence this will prevent or reduce pancreatic cancer specifically. A 2014 review of research concluded that there was evidence that consumption of citrus fruits and curcumin reduced risk of pancreatic cancer, while there was possibly a beneficial effect from whole grains, folate, selenium, and non-fried fish.In the general population, screening of large groups is not considered effective and may be harmful as of 2019, although newer techniques, and the screening of tightly targeted groups, are being evaluated. Nevertheless, regular screening with endoscopic ultrasound and MRI/CT imaging is recommended for those at high risk from inherited genetics.Use of aspirin is said to lower the risk of pancreatic cancer. Management Exocrine cancer A key assessment that is made after diagnosis is whether surgical removal of the tumor is possible (see Staging), as this is the only cure for this cancer. Whether or not surgical resection can be offered depends on how much the cancer has spread. The exact location of the tumor is also a significant factor, and CT can show how it relates to the major blood vessels passing close to the pancreas. The general health of the person must also be assessed, though age in itself is not an obstacle to surgery.Chemotherapy and, to a lesser extent, radiotherapy are likely to be offered to most people, whether or not surgery is possible. Specialists advise that the management of pancreatic cancer should be in the hands of a multidisciplinary team including specialists in several aspects of oncology, and is, therefore, best conducted in larger centers. Surgery Surgery with the intention of a cure is only possible in around one-fifth (20%) of new cases. Although CT scans help, in practice it can be difficult to determine whether the tumor can be fully removed (its "resectability"), and it may only become apparent during surgery that it is not possible to successfully remove the tumor without damaging other vital tissues. Whether or not surgical resection can be offered depends on various factors, including the precise extent of local anatomical adjacency to, or involvement of, the venous or arterial blood vessels, as well as surgical expertise and a careful consideration of projected post-operative recovery. The age of the person is not in itself a reason not to operate, but their general performance status needs to be adequate for a major operation.One particular feature that is evaluated is the encouraging presence, or discouraging absence, of a clear layer or plane of fat creating a barrier between the tumor and the vessels. Traditionally, an assessment is made of the tumors proximity to major venous or arterial vessels, in terms of "abutment" (defined as the tumor touching no more than half a blood vessels circumference without any fat to separate it), "
Pancreatic cancer	encasement" (when the tumor encloses most of the vessels circumference), or full vessel involvement.: 22 A resection that includes encased sections of blood vessels may be possible in some cases, particularly if preliminary neoadjuvant therapy is feasible, using chemotherapy: 36 and/or radiotherapy.: 29–30 Even when the operation appears to have been successful, cancerous cells are often found around the edges ("margins") of the removed tissue, when a pathologist examines them microscopically (this will always be done), indicating the cancer has not been entirely removed. Furthermore, cancer stem cells are usually not evident microscopically, and if they are present they may continue to develop and spread. An exploratory laparoscopy (a small, camera-guided surgical procedure) may therefore be performed to gain a clearer idea of the outcome of a full operation. For cancers involving the head of the pancreas, the Whipple procedure is the most commonly attempted curative surgical treatment. This is a major operation which involves removing the pancreatic head and the curve of the duodenum together ("pancreato-duodenectomy"), making a bypass for food from the stomach to the jejunum ("gastro-jejunostomy") and attaching a loop of jejunum to the cystic duct to drain bile ("cholecysto-jejunostomy"). It can be performed only if the person is likely to survive major surgery and if the cancer is localized without invading local structures or metastasizing. It can, therefore, be performed only in a minority of cases. Cancers of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy, which often also entails removal of the spleen. Nowadays, this can often be done using minimally invasive surgery.Although curative surgery no longer entails the very high death rates that occurred until the 1980s, a high proportion of people (about 30–45%) still have to be treated for a post-operative sickness that is not caused by the cancer itself. The most common complication of surgery is difficulty in emptying the stomach. Certain more limited surgical procedures may also be used to ease symptoms (see Palliative care): for instance, if the cancer is invading or compressing the duodenum or colon. In such cases, bypass surgery might overcome the obstruction and improve quality of life but is not intended as a cure. Chemotherapy After surgery, adjuvant chemotherapy with gemcitabine or 5-FU can be offered if the person is sufficiently fit, after a recovery period of one to two months. In people not suitable for curative surgery, chemotherapy may be used to extend life or improve its quality. Before surgery, neoadjuvant chemotherapy or chemoradiotherapy may be used in cases that are considered to be "borderline resectable" (see Staging) in order to reduce the cancer to a level where surgery could be beneficial. In other cases neoadjuvant therapy remains controversial, because it delays surgery.Gemcitabine was approved by the United States Food and Drug Administration (FDA) in 1997, after a clinical trial reported improvements in quality of life and a five-week improvement in median survival duration in people with advanced pancreatic cancer. This was the first chemotherapy drug approved by the FDA primarily for a nonsurvival clinical trial endpoint. Chemotherapy using gemcitabine alone was the standard for about a decade, as a number of trials testing it in combination with other drugs failed to demonstrate significantly better outcomes. However, the combination of gemcitabine with erlotinib was found to increase survival modestly, and erlotinib was licensed by the FDA for use in pancreatic cancer in 2005.The FOLFIRINOX chemotherapy regimen using four drugs was found more effective than gemcitabine, but with substantial side effects, and is thus only suitable for people with good performance status. This is also true of protein-bound paclitaxel (nab-paclitaxel), which was licensed by the FDA in 2013 for use with gemcitabine in pancreas cancer. By the end of 2013, both FOLFIRINOX and nab-paclitaxel with gemcitabine were regarded as good choices for those able to tolerate the side-effects, and gemcitabine remained an effective option for those who were not. A head-to-head trial between the two new options is awaited, and trials investigating other variations continue. However, the changes of the last few years have only increased survival times by a few months. Clinical trials are often conducted for novel adjuvant therapies. Radiotherapy The role of radiotherapy as an auxiliary (adjuvant) treatment after potentially curative surgery has been controversial since the 1980s. In the early 2000s the European Study Group for Pancreatic Cancer Research (ESPAC) showed prognostic superiority of adjuvant chemotherapy over chemoradiotherapy. The European Society for Medical Oncology recommends that adjuvant radiotherapy should only be used for people enrolled in clinical trials. However, there is a continuing tendency for clinicians in the US to be more ready to use adjuvant radiotherapy than those in Europe. Many clinical trials have tested a variety of treatment combinations since the 1980s, but have failed to settle the matter conclusively.Radiotherapy may form part of treatment to attempt to shrink a tumor to a resectable state, but its use on unresectable tumors remains controversial as there are conflicting results from clinical trials. The preliminary results of one trial, presented in 2013, "markedly reduced enthusiasm" for its use on locally advanced tumors. PanNETs Treatment of PanNETs, including the less common malignant types, may include a number of approaches. Some small tumors of less than 1 cm. that are identified incidentally, for example on a CT scan performed for other purposes, may be followed by watchful waiting. This depends on the assessed risk of surgery which is influenced by the site of the tumor and the presence of other medical problems. Tumors within the pancreas only (localized tumors), or with limited metastases, for example to the liver, may be removed by surgery. The type of surgery depends on the tumor location, and the degree of spread to lymph nodes.For localized tumors, the surgical procedure may be much less extensive than the types of surgery used to treat pancreatic adenocarcinoma described above, but otherwise surgical procedures are similar to those for exocrine tumors. The range of possible outcomes varies greatly; some types have a very high survival rate after surgery while others have a poor outlook. As all this group are rare, guidelines emphasize that treatment should be undertaken in a specialized center. Use of liver transplantation may be considered in certain cases of liver metastasis.For functioning tumors, the somatostatin analog class of medications, such as octreotide, can reduce the excessive production of hormones. Lanreotide can slow tumor growth. If the tumor is not amenable to surgical removal and is causing symptoms, targeted therapy with everolimus or sunitinib can reduce symptoms and slow progression of the disease. Standard cytotoxic chemotherapy is generally not very effective for PanNETs, but may be used when other drug treatments fail to prevent the disease from progressing, or in poorly differentiated PanNET cancers.Radiation therapy is occasionally used if there is pain due to anatomic extension, such as metastasis to bone. Some PanNETs absorb specific peptides or hormones, and these PanNETs may respond to nuclear medicine therapy with radiolabeled peptides or hormones such as iobenguane (iodine-131-MIBG). Radiofrequency ablation (RFA), cryoablation, and hepatic artery embolization may also be used. Palliative care Palliative care is medical care which focuses on treatment of symptoms from serious illness, such as cancer, and improving quality of life. Because pancreatic adenocarcinoma is usually diagnosed after it has progressed to an advanced stage, palliative care as a treatment of symptoms is often the only treatment possible.Palliative care focuses not on treating the underlying cancer, but on treating symptoms such as pain or nausea, and can assist in decision-making, including when or if hospice care will be beneficial. Pain can be managed with medications such as opioids or through procedural intervention, by a nerve block on the celiac plexus (CPB). This alters or, depending on the technique used, destroys the nerves that transmit pain from the abdomen. CPB is a safe and effective way to reduce the pain, which generally reduces the need to use opioid painkillers, which have significant negative side effects.Other symptoms or complications that can be treated with palliative surgery are obstruction by the tumor of the intestines or bile ducts. For the latter, which occurs in well over half of cases, a small metal tube called a stent may be inserted by endoscope to keep the ducts draining. Palliative care can also help treat depression that often comes with the diagnosis of pancreatic cancer.Both surgery and advanced inoperable tumors often lead to digestive system disorders from a lack of the exocrine products of the pancreas (exocrine insufficiency). These can be treated by taking pancreatin which contains manufactured pancreatic enzymes, and is best taken with food. Difficulty in emptying the stomach (delayed gastric emptying) is common and can be a serious problem, involving hospitalization. Treatment may involve a variety of approaches, including draining the stomach by nasogastric aspiration and drugs called proton-pump inhibitors or H2 antagonists, which both reduce production of gastric acid. Medications like metoclopramide can also be used to clear stomach contents. Outcomes Pancreatic adenocarcinoma and the other less common exocrine cancers have a very poor prognosis, as they are normally diagnosed at a late stage when the cancer is already locally advanced or has spread to other parts of the body. Outcomes are much better for PanNETs: Many are benign and completely without clinical symptoms, and even those cases not treatable with surgery have an average five-year survival rate of 16%, although the outlook varies considerably according to the type.For locally advanced and metastatic pancreatic adenocarcinomas, which together represent over 80% of cases, numerous trials comparing chemotherapy regimes have shown increased survival times, but not to more than one year. Overall five-year survival for pancreatic cancer in the US has improved from 2% in cases diagnosed in 1975–1977, and 4% in 1987–1989 diagnoses, to 6% in 2003–2009. In the less than 20% of cases of pancreatic adenocarcinoma with a diagnosis of a localized and small cancerous growth (less than 2 cm in Stage T1), about 20% of Americans survive to five years.About 1500 genes are linked to outcomes in pancreatic adenocarcinoma. These include both unfavorable genes, where high expression is related to poor outcome, for example C-Met and MUC-1, and favorable genes where high expression is associated with better survival, for example the transcription factor PELP1. Distribution In 2015, pancreatic cancers of all types resulted in 411,600 deaths globally. In 2014, an estimated 46,000 people in the US are expected to be diagnosed with pancreatic cancer and 40,000 to die of it. Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year. It is the seventh highest cause of death from cancer worldwide. Pancreatic cancer is the fifth most common cause of death from cancer in the United Kingdom, and the third most common in the United States.Globally pancreatic cancer is the 11th most common cancer in women and the 12th most common in men. The majority of recorded cases occur in developed countries. People from the United States have an average lifetime risk of about 1 in 67 (or 1.5%) of developing the disease, slightly higher than the figure for the UK. The disease is more common in men than women, though the difference in rates has narrowed over recent decades, probably reflecting earlier increases in female smoking. In the United States the risk for African Americans is over 50% greater than for whites, but the rates in Africa and East Asia are much lower than those in North America or Europe. The United States, Central, and eastern Europe, and Argentina and Uruguay all have high rates. PanNETs The annual incidence of clinically recognized PanNETs is low (about 5 per one million person-years) and is dominated by the non-functioning types. Somewhere between 45% and 90% of PanNETs are thought to be of the non-functioning types. Studies of autopsies have uncovered small PanNETs rather frequently, suggesting that the prevalence of tumors that remain inert and asymptomatic may be relatively high. Overall PanNETs are thought to account for about 1 to 2% of all pancreatic tumors. The definition and classification of PanNETs has changed over time, affecting what is known about their epidemiology and clinical relevance. History Recognition and diagnosis The earliest recognition of pancreatic cancer has been attributed to the 18th-century Italian scientist Giovanni Battista Morgagni, the historical father of modern-day anatomic pathology, who claimed to have traced several cases of cancer in the pancreas. Many 18th and 19th-century physicians were skeptical about the existence of the disease, given the similar appearance of pancreatitis. Some case reports were published in the 1820s and 1830s, and a genuine histopathologic diagnosis was eventually recorded by the American clinician Jacob Mendes Da Costa, who also doubted the reliability of Morgagnis interpretations. By the start of the 20th century, cancer of the head of the pancreas had become a well-established diagnosis.Regarding the recognition of PanNETs, the possibility of cancer of the islet cells was initially suggested in 1888. The first case of hyperinsulinism due to a tumor of this type was reported in 1927. Recognition of a non-insulin-secreting type of PanNET is generally ascribed to the American surgeons, R. M. Zollinger and E. H. Ellison, who gave their names to Zollinger–Ellison syndrome, after postulating the existence of a gastrin-secreting pancreatic tumor in a report of two cases of unusually severe peptic ulcers published in 1955. In 2010, the WHO recommended that PanNETs be referred to as "neuroendocrine" rather than "endocrine" tumors.Small precancerous neoplasms for many pancreatic cancers are being detected at greatly increased rates by modern medical imaging. One type, the intraductal papillary mucinous neoplasm (IPMN) was first described by Japanese researchers in 1982. It was noted in 2010 that: "For the next decade, little attention was paid to this report; however, over the subsequent 15 years, there has been a virtual explosion in the recognition of this tumor." Surgery The first reported partial pancreaticoduodenectomy was performed by the Italian surgeon Alessandro Codivilla in 1898, but the patient only survived 18 days before succumbing to complications. Early operations were compromised partly because of mistaken beliefs that people would die if their duodenum were removed, and also, at first, if the flow of pancreatic juices stopped. Later it was thought, also mistakenly, that the pancreatic duct could simply be tied up without serious adverse effects; in fact, it will very often leak later on. In 1907–1908, after some more unsuccessful operations by other surgeons, experimental procedures were tried on corpses by French surgeons.In 1912 the German surgeon Walther Kausch was the first to remove large parts of the duodenum and pancreas together (en bloc). This was in Breslau, now Wrocław, in Poland. In 1918 it was demonstrated, in operations on dogs, that it is possible to survive even after complete removal of the duodenum, but no such result was reported in human surgery until 1935, when the American surgeon Allen Oldfather Whipple published the results of a series of three operations at Columbia Presbyterian Hospital in New York. Only one of the patients had the duodenum entirely removed, but he survived for two years before dying of metastasis to the liver. The first operation was unplanned, as cancer was only discovered in the operating theater. Whipples success showed the way for the future, but the operation remained a difficult and dangerous one until recent decades. He published several refinements to his procedure, including the first total removal of the duodenum in 1940, but he only performed a total of 37 operations.The discovery in the late 1930s that vitamin K prevented bleeding with jaundice, and the development of blood transfusion as an everyday process, both improved post-operative survival, but about 25% of people never left hospital alive as late as the 1970s. In the 1970s a group of American surgeons wrote urging that the procedure was too dangerous and should be abandoned. Since then outcomes in larger centers have improved considerably, and mortality from the operation is often less than 4%.In 2006 a report was published of a series of 1,000 consecutive pancreatico-duodenectomies performed by a single surgeon from Johns Hopkins Hospital between 1969 and 2003. The rate of these operations had increased steadily over this period, with only three of them before 1980, and the median operating time reduced from 8.8 hours in the 1970s to 5.5 hours in the 2000s, and mortality within 30 days or in hospital was only 1%. Another series of 2,050 operations at the Massachusetts General Hospital between 1941 and 2011 showed a similar picture of improvement. Research directions Early-stage research on pancreatic cancer includes studies of genetics and early detection, treatment at different cancer stages, surgical strategies, and targeted therapies, such as inhibition of growth factors, immune therapies, and vaccines. Bile acids may have a role in the carcinogenesis of pancreatic cancer.A key question is the timing of events as the disease develops and progresses – particularly the role of diabetes, and how and when the disease spreads. The knowledge that new onset of diabetes can be an early sign of the disease could facilitate timely diagnosis and prevention if a workable screening strategy can be developed. The European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) trial is aiming to determine whether regular screening is appropriate for people with a family history of the disease.Keyhole surgery (laparoscopy) rather than Whipples procedure, particularly in terms of recovery time, is being evaluated. Irreversible electroporation is a relatively novel ablation technique with potential for downstaging and prolonging survival in persons with locally advanced disease, especially for tumors in proximity to peri-pancreatic vessels without risk of vascular trauma.Efforts are underway to develop new drugs, including those targeting molecular mechanisms for cancer onset, stem cells, and cell proliferation. A further approach involves the use of immunotherapy, such as oncolytic viruses. Galectin-specific mechanisms of the tumor microenvironment are under study. See also Gastrointestinal cancer Pancreatic Cancer Action Network (organization in the US) Pancreatic Cancer Action (organization in the UK) Lustgarten Foundation for Pancreatic Cancer Research (organization in the US) List of people diagnosed with pancreatic cancer Recurrence of pancreatic cancer References External links Pancreatic cancer at Curlie
Hemangiopericytoma	A hemangiopericytoma is a type of soft-tissue sarcoma that originates in the pericytes in the walls of capillaries. When inside the nervous system, although not strictly a meningioma tumor, it is a meningeal tumor with a special aggressive behavior. It was first characterized in 1942. Histopathology Hemangiopericytomas are tumors that are derived from specialized spindle shaped cells called pericytes, which line capillaries. Diagnosis Hemangiopericytoma located in the cerebral cavity is an aggressive tumor of the mesenchyme with oval nuclei with scant cytoplasm. "There is dense intercellular reticulin staining. Tumor cells can be fibroblastic, myxoid, or pericytic. These tumors, in contrast to meningiomas, do not stain with epithelial membrane antigen. They have a grade 2 or 3 biological behavior, and need to be distinguished from benign meningiomas because of their high rate of recurrence (68.2%) and metastases (Maier et al. 1992; Kleihues et al. 1993 )." Treatment Depending on the grade of the sarcoma, it is treated with surgery, chemotherapy, and/or radiotherapy. Epidemiology In one series, the median age of affected individuals was 45 years, with a 10-year survival rate of 70 percent. See also Infantile hemangiopericytoma List of cutaneous conditions References Further reading == External links ==
Infantile progressive bulbar palsy	Infantile progressive bulbar palsy is a rare type of progressive bulbar palsy that occurs in children. The disease exists in both rapid and slow onsets, and involves inflammation of the gray matter of the bulb. Infantile PBP is a disease that manifests itself in two forms: Fazio–Londe syndrome (FL) and Brown–Vialetto–Van Laere syndrome (BVVL). == References ==
Gallstone ileus	Gallstone ileus is a rare form of small bowel obstruction caused by an impaction of a gallstone within the lumen of the small intestine. Such a gallstone enters the bowel via a cholecysto-enteric fistula. The presence of large stones, >2.5 cm in diameter, within the gallbladder are thought to predispose to fistula formation by gradual erosion through the gallbladder fundus. Once a fistula has formed, a stone may travel from the gallbladder into the bowel and become lodged almost anywhere along the gastrointestinal tract. Obstruction occurs most commonly at the near the distal ileum, within 60 cm proximally to the ileocecal valve. Rarely, gallstone ileus may recur if the underlying fistula is not treated.First described by Thomas Bartholin in 1654, the name "gallstone ileus" is a misnomer because an ileus is, by definition, a non-mechanical bowel motility failure (as opposed to a mechanical obstruction by a stone). Diagnosis Diagnosis of gallstone ileus requires radiographic studies. Classic radiographic findings are known as Riglers triad: pneumobilia (air within the biliary tree) evidence of small bowel obstruction radiopaque gallstone on abdominal radiograph Treatment Initial management involves fluid resuscitation and potentially nasogastric suctioning. Since gallstone ileus constitutes a form of mechanical small bowel obstruction, it can be a surgical emergency and requires open or laparoscopic surgery to remove an impacted stone. The different strategies for surgical management are either enterolithotomy alone, allowing a delayed cholecystectomy after an inflammation-free period of 4–6 weeks (and therefore two-stage surgery) or enterolithotomy in combination with a cholecystectomy and fistula division (one-stage surgery). The different strategies for surgical management are controversial, and depend on factors such as patient fitness for surgery and comorbidities. Eponym Bouverets syndrome refers to reverse gallstone ileus where the gallstone propagates proximally and causes gastric outlet obstruction by being impacted in first part of duodenum. References == External links ==
Melkersson–Rosenthal syndrome	Melkersson–Rosenthal syndrome is a rare neurological disorder characterized by recurring facial paralysis, swelling of the face and lips (usually the upper lip: cheilitis granulomatosis) and the development of folds and furrows in the tongue (fissured tongue).: 799 Onset is in childhood or early adolescence. After recurrent attacks (ranging from days to years in between), swelling may persist and increase, eventually becoming permanent. The lip may become hard, cracked, and fissured with a reddish-brown discoloration. The cause of Melkersson–Rosenthal syndrome is unknown, but there may be a genetic predisposition. It has been noted to be especially prevalent among certain ethnic groups in Bolivia. It can be symptomatic of Crohns disease or sarcoidosis. Approximately 400 cases have been reported worldwide. Cause Not to be confused with Rosenthal syndrome a.k.a. hemophilia C which is caused by clotting factor XI deficiency. Only genetic causation is established as it is associated with twins and family members. Diagnosis Diagnosis is mainly based on clinical features. However, biopsy has been useful in diagnosis as well as in differentiating between the different types of the disease. Treatment Treatment is symptomatic and may include nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids to reduce swelling, antibiotics and immunosuppressants. Surgery may be indicated to relieve pressure on the facial nerves and reduce swelling, but its efficacy is uncertain. Massage and electrical stimulation may also be prescribed. Prognosis Melkersson–Rosenthal syndrome may recur intermittently after its first appearance. It can become a chronic disorder. Follow-up care should exclude the development of Crohns disease or sarcoidosis. Eponym The condition is named after Ernst Melkersson and Curt Rosenthal. Research The NINDS supports research on neurological disorders such as Melkersson–Rosenthal syndrome. Much of this research is aimed at increasing knowledge of these disorders and finding ways to treat, prevent, and ultimately cure them. See also List of cutaneous conditions References The original version of this article was taken from the public domain source at Melkersson–Rosenthal syndrome at nih.gov == External links ==
