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Management
Medication
As well as the routine dose of vitamin K given to newborns after birth, babies born with fetal warfarin syndrome are given additional doses intramuscularly to overcome any remaining warfarin in the circulation and prevent further bleeding. Fresh frozen plasma is also administered to raise concentrations of active blood clotting factors. If the child is anemic from extensive bleeding in-utero, red blood cell concentrate is given to restore oxygen carrying capacity. Surgical correction
Surgical interventions can be given to improve functionality and correct cosmetic abnormalities. Osteotomy (bone cutting) and zetaplasty surgeries are used to cut away abnormal tissue growths at the piriform aperture around and pharynx to reduce airway obstruction. Rhinoplasty surgery is used to restore normal appearance and function of the nose. Heart surgery may also be required to close a patent ductus arteriosus. References
External links
Datagenno - Fetal Warfarin Syndrome | Vibration white finger (VWF), also known as hand-arm vibration syndrome (HAVS) or dead finger, is a secondary form of Raynauds syndrome, an industrial injury triggered by continuous use of vibrating hand-held machinery. Use of the term vibration white finger has generally been superseded in professional usage by broader concept of HAVS, although it is still used by the general public. The symptoms of vibration white finger are the vascular component of HAVS. HAVS is a widespread recognized industrial disease affecting tens of thousands of workers. It is a disorder that affects the blood vessels, nerves, muscles, and joints of the hand, wrist, and arm. Its best known effect is vibration-induced white finger (VWF), a term introduced by the Industrial Injury Advisory Council in 1970. Injury can occur at frequencies between 5 and 2000 Hz but the greatest risk for fingers is between 50 and 300 Hz. The total risk exposure for hand and arm is calculated by the use of ISO 5349-1, which stipulates maximum damage between 8 and 16 Hz and a rapidly declining risk at higher frequencies. The ISO 5349-1 frequency risk assessment has been criticized as corresponding poorly to observational data; more recent research suggests that medium and high frequency vibrations also increase HAVS risk. Effects
Excessive exposure to hand arm vibrations can result in various patterns of diseases casually known as HAVS or VWF. | 0-1
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The American Academy of Sleep Medicines protocol for obstructive sleep apnea (OSA) recommends oral appliances for those who prefer them to CPAP and have mild to moderate sleep apnea or those that do not respond to/cannot wear a CPAP. Severe cases of OSA may be treated with an oral appliance if the patient has had a trial run with a CPAP. Oral appliances should be custom made by a dentist with training in dental sleep medicine.Mild obstructive hypopnea can often be treated by losing weight or by avoiding sleeping on ones back. Also quitting smoking, and avoiding alcohol, sedatives and hypnotics (soporifics) before sleep can be quite effective. Surgery is generally a last resort in hypopnea treatment, but is a site-specific option for the upper airway. Depending on the cause of obstruction, surgery may focus on the soft palate, the uvula, tonsils, adenoids or the tongue. There are also more complex surgeries that are performed with the adjustment of other bone structures - the mouth, nose and facial bones. Central hypopnea
People with neuromuscular disorders or hypoventilation syndromes involving failed respiratory drive experience central hypoventilation. The most common treatment for this form is the use of non-invasive ventilation such as a bilevel positive airway pressure (BPAP) machine. Etymology
The word hypopnea uses combining forms of hypo- + -pnea, from the Greek roots hypo- (meaning low, under, beneath, down, below normal) and pnoia (meaning breathing). See pronunciation information at dyspnea. See also
List of terms of lung size and activity
Bradypnea
References
http://www2.merriam-webster.com/cgi-bin/mwmednlm?book=Medical&va=hypopnea
http://www.emedicine.com/neuro/TOPIC419.HTM
http://www.sleepdex.org/dyssomnias.htm
https://www.sciencedaily.com/releases/2007/10/071015081737.htm
http://www.aasmnet.org/Resources/PracticeParameters/PP_MedicalTherapyOSA.pdf
Alcohol and health | The position, size, and quantity of tumors are considered when choosing the type of treatment for the disease. Differential diagnosis
1. Persistent hyperplastic primary vitreous is a congenital developmental anomaly of the eye resulting from failure of the embryological, primary vitreous, and hyaloid vasculature to regress, whereby the eye is shorter, develops a cataract, and may present with whitening of the pupil. 2. Coats disease is a typically unilateral disease characterised by abnormal development of blood vessels behind the retina, leading to blood vessel abnormalities in the retina and retinal detachment to mimic retinoblastoma. 3. Toxocariasis is a parasitic disease of the eye associated with exposure to infected puppies, which causes a retinal lesion leading to retinal detachment. 4. Retinopathy of prematurity is associated with low-birth-weight infants who receive supplemental oxygen in the period immediately after birth, and it involves damage to the retinal tissue and may lead to retinal detachment.If the eye examination is abnormal, further testing may include imaging studies, such as computerized tomography (CT), magnetic resonance imaging (MRI), and ultrasound. CT and MRI can help define the structure abnormalities and reveal any calcium depositions. Ultrasound can help define the height and thickness of the tumor. Bone marrow examination or lumbar puncture may also be done to determine any metastases to bones or the brain. Morphology
Gross and microscopic appearances of retinoblastoma are identical in both hereditary and sporadic types. Macroscopically, viable tumor cells are found near blood vessels, while zones of necrosis are found in relatively avascular areas. | 0-1
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Today with appropriate treatment, males with haemophilia typically have a near normal quality of life with an average lifespan approximately 10 years shorter than an unaffected male.Since the 1980s the primary leading cause of death of people with severe haemophilia has shifted from haemorrhage to HIV/AIDS acquired through treatment with contaminated blood products. The second leading cause of death related to severe haemophilia complications is intracranial haemorrhage which today accounts for one third of all deaths of people with haemophilia. Two other major causes of death include hepatitis infections causing cirrhosis and obstruction of air or blood flow due to soft tissue haemorrhage. Epidemiology
Haemophilia frequency is about 1 instance in every 10,000 births (or 1 in 5,000 male births) for haemophilia A and 1 in 50,000 births for haemophilia B. About 18,000 people in the United States have haemophilia. Each year in the US, about 400 babies are born with the disorder. Haemophilia usually occurs in males and less often in females. It is estimated that about 2,500 Canadians have haemophilia A, and about 500 Canadians have haemophilia B. History
Scientific discovery
The excessive bleeding was known to ancient people. The Talmud instructs that a boy must not be circumcised if he had two brothers who died due to complications arising from their circumcisions, and Maimonides says that this excluded paternal half-brothers. This may have been due to a concern about hemophilia. The first medical professional to describe the disease was Arab surgeon Al-Zahrawi, also known as Abulcasis. | It is composed of trapezius, latissimus dorsi, rhomboid major, rhomboid minor and levator scapulae. It is innervated by anterior rami of spinal nerves, reflecting its embryological origin outside the back. Intermediate group
The intermediate group is also known as respiratory group as it may serve a respiratory function. It is composed of serratus posterior superior and serratus posterior inferior. Like the superficial group, it is innervated by anterior rami of spinal nerves. Deep group
The deep group, also known as the intrinsic group due to its embryological origin in the back, can be further subdivided into four groups:
Spinotransversales - composed of splenius capitis and splenius cervicis. Erector spinae - composed of iliocostalis, longissismus and spinalis
Transversospinales - composed of semispinalis, multifidus and rotatores
Segmental muscles - composed of levatores costarum, interspinales and intertransversariiThe deep group is innervated by the posterior rami of spinal nerves. Organs near the back
The lungs are within the ribcage, and extend to the back of the ribcage making it possible for them to be listened into through the back. The kidneys are situated beneath the muscles in the area below the end of the ribcage, loosely connected to the peritoneum. A strike to the lower back can damage the kidneys of the person being hit. Surface of the back
The skin of the human back is thicker and has fewer nerve endings than the skin on any other part of the torso. With some notable exceptions (see, e.g. George "The Animal" Steele), it tends to have less hair than the chest on men. | 0-1
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The most potent dimer for activating signalling pathways is HER2/HER3.The epitope for pertuzumab is the domain of HER2 where it binds to HER3, and pertuzumab prevents the HER2/HER3 dimer from forming, which blocks signalling by the dimer. Trastuzumab is another monoclonal antibody against HER2; its epitope is the domain where HER2 binds to another HER2 protein. The two mAbs together prevent HER2 from functioning. Chemistry and manufacturing
Pertuzumab is an immunoglobulin G1 with a variable region against the human HER2 protein, a human-mouse monoclonal 2C4 heavy chain, disulfide bound with a human-mouse monoclonal 2C4 κ-chain.It is manufactured recombinantly in CHO cells. History
The monoclonal antibody 2C4 appears to have first been published in 1990 by scientists from Genentech, the same year that F. Hoffmann-La Roche AG acquired a majority stake in Genentech.By 2003, Genentech understood that 2C4 prevented HER2 dimerizing with other HER receptors and had begun Phase I trials, aiming for a broad range of cancers, not just ones overexpressing HER2. It was the first known HER dimerization inhibitor.In 2005, Genentech presented poor results of Phase II trials of pertuzumab as a single agent in prostate, breast, and ovarian cancers, and said that it intended to continue developing it in combination with other drugs for ovarian cancer.In 2007, Genentech dropped the trade name Omnitarg.In March 2009, Roche acquired Genentech.In 2012, the results were published of the CLEOPATRA trial, a randomized placebo-controlled Phase III trial of pertuzumab in combination with trastuzumab and docetaxel in HER2-positive metastatic breast cancer. | A sprue may refer to:
Sprue (manufacturing), a feature in molding and casting molds
Coeliac disease, also known as sprue, a disease of the small intestine
Tropical sprue, disease
Sprue Asparagus, first pickings of asparagus | 0-1
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Superficial ulcers usually heal in less than a week. Deep ulcers and descemetoceles may require corneal suturing, conjunctival grafts or conjunctival flaps, soft contact lenses, or corneal transplant. Topical corticosteroids and anesthetics should not be used on any type of corneal ulcer because they prevent healing and will often make them worse. Bioscaffold
A new bioscaffold developed by TR BioSurgical is being evaluated for refractory corneal ulcers in dogs. The study is being conducted by board certified veterinary ophthalmologists and has shown promise in healing refractory ulcers that have failed conventional treatment . Refractory corneal ulcers
Refractory corneal ulcers are superficial ulcers that heal poorly and tend to recur. They are also known as indolent ulcers or Boxer ulcers. They are believed to be caused by a defect in the basement membrane and a lack of hemidesmosomal attachments. They are recognized by undermined epithelium that surrounds the ulcer and easily peels back. Refractory corneal ulcers are most commonly seen in middle aged or older dogs and often occur in the other eye later. They are similar to Cogans cystic dystrophy in humans. Commonly affected breeds
Alaskan Malamute
American Cocker Spaniel
Boston Terrier
Boxer
Brussels Griffon
Cairn Terrier
Chesapeake Bay Retriever
Chihuahua
Chinese Shar Pei
Dachshund
Bulldog
English Springer Spaniel
German Shepherd Dog
Golden Retriever
Irish Setter
Japanese Chin
Lhasa Apso
Maltese
Pekingese
Poodle
Pug
Rottweiler
Samoyed
Shih Tzu
Silky Terrier
Weimaraner
Welsh Corgi
Welsh Springer Spaniel
West Highland White Terrier
Wirehaired Fox Terrier
Treatment
Refractory corneal ulcers can take a long time to heal, sometimes months. Topical antibiotics are used continually to prevent infection. Pain medications are given as needed. Loose epithelium is removed with a dry cotton swab under topical anesthesia. | Progressive scoliosis can generally be managed with standard instrumentation and fusion techniques. Surgical management in the craniofacial skeleton is complicated by frequent post-operative FD regrowth, and should focus on correction of functional deformities. Prophylactic optic nerve decompression increases the risk of vision loss and is contraindicated.Managing endocrinopathies is a critical component of management in FD. All patients with fibrous dysplasia should be evaluated and treated for endocrine diseases associated with McCune–Albright syndrome. In particular untreated growth hormone excess may worsen craniofacial fibrous dysplasia and increase the risk of blindness. Untreated hypophosphatemia increases bone pain and risk of fractures. See also
Cherubism
Dysplasia
McCune–Albright syndrome
References
Further reading
GeneReviews entry for Fibrous Dysplasia/McCune-Albright Syndrome
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However, educating women during pregnancy about postpartum blues may help to prepare them for these symptoms that are often unexpected and concerning in the setting of excitement and anticipation of a new baby. Mothers who develop postpartum blues often have significant shame or guilt for feelings of anxiety or depression during a time is expected to be joyful. It is important to reassure new parents that low mood symptoms after childbirth are common and transient. Obstetric providers may recommend that patients and their families prepare ahead of time to ensure the mother will have adequate support and rest after the delivery. Additionally, they should provide education and resources to family and friends about red flags of more severe perinatal psychiatric conditions that may develop, such as postpartum depression and postpartum psychosis. Treatment
Postpartum blues is a self-limited condition. Signs and symptoms are expected to resolve within two weeks of onset without any treatment. Nevertheless, there are a number of recommendations to help relieve symptoms, including:
Getting enough sleep
Taking time to relax and do activities that you enjoy
Asking for help from family and friends
Reaching out to other new parents
Avoiding alcohol and other drugs that may worsen mood symptoms
Reassurance that symptoms are very common and will resolve on their ownIf symptoms do not resolve within two weeks or if they interfere with functioning, individuals are encouraged to contact their healthcare provider. | Recent research suggests that specific social difficulties may be a result of impaired face processing. The unusual social behavior in childhood often resembles that of an autism spectrum disorder.Other characteristics sometimes associated with callosal disorders include seizures, spasticity, early feeding difficulties and/or gastric reflux, hearing impairments, abnormal head and facial features, and intellectual disability. Associated brain anomalies
Brain anomalies that can sometimes occur in syndromes that cause callosal disorders include:
Aplasia of the cerebellar vermis
Chiari malformation
Colpocephaly
Dandy–Walker syndrome
Holoprosencephaly
Hydrocephalus
Neuronal migration disorders such as grey matter heterotopia
Schizencephaly
Associated syndromes and conditions
Some syndromes that frequently include ACC are:
Acrocallosal syndrome
Aicardi syndrome
Andermann syndrome
Donnai–Barrow syndrome
Dwarfism
FG syndrome
L1CAM syndrome
Microcephalic osteodysplastic primordial dwarfism type II
Mowat–Wilson syndrome
Oculocerebrocutaneous syndrome
Saal Bulas syndrome
Septo-optic dysplasia (optic nerve hypoplasia)
Shapiro syndrome
Vici syndromeSome conditions that can sometimes be associated with ACC or other callosal disorders include:
1p36 deletion syndrome
13q deletion syndrome
CDK13-related disorder
Craniofacial abnormalities and other oral and maxillofacial pathologies
Fetal alcohol syndrome
Fetal warfarin syndrome
Genitopatellar syndrome
Gomez-Lopez-Hernandez syndrome
Joubert syndrome
Lujan–Fryns syndrome
Marden–Walker syndrome
Maternal nutritional deficiencies or infections
Metabolic disorders
Okamoto syndrome
Opitz G/BBB syndrome
Pascual-Castroviejo syndrome
Pitt–Hopkins syndrome
Sensenbrenner syndrome
Strømme syndrome
Triploid syndrome
Trisomy 9
Xia-Gibbs syndrome
Causes
Agenesis of the corpus callosum is caused by disruption to development of the fetal brain between the 3rd and 12th weeks of pregnancy. In most cases, it is not possible to know what caused an individual to have ACC or another callosal disorder. However, research suggests that some possible causes may include chromosome errors, inherited genetic factors, prenatal infections or injuries, prenatal toxic exposures, structural blockage by cysts or other brain abnormalities and metabolic disorders. | 0-1
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In contrast to NKCE and LG, extranodal NK/T cell lymphoma, nasal type: is malignant and often aggressive; causes serious, persistent, and often progressive GI tract and other symptoms; commonly involves the head and neck areas and/or multiple organs outside of the GI tract; is deeply invasive, extending beyond the lamina propia of the GI tract; and consists of lesions which contain malignant Epstein-Barr virus-infected NK cells that have numerous gene mutations and chromosome abnormalities and that center around and destroy blood vessels. Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL): MEITL is a malignant and extremely aggressive GI tract disease. It is manifested by serious, sometimes life-threatening GI tract symptoms such as GI tract obstructions and perforations; is usually localized to the small intestine but may involve other areas of the GI tact; is invasive, e.g. spreads to the submucosa; commonly metastasizes to GI tract lymph nodes; and is composed of lesions which contain Epstein-Barr virus-negative homogenously appearing, medium-sized, malignant T cells that may have mutations or other genetic abnormalities in their STAT5B, JAK3, TP53, SETD2, BRAF, KRAS, GNA12, CREBBP, and/or Myc genes. Indolent T cell lymphoproliferative disorder of the gastrointestinal tract: This recently described disease, while generally considered benign, has in rare cases been lethal with disease spreading to the bone marrow and blood. This disease is a potentially precancerous condition. | Symptoms of the disease usually remain vague and mild. == References == | 11
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Bedner, accused of severely injuring his infant daughter, sued for the right to determine whether or not she remain on life support; keeping her alive, which would have prevented a murder charge, created a motive for Bedner to act that conflicted with the apparent interests of his child. Bioethicists Jacob M. Appel and Thaddeus Mason Pope recently argued, in separate articles, that such cases justify the replacement of the accused parent with an alternative decision-maker.Child abuse also poses ethical concerns related to confidentiality, as victims may be physically or psychologically unable to report abuse to authorities. Accordingly, many jurisdictions and professional bodies have made exceptions to standard requirements for confidentiality and legal privileges in instances of child abuse. Medical professionals, including doctors, therapists, and other mental health workers typically owe a duty of confidentiality to their patients and clients, either by law or the standards of professional ethics, and cannot disclose personal information without the consent of the individual concerned. This duty conflicts with an ethical obligation to protect children from preventable harm. Accordingly, confidentiality is often waived when these professionals have a good faith suspicion that child abuse or neglect has occurred or is likely to occur and make a report to local child protection authorities. This exception allows professionals to breach confidentiality and make a report even when children or their parents or guardians have specifically instructed to the contrary. | Pricing
The British Competition and Markets Authority launched an investigation into the alleged "excessive and unfair pricing" of liothyronine tablets in 2017. It alleged that Advanz Pharma overcharged the NHS from before 2007 to July 2017. The price of a pack increased by almost 1,600% from £4.46 before it was debranded in 2007 to £258.19 by July 2017. References
External links
"Liothyronine". Drug Information Portal. U.S. National Library of Medicine. | 0-1
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Dopamine and G-protein coupling
During mania, there is an increase in neurotransmission of dopamine that causes a secondary homeostatic down-regulation, resulting in decreased neurotransmission of dopamine, which can cause depression. Additionally, the post-synaptic actions of dopamine are mediated through G-protein coupled receptors. Once dopamine is coupled to the G-protein receptors, it stimulates other secondary messenger systems that modulate neurotransmission. Studies found that in autopsies (which do not necessarily reflect living people), people with bipolar disorder had increased G-protein coupling compared to people without bipolar disorder. Lithium treatment alters the function of certain subunits of the dopamine associated G-protein, which may be part of its mechanism of action. Glutamate and NMDA receptors
Glutamate levels are observed to be elevated during mania. Lithium is thought to provide long-term mood stabilization and have anti-manic properties by modulating glutamate levels. It is proposed that lithium competes with magnesium for binding to NMDA glutamate receptor, increasing the availability of glutamate in post-synaptic neurons, leading to a homeostatic increase in glutamate re-uptake which reduces glutamatergic transmission. The NMDA receptor is also affected by other neurotransmitters such as serotonin and dopamine. Effects observed appear exclusive to lithium and have not been observed by other monovalent ions such as rubidium and caesium. GABA receptors
GABA is an inhibitory neurotransmitter that plays an important role in regulating dopamine and glutamate neurotransmission. It was found that patients with bipolar disorder had lower GABA levels, which results in excitotoxicity and can cause apoptosis (cell loss). | Lithium may lead to exacerbation of pre-existing primary hyperparathyroidism or cause an increased set-point of calcium for parathyroid hormone suppression, leading to parathyroid hyperplasia. Interactions
Lithium plasma concentrations are known to be increased with concurrent use of diuretics—especially loop diuretics (such as furosemide) and thiazides—and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. Lithium concentrations can also be increased with concurrent use of ACE inhibitors such as captopril, enalapril, and lisinopril.Lithium is primarily cleared from the body through glomerular filtration, but some is then reabsorbed together with sodium through the proximal tubule. Its levels are therefore sensitive to water and electrolyte balance. Diuretics act by lowering water and sodium levels; this causes more reabsorption of lithium in the proximal tubules so that the removal of lithium from the body is less, leading to increased blood levels of lithium. ACE inhibitors have also been shown in a retrospective case-control study to increase lithium concentrations. This is likely due to constriction of the afferent arteriole of the glomerulus, resulting in decreased glomerular filtration rate and clearance. Another possible mechanism is that ACE inhibitors can lead to a decrease in sodium and water. This will increase lithium reabsorption and its concentrations in the body.There are also drugs that can increase the clearance of lithium from the body, which can result in decreased lithium levels in the blood. These drugs include theophylline, caffeine, and acetazolamide. | 11
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As a result of absorption of ultraviolet and visible light (peak sensitivity at 400 nm, with lesser peaks between 500-625 nm) by protoporphyrin in plasma and erythrocytes when blood circulates through the dermal vessels, free radicals are formed, erythrocytes become unstable and injury to the skin is induced.A significant increase in the hepatobiliary excretion of protoporphyrin can damage the liver through both cholestatic phenomena and oxidative stress - predisposing to hepatobiliary disease of varying degrees of severity
Diagnosis
EPP is generally suspected by the presence of acute photosensitivity of the skin and can be confirmed by detection of a plasmatic fluorescence peak at 634 nm. It is also useful to find increased levels of protoporphyrin in feces and the demonstration of an excess of free protoporphyrin in erythrocytes.Screening for FECH mutation on one allele or aminolevulinic acid synthase 2 gain-of-function mutation in selected family members may be useful, especially in genetic counseling. Liver biopsy confirms hepatic disease in EPP by the presence of protoporphyrin deposits in the hepatocytes that can be observed as a brown pigment within the biliary canaliculi and the portal macrophages. Macroscopically, the cirrhotic liver can have a black color due to protoporphyrin deposits. Using polarized light the characteristic Maltese cross shape of birefringent crystalline pigment deposits is found. The examination of liver tissue under a Wood’s lamp reveals a red fluorescence due to protoporphyrin. Liver biopsy is not helpful for estimation of prognosis of liver disease. | Endemic goiter is a type of goitre that is associated with dietary iodine deficiency. Cause
Some inland areas where soil and water lacks in iodine compounds and consumption of marine foods is low are known for higher incidence of goitre. In such areas goitre is said to be "endemic". Prevention
This type of goiter is easily preventable. In most developed countries regulations have been put into force by health policy institutions requiring salt, flour or water to be fortified with iodine. Treatment
Treatment of endemic goiter is medical with iodine and thyroxine preparations. Surgery is only necessary in cases where complicated by significant compression of nearby structures. References
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Telmisartan, sold under the brand name Micardis among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination telmisartan/hydrochlorothiazide, telmisartan/cilnidipine and telmisartan/amlodipine. Compared to other drugs in its class, Telmisartan has a relatively high dosing, on average 80 mg/day. Common side effects include upper respiratory tract infections, diarrhea, and back pain. Serious side effects may include kidney problems, low blood pressure, and angioedema. Use in pregnancy may harm the baby and use when breastfeeding is not recommended. It is an angiotensin II receptor antagonist and works by blocking the effects of angiotensin II.Telmisartan was patented in 1991 and came into medical use in 1999. It is available as a generic medication. In 2018, it was the 292nd most commonly prescribed medication in the United States, with more than 1 million prescriptions. Medical uses
Telmisartan is used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. : 146
Contraindications
Telmisartan is contraindicated during pregnancy. Like other drugs affecting the renin–angiotensin system (RAS), telmisartan can cause birth defects, stillbirths, and neonatal deaths. It is not known whether the drug passes into the breast milk. Also it is contraindicated in bilateral renal artery stenosis in which it can cause kidney failure. | Likewise, with the depressed patient, electroconvulsive therapy (ECT) is more effective than pharmacotherapy.Cotards syndrome resulting from an adverse drug reaction to valacyclovir is attributed to elevated serum concentration of one of valacyclovirs metabolites, 9-carboxymethoxymethylguanine (CMMG). Successful treatment warrants cessation of valacyclovir. Hemodialysis was associated with timely clearance of CMMG and resolution of symptoms. Case studies
Society and culture
The protagonist of Charlie Kaufmans 2008 movie Synecdoche, New York, is named Caden Cotard. Throughout the film Cotard thinks he is dying, and we see other examples of Cotard delusion with scenes such as when his daughter, Olive, begins to scream about having blood in her body and, as the film goes on, Cotard disappears from the play he is writing about his own life and is portrayed by other actors as he takes the role of a cleaning lady.It is speculated that Per "Dead" Ohlin, lead vocalist for the black metal bands Mayhem and Morbid, had Cotard delusion as a result of a bullying incident in his youth that left him clinically dead for a short time. He developed an obsession with death shortly after (hence his stage name and use of corpse paint), often self-harmed onstage and among friends, and became increasingly depressed and introverted eventually resulting in his suicide in 1991. His suicide note contained the lines "I belong in the woods and have always done so. No one will understand the reason for this anyway. To give some semblance of an explanation Im not a human, this is just a dream and soon I will wake." | 0-1
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The issue arises in instances when Sauk is being taught to a school in the tribe, and an elder, who is fluent in the language, disagrees with the pronunciation being taught. Phonology
Sauk does not have many phonemes in comparison to many other languages: four vowels, two semivowels, and nine consonants. Consonants
The following consonant phonemes are given in Reinschmidt (1995):
The representation of /h/ was omitted in the 1977 syllabary. It was added back in later editions because it is an important distinctive sound in the Sauk language. Reinschmidt symbolizes /j/ as /y/, following Americanist practice. All four stops have at least two allophones each, one fortis and one lenis:
/p/ → [p, hp]
/t/ → [t, ht]
/t͡ʃ/ → [t͡ʃ, ht͡ʃ]
/k/ → [k, hk]
Reinschmidt symbolizes /j/ as /y/, following Americanist practice. Vowels
Vowel length is important in the Sauk language because of its distinctive function. Long vowels are often distinguished by the doubling of characters, such as a / aa representing two different spoken lengths. This is different for the vowel e, as an elongated version of this vowel shares the sound of the vowel in the English word bear. Reinschmidt presents four vowels, each with two allophones:
