Datasets:

HoangHa

/

wiki_medical_terms_inout

like 0

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

Please help me grasp the concept behind the medical term 'Otitis media.'

Otitis media is a group of inflammatory diseases of the middle ear. One of the two main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pulling at the ear, increased crying, and poor sleep. Decreased eating and a fever may also be present. The other main type is otitis media with effusion (OME), typically not associated with symptoms, although occasionally a feeling of fullness is described; it is defined as the presence of non-infectious fluid in the middle ear which may persist for weeks or months often after an episode of acute otitis media. Chronic suppurative otitis media (CSOM) is middle ear inflammation that results in a perforated tympanic membrane with discharge from the ear for more than six weeks. It may be a complication of acute otitis media. Pain is rarely present. All three types of otitis media may be associated with hearing loss. If children with hearing loss due to OME do not learn sign language, it may affect their ability to learn.The cause of AOM is related to childhood anatomy and immune function. Either bacteria or viruses may be involved. Risk factors include exposure to smoke, use of pacifiers, and attending daycare. It occurs more commonly among indigenous peoples and those who have cleft lip and palate or Down syndrome. OME frequently occurs following AOM and may be related to viral upper respiratory infections, irritants such as smoke, or allergies. Looking at the eardrum is important for making the correct diagnosis. Signs of AOM include bulging or a lack of movement of the tympanic membrane from a puff of air. New discharge not related to otitis externa also indicates the diagnosis.A number of measures decrease the risk of otitis media including pneumococcal and influenza vaccination, breastfeeding, and avoiding tobacco smoke. The use of pain medications for AOM is important. This may include paracetamol (acetaminophen), ibuprofen, benzocaine ear drops, or opioids. In AOM, antibiotics may speed recovery but may result in side effects. Antibiotics are often recommended in those with severe disease or under two years old. In those with less severe disease they may only be recommended in those who do not improve after two or three days. The initial antibiotic of choice is typically amoxicillin. In those with frequent infections tympanostomy tubes may decrease recurrence. In children with otitis media with effusion antibiotics may increase resolution of symptoms, but may cause diarrhoea, vomiting and skin rash.Worldwide AOM affects about 11% of people a year (about 325 to 710 million cases). Half the cases involve children less than five years of age and it is more common among males. Of those affected about 4.8% or 31 million develop chronic suppurative otitis media. The total number of people with CSOM is estimated at 65–330 million people. Before the age of ten OME affects about 80% of children at some point. Otitis media resulted in 3,200 deaths in 2015 – down from 4,900 deaths in 1990. Signs and symptoms The primary symptom of acute otitis media is ear pain; other possible symptoms include fever, reduced hearing during periods of illness, tenderness on touch of the skin above the ear, purulent discharge from the ears, irritability, ear blocking sensation and diarrhea (in infants). Since an episode of otitis media is usually precipitated by an upper respiratory tract infection (URTI), there are often accompanying symptoms like a cough and nasal discharge. One might also experience a feeling of fullness in the ear. Discharge from the ear can be caused by acute otitis media with perforation of the eardrum, chronic suppurative otitis media, tympanostomy tube otorrhea, or acute otitis externa. Trauma, such as a basilar skull fracture, can also lead to cerebrospinal fluid otorrhea (discharge of CSF from the ear) due to cerebral spinal drainage from the brain and its covering (meninges). Causes The common cause of all forms of otitis media is dysfunction of the Eustachian tube. This is usually due to inflammation of the mucous membranes in the nasopharynx, which can be caused by a viral upper respiratory tract infection (URTI), strep throat, or possibly by allergies.By reflux or aspiration of unwanted secretions from the nasopharynx into the normally sterile middle-ear space, the fluid may then become infected — usually with bacteria. The virus that caused the initial upper respiratory infection can itself be identified as the pathogen causing the infection. Diagnosis As its typical symptoms overlap with other conditions, such as acute external otitis, symptoms alone are not sufficient to predict whether acute otitis media is present; it has to be complemented by visualization of the tympanic membrane. Examiners may use a pneumatic otoscope with a rubber bulb attached to assess the mobility of the tympanic membrane. Other methods to diagnose otitis media is with a tympanometry, reflectometry or hearing test. In more severe cases, such as those with associated hearing loss or high fever, audiometry, tympanogram, temporal bone CT and MRI can be used to assess for associated complications, such as mastoid effusion, subperiosteal abscess formation, bony destruction, venous thrombosis or meningitis.Acute otitis media in children with moderate to severe bulging of the tympanic membrane or new onset of otorrhea (drainage) is not due to external otitis. Also, the diagnosis may be made in children who have mild bulging of the ear drum and recent onset of ear pain (less than 48 hours) or intense erythema (redness) of the ear drum. To confirm the diagnosis, middle-ear effusion and inflammation of the eardrum have to be identified; signs of these are fullness, bulging, cloudiness and redness of the eardrum. It is important to attempt to differentiate between acute otitis media and otitis media with effusion (OME), as antibiotics are not recommended for OME. It has been suggested that bulging of the tympanic membrane is the best sign to differentiate AOM from OME, with a bulging of the membrane suggesting AOM rather than OME.Viral otitis may result in blisters on the external side of the tympanic membrane, which is called bullous myringitis (myringa being Latin for "eardrum").However, sometimes even examination of the eardrum may not be able to confirm the diagnosis, especially if the canal is small. If wax in the ear canal obscures a clear view of the eardrum it should be removed using a blunt cerumen curette or a wire loop. Also, an upset young childs crying can cause the eardrum to look inflamed due to distension of the small blood vessels on it, mimicking the redness associated with otitis media. Acute otitis media The most common bacteria isolated from the middle ear in AOM are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Otitis media with effusion Otitis media with effusion (OME), also known as serous otitis media (SOM) or secretory otitis media (SOM), and colloquially referred to as glue ear, is fluid accumulation that can occur in the middle ear and mastoid air cells due to negative pressure produced by dysfunction of the Eustachian tube. This can be associated with a viral upper respiratory infection (URI) or bacterial infection such as otitis media. An effusion can cause conductive hearing loss if it interferes with the transmission of vibrations of middle ear bones to the vestibulocochlear nerve complex that are created by sound waves.Early-onset OME is associated with feeding of infants while lying down, early entry into group child care, parental smoking, lack, or too short a period of breastfeeding and greater amounts of time spent in group child care, particularly those with a large number of children. These risk factors increase the incidence and duration of OME during the first two years of life. Chronic suppurative otitis media Chronic suppurative otitis media (CSOM) is a chronic inflammation of the middle ear and mastoid cavity that is characterised by discharge from the middle ear through a perforated tympanic membrane for at least 6 weeks. CSOM occurs following an upper respiratory tract infection that has led to acute otitis media. This progresses to a prolonged inflammatory response causing mucosal (middle ear) oedema, ulceration and perforation. The middle ear attempts to resolve this ulceration by production of granulation tissue and polyp formation. This can lead to increased discharge and failure to arrest the inflammation, and to development of CSOM, which is also often associated with cholesteatoma. There may be enough pus that it drains to the outside of the ear (otorrhea), or the pus may be minimal enough to be seen only on examination with an otoscope or binocular microscope. Hearing impairment often accompanies this disease. People are at increased risk of developing CSOM when they have poor eustachian tube function, a history of multiple episodes of acute otitis media, live in crowded conditions, and attend paediatric day care facilities. Those with craniofacial malformations such as cleft lip and palate, Down syndrome, and microcephaly are at higher risk.Worldwide approximately 11% of the human population is affected by AOM every year, or 709 million cases. About 4.4% of the population develop CSOM.According to the World Health Organization, CSOM is a primary cause of hearing loss in children. Adults with recurrent episodes of CSOM have a higher risk of developing permanent conductive and sensorineural hearing loss. In Britain, 0.9% of children and 0.5% of adults have CSOM, with no difference between the sexes. The incidence of CSOM across the world varies dramatically where high income countries have a relatively low prevalence while in low income countries the prevalence may be up to three times as great. Each year 21,000 people worldwide die due to complications of CSOM. Adhesive otitis media Adhesive otitis media occurs when a thin retracted ear drum becomes sucked into the middle-ear space and stuck (i.e., adherent) to the ossicles and other bones of the middle ear. Prevention AOM is far less common in breastfed infants than in formula-fed infants, and the greatest protection is associated with exclusive breastfeeding (no formula use) for the first six months of life. A longer duration of breastfeeding is correlated with a longer protective effect.Pneumococcal conjugate vaccines (PCV) in early infancy decrease the risk of acute otitis media in healthy infants. PCV is recommended for all children, and, if implemented broadly, PCV would have a significant public health benefit. Influenza vaccination in children appears to reduce rates of AOM by 4% and the use of antibiotics by 11% over 6 months. However, the vaccine resulted in increased adverse-effects such as fever and runny nose. The small reduction in AOM may not justify the side effects and inconvenience of influenza vaccination every year for this purpose alone. PCV does not appear to decrease the risk of otitis media when given to high-risk infants or for older children who have previously experienced otitis media.Risk factors such as season, allergy predisposition and presence of older siblings are known to be determinants of recurrent otitis media and persistent middle-ear effusions (MEE). History of recurrence, environmental exposure to tobacco smoke, use of daycare, and lack of breastfeeding have all been associated with increased risk of development, recurrence, and persistent MEE. Pacifier use has been associated with more frequent episodes of AOM.Long-term antibiotics, while they decrease rates of infection during treatment, have an unknown effect on long-term outcomes such as hearing loss. This method of prevention has been associated with emergence of antibiotic-resistant otitic bacteria. They are thus not recommended.There is moderate evidence that the sugar substitute xylitol may reduce infection rates in those who go to daycare.Evidence does not support zinc supplementation as an effort to reduce otitis rates except maybe in those with severe malnutrition such as marasmus.Probiotics do not show evidence of preventing acute otitis media in children. Management Oral and topical pain killers are effective to treat the pain caused by otitis media. Oral agents include ibuprofen, paracetamol (acetaminophen), and opiates. Evidence for the combination over single agents is lacking. Topical agents shown to be effective include antipyrine and benzocaine ear drops. Decongestants and antihistamines, either nasal or oral, are not recommended due to the lack of benefit and concerns regarding side effects. Half of cases of ear pain in children resolve without treatment in three days and 90% resolve in seven or eight days. The use of steroids is not supported by the evidence for acute otitis media. Antibiotics It is important to weigh the benefits and harms before using antibiotics for acute otitis media. As over 82% of acute episodes settle without treatment, about 20 children must be treated to prevent one case of ear pain, 33 children to prevent one perforation, and 11 children to prevent one opposite-side ear infection. For every 14 children treated with antibiotics, one child has an episode of either vomiting, diarrhea or a rash. If pain is present, pain medications may be used. For people requiring surgery to treat otitis media with effusion, preventative antibiotics may not help reduce the risk of post-surgical complications.For bilateral acute otitis media in infants younger than 24 months of age, there is evidence that the benefits of antibiotics outweigh the harms. A 2015 Cochrane review concluded that watchful waiting is the preferred approach for children over six months with non severe acute otitis media. Most children older than 6 months of age who have acute otitis media do not benefit from treatment with antibiotics. If antibiotics are used, a narrow-spectrum antibiotic like amoxicillin is generally recommended, as broad-spectrum antibiotics may be associated with more adverse events. If there is resistance or use of amoxicillin in the last 30 days then amoxicillin-clavulanate or another penicillin derivative plus beta lactamase inhibitor is recommended. Taking amoxicillin once a day may be as effective as twice or three times a day. While less than 7 days of antibiotics have fewer side effects, more than seven days appear to be more effective. If there is no improvement after 2–3 days of treatment a change in therapy may be considered. Azithromycin appears to have less side effects than either high dose amoxicillin or amoxicillin/clavulanate. Tympanostomy tube Tympanostomy tubes (also called "grommets") are recommended with three or more episodes of acute otitis media in 6 months or four or more in a year, with at least one episode or more attacks in the preceding 6 months. There is tentative evidence that children with recurrent acute otitis media (AOM) who receive tubes have a modest improvement in the number of further AOM episodes (around one fewer episode at six months and less of an improvement at 12 months following the tubes being inserted). Evidence does not support an effect on long-term hearing or language development. A common complication of having a tympanostomy tube is otorrhea, which is a discharge from the ear. The risk of persistent tympanic membrane perforation after children have grommets inserted may be low. It is still uncertain whether or not grommets are more effective than a course of antibiotics.Oral antibiotics should not be used to treat uncomplicated acute tympanostomy tube otorrhea. They are not sufficient for the bacteria that cause this condition and have side effects including increased risk of opportunistic infection. In contrast, topical antibiotic eardrops are useful. Otitis media with effusion The decision to treat is usually made after a combination of physical exam and laboratory diagnosis, with additional testing including audiometry, tympanogram, temporal bone CT and MRI. Decongestants, glucocorticoids, and topical antibiotics are generally not effective as treatment for non-infectious, or serous, causes of mastoid effusion. Moreover, it is recommended against using antihistamines and decongestants in children with OME. In less severe cases or those without significant hearing impairment, the effusion can resolve spontaneously or with more conservative measures such as autoinflation. In more severe cases, tympanostomy tubes can be inserted, possibly with adjuvant adenoidectomy as it shows a significant benefit as far as the resolution of middle ear effusion in children with OME is concerned. Chronic suppurative otitis media Topical antibiotics are of uncertain benefit as of 2020. Some evidence suggests that topical antibiotics may be useful either alone or with antibiotics by mouth. Antiseptics are of unclear effect. Topical antibiotics (quinolones) are probably better at resolving ear discharge than antiseptics. Alternative medicine Complementary and alternative medicine is not recommended for otitis media with effusion because there is no evidence of benefit. Homeopathic treatments have not been proven to be effective for acute otitis media in a study with children. An osteopathic manipulation technique called the Galbreath technique was evaluated in one randomized controlled clinical trial; one reviewer concluded that it was promising, but a 2010 evidence report found the evidence inconclusive. Outcomes Complications of acute otitis media consists of perforation of the ear drum, infection of the mastoid space behind the ear (mastoiditis), and more rarely intracranial complications can occur, such as bacterial meningitis, brain abscess, or dural sinus thrombosis. It is estimated that each year 21,000 people die due to complications of otitis media. Membrane rupture In severe or untreated cases, the tympanic membrane may perforate, allowing the pus in the middle-ear space to drain into the ear canal. If there is enough, this drainage may be obvious. Even though the perforation of the tympanic membrane suggests a highly painful and traumatic process, it is almost always associated with a dramatic relief of pressure and pain. In a simple case of acute otitis media in an otherwise healthy person, the bodys defenses are likely to resolve the infection and the ear drum nearly always heals. An option for severe acute otitis media in which analgesics are not controlling ear pain is to perform a tympanocentesis, i.e., needle aspiration through the tympanic membrane to relieve the ear pain and to identify the causative organism(s). Hearing loss Children with recurrent episodes of acute otitis media and those with otitis media with effusion or chronic suppurative otitis media have higher risks of developing conductive and sensorineural hearing loss. Globally approximately 141 million people have mild hearing loss due to otitis media (2.1% of the population). This is more common in males (2.3%) than females (1.8%).This hearing loss is mainly due to fluid in the middle ear or rupture of the tympanic membrane. Prolonged duration of otitis media is associated with ossicular complications and, together with persistent tympanic membrane perforation, contributes to the severity of the disease and hearing loss. When a cholesteatoma or granulation tissue is present in the middle ear, the degree of hearing loss and ossicular destruction is even greater.Periods of conductive hearing loss from otitis media may have a detrimental effect on speech development in children. Some studies have linked otitis media to learning problems, attention disorders, and problems with social adaptation. Furthermore, it has been demonstrated that individuals with otitis media have more depression/anxiety-related disorders compared to individuals with normal hearing. Once the infections resolve and hearing thresholds return to normal, childhood otitis media may still cause minor and irreversible damage to the middle ear and cochlea. More research on the importance of screening all children under 4 years old for otitis media with effusion needs to be performed. Epidemiology Acute otitis media is very common in childhood. It is the most common condition for which medical care is provided in children under five years of age in the US. Acute otitis media affects 11% of people each year (709 million cases) with half occurring in those below five years. Chronic suppurative otitis media affects about 5% or 31 million of these cases with 22.6% of cases occurring annually under the age of five years. Otitis media resulted in 2,400 deaths in 2013—down from 4,900 deaths in 1990. Etymology The term otitis media is composed of otitis, Ancient Greek for "inflammation of the ear", and media, Latin for "middle". References External links Neff MJ (June 2004). "AAP, AAFP, AAO-HNS release guideline on diagnosis and management of otitis media with effusion". American Family Physician. 69 (12): 2929–31. PMID 15222658.

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

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

Tafluprost (trade names Taflotan by Santen Pharmaceutical, Zioptan by Merck in the US and Saflutan by Mundipharma in Australia) is a prostaglandin analogue. It is used topically (as eye drops) to control the progression of open-angle glaucoma and in the management of ocular hypertension, alone or in combination with other medication. It reduces intraocular pressure by increasing the outflow of aqueous fluid from the eyes. Adverse effects The most common side effect is conjunctival hyperemia, which occurs in 4 to 20% of patients. Less common side effects include stinging of the eyes, headache, and respiratory infections. Rare side effects are dyspnoea (breathing difficulties), worsening of asthma, and macular oedema. Interactions Nonsteroidal anti-inflammatory drugs (NSAIDs) can either reduce or increase the effect of tafluprost. Timolol eye drops, a common kind of glaucoma medication, does not negatively interact with this drug.No interactions with systemic (for example, oral) drugs are expected because tafluprost does not reach relevant concentrations in the bloodstream. Pharmacology Mechanism of action Tafluprost is a prodrug of the active substance, tafluprost acid, a structural and functional analogue of prostaglandin F2α (PGF2α). Tafluprost acid is a selective agonist at the prostaglandin F receptor, increasing outflow of aqueous fluid from the eyes and thus lowering intraocular pressure.Other PGF2α analogues with the same mechanism include latanoprost and travoprost. Pharmacokinetics Tafluprost, as a lipophilic ester, easily penetrates the cornea and is then activated to the carboxylic acid, tafluprost acid. Onset of action is 2 to 4 hours after application, the maximal effect is reached after 12 hours, and ocular pressure remains lowered for at least 24 hours.Tafluprost acid is inactivated by beta oxidation to 1,2-dinortafluprost acid, 1,2,3,4-tetranortafluprost acid, and its lactone, which are subsequently glucuronidated or hydroxylated. The cytochrome P450 liver enzymes play no role in the metabolism.An analogous pathway (at least up to the tetranor-metabolites) has been found for latanoprost and travoprost. == References ==

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

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

A pinguecula is a common type of conjunctival stromal degeneration in the eye. It appears as an elevated yellow-white plaque in the bulbar conjunctiva near the limbus. Calcification may also seen occasionally. Etiology The exact etiology is unknown, but it may be associated with aging and excessive exposure to UV light. Signs and symptoms It is seen as a yellow-white deposit on the conjunctiva adjacent to the limbus (the junction between the cornea and sclera). (It is to be distinguished clinically from a pterygium, which is a wedge shaped area of fibrosis that may grow onto the cornea.) A pinguecula usually does not cause any symptoms. It is most common in tropical climates and there is a direct correlation with UV exposure. Histologically, there is degeneration of the collagen fibers of the conjunctival stroma with thinning of the overlying epithelium and occasionally calcification. Actinic exposure of the thin conjunctival tissue is thought to cause fibroblasts to produce more elastin fibers, which are more twisted than normal elastin fibers and may lead to the degradation of the collagen fibers. Alternatively, it has been postulated that the sub-epithelial collagen fibers undergo degradation and assume the qualities of elastic tissue while fragmenting and twisting in a different configuration from their normal state.It is thought that the high reflectivity of the solid white scleral tissue underlying the conjunctival tissue may result in additional UV exposure to the back side of the tissue. The side of the nose also reflects sunlight on to the conjunctiva. As a result, pingueculae tend to occur more often on the nasal side of the eye. While most pingueculae are found in people over the age of 40, they are not uncommon in 20- and 30-year-old adults who spend significant time in the sun. The surface of the conjunctival tissue overlying a pinguecula interferes with the normal spreading of the tear film. The tear ferning test reveals abnormalities of the mucous component of the tear film, making it useful as a predictor of a persons tolerance of hydrophilic soft contact lenses. Contact lens intolerance can also result from the elevation of the peripheral edge of the contact lens if it overlies a pinguecula. The plural form of pinguecula is pingueculae. Pinguecula is derived from the Latin word "pinguis" for fat or grease. Associated conditions A pinguecula is one of the differential diagnoses for a limbal nodule. It may have an increased prevalence in Gauchers disease. Diagnosis Diagnosis of pinguecula is usually done by an eye care professional during routine eye examination using slit lamp. Conjunctival biopsy may be advised if malignancy is suspected. Treatment Pingueculae may enlarge slowly over time, but are a benign condition, usually requiring no treatment. Artificial tears may help to relieve discomfort, if it occurs. If cosmesis is a concern, or if there is discomfort in contact lens use, surgical excision may be done. Occasionally, a pinguecula may become inflamed, a condition called pingueculitis. The cause of pingueculitis is unknown and there are no known infectious agents associated with it. If an inflamed pinguecula is causing discomfort or cosmetic concerns, it may be treated with short course of topical steroid. Laser photocoagulation may also be used to remove pinguecula. See also Peripheral light focusing Pterygium (conjunctiva) References == External links ==

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

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

Early in the history of medicine, it was recognized that severe mental illness sometimes started abruptly in the days after childbirth, later known as postpartum psychosis or puerperal psychosis. Gradually, it became clear that this was not a single and unique phenomenon, but a group of at least twenty distinct disorders.Psychosis implies the presence of manic symptoms, stupor or catatonia, perplexity, confusion, disorders of the will and self, delusions and/or hallucinations. Psychiatric disorders that lack these symptoms are excluded; depression, however severe, is not included, unless there are psychotic features. Of this group of psychoses, postpartum bipolar disorder is overwhelmingly the most common in high-income nations. Postpartum bipolar disorder Signs and symptoms Almost every symptom known to psychiatry occurs in these mothers – every kind of delusion including the rare delusional parasitosis, delusional misidentification syndrome, Cotard delusion, erotomania, the changeling delusion, denial of pregnancy or birth, command hallucinations, disorders of the will and self, catalepsy and other symptoms of catatonia, self-mutilation and all the severe disturbances of mood. In addition, literature from the 18th century also describes symptoms not generally recognized, such as rhyming speech, enhanced intellect, and enhanced perception.As for collections of symptoms (syndromes), about 40% have puerperal mania, with increased vitality and sociability, reduced need for sleep, rapid thinking and pressured speech, euphoria and irritability, loss of inhibition, violence, recklessness and grandiosity (including religious and expansive delusions); puerperal mania is considered to be particularly severe, with highly disorganized speech, extreme excitement and eroticism.Another 25% have an acute polymorphic (cycloid) syndrome. This is a changing clinical state, with transient delusions, fragments of other syndromes, extreme fear or ecstasy, perplexity, confusion, and motility disturbances. In the past, some experts regarded this as pathognomonic (specific) for puerperal psychosis, but this syndrome is found in other settings, not just the reproductive process, and in men. These psychoses are placed in the World Health Organizations ICD-10 under the rubric of acute and transient psychotic disorders. In general psychiatry, manic and cycloid syndromes are regarded as distinct, but, studied long-term among childbearing women, the bipolar and cycloid variants are intermingled in a bewildering variety of combinations, and, in this context, it seems best to regard them as members of the same bipolar/cycloid group. Together, the manic and cycloid variants make up about two thirds of childbearing psychoses. Diagnosis Postpartum bipolar disorders must be distinguished from a long list of organic psychoses that can present in the puerperium, and from other non-organic psychoses; both of these groups are described below. It is also necessary to distinguish them from other psychiatric disorders associated with childbirth, such as anxiety disorders, depression, post-traumatic stress disorder, complaining disorders and bonding disorders (emotional rejection of the infant), which occasionally cause diagnostic difficulties. Clinical assessment requires obtaining the history from the mother herself and, because she is often severely ill, lacking in insight and unable to give a clear account of events, from at least one close relative. A social work report and, in mothers admitted to hospital, nursing observations are information sources of great value. A physical examination and laboratory investigations may disclose somatic illness complicating the obstetric events, which sometimes provokes psychosis. It is important to obtain the case records of previous episodes of mental illness, and, in patients with multiple episodes, to construct a summary of the whole course of her psychiatric history in relation to her life. In the 10th edition of the International Classification of Diseases, published in 1992, the recommendation is to classify these cases by the form of the illness, without highlighting the postpartum state. There is, however, a category F53.1, entitled severe mental and behavioural disorders associated with the puerperium, which can be used when it is not possible to diagnose some variety of affective disorder or schizophrenia. The American Psychiatric Associations Diagnostic and Statistical Manual, whose 5th edition was published in May 2013, allows the use of a peripartum onset specifier in episodes of mania, hypomania or major depression if the symptoms occur during pregnancy or the first four weeks of the puerperium. The failure to recognize postpartum psychosis, and its complexity, is unhelpful to clinicians, epidemiologists, and other researchers. Onset groups Postpartum bipolar disease belongs to the bipolar spectrum, whose disorders exist in two contrasting forms – mania and depression. They are highly heritable, and affected individuals (less than 1% of the population ) have a lifelong tendency (diathesis) to develop psychotic episodes in certain circumstances. The triggers include a number of pharmaceutical agents, surgical operations, adrenal corticosteroids, seasonal changes, menstruation and childbearing. Research into puerperal mania is, therefore, not the study of a disease-in-its-own right, but an investigation into the childbearing triggers of bipolar disorder. Psychoses triggered in the first two weeks after the birth – between the first postpartum day (or even during parturition until about the 15th day – complicate approximately 1/1,000 pregnancies. The impression is sometimes given that this is the only trigger associated with childbearing. But there is evidence of four other triggers – late postpartum, prepartum, post-abortion and weaning. Marcé, widely considered an authority on puerperal psychoses, claimed that they could be divided into early and late forms; the late form begins about six weeks after childbirth, associated with the return of the menses. His view is supported by the large number of cases in the literature with onset 4–13 weeks after the birth, mothers with serial 4-13 week onsets and some survey evidence. The evidence for a trigger acting in pregnancy is also based on the large number of reported cases, and particularly on the frequency of mothers experiencing two or more prepartum episodes. There is evidence, especially from surveys, of bipolar episodes triggered by abortion (miscarriage or termination). The evidence for a weaning trigger rests on 32 cases in the literature, of which 14 were recurrent. The relative frequency of these five triggers is given by the number of cases in the literature – just over half early postpartum onset, 20% each late postpartum and prepartum onset, and the rest post-abortion and weaning onset. In addition, episodes starting after childbirth may be triggered by adrenal corticosteroids, surgical operations (such as Caesarean section) or bromocriptine as an alternative to, or in addition to, the postpartum trigger. Course of the illness With modern treatment, a full recovery can be expected within 6–10 weeks. After recovery from the psychosis, some mothers have depression, which can last for weeks or months. About one third have a relapse, with a return of psychotic symptoms a few weeks after recovery; these relapses are not due to a failure to comply with medication, because they were often described before pharmaceutical treatment was discovered. A minority have a series of periodic relapses related to the menstrual cycle. Complete recovery, with a resumption of normal life and a normal mother-infant relationship is the rule.Many of these mothers experience other bipolar episodes, on the average about one every six years. Although suicide is almost unknown in an acute puerperal manic or cycloid episode, depressive episodes later in life carry an increased risk, and it is wise for mothers to maintain contact with psychiatric services in the long term. In the event of a further pregnancy, the recurrence rate is high – in the largest series, about three quarters had a recurrence, but not always in the early puerperium; the recurrence could occur during pregnancy, or later in the postpartum period. This suggests a link between early onset and other onset groups. Management, treatment and prevention Pre-conception counselling It is known that women with a personal or family history of puerperal psychosis or bipolar disorder are at risk of a puerperal episode. The highest risk of all (82%) is a combination of a previous postpartum episode and at least one earlier non-puerperal episode. There is a need to counsel women at high risk before they embark on pregnancy, especially those on prophylactic treatment. The issues include the teratogenic risk, the frequency of recurrence and the risks and benefit of various treatments during pregnancy and breast-feeding; a personal analysis should be made for each individual, and is best shared with close family members. The teratogenic risks of antipsychotic agents are small, but are higher with lithium and anti-convulsant agents. Carbamazepine, when taken in early pregnancy, has some teratogenic effects, but valproate is associated with spina bifida and other major malformations, and a foetal valproate syndrome; it is contra-indicated in women who may become pregnant. Given late in pregnancy, antipsychotic agents and lithium can have adverse effects on the infant. Stopping mood-stabilisers has a high risk of recurrence during pregnancy. Pre-birth planning If a woman at high risk becomes pregnant, it is essential to convene a planning meeting. This is urgent because the diagnosis of pregnancy may be late, and the birth may be premature. The meeting should be attended by primary care, obstetric and psychiatric staff, together (if possible) with the expectant mother and her family and (if appropriate) a social worker. There are many issues – pharmaceutical treatment, antenatal care, early signs of a recurrence, the management of the puerperium, and the care and safety of the infant. It is important that the psychiatric team is notified as soon as the infant is born. Home treatment and hospitalization It has been recognized since the 19th century that it is optimal for a woman with puerperal psychosis to be treated at home, where she can maintain her role as homemaker and mother to her other children, and develop her relationship with the new-born. But there are many risks, and it is essential that she is monitored by a competent adult round the clock, and visited frequently by professional staff. Home treatment is a counsel of perfection and most women will be admitted to a psychiatric hospital, many as an emergency, and usually without their babies. In a few countries, especially Australia, Belgium, France, India, the Netherlands, Switzerland and the United Kingdom, special units allow the admission of both woman and infant. Conjoint admission has many advantages, but the risks to the infant of admission to a ward full of severely ill mothers should not be understated, and the high ratio of nursing staff, required to safeguard the infants, make these among the most expensive psychiatric units. Treatment of the acute episode These mothers require sedation with anti-psychotic (neuroleptic) agents, but are liable to extrapyramidal symptoms, including the neuroleptic malignant syndrome. Since the link with bipolar disorder was recognized (about 1970), treatment with mood-stabilizing agents, such as lithium and anti-convulsant drugs, has been employed with success. Electroconvulsive therapy has the reputation of efficacy in this disorder, and it can be given during pregnancy (avoiding the risk of pharmaceutical treatment), with due precautions. But there have been no trials, and Dutch experience has shown that almost all mothers recover quickly without it. After recovery the mother may need antidepressant treatment and/or prophylactic mood stabilizers; she will need counselling about the risk of recurrence and will often appreciate psychotherapeutic support. Prevention There is much evidence that lithium can at least partly prevent episodes in mothers at high risk. It is dangerous during parturition, when pressure in the pelvis can obstruct the ureters and raise blood levels. Started after the birth its adverse effects are minimal, even in breast-fed infants. Causes The cause of postpartum bipolar disorder breaks down into two parts – the nature of the brain anomalies that predispose to manic and depressive symptoms, and the triggers that provoke these symptoms in those with the bipolar diathesis. The genetic, anatomical and neurochemical basis of bipolar disorder is at present unknown, and is one of the most important projects in psychiatry; but is not the main concern here. The challenge and opportunity presented by the childbearing psychoses is to identify the triggers of early postpartum onset and other onset groups. Considering that these psychoses have been known for centuries, little effort has so far been made to understand the underlying biology. Research has lagged far behind other areas of medicine and psychiatry. There is a dearth of knowledge and of theories. There is a much evidence of heritability, both from family studies and molecular genetics. Early onset cases occur more frequently in first time mothers, but this is not true of late postpartum or pregnancy onset. There are not many other predictors. Sleep deprivation has been suggested. Inhibition of steroid sulphatase caused behavioural abnormalities in mice. A recent hypothesis, supported by collateral studies, invokes the re-awakening of auto-immunity after its suppression during pregnancy, on the model of multiple sclerosis or autoimmune thyroiditis; a related hypothesis has proposed that abnormal immune system processes (regulatory T cell biology) and consequent changes in myelinogenesis may increase postpartum psychosis risk. Aberrant steroid hormone–dependent regulation of neuronal calcium influx via extracellular matrix proteins and membrane receptors involved in responding to the cells microenvironment might be important in conferring biological risk. Another promising lead is based on the similarity of bipolar-cycloid puerperal and menstrual psychosis; many women have had both. Late-onset puerperal psychoses, and relapses may be linked to menstruation. Since almost all reproductive onsets occur when the menstrual cycle is released from a long period of inhibition, this may be a common factor, but it can hardly explain episodes starting in the 2nd and 3rd trimesters of pregnancy. History Between the 16th and 18th centuries about 50 brief reports were published; among them is the observation that these psychoses could recur, and that they occur both in breast-feeding and non-lactating women. In 1797, Osiander, an obstetrician from Tübingen, reported two cases at length – masterly descriptions which are among the treasures of medical literature. In 1819, Esquirol conducted a survey of cases admitted to the Salpêtrière, and pioneered long-term studies. From that time, puerperal psychosis became widely known to the medical profession. In the next 200 years over 2,500 theses, articles and books were published. Among the outstanding contributions were Delays unique investigation using serial curettage and Kendells record-linkage study comparing 8 trimesters before and 8 trimesters after the birth. In the last few years, two monographs reviewed over 2,400 works, with more than 4,000 cases of childbearing psychoses from the literature and a personal series of more than 320 cases. Research directions The lack of a formal diagnosis in the DSM and ICD has hindered research. Research is needed to improve the care and treatment of affected mothers, but it is of paramount importance to investigate the causes, because this can lead to long term control and elimination of the disease. The opportunities come under the heading of clinical observation, the study of the acute episode, long-term studies, epidemiology, genetics and neuroscience. In a disorder with a strong genetic element and links to the reproductive process, costly imaging, molecular-genetic and neuroendocrinological investigations will be decisive. These depend on expert laboratory methods. It is important that the clinical study is also state-of-the-art– that scientists understand the complexity of these psychoses, and the need for multiple and reliable information sources to establish the diagnosis. Other non-organic postpartum psychoses It is much less common to encounter other acute psychoses in the puerperium. Psychogenic psychosis This is the name given to a psychosis whose theme, onset and course are all related to an extremely stressful event. The psychotic symptom is usually a delusion. Over 50 cases have been described, but usually in unusual circumstances, such as abortion or adoption, or in fathers at the time of the birth of one of their children. They are occasionally seen after normal childbirth. Paranoid and schizophrenic psychoses These are so uncommon in the puerperium that it seems reasonable to regard them as sporadic events, not puerperal complications. Early postpartum stupor Brief states of stupor have rarely been described in the first few hours or days after the birth. They are similar to parturient delirium and stupor, which are among the psychiatric disorders of childbirth. Organic postpartum psychoses There are at least a dozen organic (neuropsychiatric) psychoses that can present in pregnancy or soon after childbirth. The clinical picture is usually delirium – a global disturbance of cognition, affecting consciousness, attention, comprehension, perception and memory – but amnesic syndromes and a mania-like state also occur. The two most recent were described in 1980 and 2010, and it is quite likely that others will be described. Organic psychoses, especially those due to infection, may be more common in nations with high parturient morbidity. Infective delirium The most common organic postpartum psychosis is infective delirium. This was mentioned by Hippocrates: there are 8 cases of puerperal or post-abortion sepsis among the 17 women in the 1st and 3rd books of epidemics, all complicated by delirium. In Europe and North America the foundation of the metropolitan maternity hospitals, together with instrumental deliveries and the practice of attending necropsies, led to epidemics of streptococcal puerperal fever, resulting in maternal mortality rates up to 10%. The peak was about 1870, after which antisepsis and asepsis gradually brought them under control. These severe infections were often complicated by delirium, but it was not until the nosological advances of Chaslin and Bonhöffer that they could be distinguished from other causes of postpartum psychosis. Infective delirium hardly ever starts during pregnancy, and usually begins in the first postpartum week. The onset of sepsis and delirium are closely related, and the course parallels the infection, although about 20% of patients continue to have chronic confusional states after recovery from the infection. Recurrences after another pregnancy are rare. Their frequency began to decline at the end of the 19th century, and fell steeply after the discovery of the sulphonamides. Puerperal sepsis is still common in Bangladesh, Nigeria and Zambia. Even in the United Kingdom, cases are still occasionally seen. It would be a mistake to forget this cause of puerperal psychosis. Eclamptic and Donkin psychoses Eclampsia is the sudden eruption of convulsions in a pregnant woman, usually around the time of delivery. It is the late complication of pre-eclamptic toxaemia (gestosis). Although its frequency in nations with excellent obstetric services has fallen below 1/500 pregnancies, it is still common in many other countries. The primary pathology is in the placenta, which secretes an anti-angiogenic factor in response to ischaemia, leading to endothelial dysfunction. In fatal cases, there are arterial lesions in many organs including the brain. This is the second most frequent organic psychosis, and the second to be described. Psychoses occur in about 5% of cases, and about 240 detailed cases have been reported. It particularly affects first time mothers. Seizures may begin before, during or after labour, but the onset of psychosis is almost always postpartum. These mothers usually experience delirium but some have manic features. The duration is remarkably short, with a median duration of 8 days. This, together with the absence of a family history and of recurrences, contrasts with puerperal bipolar/cycloid psychoses. After recovery, amnesia and sometimes retrograde memory loss may occur, as well as other permanent cerebral lesions such as dysphasia, hemiplegia or blindness. A variant was described by Donkin . He had been trained by Simpson (one of those who first recognized the importance of albuminuria) in Edinburgh, and recognized that some cases of eclamptic psychosis occurred without seizures; this explains the interval between seizures (or coma) and psychosis, a gap that has occasionally exceeded 4 days: seizures and psychosis are two different consequences of severe gestosis. Donkin psychosis may not be rare: a British series included 13 possible cases; but clarifying its distinction from postpartum bipolar disorder requires prospective investigations in collaboration with obstetricians. Wernicke-Korsakoff psychosis This was described by Wernicke and Korsakoff. The pathology is damage to the core of the brain including the thalamus and mamillary bodies. Its most striking clinical feature is loss of memory, which can be permanent. It is usually found in severe alcoholics, but can also result from pernicious vomiting of pregnancy (hyperemesis gravidarum), because the requirement for thiamine is much increased in pregnancy; nearly 200 cases have been reported. The cause is vitamin B1 (thiamine) deficiency. This has been available for treatment and prevention since 1936, so the occurrence of this syndrome in pregnancy should be extinct. But these cases continue to be reported – more than 50 in this century – from all over the world, including some from countries with advanced medical services; most are due to rehydration without vitamin supplements. A pregnant woman who presents in a dehydrated state due to pernicious vomiting urgently needs thiamine, as well as intravenous fluids. Vascular disorders Various vascular disorders occasionally cause psychosis, especially cerebral venous thrombosis. Puerperal women are liable to thrombosis, especially thrombophlebitis of the leg and pelvic veins; aseptic thrombi can also form in the dural venous sinuses and the cerebral veins draining into them. Most patients present with headache, vomiting, seizures and focal signs such as hemiplegia or dysphasia, but a minority of cases have a psychiatric presentation. The incidence is about 1 in 1,000 births in Europe and North America, but much higher in India, where large series have been collected. Psychosis is occasionally associated with other arterial or venous lesions: epidural anaesthesia can, if the dura is punctured, lead to leakage of cerebrospinal fluid and subdural haematoma. Arterial occlusion may be due to thrombi, amniotic fragments or air embolism. Postpartum cerebral angiopathy is a transitory arterial spasm of medium caliber cerebral arteries; it was first described in cocaine and amphetamine addicts, but can also complicate ergot and bromocriptine prescribed to inhibit lactation. Subarachnoid haemorrhage can occur after miscarriage or childbirth. All these usually present with neurological symptoms, and occasionally with delirium. Epilepsy Women with a lifelong epileptic history are liable to psychoses during pregnancy, labour and the puerperium. Women occasionally develop epilepsy for the first time in relation to their first pregnancy, and psychotic episodes have been described. There are over 30 cases in the literature. Hypopituitarism Pituitary necrosis following postpartum haemorrhage (Sheehans syndrome) leads to failure and atrophy of the gonads, adrenal and thyroid. Chronic psychoses can supervene many years later, based on myxoedema, hypoglycaemia or Addisonian crisis. But these patients can also develop acute and recurrent psychoses, even as early as the puerperium. Water intoxication Hyponatraemia (which leads to delirium) can complicate oxytocin treatment, usually when given to induce an abortion. By 1975, 29 cases had been reported, of which three were severe or fatal. Urea cycle disorders Inborn errors of the Krebs-Henseleit urea cycle lead to hyperammonaemia. In carriers and heterozygotes, encephalopathy can develop in pregnancy or the puerperium. Cases have been described in carbamoyl phosphate synthetase 1, argino-succinate synthetase and ornithine carbamoyltransferase deficiency. Anti-NMDA receptor encephalitis The most recent form of organic childbearing psychosis to be described is encephalitis associated with antibodies to the NMDA receptor; these women often have ovarian teratomas. A Japanese review found ten reported during pregnancy and five after delivery. Other organic psychoses with a specific link to childbearing Sydenhams chorea, of which chorea gravidarum is a severe variant, has a number of psychiatric complications, which include psychosis. This usually develops during pregnancy, and occasionally after the birth or abortion. Its symptoms include severe hypnagogic hallucinations (hypnagogia), possibly the result of the extreme sleep disorder. This form of chorea was caused by streptococcal infections, which at present respond to antibiotics; it still occurs as a result of systemic lupus or anti-phospholipid syndromes. Only about 50 chorea psychoses have been reported, and only one this century; but it could return if the streptococcus escapes control. Alcohol withdrawal states (delirium tremens) occur in addicts whose intake has been interrupted by trauma or surgery; this can happen after childbirth. Postpartum confusional states have also been reported during withdrawal from opium and barbiturates. One would expect acquired immunodeficiency syndrome (HIV/AIDS) encephalitis to present in pregnancy or the puerperium, because it is a venereal disease that can progress rapidly; one case of AIDS encephalitis, presenting in the 28th week of gestation, has been reported from Haiti, and there may be others in countries where AIDS is rife. Anaemia is common in pregnancy and the puerperium, and folate deficiency has been linked to psychosis. Incidental organic psychoses The psychoses, mentioned above, all had a recognized connection with childbearing. But medical disorders with no specific link have presented with psychotic symptoms in the puerperium; in them the association seems to be fortuitous. They include neurosyphilis, encephalitis including von Economos, meningitis, cerebral tumours, thyroid disease and ischaemic heart disease. Society and culture Support In the UK, a series of workshops called "Unravelling Eve" were held in 2011, where women who had experienced postpartum depression shared their stories. Notable cases in history and fiction Harriet Sarah, Lady Mordaunt (1848–1906), formerly Harriet Moncreiffe, was the Scottish wife of an English baronet and Member of Parliament, Sir Charles Mordaunt. She was the defendant in a sensational divorce case in which the Prince of Wales (later King Edward VII) was embroiled; after a controversial trial lasting seven days, the jury determined that Lady Mordaunt had "puerperal mania" and her husbands petition for divorce was dismissed, while Lady Mordaunt was committed to an asylum.Andrea Yates had depression and, four months after the birth of her fifth child, relapsed, with psychotic features. Several weeks later she drowned all five children. Under the law in Texas, she was sentenced to life imprisonment, but, after a retrial, was committed to a mental hospital. Guy de Maupassant, in his novel Mont-Oriol (1887) described a brief postpartum psychotic episode. Charlotte Perkins Gilman, in her short story The Yellow Wallpaper (1892) described severe depression with psychotic features starting after childbirth, perhaps similar to that experienced by the author herself. Stacey Slater, a fictional character in the long-running BBC soap-opera EastEnders had postpartum psychosis in 2016, and was one of the shows biggest storylines that year. Legal status Postpartum psychosis, especially when there is a marked component of depression, has a small risk of filicide. In acute manic or cycloid cases, this risk is about 1%. Most of these incidents have occurred before the mother came under treatment, and some have been accidental. Several nations including Canada, United Kingdom, Australia, and Italy recognize postpartum mental illness as a mitigating factor in cases where mothers kill their children. In the United States, such a legal distinction was not made as of 2009, and an insanity defense is not available in all states.The United Kingdom has had the Infanticide Act since 1922. Books written about postpartum psychosis and postpartum bipolar disorder Apart from the two monographs mentioned in the text (references 1 and 86), the following books have been published about these psychoses: Ripping, Dr (1877) Die Geistesstörungen der Schwangeren, Wöchnerinnen und Säugenden. Stuttgart, Enke. Knauer O (1897) Über Puerperale Psychose für practische Ärzte. Berlin, Karger. Twomey T (2009) Understanding Postpartum Psychosis: A Temporary Madness. Westport, Praeger. Harwood D (2017) Birth of a New Brain - Healing from Postpartum Bipolar Disorder. Brentwood, Post Hill Press. References == External links ==

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

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

Podoconiosis, also known as nonfilarial elephantiasis, is a disease of the lymphatic vessels of the lower extremities that is caused by chronic exposure to irritant soils. It is the second most common cause of tropical lymphedema after lymphatic filariasis, and it is characterized by prominent swelling of the lower extremities, which leads to disfigurement and disability. Methods of prevention include wearing shoes and using floor coverings. Mainstays of treatment include daily foot hygiene, compression bandaging, and when warranted, surgery of overlying nodules. Signs and symptoms Podoconiosis causes bilateral yet asymmetrical leg swelling with overlying firm nodules. Early on, symptoms may include itching, tingling, widening of the forefoot, and swelling which then progress to soft edema, skin fibrosis, papillomatosis, and nodule formation resembling moss, giving rise to the diseases alternate name of "mossy foot" in some regions of the world. As with other forms of tropical lymphedema, chronic disease can lead to rigid toes, ulceration, and bacterial superinfection. During acute episodes of adenolymphangitis, patients may develops fevers, extremity warmth, redness, and pain. These episodes are extremely debilitating and account for many days of activity and productivity loss each year. Psychological consequences As a result of its appearance, podoconiosis can cause social stigmatization and discrimination. People with podoconiosis also report a lower quality of life than people in similar neighborhood circumstances except without podoconiosis and also higher levels of mental distress and depression. Pathophysiology According to the World Health Organization "Evidence suggests that podoconiosis is the result of a genetically determined abnormal inflammatory reaction to mineral particles in irritant red clay soils derived from volcanic deposits".The pathophysiology of podoconiosis is a combination of genetic susceptibility, possibly through associations with HLA-DQA1, HLA-DQB1, and HLA-DRB1 variants, and a cumulative exposure to irritant soil. In susceptible individuals, irritant soil particles penetrate the feet and collect in lymphatic vessels. Over time, chronic inflammation within the lymphatic vessels leads to fibrosis and occlusion. Diagnosis Differential diagnosis The differential diagnosis for podoconiosis includes other causes of tropical lymphedema, such as filariasis or leprosy, and mycetoma pedis.While filariasis is generally unilateral, podoconiosis affects the legs bilaterally albeit asymmetrically and in an ascending manner. Podoconiosis very rarely affects the groin while filariasis frequently involves the groin: a high ratio of lymphoedema/hydrocele cases in an area suggests podoconiosis as the dominant cause of lymphedema. In some cases, the history and clinical presentation alone are unable to differentiate between the two causes of tropical lymphedema. Local epidemiology can also be a clue to diagnosis, as podoconiosis is typically found in higher altitude areas with volcanic soils while filariasis is common in low-lying areas where mosquitos are prevalent. Blood smears for identification of microfilariae and antigen detection techniques can be helpful in the diagnosis of lymphatic filariasis.Lepromatous lymphedema can also mimic podoconiosis clinically, but the former will have loss of sensation in the toes and feet, thickened nerves, and trophic ulcers. Other causes of lymphedema include Kaposi sarcoma, mycetoma, and elephantiasis nostras verrucosa. Prevention Elimination of podoconiosis relies on prevention with widespread shoe implementation, stringent foot hygiene, and floor coverings. Community-based initiatives are crucial to achieving elimination of this disease. In Ethiopia, The Mossy Foot Treatment and Prevention Association (now Mossy Foot International) works to transform patients into community podoconiosis agents who in turn visit patients, teach basic treatment techniques such as foot hygiene, and educate families about the disease. This model has been adapted by several other non-government groups as they have started programs in other regions of Ethiopia. Treatment The cornerstone of prevention and treatment of podoconiosis is avoidance of exposure to irritant soils. Wearing shoes in the presence of irritant soils is the primary method of exposure reduction. In Rwanda, a country of high disease prevalence, the government has banned walking barefoot in public, in order to prevent podoconiosis and other soil-borne diseases. Increasing the availability of footwear must be coupled with education on the benefits of wearing shoes as cultural influences, such as barefoot traditions, can hinder widespread use of footwear.Once the disease has developed, rigorous foot hygiene including daily washing with soap and water, application of an emollient, and nightly elevation of the affected extremity has been shown to reduce frequency of acute attacks. Nodules will not resolve with these conservative measures, although surgical removal of the nodules can be performed. Epidemiology Podoconiosis is most frequently seen in the highland areas of Africa, India, and Central America. The highest prevalence is seen in Uganda, Tanzania, Kenya, Rwanda, Burundi, Sudan, and Ethiopia. A recent review has summarized the global distribution of podoconiosis. In some areas of Ethiopia, the prevalence is as high as 4%. The incidence of podoconiosis increases with age, likely due to cumulative exposure to irritant soil. It is very rare to see podoconiosis in the 0–5 year old age group, and the incidence rapidly rises from 6 to 20 years of age, with the highest prevalence after 45 years of age. Podoconiosis is most commonly seen in higher altitude areas with volcanic soil, and it is estimated to affect 4 million people worldwide. Productivity losses associated with the disease are significant. In Ethiopia (where 1.6 million people are estimated to be affected), the condition is thought to have caused US $200 million in lost productivity per year in 2004. History After parasitic filariae were discovered to be an important cause of tropical lymphedema in the 19th century, early investigators assumed that filariae were the sole cause of lymphedema in the tropics. It was later discovered that the distribution of tropical lymphedema and filariasis did not perfectly overlap, and researchers began to recognize that some forms of tropical lymphedema were not associated with filariasis. Ernest W Price, a British surgeon living in Ethiopia, discovered the true etiology of podoconiosis in the 1970s and 1980s by studying the lymph nodes and vessels of those afflicted with the disease. Using light microscopy, he observed macrophage cells laden with micro-particles in lymph nodes of the affected extremity. After examining the same tissue using electron microscopy, he was able to identify the presence of silicon, aluminum, and other soil metals both in the phagosomes of macrophages and adhered to the surface of lymphocytes. Price demonstrated that the lymphatic vessels of these patients experienced subendothelial edema and eventual collagenization of the lumen leading to complete blockage. He wrote a monograph on podoconiosis which was published after his death in 1990. Current situation Podoconiosis is now recognised as one of the WHO Neglected Tropical Diseases, its importance as a public health problem is well recognised in Ethiopia. Footwork is a charity which bring together public and private partners to support prevention and treatment of podoconiosis. There is an active research group led by Gail Davey at the Wellcome Trust Brighton and Sussex Centre for Global Health Research which co-ordinates research worldwide. A recent article in The Lancet includes some excellent illustrations. References External links World Health Organization section on podoconiosis

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

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

Glucarpidase (Voraxaze) is a medication used for the treatment of elevated levels of methotrexate (defined as 1 micromol/L) during treatment of cancer patients who have impaired kidney function (and thus cannot reduce the drug to safe levels sufficiently after the drug has been given). Glucarpidase is an enzyme that inactivates methotrexate rapidly after injection. Because this agent reduces systemic levels of methotrexate and could therefore interfere with efficacy, it is not recommended for use in patients with normal or only slightly impaired kidney function or in whom serum levels are normal. The main antidote for methotrexate overdoses prior to the approval of this drug were high doses of folinic acid. However, this agent was not always sufficient at preventing kidney failure due to methotrexate. Glucarpidase also degrades folinic acid so the two should not be used together (within two hours of one another). Glucarpidase, a recombinant form of the bacterial enzyme carboxypeptidase G2 converts methotrexate into glutamate and 2,4-diamino-N(10)-methylpteroic acid. These are generally much less toxic and are excreted largely by the liver. One case series in children has found that high-dose methotrexate therapy can be resumed after an instance of methotrexate-induced acute kidney injury successfully treated with glucarpidase.Adverse effects include mild and include numbness, tingling, flushing, nausea, vomiting, itching, and headache. Society and culture Legal status In November 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Voraxaze, intended to reduce toxic plasma methotrexate concentration. The applicant for this medicinal product is SERB SAS. Glucarpidase was approved for medical use in the European Union in January 2022. References External links "Glucarpidase". Drug Information Portal. U.S. National Library of Medicine.

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

What does the medical term 'Follicular thyroid cancer' encompass?

Follicular thyroid cancer accounts for 15% of thyroid cancer and occurs more commonly in women over 50 years of age. Thyroglobulin (Tg) can be used as a tumor marker for well-differentiated follicular thyroid cancer. Thyroid follicular cells are the thyroid cells responsible for the production and secretion of thyroid hormones. Cause Associated mutations Approximately one-half of follicular thyroid carcinomas have mutations in the Ras subfamily of oncogenes, most notably HRAS, NRAS, and KRAS. Mutations in MINPP1 have likewise been observed, as well as germline PTEN gene mutations responsible for Cowden syndrome of which follicular thyroid cancer is a feature. Also, a chromosomal translocation specific for follicular thyroid carcinomas is one between paired box gene 8 (PAX-8), a gene important in thyroid development, and the gene encoding peroxisome proliferator-activated receptor γ 1 (PPARγ1), a nuclear hormone receptor contributing to terminal differentiation of cells. The PAX8-PPARγ1 fusion is present in approximately one-third of follicular thyroid carcinomas, specifically those cancers with a t(2;3)(q13;p25) translocation, permitting juxtaposition of portions of both genes. Tumors tend carry either a RAS mutation or a PAX8-PPARγ1 fusion, and only rarely are both genetic abnormalities present in the same case. Thus, follicular thyroid carcinomas seem to arise by two distinct and virtually nonoverlapping molecular pathways. Hurthle cell variant Hurthle cell thyroid cancer is often considered a variant of follicular cell carcinoma. Hurthle cell forms are more likely than follicular carcinomas to be bilateral and multifocal and to metastasize to lymph nodes. Like follicular carcinoma, unilateral hemithyroidectomy is performed for non-invasive disease, and total thyroidectomy for invasive disease. Diagnosis It is difficult to correctly diagnose follicular neoplasms (FNs) on fine-needle aspiration cytology (FNAC) because it shares many cytological features with other mimicking lesions. Classification It is impossible to distinguish between follicular adenoma and carcinoma on cytological grounds. If fine needle aspiration cytology (FNAC) suggests follicular neoplasm, thyroid lobectomy should be performed to establish the histopathological diagnosis. Features sine qua non for the diagnosis of follicular carcinoma are capsular invasion and vascular invasion by tumor cells. Still, focuses of the capsular invasion should be carefully evaluated and discriminated from the capsular rupture due to FNA penetration resulting in WHAFFT (worrisome histologic alterations following FNA of thyroid). Follicular carcinoma tends to metastasize to lung and bone via the bloodstream. Papillary thyroid carcinoma commonly metastasizes to cervical lymph nodes.HMGA2 has been proposed as a marker to identify malignant tumors. Treatment Treatment is usually surgical, followed by radioiodine. Initial treatment If follicular cells are found on cytological testing, it is common to carry out hemithyroidectomy to distinguish between follicular adenoma and follicular carcinoma on histopathological examination, proceeding to completion thyroidectomy and postoperative radioiodine ablation where carcinoma is confirmed. This way total thyroidectomy is not carried out unnecessarily. Thyroidectomy is invariably followed by radioiodine treatment at levels from 50 to 200 millicuries following two weeks of a low iodine diet (LID). Occasionally treatment must be repeated if annual scans indicate remaining cancerous tissue. Some physicians favor administering the maximum safe dose (calculated based on a number of factors), while others favor administering smaller doses, which may still be effective in ablating all thyroid tissue. I-131 is used for ablation of the thyroid tissue. Minimally invasive thyroidectomy has been used in recent years in cases where the nodules are small. Finding disease recurrence Some studies have shown that thyroglobulin (Tg) testing combined with neck ultrasound is more productive in finding disease recurrence than full- or whole-body scans (WBS) using radioactive iodine. However, current protocol (in the USA) suggests a small number of clean annual WBS are required before relying on Tg testing plus neck ultrasound. When needed, whole body scans consist of withdrawal from thyroxine medication and/or injection of recombinant human Thyroid stimulating hormone (TSH). In both cases, a low iodine diet regimen must also be followed to optimize the takeup of the radioactive iodine dose. Low dose radioiodine of a few millicuries is administered. Full body nuclear medicine scan follows using a gamma camera. Scan doses of radioactive iodine may be I131 or I123. Recombinant human TSH, commercial name Thyrogen, is produced in cell culture from genetically engineered hamster cells. Prognosis The overall 5-year survival rate for follicular thyroid cancer is 91%, and the 10-year survival rate is 85%.By overall cancer staging into stages I to IV, follicular thyroid cancer has a 5-year survival rate of 100% for stages I and II, 71% for stage III, and 50% for stage IV.Compared to other variants of Follicular cell derived thyroid cancer, bone metastases are commonly associated with follicular carcinoma. In the present study a high rate of bone metastases of 34% was observed. References External links Thyroid cancer at DMOZ Archived 2017-03-14 at the Wayback Machine Cancer Management Handbook: Thyroid and Parathyroid Cancers Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer The American Thyroid Association Guidelines Taskforce (2015).

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

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

CADASIL or CADASIL syndrome, involving cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, is the most common form of hereditary stroke disorder, and is thought to be caused by mutations of the Notch 3 gene on chromosome 19. The disease belongs to a family of disorders called the leukodystrophies. The most common clinical manifestations are migraine headaches and transient ischemic attacks or strokes, which usually occur between 40 and 50 years of age, although MRI is able to detect signs of the disease years prior to clinical manifestation of disease.The condition was identified and named by French researchers Marie-Germaine Bousser and Elisabeth Tournier-Lasserve in the 1990s. Together with two other researchers, Hugues Chabriat and Anne Joutel, they received the 2019 Brain Prize for their research into the condition. Signs and symptoms CADASIL may start with attacks of migraine with aura or subcortical transient ischemic attacks or strokes, or mood disorders between 35 and 55 years of age. The disease progresses to subcortical dementia associated with pseudobulbar palsy and urinary incontinence.Ischemic strokes are the most frequent presentation of CADASIL, with approximately 85% of symptomatic individuals developing transient ischemic attacks or stroke(s). The mean age of onset of ischemic episodes is approximately 46 years (range 30–70). A classic lacunar syndrome occurs in at least two-thirds of affected patients while hemispheric strokes are much less common. It is worthy of note that ischemic strokes typically occur in the absence of traditional cardiovascular risk factors. Recurrent silent strokes, with or without clinical strokes, often lead to cognitive decline and overt subcortical dementia. A case of CADASIL presenting as schizophreniform organic psychosis has been reported. Pathophysiology The underlying pathology of CADASIL is progressive hypertrophy of the smooth muscle cells in blood vessels. Autosomal dominant mutations in the Notch 3 gene (on the long arm of chromosome 19) cause an abnormal accumulation of Notch 3 at the cytoplasmic membrane of vascular smooth muscle cells both in cerebral and extracerebral vessels, seen as granular osmiophilic deposits on electron microscopy. Leukoencephalopathy follows. Depending on the nature and position of each mutation, a consensus significant loss of betasheet structure of the Notch3 protein has been predicted using in silico analysis. Diagnosis MRIs show hypointensities on T1-weighted images and hyperintensities on T2-weighted images, usually multiple confluent white matter lesions of various sizes, are characteristic. These lesions are concentrated around the basal ganglia, peri-ventricular white matter, and the pons, and are similar to those seen in Binswanger disease. These white matter lesions are also seen in asymptomatic individuals with the mutated gene. While MRI is not used to diagnose CADASIL, it can show the progression of white matter changes even decades before onset of symptoms.The definitive test is sequencing the whole Notch 3 gene, which can be done from a sample of blood. However, as this is quite expensive and CADASIL is a systemic arteriopathy, evidence of the mutation can be found in small and medium-size arteries. Therefore, skin biopsies are often used for the diagnosis. Treatment No specific treatment for CADASIL is available. While most treatments for CADASIL patients symptoms – including migraine and stroke – are similar to those without CADASIL, these treatments are almost exclusively empiric, as data regarding their benefit to CADASIL patients are limited. Antiplatelet agents such as aspirin, dipyridamole, or clopidogrel might help prevent strokes; however, anticoagulation may be inadvisable given the propensity for microhemorrhages. Control of high blood pressure is particularly important in CADASIL patients. Short-term use of atorvastatin, a statin-type cholesterol-lowering medication, has not been shown to be beneficial in CADASIL patients cerebral hemodynamic parameters, although treatment of comorbidities such as high cholesterol is recommended. Stopping oral contraceptive pills may be recommended. Some authors advise against the use of triptan medications for migraine treatment, given their vasoconstrictive effects, although this sentiment is not universal. In this regard, the advent of the "Ditans" such as Lasmiditan, lacking vasoconstrictive effect, and the "Gepants" such as Ubrogepant and Rimegepant, are attractive alternatives, albeit not yet field-tested in this condition. As with other individuals, people with CADASIL should be encouraged to quit smoking.In one small study, around 1/3 of patients with CADASIL were found to have cerebral microhemorrhages (tiny areas of old blood) on MRI.L-arginine, a naturally occurring amino acid, has been proposed as a potential therapy for CADASIL, but as of 2017 there are no clinical studies supporting its use. Donepezil, normally used for Alzheimers Disease, was not shown not to improve executive functioning in CADASIL patients. Society and culture John Ruskin has been suggested to have had CADASIL. Ruskin reported in his diaries having visual disturbances consistent with the disease, and it has also been suggested that it might have been a factor in causing him to describe James Whistlers Nocturne in Black and Gold – The Falling Rocket as "ask[ing] two hundred guineas for throwing a pot of paint in the publics face". This resulted in the famous libel trial that resulted in a jurys awarding Whistler one farthing damages.Recent research into the illness of philosopher Friedrich Nietzsche has suggested that his mental illness and death may have been caused by CADASIL rather than tertiary syphilis. Likewise, the early death of the composer Felix Mendelssohn, at age 37, from a stroke has been potentially linked to CADASIL. His sister, Fanny Mendelssohn, was similarly affected. And James Dewar, best known as vocalist for Robin Trower, died age 59 from complications of CADASIL.In the movie The Sea Inside, one of the characters is stated to have CADASIL. See also Proteopathy CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy) References Further reading Lesnik Oberstein SA, Boon EM, Terwindt GM (June 28, 2012). CADASIL. University of Washington, Seattle. PMID 20301673. NBK1500. In Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A (1993). Pagon RA, Bird TD, Dolan CR, et al. (eds.). GeneReviews [Internet]. Seattle WA: University of Washington, Seattle. PMID 20301295. External links A patient story at The New York Times

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

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

Urinary tract obstruction is a urologic disease consisting of a decrease in the free passage of urine through one or both ureters and/or the urethra. It is a cause of urinary retention. Complete obstruction of the urinary tract requires prompt treatment for renal preservation. Any sign of infection, such as fever and chills, in the context of obstruction to urine flow constitutes a urologic emergency. Causes Causes of urinary tract obstruction include: Bladder stone and renal stone Benign prostatic hyperplasia Obstruction as a congenital disorder. Congenital urinary tract obstruction Urinary tract obstruction as a congenital disorder results in oligohydramnios which in turn can lead to the Potter sequence of atypical physical appearance. Pulmonary hypoplasia is by far the main cause of death in the early neonatal period for children with congenital lower urinary tract obstruction.Fetal surgery of congenital lower urinary tract obstruction seems to improve survival, according to a randomized yet small study. Sitting voiding position A meta-analysis on the influence of voiding position on urodynamics in healthy males and males with LUTS showed that in the sitting position, the residual urine in the bladder was significantly reduced. The other parameters, namely the maximum urinary flow and the voiding time were increased and decreased respectively. For healthy males, no influence was found on these parameters, meaning that they can urinate in either position. Diagnosis Treatment Treatment depends on the underlying cause of the obstruction and the severity of the symptoms. References == External links ==

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

I've encountered the term 'Progesterone (medication)' while reading about medical topics. What does it refer to exactly?

Progesterone (P4) is a medication and naturally occurring steroid hormone. It is a progestogen and is used in combination with estrogens mainly in hormone therapy for menopausal symptoms and low sex hormone levels in women. It is also used in women to support pregnancy and fertility and to treat gynecological disorders. Progesterone can be taken by mouth, in through the vagina, and by injection into muscle or fat, among other routes. A progesterone vaginal ring and progesterone intrauterine device used for birth control also exist in some areas of the world.Progesterone is well tolerated and often produces few or no side effects. However, a number of side effects are possible, for instance mood changes. If progesterone is taken by mouth or at high doses, certain central side effects including sedation, sleepiness, and cognitive impairment can also occur. The medication is a naturally occurring progestogen and hence is an agonist of the progesterone receptor (PR), the biological target of progestogens like endogenous progesterone. It opposes the effects of estrogens in various parts of the body like the uterus and also blocks the effects of the hormone aldosterone. In addition, progesterone has neurosteroid effects in the brain.Progesterone was first isolated in pure form in 1934. It first became available as a medication later that year. Oral micronized progesterone (OMP), which allowed progesterone to be taken by mouth, was introduced in 1980. A large number of synthetic progestogens, or progestins, have been derived from progesterone and are used as medications as well. Examples include medroxyprogesterone acetate and norethisterone. In 2019, it was the 188th most commonly prescribed medication in the United States, with more than 3 million prescriptions. Medical uses Hormone therapy Menopause Progesterone is used in combination with an estrogen as a component of menopausal hormone therapy for the treatment of menopausal symptoms in peri- and postmenopausal women. It is used specifically to provide endometrial protection against unopposed estrogen-induced endometrial hyperplasia and cancer in women with intact uteruses. A 2016 systematic review of endometrial protection with progesterone recommended 100 mg/day continuous oral progesterone, 200 mg/day cyclic oral progesterone, 45 to 100 mg/day cyclic vaginal progesterone, and 100 mg alternate-day vaginal progesterone. Twice-weekly 100 mg vaginal progesterone was also recommended, but more research is needed on this dose and endometrial monitoring may be advised. Transdermal progesterone was not recommended for endometrial protection.The REPLENISH trial was the first adequately powered study to show that continuous 100 mg/day oral progesterone with food provides adequate endometrial protection. Cyclic 200 mg/day oral progesterone has also been found to be effective in the prevention of endometrial hyperplasia, for instance in the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. However, the PEPI trial was not adequately powered to fully quantify endometrial hyperplasia or cancer risk. No adequately powered studies have assessed endometrial protection with vaginal progesterone. In any case, the Early versus Late Intervention Trial with Estradiol (ELITE) found that cyclic 45 mg/day vaginal progesterone gel showed no significant difference from placebo in endometrial cancer rates. Due to the vaginal first-pass effect, low doses of vaginal progesterone may allow for adequate endometrial protection. Although not sufficiently powered, various other smaller studies have also found endometrial protection with oral or vaginal progesterone. There is inadequate evidence for endometrial protection with transdermal progesterone cream.Oral progesterone has been found to significantly reduce hot flashes relative to placebo. The combination of an estrogen and oral progesterone likewise reduces hot flashes. Estrogen plus oral progesterone has been found to significantly improve quality of life. The combination of an estrogen and 100 to 300 mg/day oral progesterone has been found to improve sleep outcomes. Moreover, sleep was improved to a significantly better extent than estrogen plus medroxyprogesterone acetate. This may be attributable to the sedative neurosteroid effects of progesterone. Reduction of hot flashes may also help to improve sleep outcomes. Based on animal research, progesterone may be involved in sexual function in women. However, very limited clinical research suggests that progesterone does not improve sexual desire or function in women.The combination of an estrogen and oral progesterone has been found to improve bone mineral density (BMD) to a similar extent as an estrogen plus medroxyprogesterone acetate. Progestogens, including progesterone, may have beneficial effects on bone independent of those of estrogens, although more research is required to confirm this notion. The combination of an estrogen and oral or vaginal progesterone has been found to improve cardiovascular health in women in early menopause but not in women in late menopause. Estrogen therapy has a favorable influence on the blood lipid profile, which may translate to improved cardiovascular health. The addition of oral or vaginal progesterone has neutral or beneficial effects on these changes. This is in contrast to various progestins, which are known to antagonize the beneficial effects of estrogens on blood lipids. Progesterone, both alone and in combination with an estrogen, has been found to have beneficial effects on skin and to slow the rate of skin aging in postmenopausal women.In the French E3N-EPIC observational study, the risk of diabetes was significantly lower in women on menopausal hormone therapy, including with the combination of an oral or transdermal estrogen and oral progesterone or a progestin. Transgender women Progesterone is used as a component of feminizing hormone therapy for transgender women in combination with estrogens and antiandrogens. However, the addition of progestogens to HRT for transgender women is controversial and their role is unclear. Some patients and clinicians believe anecdotally that progesterone may enhance breast development, improve mood, and increase sex drive. However, there is a lack of evidence from well-designed studies to support these notions at present. In addition, progestogens can produce undesirable side effects, although bioidentical progesterone may be safer and better tolerated than synthetic progestogens like medroxyprogesterone acetate.Because some believe that progestogens are necessary for full breast development, progesterone is sometimes used in transgender women with the intention of enhancing breast development. However, a 2014 review concluded the following on the topic of progesterone for enhancing breast development in transgender women: Our knowledge concerning the natural history and effects of different cross-sex hormone therapies on breast development in [transgender] women is extremely sparse and based on low quality of evidence. Current evidence does not provide evidence that progestogens enhance breast development in [transgender] women. Neither do they prove the absence of such an effect. This prevents us from drawing any firm conclusion at this moment and demonstrates the need for further research to clarify these important clinical questions. Data on menstruating women shows there is no correlation between water retention, and levels of progesterone or estrogen. Despite this, some theorise progesterone might cause temporary breast enlargement due to local fluid retention, and may thus give a misleading appearance of breast growth. Aside from a hypothetical involvement in breast development, progestogens are not otherwise known to be involved in physical feminization.In some cases, transgender women use progesterone to alleviate symptoms of estrogen withdrawal. Estrogen must be withdrawn from transgender womens hormonal regime before they undergo sex reassignment surgery. Pregnancy support Vaginally dosed progesterone is being investigated as potentially beneficial in preventing preterm birth in women at risk for preterm birth. The initial study by Fonseca suggested that vaginal progesterone could prevent preterm birth in women with a history of preterm birth. According to a recent study, women with a short cervix that received hormonal treatment with a progesterone gel had their risk of prematurely giving birth reduced. The hormone treatment was administered vaginally every day during the second half of a pregnancy. A subsequent and larger study showed that vaginal progesterone was no better than placebo in preventing recurrent preterm birth in women with a history of a previous preterm birth, but a planned secondary analysis of the data in this trial showed that women with a short cervix at baseline in the trial had benefit in two ways: a reduction in births less than 32 weeks and a reduction in both the frequency and the time their babies were in intensive care.In another trial, vaginal progesterone was shown to be better than placebo in reducing preterm birth prior to 34 weeks in women with an extremely short cervix at baseline. An editorial by Roberto Romero discusses the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment. A meta-analysis published in 2011 found that vaginal progesterone cut the risk of premature births by 42 percent in women with short cervixes. The meta-analysis, which pooled published results of five large clinical trials, also found that the treatment cut the rate of breathing problems and reduced the need for placing a baby on a ventilator. Fertility support Progesterone is used for luteal support in assisted reproductive technology (ART) cycles such as in vitro fertilization (IVF). It is also used to correct luteal phase deficiency to prepare the endometrium for implantation in infertility therapy and is used to support early pregnancy. Birth control A progesterone vaginal ring is available for birth control when breastfeeding in a number of areas of the world. An intrauterine device containing progesterone has also been marketed under the brand name Progestasert for birth control, including previously in the United States. Gynecological disorders Progesterone is used to control persistent anovulatory bleeding. It is used in non-pregnant women with a delayed menstruation of one or more weeks, in order to allow the thickened endometrial lining to slough off. This process is termed a progesterone withdrawal bleed. Progesterone is taken orally for a short time (usually one week), after which it is discontinued and bleeding should occur. Other uses Progesterone is of unclear benefit for the reversal of mifepristone-induced abortion. Evidence is insufficient to support use in traumatic brain injury.Progesterone has been used as a topical medication applied to the scalp to treat female and male pattern hair loss. Variable effectiveness has been reported, but overall its effectiveness for this indication in both sexes has been poor. Breast pain Progesterone is approved under the brand name Progestogel as a 1% topical gel for local application to the breasts to treat breast pain in certain countries. It is not approved for systemic therapy. It has been found in clinical studies to inhibit estrogen-induced proliferation of breast epithelial cells and to abolish breast pain and tenderness in women with the condition. However, in one small study in women with cyclic breast pain it was ineffective. Vaginal progesterone has also been found to be effective in the treatment of breast pain and tenderness. Premenstrual syndrome Historically, progesterone has been widely used in the treatment of premenstrual syndrome. A 2012 Cochrane review found insufficient evidence for or against the effectiveness of progesterone for this indication. Another review of 10 studies found that progesterone was not effective for this condition, although it stated that insufficient evidence is available currently to make a definitive statement on progesterone in premenstrual syndrome. Catamenial epilepsy Progesterone can be used to treat catamenial epilepsy by supplementation during certain periods of the menstrual cycle. Available forms Progesterone is available in a variety of different forms, including oral capsules; sublingual tablets; vaginal capsules, tablets, gels, suppositories, and rings; rectal suppositories; oil solutions for intramuscular injection; and aqueous solutions for subcutaneous injection. A 1% topical progesterone gel is approved for local application to the breasts to treat breast pain, but is not indicated for systemic therapy. Progesterone was previously available as an intrauterine device for use in hormonal contraception, but this formulation was discontinued. Progesterone is also limitedly available in combination with estrogens such as estradiol and estradiol benzoate for use by intramuscular injection.In addition to approved pharmaceutical products, progesterone is available in unregulated custom compounded and over-the-counter formulations like systemic transdermal creams and other preparations. The systemic efficacy of transdermal progesterone is controversial and has not been demonstrated. Contraindications Contraindications of progesterone include hypersensitivity to progesterone or progestogens, prevention of cardiovascular disease (a Black Box warning), thrombophlebitis, thromboembolic disorder, cerebral hemorrhage, impaired liver function or disease, breast cancer, reproductive organ cancers, undiagnosed vaginal bleeding, missed menstruations, miscarriage, or a history of these conditions. Progesterone should be used with caution in people with conditions that may be adversely affected by fluid retention such as epilepsy, migraine headaches, asthma, cardiac dysfunction, and renal dysfunction. It should also be used with caution in patients with anemia, diabetes mellitus, a history of depression, previous ectopic pregnancy, and unresolved abnormal Pap smear. Use of progesterone is not recommended during pregnancy and breastfeeding. However, the medication has been deemed usually safe in breastfeeding by the American Academy of Pediatrics, but should not be used during the first four months of pregnancy. Some progesterone formulations contain benzyl alcohol, and this may cause a potentially fatal "gasping syndrome" if given to premature infants. Side effects Progesterone is well tolerated, and many clinical studies have reported no side effects. Side effects of progesterone may include abdominal cramps, back pain, breast tenderness, constipation, nausea, dizziness, edema, vaginal bleeding, hypotension, fatigue, dysphoria, depression, and irritability, among others. Central nervous system depression, such as sedation and cognitive/memory impairment, can also occur.Vaginal progesterone may be associated with vaginal irritation, itchiness, and discharge, decreased libido, painful sexual intercourse, vaginal bleeding or spotting in association with cramps, and local warmth or a "feeling of coolness" without discharge. Intramuscular injection may cause mild-to-moderate pain at the site of injection. High intramuscular doses of progesterone have been associated with increased body temperature, which may be alleviated with paracetamol treatment.Progesterone lacks undesirable off-target hormonal activity, in contrast to various progestins. As a result, it is not associated with androgenic, antiandrogenic, estrogenic, or glucocorticoid effects. Conversely, progesterone can still produce side effects related to its antimineralocorticoid and neurosteroid activity. Compared to the progestin medroxyprogesterone acetate, there are fewer reports of breast tenderness with progesterone. In addition, the magnitude and duration of vaginal bleeding with progesterone are reported to be lower than with medroxyprogesterone acetate. Central depression Progesterone can produce central nervous system depression as an adverse effect, particularly with oral administration or with high doses of progesterone. These side effects may include drowsiness, sedation, sleepiness, fatigue, sluggishness, reduced vigor, dizziness, lightheadedness, confusion, and cognitive, memory, and/or motor impairment. Limited available evidence has shown minimal or no adverse influence on cognition with oral progesterone (100–600 mg), vaginal progesterone (45 mg gel), or progesterone by intramuscular injection (25–200 mg). However, high doses of oral progesterone (300–1200 mg), vaginal progesterone (100–200 mg), and intramuscular progesterone (100–200 mg) have been found to result in dose-dependent fatigue, drowsiness, and decreased vigor. Moreover, high single doses of oral progesterone (1200 mg) produced significant cognitive and memory impairment. Intravenous infusion of high doses of progesterone (e.g., 500 mg) has been found to induce deep sleep in humans. Some individuals are more sensitive and can experience considerable sedative and hypnotic effects at lower doses of oral progesterone (e.g., 400 mg).Sedation and cognitive and memory impairment with progesterone are attributable to its inhibitory neurosteroid metabolites. These metabolites occur to a greater extent with oral progesterone, and may be minimized by switching to a parenteral route. Progesterone can also be taken before bed to avoid these side effects and to help with sleep. The neurosteroid effects of progesterone are unique to progesterone and are not shared with progestins. Breast cancer Breast cell proliferation has been found to be significantly increased by the combination of an oral estrogen plus cyclic medroxyprogesterone acetate in postmenopausal women but not by the combination of transdermal estradiol plus oral progesterone. Studies of topical estradiol and progesterone applied to the breasts for 2 weeks have been found to result in highly pharmacological local levels of estradiol and progesterone. These studies have assessed breast proliferation markers and have found increased proliferation with estradiol alone, decreased proliferation with progesterone, and no change in proliferation with estradiol and progesterone combined. In the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial, the combination of estrogen and cyclic oral progesterone resulted in a higher mammographic breast density than estrogen alone (3.1% vs. 0.9%) but a non-significantly lower breast density than the combination of estrogen and cyclic or continuous medroxyprogesterone acetate (3.1% vs. 4.4–4.6%). Higher breast density is a strong known risk factor for breast cancer. Other studies have had mixed findings however. A 2018 systematic review reported that breast density with an estrogen plus oral progesterone was significantly increased in three studies and unchanged in two studies. Changes in breast density with progesterone appear to be less than with the compared progestins.In large short-term observational studies, estrogen alone and the combination of estrogen and oral progesterone have generally not been associated with an increased risk of breast cancer. Conversely, the combination of estrogen and almost any progestin, such as medroxyprogesterone acetate or norethisterone acetate, has been associated with an increased risk of breast cancer. The only exception among progestins is dydrogesterone, which has shown similar risk to that of oral progesterone. Breast cancer risk with estrogen and progestin therapy is duration-dependent, with the risk being significantly greater with more than 5 years of exposure relative to less than 5 years. In contrast to shorter-term studies, the longer-term observations (>5 years) of the French E3N study showed significant associations of both estrogen plus oral progesterone and estrogen plus dydrogesterone with higher breast cancer risk, similarly to estrogen plus other progestogens. Oral progesterone has very low bioavailability and has relatively weak progestogenic effects. The delayed onset of breast cancer risk with estrogen plus oral progesterone is potentially consistent with a weak proliferative effect of oral progesterone on the breasts. As such, a longer duration of exposure may be necessary for a detectable increase in breast cancer risk to occur. In any case, the risk remains lower than that with most progestins. A 2018 systematic review of progesterone and breast cancer concluded that short-term use (<5 years) of an estrogen plus progesterone is not associated with a significant increase in risk of breast cancer but that long-term use (>5 years) is associated with greater risk. The conclusions for progesterone were the same in a 2019 meta-analysis of the worldwide epidemiological evidence by the Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC).Most data on breast density changes and breast cancer risk are with oral progesterone. Data on breast safety with vaginal progesterone are scarce. The Early versus Late Intervention Trial with Estradiol (ELITE) was a randomized controlled trial of about 650 postmenopausal women who used estradiol and 45 mg/day cyclic vaginal progesterone. Incidence of breast cancer was reported as an adverse effect. The absolute incidences were 10 cases in the estradiol plus vaginal progesterone group and 8 cases in the control group. However, the study was not adequately powered for quantifying breast cancer risk. Blood clots Whereas the combination of estrogen and a progestin is associated with increased risk of venous thromboembolism (VTE) relative to estrogen alone, there is no difference in risk of VTE with the combination of estrogen and oral progesterone relative to estrogen alone. Hence, in contrast to progestins, oral progesterone added to estrogen does not appear to increase coagulation or VTE risk. The reason for the differences between progesterone and progestins in terms of VTE risk are unclear. However, they may be due to very low progesterone levels and relatively weak progestogenic effects produced by oral progesterone. In contrast to oral progesterone, non-oral progesterone—which can achieve much higher progesterone levels—has not been assessed in terms of VTE risk. Overdose Progesterone is likely to be relatively safe in overdose. Levels of progesterone during pregnancy are up to 100-fold higher than during normal menstrual cycling, although levels increase gradually over the course of pregnancy. Oral dosages of progesterone of as high as 3,600 mg/day have been assessed in clinical trials, with the main side effect being sedation. There is a case report of progesterone misuse with an oral dosage of 6,400 mg per day. Administration of as much as 500 mg progesterone by intravenous infusion in humans was uneventful in terms of toxicity, but did induce deep sleep, though the individuals were still able to be awakened with sufficient stimulation. Interactions There are several notable drug interactions with progesterone. Certain selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, and sertraline may increase the GABAA receptor-related central depressant effects of progesterone by enhancing its conversion into 5α-dihydroprogesterone and allopregnanolone via activation of 3α-HSD. Progesterone potentiates the sedative effects of benzodiazepines and alcohol. Notably, there is a case report of progesterone abuse alone with very high doses. 5α-Reductase inhibitors such as finasteride and dutasteride inhibit the conversion of progesterone into the inhibitory neurosteroid allopregnanolone, and for this reason, may have the potential to reduce the sedative and related effects of progesterone.Progesterone is a weak but significant agonist of the pregnane X receptor (PXR), and has been found to induce several hepatic cytochrome P450 enzymes, such as CYP3A4, especially when concentrations are high, such as with pregnancy range levels. As such, progesterone may have the potential to accelerate the metabolism of various medications. Pharmacology Pharmacodynamics Progesterone is a progestogen, or an agonist of the nuclear progesterone receptors (PRs), the PR-A, PR-B, and PR-C. In addition, progesterone is an agonist of the membrane progesterone receptors (mPRs), including the mPRα, mPRβ, mPRγ, mPRδ, and mPRϵ. Aside from the PRs and mPRs, progesterone is a potent antimineralocorticoid, or antagonist of the mineralocorticoid receptor, the biological target of the mineralocorticoid aldosterone. In addition to its activity as a steroid hormone, progesterone is a neurosteroid. Among other neurosteroid activities, and via its active metabolites allopregnanolone and pregnanolone, progesterone is a potent positive allosteric modulator of the GABAA receptor, the major signaling receptor of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).The PRs are expressed widely throughout the body, including in the uterus, cervix, vagina, fallopian tubes, breasts, fat, skin, pituitary gland, hypothalamus, and in other areas of the brain. In accordance, progesterone has numerous effects throughout the body. Among other effects, progesterone produces changes in the female reproductive system, the breasts, and the brain. Progesterone has functional antiestrogenic effects due to its progestogenic activity, including in the uterus, cervix, and vagina. The effects of progesterone may influence health in both positive and negative ways. In addition to the aforementioned effects, progesterone has antigonadotropic effects due to its progestogenic activity, and can inhibit ovulation and suppress gonadal sex hormone production.The activities of progesterone besides those mediated by the PRs and mPRs are also of significance. Progesterone lowers blood pressure and reduces water and salt retention among other effects via its antimineralocorticoid activity. In addition, progesterone can produce sedative, hypnotic, anxiolytic, euphoric, cognitive-, memory-, and motor-impairing, anticonvulsant, and even anesthetic effects via formation of sufficiently high concentrations of its neurosteroid metabolites and consequent GABAA receptor potentiation in the brain.There are differences between progesterone and progestins, such as medroxyprogesterone acetate and norethisterone, with implications for pharmacodynamics and pharmacokinetics, as well as for efficacy, tolerability, and safety. Pharmacokinetics The pharmacokinetics of progesterone are dependent on its route of administration. The medications is approved in the form of oil-filled capsules containing micronized progesterone for oral administration, termed oral micronized progesterone or OMP. It is also available in the form of vaginal or rectal suppositories or pessaries, topical creams and gels, oil solutions for intramuscular injection, and aqueous solutions for subcutaneous injection.Routes of administration that progesterone has been used by include oral, intranasal, transdermal/topical, vaginal, rectal, intramuscular, subcutaneous, and intravenous injection. Vaginal progesterone is available in the form of progesterone capsules, tablets or inserts, gels, suppositories or pessaries, and rings. Chemistry Progesterone is a naturally occurring pregnane steroid and is also known as pregn-4-ene-3,20-dione. It has a double bond (4-ene) between the C4 and C5 positions and two ketone groups (3,20-dione), one at the C3 position and the other at the C20 position. Due to its pregnane core and C4(5) double bond, progesterone is often abbreviated as P4. It is contrasted with pregnenolone, which has a C5(6) double bond and is often abbreviated as P5. Derivatives A large number of progestins, or synthetic progestogens, have been derived from progesterone. They can be categorized into several structural groups, including derivatives of retroprogesterone, 17α-hydroxyprogesterone, 17α-methylprogesterone, and 19-norprogesterone, with a respective example from each group including dydrogesterone, medroxyprogesterone acetate, medrogestone, and promegestone. The progesterone ethers quingestrone (progesterone 3-cyclopentyl enol ether) and progesterone 3-acetyl enol ether are among the only examples that do not belong to any of these groups. Another major group of progestins, the 19-nortestosterone derivatives, exemplified by norethisterone (norethindrone) and levonorgestrel, are not derived from progesterone but rather from testosterone.A variety of synthetic inhibitory neurosteroids have been derived from progesterone and its neurosteroid metabolites, allopregnanolone and pregnanolone. Examples include alfadolone, alfaxolone, ganaxolone, hydroxydione, minaxolone, and renanolone. In addition, C3 and C20 conjugates of progesterone, such as progesterone carboxymethyloxime (progesterone 3-(O-carboxymethyl)oxime; P4-3-CMO), P1-185 (progesterone 3-O-(L-valine)-E-oxime), EIDD-1723 (progesterone 20E-[O-[(phosphonooxy)methyl]oxime] sodium salt), EIDD-036 (progesterone 20-oxime; P4-20-O), and VOLT-02 (chemical structure unreleased), have been developed as water-soluble prodrugs of progesterone and its neurosteroid metabolites. Synthesis Chemical syntheses of progesterone have been published. History Discovery and synthesis The hormonal action of progesterone was discovered in 1929. Pure crystalline progesterone was isolated in 1934 and its chemical structure was determined. Later that year, chemical synthesis of progesterone was accomplished. Shortly following its chemical synthesis, progesterone began being tested clinically in women. Injections and implants In 1933 or 1934, Schering introduced progesterone in oil solution as a medication by intramuscular injection under the brand name Proluton. This was the first pharmaceutical formulation of progesterone to be marketed for medical use. It was initially a corpus luteum extract, becoming pure synthesized progesterone only subsequently. A clinical study of the formulation was published in 1933. Multiple formulations of progesterone in oil solution for intramuscular injection, under the brand names Proluton, Progestin, and Gestone, were available by 1936. A parenteral route was used because oral progesterone had very low activity and was thought to be inactive. Progesterone was initially very expensive due to the large doses required. However, with the start of steroid manufacturing from diosgenin in the 1940s, costs greatly decreased.Subcutaneous pellet implants of progesterone were first studied in women in the late 1930s. They were the first long-acting progestogen formulation. Pellets were reported to be extruded out of the skin within a few weeks at high rates, even when implanted beneath the deep fascia, and also produced frequent inflammatory reactions at the site of implantation. In addition, they were absorbed too slowly and achieved unsatisfactorily low progesterone levels. Consequently, they were soon abandoned, in favor of other preparations such as aqueous suspensions. However, subcutaneous pellet implants of progesterone were later studied as a form of birth control in women in the 1980s and early 1990s, though no preparations were ultimately marketed.Aqueous suspensions of progesterone crystals for intramuscular injection were first described in 1944. These preparations were on the market in the 1950s under a variety of brand names including Flavolutan, Luteosan, Lutocyclin M, and Lutren, among others. Aqueous suspensions of steroids were developed because they showed much longer durations than intramuscular injection of steroids in oil solution. However, local injection site reactions, which do not occur with oil solutions, have limited the clinical use of aqueous suspensions of progesterone and other steroids. Today, a preparation with the brand name Agolutin Depot remains on the market in the Czech Republic and Slovakia. A combined preparation of progesterone, estradiol benzoate, and lidocaine remains available with the brand name Clinomin Forte in Paraguay as well. In addition to aqueous suspensions, water-in-oil emulsions of steroids were studied by 1949, and long-acting emulsions of progesterone were introduced for use by intramuscular injection under the brand names Progestin and Di-Pro-Emulsion (with estradiol benzoate) by the 1950s. Due to lack of standardization of crystal sizes, crystalline suspensions of steroids had marked variations in effect. Emulsions were said to be even more unreliable.Macrocrystalline aqueous suspensions of progesterone as well as microspheres of progesterone were investigated as potential progestogen-only injectable contraceptives and combined injectable contraceptives (with estradiol) by the late 1980s and early 1990s but were never marketed.Aqueous solutions of water-insoluble steroids were first developed via association with colloid solubility enhancers in the 1940s. An aqueous solution of progesterone for use by intravenous injection was marketed by Schering AG under the brand name Primolut Intravenous by 1962. One of its intended uses was the treatment of threatened abortion, in which rapid-acting effect was desirable. An aqueous solution of progesterone complexed with cyclodextrin to increase its water solubility was introduced for use by once-daily subcutaneous injection in Europe under the brand name Prolutex in the mid-2010s.In the 1950s, long-acting parenteral progestins such as hydroxyprogesterone caproate, medroxyprogesterone acetate, and norethisterone enanthate were developed and introduced for use by intramuscular injection. They lacked the need for frequent injections and the injection site reactions associated with progesterone by intramuscular injection and soon supplanted progesterone for parenteral therapy in most cases. Oral and sublingual The first study of oral progesterone in humans was published in 1949. It found that oral progesterone produced significant progestational effects in the endometrium in women. Prior to this study, animal research had suggested that oral progesterone was inactive, and for this reason, oral progesterone had never been evaluated in humans. A variety of other early studies of oral progesterone in humans were also published in the 1950s and 1960s. These studies generally reported oral progesterone to be only very weakly active. Oral non-micronized progesterone was introduced as a pharmaceutical medication around 1953, for instance as Cyclogesterin (1 mg estrogenic substances and 30 mg progesterone tablets) for menstrual disturbances by Upjohn, though it saw limited use. Another preparation, which contained progesterone alone, was Synderone (trademark registered by Chemical Specialties in 1952).Sublingual progesterone in women was first studied in 1944 by Robert Greenblatt. Buccal progesterone tablets were marketed by Schering under the brand name Proluton Buccal Tablets by 1949. Sublingual progesterone tablets were marketed under the brand names Progesterone Lingusorbs and Progesterone Membrettes by 1951. A sublingual tablet formulation of progesterone has been approved under the brand name Luteina in Poland and Ukraine and remains marketed today.Progesterone was the first progestogen that was found to inhibit ovulation, both in animals and in women. Injections of progesterone were first shown to inhibit ovulation in animals between 1937 and 1939. Inhibition of fertilization by administration of progesterone during the luteal phase was also demonstrated in animals between 1947 and 1949. Ovulation inhibition by progesterone in animals was subsequently re-confirmed and expanded on by Gregory Pincus and colleagues in 1953 and 1954. Findings on inhibition of ovulation by progesterone in women were first presented at the Fifth International Conference on Planned Parenthood in Tokyo, Japan in October 1955. Three different research groups presented their findings on this topic at the conference. They included Pincus (in conjunction with John Rock, who did not attend the conference); a nine-member Japanese group led by Masaomi Ishikawa; and the two-member team of Abraham Stone and Herbert Kupperman. The conference marked the beginning of a new era in the history of birth control. The results were subsequently published in scientific journals in 1956 in the case of Pincus and in 1957 in the case of Ishikawa and colleagues. Rock and Pincus also subsequently described findings from 1952 that "pseudopregnancy" therapy with a combination of high doses of diethylstilbestrol and oral progesterone prevented ovulation and pregnancy in women.Unfortunately, the use of oral progesterone as a hormonal contraceptive was plagued by problems. These included the large and by extension expensive doses required, incomplete inhibition of ovulation even at high doses, and a frequent incidence of breakthrough bleeding. At the 1955 Tokyo conference, Pincus had also presented the first findings of ovulation inhibition by oral progestins in animals, specifically 19-nortestosterone derivatives like noretynodrel and norethisterone. These progestins were far more potent than progesterone, requiring much smaller doses orally. By December 1955, inhibition of ovulation by oral noretynodrel and norethisterone had been demonstrated in women. These findings as well as results in animals were published in 1956. Noretynodrel and norethisterone did not show the problems associated with oral progesterone—in the studies, they fully inhibited ovulation and did not produce menstruation-related side effects. Consequently, oral progesterone was abandoned as a hormonal contraceptive in women. The first birth control pills to be introduced were a noretynodrel-containing product in 1957 and a norethisterone-containing product in 1963, followed by numerous others containing a diversity of progestins. Progesterone itself has never been introduced for use in birth control pills.More modern clinical studies of oral progesterone demonstrating elevated levels of progesterone and end-organ responses in women, specifically progestational endometrial changes, were published between 1980 and 1983. Up to this point, many clinicians and researchers apparently still thought that oral progesterone was inactive. It was not until almost half a century after the introduction of progesterone in medicine that a reasonably effective oral formulation of progesterone was marketed. Micronization of progesterone and suspension in oil-filled capsules, which allowed progesterone to be absorbed several-fold more efficiently by the oral route, was first studied in the late 1970s and described in the literature in 1982. This formulation, known as oral micronized progesterone (OMP), was then introduced for medical use under the brand name Utrogestan in France in 1982. Subsequently, oral micronized progesterone was introduced under the brand name Prometrium in the United States in 1998. By 1999, oral micronized progesterone had been marketed in more than 35 countries. In 2019, the first combination of oral estradiol and progesterone was introduced under the brand name Bijuva in the United States.A sustained-release (SR) formulation of oral micronized progesterone, also known as "oral natural micronized progesterone sustained release" or "oral NMP SR", was marketed in India in 2012 under the brand name Gestofit SR. Many additional brand names followed. The preparation was originally developed in 1986 by a compounding pharmacy called Madison Pharmacy Associates in Madison, Wisconsin in the United States. Vaginal, rectal, and uterine Vaginal progesterone suppositories were first studied in women by Robert Greenblatt in 1954. Shortly thereafter, vaginal progesterone suppositories were introduced for medical use under the brand name Colprosterone in 1955. Rectal progesterone suppositories were first studied in men and women by Christian Hamburger in 1965. Vaginal and rectal progesterone suppositories were introduced for use under the brand name Cyclogest by 1976. Vaginal micronized progesterone gels and capsules were introduced for medical use under brand names such as Utrogestan and Crinone in the early 1990s. Progesterone was approved in the United States as a vaginal gel in 1997 and as a vaginal insert in 2007. A progesterone contraceptive vaginal ring known as Progering was first studied in women in 1985 and continued to be researched through the 1990s. It was approved for use as a contraceptive in lactating mothers in Latin America by 2004. A second progesterone vaginal ring known as Fertiring was developed as a progesterone supplement for use during assisted reproduction and was approved in Latin America by 2007.Development of a progesterone-containing intrauterine device (IUD) for contraception began in the 1960s. Incorporation of progesterone into IUDs was initially studied to help reduce the risk of IUD expulsion. However, while addition of progesterone to IUDs showed no benefit on expulsion rates, it was unexpectedly found to induce endometrial atrophy. This led in 1976 to the development and introduction of Progestasert, a progesterone-containing product and the first progestogen-containing IUD. Unfortunately, the product had various problems that limited its use. These included a short duration of efficacy of only one year, a high cost, a relatively high 2.9% failure rate, a lack of protection against ectopic pregnancy, and difficult and sometimes painful insertions that could necessitate use of a local anesthetic or analgesic. As a result of these issues, Progestasert never became widely used, and was discontinued in 2001. It was used mostly in the United States and France while it was marketed. Transdermal and topical A topical gel formulation of progesterone, for direct application to the breasts as a local therapy for breast disorders such as breast pain, was introduced under the brand name Progestogel in Europe by 1972. No transdermal formulations of progesterone for systemic use have been successfully marketed, in spite of efforts of pharmaceutical companies towards this goal. The low potency of transdermal progesterone has thus far precluded it as a possibility. Although no formulations of transdermal progesterone are approved for systemic use, transdermal progesterone is available in the form of creams and gels from custom compounding pharmacies in some countries, and is also available over-the-counter without a prescription in the United States. However, these preparations are unregulated and have not been adequately characterized, with low and unsubstantiated effectiveness. Society and culture Generic names Progesterone is the generic name of the drug in English and its INN, USAN, USP, BAN, DCIT, and JAN, while progestérone is its name in French and its DCF. It is also referred to as progesteronum in Latin, progesterona in Spanish and Portuguese, and progesteron in German. Brand names Progesterone is marketed under a large number of brand names throughout the world. Examples of major brand names under which progesterone has been marketed include Crinone, Crinone 8%, Cyclogest, Endogest, Endometrin, Estima, Geslutin, Gesterol, Gestone, Luteina, Luteinol, Lutigest, Lutinus, Microgest, Progeffik, Progelan, Progendo, Progering, Progest, Progestaject, Progestan, Progesterone, Progestin, Progestogel, Prolutex, Proluton, Prometrium, Prontogest, Strone, Susten, Utrogest, and Utrogestan. Availability Progesterone is widely available in countries throughout the world in a variety of formulations. Progesterone in the form of oral capsules; vaginal capsules, tablets/inserts, and gels; and intramuscular oil have widespread availability. The following formulations/routes of progesterone have selective or more limited availability: A tablet of micronized progesterone which is marketed under the brand name Luteina is indicated for sublingual administration in addition to vaginal administration and is available in Poland and Ukraine. A progesterone suppository which is marketed under the brand name Cyclogest is indicated for rectal administration in addition to vaginal administration and is available in Cyprus, Hong Kong, India, Malaysia, Malta, Oman, Singapore, South Africa, Thailand, Tunisia, Turkey, the United Kingdom, and Vietnam. An aqueous solution of progesterone complexed with β-cyclodextrin for subcutaneous injection is marketed under the brand name Prolutex in the Czech Republic, Hungary, Italy, Poland, Portugal, Slovakia, Spain, and Switzerland. A non-systemic topical gel formulation of progesterone for local application to the breasts to treat breast pain is marketed under the brand name Progestogel and is available in Belgium, Bulgaria, Colombia, Ecuador, France, Georgia, Germany, Hong Kong, Lebanon, Peru, Romania, Russia, Serbia, Switzerland, Tunisia, Venezuela, and Vietnam. It was also formerly available in Italy, Portugal, and Spain, but was discontinued in these countries. A progesterone intrauterine device was previously marketed under the brand name Progestasert and was available in Canada, France, the United States, and possibly other countries, but was discontinued. Progesterone vaginal rings are marketed under the brand names Fertiring and Progering and are available in Chile, Ecuador, and Peru. A sustained-release tablet formulation of oral micronized progesterone (also known as "oral natural micronized progesterone sustained release" or "oral NMP SR") is marketed in India under the brand names Dubagest SR, Gestofit SR, and Susten SR, among many others.In addition to single-drug formulations, the following progesterone combination formulations are or have been marketed, albeit with limited availability: A combination pack of progesterone capsules for oral use and estradiol gel for transdermal use is marketed under the brand name Estrogel Propak in Canada. A combination pack of progesterone capsules and estradiol tablets for oral use is marketed in an under the brand name Duogestan in Belgium. Progesterone and estradiol in an aqueous suspension for use by intramuscular injection is marketed under the brand name Cristerona FP in Argentina. Progesterone and estradiol in microspheres in an oil solution for use by intramuscular injection is marketed under the brand name Juvenum in Mexico. Progesterone and estradiol benzoate in an oil solution for use by intramuscular injection is marketed under the brand names Duogynon, Duoton Fort T P, Emmenovis, Gestrygen, Lutofolone, Menovis, Mestrolar, Metrigen Fuerte, Nomestrol, Phenokinon-F, Prodiol, Pro-Estramon-S, Proger F, Progestediol, and Vermagest and is available in Belize, Egypt, El Salvador, Ethiopia, Guatemala, Honduras, Italy, Lebanon, Malaysia, Mexico, Nicaragua, Taiwan, Thailand, and Turkey. Progesterone and estradiol hemisuccinate in an oil solution for use by intramuscular injection is marketed under the brand name Hosterona in Argentina. Progesterone and estrone for use by intramuscular injection is marketed under the brand name Synergon in Monaco. United States As of November 2016, progesterone is available in the United States in the following formulations: Oral: Capsules: Prometrium (100 mg, 200 mg, 300 mg) Vaginal: Tablets: Endometrin (100 mg); Gels: Crinone (4%, 8%) Intramuscular injection: Oil: Progesterone (50 mg/mL)A 25 mg/mL concentration of progesterone oil for intramuscular injection and a 38 mg/device progesterone intrauterine device (Progestasert) have been discontinued.An oral combination formulation of micronized progesterone and estradiol in oil-filled capsules (brand name Bijuva) is marketed in the United States for the treatment of menopausal symptoms and endometrial hyperplasia.Progesterone is also available in unregulated custom preparations from compounding pharmacies in the United States. In addition, transdermal progesterone is available over-the-counter in the United States, although the clinical efficacy of transdermal progesterone is controversial. Research Progesterone was studied as a progestogen-only injectable contraceptive, but was never marketed. Combinations of estradiol and progesterone as a macrocrystalline aqueous suspension and as an aqueous suspension of microspheres have been studied as once-a-month combined injectable contraceptives, but were likewise never marketed.Progesterone has been assessed for the suppression of sex drive and spermatogenesis in men. In one study, 100 mg rectal suppositories of progesterone given five times per day for 9 days resulted in progesterone levels of 5.5 to 29 ng/mL and suppressed circulating testosterone and growth hormone levels by about 50% in men, but did not affect libido or erectile potency in this short treatment period. In other studies, 50 mg/day progesterone by intramuscular injection for 10 weeks in men produced azoospermia, decreased testicular size, markedly suppressed libido and erectile potency, and resulted in minimal semen volume upon ejaculation.An oil and water nanoemulsion of progesterone (particles of <1 mm in diameter) using micellar nanoparticle technology for transdermal administration known as Progestsorb NE was under development by Novavax for use in menopausal hormone therapy in the 2000s. However, development was discontinued in 2007 and the formulation was never marketed. See also Estradiol/progesterone Estradiol benzoate/progesterone Estradiol hemisuccinate/progesterone References == Further reading ==

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

Can you break down the meaning of the medical term 'Reversible cerebral vasoconstriction syndrome' for me?