Ulcer (dermatology)	An ulcer is a sore on the skin or a mucous membrane, accompanied by the disintegration of tissue. Ulcers can result in complete loss of the epidermis and often portions of the dermis and even subcutaneous fat. Ulcers are most common on the skin of the lower extremities and in the gastrointestinal tract. An ulcer that appears on the skin is often visible as an inflamed tissue with an area of reddened skin. A skin ulcer is often visible in the event of exposure to heat or cold, irritation, or a problem with blood circulation. They can also be caused due to a lack of mobility, which causes prolonged pressure on the tissues. This stress in the blood circulation is transformed to a skin ulcer, commonly known as bedsores or decubitus ulcers. Ulcers often become infected, and pus forms. Signs and symptoms Skin ulcers appear as open craters, often round, with layers of skin that have eroded. The skin around the ulcer may be red, swollen, and tender. Patients may feel pain on the skin around the ulcer, and fluid may ooze from the ulcer. In some cases, ulcers can bleed and, rarely, patients experience fever. Ulcers sometimes seem not to heal; healing, if it does occur, tends to be slow. Ulcers that heal within 12 weeks are usually classified as acute, and longer-lasting ones as chronic.Ulcers develop in stages. In stage 1 the skin is red with soft underlying tissue. In the second stage the redness of the skin becomes more pronounced, swelling appears, and there may be some blisters and loss of outer skin layers. During the next stage, the skin may become necrotic down through the deep layers of skin, and the fat beneath the skin may become exposed and visible. In stage 4, deeper necrosis usually occurs, the fat underneath the skin is completely exposed, and the muscle may also become exposed. In the last two stages the sore may cause a deeper loss of fat and necrosis of the muscle; in severe cases it can extend down to bone level, destruction of the bone may begin, and there may be sepsis of joints. Chronic ulcers may be painful. Most patients complain of constant pain at night and during the day. Chronic ulcer symptoms usually include increasing pain, friable granulation tissue, foul odour, and wound breakdown instead of healing. Symptoms tend to worsen once the wound has become infected. Venous skin ulcers that may appear on the lower leg, above the calf or on the lower ankle usually cause achy and swollen legs. If these ulcers become infected they may develop an unpleasant odour, increased tenderness and redness. Before the ulcer establishes definitively, there may be a dark red or purple skin over the affected area as well as a thickening, drying, and itchy skin. Although skin ulcers do not seem of great concern at a first glance, they are worrying conditions especially in people with diabetes, as they are at risk of developing diabetic neuropathy. Ulcers may also appear on the cheeks, soft palate, the tongue, and on the inside of the lower lip. These ulcers usually last from 7 to 14 days and can be painful. Discharges Different types of discharges from ulcer are: Serous, usually seen in healing ulcer Purulent, seen in infected ulcer. Yellow creamy discharge is observed in staphylococcal infection; bloody opalescent discharge in streptococcal infection, while greenish discharge is seen in the case of Pseudomonas infection Bloody (sanguineous), usually seen in malignant ulcers and in healing ulcers with healthy granulation tissue Seropurulent Serosanguinous Serous with sulphur granules, seen in actinomycosis Yellowish, as seen in tuberculous ulcer Causes The wounds from which ulcers arise can be caused by a wide variety of factors, but the main cause is impaired blood circulation. Especially, chronic wounds and ulcers are caused by poor circulation, either through cardiovascular issues or external pressure from a bed or a wheelchair. A very common and dangerous type of skin ulcer is caused by what are called pressure-sensitive sores, more commonly called bed sores, which are frequent in people who are bedridden or who use wheelchairs for long periods.Other causes producing skin ulcers include bacterial and viral infections, fungal infections and cancers. Blood disorders and chronic wounds can result in skin ulcers as well. Venous leg ulcers due to impaired circulation or a blood flow disorder are more common in the elderly. Rare causes of skin ulcers include pyoderma gangraenosum, lesions caused by Crohns disease or ulcerative colitis, granulomatosis with polyangiitis, morbus Behçet and infections that are usually seen in those who are immunocompromised, for example ecthyma gangraenosum. It is important to consider such causes if the skin ulcerations dont show improvement with antibiotic treatments and when other systemic symptoms are present. It is advised not to use surgical procedures on ulcerations caused by Behçet or pyoderma gangraenosum since those diseases usually exhibit pathergy. Diagnosis Grading Wagners grading of ulcer follows: Management Investigations Some of the investigations done for ulcer are:: 19 Study of discharging fluid: Culture and sensitivity Edge biopsy: Edge contains multiplying cells Radiograph of affected area to look for periostitis or osteomyelitis Fine needle aspiration cytology (FNAC) of lymph node Chest X-ray and Mantoux test in suspected tuberculous ulcer Treatment Skin ulcers may take a very long time to heal. Treatment is typically to avoid the ulcer getting infected, remove any excess discharge, maintain a moist wound environment, control the edema, and ease pain caused by nerve and tissue damage. Topical antibiotics are normally used to prevent the ulcer getting infected, and the wound or ulcer is usually kept clear of dead tissue through surgical debridement. Commonly, as a part of the treatment, patients are advised to change their lifestyle if possible and to change their diet. Improving the circulation is important in treating skin ulcers, and patients are consequently usually recommended to exercise, stop smoking, and lose weight. In recent years, advances have been made in accelerating healing of chronic wounds and ulcers. Chronic wounds produce fewer growth hormones than necessary for healing tissue, and healing may be accelerated by replacing or stimulating growth factors while controlling the formation of other substances that work against them.Leg ulcers can be prevented by using compression stockings to prevent blood pooling and back flow. It is likely that a person who has had a skin ulcer will have it again; use of compression stockings every day for at least 5 years after the skin ulcer has healed may help to prevent recurrence. There is limited evidence that negative pressure wound therapy may be effective in reducing the time to healing of leg ulcers. Specific types Arterial insufficiency ulcer: mostly located on the lateral surface of the ankle or the distal digits Cortisol ulcer: caused by long term application of cortisol (steroid) topical creams to certain skin diseases. Diabetic foot ulcer: a major complication of diabetes mellitus, and probably the major component of the diabetic foot. Venous ulcer: thought to occur due to improper functioning of venous valves, usually of the legs See also Skin lesion Skin disease List of cutaneous conditions References == External links ==
Malignant chondroid syringoma	A malignant chondroid syringoma (also known as a "malignant mixed tumour" or "MCS" ) is a very uncommon cutaneous (skin) condition characterised by an adnexal eccrine tumour.: 667 It is commonly reported to present on the trunk and extremities and behave in an aggressive manner. MCS is a cancerous subtype of its benign counterpart, chondroid syringoma, and is the least common variation that has an approximated prevalence of less that 0.005%. These tumours mainly arise "from sebaceous glands, sweat glands, and ectopic salivary glands" (Tural, Selçukbiricik, Günver, Karışmaz, and Serdengecti, 2013) and are rarely encountered in radiopathological and clinical practice. The tumours commonly appear with an asymptomatic "slow-growing, painless, solid subcutaneous or intradermal nodules with a normal margin" (Obaidat, Alsaad, and Ghazarian, 2007) and make up for less than one percent of all primary skin tumours. Commonly appearing in the limbs and body, these asymmetrical tumours range from two millimetres to more than three centimetres. MCS is one of the rarest subtypes of tumours and usually requires aggressive surgery to terminate. Despite accounting for only a small number of tumours recorded each year, malignant mixed tumours are easily confused with other skin conditions (such as epidermal cyst, pilar cyst, calcifying epithelioma, or a solitary trichoepithelioma (Tural, Selçukbiricik, Günver, Karışmaz, and Serdengecti, 2013)) and have high potential for recurrence after surgical excision. The aggressiveness of malignant chondroid syringoma varies, as 49% of cases have had local recurrence whereas some demonstrate regional lymph node or osseous metastasis. The rare neoplasms generally do not follow a determinate development path and are often difficult to diagnose.Histologically, these malignant mixed tumours have epithelial and mesenchymal components and are very large, nodular, circumscribed, and nonulcerated. They are morphologically identical to pleomorphic adenoma and have a female predilection. They range from developing deep dermal to subcutaneous nodules and metastasise at a very high rate. Malignant mixed tumours can emerge "de nova or more rarely develop from a cartilaginous syringoma."(IADVL, 2004) Causes Currently malignant mixed tumours do not have a definitive predisposing factor; however, prior physical injury has been proposed as a potential risk for the emergence of these tumours. Chondroid syringoma less than three centimetres are shown to have a heightened risk of malignancy. Other critical indicators include excessive mucoid matrix, – a connective tissue tumour with a myxoid background that is composed of "clear, mucoid substance – numerous mitoses, and poorly differentiated chondroid components." (Metzler, Schaumburg-Lever, Hornstein, and Rassner, 1996) Diagnosis Diagnosing malignant mixed tumours is difficult as there many types of tumours and their variants. Malignant chondroid syringoma is particularly challenging to distinguish from other skin tumours as it is prone to the absence of definitive symptoms and an ambiguous clinical presentation. Some signs that help determine diagnosis of malignancy include: "mitosis, nuclear atypia, pleomorphism, lymphatic invasion, and local recurrence" (IADVL, 2004). Though it is usually found within women in the forties, the youngest-recorded case was fourteen years old and the oldest was eighty-six. The tumour is described as invasive and is clinically characterised by faster growth than the benign chondroid syringoma. They can generally be diagnosed when presenting "an epithelial component, eccrine or apocrine differentiation and myoepithelial component of fluctuating prominence" (IADVL, 2004). Diagnosis is recommended to follow microscopic analysis to ensure correct examination. Treatment There currently is no established guideline for the standardised treatment of malignant chondroid syringomas, due to their rarity. However, the efficacy of treatment for malignant mixed tumours depends on the time of diagnosis. An immediate and broad surgical excision "with clear margins" (Tural, Selçukbiricik, Günver, Karışmaz, and Serdengecti, 2013) is considered curative and to be the most successful treatment. This treatment aims for the most efficacious disease control. It is largely agreed that chemotherapy and radiotherapy are ineffective yet are sometimes still recommended, yet radiotherapy reacts positively to skeletal metastasis. Combination chemotherapy for MCS is reported as unbeneficial. MCS is reported to have a high and continual risk of recurrence of metastasis, some patients experiencing metastasis nearly twenty years after the primary examination. Thus this necessitates consistent clinical follow-up in order to maintain a benign state of the tumour and achieve disease control. Prognosis Malignant mixed tumours have a poor prognosis that is deemed unpredictable due to its spread being lymphatic or blood-borne. As there have only been a limited number of cases that have been reported, prognostic points are challenging to confirm, however mainly "include size, histological type, lymph node involvement, and distant metastasis" (Garcia, Atun, and Fernando, 2016). The outcome of the prognosis is dependent on early diagnosis and complete resection. The standard duration between diagnosis and reappearance was "23 months, 50 months, and 66 months for local recurrence, nodal metastasis, and distant metastasis, [respectively]" (Watarai, Amoh, Aki, Takasu, Katsuoka, 2011). In terms of prognosis regarding recorded patients, "27% of patients died from their disease."(Tural, Selçukbiricik, Günver, Karışmaz, and Serdengecti, 2013) As early as "nine weeks"( Malik, Saxena, and Kamath, 2013) succeeding clinical surgeries, had reports of patients deaths been recorded. It has also been recorded that "one patient survived twelve years after their diagnosis."(Ka, Gnangnon, and Diouf, 2016) The tumour has a "60% rate of metastasis and mortality in the order of 25%" (Ka, Gnangnon, and Diouf, 2016) with the highest recordings of metastases being found in "lymph nodes and lung and less commonly, bone and brain." (Ka, Gnangnon, and Diouf, 2016) Recorded Cases Facial localisation of a malignant chondroid syringoma Written by Tural Selçukbiricik, Günver, Karışmaz, and Serdengecti, this report investigates the case of a slow growing bump on the face of a thirty-four-year-old woman. After undergoing an excisional biopsy, it was revealed that the nodule had developed into neurofibroma. Originally the patient had undergone excision however she sustained recurrence in under a year of the surgery. She continued to undergo excision and this led to the diagnosis of malignant chondroid syringoma. To remove the tumour, the patient first had a pathological and histopathological examination to examine the metastisation and growth pattern. According to Tural Selçukbiricik, Günver, Karışmaz, and Serdengecti, “the tumour had an expansive growing pattern and a few pleomorphic, atypical cells, and a rare mitotic activity.”(Tural Selçukbiricik, Günver, Karışmaz, and Serdengecti, 2013) They also completed thoracic, abdominal, and cranial CT scans to determine the state of metastasis. The patient has a routine check-up of every three months to ensure no recurrence occurs and so far, has not had any relapse for two years following her procedure. Malignant chondroid syringoma of the scalp This 2013 case report by Malik, Saxena, and Kamath investigates the “large, fungating, and ulcerated growth”(Malik, Saxena, and Kamath, 2013) on the scalp of a sixty-one-year-old woman. The tumour was painless and developed gradually over nine months. An initial diagnosis determined the growth to be a squamous cell malignancy of the scalp. The patient was suggested to have a CECT scan of their head. The scan revealed dural invasion and a surgical excision with primary closure was performed. The histopathology findings revealed:“small groups as well as scattered pleomorphic epithelial cells having hyperchromatic nuclei and scanty cytoplasm with one to two mitotic figures of high power field, surrounded by abundant basophilic chondromyxoid stroma, diagnostic of malignant CS.”The woman died two days after her operation after yielding a “high-grade fever and altered sensorium.”(Malik, Saxena, and Kamath, 2013) Multifocal and recurrent malignant chondroid syringoma This report follows the development of MCS on a sixty-four-year-old male patient. The masses were described as skin lesions that had developed in a nodular fashion on the patients right arm. To remove the growths, the patient underwent may surgical procedures where the nodules were effectively excised. The growth was described as a:“ten centimetre, firm, lobulated mass with skin ulceration and muscle involvement was removed. Microscopic examination revealed infiltrating nests of medium to large epithelial cells embedded in a chondromyxoid matrix with few scattered plasmacytoid myoepithelial cells. There was brisk mitosis as well as large areas of tumour necrosis. All auxiliary lymph nodes were negative for tumour.” (Garcia, Atun, and Fernando, 2016)From this information, Garcia, Atun, and Fernando diagnosed the patient with malignant chondroid syringoma. After the surgery, the patient developed further growths on the scalp, face, body, upper right arm, and right foot. He was recommended chemotherapy however died before treatment began. Lymph node metastasis after excision This journal, written by Watarai, Amoh, Aki, Takasu, and Katsuoka discusses a case of malignant chondroid syringoma on a forty-six-year-old man and the state his diagnosis 12 years after excision. Originally in 1996, the man observed an “asymptomatic, enlarging nodule” (Watarai, Amoh, Aki, Takasu, and Katsuoka, 2011) on the sole of his right foot and proceeded to undergo an initial biopsy where he was not diagnosed. Physically, the nodule was “solitary, dome-shaped, skin coloured, and firm,” (Watarai, Amoh, Aki, Takasu, and Katsuoka, 2011) and was 30 mm x 30 mm. The tumour underwent excision utilising a three-millimetre margin. The nodule was then replaced with grafting of the transplanted skin. The findings were as follows.“The surgical specimen showed a lobular proliferation of tumour cells with glandular differentiation associated with a few mitotic cells, embedded in a mucinous stroma. Immunohistochemistry showed that the majority of tumour cells were positive for PAS diastase, toluidine blue, cytokeratins (CAM5.2, CK7), S-100 protein and GCDFP-15.”Although some abnormal tumours cells were present, the recorded findings the man was diagnosed with chondroid syringoma. An ultrasound and radiography were performed and revealed no indication of metastasis. However, in 2008, the man observed inflammation in his right groin area. Another ultrasound revealed a new mass also measuring 30 mm x 30mm, which was then excised. Examination of this new tumour revealed more abnormal tumour cells compared to the first nodule of the sole of the foot. The original diagnosis was thus re-examined to be consisting of malignant chondroid syringoma cells. The patient was then treated with radiation. After eighteen months he presented no evidence of recurrence or further distant metastasis. History Hirsch and Helwig gave malignant chondroid syringoma its name in 1961 in ‘Chondroid Syringoma: Mixed Tumour of Skin, Salivary Gland Type.’ "Atypical mixed tumours of the skin,"(Hirsch and Helwig, 1961) their term for tumours characterised by "histological stigma of malignancy, local invasion, and satellite tumour nodules without proven metastases" is employed even now. As of 2011, only 43 cases have been reported. Terminology Malignant mixed tumours also go by other names including: "malignant mixed tumour of skin, cutaneous malignant mixed tumour, metastasising chondroid syringoma, and aggressive chondroid syringoma." (Ka, Gnangnon, and Diouf, 2016) See also List of cutaneous conditions Neoplasm == References ==
Synovial osteochondromatosis	Synovial osteochondromatosis (SOC) (synonyms include synovial chondromatosis, primary synovial chondromatosis, synovial chondrometaplasia) is a rare disease that creates a benign change or proliferation in the synovium or joint-lining tissue, which changes to form bone-forming cartilage. In most occurrences, there is only one joint affected, either the knee, the hip, or the elbow. Rarely involves the TMJ.The cause is unknown. In this condition, cartilaginous metaplasia takes place within the synovial membrane of the joint. Metaplastic synovium organizes into nodules. With minor trauma, nodules are shed as small bodies into the joint space. In some patients, the disease process may involve tendon sheaths and bursal sacs. Cartilaginous intra-articular bodies float freely within the synovial fluid, which they require for nutrition and growth. Progressive enlargement and ossification occur with time. If they remain free, they continue to grow larger and more calcified. In severe cases, they may occupy the entire joint space or penetrate to adjacent tissues. Also, they can deposit in the synovial lining, reestablish a blood supply, and become replaced by bone. On occasion, synovial reattachment can lead to complete reabsorption of the cartilage fragment. Signs and symptoms Chronic, progressive pain and swelling of the affected joint are exacerbated by physical activity. Joint effusion and limited range of motion are common associated features. It affects primarily large joints, including knee (>50% of cases), elbow, hip, and shoulder. SOC is twice as common in men as women. Some patients have intra-articular bodies resting in stable positions within joint recesses or bursae. These patients may be asymptomatic, with SOC merely as an incidental finding at imaging. Complications Malignant transformation to synovial chondrosarcoma. This is a very rare complication occurring in chronic cases. Treatment entails synovial excision and total joint replacement.Clicking, grating, or locking may result from acute mechanical problems due to intra-articular bodies within the affected joint. Locking may destroy articular cartilage, resulting in secondary osteoarthritis. Symptoms such as joint stiffness and aching are the result of osteoarthritis that sets in after years of persistent joint irritation. Diagnosis Radiography Typical finding is of multiple, smooth, oval-shaped calcified masses within the joint space or bursa. They have a characteristic popcorn-ball appearance of calcified cartilage. With serial imaging, masses may be found to change in size, disappear, or migrate to recessed areas of the joint. They may pass from the main joint cavity into a neighboring synovial cyst. For this reason, a mass may not be appreciated within the actual joint space itself.Additional radiographic findings include joint effusion and degenerative changes such as joint space narrowing, subchondral sclerosis, and osteophyte formation. Computed tomography CT is best utilized in earlier stages of the disease process before cartilaginous bodies have calcified (become filled with calcium). CT can effectively detect non-calcified masses or those with only minimal calcification, which allows the radiologist to distinguish this condition from a simple joint effusion. Magnetic resonance imaging MR appearance depends on the composition of the intra-articular body. Entirely cartilaginous bodies will appear isointense to muscle on T1 and hyperintense to muscle on T2 weighted images. Partly calcified intra-articular bodies demonstrate foci of absent signal on all pulse sequences. Like CT arthrography, MR with gadolinium may be used to detect intra-articular bodies that have not yet calcified. Pathology Cartilaginous bodies or osteocartilaginous bodies with central ossification may be noted. They are typically spherical in shape. Sizes range from several millimeters to several centimeters in diameter. The synovium of the involved joint demonstrates villous hyperplasia, which imparts a wrinkled appearance on gross examination. There may be cartilaginous bodies attached to the synovium. Synovial involvement may be focal or diffuse in nature. Differential diagnosis Trauma-related: Fracture with avulsed fragment Fragmentation of meniscus with calcification Degenerative joint disease related: Degenerative joint disease with detached spur Synovial proliferation: Pigmented villonodular synovitis Neoplastic: Synovial chondrosarcoma Other: Osteochondritis dissecans Sequestrum from osteomyelitis Neuropathic (Charcot) jointIntra-articular bodies in SOC typically have popcorn calcification, with a dense sclerotic border with radiolucent central region. This distinct radiographic appearance sets it apart from other causes of intra-articular bodies. Number and size of intra-articular bodies can prove helpful as well. SOC typically presents as multiple intra-articular bodies. Few or isolated intra-articular bodies are more consistent with trauma or osteoarthritis. Classification Classification is divided into primary versus secondary SOC. Primary SOC occurs in an otherwise normal joint. It is suggested by monoarticular involvement in a patient in the third to fifth decades of life. Secondary SOC occurs in older patients in joints previously affected by joint disease such as osteoarthritis. This pattern is suggested by bilateral involvement with multiple joint intra-articular bodies. Treatment Asymptomatic patients do not require therapy. Symptomatic patients should undergo arthroscopic or surgical removal of intra-articular bodies. Patients who have recurrent intra-articular bodies or in whom the entire synovial lining is metaplastic require total synovectomy. References Further reading FletcherCDM, UnniKK, MertensF, editors. Pathology and genetics of tumours of soft tissue and bone. World Health Organization classification of tumours. Lyon: IARC Press, 2002. Bianchi S, Martinoli C (July 1999). "Detection of loose bodies in joints". Radiol. Clin. North Am. 37 (4): 679–90. doi:10.1016/S0033-8389(05)70123-8. PMID 10442075. Coles MJ, Tara HH (January 1997). "Synovial chondromatosis: a case study and brief review". Am. J. Orthop. 26 (1): 37–40. PMID 9021034. Crotty JM, Monu JU, Pope TL (March 1996). "Synovial osteochondromatosis". Radiol. Clin. North Am. 34 (2): 327–42, xi. PMID 8633119. Maurice H, Crone M, Watt I (1 November 1988). "Synovial chondromatosis". J Bone Joint Surg Br. 70 (5): 807–11. doi:10.1302/0301-620X.70B5.3192585. PMID 3192585. Milgram JW, Gilden JJ, Gilula LA (January 1996). "Multiple loose bodies: formation, revascularization, and resorption. A 29-year followup study". Clin. Orthop. Relat. Res. (322): 152–7. doi:10.1097/00003086-199601000-00019. PMID 8542691. S2CID 25265519. == External links ==