/ɑ/ → [ɑ, ɑː]
/e/ → [e, eː]
/i/ → [i, iː]
/o/ → [o, oː]
Pitch and tone
Pitch and tone are important when speaking Sauk, as there is a general rule of emphasizing the first or second syllable of phrases, and slowly fades away by the end of a word. | Lymphomatoid papulosis (LyP) is a rare skin disorder. The overall prevalence rate of lymphomatoid papulosis is estimated at 1.2 to 1.9 cases per 1,000,000 population. [This is a widespread misinterpretation of a 1992 study saying "the period prevalence rate of lymphomatoid papulosis was estimated to be 1.9 per 1,000,000 population for Massachusetts and 1.2 per 1,000,000 population for Pennsylvania". The authors of that study said clearly "Our estimate of 1.2-1.9 cases per 1,000,000 population should be considered a minimum estimate of the prevalence rate". That estimate was based on the 78 patients involved in the study, not the LvP population. The study recruited 11 patients from Massachusetts and 15 from Pennsylvania ]. This rare condition has only been studied in depth since 1968. Presentation
It can appear very similar to anaplastic large cell lymphoma. Type "A" is CD30 positive, while type "B" is CD30 negative.It has been described as "clinically benign but histologically malignant." Treatment
It may respond to methotrexate or PUVA. Prognosis
It can evolve into lymphoma. See also
Cutaneous T-cell lymphoma
Parapsoriasis
Secondary cutaneous CD30+ large cell lymphoma
List of cutaneous conditions
References
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Environmental factors such as inhaling toxic fumes and cigarette smoking are not believed to play a role in DPB, and unknown environmental and other non-genetic causes—such as unidentified bacteria or viruses—have not been ruled out.Cystic fibrosis (CF), a progressive multi-system lung disease, has been considered in the search for a genetic cause of DPB. This is for a number of reasons. CF, like DPB, causes severe lung inflammation, abundant mucus production, infection, and shows a genetic predominance among Caucasians of one geographic group to the rarity of others; whereas DPB dominates among East Asians, CF mainly affects individuals of European descent. While no gene has been implicated as the cause of DPB, mutation in a specific gene—much more likely to occur in Europeans—causes CF. This mutation in the CF-causing gene is not a factor in DPB, but a unique polymorphism (variation) in this gene is known to occur in many Asians not necessarily affected by either disease. It is being investigated whether this gene in any state of mutation could contribute to DPB. Pathophysiology
Inflammation is a normal part of the human immune response, whereby leukocytes (white blood cells), including neutrophils (white blood cells that specialize in causing inflammation), gather, and chemokines (proteins released from certain cells, which activate or elicit a response from other cells) accumulate at any location in the body where bacterial or viral infections occur. Inflammation interferes with the activity of bacteria and viruses, and serves to clear them from the body. | Further, it is possible that a number of genetic recombination events around the disease locus (location on a chromosome) could have resulted in the disease being associated with HLA-B54 in the Japanese and HLA-A11 in Koreans. After further study, it was concluded that a DPB susceptibility gene is located near the HLA-B locus at chromosome 6p21.3. Within this area, the search for a genetic cause of the disease has continued.Because many genes belonging to HLA remain unidentified, positional cloning (a method used to identify a specific gene, when only its location on a chromosome is known) has been used to determine that a mucin-like gene is associated with DPB. In addition, diseases caused by identified HLA genes in the DPB-susceptibility region have been investigated. One of these, bare lymphocyte syndrome I (BLS I), exhibits a number of similarities with DPB in those affected, including chronic sinusitis, bronchiolar inflammation and nodules, and the presence of H. influenzae. Also like DPB, BLS I responds favorably to erythromycin therapy by showing a resolution of symptoms. The similarities between these two diseases, the corresponding success with the same mode of treatment, and the fact that the gene responsible for BLS I is located within the DPB-causing area of HLA narrows the establishment of a gene responsible for DPB. | 11
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Females generally have two X chromosomes, whereas males generally have one X chromosome that they inherit from their mother and one Y chromosome that they inherit from their father.If a female inherits one copy of the mutant allele for MPS II, she will usually have a normal copy of the IDS gene which can compensate for the mutant allele. This is known as being a genetic carrier. A male who inherits a defective X chromosome, though, usually does not have another X chromosome to compensate for the mutant gene. Thus, a female would need to inherit two mutant genes to develop MPS II, while a male patient only needs to inherit one mutant gene. A female carrier can be affected due to X-inactivation, which is a random process. Pathophysiology
The human body depends on a vast array of biochemical reactions to support critical functions. One of these functions is the breakdown of large biomolecules. The failure of this process is the underlying problem in Hunter syndrome and related storage disorders.The biochemistry of Hunter syndrome is related to a problem in a part of the connective tissue known as the extracellular matrix, which is made up of a variety of sugars and proteins. It helps to form the architectural framework of the body. The matrix surrounds the cells of the body in an organized meshwork and functions as the glue that holds the cells of the body together. One of the parts of the extracellular matrix is a molecule called a proteoglycan. | If carpal tunnel syndrome develops, a further decrease in hand function can occur. The bones themselves may be affected, resulting in short stature. In addition, pebbly, ivory-colored skin lesions may be found on the upper arms, legs, and upper back of some people with it. These skin lesions are considered pathognomic for the disease. Finally, the storage of GAGs in the brain can lead to delayed development with subsequent intellectual disability and progressive loss of function.The age at onset of symptoms and the presence or absence of behavioral disturbances are predictive factors of ultimate disease severity in very young patients. Behavioral disturbances can often mimic combinations of symptoms of attention deficit hyperactivity disorder, autism, obsessive compulsive disorder, and/or sensory processing disorder, although the existence and level of symptoms differ in each affected child. They often also include a lack of an appropriate sense of danger, and aggression. The behavioral symptoms of MPS II generally precede neurodegeneration and often increase in severity until the mental handicaps become more pronounced. By the time of death, most children with severe MPS II have severe mental disabilities and are completely dependent on their caretakers. Genetics
Since Hunter syndrome is an X-linked recessive disorder, it preferentially affects male patients. The IDS gene is located on the X chromosome. The IDS gene encodes for an enzyme called iduronate-2-sulfatase (I2S). A lack of this enzyme leads to a buildup of GAGs, which cause the symptoms of MPS II. | 11
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Central core disease
Central core disease or central core myopathy was first described in 1956 and usually presents in infancy or early childhood as non-progressive mild proximal weakness that persists throughout life. Central core disease is believed to be more prevalent than currently reported, as it is hard to recognize and often misdiagnosed in early childhood. Central core disease has been found to be allelic with malignant hyperthermia, which is a life-threatening anesthetic reaction that causes a rise in body temperature, muscular rigidity and muscular breakdown, grossly elevated creatine kinase, and acidosis. Central core disease is caused by a mutation in the RYR1 gene. Congenital fiber type disproportion
Congenital fiber type disproportion affects skeletal muscle, typically causing weakness in the shoulders, upper arms, thighs, and hips. Skeletal muscle is made up of two kinds of fiber, type 1 and type 2. In congenital fiber type disproportion, type 1 fibers are not only smaller but often more abundant than type 2 fibers. This leads to affected individuals being able to maintain an active lifestyle, though they usually have lower levels of stamina. Severity with this disease varies greatly, but people typically present symptoms by the age of one. Individuals do not usually worsen with time, and cases have even been reported of improvements. Multicore myopathy
Multicore myopathy also referred to as minicore myopathy, is associated with small areas of decreased oxidative activities, resulting in areas that appear in this histology as "cores". These appear through microscopy very similar to central core, however the cores are typically smaller in multicore myopathy. | History
Mitomycin was discovered in the 1950s by Japanese scientists in cultures of the microorganism Streptomyces caespitosus.It was approved based on the results of the OLYMPUS (NCT02793128) multicenter trial involving 71 subjects with low-grade UTUC. These subjects had never undergone treatment (treatment-naïve) or had recurrent low-grade non-invasive UTUC with at least one measurable papillary tumor (a tumor shaped like a small mushroom with its stem attached to the inner lining of an organ) located above the ureteropelvic junction. Subjects received mitomycin gel once a week (mitomycin gel 4 mg per mL instillations via ureteral catheter or nephrostomy tube) for six weeks and, if assessed as a complete response (complete disappearance of the papillary tumor), monthly for up to eleven additional months. Efficacy of mitomycin gel was evaluated using urine cytology (a test to look for abnormal cells in a subjectss urine), ureteroscopy (an examination of the upper urinary tract) and biopsy (if warranted) three months following the initiation of therapy.The primary endpoint was complete response at three months following initiation of therapy. A complete response was found in 41 of the 71 subjects (58%) following six treatments of mitomycin gel administered weekly. Durability of the effect of mitomycin gel in subjects with a complete response was also evaluated using urine cytology, ureteroscopy and biopsy (if warranted) every three months for a year following the initiation of therapy. | 0-1
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In addition, retrograde transport serves a quality control function, by shuttling misfolded proteins back into the ER or retaining them within the Golgi itself until proper protein folding and maturation is completed. The activity of protein-modifying enzymes, like glycosyltransferases and glycosidases, relies on the lumenal pH of the Golgi apparatus. Cisternal pH becomes increasingly acidic (lower pH) with progression from cis- to trans- regions of the Golgi. Disruption of decreasing pH can impart significant effects on the efficiency and sequence of glycosylation events. Maintenance of the pH gradient across the Golgi is instrumental for proper post-translational modification of proteins prior to secretion. Retrograde transport and pH regulation are therefore vital to the proper functioning of the Golgi apparatus. Genetic causes of WSS
Patients with both missense and/or nonsense mutations of the ATP6V0A2 gene have been shown to phenotypically express wrinkly skin syndrome (WSS) or autosomal recessive cutis laxa type II (ARCL II) (another cutis laxa disorder). Some consider WSS to be a milder variant of ARCL II, but the genetic causes of WSS are not yet known. A large number of patients with WSS and ARCL II show a loss-of-function in the a2-subunit. These mutations in ATP6V0A2 are associated with defective glycan biosynthesis and defective Golgi apparatus structure. However, the exact mechanism of how mutations in the ATP6V0A2 gene lead to these effects is unclear. Aberrant Golgi functioning and clinical symptoms of WSS
WSS is characterized by defects in the elastic fiber system that comprises the extracellular matrix of epidermal cells. | Wrinkly skin syndrome (WSS) is a rare genetic condition characterized by sagging, wrinkled skin, low skin elasticity, and delayed fontanel (soft spot) closure along with a range of other symptoms. The disorder exhibits an autosomal recessive inheritance pattern with mutations in the ATP6V0A2 gene, leading to abnormal glycosylation events. There are only about 30 known cases of WSS as of 2010. Given its rarity and symptom overlap to other dermatological conditions, reaching an accurate diagnosis is difficult and requires specialized dermatological testing. Limited treatment options are available but long-term prognosis is variable from patient-to-patient, on the basis of individual case studies. Some skin symptoms recede with increasing age while progressive neurological advancement of the disorder causes seizures and mental deterioration later in life for some patients. Symptoms and signs
The predominant clinical symptoms of wrinkly skin syndrome are wrinkled and inelastic skin over the face, backs of hands/fingers, tops of feet, and abdomen, delayed closure of the fontanel (babys soft spot), and increased palmar and plantar creases in the hands and feet, respectively.Patients may experience a wide variety of symptoms (see table). The assortment of symptoms displayed and symptom severity (particularly growth and developmental delays) vary from patient to patient. Microscopic analysis of epidermal samples of a four-month year old with WSS revealed an irregular pattern of elastic fiber distribution. Fewer elastic fibers are present in the papillary dermis and fragmented elastic fibers in the reticular dermis are observed. | 11
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These cannot be determined by plain films, as the x-ray passes through the soft tissue. A study by Giles et al., stated that sixteen of the thirty patients (53%) had retrolisthesis of L5 on S1 ranging from 2–9 mm; these patients had either intervertebral disc bulging or protrusion on CT examination ranging from 3–7 mm into the spinal canal. Fourteen patients (47%) without retrolisthesis (control group) did not show any retrolisthesis and the CT did not show any bulge/protrusion. On categorizing x-ray and CT pathology as being present or not, the well positioned i.e. true lateral plain x-ray film revealed a sensitivity and specificity of 100% ([95% Confidence Interval. = [89%–100%]) for bulge/protrusion in this preliminary study.” (7)Spinal cord compressions are also possible with patients experiencing pain, rigidity and neurologic signs that may follow some distance along nerves to cause symptoms at some distance from the location of the retrolisthesis. Diagnosis
Complete Retrolisthesis - The body of one vertebra is posterior to both the vertebral body of the segment of the spine above as well as below.Stairstepped Retrolisthesis - The body of one vertebra is posterior to the body of the spinal segment above, but is anterior to the one below.Partial Retrolisthesis - The body of one vertebra is posterior to the body of the spinal segment either above or below. (3)
Grading
Since the vertebral body in a retrolisthesis moves in a posterior direction, the grading used for spondylolistheses is of little use. | It is however useful to divide the anterior to posterior dimension of the intervertebral foramina (IVF) (4) into four equal units. A posterior displacement of up to ¼ of the IVF is graded as Grade 1, ¼ to ½ as Grade 2, ½ to ¾ as Grade 3, ¾ to total occlusion of the IVF as Grade 4. Alternatively, a measurement of the amount of displacement can also made by measuring the bone displacement in millimetres.Retrolistheses can be caused by injury and the resulting instability of the connecting soft tissues especially ligaments, discs, muscles, tendons and fascia. They may also involve muscles through spasm as a result of nerve malfunction due to pressure caused by the posterior displacement of the vertebra encroaching on the contents of the IVF. The IVFs contents include spinal (sensory and motor) nerves, arteries, veins and lymphatic vessels which cater to the nutritional and waste removal needs of the spinal cord.Degenerative spinal changes are often seen at the levels where a retrolisthesis is found. These changes are more pronounced as time progresses after injury, and are evidenced by end plate osteophytosis, disc damage, disc narrowing, desiccation and disc bulging. “A retrolisthesis hyperloads at least one disc and puts shearing forces on the anterior longitudinal ligament, the annular rings, nucleus pulposus, cartilage end plates and capsular ligaments. The bulging, twisting and straining tissues attached to the endplates pull, push and stretch it. It is worsened with time, becoming irreversible.” This is the etiology of degenerative joint disease. | 11
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The magnocellular neurons that make oxytocin are adjacent to magnocellular neurons that make vasopressin, and are similar in many respects. The oxytocin peptide is synthesized as an inactive precursor protein from the OXT gene. This precursor protein also includes the oxytocin carrier protein neurophysin I. The inactive precursor protein is progressively hydrolyzed into smaller fragments (one of which is neurophysin I) via a series of enzymes. The last hydrolysis that releases the active oxytocin nonapeptide is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM).The activity of the PAM enzyme system is dependent upon vitamin C (ascorbate), which is a necessary vitamin cofactor. By chance, sodium ascorbate by itself was found to stimulate the production of oxytocin from ovarian tissue over a range of concentrations in a dose-dependent manner. Many of the same tissues (e.g. ovaries, testes, eyes, adrenals, placenta, thymus, pancreas) where PAM (and oxytocin by default) is found are also known to store higher concentrations of vitamin C.Oxytocin is known to be metabolized by the oxytocinase, leucyl/cystinyl aminopeptidase. Other oxytocinases are also known to exist. Amastatin, bestatin (ubenimex), leupeptin, and puromycin have been found to inhibit the enzymatic degradation of oxytocin, though they also inhibit the degradation of various other peptides, such as vasopressin, met-enkephalin, and dynorphin A.
Neural sources
In the hypothalamus, oxytocin is made in magnocellular neurosecretory cells of the supraoptic and paraventricular nuclei, and is stored in Herring bodies at the axon terminals in the posterior pituitary. It is then released into the blood from the posterior lobe (neurohypophysis) of the pituitary gland. | The adjective form is "oxytocic", which refers to medicines which stimulate uterine contractions, to speed up the process of childbirth. History
The uterine-contracting properties of the principle that would later be named oxytocin were discovered by British pharmacologist Henry Hallett Dale in 1906, and its milk ejection property was described by Ott and Scott in 1910 and by Schafer and Mackenzie in 1911.In the 1920s, oxytocin and vasopressin were isolated from pituitary tissue and given their current names. Oxytocins molecular structure was determined in 1952. In the early 1950s, American biochemist Vincent du Vigneaud found that oxytocin is made up of nine amino acids, and he identified its amino acid sequence, the first polypeptide hormone to be sequenced. In 1953, du Vigneaud carried out the synthesis of oxytocin, the first polypeptide hormone to be synthesized. Du Vigneaud was awarded the Nobel Prize in 1955 for his work.Further work on different synthetic routes for oxytocin, as well as the preparation of analogues of the hormone (e.g. 4-deamido-oxytocin) was performed in the following decade by Iphigenia Photaki. Biochemistry
Estrogen has been found to increase the secretion of oxytocin and to increase the expression of its receptor, the oxytocin receptor, in the brain. In women, a single dose of estradiol has been found to be sufficient to increase circulating oxytocin concentrations. Biosynthesis
Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone (CRH) and dynorphin, for example, that act locally. | 11
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Vaginal adenosis is a benign abnormality in the vagina, commonly thought to be caused by intrauterine and neonatal exposure of diethylstilbestrol and other progestogens and nonsteroidal estrogens, however it has also been observed in otherwise healthy women and has been considered at times idiopathic or congenital. Postpubertal lesions have also been observed to grow de novo. It has a rather common incidence, of about 10% of adult women. Causes
Vaginal adenosis is characterised by the presence of metaplastic cervical or endometrial epithelium within the vaginal wall, considered as derived from Müllerian epithelium islets in later life. In women who were exposed to certain chemicals, vaginal adenosis may arise in up to 90%. Since these contraceptives were discontinued, incidence has dropped dramatically. Risk is however still present in subsequent generations due to recent exposure.It is thought steroid hormones play a stimulatory growth in adenosis formation. Vaginal adenosis is also often observed in adenocarcinoma patients. Diagnosis
Colposcopically, it presents itself similarly to columnar epithelium on the cervix, assisted with lugols solution application for diagnosis. It can be discovered as nodules or cysts on the vaginal tube, with biopsy needed for further diagnosis. As seen cytologically, epithelial and stromal cells in vaginal adenosis show characteristic fusion through the basal lamina or with stromal fibroblasts. Adenosal cells can be distinguished as mucinous, tuboendometrial, and embryonic. | Its mucinous cells resemble the normal cervical lining, while its tuboendometrial cells resemble the lining of normal fallopian tubes or endometrium.It is sometimes considered a precancerous lesion, given clear-cell adenocarcinoma patients present these lesions in close proximity to atypical tuboendometrial glands, and microglandular hyperplasia has been seen to arise from these lesions. References
Further reading
OBrien, P. C.; Noller, K. L.; Robboy, S. J.; Barnes, A. B.; Kaufman, R. H.; Tilley, B. C.; Townsend, D. E. (March 1979). "Vaginal epithelial changes in young women enrolled in the National Cooperative Diethylstilbestrol Adenosis (DESAD) project". Obstetrics & Gynecology. 53 (3): 300–308. PMID 424101. Laronda, Monica M.; Unno, Kenji; Butler, Lindsey M.; Kurita, Takeshi (2012). "The development of cervical and vaginal adenosis as a result of diethylstilbestrol exposure in utero". Differentiation. 84 (3): 252–260. doi:10.1016/j.diff.2012.05.004. ISSN 0301-4681. PMC 3443265. PMID 22682699. PMID 22682699. Ganesan, R.; Ferryman, S. R.; Waddell, C. A. (1999). "Vaginal adenosis in a patient on Tamoxifen therapy: a case report". Cytopathology. 10 (2): 127–130. doi:10.1046/j.1365-2303.1999.00162.x. ISSN 0956-5507. PMID 10211619. S2CID 33999959. Laronda, M. M.; Unno, K.; Ishi, K.; Serna, V. A.; Butler, L. M; Mills, A. A.; Orvis, G. D.; Behringer, R. R.; Deng, C.; Sinha, S.; Kurita, T. (2013). "Diethylstilbestrol induces vaginal adenosis by disrupting SMAD/RUNX1-mediated cell fate decision in the Müllerian duct epithelium". Developmental Biology 381(1): 5-16. doi: 10.1016/j.ydbio.2013.06.024. PMID 23830984. | 11
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Neuroimaging has shown functional and structural alterations in the brain. A 2017 study showed that chronic intake of opioids, such as heroin, may cause long-term effects in the orbitofrontal area (OFC), which is essential for regulating reward-related behaviors, emotional responses, and anxiety. Moreover, neuroimaging and neuropsychological studies demonstrated dysregulation of circuits associated with emotion, stress and high impulsivity. Dependence
Drug dependence is an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake). Dependence is a component of a substance use disorder. Opioid dependence can manifest as physical dependence, psychological dependence, or both.Increased brain-derived neurotrophic factor (BDNF) signaling in the ventral tegmental area (VTA) has been shown to mediate opioid-induced withdrawal symptoms via downregulation of insulin receptor substrate 2 (IRS2), protein kinase B (AKT), and mechanistic target of rapamycin complex 2 (mTORC2). As a result of downregulated signaling through these proteins, opiates cause VTA neuronal hyperexcitability and shrinkage (specifically, the size of the neuronal soma is reduced). It has been shown that when an opiate-naive person begins using opiates in concentrations that induce euphoria, BDNF signaling increases in the VTA.Upregulation of the cyclic adenosine monophosphate (cAMP) signal transduction pathway by cAMP response element binding protein (CREB), a gene transcription factor, in the nucleus accumbens is a common mechanism of psychological dependence among several classes of drugs of abuse. Upregulation of the same pathway in the locus coeruleus is also a mechanism responsible for certain aspects of opioid-induced physical dependence. | Charts of deaths involving specific opioids and classes of opioids
History
Opiate misuse has been recorded at least since 300 BC. Greek mythology describes Nepenthe (Greek “free from sorrow”) and how it was used by the hero of the Odyssey. Opioids have been used in the Near East for centuries. The purification of and isolation of opiates occurred in the early 19th century.Levacetylmethadol was previously used to treat opioid dependence. In 2003 the drugs manufacturer discontinued production. There are no available generic versions. LAAM produced long-lasting effects, which allowed the person receiving treatment to visit a clinic only three times per week, as opposed to daily as with methadone. In 2001, levacetylmethadol was removed from the European market due to reports of life-threatening ventricular rhythm disorders. In 2003, Roxane Laboratories, Inc. discontinued Orlaam in the US. See also
Benzodiazepine withdrawal syndrome
Doctor shopping
Hyperkatifeia, hypersensitivity to emotional distress in the context of opioid abuse
Physical dependence
Post-acute-withdrawal syndrome
Prescription drug abuse
References
External links
Heroin information from the National Institute on Drug Abuse
Opioid information at Opioids.Net
Opioid Dependence Treatment and Guidelines
Opioid Risk Tool (ORT) for Narcotic Abuse | 11
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These blood vessels sometimes leak, and these retinal hemorrhages may lead to the loss of central vision. Vision loss is a major issue in many PXE patients.PXE may affect the gastrointestinal and cardiovascular systems. Gastrointestinal bleeding is a rare symptom and usually involved bleeding from the stomach. In the circulatory system, intermittent claudication, a condition in which cramping pain in the leg is induced by exercise, is a prominent feature. At later stages, coronary artery disease may develop, leading to angina and myocardial infarction (heart attack). Cerebral ischemia in PXE is caused by small vessel occlusive disease. Other rare neurological complications may include intracranial aneurysms, subarachnoid and intracerebral hemorrhages. Genetics
80% of clinical cases of pseudoxanthoma elasticum have detectable mutations in the ABCC6 gene. Mutations in almost all parts of the gene have been described, of all types (missense, nonsense, splice alteration, insertion, small deletion or large deletion). Although there have been reports of autosomal dominant inheritance, the inheritance is typically autosomal recessive (both parents need to be carriers, and there is a 25% chance that a child will inherit both abnormal copies of the gene and therefore develop the condition).Strong genetic linkage was found with mutations in the ABCC6 gene, which codes for the ABCC6 protein, which is a membrane transporter from the large ATP-binding cassette transporter family. The protein is expressed in most organs, but mainly in the liver and kidney. ABCC6 mediates ATP release in the liver. | A review reporting the incidence of illnesses associated with Ludwig angina found that 18% of cases involved diabetes mellitus, 9% involved acquired immune deficiency syndrome, and another 5% were human immunodeficiency virus (HIV) positive. Diagnosis
Infections originating in the roots of teeth can be identified with a dental X-ray. A CT scan of the neck with contrast material is used to identify deep neck space infections. If there is suspicion of the infection of the chest cavity, a chest scan is sometimes done.Angioneurotic oedema, lingual carcinoma and sublingual hematoma formation following anticoagulation should be ruled out as possible diagnoses. Microbiology
There are a few methods that can be used for determining the microbiology of Ludwigs angina. Traditionally, a culture sample is collected although it has some limitations, primarily being the time-consuming and sometimes unreliable results if the culture is not processed correctly. Ludwigs angina is most often found to be polymicrobial and anaerobic. Some of the commonly found microbes are Viridans Streptococci, Staphylococci, Peptostreptococci, Prevotella, Porphyromonas and Fusobacterium. Treatment
For each patient, the treatment plan should be consider the patients stage of infection, airway control, and comorbidities. Other things to consider include physician experience, available resources, and personnel are critical factors in formulation of a treatment plan. There are four principles that guide the treatment of Ludwigs Angina: Sufficient airway management, early and aggressive antibiotic therapy, incision and drainage for any who fail medical management or form localized abscesses, and adequate nutrition and hydration support. | 0-1
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Computed tomography or ultrasound may be used instead for imaging.Urine odor in cystinuria has a smell of rotten eggs due to the increase in cystine. Genetics
Cystinuria is an autosomal recessive disease, which means that the defective gene responsible for the disease is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disease. The parents of an individual with an autosomal recessive disease both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disease. Although signs and symptoms are rare, there are some directly and indirectly associated with cystinuria. These sign and symptoms consist of 1) hematuria- blood in the urine, 2) flank pain – pain in the side due to kidney pain, 3) renal colic – intense, cramping pain due to stones in the urinary tract, 4) obstructive uropathy- urinary tract disease due to obstruction, and 5) urinary tract infections. Cause