Reversible cerebral vasoconstriction syndrome (RCVS, sometimes called Call-Fleming syndrome) is a disease characterized by a weeks-long course of thunderclap headaches, sometimes focal neurologic signs, and occasionally seizures. Symptoms are thought to arise from transient abnormalities in the blood vessels of the brain. In some cases, it may be associated with childbirth, vasoactive or illicit drug use, or complications of pregnancy. If it occurs after delivery it may be referred to as postpartum cerebral angiopathy. For the vast majority of patients, all symptoms disappear on their own within three weeks. Deficits persist in a small minority of patients, with severe complications or death being very rare. Because symptoms resemble a variety of life-threatening conditions, differential diagnosis is necessary. Signs and symptoms The key symptom of RCVS is recurrent thunderclap headaches, which over 95% of patients experience. In two-thirds of cases, it is the only symptom. These headaches are typically bilateral, very severe and peak in intensity within a minute. They may last from minutes to days, and may be accompanied by nausea, photophobia, phonophobia or vomiting. Some patients experience only one headache, but on average there are four attacks over a period of one to four weeks. A milder, residual headache persists between severe attacks for half of patients.1–17% of patients experience seizures. 8–43% of patients show neurologic problems, especially visual disturbances, but also hemiplegia, ataxia, dysarthria, aphasia, and numbness. These neurologic issues typically disappear within minutes or a few hours; more persistent symptoms may indicate a stroke. Posterior reversible encephalopathy syndrome is present in a small minority of patients.This condition features the unique property that the patients cerebral arteries can spontaneously constrict and relax back and forth over a period of time without intervention and without clinical findings. Vasospasm is common post subarachnoid hemorrhage and cerebral aneurysm, but in RCVS only 25% of patients have symptoms post subarachnoid hemorrhage. Causes The direct cause of the symptoms is believed to be either constriction or dilation of blood vessels in the brain. The pathogenesis is not known definitively, and the condition is likely to result from multiple different disease processes.Up to two-thirds of RCVS cases are associated with an underlying condition or exposure, particularly vasoactive or recreational drug use, complications of pregnancy (eclampsia and pre-eclampsia), and the adjustment period following childbirth called puerperium. Vasoactive drug use is found in about 50% of cases. Implicated drugs include selective serotonin reuptake inhibitors, weight-loss pills such as Hydroxycut, alpha-sympathomimetic decongestants, acute migraine medications, pseudoephedrine, epinephrine, cocaine, and cannabis, among many others. It sometimes follows blood transfusions, certain surgical procedures, swimming, bathing, high altitude experiences, sexual activity, exercise, or coughing. Symptoms can take days or a few months to manifest after a trigger.Following a study and publication in 2007, it is also thought SSRIs, uncontrolled hypertension, endocrine abnormality, and neurosurgical trauma are indicated to potentially cause vasospasm. Diagnosis The clinician should first rule out conditions with similar symptoms, such as subarachnoid hemorrhage, ischemic stroke, pituitary apoplexy, cerebral artery dissection, meningitis, and spontaneous cerebrospinal fluid leak. This may involve a CT scan, lumbar puncture, MRI, and other tests. Posterior reversible encephalopathy syndrome has a similar presentation, and is found in 10–38% of RCVS patients.RCVS is diagnosed by detecting diffuse reversible cerebral vasoconstriction. Catheter angiography is ideal, but computed tomography angiography and magnetic resonance angiography can identify about 70% of cases. Multiple angiographies may be necessary. Because other diseases (such as atherosclerosis) have similar angiographic presentations, it can only be conclusively diagnosed if vasoconstriction resolves within 12 weeks. Treatment As of 2014, no treatment strategy has yet been investigated in a randomized clinical trial. Verapamil, nimodipine, and other calcium channel blockers may help reduce the intensity and frequency of the headaches. A clinician may recommend rest and the avoidance of activities or vasoactive drugs which trigger symptoms (see § Causes). Analgesics and anticonvulsants can help manage pain and seizures, respectively. Prognosis All symptoms normally resolve within three weeks, and may only last days. Permanent deficits are seen in a minority of patients, ranging from under 10% to 20% in various studies. Less than 5% of patients experience progressive vasoconstriction, which can lead to stroke, progressive cerebral edema, or even death. Severe complications appear to be more common in postpartum mothers. Epidemiology The incidence of RCVS is unknown, but it is believed to be "not uncommon", and likely under-diagnosed. One small, possibly biased study found that the condition was eventually diagnosed in 45% of outpatients with sudden headache, and 46% of outpatients with thunderclap headache.The average age of onset is 42, but RCVS has been observed in patients aged from 19 months to 70 years. Children are rarely affected. It is more common in females, with a female-to-male ratio of 2.4:1. History Case studies of the condition first appeared in the 1960s, but it was not then recognized as a distinct entity. In 1983, French researchers published a case series of 11 patients, terming the condition acute benign cerebral angiopathy. Gregory Call and Marie Fleming were the first two authors of a report in which doctors from Massachusetts General Hospital, led by C. Miller Fisher, described 4 patients, alongside 12 previous case studies, with the characteristic symptoms and abnormal cerebral angiogram findings. The name Call-Fleming syndrome refers to these researchers.A 2007 review by Leonard Calabrese and colleagues proposed the name reversible cerebral vasoconstriction syndrome, which has since gained widespread acceptance. This name merges various conditions that were previously treated as distinct entities, including Call-Fleming syndrome, postpartum angiopathy, and drug-induced angiopathy. Other names may still be used for particular forms of the condition. References == External links ==

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

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

Thoracic insufficiency syndrome is the inability of the thorax to support normal respiration. It is frequently associated with chest and/or spinal abnormalities. Treatment options are limited, but include supportive pulmonary care and surgical options (thoracoplasty and/or implantation of vertical expandable prosthetic titanium rib (VEPTR) devices). == References ==

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

What is the significance of the term 'Localized lipodystrophy' in the medical field?

Localized lipodystrophy is a skin condition characterized by the loss of subcutaneous fat localized to sites of insulin injection.: 497 See also Lipodystrophy List of cutaneous conditions Skin lesion References == External links ==

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

Please help me grasp the concept behind the medical term 'Caput succedaneum.'

Caput succedaneum is a neonatal condition involving a serosanguinous, subcutaneous, extraperiosteal fluid collection with poorly defined margins caused by the pressure of the presenting part of the scalp against the dilating cervix (tourniquet effect of the cervix) during delivery.It involves bleeding below the scalp and above the periosteum. See also Cephalohematoma Cephalic Chignon (medical term) Hematoma Subgaleal hemorrhage References == External links ==

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

Can you demystify the medical term 'Conjugated estrogens' for me?

Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the sodium salts of estrogen conjugates found in horses, such as estrone sulfate and equilin sulfate. CEEs are available in the form of both natural preparations manufactured from the urine of pregnant mares and fully synthetic replications of the natural preparations. They are formulated both alone and in combination with progestins such as medroxyprogesterone acetate. CEEs are usually taken by mouth, but can also be given by application to the skin or vagina as a cream or by injection into a blood vessel or muscle.Side effects of CEEs include breast tenderness and enlargement, headache, fluid retention, and nausea among others. It may increase the risk of endometrial hyperplasia and endometrial cancer in women with an intact uterus if it is not taken together with a progestogen like progesterone. The medication may also increase the risk of blood clots, cardiovascular disease, and, when combined with most progestogens, breast cancer. CEEs are estrogens, or agonists of the estrogen receptor, the biological target of estrogens like estradiol. Compared to estradiol, certain estrogens in CEEs are more resistant to metabolism, and the medication shows relatively increased effects in certain parts of the body like the liver. This results in an increased risk of blood clots and cardiovascular problems with CEEs relative to estradiol.Premarin, the major brand of CEEs in use, is manufactured by Pfizer and was first marketed in 1941 in Canada and in 1942 in the United States. It is the most commonly used form of estrogen in menopausal hormone therapy in the United States. However, it has begun to fall out of favor relative to bioidentical estradiol, which is the most widely used form of estrogen in Europe for menopausal hormone therapy. CEEs are available widely throughout the world. An estrogen preparation very similar to CEEs but differing in source and composition is esterified estrogens. In 2017, it was the 206th most commonly prescribed medication in the United States, with more than two million prescriptions. Medical uses CEEs are a form of hormone therapy used in women. It is used most commonly in postmenopausal women who have had a hysterectomy to treat hot flashes, and burning, itching, and dryness of the vagina and surrounding areas. It must be used in combination with a progestogen in women who have not had a hysterectomy. For women already taking the medication, it can be used to treat osteoporosis, although it is not recommended solely for this use. Some lesser known uses are as a means of high-dose estrogen therapy in the treatment of breast cancer in both women and men and in the treatment of prostate cancer in men. It has been used at a dosage of 2.5 mg three times per day (7.5 mg/day total) for prostate cancer.CEEs are specifically approved in countries such as the United States and Canada for the treatment of moderate to severe vasomotor symptoms (hot flashes) and vulvovaginal atrophy (atrophic vaginitis, atrophic urethritis) associated with menopause, hypoestrogenism due to hypogonadism, ovariectomy, or primary ovarian failure, abnormal uterine bleeding, the palliative treatment of metastatic breast cancer in women, the palliative treatment of advanced androgen-dependent prostate cancer in men, and the prevention of postmenopausal osteoporosis. The intravenous formulation of CEEs is specifically used to rapidly limit bleeding in women with hemorrhage due to dysfunctional uterine bleeding.: 318 : 60 Available forms Natural CEEs, as Premarin, are available in the form of oral tablets (0.3 mg, 0.625 mg, 0.9 mg, 1.25 mg, or 2.5 mg), creams for topical or vaginal administration (0.625 mg/g), and vials for intravenous or intramuscular injection (25 mg/vial). Synthetic CEEs, such as Cenestin (Synthetic A), Enjuvia (Synthetic B), and generic formulations, are available in the form of oral tablets (0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, or 1.25 mg) and creams for topical or vaginal administration (0.625 mg/g). Contraindications Contraindications of CEEs include breast cancer and a history of venous thromboembolism, among others. Side effects The most common side effects associated with CEEs are vaginal yeast infections, vaginal spotting or bleeding, painful menses, and cramping of the legs. While there are some contradictory data, estrogen alone does not appear to increase the risk of coronary heart disease or breast cancer, unlike the case of estrogen in combination with certain progestins such as levonorgestrel or medroxyprogesterone acetate. Only a few clinical studies have assessed differences between oral CEEs and oral estradiol in terms of health parameters. Oral CEEs have been found to possess a significantly greater risk of thromboembolic and cardiovascular complications than oral estradiol (OR = 2.08) and oral esterified estrogens (OR = 1.78). However, in another study, the increase in venous thromboembolism risk with oral CEEs plus medroxyprogesterone acetate and oral estradiol plus norethisterone acetate was found to be equivalent (RR = 4.0 and 3.9, respectively). As of present, there are no randomized controlled trials that would allow for unambiguous conclusions. Overdose Estrogens, including CEEs, are relatively safe in acute overdose. Interactions Inhibitors and inducers of cytochrome P450 enzymes may interact with CEEs. Pharmacology Pharmacodynamics CEEs are a combination of estrogens, or agonists of the estrogen receptors. The major estrogen in CEEs, sodium estrone sulfate, itself is inactive, and rather serves as a prodrug of estrone and then of estradiol. The transformation of estrone sulfate to estrone is catalyzed by steroid sulfatase, and of estrone into estradiol by 17β-hydroxysteroid dehydrogenase. CEEs (as Premarin) and estrone have been found to be equivalent in potency in an animal model of estrogenic activity. On the other hand, the active forms of the equine estrogens in CEEs, such as equilin and 17β-dihydroequilin, have greater potency in the liver relative to bioidentical estradiol, similarly to synthetic estrogens like ethinylestradiol and diethylstilbestrol. This results in disproportionate effects on liver protein production compared to estradiol, although to a lesser extent than ethinylestradiol and diethylstilbestrol. In addition, 17β-dihydroequilenin has shown a selective estrogen receptor modulator (SERM)-like profile of estrogenic activity in studies with monkeys, in which beneficial effects on bone and the cardiovascular system were observed but proliferative responses in breast or endometrium were not seen, although the clinical significance of this is unknown.CEEs consists of the sodium salts of the sulfate esters of equine estrogens in a specific and consistent composition (see the table). The major estrogens in CEEs are sodium estrone sulfate and sodium equilin sulfate, which together account for approximately 71.5 to 92.0% of the total content of CEEs. CEEs are prodrugs of the active forms of the estrogens. Sodium estrone sulfate is a prodrug of estrone, which in turn is a prodrug of estradiol, while sodium equilin sulfate is a prodrug of equilin and then of 17β-dihydroequilin. As such, the major active estrogens with CEEs are estradiol and 17β-dihydroequilin, which have potent estrogenic activity and account for most of the effects of CEEs. The 17α-estrogens in CEEs such as 17α-estradiol and 17α-dihydroequilin have low estrogenicity and are thought to contribute minimally to its effects. There are many different steroids in natural CEE products like Premarin, as many as 230 compounds and including even androgens and progestogens, but only the estrogens are present in sufficient amounts to produce clinically-relevant effects.A dosage of 0.625 mg/day oral CEEs has been found to increase SHBG levels by 100%. For comparison, 1 mg/day oral estradiol increased SHBG levels by 45%, while 50 µg/day transdermal estradiol increased SHBG levels by 12%. Ethinylestradiol is more potent in its effects on liver protein synthesis than either CEEs or estradiol, with 10 µg/day oral ethinylestradiol having been found to be approximately equivalent to 1.25 mg/day CEEs. Antigonadotropic effects A preliminary study of ovulation inhibition in women found that oral CEEs was 33% effective at 1.25 mg/day and 94% at 3.75 mg/day. A dosage of oral CEEs of 2.5 mg three times daily (7.5 mg/day total) has been found to suppress total testosterone levels in men to an equivalent extent as 3 mg/day oral diethylstilbestrol, which is the minimum dosage of diethylstilbestrol required to consistently suppress total testosterone levels into the castrate range (<50 ng/dL). Pharmacokinetics CEEs are hydrolyzed in the intestines during first-pass metabolism upon oral administration. Following their absorption, they are resulfated mainly in the liver also during the first pass. Following this, they serve as a circulating reservoir and are slowly rehydrolyzed into their unconjugated active forms.Oral CEEs, at a daily dosage of 0.625 mg, achieve estrone and estradiol levels of 150 pg/mL and 30–50 pg/mL, respectively, while a daily oral dosage of 1.25 mg achieves levels of 120–200 pg/mL and 40–60 pg/mL of estrone and estradiol, respectively. The oral ingestion of 10 mg CEEs, which contains about 4.5 mg sodium estrone sulfate and 2.5 mg sodium equilin sulfate, produces maximal plasma concentrations of estrone and equilin of 1,400 pg/mL and 560 pg/mL within 3 and 5 hours, respectively. By 24 hours post-dose of 10 mg, the levels of estrone and equilin fall to 280 pg/mL and 125 pg/mL, respectively. Oral CEEs 1.25 mg/daily and oral micronized estradiol 1 mg/daily result in similar plasma concentrations of estrone and estradiol (150–300 pg/mL and 30–50 pg/mL for micronized estradiol, respectively) (oral estradiol is extensively metabolized into estrone during hepatic first-pass metabolism), although this does not account for equilin and other equine estrogens involved in the effects of CEEs, which may be significantly more potent in comparison to estrone. The pharmacokinetics of vaginal CEEs and of intravenous CEEs have been studied as well.Eoncentrations of equilin that are very high relative to those of other estrogens are produced by typical clinical doses of CEEs. With a dosage of 1.25 mg oral CEEs, equilin levels of 1,082 to 2,465 pg/mL have been observed. The clinical significance of these levels of equilin is unknown.The active forms are metabolized primarily in the liver. There is some enterohepatic recirculation of CEEs. Following a single oral dose of 0.625 CEEs, the biological half-life of estrone was 26.7 hours, of baseline-adjusted estrone was 14.8 hours, and of equilin was 11.4 hours. Chemistry CEEs are naturally occurring estrane steroids. They are in conjugate form, as the sodium salts of the C17β sulfate esters. The estrogens in CEEs, in their unconjugated active forms, include bioidentical human estrogens like estradiol and estrone as well as equine-specific estrogens such as equilin and 17β-dihydroequilin. The equine estrogens differ from human estrogens in that they have additional double bonds in the B ring of the steroid nucleus. CEEs contain both 17β-estrogens like estradiol and 17β-dihydroequilin and the C17α epimers like 17α-estradiol and 17α-dihydroequilin. History Conjugated estriol, an extract of the urine of pregnant women and sold under the brand names Progynon and Emmenin in the 1930s, was the predecessor of Premarin. Both of these products contained conjugated estrogens similarly to Premarin, but the estrogens were human estrogens as opposed to equine estrogens and the composition differed. The major active ingredient in Progynon and Emmenin was estriol glucuronide. Estrone sulfate was first isolated from the urine of pregnant mares in the late 1930s by researchers in the Department of Biochemistry at University of Toronto. Premarin was first introduced in 1941 by Wyeth Ayerst as a treatment for hot flashes and other symptoms of menopause; at that time, Wyeth Ayerst only had to prove its safety, and not its efficacy. In response to the 1962 Kefauver Harris Amendment the FDA had its efficacy reviewed, and in 1972 found it effective for menopausal symptoms and probably effective for osteoporosis. The review also determined that two estrogens – estrone sulfate and equilin sulfate – were primarily responsible for the activity of Premarin, and it laid the groundwork for Abbreviated New Drug Application (ANDA) submissions of generic versions. In 1984 an NIH consensus panel found that estrogens were effective for preventing osteoporosis and 1986 the FDA announced in the Federal Register that Premarin was effective for preventing osteoporosis. This announcement led to a rapid growth in sales, and interest from generic manufacturers to introduce generic versions.Conjugated estrogens was introduced for medical use under the brand name Premarin in Canada in 1941, in the United States in 1942, and in the United Kingdom in 1956. Society and culture Names Estrogens, conjugated is the generic name of the drug and its USP and JAN. It is also known as conjugated estrogens or as conjugated equine estrogens. The brand name Premarin is a contraction of "pregnant mares urine".CEEs are marketed under a large number of brand names throughout the world. The major brand name of the natural form of CEEs manufactured from the urine of pregnant mares is Premarin. Major brand names of fully synthetic versions of CEEs include Cenestin and Enjuvia in the United States and C.E.S. and Congest in Canada. CEEs are also formulated in combination with progestins. Major brand names of CEEs in combination with medroxyprogesterone acetate include Prempro and Premphase in the United States, Premplus in Canada, Premique in the United Kingdom and Ireland, Premia in Australia and New Zealand, and Premelle in South Africa. Prempak-C is a combination of CEEs and norgestrel which is used in the United Kingdom and Ireland, and Prempak N is a combination of CEEs and medrogestone which is used in South Africa. Many of the aforementioned brand names are also used in other, non-English-speaking countries. Availability CEEs are marketed and available widely throughout the world. This includes in all English-speaking countries, throughout Europe, Latin America, Asia, and elsewhere in the world. Usage Besides ethinylestradiol used in birth control pills, CEEs were the second most used estrogen in the U.S. in 2016, with 4.2 million total prescriptions filled. The first most used estrogen was estradiol, with 13.4 million total prescriptions filled. CEEs were the 206th most commonly prescribed medication in the U.S. that year. Health effects Research starting in 1975 showed substantially increased risk of endometrial cancer. Since 1976 the drug has carried a label warning about the risk. As part of the Womens Health Initiative sponsored by the National Institutes of Health, a large-scale clinical trial of menopausal HRT showed that long-term use of estrogen and a progestin may increase the risk of strokes, heart attacks, blood clots, and breast cancer. Following these results, Wyeth experienced a significant decline in its sales of Premarin, Prempro (CEEs and medroxyprogesterone acetate), and related products, from over $2 billion in 2002 to just over $1 billion in 2006. Litigation This drug has been the subject of litigation; more than 13,000 people have sued Wyeth between 2002 and 2009. Wyeth and Pharmacia & Upjohn prevailed in the vast majority of hormone therapy cases previously set for trial through a combination of rulings by judges, verdicts by juries, and dismissals by plaintiffs themselves. Of the companys losses, two of the jury verdicts were reversed post-trial and others are being challenged on appeal. Wyeth also won five summary judgments on Prempro cases and had 15 cases voluntarily dismissed by plaintiffs. The company won dismissals in another 3,000 cases. In 2006, Mary Daniel, in a trial in Philadelphia, was awarded $1.5 million in compensatory damages as well as undisclosed punitive damages. As of 2010, Wyeth had won the last four of five cases, most recently in Virginia, finding that they were not responsible for the breast cancer of plaintiff Georgia Torkie-Tork. Wyeth has been quoted as saying "many risk factors associated with breast cancer have been identified, but science cannot establish what role any particular risk factor or combination play in any individual womans breast cancer." Wyeths counsel in the case also noted that in the WHI trial, 99.62% of women took the drug and "did not get breast cancer." Animal welfare Animal welfare groups claim that animal husbandry and urine collection methods used in the production of CEEs cause undue stress and suffering to the mares involved. Animal activists have made claims of abuses ranging from inadequate stall size, long periods of confinement, cumbersome urine collection, and continuous breeding cycles. After reaching advanced age, many of the mares are adopted for recreation use, while some are sent to feed lots for slaughter. Despite the controversy, the USDA called the CEEs HRT industry a model of self-regulation. See also Conjugated estrogens/medroxyprogesterone acetate Conjugated estrogens/norgestrel Conjugated estrogens/methyltestosterone Bazedoxifene/conjugated estrogens Estrogenic substances Conjugated estriol List of combined sex-hormonal preparations Notes References Further reading Bhavnani, Bhagu R. (1988). "The Saga of the Ring B Unsaturated Equine Estrogens*". Endocrine Reviews. 9 (4): 396–416. doi:10.1210/edrv-9-4-396. ISSN 0163-769X. PMID 3065072. Ansbacher R (April 1993). "Bioequivalence of conjugated estrogen products". Clin Pharmacokinet. 24 (4): 271–4. doi:10.2165/00003088-199324040-00001. PMID 8387902. S2CID 7681617. OConnell MB (September 1995). "Pharmacokinetic and pharmacologic variation between different estrogen products". J Clin Pharmacol. 35 (9 Suppl): 18S–24S. doi:10.1002/j.1552-4604.1995.tb04143.x. PMID 8530713. S2CID 10159196. Egarter C, Geurts P, Boschitsch E, Speiser P, Huber J (April 1996). "The effects of estradiol valerate plus medroxyprogesterone acetate and conjugated estrogens plus medrogestone on climacteric symptoms and metabolic variables in perimenopausal women". Acta Obstet Gynecol Scand. 75 (4): 386–93. doi:10.3109/00016349609033337. PMID 8638462. S2CID 44498140. Bhavnani BR (January 1998). "Pharmacokinetics and pharmacodynamics of conjugated equine estrogens: chemistry and metabolism". Proc. Soc. Exp. Biol. Med. 217 (1): 6–16. doi:10.3181/00379727-217-44199. PMID 9421201. S2CID 45177839. Gruber DM, Huber JC (December 1999). "Conjugated estrogens--the natural SERMs". Gynecol. Endocrinol. 13 Suppl 6: 9–12. PMID 10862263. Campagnoli C, Ambroggio S, Biglia N, Sismondi P (December 1999). "Conjugated estrogens and breast cancer risk". Gynecol. Endocrinol. 13 Suppl 6: 13–9. PMID 10862264. Bhavnani BR (June 2003). "Estrogens and menopause: pharmacology of conjugated equine estrogens and their potential role in the prevention of neurodegenerative diseases such as Alzheimers". J. Steroid Biochem. Mol. Biol. 85 (2–5): 473–82. doi:10.1016/S0960-0760(03)00220-6. PMID 12943738. S2CID 45552896. Ortmann J, Traupe T, Vetter W, Barton M (May 2004). "[Postmenopausal hormone replacement therapy and cardiovascular risk: role of conjugated equine estrogens and medroxyprogesterone acetate]". Praxis (in German). 93 (21): 904–14. doi:10.1024/0369-8394.93.21.904. PMID 15216975. Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 Suppl 1: 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324. Kurabayashi T (November 2007). "[New evidence of conjugated estrogen and 17beta-estradiol for treatment and prevention of osteoporosis]". Nippon Rinsho (in Japanese). 65 Suppl 9: 369–73. PMID 18161134. Lamba G, Kaur H, Adapa S, Shah D, Malhotra BK, Rafiyath SM, Thakar K, Fernandez AC (June 2013). "Use of conjugated estrogens in life-threatening gastrointestinal bleeding in hemodialysis patients--a review". Clin. Appl. Thromb. Hemost. 19 (3): 334–7. doi:10.1177/1076029612437575. PMID 22411999. S2CID 30468265. Mirkin S, Komm BS, Pickar JH (January 2014). "Conjugated estrogens for the treatment of menopausal symptoms: a review of safety data". Expert Opin Drug Saf. 13 (1): 45–56. doi:10.1517/14740338.2013.824965. PMID 23919270. S2CID 24379298. Bhavnani BR, Stanczyk FZ (July 2014). "Pharmacology of conjugated equine estrogens: efficacy, safety and mechanism of action". J. Steroid Biochem. Mol. Biol. 142: 16–29. doi:10.1016/j.jsbmb.2013.10.011. PMID 24176763. S2CID 1360563. Mattison DR, Karyakina N, Goodman M, LaKind JS (2014). "Pharmaco- and toxicokinetics of selected exogenous and endogenous estrogens: a review of the data and identification of knowledge gaps". Crit. Rev. Toxicol. 44 (8): 696–724. doi:10.3109/10408444.2014.930813. PMID 25099693. S2CID 11212469. External links "Estrogens, conjugated". Drug Information Portal. U.S. National Library of Medicine. "Steroidal estrogens". Drug Information Portal. U.S. National Library of Medicine. WHI Follow-up Study Confirms Health Risks of Long-Term Combination Hormone Therapy Outweigh Benefits for Postmenopausal Women NIH press release, March 4, 2008

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

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

Milrinone, sold under the brand name Primacor, is a pulmonary vasodilator used in patients who have heart failure. It is a phosphodiesterase 3 inhibitor that works to increase the hearts contractility and decrease pulmonary vascular resistance. Milrinone also works to vasodilate which helps alleviate increased pressures (afterload) on the heart, thus improving its pumping action. While it has been used in people with heart failure for many years, studies suggest that milrinone may exhibit some negative side effects that have caused some debate about its use clinically.Overall, milrinone supports ventricular functioning of the heart by decreasing the degradation of cyclic adenosine monophosphate (cAMP) and thus increasing phosphorylation levels of many components in the heart that contribute to contractility and heart rate. Milrinone is used as a drug that causes positive inotropy and it will lead to an increased force of contraction. Milrinone use following cardiac surgery has been under some debate because of the potential increase risk of postoperative atrial arrhythmias. However, in the short term milrinone has been deemed beneficial to those experiencing heart failure and an effective therapy to maintain heart function following cardiac surgeries. There is no evidence of any long term beneficial effects on survival. In critically ill patients with evidence of cardiac dysfunction there is limited good quality evidence to recommend its use.Milrinone is administered IV only and eliminated unchanged in the urine. Dose adjustment is required for patients with renal impairment. Contractility in the heart People experiencing some forms of heart failure have a significant decrease in the contractile ability of muscle cells in the heart (cardiomyocytes). This impaired contractility occurs through a number of mechanisms. Some of the main problems associated with decreased contractility in those with heart failure are issues arising from imbalances in the concentration of calcium. Calcium permits myosin and actin to interact which allows initiation of contraction within the cardiomyocytes. In those with heart failure there may be a decreased amount of calcium within the cardiomyocytes reducing the available calcium to initiate contraction. When contractility is decreased the amount of blood being pumped out of the heart into circulation is decreased as well. This reduction in cardiac output can cause many systemic implications such as fatigue, syncope and other issues associated with decreased blood flow to peripheral tissues. Mechanism of action cAMP causes increased activation of protein kinase A (PKA). PKA is an enzyme that phosphorylates many elements of the contractile machinery within the heart cell. In the short term this leads to an increased force of contraction. Phosphodiesterases are enzymes responsible for the breakdown of cAMP. Therefore, when phosphodiesterases lower the level of cAMP in the cell they also lower the active fraction of PKA within the cell and reduce the force of contraction. Milrinone is a phosphodiesterase-3 inhibitor. This drug inhibits the action of phosphodiesterase-3 and thus prevents degradation of cAMP. With increased cAMP levels there is an increase in the activation of PKA. This PKA will phosphorylate many components of the cardiomyocyte such as calcium channels and components of the myofilaments. Phosphorylation of calcium channels permits an increase in calcium influx into the cell. This increase in calcium influx results in increased contractility. PKA also phosphorylates potassium channels promoting their action. Potassium channels are responsible for repolarization of the cardiomyocytes therefore increasing the rate at which cells can depolarize and generate contraction. PKA also phosphorylates components on myofilaments allowing actin and myosin to interact more easily and thus increasing contractility and the inotropic state of the heart. Milrinone allows stimulation of cardiac function independently of β-adrenergic receptors which appear to be down-regulated in those with heart failure. Clinical use Milrinone is a commonly used therapy for severe pulmonary arterial hypertension (PAH), often in combination with other medications such as sildenafil. Targeting PDE3 with optimal doses and timing, milrinone prevents allergic inflammation in HDM-driven models of allergic airway inflammation.It can be used in cardiopulmonary bypass cases, as it increases the flow in saphenous grafts and has a beneficiary effect in Left Ventricle fanction. Adverse effects Common adverse effects include ventricular arrhythmias (including ventricular ectopy and nonsustained ventricular tachycardia), supraventricular arrhythmias, hypotension, and headache. References External links Mechanism of action

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

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

Psyllium , or ispaghula , is the common name used for several members of the plant genus Plantago whose seeds are used commercially for the production of mucilage. Psyllium is mainly used as a dietary fiber to relieve symptoms of both constipation and mild diarrhea, and occasionally as a food thickener. Allergy to psyllium is common in workers frequently exposed to the substance. Use of psyllium in the diet for three weeks or longer often lowers blood cholesterol levels in people with elevated cholesterol, and can lower blood glucose levels in people with type 2 diabetes. Use of psyllium for a month or longer may produce a small reduction in systolic blood pressure.The plants from which the seeds are extracted tolerate dry and cool climates and are mainly cultivated in northern India. Uses Dietary supplements containing psyllium are sold mainly to aid weight loss, although there is little scientific evidence for such effects. Food Psyllium has been used as a thickener in ice cream and other frozen desserts. A 1.5% weight/volume ratio of psyllium mucilage exhibits binding properties that are superior to a 10% weight/volume ratio of starch mucilage. The viscosity of psyllium mucilage dispersions are relatively unaffected between temperatures of 20 and 50 °C (68 and 122 °F), by pH from 2 to 10, and by salt (sodium chloride) concentrations up to 0.15 M. Human health Constipation Psyllium is mainly used as a viscous, soluble dietary fiber that is not absorbed by the small intestine. The purely mechanical action of psyllium mucilage is to absorb excess water while stimulating normal bowel elimination. Although its main use has been as a laxative, it is more accurately regarded as a dietary fiber and as such can help reduce the symptoms of both constipation and mild diarrhea. The laxative properties of psyllium are attributed to the fiber: it absorbs water and subsequently softens the stool. It increases flatulence (gas) to some degree. High blood cholesterol In 1998, the U.S. Food and Drug Administration approved a health claim on food labels for dietary psyllium as a soluble fiber – if consumed regularly – that would reduce the risk of heart disease by lowering blood cholesterol. Clinical research demonstrated that seven grams or more per day of soluble fiber from psyllium seed husk would sufficiently lower total cholesterol and low density lipoprotein cholesterol in people with hypercholesterolemia, two accepted biomarkers for risk of coronary heart disease. The findings were later confirmed in a meta-analysis that incorporated more evidence. To be eligible for the FDA-allowed health claim, one serving of a manufactured food or dietary supplement must contain at least 1.7 g of psyllium as soluble fiber. Whole oats, barley and foods containing beta-glucan soluble fiber were included as eligible sources for the label claim. Type 2 diabetes In 2014, the U.S. Food and Drug Administration approved a qualified health claim for psyllium as a possible benefit for people with diabetes, requiring FDA-approved wording on a product label: "Psyllium husk may reduce the risk of type 2 diabetes, although the FDA has concluded that there is very little scientific evidence for this claim." A meta-analysis published after the FDA decision reported that psyllium provided before meals improved fasting blood glucose and glycated hemoglobin, but that the larger effect was seen in people diagnosed with and being treated for type 2 diabetes, and only a modest improvement for people classified as pre-diabetic. Veterinary medicine Psyllium fiber dietary supplements are used in veterinary medicine to treat sand impaction in horses to aid in elimination of sand from the horses colon. Adverse effects Fiber generally has few side effects. Psyllium can cause bowel obstructions or bezoars, if taken without adequate amounts of water. Gas or stomach bloating may also occur. Choking is a hazard if psyllium is taken without adequate water as it thickens in the throat. Allergy Psyllium can cause allergic reactions, including anaphylaxis. Psyllium may act as a potent inhalant allergen capable of eliciting asthma symptoms. Health care professionals at geriatric care hospitals, who are frequently exposed to psyllium in the laxatives administered to patients, are commonly IgE sensitized to psyllium (13.8%), and 8.6% have clinical allergy to psyllium. Pharmaceutical manufacturing employees who have been exposed to psyllium during the processing have developed occupational asthma and IgE sensitization. In order to protect sensitized workers, psyllium has an extremely low occupational exposure limit of 150 ng/m3. Mechanism of action The soluble fiber in psyllium is the polysaccharide heteroxylan, a hemicellulose.Psyllium is produced mainly for its mucilage content. The term mucilage describes a group of clear, colorless, gelling agents derived from plants. The mucilage obtained from psyllium comes from the seed coat. Mucilage is obtained by mechanical milling (i.e. grinding) of the outer layer of the seed. Mucilage yield amounts to about 25% (by weight) of the total seed yield. Plantago-seed mucilage is often referred to as husk, or psyllium husk. The milled seed mucilage is a white fibrous material that is hydrophilic, meaning that its molecular structure causes it to attract and bind to water. Upon absorbing water, the clear, colorless, mucilaginous gel that forms increases in volume by tenfold or more. Cultivation The genus Plantago contains over 200 species. P. ovata and P. psyllium are produced commercially in several European countries, Russia and surrounding countries, and India. Plantago seed, known commercially as black, French, or Spanish psyllium, is obtained from P. psyllium, also known as P. arenaria. Seed produced from P. ovata is known in trading circles as white or blonde psyllium, Indian plantago, or isabgol. Isabgol is the common name in India for P. ovata. it is known as Aspaghol in Pakistan, coming from the Persian asp and gul, meaning "horse flower", which is descriptive of the shape of the seed. India dominates the world market in the production and export of psyllium. Plantago ovata is an annual herb that grows to a height of 30–46 cm (12–18 in). Leaves are opposite, linear or linear lanceolate 1 cm × 19 cm (0.39 in × 7.48 in). The root system has a well-developed tap root with few fibrous secondary roots. A large number of flowering shoots arise from the base of the plant. Flowers are numerous, small, and white. Plants flower about 60 days after planting. The seeds are enclosed in capsules that open at maturity. The fields are generally irrigated prior to seeding to achieve ideal soil moisture, to enhance seed soil contact, and to avoid burying the seed too deeply as a result of later irrigations or rainfall. Maximum germination occurs at a seeding depth of 6 mm (1/4 in). Emerging seedlings are frost sensitive; therefore, planting should be delayed until conditions are expected to remain frost free. Seed is broadcast at 5.5 to 8.25 kg/hectare (5 to 7.5 lb/acre) in India. In Arizonan trials, seeding rates of 22 to 27.5 kg/ha (20 to 25 lb/acre) resulted in stands of 1 plant/25mm (1 inch) in 15 cm (6 inch) rows produced excellent yields. Weed control is normally achieved by one or two hand weedings early in the growing season. Control of weeds by pre-plant irrigation that germinates weed seeds followed by shallow tillage may be effective on fields with minimal weed pressure. Psyllium is a poor competitor with most weed species. Plantago wilt (Fusarium oxysporum) and downy mildew (Peronospora alta) are the major diseases of Isabgol. White grubs and aphids are the major insect pests. The flower spikes turn reddish brown at ripening, the lower leaves dry and the upper leaves yellow. The crop is harvested in the morning after the dew is gone to minimize shattering and field losses. In India, mature plants are cut 15 cm above the ground and then bound, left for a few days to dry, thrashed, and winnowed. Harvested seed must be dried to below 12% moisture to allow for cleaning, milling, and storage. Seed stored for future crops has shown a significant loss in viability after 2 years in storage. Commercial history Metamucil Introduced in 1934 by G. D. Searle & Company, Metamucil was acquired by Procter & Gamble in 1985. The name is a combination of the Greek word for change (meta) and the class of fiber that it utilizes (mucilage). In its early years, Metamucil achieved sporadic drug-store distribution as a "behind the counter" product - sold in pharmacies but not on the shelf, so that the pharmacist may counsel the purchaser on correct usage. Since 1974, the brand was also marketed to consumers by print and TV advertising and became available in food outlets. Flavored versions were added in 1979. The brand is sold as powdered drink mixes, capsules and wafers in a variety of flavors. Metamucil contains psyllium seed husks as the active ingredient. It is manufactured in Phoenix, Arizona, by Procter & Gamble. When first marketed to consumers in 1974, Metamucil was marketed as a laxative. The advertising slogan at that time was "If not nature, then Metamucil". Procter & Gamble sought to make Metamucil a household name by advertising in magazines and on television, using the claim "All fiber is not created equal". References External links USDA Plants Profile: Plantago ovata Forsk. USDA Germplasm Resources Information Network: Plantago ovata Forsk. ITIS Standard Report: Plantago ovata Forsk. USDA Plants Profile: Plantago psyllium L. USDA Germplasm Resources Information Network: Plantago psyllium L. (Plantago arenaria)

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

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

Cyprus facial neuromusculoskeletal syndrome is a rare autosomal dominant genetic disorder characterized by a "mephistophelian" appearance consisting of a ridged, thick triangular skin fold extending from the glabella up into the anterior fontanel, alongside other symptoms such as hypertelorism, widows peak, low-set ears, kyphoscoliosis congenita, congenital clubfoot, hip dislocation, and arthrogryposis. Additional findings include cataracts, decreased articular range of motion, ptosis, and ankylosis, and, less commonly, mild sensory deficits with muscle weakness and atrophy. It has been described in a large 3-generation Greek Cypriot family. == References ==

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

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

Portal vein thrombosis (PVT) is a vascular disease of the liver that occurs when a blood clot occurs in the hepatic portal vein, which can lead to increased pressure in the portal vein system and reduced blood supply to the liver. The mortality rate is approximately 1 in 10.An equivalent clot in the vasculature that exits the liver carrying deoxygenated blood to the right atrium via the inferior vena cava, is known as hepatic vein thrombosis or Budd-Chiari syndrome. Signs and symptoms Portal vein thrombosis causes upper abdominal pain, possibly accompanied by nausea and an enlarged liver and/or spleen; the abdomen may be filled with fluid (ascites). A persistent fever may result from the generalized inflammation. While abdominal pain may come and go if the thrombus forms suddenly, long-standing clot build-up can also develop without causing symptoms, leading to portal hypertension before it is diagnosed.Other symptoms can develop based on the cause. For example, if portal vein thrombosis develops due to liver cirrhosis, bleeding or other signs of liver disease may be present. If portal vein thrombosis develops due to pylephlebitis, signs of infection such as fever, chills, or night sweats may be present. Causes Slowed blood flow due to underlying cirrhosis or congestive heart failure is often implicated. The prevalence of PVT in patients with cirrhosis is unclear, with a wide variety of incidence claimed by various researchers (estimated to be 1 in 100 by some while others believe it affects nearly 1 in 4).Thrombophilia (including inherited conditions such as factor V Leiden deficiency, protein C or S deficiency, or antiphospholipid antibody syndrome) is another common cause. Nearly one-third of patients have a myeloproliferative disorder (e.g. polycythemia vera or primary thrombocytosis), most commonly due to a Janus kinase 2 (JAK2) gene mutation. Oral contraceptive use or pregnancy are other non-inherited tendencies for thrombosis.Alternatively, the portal vein may be injured as a result of pancreatitis, diverticulitis, cholangiocarcinoma, hepatocellular carcinoma (HCC), or abdominal surgery/trauma. Red flags for cancerous growth as a cause are elevated alpha fetoprotein levels, portal vein diameter greater than 2.3 cm, pulsatility on Doppler ultrasound imaging, or hyperintense hepatic arterial phase (HAP) on CT scan with contrast.PVT is also a known complication of surgical removal of the spleen. During the last several years, myeloproliferative neoplasms (MPNs) have emerged as a leading systemic cause of splanchnic vein thromboses (which include PVT). Mechanism The main portal vein is formed by the union of the splenic vein and superior mesenteric vein (SMV). It is responsible for approximately three-fourths of the liver’s blood flow, transported from much of the gastrointestinal system as well as the pancreas, gallbladder, and spleen. Cirrhosis alters bleeding pathways thus patients are simultaneously at risk of uncontrolled bleeding and forming clots. A long-standing hindrance in flow as in chronic PVT, also known as portal cavernoma, can cause an increase in the hepatic venous pressure gradient (portal hypertension) and increased blood flow through subsidiary veins. This may lead to ascites or bleeding from varices.An infected thrombus may become septic, known as pylephlebitis; if blood cultures are positive for growth at this time, the most common organism is Bacteroides. Diagnosis The diagnosis of portal vein thrombosis is usually made with imaging confirming a clot in the portal vein; ultrasound is the least invasive method and the addition of Doppler technique shows a filling defect in blood flow. PVT may be classified as either occlusive or nonocclusive based on evidence of blood flow around the clot. An alternative characterization based on site can be made: Type 1 is limited to the main portal vein, Type 2 involves only a portal vein branch (2a, or 2b if both branches are affected), and Type 3 if clot is found throughout both areas. Determination of condition severity may be derived via computed tomography (CT) with contrast, magnetic resonance imaging (MRI), or MR angiography (MRA). Those with chronic PVT may undergo upper endoscopy (esophagogastroduodenoscopy, EGD) to evaluate the presence of concurrent dilated veins (varices) in the stomach or esophagus. Other than perhaps slightly elevated transaminases, laboratory tests to evaluate liver function are typically normal. D-dimer levels in the blood may be elevated as a result of fibrin breakdown.On duplex ultrasound, demonstration of echogenic material within the portal vein, complete or partial absence of colour flow in the portal vein, presence of collateral vessels around the portal vein or gall bladder that bypass the portal vein. Treatment Treatment is aimed at opening the blocked veins to minimize complications; the duration of clot (acute versus chronic) affects treatment. Unless there are underlying reasons why it would be harmful, anticoagulation (low molecular weight heparin, followed by warfarin) is often initiated and maintained in patients who do not have cirrhosis. Anticoagulation for patients with cirrhosis who experience portal vein thrombosis is usually not advised unless they have chronic PVT 1) with thrombophilia, 2) with clot burden in the mesenteric veins, or 3) inadequate blood supply to the bowels. In more severe instances, shunts or a liver transplant may be considered. If blood flow to the gastrointestinal tract has been compromised chronically, surgery may be required to remove dead intestine.Different considerations are made in the management of PVT in pediatric patients or those who have already received a liver transplant. See also Pylephlebitis Budd–Chiari syndrome References External links Merck

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

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

Tasimelteon, sold under the brand name Hetlioz, is a medication approved by the U.S. Food and Drug Administration (FDA) in January 2014, for the treatment of non-24-hour sleep–wake disorder (also called non-24, N24 and N24HSWD). In June 2014, the European Medicines Agency (EMA) accepted an EU filing application for tasimelteon and in July 2015, the drug was approved in the European Union for the treatment of non-24-hour sleep-wake rhythm disorder in totally blind adults, but not in the rarer case of non-24 in sighted people. The most common side effects include headache, somnolence, nausea (feeling sick) and dizziness. Medical uses In the United States, tasimelteon capsules are indicated for the treatment of non-24-hour sleep–wake disorder (Non-24) in adults and for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in people sixteen years of age and older. Tasimelteon oral suspension is indicated for the treatment of nighttime sleep disturbances in SMS in children from 3 to 15 years of age.In the European Union, tasimelteon capsules are indicated for the treatment of non-24-hour sleep–wake disorder (Non-24) in totally blind adults.The capsule and liquid suspension forms of tasimelteon are not interchangeable.Tasimelteon is a selective agonist for the melatonin receptors MT1 and MT2, similar to other members of the melatonin receptor agonist class of which ramelteon (2005), melatonin (2007), and agomelatine (2009) were the first approved. As a treatment for N24HSWD, as with melatonin or other melatonin derivatives, the patient may experience improved sleep timing while taking the drug. Reversion to baseline sleep performance occurs within a month of discontinuation. Development Tasimelteon (previously known as BMS-214,778) was developed for the treatment of insomnia and other sleep disorders. A phase II trial on circadian rhythm sleep disorders was concluded in March 2005. A phase III insomnia trial was conducted in 2006. A second phase III trial on insomnia, this time concerning primary insomnia, was completed in June 2008. In 2010, the FDA granted orphan drug status to tasimelteon, then regarded as an investigational medication, for use in totally blind adults with N24HSWD. (Through mechanisms such as easing the approval process and extending exclusivity periods, orphan drug status encourages development of drugs for rare conditions that otherwise might lack sufficient commercial incentive.) On completion of Phase III trials, interpretations of the clinical trials by the research team concluded that the drug may have therapeutic potential for transient insomnia in circadian rhythm sleep disorders. A year-long (2011–2012) study at Harvard tested the use of tasimelteon in blind subjects with non-24-hour sleep-wake disorder. The drug has not been tested in children nor in any non-blind people. FDA approval In May 2013, Vanda Pharmaceuticals submitted a New Drug Application to the Food and Drug Administration for tasimelteon for the treatment of non-24-hour sleep–wake disorder in totally blind people. It was approved by the FDA on January 31, 2014, under the brand name Hetlioz. In the opinion of Public Citizen, an advocacy group, the FDA erroneously allowed it to be labelled without stating that it is only approved for use by totally blind people. However, FDA updated its press release on Oct. 2, 2014 to clarify the approved use of Hetlioz, which includes both sighted and blind individuals. The update did not change the drug labeling (prescribing information). Toxicity Experiments with rodents revealed fertility impairments, an increase in certain cancers, and serious adverse events during pregnancy at dosages in excess of what is considered the "human dose". See also Discovery and development of melatonin receptor agonists References External links "Tasimelteon". Drug Information Portal. U.S. National Library of Medicine.

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

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

Targetoid hemosiderotic hemangioma, also known as a hobnail hemangioma is a skin condition characterized by a central brown or purplish papule that is surrounded by an ecchymotic halo.It may appear similar to melanoma.It was first described by Santa Cruz and Aronberg in 1988. See also Skin lesion List of cutaneous conditions == References ==

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

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

Pioglitazone/metformin, sold under the brand name Actoplus Met among others, is a fixed-dose combination anti-diabetic medication used to improve glycemic control in adults with type 2 diabetes. It contains pioglitazone, a thiazolidinedione, and metformin, a biguanide. Mechanisms Pioglitazone is a member of the thiazolidinedione class, it decreases insulin resistance in the periphery and in the liver resulting in increased insulin dependent glucose disposal and decreased hepatic glucose output. Metformin is a member of the biguanide class, improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Indication Pioglitazone/metformin is indicated as an adjunct to diet and exercise: To improve glycemic control in patients with type 2 diabetes, or For patients who are already treated with a separate combination of pioglitazone and metformin, For patients whose diabetes is not adequately controlled with metformin alone, or For patients who have initially responded to pioglitazone alone and require additional glycemic control. Dosage and administration Use in pregnancy and lactation Pioglitazone/metformin should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women with combination of pioglitazone and metformin or its individual components. It is not known whether pioglitazone and/or metformin are secreted in human milk. Because many drugs are excreted in human milk, pioglitazone/metformin should not be administered to a breastfeeding woman. Precautions Pioglitazone/metformin should not be used in people with type 1 diabetes or for the treatment of diabetic ketoacidosis and should be used with caution in people with edema. Serum ALT levels should be evaluated prior to the initiation of therapy with combination of pioglitazone and metformin and periodically thereafter per the clinical judgment of the health care professional. Side-effects The most common side-effects are upper respiratory tract infection, diarrhea, combined edema/peripheral edema and headache, respectively. Most clinical adverse events were similar between groups treated with pioglitazone in combination with metformin and those treated with pioglitazone monotherapy. Contraindications Pioglitazone/metformin is contraindicated in people with known hypersensitivity to any components of this combination. These combination also contraindicated in renal disease which may also result from conditions, e.g., acute myocardial infarction, sepsis, acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Drug interaction Pioglitazone/metformin may interact with furosemide, nifedipine, cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) and certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control (e.g., thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid). References External links "Metformin hydrochloride mixture with pioglitazone hydrochloride". Drug Information Portal. U.S. National Library of Medicine.

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

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

Azacitidine, sold under the brand name Vidaza among others, is used for the treatment of myelodysplastic syndrome, myeloid leukemia, and juvenile myelomonocytic leukemia. It is a chemical analog of cytidine, a nucleoside in DNA and RNA. Azacitidine and its deoxy derivative, decitabine (also known as 5-aza-2′-deoxycytidine) were first synthesized in Czechoslovakia as potential chemotherapeutic agents for cancer.The most common adverse reactions in children with juvenile myelomonocytic leukemia include pyrexia, rash, upper respiratory tract infection, and anemia. Medical uses Azacitidine is indicated for the treatment of myelodysplastic syndrome, for which it received approval by the U.S. Food and Drug Administration (FDA) on May 19, 2004. In two randomized controlled trials comparing azacitidine to supportive treatment, 16% of subjects with myelodysplastic syndrome who were randomized to receive azacitidine had a complete or partial normalization of blood cell counts and bone marrow morphology, compared to none who received supportive care, and about two-thirds of patients who required blood transfusions no longer needed them after receiving azacitidine.Azacitidine is also indicated for the treatment of myeloid leukemia and juvenile myelomonocytic leukemia. Mechanism of action Azacitidine is a chemical analogue of the nucleoside cytidine, which is present in DNA and RNA. It is thought to have antineoplastic activity via two mechanisms – at low doses, by inhibiting of DNA methyltransferase, causing hypomethylation of DNA, and at high doses, by its direct cytotoxicity to abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA, resulting in cell death. Azacitidine is a ribonucleoside, so it is incorporated into RNA to a larger extent than into DNA. In contrast, decitabine (5-aza-2-deoxycytidine) is a deoxyribonucleoside, so it can only incorporate into DNA. Azacitidines incorporation into RNA leads to the disassembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and inhibition of the production of proteins. Its incorporation into DNA leads to covalent binding with DNA methyltransferases, which prevents DNA synthesis and subsequently leads to cytotoxicity. It has been shown effective against human immunodeficiency virus in vitro and human T-lymphotropic virus. Inhibition of methylation After azanucleosides such as azacitidine have been metabolized to 5-aza-2′-deoxycytidine-triphosphate (aka, decitabine-triphosphate), they can be incorporated into DNA and azacytosine can be substituted for cytosine. Azacytosine-guanine dinucleotides are recognized as substrate by the DNA methyltransferases, which catalyze the methylation reaction by a nucleophilic attack. This results in a covalent bond between the carbon-6 atom of the cytosine ring and the enzyme. The bond is normally resolved by beta-elimination through the carbon-5 atom, but this latter reaction does not occur with azacytosine because its carbon-5 is substituted by nitrogen, leaving the enzyme covalently bound to DNA and blocking its DNA methyltransferase function. In addition, the covalent protein adduction also compromises the functionality of DNA and triggers DNA damage signaling, resulting in the degradation of trapped DNA methyltransferases. As a consequence, methylation marks become lost during DNA replication. Toxicity Azacitidine causes anemia (low red blood cell counts), neutropenia (low white blood cell counts), and thrombocytopenia (low platelet counts), and patients should have frequent monitoring of their complete blood counts, at least prior to each dosing cycle. The dose may have to be adjusted based on nadir counts and hematologic response.It can also be hepatotoxic in patients with severe liver impairment, and patients with extensive liver tumors due to metastatic disease have developed progressive hepatic coma and death during azacitidine treatment, especially when their albumin levels are less than 30 g/L. It is contraindicated in patients with advanced malignant hepatic tumors.Kidney toxicity, ranging from elevated serum creatinine to kidney failure and death, have been reported in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents for conditions other than myelodysplastic syndrome. Renal tubular acidosis developed in five patients with chronic myelogenous leukemia (an unapproved use) treated with azacitidine and etoposide, and patients with renal impairment may be at increased risk for renal toxicity. Azacitidine and its metabolites are primarily excreted by the kidneys, so patients with chronic kidney disease should be closely monitored for other side effects, since their levels of azacitidine may progressively increase.Based on animal studies and its mechanism of action, azacitidine can cause severe fetal damage. Sexually active women of reproductive potential should use contraception during while receiving azacitidine and for one week after the last dose, and sexually active men with female partners of reproductive potential should use contraception during treatment and for three months following the last dose.A study undertaken to evaluate the immediate and long-term effects of a single-day exposure to Azacytidine (5-AzaC) on neurobehavioral abnormalities in mice found, that the inhibition of DNA methylation by 5-AzaC treatment causes neurodegeneration and impairs extracellular signal-regulated kinase (ERK1/2) activation and the activity-regulated cytoskeleton-associated (Arc) protein expression in neonatal mice and induces behavioral abnormalities in adult mice, as DNA methylation-mediated mechanisms appear to be necessary for the proper maturation of synaptic circuits during development, and disruption of this process by 5-AzaC could lead to abnormal cognitive function.Azacitidine can also cause nausea, vomiting, fevers, diarrhea, redness at its injection sites, constipation, bruising, petechiae, rigors, weakness, abnormally low potassium levels in the bloodstream, and many other side effects, some of which can be severe or even fatal. History The efficacy of azacitidine to treat juvenile myelomonocytic leukemia was evaluated in AZA-JMML-001 (NCT02447666), an international, multicenter, open-label study to evaluate the pharmacokinetics, pharmacodynamics, safety, and activity of azacitidine prior to hematopoietic stem cell transplantation in 18 pediatric patients with juvenile myelomonocytic leukemia. Research Azacitidine can be used in vitro to remove methyl groups from DNA. This may weaken the effects of gene silencing mechanisms that occur prior to methylation. Certain methylations are believed to secure DNA in a silenced state, and therefore demethylation may reduce the stability of silencing signals and confer relative gene activation.Azacitidine induces tumor regression on isocitrate dehydrogenase-1 mutant glioma xenografts in mice.In research, 5-azacitidine is commonly used for promoting cardiomyocyte differentiation of adult stem cells. However, it has been suggested that this drug has a compromised efficacy as a cardiac differentiation factor because it promotes the transdifferentiation of cardiac cells to skeletal myocytes.Azacitidine also has antiviral effects in animal studies as well as its anti-cancer actions, but has not been tested for clinical use. References External links "Azacitidine". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT02447666 for "Study With Azacitidine in Pediatric Subjects With Newly Diagnosed Advanced Myelodysplastic Syndrome (MDS) and Juvenile Myelomonocytic Leukemia (JMML)" at ClinicalTrials.gov

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

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

Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Some use the cutoff of 20 weeks of gestation, after which fetal death is known as a stillbirth. The most common symptom of a miscarriage is vaginal bleeding with or without pain. Sadness, anxiety, and guilt may occur afterwards. Tissue and clot-like material may leave the uterus and pass through and out of the vagina. Recurrent miscarriage may also be considered a form of infertility.Risk factors for miscarriage include being an older parent, previous miscarriage, exposure to tobacco smoke, obesity, diabetes, thyroid problems, and drug or alcohol use. About 80% of miscarriages occur in the first 12 weeks of pregnancy (the first trimester). The underlying cause in about half of cases involves chromosomal abnormalities. Diagnosis of a miscarriage may involve checking to see if the cervix is open or closed, testing blood levels of human chorionic gonadotropin (hCG), and an ultrasound. Other conditions that can produce similar symptoms include an ectopic pregnancy and implantation bleeding.Prevention is occasionally possible with good prenatal care. Avoiding drugs, alcohol, infectious diseases, and radiation may decrease the risk of miscarriage. No specific treatment is usually needed during the first 7 to 14 days. Most miscarriages will complete without additional interventions. Occasionally the medication misoprostol or a procedure such as vacuum aspiration is used to remove the remaining tissue. Women who have a blood type of rhesus negative (Rh negative) may require Rho(D) immune globulin. Pain medication may be beneficial. Emotional support may help with processing the loss.Miscarriage is the most common complication of early pregnancy. Among women who know they are pregnant, the miscarriage rate is roughly 10% to 20%, while rates among all fertilisation is around 30% to 50%. In those under the age of 35 the risk is about 10% while it is about 45% in those over the age of 40. Risk begins to increase around the age of 30. About 5% of women have two miscarriages in a row. Some recommend not using the term "abortion" in discussions with those experiencing a miscarriage in an effort to decrease distress. In Britain, the term "miscarriage" has replaced any use of the term "spontaneous abortion" in relation to pregnancy loss and in response to complaints of insensitivity towards women who had suffered such loss. An additional benefit of this change is reducing confusion among medical laymen, who may not realize that the term "spontaneous abortion" refers to a naturally-occurring medical phenomenon, and not the intentional termination of pregnancy. Signs and symptoms Signs of a miscarriage include vaginal spotting, abdominal pain, cramping, and fluid, blood clots, and tissue passing from the vagina. Bleeding can be a symptom of miscarriage, but many women also have bleeding in early pregnancy and do not miscarry. Bleeding during the first half of pregnancy may be referred to as a threatened miscarriage. Of those who seek treatment for bleeding during pregnancy, about half will miscarry. Miscarriage may be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing. Risk factors Miscarriage may occur for many reasons, not all of which can be identified. Risk factors are those things that increase the likelihood of having a miscarriage but do not necessarily cause a miscarriage. Up to 70 conditions, infections, medical procedures, lifestyle factors, occupational exposures, chemical exposure, and shift work are associated with increased risk for miscarriage. Some of these risks include endocrine, genetic, uterine, or hormonal abnormalities, reproductive tract infections, and tissue rejection caused by an autoimmune disorder. Trimesters First trimester Most clinically apparent miscarriages (two-thirds to three-quarters in various studies) occur during the first trimester. About 30% to 40% of all fertilized eggs miscarry, often before the pregnancy is known. The embryo typically dies before the pregnancy is expelled; bleeding into the decidua basalis and tissue necrosis causes uterine contractions to expel the pregnancy. Early miscarriages can be due to a developmental abnormality of the placenta or other embryonic tissues. In some instances an embryo does not form but other tissues do. This has been called a "blighted ovum".Successful implantation of the zygote into the uterus is most likely eight to ten days after fertilization. If the zygote has not implanted by day ten, implantation becomes increasingly unlikely in subsequent days.A chemical pregnancy is a pregnancy that was detected by testing but ends in miscarriage before or around the time of the next expected period.Chromosomal abnormalities are found in more than half of embryos miscarried in the first 13 weeks. Half of embryonic miscarriages (25% of all miscarriages) have an aneuploidy (abnormal number of chromosomes). Common chromosome abnormalities found in miscarriages include an autosomal trisomy (22–32%), monosomy X (5–20%), triploidy (6–8%), tetraploidy (2–4%), or other structural chromosomal abnormalities (2%). Genetic problems are more likely to occur with older parents; this may account for the higher rates observed in older women.Luteal phase progesterone deficiency may or may not be a contributing factor to miscarriage. Second and third trimesters Second trimester losses may be due to maternal factors such as uterine malformation, growths in the uterus (fibroids), or cervical problems. These conditions also may contribute to premature birth. Unlike first-trimester miscarriages, second-trimester miscarriages are less likely to be caused by a genetic abnormality; chromosomal aberrations are found in a third of cases. Infection during the third trimester can cause a miscarriage. Age The age of the pregnant woman is a significant risk factor. Miscarriage rates increase steadily with age, with more substantial increases after age 35. In those under the age of 35 the risk is about 10% while it is about 45% in those over the age of 40. Risk begins to increase around the age of 30. Paternal age is associated with increased risk. Obesity, eating disorders and caffeine Not only is obesity associated with miscarriage; it can result in sub-fertility and other adverse pregnancy outcomes. Recurrent miscarriage is also related to obesity. Women with bulimia nervosa and anorexia nervosa may have a greater risk for miscarriage. Nutrient deficiencies have not been found to impact miscarriage rates but hyperemesis gravidarum sometimes precedes a miscarriage.Caffeine consumption also has been correlated to miscarriage rates, at least at higher levels of intake. However, such higher rates are statistically significant only in certain circumstances. Vitamin supplementation has generally not shown to be effective in preventing miscarriage. Chinese traditional medicine has not been found to prevent miscarriage. Endocrine disorders Disorders of the thyroid may affect pregnancy outcomes. Related to this, iodine deficiency is strongly associated with an increased risk of miscarriage. The risk of miscarriage is increased in those with poorly controlled insulin-dependent diabetes mellitus. Women with well-controlled diabetes have the same risk of miscarriage as those without diabetes. Food poisoning Ingesting food that has been contaminated with listeriosis, toxoplasmosis, and salmonella is associated with an increased risk of miscarriage. Amniocentesis and chorionic villus sampling Amniocentesis and chorionic villus sampling (CVS) are procedures conducted to assess the fetus. A sample of amniotic fluid is obtained by the insertion of a needle through the abdomen and into the uterus. Chorionic villus sampling is a similar procedure with a sample of tissue removed rather than fluid. These procedures are not associated with pregnancy loss during the second trimester but they are associated with miscarriages and birth defects in the first trimester. Miscarriage caused by invasive prenatal diagnosis (chorionic villus sampling (CVS) and amniocentesis) is rare (about 1%). Surgery The effects of surgery on pregnancy are not well-known including the effects of bariatric surgery. Abdominal and pelvic surgery are not risk factors for miscarriage. Ovarian tumours and cysts that are removed have not been found to increase the risk of miscarriage. The exception to this is the removal of the corpus luteum from the ovary. This can cause fluctuations in the hormones necessary to maintain the pregnancy. Medications There is no significant association between antidepressant medication exposure and spontaneous abortion. The risk of miscarriage is not likely decreased by discontinuing SSRIs prior to pregnancy. Some available data suggest that there is a small increased risk of miscarriage for women taking any antidepressant, though this risk becomes less statistically significant when excluding studies of poor quality.Medicines that increase the risk of miscarriage include: retinoids nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen misoprostol methotrexate statins Immunizations Immunizations have not been found to cause miscarriage. Live vaccinations, like the MMR vaccine, can theoretically cause damage to the fetus as the live virus can cross the placenta and potentially increase the risk for miscarriage. Therefore, the Center for Disease Control (CDC) recommends against pregnant women receiving live vaccinations. However, there is no clear evidence that has shown live vaccinations to increase the risk for miscarriage or fetal abnormalities.Some live vaccinations include: MMR, varicella, certain types of the influenza vaccine, and rotavirus. Treatments for cancer Ionizing radiation levels given to a woman during cancer treatment cause miscarriage. Exposure can also impact fertility. The use of chemotherapeutic drugs used to treat childhood cancer increases the risk of future miscarriage. Pre-existing diseases Several pre-existing diseases in pregnancy can potentially increase the risk of miscarriage, including diabetes, polycystic ovary syndrome (PCOS), hypothyroidism, certain infectious diseases, and autoimmune diseases. PCOS may increase the risk of miscarriage. Two studies suggested treatment with the drug metformin significantly lowers the rate of miscarriage in women with PCOS, but the quality of these studies has been questioned. Metformin treatment in pregnancy has not been shown to be safe. In 2007 the Royal College of Obstetricians and Gynaecologists also recommended against use of the drug to prevent miscarriage. Thrombophilias or defects in coagulation and bleeding were once thought to be a risk in miscarriage but have been subsequently questioned. Severe cases of hypothyroidism increase the risk of miscarriage. The effect of milder cases of hypothyroidism on miscarriage rates has not been established. A condition called luteal phase defect (LPD) is a failure of the uterine lining to be fully prepared for pregnancy. This can keep a fertilized egg from implanting or result in miscarriage.Mycoplasma genitalium infection is associated with increased risk of preterm birth and miscarriage.Infections can increase the risk of a miscarriage: rubella (German measles), cytomegalovirus, bacterial vaginosis, HIV, chlamydia, gonorrhoea, syphilis, and malaria. Immune status Autoimmunity is a possible cause of recurrent or late-term miscarriages. In the case of an autoimmune-induced miscarriage, the womans body attacks the growing fetus or prevents normal pregnancy progression. Autoimmune disease may cause abnormalities in embryos, which in turn may lead to miscarriage. As an example, Celiac disease increases the risk of miscarriage by an odds ratio of approximately 1.4. A disruption in normal immune function can lead to the formation of antiphospholipid antibody syndrome. This will affect the ability to continue the pregnancy, and if a woman has repeated miscarriages, she can be tested for it. Approximately 15% of recurrent miscarriages are related to immunologic factors. The presence of anti-thyroid autoantibodies is associated with an increased risk with an odds ratio of 3.73 and 95% confidence interval 1.8–7.6. Having lupus also increases the risk for miscarriage. Immunohistochemical studies on decidual basalis and chorionic villi found that the imbalance of the immunological environment could be associated with recurrent pregnancy loss. Anatomical defects and trauma Fifteen per cent of women who have experienced three or more recurring miscarriages have some anatomical defect that prevents the pregnancy from being carried for the entire term. The structure of the uterus affects the ability to carry a child to term. Anatomical differences are common and can be congenital. In some women, cervical incompetence or cervical insufficiency occurs with the inability of the cervix to stay closed during the entire pregnancy. It does not cause first trimester miscarriages. In the second trimester, it is associated with an increased risk of miscarriage. It is identified after a premature birth has occurred at about 16–18 weeks into the pregnancy. During the second trimester, major trauma can result in a miscarriage. Smoking Tobacco (cigarette) smokers have an increased risk of miscarriage. There is an increased risk regardless of which parent smokes, though the risk is higher when the gestational mother smokes. Morning sickness Nausea and vomiting of pregnancy (NVP, or morning sickness) is associated with a decreased risk. Several possible causes have been suggested for morning sickness but there is still no agreement. NVP may represent a defense mechanism which discourages the mothers ingestion of foods that are harmful to the fetus; according to this model, a lower frequency of miscarriage would be an expected consequence of the different food choices made by women experiencing NVP. Chemicals and occupational exposure Chemical and occupational exposures may have some effect in pregnancy outcomes. A cause and effect relationship almost can never be established. Those chemicals that are implicated in increasing the risk for miscarriage are DDT, lead, formaldehyde, arsenic, benzene and ethylene oxide. Video display terminals and ultrasound have not been found to have an effect on the rates of miscarriage. In dental offices where nitrous oxide is used with the absence of anesthetic gas scavenging equipment, there is a greater risk of miscarriage. For women who work with cytotoxic antineoplastic chemotherapeutic agents there is a small increased risk of miscarriage. No increased risk for cosmetologists has been found. Other Alcohol increases the risk of miscarriage. Cocaine use increases the rate of miscarriage. Some infections have been associated with miscarriage. These include Ureaplasma urealyticum, Mycoplasma hominis, group B streptococci, HIV-1, and syphilis. Infections of Chlamydia trachomatis, Camphylobacter fetus, and Toxoplasma gondii have not been found to be linked to miscarriage. Subclinical infections of the lining of the womb, commonly known as chronic endometritis are also associated with poor pregnancy outcomes, compared to women with treated chronic endometritis or no chronic endometritis. Diagnosis In the case of blood loss, pain, or both, transvaginal ultrasound is performed. If a viable intrauterine pregnancy is not found with ultrasound, blood tests (serial βHCG tests) can be performed to rule out ectopic pregnancy, which is a life-threatening situation.If hypotension, tachycardia, and anemia are discovered, exclusion of an ectopic pregnancy is important.A miscarriage may be confirmed by an obstetric ultrasound and by the examination of the passed tissue. When looking for microscopic pathologic symptoms, one looks for the products of conception. Microscopically, these include villi, trophoblast, fetal parts, and background gestational changes in the endometrium. When chromosomal abnormalities are found in more than one miscarriage, genetic testing of both parents may be done. Ultrasound criteria A review article in The New England Journal of Medicine based on a consensus meeting of the Society of Radiologists in Ultrasound in America (SRU) has suggested that miscarriage should be diagnosed only if any of the following criteria are met upon ultrasonography visualization: Classification A threatened miscarriage is any bleeding during the first half of pregnancy. At investigation it may be found that the fetus remains viable and the pregnancy continues without further problems.An anembryonic pregnancy (also called an "empty sac" or "blighted ovum") is a condition where the gestational sac develops normally, while the embryonic part of the pregnancy is either absent or stops growing very early. This accounts for approximately half of miscarriages. All other miscarriages are classified as embryonic miscarriages, meaning that there is an embryo present in the gestational sac. Half of embryonic miscarriages have aneuploidy (an abnormal number of chromosomes).An inevitable miscarriage occurs when the cervix has already dilated, but the fetus has yet to be expelled. This usually will progress to a complete miscarriage. The fetus may or may not have cardiac activity. A complete miscarriage is when all products of conception have been expelled; these may include the trophoblast, chorionic villi, gestational sac, yolk sac, and fetal pole (embryo); or later in pregnancy the fetus, umbilical cord, placenta, amniotic fluid, and amniotic membrane. The presence of a pregnancy test that is still positive, as well as an empty uterus upon transvaginal ultrasonography, does, however, fulfil the definition of pregnancy of unknown location. Therefore, there may be a need for follow-up pregnancy tests to ensure that there is no remaining pregnancy, including ectopic pregnancy. An incomplete miscarriage occurs when some products of conception have been passed, but some remains inside the uterus. However, an increased distance between the uterine walls on transvaginal ultrasonography may also simply be an increased endometrial thickness and/or a polyp. The use of a Doppler ultrasound may be better in confirming the presence of significant retained products of conception in the uterine cavity. In cases of uncertainty, ectopic pregnancy must be excluded using techniques like serial beta-hCG measurements. A missed miscarriage is when the embryo or fetus has died, but a miscarriage has not yet occurred. It is also referred to as delayed miscarriage, silent miscarriage, or missed abortion.A septic miscarriage occurs when the tissue from a missed or incomplete miscarriage becomes infected, which carries the risk of spreading infection (septicaemia) and can be fatal.Recurrent miscarriage ("recurrent pregnancy loss" (RPL) or "habitual abortion") is the occurrence of multiple consecutive miscarriages; the exact number used to diagnose recurrent miscarriage varies. If the proportion of pregnancies ending in miscarriage is 15% and assuming that miscarriages are independent events, then the probability of two consecutive miscarriages is 2.25% and the probability of three consecutive miscarriages is 0.34%. The occurrence of recurrent pregnancy loss is 1%. A large majority (85%) of those who have had two miscarriages will conceive and carry normally afterward.The physical symptoms of a miscarriage vary according to the length of pregnancy, though most miscarriages cause pain or cramping. The size of blood clots and pregnancy tissue that are passed become larger with longer gestations. After 13 weeks gestation, there is a higher risk of placenta retention. Prevention Prevention of a miscarriage can sometimes be accomplished by decreasing risk factors. This may include good prenatal care, avoiding drugs and alcohol, preventing infectious diseases, and avoiding x-rays. Identifying the cause of the miscarriage may help prevent future pregnancy loss, especially in cases of recurrent miscarriage. Often there is little a person can do to prevent a miscarriage. Vitamin supplementation before or during pregnancy has not been found to affect the risk of miscarriage. Progesterone has been shown to prevent miscarriage in women with 1) vaginal bleeding early in their current pregnancy and 2) a previous history of miscarriage. Non-modifiable risk factors Preventing a miscarriage in subsequent pregnancies may be enhanced with assessments of: Modifiable risk factors Maintaining a healthy weight and good prenatal care can reduce the risk of miscarriage. Some risk factors can be minimized by avoiding the following: Smoking Cocaine use Alcohol Poor nutrition Occupational exposure to agents that can cause miscarriage Medications associated with miscarriage Drug abuse Management Women who miscarry early in their pregnancy usually do not require any subsequent medical treatment but they can benefit from support and counseling. Most early miscarriages will complete on their own; in other cases, medication treatment or aspiration of the products of conception can be used to remove remaining tissue. While bed rest has been advocated to prevent miscarriage, this has not been found to be of benefit. Those who are experiencing or who have experienced a miscarriage benefit from the use of careful medical language. Significant distress can often be managed by the ability of the clinician to clearly explain terms without suggesting that the woman or couple are somehow to blame.Evidence to support Rho(D) immune globulin after a spontaneous miscarriage is unclear. In the UK, Rho(D) immune globulin is recommended in Rh-negative women after 12 weeks gestational age and before 12 weeks gestational age in those who need surgery or medication to complete the miscarriage. Methods No treatment is necessary for a diagnosis of complete miscarriage (so long as ectopic pregnancy is ruled out). In cases of an incomplete miscarriage, empty sac, or missed abortion there are three treatment options: watchful waiting, medical management, and surgical treatment. With no treatment (watchful waiting), most miscarriages (65–80%) will pass naturally within two to six weeks. This treatment avoids the possible side effects and complications of medications and surgery, but increases the risk of mild bleeding, need for unplanned surgical treatment, and incomplete miscarriage. Medical treatment usually consists of using misoprostol (a prostaglandin) alone or in combination with mifepristone pre-treatment. These medications help the uterus to contract and expel the remaining tissue out of the body. This works within a few days in 95% of cases. Vacuum aspiration or sharp curettage can be used, with vacuum aspiration being lower-risk and more common. Delayed and incomplete miscarriage In delayed or incomplete miscarriage, treatment depends on the amount of tissue remaining in the uterus. Treatment can include surgical removal of the tissue with vacuum aspiration or misoprostol. Studies looking at the methods of anaesthesia for surgical management of incomplete miscarriage have not shown that any adaptation from normal practice is beneficial. Induced miscarriage An induced abortion may be performed by a qualified healthcare provider for women who cannot continue the pregnancy. Self-induced abortion performed by a woman or non-medical personnel can be dangerous and is still a cause of maternal mortality in some countries. In some locales it is illegal or carries heavy social stigma. However, in the United States, many choose to self-induce or self-manage their abortion and have done so safely. Sex Some organizations recommend delaying sex after a miscarriage until the bleeding has stopped to decrease the risk of infection. However, there is not sufficient evidence for the routine use of antibiotic to try to avoid infection in incomplete abortion. Others recommend delaying attempts at pregnancy until one period has occurred to make it easier to determine the dates of a subsequent pregnancy. There is no evidence that getting pregnant in that first cycle affects outcomes and an early subsequent pregnancy may actually improve outcomes. Support Organizations exist that provide information and counselling to help those who have had a miscarriage. Family and friends often conduct a memorial or burial service. Hospitals also can provide support and help memorialize the event. Depending on locale others desire to have a private ceremony. Providing appropriate support with frequent discussions and sympathetic counselling are part of evaluation and treatment. Those who experience unexplained miscarriage can be treated with emotional support. Miscarriage leave Miscarriage leave is leave of absence in relation to miscarriage. The following countries offer paid or unpaid leave to women who have had a miscarriage. The Philippines – 60 days fully paid leave for miscarriages (before 20 weeks of gestation) or emergency termination of the pregnancy (on the 20th week or after) The husband of the mother gets seven days fully paid leave up to the 4th pregnancy. India – six weeks leave New Zealand – three days bereavement leave for both parents Mauritius – two weeks leave Indonesia – six weeks leave Taiwan – five days, one week or four weeks, depending on how advanced the pregnancy was Outcomes Psychological and emotional effects Every womans personal experience of miscarriage is different, and women who have more than one miscarriage may react differently to each event.In Western cultures since the 1980s, medical providers assume that experiencing a miscarriage "is a major loss for all pregnant women". A miscarriage can result in anxiety, depression or stress for those involved. It can have an effect on the whole family. Many of those experiencing a miscarriage go through a grieving process. "Prenatal attachment" often exists that can be seen as parental sensitivity, love and preoccupation directed toward the unborn child. Serious emotional impact is usually experienced immediately after the miscarriage. Some may go through the same loss when an ectopic pregnancy is terminated. In some, the realization of the loss can take weeks. Providing family support to those experiencing the loss can be challenging because some find comfort in talking about the miscarriage while others may find the event painful to discuss. The father can have the same sense of loss. Expressing feelings of grief and loss can sometimes be harder for men. Some women are able to begin planning their next pregnancy after a few weeks of having the miscarriage. For others, planning another pregnancy can be difficult. Some facilities acknowledge the loss. Parents can name and hold their infant. They may be given mementos such as photos and footprints. Some conduct a funeral or memorial service. They may express the loss by planting a tree.Some health organizations recommend that sexual activity be delayed after the miscarriage. The menstrual cycle should resume after about three to four months. Women report that they were dissatisfied with the care they received from physicians and nurses. Subsequent pregnancies Some parents want to try to have a baby very soon after the miscarriage. The decision of trying to become pregnant again can be difficult. Reasons exist that may prompt parents to consider another pregnancy. For older mothers, there may be some sense of urgency. Other parents are optimistic that future pregnancies are likely to be successful. Many are hesitant and want to know about the risk of having another or more miscarriages. Some clinicians recommend that the women have one menstrual cycle before attempting another pregnancy. This is because the date of conception may be hard to determine. Also, the first menstrual cycle after a miscarriage can be much longer or shorter than expected. Parents may be advised to wait even longer if they have experienced late miscarriage or molar pregnancy, or are undergoing tests. Some parents wait for six months based upon recommendations from their health care provider.The risks of having another miscarriage vary according to the cause. The risk of having another miscarriage after a molar pregnancy is very low. The risk of another miscarriage is highest after the third miscarriage. Pre-conception care is available in some locales. Later cardiovascular disease There is a significant association between miscarriage and later development of coronary artery disease, but not of cerebrovascular disease. Epidemiology Among women who know they are pregnant, the miscarriage rate is roughly 10% to 20%, while rates among all fertilized zygotes are around 30% to 50%. A 2012 review found the risk of miscarriage between 5 and 20 weeks from 11% to 22%. Up to the 13th week of pregnancy, the risk of miscarriage each week was around 2%, dropping to 1% in week 14 and reducing slowly between 14 and 20 weeks.The precise rate is not known because a large number of miscarriages occur before pregnancies become established and before the woman is aware she is pregnant. Additionally, those with bleeding in early pregnancy may seek medical care more often than those not experiencing bleeding. Although some studies attempt to account for this by recruiting women who are planning pregnancies and testing for very early pregnancy, they still are not representative of the wider population.The prevalence of miscarriage increases with the age of both parents. In a Danish register-based study where the prevalence of miscarriage was 11%, the prevalence rose from 9% at 22 years of age to 84% by 48 years of age. Another, later study in 2013 found that when either parent was over the age of 40, the rate of known miscarriages doubled.In 2010, 50,000 inpatient admissions for miscarriage occurred in the UK. Terminology Most affected women and family members refer to miscarriage as the loss of a baby, rather than an embryo or fetus, and healthcare providers are expected to respect and use the language that the person chooses. Clinical terms can suggest blame, increase distress, and even cause anger. Terms that are known to cause distress in those experiencing miscarriage include: abortion (including spontaneous abortion) rather than miscarriage, habitual aborter rather than a woman experiencing recurrent pregnancy loss, products of conception rather than baby, blighted ovum rather than early pregnancy loss or delayed miscarriage, cervical incompetence rather than cervical weakness, and evacuation of retained products of conception (ERPC) rather than surgical management of miscarriage.Pregnancy loss is a broad term that is used for miscarriage, ectopic and molar pregnancies. The term fetal death applies variably in different countries and contexts, sometimes incorporating weight, and gestational age from 16 weeks in Norway, 20 weeks in the US and Australia, 24 weeks in the UK to 26 weeks in Italy and Spain. A fetus that died before birth after this gestational age may be referred to as a stillbirth. Under UK law, all stillbirths should be registered, although this does not apply to miscarriages. History The medical terminology applied to experiences during early pregnancy has changed over time. Before the 1980s, health professionals used the phrase spontaneous abortion for a miscarriage and induced abortion for a termination of the pregnancy. In the late 1980s and 1990s, doctors became more conscious of their language in relation to early pregnancy loss. Some medical authors advocated change to use of miscarriage instead of spontaneous abortion because they argued this would be more respectful and help ease a distressing experience. The change was being recommended by some in the profession in Britain in the late 1990s. In 2005 the European Society for Human Reproduction and Embryology (ESHRE) published a paper aiming to facilitate a revision of nomenclature used to describe early pregnancy events. Society and culture Societys reactions to miscarriage have changed over time. In the early 20th century, the focus was on the mothers physical health and the difficulties and disabilities that miscarriage could produce. Other reactions, such as the expense of medical treatments and relief at ending an unwanted pregnancy, were also heard. In the 1940s and 1950s, people were more likely to express relief, not because the miscarriage ended an unwanted or mistimed pregnancy, but because people believed that miscarriages were primarily caused by birth defects, and miscarrying meant that the family would not raise a child with disabilities. The dominant attitude in the mid-century was that a miscarriage, although temporarily distressing, was a blessing in disguise for the family, and that another pregnancy and a healthier baby would soon follow, especially if women trusted physicians and reduced their anxieties. Media articles were illustrated with pictures of babies, and magazine articles about miscarriage ended by introducing the healthy baby—usually a boy—that had shortly followed it.Beginning in the 1980s, miscarriage in the US was primarily framed in terms of the individual womans personal emotional reaction, and especially her grief over a tragic outcome. The subject was portrayed in the media with images of an empty crib or an isolated, grieving woman, and stories about miscarriage were published in general-interest media outlets, not just womens magazines or health magazines. Family members were encouraged to grieve, to memorialize their losses through funerals and other rituals, and to think of themselves as being parents. This shift to recognizing these emotional responses was partly due to medical and political successes, which created an expectation that pregnancies are typically planned and safe, and to womens demands that their emotional reactions no longer be dismissed by the medical establishments. It also reinforces the anti-abortion movement’s belief that human life begins at conception or early in pregnancy, and that motherhood is a desirable life goal. The modern one-size-fits-all model of grief does not fit every womans experience, and an expectation to perform grief creates unnecessary burdens for some women. The reframing of miscarriage as a private emotional experience brought less awareness of miscarriage and a sense of silence around the subject, especially compared to the public discussion of miscarriage during campaigns for access to birth control during the early 20th century, or the public campaigns to prevent miscarriages, stillbirths, and infant deaths by reducing industrial pollution during the 1970s.In places where induced abortion is illegal or carries social stigma, suspicion may surround miscarriage, complicating an already sensitive issue. In the 1960s, the use of the word miscarriage in Britain (instead of spontaneous abortion) occurred after changes in legislation. Developments in ultrasound technology (in the early 1980s) allowed them to identify earlier miscarriages.According to French statutes, an infant born before the age of viability, determined to be 28 weeks, is not registered as a child. If birth occurs after this, the infant is granted a certificate that allows women who have given birth to a stillborn child, to have a symbolic record of that child. This certificate can include a registered and given name to allow a funeral and acknowledgement of the event. Other animals Miscarriage occurs in all animals that experience pregnancy, though in such contexts it is more commonly referred to as a spontaneous abortion (the two terms are synonymous). There are a variety of known risk factors in non-human animals. For example, in sheep, miscarriage may be caused by crowding through doors, or being chased by dogs. In cows, spontaneous abortion may be caused by contagious disease, such as brucellosis or Campylobacter, but often can be controlled by vaccination. In many species of sharks and rays, stress induced miscarriage occurs frequently on capture.Other diseases are also known to make animals susceptible to miscarriage. Spontaneous abortion occurs in pregnant prairie voles when their mate is removed and they are exposed to a new male, an example of the Bruce effect, although this effect is seen less in wild populations than in the laboratory. Female mice who had spontaneous abortions showed a sharp rise in the amount of time spent with unfamiliar males preceding the abortion than those who did not. See also Pregnancy and Infant Loss Remembrance Day Citations General and cited references Hoffman, Barbara; J. Whitridge Williams (2012). Williams Gynecology (2nd ed.). New York: McGraw-Hill Medical. ISBN 978-0071716727. == External links ==

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

I need a basic explanation for the medical term 'Bat ear.'

Bat ear may refer to: Protruding ear, an abnormally protruding human ear A shape of dog ear; see Canine terminology The ear of a bat, used for echolocation The ear of a nocturnal insect, primarily used to detect calls from insectivorous bats See also Bat-eared fox

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

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

Granulomatous meningoencephalitis (GME) is an inflammatory disease of the central nervous system (CNS) of dogs and, rarely, cats. It is a form of meningoencephalitis. GME is likely second only to encephalitis caused by canine distemper virus as the most common cause of inflammatory disease of the canine CNS. The disease is more common in female dogs of young and middle age. It has a rapid onset. The lesions of GME exist mainly in the white matter of the cerebrum, brainstem, cerebellum, and spinal cord. The cause is only known to be noninfectious and is considered at this time to be idiopathic. Because lesions resemble those seen in allergic meningoencephalitis, GME is thought to have an immune-mediated cause, but it is also thought that the disease may be based on an abnormal response to an infectious agent. One study searched for viral DNA from canine herpesvirus, canine adenovirus, and canine parvovirus in brain tissue from dogs with GME, necrotizing meningoencephalitis, and necrotizing leukoencephalitis (see below for the latter two conditions), but failed to find any. Types of GME Disseminated – This is a diffuse disease throughout the CNS. It was previously known as inflammatory reticulosis. There is an accumulation of mononuclear cells and neutrophils around the blood vessels (perivascular) of the CNS. Meningitis is seen with this form of GME and causes fever and neck pain. It has an acute progression over a few weeks. Symptoms include incoordination, nystagmus, head tilt, seizures, and depression. Focal – The disease presents as a granuloma, which mimics a tumor. It usually is found in the cerebrum or cerebellopontine angle. Symptoms may be acute or develop slowly over several months and depend on the location of the lesion. Ocular – This is an uncommon form of GME and is characterized by sudden blindness caused by optic neuritis. The disease is bilateral. Ocular GME is considered to be an extension of CNS disease. The blood vessels of the posterior segment of the eye and anterior uvea have the same infiltrates of inflammatory cells as the intracranial vessels. Uveitis, retinal detachment, and secondary glaucoma may be seen. Diagnosis and treatment Cerebrospinal fluid (CSF) analysis shows a large number of white blood cells. Typically small mature lymphocytes are the majority of cells seen, with monocytes and neutrophils making up the rest. Definitive diagnosis is based on histopathology, either a brain biopsy or post-mortem evaluation (necropsy). A CT scan or MRI will show patchy, diffuse, or multifocal lesions. For a number of years, the basic treatment was some type of corticosteroid in combination with one or more immunosuppressive drugs, typically cytosine arabinoside and/or cyclosporine or other medications such as azathioprine, cyclophosphamide, or procarbazine, of which were usually added one at a time to the corticosteroid until a successful combination was found. There is evidence that treatment with radiation therapy for focal GME provides the longest periods of remission. Pug dog encephalitis Pug dog encephalitis (PDE) is an idiopathic inflammatory disease primarily affecting the prosencephalon (forebrain and thalamus). It is also known as necrotizing meningoencephalitis. The disease may be inherited in Pugs and Maltese and has been diagnosed in other breeds as well (Yorkies, Chihuahuas). The prevalence of PDE in pugs is about 1%. It differs in pathology from GME by more tissue breakdown and increased eosinophils (white blood cells). CSF analysis is also unique among inflammatory CNS diseases in dogs in that the cells are predominantly lymphocytes, instead of a mixed population of mononuclear cells. In Maltese and Pugs, there is extensive necrosis and inflammation of the gray matter of the cerebrum and subcortical white matter. The most common early symptoms are related to forebrain disease and include seizures and dementia, and later circling, head tilt, and blindness with normal pupillary light reflexes may be seen. PDE has a poor prognosis. Necrotizing leukoencephalitis In Yorkshire Terriers there can be severe mononuclear inflammation of the brainstem and periventricular cerebral white matter. Because the condition in this breed frequently affects only the white matter, it has been called necrotizing leukoencephalitis. Symptoms of brainstem and central vestibular disease predominate. Other types of noninfectious meningoencephalitis Steroid-responsive meningoencephalitis is any noninfectious meningoencephalitis that responds well to corticosteroids and usually has an excellent prognosis. This could represent mild forms of GME or PDE, but there are two separate conditions recognized also. Steroid-responsive meningitis/arteritis, also known as necrotizing vasculitis, is seen most commonly in Beagles, Boxers, Bernese Mountain Dogs, and German Shorthaired Pointers younger than two years of age. Many cases have fever, loss of appetite, and severe neck pain without other neurologic symptoms, although long-term cases may have incoordination and limb weakness or paralysis. CSF analysis shows predominantly neutrophils. In Beagles this condition is also known as Beagle pain syndrome. Eosinophilic meningoencephalomyelitis is seen mainly in Golden Retrievers. CSF analysis shows predominantly eosinophils. An acute progressive pyogranulomatous meningoencephalomyelitis is seen in mature Pointer dogs. There is monocytic and neutrophilic infiltration of the leptomeninges. Symptoms include incoordination, reluctance to move, and neck rigidity. See also Encephalitis Meningitis == References ==

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

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

Filippi syndrome, also known as Syndactyly Type I with Microcephaly and Mental Retardation, is a very rare autosomal recessive genetic disease. Only a very limited number of cases have been reported to date. Filippi Syndrome is associated with diverse symptoms of varying severity across affected individuals, for example malformation of digits, craniofacial abnormalities, intellectual disability, and growth retardation. The diagnosis of Filippi Syndrome can be done through clinical observation, radiography, and genetic testing. Filippi Syndrome cannot be cured directly as of 2022, hence the main focus of treatments is on tackling the symptoms observed on affected individuals. It was first reported in 1985. Signs and symptoms The symptoms of Filippi Syndrome can be congenital (apparent as an infant). The occurrence and severity of such symptoms are variable across affected individuals. The progression of symptoms over ones lifetime has not been thoroughly studied due to the small number of people with Filippi Syndrome globally. Malformations of digits Malformations of digits are expressed among people with Filippi Syndrome. One of the most common malformations is the webbing or fusion of digits, which is termed syndactyly. In particular, syndactyly of the third and fourth fingers or the second, third and fourth toes is termed "syndactyly type 1". The degree of syndactyly may differ across affected individuals, with some exhibiting syndactyly of soft tissues and skin only, and more severe cases exhibiting syndactyly of digital bones.Other malformations of digits include clinodactyly (curving) of the fifth fingers and brachydactyly (abnormal shortening) of digits. Brachydactyly is believed to be largely due to abnormalities arising from the bones inside the hands and feet, specifically the metacarpals and metatarsals. Craniofacial abnormalities Furthermore, most people with Filippi Syndrome exhibit craniofacial abnormalities. Craniofacial abnormalities are birth defects observed at the head or face region of affected individuals. Some of the craniofacial abnormalities present in people with Filippi Syndrome include microcephaly (having a skull that is smaller than normal), prominent/ elevated nasal bridge, hypertelorism (having ones pair of eyes further apart from each other than normal), and underdeveloped nasal alae (underdeveloped tissues surrounding the nostril). Less common craniofacial abnormalities include having a broad forehead, thin vermilion border (having a thin upper lip), and frontal hirsutism (having a hairy forehead). Mental retardation People with Filippi Syndrome may also demonstrate varying degrees of intellectual disability. Affected individuals may experience defective speech development, aphasia (experiencing difficulty in finding the appropriate words to use), vision impairment, and an inability to speak. Growth retardation Another characteristic symptom of people with Filippi Syndrome is the occurrence of growth retardation, which is also referred to as growth delay. Such growth delays may be either prenatal or postnatal, meaning that they can occur both before and after birth. In particular, delayed bone maturation can be observed in patients with Filippi Syndrome. Other symptoms People with Filippi Syndrome may exhibit some other physical abnormalities. Examples of such abnormalities include dwarfism (having a severely short stature), dislocated elbows, decreased joint mobility, muscular hypotonia (having weak muscle tone), and involuntary muscle stiffness.They may also exhibit abnormal conditions at their skin and teeth. Moreover, a portion of affected males may demonstrate cryptorchidism (a condition in which the testes fail to descend into the scrotum). Causes Filippi syndrome is a genetic disease with an autosomal recessive inheritance pattern at the Cytoskeleton Associated Protein 2 Like (CKAP2L) gene. Inheritance pattern An autosomal recessive inheritance pattern means that the disease trait is exhibited on an individual only when both copies of the disease gene in the individual demonstrate a specific pathogenic mutation. This happens when the individual inherits one copy of the mutated gene from each of their parents. In the case of Filippi Syndrome, both copies of the CKAP2L gene of an individual have to be mutated in order for them to demonstrate symptoms of the disorder. CKAP2L gene The CKAP2L gene is the human ortholog of the mouse CKAP2I (Radmis) gene. It contains 10 exons and is located on chromosome 2q14.1. It is a protein-coding gene that is associated with microtubules and some cellular structures involved in mitosis. The CKAP2L gene is essential for the proper formation of mitotic spindles during mitosis and the progression of the cell cycle of human cells. The expression pattern of the CKAP2L gene can explain the occurrence of syndactyly in Filippi Syndrome. Mutations Multiple mutations at the CKAP2L gene can cause Filippi Syndrome. Some of these mutations include a 1-base pair duplication in exon 4, a 2-base pair insertion in exon 2, a 1-base pair deletion in exon 4, and a 329-base pair deletion in exon 4 of the gene. The above mutations cause a frameshift in the gene. A frameshift mutation refers to a condition in which the reading frame of the gene is disrupted by the insertion or deletion of base pairs from the gene (if the number of inserted or deleted base pairs is not divisible by three). This frameshift mutation ultimately results in a premature termination codon (the formation of a termination codon at a position more "forward" than normal). Other mutations include a base pair transition in the start codon, which is the starting site of translation of the gene. A transition mutation occurring at this codon disrupts the codon sequence and abolishes the site. This prevents the cell from carrying out translation of the gene. Diagnosis The diagnosis of Filippi Syndrome is mostly done postnatally. Initial diagnosis of the disease relies on clinical observation of symptoms, including different degrees of syndactyly and craniofacial abnormalities, exhibited by affected individuals. Diagnosis can also be done through radiography, which checks for malformation of digits.Confirmation of diagnosis requires the use of genetic testing. Specifically, it can be done through detecting mutations in the CKAP2L gene, of which a total of eight causative variants having been identified.Genetic testing of Filippi Syndrome makes use of three major techniques: Whole Exome Sequencing, which focuses on sequencing the exons in the region of the genome coding for proteins. Next-generation Sequencing, which is a high-throughput genomic sequence analysis method that make use of flow cytometry, and is able to analyze gigabases of sequences in one instrument run. Array Based Techniques, which makes use of microarray applications to determine chromosomal abnormalities with greater precision compare to the conventional karyotyping tests. Treatment Currently, Filippi Syndrome has no direct cure. It is treated according to observed symptoms on affected individuals. Syndactyly release surgery Syndactyly exhibit varying degrees of severity in individuals. Hence not all affected individuals with this condition must undergo surgical intervention. For example, syndactyly that occurs at the proximal end of the digits may have limited effect on the normal functioning of the hand and foot, and correction through surgery is optional.Simple syndactyly is the condition of cutaneous fusion between two digits, and can be treated by surgically rebuilding the hourglass shape web space between digits. During surgery, incision is first carried out to separate the fused fingers. It is followed by reconstruction of the web spaces side walls using dorsal advancement flaps or skin grafts obtained from the affected individuals groin. After reconstruction, additional fingerpulp flaps are required for rebuilding of the nailfold between the nail bed and the surrounding skin if there is the occurrence of syndactyly at the tip of the fingers.Treatment for complex syndactyly, which refers to the bony fusion between two digits, has a higher degree of complexity. It involves the reconstruction of web space as well as highly specific surgical procedures with accordance to different types of bony fusion. It may also require separation and relocation of the flexor digitorum profundus or tendon-diverted transplantation if the structure of the tendons in the fused digits are also affected by syndactyly.Professionals usually advice that affected individuals receive surgical treatment during the first two years of life to avoid hindrance to motor ability development. Craniofacial surgery Craniofacial abnormalities can be corrected through surgical methods. Affected individuals with severe hypertelorism may undergo orbital osteotomy. The two major osteotomy methods are box osteotomy and facial bipartition, which operate from different osteotomy sites but follow the same general procedures. During surgery, part of the bone, and sometimes excessive skin, are selectively removed from the central area of the nasofrontal region, such that this part of the skull can close in and correct hypertelorism. In addition, bone grafts are placed to provide support to the eyeballs and protect them from displacement.Underdeveloped nasal alae can be corrected by orofacial reconstruction. This procedure recreates the nasal alae with the use of cartilage grafts, which are cartilage taken from the patients ear, septum or rib. Afterwards, nasolabial flaps are placed to sustain the shape of the nose, specifically the alar groove. Speech therapy Patients who are affected by speech impairments can be treated by speech therapy.Speech disability can be a manifestation of various physical or psychological causes. Symptomatic treatment of it is carried out after diagnostic tests such as video fluoroscopic barium study ("cookie swallow" test) or fiber-optic endoscopic evaluation. Despite the diversity in speech therapy techniques, most treatment plans follow the same progression: Identification of defective features Assistance with producing simple sounds; physical contact may be required to aid with motor speech disorders Refrainment of assistance that allows patient to develop self-correction ability Increase in length of syllables or speech Self-evaluation of progress and provide explanation on the cause of improvementsFor post-treatment monitoring, computer-based speech therapy that makes use of instructional software can provide computer-led practices as aftercare and quantify performances outside of conventional treatments. Epidemiology Filippi syndrome is rare, with an estimated prevalence of less than one in a million. It has around thirty cases recorded in medical literature.The number of affected males recorded is more than twice the number of affected females. However, this is insufficient to conclude that male are at a higher risk due to the small number of reported cases. However, the CDC says less than 25 cases have been reported, the National Organization for Rare Disorders says about 18 cases have been reported, while the National Center for Advancing Translational Sciences says 30 cases have been reported in literature. == References ==

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

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

Bromfenac is a nonsteroidal anti-inflammatory drug (NSAID) marketed in the US as an ophthalmic solution (brand names Prolensa and Bromday, prior formulation brand name Xibrom, which has since been discontinued) by ISTA Pharmaceuticals for short-term, local use. Prolensa and Bromday are the once-daily formulation of bromfenac, while Xibrom was approved for twice-daily administration. In the European Union, the brand name is Yellox. Bromfenac is indicated for the treatment of ocular inflammation and pain after cataract surgery. Medical uses Bromfenac is indicated for the treatment of postoperative ocular inflammation following cataract extraction.The drug has been shown to reduce macular edema and thickness of the retina (an indicator for inflammation) and improve visual acuity after surgery. Contraindications Bromfenac is contraindicated for people with adverse reactions to NSAIDs, such as asthma or rashes. Side effects Bromfenac eye drops are generally well tolerated. Comparatively common side effects in clinical studies included abnormal sensations in eye (0.5% of people treated with bromfenac), mild to moderate erosion of the cornea (0.4%), eye pruritus (0.4%), eye pain (0.3%) and redness (0.3%). Serious side effects such as corneal perforation were not reported in studies but only during post-marketing in less than one patient in 1000. Interactions No systematic interaction studies have been performed. There are no known cases of interactions with antibiotic eye drops. Blood plasma levels remain very low during bromfenac therapy, so interactions with drugs taken by mouth are unlikely. Pharmacology Mechanism of action As an NSAID, bromfenac works by inhibiting prostaglandin synthesis by blocking the cyclooxygenase (COX) enzymes. It preferably acts on COX-2 and only has a low affinity for COX-1. Pharmacokinetics Bromfenac is well absorbed through the cornea and reaches highest concentrations in the aqueous humour after 150 to 180 minutes, with a biological half-life of 1.4 hours and high drug levels being maintained for at least 12 hours. It is mainly concentrated in the aqueous humour and conjunctiva, and much less in the lens and vitreous body.Concentrations in the blood plasma are too low to be measured quantitatively. 99.8% of the substance are bound to plasma proteins. The enzyme mainly responsible for metabolization of bromfenac is CYP2C9, and metabolites include the lactam and several conjugated compounds. 82% are excreted via the urine, and 13% via the faeces.The high degree of penetration and potency of bromfenac can be attributed to the halogenation of the molecule: by adding a bromine the NSAID becomes highly lipophilic which allows for rapid, sustained drug levels in the ocular tissues. Chemistry Along with indomethacin, diclofenac and others, bromfenac belongs to the acetic acid group of NSAIDs. It is used in form of bromfenac sodium · 1.5 H2O (CAS number: 120638-55-3 ), which is soluble in water, methanol and aqueous bases, insoluble in chloroform and aqueous acids, and melts at 284 to 286 °C (543 to 547 °F) under decomposition. History For ophthalmic use, bromfenac has been prescribed more than 20,000,000 times across the world. As an eye drop, it has been available since 2000, starting in Japan where it was sold as Bronuck. It was first FDA approved for use in the United States in 2005, and it was marketed as Xibrom, twice-daily. In October 2010 Bromday received FDA approval as a new, once-daily formulation. More recently, in 2013, Prolensa has also been approved by the FDA. Bromfenac eye drops have been marketed in the European Union since 2011, and are available on worldwide markets with agreements from Bausch & Lomb, Croma-Pharma, and other companies.Bromfenac was formerly marketed in the United States by Wyeth-Ayerst in an oral formulation called Duract for short-term relief of pain (less than 10 days at a time). It was brought to market in July 1997, and was withdrawn 22 June 1998, following numerous reports of hepatotoxicity in patients who had taken the medication for longer than the recommended 10-day period. References External links "Bromfenac". Drug Information Portal. U.S. National Library of Medicine. "Bromfenac sodium". Drug Information Portal. U.S. National Library of Medicine.