Stargardt disease	Stargardt disease is the most common inherited single-gene retinal disease. In terms of the first description of the disease, it follows an autosomal recessive inheritance pattern, which has been later linked to bi-allelic ABCA4 gene variants (STGD1). However, there are Stargardt-like diseases with mimicking phenotypes that are referred to as STGD3 and STGD4, and have a autosomal dominant inheritance due to defects with ELOVL4 or PROM1 genes, respectively. It is characterized by macular degeneration that begins in childhood, adolescence or adulthood, resulting in progressive loss of vision. Signs and symptoms The presentation usually occurs in childhood or adolescence, though there is no upper age limit for presentation and late-onset is possible. The main symptom is loss of visual acuity, uncorrectable with glasses. This manifests as the lack of the ability to see fine details when reading or viewing distant objects. Symptoms typically develop before age 20 (median age of onset: ~17 years old), and include: wavy vision, blind spots, blurriness, loss of depth perception, sensitivity to glare, impaired colour vision, and difficulty adapting to dim lighting (delayed dark adaptation). There is a wide variation between individuals in the symptoms experienced as well as the rate of deterioration in vision. Vision loss can be attributed to buildup of byproducts of vitamin A in photoreceptor cells and Peripheral vision is usually less affected than fine, central (foveal) vision. Genetics Historically from Stargardt’s first description of his eponymous disease until recently, the diagnosis was based on looking at the phenotype using examination and investigation of the eye. Since the advent of genetic testing, the picture has become more complex. What was thought to be one disease is, in fact, probably at least three different diseases, each related to a different genetic change. Therefore it is currently a little confusing to define what Stargardts disease is. Stargardt disease (STGD1) is caused by bi-allelic ABCA4 gene variants (i.e., autosomal recessive). Importantly, the exact genotype (i.e., combinations of both ABCA4 variants) is highly prognostic for the age of onset and disease progression.Autosomal-dominant Stargardt-like diseases were linked to genes such as PROM1 (STGD3) or ELOVL4 (STGD4) missense mutations play a role remains to be seen.The carrier frequency in the general population of ABCA4 alleles is 5 to 10%. Different combinations of ABCA4 genes will result in widely different age of onset and retinal pathology. The severity of the disease is inversely proportional to ABCA4 function and it is thought that ABCA4 related disease has a role to play in other diseases such as retinitis pigmentosa, cone-rod dystrophies and age-related macular degeneration (AMD). STGD1: By far the most common form of Stargardt disease is the recessive form caused by mutations in the ABCA4 gene. STGD4: A rare dominant defect in the PROM1 gene. STGD3: A rare dominant form of Stargardt disease caused by mutations in the ELOVL4 gene. Late-onset Stargardt disease is associated with missense mutations outside known functional domains of ABCA4. Pathophysiology In STGD1, the genetic defect causes malfunction of the ATP-binding cassette transporter (ABCA4) protein of the visual phototransduction cycle. Defective ABCA4 leads to improper shuttling of vitamin A throughout the retina, and accelerated formation of toxic vitamin A dimers (also known as bisretinoids), and associated degradation byproducts. Vitamin A dimers and other byproducts are widely accepted as the cause of STGD1. As such, slowing the formation of vitamin A dimers might lead to a treatment for Stargardt. When vitamin A dimers and byproducts damage the retinal cells, fluorescent granules called lipofuscin in the retinal pigmented epithelium of the retina appear, as a reflecting such damage. In STGD4, a butterfly pattern of dystrophy is caused by mutations in a gene that encodes a membrane bound protein that is involved in the elongation of very long chain fatty acids (ELOVL4) Diagnosis Diagnosis is firstly clinical through history and examination usually with a Slit-lamp. If characteristic features are found the investigations undertaken will depend on locally available equipment and may include Scanning laser ophthalmoscopy which highlights areas of autofluorescence which are associated with retinal pathology. Spectral-domain optical coherence tomography, electroretinography and microperimetry are also useful for diagnostic and prognostic purposes. Fluorescein angiography is used less often than in the past. These investigations may be followed by genetic testing in order to avoid misdiagnosis. Other diseases may have overlapping phenotypic features with Stargardt Disease and the disease itself has multiple variants. In one study, 35% of patients diagnosed with Stargardt Disease through physical ophthalmic examination were found to be misdiagnosed when subsequent genetic testing was done. Genetic testing can be utilized to ensure an proper diagnosis for which the correct treatment can be applied. Treatment At present there is no treatment for Stargardt Disease. However, ophthalmologists recommend measures that could slow the rate of progression. There are no prospective clinical trials to support these recommendations, but they are based on scientific understanding of the mechanisms underlying the disease pathology. There are three strategies doctors recommend for potential harm reduction: reducing retinal exposure to damaging ultraviolet light, avoiding excess Vitamin A with the hope of lowering lipofuscin accumulation and maintaining good general health and diet.Ultra-violet light has more energy and is a more damaging wavelength spectra than visible light. In an effort to mitigate this, some ophthalmologists may recommend that the patient wears a broad-brimmed hat or sunglasses when they are outdoors. Sometimes, doctors also instruct their patients to wear yellow-tinted glasses (which filter out blue light) when indoors and in artificial light or in front of a digital screen. Certain foods, especially carrots, are rich in vitamin A, but the amount from food is not harmful. Foods with a high vitamin A content are often yellow or orange in color, such as squash, pumpkin, and sweet potato, but some, such as liver, are not. There are supplements on the market with more than a daily allowance of vitamin A that should be avoided, but each individual should discuss this with their doctor. Smoking, overweight or obesity, and poor diet quality may also contribute to more rapid degeneration. On the other hand, the consumption of oily fish, in a diet similar to that which doctors recommend for age related macular degeneration, can be used to slow the progression of the disease.Advances in technology have brought devices that help Stargardt patients who are losing their vision maintain their independence. Low-vision aids can range from hand lenses to electronic devices and can allow those losing their vision to be able to carry out daily activities. Some patients may even opt for in-person services. Prognosis The long-term prognosis for patients with Stargardt disease is widely variable and depends on the age of onset and genetic alleles.The majority of patients will progress to legal blindness, which means that central reading vision will be lost. However, perimetry and microperimetry studies indicate that the peripheral light sensitivity is preserved over a long time in a significant fraction of all patients (i.e., >50%). Stargardt disease has no impact on general health and life expectancy is normal. Some patients, usually those with the late-onset form, can maintain excellent visual acuities for extended periods and are therefore able to perform tasks such as reading or driving. Epidemiology A 2017 prospective epidemiologic study that recruited 81 patients with STGD over 12 months reported an incidence of between 1 and 1.28 per 10 000 individuals. The median age of presentation was 27 years (range 5–64 years), most (90%) were symptomatic, with a median visual acuity of Snellen equivalent 20/66. History Karl Stargardt (1875–1927) was a German ophthalmologist born in Berlin. He studied medicine at the University of Kiel, qualifying in 1899. He later became head of the Bonn University’s ophthalmology clinic, followed by a post as chair of ophthalmology at the University of Marburg. In 1909 he described 7 patients with a recessively inherited macular dystrophy, now known as Stargardt’s disease. Research There are several clinical trials in various stages involving several potential therapeutic areas, gene therapy, stem cell therapy, drug therapy and artificial retinas. In general all are testing the safety and benefits of their respective therapies in phase I or II trials. These studies are designed to evaluate the safety, dose and effectiveness in small number of people in Phase I with Phase II evaluating similar criteria in a larger population but including a greater insight into potential side effects.Gene therapy is designed to insert a copy of a corrected gene into retinal cells. The hope is to return cell function back to normal and the treatment has the potential to stop disease progression. This therapy will not restore impaired vision back to normal. The research is being undertaken by a partnership between Sanofi and Oxford BioMedica. A Lentiviral vector is used to deliver a normal gene to the target tissue via a subretinal injection. The therapy is known as SAR422459 and it has been terminated prematurely due to halt in developing the drug product.Kubota Vision is in Phase III clinical trials of a visual cycle modulator that modulates RPE65 activity to treat Stargardts. Kubota Vision published the results of a dose range study of a drug known as Emixustat, with findings that will effect dose selection for their phase III trial set to complete in June 2022.Stem-cell therapy involves injecting cells with the potential to mature into differentiated and functioning retinal cells. This therapy has the potential stop disease progression and in the long term improve vision. To improve vision this technique will need to replicate the complex multi-layered and neurally anatomy of the retina. There are a number of research groups working with stem cells one of which is Ocata Therapeutics.Alkeus Pharma is evaluating the potential of deuterated vitamin A as the drug ALK-001. The hope is that the deuterated vitamin A will reduce the build-up of toxic vitamin A metabolites in the retina and therefore slow rate of visual deterioration. To create deuterated vitamin A some of the hydrogen atoms are replaced with the isotope deuterium which has an extra neutron and is therefore twice the standard atomic weight of hydrogen. A Phase II clinical trial is taking place using ALK-001 with an estimated completion date of December 2024.MD Stem Cells, a research-physician clinical development company using autologous bone marrow derived stem cells (BMSC), has released results of the Stargardt Disease cohort within their ongoing Stem Cell Ophthalmology Study II (SCOTS2) clinical trial (NCT 03011541). Average visual improvement was 17.96% (95% CI, 16.39 to 19.53%) with 61.8% of eyes improving and 23.5% remaining stable with no adverse events occurring.Retinal implants are in the early stages of development and their use could be of benefit to many people with Visual impairment though implanting and maintaining an electrical device within the eye that interfaces with the optic nerve presents many challenges. An example of a device is made by Argus retinal prosthesis, the camera is an external device held on spectacles, the camera signal is processed and then fed via wires into the retina to terminate in some electrodes that interface with the optic nerve. References External links NCBI Genetic Testing Registry
Psoriatic erythroderma	Psoriatic erythroderma represents a form of psoriasis that affects all body sites, including the face, hands, feet, nails, trunk, and extremities.: 410–411 : 195 This specific form of psoriasis affects 3 percent of persons diagnosed with psoriasis. First-line treatments for psoriatic erythroderma include immunosuppressive medications such as methotrexate, acitretin, or ciclosporin. See also Skin lesion List of cutaneous conditions References == External links ==
Ectopic tooth	An ectopic tooth is a tooth that is not located at the dental arch caused by a faulty course during eruption. Ectopic teeth may commonly occur within the dentate region of the jaws. Rarely, the ectopic eruption may occur into the non dentate region, such as the coronoid process, mandibular condyle, maxillary sinus, nasal septum and the palate. == References ==
Epidermodysplasia verruciformis	Epidermodysplasia verruciformis (EV), also known as treeman syndrome, is an extremely rare autosomal recessive hereditary skin disorder associated with a high risk of skin cancer. It is characterized by abnormal susceptibility to human papillomaviruses (HPVs) of the skin. The resulting uncontrolled HPV infections result in the growth of scaly macules and papules resembling tree bark, particularly on the hands and feet. It is typically associated with HPV types 5 and 8, which are found in about 80% of the normal population as asymptomatic infections, although other types contribute less frequently, among them types 12, 14, 15 and 17 (which are occasionally referred to as the beta papillomaviruses).The condition usually has an onset of between the ages of one and 20 but it can occasionally be present in middle age. The condition is also known as Lewandowsky–Lutz dysplasia, named after the physicians who first documented it, Felix Lewandowsky and Wilhelm Lutz. Signs and symptoms Clinical diagnostic features are lifelong eruptions of pityriasis versicolor-like macules, flat wart-like papules, one to many cutaneous horn-like lesions, and development of cutaneous carcinomas.Patients present with flat, slightly scaly, red-brown macules on the face, neck, and body, recurring especially around the penial area, or verruca-like papillomatous lesions, seborrheic keratosis-like lesions, and pinkish-red plane papules on the hands, upper and lower extremities, and face. The initial form of EV presents with only flat, wart-like lesions over the body, whereas the malignant form shows a higher rate of polymorphic skin lesions and development of multiple cutaneous tumors.Generally, cutaneous lesions are spread over the body, but some cases have only a few lesions which are limited to one extremity. Genetics Most patients with classic EV carry bialletic loss-of-function mutations of transmembrane channel-like protein 6 (TMC6; also called EV protein 1, EVER1), TMC8 (also called EVER2), or calcium- and integrin-binding protein 1 (CIB1). The EVER1 or EVER2 genes are located adjacent to one another on chromosome 17. These genes play a role in regulating the distribution of zinc in the cell nuclei. Zinc is a necessary cofactor for many viral proteins, and the activity of EVER1/EVER2 complex appears to restrict the access of viral proteins to cellular zinc stores, limiting their growth.Other genes have also rarely been associated with this condition. These include the ras homolog gene family member H. Treatment No curative treatment against EV has been found yet. Several treatments have been suggested, and acitretin 0.5–1 mg/day for 6 months duration is the most effective treatment owing to antiproliferative and differentiation-inducing effects. Interferons can also be used effectively together with retinoids.Cimetidine was reported to be effective because of its depressing mitogen-induced lymphocyte proliferation and regulatory T cell activity features. A report by Oliveira et al. showed that cimetidine was ineffective. Hayashi et al. applied topical calcipotriol to a patient with a successful result.As mentioned, various treatment methods are offered against EV; however, most importantly, education of the patient, early diagnosis, and excision of the tumoral lesions take preference to prevent the development of cutaneous tumors. Notable cases Ion Toader In March 2007, a Romanian man named Ion Toader was diagnosed with this condition. A patient of dermatologist Carmen Madeleine Curea, his pictures appeared on numerous blogs and Romanian press sources. Curea works with Spitalul Clinic Colentina in Bucharest, Romania. Stephen Stone, past president of the American Academy of Dermatology, confirmed that this was Lewandowsky–Lutz. Toader underwent surgery in late 2013, and since then has been mostly symptom-free, with only small reappearances. Dede Koswara In November 2007, a video of a 35-year-old Indonesian man named Dede Koswara with a similar disease appeared on the Internet. His story appeared on the U.S. Discovery Channel and TLC series My Shocking Story (Extraordinary People on UKs Five) in the episode "Half Man Half Tree". On August 12, 2008, Koswaras story was the subject of an ABCs Medical Mystery episode entitled "Tree Man".On 26 August 2008, Koswara returned home following surgery to remove 6 kg (13 lb) of warts from his body. The surgery consisted of three steps: Removal of the thick carpet of warts and massive horns on his hands Removal of the smaller warts on his head, torso, and feet Covering of the hands with grafted skinIn all, 96% of the warts were removed. The surgery was documented by the Discovery Channel and TLC in the episode "Treeman: Search for the Cure". However, his warts returned and he was thought to require two surgeries per year for the rest of his life in order to manage the warts. The Discovery Channel funded a blood analysis and found he lacked an immune system antigen to fight yeast infection. He was offered to have more tests run to determine whether it is treatable, and the doctor was fairly optimistic, but he refused the treatment.According to The Jakarta Post, Koswara underwent the first of a series of new surgical procedures to remove the regrown warts in the spring of 2011. Surgery had, however, proven to be a temporary solution for Koswara, as the warts continued to re-emerge. He had thus undergone three surgical operations since his major surgery in 2008. At the end of December 2010, two doctors from the Japanese Society for Complementary and Alternative Medicine brought him a drug made from Jobs tears. The medicine was still undergoing lab tests as of 2016.Koswara died on 30 January 2016 at Hasan Sadikin Hospital, Bandung, from the complications related to his condition.In 2009, the Discovery Channel episode "Treeman Meets Treeman" reported on another Indonesian man, from the same region as Koswara, who also has the disease and was given a similar treatment for it. His treatment seemed to have worked better. Omar Tamim In 2013, one case of epidermodysplasia verruciformis was reported in Iraq. No treatment was given since the condition was initially misdiagnosed. Abul Bajandar In January 2016, a 25-year-old patient named Abul Bajandar from Khulna, Bangladesh was admitted in Dhaka Medical College and Hospital and was diagnosed with this condition. Doctors at the hospital decided to form a medical board for the treatment of the patient. Over the following year, Bajandar underwent at least 25 surgeries for the removal of the warts—weighing in excess of 5 kg (11 lb)—from his hands, feet, and legs. Bajandar’s condition returned after he interrupted treatments in May 2018. His doctors requested that he return for treatment many times. He finally returned for treatment in late 2018, but his condition had significantly worsened and spread to his feet. He will reportedly need five to six operations to get the condition back under control. In June 2019 he requested to get his hands amputated as the pain is unbearable. Sahana Khatun In January 2017 it was reported that a 10-year-old girl in Bangladesh, Sahana Khatun, was diagnosed after developing lesions four months earlier. BBC News said that the case may have been the first diagnosis in a female. Mohammed Taluli In August 2017 it was reported that a 42-year-old man from Gaza, Mohammed Taluli, had been successfully operated on at the Hadassah Medical Centre in Jerusalem. Cristhél Suyapa Martínez In October 2018, a five-year-old girl in Honduras, Cristhél Suyapa Martínez, was diagnosed with the condition. Sebastian Quinn Sebastian Quinn is a Pittsburgh man with the condition who featured as a patient on an episode of TLCs My Feet Are Killing Me in January 2021. His overseeing specialist Ebonie Vincent operated on him to manage the growths on his feet. References Further reading Yabe Y, Sadakane H (September 1975). "The virus of epidermodysplasia verruciformis: electron microscopic and fluorescent antibody studies". The Journal of Investigative Dermatology. 65 (3): 324–30. doi:10.1111/1523-1747.ep12598388. PMID 808576. Lewandowsky F, Lutz W (October 1922). "Ein Fall einer bisher nicht beschriebenen Hauterkrankung (Epidermodysplasia verruciformis)". Archiv für Dermatologie und Syphilis (in German). 141 (2): 193–203. doi:10.1007/BF01938833. S2CID 8585441. == External links ==
Distal myopathy	Distal myopathy is a group of rare genetic disorders that cause muscle damage and weakness, predominantly in the hands and/or feet. Mutation of many different genes can be causative. Many types involve dysferlin. Signs and symptoms All of the different types affect different regions of the extremities and can show up as early as 5 years of age to as late as 50 years old. Distal myopathy has slow progress therefore the patient may not know that they have it until they are in their late 40s or 50s.Miyoshi myopathy affects the posterior muscles of the lower leg, more so than the anterior muscles of the lower leg. Cause The cause of this myopathy is very hard to determine because it can be a mutation in any of at least eight genes and not all are known yet. These mutations can be inherited from one parent, autosomal dominant, or from both parents, autosomal recessive. There are eight known types of distal myopathy. Types Diagnosis In terms of diagnosis, Vocal cord and pharyngeal distal myopathy should be assessed via serum CK levels, as well as muscle biopsy of the individual suspected of being afflicted with this condition Management As of 2011, no disease modifying treatments are known. Foot drop can be managed with ankle-foot orthoses or surgical tendon transfer, in which the tibialis posterior muscle is repurposed to function as a tibialis anterior muscle. In select types of distal myopathy, evaluation of the heart may be indicated. Scoliosis and contractures can be surgically managed. References Further reading Udd, Bjarne (February 2007). "Molecular biology of distal muscular dystrophies—Sarcomeric proteins on top". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1772 (2): 145–158. doi:10.1016/j.bbadis.2006.08.005. PMID 17029922. == External links ==
Niemann–Pick disease	Niemann–Pick disease is a group of severe inherited metabolic disorders, in which sphingomyelin accumulates in lysosomes in cells (the lysosomes normally degrade material that comes from out of cells). These disorders involve the dysfunctional metabolism of sphingolipids, which are fats found in cell membranes. They can be considered as a kind of sphingolipidosis, which is included in the larger family of lysosomal storage diseases. Signs and symptoms Symptoms are related to the organs in which sphingomyelin accumulates. Enlargement of the liver and spleen (hepatosplenomegaly) may cause reduced appetite, abdominal distension, and pain. Enlargement of the spleen (splenomegaly) may also cause low levels of platelets in the blood (thrombocytopenia).Accumulation of sphingomyelin in the central nervous system (including the cerebellum) results in unsteady gait (ataxia), slurring of speech (dysarthria), and difficulty swallowing (dysphagia). Basal ganglia dysfunction causes abnormal posturing of the limbs, trunk, and face (dystonia). Upper brainstem disease results in impaired voluntary rapid eye movements (supranuclear gaze palsy). More widespread disease involving the cerebral cortex and subcortical structures causes gradual loss of intellectual abilities, causing dementia and seizures.Bones also may be affected, with the disease causing enlarged bone marrow cavities, thinned cortical bone, or a distortion of the hip bone called coxa vara. Sleep-related disorders also occur with the condition, such as sleep inversion, sleepiness during the day and wakefulness at night. Gelastic cataplexy, the sudden loss of muscle tone when the affected patient laughs, is also seen. Causes Mutations in the SMPD1 gene cause Niemann–Pick disease types A and B. They produce a deficiency in the activity of the lysosomal enzyme acid sphingomyelinase, that breaks down the lipid sphingomyelin.Mutations in NPC1 or NPC2 cause Niemann–Pick disease, type C (NPC), which affects a protein used to transport lipids.Type D originally was separated from type C to delineate a group of patients with otherwise identical disorders who shared a common Nova Scotian ancestry. Patients in this group are known to share a specific mutation in the NPC1 gene, so NPC is used for both groups. Before the molecular defects were described, the terms "Niemann–Pick type I" and "Niemann–Pick type II" were proposed to separate the high- and low-sphingomyelin forms of the disease in the early 1980s.Niemann–Pick disease is inherited in an autosomal recessive pattern, which means both copies, or both alleles of the gene, must be defective to cause the disease. "Defective" means they are altered in a way that impairs their function. Most often, the parents of a child with an autosomal recessive disorder are carriers: they have one copy of the altered gene, but are not affected because the other copy produces the enzyme. If both parents are carriers, each pregnancy has a 25% chance of producing an affected child. Genetic counseling and genetic testing are recommended for families who may be carriers of the disease. Pathophysiology Niemann–Pick diseases are a subgroup of lipid storage disorders called sphingolipidoses in which harmful quantities of fatty substances, or lipids, accumulate in the spleen, liver, lungs, bone marrow, and brain.In the classic infantile type-A variant, a missense mutation causes complete deficiency of sphingomyelinase. Sphingomyelin is a component of cell membrane including the organellar membrane, so the enzyme deficiency blocks degradation of lipid, resulting in the accumulation of sphingomyelin within lysosomes in the macrophage-monocyte phagocyte lineage. Affected cells become enlarged, sometimes up to 90 μm in diameter, secondary to the distention of lysosomes with sphingomyelin and cholesterol. Histology shows lipid-laden macrophages in the marrow and "sea-blue histiocytes" on pathology. Numerous small vacuoles of relatively uniform size are created, giving the cytoplasm a foamy appearance. Diagnosis For type A and B, levels of sphingomylinase can be measured from a blood sample. To diagnose type C, a skin sample can help determine whether the transporter is affected via the Filipin test which detects build-up of unesterified cholesterol via fluorescent staining. Classification There are four types of Niemann–Pick disease in two categories. Patients with ASM deficiency are classified into type A and B. Type A patients exhibit hepatosplenomegaly in infancy and profound central nervous system involvement and unable to survive beyond two years of age. Type B patients also show hepatosplenomegaly and pathologic alterations of their lungs but usually without the involvement of their central nervous system. Some can develop significant life-threatening complications including liver failure, hemorrhage, oxygen dependency, pulmonary infections, and splenic rupture. Some develop coronary artery or valvular heart disease. In a longitudinal natural history study, nearly 20% of the patients died. For those classified into type C, they may have mild hepatosplenomegaly, but their central nervous system is profoundly affected. Niemann–Pick disease, SMPD1-associated, which includes types A and BNiemann–Pick disease type A: classic infantile Niemann–Pick disease type B: visceralNiemann–Pick disease, type C: subacute/juvenile, includes types C1 (95% of type C) and C2. Type C is the most common form of the disease Type C2 is a rare form of the disease.Niemann–Pick disease type D (or Nova Scotia form) is now believed to be the same condition as Niemann–Pick disease type C. Two poorly characterized forms of Niemann–Pick disease have also been described as types E and F. Treatment No specific treatment is known for type A, but symptoms are treated.In adult patients with type B, physicians try to keep cholesterol levels down to normal levels. If statins are used, they monitor liver function. If the spleen is enlarged and platelet levels low, acute episodes of bleeding may require transfusions of blood products. If they have symptoms of interstitial lung disease, they may need oxygen.Anecdotally, organ transplant has been attempted with limited success. Future prospects include enzyme replacement and gene therapy. Bone marrow transplant has been tried for type B.In January 2009, Actelion announced the drug miglustat (Zavesca) had been approved in the European Union for the treatment of progressive neurological manifestations in adult patients and pediatric patients with NPC. The drug is available to patients in the United States on an experimental basis. In March 2010, the FDA requested additional preclinical and clinical information regarding Zavesca from Actelion before making a final decision on approving the drug in the United States for NPC.Olipudase alfa (Xenpozyme) was approved for medical use in Japan in March 2022. Prognosis Highly variable, infantile neurovisceral Niemann Pick disease (Type A ASMD) is usually fatal before 3 years of age. In Type B ASMD mortality before adulthood is common. But many patients live well into adulthood and may reach a normal lifespan. Diagnoses have been made in the 7th decade of life. Type C is an entirely different disorder, which also has a highly variable prognosis. Incidence The incidence among Ashkenazi Jews is estimated to be about one in 40,000 for type A of Niemann–Pick disease. The incidence of both Niemann–Pick disease types A and B in all other populations is estimated to be one in 250,000. The incidence of Niemann–Pick disease type C is estimated to be one in 150,000. History Albert Niemann published the first description of what now is known as Niemann–Pick disease, type A, in 1914. Ludwig Pick described the pathology of the disease in a series of papers in the 1930s.In 1961, the classification of Niemann–Pick disease into types A, B, and C was introduced, and also contained a type D, called the "Nova Scotian type". Genetic studies showed that type D is caused by the same gene as type C1, and the type D designation is no longer used. Research Research has been ongoing to better understand the disease and treatments for it. Pathology The loss of myelin in the central nervous system is considered to be a main pathogenic factor. Research uses animal models carrying the underlying mutation for Niemann–Pick disease, e.g. a mutation in the NPC1 gene as seen in Niemann-Pick type C disease. In this model, the expression of myelin gene regulatory factor (MRF) has been shown to be significantly decreased. MRF is a transcription factor of critical importance in the development and maintenance of myelin sheaths. A perturbation of oligodendrocyte maturation and the myelination process might, therefore, be an underlying mechanism of the neurological deficits.Curiously, in 2011 fibroblast cells derived from patients with Niemann-Pick type C1 disease were shown to be resistant to Ebola virus because of mutations in the NPC1 protein, which is needed for viral escape from the vesicular compartment.Other studies have uncovered small molecules which inhibit the receptor and may be a potential therapeutic strategy. Treatments under investigation Experimental use of arimoclomol In 2014 the European Medicines Agency (EMA) granted orphan drug designation to arimoclomol for the treatment of Niemann-Pick type C. This was followed in 2015 by the U.S. Food & Drug Administration (FDA). Dosing in a placebo-controlled phase II/III clinical trial to investigate treatment for Niemann-Pick type C (for patients with both type C1 and C2) using arimoclomol began in 2016. Experimental use of 2-hydroxypropyl-β-cyclodextrin Researchers at the University of Arizona first proposed the use of 2-hydroxypropyl-β-cyclodextrins for the treatment of Niemann-Pick Type C1 in 2001. Researchers noted that HPBCDs, with varying levels of 2-hydroxypropyl substitution, had effects in delaying neurological symptoms and in decreasing liver cholesterol storage in a Niemann-Pick mouse model. Later, researchers at the University of Texas Southwestern Medical Center found that when Niemann–Pick type C mice were injected with 2-hydroxypropyl-β-cyclodextrin (HPbCD) when they were 7 days old, they showed marked improvement in liver function, much less neurodegeneration and ultimately, they lived longer lives than the mice who did not receive this treatment. These results suggest HPbCD acutely reverses the storage defect seen in NPC.In April 2011, the U.S. National Institutes of Health (NIH), in collaboration with the Therapeutics for Rare and Neglected Diseases Program (TRND), announced they were developing a clinical trial using HPbCD for Niemann–Pick type C1 patients. A clinical trial conducted by Vtesse, LLC began in January 2013, and was completed in March 2017.On April 26, 2013, the European Medicines Agency granted International Niemann-Pick Disease Alliance (INPDA), the United Kingdom, orphan designation for HPbCD for the treatment of Niemann-Pick disease, type C.Gene therapy Gene therapy is being used clinically to treat genetic diseases including haemophilia and spinal muscular atrophy. It has been used preclinically, in a mouse model of Niemann-Pick type C, using an adeno-associated virus derived viral vector has been shown to extend lifespan following injection into the lateral ventricles of the neonatal brain. In a separate proof-of-concept study a similar vector, but with a modified capsid, was injected intravenously into Niemann-Pick type C mice at around four weeks of age; this resulted in extended lifespan and improved weight gain. Gene therapy has also been used preclinically in a mouse model of Niemann-Pick type A. Injection into the Cisterna magna at 7 weeks of age prevented motor and memory impairment and neuronal cell death. See also Lysosomal storage disease Niemann–Pick disease, type C Gauchers disease Medical genetics of Ashkenazi Jews References External links niemann at NINDS Genetics Home Reference on Niemann–Pick Disease This article incorporates public domain text from The U.S. National Library of Medicine