Cystinuria is caused by mutations in the SLC3A1 and SLC7A9 genes. These defects prevent proper reabsorption of basic, or positively charged, amino acids: cystine, lysine, ornithine, arginine. Under normal circumstances, this protein allows certain amino acids, including cystine, to be reabsorbed into the blood from the filtered fluid that will become urine. Mutations in either of these genes disrupt the ability of this transporter protein to reabsorb these amino acids, allowing them to become concentrated in the urine. | Crossed dystopia (syn.unilateral fusion cross fused renal ectopia) is a rare form of renal ectopia where both kidneys are on the same side of the spine. In many cases, the two kidneys are fused together, yet retain their own vessels and ureters. The ureter of the lower kidney crosses the midline to enter the bladder on the contralateral side. Both renal pelves can lie one above each other medial to the renal parenchyma (unilateral long kidney) or the pelvis of the crossed kidney faces laterally (unilateral "S" shaped kidney). Urogram is diagnostic. The anomaly can be diagnosed through ultrasound or urography, but surgical intervention is only necessary if there are other complications, such as tumors or pyelonephritis. == References == | 0-1
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One study suggests that simultanagnosia may result from an extreme form of competition between objects which makes it difficult for attention to be disengaged from an object once it has been selected. Patients with simultanagnosia have a restricted spatial window of visual attention and cannot see more than one object at a time. They see their world in a patchy, spotty manner. Therefore, they pick out a single object, or even components of an individual object, without being able to see the global "big picture. "A study which directly tested the relationship between the restriction of the attentional window in simultanagnosia compared with the vision of healthy participants with normal limits of visual processing confirmed the limitations of difficulties of patients with simultanagnosia.There is considerable evidence that a persons cortex is essentially divided into two functional streams: an occipital-parietal-frontal pathway that processes "where" information and an occipital-temporal-frontal pathway that provides "what" information to the individual. Oculomotor apraxia
Bálint referred to this as "psychic paralysis of gaze"—the inability to voluntarily guide eye movements, changing to a new location of visual fixation. A major symptom of Oculomotor apraxia is that a person has no control over their eye movements, however, vertical eye movements are typically unaffected. For example, they often have difficulty moving their eyes in the desired direction. In other words, the saccades (rapid eye movements) are abnormal. Because of this, most patients with Oculomotor apraxia have to turn their heads in order to follow objects coming from their peripherals. | Neuroanatomical evidence
Bálints syndrome has been found in patients with bilateral damage to the posterior parietal cortex. The primary cause of the damage and the syndrome can originate from multiple strokes, Alzheimers disease, intracranial tumors, or brain injury. Progressive multifocal leukoencephalopathy and Creutzfeldt–Jakob disease have also been found to cause this kind of damage. This syndrome is caused by damage to the posterior superior watershed areas, also known as the parietal-occipital vascular border zone (Brodmanns areas 19 and 7). Manifestations
Some telltale signs suggesting Bálints syndrome following bilateral brain insults may include:
limitation to perceive only stimuli that is presented at 35 to 40 degrees to the right. They are able to move their eyes but cannot fixate on specific visual stimuli (optic apraxia). patients field of attention is limited to one object at a time. making activities like reading difficult because each letter is perceived separately (simultanagnosia). | 11
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Notably, the conference brought together more than 170 Heads of State. While world leaders at the summit were encouraged by the reduction of poverty in some nations, they were concerned by the uneven decline of poverty within and among different regions of the globe. However, at the end of the summit, the conference attendees reaffirmed the UNs commitment to achieve the MDGs by 2015 and urged all supranational, national and non-governmental organizations to follow suit. Sustainable Development Goals
As the expiration of the Millennium Development Goals approached in 2015, the UN convened a panel to advise on a Post-2015 Development Agenda, which led to a new set of 17 goals for 2030 titled the Sustainable Development Goals (SDGs). The first goal (SDG 1) is to "End poverty in all its forms everywhere. "The HLP report, entitled A New Global Partnership: Eradicate Poverty and Transform Economies Through Sustainable Development, was published in May 2013. In the report, the HLP wrote that:
Ending extreme poverty is just the beginning, not the end. It is vital, but our vision must be broader: to start countries on the path of sustainable development – building on the foundations established by the 2012 UN Conference on Sustainable Development in Rio de Janeiro, and meeting a challenge that no country, developed or developing, has met so far. We recommend to the Secretary-General that deliberations on a new development agenda must be guided by the vision of eradicating extreme poverty once and for all, in the context of sustainable development. | A ureterocele is a congenital abnormality found in the ureter. In this condition the distal ureter balloons at its opening into the bladder, forming a sac-like pouch. It is most often associated with a duplicated collection system, where two ureters drain their respective kidney instead of one. Simple ureterocele, where the condition involves only a single ureter, represents only twenty percent of cases. Since the advent of the ultrasound, most ureteroceles are diagnosed prenatally. The pediatric and adult conditions are often found incidentally, i.e. through diagnostic imaging performed for unrelated reasons. Classification
Intravesical
Confined within the bladder
Ectopic
Some part extends to the bladder neck or urethra
Stenotic
Intravesical ureterocele with a narrow opening
Sphincteric
Ectopic ureterocele with an orifice distal to the bladder neck
Sphincterostenotic
Orifice is both stenotic and distal to the bladder neck
Cecoureterocele
Ectopic ureterocele that extends into the urethra, but the orifice is in the bladder
Signs and symptoms
The signs and symptoms of ureterocele in the latter two forms can easily be confused with other medical conditions. Symptoms can include:
Frequent urinary tract infections
Pyelonephritis
Obstructive voiding symptoms
Urinary retention
Failure to thrive
Hematuria
Cyclic abdominal pain
Urolithiasis
Cobra head sign is seen in radiography
In females: salpingitis, hydrosalpinx with sepsis or torsion. T.O. mass. Complications
Many other complications arise from ureteroceles. Redundant collection systems are usually smaller in diameter than single, and predispose the patient to impassable kidney stones. The effective "bladder within a bladder" compounds this problem by increasing the collision of uric acid particles, the process by which uric acid stones are formed. Ureterocele is also associated with poor kidney function. | 0-1
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Selective serotonin reuptake inhibitors and mirtazapine have been recommended for depression, while atypical antipsychotics are recommended for psychosis and behavioral problems. Specialist neuropsychiatric input is recommended as people may require long-term treatment with multiple medications in combination. Education
The families of individuals, and society at large, who have inherited or are at risk of inheriting HD have generations of experience of HD but may be unaware of recent breakthroughs in understanding the disease, and of the availability of genetic testing. Genetic counseling benefits these individuals by updating their knowledge, seeking to dispel any unfounded beliefs that they may have, and helping them consider their future options and plans. The Patient Education Program for Huntingtons Disease has been created to help educate family members, caretakers, and those diagnosed with Huntingtons disease. Also covered is information concerning family planning choices, care management, and other considerations. Prognosis
The length of the trinucleotide repeat accounts for 60% of the variation of the age of symptoms onset and their rate of progress. A longer repeat results in an earlier age of onset and a faster progression of symptoms. Individuals with more than sixty repeats often develop the disease before age 20, while those with fewer than 40 repeats may remain asymptomatic. The remaining variation is due to environmental factors and other genes that influence the mechanism of the disease.Life expectancy in HD is generally around 20 years following the onset of visible symptoms. Most life-threatening complications result from muscle coordination, and to a lesser extent, behavioral changes induced by declining cognitive function. | During this process, the parasite releases the toxic and soluble molecule heme. The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin, a nontoxic molecule. Hemozoin collects in the digestive vacuole as insoluble crystals.Chloroquine enters the red blood cell by simple diffusion, inhibiting the parasite cell and digestive vacuole. Chloroquine then becomes protonated (to CQ2+), as the digestive vacuole is known to be acidic (pH 4.7); chloroquine then cannot leave by diffusion. Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. Chloroquine binds to heme (or FP) to form the FP-chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function. Action of the toxic FP-chloroquine and FP results in cell lysis and ultimately parasite cell autodigestion. Parasites that do not form hemozoin are therefore resistant to chloroquine. Resistance in malaria
Since the first documentation of P. falciparum chloroquine resistance in the 1950s, resistant strains have appeared throughout East and West Africa, Southeast Asia, and South America. The effectiveness of chloroquine against P. falciparum has declined as resistant strains of the parasite evolved. Resistant parasites are able to rapidly remove chloroquine from the digestive vacuole using a transmembrane pump. Chloroquine-resistant parasites pump chloroquine out at 40 times the rate of chloroquine-sensitive parasites; the pump is coded by the P. falciparum chloroquine resistance transporter (PfCRT) gene. | 0-1
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Even if the patient wakes up, brain damage is likely to be significant enough to prevent a return to normal functioning. Long-term comas can have a significant impact on a patients family. Families of coma patients often have idealized images of the outcome based on Hollywood movie depictions of coma. Adjusting to the realities of ventilators, feeding tubes, bedsores, and muscle wasting may be difficult. Treatment decisions often involve complex ethical choices and can strain family dynamics. See also
Altitude sickness
Choking game
Hypothermia cap
Space exposure
Ulegyria
References
External links
Hypoxia experiment | Keratosis follicularis may refer to:
Dariers disease
Focal palmoplantar keratoderma with oral mucosal hyperkeratosisSee also:
Isolated dyskeratosis follicularis
Keratosis follicularis spinulosa decalvans | 0-1
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Using other signals that are parallel to the color coding, such as patterns, shapes, size or order. This not only helps color blind people, but also aids understanding by normally sighted people by providing them with multiple reinforcing cues. Using brightness contrast (different shades) in addition to color contrast (different hues)
To achieve good contrast, conventional wisdom suggests converting a (digital) design to grayscale to ensure there is sufficient brightness contrast between colors. However, this does not account for the different perceptions of brightness to different varieties of colorblindness, especially Protans, Tritans and Monochromats. Viewing the design through a CVD Simulator to ensure the information carried by color is still sufficiently conveyed. At a minimum, the design should be visible for Deutans, the most common kind of colorblindness. Maximizing the area of colors (e.g. increase size, thickness or boldness of colored element) makes the color easier to identify. Color contrast improves as the angle the color subtends on the retina increases. This applies to all types of color vision. Maximizing brightness (value) and saturation (chroma) of the colors to maximize color contrast. Converting connotative tasks to comparative tasks by including a legend, even when the meaning is considered obvious (e.g. red means danger). Avoiding denotative color tasks (color naming) when possible. Some denotative tasks can be converted to comparative tasks by depicting the actual color whenever the color name is mentioned; for example, colored typography in "purple", or "purple (█)". For denotative tasks (color naming), using the most common shades of colors. | An ameboma, also known as an amebic granuloma, is a rare complication of Entamoeba histolytica infection, where in response to the infecting amoeba there is formation of annular colonic granulation, which results in a large local lesion of the bowel. Presentation
The ameboma may manifest as a right lower quadrant abdominal mass, which may be mistaken for carcinoma, tuberculosis, Crohns disease, actinomycosis, or lymphoma. Diagnosis
Biopsy is necessary for definitive diagnosis. == References == | 0-1
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Although the US brand name is Inflectra, it is marketed in the European Union as Remsima.The FDA approved Samsung Bioepis Co., Ltd.s Renflexis (infliximab-abda) in April 2017.Biogen released another biosimilar, Flixabi, which was approved in Germany, the UK, and the Netherlands. Flixabi was approved for use in the European Union in May 2016.In December 2017, Ixifi (infliximab-qbtx) was approved in the United States.Zessly was approved for use in the European Union in May 2018.In December 2019, Avsola (infliximab-axxq) was approved in the United States.Avsola was approved for medical use in Canada in March 2020.In December 2021, Ixifi was approved for medical use in Canada. Availability/affordability
In the United States, infliximab is an expensive medication, costing about US$900 for a 100 mg dose, and is covered by almost every US medical insurance plan (though caps on many plans make it possible to be covered for only a subset of treatments in the course of a year). Infliximab is supplied as a sterile, white, lyophilized (freeze-dried) powder, so must be reconstituted and administered by a health care professional, usually in a hospital or office setting. For this reason, it is usually covered under major medical insurance rather than prescription drug coverage. The loading regimen for all approved indications occurs at weeks 0, 2, and 6 at the above dosages.In the UK, infliximab is available from the NHS for Crohns disease treatment provided three criteria are met. | Based on studies in AS, the results suggest infliximab, etanercept, and adalimumab have the potential to reduce the signs and symptoms of moderate to severely active axial involvement in PsA in patients who have had an inadequate response to NSAID (level 1a, grade A). The anti-TNF agents (infliximab and etanercept; level 1b, grade A) are more effective for the treatment of enthesitis than traditional agents. Results suggest infliximab is effective for the treatment of dactylitis in PsA. Other
It was approved for treating ankylosing spondylitis, psoriatic arthritis, psoriasis, rheumatoid arthritis.Infliximab is also prescribed (out of indication) for the treatment of Behçets disease.Infliximab is the most frequently used biological agent in treating relapsing polychondritis. Half of the patients saw benefit from this treatment, and a few other patients experienced infections that in some cases lead to death.There have been numerous case reports of the efficacy of infliximab in various inflammatory skin conditions diseases; the FDA approved infliximab for chronic severe plaque psoriasis in adults in September 2006.Infliximab has been used off-label in treating refractory sarcoidosis, where other treatments have not been effective.Infliximab has been tested in chronic obstructive pulmonary disease (COPD) but there was no evidence of benefit with the possibility of harm.Infliximab is indicated for steroid refractory checkpoint inhibitor induced colitis, at a dose of 5 to 10 mg/kg. Adverse effects
Infliximab has adverse effects, some life-threatening, common to drugs in the class of TNF inhibiting immunosuppressants (which also includes etanercept (Enbrel) and adalimumab (Humira)). | 11
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5% did not improve and declined further treatment.Of the 413 patients who improved, 74 had a recurrence of symptoms during the observation period and their symptoms responded to rest or after resumption of the exercise program.The Morrison study shows that the outcome of impingement symptoms varies with patient characteristics. Younger patients (20 years or less) and patients between 41 and 60 years of age, fared better than those who were in the 21 to 40 years age group. This may be related to the peak incidence of work, job requirements, sports and hobby related activities, that may place greater demands on the shoulder. However, patients who were older than sixty years of age had the "poorest results". It is known that the rotator cuff and adjacent structures undergo degenerative changes with ageing.The authors were unable to posit an explanation for the observation of the bimodal distribution of satisfactory results with regard to age. They concluded that it was "unclear why (those) who were twenty-one to forty years old had less satisfactory results". The poorer outcome for patients over 60 years old was thought to be potentially related to "undiagnosed full-thickness tears of the rotator cuff". References
Anderson, D., M, (2000), Dorland’s Illustrated Medical Dictionary, 29th ed, W.B. Saunders Company, Canada, 965-967. Buschbacher, R., M, Braddom, R., L. (1994). Sports medicine & rehabilitation: A sport-specific approach. Hanley and Belfus Inc, Philadelphia. Hartley, A. (1990). Practical joint assessment: A sports medicine manual, St Louis, Sydney. Further reading
Arend CF. Ultrasound of the Shoulder. Master Medical Books, 2013. | Side effects may include:
Psychological
Depression or even suicidal ideation, as well as nightmares
Apathy or anhedonia, as well as dysphoria
Anxiety, especially of the social anxiety variant
Decreased alertness, awareness, and wakefulness
Impaired attention, focus, and concentration
Decreased desire, drive, and motivation
Fatigue or lethargy or malaise or lassitude
Sedation or drowsiness or somnolence or sleepiness
Agitation or restlessness
Cognitive and memory impairment
Derealization or depersonalization, as well as mild psychosis
Sexual dysfunction including impaired libido, desire, and drive
Physiological
Dizziness, lightheadedness, or vertigo
Miosis or pupil constriction
Xerostomia or dry mouth
Gastrointestinal disturbances such as diarrhea or constipation
Headache or migraine
Myalgia or muscle aches, arthralgia or joint pain, or paresthesia ("pins and needles")
Restless legs syndrome (RLS)
Parkinsonian symptoms such as muscle tremors, rigidity, hypokinesia, or balance or postural instability
Akathisia, ataxia, dyskinesia as well as even tardive dyskinesia, or dystonia
Bells palsy or facial paralysis
Sexual dysfunction consisting of impaired erectile dysfunction or anorgasmia
Hyperprolactinemia or excess prolactin, gynecomastia/breast enlargement in males, or amenorrhoea or absence of menstrual cycles in females
Bradycardia or decreased heart rate
Hypotension or decreased blood pressure (though this may also be considered a therapeutic benefit)
Orthostatic hypotension (also known as postural hypotension)
Hepatitis, hepatotoxicity, or liver dysfunction or damage
Pancreatitis or inflammation of the pancreas
Warm autoimmune hemolytic anemia or deficiency in red blood cells (RBCs)
Myelotoxicity or bone marrow suppression, potentially leading to thrombocytopenia or blood platelet deficiency or leukopenia or white blood cell (WBC) deficiency
Hypersensitivity such as lupus erythematosus, myocarditis, or pericarditis
Lichenoid reactions such as skin lesions or rashes
Pallor
Rebound/withdrawal
Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported. Mechanism of action
The mechanism of action of methyldopa is not fully clear. | 0-1
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Similarly, the main character in Graham Greenes 1936 crime noir novel A Gun for Sale, Raven, has a cleft lip which he is sensitive about, and is described as "an ugly man dedicated to ugly deeds". In the 1976 Patricia A. McKillip novel The Night Gift, one of the high-school aged protagonists is shy because she has a cleft lip, but learns to have more confidence in herself. In the first edition of Harry Potter and the Chamber of Secrets, one of the people Gilderoy Lockhart stole credit from was a witch with a harelip who banished the Bandon Banshee. In later editions, this was changed to a witch with a hairy chin.In chapter 26 of Mark Twains The Adventures of Huckleberry Finn, Huck Finn meets the three Wilks sisters, Mary Jane, Susan, and Joanna. Joanna is described as, "the one who gives herself to good works and has a hare-lip." As a form of offensive synecdoche, Huck Finn refers to Joanna as "the hare-lip" rather than by her name. In Inheritance, the final title of Christopher Paolinis Inheritance Cycle, the main character Eragon heals a newborn girl with this condition in a display of complicated healing magic. It is stated that those within Eragons society born with this condition are often not allowed to live as they face a very hard life.Cleft lip and cleft palate are often portrayed negatively in popular culture. | For example, some teams wait on jaw correction until the child is aged 10 to 12 (argument: growth is less influential as deciduous teeth are replaced by permanent teeth, thus saving the child from repeated corrective surgeries), while other teams correct the jaw earlier (argument: less speech therapy is needed than at a later age when speech therapy becomes harder). Within teams, treatment can differ between individual cases depending on the type and severity of the cleft. Cleft lip
Within the first 2–3 months after birth, surgery is performed to close the cleft lip. While surgery to repair a cleft lip can be performed soon after birth, often the preferred age is at approximately 10 weeks of age, following the "rule of 10s" coined by surgeons Wilhelmmesen and Musgrave in 1969 (the child is at least 10 weeks of age; weighs at least 10 pounds, and has at least 10g hemoglobin). If the cleft is bilateral and extensive, two surgeries may be required to close the cleft, one side first, and the second side a few weeks later. The most common procedure to repair a cleft lip is the Millard procedure pioneered by Ralph Millard. Millard performed the first procedure at a Mobile Army Surgical Hospital (MASH) unit in Korea.Often an incomplete cleft lip requires the same surgery as complete cleft. This is done for two reasons. Firstly the group of muscles required to purse the lips run through the upper lip. To restore the complete group a full incision must be made. | 11
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Whether these concerns occur in humans is unclear. Elderly
Biophysical studies using NMR spectroscopy has provided molecular details of how inhaled anesthetics interact with three amino acid residues (G29, A30 and I31) of amyloid beta peptide and induce aggregation. This area is important as "some of the commonly used inhaled anesthetics may cause brain damage that accelerates the onset of Alzheimers disease". Physical properties
It is administered as a racemic mixture of (R)- and (S)-optical isomers. Isoflurane has a melting point of 48 - 48.5°Celsius (118 - 119°Fahrenheit) and a boiling point of 48.5 - 49 °C (119 - 120 °F). It is non-combustible but can give off irritable and toxic fumes when exposed to flame. Mechanism of action
Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated. Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABA, glutamate and glycine receptors, but has different effects on each receptor. Isoflurane acts as a positive allosteric modulator of the GABAA receptor in electrophysiology studies of neurons and recombinant receptors. It potentiates glycine receptor activity, which decreases motor function. It inhibits receptor activity in the NMDA glutamate receptor subtypes. Isoflurane inhibits conduction in activated potassium channels. Isoflurane also affects intracellular molecules. It inhibits plasma membrane calcium ATPases (PMCAs) which affects membrane fluidity by hindering the flow of Ca2+ (calcium ions) out across the membrane, this in turn affects neuron depolarization. It binds to the D subunit of ATP synthase and NADH dehydrogenase. | General anaesthesia with isoflurane reduces plasma endocannabinoid AEA concentrations, and this could be a consequence of stress reduction after loss of consciousness. History
Together with enflurane and halothane, Isoflurane began to replace the flammable ethers used in the pioneer days of surgery; this shift began in the 1940s to the 1950s. Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula. Environment
The average lifetime of isoflurane in the atmosphere is 3.2 years, its global warming potential is 510 and the yearly emissions add up to 880 tons. Veterinary use
Isoflurane is frequently used for veterinary anaesthesia. References
External links
"Isoflurane". Drug Information Portal. U.S. National Library of Medicine. U.S. Patent 3,535,388 - 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether
U.S. Patent 3,535,425 - 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether as an anesthetic agent | 11
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Some reported adverse events include changes in color vision, blood clots, and allergic reactions such as anaphylaxis. Whether the risk of venous thromboembolism (blood clots) is actually increased is a matter of debate. The risk is mentioned in the product literature, and they were reported in post marketing experience. Despite this, and the inhibitory effect of tranexamic acid on blood clot breakdown, large studies of the use of tranexamic acid have not shown an increase in the risk of venous or arterial thrombosis, even in people who had previously experienced thrombosis under other circumstances. Special populations
Tranexamic acid is categorized as pregnancy category B. No harm has been found in animal studies. Small amounts appear in breast milk if taken during lactation. If it is required for other reasons, breastfeeding may be continued. In kidney impairment, tranexamic acid is not well studied. However, due to the fact that it is 95% excreted unchanged in the urine, it should be dose adjusted in patients with renal impairment. In liver impairment, dose change is not needed as only a small amount of the drug is metabolized through the liver. Society and culture
Tranexamic acid was first synthesized in 1962 by Japanese researchers Shosuke and Utako Okamoto. It has been included in the WHO list of essential medicines. Brand names
Tranexamic acid is marketed in the U.S. and Australia in tablet form as Lysteda and in Australia, Sweden and Jordan it is marketed in an IV form and tablet form as Cyklokapron, in the UK and Sweden as Cyclo-F. | In cardiac surgery, both with and without cardiopulmonary bypass (e.g., coronary artery bypass surgery), it is used to prevent excessive blood loss. Dentistry
In the United States, tranexamic acid is FDA approved for short-term use in people with severe bleeding disorders who are about to have dental surgery. Tranexamic acid is used for a short period of time before and after the surgery to prevent major blood loss and decrease the need for blood transfusions.Tranexamic acid is used in dentistry in the form of a 5% mouth rinse after extractions or surgery in patients with prolonged bleeding time; e.g., from acquired or inherited disorders.In China, TXA is allowed in over-the-counter toothpastes, with six products using the drug. As of 2018, there are no limits on dosage, nor requirements for labeling the concentration. 0.05% TXA in toothpaste is allowed OTC in Hong Kong. <5% TXA in over-the-counter toothpaste is first patented and marketed by Lion Corporation in Japan, where it is still sold. Presence of unauthorized TXA has led to the Canadian recall of a Yunnan Baiyao toothpaste in 2019. Hematology
There is not enough evidence to support the routine use of tranexamic acid to prevent bleeding in people with blood cancers. However, there are several trials that are currently assessing this use of tranexamic acid. For people with inherited bleeding disorders (e.g. von Willebrands disease), tranexamic acid is often given. It has also been recommended for people with acquired bleeding disorders (e.g., directly acting oral anticoagulants (DOACs)) to treat serious bleeding. | 11
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Sexuality
Some people may sneeze during the initial phases of sexual arousal. Doctors suspect that the phenomenon might arise from a case of crossed wires in the autonomic nervous system, which regulates a number of functions in the body, including "waking up" the genitals during sexual arousal. The nose, like the genitals, contains erectile tissue. This phenomenon may prepare the vomeronasal organ for increased detection of pheromones.A sneeze has been compared to an orgasm, since both orgasms and sneeze reflexes involve tingling, bodily stretching, tension and release. On this subject, sexologist Vanessa Thompson from the University of Sydney states, "Sneezing and orgasms both produce feel-good chemicals called endorphins but the amount produced by a sneeze is far less than an orgasm. "According to Dr. Holly Boyer from the University of Minnesota, there is a pleasurable effect during a sneeze, where she states, "the muscle tension that builds up in your chest causes pressure, and when you sneeze and the muscles relax, it releases pressure. Anytime you release pressure, it feels good...Theres also some evidence that endorphins are released, which causes your body to feel good". Endorphins induce the brains reward system, and because sneezes occur in a quick burst, so does the pleasure. In non-humans
Sneezing is not confined to humans or even mammals. Many animals including cats, dogs, chickens and iguanas sneeze. African wild dogs use sneezing as a form of communication, especially when considering a consensus in a pack on whether or not to hunt. Some breeds of dog are predisposed to reverse sneezing. | Another less common verbal response in the United States and Canada to anothers sneeze is "Gesundheit", which is a German word that means, appropriately, "good health". Several hypotheses exist for why the custom arose of saying "bless you" or "God bless you" in the context of sneezing:
Some say it came into use during the plague pandemics of the 14th century. Blessing the individual after showing such a symptom was thought to prevent possible impending death due to the lethal disease. In Renaissance times, a superstition was formed claiming ones heart stopped for a very brief moment during the sneeze; saying bless you was a sign of prayer that the heart would not fail. It has also been stated that one says "(God) bless you" so that one does not catch the flu, cold, or any other forms of sickness.Other cultures have similar traditions:
In China, after a person sneezes they often say "百岁!" which translates to "may you live one hundred years!" the pronunciation is similar to "bless you" in English. pronunciation: [Bai Sui]
In Iran, it is common to respond to sneezing with the Persian phrase عافیت باشه âfiyat bâše, which translates to "health", similar to common European expressions. Indian culture is to respond with Krishna, similar to a blessing in western cultures. In Italy after a person sneezes the people present respond with the word "salute" (meaning: health). The louder the sneeze the more emphatic the response. In Slovakia, after a person sneezes, it is proper to say "Na zdravie!" which means "For health! | 11
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{\displaystyle d\mathbf {F} _{n}=-p\,d\mathbf {A} =-p\,\mathbf {n} \,dA.} The minus sign comes from the convention that the force is considered towards the surface element, while the normal vector points outward. The equation has meaning in that, for any surface S in contact with the fluid, the total force exerted by the fluid on that surface is the surface integral over S of the right-hand side of the above equation. It is incorrect (although rather usual) to say "the pressure is directed in such or such direction". The pressure, as a scalar, has no direction. The force given by the previous relationship to the quantity has a direction, but the pressure does not. If we change the orientation of the surface element, the direction of the normal force changes accordingly, but the pressure remains the same.Pressure is distributed to solid boundaries or across arbitrary sections of fluid normal to these boundaries or sections at every point. It is a fundamental parameter in thermodynamics, and it is conjugate to volume. Units
The SI unit for pressure is the pascal (Pa), equal to one newton per square metre (N/m2, or kg·m−1·s−2). This name for the unit was added in 1971; before that, pressure in SI was expressed simply in newtons per square metre. Other units of pressure, such as pounds per square inch (lbf/in2) and bar, are also in common use. | Clinical trial number NCT03500549 for "Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)" at ClinicalTrials.gov | 0-1
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An acute hemolytic transfusion reaction (AHTR), also called immediate hemolytic transfusion reaction, is a life-threatening reaction to receiving a blood transfusion. AHTRs occur within 24 hours of the transfusion and can be triggered by a few milliliters of blood. The reaction is triggered by host antibodies destroying donor red blood cells. AHTR typically occurs when there is an ABO blood group incompatibility, and is most severe when type A donor blood is given to a type O recipient. Signs and symptoms
Early acute hemolytic transfusion reactions are typically characterized by fever, which may be accompanied by rigors (chills). Mild cases are also typically characterized by abdominal, back, flank, or chest pain. More severe cases may be characterized by shortness of breath, low blood pressure, hemoglobinuria, and may progress to shock and disseminated intravascular coagulation. In anesthetized or unconscious patients, hematuria (blood in the urine) may be the first sign of AHTR. Other symptoms include nausea, vomiting, and wheezing. Causes
The most common cause of acute hemolytic transfusion reaction is ABO incompatibility, which is typically due to human error that results in a recipient receiving the incorrect blood product. Rarely, other blood type incompatibilities can cause AHTR, the most common of which is Kidd antigen incompatibility. Rh, Kell, and Duffy antigen incompatibility have also been implicated in AHTR. Mechanism
Antibodies against A and B blood groups (isohemagglutinins) present in the recipients blood destroy the donor red blood cells. | They also activate the coagulation cascade (blood clotting system) via factor XII, which can lead to disseminated intravascular coagulation and kidney damage. Isohemagglutinins also activate the complement cascade via C3a and C5a, which then promote inflammatory cytokine release from white blood cells. These inflammatory cytokines include IL-1, IL-6, IL-8, and TNF-alpha, which cause symptoms of low blood pressure, fever, chest pain, nausea, vomiting, and wheezing. Diagnosis
The diagnosis of AHTR is made with microscopic examination of the recipients blood and a direct antiglobulin test. The donor and recipient blood can be re-tested with a type, crossmatch, and antibody screen to determine the cause of the reaction. Treatment
Initial treatment for any type of transfusion reaction, including AHTR, is discontinuation of the transfusion. Fluid replacement and close monitoring of vital signs are important. People with AHTR are managed with supportive care, which may include diuretics, blood pressure support, and treatment of disseminated intravascular coagulation (with fresh frozen plasma, cryoprecipitate, and platelet transfusion). Furosemide is the diuretic of choice in treatment of AHTR with decreased urine output, because it increases the amount of blood that reaches the renal cortex. Mannitol may also be used. Dopamine is used for blood pressure support because it causes vasodilation (dilation of blood vessels) in the kidneys as well as increasing the cardiac output (amount of blood pumped by the heart each minute). Prognosis
The severity and prognosis of acute hemolytic transfusion depends on the rate of blood administration and the total volume of the transfusion. Approximately 2% of cases are fatal. | 11
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Complications commonly requiring this intervention include: hyperviscosity disease with severe symptoms of neurological (e.g., stroke, mental impairment, and myelitis) and/or cardiovascular (e.g., congestive heart failure, myocardial infarction) disturbances; vasculitis-driven intestinal ischemia, intestinal perforation, cholecystitis, or pancreatitis, causing acute abdominal pain, general malaise, fever, and/or bloody bowel movements; vasculitis-driven pulmonary disturbances (e.g., coughing up blood, acute respiratory failure, X-ray evidence of diffuse pulmonary infiltrates caused by diffuse alveolar hemorrhage); and severe kidney dysfunction due to intravascular deposition of immunoglobulins or vasculitis. Along with this urgent treatment, severely symptomatic patients are commonly started on therapy to treat any underlying disease; this treatment is often supplemented with anti-inflammatory drugs such as corticosteroids (e.g., dexamethasone) and/or immunosuppressive drugs. Cases where no underlying disease is known are also often treated with the latter corticosteroid and immunosuppressive medications. Type I cryoglobulinemic disease
Treatment of Type I disease is generally directed towards treating the underlying pre-malignant or malignant disorder (see plasma cell dyscrasia, Waldenströms macroglobulinemia, and chronic lymphocytic leukemia). This involves appropriate chemotherapy regimens which may include bortezomib (promotes cell death by apoptosis in cells accumulating immunoglobulins) in patients with monoclonal immunoglobulin-induced kidney failure and rituximab (antibody directed against CD20 surface antigen-bearing lymphocytes) in patients with Waldenstroms macroglobulonemia). Type II and III cryoglobulinemic disease
Treatment of mixed cryoglobulinemic disease is, similar to type I disease, directed toward treating any underlying disorder. This includes malignant (particularly Waldenströms macroglobulinemia in type II disease), infectious, or autoimmune diseases in type II and III disease. | Mixtures of monoclonal or polyclonal IgM, IgG, and/or IgA along with blood complement proteins such as C4 are the cryoglobulins associated with cases of infectious diseases, particularly hepatitis C infection, HIV infection, and Hepatitis C and HIV coinfection, and, less commonly or rarely, with cases of other infectious diseases such as hepatitis B infection, hepatitis A infection, cytomegalovirus infection, Epstein–Barr virus infection, Lyme disease, syphilis, lepromatous leprosy, Q fever, poststreptococcal nephritis, subacute bacterial endocarditis, coccidioidomycosis, malaria, schistosomiasis, echinococcosis, toxoplasmosis, and Kala-azar. These mixed-protein cryoglobulins are also associated with autoimmune diseases, particularly Sjögren syndrome, less commonly systemic lupus erythematosus and rheumatoid arthritis, and rarely polyarteritis nodosa, systemic sclerosis, temporal arteritis, polymyositis, Henoch–Schönlein purpura, pemphigus vulgaris, sarcoidosis, inflammatory bowel diseases, and others. In these mixed-protein depositions, the monoclonal or polyclonal IgM typically possesses rheumatoid factor activity and therefore binds to the Fc region of polyclonal IgG antibodies, activates the blood complement system, and complexes with complement components to form precipitates composed of IgM, IgG or IgG, and complement components, particularly complement component 4 (C4). Diagnosis
Cryoglobulinemia and cryoglobulinemic disease must be distinguished from cryofibrinogenemia or cryofibrinogenemic disease, conditions which involve the cold-induced intravascular deposition of circulating native fibrinogens. These molecules precipitate at lower temperatures (e.g., 4 °C). Since cryofibrinogens are present in plasma but greatly depleted in serum, precipitation tests for them are positive in plasma but negative in serum. Cryofibrinogenemia is occasionally found in cases of cryoglobulinemic disease. | 11
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In patients with semantic anomia, a naming deficit is accompanied by a recognition deficit. Thus, unlike patients with word selection anomia, patients with semantic anomia are unable to select the correct object from a group of objects, even when provided with the name of the target object. Disconnection anomia results from the severing of connections between sensory and language cortices. Patients with disconnection anomia may exhibit modality-specific anomia, where the anomia is limited to a specific sensory modality, such as hearing. For example, a patient who is perfectly capable of naming a target object when it is presented via certain sensory modalities like audition or touch, may be unable to name the same object when the object is presented visually. Thus, in such a case, the patients anomia arises as a consequence of a disconnect between their visual cortex and language cortices.Patients with disconnection anomia may also exhibit callosal anomia, in which damage to the corpus callosum prevents sensory information from being transmitted between the two hemispheres of the brain. Therefore, when sensory information is unable to reach the hemisphere that is language-dominant (typically the left hemisphere in most individuals), the result is anomia. For instance, if patients with this type of disconnection anomia hold an object in their left hand, this somatosensory information about the object would be sent to the right hemisphere of the brain, but then would be unable to reach the left hemisphere due to callosal damage. | Additionally, patients are able to speak with correct grammar; the main problem is finding the appropriate word to identify an object or person.Sometimes, subjects may know what to do with an object, but still not be able to give a name to the object. For example, if a subject is shown an orange and asked what it is called, the subject may be well aware that the object can be peeled and eaten, and may even be able to demonstrate this by actions or even verbal responses; however, they cannot recall that the object is called an "orange". Sometimes, when a person with this condition is multilingual, they might confuse the language they are speaking in trying to find the right word (inadvertent code-switching). Management
No method is available to completely cure anomic aphasia. However, treatments can help improve word-finding skills. Although a person with anomia may find recalling many types of words to be difficult, such as common nouns, proper nouns, verbs, etc., many studies have shown that treatment for object words, or nouns, has shown promise in rehabilitation research. The treatment includes visual aids, such as pictures, and the patient is asked to identify the object or activity. However, if that is not possible, then the patient is shown the same picture surrounded by words associated with the object or activity. Throughout the process, positive encouragement is provided. The treatment shows an increase in word finding during treatment; however, word identifying decreased two weeks after the rehabilitation period. | 11
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However, introduction of the H. influenzae type B (Hib) vaccine has dramatically decreased these infections and now non-typable H. influenzae (NTHI) is predominantly seen in clinics. Other sinusitis-causing bacterial pathogens include S. aureus and other streptococci species, anaerobic bacteria and, less commonly, Gram-negative bacteria. Viral sinusitis typically lasts for 7 to 10 days.Acute episodes of sinusitis can also result from fungal invasion. These infections are typically seen in people with diabetes or other immune deficiencies (such as AIDS or transplant on immunosuppressive antirejection medications) and can be life-threatening. In type I diabetics, ketoacidosis can be associated with sinusitis due to mucormycosis. Chronic
By definition, chronic sinusitis lasts longer than 12 weeks and can be caused by many different diseases that share chronic inflammation of the sinuses as a common symptom. It is subdivided into cases with and without polyps. When polyps are present, the condition is called chronic hyperplastic sinusitis; however, the causes are poorly understood. It may develop with anatomic derangements, including deviation of the nasal septum and the presence of concha bullosa (pneumatization of the middle concha) that inhibit the outflow of mucus, or with allergic rhinitis, asthma, cystic fibrosis, and dental infections.Chronic rhinosinusitis represents a multifactorial inflammatory disorder, rather than simply a persistent bacterial infection. The medical management of chronic rhinosinusitis is now focused upon controlling the inflammation that predisposes people to obstruction, reducing the incidence of infections. Surgery may be needed if medications are not working.Attempts have been made to provide a more consistent nomenclature for subtypes of chronic sinusitis. | Diagnosis
Classification
Sinusitis (or rhinosinusitis) is defined as an inflammation of the mucous membrane that lines the paranasal sinuses and is classified chronologically into several categories:
Acute sinusitis – A new infection that may last up to four weeks and can be subdivided symptomatically into severe and nonsevere. Some use definitions up to 12 weeks. Recurrent acute sinusitis – Four or more full episodes of acute sinusitis that occur within one year
Subacute sinusitis – An infection that lasts between four and 12 weeks, and represents a transition between acute and chronic infection. Chronic sinusitis – When the signs and symptoms last for more than 12 weeks. Acute exacerbation of chronic sinusitis – When the signs and symptoms of chronic sinusitis exacerbate, but return to baseline after treatment.Roughly 90% of adults have had sinusitis at some point in their lives. Acute
Health care providers distinguish bacterial and viral sinusitis by watchful waiting. If a person has had sinusitis for fewer than 10 days without the symptoms becoming worse, then the infection is presumed to be viral. When symptoms last more than 10 days or get worse in that time, then the infection is considered bacterial sinusitis. Pain in the teeth and bad breath are also more indicative of bacterial disease.Imaging by either X-ray, CT or MRI is generally not recommended unless complications develop. Pain caused by sinusitis is sometimes confused for pain caused by pulpitis (toothache) of the maxillary teeth, and vice versa. | 11
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Occasionally these lesions present with a green or brown hue around and within the pits.These superficial erosions are found under the toes and on the soles of the feet, and especially at the pressure bearing points such as the heel. Typically, both feet are equally affected. Rarely, the condition affects the palms. Cause
The most common cause of pitted keratolysis is Corynebacterium species. However, several other bacteria may also cause the condition, particularly Actinomyces keratolytica, Dermatophilus congolensis, Kytococcus sedentarius, and Streptomyces. Less frequently, it is due to Acinetobacter, Clostridium, Klebsiella, and Pseudomonas species. Pathogenesis
Pitted keratolysis is associated with excessive sweating of the palms or soles (palmoplantar hyperhidrosis.) The pits seen in pitted keratolysis are caused by bacteria secreting proteinase enzymes which cause the breakdown of the keratin proteins in the stratum corneum layer of the affected skin. This results in the formation of sulfur compounds which leads to a very strong and foul foot odor. The bacteria that cause pitted keratolysis thrive in warm and humid environments. Irritation is generally minimal, though occasionally burning, itching, and soreness are experienced with pitted keratolysis. Diagnosis
The diagnosis of pitted keratolysis is based primarily on the physical examination, with recognition of the classic pitted lesions and pungent odor. Dermoscopic examination can facilitate visualization of pits and pit walls. A Woods lamp may show coral red fluorescence, as seen in erythrasma. However, this finding is not uniformly present, as the condition may be caused by bacteria that do not produce fluorescent pigments. Further laboratory testing is not typically required for the diagnosis. | Pitted keratolysis (also known as Keratolysis plantare sulcatum, Keratoma plantare sulcatum, and Ringed keratolysis) is a bacterial skin infection of the foot. The infection is characterized by craterlike pits on the sole of the feet and toes, particularly weight bearing areas. The infection is caused by Corynebacterium species bacteria and Kytococcus sedentarius. Excessive sweating of the feet and use of occlusive footwear provide an environment in which these bacteria thrive and therefore increase the risk of developing pitted keratolysis.The condition is fairly common, especially in the military where wet shoes/boots are worn for extended periods of time without removing/cleaning. Skin biopsy specimens are not usually utilized, as the diagnosis of pitted keratolysis is often made by visual examination and recognition of the characteristic odor. Woods lamp examination results are inconsistent. Treatment of pitted keratolysis requires the application of antibiotics to the skin such as benzoyl peroxide, clindamycin, erythromycin, fusidic acid, or mupirocin. Prevention efforts aim to keep the feet dry by using moisture-wicking shoes and socks as well as antiperspirants. Signs and symptoms
Pitted keratolysis typically presents with white discoloration of the skin and numerous discrete, "punched-out" pitted lesions or erosions, usually located on the soles of the feet. The pits are typically 1–7 millimeters in diameter. These circular and shallow pits are characteristic of pitted keratolysis, and often overlap to produce larger areas of erosion. The appearance of this condition’s characteristic lesions becomes more pronounced when the affected area is wet or submerged in water. | 11
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Nicotine poisoning describes the symptoms of the toxic effects of nicotine following ingestion, inhalation, or skin contact. Nicotine poisoning can potentially be deadly, though serious or fatal overdoses are rare. Historically, most cases of nicotine poisoning have been the result of use of nicotine as an insecticide. More recent cases of poisoning typically appear to be in the form of Green Tobacco Sickness, or due to unintended ingestion of tobacco or tobacco products or consumption of nicotine-containing plants.Standard textbooks, databases, and safety sheets consistently state that the lethal dose of nicotine for adults is 60 mg or less (30–60 mg), but there is overwhelming data indicating that more than 0.5 g of oral nicotine is required to kill an adult.Children may become ill following ingestion of one cigarette; ingestion of more than this may cause a child to become severely ill. The nicotine in the e-liquid of an electronic cigarette can be hazardous to infants and children, through accidental ingestion or skin contact. In some cases children have become poisoned by topical medicinal creams which contain nicotine.People who harvest or cultivate tobacco may experience Green Tobacco Sickness (GTS), a type of nicotine poisoning caused by skin contact with wet tobacco leaves. This occurs most commonly in young, inexperienced tobacco harvesters who do not consume tobacco. Signs and symptoms
Nicotine poisoning tends to produce symptoms that follow a biphasic pattern. | An accidental ingestion of only 6 mg may be lethal to children.It is unlikely that a person would overdose on nicotine through smoking alone. The US Food and Drug Administration (FDA) stated in 2013: "There are no significant safety concerns associated with using more than one [over the counter] OTC [nicotine replacement therapy] NRT at the same time, or using an OTC NRT at the same time as another nicotine-containing product—including a cigarette." Ingestion of nicotine pharmaceuticals, tobacco products, or nicotine containing plants may also lead to poisoning. Smoking excessive amounts of tobacco has also led to poisoning; a case was reported where two brothers smoked 17 and 18 pipes of tobacco in succession and were both fatally poisoned. Spilling an extremely high concentration of nicotine onto the skin can result in intoxication or even death since nicotine readily passes into the bloodstream following skin contact.The recent rise in the use of electronic cigarettes, many forms of which are designed to be refilled with nicotine-containing "e-liquid" supplied in small plastic bottles, has renewed interest in nicotine overdoses, especially the possibility of young children ingesting the liquids. A 2015 Public Health England report noted an "unconfirmed newspaper report of a fatal poisoning of a two-year old child" and two published case reports of children of similar age who had recovered after ingesting e-liquid and vomiting. They also noted case reports of suicides by nicotine, where adults drank liquid containing up to 1,500 mg of nicotine. | 11
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Expectations should be managed so that patients understand the unfortunate inevitability of the disorder; however, they should also be assured that most cases of anagen effluvium are reversible and they will grow hair once chemotherapy is ceased. Patients should be instructed to avoid chemical trauma to the hair. This includes hot appliances, bleach, or color treatments in the time leading up to and during chemotherapy. If possible, patients should be given resources to obtain hairpieces or protective scarves before hair loss and educated on the benefits such garments offer, including cold protection in addition to the aesthetic component. Differential Diagnosis
The differential diagnosis for anagen effluvium includes other nonscarring alopecias such as telogen effluvium, trichotillomania, and androgenetic alopecia. These entities can be distinguished by history, hair pull test, and trichoscopy. A thorough review of systems should be completed to exclude other causes of hair loss such as nutritional deficiencies, metabolic and endocrine disorders, and infections. See also
Telogen effluvium
Noncicatricial alopecia
List of cutaneous conditions
References
== External links == | Neither drug affected latency if treatment was delayed for several months. See also
Penciclovir
Valaciclovir
References
External links
Famvir product website run by Novartis | 0-1
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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. | Chlorzoxazone (INN) is a centrally acting muscle relaxant used to treat muscle spasm and the resulting pain or discomfort. It can also be administered for acute pain in general and for tension headache (muscle contraction headache). It acts on the spinal cord by depressing reflexes. It is sold under the brand names Lorzone, Paraflex and Muscol and in combination form as Parafon Forte, a combination of chlorzoxazone and acetaminophen (paracetamol). Possible side effects include dizziness, lightheadedness, malaise, nausea, vomiting, and liver dysfunction. Used with acetaminophen it has added risk of hepatotoxicity,. Like metaxalone, its mechanism of action is still in question. It is believed that metaxalone works by altering serotonin levels and acting as a mild MAO inhibitor. The mechanism of action of chlorzoaxazone is thought to act on Gaba-A & B receptors and voltage-gated calcium channels to a degree. General central nervous system depression is the only currently accepted aspect to its medical benefits. Elucidation of the exact mechanism of action is ongoing but there is limited study due to the existence of more effective, safe muscle relaxants (ex. diazepam, cyclobenzaprine, tizanidine), greatly limiting the potential benefit of identifying novel compounds which share chlorzoxazones mechanism of action. See also
Zoxazolamine
References
Further reading
External links
"Chlorzoxazone". Drug Information Portal. U.S. National Library of Medicine. Chloroxazone Safety Data Sheet Archived 2019-07-12 at the Wayback Machine
D.F. Marsh, U.S. Patent 2,895,877 (1959) | 0-1
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Endurance sports
Marathon runners are susceptible to water intoxication if they drink too much while running. This is caused when sodium levels drop below 135 mmol/L when athletes consume large amounts of fluid. This has been noted to be the result of the encouragement of excessive fluid replacement by various guidelines. This has largely been identified in marathon runners as a dilutional hyponatremia. A study conducted on runners completing the 2002 Boston Marathon found that thirteen percent finished the race with hyponatremia. The study concluded that the strongest predictor of hyponatremia was weight gain while racing (over-hydration), and hyponatremia was just as likely to occur in runners who chose sports drinks as those who chose water. Military training
Hyponatremia and other physical conditions associated with water intoxication are more often seen in those participating in military training. One US Army study found 17 trainees were admitted to hospital over a years period for water intoxication while another found that three soldiers had died, leading to a recommendation that no more than 1-1.5L of water should be consumed per hour of heavy sweating. Overexertion and heat stress
Any activity or situation that promotes heavy sweating can lead to water intoxication when water is consumed to replace lost fluids. Persons working in extreme heat and/or humidity for long periods must take care to drink and eat in ways that help to maintain electrolyte balance. | Current investigations into the superiority of using biological grafting versus native tissue or surgical mesh indicates that using grafts provides better results. Epidemiology
A large study found a rate of 29% over the lifetime of a woman. Other studies indicate a recurrence rate as low as 3%.In the US, greater than 200,000 surgeries are performed each year for pelvic organ prolapse and 81% of these are to correct cystocele. Cystocele occurs most frequently compared to the prolapse of other pelvic organs and structure. Cystocele is found to be three times as common as vaginal vault prolapse and twice as often as posterior vaginal wall defects. The incidence of cystocele is around 9 per 100 women-years. The highest incidence of symptoms occurs between ages of 70 and 79 years. Based on population growth statistics, the number of women with prolapse will increase by a minimum of 46% by the year 2050 in the US. Surgery to correct prolapse after hysterectomy is 3.6 per 1,000 women-years. History
Notable is the mention of cystocele in many older cultures and locations. In 1500 B.C. Egyptians wrote about the "falling of the womb". In 400 B.C. a Greek physician documented his observations and treatments:
"After the patient had been tied to a ladder-like frame, she was tipped upward so that her head was toward the bottom of the frame. The frame was then moved upward and downward more or less rapidly for approximately 3–5 min. | 0-1
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Daptomycin, sold under the brand name Cubicin among others, is a lipopeptide antibiotic used in the treatment of systemic and life-threatening infections caused by Gram-positive organisms.Daptomycin was removed from the World Health Organizations List of Essential Medicines in 2019. The World Health Organization classifies daptomycin as critically important for human medicine. Medical uses
In the United States, daptomycin is indicated for use in adults for skin and skin structure infections caused by Gram-positive infections, S. aureus bacteraemia, and right-sided S. aureus endocarditis. It binds avidly to pulmonary surfactant, so cannot be used in the treatment of pneumonia. There seems to be a difference in working daptomycin on hematogenous pneumonia. Adverse effects
Common adverse drug reactions associated with daptomycin therapy include:
Cardiovascular: low blood pressure, high blood pressure, swelling
Central nervous system: insomnia
Dermatological: rash
Gastrointestinal: diarrhea, abdominal pain
Hematological: eosinophilia
Respiratory: dyspnea
Other: injection site reactions, fever, hypersensitivityLess common, but serious adverse events reported in the literature include
Hepatotoxicity: elevated transaminases
Nephrotoxicity: acute kidney injury from rhabdomyolysisAlso, myopathy and rhabdomyolysis have been reported in patients simultaneously taking statins, but whether this is due entirely to the statin or whether daptomycin potentiates this effect is unknown. Due to the limited data available, the manufacturer recommends that statins be temporarily discontinued while the patient is receiving daptomycin therapy. Creatine kinase levels are usually checked regularly while individuals undergo daptomycin therapy. In July 2010, the FDA issued a warning that daptomycin could cause life-threatening eosinophilic pneumonia. The FDA said it had identified seven confirmed cases of eosinophilic pneumonia between 2004 and 2010 and an additional 36 possible cases. | Drospirenone/estetrol, sold under the brand name Nextstellis among others, is a fixed-dose combination medication containing drospirenone, a progestin, and estetrol, an estrogen, which is used as a combined birth control pill for the prevention of pregnancy in women. It is taken by mouth.It was approved for medical use in Canada in March 2021, and in the United States in April 2021. Medical uses