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

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

Visual agnosia is an impairment in recognition of visually presented objects. It is not due to a deficit in vision (acuity, visual field, and scanning), language, memory, or intellect. While cortical blindness results from lesions to primary visual cortex, visual agnosia is often due to damage to more anterior cortex such as the posterior occipital and/or temporal lobe(s) in the brain.[2] There are two types of visual agnosia: apperceptive agnosia and associative agnosia. Recognition of visual objects occurs at two primary levels. At an apperceptive level, the features of the visual information from the retina are put together to form a perceptual representation of an object. At an associative level, the meaning of an object is attached to the perceptual representation and the object is identified. If a person is unable to recognize objects because they cannot perceive correct forms of the objects, although their knowledge of the objects is intact (i.e. they do not have anomia), they have apperceptive agnosia. If a person correctly perceives the forms and has knowledge of the objects, but cannot identify the objects, they have associative agnosia. Symptoms and signs While most cases of visual agnosia are seen in older adults who have experienced extensive brain damage, there are also cases of young children with less brain damage during developmental years acquiring the symptoms. Commonly, visual agnosia presents as an inability to recognize an object in the absence of other explanations, such as blindness or partial blindness, anomia, memory loss, etc.. Other common manifestations of visual agnosia that are generally tested for include difficulty identifying objects that look similar in shape, difficulty with identifying line drawings of objects, and recognizing objects that are shown from less common views, such as a horse from a top-down view.Within any given patient, a variety of symptoms can occur, and the impairment of ability is not only binary but can range in severity. For example, Patient SM is a prosopagnosic with a unilateral lesion to left extrastriate cortex due to an accident in his twenties who displays behavior similar to congenital prosopagnosia. Although he can recognize facial features and emotions – indeed he sometimes uses a standout feature to recognize a face – face recognition is almost impossible purely from visual stimuli, even for faces of friends, family, and himself. The disorder also affects his memory of faces, both in storing new memories of faces and recalling stored memories.Nevertheless, it is important to note the reach of symptoms to other domains. SMs object recognition is similarly impaired though not entirely; when given line drawings to identify, he was able to give names of objects with properties similar to the drawing, implying that he is able to see the features of the drawing. Similarly, copying a line drawing of a beach scene led to a simplified version of the drawing, though the main features were accounted for. For recognition of places, he is still impaired but familiar places are remembered and new places can be stored into memory. Pathophysiology Visual agnosia occurs after damage to visual association cortex or to parts of the ventral stream of vision, known as the "what pathway" of vision for its role in object recognition. This occurs even when no damage has been done to the eyes or optic tract that leads visual information into the brain; in fact, visual agnosia occurs when symptoms cannot be explained by such damage. Damage to specific areas of the ventral stream impair the ability to recognize certain categories of visual information, such as the case of prospagnosia. Patients with visual agnosia generally do not have damage to the dorsal stream of vision, known as the "where pathway" of vision because of its role determining objects position in space, allowing individuals with visual agnosia to show relatively normal visually guided behavior.For example, patient DF had lesions to the ventral surface that gave her apperceptive agnosia. One of the tasks she was tested on required her to place a card through a thin slot that could be rotated into all orientations. As an apperceptive agnosic, it would be expected that since she cannot recognize the slot, she should not be able to correctly place the card into the slot. Indeed, when she was asked to give the direction of the slot, her responses were no better than chance. Yet, when she was asked to place the card into the slot, her success was almost to the level of the controls. This implies that in the event of a ventral stream deficit, the dorsal stream can help with processing of special information to aid movement regardless of object recognition.More specifically, the lateral occipital complex appears to respond to many different types of objects. Prosopagnosia (inability to recognize faces) is due to damage of the fusiform face area (FFA). An area in the fusiform gyrus of the temporal lobe that has been strongly associated with a role in facial recognition. However, this area is not exclusive to faces; recognition of other objects of expertise are also processed in this area. The extrastriate body cortex (EBA) was found to be activated by photographs, silhouettes, or stick drawings of human bodies. The parahippocampal place area (PPA) of the limbic cortex has been found to be activated by the sight of scenes and backgrounds. Cerebral achromatopsia (the inability to discriminate between different hues) is caused by damage to the V8 area of the visual association cortex.The left hemisphere seems to play a critical role in recognizing the meaning of common objects. Diagnosis Classification Broadly, visual agnosia is divided into apperceptive and associative visual agnosia.Apperceptive agnosia is failure of object recognition even when the basic visual functions (acuity, color, motion) and other mental processing, such as language and intelligence, are normal. The brain must correctly integrate features such as edges, light intensity, and color from sensory information to form a complete percept of an object. If a failure occurs during this process, a percept of an object is not fully formed and thus it cannot be recognized. Tasks requiring copying, matching, or drawing simple figures can distinguish the individuals with apperceptive agnosia because they cannot perform such tasks.Associative agnosia is an inability to identify objects even with apparent perception and knowledge of them. It involves a higher level of processing than apperceptive agnosia. Individuals with associative agnosia can copy or match simple figures, indicating that they can perceive objects correctly. They also display the knowledge of objects when tested with tactile or verbal information. However, when tested visually, they cannot name or describe common objects. This means that there is an impairment in associating the perception of objects with the stored knowledge of them.Although visual agnosia can be general, there exist many variants that impair recognition of specific types. These variants of visual agnosia include prosopagnosia (inability to recognize faces), pure word blindness (inability to recognize words, often called "agnosic alexia" or "pure alexia"), agnosias for colors (inability to differentiate colors), agnosias for the environment (inability to recognize landmarks or difficulty with spatial layout of an environment, i.e. topographagnosia) and simultanagnosia (inability to sort out multiple objects in a visual scene). Categories and subtypes of visual agnosia The two main categories of visual agnosia are: Apperceptive visual agnosia, impaired object recognition. Individuals with apperceptive visual agnosia cannot form a whole percept of visual information. Associative visual agnosia, impaired object identification. Individuals with associative agnosia cannot give a meaning to a formed percept. The percept is created, but it would have no meaning for individuals who have an associative agnosia. Subtypes of associative visual agnosia Achromatopsia, an inability to distinguish different colors. Prosopagnosia, an inability to recognize human faces. Individuals with prosopagnosia know that they are looking at faces, but cannot recognize people by the sight of their face, even people whom they know well. Simultagnosia, an inability to recognize multiple objects in a scene, including distinct objects within a spatial layout and distinguishing between "local" objects and "global" objects, such as being able to see a tree but not the forest or vice versa. Topographagnosia, an inability to process the spatial layout of an environment, including landmark agnosia, difficulty recognizing buildings and places; difficulty building mental maps of a location or scene; and/or an inability to discern the orientation between objects in space. Pure alexia, an inability to read. Orientation agnosia: an inability to judge or determine orientation of objects. Pantomime agnosia: an inability to understand pantomimes (gestures). It appears that the inferior cortical visual cortex is critical in recognizing pantomimes. Patient CK Background Patient C.K. was born in 1961 in England and emigrated to Canada in 1980. In January 1988, C.K. sustained a head injury from a motor vehicle accident while out for a jog. Following the accident, C.K. experienced many cognitive issues, mood swings, poor memory, and temper outbursts. C.K. also had motor weakness on the left side and a left homonymous hemianopia. He recovered well, retaining normal intelligence and normal visual acuity. He was able to complete a masters degree in history, later working as a manager at a large corporation. Although his recovery was successful in other areas of cognition, C.K. still struggles to make sense of the visual world. Associative visual agnosia Magnetic resonance imaging (MRI) showed bilateral thinning of C.K.s occipital lobe which resulted in associative visual agnosia. Patients that have visual agnosia are unable to identify visually presented objects. They can identify these objects through other modalities such as touch but if presented visually, they are unable to. Associative agnosic patients cannot create a detailed representation of the visual world in their brains, they can only perceive elements of whole objects. They also cannot form associations between objects or assign meaning to objects.C.K. makes many mistakes when trying to identify objects. For example, he called an abacus "skewers on a kebab" and a badminton racquet a "fencers mask". A dart was a "feather duster" and a protractor was mistaken for a "cockpit". Despite this impairment in visual object recognition, C.K. retained many abilities such as drawing, visual imagery, and internal imagery. As a native of England, he was tasked with drawing England, marking London and where he was born. His accurate drawing of England is just one example of his excellent drawing abilities.As aforementioned, C.K. is able to identify parts of objects but cannot generate a whole representation. It should not be surprising then that his visual imagery for object size, shape, and color is intact. For example, when shown a picture of an animal, he can correctly answer questions such as "are the ears up or down?" and "is the tail long or short?" He can correctly identify colors, for example that the inside of a cantaloupe is orange. Finally, C.K. can generate internal images and perceive these generated objects. For example, Finke, Pinker, and Farah instructed C.K. to imagine a scenario where a B is rotated 90 degrees to the left, a triangle is put below, and the line in the middle is removed. C.K. can correctly identify this object as a heart by picturing this transformation in his head. Evidence for double dissociation between face and object processing Patient C.K. provided evidence for a double dissociation between face processing and visual object processing. Patients with prosopagnosia have damage to the Fusiform Face Area (FFA) and are unable to recognize upright faces. C.K. has no difficulty with face processing and matches the performance of controls when tasked with identifying upright famous faces. When shown inverted faces of famous people, C.K. performs significantly worse than controls. This is because processing inverted faces involves a piecemeal strategy. C.K.s performance is compared to patients with prosopagnosia who are impaired in face processing but perform well identifying inverted faces. This was the first evidence for a double dissociation between face and object processing suggesting a face-specific processing system. In popular culture A famous report on this condition is the title essay of Oliver Sacks book, The Man Who Mistook His Wife for a Hat. The murder suspect in the Picket Fences episode "Strangers" supposedly had agnosia. The patient in the House episode "Adverse Events" had agnosia. In the graphic novel Preacher, the character Lorie has an extreme version of agnosia resulting from being born with a single eye. For example, she perceives Arseface, a man with severe facial deformities, as resembling a young James Dean. Val Kilmers character has visual agnosia in the film At First Sight. In "Folie à Deux", a fifth-season episode of The X-Files, Mulder succumbs to the same belief as telemarketer Gary Lambert, that his boss Greg Pincus is a monster who disguises his true appearance by means of hypnosis. Scully, although believing this notion preposterous, suggests that what Mulder describes is analogous to an induced visual agnosia. The short story "Liking What You See: A Documentary" by Ted Chiang examines the cultural effects of a noninvasive medical procedure that induces a visual agnosia toward physical beauty. In the manga and anime Odd Taxi, the main character Odokawa has agnosia, which causes him to see himself and everyone around him as an animal. See also References Further reading Cant JD, Goodale MA (March 2007). "Attention to form or surface properties modulates different regions of human occipitotemporal cortex". Cereb. Cortex. 17 (3): 713–31. doi:10.1093/cercor/bhk022. PMID 16648452. Cavina-Pratesi C, Kentridge RW, Heywood CA, Milner AD (February 2010). "Separate processing of texture and form in the ventral stream: evidence from FMRI and visual agnosia". Cereb. Cortex. 20 (2): 433–46. doi:10.1093/cercor/bhp111. PMID 19478035. Goodale MA; Milner AD (2004). Sight Unseen: An Exploration of Conscious and Unconscious Vision. Oxford UK: Oxford University Press. pp. 139. ISBN 978-0-19-856807-0. OCLC 54408420. Farah M (2004). Visual Agnosia. 2nd Edition. Cambridge MA: MIT Press: Bradford Books. p. 192. ISBN 978-0-262-56203-4. OCLC 57182718.

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

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

The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium Amycolatopsis rifamycinica or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective against mycobacteria, and are therefore used to treat tuberculosis, leprosy, and mycobacterium avium complex (MAC) infections. The rifamycin group includes the "classic" rifamycin drugs as well as the rifamycin derivatives rifampicin (or rifampin), rifabutin, rifapentine, rifalazil and rifaximin. Rifamycin, sold under the trade name Aemcolo, is approved in the United States for treatment of travelers diarrhea in some circumstances. Bacterium Streptomyces mediterranei was first isolated in 1957 from a soil sample collected near the beach-side town of St Raphael in southern France. The name was originally given by two microbiologists working with the Italian drug company Group Lepetit SpA in Milan, the Italian Grazia Beretta, and Pinhas Margalith of Israel.In 1969, the bacterium was renamed Nocardia mediterranei when another scientist named Thiemann found that it has a cell wall typical of the Nocardia species. Then, in 1986, the bacterium was renamed again Amycolatopsis mediterranei, as the first species of a new genus, because a scientist named Lechevalier discovered that the cell wall lacks mycolic acid and is not able to be infected by the Nocardia and Rhodococcus phages. Based on 16S ribosomal RNA sequences, Bala et al. renamed the species in 2004 Amycolatopsis rifamycinica. First drugs Rifamycins were first isolated in 1957 from a fermentation culture of Streptomyces mediterranei at the laboratory of Gruppo Lepetit SpA in Milan by two scientist named Piero Sensi and Maria Teresa Timbal, working with the Israeli scientist Pinhas Margalith. Initially, a family of closely related antibiotics was discovered referred to as Rifamycin A, B, C, D, E. The only component of this mixture sufficiently stable to isolate in a pure form was Rifamycin B, which unfortunately was poorly active. However, further studies showed that while Rifamycin B was essentially inactive, it was spontaneously oxidized and hydrolyzed in aqueous solutions to yield the highly active Rifamycin S. Simple reduction of Rifamycin S yielded the hydroquinone form called Rifamycin SV, which became the first member of this class to enter clinical use as an intravenous antibiotic. Further chemical modification of Rifamycin SV yielded an improved analog Rifamide, which was also introduced into clinical practice, but was similarly limited to intravenous use. After an extensive modification program, Rifampin was eventually produced, which is orally available and has become a mainstay of Tuberculosis therapy Lepetit filed for patent protection of Rifamycin B in the UK in August 1958, and in the US in March 1959. The British patent GB921045 was granted in March 1963, and U.S. Patent 3,150,046 was granted in September 1964. The drug is widely regarded as having helped conquer the issue of drug-resistant tuberculosis in the 1960s. Clinical trials Rifamycins have been used for the treatment of many diseases, the most important one being HIV-related tuberculosis. A systematic review of clinical trials on alternative regimens for prevention of active tuberculosis in HIV-negative individuals with latent TB found that a weekly, directly observed regimen of rifapentine with isoniazid for three months was as effective as a daily, self-administered regimen of isoniazid for nine months. But the rifapentine-isoniazid regimen had higher rates of treatment completion and lower rates of hepatotoxicity. However, the rate of treatment-limiting adverse events was higher in the rifapentine-isoniazid regimen.The rifamycins have a unique mechanism of action, selectively inhibiting bacterial DNA-dependent RNA polymerase, and show no cross-resistance with other antibiotics in clinical use. However, despite their activity against bacteria resistant to other antibiotics, the rifamycins themselves suffer from a rather high frequency of resistance. Because of this, Rifampin and other rifamycins are typically used in combination with other antibacterial drugs. This is routinely practiced in TB therapy and serves to prevent the formation of mutants that are resistant to any of the drugs in the combination. Rifampin rapidly kills fast-dividing bacilli strains as well as "persisters" cells, which remain biologically inactive for long periods of time that allow them to evade antibiotic activity. In addition, rifabutin and rifapentine have both been used against tuberculosis acquired in HIV-positive patients. Although Tuberculosis therapy remains the most important use of Rifampin, an increasing problem with serious Multiple Drug Resistant bacterial infections has led to some use of antibiotic combinations containing Rifampin to treat them. Mechanism of action The antibacterial activity of rifamycins relies on the inhibition of bacterial DNA-dependent RNA synthesis. This is due to the high affinity of rifamycins for the prokaryotic RNA polymerase. The selectivity of the rifamycins depends on the fact that they have a very poor affinity for the analogous mammalian enzyme. Crystal structure data of the antibiotic bound to RNA polymerase indicates that rifamycin blocks synthesis by causing strong steric clashes with the growing oligonucleotide ("steric-occlusion" mechanism). If rifamycin binds the polymerase after the chain extension process has started, no inhibition is observed on the biosynthesis, consistent with a steric-occlusion mechanism. Single step high level resistance to the rifamycins occurs as the result of a single amino acid change in the bacterial DNA dependent RNA polymerase. Biosynthesis The first information on the biosynthesis of the rifamycins came from studies using the stable isotope Carbon-13 and NMR spectroscopy to establish the origin of the carbon skeleton. These studies showed that the ansa chain was derived from acetate and propionate, in common with other polyketide antibiotics. The naphthalenic chromophore was shown to derive from a propionate unit coupled with a seven carbon amino moiety of unknown origin. The general scheme of biosynthesis starts with the uncommon starting unit, 3-amino-5-hydroxybenzoic acid (AHBA), via type I polyketide pathway (PKS I) in which chain extension is performed using 2 acetate and 8 propionate units. AHBA is believed to have originated from the Shikimate pathway, however this was not incorporated into the biosynthetic mechanism. This is due to the observation that 3 amino-acid analogues converted into AHBA in cell-free extracts of A. mediterranei. The rif cluster is responsible for the biosynthesis of rifamycins. It contains genes rifG through rifN, which were shown to biosynthesize AHBA.[10] RifK, rifL, rifM, and rifN are believed to act as transaminases in order to form the AHBA precursor kanosamine. "RifH" encodes aminoDAHP synthase that catalyzes the condensation between 1-deoxy-1-imino-d-erythrose 4-phosphate and phosphoenolpyruvate. RifA through rifE encode a type I polyketide synthase module, with the loading module being a non-ribosomal peptide synthetase. In all, rifA-E assemble a linear undecaketide and are followed by rifF, which encodes an amide synthase and causes the undecaketide to release and form a macrolactam structure. Moreover, the rif cluster contains various regulatory proteins and glycosylating genes that appear to be silent. Other types of genes seem to perform post-synthase modifications of the original polyketide. Derivatives Lepetit introduced Rifampicin, an orally active rifamycin, around 1966. Rifabutin, a derivative of rifamycin S, was invented around 1975 and came onto the US market in 1993. Hoechst Marion Roussel (now part of Aventis) introduced rifapentine in 1999. Rifaximin is an oral rifamycin marketed in the US by Salix Pharmaceuticals that is poorly absorbed from the intestine. It has been used to treat hepatic encephalopathy and travelers diarrhea. Currently available rifamycins Rifampicin or Rifampin Rifabutin Rifapentine Rifaximin Aemcolo References Bibliography Sensi. et al., Farmaco Ed. Sci. (1959) 14, 146-147 - the paper announcing the discovery of the rifamycins. Thieman et al. Arch. Microbiol. (1969), 67 147-151 - the paper which renamed Streptomyces mediterranei as Nocardia mediterranei. Lechevalier et al., Int. J. Syst. Bacteriol. (1986), 36, 29) - the paper which renamed Nocardia mediterranei as Amycolatopsis mediterranei. Bala S (2004). "Reclassification of "Amycolatopsis mediterranei" DSM 46095 as "Amycolatopsis rifamycinica" sp. nov". International Journal of Systematic and Evolutionary Microbiology. 54 (4): 1145–1149. doi:10.1099/ijs.0.02901-0. PMID 15280283. - the paper with the latest name change External links "Rifamycin". Drug Information Portal. U.S. National Library of Medicine.

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

Can you demystify the medical term 'Boutonniere deformity' for me?

Boutonniere deformity is a deformed position of the fingers or toes, in which the joint nearest the knuckle (the proximal interphalangeal joint, or PIP) is permanently bent toward the palm while the farthest joint (the distal interphalangeal joint, or DIP) is bent back away (PIP flexion with DIP hyperextension). Causes include injury, inflammatory conditions like rheumatoid arthritis, and genetic conditions like Ehlers-Danlos syndrome. Pathophysiology This flexion deformity of the proximal interphalangeal joint is due to interruption of the central slip of the extensor tendon such that the lateral slips separate and the head of the proximal phalanx pops through the gap like a finger through a button hole (thus the name, from French boutonnière "button hole"). The distal joint is subsequently drawn into hyperextension because the two peripheral slips of the extensor tendon are stretched by the head of the proximal phalanx (note that the two peripheral slips are inserted into the distal phalanx, while the proximal slip is inserted into the middle phalanx). This deformity makes it difficult or impossible to extend the proximal interphalangeal joint. Diagnosis Stages Mild extension lag, passively correctable Moderate extension lag, passively correctable Mild flexion contracture Advanced flexion contractureHigher numbers indicate a more severe problem and greater likelihood of a poor outcome. Treatment Usually treated with a splint placing the proximal interphalangeal joint in extension for 4–6 weeks. Occasionally surgery is needed when splinting is unsuccessful. See also Swan neck deformity Z-deformity References Further reading Coons, Matthew S.; Green, Steven M. (August 1995). "Boutonniere deformity". Hand Clinics. 11 (3): 387–402. doi:10.1016/S0749-0712(21)00060-3. PMID 7559817. Souter, William A. (October 1974). "The Problem of Boutonniere Deformity". Clinical Orthopaedics and Related Research. 104 (104): 116–133. doi:10.1097/00003086-197410000-00012. PMID 4607222. Nalebuff, Edward A.; Millender, Lewis H. (July 1975). "Surgical Treatment of the Boutonniere Deformity in Rheumatoid Arthritis". Orthopedic Clinics of North America. 6 (3): 753–763. doi:10.1016/S0030-5898(20)30987-1. PMID 1099508. Littler, J. William; Eaton, Richard G. (October 1967). "Redistribution of Forces in the Correction of the Boutonnière Deformity". JBJS. 49 (7): 1267–1274. doi:10.2106/00004623-196749070-00002. PMID 5622971. To, Philip; Watson, Jeffry T. (January 2011). "Boutonniere Deformity". The Journal of Hand Surgery. 36 (1): 139–142. doi:10.1016/j.jhsa.2010.10.032. PMID 21193133. Massengill, James B. (November 1992). "The boutonniere deformity". Hand Clinics. 8 (4): 787–801. doi:10.1016/S0749-0712(21)00744-7. PMID 1460075. Aiache, Adrien; Barsky, Arthur J.; Weiner, Daniel L. (August 1970). "Prevention of the boutonniere deformity". Plastic and Reconstructive Surgery. 46 (2): 164–167. doi:10.1097/00006534-197008000-00010. PMID 5423482. S2CID 39268503. Curtis, Raymond M.; Reid, Robert L.; Provost, John M. (March 1983). "A staged technique for the repair of the traumatic boutonniere deformity". The Journal of Hand Surgery. 8 (2): 167–171. doi:10.1016/s0363-5023(83)80009-4. PMID 6833725. Urbaniak, James R.; Hayes, Michael G. (July 1981). "Chronic boutonniere deformity—An anatomic reconstruction". The Journal of Hand Surgery. 6 (4): 379–383. doi:10.1016/s0363-5023(81)80048-2. PMID 7252114. Dolphin, James A. (January 1965). "Extensor Tenotomy for Chronic Boutonnière Deformity of the Finger: REPORT OF TWO CASES". JBJS. 47 (1): 161–164. doi:10.2106/00004623-196547010-00011. PMID 14256963. External links Boutonniere Deformity at eMedicine

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

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

A fundic gland polyp is a type of polyp, found in the fundus of the stomach. Fundic gland polyps are found in 0.8 to 1.9% of patients who undergo esophagogastroduodenoscopy, and are more common in middle-aged women.The risk of malignancy is very low or none, when sporadic.Fundic gland polyposis is a medical syndrome with multiple fundic gland polyps. The condition has been described both in patients with familial adenomatous polyposis (FAP) and attenuated variants (AFAP), and in patients in whom it occurs sporadically. == References ==

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

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

Determinism is a philosophical view, where all events are determined completely by previously existing causes. Deterministic theories throughout the history of philosophy have developed from diverse and sometimes overlapping motives and considerations. The opposite of determinism is some kind of indeterminism (otherwise called nondeterminism) or randomness. Determinism is often contrasted with free will, although some philosophers claim that the two are compatible.Determinism is often used to mean causal determinism, which in physics is known as cause-and-effect. This is the concept that events within a given paradigm are bound by causality in such a way that any state of an object or event is completely determined by its prior states. This meaning can be distinguished from other varieties of determinism mentioned below. Debates about determinism often concern the scope of determined systems; some maintain that the entire universe is a single determinate system, and others identifying more limited determinate systems (or multiverse). Historical debates involve many philosophical positions and varieties of determinism. They include debates concerning determinism and free will, technically denoted as compatibilistic (allowing the two to coexist) and incompatibilistic (denying their coexistence is a possibility). Determinism should not be confused with the self-determination of human actions by reasons, motives, and desires. Determinism is about interactions which affect our cognitive processes in our life. It is about the cause and the result of what we have done. Cause and result are always bounded together in cognitive processes. It assumes that if an observer has sufficient information about an object or human being, that such an observer might be able to predict every consequent move of that object or human being. Determinism rarely requires that perfect prediction be practically possible. Varieties "Determinism" may commonly refer to any of the following viewpoints. Causal Causal determinism, sometimes synonymous with historical determinism (a sort of path dependence), is "the idea that every event is necessitated by antecedent events and conditions together with the laws of nature." However, it is a broad enough term to consider that:...Ones deliberations, choices, and actions will often be necessary links in the causal chain that brings something about. In other words, even though our deliberations, choices, and actions are themselves determined like everything else, it is still the case, according to causal determinism, that the occurrence or existence of yet other things depends upon our deliberating, choosing and acting in a certain way.Causal determinism proposes that there is an unbroken chain of prior occurrences stretching back to the origin of the universe. The relation between events may not be specified, nor the origin of that universe. Causal determinists believe that there is nothing in the universe that has no cause or is self-caused. Causal determinism has also been considered more generally as the idea that everything that happens or exists is caused by antecedent conditions. In the case of nomological determinism, these conditions are considered events also, implying that the future is determined completely by preceding events—a combination of prior states of the universe and the laws of nature. Yet they can also be considered metaphysical of origin (such as in the case of theological determinism). Nomological Nomological determinism, generally synonymous with physical determinism (its opposite being physical indeterminism), the most common form of causal determinism, is the notion that the past and the present dictate the future entirely and necessarily by rigid natural laws, that every occurrence results inevitably from prior events. Nomological determinism is sometimes illustrated by the thought experiment of Laplaces demon. Nomological determinism is sometimes called scientific determinism, although that is a misnomer. Necessitarianism Necessitarianism is closely related to the causal determinism described above. It is a metaphysical principle that denies all mere possibility; there is exactly one way for the world to be. Leucippus claimed there were no uncaused events, and that everything occurs for a reason and by necessity. Predeterminism Predeterminism is the idea that all events are determined in advance. The concept is often argued by invoking causal determinism, implying that there is an unbroken chain of prior occurrences stretching back to the origin of the universe. In the case of predeterminism, this chain of events has been pre-established, and human actions cannot interfere with the outcomes of this pre-established chain. Predeterminism can be used to mean such pre-established causal determinism, in which case it is categorized as a specific type of determinism. It can also be used interchangeably with causal determinism—in the context of its capacity to determine future events. Despite this, predeterminism is often considered as independent of causal determinism. Biological The term predeterminism is also frequently used in the context of biology and heredity, in which case it represents a form of biological determinism, sometimes called genetic determinism. Biological determinism is the idea that each of human behaviors, beliefs, and desires are fixed by human genetic nature. Friedrich Nietzsche explained that a human being is "determined" by his/her body, since he/she is subject to passions, impulsions and instincts. Fatalism Fatalism is normally distinguished from "determinism", as a form of teleological determinism. Fatalism is the idea that everything is fated to happen, so that humans have no control over their future. Fate has arbitrary power, and need not follow any causal or otherwise deterministic laws. Types of fatalism include hard theological determinism and the idea of predestination, where there is a God who determines all that humans will do. This may be accomplished either by knowing their actions in advance, via some form of omniscience or by decreeing their actions in advance. Theological determinism Theological determinism is a form of determinism that holds that all events that happen are either preordained (i.e., predestined) to happen by a monotheistic deity, or are destined to occur given its omniscience. Two forms of theological determinism exist, referred to as strong and weak theological determinism.Strong theological determinism is based on the concept of a creator deity dictating all events in history: "everything that happens has been predestined to happen by an omniscient, omnipotent divinity."Weak theological determinism is based on the concept of divine foreknowledge—"because Gods omniscience is perfect, what God knows about the future will inevitably happen, which means, consequently, that the future is already fixed." There exist slight variations on this categorisation, however. Some claim either that theological determinism requires predestination of all events and outcomes by the divinity—i.e., they do not classify the weaker version as theological determinism unless libertarian free will is assumed to be denied as a consequence—or that the weaker version does not constitute theological determinism at all.With respect to free will, "theological determinism is the thesis that God exists and has infallible knowledge of all true propositions including propositions about our future actions," more minimal criteria designed to encapsulate all forms of theological determinism.Theological determinism can also be seen as a form of causal determinism, in which the antecedent conditions are the nature and will of God. Some have asserted that Augustine of Hippo introduced theological determinism into Christianity in 412 CE, whereas all prior Christian authors supported free will against Stoic and Gnostic determinism. However, there are many Biblical passages that seem to support the idea of some kind of theological determinism. Adequate determinism Adequate determinism is the idea, because of quantum decoherence, that quantum indeterminacy can be ignored for most macroscopic events. Random quantum events "average out" in the limit of large numbers of particles (where the laws of quantum mechanics asymptotically approach the laws of classical mechanics). Stephen Hawking explains a similar idea: he says that the microscopic world of quantum mechanics is one of determined probabilities. That is, quantum effects rarely alter the predictions of classical mechanics, which are quite accurate (albeit still not perfectly certain) at larger scales. Something as large as an animal cell, then, would be "adequately determined" (even in light of quantum indeterminacy). Many-worlds The many-worlds interpretation accepts the linear causal sets of sequential events with adequate consistency yet also suggests constant forking of causal chains creating "multiple universes" to account for multiple outcomes from single events. Meaning the causal set of events leading to the present are all valid yet appear as a singular linear time stream within a much broader unseen conic probability field of other outcomes that "split off" from the locally observed timeline. Under this model causal sets are still "consistent" yet not exclusive to singular iterated outcomes. The interpretation sidesteps the exclusive retrospective causal chain problem of "could not have done otherwise" by suggesting "the other outcome does exist" in a set of parallel universe time streams that split off when the action occurred. This theory is sometimes described with the example of agent based choices but more involved models argue that recursive causal splitting occurs with all particle wave functions at play. This model is highly contested with multiple objections from the scientific community. Philosophical varieties Determinism in nature/nurture controversy Although some of the above forms of determinism concern human behaviors and cognition, others frame themselves as an answer to the debate on nature and nurture. They will suggest that one factor will entirely determine behavior. As scientific understanding has grown, however, the strongest versions of these theories have been widely rejected as a single-cause fallacy. In other words, the modern deterministic theories attempt to explain how the interaction of both nature and nurture is entirely predictable. The concept of heritability has been helpful in making this distinction. Biological determinism, sometimes called genetic determinism, is the idea that each of human behaviors, beliefs, and desires are fixed by human genetic nature. Behaviorism involves the idea that all behavior can be traced to specific causes—either environmental or reflexive. John B. Watson and B. F. Skinner developed this nurture-focused determinism. Cultural materialism, contends that the physical world impacts and sets constraints on human behavior. Cultural determinism, along with social determinism, is the nurture-focused theory that the culture in which we are raised determines who we are. Environmental determinism, also known as climatic or geographical determinism, proposes that the physical environment, rather than social conditions, determines culture. Supporters of environmental determinism often also support behavioral determinism. Key proponents of this notion have included Ellen Churchill Semple, Ellsworth Huntington, Thomas Griffith Taylor and possibly Jared Diamond, although his status as an environmental determinist is debated. Determinism and prediction Other deterministic theories actually seek only to highlight the importance of a particular factor in predicting the future. These theories often use the factor as a sort of guide or constraint on the future. They need not suppose that complete knowledge of that one factor would allow us to make perfect predictions. Psychological determinism can mean that humans must act according to reason, but it can also be synonymous with some sort of psychological egoism. The latter is the view that humans will always act according to their perceived best interest. Linguistic determinism proposes that language determines (or at least limits) the things that humans can think and say and thus know. The Sapir–Whorf hypothesis argues that individuals experience the world based on the grammatical structures they habitually use. Economic determinism attributes primacy to economic structure over politics in the development of human history. It is associated with the dialectical materialism of Karl Marx. Technological determinism is the theory that a societys technology drives the development of its social structure and cultural values. Structural determinism Structural determinism is the philosophical view that actions, events, and processes are predicated on and determined by structural factors. Given any particular structure or set of estimable components, it is a concept that emphasizes rational and predictable outcomes. Chilean biologists Humberto Maturana and Francisco Varela popularized the notion, writing that a living systems general order is maintained via a circular process of ongoing self-referral, and thus its organization and structure defines the changes it undergoes. According to the authors, a system can undergo changes of state (alteration of structure without loss of identity) or disintegrations (alteration of structure with loss of identity). Such changes or disintegrations are not ascertained by the elements of the disturbing agent, as each disturbance will only trigger responses in the respective system, which in turn, are determined by each system’s own structure. On an individualistic level, what this means is that human beings as free and independent entities are triggered to react by external stimuli or change in circumstance. However, their own internal state and existing physical and mental capacities determine their responses to those triggers. On a much broader societal level, structural determinists believe that larger issues in the society—especially those pertaining to minorities and subjugated communities—are predominantly assessed through existing structural conditions, making change of prevailing conditions difficult, and sometimes outright impossible. For example, the concept has been applied to the politics of race in the United States of America and other Western countries such as the United Kingdom and Australia, with structural determinists lamenting structural factors for the prevalence of racism in these countries. Additionally, Marxists have conceptualized the writings of Karl Marx within the context of structural determinism as well. For example, Louis Althusser, a structural Marxist, argues that the state, in its political, economic, and legal structures, reproduces the discourse of capitalism, in turn, allowing for the burgeoning of capitalistic structures. Proponents of the notion highlight the usefulness of structural determinism to study complicated issues related to race and gender, as it highlights often gilded structural conditions that block meaningful change. Critics call it too rigid, reductionist and inflexible. Additionally, they also criticize the notion for overemphasizing deterministic forces such as structure over the role of human agency and the ability of the people to act. These critics argue that politicians, academics, and social activists have the capability to bring about significant change despite stringent structural conditions. With free will Philosophers have debated both the truth of determinism, and the truth of free will. This creates the four possible positions in the figure. Compatibilism refers to the view that free will is, in some sense, compatible with determinism. The three incompatibilist positions deny this possibility. The hard incompatibilists hold that free will is incompatible with both determinism and indeterminism, the libertarians that determinism does not hold, and free will might exist, and the hard determinists that determinism does hold and free will does not exist. The Dutch philosopher Baruch Spinoza was a determinist thinker, and argued that human freedom can be achieved through knowledge of the causes that determine our desire and affections. He defined human servitude as the state of bondage of anyone who is aware of their own desires, but ignorant of the causes that determined them. However, the free or virtuous person becomes capable, through reason and knowledge, to be genuinely free, even as they are being "determined". For the Dutch philosopher, acting out of ones own internal necessity is genuine freedom while being driven by exterior determinations is akin to bondage. Spinozas thoughts on human servitude and liberty are respectively detailed in the fourth and fifth volumes of his work Ethics. The standard argument against free will, according to philosopher J. J. C. Smart, focuses on the implications of determinism for free will. He suggests free will is denied whether determinism is true or not. He says that if determinism is true, all actions are predicted and no one is assumed to be free; however, if determinism is false, all actions are presumed to be random and as such no one seems free because they have no part in controlling what happens. With the soul Some determinists argue that materialism does not present a complete understanding of the universe, because while it can describe determinate interactions among material things, it ignores the minds or souls of conscious beings. A number of positions can be delineated: Immaterial souls are all that exist (idealism). Immaterial souls exist and exert a non-deterministic causal influence on bodies (traditional free-will, interactionist dualism). Immaterial souls exist but are part of a deterministic framework. Immaterial souls exist, but exert no causal influence, free or determined (epiphenomenalism, occasionalism) Immaterial souls do not exist – there is no mind-body dichotomy, and there is a materialistic explanation for intuitions to the contrary. With ethics and morality Another topic of debate is the implication that determinism has on morality. Philosopher and incompatibilist Peter van Inwagen introduced this thesis, when arguments that free will is required for moral judgments, as such: The moral judgment that X should not have been done implies that something else should have been done instead. That something else should have been done instead implies that there was something else to do. That there was something else to do, implies that something else could have been done. That something else could have been done implies that there is free will. If there is no free will to have done other than X we cannot make the moral judgment that X should not have been done. History Determinism was developed by the Greek philosophers during the 7th and 6th centuries BCE by the Pre-socratic philosophers Heraclitus and Leucippus, later Aristotle, and mainly by the Stoics. Some of the main philosophers who have dealt with this issue are Marcus Aurelius, Omar Khayyám, Thomas Hobbes, Baruch Spinoza, Gottfried Leibniz, David Hume, Baron dHolbach (Paul Heinrich Dietrich), Pierre-Simon Laplace, Arthur Schopenhauer, William James, Friedrich Nietzsche, Albert Einstein, Niels Bohr, Ralph Waldo Emerson and, more recently, John Searle, Ted Honderich, and Daniel Dennett. Mecca Chiesa notes that the probabilistic or selectionistic determinism of B. F. Skinner comprised a wholly separate conception of determinism that was not mechanistic at all. Mechanistic determinism assumes that every event has an unbroken chain of prior occurrences, but a selectionistic or probabilistic model does not. Western tradition In the West, some elements of determinism have been expressed in Greece from the 6th century BCE by the Presocratics Heraclitus and Leucippus. The first notions of determinism appears to originate with the Stoics, as part of their theory of universal causal determinism. The resulting philosophical debates, which involved the confluence of elements of Aristotelian Ethics with Stoic psychology, led in the 1st–3rd centuries CE in the works of Alexander of Aphrodisias to the first recorded Western debate over determinism and freedom, an issue that is known in theology as the paradox of free will. The writings of Epictetus as well as middle Platonist and early Christian thought were instrumental in this development. Jewish philosopher Moses Maimonides said of the deterministic implications of an omniscient god: "Does God know or does He not know that a certain individual will be good or bad? If thou sayest He knows, then it necessarily follows that [that] man is compelled to act as God knew beforehand he would act, otherwise Gods knowledge would be imperfect." Newtonian mechanics Determinism in the West is often associated with Newtonian mechanics/physics, which depicts the physical matter of the universe as operating according to a set of fixed laws. The "billiard ball" hypothesis, a product of Newtonian physics, argues that once the initial conditions of the universe have been established, the rest of the history of the universe follows inevitably. If it were actually possible to have complete knowledge of physical matter and all of the laws governing that matter at any one time, then it would be theoretically possible to compute the time and place of every event that will ever occur (Laplaces demon). In this sense, the basic particles of the universe operate in the same fashion as the rolling balls on a billiard table, moving and striking each other in predictable ways to produce predictable results. Whether or not it is all-encompassing in so doing, Newtonian mechanics deals only with caused events; for example, if an object begins in a known position and is hit dead on by an object with some known velocity, then it will be pushed straight toward another predictable point. If it goes somewhere else, the Newtonians argue, one must question ones measurements of the original position of the object, the exact direction of the striking object, gravitational or other fields that were inadvertently ignored, etc. Then, they maintain, repeated experiments and improvements in accuracy will always bring ones observations closer to the theoretically predicted results. When dealing with situations on an ordinary human scale, Newtonian physics has been successful. But it fails as velocities become some substantial fraction of the speed of light and when interactions at the atomic scale are studied. Before the discovery of quantum effects and other challenges to Newtonian physics, "uncertainty" was always a term that applied to the accuracy of human knowledge about causes and effects, and not to the causes and effects themselves. Newtonian mechanics, as well as any following physical theories, are results of observations and experiments, and so they describe "how it all works" within a tolerance. However, old western scientists believed if there are any logical connections found between an observed cause and effect, there must be also some absolute natural laws behind. Belief in perfect natural laws driving everything, instead of just describing what we should expect, led to searching for a set of universal simple laws that rule the world. This movement significantly encouraged deterministic views in Western philosophy, as well as the related theological views of classical pantheism. Eastern tradition The idea that the entire universe is a deterministic system has been articulated in both Eastern and non-Eastern religions, philosophy, and literature. The ancient Arabs that inhabited the Arabian Peninsula before the advent of Islam used to profess a widespread belief in fatalism (ḳadar) alongside a fearful consideration for the sky and the stars as divine beings, which they held to be ultimately responsible for every phenomena that occurs on Earth and for the destiny of humankind. Accordingly, they shaped their entire lives in accordance with their interpretations of astral configurations and phenomena.In the I Ching and philosophical Taoism, the ebb and flow of favorable and unfavorable conditions suggests the path of least resistance is effortless (see: Wu wei). In the philosophical schools of the Indian Subcontinent, the concept of karma deals with similar philosophical issues to the western concept of determinism. Karma is understood as a spiritual mechanism which causes the eternal cycle of birth, death, and rebirth (saṃsāra). Karma, either positive or negative, accumulates according to an individuals actions throughout their life, and at their death determines the nature of their next life in the cycle of Saṃsāra. Most major religions originating in India hold this belief to some degree, most notably Hinduism, Jainism, Sikhism, and Buddhism. The views on the interaction of karma and free will are numerous, and diverge from each other. For example, in Sikhism, gods grace, gained through worship, can erase ones karmic debts, a belief which reconciles the principle of karma with a monotheistic god one must freely choose to worship. Jainists believe in compatibilism, in which the cycle of Saṃsara is a completely mechanistic process, occurring without any divine intervention. The Jains hold an atomic view of reality, in which particles of karma form the fundamental microscopic building material of the universe. Ājīvika In ancient India, the Ājīvika school of philosophy founded by Makkhali Gosāla (around 500 BCE), otherwise referred to as "Ājīvikism" in Western scholarship, upheld the Niyati ("Fate") doctrine of absolute fatalism or determinism, which negates the existence of free will and karma, and is therefore considered one of the nāstika or "heterodox" schools of Indian philosophy. The oldest descriptions of the Ājīvika fatalists and their founder Gosāla can be found both in the Buddhist and Jaina scriptures of ancient India. The predetermined fate of living beings and the impossibility to achieve liberation (moksha) from the eternal cycle of birth, death, and rebirth was the major distinctive philosophical and metaphysical doctrine of this heterodox school of Indian philosophy, annoverated among the other Śramaṇa movements that emerged in India during the Second urbanization (600–200 BCE). Buddhism Buddhist philosophy contains several concepts which some scholars describe as deterministic to various levels. One concept which is argued to support a hard determinism is the idea of dependent origination, which claims that all phenomena (dharma) are necessarily caused by some other phenomenon, which it can be said to be dependent on, like links in a massive chain. In traditional Buddhist philosophy, this concept is used to explain the functioning of the cycle of saṃsāra; all actions exert a karmic force, which will manifest results in future lives. In other words, righteous or unrighteous actions in one life will necessarily cause good or bad responses in another.Another Buddhist concept which many scholars perceive to be deterministic is the idea of non-self, or anatta. In Buddhism, attaining enlightenment involves one realizing that in humans there is no fundamental core of being which can be called the "soul", and that humans are instead made of several constantly changing factors which bind them to the cycle of Saṃsāra.Some scholars argue that the concept of non-self necessarily disproves the ideas of free will and moral culpability. If there is no autonomous self, in this view, and all events are necessarily and unchangeably caused by others, then no type of autonomy can be said to exist, moral or otherwise. However, other scholars disagree, claiming that the Buddhist conception of the universe allows for a form of compatibilism. Buddhism perceives reality occurring on two different levels, the ultimate reality which can only be truly understood by the enlightened, and the illusory and false material reality. Therefore, Buddhism perceives free will as a notion belonging to material reality, while concepts like non-self and dependent origination belong to the ultimate reality; the transition between the two can be truly understood, Buddhists claim, by one who has attained enlightenment. Modern scientific perspective Generative processes Although it was once thought by scientists that any indeterminism in quantum mechanics occurred at too small a scale to influence biological or neurological systems, there is indication that nervous systems are influenced by quantum indeterminism due to chaos theory. It is unclear what implications this has for the problem of free will given various possible reactions to the problem in the first place. Many biologists do not grant determinism: Christof Koch, for instance, argues against it, and in favour of libertarian free will, by making arguments based on generative processes (emergence). Other proponents of emergentist or generative philosophy, cognitive sciences, and evolutionary psychology, argue that a certain form of determinism (not necessarily causal) is true. They suggest instead that an illusion of free will is experienced due to the generation of infinite behaviour from the interaction of finite-deterministic set of rules and parameters. Thus the unpredictability of the emerging behaviour from deterministic processes leads to a perception of free will, even though free will as an ontological entity does not exist. As an illustration, the strategy board-games chess and Go have rigorous rules in which no information (such as cards face-values) is hidden from either player and no random events (such as dice-rolling) happen within the game. Yet, chess and especially Go with its extremely simple deterministic rules, can still have an extremely large number of unpredictable moves. When chess is simplified to 7 or fewer pieces, however, endgame tables are available that dictate which moves to play to achieve a perfect game. This implies that, given a less complex environment (with the original 32 pieces reduced to 7 or fewer pieces), a perfectly predictable game of chess is possible. In this scenario, the winning player can announce that a checkmate will happen within a given number of moves, assuming a perfect defense by the losing player, or fewer moves if the defending player chooses sub-optimal moves as the game progresses into its inevitable, predicted conclusion. By this analogy, it is suggested, the experience of free will emerges from the interaction of finite rules and deterministic parameters that generate nearly infinite and practically unpredictable behavioural responses. In theory, if all these events could be accounted for, and there were a known way to evaluate these events, the seemingly unpredictable behaviour would become predictable. Another hands-on example of generative processes is John Horton Conways playable Game of Life. Nassim Taleb is wary of such models, and coined the term "ludic fallacy." Compatibility with the existence of science Certain philosophers of science argue that, while causal determinism (in which everything including the brain/mind is subject to the laws of causality) is compatible with minds capable of science, fatalism and predestination is not. These philosophers make the distinction that causal determinism means that each step is determined by the step before and therefore allows sensory input from observational data to determine what conclusions the brain reaches, while fatalism in which the steps between do not connect an initial cause to the results would make it impossible for observational data to correct false hypotheses. This is often combined with the argument that if the brain had fixed views and the arguments were mere after-constructs with no causal effect on the conclusions, science would have been impossible and the use of arguments would have been a meaningless waste of energy with no persuasive effect on brains with fixed views. Mathematical models Many mathematical models of physical systems are deterministic. This is true of most models involving differential equations (notably, those measuring rate of change over time). Mathematical models that are not deterministic because they involve randomness are called stochastic. Because of sensitive dependence on initial conditions, some deterministic models may appear to behave non-deterministically; in such cases, a deterministic interpretation of the model may not be useful due to numerical instability and a finite amount of precision in measurement. Such considerations can motivate the consideration of a stochastic model even though the underlying system is governed by deterministic equations. Quantum and classical mechanics Day-to-day physics Since the beginning of the 20th century, quantum mechanics—the physics of the extremely small—has revealed previously concealed aspects of events. Before that, Newtonian physics—the physics of everyday life—dominated. Taken in isolation (rather than as an approximation to quantum mechanics), Newtonian physics depicts a universe in which objects move in perfectly determined ways. At the scale where humans exist and interact with the universe, Newtonian mechanics remain useful, and make relatively accurate predictions (e.g. calculating the trajectory of a bullet). But whereas in theory, absolute knowledge of the forces accelerating a bullet would produce an absolutely accurate prediction of its path, modern quantum mechanics casts reasonable doubt on this main thesis of determinism. Quantum realm Quantum physics works differently in many ways from Newtonian physics. Physicist Aaron D. OConnell explains that understanding our universe, at such small scales as atoms, requires a different logic than day-to-day life does. OConnell does not deny that it is all interconnected: the scale of human existence ultimately does emerge from the quantum scale. OConnell argues that we must simply use different models and constructs when dealing with the quantum world. Quantum mechanics is the product of a careful application of the scientific method, logic and empiricism. The Heisenberg uncertainty principle is frequently confused with the observer effect. The uncertainty principle actually describes how precisely we may measure the position and momentum of a particle at the same time—if we increase the accuracy in measuring one quantity, we are forced to lose accuracy in measuring the other. "These uncertainty relations give us that measure of freedom from the limitations of classical concepts which is necessary for a consistent description of atomic processes." This is where statistical mechanics come into play, and where physicists begin to require rather unintuitive mental models: A particles path simply cannot be exactly specified in its full quantum description. "Path" is a classical, practical attribute in our everyday life, but one that quantum particles do not meaningfully possess. The probabilities discovered in quantum mechanics do nevertheless arise from measurement (of the perceived path of the particle). As Stephen Hawking explains, the result is not traditional determinism, but rather determined probabilities. In some cases, a quantum particle may indeed trace an exact path, and the probability of finding the particles in that path is one (certain to be true). In fact, as far as prediction goes, the quantum development is at least as predictable as the classical motion, but the key is that it describes wave functions that cannot be easily expressed in ordinary language. As far as the thesis of determinism is concerned, these probabilities, at least, are quite determined. These findings from quantum mechanics have found many applications, and allow us to build transistors and lasers. Put another way: personal computers, Blu-ray players and the Internet all work because humankind discovered the determined probabilities of the quantum world.On the topic of predictable probabilities, the double-slit experiments are a popular example. Photons are fired one-by-one through a double-slit apparatus at a distant screen. They do not arrive at any single point, nor even the two points lined up with the slits (the way it might be expected of bullets fired by a fixed gun at a distant target). Instead, the light arrives in varying concentrations at widely separated points, and the distribution of its collisions with the target can be calculated reliably. In that sense the behavior of light in this apparatus is deterministic, but there is no way to predict where in the resulting interference pattern any individual photon will make its contribution (although, there may be ways to use weak measurement to acquire more information without violating the uncertainty principle). Some (including Albert Einstein) have argued that the inability to predict any more than probabilities is simply due to ignorance. The idea is that, beyond the conditions and laws can be observed or deduced, there are also hidden factors or "hidden variables" that determine absolutely in which order photons reach the detector screen. They argue that the course of the universe is absolutely determined, but that humans are screened from knowledge of the determinative factors. So, they say, it only appears that things proceed in a merely probabilistically determinative way. In actuality, they proceed in an absolutely deterministic way. John S. Bell criticized Einsteins work in his famous Bells theorem, which, under a strict set of assumptions, demonstrates that quantum mechanics can make statistical predictions that would be violated if local hidden variables really existed. A number of experiments have tried to verify such predictions, and so far they do not appear to be violated. Current experiments continue to verify the result, including the 2015 "Loophole Free Test" that plugged all known sources of error and the 2017 "Cosmic Bell Test" experiment that used cosmic data streaming from different directions toward the Earth, precluding the possibility the sources of data could have had prior interactions. Bells theorem has been criticized from the perspective of its strict set of assumptions. A foundational assumption to quantum mechanics is the Principle of locality. To abandon this assumption would require the construction of a non-local hidden variable theory. Therefore, it is possible to augment quantum mechanics with non-local hidden variables to achieve a deterministic theory that is in agreement with experiment. An example is the Bohm interpretation of quantum mechanics. Bohms Interpretation, though, violates special relativity and it is highly controversial whether or not it can be reconciled without giving up on determinism. Another foundational assumption to quantum mechanics is that of free will, which has been argued to be foundational to the scientific method as a whole. Bell acknowledged that abandoning this assumption would both allow for the maintenance of determinism as well as locality. This perspective is known as superdeterminism, and is defended by some physicists such as Sabine Hossenfelder and Tim Palmer.More advanced variations on these arguments include quantum contextuality, by Bell, Simon B. Kochen and Ernst Specker, which argues that hidden variable theories cannot be "sensible", meaning that the values of the hidden variables inherently depend on the devices used to measure them. This debate is relevant because there are possibly specific situations in which the arrival of an electron at a screen at a certain point and time would trigger one event, whereas its arrival at another point would trigger an entirely different event (e.g. see Schrödingers cat – a thought experiment used as part of a deeper debate). Thus, quantum physics casts reasonable doubt on the traditional determinism of classical, Newtonian physics in so far as reality does not seem to be absolutely determined. This was the subject of the famous Bohr–Einstein debates between Einstein and Niels Bohr and there is still no consensus.Adequate determinism (see Varieties, above) is the reason that Stephen Hawking calls libertarian free will "just an illusion". See also References Notes Bibliography Daniel Dennett (2003) Freedom Evolves. Viking Penguin. John Earman (2007) "Aspects of Determinism in Modern Physics" in Butterfield, J., and Earman, J., eds., Philosophy of Physics, Part B. North Holland: 1369–1434. George Ellis (2005) "Physics and the Real World", Physics Today. Epstein, J.M. (1999). "Agent Based Models and Generative Social Science". Complexity. IV (5): 41–60. Bibcode:1999Cmplx...4e..41E. CiteSeerX 10.1.1.118.546. doi:10.1002/(sici)1099-0526(199905/06)4:5<41::aid-cplx9>3.0.co;2-f. Epstein, J.M. and Axtell R. (1996) Growing Artificial Societies – Social Science from the Bottom. MIT Press. Harris, James A. (2005) Of Liberty and Necessity: The Free Will Debate in Eighteenth-Century British Philosophy. Clarendon Press. Kenrick, D. T.; Li, N. P.; Butner, J. (2003). "Dynamical evolutionary psychology: Individual decision rules and emergent social norms" (PDF). Psychological Review. 110 (1): 3–28. CiteSeerX 10.1.1.526.5218. doi:10.1037/0033-295x.110.1.3. PMID 12529056. S2CID 43306158. Albert Messiah, Quantum Mechanics, English translation by G. M. Temmer of Mécanique Quantique, 1966, John Wiley and Sons, vol. I, chapter IV, section III. Ernest Nagel (3 March 1960). "Determinism in history". Philosophy and Phenomenological Research. 20 (3): 291–317. doi:10.2307/2105051. JSTOR 2105051. (Online version found here) John T Roberts (2006). "Determinism". In Sahotra Sarkar; Jessica Pfeifer (eds.). The Philosophy of Science: A-M. Taylor & Francis. pp. 197 ff. ISBN 978-0415977098. Nowak A., Vallacher R.R., Tesser A., Borkowski W., (2000) "Society of Self: The emergence of collective properties in self-structure", Psychological Review 107. Further reading George Musser, "Is the Cosmos Random? (Einsteins assertion that God does not play dice with the universe has been misinterpreted)", Scientific American, vol. 313, no. 3 (September 2015), pp. 88–93. External links Stanford Encyclopedia of Philosophy entry on Causal Determinism Determinism in History from the Dictionary of the History of Ideas Philosopher Ted Honderichs Determinism web resource Determinism on Information Philosopher The Society of Natural Science Archived 26 January 2021 at the Wayback Machine Determinism and Free Will in Judaism Snooker, Pool, and Determinism Game of life:-Life is a game, how to play it

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

Please help me grasp the concept behind the medical term 'Elective mutism.'

Elective mutism is a now outdated term which was defined as a refusal to speak in almost all social situations (despite normal ability to do so), while selective mutism was considered to be a failure to speak in specific situations and is strongly associated with social anxiety disorder. In contrast to selective mutism, it was thought someone who was electively mute may not speak in any situation, as is usually shown in books and films. Elective mutism was often attributed to defiance or the effect of trauma. Those who are able to speak freely in some situations but not in others are now better described by selective mutism. History In 1877, a German physician named the disorder aphasia voluntaria to describe children who were able to speak normally but often "refused" to.In 1980, a study by Torey Hayden identified four "subtypes" of Elective Mutism: Symbiotic mutism: the most common of the forms, caused by a vocal and dominating mother and absent father (very rarely the other way around) and characterized by the use of mutism as controlling behavior around other adults. Speech phobic mutism: the least common, in which the child showed distinct fear at hearing a recording of their voice. This also involved ritualistic behaviors, which may reflect OCD, and was thought to be caused by the child having been told to keep a family secret. Reactive mutism: a reaction to trauma and/or abuse, with all children showing symptoms of depression and being notably withdrawn, usually showing no facial expressions. Notably, Hayden admits that some children put in this category had no apparent incident to react to, but they were included because of their symptoms. Passive-aggressive mutism: silence is used as a display of hostility, connected to antisocial behavior. Some of the children in her study had reportedly not been mute until age 9–12.The Diagnostic and Statistical Manual of Mental Disorders (DSM), first published in 1952, first included Elective Mutism in its third edition, published in 1980. Elective mutism was described as "a continuous refusal to speak in almost all social situations" despite normal ability to speak. While "excessive shyness" and other anxiety-related traits were listed as associated features, predisposing factors included "maternal overprotection", intellectual disability, and trauma. Elective mutism in the third edition revised (DSM III-R) is described similarly as in the third edition except for specifying that the disorder is not related to social anxiety disorder. In 1994, the fourth edition of the DSM reflected the name change to selective mutism and redefined the disorder. Cultural references Though elective mutism is no longer recognized by most psychiatrists, it is a popular character element or plot point in stories and movies. Many characters choose to stop speaking, for various reasons. Even more commonly, there are also characters who stop speaking after a traumatic incident. In both these cases, often, and almost always in the second, the character is silent in all situations. This is therefore not selective mutism, and anxiety is very rarely involved. Selective mutism itself is almost nonexistent in pop culture. The following are a few references to stories including a character who does not speak despite being physically able to. In the book Cut by Patricia McCormick, the main character, Callie, is an elective mute. In The House of the Spirits by Isabel Allende, Clara Trueba is mute after witnessing her sisters molestation and autopsy. "She could not move until the first lights of dawn appeared. Only then did she slip back into her bed, feeling within her the silence of the entire world. Silence filled her utterly." In Hannibal Rising by Thomas Harris, Hannibal Lecter is mute after witnessing his sister killed and eaten. In the book Flying Solo, the character Rachel is mute for six months after a classmate dies. In The Piano, Ada is an elective mute. She chooses to learn to speak at the end of the film. In the 1993 movie, House of Cards, Sally Matthews chooses not to speak after her father dies. In the book Halo: Ghosts of Onyx, Lucy-B091 is mute after she is one of only two survivors from her unit of 300. In the movie The Prophet Kamilas daughter, Elmitra, is depicted as mute after the death of her father. In the 2014 video game Watch Dogs, Aiden Pearces nephew, Jackson, is electively mute after the death of his sister. In the book Fifty Shades of Grey, Christian Grey is depicted as having been an elective mute from age 4, when he witnessed his birth mothers drug overdose and death and was with her body for days before being discovered, until he was 6 years old and he spoke his newly adopted baby sisters name. In John Greens narrative YouTube series Swindon Town Swoodilypoopers, midfielder Maric Maric is selectively mute. In A Good Woman Is Hard to Find, Ben Collins stops speaking after witnessing his father being knifed to death. In the season 7 episode of Little House on the Prairie "The Silent Cry", one of the two brothers is depicted as an elective mute, much of the story revolving around the issues with adopting him due to not speaking. == References ==

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

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

Lipoatrophic diabetes is a type of diabetes mellitus presenting with severe lipodystrophy in addition to the traditional signs of diabetes. See also Familial partial lipodystrophy Congenital generalized lipodystrophy External links Iglesias P, Alvarez Fidalgo P, Codoceo R, Díez J (2004). "Lipoatrophic diabetes in an elderly woman: clinical course and serum adipocytokine concentrations". Endocr J. 51 (3): 279–86. doi:10.1507/endocrj.51.279. PMID 15256772. Morse A, Whitaker M (2000). "Successful pregnancy in a woman with lipoatrophic diabetes mellitus. A case report". J Reprod Med. 45 (10): 850–2. PMID 11077638. Meyer L, Hadjadj S, Guerci B, Delbachian I, Ziegler O, Drouin P (1998). "Lipoatrophic diabetes mellitus treated by continuous subcutaneous insulin infusion". Diabetes Metab. 24 (6): 544–6. PMID 9932222.

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

What does the medical term 'Cabazitaxel' encompass?

Cabazitaxel, sold under the brand name Jevtana, is a semi-synthetic derivative of a natural taxoid. It is a microtubule inhibitor, and the fourth taxane to be approved as a cancer therapy.Cabazitaxel was developed by Sanofi-Aventis and was approved by the U.S. Food and Drug Administration (FDA) for the treatment of hormone-refractory prostate cancer in June 2010. It is available as a generic medication. Medical uses Cabazitaxel is indicated in combination with prednisone for the treatment of metastatic castration-resistant prostate cancer following docetaxel-based treatment. Mechanism of action Taxanes enhance microtubule stabilization and inhibit cellular mitosis and division. Moreover, taxanes prevent androgen receptor (AR) signaling by binding cellular microtubules and the microtubule-associated motor protein dynein, thus averting AR nuclear translocation. Clinical trials In patients with metastatic castration-resistant prostate cancer (mCRPC), overall survival (OS) is markedly enhanced with cabazitaxel versus mitoxantrone after prior docetaxel treatment. FIRSTANA (ClinicalTrials.gov identifier: NCT01308567) assessed whether cabazitaxel 20 mg/m2 (C20) or 25 mg/m2 (C25) is superior to docetaxel 75 mg/m2 (D75) in terms of OS in patients with chemotherapy-naïve mCRPC. However, C20 and C25 did not demonstrate superiority for OS versus D75 in patients with chemotherapy-naïve mCRPC. Cabazitaxel and docetaxel demonstrated different toxicity profiles, and C20 showed the overall lowest toxicity. In a phase III trial with 755 men for the treatment of castration-resistant prostate cancer, median survival was 15.1 months for patients receiving cabazitaxel versus 12.7 months for patients receiving mitoxantrone. Cabazitaxel was associated with more grade 3–4 neutropenia (81.7%) than mitoxantrone (58%). Common adverse effects with cabazitaxel include neutropenia (including febrile neutropenia) and GIT side effects appeared mainly in diarrhea, whereas, neuropathy was rarely detected. Pharmacokinetics Cabazitaxel administration causes a decrease in plasma concentrations showing triphasic kinetics: a mean half life (t1/2) of 2.6 min in the first phase, a mean t1/2 of 1.3 h in the second phase, and a mean t1/2 of 77.3 h in the third phase. Metabolism Cabazitaxel is basically metabolized in the liver by [cytochrome P450 (CYP)3A4/5 > CYP2C8], which result in seven plasma metabolites and excreted 20 metabolites. During 14 days after administration, 80% of cabazitaxel is excreted: 76% in the feces and 3.7% as a renal excretion. References External links "Cabazitaxel". Drug Information Portal. U.S. National Library of Medicine. "Cabazitaxel Accord 20 mg/mL concentrate for solution infusion: Risk of medication errors and mix-up with Jevtana (60 mg/1.5 mL) solvent infusion". European Medicines Agency (EMA). October 28, 2020. Clinical trial number NCT00417079 for "XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC)" at ClinicalTrials.gov Clinical trial number NCT01308580 for "Cabazitaxel at 20 mg/m² Compared to 25 mg/m² With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer (PROSELICA)" at ClinicalTrials.gov Clinical trial number NCT02485691 for "Cabazitaxel Versus the Switch to Alternative AR-targeted Agent (Enzalutamide or Abiraterone) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent (CARD)" at ClinicalTrials.gov

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

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

Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear, the result is virtually always death, regardless of treatment. The time period between contracting the disease and the start of symptoms is usually one to three months but can vary from less than one week to more than one year. The time depends on the distance the virus must travel along peripheral nerves to reach the central nervous system.Rabies is caused by lyssaviruses, including the rabies virus and Australian bat lyssavirus. It is spread when an infected animal bites or scratches a human or other animals. Saliva from an infected animal can also transmit rabies if the saliva comes into contact with the eyes, mouth, or nose. Globally, dogs are the most common animal involved. In countries where dogs commonly have the disease, more than 99% of rabies cases are the direct result of dog bites. In the Americas, bat bites are the most common source of rabies infections in humans, and less than 5% of cases are from dogs. Rodents are very rarely infected with rabies. The disease can be diagnosed only after the start of symptoms.Animal control and vaccination programs have decreased the risk of rabies from dogs in a number of regions of the world. Immunizing people before they are exposed is recommended for those at high risk, including those who work with bats or who spend prolonged periods in areas of the world where rabies is common. In people who have been exposed to rabies, the rabies vaccine and sometimes rabies immunoglobulin are effective in preventing the disease if the person receives the treatment before the start of rabies symptoms. Washing bites and scratches for 15 minutes with soap and water, povidone-iodine, or detergent may reduce the number of viral particles and may be somewhat effective at preventing transmission. As of 2016, only fourteen people were documented to have survived a rabies infection after showing symptoms. However, research conducted in 2010 among a population of people in Perú with a self-reported history of one or more bites from vampire bats (commonly infected with rabies), found that out of 73 individuals reporting previous bat bites, 7 people had rabies virus-neutralizing antibodies (rVNA). Since only one member of this group reported prior vaccination for rabies, the findings of the research suggest previously undocumented cases of infection and viral replication followed by an abortive infection. This could indicate that in rare cases people may have an exposure to the virus without treatment and develop natural antibodies as a result. Rabies causes about 59,000 deaths worldwide per year, about 40% of which are in children under the age of 15. More than 95% of human deaths from rabies occur in Africa and Asia.Rabies is present in more than 150 countries and on all continents but Antarctica. More than 3 billion people live in regions of the world where rabies occurs. A number of countries, including Australia and Japan, as well as much of Western Europe, do not have rabies among dogs. Many Pacific islands do not have rabies at all. It is classified as a neglected tropical disease. Etymology The name rabies is derived from the Latin rabies, "madness". This, in turn, may be related to the Sanskrit rabhas, "to rage". The Greeks derived the word lyssa, from lud or "violent"; this root is used in the genus name of the rabies virus, Lyssavirus. Signs and symptoms The period between infection and the first symptoms (incubation period) is typically 1–3 months in humans. This period may be as short as four days or longer than six years, depending on the location and severity of the wound and the amount of virus introduced. Initial symptoms of rabies are often nonspecific such as fever and headache. As rabies progresses and causes inflammation of the brain and meninges, symptoms can include slight or partial paralysis, anxiety, insomnia, confusion, agitation, abnormal behavior, paranoia, terror, and hallucinations. The person may also have fear of water.The symptoms eventually progress to delirium, and coma. Death usually occurs 2 to 10 days after first symptoms. Survival is almost unknown once symptoms have presented, even with intensive care.Rabies has also occasionally been referred to as hydrophobia ("fear of water") throughout its history. It refers to a set of symptoms in the later stages of an infection in which the person has difficulty swallowing, shows panic when presented with liquids to drink, and cannot quench their thirst. Any mammal infected with the virus may demonstrate hydrophobia. Saliva production is greatly increased, and attempts to drink, or even the intention or suggestion of drinking, may cause excruciatingly painful spasms of the muscles in the throat and larynx. Since the infected individual cannot swallow saliva and water, the virus has a much higher chance of being transmitted, because it multiplies and accumulates in the salivary glands and is transmitted through biting. Hydrophobia is commonly associated with furious rabies, which affects 80% of rabies-infected people. The remaining 20% may experience a paralytic form of rabies that is marked by muscle weakness, loss of sensation, and paralysis; this form of rabies does not usually cause fear of water. Cause Rabies is caused by a number of lyssaviruses including the rabies virus and Australian bat lyssavirus. Duvenhage lyssavirus may cause a rabies-like infection.The rabies virus is the type species of the Lyssavirus genus, in the family Rhabdoviridae, order Mononegavirales. Lyssavirions have helical symmetry, with a length of about 180 nm and a cross-section of about 75 nm. These virions are enveloped and have a single-stranded RNA genome with negative sense. The genetic information is packed as a ribonucleoprotein complex in which RNA is tightly bound by the viral nucleoprotein. The RNA genome of the virus encodes five genes whose order is highly conserved: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and the viral RNA polymerase (L).To enter cells, trimeric spikes on the exterior of the membrane of the virus interact with a specific cell receptor, the most likely one being the acetylcholine receptor. The cellular membrane pinches in a procession known as pinocytosis and allows entry of the virus into the cell by way of an endosome. The virus then uses the acidic environment, which is necessary, of that endosome and binds to its membrane simultaneously, releasing its five proteins and single-strand RNA into the cytoplasm.Once within a muscle or nerve cell, the virus undergoes replication. The L protein then transcribes five mRNA strands and a positive strand of RNA all from the original negative strand RNA using free nucleotides in the cytoplasm. These five mRNA strands are then translated into their corresponding proteins (P, L, N, G and M proteins) at free ribosomes in the cytoplasm. Some proteins require post-translative modifications. For example, the G protein travels through the rough endoplasmic reticulum, where it undergoes further folding, and is then transported to the Golgi apparatus, where a sugar group is added to it (glycosylation).When there are enough viral proteins, the viral polymerase will begin to synthesize new negative strands of RNA from the template of the positive-strand RNA. These negative strands will then form complexes with the N, P, L and M proteins and then travel to the inner membrane of the cell, where a G protein has embedded itself in the membrane. The G protein then coils around the N-P-L-M complex of proteins taking some of the host cell membrane with it, which will form the new outer envelope of the virus particle. The virus then buds from the cell.From the point of entry, the virus is neurotropic, traveling along the neural pathways into the central nervous system. The virus usually first infects muscle cells close to the site of infection, where they are able to replicate without being noticed by the hosts immune system. Once enough virus has been replicated, they begin to bind to acetylcholine receptors at the neuromuscular junction. The virus then travels through the nerve cell axon via retrograde transport, as its P protein interacts with dynein, a protein present in the cytoplasm of nerve cells. Once the virus reaches the cell body it travels rapidly to the central nervous system (CNS), replicating in motor neurons and eventually reaching the brain. After the brain is infected, the virus travels centrifugally to the peripheral and autonomic nervous systems, eventually migrating to the salivary glands, where it is ready to be transmitted to the next host.: 317 Transmission All warm-blooded species, including humans, may become infected with the rabies virus and develop symptoms. Birds were first artificially infected with rabies in 1884; however, infected birds are largely, if not wholly, asymptomatic, and recover. Other bird species have been known to develop rabies antibodies, a sign of infection, after feeding on rabies-infected mammals.The virus has also adapted to grow in cells of cold-blooded vertebrates. Most animals can be infected by the virus and can transmit the disease to humans. Worldwide, about 99% of human rabies cases come from domestic dogs. Other sources of rabies in humans include bats, monkeys, raccoons, foxes, skunks, cattle, wolves, coyotes, cats, and mongooses (normally either the small Asian mongoose or the yellow mongoose).Rabies may also spread through exposure to infected bears, domestic farm animals, groundhogs, weasels, and other wild carnivorans. However, lagomorphs, such as hares and rabbits, and small rodents, such as chipmunks, gerbils, guinea pigs, hamsters, mice, rats, and squirrels, are almost never found to be infected with rabies and are not known to transmit rabies to humans. Bites from mice, rats, or squirrels rarely require rabies prevention because these rodents are typically killed by any encounter with a larger, rabid animal, and would, therefore, not be carriers. The Virginia opossum (a marsupial, unlike the other mammals named in this paragraph, which are all eutherians/placental), has a lower internal body temperature than the rabies virus prefers and therefore is resistant but not immune to rabies. Marsupials, along with monotremes (platypuses and echidnas), typically have lower body temperatures than similarly sized eutherians.The virus is usually present in the nerves and saliva of a symptomatic rabid animal. The route of infection is usually, but not always, by a bite. In many cases, the infected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behavior. This is an example of a viral pathogen modifying the behavior of its host to facilitate its transmission to other hosts. After a typical human infection by bite, the virus enters the peripheral nervous system. It then travels retrograde along the efferent nerves toward the central nervous system. During this phase, the virus cannot be easily detected within the host, and vaccination may still confer cell-mediated immunity to prevent symptomatic rabies. When the virus reaches the brain, it rapidly causes encephalitis, the prodromal phase, which is the beginning of the symptoms. Once the patient becomes symptomatic, treatment is almost never effective and mortality is over 99%. Rabies may also inflame the spinal cord, producing transverse myelitis.Although it is theoretically possible for rabies-infected humans to transmit it to others by biting or otherwise, no such cases have ever been documented, because infected humans are usually hospitalized and necessary precautions taken. Casual contact, such as touching a person with rabies or contact with non-infectious fluid or tissue (urine, blood, feces), does not constitute an exposure and does not require post-exposure prophylaxis. But as the virus is present in sperm and vaginal secretions, it might be possible for rabies to spread through sex. There are only a handful of recorded cases of human-to-human transmission of rabies, and all occurred through organ transplants from infected donors. Diagnosis Rabies can be difficult to diagnose because, in the early stages, it is easily confused with other diseases or even with a simple aggressive temperament. The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, which is recommended by the World Health Organization (WHO). The FAT relies on the ability of a detector molecule (usually fluorescein isothiocyanate) coupled with a rabies-specific antibody, forming a conjugate, to bind to and allow the visualisation of rabies antigen using fluorescent microscopy techniques. Microscopic analysis of samples is the only direct method that allows for the identification of rabies virus-specific antigen in a short time and at a reduced cost, irrespective of geographical origin and status of the host. It has to be regarded as the first step in diagnostic procedures for all laboratories. Autolysed samples can, however, reduce the sensitivity and specificity of the FAT. The RT PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes, particularly in decomposed samples or archival specimens. The diagnosis can be reliably made from brain samples taken after death. The diagnosis can also be made from saliva, urine, and cerebrospinal fluid samples, but this is not as sensitive or reliable as brain samples. Cerebral inclusion bodies called Negri bodies are 100% diagnostic for rabies infection but are found in only about 80% of cases. If possible, the animal from which the bite was received should also be examined for rabies.Some light microscopy techniques may also be used to diagnose rabies at a tenth of the cost of traditional fluorescence microscopy techniques, allowing identification of the disease in less-developed countries. A test for rabies, known as LN34, is easier to run on a dead animals brain and might help determine who does and does not need post-exposure prevention. The test was developed by the CDC in 2018.The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, in particular infection with viruses such as herpesviruses, enteroviruses, and arboviruses such as West Nile virus. The most important viruses to rule out are herpes simplex virus type one, varicella zoster virus, and (less commonly) enteroviruses, including coxsackieviruses, echoviruses, polioviruses, and human enteroviruses 68 to 71.New causes of viral encephalitis are also possible, as was evidenced by the 1999 outbreak in Malaysia of 300 cases of encephalitis with a mortality rate of 40% caused by Nipah virus, a newly recognized paramyxovirus. Likewise, well-known viruses may be introduced into new locales, as is illustrated by the outbreak of encephalitis due to West Nile virus in the eastern United States. Prevention Almost all human exposure to rabies was fatal until a vaccine was developed in 1885 by Louis Pasteur and Émile Roux. Their original vaccine was harvested from infected rabbits, from which the virus in the nerve tissue was weakened by allowing it to dry for five to ten days. Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines. The human diploid cell rabies vaccine was started in 1967. Less expensive purified chicken embryo cell vaccine and purified vero cell rabies vaccine are now available. A recombinant vaccine called V-RG has been used in Belgium, France, Germany, and the United States to prevent outbreaks of rabies in undomesticated animals. Immunization before exposure has been used in both human and nonhuman populations, where, as in many jurisdictions, domesticated animals are required to be vaccinated. The Missouri Department of Health and Senior Services Communicable Disease Surveillance 2007 Annual Report states the following can help reduce the risk of contracting rabies:Vaccinating dogs, cats, and ferrets against rabies Keeping pets under supervision Not handling wild animals or strays Contacting an animal control officer upon observing a wild animal or a stray, especially if the animal is acting strangely If bitten by an animal, washing the wound with soap and water for 10 to 15 minutes and contacting a healthcare provider to determine if post-exposure prophylaxis is required28 September is World Rabies Day, which promotes the information, prevention, and elimination of the disease.In Asia and in parts of the Americas and Africa, dogs remain the principal host. Mandatory vaccination of animals is less effective in rural areas. Especially in developing countries, pets may not be privately kept and their destruction may be unacceptable. Oral vaccines can be safely distributed in baits, a practice that has successfully reduced rabies in rural areas of Canada, France, and the United States. In Montreal, Quebec, Canada, baits are successfully used on raccoons in the Mount-Royal Park area. Vaccination campaigns may be expensive, but cost-benefit analysis suggests baits may be a cost-effective method of control. In Ontario, a dramatic drop in rabies was recorded when an aerial bait-vaccination campaign was launched.The number of recorded human deaths from rabies in the United States has dropped from 100 or more annually in the early 20th century to one or two per year due to widespread vaccination of domestic dogs and cats and the development of human vaccines and immunoglobulin treatments. Most deaths now result from bat bites, which may go unnoticed by the victim and hence untreated. Treatment After exposure Treatment after exposure can prevent the disease if given within 10 days. The rabies vaccine is 100% effective if given early, and still has a chance of success if delivery is delayed. Every year, more than 15 million people get vaccinated after potential exposure. While this works well, the cost is significant. In the US it is recommended people receive one dose of human rabies immunoglobulin (HRIG) and four doses of rabies vaccine over a 14-day period. HRIG is expensive and makes up most of the cost of post-exposure treatment, ranging as high as several thousand dollars. In the UK, one dose of HRIG costs the National Health Service £1,000, although this is not flagged as a "high-cost medication". A full course of vaccine costs £120–180. As much as possible of HRIG should be injected around the bites, with the remainder being given by deep intramuscular injection at a site distant from the vaccination site.People who have previously been vaccinated against rabies do not need to receive the immunoglobulin—only the postexposure vaccinations on days 0 and 3. The side effects of modern cell-based vaccines are similar to the side effects of flu shots. The old nerve-tissue-based vaccination required multiple injections into the abdomen with a large needle but is inexpensive. It is being phased out and replaced by affordable World Health Organization intradermal-vaccination regimens. In children less than a year old, the lateral thigh is recommended. Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is effective in reducing the number of viral particles. Povidone-iodine or alcohol is then recommended to reduce the virus further.Awakening to find a bat in the room, or finding a bat in the room of a previously unattended child or mentally disabled or intoxicated person, is an indication for post-exposure prophylaxis (PEP). The recommendation for the precautionary use of PEP in bat encounters where no contact is recognized has been questioned in the medical literature, based on a cost–benefit analysis. However, a 2002 study has supported the protocol of precautionary administration of PEP where a child or mentally compromised individual has been alone with a bat, especially in sleep areas, where a bite or exposure may occur with the victim being unaware. After onset At least two treatment schemes have been proposed for treating rabies after the onset of symptoms, the Milwaukee Protocol and the Recife Protocol. The Milwaukee Protocol was first used in 2004 on Jeanna Giese, who became the first person known to have survived rabies without preventive treatments before symptom onset. The protocol puts a person into a chemically induced coma and uses antiviral medications to prevent fatal dysautonomia. The overall protocol is complex; the sixth version of the protocol last updated in 2018 consists of 17 pages with 22 steps of treatment, detailed monitoring, and a timeline of expected complications. The Recife Protocol follows the same principle but differs in details like termination of sedation and supplementary medication. Prognosis Vaccination after exposure, PEP, is highly successful in preventing rabies. In unvaccinated humans, rabies is virtually always fatal after neurological symptoms have developed. Epidemiology In 2010, an estimated 26,000 people died from rabies, down from 54,000 in 1990. The majority of the deaths occurred in Asia and Africa. As of 2015, India, followed by China (approximately 6,000) and the Democratic Republic of the Congo (5,600), had the most cases. A 2015 collaboration between the World Health Organization, World Organization of Animal Health (OIE), Food and Agriculture Organization of the United Nation (FAO), and Global Alliance for Rabies Control has a goal of eliminating deaths from rabies by 2030. India India has the highest rate of human rabies in the world, primarily because of stray dogs, whose number has greatly increased since a 2001 law forbade the killing of dogs. Effective control and treatment of rabies in India is hindered by a form of mass hysteria known as puppy pregnancy syndrome (PPS). Dog bite victims with PPS, male as well as female, become convinced that puppies are growing inside them, and often seek help from faith healers rather than medical services. An estimated 20,000 people die every year from rabies in India, more than a third of the global total. Australia Australia has an official rabies-free status, although Australian bat lyssavirus (ABLV), discovered in 1996, is a strain of rabies prevalent in Australian native bat populations. United States Canine-specific rabies has been eradicated in the United States. But rabies is common among wild animals in the United States, and an average of 100 dogs become infected from other wildlife each year.Due to high public awareness of the virus, efforts at vaccination of domestic animals and curtailment of feral populations, and availability of postexposure prophylaxis, incidence of rabies in humans is very rare in the United States. From 1960 to 2018, a total of 125 human rabies cases were reported in the United States; 36 (28%) were attributed to dog bites during international travel. Among the 89 infections acquired in the United States, 62 (70%) were attributed to bats. The most recent rabies death in the United States was an Illinois man who refused treatment after waking up in the night with a bat on his neck; the man died a month later. Occurring in 2021, it was the first case of human rabies in the United States in nearly three years. Europe Either no or very few cases of rabies are reported each year in Europe; cases are contracted both during travel and in Europe.In Switzerland the disease was virtually eliminated after scientists placed chicken heads laced with live attenuated vaccine in the Swiss Alps. The foxes of Switzerland, proven to be the main source of rabies in the country, ate the chicken heads and immunized themselves.Italy, after being declared rabies-free from 1997 to 2008, has witnessed a reemergence of the disease in wild animals in the Triveneto regions (Trentino-Alto Adige/Südtirol, Veneto and Friuli-Venezia Giulia), due to the spreading of an epidemic in the Balkans that also affected Austria. An extensive wild animal vaccination campaign eliminated the virus from Italy again, and it regained the rabies-free country status in 2013, the last reported case of rabies being reported in a red fox in early 2011.The United Kingdom has been free of rabies since the early 20th century except for a rabies-like virus (EBLV-2) in a few Daubentons bats. There has been one fatal case of EBLV-2 transmission to a human. There have been four deaths from rabies, transmitted abroad by dog bites, since 2000. The last infection in the UK occurred in 1922, and the last death from indigenous rabies was in 1902.Sweden and mainland Norway have been free of rabies since 1886. Bat rabies antibodies (but not the virus) have been found in bats. On Svalbard, animals can cross the arctic ice from Greenland or Russia. Mexico Mexico was certified by the World Health Organization as being free of dog-transmitted rabies in 2019 because no case of dog-human transmission had been recorded in two years. History Rabies has been known since around 2000 BC. The first written record of rabies is in the Mesopotamian Codex of Eshnunna (c. 1930 BC), which dictates that the owner of a dog showing symptoms of rabies should take preventive measures against bites. If another person were bitten by a rabid dog and later died, the owner was heavily fined.In Ancient Greece, rabies was supposed to be caused by Lyssa, the spirit of mad rage.Ineffective folk remedies abounded in the medical literature of the ancient world. The physician Scribonius Largus prescribed a poultice of cloth and hyena skin; Antaeus recommended a preparation made from the skull of a hanged man.Rabies appears to have originated in the Old World, the first epizootic in the New World occurring in Boston in 1768.Rabies was considered a scourge for its prevalence in the 19th century. In France and Belgium, where Saint Hubert was venerated, the "St Huberts Key" was heated and applied to cauterize the wound. By an application of magical thinking, dogs were branded with the key in hopes of protecting them from rabies. It was not uncommon for a person bitten by a dog merely suspected of being rabid to commit suicide or to be killed by others.In ancient times the attachment of the tongue (the lingual frenulum, a mucous membrane) was cut and removed as this was where rabies was thought to originate. This practice ceased with the discovery of the actual cause of rabies. Louis Pasteurs 1885 nerve tissue vaccine was successful, and was progressively improved to reduce often severe side-effects.In modern times, the fear of rabies has not diminished, and the disease and its symptoms, particularly agitation, have served as an inspiration for several works of zombie or similarly themed fiction, often portraying rabies as having mutated into a stronger virus which fills humans with murderous rage or incurable illness, bringing about a devastating, widespread pandemic. Other animals Rabies is infectious to mammals; three stages of central nervous system infection are recognized. The first stage is a one- to three-day period characterized by behavioral changes and is known as the prodromal stage. The second is the excitative stage, which lasts three to four days. This stage is often known as "furious rabies" for the tendency of the affected animal to be hyper-reactive to external stimuli and bite at anything near. The third is the paralytic stage and is caused by damage to motor neurons. Incoordination is seen, owing to rear limb paralysis, and drooling and difficulty swallowing is caused by paralysis of facial and throat muscles. Death is usually caused by respiratory arrest. Research Biotechnological use The outer shell of the rabies virus, stripped of its RNA contents and thus unable to cause disease, may be used as a vector for the delivery of unrelated genetic material in a research setting. It has the advantage over other pseudotyping methods for gene delivery in that the cell targeting (tissue tropism) is more specific for the central nervous system, a difficult-to-reach site, obviating the need for invasive delivery methods. It is also capable of infecting neighboring "upstream" cells, moving from one cell to axons of the next at synapses, and is thus used for retrograde tracing in neuronal circuits. Potential treatment Evidence indicates artificially increasing the permeability of the blood–brain barrier, which normally does not allow most immune cells across, promotes viral clearance. See also Global Alliance for Rabies Control Rabies in Haiti Eradication of infectious diseases Madstone (folklore) References Further reading Pankhurst, Richard. "The history and traditional treatment of rabies in Ethiopia." Medical History 14, no. 4 (1970): 378-389. External links Rabies at Curlie "Rabies". Centers for Disease Control and Prevention. Retrieved 12 August 2012. Virus Pathogen Database and Analysis Resource (ViPR): Rhabdoviridae OIEs Rabies Portal Archived 13 August 2020 at the Wayback Machine Aerophobia and Hydrophobia in Rabies Videos "Rabies virus". NCBI Taxonomy Browser. 11292.

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

Could you provide a brief overview of 'Plasma cell dyscrasias' in a medical context?