Riedels thyroiditis	Riedels thyroiditis, is a chronic form of thyroiditis. It is now believed that Riedels thyroiditis is one manifestation of a systemic disease that can affect many organ systems called IgG4-related disease. It is often a multi-organ disease affecting pancreas, liver, kidney, salivary and orbital tissues and retroperitoneum. The hallmarks of the disease are fibrosis and infiltration by IgG4 secreting plasma cells. Signs and symptoms Pathophysiology Riedels thyroiditis is characterized by a replacement of the normal thyroid parenchyma by a dense fibrosis that invades adjacent structures of the neck and extends beyond the thyroid capsule. This makes the thyroid gland stone-hard (woody) and fixed to adjacent structures. The inflammatory process infiltrates muscles and causes symptoms of tracheal compression. Surgical treatment is required to relieve tracheal or esophageal obstruction. Diagnosis It typically present as a painless, hard anterior neck mass, which progresses over weeks to years to produce symptoms of compression, including dysphagia, dyspnea choking and hoarseness. Patients may present with symptoms of hypothyroidism and hypoparathyroidism as the gland is replaced by Fibrous tissues .physical examination reveals a hard,"woody" thyroid gland with fixation to surrounding tissue. The diagnosis needs to be confirmed by open thyroid biopsy because the firm and Fibrous nature of the gland renders FNAB inadequate Treatment Therapy usually consists of prednisolone, nonetheless some cases may require surgery. Tamoxifen has been proposed as part of a treatment plan.Treatment is directed to surgical relief of compressive symptoms. Tamoxifen may also be beneficial.The type of surgery which is indicated here is isthmectomy. Prevalence Riedels thyroiditis is classified as rare. Most patients remain euthyroid, but approximately 30% of patients become hypothyroid and very few patients are hyperthyroid. It is most commonly seen in women. Eponym It is named for Bernhard Riedel. He first recognized the disease In 1883 and published its description in 1896. References == External links ==
Telangiectasia macularis eruptiva perstans	Telangiectasia macularis eruptiva perstans is persistent, pigmented, asymptomatic eruption of macules usually less than 0.5 cm in diameter with a slightly reddish-brown tinge.: 616 See also Mastocytosis Skin lesion List of cutaneous conditions References == External links ==
Morquio syndrome	Morquio syndrome, also known as Mucopolysaccharidosis Type IV (MPS IV), is a rare metabolic disorder in which the body cannot process certain types of sugar molecules called glycosaminoglycans (AKA GAGs, or mucopolysaccharides). In Morquio syndrome, the specific GAG which builds up in the body is called keratan sulfate. This birth defect, which is autosomal recessive, is a type of lysosomal storage disorder. The buildup of GAGs in different parts of the body causes symptoms in many different organ systems.: 544 In the US, the incidence rate for Morquio syndrome is estimated at between 1 in 200,000 and 1 in 300,000 live births. Signs and symptoms Patients with Morquio syndrome appear healthy at birth. Types A and B have similar presentations, but Type B generally has milder symptoms. The age of onset is usually between 1 and 3 years of age. Morquio syndrome causes progressive changes to the skeleton of the ribs and chest, which may lead to neurological complications such as nerve compression. Patients may also have hearing loss and clouded corneas. Intelligence is usually normal unless a patient has untreated hydrocephalus.Physical growth slows and often stops around age 8. Skeletal abnormalities include a bell-shaped chest, a flattening or curvature of the spine, shortened long bones, and dysplasia of the hips, knees, ankles, and wrists. The bones that stabilize the connection between the head and neck can be malformed (odontoid hypoplasia); in these cases, a surgical procedure called spinal cervical bone fusion can be lifesaving. Restricted breathing, joint stiffness, and heart disease are also common. Children with the more severe form of MPS IV may not live beyond their twenties or thirties. Cause Morquio syndrome is inherited from an autosomal recessive inherited gene. Every person has two copies of the genes needed to break down keratan sulfate, but only one healthy copy is needed. Both parents pass down one defective copy to their child, resulting in a child with no functional copies of the gene. As such, the body is incapable breaking down keratan sulfate for disposal. The incompletely broken down GAGs remain stored in cells in the body, causing progressive damage. Babies may show little sign of the disease, but as more and more cells become damaged, symptoms start to appear. Diagnosis Classification This syndrome has two forms, A and B, referred to as Morquio A and Morquio B syndrome or MPS IVA and MPS IVB. The two forms are distinguished by the gene product involved; Type A involves a malfunction in the GALNS gene, while Type B involves a malfunction of the GLB1 gene. Treatment The treatment for Morquio syndrome consists of prenatal identification and of enzyme replacement therapy. On 12 February 2014, the US Food and Drug Administration approved the drug elosulfase alfa (Vimizim) for treating Type A. Currently, there is no treatment for Type B. Prognosis The lifespan of patients with Morquio syndrome is variable and depends on the subtype. Type A is generally severe, with a life expectancy in the 20s to 30s. In 2016, a man with Morquio syndrome died at the age of 81.One study found that the mean life expectancy for patients in the United Kingdom was 25.30, with a standard deviation of 17.43 years. On average, female patients lived 4 years longer than male patients. Respiratory failure was the primary cause of death in 63% of patients. Other causes of death were cardiac failure (11%), post-traumatic organ failure (11%), complications of surgery (11%), and heart attack (4%). Life expectancy has been increasing since the 1980s. The average age at death due to respiratory failure improved from 17.42 years old in the 1980s to 30.74 years old in the 2000s. History The condition was first described, simultaneously and independently, in 1929, by Luis Morquio (1867–1935), a prominent Uruguayan physician who discovered it in Montevideo, and James Frederick Brailsford (1888–1961), an English radiologist in Birmingham, England. They both recognized the occurrence of corneal clouding, aortic valve disease, and urinary excretion of keratan sulfate. Morquio observed the disorder in four siblings in a family of Swedish descent and reported his observations in French. See also Hurler syndrome (MPS I) Hunter syndrome (MPS II) Sanfilippo syndrome (MPS III) Dwarfism References == External links ==
Disseminated superficial actinic porokeratosis	Disseminated superficial actinic porokeratosis (DSAP) is a non-contagious skin condition with apparent genetic origin in the SART3 gene.: 533 It most often presents in sun-exposed areas of the body. Some DSAP cases have been reported in patients with acute immune compromised situations, particularly in the elderly. For those with sun damaged skin, the lesions usually begin to appear in the patients 20s and increase in number and visibility in the 40s or 50s. Commonly, though not always, the number and visibility of lesions is in direct proportion to the amount of sun damage to the affected area. Lesions generally are characterized by an irregularly shaped thread-like ring that is usually the size of a pencil eraser, though lesions vary and may be half or double that size. The thread-like ring is very thin, much like fabric thread for sewing, and raised such that it is both palpable and visible. The interior of the ring may be rough like sandpaper, or smooth. The interior is often discolored, though colors vary from patient to patient. Lesions, due to their vascular nature, can also vary according to body temperature, environmental temperatures, and other external stimuli. The internal ring color is most often reddish, purplish, pink, or brown.Some patients report itching and irritation associated with the condition, and many report no notable sensation. Although no known hormonal link has been found, DSAP occurs more commonly in women.A study in 2000 was done on a Chinese family, in which a locus for a gene was located. See also Porokeratosis Skin lesion List of cutaneous conditions References == External links ==
Bickerstaff brainstem encephalitis	Bickerstaff brainstem encephalitis is a rare inflammatory disorder of the central nervous system, first described by Edwin Bickerstaff in 1951. It may also affect the peripheral nervous system, and has features in common with both Miller Fisher syndrome and Guillain–Barré syndrome. Signs and symptoms In order to diagnose Bickerstaff brainstem encephalitis, ataxia and ophthalmoplegia must be present. These are also diagnostic features of Miller Fisher syndrome, and so Bickerstaffs is only diagnosed if other features are present which exclude Miller Fisher syndrome. These may include drowsiness, coma or hyperreflexia. When the condition is defined in this way, a number of other features are commonly but not always found: among these are weakness of the limbs, the face, and/or the bulbar muscles; abnormalities of the pupils; and absent reflexes.Like some other autoimmune diseases, the condition usually follows a minor infection, such as a respiratory tract infection or gastroenteritis. Pathophysiology The clinical features and course of the condition, the associated auto-antibodies against relevant antigens, and the response to treatment, all suggest that Bickerstaff brainstem encephalitis is an autoimmune disease. However, each of these criteria fails to fit a substantial proportion of patients, and there is no single test or feature which is diagnostic of Bickerstaff brainstem encephalitis. It is, therefore, possible that a proportion of cases are due to other causes, such as infection or lymphoma, but remain undiagnosed. It is also possible that there is more than one autoimmune disease that can cause an illness that would currently be diagnosed as Bickerstaffs. There is certainly overlap between Guillain–Barré syndrome, Miller Fisher syndrome and Bickerstaff brainstem encephalitis, as well as other conditions associated with anti-ganglioside antibodies such as chronic ophthalmoplegia with anti-GQ1b antibody. and the pharyngo-cervico-brachial variant of GBS. Diagnosis Anti-GQ1b antibodies have been found in two-thirds of patients with this condition. This antibody is also found in almost all cases of Miller Fisher syndrome. The EEG is often abnormal, but shows only slow wave activity, which also occurs in many other conditions, and so is of limited value in diagnosis. Similarly, raised CSF protein levels and pleocytosis are frequent but non-specific. It was originally thought that raised CSF protein without pleocytosis (albuminocytological dissociation) was a characteristic feature, as it is in Guillain–Barré syndrome, but this has not been supported in more recent work. In only 30% of cases is an MRI brain scan abnormal. Nerve conduction studies may show an axonal polyneuropathy. Treatment Most patients reported in the literature have been given treatments suitable for autoimmune neurological diseases, such as, plasmapheresis and/or intravenous immunoglobulin, and most have made a good recovery. The condition is too rare for controlled trials to have been undertaken. References == External links ==
Thyroid dysgenesis	Thyroid dysgenesis is a cause of congenital hypothyroidism where the thyroid is missing, ectopic, or severely underdeveloped. It should not be confused with iodine deficiency, or with other forms of congenital hypothyroidism, such as thyroid dyshormonogenesis, where the thyroid is present but not functioning correctly. Congenital hypothyroidism caused by thyroid dysgenesis can be associated with PAX8. Ectopic thyroid An ectopic thyroid, also called accessory thyroid gland, is a form of thyroid dysgenesis in which an entire or parts of the thyroid located in another part of the body than what is the usual case. A completely ectopic thyroid gland may be located anywhere along the path of the descent of the thyroid during its embryological development, although it is most commonly located at the base of the tongue, just posterior to the foramen cecum of the tongue. In this location, an aberrant or ectopic thyroid gland is known as a lingual thyroid. If the thyroid fails to descend to even higher degree, then the resulting final resting point of the thyroid gland may be high in the neck, such as just below the hyoid bone. Parts of ectopic thyroid tissue ("accessory thyroid tissue") can also occur, and arises from remnants of the thyroglossal duct, and may appear anywhere along its original length. Accessory thyroid tissue may be functional, but is generally insufficient for normal function if the main thyroid gland is entirely removed.Lingual thyroid is 4-7 times more common in females, with symptoms developing during puberty, pregnancy or menopause. Lingual thyroid may be asymptomatic, or give symptoms such as dysphagia (difficulty swallowing), dysphonia (difficulty talking) and dyspnea (difficulty breathing). References == External links ==
Vulvar vestibulitis	Vulvar vestibulitis syndrome (VVS), vestibulodynia, or simply vulvar vestibulitis, is vulvodynia localized to the vulvar vestibule. It tends to be associated with a highly localized "burning" or "cutting" type of pain. Until recently, "vulvar vestibulitis" was the term used for localized vulvar pain: the suffix "-itis" would normally imply inflammation, but in fact there is little evidence to support an inflammatory process in the condition. "Vestibulodynia" is the term now recognized by the International Society for the Study of Vulvovaginal Disease.Provoked vestibulodynia, pain provoked by contact localized to the vulvar vestibule, is the most common subtype of vulvodynia among premenopausal women. The syndrome has been cited as affecting about 10% to 15% of women seeking gynecological care. Symptoms VVS is characterized by severe pain with attempted penetration of the vaginal orifice and reports of tenderness with pressure within the vulval vestibule. Usually there are no reports of pain with pressure to other surrounding areas of the vulva. The feelings of irritation and burning can persist for hours or days following sexual activity, engendering a sense of hopelessness and depression. VVS also can often cause dyspareunia.The pain may be provoked by touch or contact with an object, such as the insertion of a tampon, with vaginal intercourse, or with the pressure from sitting on a bicycle seat, provoked vestibulodynia, or it may be constant, as in the case of unprovoked, generalized vestibulodynia. Some women have had pain since their first penetration (primary vulvar vestibulitis) while some have had it after a period of time with pain-free penetration (secondary vulvar vestibulitis). Relationship problems often occur as the result of chronic frustration, disappointment, and depression associated with the condition. Causes Little is known about the cause of vestibulodynia. A number of causes may be involved, including subclinical human papillomavirus infection, chronic recurrent candidiasis, or chronic recurrent bacterial vaginosis.Muscular causes have been implicated as well, since chronic vulvar pain may be the result of chronic hypertonic perivaginal muscles, leading to vaginal tightening and subsequent pain. Some investigators have postulated the existence of neurological causes, such as vestibular neural hyperplasia. In vestibulodynia the nerves of the vulva transmit signals of pain when they normally should indicate touch, pressure, heat, or stretch. Normal sensations are processed by the brain as abnormal, which result in a heightened sensitivity, i.e. hyperalgesia. Finally, psychological factors may contribute to or exacerbate the problem, since the anticipation of pain often results in a conditioned spasmodic reflex along with sexual desire and arousal problems. Diagnosis Diagnosis is readily made by the cotton-swab test, in which pressure is applied in a circular fashion around the vulvar vestibule to assess complaints of pain. Laboratory tests are used to exclude bacterial, viral or yeast infection, and a careful examination of the vulvovaginal area is conducted to assess whether any atrophy is present. Treatment Treatment consists of general advice about hygiene and sexual behaviour, pelvic floor and desensitisation exercises, and psychological treatment by a multidisciplinary team. == References ==
Lupus erythematosus panniculitis	Lupus erythematosus panniculitis presents with subcutaneous nodules that are commonly firm, sharply defined and nontender. See also Lupus erythematosus List of cutaneous conditions References External links == External links ==
Whipples disease	Whipples disease is a rare systemic infectious disease caused by the bacterium Tropheryma whipplei. First described by George Hoyt Whipple in 1907 and commonly considered as a gastrointestinal disorder, Whipples disease primarily causes malabsorption, but may affect any part of the human body, including the heart, brain, joints, skin, lungs and the eyes. Weight loss, diarrhea, joint pain, and arthritis are common presenting symptoms, but the presentation can be highly variable in certain individuals, and about 15% of patients do not have the standard signs and symptoms.Whipples disease is significantly more common in men, with 87% of patients diagnosed being male. When recognized and treated, Whipples disease can usually be cured with long-term antibiotic therapy, but if the disease is left undiagnosed or untreated, it can ultimately be fatal. Signs and symptoms The most common symptoms are diarrhea, abdominal pain, weight loss, and joint pains. The joint pains may be due to migratory nondeforming arthritis, which may occur many years before any digestive-tract symptoms develop; they tend to involve the large joints, but can occur in any pattern and tend not to damage the joint surface to the point that the joint becomes deformed. Fever and chills occur in a small proportion of people.In its more advanced form, malabsorption (insufficient absorption of nutrients from the diet) leads to wasting and the enlargement of lymph nodes in the abdomen. Neurological symptoms (discussed below) are more common in those with the severe form of the abdominal disease. Chronic malabsorptive diarrhea leads to the poor absorption of fat, causing steatorrhea (fatty, offensive-smelling stool), flatulence, and abdominal distension. Protein-losing enteropathy may also occur, causing depletion of albumin, a blood protein, which may lead to peripheral edema caused by the lowered oncotic pressures.Hyperpigmentation of the skin occurs in almost half; some also have skin nodules. Various eye problems, such as uveitis, may occur; this is typically associated with deteriorating vision and pain in the affected eye. Endocarditis (infection of the heart valve) has been reported in a small number of cases, sometimes in people with no other symptoms of Whipples disease; this is typically noticed as breathlessness and leg swelling due to fluid accumulation as the heart is unable to pump fluid through the body.Of those affected by Whipples disease, 10–40% have problems related to the involvement of the brain; the symptoms relate to the part of the brain that is affected. The most common problems are dementia, memory loss, confusion, and decreased level of consciousness. Eye-movement disturbances and myorhythmia (rapidly repetitive movements of the muscles) of the face, together referred to as oculomasticatory myorhythmia, are highly characteristic for Whipples disease. Weakness and poor coordination of part of the body, headaches, seizures, and a number of more uncommon neurological features are present in some cases. Mechanism T. whipplei is one of the Actinomycetes, and is a distant relative of the Mycobacterium avium complex, explaining in part why Whipples disease is similar to the diseases caused by MAC bacteria. The disease is common in farmers and those exposed to soil and animals, suggesting that the infection is acquired from these sources.Individuals who are most susceptible to the disease are those with decreased ability to perform intracellular degradation of ingested pathogens or particles, particularly within macrophages. Several studies indicate that defective T-lymphocyte (particularly TH1 population) function may be an important predisposing factor for the disease. In particular, circulating cells which are CD11b (also known as integrin alpha) expressive are reduced in susceptible individuals. CD11b has a vital role in activation of macrophages to destroy intracellularly ingested T. whipplei bacteria. Diagnosis Common clinical signs and symptoms of Whipples disease include diarrhea, steatorrhea, abdominal pain, weight loss, migratory arthropathy, fever, and neurological symptoms. Weight loss and diarrhea are the most common symptoms that lead to identification of the process, but may be preceded by chronic, unexplained, relapsing episodes of nondestructive seronegative arthritis, often of large joints.Endoscopy of the duodenum and jejunum can reveal pale yellow shaggy mucosa with erythematous eroded patches in patients with classic intestinal Whipples disease, and small bowel X-rays may show some thickened folds. Other pathological findings may include enlarged mesenteric lymph nodes, hypercellularity of lamina propria with "foamy macrophages", and a concurrent decreased number of lymphocytes and plasma cells, per high power field view of the biopsy.Diagnosis is made by biopsy, usually by duodenal endoscopy, which reveals PAS-positive macrophages in the lamina propria containing nonacid-fast, Gram-positive bacilli. Immunohistochemical staining for antibodies against T. whipplei has been used to detect the organism in a variety of tissues, and a polymerase chain reaction-based assay is also available, which can be confirmatory if performed on blood, vitreous fluid, synovial fluid, heart valves, or cerebrospinal fluid. PCR of saliva, gastric or intestinal fluid, and stool specimens is highly sensitive, but not specific enough, indicating that healthy individuals can also harbor the causative bacterium without the manifestation of Whipples disease, but that a negative PCR is most likely indicative of a healthy individual. Treatment Treatment is with penicillin, ampicillin, tetracycline, or co-trimoxazole for one to two years. Any treatment lasting less than a year has a relapse rate around 40%. Expert opinion as of 2007 is that Whipples disease should be treated with doxycycline with hydroxychloroquine for 12 to 18 months. Sulfonamides (sulfadiazine or sulfamethoxazole) may be added for treatment of neurological symptoms. Epidemiology The disease is regarded as extremely rare, with an incidence (new number of cases per year) of one case per million people. The patients are predominantly male (86% in a survey of American patients), although in some countries, the rate of women receiving a diagnosis of Whipples disease has increased in recent years. It occurs predominantly in those of Caucasian ethnicity, suggesting a genetic predisposition in that population. T. whipplei appears to be an environmental organism that is commonly present in the gastrointestinal tract, but remains asymptomatic. Several lines of evidence suggest that some defect—inherited or acquired—in immunity is required for it to become pathogenic. The possible immunological defect may be specific for T. whipplei, since the disease is not associated with a substantially increased risk of other infections. The disease is usually diagnosed in middle age (median 49 years). Studies from Germany have shown that age at diagnosis has been rising since the 1960s. History Whipple described the disease in 1907 in a paper in the now-defunct Bulletin of Johns Hopkins Hospital. The patient was a 36-year-old medical missionary. Whipple referred to the disease as "intestinal lipodystrophy". It was long presumed to be an infectious disease, but the causative organism was only fully identified in 1992. In 2003, doctors from Johns Hopkins Hospital, together with the French microbiologist Didier Raoult applied novel diagnostic methods to stored tissue samples from Whipples original patient, and demonstrated T. whipplei in these tissues. See also Tropheryma whipplei Notes References External links "Whipples Disease". National Digestive Disease Information Clearinghouse NDDIC.