Drospirenone/estetrol is used as a combined birth control pill to prevent pregnancy in women. Side effects
Estetrol-containing birth control pills, similarly to estradiol-containing birth control pills, may have a lower risk of venous thromboembolism (VTE) than ethinylestradiol-containing birth control pills based on studies of coagulation. However, it is likely that another decade will be required before post-marketing epidemiological studies of VTE incidence with these birth control pills are completed and able to confirm this. Pharmacology
Pharmacodynamics
Drospirenone/estetrol has a much lower impact on liver protein synthesis, including of sex hormone-binding globulin, angiotensinogen, and coagulation factors, than does ethinylestradiol/drospirenone. Society and culture
Legal status
Drospirenone/estetrol is approved for the use of hormonal contraception in the European Union, the United States, and Canada. Brand names
Drospirenone/estetrol in sold under the brand names Nexstellis, Drovelis, and Lydisilka. See also
Birth control pill formulations
List of combined sex-hormonal preparations § Estrogens and progestogens
References
External links
"Drospirenone". Drug Information Portal. U.S. National Library of Medicine. "Estetrol". Drug Information Portal. U.S. National Library of Medicine. | 0-1
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The two main causes for this condition are sudden impact due to fall, and coccydynia caused by childbirth pressure in women. Other ways that coccydynia develops are partial dislocation of the sacrococcygeal synchondrosis that can possibly result in abnormal movement of the coccyx from excessive sitting, and repetitive trauma of the surrounding ligaments and muscles, resulting in inflammation of tissues and pain. Diagnosis
A number of different conditions can cause pain in the general area of the coccyx, but not all involve the coccyx and the muscles attached to it. The first task of diagnosis is to determine whether the pain is related to the coccyx. Physical rectal examination, high resolution x-rays and MRI scans can rule out various causes unrelated to the coccyx, such as Tarlov cysts and pain referred from higher up the spine. Note that, contrary to most anatomical textbooks, most coccyxes consist of several segments: fractured coccyx is often diagnosed when the coccyx is in fact normal or just dislocated at an intercoccygeal joint.A simple test to determine whether the coccyx is involved is injection of local anesthetic into the area. | Other studies have shown prevalence rates in Brazil of 9.9%,
Egypt 13.49%,
Romania 5.1%,
Turkey 12% where higher rates were seen in those with poor socioeconomic conditions,
and just 1% in school children in Hong Kong. In 1963, one school health clinic reported features of pityriasis alba in two fifths of their children. History
It was first described in 1923. Having been known under a variety of names, the term Pityriasis alba, coined in 1956, has stayed. See also
Leprosy
List of cutaneous conditions
Vitiligo which, by comparison, causes total loss of skin colour or on the face and tends to occur around the mouth and eyes. References
== External links == | 0-1
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Observation of monosomy 7 within the marrow is well correlated with an increased risk of developing AML and with a very poor prognosis, death generally ensuing within 2 years (unless prompt allogeneic hematopoietic progenitor cell transplant is an option). Acute myeloid leukemia
FA patients are at elevated risk for the development of AML defined as presence of 20% or more of myeloid blasts in the marrow or 5 to 20% myeloid blasts in the blood. All of the subtypes of AML can occur in FA with the exception of promyelocytic. However, myelomonocytic and acute monocytic are the most common subtypes observed. Many MDS patients diseases evolve into AML if they survive long enough. Furthermore, the risk of developing AML increases with the onset of bone-marrow failure.Although risk of developing either MDS or AML before the age of 20 is only 27%, this risk increases to 43% by the age of 30 and 52% by the age of 40. Historically, even with a marrow transplant, about a quarter of FA patients diagnosed with MDS/ALS have died from MDS/ALS-related causes within two years, although more recent published evidence suggests that earlier allogeneic hematopoietic progenitor cell transplantation in children with FA is leading to better outcomes over time. Bone marrow failure
The last major haematological complication associated with FA is bone marrow failure, defined as inadequate blood cell production. Several types of failure are observed in FA patients, and generally precede MDS and AML. | Treatment
The first line of therapy is androgens and hematopoietic growth factors, but only 50–75% of patients respond. A more permanent cure is hematopoietic stem cell transplantation. If no potential donors exist, a savior sibling can be conceived by preimplantation genetic diagnosis (PGD) to match the recipients HLA type. Prognosis
Many patients eventually develop acute myelogenous leukemia (AML). Older patients are extremely likely to develop head and neck, esophageal, gastrointestinal, vulvar and anal cancers. Patients who have had a successful bone marrow transplant and, thus, are cured of the blood problem associated with FA still must have regular examinations to watch for signs of cancer. Many patients do not reach adulthood.The overarching medical challenge that Fanconi patients face is a failure of their bone marrow to produce blood cells. In addition, Fanconi patients normally are born with a variety of birth defects. A significant number of Fanconi patients have kidney problems, trouble with their eyes, developmental delay and other serious defects, such as microcephaly (small head). References
External links
Fanconi Anemia Research Fund
GeneReviews/NCBI/NIH/UW entry on Fanconi Anemia
OMIM entries on Fanconi Anemia
Fanconi anemia at Curlie
Fanconis Anaemia on patient.info | 11
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Fewer than 5% of the cases assumed to exist have been diagnosed, and most diabetes clinics around the world are checking for KCNJ11 mutations in any persons who developed apparent insulin-dependent diabetes without the typical type 1 antibodies before 6 months of age. At least some of these people have been able to change from insulin to sulfonylurea pills after decades of injections. See also
Transient neonatal diabetes mellitus
References
External links
GeneReviews/NCBI/NIH/UW entry on Permanent Neonatal Diabetes Mellitus
DiabetesGenes - Information about diagnosis, testing and treatment of neonatal diabetes | To minimise the cleft, it is necessary to fix together the metacarpals which used to border the cleft. Through repositioning flaps, the wound can be closed. Ueba
Ueba described a less complicated surgery. Transverse flaps are used to resurface the palm, the dorsal side of the transposed digit and the ulnar part of the first web space. A tendon graft is used to connect the common extensor tendons of the border digits of the cleft to prevent digital separation during extension. The closure is simpler, but has cosmetic disadvantage because of the switch between palmar and dorsal skin. Miura and Komada
The release of the first webspace has the same principle as the Snow-Littler procedure. The difference is the closure of the first webspace; this is done by simple closure or closure with Z-plasties. History
Literature shows that cleft hand is described centuries ago. The first reference to what might be considered a cleft hand was by Ambroise Paré in 1575. Hartsink (1770) wrote the first report of true cleft hand. In 1896, the first operation of the cleft hand was performed by Doctor Charles N. Dowed of New York City. However, the first certain description of what we know as a cleft hand as we know it today was described at the end of the 19th century. Symbrachydactyly
Historically, a U-type cleft hand was also known as atypical cleft hand. The classification in which typical and atypical cleft hand are described was mostly used for clinical aspects and is shown in table 1. | 0-1
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Blocking of the eustachian tube leads to decreased pressure in the middle ear relative to the external ear, and this causes decreased motion of both the ossicles and the tympanic membrane. Acute or Serous otitis media
Chronic suppurative otitis media (CSOM)
Perforated eardrum
Tympanosclerosis or scarring of the eardrum
Cholesteatoma
Eustachian Tube Dysfunction, inflammation or mass within the nasal cavity, middle ear, or eustachian tube itself
Otosclerosis, abnormal growth of bone in or near the middle ear
Middle ear tumour
Ossicular discontinuity as a consequence of infection or temporal bone trauma
Congenital malformation of the ossicles. This can be an isolated phenomenon or can occur as part of a syndrome where development of the 1st and 2nd branchial arches is seen such as in Goldenhar syndrome, Treacher Collins syndrome, branchio-oto-renal syndrome etc. Barotrauma unequal air pressures in the external and middle ear. This can temporarily occur, for example, by the environmental pressure changes as when shifting altitude, or inside a train going into a tunnel. It is managed by any of various methods of ear clearing manoeuvres to equalize the pressures, like swallowing, yawning, or the Valsalva manoeuvre. More severe barotrauma can lead to middle ear fluid or even permanent sensorineural hearing loss. Inner ear
Third window effect caused by:
Superior canal dehiscence – which may require surgical correction. Enlarged vestibular aqueduct
Labyrinthine fistula
Presentation
Conductive hearing loss makes all sounds seem faint or muffled. The hearing loss is usually worse in lower frequencies. Congenital conductive hearing loss is identified through newborn hearing screening or may be identified because the baby has microtia or other facial abnormalities. | Causes
It is important to distinguish association and causation. The vast majority of trigger digits are idiopathic, meaning there is no known cause. Some speculate that repetitive forceful use of a digit leads to narrowing of the fibrous digital sheath in which it runs, but there is little scientific data to support this theory. The relationship of trigger finger to work activities is debatable and there are arguments for and against a relationship to hand use with no experimental evidence supporting a relationship. Diagnosis
Diagnosis is made on interview and physical examination. More than one finger may be affected at a time. It is most common in the thumb and ring finger. The triggering more often occurs while gripping an object firmly or during sleep when the palm of the subject’s hand remains closed for an extended period of time. Upon waking, the affected person may have to force the triggered fingers open with their other hand. In some, this can be a daily occurrence. Treatment
Corticosteroid injections can cure trigger digits. Treatment consists of injection of a corticosteroid such as methylprednisolone often combined with a local anesthetic (lidocaine) at the A1 pulley in the palm. The infiltration of the affected site is straightforward using standard anatomic landmarks. There is evidence that the steroid does not need to enter the sheath. The role of sonographic guidance is therefore debatable. Injection of the tendon sheath with a corticosteroid is effective over weeks to months in more than half of people. | 0-1
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This fibrosis occurs only many years after the infection and is presumed to be caused in part by soluble egg antigens and various immune cells that react to them.Recent research has shown that granuloma size is consistent with levels of IL-13, which plays a prominent role in granuloma formation and granuloma size. IL-13 receptor α 2 (IL-13Rα2) binds IL-13 with high affinity and blocks the effects of IL-13. Thus, this receptor is essential in preventing the progression of schistosomiasis from the acute to the chronic (and deadly) stage of disease. Synthetic IL-13Rα2 given to mice has resulted in significant decreases in granuloma size, implicating IL-13Rα2 as an important target in schistosomiasis.S. mansoni infection often occurs alongside those of viral hepatitis, either hepatitis B virus (HBV) or hepatitis C virus (HCV). This is due to high prevalence of schistosomiasis in areas where chronic viral hepatitis is prevalent. One important factor was the development of large reservoir of infection due to extensive schistosomiasis control programs that used intravenously administered tartar emetic since the 1960s. Co-infection is known to cause earlier liver deterioration and more severe illness. Evasion of host immunity
Adult and larval worms migrate through the hosts blood circulation avoiding the hosts immune system. The worms have many tools that help in this evasion, including the tegument, antioxidant proteins, and defenses against host membrane attack complex (MAC). The tegument coats the worm and acts as a physical barrier to host antibodies and complement. | (1995) tested the effect of temperature and pH on the ability of developing S. mansoni to lyse red blood cells. The researchers found that the parasites were best able to destroy red blood cells for their nutrients at a pH of 5.1 and a temperature of 37 °C. Locomotion
Schistosoma mansoni is locomotive in primarily two stages of its life cycle: as cercariae swimming freely through a body of freshwater to locate the epidermis of their human hosts, and as developing and fully-fledged adults, migrating throughout their primary host upon infection. Cercariae are attracted to the presence of fatty acids on the skin of their definitive host, and the parasite responds to changes in light and temperature in their freshwater medium to navigate towards the skin. Ressurreicao et al. (2015) tested the roles of various protein kinases in the ability of the parasite to navigate its medium and locate a penetrable host surface. Extracellular signal-regulated kinase and protein kinase C both respond to changes in medium temperature and light levels, and the stimulation of p38 mitogen-activated protein kinase, associated with recognition of parasite host surface, results in a glandular secretion that deteriorates the host epidermis, and allows the parasite to burrow into its host. The parasites nervous system contains bilobed ganglia and several nerve cords which splay out to every surface of the body; serotonin is a transmitter distributed widely throughout the nervous system and plays an important role in nervous reception, and stimulating mobility. | 11
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Interactions
If diazepam is administered concomitantly with other drugs, attention should be paid to the possible pharmacological interactions. Particular care should be taken with drugs that potentiate the effects of diazepam, such as barbiturates, phenothiazines, opioids, and antidepressants.Diazepam does not increase or decrease hepatic enzyme activity, and does not alter the metabolism of other compounds. No evidence would suggest diazepam alters its own metabolism with chronic administration.Agents with an effect on hepatic cytochrome P450 pathways or conjugation can alter the rate of diazepam metabolism. These interactions would be expected to be most significant with long-term diazepam therapy, and their clinical significance is variable. Diazepam increases the central depressive effects of alcohol, other hypnotics/sedatives (e.g., barbiturates), other muscle relaxants, certain antidepressants, sedative antihistamines, opioids, and antipsychotics, as well as anticonvulsants such as phenobarbital, phenytoin, and carbamazepine. The euphoriant effects of opioids may be increased, leading to increased risk of psychological dependence. Cimetidine, omeprazole, oxcarbazepine, ticlopidine, topiramate, ketoconazole, itraconazole, disulfiram, fluvoxamine, isoniazid, erythromycin, probenecid, propranolol, imipramine, ciprofloxacin, fluoxetine, and valproic acid prolong the action of diazepam by inhibiting its elimination. Alcohol in combination with diazepam may cause a synergistic enhancement of the hypotensive properties of benzodiazepines and alcohol. Oral contraceptives significantly decrease the elimination of desmethyldiazepam, a major metabolite of diazepam. Rifampin, phenytoin, carbamazepine, and phenobarbital increase the metabolism of diazepam, thus decreasing drug levels and effects. Dexamethasone and St Johns wort also increase the metabolism of diazepam. Diazepam increases the serum levels of phenobarbital. Nefazodone can cause increased blood levels of benzodiazepines. | In humans, tolerance to the anticonvulsant effects of diazepam occurs frequently. Dependence
Improper or excessive use of diazepam can lead to dependence. At a particularly high risk for diazepam misuse, substance use disorder or dependence are:
People with a history of a substance use disorder or substance dependence Diazepam increases craving for alcohol in problem alcohol consumers. Diazepam also increases the volume of alcohol consumed by problem drinkers. People with severe personality disorders, such as borderline personality disorderPatients from the aforementioned groups should be monitored very closely during therapy for signs of abuse and development of dependence. Therapy should be discontinued if any of these signs are noted, although if dependence has developed, therapy must still be discontinued gradually to avoid severe withdrawal symptoms. Long-term therapy in such instances is not recommended.People suspected of being dependent on benzodiazepine drugs should be very gradually tapered off the drug. Withdrawals can be life-threatening, particularly when excessive doses have been taken for extended periods of time. Equal prudence should be used whether dependence has occurred in therapeutic or recreational contexts.Diazepam is a good choice for tapering for those using high doses of other benzodiazepines since it has a long half-life thus withdrawal symptoms are tolerable. The process is very slow (usually from 14 to 28 weeks) but is considered safe when done appropriately. | 11
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Prognosis
The table below lists life expectancy for patients who are diagnosed with MND. Terminology
In the United States and Canada, the term motor neuron disease usually refers to the group of disorders while amyotrophic lateral sclerosis is frequently called Lou Gehrigs disease. In the United Kingdom and Australia, the term motor neuron(e) disease is used for amyotrophic lateral sclerosis, although is not uncommon to refer to the entire group.While MND refers to a specific subset of similar diseases, there are numerous other diseases of motor neurons that are referred to collectively as "motor neuron disorders", for instance the diseases belonging to the spinal muscular atrophies group. However, they are not classified as "motor neuron diseases" by the 11th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-11), which is the definition followed in this article. See also
Spinal muscular atrophies
Hereditary motor and sensory neuropathies
References
External links
Media related to Motor neuron diseases at Wikimedia Commons
Motor neuron diseases at NINDS | The next year the CDC and the National Human Genome Research Institute sponsored an examination of haemochromatosis following the discovery of the HFE gene, which helped lead to the population screenings and estimates that are still being used today. See also
Human iron metabolism
Iron deficiency
References
External links
Iron overload at Curlie
GeneReview/NCBI/NIH/UW entry on HFE-Associated Hereditary Hemochromatosis
GeneReview/NCBI/NIH/UW entry on TFR2-Related Hereditary Hemochromatosis
GeneReview/NCBI/NIH/UW entry on Juvenile Hereditary Hemochromatosis
GeneReview/NCBI/NIH/UW entry on Aceruloplasminemia | 0-1
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Future treatments
Although no treatments have been approved for use in human PVL patients, a significant amount of research is occurring in developing treatments for protection of the nervous system. Researchers have begun to examine the potential of synthetic neuroprotection to minimize the amount of lesioning in patients exposed to ischemic conditions. Prognosis
The prognosis of patients with PVL is dependent on the severity and extent of white matter damage. Some children exhibit relatively minor deficits, while others have significant deficits and disabilities. Minor tissue damage
Minor white matter damage usually is exhibited through slight developmental delays and deficits in posture, vision systems, and motor skills. Many patients exhibit spastic diplegia, a condition characterized by increased muscle tone and spasticity in the lower body. The gait of PVL patients with spastic diplegia exhibits an unusual pattern of flexing during walking. Progression
Those patients with severe white matter injury typically exhibit more extensive signs of brain damage. Infants with severe PVL suffer from extremely high levels of muscle tone and frequent seizures. Children and adults may be quadriplegic, exhibiting a loss of function or paralysis of all four limbs. Cerebral palsy
Many infants with PVL eventually develop cerebral palsy. The percentage of individuals with PVL who develop cerebral palsy is generally reported with significant variability from study to study, with estimates ranging from 20% to more than 60%. One of the reasons for this discrepancy is the large variability in severity of cerebral palsy. This range corresponds to the severity of PVL, which can also be quite variable. | This generally leads to a BUN:Cr ratio > 20 and a fractional excretion of Na of < 1% and an elevated urine osmolarity. Primary renal azotemia
Renal azotemia (acute kidney failure) typically leads to uremia. It is an intrinsic disease of the kidney, generally the result of kidney parenchymal damage. Causes include kidney failure, glomerulonephritis, acute tubular necrosis, or other kidney disease.The BUN:Cr in renal azotemia is less than 15. In cases of kidney disease, glomerular filtration rate decreases, so nothing gets filtered as well as it normally would. However, in addition to not being normally filtered, what urea does get filtered is not reabsorbed by the proximal tubule as it normally would be. This results in lower levels of urea in the blood and higher levels of urea in the urine as compared to creatinine. Creatinine filtration decreases, leading to a higher amount of creatinine in the blood. Third spacing of fluids such as peritonitis, osmotic diuresis, or low aldosterone states such as Addisons disease all elevate urea. Postrenal azotemia
Blockage of urine flow in an area below the kidneys results in postrenal azotemia. It can be caused by congenital abnormalities such as vesicoureteral reflux, blockage of the ureters by kidney stones, pregnancy, compression of the ureters by cancer, prostatic hyperplasia, or blockage of the urethra by kidney or bladder stones. Like in prerenal azotemia, there is no inherent renal disease. The increased resistance to urine flow can cause back up into the kidneys, leading to hydronephrosis.The BUN:Cr in postrenal azotemia is initially >15. | 0-1
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Therefore, any individuals who could become pregnant are advised to eat foods fortified with folic acid or take supplements in addition to eating folate-rich foods to reduce the risks of serious birth defects. In Canada, mandatory fortification of selected foods with folic acid had been shown to reduce the incidence of neural tube defects by 46% compared to incidence prior to mandatory fortification. However, relying on eating a folate-rich diet alone is not recommended for preventing neural tube defects when trying to conceive because a regular diet usually does not contain enough folate to reach pregnancy requirements. All individuals who have the ability to become pregnant are advised to get 400 micrograms of folic acid daily. This daily 400 mcg dose of folic acid can be found in most multivitamins advertised as for women. Higher doses can be found in pre-natal multivitamins but those doses may not be necessary for everyone. Individuals who have previously given birth to a child with a neural tube defect and are trying to conceive again may benefit from a supplement containing 4.0 mg daily, following advice provided by their doctor. In Canada, guidelines on folic acid intake when trying to conceive is based on a risk assessment of how likely they are to experience a neural tube defect during pregnancy. Risk is divided into high, moderate, and low risk categories. High risk would include those that had a past experience with neural tube defects, either themselves or during another pregnancy. | Theories regarding the causes of hydrancephaly include:
blockage in the carotid artery: some researchers think that a blockage of the carotid artery leads to the under-/no development of the brain. The carotid artery is the most important blood supplier of the brain. With a blockage, the brain barely receives blood. Blood is necessary for development and keeping intact of the brain. inherited condition. infections: during the pregnancy, a woman can develop an infection in the uterus what can lead to problems with the neural tube. environmental toxins: during the pregnancy, a woman can be exposed to environmental toxins what can have effect on the health of the infant. Iniencephaly
Iniencephaly is a rare neural tube defect that results in extreme bending of the head to the spine. The diagnosis can usually be made on antenatal ultrasound scanning, but if not will undoubtedly be made immediately after birth because the head is bent backwards and the face looks upwards. Usually the neck is absent. The skin of the face connects directly to the chest and the scalp connects to the upper back. Individuals with iniencephaly generally die within a few hours after birth. Spina bifida
Spina bifida is further divided into two subclasses, spina bifida cystica and spina bifida occulta. Spina bifida cystica includes meningocele and myelomeningocele. Meningocele is less severe and is characterized by herniation of the meninges, but not the spinal cord, through the opening in the spinal canal. Myelomeningocele involves herniation of the meninges as well as the spinal cord through the opening. | 11
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Raloxifene may infrequently cause serious blood clots to form in the legs, lungs, or eyes. Other reactions experienced include leg swelling/pain, trouble breathing, chest pain, and vision changes. Black box warnings were added to the label of raloxifene in 2007 warning of increased risk of death due to stroke for postmenopausal women with documented coronary heart disease or at increased risk for major coronary events, as well as increased risk for deep vein thrombosis and pulmonary embolism. The risk of venous thromboembolism with raloxifene is increased by several-fold in postmenopausal women (RR = 3.1). Raloxifene has a lower risk of thromboembolism than tamoxifen. In the MORE trial, raloxifene caused a 40% decrease in risk of cardiovascular events in women who were at increased risk for coronary artery disease, although there was no decrease in cardiovascular events for the group as a whole.A report in September 2009 from Health and Human Services Agency for Healthcare Research and Quality suggests that tamoxifen and raloxifene used to treat breast cancer, significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects.A recent human case report in July 2016 suggests that raloxifene may in fact, at some point, also stimulate breast cancer growth leading to a reduction of advanced breast cancer disease upon the withdrawal of the drug.Unlike other SERMs, such as tamoxifen, raloxifene has no risk of uterine hyperplasia or endometrial cancer (RR = 0.8).Raloxifene does not increase the incidence of breast pain or tenderness in postmenopausal women. | Research
Clinical studies of raloxifene for metastatic breast cancer in women have been conducted but found little effectiveness at 60 mg/day in those previously treated with tamoxifen, though modest effectiveness has been observed at higher doses. In contrast to tamoxifen, raloxifene is not approved for the treatment of breast cancer.Raloxifene has been studied in men for a variety of uses, such as for treatment of schizophrenia, prostate cancer, and osteoporosis. It has been studied in combination with castration and bicalutamide, a nonsteroidal antiandrogen, for the treatment of prostate cancer.Raloxifene has been studied as an adjunct in the treatment of schizophrenia in postmenopausal women. A 2017 meta-analysis concluded that it was safe and effective for this indication, although further studies with larger sample sizes are needed for confirmation. It may be effective in women with less severe symptoms.A tissue-selective estrogen-receptor complex (TSEC) of estradiol and raloxifene has been studied in postmenopausal women.Raloxifene (60 mg/day) was reported to be effective in the treatment of pubertal gynecomastia in adolescent boys in a small retrospective chart review. Other SERMs are also known to be effective in the treatment of gynecomastia.Raloxifene has been reported to augment the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs).June 18th 2020, Exscalate4CoV, the private-public consortium supported by the EU’s Horizon 2020 programme for research and innovation, led by Dompé farmaceutici and currently representing 18 partners (including Fraunhofer Institute, CINECA, Chelonia Applied Science, Swiss Institute of Bioinformatics and others) has requested access to clinical trials for the use of Raloxifene in COVID-19 patients. | 11
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After 1 day, patients exhibited significant improvement in day and night pain as well as clinician global evaluation when taking Donnatal® tablets and belladonna alkaloids, but the phenobarbital group also was statistically better for day and night pain, and the placebo group for day pain. Females taking Donnatal® tablets were 4 times more likely to experience weeks free of daytime pain compared to phenobarbital alone and twice as likely to experience weeks free of nighttime pain compared to belladonna alkaloids. Only the phenobarbital group demonstrated a significant change in pain type compared to belladonna alkaloids at the end of the study with an approximate 48% response rate. Patients on Donnatal® tablets, belladonna alkaloids, and placebo all had non-significant (p > 0.149) shifts to dull pain, 39.5%, 52.3%, and 40.4%, respectively compared to belladonna alkaloids eline. Males also showed a greater response for pain free-weeks on phenobarbital in comparison to Donnatal® tablets. All groups demonstrated an improvement in bowel movement frequency. FDA status