Plasma cell dyscrasias (also termed plasma cell disorders and plasma cell proliferative diseases) are a spectrum of progressively more severe monoclonal gammopathies in which a clone or multiple clones of pre-malignant or malignant plasma cells (sometimes in association with lymphoplasmacytoid cells or B lymphocytes) over-produce and secrete into the blood stream a myeloma protein, i.e. an abnormal monoclonal antibody or portion thereof. The exception to this rule is the disorder termed non-secretory multiple myeloma; this disorder is a form of plasma cell dyscrasia in which no myeloma protein is detected in serum or urine (at least as determined by conventional laboratory methods) of individuals who have clear evidence of an increase in clonal bone marrow plasma cells and/or evidence of clonal plasma cell-mediated tissue injury (e.g. plasmacytoma tumors). Here, a clone of plasma cells refers to group of plasma cells that are abnormal in that they have an identical genetic identity and therefore are descendants of a single genetically distinct ancestor cell. At one end of this spectrum of hematological disorders, detection of one of these myeloma proteins in an individuals blood or urine is due to a common and clinically silent disorder termed MGUS, i.e. monoclonal gammopathy of undetermined significance. At the other end of this spectrum, detection of the myeloid protein is due to a hematological malignancy, i.e. multiple myeloma, Waldenström macroglobulinemia, or other B cell-associated neoplasm, that has developed, often in a stepwise manner, from their MGUS precursors.The clinical importance of understanding this spectrum of diseases is that it can be used to: a) advise individuals on the likelihood of their condition progressing to a malignant phase; b) monitor individuals for the many complications that may occur at any stage of the dyscrasias so that they can be treated to avoid or reduce their clinical impacts; and c) monitor patients for transitions to malignancy so that the malignancy can be treated at an early stage when treatment results are best. Unless otherwise noted, the advice and monitoring given here are those recommended by the International Myeloma Working Group in 2014 and updated in 2016. Clonal plasma cells Plasma cells are key effector elements of the adaptive immune system. They contribute to immunity by making antibodies that bind with and thereby initiate the process of neutralizing specific antigens that usually are found on the surface of invading pathogens and foreign substances. Plasma cells develop from B lymphocytes (i.e. B cells) which are stimulated to undergo this maturational development by T lymphocytes during the latter cells processing of these antigens. As they are stimulated to become plasma cells, B cells refashion parts of their genome in efforts to create a new gene that encodes a functional antibody. In humans, antibodies are composed of two identical heavy chains which are of the gamma (γ), alpha (α), epsilon (ε), delta (δ), or mu (μ) subtypes and two identical light chains which are of the kappa (κ) or lambda (λ) subtypes. Antibodies are classified as IgG, IgA, IgE, IgD, and IgM based on their being made up of γ, α, ε, δ, or μ heavy chains, respectively. Formation of the genes that make these antibodies requires B cells and/or their descendent plasma cells to mutate, break, and recombine various genes at the immunoglobulin heavy chain antigen-binding locus on the long (i.e. "q") arm of human chromosome 14 at position 32.33 (notated as 14q32.33) and the immunoglobulin light chain antigen binding locus on the q arm of chromosome 22 at position 11.2 (i.e. 22 q11.2) by processes termed V(D)J recombination, somatic hypermutation, and immunoglobulin class switching. These genomic changes can go awry by placing a gene that controls cell growth an/or survival adjacent to a normally highly active antibody gene promoter and/or by causing the formation of extra chromosomes (see trisomy) or chromosomes with large deletions that result in the overexpression or under-expression, respectively, of genes that control cell growth and/or survival. In consequence of these "primary genomic changes", an expanding clone of cells develops; overproduces and secretes a monoclonal IgM, IgG, IgA, IgE, or IgD antibody, a κ or λ light chain, an α, γ, or μ heavy chain, or, very rarely, fragments of these proteins; and may accumulate "secondary genomic changes" that cause them to become malignant. The overproduced monoclonal proteins, termed myeloma proteins, commonly circulate in blood, may accumulate in urine, and are the hallmarks of plasma cell dyscrasias including their most malignant forms viz., multiple myeloma, light chain multiple myeloma, and plasma cell leukemia. IgG-secretory, IgA-secretory, and light-chain secretory multiple myeloma represent 52%, 21%, and 16%, respectively, of all multiple myeloma cases; these myelomas are associated with various types of chromosomal aberrancies and mutations. IgD-secretory multiple myeloma occurs in only 1% to 2% of multiple myeloma cases and is commonly associated with somatic mutations in the gene encoding the gV (i.e. variable) region of the monoclonal antibody. IgE-secretory multiple myeloma has been reported in <50 cases as of 2013 and is characteristically associated with translocations between the q arms of chromosome 11 and 14, i.e. t(11;14)(q13;q32) translocations.In other cases, plasma cells and/or lymphoplasmacytoid cells (a type of B cell resembling, and possible precursor to, plasma cells) suffer other kinds of mutations that lead to the production of an IgM myeloma protein. Overproduction of this myeloma protein may progress to a different form of plasma cell/lymphoplasmacytoid cell malignancy, Waldenström macroglobulinaemia. Genetic mutations thought to be involved in the development and/or progression of the latter disease include the L265P mutation in the MYD88 gene found in >90% of Waldenström macroglobulinaemia patients as well as various mutations in the CXCR gene found in 27% to 40% of Waldenström macroglobulinaemia patients.The clonal plasma cells involved in plasma cell dyscrasias exhibit a high degree of genetic instability. For example, the clonal plasma cell population formed by initial genetic alterations that lead to multiple myeloma contains cells that develop further genetic changes that enhance their survival, proliferation, tissue-injuring, and metastatic capacities. This allows the new cell clones to crowd out older cell clones and thereby establish a more malignant disease. Repetition of such genetic changes underlie the evolution of a clinically silent plasma cell dyscrasia to an overt malignancy. The progressive genetic changes in clonal plasma cells include accumulating numerous single nucleotide polymorphisms, increases and decreases in gene and chromosome copy numbers, and chromosomal translocations. Genes affected include those regulating genome stability itself (e.g. KIF2B) as well as cellular activation, proliferation, and apoptosis (e.g. CIDEC, TP52, ATM, KRAS, NRAS, Wnt, and NF-κB). In the most malignant form of plasma cell dyscrasias, primary plasma cell leukemia, the plasma cell population contains >1900 distinct DNA alterations in >600 genes.In general, the plasma cell dyscrasias are defined by 1) the presence of these genetically unstable clonal plasma cells, lymphoplasmacytoid cells, or B cells infiltrating the bone marrow or forming distinct masses in bone, and/or other tissues as defined by biopsy of involved tissues and 2) the presence of these cells myeloma proteins (i.e. intact monoclonal antibody, free light chain, free heavy chain, shortened version of these proteins, or any combination of these proteins) in blood and/or urine as defined by various types of gel electrophoresis. Obviously, the latter criterion does not apply to the rare cases of true non-secretory myeloma. Myeloma protein toxicity Myeloma proteins form as a result of gene mutations rather than physiological gene remodeling responses to an instigating foreign antigen: typically these proteins are non-functional. However, they sometimes cause serious tissue damage with the kidney being a particularly vulnerable target. The toxic effects of monoclonal proteins may occur at early stages in the plasma cell dyscrasia spectrum and require treatment independently of the mass or tissue-destructive effects of the myeloma protein-producing cells. Myeloma protein toxicities include: Monoclonal free light chains, free heavy chains, or a mixture of these chains can deposit in the kidney and other organs to cause systemic monoclonal immunoglobulin deposition disease; free κ or λ light chains can deposit selectively in the kidneys proximal tubule to cause light chain proximal tubulopathy or in the kidneys distal tubule to cause light chain myeloma cast nephropathy; and various myeloma proteins can deposit selectively in the kidneys glomeruli to cause various forms of organized deposit and non-organized deposit glomerulonephritis diseases. Free κ or λ light chains can aggregate with each other to cause extracellular amyloid deposits and a disease termed amyloidosis in which the deposits injure and ultimately lead to the failure of such organs as the kidney, heart, liver, stomach, and intestines; these deposits can also cause peripheral and autonomic neuropathies. IgM myeloma proteins or in rare cases other myeloma proteins such as IgA, free κ light chains, or free λ light chains may increase blood viscosity, deposit in peripheral blood vessels, and thereby cause vascular occlusion and gangrene of the extremities in the syndrome termed cryoglobulinemia. Monoclonal IgM myeloma proteins operating through their effects on increasing blood hyperviscosity can reduce blood flow to the central nervous system to cause blurred vision, headaches, vertigo, ataxia, and cold-induced hemolytic anemia. IgM, IgG, and to lesser extents κ and λ free light chain myeloma proteins can cause Immune thrombocytopenic purpura with extensive bleeding tendencies . Stages MGUS stage Monoclonal gammopathy of undetermined significance (MGUS), is defined as the presence in the blood or urine of a monoclonal antibody, antibody heavy chain, or antibody light chain in a person lacking symptoms or signs of a more serious plasma cell dyscrasia. The condition is typically discovered as an incidental finding when serum protein electrophoresis is done for various reasons unrelated to plasma cell dyscrasias. Protein electrophoresis generally detects one of the following patterns of monoclonal myeloma protein spikes representing: a) intact IgG, IgA, IgE, IgE, or IgM; b) intact IgG, IgA, IgE, IgD, or IgM plus high concentrations of a free (i.e. not bound to a heavy chain) κ or λ light chain; c) a free κ chain in great excess of a λ chain or a free λ chain in great excess of a κ chain; and d) free γ, δ, or μ heavy chains unbound to a light chain (free α and ε heavy chain myeloma protein spikes have not been reported). Among MGUS cases expressing an intact antibody, 70%, 15%, 12%, and 3% express either IgG, IgM, IgA, or two of these M proteins, respectively, with or without excessive levels of a light chain; these cases represent ~80% of all MGUS. About 20% of MGUS cases express either κ or λ light chains. As a group, these MGUS findings occur more commonly in men and are ~2-fold more common in individuals of African descent than Caucasians. MGUS cases expressing free γ, δ, or μ heavy chains are extremely rare. MGUS is categorized into the following sub-types based upon the identity and levels of the myeloma proteins detected as well as the prognoses for progressive disease indicated by these myeloma protein findings. Non-IgM MGUS Non-IgM MGUS, commonly termed MGUS, is diagnosed in individuals who exhibit a serum IgG, IgD, IgA, or IgE monoclonal protein with or without increased levels of blood and/or urine free κ or λ light chains. These patients typically also show small increases in bone marrow plasma cells. Further requirements for the diagnosis of non-IgM MGUS are: a) bone marrow clonal plasma cells <10% of total nucleated cells; b) absence of any of the four CRAB criteria (CRAB criteria are C = Calcium serum levels >1 milligram/deciliter above normal values and/or a serum level >11 milligram/deciliter; R = Renal insufficiency as defined by a glomerular filtration rate <40 milliliter/minute and/or a serum creatinine >2 gram/deciliter due to myeloma protein-induced kidney damaged; A = Anemia, as defined by a blood hemoglobin level >2 gram/deciliter below normal and/or <10 gram/deciliter due to the plasma cell dyscrasia rather than e.g. iron deficiency or blood loss; B = Bone lesions, i.e. ≥1 lytic (i.e. bone re-adsorbing) bone lesion due to a plasmacytoma as detected by skeletal radiography, computed tomography, or positron emission tomography-computed tomography); c) no evidence of a plasmacytoma in bone or soft tissues, of amyloidosis, or of another plasma cell disorder; d) a ratio of free serum light chains (i.e. free κ/λ or λ/κ light chain ratio) less than 100, providing that the higher light chain concentration is >100 milligram/liter; and e) a circulating blood plasma cell absolute count of <2x109 and/or <20% of total circulating nucleated cells. Presence of any one of the latter findings indicates that the plasma cell dyscrasia has progressed beyond the MGUS stage.Non-IgM MGUS is a relatively stable condition afflicting 3% of people aged 50 and 5% of people aged 70; on average, it progresses to multiple myeloma at a rate of 0.5-1% cases per year, as defined in studies following patients over a 25-year period. A study conducted by the Mayo Clinic found that MGUS associated with non-IgG myeloma proteins or with serum myeloma protein levels greater than 15 gram/liter had a greater risk per year of progression to multiple myeloma. A Spanish study group found that MGUS patients demonstrating aneuploidy (i.e. abnormal number of chromosomes) in bone marrow cells or >95% of resident bone marrow plasma cells that are clonal in nature also have a greater risk per year of progression to myeloma. In a more recent study, MGUS patients that had the presence of none, 1, 2, or 3 of the three following risk factors, serum M protein levels >15 gram/liter, a non-IgG isotype, and abnormal free light chain ratios, had 5, 32, 37, and 58% chances, respectively, of progressing to multiple myeloma within 20 years. In another study, MGUS patients with none, 1, or 2 of the following risk factors, >95% of bone marrow plasma cells that are clonal in nature and a 10% or greater rise in the levels of their monoclonal proteins within 3 years, had 2, 16, and 72% risks, respectively, of progression within 7 years. However, estimates on the risks of progression for some of these parameters are tentative and subject to change. For example, the IgA form of MGUS, while once considered to have a poorer prognosis than IgG MGUS, was found to have a prognosis similar to IgG MGUS in a more recent study. IgM MGUS While traditionally classified as such, it is not clear that IgM MGUS is a clonal plasma cell dyscrasia. IgM MGUS involves an increase in a B cell derivative with morphological features of both plasma cells and lymphocytes viz., lymphoplasmacytic cells. Studies indicate that both plasma cells and lymphoblastic cells infiltrate involved tissues and that one or perhaps both cell types harbor mutations in a) the MYD88 gene (~20% in IgM MGUS and >90% in IgM-related malignancies), almost all of which are L265P mutations (i.e. changing leucine to proline at the 265th amino acid position of the MYK88 protein thereby causing the protein to be continuously active in stimulating the same cell-activating pathways that Toll-like receptors activate intermittently and on a physiologically basis); b) the CXCR4 gene (8% in IgM MGUS, 25% in IgM-related malignancies); and c) increased gene copy number due to chromosomal rearrangements (36% in IgM MGUS, 82% in IgM-related malignancies). It is clear that each cell type contributes to different features of IgM malignancies but not clear that clonal plasma cells are critical to the development or progression of IgM MGUS. In all events, IgM MGUS is diagnosed in individuals who have serum IgM levels less than 30 gram/liter; have less than 10% of nucleated bone marrow cells with the lymphoplasmacytic morphology, and have no symptoms or findings of end organ dysfunction attributed to Waldenström macroglobulinemia such as anemia, decreases in any white blood cell count, cold agglutinin disease, hyperviscosity of blood, lymphadenopathy, hepatomegaly, splenomegaly, peripheral neuropathy, cryoglobulinemia, or constitutional symptoms.There may be a modest increase in the incidence of IgM MGUS in people of African descent. A study of 213 individuals diagnosed with IgM MGUS found that 10% at 5 years and 24% in 15 years progressed to more serious IgM-related diseases including non-Hodgkin lymphoma, Waldenstorms macroglobulinemia, systemic amyloidosis, and chronic lymphocytic leukemia. A second long-term study of 116 individuals with IgM MGUS found a 15-fold increased risk of progressing to a lymphoid malignancy, mostly to Waldenstorms macroglobulinemia. In general, progression to one of these malignant outcomes occurs at a rate of 2% to 3% per year. Individuals with higher serum IgM or lower serum albumin levels progress at faster rates than those with normal levels of these parameters. Light chain MGUS Individuals diagnosed with light chain MGUS typically do not express detectable levels of an IgG, IgA, IgD, IgE, or IgM intact myeloma protein in their blood. Rather, they overexpress a monoclonal, aberrant free κ (i.e. kappa) or λ (i.e., lambda) immunoglobulin light chain. For diagnosis, the κ and λ free light chains are quantified by immunological methods and the ratio of κ to λ light chains is used to detect unbalanced light chain synthesis that is indicative of a monoclonal light chain plasma cell dyscrasia. Light chain MGUS is defined as a disorder in which a serum κ to λ free light chain ratio falls outside the normal range of 0.26–1.65 (mean =0.9) provided that it is not associated with: a) any of the CRAB criteria, b) a bone marrow plasma cell count of 10 or a higher percentage of nucleated cells, c) evidence of amyloid deposition (see Light chain deposition disease), and d) an accumulation of 0.5 or more grams of the monoclonal light chain in the urine over a 24-hour period. As so defined, light chain MGUS comprises ~19% of all MGUS cases, occurs in ~0.8% of the general population, and progresses to light chain multiple myeloma at the very slow rate of 0.3 cases per 100 years.Some early studies have reported that a very rapid rate of progression occurs in light chain MGUS patients who have free light chain κ/λ or λ/κ ratios equal to or greater than 100 (i.e. and κ/λ ratio outside of 0.02 to 100). About 80% of individuals bearing these light chain ratios were found to progress to light chain multiple myeloma within 2 years. In consequence, these individuals were recommended for being diagnosed and treated as having light chain multiple myeloma. However, two more recent studies reported a 2-year progression rate for these patients of 64% and 30%. It is therefore suggested that the diagnosis of light chain multiple myeloma based solely on a free κ/λ light chain ratio of 0.02 to 100 may be premature. Monoclonal gammopathy of renal significance Monoclonal gammopathy of renal significance or MGRS designates any MGUS disorder that has a clinically significant impact on renal function. MGRS can be caused by the deposition of a monoclonal immunoglobulin in, and consequent injury to, the kidneys. The diagnosis of this form of MGRS is made based on the presence of: 1) a disorder meeting the criteria for MGUS; b) decreased kidney function as evidence by, e.g. a Glomerular filtration rate of <40; and c) biopsy confirmed or suspicion of cast nephropathy, glomerulonephritis, of other morphological expressions of clonal immunoglobulin-induced kidney injury. Increased excretion of a urinary monoclonal light chain (typically >0.5 gram/day), which suggests the presence of a particularly severe form of kidney injury (myeloma cast nephropathy), supports but is not a requirement for the diagnosis of MGRS. The disorder can also be caused by a monoclonal immunoglobulin that acts as an autoantibody that activates the blood complement system to cause complement-related kidney injury. This form of MGRS is usually associated with other syndromes like glomerulopathy associated with a monoclonal immunoglobulin or C4 dense deposit disease associated with a monoclonal immunoglobulin. Diagnosis depends or identifying these other syndromes and the identification of complement components on kidney biopsy. Regardless of the exact pathophysiology causing monoclonal immunoglobulin-induced kidney injury, MGRS has a greater morbidity and mortality than other forms of MGUS. Since renal dysfunction usually improves with therapy directed at the underlying plasma cell dyscrasia, MGRS may warrant treatment even when other parameters of plasma cell dyscrasia severity (e.g. low levels of serum monoclonal immunoglobulin and bone marrow plasma cells) suggest the presence of minimal, non-malignant disease. Smoldering multiple myeloma stage Smoldering multiple myeloma or SMM (also termed smoldering myeloma) is the next stage following MGUS in the spectrum of plasma cell dyscrasias. While still considered a pre-malignant condition, its chances of progressing to a malignant plasma cell dyscrasia are generally greater than that for MGUS. SMM consists of the following subtypes which represent progression of their corresponding MGUS subtypes. Non-IgM SMM Non-IgM SMM (also termed IgG and IgA SMM because of the rarity of IgD and IgE SMM) is diagnosed in asymptomatic individuals based on criteria identical to those listed above for Non-IgM MGUS except that: their intact IgG or IgA myeloma protein levels are equal to or greater than 30 grams/liter rather than 15 grams/liter; their bone marrow shows plasma cells comprise between 10% and <60% rather than <10% of nucleated cells; and/or their 24-hour urine contains 0.5 gram or greater levels of Bence Jones, i.e. light chain myeloma, proteins. individuals must also lack evidence of more recently established multiple myeloma-defining criteria viz., CRAB features, amyloidosis, more than one solitary plasmacytoma, and/or serum or urine free light chain κ to λ or λ to κ ratios of 100 or greater.Overall, the risk of Non-IgM SMM progressing to multiple myeloma is 10% per year for the first 5 years but falls off sharply to 3% per year for the next 5 years and thereafter to 1% per year. Smoldering Waldenström macroglobulinemia Smoldering Waldenström macroglobulinemia is diagnosed in asymptomatic individuals that have a serum IgM level 30 gram/liter and/or a bone marrow lymphoplasmacytoid cell infiltrate >10% of total nucleated cells. These cases should have no symptoms or findings of end organ dysfunction attributed to Waldenström macroglobulinemia such as anemia, decreases in any white blood cell count, cold agglutinin disease, hyperviscosity of blood, lymphadenopathy, hepatomegaly, splenomegaly, peripheral neuropathy, cryoglobulinemia, or constitutional symptoms.As determined by a Mayo Clinic study of 48 individuals, smoldering Waldenström macroglobulinemias risk of progression to Waldenström macroglobulinemia is estimated to be ~12% per year and then falling of sharply for at least the next 5 years to 2% per year. In this study the only factor predictive of a more rapid progress was a finding of anemia (hemoglobin level <115 grams/liter). During a 15-year follow-up, the Clinic subsequently reported that patients progressed to Waldenström macroglobulinemia, amyloidosis, or a related IgM-associated neoplasm at a rate of 6%, 39%, 59%, and 68% after the first, third, fifth, and tenth year, respectively. However, the Southwest Oncology Group in a study on 231 individuals reported that the smoldering disease progressed to overt Waldenström macroglobulinemia over 9 years in only 26% of cases. Light chain SMM Light chain smoldering multiple myeloma (light chain SMM) was previously termed idiopathic Bence Jones proteinuria. The condition is currently diagnosed in asymptomatic individuals who have a 24-hour urinary Bence Jones, i.e. light chain myeloma protein level, that is >0.5 grams and/or bone marrow plasma cells that are 10% to <60% of nucleated cells. These individuals must also; lack detectable IgG, IgA, IgD, IgE, or IgM myeloma proteins in sera; have a free κ/λ or λ/κ light chain ratio outside of 0.26 to 1.65 range but less than 100; and/or have no evidence for the presence of any one of the CRAB criteria, amyloidosis, or end organ damage attributable to the myeloma proteins or plasma cells.In a Mayo clinic study of 101 individuals with light chain SMM, the cumulative probability of progression to active multiple myeloma or light-chain amyloidosis in patients with light-chain SMM was 28%, 45%, and 56% after 5, 10, and 15 years, respectively. The major risk factors for progression were the level of urinary excretion of M protein, percentage of bone marrow plasma cells, and immunoparesis (i.e. reduced serum levels of intact immunoglobulins). Paraneoplastic complications Serious and potentially life-threatening paraneoplastic complications can occur in plasma cell dyscrasias regardless of tumor cell burden, myeloma protein levels, or the presence of other criteria suggesting the dyscrasia has entered a malignant phase. Many of these complications are caused by the tissue-destructive effects of the myeloma proteins, are predictive of a rapidly progressive disease, and require chemotherapeutic or other treatments directed at lowering the burden of the myeloma protein-producing cells. The serious paraneoplasitic diseases that complicate the plasma cell dyscrasias and may require such treatments include the following. Amyloidosis Amyloidosis is a general term for a protein misfolding syndrome that involves the deposition of a low molecular weight beta-pleated sheet-containing protein in extracellular tissues. These proteins normally circulate in the blood but may undergo conformational changes that cause them to auto-aggregate along their beta-pleated sheets to become insoluble and form fibril deposits in and outside of the circulation. These deposits disrupt tissue architecture and, in the case of light chains, directly injure cells, thereby causing potentially cataclysmic organ failures. There are 31 types of circulating proteins that can become misfolded and lead to distinctly different types of amyloidosis; among these, myeloma proteins, particularly free light chains, are the predominant cause of the disease. Increases in the levels of free κ or λ light chains are a common feature of plasma cell dyscrasias. These increases occur in: 40% of IgM MGUS, IgM SMM, and Waldenstroms macroglbulonemia cases; 60% to 70% of non-secretory multiple myelom cases; 90% to 95% of intact immunoglobulin multiple myeloma cases; and, by definition, 100% of light chain multiple myeloma cases. There are two different types of plasma cell dyscrasia-associated amyloidosis syndromes: amyloid light chain amyloidosis (AL amyloidosis) in which amyloid deposits consist of free light chains and amyloid heavy chain amyloidosis (AH amyloidosis) in which amyloid deposits contain only free heavy chains. The deposits in a third type, AHL amyloidosis, consists of both free light chains and free heavy chains. AHL amyloidosis is here, as in some recent reports, grouped with AH amyloidosis. AL Amyloidosis AL amyloidosis can occur at any stage in the plasma cell dyscrasia spectrum. Typically, patients developing this type of amyloidosis have had excess κ or λ free light chains in their urine for years before diagnosis. At diagnosis, however, they typically have a relatively small plasma cell burden (bone marrow plasma cells <5% to 7% of total nucleated cells) and in only <5% to 10% of cases do other findings indicate the presence of a malignant condition (i.e. definitive signs of multiple myeloma, Waldenström macroglobulinemia, or chronic lymphocytic leukemia associated with over-production of a clonal light chain). Nonetheless, these individuals often evidence serious involvement of the kidney (proteinuria, nephrotic syndrome) or heart (restrictive cardiomyopathy, arrhythmias) in 70% or 60% of cases, respectively, and of dysfunction in the peripheral nervous system (numbness, paresthesias) or autonomic nervous system (orthostatic hypotension) in 20% or 15% of cases, respectively. They may also exhibit evidence of liver involvement (liver failure, increases in circulating liver enzymes, bleeding due to factor X deficiency), gastrointestinal track deficiencies (malabsorption), and amyloid deposition in surface tissues (macroglossia, shoulder pad masses, cutaneous nodules). Arthritis in multiple joints, often manifested before diagnosis, is also a common feature of AL amyloidosis and has led to initial misdiagnoses of rheumatoid arthritis. Diagnosis of the disease requires evidence of increased levels of a κ or λ myeloma protein in blood and/or blood, presence of an amyloid-related organ-involvement syndrome, detection in tissues of amyloid deposition based on birefringence-staining with Congo red, and detection in tissues of κ or λ deposition based on electron microscopy or mass spectrometry. Reflecting the widespread systemic nature of the disease, patient median survival is only 8 months dating from the time of diagnosis. Treatment commonly improves this poor survival. In a Mayo Clinic study, for example, AL amyloidosis assigned stage 1, 2, 3, or 4 based on the presence of 0, 1, 2, or 3 prognostic signs (high blood levels of [cardiac troponin T]), blood levels of a marker for congestive heart failure (viz., NT-ProBNP), or free light chain ratios) had median survivals of 94.1, 40.3, 14, and 5.8 months respectively. Additional factors indicating a worse prognosis include the involvement of multiple organs, ≥ 10% bone marrow plasma cells, presence of a translocation between chromosomes 11 and 14 [i.e. t(11;14)], and chromosomal trisomy. AH Amyloidosis AH and AHL amyloidosis are extremely rare forms of systemic amyloidosis in which the amyloid deposit is a free heavy chain (AH amyloidosis) or a free heavy chain plus free light chain (AHL amyloidosis). Case reports have detected amyloid deposits containing a free γ, α, or μ heavy chain (or portions of one of these chains) accompanied in many cases by a free κ or λ light chain in primarily in the kidney but also the spleen and other tissues. AH plus AHL amyloidosis cases are ~17-fold less common than AL amyloidosis cases. The disease often presents late in its course with signs and/or symptoms of kidney failure such as those associated with the nephrotic syndrome and is therefore treated as a malignant condition. In a small study of 16 patients with renal amyloidosis, the 5 patients with AH amyloidosis and the 11 patients with AHL amyloidosis had less frequent concurrent cardiac involvement and better overall survival than 202 patients with renal AL amyloidosis. The hematological response to chemotherapy of the AH and AHL renal amyloidosis patients was comparable to those with renal AL amyloidosis. POEMS syndrome POEMS syndrome (also known as Crow–Fukase syndrome, Takatsuki disease, or PEP syndrome) is a rare and complex medical syndrome that involves a combination of syndrome-defining signs and symptoms due to the dysfunction of multiple organs. The syndrome is associated with a plasma cell dyscrasia in almost 100% of cases, pathological overexpression of certain cytokines in >95% of cases, and the lymphoproliferative disorder termed Castlemans disease in ~15% of cases. (Rare cases of POEMS have been associated with polyclonal rather than clonal plasma cells; these cases are not plasma cell dyscrasias but rather appear to be caused by the over-activity of non-malignant immune cell responses in chronic infections or autoimmune diseases.) POEMS is an acronym standing for the characteristic signs or symptoms of the syndrome: Polyneuropathy, Organomegaly, Endocrinopathy, Plasma cell disorder (typically, the plasma cell burden is low in POEMS patients), and Skin changes (e.g. hemangioma, hyperpigmentation). The syndrome is defined by the presence of; both of two major criteria, peripheral neuropathy and a clonal plasma cell dyscrasia (increased bone marrow plasma cells in ~67% of cases; ≥1 plasmacytoma in ~33% of cases); at least one other major criteria (Castlemans disease, sclerotic bone lesions, elevated serum levels of the cytokine VEGF); and at least one minor criterion (organomegaly, extravascular volume overload [e.g. ascites, edema, pleural effusion, and/or pericardial effusion], endocrinopathy [i.e. hypogonadism, defects in the hypothalamic–pituitary–adrenal axis], skin changes, papilledema, and/or hematological manifestations [i.e. thrombocytosis or polycythemia]). The monoclonal protein in POEMS patients is typically identified as IgA or IgG which in >95% of cases contains a λ chain that is restricted to either of two members of the V lambda 1 subfamily viz., IGLV1-40*01 and IGLV1-44*01 (there are 29 other members in the V lambda family). That is, the myeloma protein in POEMS is almost invariably a clonal λ light chain variant. Deletion of chromosome 13 and chromosomal translocations but not increases in chromosome number have also been reported to occur in POEMS patients.Patients with 1 or 2 isolated plasmacytomas have been successfully treated with targeted radiotherapy to obtain relief of symptoms and sometimes complete remission of disease. (Isolated plasmacytomas may regress spontaneously.) Patients with >2 plasmacytomas or symptomatic disseminated disease have been treated with chemotherapy often followed by autologous stem-cell transplantation; these treatments have been found to reduce symptoms of the disease and lead to long-term partial remissions of disease. The overall survival of POEMS patients who have been treated for their disease is relatively good for a disease occurring in patients with an average age of 50 years; one estimate of median overall survival is 14 years. POEMS patients evaluated to be in low and intermediate risk groups had ≥>85% survival at 10 years; those in the high risk group had a 40% survival over this time period. Cryoglobulinemia Cryoglobulins are proteins, principally immunoglobulins, that circulate in the blood, precipitate at temperatures <37 °C (98.6 °F), and re-solubilize upon restoring physiological blood temperatures. They are made and secreted into the blood as a result of underlying pathological conditions viz., inflammation, infection, or malignancies. Rarely, cryoglobulinemia (i.e. essential cryoglobulinemia) occurs in patients without these or other identifiable conditions. Non-essential cryoglobulonemia is classified into three types. Type 1 cryoglobulinemia (10-25% of cases) involves a circulating myeloma protein, typically IgM or IgG but in rare case reports IgA. The condition is associated with Waldenström macroglobulinemia or multiple myeloma in ~40% of type I cases, the MGUS or smoldering predecessors to these diseases in ~44% of type I cases, and other B cell lymphoproliferative disorders in ~16% of type I cases. Type II cryglobulinemia (50-60% of cases) involves circulating IgM myeloma protein with rheumatoid factor activity and therefore bound to polyclonal IgG and protein components of the blood complement system; hepatitis C virus and, far more rarely, hepatitis B virus or human immunodeficiency virus infections are the major causes of this cryoglobulinemia. Type III cryoglobulinemia (15-30% of cases) involves circulating polyclonal IgM protein with rheumatoid factor activity bound to polyclonal IgG and blood complement components; autoimmune diseases and, less commonly, hepatitis virus C infection or lymphoproliferative disorders are the cause of this type of croglobulinemia. Only types I and II are defined as plasma cell dyscrasias.Patients suffering type 1 cryoglobulinemia present with symptoms due to cold temperature-induce blood hyperviscosity and consequential interruptions of blood flow, e.g. skin lesions (lower extremity purpuric spots and papules, acrocyanosis, necrosis skin ulcers, livedo reticularis urticaria), peripheral neuropathy, blurred vision, loss of vision, hearing loss, headaches, confusion, transient ischemic attacks, chest pain, heart failure, glomerulonephritis, kidney failure, oral bleeding, and nasal bleeding. Rarely, patients may present with catastrophic decreases in blood flow to vital tissues and require emergency treatment. Symptomatic patients typically exhibit levels of a myeloma protein >5 gram/liter and can be diagnosed by simple observing the temperature-induced, reversible induction of serum precipitate formation. Patients, particularly those with catastrophic presentations, are treated with plasma exchange and/or plasmapharesis to reduce the load of circulating myeloma proteins and relieve acute symptoms. Patients with an overt malignancy are treated with the chemotherapy regimens used for Waldenstroms macroglobulinemia or multiply myeloma; patients with MGUS precursors to these diseases appear less responsive to these chemotherapeutic regimens. These patients as well as patients with overt malignancy may be treated with rituximab (kills normal and malignant B cells that bear the CD20 antigen or the proteasome inhibitor, Bortezomib.Patients suffering type II (or type III) cryoglobulinemia present with many of the symptoms of type I disease plus those of inflammatory vasculitis. Their treatments are tailored to the underlying infectious, autoimmune, or malignant disease. Type II patients associated with a monoclonal antibody and clonal plasma cells or other types of clonal B cells, are typically treated with regimens used for Walsdenstorms macroglobulonemia or multiple myeloma. Malignant stage In the malignant stage of plasma cell dyscrasias, a clearly excessive tumor cell burden causes symptoms and findings predictive of rapid, life-threatening progression of disease. These dyscrasias fall into several distinct categories. Solitary plasmacytoma Solitary plasmacytoma is an early stage malignancy with a clinical course that lies between MGUS and multiple myeloma in the spectrum of plasma cell dyscrasias. Solitary plasmacytomas typically present with local symptoms due to the growing mass of plasma cells such as the bone pain or pathologic bone fractures occurring in solitary plasmacytomas of bone or the headache, focal neurological deficits, and cranial nerve palsies occurring in extramedullary plasmacytomas of sellar and parasellar compartments of the brain. Its diagnoses must meet all four of the following criteria: biopsy-proven tumor consisting of clonal plasma cells; no evidence of any other plasmacytomas based on bone survey and MRI (or in place of MRI, CT scan); normal bone marrow examination; and absence end organ damage, CRAB features, or other signs or symptoms of systemic disease attributable to a plasma cell dyscrasia. Blood or urine myeloma proteins are usually undetectable or low in solitary plasmacytomas. Solitary plasmacytoma is a rare disease with an incidence in the USA of <450 cases per year. In a review of 1,691 cases in the US, the median age at diagnosis was 63 with males representing ~60% of all cases. The most common site of plasmacytoma involvement was bone (~58%) followed by upper or lower airway tract (~16%), soft tissue or connective tissue (~5%), central nervous system (~3%), gastrointestinal tract (~3%), skin (~1%), and all other sites (~3%). Overall median survival was 8.12 years with survival decreasing with age from 12.4 years for patients <40 to 5.2 years for patients of 60 years or older. Risk of its recurrence or progression to overt multiple myeloma within 3 years is ~10%.A subset of solitary plasmacytomas, termed solitary plasmacytoma with minimal bone marrow involvement, has the same criteria for diagnosis as solitary plasmacytoma except that bone marrow examination shows an increase in plasma cells from a normal value of ~0% to 1.5% to >~1.6% but less than 10% of total nucleated cells. While its presentations and findings are similar to solitary plasmacytoma, solitary plasmacytoma with minimal bone marrow involvement is more likely to progress, i.e. it recurs or becomes overt multiple myeloma in 20% to 60% of cases within 3 years. Solitary plasmacytomas associated with 10% or more plasma cells are diagnosed as overt multiple myeloma. Non-secretory multiple myeloma Non-secretory multiple myeloma represents a class of plasma cell dyscrasias where no myeloma protein is detected in serum or urine of patients with evidence of increased clonal bone marrow plasma cells and/or multiple plasmacytomas, particularly of the bone but also of soft tissues. While a pre-malignant phase is likely, most new cases of non-secretory multiple myeloma are brought to attention not because of incidental M protein detection which by definition is absent but because of patient symptoms indicative of malignancy possibly of plasma cell origin. The condition has been diagnosed based on biopsy-proved clonal plasma cell tumors and/or the presence in bone marrow of plasma cells at ≥10% of nucleated cells in individuals who have evidence of end organ damage attributable to an underlying plasma cell disorder. These patients typically also show one or more CRAB signs and lack evidence of a myeloma protein as measured by protein electrophoresis and immunofixation. However, more sensitive methods of detecting urinary and serum light chain myeloma proteins using enzyme-linked immunosorbent assays indicate that >60% of cases initially diagnosed as non-secretory multiple myeloma had abnormal levels of either a clonal κ or λ light chain in their urine or serum and therefore were better diagnosed as having light chain multiple myeloma. Based on the latter definition, non-secretory multiple myeloma represents ~1% of all multiple myeloma cases with formerly diagnosed non-secretory myelomas considered to be cases primarily of light chain multiple myeloma but on occasion "false non-secretors", i.e. cases in which there is evidence of myeloma protein secretion such as renal myeloma protein deposits.A Mayo Clinic study of 124 patients initially diagnosed as having non-secretory multiple myeloma were later found to be composed of 65% free light chain secretors and 35% true non-secretors. As a group, these patients response to therapy, time to disease recurrence, and overall survival were similar to typical myeloma patients. However, in a subset of patients diagnosed after 2001 and therefore treated with more effective therapy that included autologous stem-cell transplantation, prognosis was significantly better in non-secretory multiple myeloma patients (median survival 8.3 years) compared to typical myeloma patients (median survival 5.4 years). In addition, non-secretory patients exhibited a better prognosis than light chain-secretory patients. Plasma Cell Myeloma with concomitant chronic Lymphocytic Leukemia/monoclonal B-Cell Lymphocytosis Multiple myeloma occurring concurrently with chronic Lymphocytic Leukemia or its pre-malignant precursor, monoclonal B-cell lymphocytosis, is an extremely rare condition in which patients evidence findings of the plasma cell dyscrasia plus either one of the cited clonal lymphocytic diseases. Patients are typically elderly (median age of 74, range 42–91 years old) males (51 of 66 case reports) and commonly present with a combination of symptoms related to chronic lymphocytic leukemia symptoms (fatigue, autoimmune hemolytic anemia, enlargements of liver and/or spleen and lymphadenopathy) plus symptoms of multiple myelomas. Patients exhibit two distinct populations of clonal cells in their bone marrow, blood, and/or other tissues: plasma cells, which may have an immature plasmablastic morphology and small lymphocytes, which have a morphology typical of chronic lymphocytic leukemia cells. Patients blood and/or urine evidences a plasma cell-derived myeloma proteins, either IgG, IgA, or free light chain in ~50%, 20%, and 20% of cases, respectively, but may also have a second myeloma protein made by the lymphocytic cells, either an IgM or IgG. Signs and symptoms of chronic lymphocytic leukemia commonly precede those of multiple myeloma, sometimes by years. The relationship between the two clones of cells in this combined disease has not been established although one study suggests that the clonal plasma cells and clonal lymphocytes arise from a common hematological stem cell. In general, patients with plasma cell myeloma with concomitant chronic Lymphocytic Leukemia/monoclonal B-cell Lymphocytosis have been treated with the same regimens used for multiple myeloma patients unless significant complications related to the lymphocytic component of their disease (e.g. autoimmune hemolytic anemia) require treatments used in chronic lymphocytic leukemia. Some patients who lack appreciable symptoms have been followed with no specific treatment of their disease. Waldenström macroglobulinemia According to the International Workshop on Waldenströms Macroglobulinemia, the disease is diagnosed in patients that have a serum IgM monoclonal protein and a bone marrow that contains ≥10% of its nucleated cells as lymphoplasmacytic cells. There is no requirement for symptomatic disease, a particular level of IgM protein, or presence of extramedullary (i.e. non-bone) lymphoplasmacytic cell infiltrates. The overall survival for this malignancy at 5 and 10 years among >5,000 patients is 62% and 39%, respectively, with newer treatment regimens anticipated to improve these survival rates in the future. Multiple myeloma Multiple myeloma is diagnosed in patients that (except for non-secretory multiple myeloma patients) have a clonal IgG, IgA, IgD, or IgE myeloma protein in their serum and/or a clonal κ or λ light chain in their serum or urine plus either one of two sets of criteria. In the first criteria set, patients must have ≥10% bone marrow clonal plasma cells plus ≥1 of the CRAB criteria; in the second criteria set, patients must have ≥10 bone marrow clonal plasma cells plus ≥1 of the following findings, ≥60% bone marrow clonal plasma cells, a free κ/λ or λ/κ light chain ratio in serum of ≥100 (the involved clonal light chain concentration must be ≥100 milligrams/liter), and/or >1 focal bone lesion on magnetic resonance imaging. The 5 year medium survival of patients with multiple myeloma treated with currently used treatment regiments is 48.5%. Light chain multiple myeloma Light chain multiple myeloma is diagnosed in patients who have: a) the criteria for diagnosis of multiple myeloma except having a serum free light chain ratio outside the normal range of 0.26 to 1.65 without evidence of an intact immunoglobulin or free heavy chain; or b) an extreme free light chain ratio, i.e. outside the range of 0.02 to 100 (with the light chain having the lower concentration being present at >10 milligrams/liter) regardless of the stage of their plasma cell dyscrasia. At the time of diagnosis, 30% to 50% of light chain multiple myeloma patients have severe renal dysfunction or kidney failure due to light chain myeloma cast nephropathy or the nephrotoxic effects of free light chains on renal tubular cells. Patients are treated similarly to patients suffering the counterparts those with multiple myeloma except that the focus is treating or preventing kidney damage using chemotherapy to reduce production of the monoclonal light chain and thereby stopping, reversing, or preventing kidney injury. Plasma cell leukemia Plasma cell leukemia is a form of multiple myeloma in which significant numbers of typically immature appearing plasma cells, i.e. plasmablasts, circulate in the blood. Very small numbers of plasma cells may reach the circulation in non-IgM multiple myeloma, non-IgM SMM, and, exceptionally, non-IgM MGUS. In these plasma cell dyscrasias, the presence of even very small numbers of circulating plasma cells is a poor prognostic indicator. In plasma cell leukemia, however, circulating plasma cells reach far higher numbers and at these circulating levels are associated with exceptionally poor survival rates. The International Myeloma Working Group has defined the diagnostic criteria for plasma cell leukemia as the presence in blood of >2x109 plasma cells per liter or, alternatively, >20% of nucleated blood cells being plasma cells. More recently, the Group has suggested that values of 0.5x109 or 5%, respectively, may be more appropriate from a therapeutic viewpoint and therefore should be studied as a definitive criterion for the disease. A recent study supported this suggestion in finding that multiple myeloma patients with >5% circulating plasma cells had a prognosis much worse than that for multiple myeloma and similar to that for plasma cell leukemia. Flow cytometry immunophenotyping of blood cells to detect clonal phenotypes of plasma cells seen in multiple myeloma (e.g. the CD138+, CD38+, CD19−, CD4+/- phenotype) may be a more sensitive method to enumerate circulating clonal plasma cells and diagnose plasma cell leukemia.There are two forms of plasma cell leukemia: Primary plasma cell leukemia in which patients without a history of multiple myeloma present with diagnostically high levels of circulating plasma cells and Secondary plasma cell leukemia in which patients with multiple myeloma suffer their dyscrasias progression by the expansion of large numbers of their malignant plasma cells into the circulation and distant tissues. Historically, primary plasma cell leukemia was more common than the secondary form but with the increased survival of multiple myeloma patients due to new treatment regiments, more cases of secondary plasma cell leukemia are occurring; currently, the two forms occur in approximately equal numbers. Patients with primary plasma cell leukemia present with clinical findings that are less commonly found in multiple myeloma, e.g. they often have hepatomegaly, splenomegaly, lymphadenopathy, nerve and central nervous system defects, bleeding tendencies secondary to thrombocytopenia, and pleural effusions. They are less likely than multiple myeloma patients to have lytic bone lesions. In several studies of patients with either form of plasma cell leukemia, the disease was associated with clonal IgG in 28% to 56% of cases, IgA in 4% to 7% of cases, and a light chain in 23% to 44% of cases; 0-12% of patients had no myeloma protein. Medium survival for primary and secondary plasma cell dyscrasias have been 7–13 months and 2–7 months, respectively, but appear to be improving with new treatment regimens. Heavy chain disease The four heavy chain diseases are exceedingly rare conditions associated with the production, circulation in blood, and often presence in urine of a free clonal heavy chain with no detected clonal light chains. The heavy chain is non-functional and altered by having deletions, insertions, and point mutations due to somatic mutations in their respective coding genes. Beyond this commonality, however, these diseases have very different clinical differences. Furthermore, each of the heavy chain diseases appears to be due to rare variants of lymphoma and therefore is sometimes regarded as a B cell dyscrasia However, heavy chain diseases are still often classified with plasma cell dyscrasias. The heavy chain diseases are classified as α, γ, and μ heavy chain diseases and are based respectively on >400, 130, and 30-40 case reports as reviewed in a 2014 publication. α Heavy chain disease α Heavy chain disease (also termed immunoproliferative small intestinal disease or IPSID, Mediterranean lymphoma, and Seligmann disease) afflicts primarily individuals of Mediterranean, North African, and Middle Eastern descent of lower economic status. Many cases are centered in the Middle East and associated with relatively unsanitary living conditions. The disease usually appears between the ages 10 and 30 and in some cases may be an aberrant immune response to a parasite or other microorganism. The disease commonly effects the gastrointestinal tract leading to signs and symptoms of a malabsorption syndrome or, far less commonly, the respiratory tract with signs and symptoms of respiratory dysfunction. Involved tissues usually include mucosa-associated lymphoid tissues and evidence a histology of lymphoplasmacytoid infiltrates accompanied by large numbers of plasma cells and small lymphocytes. The plasma cells therein express the monoclonal α chain and therefore are clonal in nature and the sole or contributing producer of the α chain myeloma protein. Some 57% to 66% of patients present with disseminated lymphoma, 17% to 36% of patients present with a localized lymphoma, and 9% to 17% of patients lack any evidence of a lymphoplasmacytic neoplasm. A majority of the latter patients have an autoimmune disease or a chronic infection which may be responsible for, or contribute to, production of the α heavy chain. Studies indicated that a sub-set particularly of the digestive form of heavy chain disease is caused by infection. This is based on findings that the majority of α heavy chain disease patients are in the lower economic class living under unsanitary conditions, that gastrointestinal bacterial and parasitic infections have been documented in many of these patients, and that long-term (>6 months) appropriately selected antibiotic therapy has improved the condition in 33% to 71% of patients who are at an early stage of the disease and documented to be infected. However, these patients frequently relapse. Patients resistant to antibiotic trials have been treated with multiple drug chemotherapy to obtain complete remission rates of 64% and an overall 5 year survival of 67%. γ heavy chain disease γ Heavy chain disease (also termed Franklin disease or Franklins disease) presents in three patterns: a) aggressive lymphoma (57% to 66% of cases) associated with constitutional symptoms and in 50% of cases with enlargement of lymph nodes, spleen, and/or liver; b) localized lymphoma (~25% of cases) with lymphoma limited to the bone marrow or an extra-nodal site, usually the skin but sometimes the thyroid gland, parotid gland, oropharyngeal cavity, conjunctiva, or gastrointestinal tract; and c) no lymphoma (9% to 17% of cases) associated typically with a preexistent autoimmune disease but no evidence of lymphoma. Involved lymphoma-infiltrated tissues typically show a mixture of lymphoplamsmacytoid cells, plasma cells, lymphocytes, and sometimes variable numbers of eosinophils and hystiocytes. Treatment of the disease varies with its clinical severity. Patients with aggressive lymphoma have been treated with multiple drug chemotherapy, patients with limited lymphoma have been monitored for disease progression or treated locally (e.g. radiation therapy, surgical removal), and patients with no lymphoma have been monitored for progression in their diseases while being treated for any autoimmune disease that they bear. Spontaneous remissions in γ heavy chain disease have occurred. Regardless of presentation pattern, these patients may have an aggressive or indolent disease with courses ranging from the asymptomatic presence of a stable monoclonal heavy chain in the serum or urine (e.g. MGUS) to a rapid, downhill progression of a few weeks duration. γ Heavy chain disease survivorship ranged form 1 month to >20 years (medium survival 7.4 years) in a Mayo Clinic study. μ Heavy chain disease μ Heavy chain disease presents with a picture of a lymphoid neoplasm resembling either chronic lymphocytic leukemia or small lymphocytic lymphoma. This picture includes splenomegaly in virtually all cases, hepatomegaly in ~75% of cases, lymphadenopathy in ~40% of cases, and lytic bone lesions in ~20% of cases. Patients often have hypogammaglobulinemia, increases in urinary free light chains, and a bone marrow containing vacuolated plasma cells or lymphoid cells. Treatment of μ heavy chain disease had varied form observation only in asymptomatic patients to single drug or and multiple drug chemotherapy in symptomatic patients. Survival with this disease varies between <1 month to >10 years with a median survival rate of ~ 2years. See also Paraproteinemia Gammaglobulins References == External links ==

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

What is the significance of the term 'Early onset dementia' in the medical field?

Early onset dementia is dementia in which symptoms first appear before the age of 65. The term favored until about 2000 was presenile dementia; young onset dementia is also used.Early onset dementia may be caused by degenerative or vascular disease, or it may be due to other causes, such as alcohol-related dementia and other inflammatory or infectious processes. Early-onset Alzheimers disease, vascular dementia and frontotemporal lobar degeneration are the most common forms of early onset dementia, with Alzheimers accounting for between 30 and 40%. Early onset dementia may also occur, less frequently, in the Lewy body dementias (dementia with Lewy bodies and Parkinsons disease dementia), multiple sclerosis, Huntingtons disease and other conditions. References Further reading Collins JD, Henley SM, Suárez-González A (July 2020). "A systematic review of the prevalence of depression, anxiety, and apathy in frontotemporal dementia, atypical and young-onset Alzheimers disease, and inherited dementia". Int Psychogeriatr (Review): 1–20. doi:10.1017/S1041610220001118. PMID 32684177. S2CID 220653830. Ducharme S, Dols A, Laforce R, et al. (June 2020). "Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders". Brain (Review). 143 (6): 1632–1650. doi:10.1093/brain/awaa018. PMC 7849953. PMID 32129844. Nwadiugwu M (September 2021). "Early-onset dementia: key issues using a relationship-centred care approach". Postgrad Med J (Review). 97 (1151): 598–604. doi:10.1136/postgradmedj-2020-138517. PMC 8408578. PMID 32883770. Roman de Mettelinge T, Calders P, Cambier D (2021). "The Effects of Aerobic Exercise in Patients with Early-Onset Dementia: A Scoping Review". Dement Geriatr Cogn Disord (Review). 50 (1): 9–16. doi:10.1159/000516231. PMID 33957623. S2CID 233983643.

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

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

Short anagen syndrome is a condition where hair does not grow beyond a short length, due to an unusually short duration of active hair growth (anagen phase). Most cases are associated with fine blond hair. See also List of cutaneous conditions == References ==

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

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

Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxioselective anxiolytic since 1970, and an anticonvulsant since 1984. The primary drug-development goal was to provide greater anxiolytic, anti-obsessive efficacy with fewer benzodiazepine-related side effects. Medical uses Clobazam is used for its anxiolytic effect, and as an adjunctive therapy in epilepsy. As an adjunctive therapy in epilepsy, it is used in patients who have not responded to first-line drugs and in children who are refractory to first-line drugs. It is unclear if there are any benefits to clobazam over other seizure medications for children with Rolandic epilepsy or other epileptic syndromes. It is not recommended for use in children between the ages of six months and three years, unless there is a compelling need. In addition to epilepsy and severe anxiety, clobazam is also approved as a short-term (2–4 weeks) adjunctive agent in schizophrenia and other psychotic disorders to manage anxiety or agitation.Clobazam is sometimes used for refractory epilepsies. However, long-term prophylactic treatment of epilepsy may have considerable drawbacks, most importantly decreased antiepileptic effects due to drug tolerance which may render long-term therapy less effective. Other antiepileptic drugs may therefore be preferred for the long-term management of epilepsy. Furthermore, benzodiazepines may have the drawback, particularly after long-term use, of causing rebound seizures upon abrupt or over-rapid discontinuation of therapy forming part of the benzodiazepine withdrawal syndrome. Clobazam is approved in Canada for add-on use in tonic-clonic, complex partial, and myoclonic seizures. Clobazam is approved for adjunctive therapy in complex partial seizures, certain types of status epilepticus, specifically the mycolonic, myoclonic-absent, simple partial, complex partial, and tonic varieties, and non-status absence seizures. It is also approved for the treatment of anxiety. In India, clobazam is approved for use as an adjunctive therapy in epilepsy, and in acute and chronic anxiety. In Japan, clobazam is approved for adjunctive therapy in treatment-resistant epilepsy featuring complex partial seizures. In New Zealand, clobazam is marketed as Frisium In the United Kingdom clobazam (Frisium) is approved for short-term (2–4 weeks) relief of acute anxiety in patients who have not responded to other drugs, with or without insomnia and without uncontrolled clinical depression. It was not approved in the United States until October 25, 2011, when it was approved for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients 2 years of age or older. Contraindications Clobazam should be used with great care in patients with the following disorders: Myasthenia gravis. Sleep apnea. Severe liver diseases such as cirrhosis and hepatitis. Severe respiratory failure.Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals, and individuals with comorbid psychiatric disorders. Side effects In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class. Common Common side effects include fever, drooling, and constipation. Post-marketing experience Hives. Rashes. Warnings and precautions In December 2013, the FDA added warnings to the label for clobazam, that it can cause serious skin reactions, Stevens–Johnson syndrome, and toxic epidermal necrolysis, especially in the first eight weeks of treatment. Drug interactions Alcohol increases bioavailability by 50%; compounded depressant effect may precipitate life-threatening toxicity. Cimetidine increases the effects of clobazam. Valproate. Overdose Overdose and intoxication with benzodiazepines, including clobazam, may lead to CNS depression, associated with drowsiness, confusion, and lethargy, possibly progressing to ataxia, respiratory depression, hypotension, and coma or death. The risk of a fatal outcome is increased in cases of combined poisoning with other CNS depressants, including alcohol. Abuse potential and addiction Classic (non-anxioselective) benzodiazepines in animal studies have been shown to increase reward-seeking behaviours which may suggest an increased risk of addictive behavioural patterns. Clobazam abuse has been reported in some countries, according to a 1983 World Health Organisation report. Dependence and withdrawal In humans, tolerance to the anticonvulsant effects of clobazam may occur and withdrawal seizures may occur during abrupt or overrapid withdrawal.Clobazam as with other benzodiazepine drugs can lead to physical dependence, addiction, and what is known as the benzodiazepine withdrawal syndrome. Withdrawal from clobazam or other benzodiazepines after regular use often leads to withdrawal symptoms which are similar to those seen during alcohol and barbiturate withdrawal. The higher the dosage and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Benzodiazepine treatment should only be discontinued via a slow and gradual dose reduction regimen. Pharmacology Clobazam is predominantly a positive allosteric modulator at the GABAA receptor with some speculated additional activity at sodium channels and voltage-sensitive calcium channels.Like other 1,5-benzodiazepines (for example, arfendazam, lofendazam, or CP-1414S), the active metabolite N-desmethylclobazam has less affinity for the α1 subunit of the GABAA receptor compared to the 1,4-benzodiazepines. It has higher affinity for α2 containing receptors, where it has positive modulatory activity.In a double-blind placebo-controlled trial published in 1990 comparing it to clonazepam, 10 mg of clobazam was shown to be less sedative than either 0.5 mg or 1 mg of clonazepam.The α1 subtype of the GABAA receptor, was shown to be responsible for the sedative effects of diazepam by McKernan et al. in 2000, who also showed that its anxiolytic and anticonvulsant properties could still be seen in mice whose α1 receptors were insensitive to diazepam.In 1996, Nakamura et al. reported that clobazam and its active metabolite, N-desmethylclobazam (norclobazam), work by enhancing GABA-activated chloride influx at GABAA receptors, creating a hyperpolarizing, inhibitory postsynaptic potential. It was also reported that these effects were inhibited by the GABA antagonist flumazenil, and that clobazam acts more efficiently in GABA-deficient brain tissue. Metabolism Clobazam has two major metabolites: N-desmethylclobazam and 4′-hydroxyclobazam, the former of which is active. The demethylation is facilitated by CYP2C19, CYP3A4, and CYP2B6 and the 4-hydroxyclobazam by CYP2C18 and CYP2C19. Chemistry Clobazam is a 1,5-benzodiazepine, meaning that its diazepine ring has nitrogen atoms at the 1 and 5 positions (instead of the usual 1 and 4).It is not soluble in water and is available in oral form only. History Clobazam was discovered at the Maestretti Research Laboratories in Milan and was first published in 1969; Maestretti was acquired by Roussel Uclaf which became part of Sanofi. See also Benzodiazepine dependence Effects of long-term benzodiazepine use References Further reading Dean L (September 2019). "Clobazam Therapy and CYP2C19 Genotype". In Pratt VM, McLeod HL, Rubinstein WS, et al. (eds.). Medical Genetics Summaries. National Center for Biotechnology Information (NCBI). PMID 31550100. External links "Clobazam". Drug Information Portal. U.S. National Library of Medicine.

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

What does the medical term 'Phimosis' encompass?

Phimosis (from Greek φίμωσις phimōsis muzzling.) is a condition in which the ridged band of the foreskin of the penis cannot stretch to allow it to be pulled back past the glans. A balloon-like swelling under the foreskin may occur with urination. In teenagers and adults, it may result in pain during an erection, but is otherwise not painful. Those affected are at greater risk of inflammation of the glans, known as balanitis, and other complications.In young children, it is normal not to be able to pull back the foreskin at all. Over 90% of cases resolve by the age of seven, although full retraction is still prevented by preputial adhesions in over half at this age. Occasionally, phimosis may be caused by an underlying condition such as scarring due to balanitis or balanitis xerotica obliterans. This can typically be diagnosed by seeing scarring of the opening of the foreskin.Also, other pathologies should be considered in the differential diagnosis, such as congenital megaprepuce. Typically, the condition resolves without treatment by the age of 18. Efforts to pull back the foreskin during the early years of a young males life should not be attempted. For those in whom the condition does not improve further, time can be given or a steroid cream may be used to attempt to loosen the tight skin. If this method, combined with stretching exercises, is not effective, then other treatments such as circumcision may be recommended. A potential complication of phimosis is paraphimosis, where the tight foreskin becomes trapped behind the glans. Signs and symptoms At birth, the inner layer of the foreskin is sealed to the glans penis. The foreskin is usually non-retractable in early childhood, and some males may reach the age of 18 before their foreskin can be fully retracted.Medical associations advise not to retract the foreskin of an infant, in order to prevent scarring. Some argue that non-retractability may "be considered normal for males up to and including adolescence." Hill states that full retractability of the foreskin may not be achieved until late childhood or early adulthood. A Danish survey found that the mean age of first foreskin retraction is 10.4 years.Rickwood, as well as other authors, has suggested that true phimosis is over-diagnosed due to failure to distinguish between normal developmental non-retractability and a pathological condition. Some authors use the terms "physiologic" and "pathologic" to distinguish between these types of phimosis; others use the term "non-retractile foreskin" to distinguish this developmental condition from pathologic phimosis.In some cases a cause may not be clear, or it may be difficult to distinguish physiological phimosis from pathological phimosis if an infant appears to have discomfort while urinating or demonstrates obvious ballooning of the foreskin. However, ballooning does not indicate urinary obstruction.In women, a comparable condition is known as "clitoral phimosis", whereby the clitoral hood cannot be retracted, limiting exposure of the glans clitoridis. Severity Score 1: full retraction of foreskin, tight behind the glans. Score 2: partial exposure of glans, prepuce (not congenital adhesions) limiting factor. Score 3: partial retraction, meatus just visible. Score 4: slight retraction, but some distance between tip and glans, i.e. neither meatus nor glans can be exposed. Score 5: absolutely no retraction of the foreskin. Cause There are three mechanical conditions that prevent foreskin retraction: The tip of the foreskin is too narrow to pass over the glans penis. This is normal in children and adolescents. The inner surface of the foreskin is fused with the glans penis. This is normal in children and adolescents but abnormal in adults. The frenulum is too short to allow complete retraction of the foreskin (a condition called frenulum breve).Pathological phimosis (as opposed to the natural non-retractability of the foreskin in childhood) is rare, and the causes are varied. Some cases may arise from balanitis (inflammation of the glans penis).Lichen sclerosus et atrophicus (thought to be the same condition as balanitis xerotica obliterans) is regarded as a common (or even the main) cause of pathological phimosis. This is a skin condition of unknown origin that causes a whitish ring of indurated tissue (a cicatrix) to form near the tip of the prepuce. This inelastic tissue prevents retraction. Phimosis may occur after other types of chronic inflammation (such as balanoposthitis), repeated catheterization, or forcible foreskin retraction.Phimosis may also arise in untreated diabetics due to the presence of glucose in their urine giving rise to infection in the foreskin.Beaugé noted that unusual masturbation practices, such as thrusting against the bed or rubbing the foreskin forward may cause phimosis. Patients are advised to stop exacerbating masturbation techniques and are encouraged to masturbate by moving the foreskin up and down so as to mimic more closely the action of sexual intercourse. After giving this advice Beaugé noted not once did he have to recommend circumcision.Phimosis in older children and adults can vary in severity, with some able to retract their foreskin partially (relative phimosis), while others are completely unable to retract their foreskin, even when the penis is in a flaccid state (full phimosis). Treatment Physiologic phimosis, common in males 10 years of age and younger, is normal, and does not require intervention. Non-retractile foreskin usually becomes retractable during the course of puberty.If phimosis in older children or adults is not causing acute and severe problems, nonsurgical measures may be effective. Choice of treatment is often determined by whether circumcision is viewed as an option of last resort or as the preferred course. Nonsurgical Patients are advised to stop exacerbating masturbation techniques and are encouraged to masturbate by moving the foreskin up and down so as to mimic more closely the action of sexual intercourse. After giving this advice Beaugé noted not once did he have to recommend circumcision. Topical steroid creams such as betamethasone, mometasone furoate and cortisone are effective in treating phimosis and should be considered before circumcision. It is theorized that the steroids work by reducing the bodys inflammatory and immune responses, and also by thinning the skin. Gently stretching of the foreskin can be accomplished manually. Skin that is under tension expands by growing additional cells. There are different ways to stretch the phimosis. If the opening of the foreskin is already large enough, the foreskin is rolled over two fingers and these are carefully pulled apart. If the opening is still too small, flesh tunnels can be used. These are inserted into the foreskin opening and should preferably be made of silicone so that they can be folded when inserted and so that they do not interfere when worn. The diameter is gradually increased until the foreskin can be retracted without difficulty. Even phimosis with a diameter of less than a millimetre can be stretched with these rings. Rings in different sizes are also available as stretching sets. Studies involving treating phimosis using topical steroids in conjunction with stretching exercises have reported success rates of up to 96%. However, other sources claim "wildly variable reported failure rates (5 – 33 %) and lack of follow-up to adulthood." Surgical Surgical methods range from the complete removal of the foreskin to more minor operations to relieve foreskin tightness: Dorsal slit (superincision) is a single incision along the upper length of the foreskin from the tip to the corona, exposing the glans without removing any tissue. Ventral slit (subincision) is an incision along the lower length of the foreskin from the tip of the frenulum to the base of the glans, removing the frenulum in the process. Often used when frenulum breve occurs alongside the phimosis. Preputioplasty, in which a limited dorsal slit with transverse closure is made along the constricting band of skin, can be an effective alternative to circumcision. It has the advantage of only limited pain and a short healing duration relative to circumcision, while also avoiding cosmetic effects. Circumcision is sometimes performed for phimosis, and is an effective treatment; however, this method has become less common as of 2012.While circumcision prevents phimosis, studies of the incidence of healthy infants circumcised for each prevented case of phimosis are inconsistent. Prognosis The most acute complication is paraphimosis. In this condition, the glans is swollen and painful, and the foreskin is immobilized by the swelling in a partially retracted position. The proximal penis is flaccid. Some studies found phimosis to be a risk factor for urinary retention and carcinoma of the penis. Epidemiology A number of medical reports of phimosis incidence have been published over the years. They vary widely because of the difficulties of distinguishing physiological phimosis (developmental nonretractility) from pathological phimosis, definitional differences, ascertainment problems, and the multiple additional influences on post-neonatal circumcision rates in cultures where most newborn males are circumcised. A commonly cited incidence statistic for pathological phimosis is 1% of uncircumcised males. When phimosis is simply equated with nonretractility of the foreskin after age 3 years, considerably higher incidence rates have been reported. Others have described incidences in adolescents and adults as high as 50%, though it is likely that many cases of physiological phimosis or partial nonretractility were included. History According to some accounts, phimosis prevented Louis XVI of France from impregnating his wife, Marie Antoinette, for the first seven years of their marriage, but this theory was later discredited. She was 14 and he was 15 when they married in 1770. However, the presence and nature of his genital anomaly is not considered certain, and some scholars (such as Vincent Cronin and Simone Bertiere) assert that surgical repair would have been mentioned in the records of his medical treatments if this had indeed occurred. Non-retractile prepuce in adolescence is normal, common, and usually resolves with increasing maturity.US president James Garfield was assassinated by Charles Guiteau in 1881. Guiteaus autopsy report indicated that he had phimosis. At the time, this led to the speculation that Guiteaus murderous behavior was due to phimosis-induced insanity. References External links Phimosis, by the University of California, San Francisco Urology department

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

I've encountered the term 'Hydrops-ectopic calcification-moth-eaten skeletal dysplasia' while reading about medical topics. What does it refer to exactly?

Hydrops-ectopic calcification-moth-eaten skeletal dysplasia is a defect in cholesterol biosynthesis. Greenberg characterized the condition in 1988.It has been associated with the lamin B receptor. Signs and Symptoms Hydrops-ectopic calcification-moth-eaten skeletal dysplasia causes the bones in a fetus to develop abnormally. This leads to a characteristic "moth eaten" appearance of the bones when viewed under an X-ray. Micromelia, polydactyly and ectopic calcification, or the built up of calcium in the soft tissues of the body, may all occur. Eighty to ninety nine percent of effected individuals will have abnormally ossified vertebrae, abnormal pelvis bone ossification, anterior rib punctate calcifications and brachydactyly.The second defining feature of hydrops-ectopic calcification-moth-eaten skeletal dysplasia is hydrops fetalis. A condition wherein an abnormal buildup of fluids occurs in the tissues of a fetus. See also Ectopic calcification Hydrops References == External links ==

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

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

Brigatinib, sold under the brand name Alunbrig among others, is a small-molecule targeted cancer therapy being developed by Ariad Pharmaceuticals, Inc. Brigatinib acts as both an anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) inhibitor.Brigatinib could overcome resistance to osimertinib conferred by the EGFR C797S mutation if it is combined with an anti-EGFR antibody such as cetuximab or panitumumab. Mechanism of action Brigatinib is an inhibitor of ALK and mutated EGFR.ALK was first identified as a chromosomal rearrangement in anaplastic large cell lymphoma (ALCL). Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of non-small cell lung cancer (NSCLC) and neuroblastomas, as well as ALCL. Since ALK is generally not expressed in normal adult tissues, it represents a highly promising molecular target for cancer therapy. Brigatinib inhibits ROS proto-oncogene-1 fusions and EGFR mutations and has a remarkable effect on the central nervous system.Epidermal growth factor receptor (EGFR) is another validated target in NSCLC. Additionally, the T790M "gatekeeper" mutation is linked in approximately 50 percent of patients who grow resistant to first-generation EGFR inhibitors. While second-generation EGFR inhibitors are in development, clinical efficacy has been limited due to toxicity thought to be associated with inhibiting the native (endogenous or unmutated) EGFR. A therapy designed to target EGFR, the T790M mutation but avoiding inhibition of native EGFR is another promising molecular target for cancer therapy. History Regulatory approval Ariad Pharmaceuticals, Inc. filed an investigational new drug (IND) application to the US FDA on August 29, 2016.In 2016, brigatinib was granted orphan drug status by the FDA for treatment of NSCLC.On 28 April 2017, it was granted an accelerated approval from the U.S. Food and Drug Administration (FDA) for metastatic non-small cell lung cancer (NSCLC); as a 2nd-line therapy for ALK-positive NSCLC.In 2020, it was approved as first-line treatment for ALK-positive metastatic NSCLC patients. Intellectual property On 22 April 2015, Ariad Pharmaceuticals, Inc. announced the issuance of its first U.S. patent on brigatinib, the protection is through December 30, 2030. The United States Patent and Trademark Office granted U.S. Patent No. 9,012,462 under the title, "Phosphorous Derivatives as Kinase Inhibitors." Commercialization Brigatinib is manufactured by Ariad Pharmaceuticals, Inc. (NASDAQ: ARIA) which is focused on rare cancers. Ariad then was acquired by Takeda Pharmaceutical Company Limited (TSE: 4502) in February 2017 through a tender offer (for $24.00 per share in cash) and subsequent merger of Ariad with Kiku Merger Co., Inc., a wholly owned subsidiary of Takeda Pharmaceuticals U.S.A. Ariad is an indirect wholly owned subsidiary of Takeda. Names Brigatinib is the INN. References External links "Brigatinib". Drug Information Portal. U.S. National Library of Medicine.

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

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

Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the bodys response to infection causes injury to its own tissues and organs. This initial stage is followed by suppression of the immune system. Common signs and symptoms include fever, increased heart rate, increased breathing rate, and confusion. There may also be symptoms related to a specific infection, such as a cough with pneumonia, or painful urination with a kidney infection. The very young, old, and people with a weakened immune system may have no symptoms of a specific infection, and the body temperature may be low or normal instead of having a fever. Severe sepsis causes poor organ function or blood flow. The presence of low blood pressure, high blood lactate, or low urine output may suggest poor blood flow. Septic shock is low blood pressure due to sepsis that does not improve after fluid replacement.Sepsis is caused by many organisms including bacteria, viruses and fungi. Common locations for the primary infection include the lungs, brain, urinary tract, skin, and abdominal organs. Risk factors include being very young or old, a weakened immune system from conditions such as cancer or diabetes, major trauma, and burns. Previously, a sepsis diagnosis required the presence of at least two systemic inflammatory response syndrome (SIRS) criteria in the setting of presumed infection. In 2016, a shortened sequential organ failure assessment score (SOFA score), known as the quick SOFA score (qSOFA), replaced the SIRS system of diagnosis. qSOFA criteria for sepsis include at least two of the following three: increased breathing rate, change in the level of consciousness, and low blood pressure. Sepsis guidelines recommend obtaining blood cultures before starting antibiotics; however, the diagnosis does not require the blood to be infected. Medical imaging is helpful when looking for the possible location of the infection. Other potential causes of similar signs and symptoms include anaphylaxis, adrenal insufficiency, low blood volume, heart failure, and pulmonary embolism.Sepsis requires immediate treatment with intravenous fluids and antimicrobials. Ongoing care often continues in an intensive care unit. If an adequate trial of fluid replacement is not enough to maintain blood pressure, then the use of medications that raise blood pressure becomes necessary. Mechanical ventilation and dialysis may be needed to support the function of the lungs and kidneys, respectively. A central venous catheter and an arterial catheter may be placed for access to the bloodstream and to guide treatment. Other helpful measurements include cardiac output and superior vena cava oxygen saturation. People with sepsis need preventive measures for deep vein thrombosis, stress ulcers, and pressure ulcers unless other conditions prevent such interventions. Some people might benefit from tight control of blood sugar levels with insulin. The use of corticosteroids is controversial, with some reviews finding benefit, and others not.Disease severity partly determines the outcome. The risk of death from sepsis is as high as 30%, while for severe sepsis it is as high as 50%, and septic shock 80%. Sepsis affected about 49 million people in 2017, with 11 million deaths (1 in 5 deaths worldwide). In the developed world, approximately 0.2 to 3 people per 1000 are affected by sepsis yearly, resulting in about a million cases per year in the United States. Rates of disease have been increasing. Some data indicate that sepsis is more common among males than females, however, other data show a greater prevalence of the disease among women. Descriptions of sepsis date back to the time of Hippocrates. Signs and symptoms In addition to symptoms related to the actual cause, people with sepsis may have a fever, low body temperature, rapid breathing, a fast heart rate, confusion, and edema. Early signs include a rapid heart rate, decreased urination, and high blood sugar. Signs of established sepsis include confusion, metabolic acidosis (which may be accompanied by a faster breathing rate that leads to respiratory alkalosis), low blood pressure due to decreased systemic vascular resistance, higher cardiac output, and disorders in blood-clotting that may lead to organ failure. Fever is the most common presenting symptom in sepsis, but fever may be absent in some people such as the elderly or those who are immunocompromised.The drop in blood pressure seen in sepsis can cause lightheadedness and is part of the criteria for septic shock.Oxidative stress is observed in septic shock, with circulating levels of copper and vitamin C being decreased. Cause Infections leading to sepsis are usually bacterial but may be fungal, parasitic or viral. Gram-positive bacteria were the primary cause of sepsis before the introduction of antibiotics in the 1950s. After the introduction of antibiotics, gram-negative bacteria became the predominant cause of sepsis from the 1960s to the 1980s. After the 1980s, gram-positive bacteria, most commonly staphylococci, are thought to cause more than 50% of cases of sepsis. Other commonly implicated bacteria include Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella species. Fungal sepsis accounts for approximately 5% of severe sepsis and septic shock cases; the most common cause of fungal sepsis is an infection by Candida species of yeast, a frequent hospital-acquired infection. The most common causes for parasitic sepsis are Plasmodium (which leads to malaria), Schistosoma and Echinococcus. The most common sites of infection resulting in severe sepsis are the lungs, the abdomen, and the urinary tract. Typically, 50% of all sepsis cases start as an infection in the lungs. In one-third to one-half of cases, the source of infection is unclear. Pathophysiology Sepsis is caused by a combination of factors related to the particular invading pathogen(s) and to the status of the immune system of the host. The early phase of sepsis characterized by excessive inflammation (sometimes resulting in a cytokine storm) may be followed by a prolonged period of decreased functioning of the immune system. Either of these phases may prove fatal. On the other hand, systemic inflammatory response syndrome (SIRS) occurs in people without the presence of infection, for example, in those with burns, polytrauma, or the initial state in pancreatitis and chemical pneumonitis. However, sepsis also causes similar response to SIRS. Microbial factors Bacterial virulence factors, such as glycocalyx and various adhesins, allow colonization, immune evasion, and establishment of disease in the host. Sepsis caused by gram-negative bacteria is thought to be largely due to a response by the host to the lipid A component of lipopolysaccharide, also called endotoxin. Sepsis caused by gram-positive bacteria may result from an immunological response to cell wall lipoteichoic acid. Bacterial exotoxins that act as superantigens also may cause sepsis. Superantigens simultaneously bind major histocompatibility complex and T-cell receptors in the absence of antigen presentation. This forced receptor interaction induces the production of pro-inflammatory chemical signals (cytokines) by T-cells.There are a number of microbial factors that may cause the typical septic inflammatory cascade. An invading pathogen is recognized by its pathogen-associated molecular patterns (PAMPs). Examples of PAMPs include lipopolysaccharides and flagellin in gram-negative bacteria, muramyl dipeptide in the peptidoglycan of the gram-positive bacterial cell wall, and CpG bacterial DNA. These PAMPs are recognized by the pattern recognition receptors (PRRs) of the innate immune system, which may be membrane-bound or cytosolic. There are four families of PRRs: the toll-like receptors, the C-type lectin receptors, the NOD-like receptors, and the RIG-I-like receptors. Invariably, the association of a PAMP and a PRR will cause a series of intracellular signalling cascades. Consequentially, transcription factors such as nuclear factor-kappa B and activator protein-1, will up-regulate the expression of pro-inflammatory and anti-inflammatory cytokines. Host factors Upon detection of microbial antigens, the host systemic immune system is activated. Immune cells not only recognise pathogen-associated molecular patterns but also damage-associated molecular patterns from damaged tissues. An uncontrolled immune response is then activated because leukocytes are not recruited to the specific site of infection, but instead they are recruited all over the body. Then, an immunosuppression state ensues when the proinflammatory T helper cell 1 (TH1) is shifted to TH2, mediated by interleukin 10, which is known as "compensatory anti-inflammatory response syndrome". The apoptosis (cell death) of lymphocytes further worsens the immunosuppression. Neutrophils, monocytes, macrophages, dendritic cells, CD4+ T cells, and B cells all undergo apoptosis, whereas regulatory T cells are more apoptosis resistant. Subsequently, multiple organ failure ensues because tissues are unable to use oxygen efficiently due to inhibition of cytochrome c oxidase.Inflammatory responses cause multiple organ dysfunction syndrome through various mechanisms as described below. Increased permeability of the lung vessels causes leaking of fluids into alveoli, which results in pulmonary edema and acute respiratory distress syndrome (ARDS). Impaired utilization of oxygen in the liver impairs bile salt transport, causing jaundice (yellowish discoloration of the skin). In kidneys, inadequate oxygenation results in tubular epithelial cell injury (of the cells lining the kidney tubules), and thus causes acute kidney injury (AKI). Meanwhile, in the heart, impaired calcium transport, and low production of adenosine triphosphate (ATP), can cause myocardial depression, reducing cardiac contractility and causing heart failure. In the gastrointestinal tract, increased permeability of the mucosa alters the microflora, causing mucosal bleeding and paralytic ileus. In the central nervous system, direct damage of the brain cells and disturbances of neurotransmissions causes altered mental status. Cytokines such as tumor necrosis factor, interleukin 1, and interleukin 6 may activate procoagulation factors in the cells lining blood vessels, leading to endothelial damage. The damaged endothelial surface inhibits anticoagulant properties as well as increases antifibrinolysis, which may lead to intravascular clotting, the formation of blood clots in small blood vessels, and multiple organ failure.The low blood pressure seen in those with sepsis is the result of various processes, including excessive production of chemicals that dilate blood vessels such as nitric oxide, a deficiency of chemicals that constrict blood vessels such as vasopressin, and activation of ATP-sensitive potassium channels. In those with severe sepsis and septic shock, this sequence of events leads to a type of circulatory shock known as distributive shock. Diagnosis Early diagnosis is necessary to properly manage sepsis, as the initiation of rapid therapy is key to reducing deaths from severe sepsis. Some hospitals use alerts generated from electronic health records to bring attention to potential cases as early as possible. Within the first three hours of suspected sepsis, diagnostic studies should include white blood cell counts, measuring serum lactate, and obtaining appropriate cultures before starting antibiotics, so long as this does not delay their use by more than 45 minutes. To identify the causative organism(s), at least two sets of blood cultures using bottles with media for aerobic and anaerobic organisms are necessary. At least one should be drawn through the skin and one through each vascular access device (such as an IV catheter) that has been in place more than 48 hours. Bacteria are present in the blood in only about 30% of cases. Another possible method of detection is by polymerase chain reaction. If other sources of infection are suspected, cultures of these sources, such as urine, cerebrospinal fluid, wounds, or respiratory secretions, also should be obtained, as long as this does not delay the use of antibiotics.Within six hours, if blood pressure remains low despite initial fluid resuscitation of 30 mL/kg, or if initial lactate is ≥ four mmol/L (36 mg/dL), central venous pressure and central venous oxygen saturation should be measured. Lactate should be re-measured if the initial lactate was elevated. Evidence for point of care lactate measurement over usual methods of measurement, however, is poor.Within twelve hours, it is essential to diagnose or exclude any source of infection that would require emergent source control, such as a necrotizing soft tissue infection, an infection causing inflammation of the abdominal cavity lining, an infection of the bile duct, or an intestinal infarction. A pierced internal organ (free air on an abdominal X-ray or CT scan), an abnormal chest X-ray consistent with pneumonia (with focal opacification), or petechiae, purpura, or purpura fulminans may indicate the presence of an infection. Definitions Previously, SIRS criteria had been used to define sepsis. If the SIRS criteria are negative, it is very unlikely the person has sepsis; if it is positive, there is just a moderate probability that the person has sepsis. According to SIRS, there were different levels of sepsis: sepsis, severe sepsis, and septic shock. The definition of SIRS is shown below: SIRS is the presence of two or more of the following: abnormal body temperature, heart rate, respiratory rate, or blood gas, and white blood cell count. Sepsis is defined as SIRS in response to an infectious process. Severe sepsis is defined as sepsis with sepsis-induced organ dysfunction or tissue hypoperfusion (manifesting as hypotension, elevated lactate, or decreased urine output). Severe sepsis is an infectious disease state associated with multiple organ dysfunction syndrome (MODS) Septic shock is severe sepsis plus persistently low blood pressure, despite the administration of intravenous fluids.In 2016 a new consensus was reached to replace screening by systemic inflammatory response syndrome (SIRS) with the sequential organ failure assessment (SOFA score) and the abbreviated version (qSOFA). The three criteria for the qSOFA score include a respiratory rate greater than or equal to 22 breaths per minute, systolic blood pressure 100 mmHg or less and altered mental status. Sepsis is suspected when 2 of the qSOFA criteria are met. The SOFA score was intended to be used in the intensive care unit (ICU) where it is administered upon admission to the ICU and then repeated every 48 hours, whereas the qSOFA could be used outside the ICU. Some advantages of the qSOFA score are that it can be administered quickly and does not require labs. However, the American College of Chest Physicians (CHEST) raised concerns that qSOFA and SOFA criteria may lead to delayed diagnosis of serious infection, leading to delayed treatment. Although SIRS criteria can be too sensitive and not specific enough in identifying sepsis, SOFA also has its limitations and is not intended to replace the SIRS definition. qSOFA has also been found to be poorly sensitive though decently specific for the risk of death with SIRS possibly better for screening. NOTE - Surviving Sepsis Campaign 2021 Guidelines recommends "against using qSOFA compared with SIRS, NEWS, or MEWS as a single screening tool for sepsis or septic shock". End-organ dysfunction Examples of end-organ dysfunction include the following: Lungs: acute respiratory distress syndrome (ARDS) (PaO2/FiO2 ratio < 300), different ratio in pediatric acute respiratory distress syndrome Brain: encephalopathy symptoms including agitation, confusion, coma; causes may include ischemia, bleeding, formation of blood clots in small blood vessels, microabscesses, multifocal necrotizing leukoencephalopathy Liver: disruption of protein synthetic function manifests acutely as progressive disruption of blood clotting due to an inability to synthesize clotting factors and disruption of metabolic functions leads to impaired bilirubin metabolism, resulting in elevated unconjugated serum bilirubin levels Kidney: low urine output or no urine output, electrolyte abnormalities, or volume overload Heart: systolic and diastolic heart failure, likely due to chemical signals that depress myocyte function, cellular damage, manifest as a troponin leak (although not necessarily ischemic in nature)More specific definitions of end-organ dysfunction exist for SIRS in pediatrics. Cardiovascular dysfunction (after fluid resuscitation with at least 40 mL/kg of crystalloid) hypotension with blood pressure < 5th percentile for age or systolic blood pressure < 2 standard deviations below normal for age, or vasopressor requirement, or two of the following criteria: unexplained metabolic acidosis with base deficit > 5 mEq/L lactic acidosis: serum lactate 2 times the upper limit of normal oliguria (urine output < 0.5 mL/kg/h) prolonged capillary refill > 5 seconds core to peripheral temperature difference > 3 °C Respiratory dysfunction (in the absence of a cyanotic heart defect or a known chronic respiratory disease) the ratio of the arterial partial-pressure of oxygen to the fraction of oxygen in the gases inspired (PaO2/FiO2) < 300 (the definition of acute lung injury), or arterial partial-pressure of carbon dioxide (PaCO2) > 65 torr (20 mmHg) over baseline PaCO2 (evidence of hypercapnic respiratory failure), or supplemental oxygen requirement of greater than FiO2 0.5 to maintain oxygen saturation ≥ 92% Neurologic dysfunction Glasgow Coma Score (GCS) ≤ 11, or altered mental status with drop in GCS of 3 or more points in a person with developmental delay/intellectual disability Hematologic dysfunction platelet count < 80,000/mm3 or 50% drop from maximum in chronically thrombocytopenic, or international normalized ratio (INR) > 2 Disseminated intravascular coagulation Kidney dysfunction serum creatinine ≥ 2 times the upper limit of normal for age or 2-fold increase in baseline creatinine in people with chronic kidney disease Liver dysfunction (only applicable to infants > 1 month) total serum bilirubin ≥ 4 mg/dL, or alanine aminotransferase (ALT) ≥ 2 times the upper limit of normalConsensus definitions, however, continue to evolve, with the latest expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience. Biomarkers Biomarkers can help diagnosis because they can point to the presence or severity of sepsis, although their exact role in the management of sepsis remains undefined. A 2013 review concluded moderate-quality evidence exists to support the use of the procalcitonin level as a method to distinguish sepsis from non-infectious causes of SIRS. The same review found the sensitivity of the test to be 77% and the specificity to be 79%. The authors suggested that procalcitonin may serve as a helpful diagnostic marker for sepsis, but cautioned that its level alone does not definitively make the diagnosis. A 2012 systematic review found that soluble urokinase-type plasminogen activator receptor (SuPAR) is a nonspecific marker of inflammation and does not accurately diagnose sepsis. This same review concluded, however, that SuPAR has prognostic value, as higher SuPAR levels are associated with an increased rate of death in those with sepsis. Serial measurement of lactate levels (approximately every 4 to 6 hours) may guide treatment and is associated with lower mortality in sepsis. Differential diagnosis The differential diagnosis for sepsis is broad and has to examine (to exclude) the non-infectious conditions that may cause the systemic signs of SIRS: alcohol withdrawal, acute pancreatitis, burns, pulmonary embolism, thyrotoxicosis, anaphylaxis, adrenal insufficiency, and neurogenic shock. Hyperinflammatory syndromes such as hemophagocytic lymphohistiocytosis (HLH) may have similar symptoms and are on the differential diagnosis. Neonatal sepsis In common clinical usage, neonatal sepsis refers to a bacterial blood stream infection in the first month of life, such as meningitis, pneumonia, pyelonephritis, or gastroenteritis, but neonatal sepsis also may be due to infection with fungi, viruses, or parasites. Criteria with regard to hemodynamic compromise or respiratory failure are not useful because they present too late for intervention. Management Early recognition and focused management may improve the outcomes in sepsis. Current professional recommendations include a number of actions ("bundles") to be followed as soon as possible after diagnosis. Within the first three hours, someone with sepsis should have received antibiotics and, intravenous fluids if there is evidence of either low blood pressure or other evidence for inadequate blood supply to organs (as evidenced by a raised level of lactate); blood cultures also should be obtained within this time period. After six hours the blood pressure should be adequate, close monitoring of blood pressure and blood supply to organs should be in place, and the lactate should be measured again if initially it was raised. A related bundle, the "Sepsis Six", is in widespread use in the United Kingdom; this requires the administration of antibiotics within an hour of recognition, blood cultures, lactate, and hemoglobin determination, urine output monitoring, high-flow oxygen, and intravenous fluids.Apart from the timely administration of fluids and antibiotics, the management of sepsis also involves surgical drainage of infected fluid collections and appropriate support for organ dysfunction. This may include hemodialysis in kidney failure, mechanical ventilation in lung dysfunction, transfusion of blood products, and drug and fluid therapy for circulatory failure. Ensuring adequate nutrition—preferably by enteral feeding, but if necessary, by parenteral nutrition—is important during prolonged illness. Medication to prevent deep vein thrombosis and gastric ulcers also may be used. Antibiotics Two sets of blood cultures (aerobic and anaerobic) are recommended without delaying the initiation of antibiotics. Cultures from other sites such as respiratory secretions, urine, wounds, cerebrospinal fluid, and catheter insertion sites (in-situ more than 48 hours) are recommended if infections from these sites are suspected. In severe sepsis and septic shock, broad-spectrum antibiotics (usually two, a β-lactam antibiotic with broad coverage, or broad-spectrum carbapenem combined with fluoroquinolones, macrolides, or aminoglycosides) are recommended. The choice of antibiotics is important in determining the survival of the person. Some recommend they be given within one hour of making the diagnosis, stating that for every hour of delay in the administration of antibiotics, there is an associated 6% rise in mortality. Others did not find a benefit with early administration.Several factors determine the most appropriate choice for the initial antibiotic regimen. These factors include local patterns of bacterial sensitivity to antibiotics, whether the infection is thought to be a hospital or community-acquired infection, and which organ systems are thought to be infected. Antibiotic regimens should be reassessed daily and narrowed if appropriate. Treatment duration is typically 7–10 days with the type of antibiotic used directed by the results of cultures. If the culture result is negative, antibiotics should be de-escalated according to the persons clinical response or stopped altogether if an infection is not present to decrease the chances that the person is infected with multiple drug resistance organisms. In case of people having a high risk of being infected with multiple drug resistant organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii, the addition of an antibiotic specific to the gram-negative organism is recommended. For methicillin-resistant Staphylococcus aureus (MRSA), vancomycin or teicoplanin is recommended. For Legionella infection, addition of macrolide or fluoroquinolone is chosen. If fungal infection is suspected, an echinocandin, such as caspofungin or micafungin, is chosen for people with severe sepsis, followed by triazole (fluconazole and itraconazole) for less ill people. Prolonged antibiotic prophylaxis is not recommended in people who has SIRS without any infectious origin such as acute pancreatitis and burns unless sepsis is suspected.Once-daily dosing of aminoglycoside is sufficient to achieve peak plasma concentration for a clinical response without kidney toxicity. Meanwhile, for antibiotics with low volume distribution (vancomycin, teicoplanin, colistin), a loading dose is required to achieve an adequate therapeutic level to fight infections. Frequent infusions of beta-lactam antibiotics without exceeding total daily dose would help to keep the antibiotics level above minimum inhibitory concentration (MIC), thus providing a better clinical response. Giving beta-lactam antibiotics continuously may be better than giving them intermittently. Access to therapeutic drug monitoring is important to ensure adequate drug therapeutic level while at the same time preventing the drug from reaching toxic level. Intravenous fluids The Surviving Sepsis Campaign has recommended 30 mL/kg of fluid to be given in adults in the first three hours followed by fluid titration according to blood pressure, urine output, respiratory rate, and oxygen saturation with a target mean arterial pressure (MAP) of 65 mmHg. In children an initial amount of 20 mL/kg is reasonable in shock. In cases of severe sepsis and septic shock where a central venous catheter is used to measure blood pressures dynamically, fluids should be administered until the central venous pressure reaches 8–12 mmHg. Once these goals are met, the central venous oxygen saturation (ScvO2), i.e., the oxygen saturation of venous blood as it returns to the heart as measured at the vena cava, is optimized. If the ScvO2 is less than 70%, blood may be given to reach a hemoglobin of 10 g/dL and then inotropes are added until the ScvO2 is optimized. In those with acute respiratory distress syndrome (ARDS) and sufficient tissue blood fluid, more fluids should be given carefully.Crystalloid solution is recommended as the fluid of choice for resuscitation. Albumin can be used if a large amount of crystalloid is required for resuscitation. Crystalloid solutions shows little difference with hydroxyethyl starch in terms of risk of death. Starches also carry an increased risk of acute kidney injury, and need for blood transfusion. Various colloid solutions (such as modified gelatin) carry no advantage over crystalloid. Albumin also appears to be of no benefit over crystalloids. Blood products The Surviving Sepsis Campaign recommended packed red blood cells transfusion for hemoglobin levels below 70 g/L if there is no myocardial ischemia, hypoxemia, or acute bleeding. In a 2014 trial, blood transfusions to keep target hemoglobin above 70 or 90 g/L did not make any difference to survival rates; meanwhile, those with a lower threshold of transfusion received fewer transfusions in total. Erythropoietin is not recommended in the treatment of anemia with septic shock because it may precipitate blood clotting events. Fresh frozen plasma transfusion usually does not correct the underlying clotting abnormalities before a planned surgical procedure. However, platelet transfusion is suggested for platelet counts below (10 × 109/L) without any risk of bleeding, or (20 × 109/L) with high risk of bleeding, or (50 × 109/L) with active bleeding, before a planned surgery or an invasive procedure. IV immunoglobulin is not recommended because its beneficial effects are uncertain. Monoclonal and polyclonal preparations of intravenous immunoglobulin (IVIG) do not lower the rate of death in newborns and adults with sepsis. Evidence for the use of IgM-enriched polyclonal preparations of IVIG is inconsistent. On the other hand, the use of antithrombin to treat disseminated intravascular coagulation is also not useful. Meanwhile, the blood purification technique (such as hemoperfusion, plasma filtration, and coupled plasma filtration adsorption) to remove inflammatory mediators and bacterial toxins from the blood also does not demonstrate any survival benefit for septic shock. Vasopressors If the person has been sufficiently fluid resuscitated but the mean arterial pressure is not greater than 65 mmHg, vasopressors are recommended. Norepinephrine (noradrenaline) is recommended as the initial choice. Delaying initiation of vasopressor therapy during septic shock is associated with increased mortality.Norepinephrine is often used as a first-line treatment for hypotensive septic shock because evidence shows that there is a relative deficiency of vasopressin when shock continues for 24 to 48 hours. Norepinephrine raises blood pressure through a vasoconstriction effect, with little effect on stroke volume and heart rate. In some people, the required dose of vasopressor needed to increase the mean arterial pressure can become exceedingly high that it becomes toxic. In order to reduce the required dose of vasopressor, epinephrine may be added. Epinephrine is not often used as a first-line treatment for hypotensive shock because it reduces blood flow to the abdominal organs and increases lactate levels. Vasopressin can be used in septic shock because studies have shown that there is a relative deficiency of vasopressin when shock continues for 24 to 48 hours. However, vasopressin reduces blood flow to the heart, finger/toes, and abdominal organs, resulting in a lack of oxygen supply to these tissues. Dopamine is typically not recommended. Although dopamine is useful to increase the stroke volume of the heart, it causes more abnormal heart rhythms than norepinephrine and also has an immunosuppressive effect. Dopamine is not proven to have protective properties on the kidneys. Dobutamine can also be used in hypotensive septic shock to increase cardiac output and correct blood flow to the tissues. Dobutamine is not used as often as epinephrine due to its associated side effects, which include reducing blood flow to the gut. Additionally, dobutamine increases the cardiac output by abnormally increasing the heart rate. Steroids The use of steroids in sepsis is controversial. Studies do not give a clear picture as to whether and when glucocorticoids should be used. The 2016 Surviving Sepsis Campaign recommends low dose hydrocortisone only if both intravenous fluids and vasopressors are not able to adequately treat septic shock. The 2021 Surviving Sepsis Campaign recommends IV corticosteroids for adults with septic shock who have an ongoing requirement for vasopressor therapy. A 2019 Cochrane review found low-quality evidence of benefit, as did two 2019 reviews.During critical illness, a state of adrenal insufficiency and tissue resistance to corticosteroids may occur. This has been termed critical illness–related corticosteroid insufficiency. Treatment with corticosteroids might be most beneficial in those with septic shock and early severe ARDS, whereas its role in others such as those with pancreatitis or severe pneumonia is unclear. However, the exact way of determining corticosteroid insufficiency remains problematic. It should be suspected in those poorly responding to resuscitation with fluids and vasopressors. Neither ACTH stimulation testing nor random cortisol levels are recommended to confirm the diagnosis. The method of stopping glucocorticoid drugs is variable, and it is unclear whether they should be slowly decreased or simply abruptly stopped. However, the 2016 Surviving Sepsis Campaign recommended to taper steroids when vasopressors are no longer needed. Anesthesia A target tidal volume of 6 mL/kg of predicted body weight (PBW) and a plateau pressure less than 30 cm H2O is recommended for those who require ventilation due to sepsis-induced severe ARDS. High positive end expiratory pressure (PEEP) is recommended for moderate to severe ARDS in sepsis as it opens more lung units for oxygen exchange. Predicted body weight is calculated based on sex and height, and tools for this are available. Recruitment maneuvers may be necessary for severe ARDS by briefly raising the transpulmonary pressure. It is recommended that the head of the bed be raised if possible to improve ventilation. However, β2 adrenergic receptor agonists are not recommended to treat ARDS because it may reduce survival rates and precipitate abnormal heart rhythms. A spontaneous breathing trial using continuous positive airway pressure (CPAP), T piece, or inspiratory pressure augmentation can be helpful in reducing the duration of ventilation. Minimizing intermittent or continuous sedation is helpful in reducing the duration of mechanical ventilation.General anesthesia is recommended for people with sepsis who require surgical procedures to remove the infective source. Usually, inhalational and intravenous anesthetics are used. Requirements for anesthetics may be reduced in sepsis. Inhalational anesthetics can reduce the level of proinflammatory cytokines, altering leukocyte adhesion and proliferation, inducing apoptosis (cell death) of the lymphocytes, possibly with a toxic effect on mitochondrial function. Although etomidate has a minimal effect on the cardiovascular system, it is often not recommended as a medication to help with intubation in this situation due to concerns it may lead to poor adrenal function and an increased risk of death. The small amount of evidence there is, however, has not found a change in the risk of death with etomidate.Paralytic agents are not suggested for use in sepsis cases in the absence of ARDS, as a growing body of evidence points to reduced durations of mechanical ventilation, ICU and hospital stays. However, paralytic use in ARDS cases remains controversial. When appropriately used, paralytics may aid successful mechanical ventilation, however, evidence has also suggested that mechanical ventilation in severe sepsis does not improve oxygen consumption and delivery. Source control Source control refers to physical interventions to control a focus of infection and reduce conditions favorable to microorganism growth or host defense impairment, such as drainage of pus from an abscess. It is one of the oldest procedures for control of infections, giving rise to the Latin phrase Ubi pus, ibi evacua, and remains important despite the emergence of more modern treatments. Early goal directed therapy Early goal directed therapy (EGDT) is an approach to the management of severe sepsis during the initial 6 hours after diagnosis. It is a step-wise approach, with the physiologic goal of optimizing cardiac preload, afterload, and contractility. It includes giving early antibiotics. EGDT also involves monitoring of hemodynamic parameters and specific interventions to achieve key resuscitation targets which include maintaining a central venous pressure between 8–12 mmHg, a mean arterial pressure of between 65 and 90 mmHg, a central venous oxygen saturation (ScvO2) greater than 70% and a urine output of greater than 0.5 mL/kg/hour. The goal is to optimize oxygen delivery to tissues and achieve a balance between systemic oxygen delivery and demand. An appropriate decrease in serum lactate may be equivalent to ScvO2 and easier to obtain.In the original trial, early goal-directed therapy was found to reduce mortality from 46.5% to 30.5% in those with sepsis, and the Surviving Sepsis Campaign has been recommending its use. However, three more recent large randomized control trials (ProCESS, ARISE, and ProMISe), did not demonstrate a 90-day mortality benefit of early goal-directed therapy when compared to standard therapy in severe sepsis. It is likely that some parts of EGDT are more important than others. Following these trials the use of EGDT is still considered reasonable. Newborns Neonatal sepsis can be difficult to diagnose as newborns may be asymptomatic. If a newborn shows signs and symptoms suggestive of sepsis, antibiotics are immediately started and are either changed to target a specific organism identified by diagnostic testing or discontinued after an infectious cause for the symptoms has been ruled out. Despite early intervention, death occurs in 13% of children who develop septic shock, with the risk partly based on other health problems. Those without multiple organ system failures or who require only one inotropic agent mortality is low. Other Treating fever in sepsis, including people in septic shock, has not been associated with any improvement in mortality over a period of 28 days. Treatment of fever still occurs for other reasons.A 2012 Cochrane review concluded that N-acetylcysteine does not reduce mortality in those with SIRS or sepsis and may even be harmful.Recombinant activated protein C (drotrecogin alpha) was originally introduced for severe sepsis (as identified by a high APACHE II score), where it was thought to confer a survival benefit. However, subsequent studies showed that it increased adverse events—bleeding risk in particular—and did not decrease mortality. It was removed from sale in 2011. Another medication known as eritoran also has not shown benefit.In those with high blood sugar levels, insulin to bring it down to 7.8–10 mmol/L (140–180 mg/dL) is recommended with lower levels potentially worsening outcomes. Glucose levels taken from capillary blood should be interpreted with care because such measurements may not be accurate. If a person has an arterial catheter, arterial blood is recommended for blood glucose testing.Intermittent or continuous renal replacement therapy may be used if indicated. However, sodium bicarbonate is not recommended for a person with lactic acidosis secondary to hypoperfusion. Low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), and mechanical prophylaxis with intermittent pneumatic compression devices are recommended for any person with sepsis at moderate to high risk of venous thromboembolism. Stress ulcer prevention with proton-pump inhibitor (PPI) and H2 antagonist are useful in a person with risk factors of developing upper gastrointestinal bleeding (UGIB) such as on mechanical ventilation for more than 48 hours, coagulation disorders, liver disease, and renal replacement therapy. Achieving partial or full enteral feeding (delivery of nutrients through a feeding tube) is chosen as the best approach to provide nutrition for a person who is contraindicated for oral intake or unable to tolerate orally in the first seven days of sepsis when compared to intravenous nutrition. However, omega-3 fatty acids are not recommended as immune supplements for a person with sepsis or septic shock. The usage of prokinetic agents such as metoclopramide, domperidone, and erythromycin are recommended for those who are septic and unable to tolerate enteral feeding. However, these agents may precipitate prolongation of the QT interval and consequently provoke a ventricular arrhythmia such as torsades de pointes. The usage of prokinetic agents should be reassessed daily and stopped if no longer indicated. Prognosis Sepsis will prove fatal in approximately 24.4% of people, and septic shock will prove fatal in 34.7% of people within 30 days (32.2% and 38.5% after 90 days). Lactate is a useful method of determining prognosis, with those who have a level greater than 4 mmol/L having a mortality of 40% and those with a level of less than 2 mmol/L having a mortality of less than 15%.There are a number of prognostic stratification systems, such as APACHE II and Mortality in Emergency Department Sepsis. APACHE II factors in the persons age, underlying condition, and various physiologic variables to yield estimates of the risk of dying of severe sepsis. Of the individual covariates, the severity of the underlying disease most strongly influences the risk of death. Septic shock is also a strong predictor of short- and long-term mortality. Case-fatality rates are similar for culture-positive and culture-negative severe sepsis. The Mortality in Emergency Department Sepsis (MEDS) score is simpler and useful in the emergency department environment.Some people may experience severe long-term cognitive decline following an episode of severe sepsis, but the absence of baseline neuropsychological data in most people with sepsis makes the incidence of this difficult to quantify or to study. Epidemiology Sepsis causes millions of deaths globally each year and is the most common cause of death in people who have been hospitalized. The number of new cases worldwide of sepsis is estimated to be 18 million cases per year. In the United States sepsis affects approximately 3 in 1,000 people, and severe sepsis contributes to more than 200,000 deaths per year.Sepsis occurs in 1–2% of all hospitalizations and accounts for as much as 25% of ICU bed utilization. Due to it rarely being reported as a primary diagnosis (often being a complication of cancer or other illness), the incidence, mortality, and morbidity rates of sepsis are likely underestimated. A study of U.S. states found approximately 651 hospital stays per 100,000 population with a sepsis diagnosis in 2010. It is the second-leading cause of death in non-coronary intensive care unit (ICU) and the tenth-most-common cause of death overall (the first being heart disease). Children under 12 months of age and elderly people have the highest incidence of severe sepsis. Among people from the U.S. who had multiple sepsis hospital admissions in 2010, those who were discharged to a skilled nursing facility or long-term care following the initial hospitalization were more likely to be readmitted than those discharged to another form of care. A study of 18 U.S. states found that, amongst people with Medicare in 2011, sepsis was the second most common principal reason for readmission within 30 days.Several medical conditions increase a persons susceptibility to infection and developing sepsis. Common sepsis risk factors include age (especially the very young and old); conditions that weaken the immune system such as cancer, diabetes, or the absence of a spleen; and major trauma and burns.From 1979 to 2000, data from the United States National Hospital Discharge Survey showed that the incidence of sepsis increased fourfold, to 240 cases per 100,000 population, with a higher incidence in men when compared to women. However, the global prevalence of sepsis has been estimated to be higher in women. During the same time frame, the in-hospital case fatality rate was reduced from 28% to 18%. However, according to the nationwide inpatient sample from the United States, the incidence of severe sepsis increased from 200 per 10,000 population in 2003 to 300 cases in 2007 for population aged more than 18 years. The incidence rate is particularly high among infants, with an incidence of 500 cases per 100,000 population. Mortality related to sepsis increases with age, from less than 10% in the age group of 3 to 5 years to 60% by sixth decade of life. The increase in the average age of the population, alongside the presence of more people with chronic diseases or on immunosuppressive medications, and also the increase in the number of invasive procedures being performed, has led to an increased rate of sepsis. History The term "σήψις" (sepsis) was introduced by Hippocrates in the fourth century BC, and it meant the process of decay or decomposition of organic matter. In the eleventh century, Avicenna used the term "blood rot" for diseases linked to severe purulent process. Though severe systemic toxicity had already been observed, it was only in the 19th century that the specific term – sepsis – was used for this condition. The terms "septicemia", also spelled "septicaemia", and "blood poisoning" referred to the microorganisms or their toxins in the blood. The International Statistical Classification of Diseases and Related Health Problems (ICD) version 9, which was in use in the US until 2013, used the term septicemia with numerous modifiers for different diagnoses, such as "Streptococcal septicemia". All those diagnoses have been converted to sepsis, again with modifiers, in ICD-10, such as "Sepsis due to streptococcus".The current terms are dependent on the microorganism that is present: bacteremia if bacteria are present in the blood at abnormal levels and are the causative issue, viremia for viruses, and fungemia for a fungus.By the end of the 19th century, it was widely believed that microbes produced substances that could injure the mammalian host and that soluble toxins released during infection caused the fever and shock that were commonplace during severe infections. Pfeiffer coined the term endotoxin at the beginning of the 20th century to denote the pyrogenic principle associated with Vibrio cholerae. It was soon realized that endotoxins were expressed by most and perhaps all gram-negative bacteria. The lipopolysaccharide character of enteric endotoxins was elucidated in 1944 by Shear. The molecular character of this material was determined by Luderitz et al. in 1973.It was discovered in 1965 that a strain of C3H/HeJ mouse was immune to the endotoxin-induced shock. The genetic locus for this effect was dubbed Lps. These mice were also found to be hyper susceptible to infection by gram-negative bacteria. These observations were finally linked in 1998 by the discovery of the toll-like receptor gene 4 (TLR 4). Genetic mapping work, performed over a period of five years, showed that TLR4 was the sole candidate locus within the Lps critical region; this strongly implied that a mutation within TLR4 must account for the lipopolysaccharide resistance phenotype. The defect in the TLR4 gene that led to the endotoxin resistant phenotype was discovered to be due to a mutation in the cytoplasm.Controversy occurred in the scientific community over the use of mouse models in research into sepsis in 2013 when scientists published a review of the mouse immune system compared to the human immune system and showed that on a systems level, the two worked very differently; the authors noted that as of the date of their article over 150 clinical trials of sepsis had been conducted in humans, almost all of them supported by promising data in mice and that all of them had failed. The authors called for abandoning the use of mouse models in sepsis research; others rejected that but called for more caution in interpreting the results of mouse studies, and more careful design of preclinical studies. One approach is to rely more on studying biopsies and clinical data from people who have had sepsis, to try to identify biomarkers and drug targets for intervention. Society and culture Economics Sepsis was the most expensive condition treated in United States hospital stays in 2013, at an aggregate cost of $23.6 billion for nearly 1.3 million hospitalizations. Costs for sepsis hospital stays more than quadrupled since 1997 with an 11.5 percent annual increase. By payer, it was the most costly condition billed to Medicare and the uninsured, the second-most costly billed to Medicaid, and the fourth-most costly billed to private insurance. Education A large international collaboration entitled the "Surviving Sepsis Campaign" was established in 2002 to educate people about sepsis and to improve outcomes with sepsis. The Campaign has published an evidence-based review of management strategies for severe sepsis, with the aim to publish a complete set of guidelines in subsequent years. The guidelines were updated in 2016 and again in 2021.Sepsis Alliance is a charitable organization that was created to raise sepsis awareness among both the general public and healthcare professionals. Research Some authors suggest that initiating sepsis by the normally mutualistic (or neutral) members of the microbiome may not always be an accidental side effect of the deteriorating host immune system. Rather it is often an adaptive microbial response to a sudden decline of host survival chances. Under this scenario, the microbe species provoking sepsis benefit from monopolizing the future cadaver, utilizing its biomass as decomposers, and then transmitted through soil or water to establish mutualistic relations with new individuals. The bacteria Streptococcus pneumoniae, Escherichia coli, Proteus spp., Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella spp., Clostridium spp., Lactobacillus spp., Bacteroides spp. and the fungi Candida spp. are all capable of such a high level of phenotypic plasticity. Evidently, not all cases of sepsis arise through such adaptive microbial strategy switches.Paul E. Mariks "Marik protocol", also known as the "HAT" protocol, proposed a combination of hydrocortisone, vitamin C, and thiamine as a treatment for preventing sepsis for people in intensive care. Mariks own initial research, published in 2017, showed a dramatic evidence of benefit, leading to the protocol becoming popular among intensive care physicians, especially after the protocol received attention on social media and National Public Radio, leading to criticism of science by press conference from the wider medical community. Subsequent independent research failed to replicate Mariks positive results, indicating the possibility that they had been compromised by bias. A systematic review of trials in 2021 found that the claimed benefits of the protocol could not be confirmed. Another more recent review found that "HAT therapy significantly reduced the duration of vasopressor use and improved the SOFA score but appeared not to have significant benefits in other outcomes for patients with sepsis."Overall, the evidence for any role for vitamin C in the treatment of sepsis remains unclear as of 2021. References External links Sepsis at Curlie SIRS, Sepsis, and Septic Shock Criteria Archived 17 February 2015 at the Wayback Machine "Sepsis". MedlinePlus. U.S. National Library of Medicine.

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

I need a basic explanation for the medical term 'Optic nerve glioma.'

Optic nerve glioma (or optic glioma), a form of glioma which affects the optic nerve, is often one of the central nervous system manifestations of neurofibromatosis 1.Optic gliomas are usually pilocytic tumors, and can involve the optic nerve or optic chiasm. Optic gliomas are usually associated with neurofibromatosis type 1 in 30% of people with the condition.Optic nerve gliomas have low mortality but extremely high prevalence of vision loss & eye-bulging exophthalmos) in children. As of 2014, approximately 1000 cases had been reported. Diagnosis Optic nerve gliomas are diagnosed using magnetic resonance imaging (MRI) and CT scans. The tumor adopts a fusiform appearance, appearing wider in the middle and tapered at the ends. Enlargement of the optic nerve along with a downward kink in the mid-orbit is usually observed. While CT scans allow for optic nerve evaluation, MRI allows for intracranial evaluation to observe if the tumor has extended to other regions such as the optic chiasm & hypothalamus. Treatment The main goal of treating optic gliomas is to preserve vision for as long as possible. The tumor’s slow & self-limiting growth indicates that it is not immediately problematic in most benign cases, with long-term studies showing that people with optic glioma may still have stable functional vision without intervention. As a result, the first & preferred course of action is usually observation of optic glioma over time.Once the first signs of visual deterioration and/or tumor progression are observed, interventional treatments will then commence. These include radiation therapy, [[chemotherapy and surgical excision. While being the most effective therapy, radiation has shown damaging effects on the already compromised intellect as well as an increase in vascular issues & second tumor formation in children with neurofibromatosis 1. However, fractionated stereotactic radiation therapy (FSRT) is gaining traction as the most preferred interventional treatment for optic nerve glioma due to its combination of the therapeutic efficiency of radiation therapy without the negative side effects. Chemotherapy has also been shown to be a safer alternative to most radiation therapies & surgery for very young children (under the age of 3). However, the optimal chemotherapeutic therapy has not been defined, with risks of different toxicities still observed in older children. Surgery is considered the final choice of treatment, due to the high risk of blindness & damage to the affected eye. It is considered in only certain scenarios, such as relieving a cosmetically unappealing bulging eye (exophthalmos), removing an enlarging and/or expanding tumor or a combination of both. Prognosis Optic gliomas alternate between periods of inactivity and growth, making their clinical presentation variable & clinical course unpredictable. Once the optic chiasm is involved, the prognosis for life & vision worsens. References External links 00724 at CHORUS

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

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

Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic diseases toxoplasmosis and cystoisosporiasis. It is also used with dapsone as a second-line option to prevent Pneumocystis jiroveci pneumonia in people with HIV/AIDS. It was previously used for malaria but is no longer recommended due to resistance. Pyrimethamine is taken by mouth.Common side effects include gastrointestinal upset, severe allergic reactions, and bone marrow suppression. It should not be used by people with folate deficiency that has resulted in anemia. There is concern that it may increase the risk of cancer. While occasionally used in pregnancy it is unclear if pyrimethamine is safe for the baby. Pyrimethamine is classified as a folic acid antagonist. It works by inhibiting folic acid metabolism and therefore the making of DNA.Pyrimethamine was discovered in 1952 and came into medical use in 1953. It is on the World Health Organizations List of Essential Medicines. It was approved as a generic in the United States in February 2020. Medical uses Pyrimethamine is typically given with a sulfonamide and folinic acid.It is used for the treatment of toxoplasmosis, actinomycosis, and isosporiasis, and for the treatment and prevention of Pneumocystis jirovecii pneumonia. Toxoplasmosis Pyrimethamine is also used in combination with sulfadiazine to treat active toxoplasmosis. The two drugs bind the same enzymatic targets as the drugs trimethoprim and sulfamethoxazole - dihydrofolate reductase and dihydropteroate synthase, respectively.Pyrimethamine has also been used in several trials to treat retinochoroiditis. Pregnancy consideration Pyrimethamine is labeled as pregnancy category C in the United States. To date, not enough evidence on its risks in pregnancy or its effects on the fetus is available. Malaria It is primarily active against Plasmodium falciparum, but also against Plasmodium vivax. Due to the emergence of pyrimethamine-resistant strains of P. falciparum, pyrimethamine alone is seldom used now. In combination with a long-acting sulfonamide such as sulfadiazine, it was widely used, such as in Fansidar, though resistance to this combination is increasing. Contraindications Pyrimethamine is contraindicated in people with folate-deficiency anaemia. Side effects When higher doses are used, as in the treatment of toxoplasmosis, pyrimethamine can cause gastrointestinal symptoms such as nausea, vomiting, glossitis, anorexia, and diarrhea. A rash, which can be indicative of a hypersensitivity reaction, is also seen, particularly in combination with sulfonamides. Central nervous system effects include ataxia, tremors, and seizures. Hematologic side effects such as thrombocytopenia, leukopenia, and anemia can also occur. Interactions Other antifolate agents such as methotrexate and trimethoprim may potentiate the antifolate actions of pyrimethamine, leading to potential folate deficiency, anaemia, and other blood dyscrasias. Mechanism of action Pyrimethamine interferes with the regeneration of tetrahydrofolic acid from dihydrofolate by competitively inhibiting the enzyme dihydrofolate reductase. Tetrahydrofolic acid is essential for DNA and RNA synthesis in many species, including protozoa. It has also been found to reduce the expression of SOD1, a key protein involved in amyotrophic lateral sclerosis. Other medications Pyrimethamine is typically given with folinic acid and sulfadiazine. Sulfonamides (e.g. sulfadiazine) inhibit dihydropteroate synthetase, an enzyme that participates in folic acid synthesis from para-aminobenzoic acid. Hence, sulfonamides work synergistically with pyrimethamine by blocking a different enzyme needed for folic acid synthesis. Folinic acid (leucovorin) is a folic acid derivative converted to tetrahydrofolate, the primary active form of folic acid, in vivo, without relying on dihydrofolate reductase. Folinic acid reduces side effects related to folate deficiency in the patient. Mechanism of resistance Resistance to pyrimethamine is widespread. Mutations in the malarial gene for dihydrofolate reductase may reduce its effectiveness. These mutations decrease the binding affinity between pyrimethamine and dihydrofolate reductase via loss of hydrogen bonds and steric interactions. History Nobel Prize-winning American scientist Gertrude Elion developed the drug at Burroughs-Wellcome (now part of GlaxoSmithKline) to combat malaria. Pyrimethamine has been available since 1953. In 2010, GlaxoSmithKline sold the marketing rights for Daraprim to CorePharma. Impax Laboratories sought to buy CorePharma in 2014, and completed the acquisition, including Daraprim, in March 2015. In August 2015, the rights were bought by Turing Pharmaceuticals. Turing subsequently became infamous for a price hike controversy when it raised the price of a dose of the drug in the U.S. market from US$13.50 to US$750, a 5,500% increase. Society and culture Economics In the United States in 2015, Turing Pharmaceuticals was criticized for increasing the price 50-fold, from US$13.50 to $750 a tablet, leading to a cost of $75,000 for a course of treatment reported at one hospital. United States In the United States, in 2015, with Turing Pharmaceuticals acquisition of the US marketing rights for Daraprim tablets, Daraprim became a single-source and specialty pharmacy item, and the price was increased. The cost of a monthly course for a person on 75 mg dose rose to about $75,000/month at one hospital, or $750 per tablet while it was previously priced at 13.50.Outpatients could no longer obtain the medication from a community pharmacy, but only through a single dispensing pharmacy, Walgreens Specialty Pharmacy, and institutions could no longer order from their general wholesaler, but had to set up an account with the Daraprim Direct program. Presentations from Retrophin, a company formerly headed by Martin Shkreli, CEO of Turing, from which Turing acquired the rights to Daraprim, suggested that a closed distribution system could prevent generic competitors from legally obtaining the drugs for the bioequivalence studies required for FDA approval of a generic drug.Shkreli defended the price hike by saying, "If there was a company that was selling an Aston Martin at the price of a bicycle, and we buy that company and we ask to charge Toyota prices, I dont think that that should be a crime." As a result of the backlash, Shkreli hired a crisis public relations firm to help explain his funds move. Turing Pharmaceuticals announced on 24 November 2015, "that it would not reduce the list price of that drug after all", but they would offer patient assistance programs. New York Times journalist Andrew Pollack noted that these programs "are standard for companies selling extremely high-priced drugs. They enable the patients to get the drug while pushing most of the costs onto insurance companies and taxpayers."The price increase was criticized by physician groups such as HIV Medicine Associates and Infectious Diseases Society of America.In 2016, a group of high school students from Sydney Grammar supported by the University of Sydney prepared pyrimethamine as an illustration that the synthesis is comparatively easy and the price-hike unjustifiable. His team produced 3.7 g for US$20, which would have been worth between US$35,000 and US$110,000 in the United States at the time. Shkreli said the schoolboys were not competition, likely because the necessary bioequivalence studies require a sample of the existing medication provided directly by the company, and not simply purchased from a pharmacy, which Turing could decline to provide. Nonetheless, the students work was featured in The Guardian and Time magazine, and on ABC Australia, the BBC, and CNN.On 22 October 2015, Imprimis Pharmaceuticals announced it had made available compounded and customizable formulations of pyrimethamine and leucovorin in capsules to be taken by mouth starting as low as $99 for a 100-count bottle in the United States. Pyrimethamine was approved as a generic in the United States in February 2020.In January 2020 the FTC filed a case against Vyera "alleging an elaborate anticompetitive scheme to preserve a monopoly for the life-saving drug, Daraprim". A settlement was reached in December 2021. According to AP News, the settlement "requires Vyera and Phoenixus to provide up to $40 million in relief over 10 years to consumers who allegedly were fleeced by their actions and requires them to make Daraprim available to any potential generic competitor at the cost of producing the drug." According to Law360, company executive Kevin Mulleady "agreed to a seven-year ban on working for or holding more than an 8% share in most pharmaceutical companies." Other countries In India, over a dozen manufacturers sell pyrimethamine tablets, and multiple combinations of generic pyrimethamine are available for a price ranging from US$0.04 to US$0.10 each (3–7 rupees).In the UK, the same drug is available from GSK at a cost of US$20 (£13) for 30 tablets (about $0.66 each).In Australia, the drug is available in most pharmacies at a cost of US$9.35 (A$12.99) for 50 tablets (around US$0.18 each).In Brazil, the drug is available for R$0.07 a pill, or about US$0.02.In Canada, the drug was reportedly discontinued in 2013, but hospitals may make the drug in-house when it is needed. As of December 2015, Daraprim imported into Canada directly from GSK UK is available from an online pharmacy for US$2.20 per tablet.In Switzerland, the drug is available for US$9.45 (CHF9.05) for 30 tablets (around US$0.32 a piece). Research In 2011, researchers discovered that pyrimethamine can increase β-hexosaminidase activity, thus potentially slowing down the progression of late-onset Tay–Sachs disease. It is being evaluated in clinical trials as a treatment for amyotrophic lateral sclerosis. See also Sulfadoxine/pyrimethamine References External links "Pyrimethamine". Drug Information Portal. U.S. National Library of Medicine.