Tufted folliculitis	Tufted folliculitis presents with dolls hair-like bundling of follicular units, and is seen in a wide range of scarring conditions including chronic staphylococcal infection, chronic lupus erythematosus, lichen planopilaris, Graham-Little syndrome, folliculitis decalvans, acne keloidalis nuchae, immunobullous disorders, and dissecting cellulitis.: 761 See also Cicatricial alopecia List of cutaneous conditions == References ==
Panniculitis	Panniculitis is a group of diseases whose hallmark is inflammation of subcutaneous adipose tissue (the fatty layer under the skin – panniculus adiposus). Symptoms include tender skin nodules, and systemic signs such as weight loss and fatigue. Restated, an inflammatory disorder primarily localized in the subcutaneous fat is termed a "panniculitis", a group of disorders that may be challenging both for the clinician and the dermatopathologist.: 487 The general term for inflammation of any adipose tissue is steatitis. Signs and symptoms Panniculitis can also be classified based on the presence or absence of systemic symptoms. Panniculitis without systemic disease can be a result of trauma or cold. Panniculitis with systemic disease can be caused by: connective tissue disorders such as lupus erythematosus or scleroderma; lymphoproliferative disease such as lymphoma or histiocytosis; pancreatitis or pancreatic cancer; sarcoidosis with cutaneous involvement (seen in up to 20 percent); Alpha 1-antitrypsin deficiency Crohns diseaseThis is not a complete list of possible causes. Associated conditions Lipoatrophy or lipodystrophy (the loss of subcutaneous adipose tissue) can occur in any of these conditions. Diagnosis Classification It can occur in any fatty tissue (cutaneous or visceral) and is often diagnosed on the basis of a deep skin biopsy, and can be further classified by histological characteristics based on the location of the inflammatory cells (within fatty lobules or in the septa which separate them) and on the presence or absence of vasculitis.There are thus four main histological subtypes: lobular panniculitis without vasculitis (acute panniculitis, previously termed Weber–Christian disease, systemic nodular panniculitis) lobular panniculitis with vasculitis septal panniculitis without vasculitis septal panniculitis with vasculitis Lobular With vasculitis Erythema induratum, or "Bazin disease", is a panniculitis on the back of the calves. It was formerly thought to be a reaction to the tuberculum bacillus. It is now considered a panniculitis that is not associated with a single defined pathogen.Nodular vasculitis is a skin condition characterized by small, tender, reddened nodules on the legs, mostly on the calves and shins. Microscopically there are epithelioid granulomas and vasculitis in the subcutaneous tissue, making it a form of panniculitis. Most of these cases are now thought to be manifestation of tuberculosis and indeed they respond well to anti-tuberculous treatment. Without vasculitis Non-vasculitis forms of panniculitis that may occur include: Cytophagic histiocytic panniculitis was first described in 1980 by Winkelmann as a chronic histiocytic disease of the subcutaneous adipose tissue, which is characterized clinically by tender erythematous nodules, recurrent high fever, malaise, jaundice, organomegaly, serosal effusions, pancytopenia, hepatic dysfunction and coagulation abnormalities.: 494 CHP may occur either isolated or as part of cutaneous manifestations of hemophagocytic syndrome (HPS). CHP is a rare and often fatal form of panniculitis with multisystem involvement. But it can also present in a benign form involving only the subcutaneous tissue, thus having a broad clinical spectrum. Traumatic panniculitis is a panniculitis that occurs following trauma to the skin.: 492 Cold panniculitis is a panniculitis occurring after exposure to cold, most often seen in infants and young children.: 491 This condition has been described in children who suck ice or popsicles, and therefore is sometimes referred to as "popsicle panniculitis.": 491 The term was coined when a patient with a rash of unknown origin on her cheek was taken to a dermatologist. Gouty panniculitis is a panniculitis caused by deposition of uric acid crystals in gout.: 494 Pancreatic panniculitis (also known as enzymatic panniculitis, Pancreatic fat necrosis, and subcutaneous fat necrosis) is a panniculitis most commonly associated with pancreatic carcinoma, and more rarely with anatomic pancreatic abnormalities, pseudocysts, or drug-induced pancreatitis.: 493 Factitial panniculitis is a panniculitis that may be induced by the injection of organic materials, povidone, feces, saliva, vaginal fluid, and oils.: 492 With needle-shaped clefts Lipodermatosclerosis is a form of panniculitis associated with chronic venous insufficiency that presents with brown indurations on the front of the shins. It may be associated with pain and other signs of chronic venous insufficiency. The exact cause is unknown.Other forms include: Subcutaneous fat necrosis of the newborn, a form of panniculitis occurring in newborns that is usually self-resolving, that may be a result of hypoxic injury to relatively high levels of brown fat.: 492 Sclerema neonatorum, affecting premature births.: 492 Weber–Christian disease, a symmetrical form of the disease of unknown origin occurring in middle-aged women.: 492 Lupus erythematosus panniculitis, panniculitis associated with lupus erythematosus. Forms associated with use of high doses of systemic corticosteroids during rapid corticosteroid withdrawal, and from the injection of silicone or mineral oils.: 492 Septal Erythema nodosum Erythema nodosum is a form of panniculitis characterised by tender red nodules, 1–10 cm, associated with systemic symptoms including fever, malaise, and joint pain. Nodules may become bluish-purple, yellowing, and green, and subside over a period of 2–6 weeks without ulcerating or scarring. Erythema nodosum is associated with infections, including Hepatitis C, EBV and tuberculosis, Crohns disease and sarcoidosis, pregnancy, medications including sulfonamides, and some cancers, including Non-Hodgkin lymphoma and pancreatic cancer. A1AT-deficiency-associated Alpha-1 antitrypsin deficiency panniculitis is a panniculitis associated with a deficiency of the α1-antitrypsin enzyme.: 494 Treatment See also Panniculus carnosus List of cutaneous conditions References External links DermNet dermal-infiltrative/panniculitisDermAtlas -639418194
Multiple chemical sensitivity	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
Frotteurism	Frotteurism is a paraphilic interest in rubbing, usually ones pelvic area or erect penis, against a non-consenting person for sexual pleasure. It may involve touching any part of the body, including the genital area. A person who practices frotteuristic acts is known as a frotteur. Toucherism is sexual arousal based on grabbing or rubbing ones hands against an unexpecting (and non-consenting) person. It usually involves touching breasts, buttocks or genital areas, often while quickly walking across the victims path. Some psychologists consider toucherism a manifestation of frotteurism, while others distinguish the two. In clinical medicine, treatment of frotteuristic disorder involves cognitive behavioral therapy coupled with the administration of an SSRI. Etymology and history Frotteuristic acts were probably first interpreted as signs of a psychological disorder by French psychiatrist Valentin Magnan, who described three acts of "frottage" in an 1890 study. "Frottage" derives from the French verb frotter, meaning "to rub". Frotteur is a French noun literally meaning "one who rubs". It was popularized by German sexologist Richard von Krafft-Ebing in his book Psychopathia Sexualis, borrowing from Magnans French terminology. Clifford Allen later coined frotteurism in his 1969 textbook of sexual disorders.The Diagnostic and Statistical Manual of Mental Disorders called this sexual disorder by the name frottage until the third edition (DSM III-R), but changed to frotteurism in the fourth edition, and now uses frotteuristic disorder in the fifth edition. Nevertheless, the term frottage still remains in some law codes where it is synonymous with the term frotteurism. Symptoms and classification The professional handbook of the American Psychiatric Association (APA), the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, lists the following diagnostic criteria for frotteuristic disorder. Over a period of at least 6 months, recurrent and intense sexual arousal from touching or rubbing against a nonconsenting person, as manifested by fantasies, urges, or behaviors. The individual has acted on these sexual urges with a nonconsenting person, or the sexual urges or fantasies cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.If the individual has not acted on their interest and experiences no distress or impairment, they are considered to have a frotteuristic sexual interest, but not frotteuristic disorder. Some sexologists distinguish between frotteurism (as pelvic rubbing) and toucherism (as groping with hands), but the DSM does not. Sexologist Kurt Freund described frotteurism and toucherism as courtship disorders that occur at the tactile stage of human courtship. Prevalence and legality The prevalence of frotteurism is unknown. The DSM estimates that 10%–14% of men seen in clinical settings for paraphilias or hypersexuality have frotteuristic disorder, indicating that the population prevalence is lower. However, frotteuristic acts, as opposed to frotteuristic disorder, may occur in up to 30% of men in the general population. The majority of frotteurs are male and the majority of victims are female, although female on male, female on female, and male on male frotteurs exist. This activity is often done in circumstances where the victim cannot easily respond, in a public place such as a crowded train or concert. Marco Vassis story "Subway Dick" is an example of such acts in a train.Usually, such nonconsensual sexual contact is viewed as a criminal offense: a form of sexual assault albeit often classified as a misdemeanor with minor legal penalties. Conviction may result in a sentence or psychiatric treatment.Frotteurism is legal in Russia if the victim is over 16. See also Eve teasing Groping Masturbation Non-penetrative sex Sexual harassment == References ==
Bicuspid aortic valve	Bicuspid aortic valve (aka BAV) is a form of heart disease in which two of the leaflets of the aortic valve fuse during development in the womb resulting in a two-leaflet (bicuspid) valve instead of the normal three-leaflet (tricuspid) valve. BAV is the most common cause of heart disease present at birth and affects approximately 1.3% of adults. Normally, the mitral valve is the only bicuspid valve and this is situated between the hearts left atrium and left ventricle. Heart valves play a crucial role in ensuring the unidirectional flow of blood from the atrium to the ventricles, or from the ventricle to the aorta or pulmonary trunk. BAV is normally inherited. Signs and symptoms In many cases, a bicuspid aortic valve will cause no problems. People with BAV may become tired more easily than those with normal valvular function and have difficulty maintaining stamina for cardio-intensive activities due to poor heart performance caused by stress on the aortic wall. Complications Calcification BAV may become calcified later in life, which may lead to varying degrees of severity of aortic stenosis that will manifest as murmurs. If the leaflets do not close correctly, aortic regurgitation can occur. If these become severe enough, they may require heart surgery. The heart is put under more stress in order to either pump more blood through a stenotic valve or attempt to circulate regurgitation blood through a leaking valve. Ultimately there is a risk of rupture in the aortic valve due to bicuspid aortopathy which is a result of progressive aortic dilation from the stress of having only two values where three are normal. Aortic lesions One of the most notable associations with BAV is the tendency for these patients to present with ascending aortic aneurysmal lesions. The extracellular matrix of the aorta in patients with BAV shows marked deviations from that of the normal tricuspid aortic valve. It is currently believed that an increase in the ratio of MMP2 (Matrix Metalloproteinases 2) to TIMP1 (tissue inhibitors of metalloproteinase) may be responsible for the abnormal degradation of the valve matrix and therefore lead to aortic dissection and aneurysm. However, other studies have also shown MMP9 involvement with no differences in TIMP expression. The size of the proximal aorta should be evaluated carefully during the workup. The initial diameter of the aorta should be noted and annual evaluation with CT scan, or MRI to avoid ionizing radiation, should be recommended to the patient; the examination should be conducted more frequently if a change in aortic diameter is seen. From this monitoring, the type of surgery that should be offered to the patient can be determined based on the change in size of the aorta. Aortic narrowing A bicuspid aortic valve may cause the hearts aortic valve to narrow (aortic stenosis). This narrowing prevents the valve from opening fully, which reduces or blocks blood flow from the heart to the body. In some cases, the aortic valve does not close tightly, causing blood to leak backward into the left ventricle.Coarctation of the aorta (a congenital narrowing in the region of the ductus arteriosus) has also been associated with BAV. Pathophysiology Fusion of aortic valve leaflets occurs most commonly (≈80%) between the right coronary and left coronary leaflets (RL), which are the anterior leaflets of the aortic valve. Fusion also occurs between the right coronary and noncoronary leaflets (RN, ≈17%), and least commonly between the noncoronary and left coronary leaflets (≈2%). In comparison to other fusion patterns, RN leaflet fusion has a stronger association with future complications such as aortic valve regurgitation and stenosis. However, all fusion patterns associate with a specific area or areas of dilated enlargement in either the root of the ascending aorta, the ascending aorta, or the transverse aortic arch. Hemodynamics Identifying hemodynamic patterns in the aorta after left ventricle systole aids in predicting consequential complications of bicuspid aortic valve. The patient-specific risk of developing complications such as aortic aneurysms is dependent on the particular aortic leaflet fusion pattern, with each pattern varying in 4D MRI measurements of wall shear stress (WSS), blood flow velocity, asymmetrical flow displacement and flow angle of the aorta.BAV outflow is helical and occurs at high velocities (>1 m/s) throughout the ascending aorta. This is potentially more damaging to the aorta in comparison to the streamline flow and short-lived burst of high velocity at the beginning of the aorta, as seen within a healthy tricuspid valve. This eccentric outflow from the BAV results in blood hitting and reflecting off the aortic wall in a non-streamline fashion. The specific zones where blood hits is dependent on the varying BAV leaflet fusion patterns and consequently correlates with increases in WSS. WSS measurements in RL fusion indicate an increase in pressure applied predominantly to the right-anterior side of the vessel wall, while RN fusion increases WSS on the right-posterior wall. The resulting rise in WSS is supported by the asymmetrical displacement of blood flow produced by an increased angle of outflow from the BAV. Displacement is measured as the distance in millimeters from the center of the aorta to the center of the high velocity outflow. Blood does not flow centrally through the aorta in BAV, but along the right-anterior and right-posterior vessel wall for RL and RN leaflet fusion respectively. Aortic disease Identification of hemodynamics for RL, RN, and left coronary and noncoronary leaflet fusion patterns enables detection of specific aortic regions susceptible to dysfunction and the eventual development of disease. Specifically, RL and RN fusion patterns are more likely to develop into these aortic disease states. The blood flow information associated with RL fusion causes dilation of the mid-ascending aorta, while RN fusion is associated with dilation in the root, distal ascending aorta and transverse arch. BAV helical and high velocity outflow patterns are consistent with aortic dilation hemodynamics seen in those with tricuspid aortic valves. However, it is the increase and variance in WSS and flow displacement in BAV that demonstrate the importance of aortic leaflet morphology. Flow displacement measurements taken from 4D MRI may be best for detecting irregularities in hemodynamics. Displacement measurements were highly sensitive and distinguishable between different valve morphologies. Hemodynamic measurements from 4D MRI in patients with BAV are advantageous in determining the timing and location of repair surgery to the aorta in aortopathy states.Most patients with bicuspid aortic valve whose valve becomes dysfunctional will need careful follow-up and potentially valve replacement at some point in life. Regular EchoCG and MRI may be performed.If the valve is normally functioning or minimally dysfunctional, average lifespan is similar to that of those without the anomaly. Diagnosis A bicuspid aortic valve can be associated with a heart murmur located at the right second intercostal space. Often there will be differences in blood pressures between upper and lower extremities. The diagnosis can be assisted with echocardiography or magnetic resonance imaging (MRI). Four-dimensional magnetic resonance imaging (4D MRI) is a technique that defines blood flow characteristics and patterns throughout the vessels, across valves, and in compartments of the heart. Four-dimensional imaging enables accurate visualizations of blood flow patterns in a three-dimensional (3D) spatial volume, as well as in a fourth temporal dimension. Current 4D MRI systems produces high-resolution images of blood flow in just a single scan session. Classification Bicuspid aortic valves may assume three different types of configuration: "Real" bicuspid valves with two symmetric leaflets A tricuspid architecture with a fusion of two leaflets A tricuspid architecture with a fusion of three leaflets Treatment Complications stemming from structural heart issues are most often treated through surgical intervention, which could include aortic valve replacement, or balloon valvuloplasty. Prognosis BAV frequently leads to significant complications in over one-third of affected individuals which often lead to significant morbidity and mortality. Notable complications of BAV include narrowing of the aortic valve opening, backward blood flow at the aortic valve, dilation of the ascending aorta, and infection of the heart valve.If aortic regurgitation and dilation of the ascending aorta are noted in someone, they should undergo yearly surveillance with transthoracic echocardiograms if the aortic root measures 4.5 centimeters or greater in diameter. Epidemiology Bicuspid aortic valves are the most common cardiac valvular anomaly, occurring in 1–2% of the general population. It is twice as common in males as in females.Bicuspid aortic valve is a heritable condition, with a demonstrated association with mutations in the NOTCH1 gene. Its heritability ( h 2 {\displaystyle h^{2}} ) is as high as 89%. Both familial clustering and isolated valve defects have been documented. Recent studies suggest that BAV is an autosomal dominant condition with incomplete penetrance. Other congenital heart defects are associated with bicuspid aortic valve at various frequencies, including coarctation of the aorta.Bicuspid aortic valve abnormality is also the most observed cardiac defect in Turner syndrome. == References ==
Left ventricular thrombus	Left ventricular thrombus is a blood clot (thrombus) in the left ventricle of the heart. LVT is a common complication of acute myocardial infarction (AMI). Typically the clot is a mural thrombus, meaning it is on the wall of the ventricle. The primary risk of LVT is the occurrence of cardiac embolism, in which the thrombus detaches from the ventricular wall and travels through the circulation and blocks blood vessels. Blockage can be especially damaging in the heart or brain (stroke). Pathophysiology LVT occurs most often during the first 2 weeks following AMI. AMI patients most at risk display the 3 characteristics of Virchows triad: Stagnation of blood The risk of LVT formation increases as infarction size increases. A larger infarction means a larger area of tissue injury, which may be akinetic or dyskinetic, resulting in stagnation of ventricular blood. Endothelial injury Monocytes and macrophages play important roles in healing after myocardial infarction. With the absence of monocytes and macrophages, chances of LVT formation are very high. Failure to clear cellular debris from the infarct compromises the endothelial lining of the left ventricle and exposes the damaged tissue to the blood. The response is to build a thrombus composed of fibrin, red blood cells and platelets. Hypercoagulable state For several days after AMI, the levels of tissue factor and D-dimer, which are involved in coagulation, are high, which increases the risk of LVT formation. LVT may be good for the heart when tissues are severely damaged because it acts to thicken the wall, thus protecting it against rupture. Diagnosis Echocardiography is the main diagnostic tool for LVT. A distinct mass is visible in the left ventricle. Computed Tomography and Magnetic Resonance Imaging are effective, but less common ways to detect LVT, due to their costs and risks. It is possible to assess whether a thrombus will become an embolus through echocardiography. Mobility and protrusion of the thrombus are two characteristics associated with increased embolic potential. Prevention After an AMI, people should be treated to prevent LVT formation. Aspirin plus an oral anticoagulant such as warfarin are suggested for individuals at risk for thromboembolic events. Anticoagulants are also shown to reduce the risk of embolisms when a thrombus is already formed. Heparin, an injectable, fast-acting anticoagulant, is effective in high doses for preventing LVT formation after AMI. Treatment Systemic anticoagulation is considered first-line medical therapy for LVT, as it reduces the risk of systemic embolism. There are also surgical procedures for removal of a thrombus (thrombectomy). Epidemiology The rate of LVT formation after AMI is thought to be declining due to the use of better therapies and percutaneous coronary intervention used to treat myocardial infarction. In the modern era LVT formation after ST elevation MI treated with percutaneous coronary intervention is low, estimated at only 2.7%. However, incidence of LVT is considered higher in anterior wall AMI, compared with other types. References == External links ==
Obstructed labour	Obstructed labour, also known as labour dystocia, is when the baby does not exit the pelvis during childbirth due to being physically blocked, despite the uterus contracting normally. Complications for the baby include not getting enough oxygen which may result in death. It increases the risk of the mother getting an infection, having uterine rupture, or having post-partum bleeding. Long-term complications for the mother include obstetrical fistula. Obstructed labour is said to result in prolonged labour, when the active phase of labour is longer than 12 hours.The main causes of obstructed labour include: a large or abnormally positioned baby, a small pelvis, and problems with the birth canal. Abnormal positioning includes shoulder dystocia where the anterior shoulder does not pass easily below the pubic bone. Risk factors for a small pelvis include malnutrition and a lack of exposure to sunlight causing vitamin D deficiency. It is also more common in adolescence as the pelvis may not have finished growing by the time they give birth. Problems with the birth canal include a narrow vagina and perineum which may be due to female genital mutilation or tumors. A partograph is often used to track labour progression and diagnose problems. This combined with physical examination may identify obstructed labour.The treatment of obstructed labour may require cesarean section or vacuum extraction with possible surgical opening of the symphysis pubis. Other measures include: keeping the women hydrated and antibiotics if the membranes have been ruptured for more than 18 hours. In Africa and Asia obstructed labor affects between two and five percent of deliveries. In 2015 about 6.5 million cases of obstructed labour or uterine rupture occurred. This resulted in 23,000 maternal deaths down from 29,000 deaths in 1990 (about 8% of all deaths related to pregnancy). It is also one of the leading causes of stillbirth. Most deaths due to this condition occur in the developing world. Cause The main causes of obstructed labour include: a large or abnormally positioned baby, a small pelvis, and problems with the birth canal. Both the size and the position of the fetus can lead to obstructed labor. Abnormal positioning includes shoulder dystocia where the anterior shoulder does not pass easily below the pubic bone. A small pelvis of the mother can be a result of many factors. Risk factors for a small pelvis include malnutrition and a lack of exposure to sunlight causing vitamin D deficiency. A deficiency in calcium can also result in a small pelvis as the structures of the pelvic bones will be weak due to the lack of calcium. A relationship between maternal height and pelvis size is present and can be used to predict the possibility of obstructed labor. This relationship is a result of the mothers nutritional health throughout her life leading up to childbirth. Younger mothers are also at more risk for obstructed labor due to growth of the pelvis not being completed. Problems with the birth canal include a narrow vagina and perineum which may be due to female genital mutilation or tumors. All of these factors lead to a failure in the progress of labor. Evolution Obstructed labor is more common in humans than any other species and continues to be a main cause of birth complications today. Modern humans have morphologically evolved to survive as bipeds, however, bipedalism has resulted in skeletal changes that have consequently narrowed the pelvis and the birth canal. The combination of increased brain size and changes in pelvic structure are the major contributors of obstructed labor in modern humans. It is also common for obstructed labor in humans to be caused by the fetus’ broad shoulders. However, morphological shifts in pelvic structure still account for the inability of a fetus to effectively pass through the birth canal without major complications Other primates have a wider and straighter birth canal that allows a fetus to pass through more effectively. Mismatch between birth canal size and infant cranial width and length due to bipedal locomotion requirements have often been referred to as the obstetric dilemma, since compared to other great apes, modern humans have the greatest disproportion between infant cranial size and birth canal size. Shrinking of upper extremities and curvature of the spine have also affected the way modern humans give birth. Quadruped apes have longer upper limbs that allow them to reach down and pull their fetus out of the birth canal unassisted. Other primates also have a wider and straighter birth canal that allows a fetus to pass through more effectively. Modern human’s shorter upper extremities and evolution of bipedal locomotion may have placed a premium on assistance during labor. For this reason, researchers argue that assisted labor may have evolved with bipedalism. Obstructed labor has been documented as a complication of childbirth since the field of obstetrics originated. For over 1,000 years obstetricians have had to forcibly remove obstructed labor fetuses to prevent the death of the mother.Prior to the existence of the cesarean section, fetuses that were obstructed had a low survival rate. Even in the 21st century, if obstructed labor is left untreated, it could result in mother and infant death. Although surgical removal of the fetus is the preferred method of managing obstructed labor, manual removal using medical tools is also common.Obstructed labor is unique to humans compared to other primates. The evolution of humans to become obligate bipedal and increase in brain size create the problems associated with obstructed labor. In order for bipedal locomotion to be possible, many changes had to occur to the skeletal structure of humans, especially in the pelvis. Both the shape and orientation of the pelvis changed. Other primates have straighter and wider pelvises compared to humans. A narrow pelvis is better for bipedal locomotion but makes childbirth more difficult. The pelvis is sexually dimorphic, with females having a wider pelvis to be better suited for childbirth. However, the female pelvis still must accommodate for bipedal locomotion which is what creates the challenges for obstructed labor. The brain size of humans has also increased as the species has evolved, resulting in a larger head of the fetus that must exit the womb. This requires human infants to be born less developed when compared to other species. The bones of the skull are not yet fused when a human infant is born in order to prevent the head from becoming too large to exit the womb. However, the head of the fetus is still large and poses the possibility for obstructed labor. Diagnosis Obstructed labour is usually diagnosed based on physical examination. Ultrasound can be used to predict malpresentation of the fetus. In examination of the cervix once labor has begun, all examinations are compared to regular cervical assessments. The comparison between the average cervical assessment and the current state of the mother allows for a diagnosis of obstructed labor. An increasingly long time in labor also indicates a mechanical issue that is preventing the fetus from exiting the womb. Prevention Access to proper health services can reduce the prevalence of obstructed labor. Less developed areas have inadequate health services to attend to obstructed labor, resulting in a higher prevalence among less developed area. Improving nutrition of female, both before and during pregnancy, is important for reducing the risk of obstructive labor. Creating education programs about reproduction and increasing access to reproductive services such as contraception and family planning in developing areas can also reduce the prevalence of obstructed labor. Treatment Before considering surgical options, changing the posture of the mother during labor can help to progress labor. The treatment of obstructed labour may require cesarean section or vacuum extraction with possible surgical opening of the symphysis pubis. Caesarean section is an invasive method but is often the only method that will save the lives of both the mother and the infant. Symphysiotomy is the surgical opening of the symphysis pubis. This procedure can be completed more rapidly than Caesarean sections and does not require anesthesia, making it a more accessible option in places with less advanced medical technology. This procedure also leaves no scars on the uterus which makes further pregnancies and births safer for the mother. Another important factor in treating obstructed labor is monitoring the energy and hydration of the mother. Contractions of the uterus require energy, so the longer the mother is in labor the more energy she expends. When the mother is depleted of energy, the contractions become weaker and labor will become increasingly longer. Antibiotics are also an important treatment as infection is a possible result of obstructed labor. Prognosis If cesarean section is obtained in a timely manner, prognosis is good. Prolonged obstructed labour can lead to stillbirth, obstetric fistula, and maternal death. Fetal death can be caused by asphyxia. Obstructed labor is the leading cause of uterine rupture worldwide. Maternal death can result from uterine rupture, complications during caesarean section, or sepsis. Epidemiology In 2013 it resulted in 19,000 maternal deaths down from 29,000 deaths in 1990. Globally, obstructed labor accounts for 8% of maternal deaths. Etymology The word dystocia means difficult labour. Its antonym is eutocia (Ancient Greek: εὖ, romanized: eu, lit. good + Ancient Greek: τόκος, romanized: tókos, lit. childbirth) easy labour. Other terms for obstructed labour include difficult labour, abnormal labour, difficult childbirth, abnormal childbirth, and dysfunctional labour. Other animals The term can also be used in the context of various animals. Dystocia pertaining to birds and reptiles is also called egg binding. In part due to extensive selective breeding, miniature horse mares experience dystocias more frequently than other breeds. References Further reading Education material for teachers of midwifery : midwifery education modules (PDF) (2nd ed.). Geneva [Switzerland]: World Health Organization (WHO). 2008. ISBN 9789241546669.