Donnatal® is considered part of the DESI drug category and currently is listed as one of 14 drugs still under evaluation by the FDA. In response to FDA questions about Donnatal® efficacy, A. H. Robins Co. filed abbreviated new drug applications for Donnatal® tablets (ANDA 86-676), capsules (ANDA 86-677), and Elixir (ANDA 86-661). These ANDAs, with the exception of the capsule formulation, are still in force today and the FDA has not changed the review status of Donnatal® as being conditionally approved for its indication. | Donnatal is a combination medication that provides natural belladonna alkaloids in a specific fixed ratio combined with phenobarbital to provide peripheral anticholinergic/antispasmodic action and mild sedation. Donnatal is manufactured for Concordia Pharmaceuticals by IriSys, LLC. It is available as tablets and 5 mL elixir. Active ingredients are listed as: phenobarbital (16.2 mg), hyoscyamine sulfate (0.1037 mg), atropine sulfate (0.0194 mg), and scopolamine hydrobromide (0.0065 mg). The latter two ingredients are found in plants of the family Solanaceae, such as belladonna. Indication
Based on a review of this drug by the National Academy of Sciences–National Research Council and/or other information, FDA has classified the indications as follows: "possibly" effective: For use as adjunctive therapy in the treatment of irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis. May also be useful as adjunctive therapy in the treatment of duodenal ulcer. History
Clinical Research with Combinations of Belladonna Alkaloids and Phenobarbital
Clinical studies have been performed on different combinations of belladonna alkaloids and phenobarbital over the last 70 years. For example, Steigmann et al. evaluated a combination of 0.25 mg belladonna alkaloids and 50 mg phenobarbital on gastrointestinal symptoms in 93 patients. The population included 33 IBS patients. Eighteen out of 33 patients reported complete relief of symptoms and 13 reported fair response with partial relief within 24 hours. Only 2 IBS patients reported no response. | 11
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Because of this, primidone is a Category D medication.Primidone, like phenobarbital and the benzodiazepines, can also cause sedation in the newborn and also withdrawal within the first few days of life; phenobarbital is the most likely out of all of them to do that.In May 2005, Dr. M. Lopez-Gomezs team reported an association between the use of primidone and depression in epilepsy patients; this same study reported that inadequate seizure control, posttraumatic epilepsy, and polytherapy were also risk factors. Polytherapy was also associated with poor seizure control. Out of all of the risk factors, usage of primidone and inadequate seizure control were the greatest; with ORs of 4.089 and 3.084, respectively. They had been looking for factors associated with depression in epilepsy patients. Schaffer et al. 1999 reported that one of their treatment failures, a 45-year-old woman taking 50 mg a day along with lithium 600 mg/day, clozapine 12.5 mg/day, trazodone 50 mg/day, and alprazolam 4 mg/day for three and a half months experienced auditory hallucinations that led to discontinuation of primidone. It can also cause hyperactivity in children; this most commonly occurs at low serum levels. There is one case of an individual developing catatonic schizophrenia when her serum concentration of primidone went above normal.Primidone is one of the anticonvulsants associated with anticonvulsant hypersensitivity syndrome, others being carbamazepine, phenytoin, and phenobarbital. | Blood blisters can also occur in the mouth for a variety of reasons including side effects to certain medications, nutritional deficiencies, and mouth injuries. Treatment
There are several methods of healing blood blisters, including elevation of the wound combined with application of a cold pack, and application of padded dressings or splints. See also
Bleeding – Loss of blood escaping from the circulatory system
Blister – Small pocket of fluid within the upper layers of the skin
Bruise – Type of localized bleeding in tissues outside blood vessels
Cherry angioma – Small bright red dome-shaped bump on the skin
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For Cushings syndrome (glucocorticoid excess), these include weight gain, muscle wasting, purple lines on the abdomen, a fatty "buffalo hump" on the neck, a "moon-like" face, and thinning, fragile skin. Virilism (androgen excess) is most obvious in women, and may produce excess facial and body hair, acne, enlargement of the clitoris, deepening of the voice, coarsening of facial features, cessation of menstruation. Conn syndrome (mineralcorticoid excess) is marked by high blood pressure, which can result in headache and hypokalemia (low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations), low plasma renin activity, and high serum aldosterone. Feminization (estrogen excess) is most readily noted in men, and includes breast enlargement, decreased libido, and impotence. Pathophysiology
The main etiologic factor of ACC is unknown, although families with Li–Fraumeni syndrome, caused by an inherited inactivation mutation in TP53, have increased risk. Several genes have been shown to be recurrently mutated, including TP53, CTNNB1, MEN1, PRKAR1A, RPL22, and DAXX. The telomerase gene TERT is often amplified while ZNRF3 and CDKN2A are often homozygously deleted. The genes h19, insulin-like growth factor II (IGF-II), and p57kip2 are important for fetal growth and development. They are located on chromosome 11p. Expression of the h19 gene is markedly reduced in both nonfunctioning and functioning adrenal cortical carcinomas, especially in tumors producing cortisol and aldosterone. Also, a loss occurs of activity of the p57kip2 gene product in virilizing adenomas and adrenal cortical carcinomas. In contrast, IGF-II gene expression has been shown to be high in adrenal cortical carcinomas. | Pathology
Adrenal tumors are often not biopsied prior to surgery, so diagnosis is confirmed on examination of the surgical specimen by a pathologist. Grossly, ACCs are often large, with a tan-yellow cut surface, and areas of hemorrhage and necrosis. On microscopic examination, the tumor usually displays sheets of atypical cells with some resemblance to the cells of the normal adrenal cortex. The presence of invasion and mitotic activity help differentiate small cancers from adrenocortical adenomas. Several relatively rare variants of ACC include:
Oncocytic adrenal cortical carcinoma
Myxoid adrenal cortical carcinoma
Carcinosarcoma
Adenosquamous adrenocortical carcinoma
Clear cell adrenal cortical carcinoma
Differential diagnosis
Differential diagnosis includes:
Adrenocortical adenoma
Renal cell carcinoma
Pheochromocytoma
Hepatocellular carcinomaAdrenocortical carcinomas are most commonly distinguished from adrenocortical adenomas (their benign counterparts) by the Weiss system, as follows:
Total score indicates:
0-2: Adrenocortical adenoma
3: Undetermined
4-9: Adrenocortical carcinoma
Treatment
The only curative treatment is complete surgical excision of the tumor, which can be performed even in the case of invasion into large blood vessels, such as the renal vein or inferior vena cava. The 5-year survival rate after successful surgery is 50–60%, but unfortunately, many patients are not surgical candidates. Radiation therapy and radiofrequency ablation may be used for palliation in patients who are not surgical candidates. Minimally invasive surgical techniques remain controversial due to the absence of long-term data, with a particular concern for rates of recurrence and peritoneal carcinomatosis.Chemotherapy regimens typically include the drug mitotane, an inhibitor of steroid synthesis, which is toxic to cells of the adrenal cortex, as well as standard cytotoxic drugs. | 11
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A third daughter cell may end up with the missing chromosome. Multipolar spindles: more than two spindle poles form. Such a mitotic division would result in one daughter cell for each spindle pole; each cell may possess an unpredictable complement of chromosomes. Monopolar spindle: only a single spindle pole forms. This produces a single daughter cell with its copy number doubled. A tetraploid intermediate may be produced as the end-result of the monopolar spindle mechanism. In such a case, the cell has double the copy number of a normal cell, and produces double the number of spindle poles as well. This results in four daughter cells with an unpredictable complement of chromosomes, but in the normal copy number. Somatic mosaicism in the nervous system
Mosaicism for aneuploid chromosome content may be part of the constitutional make-up of the mammalian brain. In the normal human brain, brain samples from six individuals ranging from 2–86 years of age had mosaicism for chromosome 21 aneuploidy (average of 4% of neurons analyzed). This low-level aneuploidy appears to arise from chromosomal segregation defects during cell division in neuronal precursor cells, and neurons containing such aneuploid chromosome content reportedly integrate into normal circuits. However, recent research using single-cell sequencing has challenged these findings, and has suggested that aneuploidy in the brain is actually very rare. Somatic mosaicism in cancer
Aneuploidy is consistently observed in virtually all cancers. The German biologist Theodor Boveri was first to propose a causative role for aneuploidy in cancer. | For instance, one of the main predictors of a successful recovery is dependent on the number of continuous days a user is able to stay off of the substance. Alternative holistic treatments such as physical exercise and Meditation has been proven effective in reducing cocaine cravings. Other non-pharmacological treatments such as acupuncture and hypnosis have been explored, but without conclusive results. Medications
Numerous medications have been investigated for use in cocaine dependence, but as of 2015, none of them were considered to be effective. Anticonvulsants, such as carbamazepine, gabapentin, lamotrigine, and topiramate, do not appear to be effective as treatment. Limited evidence suggests that antipsychotics are also ineffective for treatment of cocaine dependence. Few studies have examined bupropion (a novel antidepressant) for cocaine dependence; however, trials performed thus far have not shown it to be an effective form of treatment for this purpose.The National Institute on Drug Abuse (NIDA) of the U.S. National Institutes of Health is researching modafinil, a narcolepsy drug and mild stimulant, as a potential cocaine treatment. Ibogaine has been under investigation as a treatment for cocaine dependency and is used in clinics in Mexico, the Netherlands and Canada. It was legal for a time in Costa Rica, but has been illegal since 2018. It is illegal to use in many countries, such as Sweden, Norway, the United Kingdom, and in the United States. Other medications that have been investigated for this purpose include acetylcysteine, baclofen, and vanoxerine. Medications such as phenelzine, have been used to cause an "aversion reaction" when administered with cocaine. | 0-1
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The plasma protein binding of norelgestromin is approximately 99% and it is bound to albumin but not to SHBG. Conversely, levonorgestrel is approximately 98% bound to plasma proteins and is bound to both albumin and SHBG.Norgestimate is extensively metabolized into its active metabolites during first-pass metabolism in the liver and intestines. The major metabolite of norgestimate is norelgestromin and is formed from norgestimate via deacetylation in the liver and intestines. A more minor metabolite of norgestimate is levonorgestrel, which accounts for 20 to 25% (22 ± 6%) of an administered dose or about 40 to 70 µg norgestimate, and a very minor metabolite of norgestimate is levonorgestrel 17β-acetate. Both of these metabolites are active similarly to norgelstromin. With a typical oral contraceptive dosage of norgestimate of 200 to 250 µg/day, an amount of 50 to 60 µg/day levonorgestrel may be produced. This is similar to the ovulation-inhibiting dosage of levonorgestrel, and suggests that norgestimate may act in considerable part as a prodrug specifically of levonorgestrel. Following their formation, the active metabolites of norgestimate are inactivated via reduction, hydroxylation, and conjugation into levonorgestrel metabolites. The terminal half-life of norelgestromin is between 17 and 37 hours and of levonorgestrel is between 24 and 32 hours. The metabolites of norgestimate are eliminated 47% in urine and 37% in feces. Unchanged norgestimate is undetectable in urine. Chemistry
Norgestimate, also known as 17α-ethynyl-18-methyl-19-nortestosterone 3-oxime 17β-acetate or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one 3-oxime 17β-acetate, is a synthetic estrane steroid and a derivative of testosterone. It is a racemic mixture of E and Z isomers. | In addition to their lack of affinity for the androgen receptor, norgestimate and norelgestromin have virtually no affinity for SHBG, and therefore do not displace testosterone from this carrier protein (although levonorgestrel does still bind with high affinity to SHBG and hence could increase free testosterone levels via occupation of SHBG). In accordance, clinical trials of norgestimate have observed minimal androgenic side effects in women treated with the medication. As an example, clinical studies have found that norgestimate does not appreciably inhibit the increase in SHBG levels produced by ethinylestradiol. This is of interest because estrogens increase and androgens decrease liver production of SHBG and by extension circulating levels of SHBG.The relative binding affinity of norgestimate and its metabolite norelgestromin for the rat prostatic androgen receptor (AR) are 0.3% and 1.3% of those of dihydrotestosterone (DHT), respectively, whereas the respective values for levonorgestrel and gestodene are 22% and 15%. Based on these findings, the ratios of AR to PR binding are 219 for norgestimate and 48 for norelgestromin, whereas the ratios for progesterone, levonorgestrel, and gestodene are 93, 11, and 28, respectively. As such, norgestimate and norelgestromin would appear to have much lower androgenic potency than other 19-nortestosterone progestins. However, levonorgestrel is an important metabolite of both norgestimate and norelgestromin, and it may serve to increase their androgenic potency to some degree.When norgestimate is combined with ethinylestradiol, which is potently antiandrogenic, there are only antiandrogenic effects overall and the combination is suitable for treatment of hyperandrogenism. | 11
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Their most distinctive external feature is the presence of two suckers, one close to the mouth, and the other on the underside of the animal.The body surface of trematodes comprises a tough syncytial tegument, which helps protect against digestive enzymes in those species that inhabit the gut of larger animals. It is also the surface of gas exchange; there are no respiratory organs.The mouth is located at the forward end of the animal, and opens into a muscular, pumping pharynx. The pharynx connects, via a short oesophagus, to one or two blind-ending caeca, which occupy most of the length of the body. In some species, the caeca are themselves branched. As in other flatworms, there is no anus, and waste material must be egested through the mouth.Although the excretion of nitrogenous waste occurs mostly through the tegument, trematodes do possess an excretory system, which is instead mainly concerned with osmoregulation. This consists of two or more protonephridia, with those on each side of the body opening into a collecting duct. The two collecting ducts typically meet up at a single bladder, opening to the exterior through one or two pores near the posterior end of the animal.The brain consists of a pair of ganglia in the head region, from which two or three pairs of nerve cords run down the length of the body. The nerve cords running along the ventral surface are always the largest, while the dorsal cords are present only in the Aspidogastrea. | This stage is known as the sporocyst and it forms a central body in the snails digestive gland that extends into a brood sac in the snails head, muscular foot and eye-stalks. It is in the central body of the sporocyst where the parasite replicates itself, producing many tiny embryos (redia). These embryos move to the brood sac and mature into cercaria. Life cycle adaptations
Trematodes have a large variation of forms throughout their life cycles. Individual trematode parasites life cycles may vary from this list. They have five larval stages along with the cystic and fully matured adult phases. Trematodes are released from the definitive host as eggs, which have evolved to withstand the harsh environment
Released from the egg which hatches into the miracidium. This infects the first intermediate host in one of two ways, either active or passive transmission. The first host is normally a mollusk. a) Active transmission has adapted for dispersal in space as a free swimming ciliated miracidium with adaptations for recognizing and penetrating the first intermediate host. b) Passive transmission has adapted for dispersal in time and infects the first intermediate host contained within the egg. The sporocyst forms inside the snail first intermediate host and feeds through diffusion across the tegument. The rediae also forms inside the snail first intermediate host and feeds through a developed pharynx. Either the rediae or the sporocyst develops into the cercariae through polyembryony in the snail. The cercariae are adapted for dispersal in space and exhibit a large variety in morphology. | 11
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These are congregations of proteins and lipids (including sphingolipids and cholesterol) that float within the cell membrane, and play a role in the regulation of membrane function. Lipid rafts are more ordered or rigid than the membrane bilayer surrounding them. Their involvement in regulation stems mostly from their association with proteins; upon binding substrates, some proteins have a higher affinity for attaching to lipid rafts. This brings them in close proximity with other proteins, allowing them to affect signaling pathways. Cholesterol specifically acts as a spacer and a glue for lipid rafts; absence of cholesterol leads to the dissociation of proteins.Given its prevalence in cell membranes, cholesterol is highly involved in certain transport processes. It may influence the function of ion channels and other membrane transporters. For example, cholesterol is necessary for the ligand binding activity of the serotonin receptor. In addition, it appears to be very important in exocytosis. Cholesterol modulates the properties of the membrane (such as membrane curvature), and may regulate the fusion of vesicles with the cell membrane. It may also facilitate the recruitment of complexes necessary for exocytosis. Given that neurons rely heavily on exocytosis for the transmission of impulses, cholesterol is a very important part of the nervous system. One particularly relevant pathway in which cholesterol takes place is the Hedgehog signaling pathway. This pathway is very important during embryonic development, and involved in deciding the fate of cells (i.e., which tissue they need to migrate to). | An ingrown nail, also known as onychocryptosis from Greek: ὄνυξ (onyx) nail and κρυπτός (kryptos) hidden, is a common form of nail disease. It is an often painful condition in which the nail grows so that it cuts into one or both sides of the paronychium or nail bed. While ingrown nails can occur in the nails of both the hands and the feet, they occur most commonly with the toenails (as opposed to fingernails), and for the most part are only problematic and painful on the big toe. A common conception is that the nail enters into the paronychium, but an "ingrown toenail" can simply be overgrown toe skin. The condition starts first from a microbial inflammation of the paronychium, and then a granuloma, which results in a nail buried inside of the granuloma. A true ingrown toenail is caused by actual penetration of flesh by a sliver of toenail. Signs and symptoms
Symptoms of an ingrown nail include pain along the margins of the nail (caused by hypergranulation that occurs around the aforementioned margins), worsening of pain when wearing tight footwear, and sensitivity to pressure of any kind, even the weight of bedsheets. Bumping of an affected toe can produce sharp and even excruciating pain as the tissue is punctured further by the nail. By the very nature of the condition, ingrown nails become easily infected unless special care is taken early to treat the condition by keeping the area clean. | 0-1
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The conclusion of the Cochrane Review was that further research could modify what is now regarding the effectiveness of the evaluated interventions.The Institute for Occupational Safety and Health of the German Social Accident Insurance has created a hearing impairment calculator based on the ISO 1999 model for studying threshold shift in relatively homogeneous groups of people, such as workers with the same type of job. The ISO 1999 model estimates how much hearing impairment in a group can be ascribed to age and noise exposure. The result is calculated via an algebraic equation that uses the A-weighted sound exposure level, how many years the people were exposed to this noise, how old the people are, and their sex. The models estimations are only useful for people without hearing loss due to non-job related exposure and can be used for prevention activities. | This choice depends on the level of hearing loss, type of hearing loss, and personal preference. Hearing aid applications are one of the options for hearing loss management. For people with bilateral hearing loss, it is not clear if bilateral hearing aids (hearing aids in both ears) are better than a unilateral hearing aid (hearing aid in one ear). Epidemiology
Globally, hearing loss affects about 10% of the population to some degree. It caused moderate to severe disability in 124.2 million people as of 2004 (107.9 million of whom are in low and middle income countries). Of these 65 million acquired the condition during childhood. At birth ~3 per 1000 in developed countries and more than 6 per 1000 in developing countries have hearing problems.Hearing loss increases with age. In those between 20 and 35 rates of hearing loss are 3% while in those 44 to 55 it is 11% and in those 65 to 85 it is 43%.A 2017 report by the World Health Organization estimated the costs of unaddressed hearing loss and the cost-effectiveness of interventions, for the health-care sector, for the education sector and as broad societal costs. Globally, the annual cost of unaddressed hearing loss was estimated to be in the range of $750–790 billion international dollars. The International Organization for Standardization (ISO) developed the ISO 1999 standards for the estimation of hearing thresholds and noise-induced hearing impairment. | 11
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Treatment with oral supplementation of high amounts of riboflavin is lifesaving.Other inborn errors of metabolism include riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency, also known as a subset of glutaric acidemia type 2, and the C677T variant of the methylenetetrahydrofolate reductase enzyme, which in adults has been associated with risk of high blood pressure. Diagnosis and assessment
The assessment of riboflavin status is essential for confirming cases with non-specific symptoms whenever deficiency is suspected. Total riboflavin excretion in healthy adults with normal riboflavin intake is about 120 micrograms per day, while excretion of less than 40 micrograms per day indicates deficiency. Riboflavin excretion rates decrease as a person ages, but increase during periods of chronic stress and the use of some prescription drugs.Indicators used in humans are erythrocyte glutathione reductase (EGR), erythrocyte flavin concentration and urinary excretion. The erythrocyte glutathione reductase activity coefficient (EGRAC) provides a measure of tissue saturation and long-term riboflavin status. Results are expressed as an activity coefficient ratio, determined by enzyme activity with and without the addition of FAD to the culture medium. An EGRAC of 1.0 to 1.2 indicates that adequate amounts of riboflavin are present; 1.2 to 1.4 is considered low, greater than 1.4 indicates deficient. For the less sensitive "erythrocyte flavin method", values greater than 400 nmol/L are considered adequate and values below 270 nmol/L are considered deficient. Urinary excretion is expressed as nmol of riboflavin per gram of creatinine. Low is defined as in the range of 50 to 72 nmol/g. Deficient is below 50 nmol/g. | A study of monoclonal protein levels conducted in Ghana showed a prevalence of MGUS of approximately 5.9% in African men over the age of 50.In 2009, prospective data demonstrated that all or almost all cases of multiple myeloma are preceded by MGUS. In addition to multiple myeloma, MGUS may also progress to Waldenströms macroglobulinemia or primary amyloidosis. See also
Monoclonal gammopathy
Plasma cell dyscrasia
Monoclonal gammopathy of renal significance
References
Further reading
== External links == | 0-1
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In the study, nutritional supplementation contained 250kcal, consisting of 6g of lipids, 40g of carbohydrates, 9g of protein, vitamins and minerals, consumed three times per day. Nutritional intervention also significantly prolonged the time between the diagnosis of TTTS and delivery (9.4 ± 3.7 weeks versus 4.6 ± 6.5 weeks; P = 0.014). The earlier nutritional regimen was introduced, the lesser chance of detecting TTTS ( P = 0.001). Although not statistically significant, dietary intervention was also associated with lower Quintero stage, fewer invasive treatments, and lower twin birth weight discordance.Diet supplementation appears to counter maternal metabolic abnormalities in monochorionic twin pregnancies and improve perinatal outcomes in TTTS when combined with the standard therapeutic options. Nutritional therapy appears to be most effective in mitigating cases that are caught in Quintero Stage I, little effect has been observed in those that are beyond Stage I. Epidemiology
Based on recent (2005) US NCHS data, the rate of multiple births is now approximately 3.4% (4,138,349 total births, of which 139,816 were twins or higher-order multiple births). The majority of identical twins share a common (monochorionic) placenta, and of these approximately 15% go on to develop TTTS. | Even with treatment, the condition is associated with premature birth and a risk of cerebral palsy in a surviving fetus. Around 5–15% of identical twin fetuses will go on to develop TTTS. The condition was first described by German obstetrician Friedrich Schatz in 1875. Cause
As a result of sharing a single placenta, the blood supplies of monochorionic twin fetuses can become connected, so that they share blood circulation: although each fetus uses its own portion of the placenta, the connecting blood vessels within the placenta allow blood to pass from one twin to the other. It is thought that most monochorionic placentae have these "shared connections" that cross the placenta, with the net flow volumes being equal between them. This state is sometimes referred to as "flow balance". When the placenta has deep vein–artery connection, this can cause blood flow to become unbalanced.Depending on the number, type and direction of the interconnecting blood vessels (anastomoses), blood can be transferred disproportionately from one twin (the "donor") to the other (the "recipient"), due to a state of "flow imbalance" imparted by new blood vessel growth across the placental "equator", the line that divides each babys proportion of the shared placenta. This state of transfusion causes the donor twin to have decreased blood volume, retarding the donors development and growth, and also decreased urinary output, leading to a lower than normal level of amniotic fluid (becoming oligohydramnios). | 11
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Management
Management depends upon the presenting symptoms. In most people who are hemodynamically stable without high-risk coronary involvement, conservative medical management with blood pressure control is recommended. In these people, especially if angiography demonstrates adequate coronary flow, the most likely course usually leads to spontaneous healing, often within 30 days. Anti-coagulation should be discontinued upon diagnosis of SCAD on coronary angiography as continuation of anti-coagulation may lead to hematoma and dissection propagation.In cases involving high-risk coronaries, hemodynamic instability, or a lack of improvement or worsening after initial attempts at treatment, urgent treatment with coronary stents or coronary artery bypass surgery may be necessary. Stents carry the risk of worsening the dissection or have an increased risk of other complications as the vessel walls in SCAD are already weak due to the disease before introducing the stent. Large studies into coronary artery bypass surgery are lacking, but this approach is used to redirect blood to the heart around the affected area for cases involving the left main coronary artery or when other approaches fail.Angina, or chest pain due to coronary insufficiency may persist for months after SCAD, sometimes even when repeat angiography shows vessel healing. Anti-anginal agents such as nitrates, calcium channel blockers and ranolazine are indicated as anti-anginal pharmacologic agents after SCAD. Control of hypertension is also indicated after SCAD, with beta blockers especially showing a reduction in the recurrence of SCAD. | Monorchism (also monorchidism) is the state of having only one testicle within the scrotum. Terminology
An individual having monorchism can be referred to as monorchid. Causes
This can be due to:
One testicle not descending into the scrotum during normal embryonic or fetal development (3–4% of normal live births), also known as undescended testis or cryptorchidism. In this case the testis is within the abdominal cavity, somewhere along the normal route of descent – most commonly, within the inguinal canal. Such a testis has an increased risk of malignancy. One testicle may disappear during development (the so-called vanishing testis) due to some intrauterine insult. This is thought to be most likely vascular, such as testicular torsion. One testicle may have been surgically removed through orchiectomy. One testicle may be injured. Notable cases
Due to testicular cancer
Lance Armstrong, American bicyclist. Ashley Gray, Ironman triathlete
Frank Church, late U.S. Senator and a presidential aspirant in 1976. His monorchism was revealed publicly during the 1976 presidential campaign. Tom Green, Canadian comedian-actor. Richard Herring, English comedian and writer
John Kruk, former baseball player
Mark Latham, former Australian politician. Geoff Horsfield, English footballer. Nenê, Brazilian basketball player. Kevin Curtis, American football player. Nigel Farage, former leader of the UK Independence Party. Bobby Moore, English footballer and World Cup winner. Jimmy White, English snooker player. Due to injury
Archibald Douglas, 4th Earl of Douglas, magnate of the Kingdom of Scotland, and Peer of France. Lost in 1403, while fighting at the Battle of Shrewsbury (The previous year he had lost an eye at the Battle of Homildon Hill). | 0-1