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

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

Carisoprodol, sold under the brand name Soma among others, is a medication used for musculoskeletal pain. Use is only approved for up to three weeks. Effects generally begin within half an hour and last for up to six hours. It is taken orally.Common side effects include headache, dizziness, and sleepiness. Serious side effect may include addiction, allergic reactions, and seizures. In people with a sulfa allergy certain formulations may result in problems. Safety during pregnancy and breastfeeding is not clear. How it works is not clear. Some of its effects are believed to occur following being converted into meprobamate.Carisoprodol was approved for medical use in the United States in 1959. Its approval in Europe was withdrawn in 2008. It is available as a generic medication. In 2017, it was the 255th most commonly prescribed medication in the United States, with more than one million prescriptions. In the United States, it is a Schedule IV controlled substance. Medical uses Carisoprodol is meant to be used along with rest, physical therapy and other measures to relax muscles after strains, sprains and muscle injuries. It comes in tablet format and is taken by the mouth three times a day and before bed. Side effects The usual dose of 350 mg is unlikely to engender prominent side effects other than somnolence, and mild to significant euphoria or dysphoria, but the euphoria is generally short-lived due to the fast metabolism of carisoprodol into meprobamate and other metabolites; the euphoria derived is, according to new research, most likely due to carisoprodols inherent, potent anxiolytic effects that are far stronger than those produced by its primary metabolite, meprobamate, which is often misblamed for the drug-seeking associated with carisoprodol, as carisoprodol itself is responsible for the significantly more intense central nervous system effects than meprobamate alone. Carisoprodol has a qualitatively different set of effects to that of meprobamate (Miltown). The medication is well tolerated and without adverse effects in the majority of patients for whom it is indicated. In some patients, however, and/or early in therapy, carisoprodol can have the full spectrum of sedative side effects and can impair the patients ability to operate a firearm, motor vehicles, and other machinery of various types, especially when taken with medications containing alcohol, in which case an alternative medication would be considered. The intensity of the side effects of carisoprodol tends to lessen as therapy continues, as is the case with many other drugs. Other side effects include: dizziness, clumsiness, headache, fast heart rate, upset stomach, vomiting and skin rash.The interaction of carisoprodol with essentially all opioids, and other centrally acting analgesics, but especially codeine, those of the codeine-derived subgroup of the semisynthetic class (ethylmorphine, dihydrocodeine, hydrocodone, oxycodone, nicocodeine, benzylmorphine, the various acetylated codeine derivatives including acetyldihydrocodeine, dihydroisocodeine, nicodicodeine and others) which allows the use of a smaller dose of the opioid to have a given effect, is useful in general and especially where skeletal muscle injury and/or spasm is a large part of the problem. The potentiation effect is also useful in other pain situations and is also especially useful with opioids of the open-chain class, such as methadone, levomethadone, ketobemidone, phenadoxone and others. In recreational drug users, deaths have resulted from combining doses of hydrocodone and carisoprodol. Another danger of misuse of carisoprodol and opiates is the potential to aspirate while unconscious.Meprobamate and other muscle-relaxing drugs often were subjects of misuse in the 1950s and 60s. Overdose cases were reported as early as 1957, and have been reported on several occasions since then.Carisoprodol is metabolized by the liver and excreted by the kidneys so this drug must be used with caution with patients that have impaired hepatic or renal function. Because of potential for more severe side effects, this drug is on the list to avoid for elderly people. Withdrawal Carisoprodol, meprobamate, and related drugs such as tybamate, have the potential to produce physical dependence of the barbiturate type following periods of prolonged use. Withdrawal of the drug after extensive use may require hospitalization in medically compromised patients. In severe cases the withdrawal can mimic the symptoms of alcohol withdrawal including the potentially lethal status epilepticus. Psychological dependence has also been linked to carisoprodol use although this is much less severe than with meprobamate itself (presumably due to the slower onset of effects). Psychological dependence is more common in those who use carisoprodol non-medically and those who have a history of substance use (particularly sedatives or alcohol). It may reach clinical significance before physiological tolerance and dependence have occurred and (as with benzodiazepines) has been demonstrated to persist to varying degrees of severity for months or years after discontinuation. Discontinuation of carisoprodol, as with all GABA-ergics, can result in cognitive changes which persist for weeks, months, or rarely even years including greatly increased anxiety and depression, social withdrawal, hair-trigger agitation/aggression, chronic insomnia, new or aggravated (often illogical) phobias, reduced IQ, short term and long-term memory loss, and dozens of other sequelae. The effects, severity, and duration appear to be slightly dose-dependent but are mainly determined by the patients pattern of use (taken as prescribed, taken in bulk doses, mixed with other drugs, a combination of the above, etc.), genetic predisposition to substance use, and a history of substance use all increase the patients risk of persistent discontinuation syndrome symptoms. Treatment for physical withdrawal generally involves switching the patient to a long-acting benzodiazepine such as diazepam or clonazepam then slowly titrating them off the replacement drug completely at a rate which is both reasonably comfortable for the patient but rapid enough for the managing physician to consider the rate of progress acceptable (overly rapid dose reduction greatly increases the risk of patient non-compliance such as the use of illicitly obtained alternative sedatives and/or alcohol). Psychotherapy and cognitive behavioral therapy have demonstrated moderate success in reducing the rebound anxiety which results upon carisoprodol discontinuation but only when combined with regular and active attendance to a substance use support group.Carisoprodol withdrawal can be life-threatening (especially in high dose users and those who attempt to quit "cold turkey"). Medical supervision is recommended, with gradual reduction of dose of carisoprodol or a substituted medication, typical of other depressant drugs. Non-medical use Combining a muscle relaxant like carisoprodol with opioids and benzodiazepines is referred to as "The Holy Trinity" as it has been reported to increase the power of the "high".Recreational users of carisoprodol usually seek its potentially heavy sedating, relaxant, and anxiolytic effects. Also, because of its potentiating effects on narcotics, it is often used in conjunction with many opioid drugs. Also it is not detected on standard drug testing screens. On 26 March 2010 the DEA issued a Notice of Hearing on proposed rule making in respect to the placement of carisoprodol in schedule IV of the Controlled Substances Act. The DEA ended up classifying it under schedule IV. Carisoprodol is sometimes mixed with date rape drugs.Many overdoses have resulted from recreational users combining these drugs to combine their individual effects without being aware of the enzyme-induction induced potentiation. Overdose As with other GABAergic drugs, combination with other GABAergic drugs, including alcohol, as well as with sedatives in general, possess a significant risk to the user in the form of overdose. Overdose symptoms are similar to those of other GABAergics including excessive sedation and unresponsiveness to stimuli, severe ataxia, amnesia, confusion, agitation, intoxication and inappropriate (potentially violent) behavior. Severe overdoses may present with respiratory depression (and subsequent pulmonary aspiration), coma, and death.Carisoprodol is not detected on all toxicology tests which may delay diagnosis of overdose. Overdose symptoms in combination with opiates are similar but are distinguished by the presentation of normal or pinpoint pupils, which are generally unresponsive to light. Carisoprodol (as with its metabolite meprobamate) is particularly dangerous in combination with alcohol. Flumazenil (the benzodiazepine antidote) is not effective in the management of carisoprodol overdose as carisoprodol acts at the barbiturate binding site. Treatment mirrors that of barbiturate overdoses and is generally supportive, including the administration of mechanical respiration and pressors as implicated (and in rare cases, bemegride). Total amnesia of the experience is not uncommon following recovery.In 2014 actress Skye McCole Bartusiak died of an overdose due to the combined effects of carisoprodol, hydrocodone and difluoroethane. Pharmacology Pharmacodynamics Carisoprodol, has a chemical structure similar to Glutamate, a neurotransmitter, and dimethylglycine. Upon analysis, this pharmacological agent seems to be an agonist of the NMDA receptor, with an unknown [Km]. Because excess Glutamate causes excitotoxicity and neuronal apoptosis, Carisoprodol overdose may also lead to NMDA related toxicity, thus inducing seizures at high doses, and muscle relaxation upon administration. Carisoprodols structural similarity to Meprobamate indicates GABAergic activity, including GABA A agonism, similar to the mechanism of benzodiazepines. This will allow for further muscle relaxation and anxiety reduction. Therefore, Carisoprodol, at low to moderate dosages, may be clinically indicated for absent seizures, yet exacerbate Tonic-clonic seizures. Pharmacokinetics Carisoprodol has a rapid, 30-minute onset of action, with the aforementioned effects lasting about two to six hours. It is metabolized in the liver via the cytochrome P450 oxidase isozyme CYP2C19, excreted by the kidneys and has about an eight-hour half-life. In patients with low levels of CYP2C19 (poor metabolizers), standard doses can lead to increased concentrations of carisoprodol (up-to a four-fold increase). A considerable proportion of carisoprodol is metabolized to meprobamate, which is a known addictive substance; this could account for the addictive potential of carisoprodol (meprobamate levels reach higher peak plasma levels than carisoprodol itself following administration). As mentioned above, carisoprodol appears to have strong anxiolytic effects on its own; however, a large part of its effects also come from the fact that it is metabolized into meprobamate: at least a 25% of the carisoprodol administered will be transformed into meprobamate which means that meprobamate is 3.25× stronger than carisoprodol (although this rate varies from person to person according to their levels of CYP2C19 enzymes in their livers with some people having considerably higher levels) or, in other words, 200 mg of meprobamate (which is the lowest standard dose) is equivalent to 650 mg of carisoprodol. As such, meprobamate is believed to play a significant role in the effects of carisoprodol and meprobamates long half-life results in bioaccumulation following extended periods of carisoprodol administration. It is slightly soluble in water and freely soluble in ethanol, chloroform and acetone. The drugs solubility is practically independent of pH. History On 1 June 1959, several American pharmacologists convened at Wayne State University in Detroit, Michigan to discuss a newly discovered structural analogue of meprobamate. The substitution of one hydrogen atom with an isopropyl group on one of the carbamyl nitrogens was intended to yield a drug with new pharmacological properties. It had been developed by Frank Berger at Wallace Laboratories and was named carisoprodol.Building on meprobamates pharmacological effects, carisoprodol was intended to have better muscle relaxing properties, less potential for addiction, and a lower risk of overdose. Carisoprodols effect profile did indeed turn out to differ significantly with respect to meprobamate, with carisoprodol possessing stronger muscle relaxant and analgesic effects. Usage and legal status Norway Reports from Norway have shown carisoprodol has addictive potential as a prodrug of meprobamate and/or potentiator of hydrocodone, oxycodone, codeine, and similar drugs. In May 2008 it was taken off the market in Norway. European Union In the EU, the European Medicines Agency issued a release recommending member states suspend marketing authorization for this product in the treatment of acute (not chronic) back pain.As of November 2007, carisoprodol has been taken off the market in Sweden due to problems with dependence and side effects. The agency overseeing pharmaceuticals considered other drugs used with the same indications as carisoprodol to have the same or better effects without the risks of the drug. United States Until 12 December 2011, when the administrator of the Drug Enforcement Administration (DEA) issued the final ruling placing the substance carisoprodol into Schedule IV of the Controlled Substances Act (CSA), carisoprodol was not a controlled substance. The placement of carisoprodol into Schedule IV was effective 11 January 2012.Carisoprodol is available generically as 350 mg and, more recently, 250 mg tablets. Compounded tablets with acetaminophen and codeine are also available. Canada Federally, carisoprodol is a prescription drug (Schedule I, sub-schedule F1). Provincial regulations vary. It is no longer readily available. Indonesia In September 2013, carisoprodol was taken off the market due to problems with diversion, dependence and side effects. In September 2017, one child died and 50 had seizures when PCC, which stands for "Paracetamol Caffeine Carisoprodol" was mixed (probably illicit) into childrens drinks in elementary and junior high schools in Kendari. Notes References Further reading External links "Carisoprodol". Drug Information Portal. U.S. National Library of Medicine.

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

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

Naloxone, sold under the brand names Narcan (4 mg) and Kloxxado (8 mg) among others, is a medication used to reverse the effects of opioids. It is commonly used to counter decreased breathing in opioid overdose. Effects begin within two minutes when given intravenously, and within five minutes when injected into a muscle. The medicine can also be administered by spraying it into a persons nose. Naloxone commonly blocks the effects of opioids for 30 to 90 minutes. Multiple doses may be required, as the duration of action of some opioids is greater than that of naloxone.Administration to opioid-dependent individuals may cause symptoms of opioid withdrawal, including restlessness, agitation, nausea, vomiting, a fast heart rate, and sweating. To prevent this, small doses every few minutes can be given until the desired effect is reached. In those with previous heart disease or taking medications that negatively affect the heart, further heart problems have occurred. It appears to be safe in pregnancy, after having been given to a limited number of women. Naloxone is a non-selective and competitive opioid receptor antagonist. It works by reversing the depression of the central nervous system and respiratory system caused by opioids. Naloxone generally has no effect on those not using opioids, has no abuse potential, and is recommended by the World Health Organization for distribution to anyone likely to encounter a fatal opioid overdose, including emergency personnel and friends and family members of those using opioids. Naloxone was patented in 1961 and approved for opioid overdose in the United States in 1971. It is on the World Health Organizations List of Essential Medicines. Naloxone is available as a generic medication. In April 2021, the U.S. Food and Drug Administration (FDA) approved a higher dose naloxone hydrochloride nasal spray product (Kloxxado) intended to treat opioid overdose from fentanyl and its analogues, which are many times stronger than heroin. Medical uses Opioid overdose Naloxone is useful in treating both acute opioid overdose and respiratory or mental depression due to opioids. Whether it is useful in those in cardiac arrest due to an opioid overdose is unclear.It is included as a part of emergency overdose response kits distributed to heroin and other opioid drug users, and to emergency responders. This has been shown to reduce rates of deaths due to overdose. A prescription for naloxone is recommended if a person is on a high dose of opioid (>100 mg of morphine equivalence/day), is prescribed any dose of opioid accompanied by a benzodiazepine, or is suspected or known to use opioids nonmedically. Prescribing naloxone should be accompanied by standard education that includes preventing, identifying, and responding to an overdose; rescue breathing; and calling emergency services.Distribution of naloxone to individuals likely to encounter people who overdose is part of the harm reduction initiatives that have spread throughout the US and the world. This approach to dealing with substance use disorder is to treat it as a medical problem and focusing efforts on reducing the harm produced directly (e.g., overdose) and indirectly (exposure to infectious disease). Clonidine overdose Naloxone can also be used as an antidote in overdose of clonidine, a medication that lowers blood pressure. Clonidine overdoses are of special relevance for children, in whom even small doses can cause significant harm. However, there is controversy regarding naloxones efficacy in treating the symptoms of clonidine overdose, namely slow heart rate, low blood pressure, and confusion/somnolence. Case reports that used doses of 0.1 mg/kg (maximum of 2 mg/dose) repeated every 1–2 minutes (10 mg total dose) have shown inconsistent benefit. As the doses used throughout the literature vary, it is difficult to form a conclusion regarding the benefit of naloxone in this setting. The mechanism for naloxones proposed benefit in clonidine overdose is unclear, but it has been suggested that endogenous opioid receptors mediate the sympathetic nervous system in the brain and elsewhere in the body. Some poison control centers recommend naloxone in the setting of clonidine overdose, including intravenous bolus doses of up to 10 mg naloxone. Preventing recreational opioid use Naloxone is poorly absorbed when taken by mouth, so it is commonly combined with a number of oral opioid preparations, including buprenorphine and pentazocine, so that when taken by mouth, only the opioid has an effect. However, if the opioid and naloxone combination is injected, the naloxone blocks the effect of the opioid. This combination is used in an effort to prevent non-medical use. Other uses Naloxone can be used to treat opioid induced itchiness and constipation.A 2003 meta-analysis of existing research showed naloxone to improve blood flow in patients with shock, including septic, cardiogenic, hemorrhagic, or spinal shock, but could not determine if this reduced patient deaths.Naloxone has been used experimentally in the treatment of congenital insensitivity to pain with anhidrosis. Special populations Pregnancy and breastfeeding Naloxone is pregnancy category B or C in the United States. Studies in rodents given a daily maximum dose of 10 mg naloxone showed no harmful effects to the fetus, although human studies are lacking and the drug does cross the placenta, which may lead to the precipitation of withdrawal in the fetus. In this setting, further research is needed before safety can be assured, so naloxone should be used during pregnancy only if it is a medical necessity.Whether naloxone is excreted in breast milk is unknown, however, it is not orally bioavailable and therefore is unlikely to affect a breastfeeding infant. Children Naloxone can be used on infants who were exposed to intrauterine opiates administered to mothers during delivery. However, there is insufficient evidence for the use of naloxone to lower cardiorespiratory and neurological depression in these infants. Infants exposed to high concentrations of opiates during pregnancy may have CNS damage in the setting of perinatal asphyxia. Naloxone has been studied to improve outcomes in this population, however the evidence is currently weak.Intravenous, intramuscular, or subcutaneous administration of naloxone can be given to children and neonates to reverse opiate effects. The American Academy of Pediatrics recommends only intravenous administration as the other two forms can cause unpredictable absorption. After a dose is given, the child should be monitored for at least 24 hours. For children with low blood pressure due to septic shock, naloxone safety and effectiveness are not established. Geriatric use For patients 65 years and older, it is unclear if there is a difference in response. However, older people often have decreased liver and kidney function that may lead to an increased level of naloxone in their body. Side effects Naloxone has little to no effect if opioids are not present. In people with opioids in their system, it may cause increased sweating, nausea, restlessness, trembling, vomiting, flushing, and headache, and has in rare cases been associated with heart rhythm changes, seizures, and pulmonary edema.Besides the side effects listed above, naloxone also has other adverse events, such as other cardiovascular effects (hypertension, hypotension, tachycardia, ventricular fibrillation, ventricular tachycardia) and central nervous system effects, such as agitation, body pain, brain disease, and coma. In addition to these adverse effects, naloxone is also contraindicated in people with hypersensitivity to naloxone or any of its formulation components.Naloxone has been shown to block the action of pain-lowering endorphins the body produces naturally. These endorphins likely operate on the same opioid receptors that naloxone blocks. It is capable of blocking a placebo pain-lowering response, if the placebo is administered together with a hidden or blind injection of naloxone. Other studies have found that placebo alone can activate the bodys μ-opioid endorphin system, delivering pain relief by the same receptor mechanism as morphine.Naloxone should be used with caution in people with cardiovascular disease as well as those that are currently taking medications that could have adverse effects on the cardiovascular system such as causing low blood pressure, fluid accumulation in the lungs (pulmonary edema), and abnormal heart rhythms. There have been reports of abrupt reversals with opioid antagonists leading to pulmonary edema and ventricular fibrillation. Hypersensitivities Naloxone preparations may contain methylparaben and propylparaben and are inappropriate for use by people with a paraben hypersensitivity. If a person is sensitive to nalmefene or naltrexone, naloxone should be used with caution as these three medications are structurally similar. Cross-sensitivity among these drugs is unknown. Preservative-free preparations are available for those with paraben hypersensitivities. Pharmacology Pharmacodynamics Naloxone is a lipophilic compound that acts as a non-selective and competitive opioid receptor antagonist. The pharmacologically active isomer of naloxone is (−)-naloxone. Naloxones binding affinity is highest for the μ-opioid receptor (MOR), then the δ-opioid receptor (DOR), and lowest for the κ-opioid receptor (KOR); naloxone has negligible affinity for the nociceptin receptor.If naloxone is administered in the absence of concomitant opioid use, no functional pharmacological activity occurs, except the inability of the body to combat pain naturally. In contrast to direct opiate agonists, which elicit opiate withdrawal symptoms when discontinued in opiate-tolerant people, no evidence indicates the development of tolerance or dependence on naloxone. The mechanism of action is not completely understood, but studies suggest it functions to produce withdrawal symptoms by competing for opioid receptors within the brain (a competitive antagonist, not a direct agonist), thereby preventing the action of both endogenous and xenobiotic opioids on these receptors without directly producing any effects itself.A single administration of naloxone at a relatively high dose of 2 mg by intravenous injection has been found to produce brain MOR blockade of 80% at 5 minutes, 47% at 2 hours, 44% at 4 hours, and 8% at 8 hours. A low dose (2 μg/kg) produced brain MOR blockade of 42% at 5 minutes, 6% at 2 hours, 33% at 4 hours, and 10% at 8 hours. Intranasal administration of naloxone via nasal spray has likewise been found to rapidly occupy brain MORs, with peak occupancy occurring at 20 minutes, peak occupancies of 67% at a dose of 2 mg and 85% with 4 mg, and an estimated half-life of occupancy disappearance of approximately 100 minutes (1.67 hours). Pharmacokinetics When administered parenterally (non-orally or non-rectally, e.g., intravenously or by injection), as is most common, naloxone has a rapid distribution throughout the body. The mean serum half-life has been shown to range from 30 to 81 minutes, shorter than the average half-life of some opiates, necessitating repeat dosing if opioid receptors must be stopped from triggering for an extended period. Naloxone is primarily metabolized by the liver. Its major metabolite is naloxone-3-glucuronide, which is excreted in the urine. For people with liver diseases such as alcoholic liver disease or hepatitis, naloxone usage has not been shown to increase serum liver enzyme levels.Naloxone has low systemic bioavailability when taken by mouth due to hepatic first-pass metabolism, but it does block opioid receptors that are located in the intestine. Chemistry Naloxone, also known as N-allylnoroxymorphone or as 17-allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one, is a synthetic morphinan derivative and was derived from oxymorphone (14-hydroxydihydromorphinone), an opioid analgesic. Oxymorphone, in turn, was derived from morphine, an opioid analgesic and naturally occurring constituent of the opium poppy. Naloxone is a racemic mixture of two enantiomers, (–)-naloxone (levonaloxone) and (+)-naloxone (dextronaloxone), only the former of which is active at opioid receptors. The drug is highly lipophilic, allowing it to rapidly penetrate the brain and to achieve a far greater brain to serum ratio than that of morphine. Opioid antagonists related to naloxone include cyprodime, nalmefene, nalodeine, naloxol, and naltrexone.The chemical half-life of naloxone is such that injection and nasal forms have been marketed with 24-month and 18-month shelf-lives, respectively. A 2018 study noted that the nasal and injection forms presented as chemically stable to 36- and 28-months, respectively, which prompted an as yet incomplete five-year stability study to be initiated. This suggests that expired caches of material in community and healthcare settings may still be efficacious substantially beyond their labeled expiration dates. History Naloxone was patented in 1961 by Mozes J. Lewenstein, Jack Fishman, and the company Sankyo. It was approved for opioid use disorder treatment in the United States in 1971, with opioid overdose prevention kits being distributed by many states to medically untrained people beginning in 1996. From the period of 1996 to 2014, the CDC estimates over 26,000 cases of opioid overdose have been reversed using the kits.Naloxone (Nyxoid) was approved for use in the European Union in September 2017. Society and culture Names Naloxone is the generic name of the medication and its INN, BAN, DCF, DCIT, and JAN, while naloxone hydrochloride is its USAN and BANM.The patent has expired and it is available as a generic medication. Several of the newer formulations use patented dispensers (spray mechanisms or autoinjectors), and patent disputes over generic forms of the nasal spray were litigated between 2016 and 2020, when a judge ruled in favor of Teva, the generic manufacturer. Teva announced entry of the first generic nasal spray formulation in December 2021. Brand names of naloxone include Narcan, Kloxxado, Nalone, Evzio, Prenoxad Injection, Narcanti, Narcotan, and Zimhi, among others. Identification The CAS number of naloxone is 465-65-6; the anhydrous hydrochloride salt has CAS 357-08-4 and the hydrochloride salt with 2 molecules of water, hydrochloride dihydrate, has CAS 51481-60-8 Routes of administration Intravenous In hospital settings, naloxone is commonly injected intravenously, with an onset of 1–2 minutes and a duration of up to 45 minutes. While the onset is achieved fastest through IV than through other routes of administration, it may be difficult to obtain venous access in patients who use IV drugs chronically. This may be an issue under emergency conditions. Intramuscular or subcutaneous Naloxone can also be administered via intramuscular or subcutaneous injection. The onset of naloxone provided through this route is 2 to 5 minutes with a duration of around 30-120min. Naloxone administered intramuscularly are provided through pre-filled syringes, vials, and auto-injector. Evzio is the only auto-injector on the market and can be used both intramuscularly and subcutaneously. It is pocket-sized and can be used in non-medical settings such as in the home. It is designed for use by laypersons, including family members and caregivers of opioid users at-risk for an opioid emergency, such as an overdose. According to the FDAs National Drug Code Directory, a generic version of the auto-injector began to be marketed at the end of 2019. Intranasal Administration of naloxone intranasally is recommended for people who are unconscious or unresponsive. While the onset of action is slightly delayed in this method of administration, the ease of use and portability are what make naloxone nasal sprays useful.Narcan Nasal Spray was approved in 2015 and was the first FDA-approved nasal spray for emergency treatment or suspected overdose. Narcan Nasal Spray is prepackaged, requires no assembly, and delivers a consistent 4 mg dose of naloxone. It was developed in a partnership between LightLake Therapeutics and the National Institute on Drug Abuse. The approval process was fast-tracked. A generic version of the nasal spray was approved in the United States in 2019, though did not come to market until 2021.In 2021, the FDA approved Kloxxado, a 8 mg dose of intranasal naloxone developed by Hikma Pharmaceuticals. Citing the frequent need for multiple 4 mg doses of Narcan to successfully reverse overdose, packs of Kloxxado Nasal Spray contain two pre-packaged nasal spray devices, each containing 8 mg of naloxone. However, a wedge device (nasal atomizer) can also be attached to a syringe that may also be used to create a mist to deliver the drug to the nasal mucosa. This is useful near facilities where many overdoses occur that already stock injectors. Storage Naloxone should be stored at room temperature and protected from light. For the auto-injector, naloxone should be stored in the outer case provided. If the product is cloudy, discolored, or contains particulate matter, use is not recommended. Legal status and availability to law enforcement and emergency personnel In the United States, naloxone is ostensibly available without a prescription in every state with the exception of Hawaii. In reality, not all pharmacies stock or dispense naloxone. Depending on the pharmacy, a pharmacist may have to write a prescription or not be able to give naloxone to comply with accounting rules, as naloxone is still considered a prescription-only medication under FDA rules. As of mid-2019, officials in 29 states had issued standing orders to enable licensed pharmacists to provide naloxone to patients without the individual first visiting a prescriber. Prescribers working with harm reduction or low threshold treatment programs have also issued standing orders to enable these organizations to distribute naloxone to their clients. A standing order, also referred to as a "non-patient specific prescription" is written by a physician, nurse or other prescriber to authorize medicine distribution outside the doctor-patient relationship. In the case of naloxone, these orders are meant to facilitate naloxone distribution to people using opioids, family members and friends. Over 200 naloxone distribution programs utilize licensed prescribers to distribute the drug through such orders, or through the authority of pharmacists (as with Californias legal proision, AB1535).Laws and policies in many US jurisdictions have been changed in recent years to allow wider distribution of naloxone. In addition to laws or regulations permitting distribution of medicine to at risk individuals and families, some 36 states have passed laws that provide naloxone prescribers with immunity against both civil and criminal liabilities. While paramedics in the US have carried naloxone for decades, law enforcement officers in many states throughout the country carry naloxone to reverse the effects of heroin overdoses when reaching the location before paramedics. As of July 12, 2015, law enforcement departments in 28 US states are allowed to or required to carry naloxone to quickly respond to opioid overdoses. Programs training fire personnel in opioid overdose response using naloxone have also shown promise in the US, and efforts to integrate opioid fatality prevention into emergency response have grown due to the US overdose crisis.Following the use of the nasal spray device by police officers on Staten Island in New York, an additional 20,000 police officers will begin carrying naloxone in mid-2014. The states Office of the Attorney General will provide US$1.2 million to supply nearly 20,000 kits. Police Commissioner William Bratton said: "Naloxone gives individuals a second chance to get help". Emergency Medical Service Providers (EMS) routinely administer naloxone, except where basic Emergency Medical Technicians are prohibited by policy or by state law. In efforts to encourage citizens to seek help for possible opioid overdoses, many states have adopted Good Samaritan laws that provide immunity against certain criminal liabilities for anybody who, in good faith, seeks emergency medical care for either themselves or someone around them who may be experiencing an opioid overdose.States including Vermont and Virginia have developed programs that mandate the prescription of naloxone when a prescription has exceeded a certain level of morphine milliequivalents per day as preventative measures against overdose. Healthcare institution-based naloxone prescription programs have also helped reduce rates of opioid overdose in North Carolina, and have been replicated in the US military.In Canada, naloxone single-use syringe kits are distributed and available at various clinics and emergency rooms. Alberta Health Services is increasing the distribution points for naloxone kits at all emergency rooms, and various pharmacies and clinics province-wide. All Edmonton Police Service and Calgary Police Service patrol cars carry an emergency single-use naloxone syringe kit. Some Royal Canadian Mounted Police patrol vehicles also carry the drug, occasionally in excess to help distribute naloxone among users and concerned family/friends. Nurses, paramedics, medical technicians, and emergency medical responders can also prescribe and distribute the drug. As of February 2016, pharmacies across Alberta and some other Canadian jurisdictions are allowed to distribute single-use take-home naloxone kits or prescribe the drug to people using opioids.Following Alberta Health Services, Health Canada reviewed the prescription-only status of naloxone, resulting in plans to remove it in 2016, making naloxone more accessible. Due to the rising number of drug deaths across the country, Health Canada proposed a change to make naloxone more widely available to Canadians in support of efforts to address the growing number of opioid overdoses. In March 2016, Health Canada did change the prescription status of naloxone, as "pharmacies are now able to proactively give out naloxone to those who might experience or witness an opioid overdose." Community access Schools, government agencies, and nonprofit organizations hold training programs to educate laypeople on the proper use of naloxone and to send them home with medicine. It is estimated that programs like these have helped to reverse more than 26,000 overdoses in the US. Harm reduction organizations providing needle and syringes to those injecting drugs have been particularly involved in naloxone distribution, purchasing medicine at discounted rates through a Buyers Club and distributing more than 3 million vials to those at high risk or likely to be with those at high risk between 2017 and 2020 alone. In a survey of US laypersons in December 2021, most people believed the scientifically-supported idea that trained bystanders can reverse overdoses with naloxone.A survey of US naloxone prescription programs in 2010 revealed that 21 out of 48 programs reported challenges in obtaining naloxone in the months leading up to the survey, due mainly to either cost increases that outstripped allocated funding or the suppliers inability to fill orders. The approximate cost of a 1 ml ampoule of naloxone in the US is estimated to be significantly higher than in most other countries.Take-home naloxone programs for people who use opioids is under way in many North American cities. CDC estimates that the US programs for drug users and their caregivers prescribing take-home doses of naloxone and training on its use prevented 10,000 opioid overdose deaths by 2014.In Australia, as of February 1, 2016, some forms of naloxone are available "over the counter" in pharmacies without a prescription. It comes in single-use filled syringe similar to law enforcement kits. A single dose costs AU$20; for those with a prescription, five doses can bought for AU$40, amounting to a rate of eight dollars per dose (2019).In Alberta, in addition to pharmacy distribution, take-home naloxone kits are available and commonly distributed in most drug treatment or rehabilitation centres.In Europe, take home naloxone pilots were launched in the Channel Islands and in Berlin in the late 1990s. In 2008 the Welsh Assembly government announced its intention to establish demonstration sites for take-home naloxone, and in 2010 Scotland instituted a national naloxone program. Inspired by North American and European efforts, non-governmental organizations running programs to train drug users as overdose responders and supply them with naloxone are now operational in Russia, Ukraine, Georgia, Kazakhstan, Tajikistan, Afghanistan, China, Vietnam, and Thailand. Noting the high risk of overdose among people with HIV who inject drugs, international HIV donors including the Presidents Emergency Plan for AIDS Relief, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and the Open Society Foundations, have supported the purchase and distribution of naloxone to those at risk in low- and middle income countries.In 2017, Next Harm Reduction in New York State began distributing naloxone and other harm reduction supplies by mail to those in the US unable to get them locally.In 2018, a maker of naloxone announced it would provide a free kit including two doses of the nasal spray, as well as educational materials, to each of the 16,568 public libraries and 2,700 YMCAs in the U.S. Media The 2013 documentary film Reach for Me: Fighting to End the American Drug Overdose Epidemic interviews people involved in naloxone programs aiming to make naloxone available to opioid users and people with chronic pain. Criticism Some political commentators, law enforcement workers, and addiction specialists have argued naloxone enables opioid addiction and worsens the crisis. Some police officers report reviving the same addict multiple times and that the availability of naloxone have allowed some addicts to push their use over the edge. Conservative radio host Lars Larson noted that naloxone only works for an hour, and if a person does not receive stabilizing medical help in that time, the addict just overdoses again. Other critics have noted Narcan nasal sprays American manufacturer views colleges, schools, libraries, and community centers as "untapped markets" and a "growth opportunity." Narcans manufacturer also charges $150 for the nasal spray and aggressively sues competitors looking to market a cheaper unauthorized generic version of the drug. The public relations effort to raise awareness of naloxone and promote policies such as bulk purchases by police departments obviously increases sales. See also Buprenorphine/naloxone Oxycodone/naloxone Naloxazone, the hydrazone analog References Further reading Naloxone, Flumazenil and Dantrolene as Antidotes. IPCS/CEC Evaluation of Antidotes Series. Vol. 1. Cambridge University Press. 1993. ISBN 0-521-45459-X. EUR 14797 EN. External links "Naloxone". Drug Information Portal. U.S. National Library of Medicine. "Naloxone hydrochloride". Drug Information Portal. U.S. National Library of Medicine. "Naloxone Nasal Spray". MedlinePlus. "Naloxone". Substance Abuse and Mental Health Services Administration (SAMHSA). "FDA recommends health care professionals discuss naloxone with all patients when prescribing opioid pain relievers or medicines to treat opioid use disorder". U.S. Food and Drug Administration (FDA). 23 July 2020.</ref>

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

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

Promethazine is a first-generation antihistamine and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people who are agitated or anxious. Promethazine is available by mouth in syrup or tablet dosage forms, as a rectal suppository, or by injection into a muscle.Common side effects of promethazine include confusion and sleepiness; consumption of alcohol or other sedatives can make these symptoms worse. It is unclear if use of promethazine during pregnancy or breastfeeding is safe for the baby. Use of promethazine is not recommended in those less than two years old, due to potentially negative effects on breathing. Use of promethazine by injection into a vein is not recommended, due to potential skin damage. Promethazine is in the phenothiazine family of medications.Promethazine was made in the 1940s by a team of scientists from Rhône-Poulenc laboratories. It was approved for medical use in the United States in 1951. It is a generic medication and is available under many brand names globally. In 2019, it was the 174th most commonly prescribed medication in the United States, with more than 3 million prescriptions. Medical uses Promethazine has a variety of medical uses, including: Sedation For nausea and vomiting associated with anesthesia or chemotherapy. It is commonly used postoperatively as an antiemetic. The antiemetic activity increases with increased dosing; however, side effects also increase, which often limits maximal dosing. For moderate to severe morning sickness and hyperemesis gravidarum: In the UK, promethazine is drug of first choice, being preferred as an older drug with which there is a greater experience of use in pregnancy (second in line being metoclopramide or prochlorperazine). For allergies such as hay fever and together with other medications in anaphylaxis To aid with symptoms of the common cold Motion sickness, including space sickness Hemolytic disease of the newborn Anxiety before surgery Side effects Some documented side effects include: Tardive dyskinesia, pseudoparkinsonism, acute dystonia (effects due to dopamine D2 receptor antagonism) Confusion in the elderly Drowsiness, dizziness, fatigue, more rarely vertigo Known to have effects on serotonin and dopamine receptors. Dry mouth Nausea Respiratory depression in patients under age of two and in those with severely compromised pulmonary function Blurred vision, xerostomia, dry nasal passages, dilated pupils, constipation, and urinary retention. (due to cholinergic effects) Chest discomfort/pressure (In children less than 2 years old) AkathisiaLess frequent: Cardiovascular side effects to include arrhythmias and hypotension Neuroleptic malignant syndrome Liver damage and cholestatic jaundice Bone marrow suppression, potentially resulting in agranulocytosis, thrombocytopenia, and leukopenia Depression of the thermoregulatory mechanism resulting in hypothermia/hyperthermiaRare side effects include: SeizuresBecause of potential for more severe side effects, this drug is on the list to avoid in the elderly. In many countries (including the US and UK), promethazine is contraindicated in children less than two years of age, and strongly cautioned against in children between two and six, due to problems with respiratory depression and sleep apnea.Promethazine is listed as one of the drugs of highest anticholinergic activity in a study of anticholinergenic burden, including long-term cognitive impairment. Pharmacology Promethazine, a phenothiazine derivative, is structurally different from the neuroleptic phenothiazines, with similar but different effects. It acts primarily as a strong antagonist of the H1 receptor (antihistamine) and a moderate mACh receptor antagonist (anticholinergic), and also has weak to moderate affinity for the 5-HT2A, 5-HT2C, D2, and α1-adrenergic receptors, where it acts as an antagonist at all sites, as well. New studies have shown that promethazine acts as a strong non-competitive selective NMDA receptor antagonist; which might promote sedation in addition with the strong antihistaminergic effects of the H1 receptor, but also as a weaker analgesic. It does not however affect the AMPA receptors.Another notable use of promethazine is as a local anesthetic, by blockage of sodium channels. Chemistry Solid promethazine hydrochloride is a white to faint-yellow, practically odorless, crystalline powder. Slow oxidation may occur upon prolonged exposure to air, usually causing blue discoloration. Its hydrochloride salt is freely soluble in water and somewhat soluble in alcohol. Promethazine is a chiral compound, occurring as a mixture of enantiomers. History Promethazine was first synthesized by a group at Rhone-Poulenc (which later became part of Sanofi) led by Paul Charpentier in the early 1940s. The team was seeking to improve on diphenhydramine; the same line on medical chemistry led to the creation of chlorpromazine. Society and culture As of July 2017 it was marketed under many brand names worldwide: Allersoothe, Antiallersin, Anvomin, Atosil, Avomine, Closin N, Codopalm, Diphergan, Farganesse, Fenazil, Fenergan, Fenezal, Frinova, Hiberna, Histabil, Histaloc, Histantil, Histazin, Histazine, Histerzin, Lenazine, Lergigan, Nufapreg, Otosil, Pamergan, Pharmaniaga, Phenadoz, Phenerex, Phenergan, Phénergan, Pipolphen, Polfergan, Proazamine, Progene, Prohist, Promet, Prometal, Prometazin, Prometazina, Promethazin, Prométhazine, Promethazinum, Promethegan, Promezin, Proneurin, Prothazin, Prothiazine, Prozin, Pyrethia, Quitazine, Reactifargan, Receptozine, Romergan, Sominex, Sylomet, Xepagan, Zinmet, and Zoralix. It is also marketed in many combination drug formulations: with carbocisteine as Actithiol Antihistaminico, Mucoease, Mucoprom, Mucotal Prometazine, and Rhinathiol; with paracetamol (acetaminophen) as Algotropyl, Calmkid, Fevril, Phen Plus, and Velpro-P; with paracetamol and dextromethorphan as Choligrip na noc, Coldrex Nočná Liečba, Fedril Night Cold and Flu, Night Nurse, and Tachinotte; with paracetamol, phenylephrine, and salicylamide as Flukit; with dextromethorphan as Axcel Dextrozine and Hosedyl DM; with dextromethorphan and ephedrine as Methorsedyl; with dextromethorphan and pseudoephedrine as Sedilix-DM; with dextromethorphan and phenylephedrine as Sedilix-RX; with pholcodine as Codo-Q Junior and Tixylix; with pholcodine and ephedrine as Phensedyl Dry Cough Linctus; with pholcodine and phenylephedrine as Russedyl Compound Linctus; with pholcodine and phenylpropanolamine as Triple P; with codeine as Kefei and Procodin; with codeine and ephedrine as Dhasedyl, Fendyl, and P.E.C.; with ephedrine and dextromethorphan as Dhasedyl DM; with glutamic acid as Psico-Soma, and Psicosoma; with noscapine as Tussisedal; and with chlorpromazine and phenobarbital as Vegetamin. Recreational use The recreational drug lean, also known as purple drank among other names, often contains a combination of promethazine with codeine-containing cold medication. Product liability lawsuit In 2009, the US Supreme Court ruled on a product liability case involving promethazine. Diana Levine, a woman with a migraine, was administered Wyeths Phenergan via IV push. The drug was injected improperly, resulting in gangrene and subsequent amputation of her right forearm below the elbow. A state jury awarded her $6 million in punitive damages. The case was appealed to the Supreme Court on grounds of federal preemption and substantive due process. The Supreme Court upheld the lower courts rulings, stating that "Wyeth could have unilaterally added a stronger warning about IV-push administration" without acting in opposition to federal law. In effect, this means drug manufacturers can be held liable for injuries if warnings of potential adverse effects, approved by the US Food and Drug Administration (FDA), are deemed insufficient by state courts. On September 9, 2009, the FDA required a boxed warning be put on promethazine for injection, stating the contraindication for subcutaneous administration. The preferred administrative route is intramuscular, which reduces risk of surrounding muscle and tissue damage. References External links "Promethazine". U.S. National Library of Medicine and National Institutes of Health.

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

What does the medical term 'Infantile systemic hyalinosis' encompass?

Infantile systemic hyalinosis is an allelic autosomal-recessive condition characterized by multiple skin nodules, hyaline deposition, gingival hypertrophy, osteolytic bone lesions and joint contractures.: 606 Genetics This disease is caused by mutations in the CMG2 gene (ANTXR2). Diagnosis Management See also Skin lesion List of cutaneous conditions References External links GeneReview/NIH/UW entry on Hyalinosis, Inherited Systemic

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

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

Neonatal sepsis is a type of neonatal infection and specifically refers to the presence in a newborn baby of a bacterial blood stream infection (BSI) (such as meningitis, pneumonia, pyelonephritis, or gastroenteritis) in the setting of fever. Older textbooks may refer to neonatal sepsis as "sepsis neonatorum". Criteria with regards to hemodynamic compromise or respiratory failure are not useful clinically because these symptoms often do not arise in neonates until death is imminent and unpreventable. Neonatal sepsis is divided into two categories: early-onset sepsis (EOS) and late-onset sepsis (LOS). EOS refers to sepsis presenting in the first 7 days of life (although some refer to EOS as within the first 72 hours of life), with LOS referring to presentation of sepsis after 7 days (or 72 hours, depending on the system used). Neonatal sepsis is the single most common cause of neonatal death in hospital as well as community in developing country. It is difficult to clinically exclude sepsis in newborns less than 90 days old that have fever (defined as a temperature > 38 °C (100.4 °F). Except in the case of obvious acute viral bronchiolitis, the current practice in newborns less than 30 days old is to perform a complete workup including complete blood count with differential, blood culture, urinalysis, urine culture, and cerebrospinal fluid (CSF) studies and CSF culture, admit the newborn to the hospital, and treat empirically for serious bacterial infection for at least 48 hours until cultures are demonstrated to show no growth. Attempts have been made to see whether it is possible to risk stratify newborns in order to decide if a newborn can be safely monitored at home without treatment despite having a fever. One such attempt is the Rochester criteria. Signs and symptoms The signs of sepsis are non-specific and include: Body temperature changes Breathing problems Diarrhea Low blood sugar (hypoglycemia) Reduced movements Reduced sucking Seizures Bradycardia Swollen belly area Vomiting Yellow skin and whites of the eyes (jaundice). hemorrhagic rashA heart rate above 160 can also be an indicator of sepsis, this tachycardia can present up to 24 hours before the onset of other signs. Risk factors A study performed at Strong Memorial Hospital in Rochester, New York, showed that infants ≤ 60 days old meeting the following criteria were at low-risk for having a serious bacterial illness: generally well-appearing previously healthy full term (at ≥37 weeks gestation) no antibiotics perinatally no unexplained hyperbilirubinemia that required treatment no antibiotics since discharge no hospitalizations no chronic illness discharged at the same time or before the mother no evidence of skin, soft tissue, bone, joint, or ear infection White blood cells (WBCs) count 5,000-15,000/mm3 absolute band count ≤ 1,500/mm3 urine WBC count ≤ 10 per high power field (hpf) stool WBC count ≤ 5 per high power field (hpf) only in infants with diarrheaThose meeting these criteria likely do not require a lumbar puncture, and are felt to be safe for discharge home without antibiotic treatment, or with a single dose of intramuscular antibiotics, but will still require close outpatient follow-up. One risk for Group B streptococcal infection (GBS) is preterm rupture of membranes. Screening women for GBS (via vaginal and rectal swabbing) and treating culture positive women with intrapartum chemoprophylaxis is reducing the number of neonatal sepsis caused by GBS. Abnormal heart rate characteristics (HRC) of transient decelerations and reduced baseline variability in heart rate are a risk factor for impending neonatal sepsis. Diagnosis Neonatal sepsis screening: DLC (differential leukocyte count) showing increased numbers of polymorphs. DLC: band cells > 20%. increased haptoglobins. micro ESR (erythrocyte sedimentation rate) titer > 15mm. gastric aspirate showing > 5 polymorphs per high power field. newborn CSF (cerebrospinal fluid) screen: showing increased cells and proteins. suggestive history of chorioamnionitis, PROM (premature rupture of membranes), etc...Culturing for microorganisms from a sample of CSF, blood or urine, is the gold standard test for definitive diagnosis of neonatal sepsis. This can give false negatives due to the low sensitivity of culture methods and because of concomitant antibiotic therapy. Lumbar punctures should be done when possible as 10-15% presenting with sepsis also have meningitis, which warrants an antibiotic with a high CSF penetration.CRP is not very accurate in picking up cases. Treatment Note that, in neonates, sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until hemodynamic and respiratory collapse is imminent, so, if there is even a remote suspicion of sepsis, they are frequently treated with antibiotics empirically until cultures are sufficiently proven to be negative. In addition to fluid resuscitation and supportive care, a common antibiotic regimen in infants with suspected sepsis is a beta-lactam antibiotic (usually ampicillin) in combination with an aminoglycoside (usually gentamicin) or a third-generation cephalosporin (usually cefotaxime—ceftriaxone is generally avoided in neonates due to the theoretical risk of kernicterus.) The organisms which are targeted are species that predominate in the female genitourinary tract and to which neonates are especially vulnerable to, specifically Group B Streptococcus, Escherichia coli, and Listeria monocytogenes (This is the main rationale for using ampicillin versus other beta-lactams.) Of course, neonates are also vulnerable to other common pathogens that can cause meningitis and bacteremia such as Streptococcus pneumoniae and Neisseria meningitidis. Although uncommon, if anaerobic species are suspected (such as in cases where necrotizing enterocolitis or intestinal perforation is a concern, clindamycin is often added.Granulocyte-macrophage colony stimulating factor (GM-CSF) is sometimes used in neonatal sepsis. However, a 2009 study found that GM-CSF corrects neutropenia if present but it has no effect on reducing sepsis or improving surviva. Antibiotic Overtreatment In cases of suspected Early Onset Sepsis (EOS) one of the treatments is empirical antibiotics. The strategy of clinicians utilizing antibiotics as a course of treatment for EOS has resulted in the overtreatment of antibiotics to infants suspected of having signs of EOS. There are several consequences to the overtreatment of antibiotics in newborns including "microbiome alterations, which are linked to the development of asthma, food allergies, and childhood obesity". Another risk in the early introduction of antibiotics in infants is the increase in the development of antibiotic-resistant strains of infectious disease. Current methods of treatment for EOS are often implemented before a positive sepsis blood culture is found. In the last two decades (2000-2020), the use of intrapartum antibiotics has reduced the incidence of EOS. The current challenge faced by clinicians is mainly weighing the risk and benefits of the possibility of antibiotic overtreatment vs. the effects of sepsis. Epidemiology Since the 1990s early-onset sepsis has declined because of screening of group B streptococcus. The cause of early-onset neonatal sepsis are pathogens that contaminate the placenta, vaginal canal, cervix, or amniotic fluid, and these pathogens can affect the baby either in the womb or during labor. Early-onset neonatal sepsis is found to be 0.77 to 1 per 100,000 live births in the U.S. In premature babies, the incidence and mortality rates are higher due to the weakness of their immune system. For infants with low birth weight, cases of early-onset sepsis is found to be about 26 per 1,000 and 8 per 1,000 live births. Certain populations of babies are at more risk as well. Mothers who have poor healthcare, low socioeconomic status, substance abuse, or are African American have higher rates of neonatal sepsis. In fact, African American preterm babies have the highest rate of infection and mortality. 5.14 of every 1,000 live births and 24.4% case fatality ratio, respectively. The mother is not the only one who can contract the bacteria that contributes to sepsis. The child can contribute to the onset of sepsis through multiple factors. Mothers contribute to the risk through a variety of ways like diets during pregnancy and potential intake of foods that are contaminated, through invasive procedures like amniocentesis and cervical cerclage, or contamination of bacteria in the vaginal canal. Infants can contribute to early-onset sepsis through prematurity, congenital anomalies, complicated birth or instrument assisted birth, and low APGAR scores. Testing for neonatal sepsis is done because of how little it physically presents itself in babies. Infants showing no signs of neonatal sepsis will have a sepsis workup done only if concerning factors are shown. Only a small percentage of infants will have a sepsis workup done. Of this small population only 3% to 8% will show positive cultures. Research Trials of probiotics for prevention of neonatal sepsis have generally been too small and statistically underpowered to detect any benefit, but a randomized controlled trial that enrolled 4,556 neonates in India reported that probiotics significantly reduced the risk of developing sepsis. The probiotic used in the trial was Lactobacillus plantarum. A very large meta-analysis investigated the effect of probiotics on preventing late-onset sepsis (LOS) in neonates. Probiotics were found to reduce the risk of LOS, but only in babies who were fed human milk exclusively. It is difficult to distinguish if the prevention was a result of the probiotic supplementation or if it was a result of the properties of human milk. It is also still unclear if probiotic administration reduces LOS risk in extremely low birth weight infants due to the limited number of studies that investigated it. Out of the 37 studies included in this systematic review, none indicated any safety problems related to the probiotics. It would be beneficial to clarify the relationship between probiotic supplementation and human milk for future studies in order to prevent late onset sepsis in neonates.In a randomized controlled trial of 3,003 very low birth weight (VLBW) infants, Heart Rate Characteristics (HRC) monitoring reduced all-cause mortality by 22%, mortality after infection by 40%, reduced length of stay in the NICU after controlling for improved survival, and reduced mortality as well as mortality-or-severe-cerebral-palsy at 18–22 months corrected age among the extremely low birth weight (ELBW) patients. Neonatal Early-Onset Sepsis Calculator From 1993 to 2007, doctors at Kaiser Permanente Medical Care Program hospitals, Brigham Womens Hospital, and Beth Israel-Deaconess Medical Center conducted a nested case-control study in an effort to create a better quantitative method for determining risk factors for neonatal early-onset sepsis. The study examined over 600,000 live births of infants born less than or equal to 34 weeks gestation. The study used measures of health available at the time of birth such as highest intrapartum maternal temperature, rupture of membranes, whether or not the mother has group b streptococcus, and if the mother was given any intrapartum antibiotics. Intrapartum prophylaxis is a strategy for "the secondary prevention of early-onset GBS disease in newborns" that could lead to EOS. The Sepsis Risk Calculator (SRS) is meant to be another clinical measure that physicians can use in conjunction with physical examination.An evaluation of the SRS was done in an independent retrospective cohort study by doctors at a University Hospital in Greece. The study aimed to "compare our clinical practice based on risk-factor guidance with that projected through the application of the SRC". The study incorporated 2,084 infants and found that "The adoption of SRC would have significantly reduced antibiotic usage; however, a significant portion of cases with clinical EOS would have been missed". Another study evaluated the impact of Integrating the SRC into the electronic health record in order to "improve compliance and accuracy through automation". The study concluded that the integration of the EOS into the electronic health record system "significantly increased calculator accuracy". References == External links ==

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

What does the medical term 'Telecanthus' encompass?

Telecanthus, or dystopia canthorum, refers to increased distance between the inner corners of the eyelids (medial canthi), while the inter-pupillary distance is normal. This is in contrast to hypertelorism, in which the distance between the whole eyes is increased. Telecanthus and hypertelorism are each associated with multiple congenital disorders. The distance between the inner corners of the eyelids is called the intercanthal distance. In most people, the intercanthal distance is equal to the width of each eye (the distance between the inner and outer corners of each eye). The average interpupillary distance is 60–62 millimeters (mm), which corresponds to an intercanthal distance of approximately 30–31 mm.Traumatic telecanthus refers to telecanthus resulting from traumatic injury to the nasal-orbital-ethmoid (NOE) complex. The diagnosis of traumatic telecanthus requires a measurement in excess of those normative values. The pathology can be either unilateral or bilateral, with the former more difficult to measure. Systemic associations Telecanthus is often associated with many congenital disorders. Congenital disorders such as Down syndrome, fetal alcohol syndrome, cri du chat syndrome, Klinefelter syndrome, Turner syndrome, Ehlers–Danlos syndrome, Waardenburg syndrome often present with prominent epicanthal folds, and if these folds are nasal (as they most commonly are) they will cause telecanthus. Etymology Telecanthus comes from the Greek word τῆλε (tele, "far") and the Latin word canthus, meaning corner of the eyelid. Dystopia canthorum comes from the Greek δυσ- (dus-, “bad”) and τόπος (tópos, “place”) and the Latin word canthorum ("of the canthi"). See also Blepharophimosis, reduced size of the eyelid openings, which can result in telecanthus == References ==

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

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

Albendazole, also known as albendazolum, is a medication used for the treatment of a variety of parasitic worm infestations. It is useful for giardiasis, trichuriasis, filariasis, neurocysticercosis, hydatid disease, pinworm disease, and ascariasis, among other diseases. It is taken orally.Common side effects include nausea, abdominal pains, and headaches. Potentially serious side effects include bone marrow suppression which usually improves on stopping the medication. Liver inflammation has been reported and those with prior liver problems are at greater risk. It is pregnancy category C in the United States and category D in Australia, meaning it may cause harm if taken by pregnant women. Albendazole is a broad-spectrum antihelminthic agent of the benzimidazole type.Albendazole was developed in 1975. It is on the World Health Organizations List of Essential Medicines. Medical uses Albendazole is an effective treatment for: Flatworms Fasciolosis Cestodes (tapeworms), as an alternative to praziquantel or niclosamide for adult beef tapeworms (Taenia saginata) and as an alternative to praziquantel for pork tapeworms (T. solium). It is also given for infections by T. crassiceps. Though praziquantel is often better at treating tapeworm infections, albendazole is used more often in endemic countries due to being cheaper and having a broader spectrum.Cysticercosis (especially neurocysticercosis), which is caused by the larval form of the pork tapeworm (i.e. albendazole is the drug of choice for larval pork tapeworms, but not adult pork tapeworms). Old cysts are not affected. Hydatid disease (aka echinococcosis) of the liver, lung, and peritoneum (caused by the larval form of the dog tapeworm, Echinococcus granulosus) or of the alveoli (caused by E. multilocularis) when surgical excision is not possible. Some suggest that alveolar and cystic echinococcosis require lifelong treatment with albendazole, which only prevents the parasites from growing and reproducing rather than killing them outright. Nematodes Ascariasis, which can be cured with a single dose of albendazole. Baylisascariasis, caused by the raccoon roundworm. If treatment with Albendazole is initiated within 72 hours of ingestion of the egg-containing raccoon feces, good results (95%-100% efficacy, with Albendazole being orally administered for a 10-day period) can be expected. Corticosteroids are sometimes added in cases of eye and CNS infections. Enterobiasis (pinworm infection) Filariasis; since albendazoles disintegration of the microfilarie ("pre-larva") can cause an allergic reaction, antihistamines or corticosteroids are sometimes added to treatment. In cases of lymphatic filariasis (elephantiasis) caused by Wuchereria bancrofti or Brugia malayi, albendazole is sometimes given as an adjunct to ivermectin or diethylcarbamazine in order to suppress microfilaremia. It can also be given for loa loa filariasis as an adjunct or replacement to diethylcarbamazine. Albendazole has an embryotoxic effect on Loa loa adults and thus slowly reduces microfilaremia. Gnathostomiasis when caused by Gnathostoma spinigerum. Albendazole has a similar effectiveness to ivermectin in these cases, though it needs to be given for 21 days rather than the 2 days needed for ivermectin. Gongylonemiasis Hookworm infections, including cutaneous larva migrans caused by hookworms in the genus Ancylostoma. A single dose of albendazole is sufficient to treat intestinal infestations by A. duodenale or Necator americanus Intestinal capillariasis, as an alternative to mebendazole Mansonelliasis when caused by Mansonella perstans. Albendazole works against the adult worms but not against the younger microfilariae. Oesophagostomumiasis, when caused by Oesophagostomum bifurcum Strongyloidiasis, as an alternative to ivermectin or thiabendazole Albendazole can be given with diethylcarbamazine to lower microfilaremia levels. Toxocariasis, also called "visceral larva migrans", when caused by the dog roundworm Toxocara canis or cat roundworm T. catis. Corticosteroids can be added in severe cases, and surgery might be required to repair secondary damage. Trichinosis, when caused by Trichinella spiralis or T. pseudospiralis. Albendazole has a similar efficacy to thiabendazole, but fewer side effects. It works best when given early, acting on the adult worms in the intestine before they generate larva that can penetrate the muscle and cause a more widespread infection. Corticosteroids are sometimes added on to prevent inflammation caused by dying larva. Trichostrongyliasis, as an alternative to pyrantel pamoate. A single dose is sufficient for treatment. Trichuriasis (whipworm infection), sometimes considered as an alternative to mebendazole and sometimes considered to be the drug of choice. Only a single dose of albendazole is needed. It can also be given with ivermectin. Giardiasis, as an alternative or adjunct to metronidazole, especially in children Microsporidiosis, including ocular microsporidiosis caused by Encephalitozoon hellem or E. cuniculi, when combined with topical fumagillin Granulomatous amoebic encephalitis, when caused by the ameba Balamuthia mandrillaris, in combination with miltefosine and fluconazole Arthropods Crusted scabies, when combined with topical crotamiton and salicylic acid Head lice infestation, though ivermectin is much better Intestinal myiasisThough albendazole is effective in treating many diseases, it is only FDA-approved for treating hydatid disease caused by dog tapeworm larvae and neurocysticercosis caused by pork tapeworm larvae. Pregnancy Albendazole is a pregnancy class D drug in Australia and pregnancy class C in the United States. It is contraindicated in the first trimester of pregnancy, and should be avoided up to one month before conception. While studies in pregnant rats and rabbits have shown albendazole to be teratogenic, albendazole has been found to be safe in humans during the second and third trimesters. It can, however, possibly cause infantile eczema when given during pregnancy.In pregnant dogs, albendazole use has led to puppies with reduced weight and with cleft palates. Birds have lower rates of laying eggs and hatching when given albendazole.Albendazole sulfoxide is secreted into breast milk at around 1.5% of the maternal dose, though oral absorption is poor enough that it is unlikely to affect nursing infants. Contraindications Hypersensitivity to the benzimidazole class of compounds contraindicates its use. Side effects The most common side effects by albendazole are experienced by over 10% of people and include headache and abnormal liver function. Elevation of liver enzymes occur in 16% of patients receiving treatment specifically for hydatid disease and goes away when treatment ends. Liver enzymes usually increase to two to four times the normal levels (a mild to moderate increase). An estimated 1–10% of people experience abdominal pain, nausea or vomiting, dizziness or vertigo, increased intracranial pressure, meningeal signs, temporary hair loss, and fever. The headache, nausea, and vomiting are thought to be caused by the sudden destruction of cysticerci (tapeworm larvae), which causes acute inflammation. Fewer than 1% of people get hypersensitivity reactions such as rashes and hives, leukopenias (drop in white blood cell levels) such as agranulocytosis and granulocytopenia, thrombocytopenia (reduced platelet count), pancytopenia (drop in white blood cells, red blood cells, and platelets), hepatitis, acute liver failure, acute kidney injury, irreversible bone marrow suppression, and aplastic anemia.Side effects can be different when treating for hydatid disease versus neurocysticercosis: for example, those being treated for the former are more likely to experience elevated liver enzymes and abdominal pain, while those being treated for the latter are more likely to experience headache. Treating hydatid disease can also unmask undiagnosed neurocysticercosis. People receiving albendazole for the treatment of neurocysticercosis can have neurological side effects such as seizures, increased intracranial pressure, and focal signs caused by the inflammatory reaction that occurs when parasites in the brain are killed. Steroids and anticonvulsants are often given with albendazole when treating neurocysticercosis to avoid these effects. Those being treated for retinal neurocysticercosis can face retinal damage if they are not first checked for ocular cysticeri, since changes to existing lesions in the eye by albendazole can cause permanent blindness. Overdose Because of its low solubility, albendazole often cannot be absorbed in high enough quantities to be toxic. The oral LD50 of albendazole in rats was found to be 2,500 mg/kg. It takes 20 times the normal dose to kill a sheep, and 30 times the normal dose to kill cattle. Overdose affects the liver, testicles, and GI tract the most. It can manifest with lethargy, loss of appetite, vomiting, diarrhea, intestinal cramps, dizziness, convulsions, and sleepiness. There is no specified antidote. Interactions The antiepileptics carbamazepine, phenytoin, and phenobarbital lower the plasma concentration and the half life of albendazole sulfoxides R(+) enantiomer. The antacid cimetidine heightens serum albendazole concentrations, increases the half life of albendazole, and doubles albendazole sulfoxide levels in bile. It was originally thought to work by increasing albendazole bioavailability directly; however, it is now known that cimetidine inhibits the breakdown of albendazole sulfoxide by interfering with CYP3A4. The half-life of albendazole sulfoxide thus increases from 7.4 hours to 19 hours. This might be a helpful interaction on more severe cases, because it boosts the potency of albendazole. Paradoxically, cimetidine also inhibits the absorption of albendazole by reducing gastric acidity.Several other interactions exist. Corticosteroids increase the steady-state plasma concentration of albendazole sulfoxide; dexamethasone, for example, can increase the concentration by 56% by inhibiting the elimination of albendazole sulfoxide. The anti-parasitic praziquantel increases the maximum plasma concentration of albendazole sulfoxide by 50%, and the anti-parasitic levamisole increases the AUC (total drug exposure) by 75%. Grapefruit inhibits the metabolism of albendazole within the intestinal mucosa. Finally, long-term administration of the antiretroviral ritonavir, which works as a CYP3A4 inhibitor, decreases the maximum concentration of albendazole in the plasma as well as the AUC. Pharmacology Mechanism of action As a vermicide, albendazole causes degenerative alterations in the intestinal cells of the worm by binding to the colchicine-sensitive site of β-tubulin, thus inhibiting its polymerization or assembly into microtubules (it binds much better to the β-tubulin of parasites than that of mammals). Albendazole leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. Albendazole also prevents the formation of spindle fibers needed for cell division, which in turn blocks egg production and development; existing eggs are prevented from hatching. Cell motility, maintenance of cell shape, and intracellular transport are also disrupted. At higher concentrations, it disrupts the helminths metabolic pathways by inhibiting metabolic enzymes such as malate dehydrogenase and fumarate reductase, with inhibition of the latter leading to less energy produced by the Krebs cycle. Due to diminished ATP production, the parasite is immobilized and eventually dies. Some parasites have evolved some resistance to albendazole by having a different set of acids constituting β-tubulin, decreasing the binding affinity of albendazole. Some are not vulnerable to albendazole itself but instead live in symbiosis with Wolbachia. Wolbachia are necessary to the parasitic worms moulting and population reduction by albendazole prevents this and kills the adults. Pharmacokinetics Oral absorption of albendazole varies among species, with 1–5% of the drug being successfully absorbed in humans, 20–30% in rats, and 50% in cattle.The absorption also largely depends on gastric pH. People have varying gastric pHs on empty stomachs, and thus absorption from one person to another can vary wildly when taken without food. Generally, the absorption in the GI tract is poor due to albendazoles low solubility in water. It is, however, better absorbed than other benzimidazole carbamates. Food stimulates gastric acid secretion, lowering the pH and making albendazole more soluble and thus more easily absorbed. Oral absorption is especially increased with a fatty meal, as albendazole dissolves better in lipids, allowing it to cross the lipid barrier created by the mucus surface of the GI tract. To target intestinal parasites, albendazole is taken on an empty stomach to stay within the gut.Absorption is also affected by how much of the albendazole is degraded within the small intestine by metabolic enzymes in the villi. The pharmacokinetics of albendazole differ slightly between men and women: women have a lower oral clearance and volume of distribution, while men have a lower serum peak concentration.Albendazole undergoes very fast 1st-pass metabolism in all species, such that the unchanged drug is undetectable in plasma. Most of it is oxidized into albendazole sulfoxide (also known as ricobendazole and albendazole oxide) in the liver by cytochrome P450 oxidases (CYPs) and a flavin-containing monooxygenase (FMO), which was discovered later. In humans, the cytochrome P450 oxidases are thought to include CYP3A4 and CYP1A1, while those in the rats are thought to be CYP2C6 and CYP2A1.Oxidation to albendazole sulfoxide by FMO produces R(+) enantiomers, while oxidation the cytochromes and by some enzymes in the gut epithelium produce S(-). Different species produce the R(+) and S(-) enantiomers in different quantities; humans, dogs, and most other species produce the R(+) enantiomer more (with the human AUC ratio being 80:20). Compared to the S(-) enantiomer, the R(+) has greater pharmacological activity, lasts longer in the bloodstream, is found in higher concentrations in the infected host tissues, and is found in higher concentrations within the parasites themselves. Some albendazole is also converted to hydroxyalbendazole, mainly by CYP2J2.For systemic parasites, albendazole acts as a prodrug, while albendazole sulfoxide reaches systemic circulation and acts as the real antihelminthic. Albendazole sulfoxide is able to cross the blood-brain barrier and enter the cerebrospinal fluid at 43% of plasma concentrations; its ability to enter the central nervous system allows it to treat neurocystocercosis.Albendazole sulfoxide is converted to the inactive albendazole sulfone by cytochrome P450 oxidases, thought to include CYP3A4 or CYP2C. Other inactive metabolites include: 2-aminosulfone, ω-hydroxysulfone, and β-hydroxysulfone. The major final metabolites that are excreted by humans are: methyl [5-(propylsulfonyl-1H-benzimidazol-2-yl)] carbamate, methyl [6-hydroxy 5-(n-propylsulfonyl)-1H-benzimidazole-2-yl)] carbamate, methyl [5-(n-propylsulfinyl)-1H-benzimidazole-2-yl)] carbamate, 5-(n-propylsulfonyl)-1H-benzimidazole-2-yl amine, and 5-(n-propysulfinyl)-1H-benzimidazole-2-yl amine.There are also some minor hydroxylated sulfated or glucuronidated derivatives. No unchanged albendazole is excreted, as it is metabolized too quickly.In humans, the metabolites are excreted mostly in bile, with only a small amount being excreted in the urine (less than 1%) and feces. In ruminants, 60–70% of the metabolites are excreted in the urine.Like all benzimidazoles, albendazole has no residual effect, and thus protects poorly against reinfestations. History Albendazole, patented in 1975, was invented by Robert J. Gyurik and Vassilios J. Theodorides and assigned to SmithKline Corporation. It was introduced in 1977 as an antihelminthic for sheep in Australia, and was registered for human use in 1982. Society and culture Brand names Brand names include: Albenza, Alworm, Andazol, Eskazole, Noworm, Zentel, Alben-G, ABZ, Cidazole, Wormnil etc. Cost In Raleigh, North Carolina, the brand-name prescription cost was around US$800, and US$540 for the generic. The pharmaceutical company Amedra increased the price after purchasing the rights to the drug, instead of lowering it as generics are predicted to do, drawing criticism from patients rights advocates.In 2013, GlaxoSmithKline donated 763 million albendazole tablets for the treatment and prevention of parasitic infections in developing countries, bringing the total to over 4 billion tablets donated since 1998. Veterinary use Albendazole is mainly used in cattle and sheep, but has found some use in cats and dogs as well; it is also used in ratite birds for flagellate parasites and tapeworms. It is also used off-label to treat endoparasites in goats and pigs. Albendazole has been used as an anthelminthic and for control of flukes in a variety of animal species, including cattle, sheep, goats, swine, camels, dogs, cats, elephants, poultry, and others. Side effects include anorexia in dogs and lethargy, depression, and anorexia in cats, with more than 10% of dogs and cats having anorexia. Of dogs and cats, 1–10% experience elevated liver enzymes, nausea, vomiting, and diarrhea. Less than 1% experience neutropenia or aplastic anemia, though these require a use of at least 5 days. While it is also associated with bone marrow suppression and toxicity in cats and dogs at high doses, albendazole has a higher margin of safety in other species. Thus, it is usually only prescribed in cats and dogs when an infection is present that is resistant to the commonly prescribed metronidazole and fenbendazole.It is extensively used for ruminant livestock in Latin America. It is marketed for this purpose by Zoetis (formerly Pfizer Animal Health) in numerous countries (including the United States and Canada) as Valbazen in oral suspension and paste formulations; by Interchemie in the Netherlands and elsewhere as Albenol-100; by Channelle Animal Health Ltd. in the United Kingdom as Albex; and by Ravensdown in New Zealand (as Albendazole). Although most formulations are administered orally, Ricomax (ricobendazole, or albendazole sulfoxide) is administered by subcutaneous injection.Albendazole has greater bioavailability in ruminants: some albendazole sulfoxide, when released back into the rumen, is reduced to albendazole by the resident microbiota, with a preference of the (+) enantiomer being the substrate. Cats and dogs, having no rumen reservoir, sometimes need higher or more frequent doses as compared to ruminants. In dogs, albendazole sulfoxide is detectable in the plasma for less than 12 hours, but in sheep and goats, it remains at measurable levels for around three days. Meat The limitations in early pregnancy are due to a limited period during which teratogenic effects may occur. Summarized research data relating to the durations of these preslaughter and early pregnancy periods when albendazole should not be administered are found in US FDA NADA 110-048 (cattle) and 140-934 (sheep). Some data and inferences regarding goats are found in US FDA Supplemental NADA 110-048 (approved January 24, 2008). Maximum residue limits (MRLs) for albendazole in food, adopted by the FAO/WHO Codex Alimentarius in 1993, are 5000, 5000, 100, and 100 micrograms per kilogram of body weight (μg/kg) for kidney, liver, fat, and muscle, respectively, and 100 μg/L for milk. For analysis purposes, MRLs of various nations may pertain to concentration of a marker substance which has been correlated with concentrations of the administered substance and its metabolized products. For example, in Canada, the marker substance specified by Health Canada is albendazole-2-aminosulfone, for which the MRL in liver of cattle is 200 μg/kg. There is a 27 days cattle withdrawal time for meat. Research Albendazole and related compounds or metabolites like albendazole sulfone (ALB-SO2) exhibit antibacterial effects via an unknown, possibly FtsZ-related, mechanism. It inhibits division of Wolbachia and Mycobacterium tuberculosis, turning them into a long "filament" shape as they grow and fail to divide. Since Brugia malayi relies on symbiotic Wolbachia, this would mean that albendazole is targeting both the worm and its essential symbioant. See also Mebendazole Eradication of infectious disease Neglected tropical diseases References External links The Carter Center Lymphatic Filariasis Elimination Program MedicineNet article Albenza description at RxList "Albendazole". Drug Information Portal. U.S. National Library of Medicine.

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

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

Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.Chemically, nitazoxanide is the prototype member of the thiazolides, a class of drugs which are synthetic nitrothiazolyl-salicylamide derivatives with antiparasitic and antiviral activity. Tizoxanide, an active metabolite of nitazoxanide in humans, is also an antiparasitic drug of the thiazolide class.Nitazoxanide tablets were approved as a generic medication in the United States in 2020. Uses Nitazoxanide is an effective first-line treatment for infection by Blastocystis species and is indicated for the treatment of infection by Cryptosporidium parvum or Giardia lamblia in immunocompetent adults and children. It is also an effective treatment option for infections caused by other protozoa and helminths (e.g., Entamoeba histolytica, Hymenolepis nana, Ascaris lumbricoides, and Cyclospora cayetanensis). Chronic hepatitis B Nitazoxanide alone has shown preliminary evidence of efficacy in the treatment of chronic hepatitis B over a one-year course of therapy. Nitazoxanide 500 mg twice daily resulted in a decrease in serum HBV DNA in all of 4 HBeAg-positive patients, with undetectable HBV DNA in 2 of 4 patients, loss of HBeAg in 3 patients, and loss of HBsAg in one patient. Seven of 8 HBeAg-negative patients treated with nitazoxanide 500 mg twice daily had undetectable HBV DNA and 2 had loss of HBsAg. Additionally, nitazoxanide monotherapy in one case and nitazoxanide plus adefovir in another case resulted in undetectable HBV DNA, loss of HBeAg and loss of HBsAg. These preliminary studies showed a higher rate of HBsAg loss than any currently licensed therapy for chronic hepatitis B. The similar mechanism of action of interferon and nitazoxanide suggest that stand-alone nitazoxanide therapy or nitazoxanide in concert with nucleos(t)ide analogs have the potential to increase loss of HBsAg, which is the ultimate end-point of therapy. A formal phase 2 study is being planned for 2009. Chronic hepatitis C Romark initially decided to focus on the possibility of treating chronic hepatitis C with nitazoxanide. The drug garnered interest from the hepatology community after three phase II clinical trials involving the treatment of hepatitis C with nitazoxanide produced positive results for treatment efficacy and similar tolerability to placebo without any signs of toxicity. A meta-analysis from 2014 concluded that the previous held trials were of low-quality and with held with a risk of bias. The authors concluded that more randomized trials with low risk of bias are needed to determine if Nitazoxanide can be used as an effective treatment for chronic hepatitis C patients. Contraindications Nitazoxanide is contraindicated only in individuals who have experienced a hypersensitivity reaction to nitazoxanide or the inactive ingredients of a nitazoxanide formulation. Adverse effects The side effects of nitazoxanide do not significantly differ from a placebo treatment for giardiasis; these symptoms include stomach pain, headache, upset stomach, vomiting, discolored urine, excessive urinating, skin rash, itching, fever, flu syndrome, and others. Nitazoxanide does not appear to cause any significant adverse effects when taken by healthy adults. Overdose Information on nitazoxanide overdose is limited. Oral doses of 4 grams in healthy adults do not appear to cause any significant adverse effects. In various animals, the oral LD50 is higher than 10 g/kg. Interactions Due to the exceptionally high plasma protein binding (>99.9%) of nitazoxanides metabolite, tizoxanide, the concurrent use of nitazoxanide with other highly plasma protein-bound drugs with narrow therapeutic indices (e.g., warfarin) increases the risk of drug toxicity. In vitro evidence suggests that nitazoxanide does not affect the CYP450 system. Pharmacology Pharmacodynamics The anti-protozoal activity of nitazoxanide is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron-transfer reaction that is essential to anaerobic energy metabolism. PFOR inhibition may also contribute to its activity against anaerobic bacteria.It has also been shown to have activity against influenza A virus in vitro. The mechanism appears to be by selectively blocking the maturation of the viral hemagglutinin at a stage preceding resistance to endoglycosidase H digestion. This impairs hemagglutinin intracellular trafficking and insertion of the protein into the host plasma membrane. Nitazoxanide modulates a variety of other pathways in vitro, including glutathione-S-transferase and glutamate-gated chloride ion channels in nematodes, respiration and other pathways in bacteria and cancer cells, and viral and host transcriptional factors. Pharmacokinetics Following oral administration, nitazoxanide is rapidly hydrolyzed to the pharmacologically active metabolite, tizoxanide, which is 99% protein bound. Tizoxanide is then glucuronide conjugated into the active metabolite, tizoxanide glucuronide. Peak plasma concentrations of the metabolites tizoxanide and tizoxanide glucuronide are observed 1–4 hours after oral administration of nitazoxanide, whereas nitazoxanide itself is not detected in blood plasma.Roughly 2⁄3 of an oral dose of nitazoxanide is excreted as its metabolites in feces, while the remainder of the dose excreted in urine. Tizoxanide is excreted in the urine, bile and feces. Tizoxanide glucuronide is excreted in urine and bile. Chemistry Nitazoxanide is the prototype member of the thiazolides, which is a drug class of structurally-related broad-spectrum antiparasitic compounds. Nitazoxanide is a light yellow crystalline powder. It is poorly soluble in ethanol and practically insoluble in water. History Nitazoxanide was originally discovered in the 1980s by Jean-François Rossignol at the Pasteur Institute. Initial studies demonstrated activity versus tapeworms. In vitro studies demonstrated much broader activity. Dr. Rossignol co-founded Romark Laboratories, with the goal of bringing nitazoxanide to market as an anti-parasitic drug. Initial studies in the USA were conducted in collaboration with Unimed Pharmaceuticals, Inc. (Marietta, GA) and focused on development of the drug for treatment of cryptosporidiosis in AIDS. Controlled trials began shortly after the advent of effective anti-retroviral therapies. The trials were abandoned due to poor enrollment and the FDA rejected an application based on uncontrolled studies. Subsequently, Romark launched a series of controlled trials. A placebo-controlled study of nitazoxanide in cryptosporidiosis demonstrated significant clinical improvement in adults and children with mild illness. Among malnourished children in Zambia with chronic cryptosporidiosis, a three-day course of therapy led to clinical and parasitologic improvement and improved survival. In Zambia and in a study conducted in Mexico, nitazoxanide was not successful in the treatment of cryptosporidiosis in advanced infection with human immunodeficiency virus at the doses used. However, it was effective in patients with higher CD4 counts. In treatment of giardiasis, nitazoxanide was superior to placebo and comparable to metronidazole. Nitazoxanide was successful in the treatment of metronidazole-resistant giardiasis. Studies have suggested efficacy in the treatment of cyclosporiasis, isosporiasis, and amebiasis. Recent studies have also found it to be effective against beef tapeworm(Taenia saginata). Pharmaceutical products Dosage forms Nitazoxanide is currently available in two oral dosage forms: a tablet (500 mg) and an oral suspension (100 mg per 5 ml when reconstituted).An extended release tablet (675 mg) has been used in clinical trials for chronic hepatitis C; however, this form is not currently marketed or available for prescription. Brand names Nitazoxanide is sold under the brand names Adonid, Alinia, Allpar, Annita, Celectan, Colufase, Daxon, Dexidex, Diatazox, Kidonax, Mitafar, Nanazoxid, Parazoxanide, Netazox, Niazid, Nitamax, Nitax, Nitaxide, Nitaz, Nizonide, NT-TOX, Pacovanton, Paramix, Toza, and Zox. Research As of September 2015, nitazoxanide was in phase 3 clinical trials for the treatment influenza due to its inhibitory effect on a broad range of influenza virus subtypes and efficacy against influenza viruses that are resistant to neuraminidase inhibitors like oseltamivir. Nitazoxanide is also being researched as a potential treatment for COVID-19, chronic hepatitis B, chronic hepatitis C, rotavirus and norovirus gastroenteritis. References Further reading "Parasitic infections". Am J Transplant. 4 (Suppl 10): 142–55. October 2004. doi:10.1111/j.1600-6135.2004.00677.x. PMID 15504227. S2CID 5742723. External links "Nitazoxanide". Drug Information Portal. U.S. National Library of Medicine.