Erythema marginatum	Erythema marginatum is a type of erythema (redness of the skin or mucous membranes) involving pink rings on the torso and inner surfaces of the limbs which come and go for as long as several months. It is found primarily on extensor surfaces.An association with bradykinin has been proposed in the case of hereditary angioedema. Presentation The rings are barely raised and are non-itchy. The face is generally spared. Associated conditions It occurs in less than 5% of patients with rheumatic fever, but is considered a major Jones criterion when it does occur. The four other major criteria include carditis, polyarthritis, Sydenhams chorea, and subcutaneous nodules. In this case, it is often associated with Group A streptococcal infection, otherwise known as Streptococcus pyogenes infection, which can be detected with an ASO titer.It is an early feature of rheumatic fever and not pathognomonic of it. It may be associated with mild myocarditis (inflammation of heart muscle). It is also seen in conditions like allergic drug reactions, sepsis and glomerulonephritis.It often occurs as a harbinger of attacks in hereditary angioedema. In this case it may occur several hours or up to a day before an attack. Diagnosis Types Some sources distinguish between the following: "Erythema marginatum rheumaticum" "Erythema marginatum perstans" Treatment Erythema marginatum can be treated with hydrocortisone and adrenocorticotropc hormone (ACTH). References == External links ==
Organic personality disorder	Organic personality disorder (OPD) or secondary personality change, is a condition described in the ICD-10 and ICD-11 respectively. It is characterized by a significant personality change featuring abnormal behavior due to an underlying traumatic brain injury or another pathophysiological medical condition affecting the brain. Abnormal behavior can include but is not limited to apathy, paranoia and disinhibition.In the ICD-10, it is described as a mental disorder and not included in the classification group of personality disorders. In the ICD-11, it is described as a syndrome. The condition has not been described in any edition of the Diagnostic and Statistical Manual of Mental Disorders. Signs and symptoms OPD is associated with a large variety of symptoms, such as deficits in cognitive function, dysfunctional/abnormal behaviour, psychosis, neurosis, higher irritability and altered emotional expression. Those with OPD can experience emotional lability, meaning that their emotional expressions are unstable and fluctuating. In addition, patients may show a reduction in ability of perseverance with goals and they disinhibition, often characterised by inappropriate sexual and antisocial behavior. Those affected can experience cognitive disturbances, suspiciousness and paranoia. Altered language processing in the brain can also occur. Furthermore, patients may show changes in their sexual preference and hyposexuality symptoms. Causes OPD is associated with "personality change due to general medical condition". The OPD is included in a group of personality and behavioural disorders - in the ICD-10 this is "Personality and behavioural disorders due to brain disease, damage and dysfunction", and in the ICD-11 this is "Secondary Mental or Behavioural Syndromes Associated with Disorders or Diseases Classified Elsewhere". This mental health disorder can be caused by disease, brain damages or dysfunctions in specific brain areas in frontal lobe. The most common reason for this profound change in personality is the traumatic brain injury. Children whose brain areas have been injured or damaged, may present with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder or OPD.OPD is most often caused by lesions in three brain areas of frontal lobe: traumatic brain injuries in orbitofrontal cortex, anterior cingulate cortex and dorsolateral prefrontal cortex. OPD may also be caused by lesions in other circumscribed brain areas.Another common feature of personality of patients with OPD is their dysfunctional and maladaptive behaviour that causes serious problems in these patients, because they face problems with pursuit and achievement of their goals. Patients with OPD express a feeling of unreasonable satisfaction and euphoria. Patients can show aggressive behaviour and these dysfunctions in behaviour can have effects on interpersonal relationships. One explanation of signs of anger and aggression is due to an inability to handle their impulses, this type of aggression being called "impulsive aggression". Diagnosis ICD-11 In the ICD-11, the condition is called secondary personality change rather than organic personality disorder. To meet diagnosis there must be a clinically significant personality disturbance that represents a change from the individual’s previous characteristic personality pattern. This personality disturbance must be explainable directly as a result from a pathophysiological health condition affecting the brain. The duration, onset, and remission of the health condition, along with responses to treatment of the underlying health condition, must be consistent with presentations of the personality disturbance. There are seven sub-classifications of secondary personality change based on disturbances of affect, which includes "constricted", "blunted", "flat", "labile" and "inappropriate", along with other specified and unspecified categories. ICD-10 In the ICD-10 there were no specifically listed diagnostic criteria. It is characterized by "a significant alteration of the habitual patterns of behaviour displayed by the subject premorbidly, involving the expression of emotions, needs and impulses." Cognition, thought functions and sexuality are mentioned as potentially altered or affected. Two "organic" and three "syndrome" underlying causes are mentioned respectively: "pseudopsychopathic personality", "pseudoretarded personality", "frontal lobe damage", "limbic epilepsy personality" and post-lobotomy. Differential diagnosis Being an organic disorder, differential diagnosis between mental disorders and OPD is necessary. According to the ICD-11, specific considerations for differential diagnosis include delerium, dementia, personality disorders, impulse control disorder, and addictive behavior syndrome. For differential diagnosis in the ICD-10, along with personality disorders, there are two mentioned conditions in the in the ICD-10 under the same diagnostic category "F07" for consideration: postencephalitic parkinsonism (called "postencephalitic syndrome" in the ICD-10) and post-concussion syndrome. Patients with OPD may present similar symptoms to Huntingtons disease. The symptoms of apathy and irritability are common between these two conditions. OPD is somewhat similar to temporal lobe epilepsy, as patients who have chronic epilepsy may also express aggressive behaviours. Another similar symptom between Temporal lobe epilepsy and OPD is epileptic seizures. The symptom of epileptic seizure has influence on patients personality that means it causes behavioural alterations. Temporal lobe epilepsy is associated with the hyperexcitability of the medial temporal lobe of patients. Treatment Patients with OPD show a wide variety of sudden behavioural changes and dysfunctions. There is little information about the treatment of OPD. The pharmacological approach is the most common therapy among patients with OPD. However, the choice of drug therapy relies on the seriousness of patients situation and what symptoms are shown. The choice and administration of specific drugs contribute to the reduction of symptoms of OPD. For this reason, it is crucial for patients treatment to be assessed by clinical psychologists and psychiatrists before the administration of drugs. The dysfunctions in expression of behaviour of patients with OPD and the development of symptom of irritability, which are caused by aggressive and self-injurious behaviours, can be dealt with the administration of carbamazepine. Moreover, the symptoms of this disorder can be decreased by the administration of valproic acid. Also, emotional irritability and signs of depression can be dealt with the use of nortriptyline and low-dose thioridazine. Except from the symptom of irritability, patients express aggressive behaviours. For effective treatment of anger and aggression, carbamazepine, phenobarbital, benztropine and haloperidol may be used. In addition, the use of propranolol may decrease the frequent behaviours of rage attacks.It is important for patients to take part in psychotherapy during drug therapy. In this way, many of the adverse effects of the medications, both physiological and behavioural, can be lessened or avoided entirely. Clinicians can provide useful and helpful support to patients during these psychotherapy sessions. See also Organic mental disorder == References ==
Desquamative interstitial pneumonia	Desquamative interstitial pneumonia (DIP) is a form of idiopathic interstitial pneumonia featuring elevated numbers of macrophages within the alveoli (air sacs) of the lung. The alveolar macrophages have a characteristic light brown pigmentation and accumulate in the alveolar lumen and septa regions of the lower lobes of the lungs. The typical effects of the macrophage accumulation are inflammation and later fibrosis (thickening and stiffness) of the lung tissue.The term DIP is a misnomer. Its name is derived from the former belief that these macrophages were pneumocytes that had desquamated.It is associated with patients with a history of smoking. Since more than 80% of cases occur in smokers, it has been suggested that the term DIP should be discarded and the subset occurring in smokers should be replaced with more accurate terms such as smoking-related interstitial fibrosis (SRIF). Although smoking is the most common cause, studies have shown a relationship between occupational exposures and the development of DIP, including occupational dust, fire-extinguisher powder, diesel fumes, nylon filaments and beryllium and copper dust. Additionally, DIP has been observed in children where it typically presents as a result of surfactant protein gene mutations, indicating that the disease is not always acquired in adulthood.Smoking cessation and avoidance of secondhand smoke exposure are both crucial to preventing disease progression, however, treatment with corticosteroids and immunosuppressive therapy has been reported to be effective pharmacologic intervention. Treatment with methylprednisolone has been reported. References == External links ==
Biceps	The biceps or biceps brachii (Latin: musculus biceps brachii, "two-headed muscle of the arm") is a large muscle that lies on the front of the upper arm between the shoulder and the elbow. Both heads of the muscle arise on the scapula and join to form a single muscle belly which is attached to the upper forearm. While the biceps crosses both the shoulder and elbow joints, its main function is at the elbow where it flexes the forearm and supinates the forearm. Both these movements are used when opening a bottle with a corkscrew: first biceps screws in the cork (supination), then it pulls the cork out (flexion). Structure The biceps is one of three muscles in the anterior compartment of the upper arm, along with the brachialis muscle and the coracobrachialis muscle, with which the biceps shares a nerve supply. The biceps muscle has two heads, the short head and the long head, distinguished according to their origin at the coracoid process and supraglenoid tubercle of the scapula, respectively. From its origin on the glenoid, the long head remains tendinous as it passes through the shoulder joint and through the intertubercular groove of the humerus. Extending from its origin on the coracoid, the tendon of the short head runs adjacent to the tendon of the coracobrachialis as the conjoint tendon. Unlike the other muscles in the anterior compartment of the arm, the biceps muscle crosses two joints, the shoulder joint and the elbow joint. Both heads of the biceps join in the middle upper arm to form a single muscle mass usually near the insertion of the deltoid to form a common muscle belly, although several anatomic studies have demonstrated that the muscle bellies remain distinct structures without confluent fibers. As the muscle extends distally, the two heads rotate 90 degrees externally before inserting onto the radial tuberosity. The short head inserts distally on the tuberosity while the long head inserts proximally closer to the apex of the tuberosity. The bicipital aponeurosis, also called the lacertus fibrosus, is a thick fascial band that organizes close to the musculotendinous junction of the biceps and radiates over and inserts onto the ulnar part of the antebrachial fascia.The tendon that attaches to the radial tuberosity is partially or completely surrounded by a bursa, the bicipitoradial bursa, which ensures frictionless motion between the biceps tendon and the proximal radius during pronation and supination of the forearm.Two muscles lie underneath the biceps brachii. These are the coracobrachialis muscle, which like the biceps attaches to the coracoid process of the scapula, and the brachialis muscle which connects to the ulna and along the mid-shaft of the humerus. Besides those, the brachioradialis muscle is adjacent to the biceps and also inserts on the radius bone, though more distally. Variation Traditionally described as a two-headed muscle, biceps brachii is one of the most variable muscles of the human body and has a third head arising from the humerus in 10% of cases (normal variation)—most commonly originating near the insertion of the coracobrachialis and joining the short head—but four, five, and even seven supernumerary heads have been reported in rare cases.One study found a higher than expected number of female cadavers with a third head of biceps brachii, equal incidence between sides of the body, and uniform innervation by musculocutaneous nerve.The distal biceps tendons are completely separated in 40% and bifurcated in 25% of cases. Nerve supply The biceps shares its nerve supply with the other two muscles of the anterior compartment. The muscles are supplied by the musculocutaneous nerve. Fibers of the fifth, sixth and seventh cervical nerves make up the components of the musculocutaneous nerve which supply the biceps. Blood supply The blood supply of the biceps is the brachial artery. The distal tendon of the biceps can be useful for palpating the brachial pulse, as the artery runs medial to the tendon in the cubital fossa. Function The biceps works across three joints. The most important of these functions is to supinate the forearm and flex the elbow. Besides, the long head of biceps prevents the upward displacement of the head of the humerus. In more detail, the actions are, by joint: Proximal radioulnar joint of the elbow – The biceps brachii functions as a powerful supinator of the forearm, i.e. it turns the palm upwards. This action, which is aided by the supinator muscle, requires the humeroulnar joint of the elbow to be at least partially flexed. If the humeroulnar joint, is fully extended, supination is then primarily carried out by the supinator muscle. The biceps is a particularly powerful supinator of the forearm due to the distal attachment of the muscle at the radial tuberosity, on the opposite side of the bone from the supinator muscle. When flexed, the biceps effectively pulls the radius back into its neutral supinated position in concert with the supinator muscle.: 346–347 Humeroulnar joint of the elbow – The biceps brachii also functions as an important flexor of the forearm, particularly when the forearm is supinated. Functionally, this action is performed when lifting an object, such as a bag of groceries or when performing a biceps curl. When the forearm is in pronation (the palm faces the ground), the brachialis, brachioradialis, and supinator function to flex the forearm, with minimal contribution from the biceps brachii. It is also important to note that regardless of forearm position, (supinated, pronated, or neutral) the force exerted by the biceps brachii remains the same; however, the brachioradialis has a much greater change in exertion depending on position than the biceps during concentric contractions. That is, the biceps can only exert so much force, and as forearm position changes, other muscles must compensate. Glenohumeral joint (shoulder joint) – Several weaker functions occur at the glenohumeral joint. The biceps brachii weakly assists in forward flexion of the shoulder joint (bringing the arm forward and upwards). It may also contribute to abduction (bringing the arm out to the side) when the arm is externally (or laterally) rotated. The short head of the biceps brachii also assists with horizontal adduction (bringing the arm across the body) when the arm is internally (or medially) rotated. Finally, the short head of the biceps brachii, due to its attachment to the scapula (or shoulder blade), assists with stabilization of the shoulder joint when a heavy weight is carried in the arm. The tendon of the long head of the biceps also assists in holding the head of the humerus in the glenoid cavity.: 295 Motor units in the lateral portion of the long head of the biceps are preferentially activated during elbow flexion, while motor units in the medial portion are preferentially activated during forearm supination.The biceps are usually attributed as representative of strength within a variety of worldwide cultures. Clinical significance The proximal tendons of the biceps brachii are commonly involved in pathological processes and are a frequent cause of anterior shoulder pain. Disorders of the distal biceps brachii tendon include insertional tendonitis and partial or complete tears of the tendon. Partial tears are usually characterized by pain and enlargement and abnormal contour of the tendon. Complete tears occur as avulsion of the tendinous portion of the biceps away from its insertion on the tuberosity of the radius, and is often accompanied by a palpable, audible "pop" and immediate pain and soft tissue swelling.A soft-tissue mass is sometimes encountered in the anterior aspect of the arm, the so-called Reverse Popeye deformity, which paradoxically leads to a decreased strength during flexion of the elbow and supination of the forearm. Tendon rupture Tears of the biceps brachii may occur during athletic activities, however avulsion injuries of the distal biceps tendon are frequently occupational in nature and sustained during forceful, eccentric contraction of the biceps muscle while lifting.Treatment of a biceps tear depends on the severity of the injury. In most cases, the muscle will heal over time with no corrective surgery. Applying cold pressure and using anti-inflammatory medications will ease pain and reduce swelling. More severe injuries require surgery and post-op physical therapy to regain strength and functionality in the muscle. Corrective surgeries of this nature are typically reserved for elite athletes who rely on a complete recovery. Training The biceps can be strengthened using weight and resistance training. Examples of well known biceps exercises are the chin-up and biceps curl. Etymology and grammar The biceps brachii muscle is the one that gave all muscles their name: it comes from the Latin musculus, "little mouse", because the appearance of the flexed biceps resembles the back of a mouse. The same phenomenon occurred in Greek, in which μῦς, mȳs, means both "mouse" and "muscle".The term biceps brachii is a Latin phrase meaning "two-headed [muscle] of the arm", in reference to the fact that the muscle consists of two bundles of muscle, each with its own origin, sharing a common insertion point near the elbow joint. The proper plural form of the Latin adjective biceps is bicipites, a form not in general English use. Instead, biceps is used in both singular and plural (i.e., when referring to both arms). The English form bicep [sic], attested from 1939, is a back formation derived from misinterpreting the s of biceps as the English plural marker -s. History Leonardo da Vinci expressed the original idea of the biceps acting as a supinator in a series of annotated drawings made between 1505 and 1510; in which the principle of the biceps as a supinator, as well as its role as a flexor to the elbow were devised. However, this function remained undiscovered by the medical community as da Vinci was not regarded as a teacher of anatomy, nor were his results publicly released. It was not until 1713 that this movement was re-discovered by William Cheselden and subsequently recorded for the medical community. It was rewritten several times by different authors wishing to present information to different audiences. The most notable recent expansion upon Cheseldens recordings was written by Guillaume Duchenne in 1867, in a journal named Physiology of Motion. To this day it remains one of the major references on supination action of the biceps brachii. Other species Neanderthals In Neanderthals, the radial bicipital tuberosities were larger than in modern humans, which suggests they were probably able to use their biceps for supination over a wider range of pronation-supination. It is possible that they relied more on their biceps for forceful supination without the assistance of the supinator muscle like in modern humans, and thus that they used a different movement when throwing. Horses In the horse, the biceps function is to extend the shoulder and flex the elbow. It is composed of two short-fibred heads separated longitudinally by a thick internal tendon which stretches from the origin on the supraglenoid tubercle to the insertion on the medial radial tuberosity. This tendon can withstand very large forces when the biceps is stretched. From this internal tendon a strip of tendon, the lacertus fibrosus, connects the muscle with the extensor carpi radialis -- an important feature in the horses stay apparatus (through which the horse can rest and sleep whilst standing.) References External links Anatomy photo:06:05-0102 at the SUNY Downstate Medical Center
Pes anserinus (leg)	Pes anserinus ("goose foot") refers to the conjoined tendons of three muscles of the thigh. It inserts onto the anteromedial (front and inside) surface of the proximal tibia. The muscles are the sartorius, gracilis and semitendinosus sometimes referred to as the guy ropes. The name "goose foot" arises from the three-pronged manner in which the conjoined tendon inserts onto the tibia. Structure The three tendons, from front to back, that conjoin to form the pes anserinus come from the sartorius muscle, the gracilis muscle, and the semitendinosus muscle. It inserts onto the proximal anteromedial surface of the tibia.The pes anserinus is around 5 cm below the medial tibial joint line. It lies superficial to the tibial insertion of the medial collateral ligament of the knee. Clinical significance Pes anserine bursitis is a cause of chronic knee pain and weakness. It occurs when the medial portion of the knee is inflamed. If the bursa underlying the tendons of the sartorius, gracilis, and semitendinosus gets irritated from overuse or injury, a person can develop this ailment. This condition usually occurs in athletes from overuse. This pathology is characterized by pain, swelling, and / or tenderness.The semitendinosus tendon can be used in certain techniques for reconstruction of the anterior cruciate ligament. History The name "goose foot" arises from the three-pronged manner in which the conjoined tendon inserts onto the tibia. Additional Images References External links Pes anserinus at the Duke University Health Systems Orthopedics program