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Enzymatic production of adenosine can be anti-inflammatory or immunosuppressive. Adenosine receptors
All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further classified based on their ability to either stimulate or inhibit adenylate cyclase activity. The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates adenylate cyclase activity. In addition, A1 receptors couple to Go, which has been reported to mediate adenosine inhibition of Ca2+ conductance, whereas A2B and A3 receptors also couple to Gq and stimulate phospholipase activity. Researchers at Cornell University have recently shown adenosine receptors to be key in opening the blood-brain barrier (BBB). Mice dosed with adenosine have shown increased transport across the BBB of amyloid plaque antibodies and prodrugs associated with Parkinsons disease, Alzheimers, multiple sclerosis, and cancers of the central nervous system. Ghrelin/growth hormone secretagogue receptor
Adenosine is an endogenous agonist of the ghrelin/growth hormone secretagogue receptor. However, while it is able to increase appetite, unlike other agonists of this receptor, adenosine is unable to induce the secretion of growth hormone and increase its plasma levels. Mechanism of action
When it is administered intravenously, adenosine causes transient heart block in the atrioventricular (AV) node. This is mediated via the A1 receptor, inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing K+ efflux via inward rectifier K+ channels, subsequently inhibiting Ca2+ current. It also causes endothelial-dependent relaxation of smooth muscle as is found inside the artery walls. | Lymphangiomatosis is a condition where a lymphangioma is not present in a single localised mass, but in a widespread or multifocal manner. It is a rare type of tumor which results from an abnormal development of the lymphatic system.It is thought to be the result of congenital errors of lymphatic development occurring prior to the 20th week of gestation. Lymphangiomatosis is a condition marked by the presence of cysts that result from an increase both in the size and number of thin-walled lymphatic channels that are abnormally interconnected and dilated. 75% of cases involve multiple organs. It typically presents by age 20 and, although it is technically benign, these deranged lymphatics tend to invade surrounding tissues and cause problems due to invasion and/or compression of adjacent structures. The condition is most common in the bones and lungs and shares some characteristics with Gorham’s disease. Up to 75% of patients with lymphangiomatosis have bone involvement, leading some to conclude that lymphangiomatosis and Gorham’s disease should be considered as a spectrum of disease rather than separate diseases. When it occurs in the lungs, lymphangiomatosis has serious consequences and is most aggressive in the youngest children. When the condition extends into the chest it commonly results in the accumulation of chyle in the linings of the heart and/or lungs.Chyle is composed of lymph fluid and fats that are absorbed from the small intestine by specialized lymphatic vessels called lacteals during digestion. | 0-1
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Insects, birds and mammals play roles in literature and film, such as in giant bug movies.Animals including insects and mammals feature in mythology and religion. In both Japan and Europe, a butterfly was seen as the personification of a persons soul, while the scarab beetle was sacred in ancient Egypt. Among the mammals, cattle, deer, horses, lions, bats, bears, and wolves are the subjects of myths and worship. The signs of the Western and Chinese zodiacs are based on animals. See also
Animal attacks
Animal coloration
Ethology
Fauna
List of animal names
Lists of organisms by population
Notes
References
External links
Tree of Life Project Archived 12 June 2011 at the Wayback Machine
Animal Diversity Web – University of Michigans database of animals
ARKive – multimedia database of endangered/protected species | Lichen myxedematosus is a group of cutaneous disorders considered mucinoses. : 183 Conditions included in this group are:: 183
Generalized lichen myxedematosus
Localized lichen myxedematosusDiscrete papular lichen myxedematosus
Acral persistent papular mucinosis
Self-healing papular mucinosisSelf-healing juvenile cutaneous mucinosisPapular mucinosis of infancy
Atypical lichen myxedematosus
Atypical tuberous myxedema
See also
List of cutaneous conditions
References
== External links == | 0-1
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If the patient has focal neurological deficits, papilledema, a Glasgow Coma Score less than 12, or a recent history of seizures, lumbar puncture should be reconsidered.Differential diagnosis for viral meningitis includes meningitis caused by bacteria, mycoplasma, fungus, and drugs such as NSAIDS, TMP-SMX, IVIG. Further considerations include brain tumors, lupus, vasculitis, and Kawasaki disease in the pediatric population. Treatment
Because there is no clinical differentiation between bacterial and viral meningitis, people with suspected disease should be sent to the hospital for further evaluation. Treatment for viral meningitis is generally supportive. Rest, hydration, antipyretics, and pain or anti-inflammatory medications may be given as needed. However, if there is initial uncertainty as to whether the meningitis is bacterial or viral in origin, empiric antibiotics are often given until bacterial infection is ruled out.Herpes simplex virus, varicella zoster virus and cytomegalovirus have a specific antiviral therapy. For herpes the treatment of choice is aciclovir. If encephalitis is suspected, empiric treatment with IV aciclovir is often warranted.Surgical management is indicated where there is extremely increased intracranial pressure, infection of an adjacent bony structure (e.g. mastoiditis), skull fracture, or abscess formation.The majority of people that have viral meningitis get better within 7–10 days. Epidemiology
From 1988 to 1999, about 36,000 cases occurred each year. As recently as 2017, the incidence in the U.S. alone increased to 75,000 cases per year for enteroviral meningitis. | Pai syndrome, also known as Median cleft of the upper lip-corpus callosum lipoma-midline facial cutaneous polyps syndrome, is a very rare genetic disorder which is characterized by nervous system, cutaneous, ocular, nasal and bucal anomalies with facial dysmorphisms. Signs and symptoms
List of common symptoms:
Depressed nasal bridge
Median cleft lip
Central nervous system lipomas. Nasal polyposis
Presence of skin tags
Subcutaneous noduleList of not-so-common symptoms:[2]
Oral frenulum abnormalities
Bifid uvula
Hypertelorism
TelecanthusList of uncommon symptoms:[2]
Missing/underdeveloped corpus callosum
Down-slanting parpebral fissures
Encephalocele
Coloboma
Nose defects
Frontal bossing
High palate
Causes
A specific, shared genetic cause hasnt been found. The closest thing to it was a case reported by Masuno et al. of a Japanese girl with symptoms of the disorder plus short stature and intellectual disabilities with a spontaneous reciprocal translocation. This translocation involved chromosome Xq28 and chromosome 16q11.2 (more specifically, 46,X,t(X;16)(q28;q11.2). Epidemiology
According to OMIM, 18 cases have been described in medical literature, but according to ORPHAnet, 67 cases have been described. == References == | 0-1
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The announcer then reminded the listener that Anacin was available "at any drug counter", and "comes in handy (tin) boxes of 12 and 30, and economical family-size bottles of 50 and 100", usually spelling out its name at the end of the commercial.Anacin sponsored the first made-for-television sitcom, Mary Kay and Johnny. Unsure of how many viewers would be watching when they sponsored the show in 1947, Anacin ran a simple test, offering a free mirror to the first 200 viewers to write for one. The offer drew over 9,000 responses, overwhelming the sponsor but proving television was a viable advertising medium.Anacin was also a leading sponsor of the television soaps Love of Life, The Secret Storm and the early years of The Young and the Restless. Anacin is one of the earliest and best examples of a concerted television marketing campaign, created for them in the late 1950s by Rosser Reeves of the Ted Bates ad agency. Many people remember the commercials advertising "tension producing" situations, and the "hammers in the head" advertisement with the slogan "Tension. Pressure. Pain." An Anacin advertisement in 1962 featured a mother trying to assist her grown daughter with various chores, such as preparing a meal. "Dont you think it needs a little salt? ", the mother would say, only to have her nerve-racked daughter shout, "Mother, please, Id rather do it myself!" As the mother wilted, the daughter would emote and rub her head, with her inner voice saying, "Control yourself! | Sure, youve got a headache, youre tense, irritable, but dont take it out on her!" Another commercial had a wife greeting her husband as he pulled into their driveway in his car; the husband responded by yelling "Helen, cant you keep Billys bike out of the driveway?!?" These advertisement scenarios became popular and were parodied a number of times, including in the Allan Sherman song "Headaches", the 1966 film The Silencers and the 1980 film Airplane. The medication was mentioned in the book "The Shining" by Stephen King. Anacin had a large advertisement behind the center field fence of Yankee Stadium from the 1950s through 1973, until the stadiums 1974-75 renovation. Products
Anacin covers a family of pain relievers. There are currently two different formulations:
Anacin Regular Strength – contains 400 mg ASA (aspirin) and 32 mg caffeine per tablet. Anacin Max Strength – contains 500 mg ASA and 32 mg caffeine per tablet. Side effects
Anacins side effects may include dizziness, heartburn, irritability, nausea, nervousness, rashes, hives, bloody stools, drowsiness, hearing loss, ringing in the ears, and trouble sleeping. See also
Anadin, an Anacin brand sold in the United Kingdom, launched in 1932. References
External links
Official website
Prestige Brands Anacin
Insight Pharmaceuticals - Anacin | 11
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They may show up as restlessness, irritability, increased sexual frustration, apathy, sluggishness, neediness, dissatisfaction with a mate, or weepiness over the days or weeks after intense sexual stimulation. Such phenomena may be part of human mating physiology itself. Sexual headache is a distinct condition characterized by headaches that usually begin before or during orgasm. Mechanism
The cause of POIS is unknown. Some doctors hypothesize that POIS is caused by an auto-immune reaction. Other doctors suspect a hormone imbalance as the cause. Different causes have also been proposed. None of the proposed causes fully explain the disease. Allergy hypothesis
According to one hypothesis, "POIS is caused by Type-I and Type-IV allergy to the males own semen". This was conditioned by another study stating "IgE-mediated semen allergy in men may not be the potential mechanism of POIS".Alternatively, POIS could be caused by an auto-immune reaction not to semen, but to a different substance released during ejaculation, such as cytokines. Hormone hypothesis
According to another hypothesis, POIS is caused by a hormone imbalance, such as low progesterone, low cortisol, low testosterone, elevated prolactin, hypothyroidism, or low DHEA.POIS could be caused by a defect in neurosteroid precursor synthesis. If so, the same treatment may not be effective for all individuals. Different individuals could have different missing precursors leading to a deficiency of the same neurosteroid, causing similar symptoms. Withdrawal hypothesis
The majority of POIS symptoms like fatigue, muscle pains, sweating, mood disturbances, irritability, and poor concentration are also caused by withdrawal from different drug classes and natural reinforcers. | A study in 2017 correlated several inflammatory diseases of the respiration tract with objective evidence of damp-caused damage in homes.The WHO has classified the reported symptoms into broad categories, including: mucous membrane irritation (eye, nose, and throat irritation), neurotoxic effects (headaches, fatigue, and irritability), asthma and asthma-like symptoms (chest tightness and wheezing), skin dryness and irritation, gastrointestinal complaints and more.Several sick occupants may report individual symptoms which do not appear to be connected. The key to discovery is the increased incidence of illnesses in general with onset or exacerbation within a fairly close time frame – usually within a period of weeks. In most cases, SBS symptoms will be relieved soon after the occupants leave the particular room or zone. However, there can be lingering effects of various neurotoxins, which may not clear up when the occupant leaves the building. In some cases – particularly in sensitive individuals – there can be long-term health effects. Cause
ASHRAE has recognized that polluted urban air, designated within the United States Environmental Protection Agency (EPA)s air quality ratings as unacceptable, requires the installation of treatment such as filtration for which the HVAC practitioners generally apply carbon-impregnated filters and their likes. Different toxins will aggravate the human body in different ways. Some people are more allergic to mold, while others are highly sensitive to dust. Inadequate ventilation will exaggerate small problems (such as deteriorating fiberglass insulation or cooking fumes) into a much more serious indoor air quality problem. | 0-1
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According to Homer, the Cyclopes have no ships, nor ship-wrights, nor other craftsman, and know nothing of agriculture. They have no regard for Zeus or the other gods, for the Cyclopes hold themselves to be "better far than they".Homer says that "godlike" Polyphemus, the son of Poseidon and the nymph Thoosa, the daughter of Phorcys, is the "greatest among all the Cyclopes". Homer describes Polyphemus as a shepherd who:
mingled not with others, but lived apart, with his heart set on lawlessness. For he was fashioned a wondrous monster, and was not like a man that lives by bread, but like a wooded peak of lofty mountains, which stands out to view alone, apart from the rest, ... [and as] a savage man that knew naught of justice or of law. Although Homer does not say explicitly that Polyphemus is one-eyed, for the account of his blinding to make sense he must be. If Homer meant for the other Cyclopes to be assumed (as they usually are) to be like Polyphemus, then they too will be one-eyed sons of Poseidon; however Homer says nothing explicit about either the parentage or appearance of the other Cyclopes. Euripides
The Hesiodic Cyclopes: makers of Zeus thunderbolts, the Homeric Cyclopes: brothers of Polyphemus, and the Cyclopean wall-builders, all figure in the plays of the fifth-century BC playwright Euripides. In his play Alcestis, where we are told that the Cyclopes who forged Zeus thunderbolts, were killed by Apollo. The prologue of that play has Apollo explain:
House of Admetus! | Fludroxycortide (INN, BAN, JAN), also known as flurandrenolide (USAN) and flurandrenolone, is a synthetic topical corticosteroid and is used as an anti-inflammatory treatment for use on skin irritations. Trade names include Haelan (Typharm, UK) and Cordran (by Watson Pharmaceuticals, US).Fludroxycortide is available in ointment, cream and as an impregnated tape (Haelan tape, Cordran tape). Licensed indications in the United Kingdom include recalcitrant dermatoses. == References == | 0-1
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However, zinc supplements should not be administered alone, because many in the developing world have several deficiencies, and zinc interacts with other micronutrients. While zinc deficiency is usually due to insufficient dietary intake, it can be associated with malabsorption, acrodermatitis enteropathica, chronic liver disease, chronic renal disease, sickle cell disease, diabetes, malignancy, and other chronic illnesses.In the United States, a federal survey of food consumption determined that for women and men over the age of 19, average consumption was 9.7 and 14.2 mg/day, respectively. For women, 17% consumed less than the EAR, for men 11%. The percentages below EAR increased with age. The most recent published update of the survey (NHANES 2013–2014) reported lower averages – 9.3 and 13.2 mg/day – again with intake decreasing with age.Symptoms of mild zinc deficiency are diverse. Clinical outcomes include depressed growth, diarrhea, impotence and delayed sexual maturation, alopecia, eye and skin lesions, impaired appetite, altered cognition, impaired immune functions, defects in carbohydrate utilization, and reproductive teratogenesis. Zinc deficiency depresses immunity, but excessive zinc does also.Despite some concerns, western vegetarians and vegans do not suffer any more from overt zinc deficiency than meat-eaters. Major plant sources of zinc include cooked dried beans, sea vegetables, fortified cereals, soy foods, nuts, peas, and seeds. However, phytates in many whole-grains and fibers may interfere with zinc absorption and marginal zinc intake has poorly understood effects. The zinc chelator phytate, found in seeds and cereal bran, can contribute to zinc malabsorption. | Common causes include kidney failure, hypoaldosteronism, and rhabdomyolysis. A number of medications can also cause high blood potassium including spironolactone, NSAIDs, and angiotensin converting enzyme inhibitors.There is no universally accepted definition of what level of hyperkalemia is mild, moderate, or severe. However, if hyperkalemia causes any ECG change it is considered a medical emergency due to a risk of potentially fatal abnormal heart rhythms and is treated urgently. Potassium levels greater than 6.5 to 7.0 mmol/L in the absence of ECG changes are managed aggressively. Several approaches are used to treat hyperkalemia. Other approved potassium binders in the United States include patiromer and sodium polystyrene sulfonate.Hyperkalemia, particularly if severe, is a marker for an increased risk of death. However, there is disagreement regarding whether a modestly elevated levels directly causes problems. One viewpoint is that mild to moderate hyperkalemia is a secondary effect that denotes underlying medical problems. Accordingly, these problems are both proximate and ultimate causes of death,
History
Regulatory
In the United States, regulatory approval of ZS-9 was rejected by the Food and Drug Administration (FDA) in May 2016, due to issues associated with manufacturing. On May 18, 2018, the FDA approved sodium zirconium cyclosilicate for treatment of adults with hyperkalemia.It was first practically synthesized by UOP in the late 1990s. | 0-1
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Mycoplasma is a genus of bacteria that, like the other members of the class Mollicutes, lack a cell wall around their cell membranes. Peptidoglycan (murein) is absent. This characteristic makes them naturally resistant to antibiotics that target cell wall synthesis (like the beta-lactam antibiotics). They can be parasitic or saprotrophic. Several species are pathogenic in humans, including M. pneumoniae, which is an important cause of "walking" pneumonia and other respiratory disorders, and M. genitalium, which is believed to be involved in pelvic inflammatory diseases. Mycoplasma species (like the other species of the class Mollicutes) are among the smallest organisms yet discovered, can survive without oxygen, and come in various shapes. For example, M. genitalium is flask-shaped (about 300 x 600 nm), while M. pneumoniae is more elongated (about 100 x 1000 nm), many Mycoplasma species are coccoid. Hundreds of Mycoplasma species infect animals.The trivial name “mycoplasma” (plural mycoplasmas or mycoplasms) is commonly used for all members of the class Mollicutes. In scientific classification, the designation Mycoplasma refers exclusively to the genus, a member of the Mycoplasmataceae, the only family of the order Mycoplasmatales (see “scientific classification”). Etymology
The term "mycoplasma", from the Greek μύκης, mykes (fungus) and πλάσμα, plasma (formed), was first used by Albert Bernhard Frank in 1889 to describe an altered state of plant cell cytoplasm resulting from infiltration by fungus-like microorganisms. | 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. | 0-1
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Extracardiac manifestations include:
Macroglossia
Periorbital bruising
Loss of the third and fourth heart sound
Thromboembolisms
Symmetric sensory neuropathy (such as bilateral carpal tunnel)
Postural hypotension (secondary to autonomic neuropathy)
Nephrotic syndrome (secondary to free light chain damage to the kidneys/deposition of amyloid in the kidneys)
Cause
The general cause of cardiac amyloidosis is the misfolding of a specific protein precursor depending on the amyloidosis type. Protein precursors include immunoglobulin-derived light chains and transthyretin mutations. The misfolding of the protein causes it to have insoluble beta-pleated sheets, creating an amyloid. Amyloid, the aggregation, or clumping, of proteins, is resistant to degradation by the body. Amyloids are mostly fibrils, while also containing a P component, apolipoprotein, collagen, fibronectin, and laminin. The P component, a pentameric protein, stabilizes the fibrils of the amyloid, which reduces their clearance from the body. Deposits of the amyloids can occur throughout the body, including the heart, liver, kidneys, spleen, adrenal glands, and bones. Deposits in the extracellular cardiac space can stiffen the heart, resulting in restriction of the ventricles. This restriction in ventricular motion results in a decreased ability for the heart to pump efficiently, leading to the various symptoms associated with cardiac amyloidosis. Diagnosis
Echocardiography
Echocardiography is a safe and non-invasive method that can be used to assess the structural and functional disease of the heart. Amyloidosis presents with ventricle and valvular thickening, biatrial enlargement, restrictive filling pattern, with normal to mildly reduced systolic function and decreased diastolic filling. An echo can be used to evaluate for prognosis of the disease, measuring the different strains within the heart. | Diagnostic tests includes serum and urine electrophoresis, laboratory testing for the determination of elevated levels of troponin and BNP, and ECGs showing low QRS voltages. Familial (ATTRm-CM)
This type is caused by mutations of proteins involved in amyloid formation, including transthyretin (TTR), fibrinogen, apolipoprotein A1, or apolipoprotein A2. Due to the multiple number of potential genetic causes the incidence of this form is variable. The vast majority of familial cardiac amyloidosis still present after the age of 60. A common mutation is the TTR gene mutation Val122Ile. It is estimated that 3.5–4% of African Americans in The United States have the Val 122lle mutation. This type of amyloidosis can be identified by genetic testing for protein mutation. For the diagnosis of familial cardiac amyloidosis to be made a biopsy with histological evaluation must be obtained. In this histological evaluation special stains are utilized to visualize the amyloid deposits. One such stain is Congo Red, which binds specifically to the amyloid deposit and can be characterized by various lighting methods. Under polarized light, the amyloid deposits while show pathognomonic apple green birefringence, and under plain light the deposits will appear a light salmon pink color. Familial amyloidosis symptoms are centered around neuropathological and cardiac problems. Cardiac manifestations of the TTR mutation present more often in The United States. Wild-type (ATTRwt-CM)
This type is considered the wild-type mutation which leads to the development of TTR deposits. It usually affects males over 70 years with the manifestation of carpal tunnel syndrome. | 11
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Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a subtype of chronic lymphocytic leukemia (CLL). Hairy cell leukemia makes up about 2% of all leukemias, with fewer than 2,000 new cases diagnosed annually in North America and Western Europe combined. Hairy cell leukemia (HCL) was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis, and its characterization was significantly advanced by Bertha Bouroncle and colleagues at the Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the "hairy" appearance of the malignant B cells under a microscope. Signs and symptoms
In HCL, the "hairy cells" (malignant B lymphocytes) accumulate in the bone marrow, interfering with the production of normal white blood cells, red blood cells, and platelets. Consequently, patients may develop infections related to low white blood cell count, anemia and fatigue due to a lack of red blood cells, or easy bleeding due to a low platelet count. | Senna glycoside, also known as sennoside or senna, is a medication used to treat constipation and empty the large intestine before surgery. The medication is taken by mouth or via the rectum. It typically begins working in around 30 minutes when given by rectum and within twelve hours when given by mouth. It is a weaker laxative than bisacodyl or castor oil.Common side effects of senna glycoside include abdominal cramps. It is not recommended for long-term use, as it may result in poor bowel function or electrolyte problems. While no harm has been found to result from use while breastfeeding, such use is not typically recommended. It is not typically recommended in children. Senna may change urine to a somewhat reddish color. Senna derivatives are a type of stimulant laxative and are of the anthraquinone type. While its mechanism of action is not entirely clear, senna is thought to act by increasing fluid secretion within and contraction of the large intestine.It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. Sennosides come from the group of plants Senna. In plant form, it has been used at least since the 700s CE. In 2019, it was the 344th most commonly prescribed medication in the United States, with fewer than one million prescriptions. It is sold under a number of brand names including Ex-Lax and Senokot. | 0-1
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It is generally regarded as a medical problem when at least 10% of a persons body weight has been lost in six months or 5% in the last month. Another criterion used for assessing weight that is too low is the body mass index (BMI). However, even lesser amounts of weight loss can be a cause for serious concern in a frail elderly person.Unintentional weight loss can occur because of an inadequately nutritious diet relative to a persons energy needs (generally called malnutrition). Disease processes, changes in metabolism, hormonal changes, medications or other treatments, disease- or treatment-related dietary changes, or reduced appetite associated with a disease or treatment can also cause unintentional weight loss. Poor nutrient utilization can lead to weight loss, and can be caused by fistulae in the gastrointestinal tract, diarrhea, drug-nutrient interaction, enzyme depletion and muscle atrophy.Continuing weight loss may deteriorate into wasting, a vaguely defined condition called cachexia. Cachexia differs from starvation in part because it involves a systemic inflammatory response. It is associated with poorer outcomes. In the advanced stages of progressive disease, metabolism can change so that they lose weight even when they are getting what is normally regarded as adequate nutrition and the body cannot compensate. This leads to a condition called anorexia cachexia syndrome (ACS) and additional nutrition or supplementation is unlikely to help. | Myths
Some popular beliefs attached to weight loss have been shown to either have less effect on weight loss than commonly believed or are actively unhealthy. According to Harvard Health, the idea of metabolic rate being the "key to weight" is "part truth and part myth" as while metabolism does affect weight loss, external forces such as diet and exercise have an equal effect. They also commented that the idea of changing ones rate of metabolism is under debate. Diet plans in fitness magazines are also often believed to be effective but may actually be harmful by limiting the daily intake of important calories and nutrients which can be detrimental depending on the person and are even capable of driving individuals away from weight loss. Health effects
Obesity increases health risks, including diabetes, cancer, cardiovascular disease, high blood pressure, and non-alcoholic fatty liver disease, to name a few. Reduction of obesity lowers those risks. A 1-kg loss of body weight has been associated with an approximate 1-mm Hg drop in blood pressure. Intentional weight loss is associated with cognitive performance improvements in overweight and obese individuals. See also
Anorexia
Cigarette smoking for weight loss
Dieting
Physical exercise
Weight gain
References
External links
Weight loss at Curlie
Health benefits of losing weight By IQWiG at PubMed Health
Weight-control Information Network Archived 12 February 2015 at the Wayback Machine U.S. National Institutes of Health
Nutrition in cancer care By NCI at PubMed Health
Unintentional weight loss | 11
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Erythromelalgia or Mitchells disease (after Silas Weir Mitchell) is a rare vascular peripheral pain disorder in which blood vessels, usually in the lower extremities or hands, are episodically blocked (frequently on and off daily), then become hyperemic and inflamed. There is severe burning pain (in the small fiber sensory nerves) and skin redness. The attacks are periodic and are commonly triggered by heat, pressure, mild activity, exertion, insomnia or stress. Erythromelalgia may occur either as a primary or secondary disorder (i.e. a disorder in and of itself or a symptom of another condition). Secondary erythromelalgia can result from small fiber peripheral neuropathy of any cause, polycythemia vera, essential thrombocytosis, hypercholesterolemia, mushroom or mercury poisoning, and some autoimmune disorders. Primary erythromelalgia is caused by mutation of the voltage-gated sodium channel α-subunit gene SCN9A. In 2004 erythromelalgia became the first human disorder in which it has been possible to associate an ion channel mutation with chronic neuropathic pain, when its link to the SCN9A gene was initially published in the Journal of Medical Genetics. Later that year, in an article in The Journal of Neuroscience, Cummins et al., demonstrated, using voltage clamp recordings, that these mutations enhanced the function of NaV1.7 sodium channels, which are preferentially expressed within peripheral neurons. | These differences in excitability alterations between the sympathetic nervous system and nociceptors is due to different expression of sodium channels other than NaV1.7 in them.What causes epidemic erythromelalgia in southern China remains unknown although several erythromelalgia-associated poxviruses were isolated from throat swabs of several patients at different counties and from two different seasons. Side effect of medication