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

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

Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.Hepatitis is most commonly caused by the virus hepatovirus A, B, C, D, and E. Other viruses can also cause liver inflammation, including cytomegalovirus, Epstein–Barr virus, and yellow fever virus. Other common causes of hepatitis include heavy alcohol use, certain medications, toxins, other infections, autoimmune diseases, and non-alcoholic steatohepatitis (NASH). Hepatitis A and E are mainly spread by contaminated food and water. Hepatitis B is mainly sexually transmitted, but may also be passed from mother to baby during pregnancy or childbirth and spread through infected blood. Hepatitis C is commonly spread through infected blood such as may occur during needle sharing by intravenous drug users. Hepatitis D can only infect people already infected with hepatitis B.Hepatitis A, B, and D are preventable with immunization. Medications may be used to treat chronic viral hepatitis. Antiviral medications are recommended in all with chronic hepatitis C, except those with conditions that limit their life expectancy. There is no specific treatment for NASH; physical activity, a healthy diet, and weight loss are recommended. Autoimmune hepatitis may be treated with medications to suppress the immune system. A liver transplant may be an option in both acute and chronic liver failure.Worldwide in 2015, hepatitis A occurred in about 114 million people, chronic hepatitis B affected about 343 million people and chronic hepatitis C about 142 million people. In the United States, NASH affects about 11 million people and alcoholic hepatitis affects about 5 million people. Hepatitis results in more than a million deaths a year, most of which occur indirectly from liver scarring or liver cancer. In the United States, hepatitis A is estimated to occur in about 2,500 people a year and results in about 75 deaths. The word is derived from the Greek hêpar (ἧπαρ), meaning "liver", and -itis (-ῖτις), meaning "inflammation". Signs and symptoms Hepatitis has a broad spectrum of presentations that range from a complete lack of symptoms to severe liver failure. The acute form of hepatitis, generally caused by viral infection, is characterized by constitutional symptoms that are typically self-limiting. Chronic hepatitis presents similarly, but can manifest signs and symptoms specific to liver dysfunction with long-standing inflammation and damage to the organ. Acute hepatitis Acute viral hepatitis follows three distinct phases: The initial prodromal phase (preceding symptoms) involves non-specific and flu-like symptoms common to many acute viral infections. These include fatigue, nausea, vomiting, poor appetite, joint pain, and headaches. Fever, when present, is most common in cases of hepatitis A and E. Late in this phase, people can experience liver-specific symptoms, including choluria (dark urine) and clay-colored stools. Yellowing of the skin and whites of the eyes follow the prodrome after about 1–2 weeks and can last for up to 4 weeks. The non-specific symptoms seen in the prodromal typically resolve by this time, but people will develop an enlarged liver and right upper abdominal pain or discomfort. 10–20% of people will also experience an enlarged spleen, while some people will also experience a mild unintentional weight loss. The recovery phase is characterized by resolution of the clinical symptoms of hepatitis with persistent elevations in liver lab values and potentially a persistently enlarged liver. All cases of hepatitis A and E are expected to fully resolve after 1–2 months. Most hepatitis B cases are also self-limiting and will resolve in 3–4 months. Few cases of hepatitis C will resolve completely.Both drug-induced hepatitis and autoimmune hepatitis can present very similarly to acute viral hepatitis, with slight variations in symptoms depending on the cause. Cases of drug-induced hepatitis can manifest with systemic signs of an allergic reaction including rash, fever, serositis (inflammation of membranes lining certain organs), elevated eosinophils (a type of white blood cell), and suppression of bone marrow activity. Fulminant hepatitis Fulminant hepatitis, or massive hepatic cell death, is a rare and life-threatening complication of acute hepatitis that can occur in cases of hepatitis B, D, and E, in addition to drug-induced and autoimmune hepatitis. The complication more frequently occurs in instances of hepatitis B and D co-infection at a rate of 2–20% and in pregnant women with hepatitis E at rate of 15–20% of cases. In addition to the signs of acute hepatitis, people can also demonstrate signs of coagulopathy (abnormal coagulation studies with easy bruising and bleeding) and encephalopathy (confusion, disorientation, and sleepiness). Mortality due to fulminant hepatitis is typically the result of various complications including cerebral edema, gastrointestinal bleeding, sepsis, respiratory failure, or kidney failure. Chronic hepatitis Acute cases of hepatitis are seen to be resolved well within a six-month period. When hepatitis is continued for more than six months it is termed chronic hepatitis. Chronic hepatitis is often asymptomatic early in its course and is detected only by liver laboratory studies for screening purposes or to evaluate non-specific symptoms. As the inflammation progresses, patients can develop constitutional symptoms similar to acute hepatitis, including fatigue, nausea, vomiting, poor appetite, and joint pain. Jaundice can occur as well, but much later in the disease process and is typically a sign of advanced disease. Chronic hepatitis interferes with hormonal functions of the liver which can result in acne, hirsutism (abnormal hair growth), and amenorrhea (lack of menstrual period) in women. Extensive damage and scarring of the liver over time defines cirrhosis, a condition in which the livers ability to function is permanently impeded. This results in jaundice, weight loss, coagulopathy, ascites (abdominal fluid collection), and peripheral edema (leg swelling). Cirrhosis can lead to other life-threatening complications such as hepatic encephalopathy, esophageal varices, hepatorenal syndrome, and liver cancer. Causes Causes of hepatitis can be divided into the following major categories: infectious, metabolic, ischemic, autoimmune, genetic, and other. Infectious agents include viruses, bacteria, and parasites. Metabolic causes include prescription medications, toxins (most notably alcohol), and non-alcoholic fatty liver disease. Autoimmune and genetic causes of hepatitis involve genetic predispositions and tend to affect characteristic populations. Infectious Viral hepatitis Viral hepatitis is the most common type of hepatitis worldwide, especially in Asia and Africa. Viral hepatitis is caused by five different viruses (hepatitis A, B, C, D, and E). Hepatitis A and hepatitis E behave similarly: they are both transmitted by the fecal–oral route, are more common in developing countries, and are self-limiting illnesses that do not lead to chronic hepatitis.Hepatitis B, hepatitis C, and hepatitis D are transmitted when blood or mucous membranes are exposed to infected blood and body fluids, such as semen and vaginal secretions. Viral particles have also been found in saliva and breastmilk. Kissing, sharing utensils, and breastfeeding do not lead to transmission unless these fluids are introduced into open sores or cuts. Many families who do not have safe drinking water or live in unhygienic homes have contracted hepatitis because saliva and blood droplets are often carried through the water and blood-borne illnesses spread quickly in unsanitary settings.Hepatitis B and C can present either acutely or chronically. Hepatitis D is a defective virus that requires hepatitis B to replicate and is only found with hepatitis B co-infection. In adults, hepatitis B infection is most commonly self-limiting, with less than 5% progressing to chronic state, and 20 to 30% of those chronically infected developing cirrhosis or liver cancer. Infection in infants and children frequently leads to chronic infection.Unlike hepatitis B, most cases of hepatitis C lead to chronic infection. Hepatitis C is the second most common cause of cirrhosis in the US (second to alcoholic hepatitis). In the 1970s and 1980s, blood transfusions were a major factor in spreading hepatitis C virus. Since widespread screening of blood products for hepatitis C began in 1992, the risk of acquiring hepatitis C from a blood transfusion has decreased from approximately 10% in the 1970s to 1 in 2 million currently. Parasitic hepatitis Parasites can also infect the liver and activate the immune response, resulting in symptoms of acute hepatitis with increased serum IgE (though chronic hepatitis is possible with chronic infections). Of the protozoans, Trypanosoma cruzi, Leishmania species, and the malaria-causing Plasmodium species all can cause liver inflammation. Another protozoan, Entamoeba histolytica, causes hepatitis with distinct liver abscesses.Of the worms, the cestode Echinococcus granulosus, also known as the dog tapeworm, infects the liver and forms characteristic hepatic hydatid cysts. The liver flukes Fasciola hepatica and Clonorchis sinensis live in the bile ducts and cause progressive hepatitis and liver fibrosis. Bacterial hepatitis Bacterial infection of the liver commonly results in pyogenic liver abscesses, acute hepatitis, or granulomatous (or chronic) liver disease. Pyogenic abscesses commonly involve enteric bacteria such as Escherichia coli and Klebsiella pneumoniae and are composed of multiple bacteria up to 50% of the time. Acute hepatitis is caused by Neisseria meningitidis, Neisseria gonorrhoeae, Bartonella henselae, Borrelia burgdorferi, salmonella species, brucella species and campylobacter species. Chronic or granulomatous hepatitis is seen with infection from mycobacteria species, Tropheryma whipplei, Treponema pallidum, Coxiella burnetii, and rickettsia species. Metabolic Alcoholic hepatitis Excessive alcohol consumption is a significant cause of hepatitis and is the most common cause of cirrhosis in the U.S. Alcoholic hepatitis is within the spectrum of alcoholic liver disease. This ranges in order of severity and reversibility from alcoholic steatosis (least severe, most reversible), alcoholic hepatitis, cirrhosis, and liver cancer (most severe, least reversible). Hepatitis usually develops over years-long exposure to alcohol, occurring in 10 to 20% of alcoholics. The most important risk factors for the development of alcoholic hepatitis are quantity and duration of alcohol intake. Long-term alcohol intake in excess of 80 grams of alcohol a day in men and 40 grams a day in women is associated with development of alcoholic hepatitis (1 beer or 4 ounces of wine is equivalent to 12g of alcohol). Alcoholic hepatitis can vary from asymptomatic hepatomegaly (enlarged liver) to symptoms of acute or chronic hepatitis to liver failure. Toxic and drug-induced hepatitis Many chemical agents, including medications, industrial toxins, and herbal and dietary supplements, can cause hepatitis. The spectrum of drug-induced liver injury varies from acute hepatitis to chronic hepatitis to acute liver failure. Toxins and medications can cause liver injury through a variety of mechanisms, including direct cell damage, disruption of cell metabolism, and causing structural changes. Some drugs such as paracetamol exhibit predictable dose-dependent liver damage while others such as isoniazid cause idiosyncratic and unpredictable reactions that vary by person. There are wide variations in the mechanisms of liver injury and latency period from exposure to development of clinical illness.Many types of drugs can cause liver injury, including the analgesic paracetamol; antibiotics such as isoniazid, nitrofurantoin, amoxicillin-clavulanate, erythromycin, and trimethoprim-sulfamethoxazole; anticonvulsants such as valproate and phenytoin; cholesterol-lowering statins; steroids such as oral contraceptives and anabolic steroids; and highly active anti-retroviral therapy used in the treatment of HIV/AIDS. Of these, amoxicillin-clavulanate is the most common cause of drug-induced liver injury, and paracetamol toxicity the most common cause of acute liver failure in the United States and Europe.Herbal remedies and dietary supplements are another important cause of hepatitis; these are the most common causes of drug-induced hepatitis in Korea. The United-States-based Drug Induced Liver Injury Network linked more than 16% of cases of hepatotoxicity to herbal and dietary supplements. In the United States, herbal and dietary supplements – unlike pharmaceutical drugs – are unregulated by the Food and Drug Administration. The National Institutes of Health maintains the LiverTox Archived 2019-07-24 at the Wayback Machine database for consumers to track all known prescription and non-prescription compounds associated with liver injury.Exposure to other hepatotoxins can occur accidentally or intentionally through ingestion, inhalation, and skin absorption. The industrial toxin carbon tetrachloride and the wild mushroom Amanita phalloides are other known hepatotoxins. Non-alcoholic fatty liver disease Non-alcoholic hepatitis is within the spectrum of non-alcoholic liver disease (NALD), which ranges in severity and reversibility from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) to cirrhosis to liver cancer, similar to the spectrum of alcoholic liver disease.Non-alcoholic liver disease occurs in people with little or no history of alcohol use, and is instead strongly associated with metabolic syndrome, obesity, insulin resistance and diabetes, and hypertriglyceridemia. Over time, non-alcoholic fatty liver disease can progress to non-alcoholic steatohepatitis, which additionally involves liver cell death, liver inflammation and possible fibrosis. Factors accelerating progression from NAFLD to NASH are obesity, older age, non-African American ethnicity, female gender, diabetes mellitus, hypertension, higher ALT or AST level, higher AST/ALT ratio, low platelet count, and an ultrasound steatosis score.In the early stages (as with NAFLD and early NASH), most patients are asymptomatic or have mild right upper quadrant pain, and diagnosis is suspected on the basis of abnormal liver function tests. As the disease progresses, symptoms typical of chronic hepatitis may develop. While imaging can show fatty liver, only liver biopsy can demonstrate inflammation and fibrosis characteristic of NASH. 9 to 25% of patients with NASH develop cirrhosis. NASH is recognized as the third most common cause of liver disease in the United States. Autoimmune Autoimmune hepatitis is a chronic disease caused by an abnormal immune response against liver cells. The disease is thought to have a genetic predisposition as it is associated with certain human leukocyte antigens involved in the immune response. As in other autoimmune diseases, circulating auto-antibodies may be present and are helpful in diagnosis. Auto-antibodies found in patients with autoimmune hepatitis include the sensitive but less specific anti-nuclear antibody (ANA), smooth muscle antibody (SMA), and atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA). Other autoantibodies that are less common but more specific to autoimmune hepatitis are the antibodies against liver kidney microsome 1 (LKM1) and soluble liver antigen (SLA). Autoimmune hepatitis can also be triggered by drugs (such as nitrofurantoin, hydralazine, and methyldopa), after liver transplant, or by viruses (such as hepatitis A, Epstein-Barr virus, or measles).Autoimmune hepatitis can present anywhere within the spectrum from asymptomatic to acute or chronic hepatitis to fulminant liver failure. Patients are asymptomatic 25–34% of the time, and the diagnosis is suspected on the basis of abnormal liver function tests. Some studies show between 25% and 75% of cases present with signs and symptoms of acute hepatitis. As with other autoimmune diseases, autoimmune hepatitis usually affects young females (though it can affect patients of either sex of any age), and patients can exhibit classic signs and symptoms of autoimmunity such as fatigue, anemia, anorexia, amenorrhea, acne, arthritis, pleurisy, thyroiditis, ulcerative colitis, nephritis, and maculopapular rash. Autoimmune hepatitis increases the risk for cirrhosis, and the risk for liver cancer is increased by about 1% for each year of the disease.Many people with autoimmune hepatitis have other autoimmune diseases. Autoimmune hepatitis is distinct from the other autoimmune diseases of the liver, primary biliary cirrhosis and primary sclerosing cholangitis, both of which can also lead to scarring, fibrosis, and cirrhosis of the liver. Genetic Genetic causes of hepatitis include alpha-1-antitrypsin deficiency, hemochromatosis, and Wilsons disease. In alpha-1-antitrypsin deficiency, a co-dominant mutation in the gene for alpha-1-antitrypsin results in the abnormal accumulation of the mutant AAT protein within liver cells, leading to liver disease. Hemochromatosis and Wilsons disease are both autosomal recessive diseases involving abnormal storage of minerals. In hemochromatosis, excess amounts of iron accumulate in multiple body sites, including the liver, which can lead to cirrhosis. In Wilsons disease, excess amounts of copper accumulate in the liver and brain, causing cirrhosis and dementia.When the liver is involved, alpha-1-antitrypsin deficiency and Wilsons disease tend to present as hepatitis in the neonatal period or in childhood. Hemochromatosis typically presents in adulthood, with the onset of clinical disease usually after age 50. Ischemic hepatitis Ischemic hepatitis (also known as shock liver) results from reduced blood flow to the liver as in shock, heart failure, or vascular insufficiency. The condition is most often associated with heart failure but can also be caused by shock or sepsis. Blood testing of a person with ischemic hepatitis will show very high levels of transaminase enzymes (AST and ALT). The condition usually resolves if the underlying cause is treated successfully. Ischemic hepatitis rarely causes permanent liver damage. Other Hepatitis can also occur in neonates and is attributable to a variety of causes, some of which are not typically seen in adults. Congenital or perinatal infection with the hepatitis viruses, toxoplasma, rubella, cytomegalovirus, and syphilis can cause neonatal hepatitis. Structural abnormalities such as biliary atresia and choledochal cysts can lead to cholestatic liver injury leading to neonatal hepatitis. Metabolic diseases such as glycogen storage disorders and lysosomal storage disorders are also implicated. Neonatal hepatitis can be idiopathic, and in such cases, biopsy often shows large multinucleated cells in the liver tissue. This disease is termed giant cell hepatitis and may be associated with viral infection, autoimmune disorders, and drug toxicity. Mechanism The specific mechanism varies and depends on the underlying cause of the hepatitis. Generally, there is an initial insult that causes liver injury and activation of an inflammatory response, which can become chronic, leading to progressive fibrosis and cirrhosis. Viral hepatitis The pathway by which hepatic viruses cause viral hepatitis is best understood in the case of hepatitis B and C. The viruses do not directly activate apoptosis (cell death). Rather, infection of liver cells activates the innate and adaptive arms of the immune system leading to an inflammatory response which causes cellular damage and death, including viral-induced apoptosis via the induction of the death receptor-mediated signaling pathway. Depending on the strength of the immune response, the types of immune cells involved and the ability of the virus to evade the bodys defense, infection can either lead to clearance (acute disease) or persistence (chronic disease) of the virus. The chronic presence of the virus within liver cells results in multiple waves of inflammation, injury and wound healing that over time lead to scarring or fibrosis and culminate in hepatocellular carcinoma. People with impaired immune response are at greater risk of developing chronic infection. Natural killer cells are the primary drivers of the initial innate response and create a cytokine environment that results in the recruitment of CD4 T-helper and CD8 cytotoxic T-cells. Type I interferons are the cytokines that drive the antiviral response. In chronic Hepatitis B and C, natural killer cell function is impaired. Steatohepatitis Steatohepatitis is seen in both alcoholic and non-alcoholic liver disease and is the culmination of a cascade of events that began with injury. In the case of non-alcoholic steatohepatitis, this cascade is initiated by changes in metabolism associated with obesity, insulin resistance, and lipid dysregulation. In alcoholic hepatitis, chronic excess alcohol use is the culprit. Though the inciting event may differ, the progression of events is similar and begins with accumulation of free fatty acids (FFA) and their breakdown products in the liver cells in a process called steatosis. This initially reversible process overwhelms the hepatocytes ability to maintain lipid homeostasis leading to a toxic effect as fat molecules accumulate and are broken down in the setting of an oxidative stress response. Over time, this abnormal lipid deposition triggers the immune system via toll-like receptor 4 (TLR4) resulting in the production of inflammatory cytokines such as TNF that cause liver cell injury and death. These events mark the transition to steatohepatitis and in the setting of chronic injury, fibrosis eventually develops setting up events that lead to cirrhosis and hepatocellular carcinoma. Microscopically, changes that can be seen include steatosis with large and swollen hepatocytes (ballooning), evidence of cellular injury and cell death (apoptosis, necrosis), evidence of inflammation in particular in zone 3 of the liver, variable degrees of fibrosis and Mallory bodies. Diagnosis Diagnosis of hepatitis is made on the basis of some or all of the following: a persons signs and symptoms, medical history including sexual and substance use history, blood tests, imaging, and liver biopsy. In general, for viral hepatitis and other acute causes of hepatitis, the persons blood tests and clinical picture are sufficient for diagnosis. For other causes of hepatitis, especially chronic causes, blood tests may not be useful. In this case, liver biopsy is the gold standard for establishing the diagnosis: histopathologic analysis is able to reveal the precise extent and pattern of inflammation and fibrosis. Biopsy is typically not the initial diagnostic test because it is invasive and is associated with a small but significant risk of bleeding that is increased in people with liver injury and cirrhosis.Blood testing includes liver enzymes, serology (i.e. for autoantibodies), nucleic acid testing (i.e. for hepatitis virus DNA/RNA), blood chemistry, and complete blood count. Characteristic patterns of liver enzyme abnormalities can point to certain causes or stages of hepatitis. Generally, AST and ALT are elevated in most cases of hepatitis regardless of whether the person shows any symptoms. The degree of elevation (i.e. levels in the hundreds vs. in the thousands), the predominance for AST vs. ALT elevation, and the ratio between AST and ALT are informative of the diagnosis.Ultrasound, CT, and MRI can all identify steatosis (fatty changes) of the liver tissue and nodularity of the liver surface suggestive of cirrhosis. CT and especially MRI are able to provide a higher level of detail, allowing visualization and characterize such structures as vessels and tumors within the liver. Unlike steatosis and cirrhosis, no imaging test is able to detect liver inflammation (i.e. hepatitis) or fibrosis. Liver biopsy is the only definitive diagnostic test that is able to assess inflammation and fibrosis of the liver. Viral hepatitis Viral hepatitis is primarily diagnosed through blood tests for levels of viral antigens (such as the hepatitis B surface or core antigen), anti-viral antibodies (such as the anti-hepatitis B surface antibody or anti-hepatitis A antibody), or viral DNA/RNA. In early infection (i.e. within 1 week), IgM antibodies are found in the blood. In late infection and after recovery, IgG antibodies are present and remain in the body for up to years. Therefore, when a patient is positive for IgG antibody but negative for IgM antibody, he is considered immune from the virus via either prior infection and recovery or prior vaccination.In the case of hepatitis B, blood tests exist for multiple virus antigens (which are different components of the virion particle) and antibodies. The combination of antigen and antibody positivity can provide information about the stage of infection (acute or chronic), the degree of viral replication, and the infectivity of the virus. Alcoholic versus non-alcoholic The most apparent distinguishing factor between alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) is a history of excessive alcohol use. Thus, in patients who have no or negligible alcohol use, the diagnosis is unlikely to be alcoholic hepatitis. In those who drink alcohol, the diagnosis may just as likely be alcoholic or nonalcoholic hepatitis especially if there is concurrent obesity, diabetes, and metabolic syndrome. In this case, alcoholic and nonalcoholic hepatitis can be distinguished by the pattern of liver enzyme abnormalities; specifically, in alcoholic steatohepatitis AST>ALT with ratio of AST:ALT>2:1 while in nonalcoholic steatohepatitis ALT>AST with ratio of ALT:AST>1.5:1.Liver biopsies show identical findings in patients with ASH and NASH, specifically, the presence of polymorphonuclear infiltration, hepatocyte necrosis and apoptosis in the form of ballooning degeneration, Mallory bodies, and fibrosis around veins and sinuses. Virus screening The purpose of screening for viral hepatitis is to identify people infected with the disease as early as possible, even before symptoms and transaminase elevations may be present. This allows for early treatment, which can both prevent disease progression and decrease the likelihood of transmission to others. Hepatitis A Hepatitis A causes an acute illness that does not progress to chronic liver disease. Therefore, the role of screening is to assess immune status in people who are at high risk of contracting the virus, as well as in people with known liver disease for whom hepatitis A infection could lead to liver failure. People in these groups who are not already immune can receive the hepatitis A vaccine. Those at high risk and in need of screening include: People with poor sanitary habits such as not washing hands after using the restroom or changing diapers People who do not have access to clean water People in close contact (either living with or having sexual contact) with someone who has hepatitis A People who use illicit drugs People with liver disease People traveling to an area with endemic hepatitis AThe presence of anti-hepatitis A IgG in the blood indicates past infection with the virus or prior vaccination. Hepatitis B The CDC, WHO, USPSTF, and ACOG recommend routine hepatitis B screening for certain high-risk populations. Specifically, these populations include people who are: Born in countries where the prevalence of hepatitis B is high (defined as ≥2% of the population), whether or not they have been vaccinated Born in the United States whose parents are from countries where the prevalence of hepatitis B is very high (defined as ≥8% of the population), and who were not vaccinated HIV positive Intravenous drug users Men who have sex with men In close contact with (i.e. live or have sex with) people known to have hepatitis B Pregnant Beginning immunosuppressive or cytotoxic therapy Found to have elevated liver enzymes without a known cause Blood, organ, or tissue donors Incarcerated On hemodialysisScreening consists of a blood test that detects hepatitis B surface antigen (HBsAg). If HBsAg is present, a second test – usually done on the same blood sample – that detects the antibody for the hepatitis B core antigen (anti-HBcAg) can differentiate between acute and chronic infection. People who are high-risk whose blood tests negative for HBsAg can receive the hepatitis B vaccine to prevent future infection. Hepatitis C The CDC, WHO, USPSTF, AASLD, and ACOG recommend screening people at high risk for hepatitis C infection. These populations include people who are: Intravenous drug users (past or current) Intranasal illicit drug users HIV-positive Men who have sex with men Incarcerated, or who have been in the past On long-term hemodialysis, or who have been in the past Recipients of tattoos in an "unregulated setting" Recipients of blood products or organs prior to 1992 in the United States Adults in the United States born between 1945 and 1965 Born to HCV-positive mothers Pregnant, and engaging in high-risk behaviors Workers in a healthcare setting who have had a needlestick injury Blood or organ donors. Sex workersFor people in the groups above whose exposure is ongoing, screening should be periodic, though there is no set optimal screening interval. The AASLD recommends screening men who have sex with men who are HIV-positive annually. People born in the US between 1945 and 1965 should be screened once (unless they have other exposure risks).Screening consists of a blood test that detects anti-hepatitis C virus antibody. If anti-hepatitis C virus antibody is present, a confirmatory test to detect HCV RNA indicates chronic disease. Hepatitis D The CDC, WHO, USPSTF, AASLD, and ACOG recommend screening people at high risk for hepatitis D infection. These populations include people who are: Intravenous drug users (past or current) Intranasal illicit drug users Incarcerated, or who have been in the past Workers in a healthcare setting who have had a needlestick injury Blood or organ donors. Sex workersHepatitis D is extremely rare. Symptoms include chronic diarrhea, anal and intestinal blisters, purple urine, and burnt popcorn scented breath. Screening consists of a blood test that detects the anti-hepitits D virus antibbody. If anti-hepitits D virus antibody is present, a confirmatory test to detect HDV RNA DNA inidicates chronic disease. Prevention Vaccines Hepatitis A The CDC recommends the hepatitis A vaccine for all children beginning at age one, as well as for those who have not been previously immunized and are at high risk for contracting the disease.For children 12 months of age or older, the vaccination is given as a shot into the muscle in two doses 6–18 months apart and should be started before the age 24 months. The dosing is slightly different for adults depending on the type of the vaccine. If the vaccine is for hepatitis A only, two doses are given 6–18 months apart depending on the manufacturer. If the vaccine is combined hepatitis A and hepatitis B, up to 4 doses may be required. Hepatitis B The CDC recommends the routine vaccination of all children under the age of 19 with the hepatitis B vaccine. They also recommend it for those who desire it or are at high risk.Routine vaccination for hepatitis B starts with the first dose administered as a shot into the muscle before the newborn is discharged from the hospital. An additional two doses should be administered before the child is 18 months.For babies born to a mother with hepatitis B surface antigen positivity, the first dose is unique – in addition to the vaccine, the hepatitis immune globulin should also be administered, both within 12 hours of birth. These newborns should also be regularly tested for infection for at least the first year of life.There is also a combination formulation that includes both hepatitis A and B vaccines. Other There are currently no vaccines available in the United States for hepatitis C or E. In 2015, a group in China published an article regarding the development of a vaccine for hepatitis E. As of March 2016, the United States government was in the process of recruiting participants for the phase IV trial of the hepatitis E vaccine. Behavioral changes Hepatitis A Because hepatitis A is transmitted primarily through the oral-fecal route, the mainstay of prevention aside from vaccination is good hygiene, access to clean water and proper handling of sewage. Hepatitis B and C As hepatitis B and C are transmitted through blood and multiple bodily fluids, prevention is aimed at screening blood prior to transfusion, abstaining from the use of injection drugs, safe needle and sharps practices in healthcare settings, and safe sex practices. Hepatitis D The hepatitis D virus requires that a person first be infected with hepatitis B virus, so prevention efforts should focus on limiting the spread of hepatitis B. In people who have chronic hepatitis B infection and are at risk for superinfection with the hepatitis D virus, the preventive strategies are the same as for hepatitis B. Hepatitis E Hepatitis E is spread primarily through the oral-fecal route but may also be spread by blood and from mother to fetus. The mainstay of hepatitis E prevention is similar to that for hepatitis A (namely, good hygiene and clean water practices). Alcoholic hepatitis As excessive alcohol consumption can lead to hepatitis and cirrhosis, the following are maximal recommendations for alcohol consumption: Women – ≤ 3 drinks on any given day and ≤ 7 drinks per week Men – ≤ 4 drinks on any given day and ≤ 14 drinks per week Successes Hepatitis A In the United States, universal immunization has led to a two-thirds decrease in hospital admissions and medical expenses due to hepatitis A. Hepatitis B In the United States new cases of hepatitis B decreased 75% from 1990 to 2004. The group that saw the greatest decrease was children and adolescents, likely reflecting the implementation of the 1999 guidelines. Hepatitis C Hepatitis C infections each year had been declining since the 1980s, but began to increase again in 2006. The data are unclear as to whether the decline can be attributed to needle exchange programmes. Alcoholic hepatitis Because people with alcoholic hepatitis may have no symptoms, it can be difficult to diagnose and the number of people with the disease is probably higher than many estimates. Programs such as Alcoholics Anonymous have been successful in decreasing death due to cirrhosis, but it is difficult to evaluate their success in decreasing the incidence of alcoholic hepatitis. Treatment The treatment of hepatitis varies according to the type, whether it is acute or chronic, and the severity of the disease. Activity: Many people with hepatitis prefer bed rest, though it is not necessary to avoid all physical activity while recovering. Diet: A high-calorie diet is recommended. Many people develop nausea and cannot tolerate food later in the day, so the bulk of intake may be concentrated in the earlier part of the day. In the acute phase of the disease, intravenous feeding may be needed if patients cannot tolerate food and have poor oral intake subsequent to nausea and vomiting. Drugs: People with hepatitis should avoid taking drugs metabolized by the liver. Glucocorticoids are not recommended as a treatment option for acute viral hepatitis and may even cause harm, such as development of chronic hepatitis. Precautions: Universal precautions should be observed. Isolation is usually not needed, except in cases of hepatitis A and E who have fecal incontinence, and in cases of hepatitis B and C who have uncontrolled bleeding. Hepatitis A Hepatitis A usually does not progress to a chronic state, and rarely requires hospitalization. Treatment is supportive and includes such measures as providing intravenous (IV) hydration and maintaining adequate nutrition.Rarely, people with the hepatitis A virus can rapidly develop liver failure, termed fulminant hepatic failure, especially the elderly and those who had a pre-existing liver disease, especially hepatitis C. Mortality risk factors include greater age and chronic hepatitis C. In these cases, more aggressive supportive therapy and liver transplant may be necessary. Hepatitis B Acute In healthy patients, 95–99% recover with no long-lasting effects, and antiviral treatment is not warranted. Age and comorbid conditions can result in a more prolonged and severe illness. Certain patients warrant hospitalization, especially those who present with clinical signs of ascites, peripheral edema, and hepatic encephalopathy, and laboratory signs of hypoglycemia, prolonged prothrombin time, low serum albumin, and very high serum bilirubin.In these rare, more severe acute cases, patients have been successfully treated with antiviral therapy similar to that used in cases of chronic hepatitis B, with nucleoside analogues such as entecavir or tenofovir. As there is a dearth of clinical trial data and the drugs used to treat are prone to developing resistance, experts recommend reserving treatment for severe acute cases, not mild to moderate. Chronic Chronic hepatitis B management aims to control viral replication, which is correlated with progression of disease. Seven drugs are approved in the United States: Injectable interferon alpha was the first therapy approved for chronic hepatitis B. It has several side effects, most of which are reversible with removal of therapy, but it has been supplanted by newer treatments for this indication. These include long-acting interferon bound to polyethylene glycol (pegylated interferon) and the oral nucleoside analogues. Pegylated interferon (PEG IFN) is dosed just once a week as a subcutaneous injection and is both more convenient and effective than standard interferon. Although it does not develop resistance as do many of the oral antivirals, it is poorly tolerated and requires close monitoring. PEG IFN is estimated to cost about $18,000 per year in the United States, compared to $2,500–8,700 for the oral medications. Its treatment duration is 48 weeks, unlike oral antivirals which require indefinite treatment for most patients (minimum one year). PEG IFN is not effective in patients with high levels of viral activity and cannot be used in immunosuppressed patients or those with cirrhosis. Lamivudine was the first approved oral nucleoside analogue. While effective and potent, lamivudine has been replaced by newer, more potent treatments in the Western world and is no longer recommended as first-line treatment. It is still used in areas where newer agents either have not been approved or are too costly. Generally, the course of treatment is a minimum of one year with a minimum of six additional months of "consolidation therapy." Based on viral response, longer therapy may be required, and certain patients require indefinite long-term therapy. Due to a less robust response in Asian patients, consolidation therapy is recommended to be extended to at least a year. All patients should be monitored for viral reactivation, which if identified, requires restarting treatment. Lamivudine is generally safe and well tolerated. Many patients develop resistance, which is correlated with longer treatment duration. If this occurs, an additional antiviral is added. Lamivudine as a single treatment is contraindicated in patients coinfected with HIV, as resistance develops rapidly, but it can be used as part of a multidrug regimen. Adefovir dipivoxil, a nucleotide analogue, has been used to supplement lamivudine in patients who develop resistance, but is no longer recommended as first-line therapy. Entecavir is safe, well tolerated, less prone to developing resistance, and the most potent of the existing hepatitis B antivirals; it is thus a first-line treatment choice. It is not recommended for lamivudine-resistant patients or as monotherapy in patients who are HIV positive. Telbivudine is effective but not recommended as first-line treatment; as compared to entecavir, it is both less potent and more resistance prone. Tenofovir is a nucleotide analogue and an antiretroviral drug that is also used to treat HIV infection. It is preferred to adefovir both in lamivudine-resistant patients and as initial treatment since it is both more potent and less likely to develop resistance.First-line treatments currently used include PEG IFN, entecavir, and tenofovir, subject to patient and physician preference. Treatment initiation is guided by recommendations issued by The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) and is based on detectable viral levels, HBeAg positive or negative status, ALT levels, and in certain cases, family history of HCC and liver biopsy. In patients with compensated cirrhosis, treatment is recommended regardless of HBeAg status or ALT level, but recommendations differ regarding HBV DNA levels; AASLD recommends treating at DNA levels detectable above 2x103 IU/mL; EASL and WHO recommend treating when HBV DNA levels are detectable at any level. In patients with decompensated cirrhosis, treatment and evaluation for liver transplantation are recommended in all cases if HBV DNA is detectable. Currently, multidrug treatment is not recommended in treatment of chronic HBV as it is no more effective in the long term than individual treatment with entecavir or tenofovir. Hepatitis C The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) recommend antiviral treatment for all patients with chronic hepatitis C infection except for those with additional chronic medical conditions that limit their life expectancy.Once it is acquired, persistence of the hepatitis C virus is the rule, resulting in chronic hepatitis C. The goal of treatment is prevention of hepatocellular carcinoma (HCC). The best way to reduce the long-term risk of HCC is to achieve sustained virological response (SVR). SVR is defined as an undetectable viral load at 12 weeks after treatment completion and indicates a cure. Currently available treatments include indirect and direct acting antiviral drugs. The indirect acting antivirals include pegylated interferon (PEG IFN) and ribavirin (RBV), which in combination have historically been the basis of therapy for HCV. Duration of and response to these treatments varies based on genotype. These agents are poorly tolerated but are still used in some resource-poor areas. In high-resource countries, they have been supplanted by direct acting antiviral agents, which first appeared in 2011; these agents target proteins responsible for viral replication and include the following three classes: NS3/4A protease inhibitors, including telaprevir, boceprevir, simeprevir, and others NS5A inhibitors, including ledipasvir, daclatasvir, and others NS5B polymerase inhibitors, including sofosbuvir, dasabuvir, and othersThese drugs are used in various combinations, sometimes combined with ribavirin, based on the patients genotype, delineated as genotypes 1–6. Genotype 1 (GT1), which is the most prevalent genotype in the United States and around the world, can now be cured with a direct acting antiviral regimen. First-line therapy for GT1 is a combination of sofosbuvir and ledipasvir (SOF/LDV) for 12 weeks for most patients, including those with advanced fibrosis or cirrhosis. Certain patients with early disease need only 8 weeks of treatment while those with advanced fibrosis or cirrhosis who have not responded to prior treatment require 24 weeks. Cost remains a major factor limiting access to these drugs, particularly in low-resource nations; the cost of the 12-week GT1 regimen (SOF/LDV) has been estimated at US$94,500. Hepatitis D Hepatitis D is difficult to treat, and effective treatments are lacking. Interferon alpha has proven effective at inhibiting viral activity but only on a temporary basis. Hepatitis E Similar to hepatitis A, treatment of hepatitis E is supportive and includes rest and ensuring adequate nutrition and hydration. Hospitalization may be required for particularly severe cases or for pregnant women. Alcoholic hepatitis First-line treatment of alcoholic hepatitis is treatment of alcoholism. For those who abstain completely from alcohol, reversal of liver disease and a longer life are possible; patients at every disease stage have been shown to benefit by prevention of additional liver injury. In addition to referral to psychotherapy and other treatment programs, treatment should include nutritional and psychosocial evaluation and treatment. Patients should also be treated appropriately for related signs and symptoms, such as ascites, hepatic encephalopathy, and infection.Severe alcoholic hepatitis has a poor prognosis and is notoriously difficult to treat. Without any treatment, 20-50% of patients may die within a month, but evidence shows treatment may extend life beyond one month (i.e., reduce short-term mortality). Available treatment options include pentoxifylline (PTX), which is a nonspecific TNF inhibitor, corticosteroids, such as prednisone or prednisolone (CS), corticosteroids with N-acetylcysteine (CS with NAC), and corticosteroids with pentoxifylline (CS with PTX). Data suggest that CS alone or CS with NAC are most effective at reducing short-term mortality. Unfortunately, corticosteroids are contraindicated in some patients, such as those who have active gastrointestinal bleeding, infection, kidney failure, or pancreatitis. In these cases PTX may be considered on a case-by-case basis in lieu of CS; some evidence shows PTX is better than no treatment at all and may be comparable to CS while other data show no evidence of benefit over placebo. Unfortunately, there are currently no drug treatments that decrease these patients risk of dying in the longer term, at 3–12 months and beyond.Weak evidence suggests milk thistle extracts may improve survival in alcoholic liver disease and improve certain liver tests (serum bilirubin and GGT) without causing side effects, but a firm recommendation cannot be made for or against milk thistle without further study. The modified Maddreys discriminant function may be used to evaluate the severity and prognosis in alcoholic hepatitis and evaluates the efficacy of using alcoholic hepatitis corticosteroid treatment. Autoimmune hepatitis Autoimmune hepatitis is commonly treated by immunosuppressants such as the corticosteroids prednisone or prednisolone, the active version of prednisolone that does not require liver synthesis, either alone or in combination with azathioprine, and some have suggested the combination therapy is preferred to allow for lower doses of corticosteroids to reduce associated side effects, although the result of treatment efficacy is comparative.Treatment of autoimmune hepatitis consists of two phases; an initial and maintenance phase. The initial phase consists of higher doses of corticosteroids which are tapered down over a number of weeks to a lower dose. If used in combination, azathioprine is given during the initial phase as well. Once the initial phase has been completed, a maintenance phase that consists of lower dose corticosteroids, and in combination therapy, azathioprine until liver blood markers are normalized. Treatment results in 66-91% of patients achieving normal liver test values in two years, with the average being 22 months. Prognosis Acute hepatitis Nearly all patients with hepatitis A infections recover completely without complications if they were healthy prior to the infection. Similarly, acute hepatitis B infections have a favorable course towards complete recovery in 95–99% of patients. Certain factors may portend a poorer outcome, such as co-morbid medical conditions or initial presenting symptoms of ascites, edema, or encephalopathy. Overall, the mortality rate for acute hepatitis is low: ~0.1% in total for cases of hepatitis A and B, but rates can be higher in certain populations (super infection with both hepatitis B and D, pregnant women, etc.).In contrast to hepatitis A & B, hepatitis C carries a much higher risk of progressing to chronic hepatitis, approaching 85–90%. Cirrhosis has been reported to develop in 20–50% of patients with chronic hepatitis C.Other rare complications of acute hepatitis include pancreatitis, aplastic anemia, peripheral neuropathy, and myocarditis. Fulminant hepatitis Despite the relatively benign course of most viral cases of hepatitis, fulminant hepatitis represents a rare but feared complication. Fulminant hepatitis most commonly occurs in hepatitis B, D, and E. About 1–2% of cases of hepatitis E can lead to fulminant hepatitis, but pregnant women are particularly susceptible, occurring in up to 20% of cases. Mortality rates in cases of fulminant hepatitis rise over 80%, but those patients that do survive often make a complete recovery. Liver transplantation can be life-saving in patients with fulminant liver failure.Hepatitis D infections can transform benign cases of hepatitis B into severe, progressive hepatitis, a phenomenon known as superinfection. Chronic hepatitis Acute hepatitis B infections become less likely to progress to chronic forms as the age of the patient increases, with rates of progression approaching 90% in vertically transmitted cases of infants compared to 1% risk in young adults. Overall, the five-year survival rate for chronic hepatitis B ranges from 97% in mild cases to 55% in severe cases with cirrhosis.Most patients who acquire hepatitis D at the same time as hepatitis B (co-infection) recover without developing a chronic infection. In people with hepatitis B who later acquire hepatitis D (superinfection), chronic infection is much more common at 80-90%, and liver disease progression is accelerated.Chronic hepatitis C progresses towards cirrhosis, with estimates of cirrhosis prevalence of 16% at 20 years after infection. While the major causes of mortality in hepatitis C is end stage liver disease, hepatocellular carcinoma is an important additional long term complication and cause of death in chronic hepatitis. Rates of mortality increase with progression of the underlying liver disease. Series of patients with compensated cirrhosis due to HCV have shown 3,5, and 10-year survival rates of 96, 91, and 79% respectively. The 5-year survival rate drops to 50% upon if the cirrhosis becomes decompensated. Epidemiology Viral hepatitis Hepatitis A Hepatitis A is found throughout the world and manifests as large outbreaks and epidemics associated with fecal contamination of water and food sources. Hepatitis A viral infection is predominant in children ages 5–14 with rare infection of infants. Infected children have little to no apparent clinical illness, in contrast to adults in whom greater than 80% are symptomatic if infected. Infection rates are highest in low resource countries with inadequate public sanitation and large concentrated populations. In such regions, as much as 90% of children younger than 10 years old have been infected and are immune, corresponding both to lower rates of clinically symptomatic disease and outbreaks. The availability of a childhood vaccine has significantly reduced infections in the United States, with incidence declining by more than 95% as of 2013. Paradoxically, the highest rates of new infection now occur in young adults and adults who present with worse clinical illness. Specific populations at greatest risk include: travelers to endemic regions, men who have sex with men, those with occupational exposure to non-human primates, people with clotting disorders who have received clotting factors, people with history of chronic liver disease in whom co-infection with hepatitis A can lead to fulminant hepatitis, and intravenous drug users (rare). Hepatitis B Hepatitis B is the most common cause of viral hepatitis in the world with more than 240 million chronic carriers of the virus, 1 million of whom are in the United States. In approximately two-thirds of patients who develop acute hepatitis B infection, no identifiable exposure is evident. Of those acutely infected, 25% become lifetime carriers of the virus. Risk of infection is highest among intravenous drug users, people with high-risk sexual behaviors, healthcare workers, people who had multiple transfusions, organ transplant patients, dialysis patients and newborns infected during the birthing process. Close to 780,000 deaths in the world are attributed to hepatitis B. The most endemic regions are in sub-Saharan Africa and East Asia, where as many as 10% of adults are chronic carriers. Carrier rates in developed nations are significantly lower, encompassing less than 1% of the population. In endemic regions, transmission is thought to be associated with exposure during birth and close contact between young infants. Hepatitis C Chronic hepatitis C is a major cause of liver cirrhosis and hepatocellular carcinoma. It is a common medical reason for liver transplantation due to its severe complications. It is estimated that 130–180 million people in the world are affected by this disease representing a little more than 3% of the world population. In the developing regions of Africa, Asia and South America, prevalence can be as high as 10% of the population. In Egypt, rates of hepatitis C infection as high as 20% have been documented and are associated with iatrogenic contamination related to schistosomiasis treatment in the 1950s–1980s. Currently in the United States, approximately 3.5 million adults are estimated to be infected. Hepatitis C is particularly prevalent among people born between 1945 and 1965, a group of about 800,000 people, with prevalence as high as 3.2% versus 1.6% in the general U.S. population. Most chronic carriers of hepatitis C are unaware of their infection status. The most common mode of transmission of hepatitis C virus is exposure to blood products via blood transfusions (prior to 1992) and intravenous drug injection. A history of intravenous drug injection is the most important risk factor for chronic hepatitis C. Other susceptible populations include those engaged in high-risk sexual behavior, infants of infected mothers, and healthcare workers. Hepatitis D The hepatitis D virus causes chronic and fulminant hepatitis in the context of co-infection with the hepatitis B virus. It is primarily transmitted via non-sexual contact and via needles. Susceptibility to hepatitis D differs by geographic region. In the United States and Northern Europe, populations at risk are intravenous drug users and people who receive multiple transfusions. In the Mediterranean, hepatitis D is predominant among hepatitis B virus co-infected people. Hepatitis E Similar to Hepatitis A, hepatitis E manifests as large outbreaks and epidemics associated with fecal contamination of water sources. It accounts for more than 55,000 deaths annually with approximately 20 million people worldwide thought to be infected with the virus. It affects predominantly young adults, causing acute hepatitis. In infected pregnant women, Hepatitis E infection can lead to fulminant hepatitis with third trimester mortality rates as high as 30%. Those with weakened immune systems, such as organ transplant recipients, are also susceptible. Infection is rare in the United States but rates are high in the developing world (Africa, Asia, Central America, Middle East). Many genotypes exist and are differentially distributed around the world. There is some evidence of hepatitis E infection of animals, serving as a reservoir for human infection. Alcoholic hepatitis Alcoholic hepatitis (AH) in its severe form has a one-month mortality as high as 50%. Most people who develop AH are men but women are at higher risk of developing AH and its complications likely secondary to high body fat and differences in alcohol metabolism. Other contributing factors include younger age <60, binge pattern drinking, poor nutritional status, obesity and hepatitis C co-infection. It is estimated that as much as 20% of people with AH are also infected with hepatitis C. In this population, the presence of hepatitis C virus leads to more severe disease with faster progression to cirrhosis, hepatocellular carcinoma and increased mortality. Obesity increases the likelihood of progression to cirrhosis in cases of alcoholic hepatitis. It is estimated that 70% of people who have AH will progress to cirrhosis. Non-alcoholic steatohepatitis Non-alcoholic steatohepatitis (NASH) is projected to become the top reason for liver transplantation in the United States by 2020, supplanting chronic liver disease due to hepatitis C. About 20–45% of the U.S. population have NAFLD and 6% have NASH. The estimated prevalence of NASH in the world is 3–5%. Of NASH patients who develop cirrhosis, about 2% per year will likely progress to hepatocellular carcinoma. Worldwide, the estimated prevalence of hepatocellular carcinoma related to NAFLD is 15–30%. NASH is thought to be the primary cause of cirrhosis in approximately 25% of patients in the United States, representing 1–2% of the general population. History Early observations Initial accounts of a syndrome that we now think is likely to be hepatitis begin to occur around 3000 B.C. Clay tablets that served as medical handbooks for the ancient Sumerians described the first observations of jaundice. The Sumerians believed that the liver was the home of the soul, and attributed the findings of jaundice to the attack of the liver by a devil named Ahhazu.Around 400 B.C., Hippocrates recorded the first documentation of an epidemic jaundice, in particular noting the uniquely fulminant course of a cohort of patients who all died within two weeks. He wrote, "The bile contained in the liver is full of phlegm and blood, and erupts...After such an eruption, the patient soon raves, becomes angry, talks nonsense and barks like a dog."Given the poor sanitary conditions of war, infectious jaundice played a large role as a major cause of mortality among troops in the Napoleonic Wars, the American Revolutionary War, and both World Wars. During World War II, estimates of soldiers affected by hepatitis were upwards of 10 million. During World War II, soldiers received vaccines against diseases such as yellow fever, but these vaccines were stabilized with human serum, presumably contaminated with hepatitis viruses, which often created epidemics of hepatitis. It was suspected these epidemics were due to a separate infectious agent, and not due to the yellow fever virus itself, after noting 89 cases of jaundice in the months after vaccination out of a total 3,100 patients that were vaccinated. After changing the seed virus strain, no cases of jaundice were observed in the subsequent 8,000 vaccinations. Willowbrook State School experiments A New York University researcher named Saul Krugman continued this research into the 1950s and 1960s, most infamously with his experiments on mentally disabled children at the Willowbrook State School in New York, a crowded urban facility where hepatitis infections were highly endemic to the student body. Krugman injected students with gamma globulin, a type of antibody. After observing the temporary protection against infection this antibody provided, he then tried injected live hepatitis virus into students. Krugman also controversially took feces from infected students, blended it into milkshakes, and fed it to newly admitted children.His research was received with much controversy, as people protested the questionable ethics surrounding the chosen target population. Henry Beecher was one of the foremost critics in an article in the New England Journal of Medicine in 1966, arguing that parents were unaware to the risks of consent and that the research was done to benefit others at the expense of children. Moreover, he argued that poor families with mentally disabled children often felt pressured to join the research project to gain admission to the school, with all of the educational and support resources that would come along with it. Others in the medical community spoke out in support of Krugmans research in terms of its widespread benefits and understanding of the hepatitis virus, and Willowbrook continues to be a commonly cited example in debates about medical ethics. Australia antigen The next insight regarding hepatitis B was a serendipitous one by Dr. Baruch Blumberg, a researcher at the NIH who did not set out to research hepatitis, but rather studied lipoprotein genetics. He travelled across the globe collecting blood samples, investigating the interplay between disease, environment, and genetics with the goal of designing targeted interventions for at-risk people that could prevent them from getting sick. He noticed an unexpected interaction between the blood of a patient with hemophilia that had received multiple transfusions and a protein found in the blood of an indigenous Australian person. He named the protein the "Australia antigen" and made it the focus of his research. He found a higher prevalence of the protein in the blood of patients from developing countries, compared to those from developed ones, and noted associations of the antigen with other diseases like leukemia and Down Syndrome. Eventually, he came to the unifying conclusion that the Australia antigen was associated with viral hepatitis. In 1970, David Dane first isolated the hepatitis B virion at Londons Middlesex Hospital, and named the virion the 42-nm "Dane particle". Based on its association with the surface of the hepatitis B virus, the Australia antigen was renamed to "hepatitis B surface antigen" or HBsAg. Blumberg continued to study the antigen, and eventually developed the first hepatitis B vaccine using plasma rich in HBsAg, for which he received the Nobel Prize in Medicine in 1976. Society and culture Economic burden Overall, hepatitis accounts for a significant portion of healthcare expenditures in both developing and developed nations, and is expected to rise in several developing countries. While hepatitis A infections are self-limited events, they are associated with significant costs in the United States. It has been estimated that direct and indirect costs are approximately $1817 and $2459 respectively per case, and that an average of 27 work days is lost per infected adult. A 1997 report demonstrated that a single hospitalization related to hepatitis A cost an average of $6,900 and resulted in around $500 million in total annual healthcare costs. Cost effectiveness studies have found widespread vaccination of adults to not be feasible, but have stated that a combination hepatitis A and B vaccination of children and at risk groups (people from endemic areas, healthcare workers) may be.Hepatitis B accounts for a much larger percentage of health care spending in endemic regions like Asia. In 1997 it accounted for 3.2% of South Koreas total health care expenditures and resulted in $696 million in direct costs. A large majority of that sum was spent on treating disease symptoms and complications. Chronic hepatitis B infections are not as endemic in the United States, but accounted for $357 million in hospitalization costs in the year 1990. That number grew to $1.5 billion in 2003, but remained stable as of 2006, which may be attributable to the introduction of effective drug therapies and vaccination campaigns.People infected with chronic hepatitis C tend to be frequent users of the health care system globally. It has been estimated that a person infected with hepatitis C in the United States will result in a monthly cost of $691. That number nearly doubles to $1,227 for people with compensated (stable) cirrhosis, while the monthly cost of people with decompensated (worsening) cirrhosis is almost five times as large at $3,682. The wide-ranging effects of hepatitis make it difficult to estimate indirect costs, but studies have speculated that the total cost is $6.5 billion annually in the United States. In Canada, 56% of HCV related costs are attributable to cirrhosis and total expenditures related to the virus are expected to peak at CAD$396 million in the year 2032. 2003 Monaca outbreak The largest outbreak of hepatitis A virus in United States history occurred among people who ate at a now-defunct Mexican food restaurant located in Monaca, Pennsylvania in late 2003. Over 550 people who visited the restaurant between September and October 2003 were infected with the virus, three of whom died as a direct result. The outbreak was brought to the attention of health officials when local emergency medicine physicians noticed a significant increase in cases of hepatitis A in the county. After conducting its investigation, the CDC attributed the source of the outbreak to the use of contaminated raw green onion. The restaurant was purchasing its green onion stock from farms in Mexico at the time. It is believed that the green onions may have been contaminated through the use of contaminated water for crop irrigation, rinsing, or icing or by handling of the vegetables by infected people. Green onion had caused similar outbreaks of hepatitis A in the southern United States prior to this, but not to the same magnitude. The CDC believes that the restaurants use of a large communal bucket for chopped raw green onion allowed non-contaminated plants to be mixed with contaminated ones, increasing the number of vectors of infection and amplifying the outbreak. The restaurant was closed once it was discovered to be the source, and over 9,000 people were given hepatitis A immune globulin because they had either eaten at the restaurant or had been in close contact with someone who had. Special populations HIV co-infection Persons infected with HIV have a particularly high burden of HIV-HCV co-infection. In a recent study by the WHO, the likelihood of being infected with hepatitis C virus was six times greater in those who also had HIV. The prevalence of HIV-HCV co-infection worldwide was estimated to be 6.2% representing more than 2.2 million people. Intravenous drug use was an independent risk factor for HCV infection. In the WHO study, the prevalence of HIV-HCV co-infection was markedly higher at 82.4% in those who injected drugs compared to the general population (2.4%). In a study of HIV-HCV co-infection among HIV positive men who have sex with men (MSM), the overall prevalence of anti-hepatitis C antibodies was estimated to be 8.1% and increased to 40% among HIV positive MSM who also injected drugs. Pregnancy Hepatitis B Vertical transmission is a significant contributor of new HBV cases each year, with 35–50% of transmission from mother to neonate in endemic countries. Vertical transmission occurs largely via a neonates exposure to maternal blood and vaginal secretions during birth. While the risk of progression to chronic infection is approximately 5% among adults who contract the virus, it is as high as 95% among neonates subject to vertical transmission. The risk of viral transmission is approximately 10–20% when maternal blood is positive for HBsAg, and up to 90% when also positive for HBeAg.Given the high risk of perinatal transmission, the CDC recommends screening all pregnant women for HBV at their first prenatal visit. It is safe for non-immune pregnant women to receive the HBV vaccine. Based on the limited available evidence, the American Association for the Study of Liver Diseases (AASLD) recommends antiviral therapy in pregnant women whose viral load exceeds 200,000 IU/mL. A growing body of evidence shows that antiviral therapy initiated in the third trimester significantly reduces transmission to the neonate. A systematic review of the Antiretroviral Pregnancy Registry database found that there was no increased risk of congenital anomalies with Tenofovir; for this reason, along with its potency and low risk of resistance, the AASLD recommends this drug. A 2010 systematic review and meta-analysis found that Lamivudine initiated early in the third trimester also significantly reduced mother-to-child transmission of HBV, without any known adverse effects.The ACOG states that the evidence available does not suggest any particular mode of delivery (i.e. vaginal vs. cesarean) is better at reducing vertical transmission in mothers with HBV.The WHO and CDC recommend that neonates born to mothers with HBV should receive hepatitis B immune globulin (HBIG) as well as the HBV vaccine within 12 hours of birth. For infants who have received HBIG and the HBV vaccine, breastfeeding is safe. Hepatitis C Estimates of the rate of HCV vertical transmission range from 2–8%; a 2014 systematic review and meta-analysis found the risk to be 5.8% in HCV-positive, HIV-negative women. The same study found the risk of vertical transmission to be 10.8% in HCV-positive, HIV-positive women. Other studies have found the risk of vertical transmission to be as high as 44% among HIV-positive women. The risk of vertical transmission is higher when the virus is detectable in the mothers blood.Evidence does not indicate that mode of delivery (i.e. vaginal vs. cesarean) has an effect on vertical transmission.For women who are HCV-positive and HIV-negative, breastfeeding is safe. CDC guidelines suggest avoiding it if a womans nipples are cracked or bleeding to reduce the risk of transmission. Hepatitis E Pregnant women who contract HEV are at significant risk of developing fulminant hepatitis with maternal mortality rates as high as 20–30%, most commonly in the third trimester . A 2016 systematic review and meta-analysis of 47 studies that included 3968 people found maternal case-fatality rates (CFR) of 20.8% and fetal CFR of 34.2%; among women who developed fulminant hepatic failure, CFR was 61.2%. See also World Hepatitis Day References External links WHO fact sheet of hepatitis Viral Hepatitis at the Centers for Disease Control

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

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

Vitiligo is a disorder that causes the skin to lose its color. Specific causes are unknown but studies suggest a link to immune system changes. Signs and symptoms The only sign of vitiligo is the presence of pale patchy areas of depigmented skin which tend to occur on the extremities. Some people may experience itching before a new patch occurs. The patches are initially small, but often grow and change shape. When skin lesions occur, they are most prominent on the face, hands and wrists. The loss of skin pigmentation is particularly noticeable around body orifices, such as the mouth, eyes, nostrils, genitalia and umbilicus. Some lesions have increased skin pigment around the edges. Those affected by vitiligo who are stigmatized for their condition may experience depression and similar mood disorders. Causes Although multiple hypotheses have been suggested as potential triggers that cause vitiligo, studies strongly imply that changes in the immune system are responsible for the condition. Vitiligo has been proposed to be a multifactorial disease with genetic susceptibility and environmental factors both thought to play a role.The TYR gene encodes the protein tyrosinase, which is not a component of the immune system, but is an enzyme of the melanocyte that catalyzes melanin biosynthesis, and a major autoantigen in generalized vitiligo. The National Institutes of Health states that some believe that sunburns can cause or exacerbate the condition, but that this idea is not well-supported by good evidence. Immune Variations in genes that are part of the immune system or part of melanocytes have both been associated with vitiligo. It is also thought to be caused by the immune system attacking and destroying the melanocytes of the skin. A genome wide association study found approximately 36 independent susceptibility loci for generalized vitiligo. Autoimmune associations Vitiligo is sometimes associated with autoimmune and inflammatory diseases such as Hashimotos thyroiditis, scleroderma, rheumatoid arthritis, type 1 diabetes mellitus, psoriasis, Addisons disease, pernicious anemia, alopecia areata, systemic lupus erythematosus, and celiac disease.Among the inflammatory products of NALP1 are caspase 1 and caspase 7, which activate the inflammatory cytokine interleukin-1β. Interleukin-1β and interleukin-18 are expressed at high levels in people with vitiligo. In one of the mutations, the amino acid leucine in the NALP1 protein was replaced by histidine (Leu155 → His). The original protein and sequence is highly conserved in evolution, and is found in humans, chimpanzee, rhesus monkey, and the bush baby. Addisons disease (typically an autoimmune destruction of the adrenal glands) may also be seen in individuals with vitiligo. Diagnosis An ultraviolet light can be used in the early phase of this disease for identification and to determine the effectiveness of treatment. Using a Woods light, skin will change colour (fluoresce) when it is affected by certain bacteria, fungi, and changes to pigmentation of the skin. Classification Classification attempts to quantify vitiligo have been analyzed as being somewhat inconsistent, while recent consensus have agreed to a system of segmental vitiligo (SV) and non-segmental vitiligo (NSV). NSV is the most common type of vitiligo. Non-segmental In non-segmental vitiligo (NSV), there is usually some form of symmetry in the location of the patches of depigmentation. New patches also appear over time and can be generalized over large portions of the body or localized to a particular area. Extreme cases of vitiligo, to the extent that little pigmented skin remains, are referred to as vitiligo universalis. NSV can come about at any age (unlike segmental vitiligo, which is far more prevalent in teenage years).Classes of non-segmental vitiligo include the following: Generalized vitiligo: the most common pattern, wide and randomly distributed areas of depigmentation Universal vitiligo: depigmentation encompasses most of the body Focal vitiligo: one or a few scattered macules in one area, most common in children Acrofacial vitiligo: fingers and periorificial areas Mucosal vitiligo: depigmentation of only the mucous membranes Segmental Segmental vitiligo (SV) differs in appearance, cause, and frequency of associated illnesses. Its treatment is different from that of NSV. It tends to affect areas of skin that are associated with dorsal roots from the spinal cord and is most often unilateral. It is much more stable/static in course and its association with autoimmune diseases appears to be weaker than that of generalized vitiligo. SV does not improve with topical therapies or UV light, however surgical treatments such as cellular grafting can be effective. Differential diagnosis Chemical leukoderma is a similar condition due to multiple exposures to chemicals. Vitiligo however is a risk factor. Triggers may include inflammatory skin conditions, burns, intralesional steroid injections and abrasions.Other conditions with similar symptoms include the following: Albinism Halo nevus Idiopathic guttate hypomelanosis (white sunspots) Piebaldism Pityriasis alba Postinflammatory hypopigmentation Primary adrenal insufficiency Progressive macular hypomelanosis Tinea versicolor Tuberculoid leprosy Treatment There is no cure for vitiligo but several treatment options are available. The best evidence is for applied steroids and the combination of ultraviolet light in combination with creams. Due to the higher risks of skin cancer, the United Kingdoms National Health Service suggests phototherapy be used only if primary treatments are ineffective. Lesions located on the hands, feet, and joints are the most difficult to repigment; those on the face are easiest to return to the natural skin color as the skin is thinner in nature. Immune mediators Topical preparations of immune suppressing medications including glucocorticoids (such as 0.05% clobetasol or 0.10% betamethasone) and calcineurin inhibitors (such as tacrolimus or pimecrolimus) are considered to be first-line vitiligo treatments.In July 2022, ruxolitinib cream (sold under the brand name Opzelura) was approved for medical use in the United States for the treatment of vitiligo. Phototherapy Phototherapy is considered a second-line treatment for vitiligo. Exposing the skin to light from UVB lamps is the most common treatment for vitiligo. The treatments can be done at home with an UVB lamp or in a clinic. The exposure time is managed so that the skin does not suffer overexposure. Treatment can take a few weeks if the spots are on the neck and face and if they existed not more than 3 years. If the spots are on the hands and legs and have been there for more than 3 years, it can take a few months. Phototherapy sessions are done 2–3 times a week. Spots on a large area of the body may require full body treatment in a clinic or hospital. UVB broadband and narrowband lamps can be used, but narrowband ultraviolet peaked around 311 nm is the choice. It has been constitutively reported that a combination of UVB phototherapy with other topical treatments improves re-pigmentation. However, some people with vitiligo may not see any changes to skin or re-pigmentation occurring. A serious potential side effect involves the risk of developing skin cancer, the same risk as an overexposure to natural sunlight.Ultraviolet light (UVA) treatments are normally carried out in a hospital clinic. Psoralen and ultraviolet A light (PUVA) treatment involves taking a drug that increases the skins sensitivity to ultraviolet light, then exposing the skin to high doses of UVA light. Treatment is required twice a week for 6–12 months or longer. Because of the high doses of UVA and psoralen, PUVA may cause side effects such as sunburn-type reactions or skin freckling.Narrowband ultraviolet B (NBUVB) phototherapy lacks the side-effects caused by psoralens and is as effective as PUVA. As with PUVA, treatment is carried out twice weekly in a clinic or every day at home, and there is no need to use psoralen. Longer treatment is often recommended, and at least 6 months may be required for effects to phototherapy. NBUVB phototherapy appears better than PUVA therapy with the most effective response on the face and neck.With respect to improved repigmentation: topical calcineurin inhibitors plus phototherapy are better than phototherapy alone, hydrocortisone plus laser light is better than laser light alone, gingko biloba is better than placebo, and oral mini-pulse of prednisolone (OMP) plus NB-UVB is better than OMP alone. Skin camouflage In mild cases, vitiligo patches can be hidden with makeup or other cosmetic camouflage solutions. If the affected person is pale-skinned, the patches can be made less visible by avoiding tanning of unaffected skin. De-pigmenting In cases of extensive vitiligo the option to de-pigment the unaffected skin with topical drugs like monobenzone, mequinol, or hydroquinone may be considered to render the skin an even color. The removal of all the skin pigment with monobenzone is permanent and vigorous. Sun-safety must be adhered to for life to avoid severe sunburn and melanomas. Depigmentation takes about a year to complete. History Descriptions of a disease believed to be vitiligo date back to a passage in the medical text Ebers Papyrus c. 1500 BCE in ancient Egypt. Mentions of whitening of the skin were also present c. 1400 BCE in sacred Indian texts such as Atharvaveda. The Hebrew word "Tzaraath" from the Old Testament book of Leviticus dating to 1280 BCE (or 1312 BCE) described a group of skin diseases associated with white spots, and a subsequent translation to Greek led to continued conflation of those with vitiligo with leprosy and spiritual uncleanliness.Medical sources in the ancient world such as Hippocrates often did not differentiate between vitiligo and leprosy, often grouping these diseases together. The name "vitiligo" was first used by the Roman physician Aulus Cornelius Celsus in his classic medical text De Medicina.The etymology of the term "vitiligo" is believed to be derived from "vitium", meaning "defect" or "blemish". Society and culture The change in appearance caused by vitiligo can affect a persons emotional and psychological well-being and may create difficulty in becoming or remaining employed, particularly if vitiligo develops on visible areas of the body, such as the face, hands or arms. Participating in a vitiligo support group may improve social coping skills and emotional resilience. Notable cases include US pop singer Michael Jackson, Canadian fashion model Winnie Harlow, US actor David Dastmalchian and Argentine musician Charly García. French actor Michaël Youn is also affected, as is former French Prime Minister Edouard Philippe. Research As of July 2013, afamelanotide is in phase II and III clinical trials for vitiligo and other skin diseases.A medication for rheumatoid arthritis, tofacitinib, has been tested for the treatment of vitiligo.In October 1992, a scientific report was published of successfully transplanting melanocytes to vitiligo-affected areas, effectively re-pigmenting the region. The procedure involved taking a thin layer of pigmented skin from the persons gluteal region. Melanocytes were then separated out to a cellular suspension that was expanded in culture. The area to be treated was then denuded with a dermabrader and the melanocytes graft applied. Between 70 and 85 percent of people with vitiligo experienced nearly complete repigmentation of their skin. The longevity of the repigmentation differed from person to person. References External links Vitiligo at Curlie Questions and Answers about Vitiligo – US National Institute of Arthritis and Musculoskeletal and Skin Diseases

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

Could you provide a brief overview of 'Butalbital/acetaminophen' in a medical context?

Butalbital/acetaminophen, sold under the brand name Butapap among others, is a combination medication used to treat tension headaches and migraine headaches. It contains butalbital, a barbiturate and paracetamol (acetaminophen), an analgesic. Versions also containing caffeine are sold under the brand name Fioricet among others. It is taken by mouth. The combination is also sold with codeine.The most common side effects include sleepiness, dizziness, trouble breathing, and abdominal pain. Other severe side effects may include liver problems, confusion, addiction, and allergic reactions. Frequent use may result in medication overuse headache. Barbiturate withdrawal may occur if rapidly stopped following long term use. Use is not generally recommended during pregnancy or breastfeeding.The combination was approved for medical use in the United States in 1984. It is available as a generic medication. In 2019, the combination butalbital/acetaminophen/caffeine was the 228th most commonly prescribed medication in the United States, with more than 2 million prescriptions. In the United States it is a schedule III controlled substance in some states but not federally. It is banned in a number of European countries. Medical uses Butalbital/acetaminophen is indicated for the treatment of tension headaches.Butalbital/acetaminophen/caffeine is indicated for the treatment of tension headaches. Side effects Commonly reported side effects include euphoria, dizziness or lightheadedness, drowsiness or sedation, intoxication, nausea, vomiting, dependence, shortness of breath, and abdominal pain.Prolonged use can cause rebound headaches.Rarely, use of barbiturates can lead to Stevens–Johnson syndrome. Overdose Butalbital exerts its toxicity through excessive sedation, resulting in respiratory depression and ultimately death via hypoxia. Nonlethal overdoses may also result in coma and death. There is no specific antidote to barbiturate overdose; treatment is supportive, generally including the administration of intravenous saline, naloxone, thiamine, glucose, sodium bicarbonate to alkalize the urine and increase rate of excretion, and activated charcoal via nasogastric tube.Acetaminophen exerts its toxicity through the production of a toxic metabolite that can cause liver damage at doses as low as four grams. Larger doses can precipitate acute liver failure, acute kidney injury, or gastrointestinal bleeding; death has been known to occur with ingestion of ten to fifteen grams. The specific antidote to acetaminophen overdose is N-acetylcysteine. Mechanism of action Butalbital exerts a generalized depressant effect on the central nervous system and, in very high doses, has peripheral effects. Acetaminophen has analgesic and antipyretic effects mediated by a metabolite that acts at cannabinoid receptors. Caffeine is thought to produce constriction of cerebral blood vessels and serves to counteract the sedative effect of butalbital.Butalbital has a half-life of about 35 hours. Acetaminophen has a half-life of about 1.25 to 3 hours, but may be increased by liver damage and after an overdose. Caffeine has a half-life of about 2.5 to 4.5 hours. References External links "Acetaminophen mixture with butalbital". Drug Information Portal. U.S. National Library of Medicine. "Acetaminophen mixture with butalbital and caffeine". Drug Information Portal. U.S. National Library of Medicine.

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

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

Nephrocalcinosis, once known as Albrights calcinosis after Fuller Albright, is a term originally used to describe deposition of calcium salts in the renal parenchyma due to hyperparathyroidism. The term nephrocalcinosis is used to describe the deposition of both calcium oxalate and calcium phosphate. It may cause acute kidney injury. It is now more commonly used to describe diffuse, fine, renal parenchymal calcification in radiology. It is caused by multiple different conditions and is determined progressive kidney dysfunction. These outlines eventually come together to form a dense mass. During its early stages, nephrocalcinosis is visible on x-ray, and appears as a fine granular mottling over the renal outlines. It is most commonly seen as an incidental finding with medullary sponge kidney on an abdominal x-ray. It may be severe enough to cause (as well as be caused by) renal tubular acidosis or even end stage kidney disease, due to disruption of the kidney tissue by the deposited calcium. Signs and symptoms Though this condition is usually asymptomatic, if symptoms are present they are usually related to the causative process, (e.g. hypercalcemia). Some of the symptoms that can happen are blood in the urine, fever and chills, nausea and vomiting, severe pain in the belly area, flanks of the back, groin, or testicles. These include renal colic, polyuria and polydipsia: Renal colic is usually caused by pre-existing nephrolithiasis, as may occur in patients with chronic hypercalciuria. Less commonly, it can result from calcified bodies moving into the calyceal system. Nocturia, polyuria, and polydipsia from reduced urinary concentrating capacity (i.e. nephrogenic diabetes insipidus) as can be seen in hypercalcemia, medullary nephrocalcinosis of any cause, or in children with Bartter syndrome in whom essential tubular salt reabsorption is compromised.There are several causes of nephrocalcinosis that are typically acute and present only with kidney failure. These include tumor lysis syndrome, acute phosphate nephropathy, and occasional cases of enteric hyperoxaluria. Cause Nephrocalcinosis is connected with conditions that cause hypercalcemia, hyperphosphatemia, and the increased excretion of calcium, phosphate, and/or oxalate in the urine. A high urine pH can lead to Nephrocalcinosis but only if it is accompanied by hypercalciuria and hypocitraturia, since having a normal urinary citrate usually inhibits the crystallization of calcium. In conjunction with Nephrocalcinosis, hypercalcemia and hypercalciuria the following can occur: Primary hyperparathyroidism: Nephrocalcinosis is one of the most common symptoms of primary hyperparathyroidism. Sarcoidosis: Nephrocalcinosis is one of the most common symptoms. Vitamin D: This can cause nephrocalcinosis because of Vitamin D therapy because it increases the absorption of ingested calcium and bone resorption, resulting in hypercalcemia and hypercalciuria. Medullary nephrocalcinosis Medullary sponge kidney Distal renal tubular acidosis Hyperoxaluria Renal papillary necrosisAnd other causes of hypercalcemia (and thus hypercalciuria) Immobilization (leading to hypercalcemia and hypercalciuria) Milk-alkali syndrome Hypervitaminosis D Multiple myeloma Hypercalciuria without hypercalcemia These conditions can cause nephrocalcinosis in association with hypercalciuria without hypercalcemia: Distal renal tubular acidosis Medullary sponge kidney Neonatal nephrocalcinosis and loop diuretics Inherited tubulopathies Chronic hypokalemia Beta thalassemia Mechanism Nephrocalcinosis is caused by an increase in the urinary excretion of calcium, phosphate, and/or oxalate. Nephrocalcinosis is closely associated with nephrolithiasis, and patients frequently present with both conditions, however there have been cases where one occurs without the other. Calcium oxalate and calcium phosphate crystals form when the concentration of the reactants exceeds the limit. The deposits are collected in the inner medullary interstitium in the basement membranes of the thin limbs of the loop of Henle. The calcium phosphate plaques can enlarge into the surrounding interstitial tissue, or even rupture into the tubule lumen and can promote calcium oxalate stone formation. Diagnosis Nephrocalcinosis is diagnosed for the most part by imaging techniques. The imagings used are ultrasound (US), abdominal plain film and CT imaging. Of the 3 techniques CT and US are the more preferred. Nephrocalcinosis is considered present if at least two radiologists make the diagnosis on US and/or CT. In some cases a renal biopsy is done instead if imaging is not enough to confirm nephrocalcinosis. Once the diagnosis is confirmed additional testing is needed to find the underlying cause because the underlying condition may require treatment for reasons independent of nephrocalcinosis. These additional tests will measure serum, electrolytes, calcium, and phosphate, and the urine pH. If no underlying cause can be found then urine collection should be done for 24 hours and measurements of the excretion of calcium, phosphate, oxalate, citrate, and creatinine are looked at. Stages of nephrocalcinosis Chemical or Molecular nephrocalcinosis: Defined as a measurable increase in intracellular calcium concentrations, however, it is not visible through X-ray or microscopically. Microscopic nephrocalcinosis: Occurs when depositis are visible by light microscope by obtaining a tissue sample from a biopsy. However, this cannot be seen in an X-ray. Macroscopic nephrocalcinosis: Occurs when calcification can be seen through X-ray imaging. Treatment Increasing fluid intake to yield a urine output of greater than 2 liters a day can be advantageous for all patients with nephrocalcinosis. Patients with hypercalciuria can reduce calcium excretion by restricting animal protein, limiting sodium intake to less than 100 meq a day and being lax of potassium intake. If changing ones diet alone does not result in a suitable reduction of hypercalciuria, a thiazide diuretic can be administered in patients who do not have hypercalcemia. Citrate can increase the solubility of calcium in urine and limit the development of nephrocalcinosis. Citrate is not given to patients who have urine pH equal to or greater than 7. Prognosis The prognosis of nephrocalcinosis is determined by the underlying cause. Most cases of nephrocalcinosis do not progress to end stage renal disease, however if not treated it can lead to renal dysfunction this includes primary hyperoxaluria, hypomagnesemic hypercalciuric nephrocalcinosis and Dents disease. Once nephrocalcinosis is found, it is unlikely to be reversed, however, partial reversal has been reported in patients who have had successful treatment of hypercalciuria and hyperoxaluria following corrective intestinal surgery. Recent research In recent findings they have found that there is a genetic predisposition to nephrocalciosis, however the specific genetic and epigenetic factors are not clear. There seems to be multiple genetic factors that regulate the excretion of the different urinary risk factors. There has been some correlation seen that shows gene polymorphisms related to stone formation for calcium-sensing receptor and vitamin D receptors. Repeated calcium stones associated with medullary sponge kidney may be related to an autosomal dominant mutation of a still unknown gene, however the genes is GDNF seems to be a gene involved in renal morphogenesis. In conjunction with the gene research is another theory of how the disease manifests. This is called the free particle theory. This theory says that the increasing concentration of lithogenic solutes along the segments of the nephron leads to the formation, growth, and collection of crystals that might get trapped in the tubular lumen and begin the process of stone formation. Some of the backing behind this theory is the speed of growth of the crystals, the diameter of the segments of the nephron, and the transit time in the nephron. All of these combined show more and more support for this theory. References == External links ==

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

Can you break down the meaning of the medical term 'Acute monocytic leukemia' for me?

Acute monocytic leukemia (AMoL, or AML-M5) is a type of acute myeloid leukemia. In AML-M5 >80% of the leukemic cells are of monocytic lineage. This cancer is characterized by a dominance of monocytes in the bone marrow. There is an overproduction of monocytes that the body does not need in the periphery. These overproduced monocytes interfere with normal immune cell production which causes many health complications for the infected individual. Causes The pathology of AML involves abnormal proliferation and differentiation of a population of myeloid stem cells. Genetic mutations are identified in the majority of cases. A common genetic mutation identified in these cases are characterized as chromosomal translocations where information from one chromosome is exchanged to a non-homologous chromosome creating an unusual rearrangement of chromosomes. This translocation is often abbreviated as t(#of one chromosome involved, #of other chromosome involved). M5 is associated with characteristic chromosomal abnormalities, often involving chromosome 11, such as t(9;11), affecting the MLL (KMTA2) locus at 11q23; however MLL translocations are also found in other leukemia subtypes. The t(8;16) translocation in AMoL is associated with hemophagocytosis. These translocations yield the formation of chimeric proteins (RUNX1-RUNX1T1 and PML-RARA, respectively) which disrupt normal myeloid precursor development. Secondary leukaemia, which may include AML-M5, has been associated with exposure to epipodophyllotoxins, such as etoposide.Many cases of AML-M5 are seen to have enhanced phosphorylation of the STAT3 protein due to increased induction of cytokines thus increasing cell proliferation and survival. Finally, genetic mutations involved in epigenetic regulation are associated with this leukemia, as they have downstream effects on cell differentiation and proliferation. Excessive cytokine release could be a byproduct of skewed epigenetic regulation. Diagnosis In order to fulfill World Health Organization (WHO) criteria for AML-5, a patient must have greater than 20% blasts in the bone marrow, and of these, greater than 80% must be of the monocytic lineage. A further subclassification (M5a versus M5b) is made depending on whether the monocytic cells are predominantly monoblasts (>80%) (acute monoblastic leukemia) or a mixture of monoblasts and promonocytes (<80% blasts). Monoblasts can be distinguished by having a roughly circular nucleus, delicate lacy chromatin, and abundant, often basophilic cytoplasm. These cells may also have pseudopods. By contrast, promonocytes have a more convoluted nucleus, and their cytoplasm may contain metachromatic granules. Monoblasts are typically MPO-negative and promonocytes are MPO variable. Both monoblasts and promonocytes stain positive for non-specific esterase (NSE), however NSE may often be negative. Immunophenotypically, M5-AML variably express myeloid (CD13, CD33) and monocytic (CD11b, CD11c) markers. Cells may aberrantly express B-cell marker CD20 and the NK marker CD56. Monoblasts may be positive for CD34. Treatment AML-M5 is treated with intensive chemotherapy (such as anthracyclines) or with bone marrow transplantation. Tyrosine kinase receptor inhibitors are a prominent treatment developed to combat the over activation of cell proliferation proteins induced by AML-5. Inhibiting the STAT3 protein is another useful form of treatment. References External links Image at hmds.org.uk

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

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

Hyperoxia occurs when cells, tissues and organs are exposed to an excess supply of oxygen (O2) or higher than normal partial pressure of oxygen.In medicine, it refers to excess oxygen in the lungs or other body tissues, which can be caused by breathing air or oxygen at pressures greater than normal atmospheric pressure. This kind of hyperoxia can lead to oxygen toxicity, caused from the harmful effects of breathing molecular oxygen at elevated partial pressures. Hyperoxia is the opposite of hypoxia; hyperoxia refers to a state in which oxygen supply is excessive, and hypoxia refers to a state in which oxygen supply is insufficient. In the environment, it refers to excess oxygen in a body of water or other habitat. Signs and symptoms Associated with hyperoxia is an increased level of reactive oxygen species (ROS), which are chemically reactive molecules containing oxygen. These oxygen containing molecules can damage lipids, proteins, and nucleic acids, and react with surrounding biological tissues. The human body has naturally occurring antioxidants to combat reactive molecules, but the protective antioxidant defenses can become depleted by abundant reactive oxygen species, resulting in oxidation of the tissues and organs.The symptoms produced from breathing high concentrations of oxygen for extended periods have been studied in a variety of animals, such as frogs, turtles, pigeons, mice, rats, guinea pigs, cats, dogs and monkeys. The majority of these studies reported the occurrence of irritation, congestion and edema of the lungs, and even death following prolonged exposures. Oxygen toxicity The supplementation of oxygen can lead to oxygen toxicity, also known as oxygen toxicity syndrome, oxygen intoxication, and oxygen poisoning. There are two main types of oxygen toxicity: central nervous system (CNS) toxicity, and pulmonary and ocular toxicity.Temporary exposure to high partial pressures of oxygen at greater than atmospheric pressure can lead to central nervous system toxicity (CNS). An early but serious sign of CNS oxygen toxicity is a grand-mal seizure, also known as a generalized tonic-clonic seizure. This type of seizure consists of a loss of consciousness and violent muscle contractions. Signs and symptoms of oxygen toxicity are usually prevalent, but there are no standard warning signs that a seizure is about to ensue. The convulsion caused by oxygen toxicity does not lead to hypoxia, a side effect common to most seizures, because the body has an excess amount of oxygen when the convulsion begins. The seizures can lead to drowning, however, if the convulsion is suffered by a diver still in the water.Prolonged exposure to higher oxygen levels at atmospheric pressure can lead to pulmonary and ocular toxicity. Symptoms of oxygen toxicity may include disorientation, respiratory problems, myopia, or accelerated development of cataracts. Prolonged exposure to higher than normal partial pressures of oxygen can result in oxidative damage to cell membranes. Signs of pulmonary (lung) oxygen toxicity begin with slight irritation in the trachea. A mild cough usually ensues, followed by greater irritation and a worse cough until breathing becomes quite painful and the cough becomes uncontrollable. If supplementation of oxygen is continued, the individual will notice tightness in the chest, difficulty breathing, shortness of breath, and if exposure is continued, fatality due to lack of oxygen. Cause Oxygen supplied at greater than atmospheric pressure has been known to damage plants, animals, and aerobic bacteria such as Escherichia coli. The damaging effects vary depending on the specimen used, its age, physiological state, and diet.The supplementation of oxygen has been a common procedure of prehospital treatment for many years. Guidelines include cautions about chronic obstructive pulmonary disease (COPD). These guidelines stress the use of 28% oxygen masks and caution the dangers of hyperoxia. Long-term use of supplemental oxygen improves survival in patients with COPD, but can lead to lung injury.An additional cause of hyperoxia is related to underwater diving with breathing apparatus. Underwater divers breath a mixture of gasses which must include oxygen, and the partial pressure of any given gas mixture will increase with depth. A mixture known as nitrox is used to reduce the risk of decompression sickness by substituting oxygen for part of the nitrogen content. Breathing nitrox can lead to hyperoxia due to the high partial pressure of oxygen if used too deep or for too long. Protocols for the safe use of raised oxygen partial pressure in diving are well established and used routinely by recreational scuba divers, military combat divers and professional saturation divers alike. The highest risk of hyperoxia is in hyperbaric oxygen therapy, where it is a high probability side effect of the treatment for more serious conditions, and is considered an acceptable risk as it can be managed effectively without apparent long term effects. Diagnosis Treatment Oxygen supplementation is used to treat tissue hypoxia and to relieve arterial hypoxemia. High concentrations of oxygen are often given to patients with chronic obstructive pulmonary disease (COPD) or acute lung injury (ALI). Supplementing oxygen is known to cause tissue damage, with toxicity increasing with the increase of oxygen concentrations and exposure pressures. Unfortunately, the supplementation of oxygen is necessary if an individual is not able to obtain sufficient oxygen through respiration and perfusion. To decrease the chances of hyperoxia, the therapist should use the lowest concentration of oxygen required by an individual. At this time, there are no known alternatives to oxygen supplementation. See also Hypoxia – Medical condition caused by lack of oxygen in the tissues Hypoxemia – Abnormally low level of oxygen in the blood Oxygen toxicity – Toxic effects of breathing in oxygen at high concentrations Hyperbaric medicine – Medical treatment at raised ambient pressure == References ==

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

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

Ophthalmoparesis refers to weakness (-paresis) or paralysis (-plegia) of one or more extraocular muscles which are responsible for eye movements. It is a physical finding in certain neurologic, ophthalmologic, and endocrine disease. Internal ophthalmoplegia means involvement limited to the pupillary sphincter and ciliary muscle. External ophthalmoplegia refers to involvement of only the extraocular muscles. Complete ophthalmoplegia indicates involvement of both. Causes Ophthalmoparesis can result from disorders of various parts of the eye and nervous system: Infection around the eye. Ophthalmoplegia is an important finding in orbital cellulitis. The orbit of the eye, including mechanical restrictions of eye movement, as in Graves disease. The muscle, as in progressive external ophthalmoplegia or Kearns–Sayre syndrome. The neuromuscular junction, as in myasthenia gravis. The relevant cranial nerves (specifically the oculomotor, trochlear, and abducens), as in cavernous sinus syndrome or raised intracranial pressure. The brainstem nuclei of these nerves, as in certain patterns of brainstem stroke such as Fovilles syndrome. White matter tracts connecting these nuclei, as in internuclear ophthalmoplegia, an occasional finding in multiple sclerosis. Dorsal midbrain structures, as in Parinauds syndrome. Certain parts of the cerebral cortex (including the frontal eye fields), as in stroke. Toxic envenomation by mambas, taipans, and kraits.Thiamine deficiency can cause ophthalmoparesis in susceptible persons; this is part of the syndrome called Wernicke encephalopathy. The causal pathway by which this occurs is unknown. Intoxication with certain substances, such as phenytoin, can also cause ophthalmoparesis. Diagnosis Classification Ophthalmoparesis can involve any or all of the extraocular muscles, which include the superior recti, inferior recti, medial recti, lateral recti, inferior oblique and superior oblique muscles. It can also be classified by the directions of affected movements, e.g. "vertical ophthalmoparesis". Treatment Treatment and prognosis depend on the underlying condition. For example, in thiamine deficiency, treatment would be the immediate administration of vitamin B1. See also Paresis References == External links ==

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

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

Sarcoidosis, an inflammatory disease, involves the skin in about 25% of patients. The most common lesions are erythema nodosum, plaques, maculopapular eruptions, subcutaneous nodules, and lupus pernio. Treatment is not required, since the lesions usually resolve spontaneously in two to four weeks. Although it may be disfiguring, cutaneous sarcoidosis rarely causes major problems. Classification Morphology Ulcerative sarcoidosis is a cutaneous condition affecting roughly 5% of people with sarcoidosis.: 710 Annular sarcoidosis is a cutaneous condition characterized by papular skin lesions arranged in annular patterns, usually with a red-brown hue.: 709 Pattern Morpheaform sarcoidosis is a very rare cutaneous condition characterized by specific cutaneous skin lesions of sarcoidosis accompanied by substantial fibrosis, simulating morphea.: 711 Erythrodermic sarcoidosis is a cutaneous condition and very rare form of sarcoidosis.: 710 Hypopigmented sarcoidosis is a cutaneous condition characterized by areas of hypopigmented skin. It is usually diagnosed in darkly pigmented races and may be the earliest sign of sarcoidosis.: 709 Papular sarcoid is a cutaneous condition characterized by papules, which are the most common morphology of cutaneous sarcoidosis.: 708 Ichthyosiform sarcoidosis is a cutaneous condition resembling ichthyosis vulgaris or acquired ichthyosis, with fine scaling usually on the distal extremities, by caused by sarcoidosis.: 710 Location Subcutaneous sarcoidosis (also known as "Darier–Roussy disease" and "Darier-Roussy sarcoid") is a cutaneous condition characterized by numerous 0.5- to 0.3-cm deep-seated nodules on the trunk and extremities.: 710 Scar sarcoid (also known as "Sarcoidosis in scars") is a cutaneous condition characterized by infiltration and elevation of tattoos and old flat scars due to sarcoidosis.: 710 Mucosal sarcoidosis is a cutaneous condition characterized by pinhead-sized papules that may be grouped and fused together to form a flat plaque.: 711 Erythrodermic sarcoidosis is a cutaneous condition and very rare form of sarcoidosis.: 710 References == External links ==

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

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

A supernumerary kidney is an additional kidney to the number usually present in an organism. This often develops as the result of splitting of the nephrogenic blastema, or from separate metanephric blastemas into which partially or completely reduplicated ureteral stalks enter to form separate capsulated kidneys; in some cases the separation of the reduplicated organ is incomplete (fused supernumerary kidney). Less than a hundred cases are known of one or two supernumerary kidneys. See also Supernumerary body part References Luciano A. Favorito; Ana Raquel M. Morais (May–June 2012). "Evaluation of supernumerary kidney with fusion using magnetic resonance image". IBJU. 38 (3): 428–429. doi:10.1590/s1677-55382012000300018. PMID 22765860.

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

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

Pyrantel is a medication used to treat a number of parasitic worm infections. This includes ascariasis, hookworm infections, enterobiasis (pinworm infection), trichostrongyliasis, and trichinellosis. It is taken by mouth.Side effects include nausea, headache, dizziness, trouble sleeping, and rash. A lower dose should be used in people with liver disease. While it does not appear to be harmful during pregnancy, it has not been studied for this use. It is unclear if it is safe for use during breastfeeding. It is in the antihelmintic family of medications. It works by paralyzing worms.Pyrantel was initially described in 1965. It is on the World Health Organizations List of Essential Medicines. Pyrantel is available as a generic medication. It costs less than US$25 per course of treatment in the United States. It may also be used to treat worms in a number of other animals. Pregnancy and breastfeeding Pyrantel pamoate is considered a pregnancy category C drug for use during pregnancy for humans, but is in category A for canines and felines. Pyrantel is considered safe to use in nursing animals. Mechanism of action Pyrantel pamoate acts as a depolarizing neuromuscular blocking agent, thereby causing sudden contraction, followed by paralysis, of the helminths. This has the result of causing the worm to "lose its grip" on the intestinal wall and be passed out of the system by natural process. Since Pyrantel is poorly absorbed by the hosts intestine, the host is unaffected by the small dosage of medication used. Spastic (tetanic) paralyzing agents, in particular pyrantel pamoate, may induce complete intestinal obstruction in a heavy worm load. This obstruction is usually in the form of a worm impaction and happens when a very small, but heavily parasitized animal is treated and tries to pass a large number of dislodged worms at once. Worms usually pass in normal stool or with diarrhea, straining, and occasional vomiting. Names There are a number of brands, including "Reeses Pinworm Medicine", "Pin-X", "Pin-Rid","PYRANTRIN", "COMBANTRIN", "Anthel", "Helmintox", "Helmex", "Strongid" and Drontal Cat. References External links "Pyrantel". Drug Information Portal. U.S. National Library of Medicine.

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

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

Self-harm is intentional behavior that is considered harmful to oneself. This is most commonly regarded as direct injury of ones own skin tissues usually without a suicidal intention. Other terms such as cutting, self-injury and self-mutilation have been used for any self-harming behavior regardless of suicidal intent. It is not the same as masochism, as no sexual or nonsexual pleasure is obtained. The most common form of self-harm is using a sharp object to cut the skin. Other forms include scratching, hitting, or burning body parts. While earlier usage included interfering with wound healing, excessive skin-picking, hair-pulling, and the ingestion of toxins, current usage distinguishes these behaviors from self-harm. Likewise, tissue damage from drug abuse or eating disorders is not considered self-harm because it is ordinarily an unintended side-effect but context may be needed as intent for such acts varies.Although self-harm is by definition non-suicidal, it may still be life-threatening. People who do self-harm are more likely to die by suicide, and self-harm is found in 40–60% of suicides. Still, only a minority of self-harmers are suicidal.The desire to self-harm is a common symptom of some personality disorders. People with other mental disorders may also self-harm, including those with depression, anxiety disorders, substance abuse, mood disorders, eating disorders, post-traumatic stress disorder, schizophrenia, dissociative disorders and gender dysphoria. Studies also provide strong support for a self-punishment function, and modest evidence for anti-dissociation, interpersonal-influence, anti-suicide, sensation-seeking, and interpersonal boundaries functions. Self-harm can also occur in high-functioning individuals who have no underlying mental health diagnosis. The motivations for self-harm vary. Some use it as a coping mechanism to provide temporary relief of intense feelings such as anxiety, depression, stress, emotional numbness, or a sense of failure. Self-harm is often associated with a history of trauma, including emotional and sexual abuse. There are a number of different methods that can be used to treat self-harm and which concentrate on either treating the underlying causes or on treating the behavior itself. Other approaches involve avoidance techniques, which focus on keeping the individual occupied with other activities, or replacing the act of self-harm with safer methods that do not lead to permanent damage.Self-harm is most common between the ages of 12 and 24. Self-harm in childhood is relatively rare, but the rate has been increasing since the 1980s. Self-harm can also occur in the elderly population. The risk of serious injury and suicide is higher in older people who self-harm. Captive animals, such as birds and monkeys, are also known to participate in self-harming behavior. Classification Self-harm (SH), also referred to as self-injury (SI), self-inflicted violence (SIV), nonsuicidal self injury (NSSI) or self-injurious behavior (SIB), are different terms to ascribe behaviors where demonstrable injury is self-inflicted. The behavior involves deliberate tissue damage that is usually performed without suicidal intent. The most common form of self-harm involves cutting of the skin using a sharp object, e. g. a knife or razor blade. The term self-mutilation is also sometimes used, although this phrase evokes connotations that some find worrisome, inaccurate, or offensive. Self-inflicted wounds is a specific term associated with soldiers to describe non-lethal injuries inflicted in order to obtain early dismissal from combat. This differs from the common definition of self-harm, as damage is inflicted for a specific secondary purpose. A broader definition of self-harm might also include those who inflict harm on their bodies by means of disordered eating.The older literature has used several different terms. For this reason research in the past decades has inconsistently focused on self-harming behavior without and with suicidal intent (including suicide attempts) with varying definitions leading to inconsistent and unclear results.Nonsuicidal self-injury (NSSI) has been listed in section 2 of the DSM-5-TR under the category "other conditions that may be a focus of clinical attention". While NSSI is not a separate mental disorder, the DSM-5-TR adds a diagnostic code for the condition in-line with the ICD. The disorder is defined as intentional self-inflicted injury without the intent of dying by suicide. Criteria for NSSI include five or more days of self-inflicted harm over the course of one year without suicidal intent, and the individual must have been motivated by seeking relief from a negative state, resolving an interpersonal difficulty, or achieving a positive state.A common belief regarding self-harm is that it is an attention-seeking behavior; however, in many cases, this is inaccurate. Many self-harmers are very self-conscious of their wounds and scars and feel guilty about their behavior, leading them to go to great lengths to conceal their behavior from others. They may offer alternative explanations for their injuries, or conceal their scars with clothing. Self-harm in such individuals may not be associated with suicidal or para-suicidal behavior. People who self-harm are not usually seeking to end their own life; it has been suggested instead that they are using self-harm as a coping mechanism to relieve emotional pain or discomfort or as an attempt to communicate distress.Studies of individuals with developmental disabilities (such as intellectual disability) have shown self-harm being dependent on environmental factors such as obtaining attention or escape from demands. Some individuals may have dissociation harboring a desire to feel real or to fit into societys rules. Signs and symptoms Eighty percent of self-harm involves stabbing or cutting the skin with a sharp object, sometimes breaking through the skin entirely. However, the number of self-harm methods are only limited by an individuals inventiveness and their determination to harm themselves; this includes burning, self-poisoning, alcohol abuse, self-embedding of objects, hair pulling, bruising/hitting ones self, scratching to hurt ones self, knowingly abusing over-the-counter or prescription drugs, and forms of self-harm related to anorexia and bulimia. The locations of self-harm are often areas of the body that are easily hidden and concealed from the detection of others. As well as defining self-harm in terms of the act of damaging the body, it may be more accurate to define self-harm in terms of the intent, and the emotional distress that the person is attempting to deal with. Neither the DSM-IV-TR nor the ICD-10 provide diagnostic criteria for self-harm. It is often seen as only a symptom of an underlying disorder, though many people who self-harm would like this to be addressed. Common signs that a person may be engaging in self-harm include the following: they ensure that there are always harmful objects close by, they are experiencing difficulties in their personal relationships, their behavior becomes unpredictable, they question their worth and identity, they make statements that display helplessness and hopelessness. Cause Mental disorder Although some people who self-harm do not have any form of recognized mental disorder, many people experiencing various forms of mental illnesses do have a higher risk of self-harm. The key areas of disorder which exhibit an increased risk include autism spectrum disorders, borderline personality disorder, dissociative disorders, bipolar disorder, depression, phobias, and conduct disorders. As many as 70% of individuals with borderline personality disorder engage in self-harm. An estimated 30% of individuals with autism spectrum disorders engage in self-harm at some point, including eye-poking, skin-picking, hand-biting, and head-banging. Schizophrenia may also be a contributing factor for self-harm. Those diagnosed with schizophrenia have a high risk of suicide, which is particularly greater in younger patients as they may not have an insight into the serious effects that the disorder can have on their lives. There are parallels between self-harm and Münchausen syndrome, a psychiatric disorder in which individuals feign illness or trauma. There may be a common ground of inner distress culminating in self-directed harm in a Münchausen patient. However, a desire to deceive medical personnel in order to gain treatment and attention is more important in Münchausens than in self-harm. Psychological factors Self-harm is frequently described as an experience of depersonalization or a dissociative state. Abuse during childhood is accepted as a primary social factor increasing the incidence of self-harm, as is bereavement, and troubled parental or partner relationships. Factors such as war, poverty, unemployment, and substance abuse may also contribute. Other predictors of self-harm and suicidal behavior include feelings of entrapment, defeat, lack of belonging, and perceiving oneself as a burden along with having an impulsive personality and/or less effective social problem-solving skills. The onset of puberty, including the onset of sexual activity, often correlates with the onset of self-harm; this is because the pubertal period is associated with neurodevelopmental vulnerability and comes with an increased risk of emotional disorders and risk-taking behaviors. Transgender adolescents are significantly more likely to engage in self-harm than their cisgender peers. This can be attributed to distress caused by gender dysphoria as well as increased likelihoods of experiencing bullying, abuse, and mental illness. Genetics The most distinctive characteristic of the rare genetic condition, Lesch–Nyhan syndrome, is self-harm and may include biting and head-banging. Genetics may contribute to the risk of developing other psychological conditions, such as anxiety or depression, which could in turn lead to self-harming behavior. However, the link between genetics and self-harm in otherwise healthy patients is largely inconclusive. Drugs and alcohol Substance misuse, dependence and withdrawal are associated with self-harm. Benzodiazepine dependence as well as benzodiazepine withdrawal is associated with self-harming behavior in young people. Alcohol is a major risk factor for self-harm. A study which analysed self-harm presentations to emergency rooms in Northern Ireland found that alcohol was a major contributing factor and involved in 63.8% of self-harm presentations. A recent study in the relation between cannabis use and deliberate self-harm (DSH) in Norway and England found that, in general, cannabis use may not be a specific risk factor for DSH in young adolescents. Smoking has also been associated with self-harm in adolescents; one study found that suicide attempts were four times higher for adolescents that smoke than for those that do not. A more recent meta-analysis on literature concerning the association between cannabis use and self-injurious behaviors has defined the extent of this association, which is significant both at the cross-sectional (odds ratio = 1.569, 95% confidence interval [1.167-2.108]) and longitudinal (odds ratio = 2.569, 95% confidence interval [2.207-3.256]) levels, and highlighting the role of the chronic use of the substance, and the presence of depressive symptoms or of mental disorders as factors that might increase the risk of self-injury among cannabis users. Pathophysiology Self-harm is not typically suicidal behavior, although there is the possibility that a self-inflicted injury may result in life-threatening damage. Although the person may not recognise the connection, self-harm often becomes a response to profound and overwhelming emotional pain that cannot be resolved in a more functional way.The motivations for self-harm vary, as it may be used to fulfill a number of different functions. These functions include self-harm being used as a coping mechanism which provides temporary relief of intense feelings such as anxiety, depression, stress, emotional numbness and a sense of failure or self-loathing. There is also a positive statistical correlation between self-harm and emotional abuse. Self-harm may become a means of managing and controlling pain, in contrast to the pain experienced earlier in the persons life over which they had no control (e.g., through abuse).Other motives for self-harm do not fit into medicalized models of behavior and may seem incomprehensible to others, as demonstrated by this quotation: "My motivations for self-harming were diverse, but included examining the interior of my arms for hydraulic lines. This may sound strange."Assessment of motives in a medical setting is usually based on precursors to the incident, circumstances, and information from the patient. However, limited studies show that professional assessments tend to suggest more manipulative or punitive motives than personal assessments.A UK Office for National Statistics study reported only two motives: "to draw attention" and "because of anger". For some people, harming themselves can be a means of drawing attention to the need for help and to ask for assistance in an indirect way. It may also be an attempt to affect others and to manipulate them in some way emotionally. However, those with chronic, repetitive self-harm often do not want attention and hide their scars carefully.Many people who self-harm state that it allows them to "go away" or dissociate, separating the mind from feelings that are causing anguish. This may be achieved by tricking the mind into believing that the present suffering being felt is caused by the self-harm instead of the issues they were facing previously: the physical pain therefore acts as a distraction from the original emotional pain. To complement this theory, one can consider the need to "stop" feeling emotional pain and mental agitation. "A person may be hyper-sensitive and overwhelmed; a great many thoughts may be revolving within their mind, and they may either become triggered or could make a decision to stop the overwhelming feelings."Alternatively, self-harm may be a means of feeling something, even if the sensation is unpleasant and painful. Those who self-harm sometimes describe feelings of emptiness or numbness (anhedonia), and physical pain may be a relief from these feelings. "A person may be detached from themselves, detached from life, numb and unfeeling. They may then recognise the need to function more, or have a desire to feel real again, and a decision is made to create sensation and wake up."Those who engage in self-harm face the contradictory reality of harming themselves while at the same time obtaining relief from this act. It may even be hard for some to actually initiate cutting, but they often do because they know the relief that will follow. For some self-harmers this relief is primarily psychological while for others this feeling of relief comes from the beta endorphins released in the brain. Endorphins are endogenous opioids that are released in response to physical injury, acting as natural painkillers and inducing pleasant feelings, and in response to self-harm would act to reduce tension and emotional distress. Many self-harmers report feeling very little to no pain while self-harming and, for some, deliberate self-harm may become a means of seeking pleasure. As a coping mechanism, self-harm can become psychologically addictive because, to the self-harmer, it works; it enables them to deal with intense stress in the current moment. The patterns sometimes created by it, such as specific time intervals between acts of self-harm, can also create a behavioral pattern that can result in a wanting or craving to fulfill thoughts of self-harm. Autonomic nervous system Emotional pain activates the same regions of the brain as physical pain, so emotional stress can be a significantly intolerable state for some people. Some of this is environmental and some of this is due to physiological differences in responding. The autonomic nervous system is composed of two components: the sympathetic nervous system controls arousal and physical activation (e.g., the fight-or-flight response) and the parasympathetic nervous system controls physical processes that are automatic (e.g., saliva production). The sympathetic nervous system innervates (e.g., is physically connected to and regulates) many parts of the body involved in stress responses. Studies of adolescents have shown that adolescents who self-injure have greater physiological reactivity (e.g., skin conductance) to stress than adolescents who do not self-injure. This stress response persists over time, staying constant or even increasing in self-injuring adolescents, but gradually decreases in adolescents who do not self-injure. Treatment Several forms of psychosocial treatments can be used in self-harm including dialectical behavior therapy. Psychiatric and personality disorders are common in individuals who self-harm and as a result self-harm may be an indicator of depression and/or other psychological problems. Many people who self-harm have moderate or severe depression and therefore treatment with antidepressant medications may often be used. There is tentative evidence for the medication flupentixol; however, greater study is required before it can be recommended. Therapy Dialectical behavior therapy for adolescents (DBT-A) is a well-established treatment for self-injurious behavior in youth and probably useful for decreasing the risk of non suicidal self injury. Several other treatments including integrated CBT (I-CBT), attachment-based family therapy (ABFT), resourceful adolescent parent program (RAP-P), intensive interpersonal psychotherapy for adolescents (IPT-A-IN), mentalization-based treatment for adolescents (MBT-A), and integrated family therapy are probably efficacious. Cognitive behavioral therapy may also be used to assist those with Axis I diagnoses, such as depression, schizophrenia, and bipolar disorder. Dialectical behavior therapy (DBT) can be successful for those individuals exhibiting a personality disorder, and could potentially be used for those with other mental disorders who exhibit self-harming behavior. Diagnosis and treatment of the causes of self-harm is thought by many to be the best approach to treating self-harm. But in some cases, particularly in people with a personality disorder, this is not very effective, so more clinicians are starting to take a DBT approach in order to reduce the behavior itself. People who rely on habitual self-harm are sometimes hospitalized, based on their stability, their ability and especially their willingness to get help. In adolescents multisystem therapy shows promise. Pharmacotherapy has not been tested as a treatment for adolescents who self-harmed.A meta-analysis found that psychological therapy is effective in reducing self-harm. The proportion of the adolescents who self-harmed over the follow-up period was lower in the intervention groups (28%) than in controls (33%). Psychological therapies with the largest effect sizes were dialectical behavior therapy (DBT), cognitive-behavioral therapy (CBT), and mentalization-based therapy (MBT).In individuals with developmental disabilities, occurrence of self-harm is often demonstrated to be related to its effects on the environment, such as obtaining attention or desired materials or escaping demands. As developmentally disabled individuals often have communication or social deficits, self-harm may be their way of obtaining these things which they are otherwise unable to obtain in a socially appropriate way (such as by asking). One approach for treating self-harm thus is to teach an alternative, appropriate response which obtains the same result as the self-harm. Avoidance techniques Generating alternative behaviors that the person can engage in instead of self-harm is one successful behavioral method that is employed to avoid self-harm. Techniques, aimed at keeping busy, may include journaling, taking a walk, participating in sports or exercise or being around friends when the person has the urge to harm themselves. The removal of objects used for self-harm from easy reach is also helpful for resisting self-harming urges. The provision of a card that allows the person to make emergency contact with counselling services should the urge to self-harm arise may also help prevent the act of self-harm. Alternative and safer methods of self-harm that do not lead to permanent damage, for example the snapping of a rubber band on the wrist, may also help calm the urge to self-harm. Using biofeedback may help raise self-awareness of certain pre-occupations or particular mental state or mood that precede bouts of self-harming behavior, and help identify techniques to avoid those pre-occupations before they lead to self-harm. Any avoidance or coping strategy must be appropriate to the individuals motivation and reason for harming. Epidemiology It is difficult to gain an accurate picture of incidence and prevalence of self-harm. This is due in a part to a lack of sufficient numbers of dedicated research centres to provide a continuous monitoring system. However, even with sufficient resources, statistical estimates are crude since most incidences of self-harm are undisclosed to the medical profession as acts of self-harm are frequently carried out in secret, and wounds may be superficial and easily treated by the individual. Recorded figures can be based on three sources: psychiatric samples, hospital admissions and general population surveys.The World Health Organization estimates that, as of 2010, 880,000 deaths occur as a result of self-harm. About 10% of admissions to medical wards in the UK are as a result of self-harm, the majority of which are drug overdoses. However, studies based only on hospital admissions may hide the larger group of self-harmers who do not need or seek hospital treatment for their injuries, instead treating themselves. Many adolescents who present to general hospitals with deliberate self-harm report previous episodes for which they did not receive medical attention. In the United States up to 4% of adults self-harm with approximately 1% of the population engaging in chronic or severe self-harm.Current research suggests that the rates of self-harm are much higher among young people with the average age of onset between 14 and 24. The earliest reported incidents of self-harm are in children between 5 and 7 years old. In the UK in 2008 rates of self-harm in young people could be as high as 33%. In addition there appears to be an increased risk of self-harm in college students than among the general population. In a study of undergraduate students in the US, 9.8% of the students surveyed indicated that they had purposefully cut or burned themselves on at least one occasion in the past. When the definition of self-harm was expanded to include head-banging, scratching oneself, and hitting oneself along with cutting and burning, 32% of the sample said they had done this. In Ireland, a study found that instances of hospital-treated self-harm were much higher in city and urban districts, than in rural settings. The CASE (Child & Adolescent Self-harm in Europe) study suggests that the life-time risk of self-injury is ~1:7 for women and ~1:25 for men. Gender differences In general, the latest aggregated research has found no difference in the prevalence of self-harm between men and women. This is in contrast to past research which indicated that up to four times as many females as males have direct experience of self-harm. However, caution is needed in seeing self-harm as a greater problem for females, since males may engage in different forms of self-harm (e.g., hitting themselves) which could be easier to hide or explained as the result of different circumstances. Hence, there remain widely opposing views as to whether the gender paradox is a real phenomenon, or merely the artifact of bias in data collection.The WHO/EURO Multicentre Study of Suicide, established in 1989, demonstrated that, for each age group, the female rate of self-harm exceeded that of the males, with the highest rate among females in the 13–24 age group and the highest rate among males in the 12–34 age group. However, this discrepancy has been known to vary significantly depending upon population and methodological criteria, consistent with wide-ranging uncertainties in gathering and interpreting data regarding rates of self-harm in general. Such problems have sometimes been the focus of criticism in the context of broader psychosocial interpretation. For example, feminist author Barbara Brickman has speculated that reported gender differences in rates of self-harm are due to deliberate socially biased methodological and sampling errors, directly blaming medical discourse for pathologising the female.This gender discrepancy is often distorted in specific populations where rates of self-harm are inordinately high, which may have implications on the significance and interpretation of psychosocial factors other than gender. A study in 2003 found an extremely high prevalence of self-harm among 428 homeless and runaway youths (aged 16–19) with 72% of males and 66% of females reporting a history of self-harm. However, in 2008, a study of young people and self-harm saw the gender gap widen in the opposite direction, with 32% of young females, and 22% of young males admitting to self-harm. Studies also indicate that males who self-harm may also be at a greater risk of completing suicide.There does not appear to be a difference in motivation for self-harm in adolescent males and females. Triggering factors such as low self-esteem and having friends and family members who self-harm are also common between both males and females. One limited study found that, among those young individuals who do self-harm, both genders are just as equally likely to use the method of skin-cutting. However, females who self-cut are more likely than males to explain their self-harm episode by saying that they had wanted to punish themselves. In New Zealand, more females are hospitalized for intentional self-harm than males. Females more commonly choose methods such as self-poisoning that generally are not fatal, but still serious enough to require hospitalization. Elderly In a study of a district general hospital in the UK, 5.4% of all the hospitals self-harm cases were aged over 65. The male to female ratio was 2:3 although the self-harm rates for males and females over 65 in the local population were identical. Over 90% had depressive conditions, and 63% had significant physical illness. Under 10% of the patients gave a history of earlier self-harm, while both the repetition and suicide rates were very low, which could be explained by the absence of factors known to be associated with repetition, such as personality disorder and alcohol abuse. However, NICE Guidance on Self-harm in the UK suggests that older people who self-harm are at a greater risk of completing suicide, with 1 in 5 older people who self-harm going on to end their life. A study completed in Ireland showed that older Irish adults have high rates of deliberate self-harm, but comparatively low rates of suicide. Developing world Only recently have attempts to improve health in the developing world concentrated on not only physical illness but also mental health. Deliberate self-harm is common in the developing world. Research into self-harm in the developing world is however still very limited although an important case study is that of Sri Lanka, which is a country exhibiting a high incidence of suicide and self-poisoning with agricultural pesticides or natural poisons. Many people admitted for deliberate self-poisoning during a study by Eddleston et al. were young and few expressed a desire to die, but death was relatively common in the young in these cases. The improvement of medical management of acute poisoning in the developing world is poor and improvements are required in order to reduce mortality. Some of the causes of deliberate self-poisoning in Sri Lankan adolescents included bereavement and harsh discipline by parents. The coping mechanisms are being spread in local communities as people are surrounded by others who have previously deliberately harmed themselves or attempted suicide. One way of reducing self-harm would be to limit access to poisons; however many cases involve pesticides or yellow oleander seeds, and the reduction of access to these agents would be difficult. Great potential for the reduction of self-harm lies in education and prevention, but limited resources in the developing world make these methods challenging. Prison inmates Deliberate self-harm is especially prevalent in prison populations. A proposed explanation for this is that prisons are often violent places, and prisoners who wish to avoid physical confrontations may resort to self-harm as a ruse, either to convince other prisoners that they are dangerously insane and resilient to pain or to obtain protection from the prison authorities. Self-harm also occurs frequently in inmates who are placed in solitary confinement. History Self-harm was, and in some cases continues to be, a ritual practice in many cultures and religions. The Maya priesthood performed auto-sacrifice by cutting and piercing their bodies in order to draw blood. A reference to the priests of Baal "cutting themselves with blades until blood flowed" can be found in the Hebrew Bible. However, in Judaism, such self-harm is forbidden under Mosaic law. It occurred in ancient Canaanite mourning rituals, as described in the Ras Shamra tablets. Self-harm is practized in Hinduism by the ascetics known as sadhus. In Catholicism it is known as mortification of the flesh. Some branches of Islam mark the Day of Ashura, the commemoration of the martyrdom of Imam Hussein, with a ritual of self-flagellation, using chains and swords.Dueling scars such as those acquired through academic fencing at certain traditional German universities are an early example of scarification in European society. Sometimes, students who did not fence would scar themselves with razors in imitation.Constance Lytton, a prominent suffragette, used a stint in Holloway Prison during March 1909 to mutilate her body. Her plan was to carve Votes for Women from her breast to her cheek, so that it would always be visible. But after completing the V on her breast and ribs she requested sterile dressings to avoid blood poisoning, and her plan was aborted by the authorities. She wrote of this in her memoir Prisons and Prisoners. Kikuyu girls cut each others vulvas in the 1950s as a symbol of defiance, in the context of the campaign against female genital mutilation in colonial Kenya. The movement came to be known as Ngaitana ("I will circumcise myself"), because to avoid naming their friends the girls said they had cut themselves. Historian Lynn Thomas described the episode as significant in the history of FGM because it made clear that its victims were also its perpetrators. Classification The term "self-mutilation" occurred in a study by L. E. Emerson in 1913 where he considered self-cutting a symbolic substitution for masturbation. The term reappeared in an article in 1935 and a book in 1938 when Karl Menninger refined his conceptual definitions of self-mutilation. His study on self-destructiveness differentiated between suicidal behaviors and self-mutilation. For Menninger, self-mutilation was a non-fatal expression of an attenuated death wish and thus coined the term partial suicide. He began a classification system of six types: neurotic – nail-biters, pickers, extreme hair removal and unnecessary cosmetic surgery. religious – self-flagellants and others. puberty rites – hymen removal, circumcision or clitoral alteration. psychotic – eye or ear removal, genital self-mutilation and extreme amputation organic brain diseases – which allow repetitive head-banging, hand-biting, finger-fracturing or eye removal. conventional – nail-clipping, trimming of hair and shaving beards.Pao (1969) differentiated between delicate (low lethality) and coarse (high lethality) self-mutilators who cut. The "delicate" cutters were young, multiple episodic of superficial cuts and generally had borderline personality disorder diagnosis. The "coarse" cutters were older and generally psychotic. Ross and McKay (1979) categorized self-mutilators into 9 groups: cutting, biting, abrading, severing, inserting, burning, ingesting or inhaling, hitting, and constricting.After the 1970s the focus of self-harm shifted from Freudian psycho-sexual drives of the patients.Walsh and Rosen (1988) created four categories numbered by Roman numerals I–IV, defining Self-mutilation as rows II, III and IV. Favazza and Rosenthal (1993) reviewed hundreds of studies and divided self-mutilation into two categories: culturally sanctioned self-mutilation and deviant self-mutilation. Favazza also created two subcategories of sanctioned self-mutilations; rituals and practices. The rituals are mutilations repeated generationally and "reflect the traditions, symbolism, and beliefs of a society" (p. 226). Practices are historically transient and cosmetic such as piercing of earlobes, nose, eyebrows as well as male circumcision (for non-Jews) while Deviant self-mutilation is equivalent to self-harm. Awareness and opposition There are many movements among the general self-harm community to make self-harm itself and treatment better known to mental health professionals, as well as the general public. For example, March 1 is designated as Self-injury Awareness Day (SIAD) around the world. On this day, some people choose to be more open about their own self-harm, and awareness organizations make special efforts to raise awareness about self-harm. Other animals Self-harm in non-human mammals is a well-established but not widely known phenomenon. Its study under zoo or laboratory conditions could lead to a better understanding of self-harm in human patients.Zoo or laboratory rearing and isolation are important factors leading to increased susceptibility to self-harm in higher mammals, e.g., macaque monkeys. Non-primate mammals are also known to mutilate themselves under laboratory conditions after administration of drugs. For example, pemoline, clonidine, amphetamine, and very high (toxic) doses of caffeine or theophylline are known to precipitate self-harm in lab animals.In dogs, canine obsessive-compulsive disorder can lead to self-inflicted injuries, for example canine lick granuloma. Captive birds are sometimes known to engage in feather-plucking, causing damage to feathers that can range from feather shredding to the removal of most or all feathers within the birds reach, or even the mutilation of skin or muscle tissue.Breeders of show mice have noticed similar behaviors. One known as "barbering" involves a mouse obsessively grooming the whiskers and facial fur off of themselves and cage-mates. See also Self-destructive behavior Self-hatred Self-Injurious Behavior Inhibiting System References External links Information about self-harm from the Royal College of Psychiatrists

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

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

A varicocele is an abnormal enlargement of the pampiniform venous plexus in the scrotum. This plexus of veins drains blood from the testicles back to the heart. The vessels originate in the abdomen and course down through the inguinal canal as part of the spermatic cord on their way to the testis. Varicoceles occur in around 15% to 20% of all men. The incidence of varicocele increase with age. Signs and symptoms Varicocele might be noticed as soft lumps, usually above the testicle and mostly on the left side of the scrotum. Right-sided and bilateral varicocele does also occur. Men with varicocele can feel symptoms of pain or heaviness in their scrotum. Large varicoceles present as plexus of veins and may be described as "bag of worms". Varicocele is sometimes discovered when investigating the cause of male infertility. Cause There are three main theories as to the anatomical cause; the first has to do with the geometry of the veins, wherein the vein on the left side connects to the larger outflowing vein at a right angle, which tends to fail; the second is that valves that are supposed to prevent backflow fail (venous insufficiency); the third is due to excessive pressure in upstream arteries, created by nutcracker syndrome. Pathophysiology Often the greatest concern with respect to varicocele is its effect on male fertility. The relationship between varicocele and infertility is unclear. Some men with the condition are fertile, some have sperm that are normal in shape and move normally but are compromised in function, and some have sperm with abnormal shapes or that do not move well. Theories as to how varicocele affects sperm function include damage via excess heat caused by the blood pooling and oxidative stress on sperm.Tobacco smoking and mutations in the gene expressing glutathione S-transferase Mu 1 both put men at risk for infertility; these factors may also exacerbate the risk that varicocele will affect fertility. Diagnosis Following discovery of the sign of swelling comprising a mass, varicocele can be confirmed with scrotal ultrasound, which will show dilation of the vessels of the pampiniform plexus to be greater than 2 mm. Imaging Manual examination of scrotum is required for proper interpretation of ultrasound images. During ultrasound examination, diameters of veins in pampiniform plexus are measured and regurgitation is measured. The subject is then instructed to stand up and Valsalva maneuver is performed. The diameter is then measured and changes in blood flow direction is recorded to assess any regurgitation. Treatment The two most common surgical approaches are retroperitoneal (abdominal using laparoscopic surgery), infrainguinal/subinguinal (below the groin) and inguinal (groin using percutaneous embolization). Possible complications of this procedure include hematoma (bleeding into tissues), hydrocele (accumulation of fluid around the affected testicle), infection, or injury to the scrotal tissue or structures. In addition, injury to the artery that supplies the testicle may occur, resulting in a loss of a testicle. Prognosis Whether having varicocele surgery or embolization improves male fertility is controversial, as good clinical data is lacking. There is tentative evidence that varicocelectomy may improve fertility in those with obvious findings and abnormal sperm; however, this has a number needed to treat of 7 for varicocelectomy and 17 for embolization. There are also studies showing that the regular surgery has no significant effect on infertility. A 2012 Cochrane review (updated in 2021) found tentative but unclear evidence of improved fertility among males treated for varicocele. Evidence for sclerotherapy is unclear as of 2015. Epidemiology Around 15% to 20% of all adult males, up to 35% to 40% of men who are evaluated for male infertility, and around 80% of men who are infertile due to some other cause, have varicocele. == References ==

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

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

Nephrogenic diabetes insipidus, also known as renal diabetes insipidus, is a form of diabetes insipidus primarily due to pathology of the kidney. This is in contrast to central or neurogenic diabetes insipidus, which is caused by insufficient levels of antidiuretic hormone (also called vasopressin). Nephrogenic diabetes insipidus is caused by an improper response of the kidney to antidiuretic hormone, leading to a decrease in the ability of the kidney to concentrate the urine by removing free water. Signs and symptoms The clinical manifestation is similar to neurogenic diabetes insipidus, presenting with polydipsia (excessive thirst) and polyuria (excretion of a large amount of dilute urine). Dehydration is common, and incontinence can occur secondary to chronic bladder distension. On investigation, there will be an increased plasma osmolarity and decreased urine osmolarity. As pituitary function is normal, antidiuretic hormone levels are likely to be abnormal or raised. Polyuria will continue as long as the patient is able to drink. If the patient is unable to drink and is still unable to concentrate the urine, then hypernatremia will ensue with its neurologic symptoms. Causes Acquired Nephrogenic diabetes insipidus is most common in its acquired forms, meaning that the defect was not present at birth. These acquired forms have numerous potential causes. The most obvious cause is a kidney or systemic disorder, including amyloidosis, polycystic kidney disease, electrolyte imbalance, or some other kidney defect.The major causes of acquired nephrogenic diabetes insipidus that produce clinical symptoms (e.g., polyuria) in the adult are lithium toxicity and high blood calcium. About 80% of lithium ingested appears to affect the proximal tubules by entering the collecting tubule cells through sodium channels, accumulating and interfering with the normal response to antidiuretic hormone in a mechanism that is not yet fully understood. High blood calcium causes natriuresis (increased sodium loss in the urine) and water diuresis, in part by its effect through the calcium-sensing receptor. Osmotic Other causes of acquired nephrogenic diabetes insipidus include hypokalemia (low blood potassium), post-obstructive polyuria, sickle cell disease or trait, amyloidosis, Sjögren syndrome, renal cystic disease, Bartter syndrome, and various medications (amphotericin B, orlistat, ifosfamide, ofloxacin, cidofovir, vaptans).In addition to kidney and systemic disorders, nephrogenic diabetes insipidus can present itself as a side effect of some medications. The most common and well known of these medications is lithium, although there are many other medications that cause this effect with lesser frequency. Hereditary This form of diabetes insipidus can also be hereditary due to defects in the following genes: Diagnosis Differential diagnosis includes nephrogenic diabetes insipidus, neurogenic/central diabetes insipidus and psychogenic polydipsia. They may be differentiated by using the water deprivation test. Recently, lab assays for antidiuretic hormone are available and can aid in diagnosis. If able to rehydrate properly, sodium concentration should be nearer to the maximum of the normal range. This, however, is not a diagnostic finding, as it depends on patient hydration.Desmopressin can also be used; if the patient is able to concentrate urine following administration of desmopressin, then the cause of the diabetes insipidus is neurogenic diabetes insipidus; if no response occurs to desmopressin, then the cause is likely to be nephrogenic. Treatment Persons with nephrogenic diabetes insipidus will need to consume enough fluids to equal the amount of urine produced. Any underlying cause such as high blood calcium must be corrected to treat nephrogenic diabetes insipidus. The first line of treatment is hydrochlorothiazide and amiloride. Patients may also consider a low-salt and low-protein diet.Thiazide diuretics are used in treatment because diabetes insipidus causes the excretion of more sodium than water, while maintaining the corticomedullary gradient (not maintained when using loop diuretics). The maintained corticomedullary gradient allows more absorption of water in the collecting duct. This improves the blood osmolarity and prevents hypernatremia.High serum osmolarity stimulates polydipsia in an attempt to dilute the serum back to normal and provide free water for excreting the excess serum solutes. However, since the patient is unable to concentrate urine to excrete the excess solutes, the resulting urine fails to decrease serum osmolarity and the cycle repeats itself, hence polyuria. Etymology The name of the disease comes from: diabetes: from Latin: diabetes, from Ancient Greek: διαβήτης diabḗtēs "a passer-through; siphon", from Greek διαβαίνειν diabaínein "to pass through", from δια- dia- "through" + βαίνειν baínein "to go". insipidus: from Late Latin: insipidus "tasteless," from Latin in- "not" + sapidus "tasty", from sapere "to taste".This is because patients experience polyuria (an excretion of over 2.5 liters of urine per day), and the urine does not have an elevated glucose concentration, as opposed to diabetes mellitus. The two diseases were named (in ancient times) for the fact that one features polyuria in which the urine tastes sweet, whereas the other features polyuria in which the urine tastes unremarkable.Although they share part of their names, diabetes mellitus and diabetes insipidus are two separate conditions. Both cause excessive urination (hence the similarity in name), but whereas diabetes insipidus is a problem with the production of antidiuretic hormone (neurogenic diabetes insipidus) or the kidneys response to antidiuretic hormone (nephrogenic diabetes insipidus), diabetes mellitus causes polyuria via osmotic diuresis, due to the high blood sugar leaking into the urine, taking excess water along with it. References == External links ==

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

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

Polioencephalitis is a viral infection of the brain, causing inflammation within the grey matter of the brain stem. The virus has an affinity for neuronal cell bodies and has been found to affect mostly the midbrain, pons, medulla and cerebellum of most infected patients. The infection can reach up through the thalamus and hypothalamus and possibly reach the cerebral hemispheres. The infection is caused by the poliomyelitis virus which is a single-stranded, positive sense RNA virus surrounded by a non-enveloped capsid. Humans are the only known natural hosts of this virus. The disease has been eliminated from the U.S. since the mid-twentieth century, but is still found in certain areas of the world such as Africa. Signs and symptoms Signs and symptoms may vary and some individuals may not experience any symptoms at all. The most common reported symptom of polioencephalitis is fatigue. Fatigue is associated with difficulty in attention, cognition, and maintaining wakefulness Some individuals experience psychiatric symptoms that include anxious mood, pain, insomnia, and depressed mood. Confusion and disorientation of time and space have also been reported. Motor symptoms vary more from patient to patient, but can include incoordination and tremors, nystagmus, loss of conjugate eye movements, rigidity and hemiparesis. Mechanism The poliomyelitis virus is an enterovirus that enters through the mouth and multiplies in the throat and epithelial cells of the gastrointestinal tract. It will then move to the bloodstream and is carried to the central nervous system. Once in the CNS, the virus will attach to a host cell by binding with a cell surface receptor. The host cell surface receptor is a glycoprotein that has been recently identified as CD155. Once the virus has bound to the host cell, it will penetrate the host cell membrane and begin the replication of its genome. Many cells contain the surface receptor CD155; however, manifestation of this disease does not occur in all cells. The reason for incidence of the disease in only certain areas of the brain such as the brainstem is unknown. Once areas of the brain have been invaded by the virus, inflammation will occur. During inflammation, the brain’s tissues become swollen due to the body’s immune system response to the infection. Fluid, white blood cells, dead cellular debris and inactivated viruses resulting from the actions of the immune response can significantly alter the fluid surrounding healthy neurons. The function of these healthy neurons can decline due to disruptions in the cell membrane affecting electrical properties of the neuron or by interfering with the blood supply causing anoxic cellular damage. Depending on which neurons are damaged will result in a variety of different symptoms. Diagnosis If someone is suspected of having polioencephalitis a sample of throat secretions, stool or cerebrospinal fluid is checked for the virus. Blood tests can be done to detect antibodies against viral antigens and foreign proteins. Virus isolation is the most sensitive method and it is most likely to be isolated from stool samples. Once isolated, RT-PCR is used to differentiate naturally occurring strains from vaccine-like strains. Prevention The virus is most often spread by person to person contact with the stool or saliva of the infected person. Two types of vaccines have been developed to prevent the occurrence and spread of the poliomyelitis virus. The first is an inactivated, or killed, form of the virus and the second is an attenuated, or weakened, form of the virus. The development of vaccines has successfully eliminated the disease from the United States. There are continued vaccination efforts in the U.S. to maintain this success rate as this disease still occurs in some areas of the world. Treatment There is no cure for polioencephalitis so prevention is essential. Many people that become infected will not develop symptoms and their prognosis is excellent. However, the prognosis is dependent on the amount of cellular damage done by the virus and the area of the brain affected. Many people that develop more severe symptoms can have lifelong disabilities or it can lead to death. Supportive treatments include bed rest, pain relievers, and a nutritious diet. Many drugs have been used to treat psychiatric symptoms such as Clonazepam for insomnia and Desvenlafaxine or Citalopram for depressed mood. Recent research Research into the mechanism of this disease stalled with the development of the vaccines in the mid-twentieth century. However, with the recent identification of the cell surface receptor CD155 new interest has resurfaced in this disease. Experiments on transgenic mice are investigating the initial sites of viral replication in the host and how the virus moves from the bloodstream into the central nervous system. Research into the host range of the virus has also been of interest. The host range of a virus is determined by the interaction of the virus with host cellular receptors such as CD155. Comparison of the amino acid sequence in the binding domain of the host cell receptor is highly variable among mammalian species. Rapid changes in the sequence of the binding domain have restricted the host range of the poliovirus. Targeting of the brain and spinal cord have also come under investigation. The restricted tropism maybe due to organ specific differences in the initiation of translation by the virus internal ribosome entry site. == References ==

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

What is the significance of the term 'Mesenteric cyst' in the medical field?