Limbal stem cell	Limbal stem cells, also known as corneal epithelial stem cells, are stem cells located in the basal epithelial layer of the corneal limbus. They form the border between the cornea and the sclera. Characteristics of limbal stem cells include a slow turnover rate, high proliferative potential, clonogenicity, expression of stem cell markers, as well as the ability to regenerate the entire corneal epithelium. Limbal stem cell proliferation has the role of maintaining the cornea; for example, by replacing cells that are lost via tears. Additionally, these cells also prevent the conjunctival epithelial cells from migrating onto the surface of the cornea. Medical conditions and treatments Damage to the limbus can lead to limbal stem cell deficiency (LSCD); this may be primary - related to an insufficient stromal microenvironment to support stem cell functions, such as aniridia, and other congenital conditions, or secondary – caused by external factors that destroy the limbal stem cells, such as chemical or thermal burns, radiation, surgery, infection, use of contact lenses, or certain drugs. Signs and symptoms include: conjunctivalisation, corneal vascularisation, edema, ocular discomfort or pain, visual impairment, and blindness, which are likely associated with failure in the process of regenerating the corneal epithelium. Immediate management aims to limit traumatic or chemical damage to the limbus, control inflammation, and help achieve a healthy corneal epithelium. Initial treatment after trauma/injury includes preservative-free artificial tears, topical steroids, ‘bandage’ contact lenses, and autologous eye drops (eye drops manufactured from the patients own blood serum and plasma). Once the corneal surface has stabilized, surgery is the main approach to treatment. Types of surgeries: In the case of a partial LSCD:, a sequential sector conjunctival epitheliectomy (SSCE) can be performed to remove any tissue (pannus) that has grown over the cornea. This procedure is sometimes used as a temporary measure until further surgical interventions are possible. Transplantation of amniotic membrane from a placenta may also help. Although amniotic membrane does not have stem cells of its own, it supports regeneration of limbal stem cells. However, further surgical intervention may be needed if these approaches are unsuccessful, or when disease is more severe. Conjunctival limbal autograft (CLAU) involves transplantation of limbal tissue from a patients healthy eye. As the procedure is achieved by transplanting autologous limbal stem cells from the patients healthy eye, there is no risk of immune rejection, and hence no need for systemic immunosuppression. However, this procedure represents a risk for the donor eye, as the patient already has one eye damaged. In the case of bilateral LSCD, where both eyes are affected, it may be possible to transplant limbal tissue from a living donor (usually a relative). This is known as a conjunctival limbal allograft (CLAL). CLAL can be performed with both partial or total LSCD, the donor tissue is usually from a sibling or parent. As with CLAU, only a part of the donor limbus can be transplanted, as a live donor is being used. Being an allogenic transplant, immunosuppression is required, due to the risk of rejection. Kerato-limbal allograft (KLAL) involves transplantation from someone who has died and donated their organs. KLAL can be used for cases of bilateral LSCD when a living related donor is not available, or for patients with unilateral LSCD, who dont want to jeopardise their healthy eye. However, most of these types of transplant fail within five years. KLAL has a number of limitations: the graft is usually up to 24 hours old before retrieval and a further period of time is often required to screen the cadavers blood before the tissue can be used; often the limbus is found to be damaged as the tissue is not immunocompatible, there is a high risk of rejection between the recipient and the donor cadaver and studies report only a temporary success in term of transplant effectiveness, with most failing after 5 years. A recent procedure, less invasive than CLAU, which so far has been tested only in unilateral cases, is simple limbal epithelial transplantation (SLET). In this procedure, healthy limbal tissue from the patients good eye is cut into a number of pieces and transferred directly to human amniotic membrane covering the cornea in the damaged eye. Studies published so far have only investigated the procedure in unilaterally affected patients, and the long-term effectiveness of the technique is yet to be proven. Another recent innovation is cultivated limbal epithelial transplant (CLET), either autologous (where donor and recipient are the same patient) or allogenic (where donor and recipient are different patients). This approach can be used when either one or both eyes are affected, providing there is sufficient limbal tissue available (1–2 mm2). A small sample of limbal cells is taken from a healthy part of the eye, and grown in a sterile laboratory to produce a sheet of cells sufficient for transplantation. Once transplanted, they multiply and regrow the corneal epithelium. The manufacturing process is designed to ensure implantation of the right number, size and quality of cells. CLET avoids some of the issues faced by other limbal transplantation procedures and does not pose a threat to the integrity of the donor eye. It also offers the possibility of re-grafting in case of failure of the first graft or need for a further graft. Types There are three types of clonogenic keratinocytes involved in the generation of the corneal epithelium: holoclones, meroclones and paraclones. 1- Holoclones: as true stem cells, have the greatest growth potential, and give rise to 2-meroclones, which have a much lower proliferative capacity, but frequently divide. 3- Paraclones have even lower proliferative capacity. Both meroclones and paraclones are known as transient amplifying cells and their purpose is to form a stratified squamous epithelium. All three types of keratinocytes are present in the basal layer of the limbus, with holoclones in the least abundance (10%–15%). The basal layer of the cornea is populated by meroclones and paraclones at the periphery, and only paraclones in the central cornea, reflecting the above process of cell division and differentiation. Holoclones are identified by high expression of the marker p63 and are also known as p63 bright cells. Society and culture In February 2015, the European Commission approved autologous CLET using the stem cell therapy Holoclar for people with severe LSCD due to corneal burns. This is the first time that a stem cell therapy (other than the use of umbilical cord stem cells) has been approved by any regulatory agency in the world. It was created by Graziella Pellegrini and Michele de Luca. Holoclar is a tissue-engineered product that comprises ex vivo expanded autologous human corneal epithelial cells including stem cells, which replace limbal stem cells in patients where the limbus has been destroyed by ocular burns. The use of p63 transcription factor as a biomarker of potency ensures specified amount of stem cells needed for clinical success. Clinically relevant long-term beneficial results have been documented in the treatment of patients with LSCD due to physical or chemical ocular burns. See also List of human cell types derived from the germ layers Figures References Further reading Pellegrini G, Ardigò D, Milazzo G, Iotti G, Guatelli P, Pelosi D, De Luca M (January 2018). "Navigating Market Authorization: The Path Holoclar Took to Become the First Stem Cell Product Approved in the European Union". Stem Cells Transl Med. 7 (1): 146–154. doi:10.1002/sctm.17-0003. PMC 5746151. PMID 29280318. External links Limbal epithelial stem cells of the cornea
Frontal fibrosing alopecia	Frontal fibrosing alopecia is the frontotemporal hairline recession and eyebrow loss in postmenopausal women that is associated with perifollicular erythema, especially along the hairline.: 648 It is considered to be a clinical variant of lichen planopilaris. Presentation There is loss of both terminal and vellus hairs that occurs in a bandlike pattern on the frontotemporal scalp. It is a scarring alopecia that has been associated with facial papules, glabellar red dots, a loss of eyebrows, and prominent venous vasculature in the forehead. Facial hyperpigmentation may occur in dark-skinned patients if association with lichen planus pigmentosus is present. Associations Frontal fibrosing alopecia has been most often reported in post-menopausal women with higher levels of affluence and a negative smoking history. Autoimmune disease is found in 30% of patients. Pathogenesis Although the pathogenesis of frontal fibrosing alopecia is poorly understood, autoimmune reaction and hormonal factors may play a role. Diagnostic Perifollicular erythema and scarring white patches are seen on dermoscopy. On scalp biopsy, lymphocytic and granulomatous perifolliculitis with eccentric atrophy of follicular epithelia and perifollicular fibrosis are visualized. Differential diagnosis Important diagnoses to consider include female pattern hair loss (FPHL), chronic telogen effluvium (CTE), and alopecia areata (AA). FPHL is a non-scarring progressive miniaturization of the hair follicle with one of three different characteristic patterns. CTE is an idiopathic disease causing increased hair shedding and bi-temporal recession, usually in middle aged women. AA is an autoimmune attack of hair follicles that usually causes hair to fall out in small round patches. Treatment Improvement or stabilization of the condition has been reported with topical and intralesional corticosteroids, antibiotics, hydroxychloroquine, topical and oral immunomodulators, tacrolimus, and most recently, 5α-reductase inhibitors. In one study, the use of antiandrogens (finasteride or dutasteride) was associated with improvement in 47% and stabilization in 53% of patients Recently, successful treatment of facial papules in patients with frontal fibrosing alopecia was described with oral isotretinoin. See also Skin lesion References == External links ==
Tibial nerve	The tibial nerve is a branch of the sciatic nerve. The tibial nerve passes through the popliteal fossa to pass below the arch of soleus. Structure Popliteal fossa The tibial nerve is the larger terminal branch of the sciatic nerve with root values of L4, L5, S1, S2, and S3. It lies superficial (or posterior) to the popliteal vessels, extending from the superior angle to the inferior angle of the popliteal fossa, crossing the popliteal vessels from lateral to medial side. It gives off branches as shown below: Muscular branches - Muscular branches arise from the distal part of the popliteal fossa. It supplies the medial and lateral heads of gastrocnemius, soleus, plantaris and popliteus muscles. Nerve to popliteus crosses the popliteus muscle, runs downwards and laterally, winds around the lower border of the popliteus to supply the deep (or anterior) surface of the popliteus. This nerve also supplies the tibialis posterior muscle, superior tibiofibular joint, tibia bone, interosseous membrane of leg, and the inferior tibiofibular joint. Cutaneous branches - Tibial nerve also gives off a cutaneous nerve called the medial sural nerve from the middle of the popliteal fossa and exits at the inferior angle. It supplies the skin of the lower half of the back of the leg and lateral border of the foot until the tip of the little toe. Articular branches - There are three articular branches arises from the upper part of the fossa: superior medial genicular nerve (located on the surface of medial condyle of femur, middle genicular nerve (pierces the posterior capsule of the knee joint to supply the structures located in the intercondylar notch of the femur, and inferior genicular nerve (runs along the upper border of the popliteus to reach the medial condyle of tibia). Back of the leg At the inferior angle of the popliteal fossa, tibial nerve passes deep to the tendinous arch of soleus to enter the back of the leg. In the leg, it runs downwards and medially to reach the posteromedial side of the ankle, midway between the medial malleolus and medial tubercle of the calcaneum. It terminates deep to the flexor retinaculum at the origin of the abductor hallucis by dividing into medial and lateral plantar nerves to supply the foot. The tibial nerve gives off several branches to supply the back of the leg: Muscular branches - Supplies tibialis posterior, flexor digitorum longus, flexor hallucis longus, and deep part of soleus. Cutaneus branches - The medial calcaneal nerve pierces the flexor retinaculum to supply the skin of the back and lower surface of the heel. Articular branches - Supplies the ankle joint Foot In the foot, the nerve terminates by dividing into medial and lateral plantar branches. Medial plantar nerve - It is the larger terminal branch of the tibial nerve. It passes between the abductor hallucis and flexor digitorum brevis to divide further into branches. Its distribution resembles to that of the distribution of median nerve in the hand. Its muscular branches supply the abductor hallucis, the flexor digitorum brevis, the flexor hallucis brevis and the first lumbrical. Cutaneous distribution of the medial plantar nerve supplies the medial sole and medial three and one half toes through four digital branches. Each digital branch give off a dorsal branch to supply the nail beds on the dorsum. This nerve also gives off articular branches to supply the bones of the tarsus and metatarsus. Lateral plantar nerve - It is the smaller terminal branch of the tibial nerve. It courses laterally and forward until the base of fifth metatarsal bone, where it divides into superficial and deep branches. Its distribution resembles to the distribution of ulnar nerve in the hand. The main trunk of the nerve supplies two muscles: flexor digitorum accessorius and abductor digiti minimi. This nerve also supplies the skin of the sole. The superficial branch is divided into medial and lateral branches. The lateral branch supplies three muscles: flexor digiti minimi, 3rd and 4th interossei, and the skin over the lateral side of the toe. The medial branch communicates with the medial plantar nerve and supplies the skin over the fourth interdigital cleft. The deep branch supplies the 2nd, 3rd, and 4th lumbricals, first and second plantar interossei and adductor hallucis. Clinical Significance Damage to the tibial nerve is rare, and is often a result of direct trauma, entrapment through narrow space or compression for long period of time. Damage results in loss of plantar flexion, loss of flexion of toes and weakened inversion (The tibialis anterior can still invert the foot). Additional images References External links Tibial nerve at the Duke University Health Systems Orthopedics program
Dentin dysplasia	Dentin dysplasia (DD) is a rare genetic developmental disorder affecting dentine production of the teeth, commonly exhibiting an autosomal dominant inheritance that causes malformation of the root. It affects both primary and permanent dentitions in approximately 1 in every 100,000 patients. It is characterized by presence of normal enamel but atypical dentin with abnormal pulpal morphology. Witkop in 1972 classified DD into two types which are Type I (DD-1) is the radicular type, and type II (DD-2) is the coronal type. DD-1 has been further divided into 4 different subtypes (DD-1a,1b,1c,1d) based on the radiographic features. Signs and symptoms Clinically the teeth look normal in colour and morphologic appearance; however, they are commonly very mobile and exfoliated prematurely.Both primary and permanent dentitions can be affected by either type I or type II dentin dysplasia. However, deciduous teeth affected by type II dentin dysplasia have a characteristic blue-amber discolouration, whilst the other dentition appears normal. Causes The mutation in collagen type 1 (COL1 A1, COL1 A2) causes DI-1. It is similar to the systemic condition dental features known as osteogenesis imperfect. DI-2, DI-3 and DD-2 share the same genetic mutation of dentin sialophosphoprotein, that is located on chromosome 4. They are autosomal-dominant diseases with complete penetrance and variable expressivity. Due to the same genetic mutation, these diseases would often result in overlapping clinical and radiographic features. Therefore, prevailing theories suggests that DI-2, DI-3 and DD-2 are categorized as a single disease entity with variable severity of expression. However, the causes of DD-1 have yet to be theorized. Diagnosis Diagnosis is mostly based on general examination and radiographs, and it should be taken when abnormality of the teeth is suspected as most of the affected teeth have normal clinical appearance.Differential diagnosis is very important to have a definitive diagnosis as some radiographic or histologic features of dentine dysplasia may bear a resemblance to different disorders: Dentinogenesis imperfecta Odontodysplasia Calcinosis Osteogenesis imperfecta Ehlers–Danlos syndromes Goldblatt syndrome Schimke immuno-osseous dysplasia Brachio-skeleto-genital syndrome. Type I: Radicular type Type I has been known as radicular dentine dysplasia because the teeth have undeveloped root(s) with abnormal pulp tissue. Morphology and colour of the crown mostly appear normal, but occasionally teeth appear slightly amber coloured or bluish-brown shine in primary teeth with no or only immature root development. The teeth are mostly maligned and have higher risk of fracture. Radiographic feature In other words, affected primary teeth usually have abnormal shaped or shorter than normal roots. “Crescent/half-moon shaped” pulp chamber remnant in permanent teeth can be seen on x-rays. The roots may appear to be darker or radiolucent/pointy and short with apical constriction. Dentine is laid down abnormally and causes excessive growth within the pulp chamber. This will reduce the pulp space and eventually cause incomplete and total pulp chamber obliteration in permanent teeth. Sometimes periapical pathology or cysts can be seen around the root apex. Most cases of DD associated with peri-apical radiolucency/ pathology have been diagnosed as radicular cysts, but some of them have been as diagnosed peri-apical grauloma instead. Type II: Coronal type Type II would mostly cause discolouration to the primary teeth. Affected teeth usually appear as brownish-blue, brown or yellow. Translucent “opalescence” is often one of the characteristics to describe teeth with DD-2. In some cases teeth might show slightly amber coloured but in most of the cases permanent teeth are unaffected and appear normal regardless of colour, shape and size. Dental X-rays are the key to diagnose dentine dysplasia, especially on permanent teeth. Abnormalities of the pulp chamber is the main characteristic to make a definitive diagnosis.In the primary teeth, coronal dentin dysplasia may appear similar to Dentinogenesis Imperfecta type II (DG-II) but if abnormalities features appear to be more pronounced in the permanent teeth, then consider changing the diagnosis to DGI-II instead of DD-2. Radiographic features In coronal type, teeth show normal roots containing enlarged pulp with abnormal extensions towards the roots, which is often described as “thistle tube” shaped on dental radiographs. As well as this, numerous pulp stones can be often found in the pulp chambers due to abnormal calcifications. In primary teeth, the pulp chamber is usually completely obliterated but in permanent teeth, the pulp may become partially obliterated after eruption. Histological features There are a few studies and proposals that were designed to explain the pathogenesis of DD but the main reason of the cause still remains unclear in the dental literature. Logan et al., suggested that dental papilla is the cause of abnormal root growth or development. They also proposed that calcification of multiple degenerative foci within the papillae reduce the growth and eventually leads to pulpal obliteration. Wesley et al., suggested that odontoblasts with abnormal function and/ or differentiation are mainly due to atypical interaction between odontoblasts and ameloblasts. Histopathologically, deeper layer of the teeth shows abnormal dentine tubular pattern with unstructured, unorganised, atubular areas with normal enamel appearance. Globular or small mass of rounded or irregular shape of atypical dentine is often seen in the pulp. Treatment With various options available to dentists, the treatment of this condition can still be difficult. Endodontic treatment is not advised for teeth with complete obliteration of root canals and pulp chambers. An alternative treatment for teeth with periapical abscesses and pulpal necrosis is dental extraction. Retrograde fillings and periapical surgery is a treatment option for teeth with longer roots, as well as orthodontic treatment. However, orthodontic treatment can lead to even more resorption of the roots, which could lead to further tooth mobility and premature exfoliation. Another proposed treatment, for successful oral rehabilitation, is to extract all teeth, curette any cysts and provide the patient with a complete denture. A combination of bone grafting and a sinus lift technique can also be successful to accomplish implant placement. Management The best method of maintaining the health of teeth is to practice exemplary oral hygiene. More tooth loss is likely to occur if intervention takes place. However, factors such as present complaint, patient age, severity of the problem, can affect the treatment plan or options. Stainless steel crowns Stainless steel crowns which also known as "hall crowns" can prevent tooth wear and maintain occlusal dimension in affected primary teeth. However, if demanded, composite facings or composite strip crowns can be added for aesthetic reasons. Endodontics Treatment Endodontic intervention can help conserve the existing health of affected permanent teeth. It is difficult to perform an endodontic therapy on teeth that develop abscesses as a resultant of obliteration of the pulp chambers and root canals. An alternative to conventional therapy would be retrograde filling and periapical curettage. However, these therapies are not recommended for teeth with roots that are too short. Removable dentures Teeth with short thin roots and marked cervical constrictions are less favourable for indirect restorations such as crown placements. If endodontics treatment fails, and abscess develops around the root apex, extraction of the affected teeth would be the best treatment option. Dentures or over dentures can be considered, as rehabilitation until growth is completed. Cast partial dentures could also be an alternative treatment option and it only works if there are a few teeth that has enough root length to serve as retentive purpose. Dental implants Dental implant is one of the treatment options that can be considered when growth is fully attained. For patients who experience maxillo-mandibular alveolar atrophy due to early loss of teeth, alveolar ridge augmentation procedure is recommended prior to the implant placement. Both onlay bone grafting and sinus lift techniques can be carried out together to accomplish implant placement. References == External links ==
Potts puffy tumor	Potts puffy tumor, first described by Sir Percivall Pott in 1760, is a rare clinical entity characterized by subperiosteal abscess associated with osteomyelitis. It is characterized by an osteomyelitis of the frontal bone, either direct or through haematogenic spread. This results in a swelling on the forehead, hence the name. The infection can also spread inwards, leading to an intracranial abscess. Potts puffy tumor can be associated with cortical vein thrombosis, epidural abscess, subdural empyema, and brain abscess. The cause of vein thrombosis is explained by venous drainage of the frontal sinus, which occurs through diploic veins, which communicate with the dural venous plexus; septic thrombi can potentially evolve from foci within the frontal sinus and propagate through this venous system. This type of chronic osteomyelitis of the frontal bone is confused with acute sub-periosteal abscess of the frontal bone, which presents as a discrete collection over the frontal sinus. Although it can affect all ages, it is mostly found among teenagers and adolescents. It is usually seen as a complication of frontal sinusitis or trauma. Medical imaging can be of use in the diagnosis and evaluation of the underlying cause and extent of the condition. Ultrasound is able to identify frontal bone osteomyelitis, while computed tomography (CT) can evaluate bony erosion, and along with magnetic resonance imaging (MRI), can better appreciate the underlying cause and extent of possible intra-cranial extension/involvement. Cause Frontal sinusitis, acute or chronic. Frontal trauma, usually blunt. Some cases have been seen in a context of intranasal substance abuse (cocaine, methamphetamine). Post-surgical: after frontal sinus reconstruction Diagnosis Diagnosis is suspected clinically and is confirmed using cross sectional imaging of the sinuses and brain. The patient typically presents with a headache overlying the frontal sinuses and an associated forehead swelling. This is often preceded by a history of chronic rhinosinusitis.Plain X Rays can be used to demonstrate the location of this swelling, but the gold standard for diagnosis is a cross sectional CT scan of the sinuses and brain, aided by contrast to delineate the abscess itself. Treatment The patient requires admission for intravenous anti-microbial treatment. Definitively, the abscess is drained via a combination of open and/or endoscopic approaches by an otolaryngologist, with the exact approach dependent on surgical skill set. At the very least, the abscess is trephined externally as an emergency. Any associated frontal sinus table fracture can be managed electively. Intracranial extension requires referral to the neurosurgery. References External links Karaman E, Hacizade Y, Isildak H, Kaytaz A (2008). "Potts puffy tumor". J Craniofac Surg. 19 (6): 1694–7. doi:10.1097/SCS.0b013e31818b432e. PMID 19098585.