A mesenteric cyst (MeSH C04.182.473) is a cyst in the mesenterium, and is one of the rarest abdominal tumors, with approximately 822 cases reported since 1507. The incidence is between 1 per 100,000 to 1 per 250,000 hospital admissions.Tillauxs triad named after the French surgeon Paul Jules Tillaux can be seen in cases of mesenteric cyst. It consists of the following signs: a fluctuating swelling near the umbilicus, freely mobile in the direction perpendicular to the attachment of mesentry, with a zone of resonance around the swelling.It is basically of two types : 1. Chylolymphatic most common type, thin wall, lined by flat endotheliun, clear chylous fluid present, separate blood vessels 2. Enterogenous-thick wall, lined by columnar, mucinous fluid present common blood supply == References ==

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

What does the medical term 'Tenecteplase' encompass?

Tenecteplase, sold under the trade names TNKase, Metalyse and Elaxim, is an enzyme used as a thrombolytic drug. Tenecteplase is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established mammalian cell line (Chinese hamster ovary cells). Tenecteplase is a 527 amino acid glycoprotein developed by introducing the following modifications to the complementary DNA (cDNA) for natural human tPA: a substitution of threonine 103 with asparagine, and a substitution of asparagine 117 with glutamine, both within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296–299 in the protease domain. Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and selectively converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor (PAI-1) compared to native t-PA. The abbreviation TNK is common for referring to tenecteplase, but abbreviating drug names is not best practice in medicine, and in fact "TNK" is one of the examples given on the Institute for Safe Medication Practices (ISMP) do-not-use list. Research Researchers at Newcastle University in Australia say they have had a significant breakthrough in treating stroke patients using the commonly used drug. The findings were published in the New England Medical Journal. Though safety has been established through previous clinical trials, there is ongoing debate about whether this is an effective treatment for ischemic stroke, and significant ongoing discussion between Emergency Physicians, Neurologists and Pharmacists about whether this treatment should be used for that indication. The American Heart Association/American Stroke Association 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke supports considering tenecteplase over alteplase in patients without contraindication to intravenous thrombolytics. Pharmacokinetics Distribution: approximates plasma volume Metabolism: Primarily hepatic Half-life elimination: Biphasic: Initial: 20–24 minutes; Terminal: 90–130 minutes Excretion: Clearance: Plasma: 99-119 mL/minute Gallery References Further reading External links MedlinePlus DrugInfo uspdi-500145

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

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

Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, usually from the Sun. Common symptoms in humans and animals include: red or reddish skin that is hot to the touch or painful, general fatigue, and mild dizziness. Other symptoms include blistering, peeling skin, swelling, itching, and nausea. Excessive UV radiation is the leading cause of (primarily) non-malignant skin tumors, and in extreme cases can be life-threatening. Sunburn is an inflammatory response in the tissue triggered by direct DNA damage by UV radiation. When the cells DNA is overly damaged by UV radiation, type I cell-death is triggered and the tissue is replaced.Sun protective measures including sunscreen and sun protective clothing are widely accepted to prevent sunburn and some types of skin cancer. Special populations, including children, are especially susceptible to sunburn and protective measures should be used to prevent damage. Signs and symptoms Typically, there is initial redness, followed by varying degrees of pain, proportional in severity to both the duration and intensity of exposure. Other symptoms can include blistering, swelling (edema), itching (pruritus), peeling skin, rash, nausea, fever, chills, and fainting (syncope). Also, a small amount of heat is given off from the burn, caused by the concentration of blood in the healing process, giving a warm feeling to the affected area. Sunburns may be classified as superficial, or partial thickness burns. Blistering is a sign of second degree sunburn. Variations Minor sunburns typically cause nothing more than slight redness and tenderness to the affected areas. In more serious cases, blistering can occur. Extreme sunburns can be painful to the point of debilitation and may require hospital care. Duration Sunburn can occur in less than 15 minutes, and in seconds when exposed to non-shielded welding arcs or other sources of intense ultraviolet light. Nevertheless, the inflicted harm is often not immediately obvious. After the exposure, skin may turn red in as little as 30 minutes but most often takes 2 to 6 hours. Pain is usually strongest 6 to 48 hours after exposure. The burn continues to develop for 1 to 3 days, occasionally followed by peeling skin in 3 to 8 days. Some peeling and itching may continue for several weeks. Skin cancer Ultraviolet radiation causes sunburns and increases the risk of three types of skin cancer: melanoma, basal-cell carcinoma and squamous-cell carcinoma. Of greatest concern is that the melanoma risk increases in a dose-dependent manner with the number of a persons lifetime cumulative episodes of sunburn. It has been estimated that over 1/3 of melanomas in the United States and Australia could be prevented with regular sunscreen use. Causes Sunburn is caused by UV radiation from the sun, but "sunburn" may result from artificial sources, such as tanning lamps, welding arcs, or ultraviolet germicidal irradiation. It is a reaction of the body to direct DNA damage from UVB light. This damage is mainly the formation of a thymine dimer. The damage is recognized by the body, which then triggers several defense mechanisms, including DNA repair to revert the damage, apoptosis and peeling to remove irreparably damaged skin cells, and increased melanin production to prevent future damage. Melanin readily absorbs UV wavelength light, acting as a photoprotectant. By preventing UV photons from disrupting chemical bonds, melanin inhibits both the direct alteration of DNA and the generation of free radicals, thus indirect DNA damage. However, human melanocytes contain over 2,000 genomic sites that are highly sensitive to UV, and such sites can be up to 170-fold more sensitive to UV induction of cyclobutane pyrimidine dimers than the average site These sensitive sites often occur at biologically significant locations near genes. Sunburn causes an inflammation process, including production of prostanoids and bradykinin. These chemical compounds increase sensitivity to heat by reducing the threshold of heat receptor (TRPV1) activation from 109 °F (43 °C) to 85 °F (29 °C). The pain may be caused by overproduction of a protein called CXCL5, which activates nerve fibers.Skin type determines the ease of sunburn. In general, people with lighter skin tone and limited capacity to develop a tan after UV radiation exposure have a greater risk of sunburn. The Fitzpatricks Skin phototypes classification describes the normal variations of skin responses to UV radiation. Persons with type I skin have the greatest capacity to sunburn and type VI have the least capacity to burn. However, all skin types can develop sunburn.Fitzpatricks skin phototypes: Type 0: Albino Type I: Pale white skin, burns easily, does not tan Type II: White skin, burns easily, tans with difficulty Type III: White skin, may burn but tans easily Type IV: Light brown/olive skin, hardly burns, tans easily Type V: Brown skin, usually does not burn, tans easily Type VI: Black skin, very unlikely to burn, becomes darker with UV radiation exposureAge also affects how skin reacts to sun. Children younger than six and adults older than sixty are more sensitive to sunlight.There are certain genetic conditions, for example xeroderma pigmentosum, that increase a persons susceptibility to sunburn and subsequent skin cancers. These conditions involve defects in DNA repair mechanisms which in turn decreases the ability to repair DNA that has been damaged by UV radiation. Medications The risk of a sunburn can be increased by pharmaceutical products that sensitize users to UV radiation. Certain antibiotics, oral contraceptives, antidepressants, acne medications, and tranquillizers have this effect. UV intensity The UV Index indicates the risk of getting a sunburn at a given time and location. Contributing factors include: The time of day. In most locations, the suns rays are strongest between approximately 10 am and 4 pm daylight saving time. Cloud cover. UV is partially blocked by clouds; but even on an overcast day, a significant percentage of the suns damaging UV radiation can pass through clouds. Proximity to reflective surfaces, such as water, sand, concrete, snow, and ice. All of these reflect the suns rays and can cause sunburns. The season of the year. The position of the sun in late spring and early summer can cause a more-severe sunburn. Altitude. At a higher altitude it is easier to become burnt, because there is less of the earths atmosphere to block the sunlight. UV exposure increases about 4% for every 1000 ft (305 m) gain in elevation. Proximity to the equator (latitude). Between the polar and tropical regions, the closer to the equator, the more direct sunlight passes through the atmosphere over the course of a year. For example, the southern United States gets fifty percent more sunlight than the northern United States. Because of variations in the intensity of UV radiation passing through the atmosphere, the risk of sunburn increases with proximity to the tropic latitudes, located between 23.5° north and south latitude. All else being equal (e.g., cloud cover, ozone layer, terrain, etc.), over the course of a full year, each location within the tropic or polar regions receives approximately the same amount of UV radiation. In the temperate zones between 23.5° and 66.5°, UV radiation varies substantially by latitude and season. The higher the latitude, the lower the intensity of the UV rays. Intensity in the northern hemisphere is greatest during the months of May, June and July—and in the southern hemisphere, November, December and January. On a minute-by-minute basis, the amount of UV radiation is dependent on the angle of the sun. This is easily determined by the height ratio of any object to the size of its shadow (if the height is measured vertical to the earths gravitational field, the projected shadow is ideally measured on a flat, level surface; furthermore, for objects wider than skulls or poles, the height and length are best measured relative to the same occluding edge). The greatest risk is at solar noon, when shadows are at their minimum and the suns radiation passes most directly through the atmosphere. Regardless of ones latitude (assuming no other variables), equal shadow lengths mean equal amounts of UV radiation. The skin and eyes are most sensitive to damage by UV at 265–275 nm wavelength, which is in the lower UVC band that is almost never encountered except from artificial sources like welding arcs. Most sunburn is caused by longer wavelengths, simply because those are more prevalent in sunlight at ground level. Ozone depletion In recent decades, the incidence and severity of sunburn have increased worldwide, partly because of chemical damage to the atmospheres ozone layer. Between the 1970s and the 2000s, average stratospheric ozone decreased by approximately 4%, contributing an approximate 4% increase to the average UV intensity at the earths surface. Ozone depletion and the seasonal "ozone hole" have led to much larger changes in some locations, especially in the southern hemisphere. Tanning Suntans, which naturally develop in some individuals as a protective mechanism against the sun, are viewed by most in the Western world as desirable. This has led to an overall increase in exposure to UV radiation from both the natural sun and tanning lamps. Suntans can provide a modest sun protection factor (SPF) of 3, meaning that tanned skin would tolerate up to three times the UV exposure as pale skin.Sunburns associated with indoor tanning can be severe.The World Health Organization, American Academy of Dermatology, and the Skin Cancer Foundation recommend avoiding artificial UV sources such as tanning beds, and do not recommend suntans as a form of sun protection. Diagnosis Differential diagnosis The differential diagnosis of sunburn includes other skin pathology induced by UV radiation including photoallergic reactions, phototoxic reactions to topical or systemic medications, and other dermatologic disorders that are aggravated by exposure to sunlight. Considerations for diagnosis include duration and intensity of UV exposure, use of topical or systemic medications, history of dermatologic disease, and nutritional status. Phototoxic reactions: Non-immunological response to sunlight interacting with certain drugs and chemicals in the skin which resembles an exaggerated sunburn. Common drugs that may cause a phototoxic reaction include amiodarone, dacarbazine, fluoroquinolones, 5-fluorouracil, furosemide, nalidixic acid, phenothiazines, psoralens, retinoids, sulfonamides, sulfonylureas, tetracyclines, thiazides, and vinblastine. Photoallergic reactions: Uncommon immunological response to sunlight interacting with certain drugs and chemicals in the skin. When in excited state by UVR, these drugs and chemicals form free radicals that react to form functional antigens and induce a Type IV hypersensitivity reaction. These drugs include 6-methylcoumarin, aminobenzoic acid and esters, chlorpromazine, promethazine, diclofenac, sulfonamides, and sulfonylureas. Unlike phototoxic reactions which resemble exaggerated sunburns, photoallergic reactions can cause intense itching and can lead to thickening of the skin. Phytophotodermatitis: UV radiation induces inflammation of the skin after contact with certain plants (including limes, celery, and meadow grass). Causes pain, redness, and blistering of the skin in the distribution of plant exposure. Polymorphic light eruption: Recurrent abnormal reaction to UVR. It can present in various ways including pink-to-red bumps, blisters, plaques and urticaria. Solar urticaria: UVR-induced wheals that occurs within minutes of exposure and fades within hours. Other skin diseases exacerbated by sunlight: Several dermatologic conditions can increase in severity with exposure to UVR. These include systemic lupus erythematosus (SLE), dermatomyositis, acne, atopic dermatitis, and rosacea.Additionally, since sunburn is a type of radiation burn, it can initially hide a severe exposure to radioactivity resulting in acute radiation syndrome or other radiation-induced illnesses, especially if the exposure occurred under sunny conditions. For instance, the difference between the erythema caused by sunburn and other radiation burns is not immediately obvious. Symptoms common to heat illness and the prodromic stage of acute radiation syndrome like nausea, vomiting, fever, weakness/fatigue, dizziness or seizure can add to further diagnostic confusion. Prevention The most effective way to prevent sunburn is to reduce the amount of UV radiation reaching the skin. The World Health Organization, American Academy of Dermatology, and Skin Cancer Foundation recommend the following measures to prevent excessive UV exposure and skin cancer: Limiting sun exposure between the hours of 10 am and 4 pm, when UV rays are the strongest Seeking shade when UV rays are most intense Wearing sun-protective clothing including a wide brim hat, sunglasses, and tightly-woven, loose-fitting clothing Using sunscreen Avoiding tanning beds and artificial UV exposure UV intensity The strength of sunlight is published in many locations as a UV Index. Sunlight is generally strongest when the sun is close to the highest point in the sky. Due to time zones and daylight saving time, this is not necessarily at 12 noon, but often one to two hours later. Seeking shade including using umbrellas and canopies can reduce the amount of UV exposure, but does not block all UV rays. The WHO recommends following the shadow rule: "Watch your shadow – Short shadow, seek shade!" Grapes A 2022 study found that eating 60 grapes a day can stop you getting sunburn. Scientists found people who ate three-quarters of a punnet every day for two weeks were better protected against damage to the skin from ultraviolet light. Polyphenols found naturally in the fruits are thought to be responsible for the resistance. Sunscreen Commercial preparations are available that block UV light, known as sunscreens or sunblocks. They have a sun protection factor (SPF) rating, based on the sunblocks ability to suppress sunburn: The higher the SPF rating, the lower the amount of direct DNA damage. The stated protection factors are correct only if 2 mg of sunscreen is applied per square cm of exposed skin. This translates into about 28 mL (1 oz) to cover the whole body of an adult male, which is much more than many people use in practice. Sunscreens function as chemicals such as oxybenzone and dioxybenzone (organic sunscreens) or opaque materials such as zinc oxide or titanium oxide (inorganic sunscreens) that both mainly absorb UV radiation. Chemical and mineral sunscreens vary in the wavelengths of UV radiation blocked. Broad-spectrum sunscreens contain filters that protect against UVA radiation as well as UVB. Although UVA radiation does not primarily cause sunburn, it does contribute to skin aging and an increased risk of skin cancer. Sunscreen is effective and thus recommended for preventing melanoma and squamous cell carcinoma. There is little evidence that it is effective in preventing basal cell carcinoma. Typical use of sunscreen does not usually result in vitamin D deficiency, but extensive usage may. Recommendations Research has shown that the best sunscreen protection is achieved by application 15 to 30 minutes before exposure, followed by one reapplication 15 to 30 minutes after exposure begins. Further reapplication is necessary only after activities such as swimming, sweating, and rubbing. This varies based on the indications and protection shown on the label—from as little as 80 minutes in water to a few hours, depending on the product selected. The American Academy of Dermatology recommends the following criteria in selecting a sunscreen: Broad spectrum: protects against both UVA and UVB rays SPF 30 or higher Water resistant: sunscreens are classified as water resistant based on time, either 40 minutes, 80 minutes, or not water resistant Eyes The eyes are also sensitive to sun exposure at about the same UV wavelengths as skin; snow blindness is essentially sunburn of the cornea. Wrap-around sunglasses or the use by spectacle-wearers of glasses that block UV light reduce the harmful radiation. UV light has been implicated in the development of age-related macular degeneration, pterygium and cataract. Concentrated clusters of melanin, commonly known as freckles, are often found within the iris. The tender skin of the eyelids can also become sunburned, and can be especially irritating. Lips The lips can become chapped (cheilitis) by sun exposure. Sunscreen on the lips does not have a pleasant taste and might be removed by saliva. Some lip balms (ChapSticks) have SPF ratings and contain sunscreens. Feet The skin of the feet is often tender and protected, so sudden prolonged exposure to UV radiation can be particularly painful and damaging to the top of the foot. Protective measures include sunscreen, socks, and swimwear or swimgear that covers the foot. Diet Dietary factors influence susceptibility to sunburn, recovery from sunburn, and risk of secondary complications from sunburn. Several dietary antioxidants, including essential vitamins, have been shown to have some effectiveness for protecting against sunburn and skin damage associated with ultraviolet radiation, in both human and animal studies. Supplementation with Vitamin C and Vitamin E was shown in one study to reduce the amount of sunburn after a controlled amount of UV exposure. A review of scientific literature through 2007 found that beta carotene (Vitamin A) supplementation had a protective effect against sunburn, but that the effects were only evident in the long-term, with studies of supplementation for periods less than 10 weeks in duration failing to show any effects. There is also evidence that common foods may have some protective ability against sunburn if taken for a period before the exposure. Protecting children Babies and children are particularly susceptible to UV damage which increases their risk of both melanoma and non-melanoma skin cancers later in life. Children should not sunburn at any age and protective measures can ensure their future risk of skin cancer is reduced. Infants 0–6 months: Children under 6mo generally have skin too sensitive for sunscreen and protective measures should focus on avoiding excessive UV exposure by using window mesh covers, wide brim hats, loose clothing that covers skin, and reducing UV exposure between the hours of 10am and 4pm. Infants 6–12 months: Sunscreen can safely be used on infants this age. It is recommended to apply a broad-spectrum, water-resistant SPF 30+ sunscreen to exposed areas as well as avoid excessive UV exposure by using wide-brim hats and protective clothing. Toddlers and Preschool-aged children: Apply a broad-spectrum, water-resistant SPF 30+ sunscreen to exposed areas, use wide-brim hats and sunglasses, avoid peak UV intensity hours of 10am-4pm and seek shade. Sun protective clothing with a SPF rating can also provide additional protection. Artificial UV exposure The WHO recommends that artificial UV exposure including tanning beds should be avoided as no safe dose has been established. When one is exposed to any artificial source of occupational UV, special protective clothing (for example, welding helmets/shields) should be worn. Such sources can produce UVC, an extremely carcinogenic wavelength of UV which ordinarily is not present in normal sunlight, having been filtered out by the atmosphere. Treatment The primary measure of treatment is avoiding further exposure to the sun. The best treatment for most sunburns is time; most sunburns heal completely within a few weeks. The American Academy of Dermatology recommends the following for the treatment of sunburn: For pain relief, take cool baths or showers frequently. Use soothing moisturizers that contain aloe vera or soy. Anti-inflammatory medications such as ibuprofen or aspirin can help with pain. Keep hydrated and drink extra water. Do not pop blisters on a sunburn; let them heal on their own instead. Protect sunburned skin (see: Sun protective clothing and Sunscreen) with loose clothing when going outside to prevent further damage while not irritating the sunburn.Non-steroidal anti-inflammatory drugs (NSAIDs; such as ibuprofen or naproxen), and aspirin may decrease redness and pain. Local anesthetics such as benzocaine, however, are contraindicated. Schwellnus et al. state that topical steroids (such as hydrocortisone cream) do not help with sunburns, although the American Academy of Dermatology says they can be used on especially sore areas. While lidocaine cream (a local anesthetic) is often used as a sunburn treatment, there is little evidence for the effectiveness of such use.A home treatment that may help the discomfort is using cool and wet cloths on the sunburned areas. Applying soothing lotions that contain aloe vera to the sunburn areas was supported by multiple studies, though others have found aloe vera to have no effect. Note that aloe vera has no ability to protect people from new or further sunburn. Another home treatment is using a moisturizer that contains soy.A sunburn draws fluid to the skins surface and away from the rest of the body. Drinking extra water is recommended to help prevent dehydration. See also Sun tanning Freckles Skin cancer Snow blindness Chapped lips References External links Sunburn at Curlie

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

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

Laxatives, purgatives, or aperients are substances that loosen stools and increase bowel movements. They are used to treat and prevent constipation. Laxatives vary as to how they work and the side effects they may have. Certain stimulant, lubricant and saline laxatives are used to evacuate the colon for rectal and bowel examinations, and may be supplemented by enemas under certain circumstances. Sufficiently high doses of laxatives may cause diarrhea. Some laxatives combine more than one active ingredient. Laxatives may be administered orally or rectally. Types Bulk-forming agents Bulk-forming laxatives, also known as roughage, are substances, such as fiber in food and hydrophilic agents in over-the-counter drugs, that add bulk and water to stools so that they can pass more easily through the intestines (lower part of the digestive tract).Properties Site of action: small and large intestines Onset of action: 12–72 hours Examples: dietary fiber, Metamucil, Citrucel, FiberConBulk-forming agents generally have the gentlest of effects among laxatives, making them ideal for long-term maintenance of regular bowel movements. Dietary fiber Foods that help with laxation include fiber-rich foods. Dietary fiber includes insoluble fiber and soluble fiber, such as: Fruits, such as bananas, though this depends on their ripeness, kiwifruits, prunes, apples (with skin), pears (with skin), and raspberries Vegetables, such as broccoli, string beans, kale, spinach, cooked winter squash, cooked taro and poi, cooked peas, and baked potatoes (with skin) Whole grains Bran products Nuts Legumes, such as beans, peas, and lentils Emollient agents (stool softeners) Emollient laxatives, also known as stool softeners, are anionic surfactants that enable additional water and fats to be incorporated in the stool, making it easier for them to move through the gastrointestinal tract. Properties Site of action: small and large intestines Onset of action: 12–72 hours Examples: Docusate (Colace, Diocto), Gibs-EzeEmollient agents prevent constipation rather than treating long-term constipation. Lubricant agents Lubricant laxatives are substances that coat the stool with slippery lipids and decrease colonic absorption of water so that the stool slides through the colon more easily. Lubricant laxatives also increase the weight of stool and decrease intestinal transit time.Properties Site of action: colon Onset of action: 6–8 hours Example: mineral oilMineral oil is the only nonprescription lubricant. Mineral oil may decrease the absorption of fat-soluble vitamins and some minerals.One example is Liquid paraffin. Hyperosmotic agents Hyperosmotic laxatives are substances that cause the intestines to hold more water within and create an osmotic effect that stimulates a bowel movement.Properties Site of action: colon Onset of action: 12–72 hours (oral), 0.25–1 hour (rectal) Examples: glycerin suppositories (Hallens), sorbitol, lactulose, and PEG (Colyte, MiraLax)Lactulose works by the osmotic effect, which retains water in the colon; lowering the pH through bacterial fermentation to lactic, formic and acetic acid; and increasing colonic peristalsis. Lactulose is also indicated in portal-systemic encephalopathy. Glycerin suppositories work mostly by hyperosmotic action, but the sodium stearate in the preparation also causes local irritation to the colon. Solutions of polyethylene glycol and electrolytes (sodium chloride, sodium bicarbonate, potassium chloride, and sometimes sodium sulfate) are used for whole bowel irrigation, a process designed to prepare the bowel for surgery or colonoscopy and to treat certain types of poisoning. Brand names for these solutions include GoLytely, GlycoLax, Cosmocol, CoLyte, Miralax, Movicol, NuLytely, Suprep, and Fortrans. Solutions of sorbitol (SoftLax) have similar effects. Saline laxative agents Saline laxatives are non-absorbable osmotically active substances that attract and retain water in the intestinal lumen, increasing intraluminal pressure that mechanically stimulates evacuation of the bowel. Magnesium-containing agents also cause the release of cholecystokinin, which increases intestinal motility and fluid secretion. Saline laxatives may alter a patients fluid and electrolyte balance. Properties Site of action: small and large intestines Onset of action: 0.5–3 hours (oral), 2–15 minutes (rectal) Examples: sodium phosphate (and variants), magnesium citrate, magnesium hydroxide (milk of magnesia), and magnesium sulfate (Epsom salt) Stimulant agents Stimulant laxatives are substances that act on the intestinal mucosa or nerve plexus, altering water and electrolyte secretion. They also stimulate peristaltic action and can be dangerous under certain circumstances.Properties Site of action: colon Onset of action: 6–10 hours Examples: senna, bisacodylProlonged use of stimulant laxatives can create drug dependence by damaging the colons haustral folds, making a user less able to move feces through the colon on their own. A study of patients with chronic constipation found that 28% of chronic stimulant laxative users lost haustral folds over the course of one year, while none of the control group did. Miscellaneous Castor oil is a glyceride that is hydrolyzed by pancreatic lipase to ricinoleic acid, which produces laxative action by an unknown mechanism. Properties Site of action: colon,small intestine (see below) Onset of action: 2–6 hours Examples: castor oilLong-term use of castor oil may result in loss of fluid, electrolytes, and nutrients. Serotonin agonist These are motility stimulants that work through activation of 5-HT4 receptors of the enteric nervous system in the gastrointestinal tract. However, some have been discontinued or restricted due to potentially harmful cardiovascular side-effects. Tegaserod (brand name Zelnorm) was removed from the general U.S. and Canadian markets in 2007, due to reports of increased risks of heart attack or stroke. It is still available to physicians for patients in emergency situations that are life-threatening or require hospitalization.Prucalopride (brand name Resolor) is a current drug approved for use in the EU since October 15, 2009, in Canada (brand name Resotran) since December 7, 2011, and in the United States since December 2018. Chloride channel activators Lubiprostone is used in the management of chronic idiopathic constipation and irritable bowel syndrome. It causes the intestines to produce a chloride-rich fluid secretion that softens the stool, increases motility, and promotes spontaneous bowel movements (SBM). Comparison of available agents Effectiveness For adults, a randomized controlled trial found PEG (MiraLax or GlycoLax) 17 grams once per day to be superior to tegaserod at 6 mg twice per day. A randomized controlled trial found greater improvement from two sachets (26 grams) of PEG versus two sachets (20 grams) of lactulose. 17 grams per day of PEG has been effective and safe in a randomized controlled trial for six months. Another randomized controlled trial found no difference between sorbitol and lactulose.For children, PEG was found to be more effective than lactulose. Problems with use Laxative abuse Some of the less significant adverse effects of laxative abuse include dehydration (which causes tremors, weakness, fainting, blurred vision, kidney damage), low blood pressure, fast heart rate, postural dizziness and fainting; however, laxative abuse can lead to potentially fatal acid-base and electrolyte imbalances. For example, severe hypokalaemia has been associated with distal renal tubular acidosis from laxative abuse. Metabolic alkalosis is the most common acid-base imbalance observed. Other significant adverse effects include rhabdomyolysis, steatorrhoea, inflammation and ulceration of colonic mucosa, pancreatitis, kidney failure, factitious diarrhea and other problems. The colon will need more quantities of laxatives to keep functioning, this will result in a lazy colon, infections, irritable bowel syndrome, and potential liver damages. Although some patients with eating disorders such as anorexia nervosa and bulimia nervosa abuse laxatives in an attempt to lose weight, laxatives act to speed up the transit of feces through the large intestine, which occurs after the absorption of nutrients in the small intestine is already complete. Thus, studies of laxative abuse have found that effects on body weight reflect primarily temporary losses of body water rather than energy (calorie) loss. Laxative gut Physicians warn against the chronic use of stimulant laxatives due to concern that chronic use could cause the colonic tissues to get worn out over time and not be able to expel feces due to long-term overstimulation. A common finding in patients having used stimulant laxatives is a brown pigment deposited in the intestinal tissue, known as melanosis coli. Historical and health fraud uses Laxatives, once called physicks or purgatives, were used extensively in pre-modern medicine to treat many conditions for which they are now generally regarded as ineffective in evidence-based medicine. Likewise, laxatives (often termed colon cleanses) may be promoted in alternative medicine for various conditions of quackery, such as "mucoid plaque". See also == References ==

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

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

Polydipsia is excessive thirst or excess drinking. The word derives from the Greek πολυδίψιος (poludípsios) "very thirsty", which is derived from πολύς (polús, "much, many") + δίψα (dípsa, "thirst"). Polydipsia is a nonspecific symptom in various medical disorders. It also occurs as an abnormal behaviour in some non-human animals, such as in birds. Causes Diabetes Polydipsia can be characteristic of diabetes mellitus, often as an initial symptom. It is observed in cases of poorly controlled diabetes, which is sometimes the result of low patient adherence to anti-diabetic medication.Diabetes insipidus ("tasteless" diabetes, as opposed to diabetes mellitus) can also cause polydipsia. Other physiological causes It can also be caused by a change in the osmolality of the extracellular fluids of the body, hypokalemia, decreased blood volume (as occurs during major hemorrhage), and other conditions that create a water deficit. This is usually a result of osmotic diuresis. Polydipsia is also a symptom of anticholinergic poisoning. Zinc is also known to reduce symptoms of polydipsia by causing the body to absorb fluids more efficiently (reduction of diarrhea, induces constipation) and it causes the body to retain more sodium; thus a zinc deficiency can be a possible cause. The combination of polydipsia and (nocturnal) polyuria is also seen in (primary) hyperaldosteronism (which often goes with hypokalemia). Antipsychotics can have side effects such as dry mouth that may make the patient feel thirsty. Primary polydipsia Primary polydipsia describes excessive thirst and water intake caused in the absence of physiological stimuli to drink. This includes both psychogenic primary polydipsia and non-psychogenic primary polydipsia, such as in patients with autoimmune chronic hepatitis with severely elevated globulin levels.Psychogenic polydipsia is an excessive water intake seen in some patients with mental illnesses such as schizophrenia, or with developmental disabilities. It should be taken very seriously, as the amount of water ingested exceeds the amount that can be excreted by the kidneys, and can on rare occasions be life-threatening as the bodys serum sodium level is diluted to an extent that seizures and cardiac arrest can occur. While psychogenic polydipsia is generally not found outside the population of serious mental disorders, there is some anecdotal evidence of a milder form (typically called habit polydipsia or habit drinking) that can be found in the absence of psychosis or other mental conditions. The excessive levels of fluid intake may result in a false diagnosis of diabetes insipidus, since the chronic ingestion of excessive water can produce diagnostic results that closely mimic those of mild diabetes insipidus. As discussed in the entry on diabetes insipidus, "Habit drinking (in its severest form termed psychogenic polydipsia) is the most common imitator of diabetes insipidus at all ages. While many adult cases in the medical literature are associated with mental disorders, most patients with habit polydipsia have no other detectable disease. The distinction is made during the water deprivation test, as some degree of urinary concentration above isosmolar is usually obtained before the patient becomes dehydrated." However, prior to a water deprivation test, consideration should be given to a psychiatric consult to see whether it is possible to rule out psychogenic polydipsia or habit polydipsia. Diagnosis Polydipsia is a symptom (evidence of a disease state), not a disease in itself. As it is often accompanied by polyuria (excessive urination) and low sodium levels. Investigations directed at diagnosing diabetes insipidus and diabetes mellitus can be useful. Blood serum tests can also provide useful information about the osmolality of the bodys extracellular fluids. A decrease in osmolality caused by excess water intake will decrease the serum concentration of red blood cells, blood urea nitrogen (BUN), and sodium. See also References == External links ==

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

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

Crush syndrome (also traumatic rhabdomyolysis or Bywaters syndrome) is a medical condition characterized by major shock and kidney failure after a crushing injury to skeletal muscle. Crush injury is compression of the arms, legs, or other parts of the body that causes muscle swelling and/or neurological disturbances in the affected areas of the body, while crush syndrome is localized crush injury with systemic manifestations. Cases occur commonly in catastrophes such as earthquakes, to individuals that have been trapped under fallen or moving masonry. People with crushing damage present some of the greatest challenges in field medicine, and may need a physicians attention on the site of their injury. Appropriate physiological preparation of the injured is mandatory. It may be possible to free the patient without amputation; however, field amputations may be necessary in drastic situations. Pathophysiology Seigo Minami, a Japanese physician, first reported the crush syndrome in 1923. He studied the pathology of three soldiers who died in World War I due to kidney failure. The renal changes were due to the buildup of excess myoglobin, resulting from the destruction of muscles from lack of oxygen. These changes can also be seen in persons who are buried alive. The progressive acute kidney failure is because of acute tubular necrosis. The syndrome was later described by British physician Eric Bywaters in patients during the 1941 wartime bombing of London (the Blitz). It is a reperfusion injury that appears after the release of the crushing pressure. The mechanism is believed to be the release into the bloodstream of muscle breakdown products—notably myoglobin, potassium and phosphorus—that are the products of rhabdomyolysis (the breakdown of skeletal muscle damaged by ischemic conditions). The specific action on the kidneys is not understood completely, but may be due partly to nephrotoxic metabolites of myoglobin. The most devastating systemic effects can occur when the crushing pressure is suddenly released, without proper preparation of the patient, causing reperfusion syndrome. In addition to tissue directly suffering the crush mechanism, tissue is then subjected to sudden reoxygenation in the limbs and extremities. Without proper preparation, the patient, with pain control, may be cheerful before recovery, but die shortly thereafter. This sudden failure is called the "smiling death".These systemic effects are caused by a traumatic rhabdomyolysis. As muscle cells die, they absorb sodium, water and calcium; the rhabdomyolysis releases potassium, myoglobin, phosphate, thromboplastin, creatine and creatine kinase.Crush syndrome can directly come from compartment syndrome, if the injury is left untreated. Symptoms include the 5 Ps: pain, pallor, paresthesias (pins and needles), paralysis, and pulselessness. Treatment There is no distinct treatment option that can undo the effects and damage from rhabdomyolysis because it is a necrosis. However, the rate of the pathology that can lead to more complications can be decreased by acting early and consistently. Overall treatment depends on preventing kidney failure (renal failure) which is done by rehydrating the patient. It also depends on making urine have a more basic pH (alkalinization of urine). Immediate untreated crush syndrome death is caused by severe head injury, torso injury with damaged abdominal organs, and asphyxia (excessive loss of oxygen). Early untreated crush syndrome death is caused by hyperkalemia and by hypovolemic shock. Late untreated crush syndrome death is caused by renal failure, coagulopathy and hemorrhage, and sepsis.Due to the risk of crush syndrome, current recommendation to nonprofessional first-aiders (in the UK) is to not release those with a crush injury who have been trapped for more than 15 minutes. Treatment consists of not releasing the tourniquet, overloading the patient with fluid using Dextran 4000 IU, and slow release of pressure. If pressure is released during first aid, then fluid is restricted and an input-output chart for the patient is maintained, and proteins are decreased in the diet. Field management As mentioned, permissive hypotension (restrictive fluid therapy) is unwise. Careful fluid overload and administration of intravenous sodium bicarbonate is wise, especially if the crushing weight is on the patient for more than 4 hours, but often if it persists more than one hour. The San Francisco emergency services protocol calls for a basic adult dose of a 2 L bolus of normal saline followed by 500 mL/h, limited for "pediatric patients and patients with history of cardiac or renal dysfunction."Use of a tourniquet can stall the life-threatening consequences of a crush related injury and can be a second option if the person cannot immediately have the fluids that were lost be medically replaced back into the body. Tourniquet measures should be taken if the person has been entrapped for more than 2 hours. Initial hospital management The clinician must protect the patient against hypotension, kidney failure, acidosis, hyperkalemia and hypocalcemia. Admission to an intensive care unit, preferably one experienced in trauma medicine, may be appropriate; even well-seeming patients need observation. Treat open wounds as surgically appropriate, with debridement, antibiotics and tetanus toxoid; apply ice to injured areas. Breathing and circulation must be checked out and the patient should be given oxygen if eligible. Oral or intravenous fluids must be given depending on the measured amounts of electrolytes, arterial blood gases, and muscle enzymes.Intravenous hydration of up to 1.5 L/h should continue to prevent hypotension. A urinary output of at least 300 mL/h should be maintained with IV fluids and mannitol, and hemodialysis considered if an increase in urine is not achieved. Use intravenous sodium bicarbonate to keep the urine pH at 6.5 or greater, to prevent myoglobin and uric acid deposition in kidneys. To prevent hyperkalemia/hypocalcemia, consider the following adult doses: calcium gluconate 10% 10 mL or calcium chloride 10% 5 mL IV over 2 minutes sodium bicarbonate 1 meq/kg IV slow push regular insulin 5–10 U 50% glucose 1–2 ampules IV bolus kayexalate 25–50 g with sorbitol 20% 100 mL by mouth or rectum.Even so, abnormal heart rhythms may develop; electrocardiographic monitoring is advised, and specific treatment begun promptly. References Sever MS, Vanholder R, Lameire N (2006). "Management of crush-related injuries after disasters". The New England Journal of Medicine. 354 (10): 1052–63. doi:10.1056/NEJMra054329. PMID 16525142. External links Life or Limb: What happens when your leg gets trapped under a building?

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

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

Reticulocytosis is a condition where there is an increase in reticulocytes, immature red blood cells. It is commonly seen in anemia. They are seen on blood films when the bone marrow is highly active in an attempt to replace red blood cell loss such as in haemolytic anaemia, haemorrhage. == External links ==

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

Could you provide a brief overview of 'Chronic sclerosing sialadenitis' in a medical context?

Chronic sclerosing sialadenitis is a chronic (long-lasting) inflammatory condition affecting the salivary gland. Relatively rare in occurrence, this condition is benign, but presents as hard, indurated and enlarged masses that are clinically indistinguishable from salivary gland neoplasms or tumors. It is now regarded as a manifestation of IgG4-related disease.Involvement of the submandibular glands is also known as Küttners tumor, named after Hermann Küttner (1870–1932), a German Oral and Maxillofacial Surgeon, who reported four cases of submandibular gland lesions for the first time in 1896. Presentation The inflammatory lesions in Küttners tumor may occur on one side (unilateral) or both sides (bilateral), predominantly involving the submandibular gland, but is also known to occur in other major and minor salivary glands, including the parotid gland. Overall, salivary gland tumors are relatively rare, with approximately 2.5–3 cases per 100,000 people per year seen in the Western world; however, salivary gland malignancies account for 3–5% of all head and neck cancers. However, salivary tumors show a great deal of morphological diversity, as well as variations in the nature of the lesion (malignant vs. benign): approximately 20% to 25% of parotid tumors, 35% to 40% of submandibular tumors, and more than 90% of sublingual gland tumors are malignant. This situation underscores the diagnostic challenges in respect of Küttners tumor; despite being benign, this condition mimics the clinical appearance of malignancy in the salivary gland. The swollen masses of Küttners tumor are generally painful, and patients are advised surgical resection (known as sialadenectomy) of a part or whole of the glandular tissue upon suspicion of possible malignancy. It is only upon post-surgical histopathology of the excised mass that the diagnosis of Küttners tumor is definitively made. Histological features The histopathological features that characterize Küttners tumor include: Heavy infiltration of the glandular tissue by lymphocytes (predominantly activated B-cells and helper T-cells) as well as plasma cells (collectively known as Lymphoplasmacytic Infiltrate). Presence of reactive lymphoid follicles in the infiltrate, marked by a lack of atypical lymphoid cells (this is in sharp contrast to the presentations in lymphoma). Atrophy and loss of acini (groups of secretory cells found in the salivary glands). Encasement of the glandular ducts in thick fibrous tissues, as a result of chronic presence of inflammatory infiltrate in that area - a condition known as periductal fibrosis. Eventual periductal and interlobular (inside the gland) sclerosis (replacement of regular tissue with hard connective tissue). Pathogenesis The cause and pathogenesis of this chronic condition are not very well understood. Several factors have been postulated: Formation of a hard salivary calculus or sialolith by accumulation of calcium salts in the duct of the salivary gland (a process known as Sialolithiasis). This has been proposed as the most common cause for Küttners tumor of the submandibular gland, with sialoliths observed in an appreciable proportion of cases. However, sialolith involvement may not be found in many cases. Abnormalities of the salivary gland ducts leading to excessive accumulation or retention of ductal secretions, which can excite chronic inflammations. Immune, especially autoimmune, cause - which has gained steam, given the observation that the tissue of the glands is overrun with lymphoid immune cells and fibrous connective tissue, as well as corroboration from markedly similar lesions (with histologic and immunohistochemical findings) seen elsewhere in the body. The presence of abundant Immunoglobulin G4 (IgG4) associated with Plasma cells infiltrating into the salivary glands, as well as increased serum IgG4 concentration, has been noted with patients with Küttners tumor.This chronic condition is primarily observed in adult (40–70 years) patients. However, Küttners tumor, with prominent immunopathological features, has been described in an 11-year-old boy in Brazil in 2012. Diagnosis Given the difficulties of a definitive pre-operative diagnosis, the clinical entity of Küttners tumor has so far remained significantly under-reported and under-recognized. In recent times, armed with a better understanding of the occurrences and observable features of this condition, surgeons are increasingly depending upon pre-operative ultrasonography along with Fine-needle aspiration cytological (FNAC) examinations to make an accurate presumptive diagnosis, and according to one estimate, about 44% of patients undergoing submandibular resection are found to have this condition. In the ultrasonogram, Küttners tumor is characterized by a diffuse, heterogeneous zone of echo-shadows. The FNAC finds cells greatly reduced in number (called paucicellularity) along with scattered tubular ducts against a backdrop of lymphoplasmacytic infiltration and fibrous depositions. There may be a reduced but moderate number of cells and ducts enveloped in fibrous sheaths, as well as fibrous proliferation of the glands septa. The cytologic findings by themselves may not be specific, and the diagnosis requires adjunct consideration of both the ultrasonogram and clinical presentation. Application of magnetic resonance imaging (MRI) has been tried to non-invasively examine the morphological variations in Küttners tumor and differentiate them from those seen in malignant tumors; while MRI findings of the affected tissue and the pattern of cellular infiltration may offer some diagnostic clues for this condition, so far the results have been inconclusive. Existing treatment Standard, and most effective, therapy to date is glandular sialadenectomy, which is associated with fairly low operative morbidity; however, in recent times, the administration of steroid (which can shrink the inflammatory lesion and is known to reduce serum IgG4 values) has been considered favorably, and may be useful in younger patients or those who refuse surgery. See also Sialadenitis References == External links ==

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

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

Cryptococcosis is a potentially fatal fungal infection of mainly the lungs, presenting as a pneumonia, and brain, where it appears as a meningitis. Cough, difficulty breathing, chest pain and fever are seen when the lungs are infected. When the brain is infected, symptoms include headache, fever, neck pain, nausea and vomiting, light sensitivity and confusion or changes in behaviour. It can also affect other parts of the body including skin, where it may appear as several fluid-filled nodules with dead tissue.It is caused by the fungi Cryptococcus neoformans or less commonly Cryptococcus gattii, and is acquired by breathing in the spores from the air. These fungi are found around the world in soil, decaying wood, pigeon droppings, and in the hollows of some species of trees. Whereas C. neoformans infects generally people with HIV/AIDS and those on immunosuppressant drugs and does not usually affect fit and healthy people, C. gattii (found in some parts of Canada and the US) does. Once breathed in, the dried yeast cells colonize the lungs, where they are either cleared by immune cells, lie dormant, or cause infection and spread.Diagnosis is by isolating Cryptococcus from a sample of affected tissue or direct observation of the fungus by using staining of body fluids. It can be cultured from a cerebrospinal fluid, sputum, and skin biopsy. Treatment is with fluconazole or amphotericin B.Data from 2009 estimated that of the almost one million cases of cryptococcal meningitis that occurred worldwide annually, 700,000 occurred in sub-Saharan Africa and 600,000 per year died. Cryptococcosis was rare before the 1970s which saw an increase in at-risk groups such as people with organ transplant or on immunosuppressant medications. The number of cases escalated in the mid-1980s with over 80% occurring in people with HIV/AIDS. Pigeon breeders (or fanciers) are known to have a high incidence of cryptococcal infections including PCC due to Cryptococcus association with pigeon droppings. Classification Cryptococcus is generally classified according to how it is acquired and its site. It typically begins in the lungs before spreading to other parts of the body, particularly the brain and nervous system. The skin type is less common. Signs and symptoms Cough, shortness of breath, chest pain and fever are seen when the lungs are infected, appearing like a pneumonia. There may also be feeling of tiredness. When the brain is infected, symptoms include headache, fever, neck pain, nausea and vomiting, light sensitivity, confusion or changes in behaviour. It can also affect other parts of the body including skin, eyes, bones and prostate. In the skin, it may appear as several fluid-filled nodules with dead tissue. Depending on the site of infection, other features may include loss of vision, blurred vision, inability to move an eye and memory loss.Symptom onset is often sudden when lungs are infected and gradual over several weeks when the central nervous system is affected. Cause Cryptococcosis is a common opportunistic infection for AIDS, and is particularly common among people living with AIDS in Africa. Other conditions that pose an increased risk include certain malignancies (such as lymphoma), liver cirrhosis, organ transplants, and long-term corticosteroid therapy.Distribution is worldwide in soil. The prevalence of cryptococcosis has been increasing over the past 50 years for many reasons, including the increase in incidence of AIDS and the expanded use of immunosuppressive drugs.In humans, C. neoformans chiefly infects the skin, lungs, and central nervous system (causing meningitis). Less commonly it may affect other organs such as the eye or prostate. Primary Cutaneous Cryptococcosis Primary Cutaneous Cryptococcosis (PCC) is a distinct clinical diagnosis separate from the secondary cutaneous cryptococcosis that is spread from systematic infection. Males are more likely to develop the infection and a 2020 study showed that the sex bias may be due to a growth hormone, produced by C. neoformans called gibberellic acid (GA) that is upregulated by testosterone. The upper limbs account for a majority of infections. Isolates found in PCC include Cryptococcus neoformans (most common), Cryptococcus gattii, and Cryptococcus laurentii. Prognosis for PCC is generally good outside of disseminated infection.Morphologic description of the lesions show umbilicated papules, nodules, and violaceous plaques that can mimic other cutaneous diseases like molluscum contagiosum and Kaposis sarcoma. These lesions may be present months before other signs of system infection in patients with AIDS. Pulmonary Cryptococcosis Cryptococcus (both C. neoformans and C. gattii) plays a common role in pulmonary invasive mycosis seen in adults with HIV and other immunocompromised conditions. It also affects healthy adults at a much lower frequency and severity as healthy hosts may have no or mild symptoms. Immune-competent hosts may not seek or require treatment, but careful observation may be important. Cryptococcal pneumonia has a potential to disseminate to the central nervous system (CNS) especially in immunocompromised individuals.Pulmonary cryptococcosis has a worldwide distribution and is commonly underdiagnosed due to limitations in diagnostic capabilities. Since pulmonary nodules are its most common radiological feature, it can clinically and radiologically mimic lung cancer, TB, and other pulmonary mycoses. The sensitivity of cultures and the Cryptococcal (CrAg) antigen with lateral flow device on serum are rarely positive in the absence of disseminated disease. Moreover, pulmonary cryptococcosis worsen the prognosis of cryptococcal meningitis. Cryptococcal meningitis Cryptococcal meningitis (infection of the meninges, the tissue covering the brain) is believed to result from dissemination of the fungus from either an observed or unappreciated pulmonary infection. Often there is also silent dissemination throughout the brain when meningitis is present. People with defects in their cell-mediated immunity, for example, people with AIDS, are especially susceptible to disseminated cryptococcosis. Cryptococcosis is often fatal, even if treated. It is estimated that the three-month case-fatality rate is 9% in high-income regions, 55% in low/middle-income regions, and 70% in sub-Saharan Africa. As of 2009 there were globally approximately 958,000 annual cases and 625,000 deaths within three months after infection.Although C. neoformans infection most commonly occurs as an opportunistic infection in immunocompromised people (such as those living with AIDS), C. gattii often infects immunocompetent people as well.Cryptococcus (both C. neoformans and C. gattii) is the dominant and leading etiologic agent of meningitis in adults with HIV and is considered an "emerging" disease in healthy adults. Though the rate of infection is clearly higher with immunocompromised individuals, some studies suggest a higher mortality rate in patients with non-HIV cryptococcal meningitis secondary to the role of T-cell mediated reaction and injury. CD4+ T cells have proven roles in the defense against Cryptococcus, but it can also contribute to clinical deterioration due its inflammatory response. Diagnosis Dependent on the infectious syndrome, symptoms include fever, fatigue, dry cough, headache, blurred vision, and confusion. Symptom onset is often subacute, progressively worsened over several weeks. The two most common presentations are meningitis (an infection in and around the brain) and pulmonary (lung) infection.Any person who is found to have cryptococcosis at a site outside of the central nervous system (e.g., pulmonary cryptococcosis), a lumbar puncture is indicated to evaluate the cerebrospinal fluid (CSF) for evidence of cryptococcal meningitis, even if they do not have signs or symptoms of CNS disease. Detection of cryptococcal antigen (capsular material) by culture of CSF, sputum and urine provides definitive diagnosis. Blood cultures may be positive in heavy infections. India ink of the CSF is a traditional microscopic method of diagnosis, although the sensitivity is poor in early infection, and may miss 15–20% of patients with culture-positive cryptococcal meningitis. Unusual morphological forms are rarely seen. Cryptococcal antigen from cerebrospinal fluid is the best test for diagnosis of cryptococcal meningitis in terms of sensitivity. Apart from conventional methods of detection like direct microscopy and culture, rapid diagnostic methods to detect cryptococcal antigen by latex agglutination test, lateral flow immunochromatographic assay (LFA), or enzyme immunoassay (EIA). A new cryptococcal antigen LFA was FDA approved in July 2011. Polymerase chain reaction (PCR) has been used on tissue specimens. Cryptococcosis can rarely occur in the non-immunosuppressed people, particularly with Cryptococcus gattii. Prevention Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rates of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL. Cryptococcal antigen screen and preemptive treatment with fluconazole is cost saving to the healthcare system by avoiding cryptococcal meningitis. The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4<100 cells/μL. This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy. Cryptococcosis accounts for 20-25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4<100 cells/μL.Antifungal prophylaxis such as fluconazole and itraconazole reduces the risk of contracting cryptococcosis in those with low CD4 cell count and high risk of developing such disease in a setting of cryptococcal antigen screening tests are not available. Treatment Treatment options in persons without HIV-infection have not been well studied. Intravenous Amphotericin B combined with flucytosine by mouth is recommended for initial treatment (induction therapy).People living with AIDS often have a greater burden of disease and higher mortality (30–70% at 10-weeks), but recommended therapy is with amphotericin B and flucytosine. Where flucytosine is not available (many low and middle income countries), fluconazole should be used with amphotericin. Amphotericin-based induction therapy has much greater microbiologic activity than fluconazole monotherapy with 30% better survival at 10-weeks. Based on a systematic review of existing data, the most cost-effective induction treatment in resource-limited settings appears to be one week of amphotericin B coupled with high-dose fluconazole. After initial induction treatment as above, typical consolidation therapy is with oral fluconazole for at least 8 weeks used with secondary prophylaxis with fluconazole thereafter.The decision on when to start treatment for HIV appears to be very different than other opportunistic infections. A large multi-site trial supports deferring ART for 4–6 weeks was overall preferable with 15% better 1-year survival than earlier ART initiation at 1–2 weeks after diagnosis. A 2018 Cochrane review also supports the delayed starting of treatment until cryptococcosis starts improving with antifungal treatment. IRIS The immune reconstitution inflammatory syndrome (IRIS) has been described in those with normal immune function with meningitis caused by C. gattii and C. grubii. The increasing inflammation can cause brain injury or be fatal. Epidemiology Data from 2009 estimated that of the almost one million cases of cryptococcal meningitis that occurred worldwide annually, 700,000 occurred in sub-Saharan Africa and 600,000 per year died. Other animals Cryptococcosis is also seen in cats and occasionally dogs. It is the most common deep fungal disease in cats, usually leading to chronic infection of the nose and sinuses, and skin ulcers. Cats may develop a bump over the bridge of the nose from local tissue inflammation. It can be associated with FeLV infection in cats. Cryptococcosis is most common in dogs and cats but cattle, sheep, goats, horses, wild animals, and birds can also be infected. Soil, fowl manure, and pigeon droppings are among the sources of infection. References Further reading Perfect JR, et al. (2010). "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america". Clinical Infectious Diseases. 50 (3): 291–322. doi:10.1086/649858. PMC 5826644. PMID 20047480. Gullo FP, et al. (2013). "Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment". European Journal of Clinical Microbiology & Infectious Diseases. 32 (11): 1377–1391. doi:10.1007/s10096-013-1915-8. PMID 24141976. S2CID 11317427. Perfect JR, et al. (2005). "Cryptococcus neoformans: a sugar-coated killer with designer genes". FEMS Immunology and Medical Microbiology. 45 (11): 395–404. doi:10.1016/j.femsim.2005.06.005. PMID 16055314. (Review) External links Medscape entry on cryptococcosis

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

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

Hypothyroidism (also called underactive thyroid, low thyroid or hypothyreosis) is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as poor ability to tolerate cold, a feeling of tiredness, constipation, slow heart rate, depression, and weight gain. Occasionally there may be swelling of the front part of the neck due to goiter. Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.Worldwide, too little iodine in the diet is the most common cause of hypothyroidism. Hashimotos thyroiditis is the most common cause of hypothyroidism in countries with sufficient dietary iodine. Less common causes include previous treatment with radioactive iodine, injury to the hypothalamus or the anterior pituitary gland, certain medications, a lack of a functioning thyroid at birth, or previous thyroid surgery. The diagnosis of hypothyroidism, when suspected, can be confirmed with blood tests measuring thyroid-stimulating hormone (TSH) and thyroxine levels.Salt iodization has prevented hypothyroidism in many populations. Thyroid hormone replacement with levothyroxine treats hypothyroidism. Medical professionals adjust the dose according to symptoms and normalization of the thyroxine and TSH levels. Thyroid medication is safe in pregnancy. Although an adequate amount of dietary iodine is important, too much may worsen specific forms of hypothyroidism.Worldwide about one billion people are estimated to be iodine-deficient; however, it is unknown how often this results in hypothyroidism. In the United States, hypothyroidism occurs in 0.3–0.4% of people. Subclinical hypothyroidism, a milder form of hypothyroidism characterized by normal thyroxine levels and an elevated TSH level, is thought to occur in 4.3–8.5% of people in the United States. Hypothyroidism is more common in women than in men. People over the age of 60 are more commonly affected. Dogs are also known to develop hypothyroidism, as are cats and horses, albeit more rarely. The word hypothyroidism is from Greek hypo- reduced, thyreos shield, and eidos form. Signs and symptoms People with hypothyroidism often have no or only mild symptoms. Numerous symptoms and signs are associated with hypothyroidism and can be related to the underlying cause, or a direct effect of having not enough thyroid hormones. Hashimotos thyroiditis may present with the mass effect of a goiter (enlarged thyroid gland). In middle-aged women, the symptoms may be mistaken for those of menopause. Delayed relaxation after testing the ankle jerk reflex is a characteristic sign of hypothyroidism and is associated with the severity of the hormone deficit. Myxedema coma Myxedema coma is a rare but life-threatening state of extreme hypothyroidism. It may occur in those with established hypothyroidism when they develop an acute illness. Myxedema coma can be the first presentation of hypothyroidism. People with myxedema coma typically have a low body temperature without shivering, confusion, a slow heart rate and reduced breathing effort. There may be physical signs suggestive of hypothyroidism, such as skin changes or enlargement of the tongue. Pregnancy Even mild or subclinical hypothyroidism leads to possible infertility and an increased risk of miscarriage. Hypothyroidism in early pregnancy, even with limited or no symptoms, may increase the risk of pre-eclampsia, offspring with lower intelligence, and the risk of infant death around the time of birth. Women are affected by hypothyroidism in 0.3–0.5% of pregnancies. Subclinical hypothyroidism during pregnancy is associated with gestational diabetes, low birth-weight, placental abruption, and the birth of the baby before 37 weeks of pregnancy. Children Newborn children with hypothyroidism may have normal birth weight and height (although the head may be larger than expected and the posterior fontanelle may be open). Some may have drowsiness, decreased muscle tone, a hoarse-sounding cry, feeding difficulties, constipation, an enlarged tongue, umbilical hernia, dry skin, a decreased body temperature, and jaundice. A goiter is rare, although it may develop later in children who have a thyroid gland that does not produce functioning thyroid hormone. A goiter may also develop in children growing up in areas with iodine deficiency. Normal growth and development may be delayed, and not treating infants may lead to an intellectual impairment (IQ 6–15 points lower in severe cases). Other problems include the following: difficulty with large scale and fine motor skills and coordination, reduced muscle tone, squinting, decreased attention span, and delayed speaking. Tooth eruption may be delayed.In older children and adolescents, the symptoms of hypothyroidism may include fatigue, cold intolerance, sleepiness, muscle weakness, constipation, a delay in growth, overweight for height, pallor, coarse and thick skin, increased body hair, irregular menstrual cycles in girls, and delayed puberty. Signs may include delayed relaxation of the ankle reflex and a slow heartbeat. A goiter may be present with a completely enlarged thyroid gland; sometimes only part of the thyroid is enlarged and it can be knobby. Related disorders Thyroid hormone abnormalities are common in major psychiatric disorders including bipolar disorder; clinical research has shown there is a high rate of thyroid dysfunction in mood disorders and schizophrenia-spectrum disorders, concluding that there is a case for screening for the latter among people with thyroid illness. Causes Hypothyroidism is caused by inadequate function of the gland itself (primary hypothyroidism), inadequate stimulation by thyroid-stimulating hormone from the pituitary gland (secondary hypothyroidism), or inadequate release of thyrotropin-releasing hormone from the brains hypothalamus (tertiary hypothyroidism). Primary hypothyroidism is about a thousandfold more common than central hypothyroidism.Iodine deficiency is the most common cause of primary hypothyroidism and endemic goiter worldwide. In areas of the world with sufficient dietary iodine, hypothyroidism is most commonly caused by the autoimmune disease Hashimotos thyroiditis (chronic autoimmune thyroiditis). Hashimotos may be associated with a goiter. It is characterized by infiltration of the thyroid gland with T lymphocytes and autoantibodies against specific thyroid antigens such as thyroid peroxidase, thyroglobulin and the TSH receptor.After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards. This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.Autoimmune thyroiditis (Hashimotos) is associated with other immune-mediated diseases such as diabetes mellitus type 1, pernicious anemia, myasthenia gravis, celiac disease, rheumatoid arthritis and systemic lupus erythematosus. It may occur as part of autoimmune polyendocrine syndrome (type 1 and type 2).Iatrogenic hypothyroidism can be surgical (a result of thyroidectomy, usually for thyroid nodules or cancer) or following radioiodine ablation (usually for Graves disease). Pathophysiology Thyroid hormone is required for the normal functioning of numerous tissues in the body. In healthy individuals, the thyroid gland predominantly secretes thyroxine (T4), which is converted into triiodothyronine (T3) in other organs by the selenium-dependent enzyme iodothyronine deiodinase. Triiodothyronine binds to the thyroid hormone receptor in the nucleus of cells, where it stimulates the turning on of particular genes and the production of specific proteins. Additionally, the hormone binds to integrin αvβ3 on the cell membrane, thereby stimulating the sodium–hydrogen antiporter and processes such as formation of blood vessels and cell growth. In blood, almost all thyroid hormone (99.97%) are bound to plasma proteins such as thyroxine-binding globulin; only the free unbound thyroid hormone is biologically active.The thyroid gland is the only source of thyroid hormone in the body; the process requires iodine and the amino acid tyrosine. Iodine in the bloodstream is taken up by the gland and incorporated into thyroglobulin molecules. The process is controlled by the thyroid-stimulating hormone (TSH, thyrotropin), which is secreted by the pituitary. Not enough iodine, or not enough TSH, can result in decreased production of thyroid hormones.The hypothalamic–pituitary–thyroid axis plays a key role in maintaining thyroid hormone levels within normal limits. Production of TSH by the anterior pituitary gland is stimulated in turn by thyrotropin-releasing hormone (TRH), released from the hypothalamus. Production of TSH and TRH is decreased by thyroxine by a negative feedback process. Not enough TRH, which is uncommon, can lead to not enough TSH and thereby to not enough thyroid hormone production.Pregnancy leads to marked changes in thyroid hormone physiology. The gland is increased in size by 10%, thyroxine production is increased by 50%, and iodine requirements are increased. Many women have normal thyroid function but have immunological evidence of thyroid autoimmunity (as evidenced by autoantibodies) or are iodine deficient, and develop evidence of hypothyroidism before or after giving birth. Diagnosis Laboratory testing of thyroid stimulating hormone levels in the blood is considered the best initial test for hypothyroidism; a second TSH level is often obtained several weeks later for confirmation. Levels may be abnormal in the context of other illnesses, and TSH testing in hospitalized people is discouraged unless thyroid dysfunction is strongly suspected, as the cause of the acute illness. An elevated TSH level indicates that the thyroid gland is not producing enough thyroid hormone, and free T4 levels are then often obtained. Measuring T3 is discouraged by the AACE in the assessment for hypothyroidism. In England and Wales, the National Institute for Health and Care Excellence (NICE) recommends routine T4 testing in children, and T3 testing in both adults and children if central hypothyroidism is suspected and the TSH is low. There are a number of symptom rating scales for hypothyroidism; they provide a degree of objectivity but have limited use for diagnosis. Many cases of hypothyroidism are associated with mild elevations in creatine kinase and liver enzymes in the blood. They typically return to normal when hypothyroidism has been fully treated. Levels of cholesterol, low-density lipoprotein and lipoprotein (a) can be elevated; the impact of subclinical hypothyroidism on lipid parameters is less well-defined.Very severe hypothyroidism and myxedema coma are characteristically associated with low sodium levels in the blood together with elevations in antidiuretic hormone, as well as acute worsening of kidney function due to a number of causes. In most causes, however, it is unclear if the relationship is causal.A diagnosis of hypothyroidism without any lumps or masses felt within the thyroid gland does not require thyroid imaging; however, if the thyroid feels abnormal, diagnostic imaging is then recommended. The presence of antibodies against thyroid peroxidase (TPO) makes it more likely that thyroid nodules are caused by autoimmune thyroiditis, but if there is any doubt, a needle biopsy may be required. Central If the TSH level is normal or low and serum free T4 levels are low, this is suggestive of central hypothyroidism (not enough TSH or TRH secretion by the pituitary gland or hypothalamus). There may be other features of hypopituitarism, such as menstrual cycle abnormalities and adrenal insufficiency. There might also be symptoms of a pituitary mass such as headaches and vision changes. Central hypothyroidism should be investigated further to determine the underlying cause. Overt In overt primary hypothyroidism, TSH levels are high and T4 and T3 levels are low. Overt hypothyroidism may also be diagnosed in those who have a TSH on multiple occasions of greater than 5mIU/L, appropriate symptoms, and only a borderline low T4. It may also be diagnosed in those with a TSH of greater than 10mIU/L. Subclinical Subclinical hypothyroidism is a milder form of hypothyroidism characterized by an elevated serum TSH level, but with a normal serum free thyroxine level. This milder form of hypothyroidism is most commonly caused by Hashimotos thyroiditis. In adults it is diagnosed when TSH levels are greater than 5 mIU/L and less than 10mIU/L. The presentation of subclinical hypothyroidism is variable and classic signs and symptoms of hypothyroidism may not be observed. Of people with subclinical hypothyroidism, a proportion will develop overt hypothyroidism each year. In those with detectable antibodies against thyroid peroxidase (TPO), this occurs in 4.3%, while in those with no detectable antibodies, this occurs in 2.6%. Those with subclinical hypothyroidism and detectable anti-TPO antibodies who do not require treatment should have repeat thyroid function tests more frequently (e.g. yearly) compared with those who do not have antibodies. Pregnancy During pregnancy, the thyroid gland must produce 50% more thyroid hormone to provide enough thyroid hormone for the developing fetus and the expectant mother. In pregnancy, free thyroxine levels may be lower than anticipated due to increased binding to thyroid binding globulin and decreased binding to albumin. They should either be corrected for the stage of pregnancy, or total thyroxine levels should be used instead for diagnosis. TSH values may also be lower than normal (particularly in the first trimester) and the normal range should be adjusted for the stage of pregnancy.In pregnancy, subclinical hypothyroidism is defined as a TSH between 2.5 and 10 mIU/L with a normal thyroxine level, while those with TSH above 10 mIU/L are considered to be overtly hypothyroid even if the thyroxine level is normal. Antibodies against TPO may be important in making decisions about treatment, and should, therefore, be determined in women with abnormal thyroid function tests.Determination of TPO antibodies may be considered as part of the assessment of recurrent miscarriage, as subtle thyroid dysfunction can be associated with pregnancy loss, but this recommendation is not universal, and presence of thyroid antibodies may not predict future outcome. Prevention Hypothyroidism may be prevented in a population by adding iodine to commonly used foods. This public health measure has eliminated endemic childhood hypothyroidism in countries where it was once common. In addition to promoting the consumption of iodine-rich foods such as dairy and fish, many countries with moderate iodine deficiency have implemented universal salt iodization. Encouraged by the World Health Organization, 70% of the worlds population across 130 countries are receiving iodized salt. In some countries, iodized salt is added to bread. Despite this, iodine deficiency has reappeared in some Western countries as a result of attempts to reduce salt intake.Pregnant and breastfeeding women, who require 66% more daily iodine than non-pregnant women, may still not be getting enough iodine. The World Health Organization recommends a daily intake of 250 µg for pregnant and breastfeeding women. As many women will not achieve this from dietary sources alone, the American Thyroid Association recommends a 150 µg daily supplement by mouth. Screening Screening for hypothyroidism is performed in the newborn period in many countries, generally using TSH. This has led to the early identification of many cases and thus the prevention of developmental delay. It is the most widely used newborn screening test worldwide. While TSH-based screening will identify the most common causes, the addition of T4 testing is required to pick up the rarer central causes of neonatal hypothyroidism. If T4 determination is included in the screening done at birth, this will identify cases of congenital hypothyroidism of central origin in 1:16,000 to 1:160,000 children. Considering that these children usually have other pituitary hormone deficiencies, early identification of these cases may prevent complications.In adults, widespread screening of the general population is a matter of debate. Some organizations (such as the United States Preventive Services Task Force) state that evidence is insufficient to support routine screening, while others (such as the American Thyroid Association) recommend either intermittent testing above a certain age in all sexes or only in women. Targeted screening may be appropriate in a number of situations where hypothyroidism is common: other autoimmune diseases, a strong family history of thyroid disease, those who have received radioiodine or other radiation therapy to the neck, those who have previously undergone thyroid surgery, those with an abnormal thyroid examination, those with psychiatric disorders, people taking amiodarone or lithium, and those with a number of health conditions (such as certain heart and skin conditions). Yearly thyroid function tests are recommended in people with Down syndrome, as they are at higher risk of thyroid disease. Guidelines for England and Wales from the National Institute for Health and Care Excellence (NICE) recommend testing for thyroid disease in people with type 1 diabetes and new-onset atrial fibrillation, and suggests testing in those with depression or unexplained anxiety (all ages), in children with abnormal growth, or unexplained change in behaviour or school performance. On diagnosis of autoimmune thyroid disease, NICE also recommends screening for celiac disease. Management Hormone replacement Most people with hypothyroidism symptoms and confirmed thyroxine deficiency are treated with a synthetic long-acting form of thyroxine, known as levothyroxine (L-thyroxine). In young and otherwise healthy people with overt hypothyroidism, a full replacement dose (adjusted by weight) can be started immediately; in the elderly and people with heart disease a lower starting dose is recommended to prevent over supplementation and risk of complications. Lower doses may be sufficient in those with subclinical hypothyroidism, while people with central hypothyroidism may require a higher than average dose.Blood free thyroxine and TSH levels are monitored to help determine whether the dose is adequate. This is done 4–8 weeks after the start of treatment or a change in levothyroxine dose. Once the adequate replacement dose has been established, the tests can be repeated after 6 and then 12 months, unless there is a change in symptoms. Normalization of TSH does not mean that other abnormalities associated with hypothyroidism improve entirely, such as elevated cholesterol levels.In people with central/secondary hypothyroidism, TSH is not a reliable marker of hormone replacement and decisions are based mainly on the free T4 level. Levothyroxine is best taken 30–60 minutes before breakfast, or four hours after food, as certain substances such as food and calcium can inhibit the absorption of levothyroxine. There is no direct way of increasing thyroid hormone secretion by the thyroid gland. Liothyronine Treatment with liothyronine alone has not received enough study to make a recommendation as to its use; due to its shorter half-life it would need to be taken more often than levothyroxine.Adding liothyronine (synthetic T3) to levothyroxine has been suggested as a measure to provide better symptom control, but this has not been confirmed by studies. In 2007, the British Thyroid Association stated that combined T4 and T3 therapy carried a higher rate of side effects and no benefit over T4 alone. Similarly, American guidelines discourage combination therapy due to a lack of evidence, although they acknowledge that some people feel better when receiving combination treatment. Guidelines by NICE for England and Wales discourage liothyronine.People with hypothyroidism who do not feel well despite optimal levothyroxine dosing may request adjunctive treatment with liothyronine. A 2012 guideline from the European Thyroid Association recommends that support should be offered with regards to the chronic nature of the disease and that other causes of the symptoms should be excluded. Addition of liothyronine should be regarded as experimental, initially only for a trial period of 3 months, and in a set ratio to the current dose of levothyroxine. The guideline explicitly aims to enhance the safety of this approach and to counter its indiscriminate use. Desiccated animal thyroid Desiccated thyroid extract is an animal-based thyroid gland extract, most commonly from pigs. It is a combination therapy, containing forms of T4 and T3. It also contains calcitonin (a hormone produced in the thyroid gland involved in the regulation of calcium levels), T1 and T2; these are not present in synthetic hormone medication. This extract was once a mainstream hypothyroidism treatment, but its use today is unsupported by evidence; British Thyroid Association and American professional guidelines discourage its use, as does NICE. Subclinical hypothyroidism There is no evidence of a benefit from treating subclinical hypothyroidism in those who are not pregnant, and there are potential risks of overtreatment. Untreated subclinical hypothyroidism may be associated with a modest increase in the risk of coronary artery disease when the TSH is over 10 mIU/L. A 2007 review found no benefit of thyroid hormone replacement except for "some parameters of lipid profiles and left ventricular function". There is no association between subclinical hypothyroidism and an increased risk of bone fractures, nor is there a link with cognitive decline.Since 2008, consensus American opinion has been that in general people with TSH under 10 to 20 mIU/L do not require treatment.American guidelines recommend that treatment should be considered in people with symptoms of hypothyroidism, detectable antibodies against thyroid peroxidase, a history of heart disease or are at an increased risk for heart disease, if the TSH is elevated but below 10 mIU/L. NICE recommends that those with a TSH above 10 mIU/L should be treated in the same way as overt hypothyroidism. Those with an elevated TSH but below 10 mIU/L who have symptoms suggestive of hypothyroidism should have a trial of treatment but with the aim to stopping this if the symptoms persist despite normalisation of the TSH.A recent meta-analysis, however, found an increased risk for cardiovascular death in subclinical hypothyreoidism. Myxedema coma Myxedema coma or severe decompensated hypothyroidism usually requires admission to the intensive care, close observation and treatment of abnormalities in breathing, temperature control, blood pressure, and sodium levels. Mechanical ventilation may be required, as well as fluid replacement, vasopressor agents, careful rewarming, and corticosteroids (for possible adrenal insufficiency which can occur together with hypothyroidism). Careful correction of low sodium levels may be achieved with hypertonic saline solutions or vasopressin receptor antagonists. For rapid treatment of the hypothyroidism, levothyroxine or liothyronine may be administered intravenously, particularly if the level of consciousness is too low to be able to safely swallow medication. While administration through a nasogastric tube is possible, this may be unsafe and is discouraged. Pregnancy In women with known hypothyroidism who become pregnant, it is recommended that serum TSH levels are closely monitored. Levothyroxine should be used to keep TSH levels within the normal range for that trimester. The first trimester normal range is below 2.5 mIU/L and the second and third trimesters normal range is below 3.0 mIU/L. Treatment should be guided by total (rather than free) thyroxine or by the free T4 index. Similarly to TSH, the thyroxine results should be interpreted according to the appropriate reference range for that stage of pregnancy. The levothyroxine dose often needs to be increased after pregnancy is confirmed, although this is based on limited evidence and some recommend that it is not always required; decisions may need to based on TSH levels.Women with anti-TPO antibodies who are trying to become pregnant (naturally or by assisted means) may require thyroid hormone supplementation even if the TSH level is normal. This is particularly true if they have had previous miscarriages or have been hypothyroid in the past. Supplementary levothyroxine may reduce the risk of preterm birth and possibly miscarriage. The recommendation is stronger in pregnant women with subclinical hypothyroidism (defined as TSH 2.5–10 mIU/L) who are anti-TPO positive, in view of the risk of overt hypothyroidism. If a decision is made not to treat, close monitoring of the thyroid function (every 4 weeks in the first 20 weeks of pregnancy) is recommended. If anti-TPO is not positive, treatment for subclinical hypothyroidism is not currently recommended. It has been suggested that many of the aforementioned recommendations could lead to unnecessary treatment, in the sense that the TSH cutoff levels may be too restrictive in some ethnic groups; there may be little benefit from treatment of subclinical hypothyroidism in certain cases. Alternative medicine The effectiveness and safety of using Chinese herbal medicines to treat hypothyroidism is not known. Epidemiology Worldwide about one billion people are estimated to be iodine deficient; however, it is unknown how often this results in hypothyroidism. In large population-based studies in Western countries with sufficient dietary iodine, 0.3–0.4% of the population have overt hypothyroidism. A larger proportion, 4.3–8.5%, have subclinical hypothyroidism. Undiagnosed hypothyroidism is estimated to affect about 4–7% of community-derived populations in the US and Europe. Of people with subclinical hypothyroidism, 80% have a TSH level below the 10 mIU/L mark regarded as the threshold for treatment. Children with subclinical hypothyroidism often return to normal thyroid function, and a small proportion develops overt hypothyroidism (as predicted by evolving antibody and TSH levels, the presence of celiac disease, and the presence of a goiter).Women are more likely to develop hypothyroidism than men. In population-based studies, women were seven times more likely than men to have TSH levels above 10 mU/L. 2–4% of people with subclinical hypothyroidism will progress to overt hypothyroidism each year. The risk is higher in those with antibodies against thyroid peroxidase. Subclinical hypothyroidism is estimated to affect approximately 2% of children; in adults, subclinical hypothyroidism is more common in the elderly, and in Caucasians. There is a much higher rate of thyroid disorders, the most common of which is hypothyroidism, in individuals with Down syndrome and Turner syndrome.Very severe hypothyroidism and myxedema coma are rare, with it estimated to occur in 0.22 per million people a year. The majority of cases occur in women over 60 years of age, although it may happen in all age groups.Most hypothyroidism is primary in nature. Central/secondary hypothyroidism affects 1:20,000 to 1:80,000 of the population, or about one out of every thousand people with hypothyroidism. History In 1811, Bernard Courtois discovered iodine was present in seaweed, and iodine intake was linked with goiter size in 1820 by Jean-Francois Coindet. Gaspard Adolphe Chatin proposed in 1852 that endemic goiter was the result of not enough iodine intake, and Eugen Baumann demonstrated iodine in thyroid tissue in 1896.The first cases of myxedema were recognized in the mid-19th century (the 1870s), but its connection to the thyroid was not discovered until the 1880s when myxedema was observed in people following the removal of the thyroid gland (thyroidectomy). The link was further confirmed in the late 19th century when people and animals who had had their thyroid removed showed improvement in symptoms with transplantation of animal thyroid tissue. The severity of myxedema, and its associated risk of mortality and complications, created interest in discovering effective treatments for hypothyroidism. Transplantation of thyroid tissue demonstrated some efficacy, but recurrences of hypothyroidism was relatively common, and sometimes required multiple repeat transplantations of thyroid tissue.In 1891, the English physician George Redmayne Murray introduced subcutaneously injected sheep thyroid extract, followed shortly after by an oral formulation. Purified thyroxine was introduced in 1914 and in the 1930s synthetic thyroxine became available, although desiccated animal thyroid extract remained widely used. Liothyronine was identified in 1952.Early attempts at titrating therapy for hypothyroidism proved difficult. After hypothyroidism was found to cause a lower basal metabolic rate, this was used as a marker to guide adjustments in therapy in the early 20th century (around 1915). However, a low basal metabolic rate was known to be non-specific, also present in malnutrition. The first laboratory test to be helpful in assessing thyroid status was the serum protein-bound iodine, which came into use around the 1950s. In 1971, the thyroid stimulating hormone (TSH) radioimmunoassay was developed, which was the most specific marker for assessing thyroid status in patients. Many people who were being treated based on basal metabolic rate, minimizing hypothyroid symptoms, or based on serum protein-bound iodine, were found to have excessive thyroid hormone. The following year, in 1972, a T3 radioimmunoassay was developed, and in 1974, a T4 radioimmunoassay was developed. Other animals In veterinary practice, dogs are the species most commonly affected by hypothyroidism. The majority of cases occur as a result of primary hypothyroidism, of which two types are recognized: lymphocytic thyroiditis, which is probably immune-driven and leads to destruction and fibrosis of the thyroid gland, and idiopathic atrophy, which leads to the gradual replacement of the gland by fatty tissue. There is often lethargy, cold intolerance, exercise intolerance, and weight gain. Furthermore, skin changes and fertility problems are seen in dogs with hypothyroidism, as well as a number of other symptoms. The signs of myxedema can be seen in dogs, with prominence of skin folds on the forehead, and cases of myxedema coma are encountered. The diagnosis can be confirmed by blood test, as the clinical impression alone may lead to overdiagnosis. Lymphocytic thyroiditis is associated with detectable antibodies against thyroglobulin, although they typically become undetectable in advanced disease. Treatment is with thyroid hormone replacement.Other species that are less commonly affected include cats and horses, as well as other large domestic animals. In cats, hypothyroidism is usually the result of other medical treatment such as surgery or radiation. In young horses, congenital hypothyroidism has been reported predominantly in Western Canada and has been linked with the mothers diet. References External links Hypothyroidism at Curlie "Hypothyroidism information for patients". American Thyroid Association. Retrieved 2017-03-25. "UK Guidelines for the use of thyroid function tests" (PDF). The Association for Clinical Biochemistry, British Thyroid Association and British Thyroid Foundation. 2006. Retrieved 2013-12-25. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S (March 2017). "2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum". Thyroid. 27 (3): 315–389. doi:10.1089/thy.2016.0457. PMC 3472679. PMID 28056690.

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

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

Alcohol dependence is a previous (DSM-IV and ICD-10) psychiatric diagnosis in which an individual is physically or psychologically dependent upon alcohol (also chemically known as ethanol). In 2013, it was reclassified as alcohol use disorder in DSM-5, which combined alcohol dependence and alcohol abuse into this diagnosis. Definition Diagnosis DSM: Alcohol dependence According to the DSM-IV criteria for alcohol dependence, at least three out of seven of the following criteria must be manifest during a 12-month period: Tolerance Withdrawal symptoms or clinically defined alcohol withdrawal syndrome Use in larger amounts or for longer periods than intended Persistent desire or unsuccessful efforts to cut down on alcohol use Time is spent obtaining alcohol or recovering from effects Social, occupational and recreational pursuits are given up or reduced because of alcohol use Use is continued despite knowledge of alcohol-related harm (physical or psychological) Other alcohol-related disorders Because only 3 of the 7 DSM-IV criteria for alcohol dependence are required, not all patients meet the same criteria and therefore not all have the same symptoms and problems related to drinking. Not everyone with alcohol dependence, therefore, experiences physiological dependence. Alcohol dependence is differentiated from alcohol abuse by the presence of symptoms such as tolerance and withdrawal. Both alcohol dependence and alcohol abuse are sometimes referred to by the less specific term alcoholism. However, many definitions of alcoholism exist, and only some are compatible with alcohol abuse. There are two major differences between alcohol dependence and alcoholism as generally accepted by the medical community. Alcohol dependence refers to an entity in which only alcohol is the involved addictive agent. Alcoholism refers to an entity in which alcohol or any cross-tolerant addictive agent is involved. In alcohol dependence, reduction of alcohol, as defined within DSM-IV, can be attained by learning to control the use of alcohol. That is, a client can be offered a social learning approach that helps them to cope with external pressures by re-learning their pattern of drinking alcohol. In alcoholism, patients are generally not presumed to be in remission unless they are abstinent from alcohol.The following elements are the template for which the degree of dependence is judged: Narrowing of the drinking repertoire. Increased salience of the need for alcohol over competing needs and responsibilities. An acquired tolerance to alcohol. Withdrawal symptoms. Relief or avoidance of withdrawal symptoms by further drinking. Subjective awareness of compulsion to drink. Reinstatement after abstinence. Screening AUDIT has replaced older screening tools such as CAGE but there are many shorter alcohol screening tools, mostly derived from the AUDIT. The Severity of Alcohol Dependence Questionnaire (SAD-Q) is a more specific twenty-item inventory for assessing the presence and severity of alcohol dependence. AUDIT The Alcohol Use Disorders Identification Test (AUDIT) is considered the most accurate alcohol screening tool for identifying potential alcohol misuse, including dependence. It was developed by the World Health Organisation, designed initially for use in primary healthcare settings with supporting guidance. CAGE The CAGE questionnaire, the name of which is an acronym of its four questions, is a widely used method of screening for alcoholism. Online version of the CAGE questionnaire SADQ The Severity of Alcohol Dependence Questionnaire (SADQ or SAD-Q) is a 20 item clinical screening tool designed to measure the presence and level of alcohol dependence. Withdrawal Withdrawals from alcohol dependence is a common side effect that occurs when a person with the dependency stops drinking abruptly or even cuts back on their drinking after a prolonged period of indulgence. Withdrawal from alcohol dependence can vary from mild, moderate to severe, depending on several factors such as: how long the person has been drinking, are they a binge drinker, do they relapse chronically, how much do they drink daily. All these factors can vary from one person to the next depending on psychological, environmental, and biological factors. Some common withdrawal side effects are as listed: Mild Nausea Vomiting Rapid heartbeat Elevated blood pressure Fatigue Body aches / tremors Anxiety / Irritability / Depression Fuzzy brain Issues with sleeping Severe Vomiting Hypertensive crisis Seizures / Tremors Delusions / Hallucinations Dehydration Fever Chills / Shakes Extreme mood lability Mental pandemonium Little to no appetiteThe spectrum of alcohol withdrawal symptoms range from such minor symptoms as insomnia and tremulousness to severe complications such as withdrawal seizures and delirium tremens. Alcohol withdrawal syndrome can be very tricky to diagnose, due to other preliminary conditions that may exist from individual to individual. Treatment Treatments for alcohol dependence can be separated into two groups, those directed towards severely alcohol-dependent people, and those focused for those at risk of becoming dependent on alcohol. Treatment for alcohol dependence often involves utilizing relapse prevention, support groups, psychotherapy, and setting short-term goals. The Twelve-Step Program is also a popular faith-based process used by those wishing to recover from alcohol dependence.The ultimate goal when it comes to treating alcohol dependence or as the DSM-5 now calls it alcohol use disorder, is to help with establishing abstinence from drinking. There are several other benefits that come along with treatment. For some, it is reconnecting with themselves and obtaining self-esteem and confidence, a healthier lifestyle (physically and mentally), creating new relationships with other like-minded people as well as rekindling or mending old relationships if possible. The treatment process consists typically of two parts short-term and long-term. First, there is the path to abstinence and/or recovery. There are several reasons why someone with alcohol use disorder or alcohol dependency would seek treatment. This can either be a personal reason or because of law enforcement. There is a series of different levels of treatment processes depending on the severity subtype. Some would or could benefit from medication treatment with psychosocial treatment, while others could just benefit from psychosocial treatment. Listed below are different some different types of treatments that are used with treating alcohol dependency/alcohol use disorder depending on several factors that vary from person to person. Types of treatments: Withdrawals (no medication aid needed) Withdrawals (depending on severity of symptoms, could be accompanied with supervision by medical personal and medication) Psychosocial treatment (counseling, CBT, psychoeducation, assertive community treatment) Alcoholics Anonymous Inpatient or outpatient programs Social services (case management) Al-Anon/Alateen Epidemiology About 12% of American adults have had an alcohol dependence problem at some time in their life. In the UK the NHS estimates that around 9% of men and 4% of UK women show signs of alcohol dependence. History The term alcohol dependence has replaced alcoholism as a term in order that individuals do not internalize the idea of cure and disease, but can approach alcohol as a chemical they may depend upon to cope with outside pressures. The contemporary definition of alcohol dependence is still based upon early research. There has been considerable scientific effort over the past several decades to identify and understand the core features of alcohol dependence. This work began in 1976, when the British psychiatrist Griffith Edwards and his American colleague Milton M. Gross collaborated to produce a formulation of what had previously been understood as alcoholism – the alcohol dependence syndrome. The alcohol dependence syndrome was seen as a cluster of seven elements that concur. It was argued that not all elements may be present in every case, but the picture is sufficiently regular and coherent to permit clinical recognition. The syndrome was also considered to exist in degrees of severity rather than as a categorical absolute. Thus, the proper question is not whether a person is dependent on alcohol, but how far along the path of dependence has a person progressed. See also Alcohol intoxication Alcoholic drink Alcohol-related dementia CRAFFT Screening Test Disulfiram-like drug High-functioning alcoholic Long-term effects of alcohol consumption Paddington alcohol test Notes External links Arnold Little, MD Alcohol Dependence – extensive article SADD – Short Alcohol Dependence Data Questionnaire. A brief, self-administered questionnaire sometimes utilised in individual or group treatments. R.R.Garifullin Using coding therapy to treat alcohol and drug addiction. Manipulations in psychotherapy. Rostov-on-Don, Feniks, 251 p. 2004. 251 p. ISBN 5-222-04382-7

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

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

Fosdenopterin (or cyclic pyranopterin monophosphate, cPMP), sold under the brand name Nulibry, is a medication used to reduce the risk of death due to a rare genetic disease known as molybdenum cofactor deficiency type A.The most common side effects include complications related to the intravenous line, fever, respiratory infections, vomiting, gastroenteritis, and diarrhea.Fosdenopterin was approved for medical use in the United States in February 2021, It is the first medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of molybdenum cofactor deficiency type A. and in the European Union in September 2022. Medical uses Fosdenopterin is indicated to reduce the risk of mortality in people with molybdenum cofactor deficiency (MoCD) type A. Mechanism of action People with molybdenum cofactor deficiency type A cannot produce cyclic pyranopterin monophosphate (cPMP) in their body. Fosdenopterin is an intravenous medication that replaces the missing cPMP. cPMP is a precursor to molybdopterin, which is required for the enzyme activity of sulfite oxidase, xanthine dehydrogenase/oxidase and aldehyde oxidase. History Fosdenopterin was developed at the German universities TU Braunschweig and the University of Cologne.The effectiveness of fosdenopterin for the treatment of MoCD-A was demonstrated in thirteen treated participants compared to eighteen matched, untreated participants. The participants treated with fosdenopterin had a survival rate of 84% at three years, compared to 55% for the untreated participants.The U.S. Food and Drug Administration (FDA) granted the application for fosdenopterin priority review, breakthrough therapy, and orphan drug designations along with a rare pediatric disease priority review voucher. The FDA granted the approval of Nulibry to Origin Biosciences, Inc., in February 2021. Society and culture Legal status On 21 July 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Nulibry, intended for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A. The applicant for this medicinal product is Comharsa Life Sciences Ltd. Fosdenopterin was approved for medical use in the European Union in September 2022. References External links "Fosdenopterin". Drug Information Portal. U.S. National Library of Medicine.

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

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

Cochlear hydrops (or cochlear Menieres or cochlear endolymphatic hydrops) is a condition of the inner ear involving a pathological increase of fluid affecting the cochlea. This results in swelling that can lead to hearing loss or changes in hearing perception. It is a form of endolymphatic hydrops and related to Menieres disease. Cochlear hydrops refers to a case of inner-ear hydrops that only involves auditory symptoms and does not cause vestibular issues. Cause and behavior Cochlear hydrops refers to an increase in endolymphatic fluid in the inner ear. This build-up is either due to an overproduction or insufficient drainage of endolymph in the constant regulation of fluid in the inner ear. Usually, only one ear is affected. The root cause of the process is unclear and may vary from patient to patient, but can have auto-immune, viral, and/or allergic triggers, among others.The build-up of endolymph creates pressure in the scala media. This causes its diameter to increase, and the vestibular membrane to curve outwards in the direction of the vestibule. The changes to the membrane can result in changes to either the hearing perception or hearing threshold of a patient.Episodes are usually cyclical and symptoms fluctuate through time. Patients may be symptom-free between episodes, which themselves may progressively worsen, improve, or remain constant in severity or duration. For some, permanent damage occurs, and they may be left with long-term hearing loss, hearing distortion, tinnitus, and/or a feeling of fullness in the affected ear(s).A study looking at spiral ganglion cell counts compared to hair cell counts in the inner ear of patients who had Menieres disease found that they maintained more hair cells than spinal ganglion cells. Thus, it could be possible that hydrops affects auditory nerves more than hair cells. In contrast, a 2021 article by Richard Gacek posits that the hearing loss is actually caused by toxic nucleic acids that are released to the outer hair cells: "Since the outer hair cells (OHC) are freely surrounded by perilymph, their walls and nerve terminals are also bathed in this fluid. The few type-II spiral ganglion cells in contact with the OHC are unlikely to play a significant role in hearing loss because of their low numbers and the lack of a known connection to the central auditory pathway." Symptoms Cochlear hydrops preferentially affects the apex of the cochlea where low-frequency sounds are interpreted. Due to the fluid imbalance in this area, parts of the cochlea are stretched or under more tension than usual, which can lead to distortions of sound, changes in pitch perception, or hearing loss, all usually in the low frequencies. Common symptoms include: Low-frequency sensorineural hearing loss. A feeling of fullness in the ear. Tinnitus (ringing in the ear). Diplacusis (the perception of sound being a different pitch in one ear). Hyperacusis (an intolerance to loud sounds). Depression or anxiety that the condition will worsen or progress to Menieres disease.As with Menieres disease, atypical, early, or mild cases may only present some symptoms. Diagnosis Diagnosis is based on symptoms and a hearing test that documents a loss in the low and mid frequencies, usually only in one ear. For patients with mild or atypical hydrops, the hearing thresholds may be normal, but they may experience a subjective, unilateral distortion of sounds in lower frequencies, such as diplacusis or that voices are sounding "robotic". Patients may also mention a feeling of pressure or fullness in the ear.To objectively test for the presence of hydrops, an electrocochleography (or ECOG) procedure can be done to detect elevated inner ear pressure. It is also possible to reveal the presence of hydrops with an MRI.If vertigo is experienced, the diagnosis progresses to Menieres disease. This occurs if the fluid increase leads to a leak or rupture of the membranes in the inner ear, causing a mixture of perilymph and endolymph. Treatment Treatment for cochlear hydrops is the same as for Menieres disease. Currently, no cure exists for either.If a patient has undergone sudden sensorineural hearing loss, a course of steroids is often prescribed in an attempt to recover the hearing. Steroids may be injected directly through the eardrum.Like Menieres Disease, a low salt diet is recommended as a preventative measure. A diuretic may be prescribed to help lower salt content.Betahistine is the most widely prescribed medication for the treatment of Menieres disease. The drug is thought to increase blood flow to the inner ear and to prevent the frequency and intensity of episodes. While Betahistine is considered safe, there is insufficient evidence that it is an effective treatment. It is not FDA approved in the United States, yet has still been clinically observed to benefit patients, and is considered safer and more effective than diuretics. Betahistine at high doses (such as 144 mg/day) can yield similar vertigo control as intratympanic dexamethasone.Antivirals have been proven effective for those who suspect a viral cause for their cochlear Hydrops.For some, surgery may be effective, such as an endolymphatic sac decompression. Surgery is often reserved for cases where other measures have proven ineffective and/or when vestibular issues are the main complaint, as it runs the risk of causing hearing or other nerve damage. Prognosis The symptoms of cochlear hydrops fluctuate, and the condition tends to stabilize or go away on its own after several years. However, because the organ of Corti undergoes stress during the hydrops episodes, long-term hearing loss, tinnitus, or hyperacusis is possible. It is considered by some that cochlear hydrops is an early form of Menieres disease. However, while all people with Menieres disease have some form of hydrops, the majority of cochlear hydrops patients do not go on to develop Menieres disease. It takes an average of one year from the onset of symptoms for someone to develop full Menieres disease, if at all. Relationship to Menieres Disease The data on how often progression to Menieres disease occurs is mixed, but the majority of recent studies suggest a low likelihood. A 1984 study from Japan looked at patients with Menieres disease and classified them into subcategories based on their first symptoms. The study found that the majority of patients with Menieres disease (104 out of 163, or 63.80%) presented vertigo with their first symptoms, and only 59 out of 163 (36.19%) of patients presented with cochlear symptoms first, such as "tinnitus or deafness." However, the study found that 59 out of 74 (79.72%) patients who started out with a cochlear hydrops diagnosis progressed to Menieres disease, and concluded that "cochlear Menieres disease frequently develops into Menieres disease."Conversely, A 2006 study from doctors at the House Ear Institute found that “conversion from cochlear hydrops to Menieres disease occurred in 33%” of diagnosed patients in a study including 46 subjects. A 2009 study from Japan found that only about 10% of their diagnosed patients with sudden low-frequency hearing loss (SLFHL) went on to develop full Menieres disease, and about 18% with recurring SLFHL developed Menieres disease. From this study, about 70% of patients who did not develop Menieres Disease maintained their hearing in the end. 30% went on to have lasting hearing difficulty, reported from a ten-year follow-up.A 2018 study from Korea found the chance of progression to Menieres disease of all participants with SLFHL to be 9.38% with an average progression time of 1.7±1.4 years, but when limited to patients with recurring symptoms "it was confirmed that about half (46.88%) of them progressed to Menieres disease." However, the study was said to have limitations as "hearing fluctuations and the possibility of transitioning to Menieres disease in the non-relapse group could not be completely ruled out." == References ==

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

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

Etomidate (USAN, INN, BAN; marketed as Amidate) is a short-acting intravenous anaesthetic agent used for the induction of general anaesthesia and sedation for short procedures such as reduction of dislocated joints, tracheal intubation, cardioversion and electroconvulsive therapy. It was developed at Janssen Pharmaceutica in 1964 and was introduced as an intravenous agent in 1972 in Europe and in 1983 in the United States.The most common side effects include venous pain on injection and skeletal muscle movements. Medical uses Sedation and anesthesia In emergency settings, etomidate can be used as a sedative hypnotic agent. It is used for conscious sedation and as a part of a rapid sequence induction to induce anaesthesia. It is used as an anaesthetic agent since it has a rapid onset of action and a safe cardiovascular risk profile, and therefore is less likely to cause a significant drop in blood pressure than other induction agents. In addition, etomidate is often used because of its easy dosing profile, limited suppression of ventilation, lack of histamine liberation and protection from myocardial and cerebral ischemia. Thus, etomidate is a good induction agent for people who are hemodynamically unstable. Etomidate also has interesting characteristics for people with traumatic brain injury because it is one of the only anesthetic agents able to decrease intracranial pressure and maintain a normal arterial pressure.In those with sepsis, one dose of the medication does not appear to affect the risk of death. Speech and memory test Another use for etomidate is to determine speech lateralization in people prior to performing lobectomies to remove epileptogenic centres in the brain. This is called the etomidate speech and memory test, or eSAM, and is used at the Montreal Neurological Institute. However, only retrospective cohort studies support the use and safety of etomidate for this test. Steroidogenesis inhibitor In addition to its action and use as an anesthetic, etomidate has also been found to directly inhibit the enzymatic biosynthesis of steroid hormones, including corticosteroids in the adrenal gland. As the only adrenal steroidogenesis inhibitor available for intravenous or parenteral administration, it is useful in situations in which rapid control of hypercortisolism is necessary or in which oral administration is unfeasible. Use in executions The U.S. state of Florida used the drug in a death penalty procedure when Mark James Asay, 53, was executed on August 24, 2017. He became the first person in the U.S. to be executed with etomidate as one of the drugs. Etomidate replaces midazolam as the sedative. Drug companies have made it harder to buy midazolam for executions. The etomidate was followed by rocuronium bromide, a paralytic, and finally, potassium acetate in place of the commonly used potassium chloride injection to stop the heart. Potassium acetate was first used for this purpose inadvertently in a 2015 execution in Oklahoma. Adverse effects Etomidate suppresses corticosteroid synthesis in the adrenal cortex by reversibly inhibiting 11β-hydroxylase, an enzyme important in adrenal steroid production; it leads to primary adrenal suppression. Using a continuous etomidate infusion for sedation of critically ill trauma patients in intensive care units has been associated with increased mortality due to adrenal suppression. Continuous intravenous administration of etomidate leads to adrenocortical dysfunction. The mortality of patients exposed to a continuous infusion of etomidate for more than 5 days increased from 25% to 44%, mainly due to infectious causes such as pneumonia.Because of etomidate-induced adrenal suppression, its use for patients with sepsis is controversial. Cortisol levels have been reported to be suppressed up to 72 hours after a single bolus of etomidate in this population at risk for adrenal insufficiency. For this reason, many authors have suggested that etomidate should never be used for critically ill patients with septic shock because it could increase mortality. However, other authors continue to defend etomidates use for septic patients because of etomidates safe hemodynamic profile and lack of clear evidence of harm. A study by Jabre et al. showed that a single dose of etomidate used for Rapid Sequence Induction prior to endrotracheal intubation has no effect on mortality compared to ketamine even though etomidate did cause transient adrenal suppression. In addition, a recent meta-analysis done by Hohl could not conclude that etomidate increased mortality. The authors of this meta-analysis concluded more studies were needed because of lack of statistical power to conclude definitively about the effect of etomidate on mortality. Thus, Hohl suggests a burden to prove etomidate is safe for use in septic patients, and more research is needed before it is used. Other authors advise giving a prophylactic dose of steroids (e.g. hydrocortisone) if etomidate is used, but only one small prospective controlled study in patients undergoing colorectal surgery has verified the safety of giving stress dose corticosteroids to all patients receiving etomidate. In a retrospective review of almost 32,000 people, etomidate, when used for the induction of anaesthesia, was associated 2.5-fold increase in the risk of dying compared with those given propofol. People given etomidate also had significantly greater odds of having cardiovascular morbidity and significantly longer hospital stay. These results, especially given the large size of study, strongly suggest that, at the very least, clinicians should use etomidate judiciously. However, given this is a retrospective study, it is clearly misinterpreting how etomidate is typically used: etomidate is a drug that is reserved for sicker patients whom may not tolerate the more severe hemodynamic liability (towards lower mean pressures) and, thus the bias of this retrospective study is inconclusive, at best.In people with traumatic brain injury, etomidate use is associated with a blunting of an ACTH stimulation test. The clinical impact of this effect has yet to be determined. In addition, concurrent use of etomidate with opioids and/or benzodiazepines, is hypothesized to exacerbate etomidate-related adrenal insufficiency. However, only retrospective evidence of this effect exists and prospective studies are needed to measure the clinical impact of this interaction. Etomidate is associated with a high incidence of burning on injection, postoperative nausea and vomiting, and superficial thrombophlebitis (with rates higher than propofol). Pharmacology Pharmacodynamics (R)-Etomidate is tenfold more potent than its (S)-enantiomer. At low concentrations (R)-etomidate is a modulator at GABAA receptors containing β2 and β3 subunits. At higher concentrations, it can elicit currents in the absence of GABA and behaves as an allosteric agonist. Its binding site is located in the transmembrane section of this receptor between the beta and alpha subunits (β+α−). β3-containing GABAA receptors are involved in the anesthetic actions of etomidate, while the β2-containing receptors are involved in some of the sedation and other actions that can be elicited by this drug. Pharmacokinetics At the typical dose, anesthesia is induced for the duration of about 5–10 minutes, though the half-life of drug metabolism is about 75 minutes, because etomidate is redistributed from the plasma to other tissues. Onset of action: 30–60 seconds Peak effect: 1 minute Duration: 3–5 minutes; terminated by redistribution Distribution: Vd: 2–4.5 L/kg Protein binding: 76% Metabolism: Hepatic and plasma esterases Half-life distribution: 2.7 minutes Half-life redistribution: 29 minutes Half-life elimination: 2.9 to 5.3 hours Metabolism Etomidate is highly protein-bound in blood plasma and is metabolised by hepatic and plasma esterases to inactive products. It exhibits a biexponential decline. Formulation Etomidate is usually presented as a clear colourless solution for injection containing 2 mg/ml of etomidate in an aqueous solution of 35% propylene glycol, although a lipid emulsion preparation (of equivalent strength) has also been introduced. Etomidate was originally formulated as a racemic mixture, but the R form is substantially more active than its enantiomer. It was later reformulated as a single-enantiomer drug, becoming the first general anesthetic in that class to be used clinically. References Citations Sources External links "Etomidate". Drug Information Portal. U.S. National Library of Medicine.