Inclusion body myositis	Inclusion body myositis (IBM) () (sometimes called sporadic inclusion body myositis, sIBM) is the most common inflammatory muscle disease in older adults. The disease is characterized by slowly progressive weakness and wasting of both proximal muscles (located on or close to the torso) and distal muscles (close to hands or feet), most apparent in the finger flexors and knee extensors. IBM is often confused with an entirely different class of diseases, called hereditary inclusion body myopathies (hIBM). The "M" in hIBM is an abbreviation for "myopathy" while the "M" in IBM is for "myositis". In IBM, two processes appear to occur in the muscles in parallel, one autoimmune and the other degenerative. Inflammation is evident from the invasion of muscle fibers by immune cells. Degeneration is characterized by the appearance of holes, deposits of abnormal proteins, and filamentous inclusions in the muscle fibers. sIBM is a rare disease, with a prevalence ranging from 1 to 71 individuals per million.Weakness comes on slowly (over months to years) in an asymmetric manner and progresses steadily, leading to severe weakness and wasting of arm and leg muscles. IBM is more common in men than women. Patients may become unable to perform activities of daily living and most require assistive devices within 5 to 10 years of symptom onset. sIBM does not significantly affect life expectancy, although death related to malnutrition and respiratory failure can occur. The risk of serious injury due to falls is increased. There is no effective treatment for the disease as of 2019. Classification and terminology IBM stands for "inclusion body myositis:, not "inclusion body myopathy." The inclusion body refers to a histological finding of rimmed vacules in muscle tissue. However, IBM does not refer to the collection of diseases that feature these inclusion bodies. It refers to a specific disease entity.Multiple genetic diseases that feature inclusion bodies have been grouped into "hereditary inclusion body myopathies (hIBM)." Myopathy is used because inflammation is not a prominent finding. There is inconsistency in what individual disease entities fall under the category of hIBM. The term "sporadic inclusion body myositis" (sIBM) was introduced as a way to refer to IBM to avoid confusion with hIBM. However, one author discourages use of sIBM, as it implies that IBM and hIBM differ only in inheritance; they actually have unrelated mechanisms and manifestations of disease. Signs and symptoms sIBM causes progressive muscle weakness. How sIBM affects individuals is variable, including the age of onset (which generally varies from the forties upwards) and rate of progression. Because of this variability, there is no "textbook case".Common early symptoms include frequent tripping and falling and difficulty going up stairs. Foot drop in one or both feet can occur. Part of the cause for this dysfunction is the early involvement of the quadriceps muscles. Weakness of the tibialis anterior muscle is responsible for foot drop. Another common early symptom is trouble manipulating the fingers, such as difficulty with tasks such as turning doorknobs or gripping keys. Weakness of finger flexion and ankle dorsiflexion occurs early. sIBM also preferentially affects the wrist flexors, biceps, and triceps.During the course of the illness, the patients mobility is progressively restricted as it becomes difficult to bend down, reach for things, and walk quickly. Many patients say they have balance problems and fall easily, as the muscles cannot compensate for an off-balanced posture. Because sIBM makes the leg muscles weak and unstable, patients are very vulnerable to serious injury from tripping or falling down. Although pain has not been traditionally part of the "textbook" description, many patients report severe muscle pain, especially in the thighs. Progressive difficulty swallowing (dysphagia) is present in 40 to 85% of IBM cases and often leads to death from aspiration pneumonia.IBM can also result in diminished capacity for aerobic exercise. This decline is most likely a consequence of the sedentary lifestyle leading to disuse muscle atrophy that is often associated with the symptoms of IBM (i.e. progressive muscle weakness, decreased mobility, and increased level of fatigue). Therefore, one focus of treatment should be the improvement of aerobic capacity.Patients with sIBM usually eventually need to resort to a cane or a walker and in most cases, a wheelchair eventually becomes a necessity. "The progressive course of s-IBM leads slowly to severe disability. Finger functions can become very impaired, such as manipulating pens, keys, buttons, and zippers, pulling handles, and firmly grasping handshakes. Arising from a chair becomes difficult. Walking becomes more precarious. Sudden falls, sometimes resulting in major injury to the skull or other bones, can occur, even from walking on minimally irregular ground or from other minor imbalances outside or in the home, due to weakness of quadriceps and gluteus muscles depriving the patient of automatic posture maintenance. A foot-drop can increase the likelihood of tripping. Dysphagia can occur, usually caused by upper esophageal constriction that often can be symptomatically improved, for several months to years, by bougie dilation per a GI or ENT physician. Respiratory muscle weakness can sometimes eventuate." Causes The cause of IBM is unknown. IBM likely results from the interaction of a number of genetic and environmental factors.There are two major theories about how sIBM is caused. One hypothesis suggests that the inflammation-immune reaction, caused by an unknown trigger – likely an undiscovered virus or an autoimmune disorder – is the primary cause of sIBM and that the degeneration of muscle fibers and protein abnormalities are secondary features. Despite the arguments "in favor of an adaptive immune response in sIBM, a purely autoimmune hypothesis for sIBM is untenable because of the diseases resistance to most immunotherapy."The second school of thought advocates the theory that sIBM is a degenerative disorder related to aging of the muscle fibers and that abnormal, potentially pathogenic protein accumulations in myofibrils play a key causative role in sIBM (apparently before the immune system comes into play). This hypothesis emphasizes the abnormal intracellular accumulation of many proteins, protein aggregation and misfolding, proteosome inhibition, and endoplasmic reticulum (ER) stress.One review discusses the "limitations in the beta-amyloid-mediated theory of IBM myofiber injury."Dalakas (2006) suggested that a chain of events causes IBM – some sort of virus, likely a retrovirus, triggers the cloning of T cells. These T cells appear to be driven by specific antigens to invade muscle fibers. In people with sIBM, the muscle cells display "flags" telling the immune system that they are infected or damaged (the muscles ubiquitously express MHC class I antigens) and this immune process leads to the death of muscle cells. The chronic stimulation of these antigens also causes stress inside the muscle cell in the endoplasmic reticulum (ER) and this ER stress may be enough to cause a self-sustaining T cell response (even after a virus has dissipated). In addition, this ER stress may cause the misfolding of protein. The ER is in charge of processing and folding molecules carrying antigens. In IBM, muscle fibers are overloaded with these major histocompatibility complex (MHC) molecules that carry the antigen protein pieces, leading to more ER stress and more protein misfolding.A self-sustaining T cell response would make sIBM a type of autoimmune disorder. When studied carefully, it has not been possible to detect an ongoing viral infection in the muscles. One theory is that a chronic viral infection might be the initial triggering factor setting IBM in motion. There have been a handful of IBM cases – approximately 15 – that have shown clear evidence of a virus called HTLV-1. The HTLV-1 virus can cause leukemia, but in most cases lies dormant and most people end up being lifelong carriers of the virus. One review says that the best evidence points towards a connection with some type of retrovirus and that a retroviral infection combined with immune recognition of the retrovirus is enough to trigger the inflammation process. amyloid protein The hypothesis that beta amyloid protein is key to IBM has been supported in a mouse model using an Aβ vaccine that was found to be effective against inclusion body myositis in mouse models. Although this vaccine is likely, not safe for human use, it still shows that attacking Aβ has efficacy in mice against IBM. Following up on earlier leads, the Greenberg group report finding that the protein TDP-43 is a very prominent and highly sensitive and specific feature of IBM. This protein is normally found within the nucleus but in IBM is found in the cytoplasm of the cell. This important advance should help develop a new screening technique for IBM and may provide clues in terms of a therapeutic approach Genetics sIBM is not inherited and is not passed on to the children of IBM patients. There are genetic features that do not directly cause IBM but that appear to predispose a person to getting IBM – having this particular combination of genes increases ones susceptibility to getting IBM. Some 67% of IBM patients have a particular combination of human leukocyte antigen genes in a section of the 8.1 ancestral haplotype in the center of the MHC class II region. sIBM is not passed on from generation to generation, although the susceptibility region of genes may be.There are also several rare forms of hereditary inclusion body myopathy that are linked to specific genetic defects and that are passed on from generation to generation. Since these forms do not show features of muscle inflammation, they are classified as myopathies rather than forms of myositis. Because they do not display inflammation as a primary symptom, they may in fact be similar, but different diseases to sporadic inclusion body myositis. There are several different types, each inherited in different ways. See hereditary inclusion body myopathy.A 2007 review concluded there is no indication that the genes responsible for the familial or hereditary conditions are involved in sIBM. Diagnosis Elevated creatine kinase (CK) levels in the blood (at most ~10 times normal) are typical in sIBM but affected individuals can also present with normal CK levels. Electromyography (EMG) studies display variable abnormalities such as increased insertional activity, increased spontaneous activity (fibrillation potentials and sharp waves), and large/broad or short/narrow motor unit potentials. On EMG, recruitment patterns can be reduced or increased. Findings can vary even within the same muscle of an affected individual. Muscle biopsy may display several common findings including; inflammatory cells invading muscle cells, vacuolar degeneration, and inclusion bodies of aggregations of multiple proteins. sIBM is a challenge to the pathologist and even with a biopsy, diagnosis can be ambiguous.A diagnosis of inclusion body myositis was historically dependent on muscle biopsy results. Antibodies to cytoplasmic 5-nucleotidase (cN1A; NT5C1A) have been strongly associated with the condition. However, other inflammatory conditions, such as lupus, can have a positive anti-NT5C1A. As of 2019, it remains to be established whether a positive anti-NT5C1A antibody test can make muscle biopsy unneeded. Muscle imaging can help establish the pattern of muscle involvement and selection of a biopsy site. Differential diagnosis IBM is often initially misdiagnosed as polymyositis. A course of prednisone is typically completed with no improvement and eventually, sIBM is confirmed. sIBM weakness comes on over months or years and progresses steadily, whereas polymyositis has an onset of weeks or months. Muscular dystrophy (e.g. limb girdle muscular dystrophy) must be considered as well. sIBM can be mistaken for physical deconditioning.Hereditary myopathies can mimic sIBM, both in signs and symptoms and in the appearance of muscle biopsies. A small percentage of those initially diagnosed with sIBM are later found to have pathogenic mutations in the genes VCP and SQSTM1, which are known to cause hIBM.IBM has a distinctive pattern of muscle involvement that distinguishes it among inflammatory myopathies. Characteristic of IBM is weakness of finger flexion, knee extension, and ankle dorsiflexion. Other inflammatory myopathies cause a proximal muscle weakness pattern, such as weakness of hip flexion, abduction, and extension, as well as shoulder abduction. IBM and other inflammatory myopathies both cause bicep/tricep weakness. Classification The common type is sIBM; it strikes individuals apparently at random. There is a type that has been observed in multiple siblings in the same generation in several families, termed familial inflammatory sIBM, but it is not passed on from generation to generation. There are also several very rare forms of hereditary inclusion body myopathy (hIBM) that are linked to specific genetic defects and that are passed on from generation to generation, each inherited in different ways. Management There is no standard course of treatment to slow or stop the progression of the disease as of 2019. sIBM patients do not reliably respond to anti-inflammatory, immunosuppressant, or immunomodulatory medications. Most of disease management is supportive care. Prevention of falls is an important consideration. There is no consensus on exercise guidelines; however, physical therapy is recommended to teach the patient a home exercise program, to teach how to compensate during mobility-gait training with an assistive device, transfers and bed mobility. An exercise regimen preferentially minimizes a patients risk of injury and corresponds to the patients goals. Other related disorders When sIBM was originally described, the major feature noted was muscle inflammation. Two other disorders were also known to display muscle inflammation, and sIBM was classified along with them. They are dermatomyositis (DM) and polymyositis (PM) and all three illnesses were called idiopathic (of unknown origin) myositis or inflammatory myopathies.It appears that sIBM and polymyositis share some features, especially the initial sequence of immune system activation, however, polymyositis comes on over weeks or months, does not display the subsequent muscle degeneration and protein abnormalities as seen in IBM, and as well, polymyositis tends to respond well to treatments, IBM does not. IBM is often confused with (misdiagnosed as) polymyositis. Polymyositis that does not respond to treatment is likely IBM.Dermatomyositis shares a number of similar physical symptoms and histopathological traits as polymyositis, but exhibits a skin rash not seen in polymyositis or sIBM. It may have different root causes unrelated to either polymyositis or sIBM.Mutations in valosin-containing protein (VCP) cause multisystem proteinopathy (MSP), which can present (among others) as a rare form of inclusion body myopathy. Epidemiology Prevalence of disease in a rigorous meta-analysis in 2017 was 46 patients per million. The earliest published prevalence was in 2000 and put at 5 per million. A 2017 study in Ireland reported 112 per million. It is not believed that the disease prevalence is increasing with time, but rather diagnostics and reporting are improving.Estimates of the mean age of onset range from 61 to 68 years old. Society and culture In the biographical drama film Father Stu, the protagonist, a boxer-turned-Catholic priest, has sIBM. See also Inflammatory myopathies References External links GeneReview/NIH/UW entry on Inclusion Body Myopathy 2
Azotemia	Azotemia (azot, "nitrogen" + -emia, "blood condition") is a medical condition characterized by abnormally high levels of nitrogen-containing compounds (such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds) in the blood. It is largely related to insufficient or dysfunctional filtering of blood by the kidneys. It can lead to uremia and acute kidney injury (kidney failure) if not controlled. Types Azotemia has three classifications, depending on its causative origin: prerenal azotemia, renal azotemia, and postrenal azotemia.Measurements of urea and creatinine (Cr) in the blood are used to assess renal function. For historical reasons, the lab test measuring urea is known as "blood urea nitrogen" (BUN). The BUN:Cr ratio is a useful measure in determining the type of azotemia and will be discussed in each section below. A normal BUN:Cr is equal to 15. Prerenal azotemia Prerenal azotemia is caused by a decrease in blood flow (hypoperfusion) to the kidneys. However, there is no inherent kidney disease. It can occur following hemorrhage, shock, volume depletion, congestive heart failure, adrenal insufficiency, and narrowing of the renal artery among other things.The BUN:Cr in prerenal azotemia is greater than 20. The reason for this lies in the mechanism of filtration of urea and creatinine. Renal Plasma Flow (RPF) is decreased due to hypoperfusion which results in a proportional decrease in GFR. In turn, the decreased flow and pressure to the kidney will be sensed by baroreceptors in the Juxtaglomerular (JG) Cells of the afferent arteriole. If the decrease in blood pressure is systemic (rather than occlusion of the renal artery) baroreceptors in the carotid sinus and aortic arch will be stimulated. This leads to sympathetic nerve activation, resulting in renin secretion through β 1 -receptors. Constriction of the afferent arterioles causes a decrease in the intraglomerular pressure, reducing GFR proportionally. Renin is the main effector of the juxtaglomerular baroreceptors. Renin is secreted from granules in the JG cells, and once in the blood stream, it acts as a protease to convert angiotensinogen to angiotensin I, which is converted by angiotensin converting enzyme, to angiotensin II, which, in turn, stimulates aldosterone release. Increased aldosterone levels results in salt and water absorption in the distal collecting tubule.A decrease in volume or pressure is a nonosmotic stimulus for antidiuretic hormone production in the hypothalamus, which exerts its effect in the medullary collecting duct for water reabsorption. Through unknown mechanisms, activation of the sympathetic nervous system leads to enhanced proximal tubular reabsorption of salt and water, as well as urea (BUN), calcium, uric acid, and bicarbonate. The net result of these 4 mechanisms of salt and water retention is decreased output and decreased urinary excretion of sodium (< 20 mEq/L). The increased reabsorption of Na leads to increased water and urea reabsorption from the proximal tubules of the kidney back into the blood. In contrast, creatinine is actually secreted in the proximal tubule. This generally leads to a BUN:Cr ratio > 20 and a fractional excretion of Na of < 1% and an elevated urine osmolarity. Primary renal azotemia Renal azotemia (acute kidney failure) typically leads to uremia. It is an intrinsic disease of the kidney, generally the result of kidney parenchymal damage. Causes include kidney failure, glomerulonephritis, acute tubular necrosis, or other kidney disease.The BUN:Cr in renal azotemia is less than 15. In cases of kidney disease, glomerular filtration rate decreases, so nothing gets filtered as well as it normally would. However, in addition to not being normally filtered, what urea does get filtered is not reabsorbed by the proximal tubule as it normally would be. This results in lower levels of urea in the blood and higher levels of urea in the urine as compared to creatinine. Creatinine filtration decreases, leading to a higher amount of creatinine in the blood. Third spacing of fluids such as peritonitis, osmotic diuresis, or low aldosterone states such as Addisons disease all elevate urea. Postrenal azotemia Blockage of urine flow in an area below the kidneys results in postrenal azotemia. It can be caused by congenital abnormalities such as vesicoureteral reflux, blockage of the ureters by kidney stones, pregnancy, compression of the ureters by cancer, prostatic hyperplasia, or blockage of the urethra by kidney or bladder stones. Like in prerenal azotemia, there is no inherent renal disease. The increased resistance to urine flow can cause back up into the kidneys, leading to hydronephrosis.The BUN:Cr in postrenal azotemia is initially >15. The increased nephron tubular pressure (due to fluid back-up) causes increased reabsorption of urea, elevating it abnormally relative to creatinine. Persistent obstruction damages the tubular epithelium over time, and renal azotemia will result with a decreased BUN:Cr ratio. Signs and symptoms Oliguria or anuria (decreased or absent urine output) Fatigue Asterixis (flapping tremor) Decreased alertness Confusion Pale skin Tachycardia (rapid pulse) Xerostomia (dry mouth) Thirst Edema, anasarca (swelling) Orthostatic blood pressure (fluctuates depending on body position) Uremic frost, a condition that occurs when urea and urea derivatives are secreted through the skin in sweat, which evaporates away to leave solid uric compounds, resembling a frost.A urinalysis will typically show a decreased urine sodium level, a high urine creatinine-to-serum creatinine ratio, a high urine urea-to-serum urea ratio, and concentrated urine (determined by osmolality and specific gravity). None of these is particularly useful in diagnosis.In pre-renal and post-renal azotemias, elevation of urea exceeds that of the creatinine (i.e., BUN>12*creatinine). This is because urea is readily reabsorbed by the kidneys while creatinine is not. In congestive heart failure (a cause of pre-renal azotemia) or any other condition that causes poor perfusion of kidneys, the sluggish flow of glomerular filtrate results in excessive absorption of urea and elevation of its value in blood. Creatinine, however, is not absorbable and therefore does not rise significantly. Stasis of urine in post-renal azotemia has the same effect. Treatment Prompt treatment of some causes of azotemia can result in restoration of kidney function; delayed treatment may result in permanent loss of renal function. Treatment may include hemodialysis or peritoneal dialysis, medications to increase cardiac output and increase blood pressure, and the treatment of the condition that caused the azotemia. See also Kidney failure Nephrology References == External links ==
Melorheostosis	Melorheostosis is a medical developmental disorder and mesenchymal dysplasia in which the bony cortex widens and becomes hyperdense in a sclerotomal distribution. The condition begins in childhood and is characterized by thickening of the bones. Pain is a frequent symptom and the bone can have the appearance of dripping candle wax. Cause A randomly occurring somatic mutation of the MAP2K1 gene during fetal development is believed to be the cause. It is not known if LEMD3 mutations can cause isolated melorheostosis in the absence of osteopoikilosis or Buschke–Ollendorff syndrome. Diagnosis Melorheostosis is a mesenchymal dysplasia manifesting as regions of dripping wax appearance or flowing candle wax appearance. The disorder can be detected by radiograph due to thickening of bony cortex resembling "dripping candle wax." It is included on the spectrum of developmental bone dysplasias including pycnodysostosis and osteopoikilosis. The disorder tends to be unilateral and monostotic (i.e. affecting a single bone), with only one limb typically involved. Cases with involvement of multiple limbs, ribs, and bones in the spine have also been reported. There are no reported cases of involvement of skull or facial bones. Melorheostosis can be associated with pain, physical deformity, skin and circulation problems, contractures, and functional limitation. It is also associated with a benign inner ear dysplasia known as osteosclerosis. Treatment The disorder is progressive, with the ultimate severity of symptoms often depending on age of onset. In severe cases amputation has been performed when conservative measures such as physical therapy and regional anesthetics have been ineffective. See also List of radiographic findings associated with cutaneous conditions References External links 01061 at CHORUS
Snapping hip syndrome	Snapping hip syndrome, also referred to as dancers hip, is a medical condition characterized by a snapping sensation felt when the hip is flexed and extended. This may be accompanied by a snapping or popping noise and pain or discomfort. Pain often decreases with rest and diminished activity. Snapping hip syndrome is commonly classified by the location of the snapping as either extra- articular or intra-articular. Symptoms In some cases, an audible snapping or popping noise as the tendon at the hip flexor crease moves from flexion (knee toward waist) to extension (knee down and hip joint straightened). It can be painless. After extended exercise, pain or discomfort may be present caused by inflammation of the iliopsoas bursae. Pain often decreases with rest and diminished activity. Symptoms usually last months or years without treatment and can be very painful. Extra-articular Lateral extra articularThe more common lateral extra-articular type of snapping hip syndrome occurs when the iliotibial band, tensor fasciae latae, or gluteus medius tendon slides back and forth across the greater trochanter. This normal action becomes a snapping hip syndrome when one of these connective tissue bands thickens and catches with motion. The underlying bursa may also become inflamed, causing a painful external snapping hip syndrome. Medial extra-articularLess commonly, the iliopsoas tendon catches on the anterior inferior iliac spine, the lesser trochanter, or the iliopectineal ridge during hip extension, as the tendon moves from an anterior lateral (front, side) to a posterior medial (back, middle) position. With overuse, the resultant friction may eventually cause painful symptoms, resulting in muscle trauma, bursitis, or inflammation in the area. Intra-articular Because the iliopsoas or hip flexor crosses directly over the anterior superior labrum of the hip, an intra-articular hip derangement (i.e. labral tears, hip impingement, loose bodies) can lead to an effusion that subsequently produces internal snapping hip symptoms. Causes The causes of snapping hip syndrome are not fully understood. The onset is often insidious with reports of a "non-painful" sensation or audible snapping, clicking, or popping with certain activities. Individuals often ignore the "snapping" sensation, which may lead to future discomfort with activity. Athletes appear to have an increased risk of snapping hip syndrome due to repetitive and physically demanding movements. Among athletes such as ballet dancers, gymnasts, horse riders, track and field athletes and soccer players, military training, or any vigorous exerciser, repeated hip flexion can lead to injury. In excessive weightlifting or running, the cause is usually attributed to extreme thickening of the tendons in the hip region. Snapping hip syndrome most often occurs in people who are 15 to 40 years old. Extra-articular Extra-articular snapping hip syndrome is commonly associated with leg length difference (usually the long side is symptomatic), tightness in the iliotibial band (ITB) on the involved side, weakness in hip abductors and external rotators, poor lumbopelvic stability and abnormal foot mechanics (overpronation). Popping during external snapping hip (lateral-extra articular), occurs when the thickened posterior aspect of the ITB or the anterior gluteus maximus rubs over the greater trochanter as the hip is extended. Internal snapping hip (medial-extra articular) is usually described by the patient as a snapping or locking of the hip with an audible snap and occurs when the iliopsoas tendon snaps over underlying bony prominences. Almost half of patients with internal snapping hip also have inter-articular pathology. Intra-articular The causes of intra-articular snapping hip syndrome seem to be broadly similar to those of the extra-articular type, but often include an underlying mechanical problem in the lower extremity. The pain associated with the internal variety tends to be more intense and therefore more debilitating than with the external variety. Intra-articular snapping hip syndrome is often indicative of injury such as a torn acetabular labrum, ligamentum teres tears, loose bodies, articular cartilage damage, or synovial chondromatosis (cartilage formations in the synovial membrane of the joint). Diagnostic Ultrasound during hip motion may visualize tendon subluxation and any accompanying bursitis when evaluating for iliopsoas involvement in medial extra-articular cases. MRI can sometimes identify intra-articular causes of snapping hip syndrome. Treatment This condition is usually curable with appropriate treatment, or sometimes it heals spontaneously. If it is painless, there is little cause for concern. Correcting any contributing biomechanical abnormalities and stretching tightened muscles, such as the iliopsoas muscle or iliotibial band, is the goal of treatment to prevent recurrence.Referral to an appropriate professional for an accurate diagnosis is necessary if self treatment is not successful or the injury is interfering with normal activities. Medical treatment of the condition requires determination of the underlying pathology and tailoring therapy to the cause. The examiner may check muscle-tendon length and strength, perform joint mobility testing, and palpate the affected hip over the greater trochanter for lateral symptoms during an activity such as walking. Self-treatment A self-treatment recommended by the U.S. Army for a soft tissue injury of the iliopsoas muscle treatment, like for other soft tissue injuries, is a HI-RICE (Hydration, Ibuprofen, Rest, Ice, Compression, Elevation) regimen lasting for at least 48 to 72 hours after the onset of pain. "Rest" includes such commonsense prescriptions as avoiding running or hiking (especially on hills), and avoiding exercises such as jumping jacks, sit-ups or leg lifts/flutter kicks. Stretching of the tight structures (piriformis, hip abductor, and hip flexor muscle) may alleviate the symptoms. The involved muscle is stretched (for 30 seconds), repeated three times separated by 30 second to 1 minute rest periods, in sets performed two times daily for six to eight weeks. This should allow one to progress back into jogging until symptoms disappear. Injection based treatments Injections are usually focused on the iliopsoas bursa. Corticosteroid injections are common, but usually only last weeks to months. In addition, corticosteroid side effects can include weight gain, weakening of the surrounding tissues, and even osteoporosis, with regular use. Cellular based therapy may have a role in future injection based treatments, though there is no current research proving the effectiveness of these therapies. Surgical treatment If medicine or physical therapy is ineffective or abnormal structures are found, surgery may be recommended. Surgical treatment is rarely necessary unless intra-articular pathology is present. In patients with persistently painful iliopsoas symptoms surgical release of the contracted iliopsoas tendon has been used since 1984. Iliopsoas and iliotibial band lengthening can be done arthroscopically. Postop, these patients will usually undergo extensive physical therapy; regaining full strength may take up to 9–12 months. Rehabilitation Patients may require intermittent NSAID therapy or simple analgesics as they progress in activities. If persistent pain caused by bursitis continues, a corticosteroid injection may be beneficial. Physical therapy, or athletic training therapy, and rehabilitation Both active and passive stretching exercises that include hip and knee extension should be the focus of the program. Stretching the hip into extension and limiting excessive knee flexion avoids placing the rectus femoris in a position of passive insufficiency, thereby maximizing the stretch to the iliopsoas tendon. Strengthening exercises for the hip flexors may also be an appropriate component of the program. A non-steroidal anti-inflammatory drug regimen as well as activity modification or activity progression (or both) may be used. Once symptoms have decreased a maintenance program of stretching and strengthening can be initiated. Light aerobic activity (warmup) followed by stretching and strengthening of the proper hamstring, hip flexors, and iliotibial band length is important for reducing recurrences. Conservative measures may resolve the problem in six to eight weeks.. Massage or self-myofascial release may be an effective intervention for external snapping hip syndromes. It is suggested that using soft-tissue modalities to target the iliopsoas for medial extra-articulate snapping hip syndrome and gluteus maximus, tensor fasciae latae, and ITB complex for lateral extras-articulate napping hip syndrome may be effective in treating symptoms of snapping hip syndrome. See also Femoral acetabular impingement Iliotibial band syndrome References == External links ==

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