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

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

Croup, also known as laryngotracheobronchitis, is a type of respiratory infection that is usually caused by a virus. The infection leads to swelling inside the trachea, which interferes with normal breathing and produces the classic symptoms of "barking/brassy" cough, inspiratory stridor and a hoarse voice. Fever and runny nose may also be present. These symptoms may be mild, moderate, or severe. Often it starts or is worse at night and normally lasts one to two days.Croup can be caused by a number of viruses including parainfluenza and influenza virus. Rarely is it due to a bacterial infection. Croup is typically diagnosed based on signs and symptoms after potentially more severe causes, such as epiglottitis or an airway foreign body, have been ruled out. Further investigations, such as blood tests, X-rays and cultures, are usually not needed.Many cases of croup are preventable by immunization for influenza and diphtheria. Most cases of croup are mild and the child can be treated at home with supportive care. Croup is usually treated with a single dose of steroids by mouth. In more severe cases inhaled epinephrine may also be used. Hospitalization is required in one to five percent of cases.Croup is a relatively common condition that affects about 15% of children at some point. It most commonly occurs between six months and five years of age but may rarely be seen in children as old as fifteen. It is slightly more common in males than females. It occurs most often in autumn. Before vaccination, croup was frequently caused by diphtheria and was often fatal. This cause is now very rare in the Western world due to the success of the diphtheria vaccine. Signs and symptoms Croup is characterized by a "barking" cough, stridor, hoarseness, and difficult breathing which usually worsens at night. The "barking" cough is often described as resembling the call of a sea lion. The stridor is worsened by agitation or crying, and if it can be heard at rest, it may indicate critical narrowing of the airways. As croup worsens, stridor may decrease considerably.Other symptoms include fever, coryza (symptoms typical of the common cold), and indrawing of the chest wall–known as Hoovers sign. Drooling or a very sick appearance can indicate other medical conditions, such as epiglottitis or tracheitis. Causes Croup is usually deemed to be due to a viral infection. Others use the term more broadly, to include acute laryngotracheitis (laryngitis and tracheitis together), spasmodic croup, laryngeal diphtheria, bacterial tracheitis, laryngotracheobronchitis, and laryngotracheobronchopneumonitis. The first two conditions involve a viral infection and are generally milder with respect to symptomatology; the last four are due to bacterial infection and are usually of greater severity. Viral Viral croup or acute laryngotracheitis is most commonly caused by parainfluenza virus (a member of the paramyxovirus family), primarily types 1 and 2, in 75% of cases. Other viral causes include influenza A and B, measles, adenovirus and respiratory syncytial virus (RSV). Spasmodic croup is caused by the same group of viruses as acute laryngotracheitis, but lacks the usual signs of infection (such as fever, sore throat, and increased white blood cell count). Treatment, and response to treatment, are also similar. Bacteria and cocci Croup caused by a bacterial infection is rare. Bacterial croup may be divided into laryngeal diphtheria, bacterial tracheitis, laryngotracheobronchitis, and laryngotracheobronchopneumonitis. Laryngeal diphtheria is due to Corynebacterium diphtheriae while bacterial tracheitis, laryngotracheobronchitis, and laryngotracheobronchopneumonitis are usually due to a primary viral infection with secondary bacterial growth. The most common cocci implicated are Staphylococcus aureus and Streptococcus pneumoniae, while the most common bacteria are Haemophilus influenzae, and Moraxella catarrhalis. Pathophysiology The viral infection that causes croup leads to swelling of the larynx, trachea, and large bronchi due to infiltration of white blood cells (especially histiocytes, lymphocytes, plasma cells, and neutrophils). Swelling produces airway obstruction which, when significant, leads to dramatically increased work of breathing and the characteristic turbulent, noisy airflow known as stridor. Diagnosis Croup is typically diagnosed based on signs and symptoms. The first step is to exclude other obstructive conditions of the upper airway, especially epiglottitis, an airway foreign body, subglottic stenosis, angioedema, retropharyngeal abscess, and bacterial tracheitis.A frontal X-ray of the neck is not routinely performed, but if it is done, it may show a characteristic narrowing of the trachea, called the steeple sign, because of the subglottic stenosis, which resembles a steeple in shape. The steeple sign is suggestive of the diagnosis, but is absent in half of cases.Other investigations (such as blood tests and viral culture) are discouraged, as they may cause unnecessary agitation and thus worsen the stress on the compromised airway. While viral cultures, obtained via nasopharyngeal aspiration, can be used to confirm the exact cause, these are usually restricted to research settings. Bacterial infection should be considered if a person does not improve with standard treatment, at which point further investigations may be indicated. Severity The most commonly used system for classifying the severity of croup is the Westley score. It is primarily used for research purposes rather than in clinical practice. It is the sum of points assigned for five factors: level of consciousness, cyanosis, stridor, air entry, and retractions. The points given for each factor is listed in the adjacent table, and the final score ranges from 0 to 17. A total score of ≤ 2 indicates mild croup. The characteristic barking cough and hoarseness may be present, but there is no stridor at rest. A total score of 3–5 is classified as moderate croup. It presents with easily heard stridor, but with few other signs. A total score of 6–11 is severe croup. It also presents with obvious stridor, but also features marked chest wall indrawing. A total score of ≥ 12 indicates impending respiratory failure. The barking cough and stridor may no longer be prominent at this stage.85% of children presenting to the emergency department have mild disease; severe croup is rare (<1%). Prevention Croup is contagious during the first few days of the infection. Basic hygiene including hand washing can prevent transmission. There are no vaccines that have been developed to prevent croup, however, many cases of croup have been prevented by immunization for influenza and diphtheria. At one time, croup referred to a diphtherial disease, but with vaccination, diphtheria is now rare in the developed world. Treatment Most children with croup have mild symptoms and supportive care at home is effective. For children with moderate to severe croup, treatment with corticosteroids and nebulized epinephrine may be suggested. Steroids are given routinely, with epinephrine used in severe cases. Children with oxygen saturation less than 92% should receive oxygen, and those with severe croup may be hospitalized for observation. In very rare severe cases of croup that result in respiratory failure, emergency intubation and ventilation may be required. With treatment, less than 0.2% of children require endotracheal intubation. Since croup is usually a viral disease, antibiotics are not used unless secondary bacterial infection is suspected. The use of cough medicines, which usually contain dextromethorphan or guaifenesin, are also discouraged. Supportive care Supportive care for children with croup includes resting and keeping the child hydrated. Infections that are mild are suggested to be treated at home. Croup is contagious so washing hands is important. Children with croup should generally be kept as calm as possible. Over the counter medications for pain and fever may be helpful to keep the child comfortable. There is some evidence that cool or warm mist may be helpful, however, the effectiveness of this approach is not clear. If the child is showing signs is distress while breathing (inspiratory stridor, working hard to breath, blue (or blue-ish) coloured lips, or decrease in the level of alertness), immediate medical evaluation by a doctor is required. Steroids Corticosteroids, such as dexamethasone and budesonide, have been shown to improve outcomes in children with all severities of croup, however, the benefits may be delayed. Significant relief may be obtained as early as two hours after administration. While effective when given by injection, or by inhalation, giving the medication by mouth is preferred. A single dose is usually all that is required, and is generally considered to be quite safe. Dexamethasone at doses of 0.15, 0.3 and 0.6 mg/kg appear to be all equally effective. Epinephrine Moderate to severe croup (for example, in the case of severe stridor) may be improved temporarily with nebulized epinephrine. While epinephrine typically produces a reduction in croup severity within 10–30 minutes, the benefits are short-lived and last for only about 2 hours. If the condition remains improved for 2–4 hours after treatment and no other complications arise, the child is typically discharged from the hospital. Epinephrine treatment is associated with potential adverse effects (usually related to the dose of epinephrine) including tachycardia, arrhythmias, and hypertension. Oxygen More severe cases of croup may require treatment with oxygen. If oxygen is needed, "blow-by" administration (holding an oxygen source near the childs face) is recommended, as it causes less agitation than use of a mask. Other While other treatments for croup have been studied, none has sufficient evidence to support its use. There is tentative evidence that breathing heliox (a mixture of helium and oxygen) to decrease the work of breathing is useful in those with severe disease, however, there is uncertainty in the effectiveness and the potential adverse effects and/or side effects are not well known. In cases of possible secondary bacterial infection, the antibiotics vancomycin and cefotaxime are recommended. In severe cases associated with influenza A or B infections, the antiviral neuraminidase inhibitors may be administered. Prognosis Viral croup is usually a self-limiting disease, with half of cases resolving in a day and 80% of cases in two days. It can very rarely result in death from respiratory failure and/or cardiac arrest. Symptoms usually improve within two days, but may last for up to seven days. Other uncommon complications include bacterial tracheitis, pneumonia, and pulmonary edema. Epidemiology Croup affects about 15% of children, and usually presents between the ages of 6 months and 5–6 years. It accounts for about 5% of hospital admissions in this population. In rare cases, it may occur in children as young as 3 months and as old as 15 years. Males are affected 50% more frequently than are females, and there is an increased prevalence in autumn. History The word croup comes from the Early Modern English verb croup, meaning "to cry hoarsely." The noun describing the disease originated in southeastern Scotland and became widespread after Edinburgh physician Francis Home published the 1765 treatise An Inquiry into the Nature, Cause, and Cure of the Croup.Diphtheritic croup has been known since the time of Homers ancient Greece, and it was not until 1826 that viral croup was differentiated from croup due to diphtheria by Bretonneau. Viral croup was then called "faux-croup" by the French and often called "false croup" in English, as "croup" or "true croup" then most often referred to the disease caused by the diphtheria bacterium. False croup has also been known as pseudo croup or spasmodic croup. Croup due to diphtheria has become nearly unknown in affluent countries in modern times due to the advent of effective immunization.One famous fatality of croup was Napoleons designated heir, Napoléon Charles Bonaparte. His death in 1807 left Napoleon without an heir and contributed to his decision to divorce from his wife, the Empress Josephine de Beauharnais. References External links "Croup". MedlinePlus. U.S. National Library of Medicine.

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

What does the medical term 'Tolcapone' encompass?

Tolcapone, sold under the brand name Tasmar, is a medication used to treat Parkinsons disease (PD). It is a selective, potent and reversible nitrocatechol-type inhibitor of the enzyme catechol-O-methyltransferase (COMT). It has demonstrated significant liver toxicity, which has led to suspension of marketing authorisations in a number of countries. In comparison with entacapone, another nitrocatechol COMT inhibitor, tolcapone has a longer half life (2.9 hours vs. 0.8 hours) and can better penetrate the blood–brain barrier, acting both in the central nervous system and in the periphery. However, entacapone is less toxic for the liver. Medical uses Tolcapone is used in the treatment of Parkinsons disease as an adjunct to levodopa/carbidopa or levodopa/benserazide medications. Levodopa is a prodrug for dopamine, which reduces Parkinson symptoms; carbidopa and benserazide are aromatic L-amino acid decarboxylase (AADC) inhibitors.Without administration of tolcapone, the beneficial effects of levodopa tend to wear off more quickly, resulting in motor fluctuations. Contraindications Combining tolcapone with non-selective monoamine oxidase inhibitors such as phenelzine or tranylcypromine is contraindicated. Tolcapone is also contraindicated for people with liver diseases or increased liver enzymes. Side effects Tolcapone has demonstrated significant liver toxicity (hepatotoxicity) that limits the drugs utility. Entacapone is an alternative, largely since it has a more favorable toxicity profile. The hepatotoxicity can be related to elevated levels of transaminases, but studies have shown that minimal risk exists for those without preexisting liver conditions when their enzyme levels were being monitored. No clear mechanism is implicated, but it has been hypothesized that it has something to do with abnormal mitochondrial respiration due to the uncoupling of oxidative phosphorylation.Other side effects regard the increase in dopaminergic activity, including digestive symptoms. Treatment with tolcapone runs the risk of eliciting or prolonging dyskinesia; this can be counteracted by decreasing the dose of levodopa. This occurs because the administration of tolcapone results in the accumulation of the biological methyl donor S-adenosyl-L-methionine (SAM) in the striatum that induces Parkinson symptoms.Digestive symptoms include nausea and diarrhea; further dopaminergic side effects include orthostatic hypotension, dry mouth, sweating and dizziness. Tolcapone causes more severe diarrhea than entacapone; this was the most common reason for therapy termination in studies. Urine discoloration comes from yellow tolcapone metabolites being excreted in the urine and is harmless. Interactions While increase of dopamine levels is a desired interaction, tolcapone can theoretically also increase the levels of other drugs metabolised by COMT, such as the AADC inhibitors carbidopa and benzerazide, as well as methyldopa, dobutamine, apomorphine, adrenaline, and isoprenaline. In studies, a slight interaction with benzerazide was seen, but not with carbidopa. Other interactions with this group of drugs have not been studied. A related type of theoretical interactions is with drugs that increase catecholamine concentrations, such as monoamine oxidase (MAO) inhibitors and noradrenaline reuptake inhibitors; these also showed only slight effects in practice. Combination with non-selective MAO inhibitors might be dangerous.Due to its affinity to the liver enzyme CYP2C9, interactions with drugs being metabolised by this enzyme are also possible, but unlikely. No interaction with tolbutamide, a 2C9 substrate, was observed in studies. Pharmacology Mechanism of action Tolcapone selectively and reversibly binds to the catalytic site of COMT in both the periphery and the central nervous system (CNS) with greater affinity than any of the three catecholamines, including levodopa. It thereby prevents the 3-O-methylation of levodopa by COMT in the periphery, which produces 3-O-methyldopa, a major metabolite that competes with levodopa to cross the blood–brain barrier. More of the levodopa that is administered reaches the CNS. Additionally, levodopa that has already reached the CNS, after being converted to dopamine, will not be degraded as quickly when tolcapone inhibits COMT activity. Thus, tolcapone improves the bioavailability and reduces the clearance of levodopa and subsequently dopamine from the CNS. The strength of the binding affinity of tolcapone, represented by the inhibition constant Ki (2.5 nM), can be thought of as the dissociation constant for enzyme and inhibitor complex kinetics. Maximum catalytic activity denotes the efficacy of tolcapone (Vmax = 58.4 pmol/min·mg). Pharmacokinetics Tolcapone is quickly absorbed from the gut to about 85%. It has an absolute bioavailability of 65%, which is only slightly decreased when taken with food. The substance reaches highest blood plasma concentrations after about two hours. When in the bloodstream, it is almost completely (>99.9%) bound to plasma proteins, primarily albumin. The main inactivation step is glucuronidation; other processes are methylation by COMT, hydroxylation by CYP3A4 and CYP2A6 with subsequent oxidation to a carboxylic acid, and possibly a minor path with reduction to an amine with subsequent acetylation.The half-life of tolcapone is two to three hours, the volume of distribution (Vd) being 0.3 L/kg (21 L in an average 70 kg person). 60% of the metabolites are excreted via the urine and 40% via the feces. Only 0.5% of the drug are excreted in unchanged form via the urine. 99% of tolcapone is in monoanionic form in the body because the physiological pH is 7.4. Tolcapone penetrates the blood–brain barrier much better than two other nitrocatechols, nitecapone and entacapone, because it has higher lipophilicity due to its R-substituent. Partition coefficients quantify the ability of the molecule to cross the blood–brain barrier. LogPIdce= 0.2, –1.4, –0.4 for tolcapone, nitecapone and entacopone respectively. Partition coefficients in this case were measured in 1,2-dichloroethane/H2O solution which caused molecules to be in ionized form. There is no current explanation for how these charged molecules permeate the blood–brain barrier. Chemistry Tolcapone is an intensely yellow, odorless, bitter tasting, non-hygroscopic, crystalline compound with a relative molecular mass of 273.25 g/mol. It melts at 143 to 146 °C (289 to 295 °F), is practically insoluble in water and acids but soluble in 0.1 M aqueous sodium hydroxide solution. The pKa values are 4.5 and 10.6 for the two phenyl groups; and the maximum absorption is at 268 nm (in 0.1 M hydrochloric acid / ethanol). Its chemical name is 3,4-dihydroxy-4-methyl-5-nitrobenzophenone. Synthesis A synthesis of tolcapone proposed in 2008, begins with a Grignard reaction between a benzaldehyde derivative and p-tolyl magnesium bromide. The alcohol thus produced is then converted to a ketone using sodium t-butoxide. The benzyl protecting group is removed by palladium-catalyzed hydrogenation in the presence of ammonium formate. A nitro group is introduced at the 5-position adjacent to the hydroxyl group unmasked in the cleavage of the benzyl ether. The synthesis ends with cleavage of the methoxy group using aluminum chloride to yield the product alcohol. History Tolcapone was introduced into the European market in August 1997, and subsequently into the United States market in March 1998. Liver toxicity was reported in four people who were administered tolcapone, three people died due to complications. Consequentially, the marketing authorization of tolcapone was suspended from December, 1998 until August, 2004 when it was lifted. In November 1998, the company that manufactured tolcapone voluntarily removed the drug from the market. The authorization was then renewed in August 2009.As a result of reported complications, the U.S. Food and Drug Administration (FDA) issued a black box warning for tolcapone and label revisions that aimed to regulate the monitoring of those prescribed tolcapone for Parkinsons disease in November 1998. A number of other countries withdrew tolcapone from the market; Australia in February 1999, Bulgaria in April 1999, Iceland in November 1998, Lithuania in December 1998. Research Because of preliminary data suggesting the drug may have activity, the U.S. FDA has granted tolcapone "orphan drug status" in studies aiming at the treatment of familial transthyretin amyloidosis (ATTR). However, tolcapone is not FDA approved for the treatment of this disease. References External links "Tolcapone". Drug Information Portal. U.S. National Library of Medicine.

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

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

Bendamustine, sold under the brand name Treanda among others, is a chemotherapy medication used in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkins lymphoma. It is given by injection into a vein.Common side effects include low blood cell counts, fever, nausea, diarrhea, loss of appetite, cough, and rash. Other severe side effects include allergic reactions and increased risk of infection. Use in pregnancy is known to harm the baby. Bendamustine is in the alkylating agents family of medication. It works by interfering with the function of DNA and RNA.Bendamustine was approved for medical use in the United States in 2008. It is on the World Health Organizations List of Essential Medicines. The cost in the United Kingdom for the NHS is about 275.81 pounds per 100 mg vial. It was originally made from nitrogen mustard. Medical uses Bendamustine has been used both as sole therapy and in combination with other agents including etoposide, fludarabine, mitoxantrone, methotrexate, prednisone, rituximab, vincristine and 90Y-ibritumomab tiuxetan. Lymphomas One combination for stage III/IV relapsed or refractory indolent lymphomas and mantle cell lymphoma (MCL), with or without prior rituximab-containing chemoimmunotherapy treatment, is bendamustine with mitoxantrone and rituximab. In Germany in 2012 it has become the first line treatment of choice for indolent lymphoma. After trial results released in June 2012 showed that it more than doubled disease progression-free survival when given along with rituximab. The combination also left patients with fewer side effects than the older R-CHOP treatment. Adverse effects Common adverse reactions are typical for the class of nitrogen mustards, and include nausea, fatigue, vomiting, diarrhea, fever, constipation, loss of appetite, cough, headache, unintentional weight loss, difficulty breathing, rashes, and stomatitis, as well as immunosuppression, anemia, and low platelet counts. Notably, this drug has a low incidence of hair loss (alopecia) unlike most other chemotherapy drugs. Warning Bendamustine solution is not compatible with Closed System Transfer Devices (CSTD) Situation: *Most CSTD vendors have adapted their system to become compatible. FDA issued a warning on March 11, 2015, not to use bendamustine solution with CSTDs, adapters and syringes which contain either polycarbonate or acrylonitrile-butadiene-styrene (ABS) due to the incompatibility with N,N-dimethylacetamide (DMA).Background: PhaSealR & SpirosR CSTDs contain either polycarbonate or ABS can dissolve when coming into contact with bendamustine (which contains DMA).Assessment: This can lead to device failure, possible product contamination, and potential serious adverse health consequences, including skin reactions in health care professionals preparing and administering this product and the risk of small blood vessel blockage in patients.Recommendations: Immediately, stop using all PhaSealR &/or SpirosR products including adapters when preparing & administering bendamustine. Only use polypropylene syringes with bendamustine. These syringes are translucent in appearance. Continue to use all universal PPE & safety precautions for hazardous drugs when preparing & administering bendamustine. Pharmacology Bendamustine is a white, water-soluble microcrystalline powder with amphoteric properties. It acts as an alkylating agent causing intra-strand and inter-strand cross-links between DNA bases. After intravenous infusion it is extensively metabolised in the liver by cytochrome p450. More than 95% of the drug is bound to protein – primarily albumin. Only free bendamustine is active. Elimination is biphasic with a half-life of 6–10 minutes and a terminal half-life of approximately 30 minutes. It is eliminated primarily through the kidneys. History Bendamustine was first made in 1963 by Ozegowski and Krebs in East Germany (the former German Democratic Republic). Until 1990 it was available only in East Germany. East German researchers found that it was useful for treating chronic lymphocytic leukemia, Hodgkins disease, non-Hodgkins lymphoma, multiple myeloma and lung cancer. Bendamustine received its first marketing approval in Germany, where it is marketed under the tradename Ribomustin, by Astellas Pharma GmbHs licensee, Mundipharma International Corporation Limited. It is indicated as a single-agent or in combination with other anti-cancer agents for indolent non-Hodgkins lymphoma, multiple myeloma, and chronic lymphocytic leukemia. SymBio Pharmaceuticals Ltd. holds exclusive rights to develop and market bendamustine HCl in Japan and selected Asia Pacific Rim countries. In March 2008, Cephalon received approval from the United States Food and Drug Administration to market bendamustine in the US, where it is sold under the tradename Treanda, for treatment of chronic lymphocytic leukemia.In October 2008, the FDA granted further approval to market Treanda for the treatment of indolent B-cell non-Hodgkins lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Research It is also being studied for the treatment of sarcoma. It is also being investigated in phase II trials for the non-cancer treatment of AL amyloidosis. References External links "Bendamustine". Drug Information Portal. U.S. National Library of Medicine.

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

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

Meconium peritonitis refers to rupture of the bowel prior to birth, resulting in fetal stool (meconium) escaping into the surrounding space (peritoneum) leading to inflammation (peritonitis). Despite the bowel rupture, many infants born after meconium peritonitis in utero have normal bowels and have no further issues. Infants with cystic fibrosis are at increased risk for meconium peritonitis. Signs and symptoms Diagnosis Twenty percent of infants born with meconium peritonitis will have vomiting and dilated bowels on x-rays which necessitates surgery. Meconium peritonitis is sometimes diagnosed on prenatal ultrasound where it appears as calcifications within the peritoneum. Treatment Adhesiolysis partial resection of pseudocyst covering enterostomy. History Meconium peritonitis was first described in 1838 by Carl von Rokitansky. References == External links ==

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

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

Spondylolisthesis is the displacement of one spinal vertebra compared to another. While some medical dictionaries define spondylolisthesis specifically as the forward or anterior displacement of a vertebra over the vertebra inferior to it (or the sacrum), it is often defined in medical textbooks as displacement in any direction. Spondylolisthesis is graded based upon the degree of slippage of one vertebral body relative to the subsequent adjacent vertebral body. Spondylolisthesis is classified as one of the six major etiologies: degenerative, traumatic, dysplastic, isthmic, pathologic, or post-surgical. Spondylolisthesis most commonly occurs in the lumbar spine, primarily at the L5-S1 level with the L5 vertebral body anteriorly translating over the S1 vertebral body. Types Olisthesis (synonym olisthy) is a term that more explicitly denotes displacement in any direction. Forward or anterior displacement can specifically be called anterolisthesis. Anterolisthesis commonly involves the fifth lumbar vertebra. Backward displacement is called retrolisthesis. Lateral displacement is called lateral listhesis or laterolisthesis.A hangmans fracture is a specific type of spondylolisthesis where the second cervical vertebra (C2) is displaced anteriorly relative to the C3 vertebra due to fractures of the C2 vertebras pedicles. Anterolisthesis Classification Anterolisthesis can be categorized by cause, location and severity. By causes Degenerative anterolisthesis (a.k.a. type 3) is a disease of the older adult that develops as a result of facet arthritis and joint remodeling. Joint arthritis, and ligamentum flavum weakness, may result in slippage of a vertebra. Degenerative forms are more likely to occur in women, persons older than fifty, and African Americans. Traumatic anterolisthesis is rare and results from acute fractures in the neural arch, other than the pars. Dysplastic anterolisthesis (a.k.a. type 1) results from congenital abnormalities of the upper sacral facets or inferior facets of the fifth lumbar vertebra, and accounts for 14% to 21% of all anterolisthesis. Isthmic anterolisthesis (a.k.a. type 2) is caused by a defect in the pars interarticularis but it can also be seen with an elongated pars. Pathologic anterolisthesis (a.k.a. type 5) is caused by either infection or a malignancy. Post-surgical/iatrogenic anterolisthesis (a.k.a. type 6) is caused by complications after surgery. By location Anterolisthesis location includes which vertebrae are involved, and may also specify which parts of the vertebrae are affected. Isthmic anterolisthesis is where there is a defect in the pars interarticularis. It is the most common form of spondylolisthesis; also called spondylolytic spondylolisthesis, it occurs with a reported prevalence of 5–7 percent in the US population. A slip or fracture of the intravertebral joint is usually acquired between the ages of 6 and 16 years, but remains unnoticed until adulthood. Roughly 90 percent of these isthmic slips are low-grade (less than 50 percent slip) and 10 percent are high-grade (greater than 50 percent slip). It is divided into three subtypes: A: pars fatigue fracture B: pars elongation due to multiple healed stress effects C: pars acute fracture Severity Classification by degree of the slippage, as measured as percentage of the width of the vertebral body: Grade I spondylolisthesis accounts for approximately 75% of all cases. Grade I: 0–25% Grade II: 25- 50% Grade III: 50–75% Grade IV: 75–100% Grade V: greater than 100% Signs and symptoms Symptoms of lumbar anterolisthesis include: A general stiffening of the back and a tightening of the hamstrings, with a resulting change in both posture and gait. A leaning-forward or semi-kyphotic posture may be seen, due to compensatory changes. A "waddle" may be seen in more advanced causes, due to compensatory pelvic rotation due to decreased lumbar spine rotation. A result of the change in gait is often a noticeable atrophy in the gluteal muscles due to lack of use. Generalized lower-back pain may also be seen, with intermittent shooting pain from the buttocks to the posterior thigh, and/or lower leg via the sciatic nerve.Other symptoms may include tingling and numbness. Coughing and sneezing can intensify the pain. An individual may also note a "slipping sensation" when moving into an upright position. Sitting and trying to stand up may be painful and difficult. Physical Exam The major components of the physical exam for spondylolisthesis consists of observation, palpation, and maneuvers. The most common finding is pain with lumbar extension. The following physical involves specific assessment for spondylolisthesis. However, a general examination, most importantly neurological examination, must be done to rule out alternative causes for signs and symptoms. Neurological examination is often normal in patients with spondylolisthesis, but lumbosacral radiculopathy is commonly seen in patients with degenerate spondylolisthesis. Observation The patient should be observed walking and standing. Most patients present with a normal gait. An abnormal gait is often the sign of a high grade case. A patient with high grade spondylolisthesis may present with a posterior pelvic tilt causing a loss in the normal contour of the buttocks. An antalgic gait, rounded back and decreased hip extension, can result from severe pain. While standing, the patient should be observed from the front, back, and sides. Increased and decreased lumbar lordosis, inward curvature of the lower spine, has been seen. Palpation Detection of spondylolisthesis by palpation is most often done by palpating for the spinous process. Each level of the lumbar spine should be palpated. Spinous process palpation by itself is not a definitive method for the detection of spondylolisthesis. Maneuvers Spinal range of motion testing – Range of motion limitations may be seen. Lumbar hyperextension – Extension often elicits pain. This can be assessed by having the patient hyperextend the lumbar spine, provide resistance against back extensions, or undergo repeated lumbar extensions. Sport-specific motion – Patient can be asked to repeat aggravating movements that they experience during their activity. During the movement, ask patient to point to any places with focal pain. Straight leg raise – Maneuver used to assess for hamstring tightness. The straight leg raise has been found to be positive in only 10% of patients with spondylolisthesis. Muscle strength exercises – Lower abdominal, gluteal, and lumbar extensors should be assessed for weakness. Weakness in these muscles can increase lordosis and contribute to sacroiliac instability. Abdominal flexor strength can be assessed with the abdominal flexor endurance test. The test involves the patient lying supine while holding a 45 degree flexed trunk and 90 degree flexed knees for 30 seconds. Gluteal strength can be assessed with a single-leg squat. Lastly, lumbar extension can be assessed with a single-leg bridge. Diagnostic Imaging In adults with non-specific low back pain, strong evidence suggests medical imaging should not be done within the first six weeks. It is also suggested to avoid advanced imaging, such as CT or MRI, for adults without neurological symptoms or "red flags" in the patients history. General recommendations for initial low back pain treatment is remaining active, avoiding twisting and bending, avoiding activities that worsen pain, avoiding bed rest, and possibly initiating a trial of non-steroidal anti-inflammatory drugs after consulting a physician. Children and adolescents with persistent low back pain may require earlier imaging and should be seen by physician. Once imaging is deemed necessary, a combination of plain radiography, computed tomography, and magnetic resonance imaging may be used. Images are most often taken of the lumbar spine due to spondylolisthesis most commonly involving the lumbar region. Images of the thoracic spine can be taken if a patients history and physical suggest thoracic involvement. Plain Radiography (X-Ray) Plain radiography is often the first step in medical imaging. Anteroposterior (front-back) and lateral (side) images are used to allow the physician to view the spine at multiple angles. Oblique view are no longer recommended. In evaluating for spondylolithesis, plain radiographs provide information on the positioning and structural integrity of the spine. Therefore, if further detail is needed a physician may request advanced imaging. Magnetic Resonance Imaging (MRI) Magnetic resonance imaging is the preferred advanced imaging technique for evaluation of spondylolisthesis. Preference is due to effectiveness, lack of radiation exposure, and ability to evaluate for soft tissue abnormalities and spinal canal involvement. MRI is limited in its ability to evaluate fractures in great detail, compared to other advanced imaging modalities. Computed Tomography (CT) Computed tomography can be helpful in evaluating bony vertebral abnormalities, such as fractures. This can be helpful in determining if the fracture is a new, old, and/or progressing fracture. CT use in spondylolisthesis evaluation is controversial due to high radiation exposure. Treatment Spondylolisthesis patients without symptoms do not need to be treated. Conservative Non-operative management, also referred to as conservative treatment, is the recommended treatment for spondylolisthesis in most cases with or without neurological symptoms. Most patients with spondylolisthesis respond to conservative treatment. Conservative treatment consists primarily of physical therapy, intermittent bracing, aerobic exercise, pharmacological intervention, and epidural steroid injections. The majority of patients with degenerative spondylolisthesis do not require surgical intervention. Physical therapy can evaluate and address postural and compensatory movement abnormalities. Physical therapy primarily includes spinal flexion and extension exercises with a focus on core stabilization and muscle strengthening. In particular, lumbar spondylolisthesis may benefit from core stabilization exercises focusing on lower abdominal, lumbar muscles, hamstrings, and hip flexors, which may temporarily or permanently improve symptoms and improve general function. Some patients may benefit from bracing in combination with physical therapy. Additionally, bracing was found to be beneficial when performed immediately following the onset of symptoms, in particular patients with lumbar pars interarticular defects. Exercises such as cycling, elliptical training, swimming, and walking are considered low-impact aerobic exercises and are recommended for pain relief. Anti-inflammatory medications (NSAIDS) in combination with paracetamol can be tried initially. If a severe radicular component is present, a short course of oral steroids such as prednisone or methylprednisolone can be considered. Epidural steroid injections, either interlaminal or transforaminal, performed under fluoroscopic guidance can help with severe radicular (leg) pain, but lacks conclusive benefit in relieving back pain in lumbar spondylolisthesis. Chiropractic Specific spinal manipulation identifies the joints that are restricted or those that show abnormal motion. A gentle thrusting technique that helps to return motion to the joint by stretching the soft tissues and stimulating the nervous system. The purpose is to facilitate movement above and below the anterior slipped vertebrae. Other techniques are non thrusting flexion distraction or instrument assisted adjusting. Surgical There are no clear radiological or medical guidelines or indications for surgical interventions in degenerative spondylolisthesis. A minimum of three months of conservative management should be completed prior to considering surgical intervention. Three indications for potential surgical treatment are as follows: persistent or recurrent back pain or neurologic pain with a persistent reduction of quality of life despite a reasonable trial of conservative (non-operative) management, new or worsening bladder or bowel symptoms, or a new or worsening neurological deficit. Both minimally invasive and open surgical techniques are used to treat anterolisthesis. Retrolisthesis A retrolisthesis is a posterior displacement of one vertebral body with respect to the subjacent vertebra to a degree less than a luxation (dislocation). Retrolistheses are most easily diagnosed on lateral x-ray views of the spine. Views, where care has been taken to expose for a true lateral view without any rotation, offer the best diagnostic quality. Retrolistheses are found most prominently in the cervical and lumbar region, but can also be seen in the thoracic area. History Spondylolisthesis was first described in 1782 by Belgian obstetrician Herbinaux. He reported a bony prominence anterior to the sacrum that obstructed the vagina of a small number of patients. The term “spondylolisthesis” was coined in 1854 from the Greek σπονδυλος, "spondylos" = "vertebra" and ὀλίσθησης "olisthesis" = "slipping, sliding," See also Spondylosis Spondylolysis Failed back syndrome Joint dislocation References == External links ==

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

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

Oxaprozin, also known as oxaprozinum, is a nonsteroidal anti-inflammatory drug (NSAID), used to relieve the inflammation, swelling, stiffness, and joint pain associated with osteoarthritis and rheumatoid arthritis. Chemically, it is a propionic acid derivative. Safety and efficacy has been established in children over 6 years with juvenile rheumatoid arthritis only, and there is an increased risk of adverse reactions in the elderly population. It was patented in 1967 and approved for medical use in 1983. Medical uses In 2015, oxaprozin was one of twenty NSAIDs included in a clinical trial to compare the efficacy of NSAIDs in the short-term treatment of ankylosing spondylitis (AS). The NSAIDs were compared by completing randomized controlled trials of NSAIDs in patients with active AS. Efficacy reported at 2–12 weeks and adverse effects were examined. Efficacy was measured by change in pain score and change in the duration of morning stiffness. A total of 26 trials with a total of 3410 participants were completed (58% of the trials had fewer than 50 participants). While all 20 NSAIDs were found to reduce more pain than the placebo, 15 were found to be significantly better. In regards to the decrease of morning stiffness and the likelihood of adverse events, there was no significant difference between NSAIDs. It was concluded that etoricoxib was more effective in reducing pain of AS, however due to small studies and insufficient evidence, no one NSAID could be determined to be the most effective treatment of AS. After etoricoxib, patients taking oxaprozin experienced the least amount of pain with fewer adverse effects than naproxen. Adverse effects In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy. History Oxaprozin was developed and patented by Wyeth-Ayerst. The US patent 3578671, Oxazoles, was filed November 6, 1967 and published May 11, 1971. Following the filing of the patent, the first description of oxaprozin exhibiting anti-inflammatory properties was outlined in the article Diaryloxazole and diaylthiazolealkanoci acids: two novel series of non-steroidal anti-inflammatory agents. This article was published in Nature in 1968. In December 1988, Wyeth-Ayerst licensed the marketing rights for the US, Canada, Puerto Rico, and the Caribbean to Searle.Daypro became available January 5, 1993. Upon its release, “The Pink Sheet” estimated that the average whole sale price of Searles Daypro was $112.30 for 100 (600 mg) tablets. The price was comparable to other prescription NSAIDs. Society and culture FDA approval The oxaprozin new drug application (NDA 18-841) was submitted to the FDA on August 10, 1982. The drug was granted an “NDA Day” review on June 15–16, 1992. After Searle agreed to complete seven Phase IV postmarketing studies on October 22, the FDA approved Daypro on October 29, 1992.Since the approval of Daypro by Searle, other companies have submitted abbreviated new drug applications (ANDAs) to the FDA. Daypro by Searle is listed as the Reference Listed Drug to prove the bioequivalence of the ANDAs. Below is a table listing all of the approved oxaprozin products. Recalls Advantage Dose LLC recalled oxaprozin tablets on November 26, 2008. The company was not in conformance with cGMP. (Recall #D-837-2009) == References ==

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

I need a basic explanation for the medical term 'Antenatal depression.'

Antenatal depression, also known as prenatal or perinatal depression, is a form of clinical depression that can affect a woman during pregnancy, and can be a precursor to postpartum depression if not properly treated. It is estimated that 7% to 20% of pregnant women are affected by this condition. Any form of prenatal stress felt by the mother can have negative effects on various aspects of fetal development, which can cause harm to the mother and child. Even after birth, a child born from a depressed or stressed mother feels the affects. The child is less active and can also experience emotional distress. Antenatal depression can be caused by the stress and worry that pregnancy can bring, but at a more severe level. Other triggers include unplanned pregnancy, difficulty becoming pregnant, history of abuse, and economic or family situations.Commonly, symptoms involve how the patient views herself, how she feels about going through such a life changing event, the restrictions on the mothers lifestyle that motherhood will place, or how the partner or family feel about the baby. Pregnancy places significant strain on a womans body, so stress, mood swings, sadness, irritability, pain, and memory changes are to be expected. Left untreated, antenatal depression can be extremely dangerous for the health of the mother and the baby. It is highly recommended that mothers who feel they are experiencing antenatal depression have a discussion about it with their health care provider. Mothers with a history of mental health issues should also talk to their doctor about it early in the pregnancy to help with possible depressive symptoms. Signs and symptoms Antenatal depression is classified based on a womans symptoms. During pregnancy, a lot of changes to mood, memory, eating habits, and sleep are common. When these common traits become severe, and begin to alter ones day-to-day life, that is when it is considered to be antenatal depression. Symptoms of antenatal depression are: Inability to concentrate. Overwhelming anxiety and fear. Difficulty remembering. Feeling emotionally numb. Extreme irritability. Sleeping too much or not enough, or restless sleep. Extreme or unending fatigue. Desire to over eat, or not eat at all. Weight loss/gain unrelated to pregnancy. Loss of interest in sex. A sense of dread about everything, including the pregnancy. Feelings of failure, or guilt. Persistent sadness. Thoughts of suicide, or death.Other symptoms can include the inability to get excited about the pregnancy, and/or baby, a feeling of disconnection with the baby, and an inability to form/feel a bond with the developing baby. This can drastically affect the relationship between the mother and the baby, and can drastically affect the mothers capacity for self-care. Such inadequacies can lead to even greater risk factors for the mother. Antenatal depression can be triggered by various causes, including relationship problems, family or personal history of depression, infertility, previous pregnancy loss, complications in pregnancy, and a history of abuse or trauma. Onset and duration of symptoms Antenatal depression can be caused by many factors. Often it is associated with the fear and stress of the pregnancy. Other factors include unintended pregnancy, hyperemesis gravidarum, financial issues, living arrangements and relationships with the father and family. Typically, depression symptoms associated with pregnancy are categorized as postnatal depression, due to the onset of symptoms occurring after childbirth has occurred. The following is a breakdown of when a group of various women began to feel the onset of symptoms associated with depression: 11.8 percent at 18 weeks 13.5 percent at 32 weeks 9.1 percent 8 weeks after the birth 8.1 percent 8 months after the birthIn a recent article posted by The BabyCenter, the authors stated that "For years, experts mistakenly believed that pregnancy hormones protected against depression, leaving women more vulnerable to the illness only after the baby was born and their hormone levels plunged." This is a possible explanation as to why antenatal depression has just recently been identified. Prevalence and causes The prevalence of antenatal depression differs slightly by region of world. In the United States, antenatal depression is experienced in as many as 16% of pregnant women, while in South Asia it is experienced in as many as 24% of pregnant women. Its becoming more prevalent as more medical studies are being done. Antenatal depression was once thought to simply be the normal stress associated with any pregnancy, and was waved off as a common ailment. It can be caused by many factors, usually though involving aspects of the mothers personal life, such as family, economic standing, relationship status, etc. It can also be caused by hormonal and physical changes that are associated with pregnancy. Additional risk factors include lack of social support, marital dissatisfaction, discriminatory work environments, history of domestic abuse, and unplanned or unwanted pregnancy. Studies have determined that there may be a connection between antenatal and postpartum depression in women with lower vitamin D levels. There is a higher risk of antenatal depression in woman living in low-income countries who deal with less access to quality healthcare, have economic issues, and dont have a good support system. Screening Perinatal mental health screenings are important in detecting and diagnosing antenatal and postpartum depression early. The American College of Obstetricians and Gynecologists is one of the many maternal health organizations that strongly encourage universal screening for expectant and postpartum women for depression as part of routine obstetric care. In fact, many states, including California have already legislated laws that require providers to screen patients during visits because they recognize that early screenings can expedite the process in receiving effective treatment. The Patient Health Questionnaire 9 (PHQ-9) is a screening tool typically used to detect depression. Another tool, the Edinburgh Postnatal Depression Scale, was developed for the postnatal period, but has also been validated for use during pregnancy.PHQ-9 is a reliable depression severity scale that was formulated in accordance with DSM-IV criteria for depression, consisting of 9 items correlating to the 9 criteria listed in DSM-IV. It is a shortened version of the PHQ and has been assessed for comparable sensitivity and specificity. The screening test is self-administered to patients and are usually performed at the primary care clinic.However, it is not enough to just provide mental health screenings to at risk patients. Interventions such as referrals to treatment and mental health monitoring should be implemented in health care systems in order to ensure these women are helped consistently throughout their recovery journey.Studies suggest that obese woman tend to develop mental health issues more frequently and should discuss any symptoms with their doctor at the first prenatal appointment. Treatment Treatment for antenatal depression poses many challenges because the baby is also affected by any treatment given to the mother. There are both non-pharmacological and pharmacological treatment options which can be considered by women with antenatal depression. Non-pharmacological Therapy Psychotherapy Psychotherapy is recommended for any woman with antenatal depression, as it is an effective way for the mother to express her feelings in her own words. Specifically, Cognitive Behavioral Therapy effectively helps decrease symptoms of antenatal depression. In addition to psychotherapy, being seen by a psychiatrist is recommended as they can assess if medications will be beneficial and make specific medication recommendations, if warranted. Familial support may also play a role in helping with the emotional aspects of antenatal depression.While mental health specialists are trained in providing counseling interventions, results from a recent systematic review and meta-analysis of the literature found that nonspecialist providers, such as lay counselors, nurses, midwives, and teachers with no formal training in counseling interventions, often fill a gap in providing effective services related to depression and anxiety treatments. Exercise Therapy Studies suggest that forms of exercise can help with depressive symptoms both before and after birth, but not prevent it entirely.Exercise options that have been studied to help reduce symptoms: Yoga Walking Stretching Aerobic exercise Medications When discussing medication options for antenatal depression, it is important to ask the prescribing healthcare provider to share more details about all the risks and benefits of the available medications. During pregnancy, there are two main kinds of antidepressants used during pregnancy; tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). Once prescribed, anti-depressant medication has been found to be extremely effective in treating antenatal depression. Patients can expect to feel an improvement in mood in roughly 2 to 3 weeks on average, and can begin to feel themselves truly connect with their baby. Reported benefits of medication include returned appetite, increased mood, increased energy, and better concentration. Side effects are minor, though they are reported in some cases. Currently, no abnormalities of the baby have been associated with the use of antidepressants during pregnancy. It may be true that maternal SSRI use during pregnancy can lead to difficulty for their newborn adjusting to conditions outside of the womb immediately following birth. Some studies indicate that infants with exposure to SSRIs in the second and third trimester were more likely to be admitted to intensive care following their birth for respiratory, cardiac, low weight and other reasons, and that infants with prenatal SSRI exposure exhibited less motor control upon delivery than infants who were not exposed to SSRIs. Newborns who were exposed to SSRIs for five months or more prior to birth were at a greater risk for lower Apgar scores 1 and 5 minutes after delivery, indicating they were of lesser health than newborns who were not exposed to SSRIs before birth. However, prenatal SSRI exposure was not found to have a significant impact the long-term mental and physical health of the children. These results are not independent of any effects of prenatal depression on infants. Connection to postpartum depression and parenting stress Studies have found a strong link between antenatal depression and postpartum depression in women. In other words, women who have antenatal depression are very likely to also develop postpartum depression. The cause of this is based on the continuation of the antenatal depression into postpartum. In a logistical light, it makes sense that women who are depressed during their pregnancy will also be depressed following the birth of their child. This being said there are some factors that determine exclusively the presence of postpartum depression that are not necessarily linked with antenatal depression. These examples include variables like socioeconomic class, if a pregnancy was planned or not, and the parents relationship prior to conception and delivery of the child.In reference to a recent study by Coburn et al., the authors found that in addition to prenatal effects, higher maternal depressive symptoms during the postpartum period (12 weeks) were associated with more infant health concerns. This is consistent with other findings among low-SES Mexican-American women and their infants. Women with prenatal depressive symptoms are more likely to develop postpartum depression, which can also have negative consequences on children, such as emotional and behavior problems, attachment difficulties, cognitive deficits, physical growth and development, and feeding habits and attitudes. Related, maternal depression affects parenting behaviors, which in turn could affect child outcomes. Thus, womens mental health throughout the perinatal period should be a priority, not only to support women, but also to promote optimal functioning for their infants. Antenatal Depression and Infant Health Depression during pregnancy is associated with an increased risk of spontaneous abortion. In a review by Frazier et al., acute and chronic stress during pregnancy can diminish proper immunological activity crucial during pregnancy, and can possibly induce spontaneous abortion. There is still a debate on whether the miscarriage is due to the depressive disease state or the anti-depressant medication. A large study conducted in Denmark observed that there was a higher incidence of first trimester miscarriage in depressed women not exposed to SSRI compared to non-depressed women exposed to SSRI, indicating that the miscarriage may be associated with the psychological state of the mother rather than the anti-depressant. Depressive symptoms in pregnant women are linked with poor health outcomes in infants. The rates of hospitalization are found increased for infants who are born to women with high depression levels during pregnancy. Reduced breastfeeding, poor physical growth, lower birth weight, early gestational age and high rates of diarrheal infection are some of the reported outcomes of poor health among infants born to depressed pregnant women. In fact, positive antenatal screenings administered in the first or third trimester are found to be high risk factors for early cessation in breastfeeding. Studies also report that the environmental effects of maternal depression affect the developing fetus to such an extent that the impact can be seen during adulthood of the offspring. The effects are worse for women from low socio-economic backgrounds. In a recent study by Coburn et al., maternal prenatal depressive symptoms predicted significantly higher number of infant health concerns at 12-weeks (3 months) of age. The health concerns included rash, colic, cold, fever, cough, diarrhea, ear infections, and vomiting. Additional concerns for women in low-income backgrounds includes low birth rate and preterm births.An interesting and informative area of research has been done to see the role of confounding variables in relationship of maternal prenatal depression with infant health concerns. Age of mother, romantic partner, education, household income, immigrant status, and number of other children, breastfeeding, gestational age, birth weight are some of the mediating or moderating factors which are found correlated with infant health concerns. The studies of post-partum depressive symptoms are relatively more than those of prenatal depression and the studies should look into the role of various factors during pregnancy that may impact the health of infants, even continuing into adulthood. Male Perspective for Antenatal Depression Fathers can also experience depression during their partners pregnancy, commonly displayed as fatigue or changes in sleep and eating patterns. Men whose partners are women struggling with antenatal or postnatal depression often find themselves receiving less affection and intimacy from their partners. If symptoms of antenatal depression arise, it is recommended for fathers to provide encouragement for their partners to discuss their condition with a healthcare provider. It is also important for the father to also seek support for himself. In a research performed in Sweden observing 366,499 births, newly diagnosed paternal depression around the time of conception or during pregnancy was associated with an increased risk of preterm birth. However, a preexisting paternal depression did not show any correlation, which may be due to the mothers perception of the changes in her partners mood. See also Depression Gender disappointment Mood swings Postpartum depression Pregnancy Postpartum psychosis References Further reading Andrade C (2018). "Prenatal Depression and Infant Health: The Importance of Inadequately Measured, Unmeasured, and Unknown Confounds". Indian Journal of Psychological Medicine. 40 (4): 395–397. doi:10.4103/IJPSYM.IJPSYM_232_18. PMC 6065138. PMID 30093759.

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

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

Enterocolitis is an inflammation of the digestive tract, involving enteritis of the small intestine and colitis of the colon. It may be caused by various infections, with bacteria, viruses, fungi, parasites, or other causes. Common clinical manifestations of enterocolitis are frequent diarrheal defecations, with or without nausea, vomiting, abdominal pain, fever, chills, alteration of general condition. General manifestations are given by the dissemination of the infectious agent or its toxins throughout the body, or – most frequently – by significant losses of water and minerals, the consequence of diarrhea and vomiting. Cause Among the causal agents of acute enterocolitis are: bacteria: Salmonella, Shigella, Escherichia coli (E. coli), Campylobacter etc. viruses: enteroviruses, rotaviruses, Norovirus, adenoviruses fungi: candidiasis, especially in immunosuppressed patients or who have previously received prolonged antibiotic treatment parasites: Giardia lamblia (with high frequency of infestation in the population, but not always with clinical manifestations), Balantidium coli, Blastocystis homnis, Cryptosporidium (diarrhea in people with immunosuppression), Entamoeba histolytica (produces the amebian dysentery, common in tropical areas). Diagnosis Types Specific types of enterocolitis include: necrotizing enterocolitis (most common in premature infants) pseudomembranous enterocolitis (also called "Pseudomembranous colitis") Treatment Treatment depends on aetiology e.g. Antibiotics such as metronidazole for bacteria infection, antiviral drug therapy for viral infection and anti-helminths for parasitic infections See also Gastroenteritis References == External links ==

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

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

Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a symptom of Parkinsons disease shown as muscle rigidity and an inability to produce movement. It is also associated with mental health disorders and prolonged inactivity due to illness, amongst other diseases. The other category of movement disorder is hyperkinesia that features an exaggeration of unwanted movement, such as twitching or writhing in Huntingtons disease or Tourette syndrome. Spectrum of disorders Hypokinesia describes a variety of more specific disorders: Causes The most common cause of Hypokinesia is Parkinsons disease, and conditions related to Parkinsons disease. Other conditions may also cause slowness of movements. These include hypothyroidism and severe depression. These conditions need to be carefully ruled out, before a diagnosis of Parkinsonism is made. The remainder of this article describes Hypokinesia associated with Parkinsons disease, and conditions related to Parkinsons disease. Pathophysiology Associated neurotransmitters Dopamine The main neurotransmitter thought to be involved in hypokinesia is dopamine. Essential to the basal ganglionic-thalamocortical loop, which processes motor function, dopamine depletion is common in these areas of hypokinesic patients. Bradykinesia is correlated with lateralized dopaminergic depletion in the substantia nigra. The dopamine pathway in the substantia nigra is essential to motor function, and commonly a lesion in this area correlates with displayed hypokinesia. Tremor and rigidity, however, seem to be only partially due to dopamine deficits in the substantia nigra, suggesting other processes are involved in motor control. Treatments for hypokinesia often either attempt to prevent dopamine degradation by MAO-B or increase the amount of neurotransmitter present in the system.GABA and glutamate The inhibitory neurotransmitter GABA and the excitatory glutamate are found in many parts of the central nervous system, including in the motor pathways that involve hypokinesia. In one pathway, glutamate in the substantia nigra excites the release of GABA into the thalamus, which then inhibits the release of glutamate in the cortex and thereby reduces motor activity. If too much glutamate is initially in the substantia nigra, then through interaction with GABA in the thalamus and glutamate in the cortex, movements will be reduced or will not occur at all.Another direct pathway from the basal ganglia sends GABA inhibitory messages to the globus pallidus and substantia nigra, which then send GABA to the thalamus. In the indirect pathway, the basal ganglia send GABA to the globus pallidus which then sends it to the subthalamic nucleus, which then disinhibited sends glutamate to the output structures of the basal ganglia. Inhibition of GABA release could disrupt the feedback loop to the basal ganglia and produce hypokinesic movements.GABA and glutamate often interact with each other and with dopamine directly. In the basal ganglia, the nigrostriatal pathway is where GABA and dopamine are housed in the same neurons and released together. Neurobiology Hypokinetic symptoms arise from damage to the basal ganglia, which plays a role in producing force and computing the effort necessary to make a movement. Two possible neural pathways enable the basal ganglia to produce movement. When activated, the direct pathway sends sensory and motor information from the cerebral cortex to the first structure of the basal ganglia, the putamen. That information directly inhibits the globus pallidus internal and allows free movement. The indirect pathway, traveling through the putamen, globus pallidus external, and subthalamic nucleus, activates the globus pallidus internal threshold and inhibits the thalamus from communicating with the motor cortex, producing hypokinetic symptoms. When levels of dopamine decrease, the normal wave-firing pattern of basal ganglia neural oscillations changes and the tendency for oscillations increases, particularly in the beta wave of the basal ganglia. Recent research indicates, when oscillations fire simultaneously, processing is disrupted at the thalamus and cortex, affecting activities such as motor planning and sequence learning, as well as causing hypokinetic tremors. Treatments Dopaminergic drugs Dopaminergic drugs are commonly used in the early stages of the hypokinesia to treat patients. With increased intake, though, they can become ineffective because of the development of noradrenergic lesions. While initially the dopaminergic drugs may be effective, these noradrenergic lesions are associated with hypokinesic gait disorder development later on.Some Parkinsons patients are unable to move during sleep, prompting the diagnosis of "nocturnal hypokinesia". Physicians have experienced success treating this sleep disorder with slow-release or night-time dopaminergic drugs, and in some cases, continuous stimulation by the dopamine agonist rotigotine. Despite improved mobility during sleep, many Parkinsons patients report an extremely uncomfortable sleeping experience even after dopaminergic treatments. Deep brain stimulation Once the reaction to dopaminergic drugs begins to fluctuate in Parkinsons patients, deep brain stimulation (DBS) of the subthalamic nucleus and internal globus pallidus is often used to treat hypokinesia. DBS, like dopaminergic drugs, initially provides relief, but chronic use causes worse hypokinesia and freezing of gait. Lower-frequency DBS in irregular patterns has been shown to be more effective and less detrimental in treatment. Posteroventral pallidotomy (PVP) is a specific kind of DBS that destroys a small part of the globus pallidus by scarring the neural tissue, reducing brain activity and therefore tremors and rigidity. PVP is suspected to recalibrate basal ganglia activity in the thalamocortical pathway. PVP in the dominant hemisphere has been reported to disrupt executive function verbal processing abilities, and bilateral PVP may disturb processes of focused attention.Many akinesia patients also form a linguistic akinesia in which their ability to produce verbal movements mirrors their physical akinesia symptoms, especially after unsuccessful PVP. Patients are usually able to maintain normal levels of fluency, but often stop midsentence, unable to remember or produce a desired word. According to a study of Parkinsons patients with articulatory hypokinesia, subjects with faster rates of speech experienced more problems trying to produce conversational language than those who normally spoke at slower rates. Methylphenidate Methylphenidate, commonly used to treat ADHD, has been used in conjunction with levodopa to treat hypokinesia in the short term. The two work together to increase dopamine levels in the striatum and prefrontal cortex. Methylphenidate mainly inhibits dopamine and noradrenaline reuptake by blocking presynaptic transporters, and levodopa increases the amount of dopamine, generally improving hypokinesic gait. Some patients, however, have adverse reactions of nausea and headache to the treatment and the long-term effects of the drug treatment still need to be assessed. Stem cells New treatments include increasing the number of dopamine cells by transplanting stem cells into the basal ganglia or stimulating endogenous stem cell production and movement to the basal ganglia. The successful integration of stem cells can relieve hypokinetic symptoms and decrease the necessary dose of dopaminergic drugs. However, a variety of complications, including possible tumor formation, inappropriate cell migration, rejection of cells by the immune system, and cerebral hemorrhage are possible, causing many physicians to believe the risks outweigh the possible benefits. NOP receptor antagonists Another treatment, still in an experimental stage, is the administration of nociception FQ peptide (NOP) receptor antagonists. This treatment has been shown to reduce hypokinesia in animal studies when increasing nociception FQ in the substantia nigra and subthalamic nucleus. Low doses can be taken with dopaminergic treatment to decrease the amount of L-dopa needed, which can reduce its long-term side effects and improve motor performance. Dance therapy Dance therapy has also been shown to reduce hypokinesic movements and rigidity, though targeted more at the muscular aspects of the disorder than the neural activity. Associations Cognitive impairment Bradykinesia has been shown to precede impairment of executive functions, working memory, and attention. These cognitive deficiencies can be tied to nonfunction of the basal ganglia and prefrontal cortex, which is also linked to the motor-dysfunction of hypokinesia. Tremor and rigidity have not had observable connections to cognitive impairments, supporting the idea that they are not as involved in the dopamine pathway in the basal ganglionic-thalamocortical loop. Dopaminergic treatments have shown improvement in cognitive functions associated with hypokinesia, suggesting they are also dependent on dopamine levels in the system. Motor motivation Often debated is whether the efficiency, vigor, and speed of movements in patients with hypokinesia are tied to motivation for rewarding and against punishing stimuli. The basal ganglia have been tied to the incentives behind movement, therefore suggesting a cost/benefit analysis of planned movement could be affected in hypokinesia. Rewards have not been shown to change the aspects of a hypokinesic individuals movement. In fact, the motor planning and control of a patient with hypokinesia is already as efficient as possible (as shown by slightly faster, but generally the same movement after deep brain stimulation of the subthalamic nucleus). This suggests that hypokinetic individuals simply have a narrower range of movement that does not increase relative to motivation.Other studies have come to the same conclusion about rewards and hypokinesia, but have shown that aversive stimuli can, in fact, reduce hypokinesic movement. Dopamine is either less involved or has a more complex role in the response to punishment than it does to rewards, as the hypodopaminergic striatum allows more movement in response to aversive stimuli. Demographic differentiation Gender More men than women typically develop hypokinesia, which is reflected in young and middle-aged populations where females have displayed higher levels of nigrostriatal dopamine than males. In the elderly, however, this differentiation is not present. Typically, women exhibit more tremor in the beginning development of hypokinesia. In the disorder, men tend to display more rigidity and women more bradykinesic motor behavior.Age of onset Hypokinesia is displayed in the brain and outwardly slightly different depending on when an individual is first affected. In young-onset hypokinesia (younger than 45 years of age), typically slightly more cell loss occurs in the substantia nigra with more displayed dystonia and muscle stiffness. In old-onset hypokinesia (older than 70 years of age), typically more of a hypokinesic gait and difficulty walking and no dystonia are seen. Both onsets can display resting tremor, although more generally found in old-onset cases. Symptoms Stress causes alterations of cerebral circulation, increasing blood flow in the supramarginal gyrus and angular gyrus of the parietal lobe, the frontal lobe, and the superior temporal gyrus of the left hemisphere. Also, an increase in cardiac activity and change in the tonus of the heart vessels occurs, which is an elementary indication of stress development. In patients with normal stress, an adaptive fight-or-flight response is usually triggered by sympathetic nervous system activation. Hypokinesia patients experience these typical stress symptoms on a regular basis because of damage to the basal ganglia system. Therefore, when a hypokinesia victim is under stress, he or she does not display a typical fight-or-flight response, placing the patient under greater danger from potentially harmful stimuli. Low-impact exercise, elimination of drug and alcohol use, and regular meditation can help to restore normal stress responses in hypokinesia patients. Connections to other medical conditions Though it is often most associated with Parkinsons disease, hypokinesia can be present in a wide variety of other conditions. See also Akinetic mutism Hyperkinesia == References ==

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

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

Synucleinopathies (also called α-Synucleinopathies) are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells. There are three main types of synucleinopathy: Parkinsons disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Other rare disorders, such as various neuroaxonal dystrophies, also have α-synuclein pathologies. Additionally, autopsy studies have shown that around 6% of sporadic Alzheimers Disease exhibit α-synuclein positive Lewy pathology, and are sub-classed as Alzheimers Disease with Amygdalar Restricted Lewy Bodies (AD/ALB). Presentation The synucleinopathies have shared features of parkinsonism, impaired cognition, sleep disorders, and visual hallucinations.Synucleinopathies can sometimes overlap with tauopathies, possibly because of interaction between the synuclein and tau proteins.REM sleep behavior disorder (RBD) is a parasomnia in which individuals with RBD lose the paralysis of muscles (atonia) that is normal during rapid eye movement (REM) sleep, and act out their dreams or have other abnormal movements or vocalizations. Abnormal sleep behaviors may appear decades before any other symptoms, often as an early sign of a synucleinopathy. On autopsy, 94 to 98% of individuals with polysomnography-confirmed RBD are found to have a synucleinopathy—most commonly DLB or PD. Other symptoms of the specific synucleinopathy usually manifest within 15 years of the diagnosis of RBD, but may emerge up to 50 years after RBD diagnosis.Alpha-synuclein deposits can affect the cardiac muscle and blood vessels. Almost all people with synucleinopathies have cardiovascular dysfunction, although most are asymptomatic.From chewing to defecation, alpha-synuclein deposits affect every level of gastrointestinal function. Symptoms include upper gastrointestinal tract dysfunction such as delayed gastric emptying or lower gastrointestinal dysfunction, such as constipation and prolonged stool transit time.Urinary retention, waking at night to urinate, increased urinary frequency and urgency, and over- or underactive bladder are common in people with synucleinopathies. Sexual dysfunction usually appears early in synucleinopathies, and may include erectile dysfunction, and difficulties achieving orgasm or ejaculating. Diagnosis Differential diagnosis Persons with PD are typically less caught up in their visual hallucinations than those with DLB. There is a lower incidence of tremor at rest in DLB than in PD, and signs of parkinsonism in DLB are more symmetrical. In MSA, autonomic dysfunction appears earlier and is more severe, and is accompanied by uncoordinated movements, while visual hallucinations and fluctuating cognition are less common than in DLB. Urinary difficulties are one of the earliest symptoms with MSA, and are often severe. DNA damage Alpha-synuclein modulates DNA repair processes, including the repair of DNA double-strand breaks by the non-homologous end joining pathway. The DNA repair function of alpha-synuclein appears to be compromised in Lewy body inclusion bearing neurons, and this may trigger cell death. Study of synucleinopathy mouse models of Parkinson’s disease indicates that alpha-synuclein pathogenesis is associated with increased DNA damage and activation of the DNA damage response. See also Proteopathy Lewy body == References ==

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

Could you please explain the term 'Haloperidol decanoate' in simple language?

Haloperidol decanoate, sold under the brand name Haldol Decanoate among others, is a typical antipsychotic which is used in the treatment of schizophrenia. It is administered by injection into muscle at a dose of 100 to 200 mg once every 4 weeks or monthly. The dorsogluteal site is recommended. A 3.75-cm (1.5-inch), 21-gauge needle is generally used, but obese individuals may require a 6.5-cm (2.5-inch) needle to ensure that the drug is indeed injected intramuscularly and not subcutaneously. Haloperidol decanoate is provided in the form of 50 or 100 mg/mL oil solution of sesame oil and benzyl alcohol in ampoules or pre-filled syringes. Its elimination half-life after multiple doses is 21 days. The medication is marketed in many countries throughout the world. See also List of antipsychotics § Antipsychotic esters == References ==

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

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

Cetirizine, sold under the brand name Zyrtec among others, is a second-generation antihistamine used to treat allergic rhinitis (hay fever), dermatitis, and urticaria (hives). It is taken by mouth. Effects generally begin within thirty minutes and last for about a day. The degree of benefit is similar to other antihistamines such as diphenhydramine.Common side effects include sleepiness, dry mouth, headache, and abdominal pain. The degree of sleepiness that occurs is generally less than with first generation antihistamines. Use in pregnancy appears safe, but use during breastfeeding is not recommended. The medication works by blocking histamine H1 receptors, mostly outside the brain.It was patented in 1981 and came into medical use in 1987. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. In 2020, it was the 52nd most commonly prescribed medication in the United States, with more than 13 million prescriptions. Medical uses Allergies Cetirizines primary indication is for hay fever and other allergies. Because the symptoms of itching and redness in these conditions are caused by histamine acting on the H1 receptor, blocking those receptors temporarily relieves those symptoms.Cetirizine is also commonly prescribed to treat acute and (in particular cases) chronic urticaria, more efficiently than any other second-generation antihistamine. Available forms Cetirizine is available over-the-counter in the US in the form of 5 and 10 mg tablets. A 20 mg strength is available by prescription only. It is also available as a 1 mg/mL syrup for oral administration by prescription. In the UK, up to 30 tablets of 10 mg are on the general sales list (of pharmaceuticals) and can be purchased without a prescription and without pharmacist supervision. The drug can be in the form of tablets, capsules or a syrup. Adverse effects Commonly reported side effects of cetirizine include headache, dry mouth, drowsiness, and fatigue, while more serious but rare adverse effects reported include tachycardia and edema.Discontinuing cetirizine after prolonged use (typically, use beyond six months) may result in generalized itching. Pharmacology Pharmacodynamics Cetirizine acts as a highly selective antagonist of the histamine H1 receptor. The Ki values for the H1 receptor are approximately 6 nM for cetirizine, 3 nM for levocetirizine, and 100 nM for dextrocetirizine, indicating that the levorotatory enantiomer is the main active form. Cetirizine has 600-fold or greater selectivity for the H1 receptor over a wide variety of other sites, including muscarinic acetylcholine, serotonin, dopamine, and α-adrenergic receptors, among many others. The drug shows 20,000-fold or greater selectivity for the H1 receptor over the five muscarinic acetylcholine receptors, and hence does not exhibit anticholinergic effects. It shows negligible inhibition of the hERG channel (IC50 > 30 μM) and no cardiotoxicity has been observed with cetirizine at doses of up to 60 mg/day, six times the normal recommended dose and the highest dose of cetirizine that has been studied in healthy subjects.Cetirizine crosses the blood-brain barrier only slightly, and for this reason, produces minimal sedation compared to many other antihistamines. A positron emission tomography (PET) study found that brain occupancy of the H1 receptor was 12.6% for 10 mg cetirizine, 25.2% for 20 mg cetirizine, and 67.6% for 30 mg hydroxyzine. (A 10 mg dose of cetirizine equals about a 30 mg dose of hydroxyzine in terms of peripheral antihistamine effect.) PET studies with antihistamines have found that brain H1 receptor occupancy of more than 50% is associated with a high prevalence of somnolence and cognitive decline, whereas brain H1 receptor occupancy of less than 20% is considered to be non-sedative. In accordance, H1 receptor occupancy correlated well with subjective sleepiness for 30 mg hydroxyzine but there was no correlation for 10 or 20 mg cetirizine. As such, brain penetration and brain H1 receptor occupancy by cetirizine are dose-dependent, and in accordance, while cetirizine at doses of 5 to 10 mg have been reported to be non-sedating or mildly sedating, a higher dose of 20 mg has been found to induce significant drowsiness in other studies.Cetirizine also shows anti-inflammatory properties independent of H1 receptors. The effect is exhibited through suppression of the NF-κB pathway, and by regulating the release of cytokines and chemokines, thereby regulating the recruitment of inflammatory cells. It has been shown to inhibit eosinophil chemotaxis and LTB4 release. At a dosage of 20 mg, Boone et al. found that it inhibited the expression of VCAM-1 in patients with atopic dermatitis. Pharmacokinetics Absorption Cetirizine is rapidly and extensively absorbed upon oral administration in tablet or syrup form. The oral bioavailability of cetirizine is at least 70% and of levocetirizine is at least 85%. The Tmax of cetirizine is approximately 1.0 hour regardless of formulation. The pharmacokinetics of cetirizine have been found to increase linearly with dose across a range of 5 to 60 mg. Its Cmax following a single dose has been found to be 257 ng/mL for 10 mg and 580 ng/mL for 20 mg. Food has no effect on the bioavailability of cetirizine but has been found to delay the Tmax by 1.7 hours (i.e., to approximately 2.7 hours) and to decrease the Cmax by 23%. Similar findings were reported for levocetirizine, which had its Tmax delayed by 1.25 hours and its Cmax decreased by about 36% when administered with a high-fat meal. Steady-state levels of cetirizine occur within 3 days and there is no accumulation of the drug with chronic administration. Following once-daily administration of 10 mg cetirizine for ten days, the mean Cmax was 311 ng/mL. Distribution The mean plasma protein binding of cetirizine has been found to be 93 to 96% across a range of 25 to 1,000 ng/mL independent of concentration. Plasma protein binding of 88 to 96% has also been reported across multiple studies. The drug is bound to albumin with high affinity, while α1-acid glycoprotein and lipoproteins contribute much less to total plasma protein binding. The unbound or free fraction of levocetirizine has been reported to be 8%. The true volume of distribution of cetirizine is unknown but is estimated to be 0.3 to 0.45 L/kg. Cetirizine poorly and slowly crosses the blood-brain barrier, which is thought to be due to its chemical properties and its activity as a P-glycoprotein substrate. Metabolism Cetirizine does not undergo extensive metabolism. It is notably not metabolized by the cytochrome P450 system. Because of this, it does not interact significantly with drugs that inhibit or induce cytochrome P450 enzymes such as theophylline, erythromycin, clarithromycin, cimetidine, or alcohol. While cetirizine does not undergo extensive metabolism or metabolism by the cytochrome P450 enzyme, it does undergo some metabolism by other means, the metabolic pathways of which include oxidation and conjugation. Plasma radioactivity attributed to unchanged cetirizine is more than 90% at 2 hours, 80% at 10 hours, and 70% at 24 hours, indicating limited and slow metabolism. The enzymes responsible for transformation of cetirizine have not been identified. Elimination Cetirizine is eliminated approximately 70 to 85% in the urine and 10 to 13% in the feces. About 50 or 60% of cetirizine eliminated in the urine is unchanged. It is eliminated in the urine via an active transport mechanism. The elimination half-life of cetirizine ranges from 6.5 to 10 hours in healthy adults, with a mean across studies of approximately 8.3 hours. Its duration of action is at least 24 hours. The elimination half-life of cetirizine is increased in the elderly (to 12 hours), in hepatic impairment (to 14 hours), and in renal impairment (to 20 hours). Chemistry Cetirizine contains L- and D-stereoisomers. Chemically, levocetirizine is the active L-enantiomer of cetirizine. The drug is a member of the diphenylmethylpiperazine group of antihistamines. Analogues include cyclizine and hydroxyzine. Synthesis The 1-(4-chlorophenylmethyl)-piperazine is alkylated with methyl (2-chloroethoxy)-acetate in the presence of sodium carbonate and xylene solvent to produce the Sn2 substitution product in 28% yield. Saponification of the acetate ester is done by refluxing with potassium hydroxide in absolute ethanol to afford a 56% yield of the potassium salt intermediate. This is then hydrolyzed with aqueous HCl and extracted to give an 81% yield of the carboxylic acid product. Availability Formerly prescription-only in many countries, cetirizine is now available without prescription in most countries. In some countries it is available over-the-counter only in packages containing seven or ten 10 mg doses.Like many other antihistamine medications, cetirizine is commonly prescribed in combination with pseudoephedrine, a decongestant. These combinations are often marketed using the same brand name as the cetirizine with a "-D" suffix (Zyrtec-D, Virlix-D, etc.)Cetirizine is marketed under the brand names Alatrol, Alerid, Alzene, Cerchio, Cetirin, Cetriz, Cetzine, Cezin, Cetgel, Cirrus, Histec, Histazine, Humex, Letizen, Okacet (Cipla), Piriteze, Reactine, Razene, Rigix, Sensahist (Oethmann, South Africa), Triz, Zetop, Zirtec, Zirtek, Zodac, Zyllergy, Zynor, Zyrlek, and Zyrtec (Johnson & Johnson), among others. References External links "Cetirizine". Drug Information Portal. U.S. National Library of Medicine. Cetirizine Tablet Uses In Hindi

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

Can you demystify the medical term 'Liver fluke' for me?

Liver fluke is a collective name of a polyphyletic group of parasitic trematodes under the phylum Platyhelminthes. They are principally parasites of the liver of various mammals, including humans. Capable of moving along the blood circulation, they can occur also in bile ducts, gallbladder, and liver parenchyma. In these organs, they produce pathological lesions leading to parasitic diseases. They have complex life cycles requiring two or three different hosts, with free-living larval stages in water. Biology The body of liver flukes is leaf-like and flattened. The body is covered with a tegument. They are hermaphrodites having complete sets of both male and female reproductive systems. They have simple digestive systems and primarily feed on blood. The anterior end is the oral sucker opening into the mouth. Inside, mouth lead to a small pharynx which is followed by an extended intestine that runs through the entire length of the body. The intestine is heavily branched and anus is absent. Instead, the intestine runs along an excretory canal that opens at the posterior end. Adult flukes produce eggs that are passed out through the excretory pore. The eggs infect different species of snails (as intermediate hosts) in which they grow into larvae. The larvae are released into the environment from where the definitive hosts (humans and other mammals) get the infection. In some species, another intermediate host is required, generally a cyprinid fish. In this case, the definitive hosts are infected from eating infected fish. Hence, they are food-borne parasites. Pathogenicity Liver fluke infections cause serious medical and veterinary diseases. Fasciolosis of sheep, goats and cattle, is the major cause of economic losses in dairy and meat industry. Fasciolosis of humans produces clinical symptoms such as fever, nausea, swollen liver, extreme abdominal pain, jaundice and anemia.Clonorchiasis and opisthorchiasis (due to Opisthorchis viverrini) are particularly dangerous. They can survive for several decades in humans causing chronic inflammation of the bile ducts, epithelial hyperplasia, periductal fibrosis and bile duct dilatation. In many infections these symptoms cause further complications such as stone formation, recurrent pyogenic cholangitis and cancer (cholangiocarcinoma). Opisthorchiasis is particularly the leading cause of cholangiocarcinoma in Thailand and Laos. Both clonorchiasis and opisthorchiasis are classified as Group 1 human biological agents (carcinogens) by International Agency of Research on Cancer (IARC). Species Species of liver fluke include: Clonorchis sinensis (the Chinese liver fluke, or the Oriental liver fluke) Dicrocoelium dendriticum (the lancet liver fluke) Dicrocoelium hospes Fasciola hepatica (the sheep liver fluke) Fascioloides magna (the giant liver fluke) Fasciola gigantica Fasciola jacksoni Metorchis conjunctus Metorchis albidus Protofasciola robusta Parafasciolopsis fasciomorphae Opisthorchis viverrini (Southeast Asian liver fluke) Opisthorchis felineus (Cat liver fluke) Opisthorchis guayaquilensis See also The Integrated Opisthorchiasis Control Program == References ==

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

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

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

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

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

Chemosis is the swelling (or edema) of the conjunctiva. The term derives from the Greek chem- meaning chemical and -osis meaning denoting action. A chemical reaction, or in this case, a chemical reaction of the conjunctiva which is due to the oozing of exudate from abnormally permeable capillaries. In general, chemosis is a nonspecific sign of eye irritation. The outer surface covering appears to have fluid in it. The conjunctiva becomes swollen and gelatinous in appearance. Often, the eye area swells so much that the eyes become difficult or impossible to close fully. Sometimes, it may also appear as if the eyeball has moved slightly backwards from the white part of the eye due to the fluid filled in the conjunctiva all over the eyes except the iris. The iris is not covered by this fluid and so it appears to be moved slightly inwards. Causes It is usually caused by allergies or viral infections, often inciting excessive eye rubbing. Chemosis is also included in the Chandler Classification system of orbital infections. If chemosis has occurred due to excessive rubbing of the eye, the first aid to be given is a cold water wash for eyes.Other causes of chemosis include: Superior vena cava obstruction, accompanied by facial oedema Hyperthyroidism, associated with exophthalmos, periorbital puffiness, lid retraction, and lid lag Cavernous sinus thrombosis, associated with infection of the paranasal sinuses, proptosis, periorbital oedema, retinal haemorrhages, papilledema, extraocular movement abnormalities, and trigeminal nerve sensory loss Carotid-cavernous fistula - classic triad of chemosis, pulsatile proptosis, and ocular bruit Cluster headache Trichinellosis Systemic lupus erythematosus (SLE) Angioedema Acute glaucoma Panophthalmitis Orbital cellulitis Gonorrheal conjunctivitis Dacryocystitis Spitting cobra venom to the eye High concentrations of phenacyl chloride in chemical mace spray Urticaria Trauma HSV Keratitis Post surgical Mucor Rhabdomyosarcoma of the orbit Diagnosis An eye doctor may most often diagnose chemosis by doing a physical examination of the affected area. They can also ask questions about the severity and length of other symptoms. Treatment Treatment depends on the cause of the chemosis. References == External links ==

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

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

Cerebral vasculitis (sometimes the word angiitis is used instead of "vasculitis") is vasculitis (inflammation of the blood vessel wall) involving the brain and occasionally the spinal cord. It affects all of the vessels: very small blood vessels (capillaries), medium-size blood vessels (arterioles and venules), or large blood vessels (arteries and veins). If blood flow in a vessel with vasculitis is reduced or stopped, the parts of the body that receive blood from that vessel begins to die. It may produce a wide range of neurological symptoms, such as headache, skin rashes, feeling very tired, joint pains, difficulty moving or coordinating part of the body, changes in sensation, and alterations in perception, thought or behavior, as well as the phenomena of a mass lesion in the brain leading to coma and herniation. Some of its signs and symptoms may resemble multiple sclerosis. 10% have associated bleeding in the brain. Causes "Primary" angiitis/vasculitis of the central nervous system (PACNS) is said to be present if there is no underlying cause. The exact mechanism of the primary disease is unknown, but the fundamental mechanism of all vasculitides is autoimmunity. Other possible secondary causes of cerebral vasculitis are infections, systemic auto-immune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, medications and drugs (amphetamine, cocaine and heroin), some forms of cancer (lymphomas, leukemia and lung cancer) and other forms of systemic vasculitis such as granulomatosis with polyangiitis, polyarteritis nodosa or Behçets disease. It may imitate, and is in turn imitated by, a number of other diseases that affect the blood vessels of the brain diffusely such as fibromuscular dysplasia and thrombotic thrombocytopenic purpura. Diagnosis Cerebral angiography and magnetic resonance imaging, family medical history, symptoms, a complete physical examination, and ultimately biopsy of the brain, are often required for the diagnosis. Also, many lab tests must be done for the diagnosis; tests may reveal anemia (a shortage of red blood cells), a high white blood cell count, a high platelet count, allergic reactions, immune complexes, antibodies (tools the body uses to fight off threats) and elevation of inflammatory markers. Another crucial part in the diagnosis of cerebral vasculitis is the use of imaging techniques. Techniques such as conventional digital subtraction angiography (DSA) and magnetic resonance imaging (MRI) are used to find and monitor cerebral involvement. Treatment Treatment is first with many different high-dose steroids, namely glucocorticoids. Then, if symptoms do not improve additional immunosuppression such as cyclophosphamide are added to decrease the immune systems attack on the bodys own tissues. Cerebral vasculitis is a very rare condition that is difficult to diagnose, and as a result there are significant variations in the way it is diagnosed and treated. Specific Diseases Giant cell arteritis (GCA) (Also known as temporal arteritis) Symptoms Fever general uneasiness weight loss inflammation of the muscles causing stiffness in the shoulders; neck; and/or upper arms persisting headache pain in the jaw or ear while eating double vision partial loss of vision or blind spots (on rare occasions) stroke. Diagnostic criteria Three or more of the following five criteria must be met: Age 50 years or more New developed headache Tenderness of the superficial temporal artery Elevated sedimentation rate, at least 50 mm/hour (blood test that reveals inflammatory activity) Giant cell arteritis in a biopsy specimen from the temporal artery Takayasus arteritis Symptoms Starts with nonspecific symptoms such as: Localized joint pain Fever Fatigue Headaches Rashes Weight loss Diagnosis usually does not happen until the blockage causes deficient blood flow to the extremities or to a stroke. Classification criteria Three or more of the following six criteria must be met: Age when disease starts is under 50 Decreased brachial artery pulse Systolic blood pressure differs by more than 10mmHg between arms Cramping caused by exercise in the extremities Abnormal sounds (through stethoscope) over subclavian arteries or abdominal aorta A narrowing or blockage in the aorta, its primary branches, or large arteries as seen through a radiograph of the arteries. Treatment therapy 50% of patients respond to corticosteroid therapy alone in early phases Methotrexate or Azathioprine are an alternative to corticosteroid immunosuppressants There have been studies on Mycophenolate mofetil and anti-TNF therapies In Takayasu’s arteritis it is vital to combine drug treatments often with low-dose aspirin or statin Polyarteritis nodosa (PAN) Symptoms Systemic illness with fever General feeling of discomfort or uneasiness with cause difficult to identify Weight loss Arthritis Black discoloration of skin primarily on the extremities Severe inadequate blood supply to the extremities Ischemic stroke, hemorrhages and a progressive encephalopathy with or without seizures may occur Diagnostic Criteria Three or more of the following ten criteria are required: More than 4 kg (8.8 lb) weight loss Lace-like purplish discoloration of the skin (livedo reticularis) Testicular pain Pain in a muscle or group of muscles (myalgias) Damage to peripheral nerves Elevation of blood pressure by more than 90 mmHg Creatinine serum levels greater than 1,5 mg/dl Hepatitis B or C virus antibodies An aneurysm or occlusion as shown in a pathologic arteriography Histology findings typical of PAN Treatment therapy In PAN not associated with a hepatitis virus: prednisone and cyclophosphamide therapy. In case of emergency, plasmapheresis may be tried In PAN associated with a hepatitis virus: combination therapy of prednisone along with a virustatic, such as lamivudine (Hepatitis B) or interferon-alpha and ribavirin (Hepatitis C) Granulomatosis with polyangiitis (GPA) Symptoms Men are affected twice as often as women Compression of structures surrounding the nose and paranasal sinuses Diabetes insipidus Abnormal protrusion of the eyeball(s) Nonseptic meningitis Affection of the lung and kidney due to destruction of the arteries and veins Ischemic stroke, hemorrhages, or encephalopathy with possible seizures Diagnostic Criteria Two or more of the following four criteria are required: Necrotizing ulcerating inflammation of nose, sinuses, mouth or pharynx Irregular lung infiltrates Nephritis Granulomatous vascular and perivascular inflammation Treatment Therapy Corticosteroids (e.g., Prednisolone) Cyclophosphamide Azathioprine Mycophenolate mofetil References == External links ==

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

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

Breast hypertrophy is a rare medical condition of the breast connective tissues in which the breasts become excessively large. The condition is often divided based on the severity into two types, macromastia and gigantomastia. Hypertrophy of the breast tissues may be caused by increased histologic sensitivity to certain hormones such as female sex hormones, prolactin, and growth factors. Breast hypertrophy is a benign progressive enlargement, which can occur in both breasts (bilateral) or only in one breast (unilateral). It was first scientifically described in 1648. Description and types The indication is an excess breast weight that exceeds approximately 3% of the total body weight. There are varying definitions of what is considered to be excessive breast tissue, that is the expected breast tissue plus extraordinary breast tissue, ranging from as little as 0.6 kilograms (1.3 lb) up to 2.5 kilograms (5.5 lb) with most physicians defining macromastia as excessive tissue of over 1.5 kilograms (3.3 lb). Some resources distinguish between macromastia (Greek, macro: large, mastos: breast), where excessive tissue is less than 2.5 kg, and gigantomastia (Greek, gigantikos: giant), where excessive tissue is more than 2.5 kg. The enlargement can cause muscular discomfort and over-stretching of the skin envelope, which can lead in some cases to ulceration.Hypertrophy of the breast can affect the breasts equally, but usually affects one breast more than the other, thereby causing asymmetry, when one breast is larger than the other. The condition can also individually affect the nipples and areola instead of or in addition to the entire breast. The effect can produce a minor size variation to an extremely large breast asymmetry. Breast hypertrophy is classified in one of five ways: as either pubertal (virginal hypertrophy), gestational (gravid macromastia), in adult women without any obvious cause, associated with penicillamine therapy, and associated with extreme obesity. Many definitions of macromastia and gigantomastia are based on the term of "excessive breast tissue", and are therefore somewhat arbitrary. A total of 115 cases of breast hypertrophy had been reported in the literature as of 2008. Virginal breast hypertrophy When gigantomastia occurs in young women during puberty, the medical condition is known as juvenile macromastia or juvenile gigantomastia and sometimes as virginal breast hypertrophy or virginal mammary hypertrophy. Along with the excessive breast size, other symptoms include red, itchy lesions and pain in the breasts. A diagnosis is made when an adolescents breasts grow rapidly and achieve great weight, usually soon after her first menstrual period. Some doctors suggest that the rapid breast development occurs before the onset of menstruation.Some women with virginal breast hypertrophy experience breast growth at a steady rate for several years, after which the breasts rapidly develop exceeding normal growth. Some adolescent females experience minimal or negligible breast growth until their breasts suddenly grow very rapidly in a short period of time. This may cause considerable physical discomfort. Women with VBH often experience an excessive growth of their nipples as well. In severe cases of VBH, hypertrophy of the clitoris occurs.At the onset of puberty, some females with who have experienced little or no breast development can reportedly reach three or more cup sizes within a few days (see below).As of 1992, 70 cases of virginal breast hypertrophy had been reported. Gestational breast hypertrophy This same effect can also occur at the onset of pregnancy or between the 16th to 20th week of gestation. When the swelling in the connective tissue occurs after birth, it can negatively impact long term milk supply. The swelling increases with each subsequent pregnancy. The extremely rapid growth of the breasts can result in intense heat. The womans breasts can generate extraordinary discomfort, turning feverish, red, itchy, and even causing the skin to peel. The swelling can suppress the milk supply, pinching off the milk ducts, and leading to mastitis.Gestational gigantomastia is estimated to in 1 out of every 28,000 to 100,000 pregnancies.Breast size in women with gestational breast hypertrophy typically reverts to approximately pre-pregnancy size or near it after pregnancy and cessation of breastfeeding. This is not always the case however and in some only partial reduction in breast size may occur, necessitating surgical breast reduction. Other types of breast hypertrophy Only 15% of cases of breast hypertrophy are unrelated to puberty or pregnancy. Other types and causes of breast hypertrophy include idiopathic, drug-induced (e.g., penicillamine, cyclosporine, bucillamine), autoimmunity-associated, tumors, and syndromes. Two case reports of prepubertal breast hypertrophy, both in infants, have been reported. Causes The underlying cause of the rapidly growing breast connective tissue, resulting in gigantic proportions, has not been well elucidated. However, proposed factors have included increased levels/expression of or heightened sensitivity to certain hormones (e.g., estrogen, progesterone, and prolactin) and/or growth factors (e.g., hepatocyte growth factor, insulin-like growth factor 1, and epidermal growth factor) in the breasts. Macromastic breasts are reported to be composed mainly of adipose and fibrous tissue, while glandular tissue remains essentially stable.Macromastia occurs in approximately half of women with aromatase excess syndrome (a condition of hyperestrogenism). Hyperprolactinemia has been reported as a cause of some cases of macromastia. Macromastia has also been associated with hypercalcemia (which is thought to be due to excessive production of parathyroid hormone-related protein) and, rarely, systemic lupus erythematosus and pseudoangiomatous stromal hyperplasia. It is also notable that approximately two-thirds of women with macromastia are obese. Aside from aromatase (as in aromatase excess syndrome), at least two other genetic mutations (one in PTEN) have been implicated in causing macromastia.A handful of drugs have been associated with gigantomastia, including penicillamine, bucillamine, neothetazone, ciclosporin, indinavir, and prednisolone. Treatment Medical treatment has not proven consistently effective. Medical regimens have included tamoxifen, progesterone, bromocriptine, the gonadotropin-releasing hormone agonist leuprorelin, and testosterone. Gestational macromastia has been treated with breast reduction drugs alone without surgery. Surgical therapy includes reduction mammaplasty and mastectomy. However, breast reduction is not clinically indicated unless at least 1.8 kg (4 lb) of tissue per breast needs to be removed. In the majority of cases of macromastia, surgery is medically unnecessary, depending on body height. Topical treatment includes regimens of ice to cool the breasts.Treatment of hyperprolactinemia-associated macromastia with D2 receptor agonists such as bromocriptine and cabergoline has been found to be effective in some, but not all cases. Danazol, an antiestrogen and weak androgen, has also been found to be effective in the treatment of macromastia.When hypertrophy occurs in adolescence, noninvasive treatments, including pharmaceutical treatment, hormone therapy, and steroid use are not usually recommended due to known and unknown side effects. Once breast growth rate has stabilized, breast reduction may be an appropriate choice. In some instances after aggressive or surgical treatment, the breast may continue to grow or re-grow, a complete mastectomy may be recommended as a last resort. Pregnancy is recognized as the second most common reason for hypertrophy. When secondary to pregnancy, it may resolve itself without treatment after the pregnancy ends. Society and culture Difficulties Extremely large breasts are a source of considerable attention. Some women try to hide or mask their breasts with special clothing, including minimizing bras. Women with this condition may be subject to psychological problems due to unwanted attention or harassment. Depression is common in those affected. In the case of a 12-year-old Japanese girl reported in 1993, her "massively enlarged" breasts caused her "intense psychological problems, incapacitating her in school activities and social relations". Actress Soleil Moon Frye, who starred as a child in the sitcom Punky Brewster, reported in an interview with People magazine that boys taunted her, calling her "Hey, Punky Boobster!". It affected her professional and social life negatively. "People started to think of me as a bimbo", she said in the interview. "I couldnt sit up straight without people looking at me like I was a prostitute", Frye said.Finding large bra-sizes and styles that fit is challenging. Also, larger bras are more costly, challenging to find, and unflattering to the wearer. Ill-fitting bras with narrow straps can cause chronic irritation, redness, and indentations in the shoulders. Skin rashes under the breasts are common, particularly during warm weather. Heavy breasts may cause headaches, neck pain, upper and lower back pain, and numbness or tingling in the fingers. There is a possible connection between macromastia and carpal-tunnel-syndrome. Medical insurance coverage Insurance companies in the United States typically require the physician to provide evidence that a womans large breasts cause headaches or back and neck pain before they will pay for reduction mammoplasty. Insurance companies also mandate a woman who is overweight, which is often the case with gigantomastia, to first lose a certain amount of weight. They also commonly require the patient to try alternative treatments like physical therapy for a year or more. Reported instances Gigantomastia One early and extreme case study of gigantomastia dates to 1670. The patient died four months after the onset of enlargement. One breast removed after the womans death weighed 29 kg (64 lb). On April 17, 1848, a 42-year-old woman named Lu-shi was treated for hypertrophy in a Chinese hospital. She was treated by a missionary physician. On December 24, 1849, the left breast, measuring 67 cm (26.5 in) in circumference, and weighing 2.7 kg (6 lb), was removed in a procedure lasting three and a half minutes. The right breast was removed one month later. It measured 61 cm (24 in) in circumference and weighed 2.5 kg (5.5 lb).In 2005, a woman reported that her breasts grew at puberty from nothing to a C cup in one month. When she became pregnant for the first time, her breasts increased two cup sizes in a few days. Immediately after her first birth, her breasts grew three cup sizes. After her second child was born, her breasts increased six cup sizes. After her third childbirth, they grew 10 cup sizes, and after her fourth child was born, they grew nine cup sizes. In this instance, the swelling abated about 10 days after childbirth, but her bra cup size remained E to a G for the next year. About one year postpartum, her breasts rapidly atrophied to AA cup size.One of the most severe cases of macromastia was reported from Ilorin in Nigeria. In 2007, Dr Ganiyu Adebisi Rahman and his colleagues reported the case of a 26-year-old woman who presented with massive swelling of her breasts and bilateral axillary swellings of 6 years duration. Dr Rahman led a team of surgeons in Ilorin to perform a total bilateral excision of the hypertrophied axillary breasts, and bilateral breast amputation with composite nipple-areola complex graft of the normally located breasts. The total weight of the breast tissues removed was 44.8 kilograms.Another extreme case was observed in 2008 in Maria Vittoria Hospital in Turin, Italy, where the amount removed from both breasts was 17.2 kg (38 lb). The growth occurred during puberty making it a case of juvenile gigantomastia, but the patient did not seek treatment until the age of 29. Another extreme case was observed on August 28, 2003, when a 24-year-old woman was admitted to the Clinical Center Skopje in Macedonia with gigantomastia of pregnancy and the amount later removed from both breasts was 15 kg (33 lb) in total. A second case in Macedonia was reported when the breasts of a 30-year-old woman from a remote mountain village in eastern Macedonia suddenly grew to more than 30 kilograms (66 lb) total.As the disorder becomes more widely known, media reports have increased. French Canadian Isabelle Lanthier appeared on Montel Williams talk show where she told how her chest grew from 86 cm (34 in) to 133 cm (52.5 in) in five months during her pregnancy. At their largest, one breast weighed 6.8 kg (15 lb) and the other 5.4 kg (12 lb). Her husband custom-made a special bra to support her breasts.In 2007, a Chilean TV station covered the story of 32-year-old Yasna Galleguillos from Antofagasta, who experienced ongoing back pain, making everyday tasks very difficult to perform. She underwent breast reduction surgery to relieve her pain. Surgeons removed 4.25 kilograms (9.4 lb) from one breast and 3.33 kilograms (7.3 lb) from the other breast.On October 29, 2009, the Philippine television network GMA News and Public Affairs, producers of Wish Ko Lang ("Just My Wish") hosted by Vicky Morales, profiled the story of Pilma Cabrijas, a 30-year-old woman affected by gigantomastia. The woman was told by a folk healer that her condition may have been caused by a curse. The measured bust circumference without appropriate bra support was 160 cm (63 in). The weight of her breasts was not reported in detail, but seemed to weigh "as much as two children." She had breast reduction surgery performed, but her breasts regrew. The producers of Wish Ko Lang paid for additional surgery. Virginal breast hypertrophy In 1993, the Japanese journal Surgery Today reported on the case of a 12-year-old girl. Only 152 centimetres (60 in) tall and weighing 43 kilograms (95 lb), her breasts began to develop at age 11 before the onset of menstruation. Over the next eight months, both breasts grew abnormally large, and physicians treating her found that her physiological development was normal except for her breasts. The weight produced by their symmetrical and massive enlargement resulted in marked curvature of the spine. Lab tests of her blood for hormones and biochemical substances showed normal values, though tests revealed that it might have been caused by hypersensitivity to estrogen. She underwent a bilateral reduction mammoplasty. Surgeons removed 2 kilograms (4.4 lb) of tissue from her right breast and 1.9 kilograms (4.2 lb) from her left breast. She was administered tamoxifen afterward to suppress breast regrowth.A more severe case of virginal breast hypertrophy of an 11-year-old girl was reported in 2008. The breasts had begun to grow rapidly at puberty and had reached the point of causing physical impairment and respiratory compromise after one year. The skin was intact without any ulcerations. Blood chemistry and endocrine investigation was normal. A bilateral reduction mammaplasty with free nipple grafts was performed. Six kg of the right breast and 6.5 kg of the left breast were removed, resulting in a removal of 12.5 kg of tissue in all (24% of the total body weight). See also Mammoplasia Norma Stitz References Further reading Touraine, P. (2005). "Breast Inflammatory Gigantomastia in a Context of Immune-Mediated Diseases". Journal of Clinical Endocrinology & Metabolism. 90 (9): 5287–5294. doi:10.1210/jc.2005-0642. PMID 15972574. Oladele, AO; Olabanji, JK; Alabi, GH (2007). "Reduction mammoplasty: The experience in Ile-Ife, Nigeria". Nigerian Journal of Medicine. 16 (3): 261–267. PMID 17937167. Netscher, David T.; Mosharrafa, ALI M.; Laucirica, Rodolfo (1996). "Massive Asymmetric Virginal Breast Hypertrophy". Southern Medical Journal. 89 (4): 434–7. doi:10.1097/00007611-199604000-00019. PMID 8614890. U.S.A. Library of Congress - Healthy Breasts: A Primer John Blair Deaver (1917). The Breast: Its Anomalies, Its Diseases, and Their Treatment. P. Blakistons Son & Co. p. 102. Joseph, Jacques (1987). Rhinoplasty and facial plastic surgery with a supplement on mammaplasty and other operations in the field of plastic surgery of the body: an atlas and textbook. Phoenix: Columella Press. p. 755. ISBN 0-9605972-1-2. Plummer, Samuel C.; Bump, Warner S. (1927). "Massive Hypertrophy of the Breasts". Annals of Surgery. 85 (1): 61–6. doi:10.1097/00000658-192701000-00008. PMC 1399262. PMID 17865606. Warren, John Collins (1900). The International text-book of surgery. Vol. II. Saunders. p. 234. Erichsen, John Eric (1885). The Science and art of surgery. Vol. II. H. C. Leas Son & Company. pp. 693–694. Ochsner, Albert John (1921). Surgical Diagnosis and Treatment: By American Authors. Lea & Febiger. p. 147. External links Media related to Hypertrophy of breast at Wikimedia Commons