Several medications, including verapamil and nifedipine, as well as ergot derivatives such as bromocriptine and pergolide, have been associated with medication-induced erythromelalgia. Mushroom poisoning
The consumption of two species of related fungi, Clitocybe acromelalga from Japan, and Clitocybe amoenolens from France, has led to several cases of mushroom-induced erythromelalgia which lasted from 8 days to 5 months. Possible infectious cause
An epidemic form of this syndrome occurs in secondary school students in rural areas of China. A large epidemic erythromelalgia was occurred in Hubei province of China in 1987 and the disease was characterized by burning pain in the toes and soles of the feet, accompanied by foot redness, congestion, and edema; a few patients had fever, palpitations, headache, and joint pain. 60.6% of patients had a common cold before the onset of erythromelalgia and 91.2% had pharyngitis. Subsequently, a virus - erythromelalgia-related poxvirus (ERPV) - was repeatedly isolated from throat swabs of six separate patients from two different counties and Wuhan city in Hubei province. The genome of this virus has been sequenced and it appears that this virus is related to a strain of mousepox. | 11
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Prolactin blood levels are typically correlated to the size the tumors. Pituitary tumors smaller than 10 mm in diameter, or microadenomas, tend to have prolactin levels <200 ng/mL. Macroadenomas larger than 10 mm in diameter possess prolactin >1000 ng/mL.Hyperprolactinemia inhibits the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which in turn inhibits the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland and results in diminished gonadal sex hormone production (termed hypogonadism). This is the cause of many of the symptoms described below. In many people, elevated prolactin levels remain unexplained and may represent a form of hypothalamic–pituitary–adrenal axis dysregulation. Physiological causes
Physiological (i.e., non-pathological) causes include: ovulation, pregnancy, breastfeeding, chest wall injury, stress, stress-associated REM sleep, and exercise. During pregnancy, prolactin levels can range up to 600 ng/mL, depending on estrogen concentration. At 6 weeks post-birth (postpartum), estradiol concentrations decrease, and prolactin concentrations return to normal even during breastfeeding. Stress-related factors include physical, exercise, hypoglycemia, myocardial infarction, and surgery. Coitus and sleep can also contribute to an increased prolactin release. Medications
Prolactin secretion in the pituitary is normally suppressed by the brain chemical dopamine, which binds to dopamine receptors. Drugs that block the effects of dopamine at the pituitary or deplete dopamine stores in the brain may cause the pituitary to secrete prolactin without an inhibitory effect. | If TSH levels are elevated, hyperprolactinemia is secondary to hypothyroidism and treated accordingly. If TSH levels are normal, an MRI or CT scan is conducted to assess for any pituitary adenomas. Although hyperprolactinemia is often uncommon in postmenopausal women, prolactinomas detected after menopause are typically macroadenomas. While a plain X-ray of the bones surrounding the pituitary may reveal the presence of a large macroadenoma, small microadenomas will not be apparent. Magnetic resonance imaging (MRI) is the most sensitive test for detecting pituitary tumors and determining their size. MRI scans may be repeated periodically to assess tumor progression and the effects of therapy. Computed Tomography (CT scan) is another indicator of abnormalities in pituitary gland size; it also gives an image of the pituitary, but is less sensitive than the MRI. In addition to assessing the size of the pituitary tumor, physicians also look for damage to surrounding tissues, and perform tests to assess whether production of other pituitary hormones are normal. Depending on the size of the tumor, physicians may request an eye exam that includes the measurement of visual fields.However, a high measurement of prolactin may also result from the presence of macroprolactin, otherwise known as big prolactin or big-big prolactin, in the serum. Macroprolactin occurs when prolactin polymerizes together and can bind with IgG to form complexes. Although this can result in high prolactin levels in some assay tests, macroprolactin is biologically inactive and will not cause symptoms typical of hyperprolactinemia. | 11
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Because of the temporal and spatial complexity of the developmental trajectory, there are many potential causes of neurodevelopmental disorders that may affect different areas of the nervous system at different times and ages. These range from social deprivation, genetic and metabolic diseases, immune disorders, infectious diseases, nutritional factors, physical trauma, and toxic and environmental factors. Some neurodevelopmental disorders, such as autism and other pervasive developmental disorders, are considered multifactorial syndromes which have many causes that converge to a more specific neurodevelopmental manifestation. Social deprivation
Deprivation from social and emotional care causes severe delays in brain and cognitive development. Studies with children growing up in Romanian orphanages during Nicolae Ceauşescus regime reveal profound effects of social deprivation and language deprivation on the developing brain. These effects are time-dependent. The longer children stayed in negligent institutional care, the greater the consequences. By contrast, adoption at an early age mitigated some of the effects of earlier institutionalization (abnormal psychology). Genetic disorders
A prominent example of a genetically determined neurodevelopmental disorder is Trisomy 21, also known as Down syndrome. This disorder usually results from an extra chromosome 21, although in uncommon instances it is related to other chromosomal abnormalities such as translocation of the genetic material. It is characterized by short stature, epicanthal (eyelid) folds, abnormal fingerprints, and palm prints, heart defects, poor muscle tone (delay of neurological development), and intellectual disabilities (delay of intellectual development).Less commonly known genetically determined neurodevelopmental disorders include Fragile X syndrome. | Acarbose (INN) is an anti-diabetic drug used to treat diabetes mellitus type 2 and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay (Bayer AG), in North America as Precose (Bayer Pharmaceuticals), and in Canada as Prandase (Bayer AG). It is cheap and popular in China, but not in the U.S. One physician explains the use in the U.S. is limited because it is not potent enough to justify the side effects of diarrhea and flatulence. However, a recent large study concludes "acarbose is effective, safe and well tolerated in a large cohort of Asian patients with type 2 diabetes." A possible explanation for the differing opinions is an observation that acarbose is significantly more effective in patients eating a relatively high carbohydrate Eastern diet.It is a starch blocker, and inhibits alpha glucosidase, an intestinal enzyme that releases glucose from larger carbohydrates. It is composed of an acarviosin moiety with a maltose at the reducing terminus. Acarbose is also degraded to maltose and acarviosin by the glucosidase cyclomaltodextrinase from gut bacteria Lactobacillus plantarum. Natural distribution
In nature, acarbose is synthesized by soil bacteria Actinoplanes sp through its precursor valienamine. And acarbose is also degraded by gut bacteria Lactobacillus plantarum and soil bacteria Thermus sp by acarbose degrading glucosidases. Mechanism of action
Acarbose inhibits enzymes (glycoside hydrolases) needed to digest carbohydrates, specifically, alpha-glucosidase enzymes in the brush border of the small intestines, and pancreatic alpha-amylase. It locks up the enzymes by mimicking the transisition state of the substrate with its amine linkage. | 0-1
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Among cases that are detected by routine amniocentesis or chorionic villus sampling, one study found that the prevalence of Turner syndrome among tested pregnancies was 5.58 and 13.3 times higher, respectively, than among live neonates in a similar population. Cause
Turner syndrome is caused by the absence of one complete or partial copy of the X chromosome in some or all the cells. The abnormal cells may have only one X (monosomy) (45,X) or they may be affected by one of several types of partial monosomy like a deletion of the short p arm of one X chromosome (46,X,del(Xp)) or the presence of an isochromosome with two q arms (46,X,i(Xq)) Turner syndrome has distinct features due to the lack of pseudoautosomal regions, which are typically spared from X-inactivation. In mosaic individuals, cells with X monosomy (45,X) may occur along with cells that are normal (46,XX), cells that have partial monosomies, or cells that have a Y chromosome (46,XY). The presence of mosaicism is estimated to be relatively common in affected individuals (67–90%).The (46,X,i(Xq) isochromosome in the Turner syndrome is classified as an small supernumerary marker chromosome (sSMC). Two of the types of sSMCs in this syndrome contain parts of the genetic material from either an X or, much less frequently, Y chromosome and may or may not contain an XIST gene. In normal females, the XIST gene occurs on the X chromosome inherited from her mother but not on the X chromosome inherited from her father. | : 84 In girls with Turner syndrome who do not experience spontaneous puberty, exogenous estrogen is used to induce and maintain feminization. Estrogen replacement is recommended to begin at around age 11–12, although some parents prefer to delay the induction of puberty in girls with lower social and emotional preparedness. The dose of estrogen in induced puberty begins at 10% of adult estrogen levels and is steadily increased at six-month intervals, with a full adult dose attained two to three years after the beginning of treatment. Estrogen replacement may interfere with growth hormone therapy, due to the closing effects of estrogen on growth plates; individuals must weigh up their preferences for taller height versus greater feminization. : 97–103
Fertility
Women with Turner syndrome are infertile. Only 2%–5% are capable of pregnancy without fertility treatment, most with mosaic karyotypes. Early in gestation, fetuses with Turner syndrome have a normal number of gametes in their developing ovaries, but this starts decreasingly rapidly as early as 18 weeks of pregnancy; by birth, girls with the condition have markedly reduced follicular counts. Women with Turner syndrome who wish to raise families but are incapable of conception with their own oocytes have the options of adoption or of pregnancy with donor eggs; the latter has a comparable success rate to donor pregnancy in women with 46,XX karyotypes.Pregnancy in Turner syndrome is inherently high-risk; the maternal death rate is 2%.Usually, estrogen replacement therapy is used to spur the growth of secondary sexual characteristics at the time when puberty should onset. | 11
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Desloratadine/pseudoephedrine, sold under the brand name Clarinex-D among others, is a medication used for the treatment of seasonal allergic rhinitis.Desloratadine/pseudoephedrine was approved for use in the United States in 2005 and in the European Union in July 2007. Medical uses
Desloratadine/pseudoephedrine is indicated for the symptomatic treatment of seasonal allergic rhinitis when accompanied by nasal congestion. References
Further reading
Anolik R (June 2009). "Desloratadine and pseudoephedrine combination therapy as a comprehensive treatment for allergic rhinitis and nasal congestion". Expert Opin Drug Metab Toxicol. 5 (6): 683–94. doi:10.1517/17425250902980187. PMID 19473112. S2CID 22633518. External links
"Desloratadine mixture with pseudoephedrine". Drug Information Portal. U.S. National Library of Medicine. | Haemophilus influenzae: 0.03 μg/mL - 128 μg/mL
Staphylcoccus aureus: 0.6 μg/mL - 128 μg/mL
Streptococcus pyogenes: 0.06 μg/mL - 4 μg/mL
Cautions and contraindications
Cautions include known sensitivity to beta-lactam antibacterials, such as penicillins (Cefaclor should be avoided if there is a history of immediate hypersensitivity reaction); renal impairment (no dose adjustment required, although manufacturer advises caution); pregnancy and breast-feeding (but appropriate to use); false positive urinary glucose (if tested for reducing substances) and false positive Coombs test. Cefaclor has also been reported to cause a serum sickness-like reaction in children.Cefaclor is contraindicated in case of hypersensitivity (i.e. allergy) to cephalosporins. Side effects
The principal side effect of the cephalosporins is hypersensitivity. Penicillin-sensitive patients will also be allergic to the cephalosporins, depending on the cephalosporin generation. The previous percentage of 10% cross reactivity rates are often overestimated. Allergic reactions may present as, for example, rashes, pruritus (itching), urticaria, serum sickness-like reactions with rashes, fever and arthralgia, and anaphylaxis. The frequency and severity of serum sickness-like reactions in children has led researchers to question its role in pediatric illness. Other side effects include gastrointestinal disturbances (e.g. diarrhea, nausea and vomiting, abdominal discomfort, disturbances in liver enzymes, transient hepatitis and cholestatic jaundice), headache, and Stevens–Johnson syndrome. Rare side effects include eosinophilia and blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia); reversible interstitial nephritis; hyperactivity, nervousness, sleep disturbances, hallucinations, confusion, hypertonia, and dizziness. Toxic epidermal necrolysis has been reported. | 0-1
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Pertuzumab/trastuzumab/hyaluronidase, sold under the brand name Phesgo, is a fixed-dose combination medication to treat adults with HER2-positive breast cancer that has spread to other parts of the body, and for treatment of adults with early HER2-positive breast cancer. It contains pertuzumab, trastuzumab, and hyaluronidase–zzxf. It is injected under the skin via subcutaneous injection in the thigh. In the European Union, Phesgo contains the active ingredients pertuzumab and trastuzumab along with the enzyme vorhyaluronidase alfa.The most common side effects include alopecia (hair loss), nausea, diarrhea, anemia (reduced number of red blood cells) and asthenia (lack of energy). It can cause worsening of chemotherapy induced neutropenia (low level of white blood cells). It may cause harm to a developing fetus or a newborn baby.HER2-positive breast cancer, which makes up approximately one-fifth of breast cancers, has too much of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. Pertuzumab and trastuzumab bind to sites on HER2 and disrupt signaling to stop cancer cell growth. | investigated the frequency, causes and risk factors for adrenal crisis in patients with chronic adrenal insufficiency. See also
Stress dose
References
External links
Acute adrenal crisis on PubmedHealth
Adrenal Crisis on Patient.info | 0-1
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For these worms, diagnosis relies upon skin snips and can be carried out at any time. Concentration methods
Various concentration methods are applied: membrane filter, Knotts concentration method, and sedimentation technique.Polymerase chain reaction (PCR) and antigenic assays, which detect circulating filarial antigens, are also available for making the diagnosis. The latter are particularly useful in amicrofilaraemic cases. Spot tests for antigen are far more sensitive, and allow the test to be done anytime, rather in the late hours. Lymph node aspirate and chylous fluid may also yield microfilariae. Medical imaging, such as CT or MRI, may reveal "filarial dance sign" in the chylous fluid; X-ray tests can show calcified adult worms in lymphatics. The DEC provocation test is performed to obtain satisfying numbers of parasites in daytime samples. Xenodiagnosis is now obsolete, and eosinophilia is a nonspecific primary sign. Treatment
The recommended treatment for people outside the United States is albendazole combined with ivermectin. A combination of diethylcarbamazine and albendazole is also effective. Side effects of the drugs include nausea, vomiting, and headaches. All of these treatments are microfilaricides; they have no effect on the adult worms. While the drugs are critical for treatment of the individual, proper hygiene is also required. There is good evidence that albendazole alone; or addition of albendazole to diethylcarbamazine or ivermectin, makes minimal difference in clearing microfilaria or adult worms from blood circulation. | Diethylcarbamazine-medicated salt is effective in controlling lymphatic filariasis while maintaining its coverage at 90% in the community for six months.Different trials were made to use the known drug at its maximum capacity in absence of new drugs. In a study from India, it was shown that a formulation of albendazole had better anti-filarial efficacy than albendazole itself.In 2003, the common antibiotic doxycycline was suggested for treating elephantiasis. Filarial parasites have symbiotic bacteria in the genus Wolbachia, which live inside the worm and seem to play a major role in both its reproduction and the development of the disease. This drug has shown signs of inhibiting the reproduction of the bacteria, further inducing sterility. Clinical trials in June 2005 by the Liverpool School of Tropical Medicine reported an eight-week course almost eliminated microfilaraemia. Society and culture
Research teams
In 2015 William C. Campbell and Satoshi Ōmura were co-awarded half of that years Nobel prize in Physiology or Medicine for the discovery of the drug avermectin, which, in the further developed form ivermectin, has decreased the occurrence of lymphatic filariasis. Prospects for elimination
Filarial diseases in humans offer prospects for elimination by means of vermicidal treatment. If the human link in the chain of infection can be broken, then notionally the disease could be wiped out in a season. In practice it is not quite so simple, and there are complications in that multiple species overlap in certain regions and double infections are common. | 11
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The HFE gene has three often observed genetic variants:
rs1799945, c.187C>G, p.His63Asp (H63D);
rs1800562, c.845G>A, p. Cys282Tyr (C282Y);
rs1800730, c.193A>T, p.Ser65Cys (S65C).The worldwide prevalence rates for H63D, C282Y and S65C (minor allele frequencies) are 10%, 3% and 1% respectively.The C282Y allele is a transition point mutation from guanine to adenine at nucleotide 845 in HFE, resulting in a missense mutation that replaces the cysteine residue at position 282 with a tyrosine amino acid. Heterozygotes for either allele can manifest clinical iron overload, if they have two of any alleles. This makes them compound heterozygous for haemochromatosis and puts them greatly at risk of storing excess iron in the body. Homozygosity for the C282Y genetic variant is the most common genotype responsible for clinical iron accumulation, though heterozygosity for C282Y/H63D variants, so-called compound heterozygotes, results in clinically evident iron overload. Considerable debate exists regarding the penetrance—the probability of clinical expression of the trait given the genotype— for clinical disease in homozygotes. Most males homozygous for HFE C282Y show at least one manifestation of iron-storage disease by middle age. Individuals with the relevant genetic variants may never develop iron overload. Phenotypic expression is present in 70% of C282Y homozygotes with less than 10% going on to experience severe iron overload and organ damage. The H63D variant is just a gene polymorphism, and if there are no other changes, it may not have clinical significance. In a 2014 study, H63D homozygosity was associated with an elevated mean ferritin level, but only 6.7% had documented iron overload at follow-up. | Finally, several groups reported their findings in a series of patients with haemmochromatosis where they discovered the existence of the C282Y mutation in about 85-90% of the cases. The discovery has led to improved clinical medicine and liver disease evaluation. References
External links
GeneReview/NIH/UW entry on HFE-Associated Hereditary Hemochromatosis
Hereditary haemochromatosis at Curlie | 11
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The droplets that are driven into the airstream and into the lung fields are lofted by way of Bernoullis principle. There is also a condition called oxidative damage that occurs when concentrations of pure oxygen come into prolonged contact with cells and this damages the cilia of the cells, thus inhibiting their action as part of the bodys first line of defense. Whether bacteria also travel from the sinuses or the stomach into the lungs is, as of 2005, controversial. However, spread to the lungs from the blood stream or the gut is uncommon. Once inside the lungs, bacteria then take advantage of any deficiencies in the immune system (such as due to malnutrition or chemotherapy) and multiply. Patients with VAP demonstrate impaired function of key immune cells, including the neutrophil, both in the blood and in the alveolar space, with this impairment being driven by pro-inflammatory molecules such as C5a. These defects in immune function appear to be causally linked to the development of VAP, as they are seen before clinical infection develops. A combination of bacterial damage and consequences of the immune response lead to disruption of gas exchange with resulting symptoms. Diagnosis
Diagnosis of ventilator-associated pneumonia is difficult and is not standardized. | Laboratory animal studies are usually cited in the literature. In serious drug dependency (high tolerance), 2000–3000 mg per day can be tolerated. Pharmacology
Pharmacodynamics
Morphine is the prototypical opioid and is the standard against which other opioids are tested. It interacts predominantly with the μ–δ-opioid (Mu-Delta) receptor heteromer. The μ-binding sites are discretely distributed in the human brain, with high densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They are also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in the spinal nucleus of the trigeminal nerve.Morphine is a phenanthrene opioid receptor agonist – its main effect is binding to and activating the μ-opioid receptor (MOR) in the central nervous system. Its intrinsic activity at the MOR is heavily dependent on the assay and tissue being tested; in some situations it is a full agonist while in others it can be a partial agonist or even antagonist. In clinical settings, morphine exerts its principal pharmacological effect on the central nervous system and gastrointestinal tract. Its primary actions of therapeutic value are analgesia and sedation. Activation of the MOR is associated with analgesia, sedation, euphoria, physical dependence, and respiratory depression. Morphine is also a κ-opioid receptor (KOR) and δ-opioid receptor (DOR) agonist. Activation of the KOR is associated with spinal analgesia, miosis (pinpoint pupils), and psychotomimetic effects. The DOR is thought to play a role in analgesia. | 0-1
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While piblokto can often be confused with other conditions (including epilepsy), in which failure to intervene can lead to the victim coming to harm, most cases tend to be benign. Skepticism
Although piblokto has a place in the historical record and official medical canons, a number of Arctic researchers and Arctic residents doubt its existence. The phenomenon, they suggest, may be more rooted in the experience and behavior of the early European explorers than the Inuit themselves.In 1988 Parks Canada historian Lyle Dick began a substantial challenge to the concept that piblokto exists at all. Dick examined the original records of the European Arctic explorers, and ethnographic and linguistic reports on Inughuit societies, and discovered that not only is the majority of academic speculation into piblokto based on reports of only eight cases, but the word "piblokto" / "pibloktoq" does not exist within Inuktun (the Inughuit language); possibly, Dick concluded, this may have been the result of errors in phonetic transcription. In a 1995 paper published in the journal Arctic Anthropology, and in his 2001 book Muskox land: Ellesmere Island in the Age of Contact, Dick suggests that piblokto is a "phantom phenomenon", arising more from the Inuhuit reaction to European explorers in their midst.Similarly, Hughes and Simons have described piblokto as a "catch-all rubric under which explorers lumped various Inuhuit anxiety reactions, expressions of resistance to patriarchy or sexual coercion, and shamanistic practice". | Abfraction is a theoretical concept explaining a loss of tooth structure not caused by tooth decay (non-carious cervical lesions). It is suggested that these lesions are caused by forces placed on the teeth during biting, eating, chewing and grinding; the enamel, especially at the cementoenamel junction (CEJ), undergoes large amounts of stress, causing micro fractures and tooth tissue loss. Abfraction appears to be a modern condition, with examples of non-carious cervical lesions in the archaeological record typically caused by other factors. Definition
Abfraction is a form of non-carious tooth tissue loss that occurs along the gingival margin. In other words, abfraction is a mechanical loss of tooth structure that is not caused by tooth decay, located along the gum line. There is theoretical evidence to support the concept of abfraction, but little experimental evidence exists.The term abfraction was first published in 1991 in a journal article dedicated to distinguishing the lesion. The article was titled "Abfractions: A New Classification of Hard Tissue Lesions of Teeth" by John O. Grippo. This article introduced the definition of abfraction as a "pathologic loss of hard tissue tooth substance caused by bio mechanical loading forces". This article was the first to establish abfraction as a new form of lesion, differing from abrasion, attrition, and erosion.Tooth tissue is gradually weakened causing tissue loss through fracture and chipping or successively worn away leaving a non-carious lesion on the tooth surface. These lesions occur in both the dentine and enamel of the tooth. | 0-1
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Laminitis is a disease that affects the feet of ungulates and is found mostly in horses and cattle. Clinical signs include foot tenderness progressing to inability to walk, increased digital pulses, and increased temperature in the hooves. Severe cases with outwardly visible clinical signs are known by the colloquial term founder, and progression of the disease will lead to perforation of the coffin bone through the sole of the hoof or being unable to stand up, requiring euthanasia. Laminae
The bones of the hoof are suspended within the axial hooves of ungulates by layers of modified skin cells, known as laminae or lamellae, which act as shock absorbers during locomotion. In horses, there are about 550–600 pairs of primary epidermal laminae, each with 150–200 secondary laminae projection from their surface. These interdigitate with equivalent structures on the surface of the coffin bone (PIII, P3, the third phalanx, pedal bone, or distal phalanx), known as dermal laminae. The secondary laminae contain basal cells which attach via hemidesmosomes to the basement membrane. The basement membrane is then attached to the coffin bone via the connective tissue of the dermis. Pathophysiology
Laminitis literally means inflammation of the laminae, and while it remains controversial whether this is the primary mechanism of disease, evidence of inflammation occurs very early in some instances of the disease. A severe inflammatory event is thought to damage the basal epithelial cells, resulting in dysfunction of the hemidesmosomes and subsequent reduction in adherence between the epithelial cells and the basement membrane. | Tendency to lie down whenever possible, and recumbency in extreme cases
Change in the outward appearance of the hoof in cases of chronic laminitis: dished (concave) dorsal hoof wall, "founder rings" (growth rings that are wider at the heel than the toe), a sole that is either flat or convex just dorsal to the apex of the frog which indicates P3 has displaced or penetrated, widening of the white line at the toe with or without bruising, "clubbing" of the foot. Change in the appearance of the coronary band: hair that does not lie in a normal position (not against the hoof wall), indentation or rim just above the hoof capsule allowing palpation behind the coronary band. In cases of sinking, it may be possible to palpate a groove between the coronary band and the skin of the pastern. Lameness evaluation
Hoof testingLaminitic horses are generally sore to pressure from hoof testers applied over the toe area. However, there is risk of a false negative if the horse naturally has a thick sole, or if the hoof capsule is about to slough. Obel grading systemThe severity of lameness is qualified using the Obel grading system:
Obel grade 1: Horse shifts weight between affected feet or continuously lifts feet up. It is sound at the walk but displays a shortened stride at the trot. Obel grade 2: Horse displays a stilted, stiff gait, although is willing to walk. It is possible to easily lift a front foot and have the horse take all of its weight on the contralateral limb. | 11
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Studies have sought to delineate the sequence of events following Ivermectin treatment that lead to neurologic SAE and sometimes death, while also trying to understand the mechanisms of adverse reactions to develop more appropriate treatments.In a study looking at mass Ivermectin treatment in Cameroon, one of the greatest endemic regions for both onchocerciasis and loiasis, a sequence of events in the clinical manifestation of adverse effects was outlined.It was noted that the patients used in this study had a L. loa microfilarial load of greater than 3,000 per ml of blood.Within 12–24 hours post-Ivermectin treatment (D1), individuals complained of fatigue, anorexia, and headache, joint and lumbar pain—a bent forward walk was characteristic during this initial stage accompanied by fever. Stomach pain and diarrhea were also reported in several individuals.By day 2 (D2), many patients experienced confusion, agitation, dysarthria, mutism and incontinence. Some cases of coma were reported as early as D2. The severity of adverse effects increased with higher microfilarial loads. Hemorrhaging of the eye, particularly the retinal and conjunctiva regions, is another common sign associated with SAE of Ivermectin treatment in patients with L. loa infections and is observed between D2 and D5 post-treatment. This can be visible for up to 5 weeks following treatment and has increased severity with higher microfilarial loads.Haematuria and proteinuria have also been observed following Ivermectin treatment, but this is common when using Ivermectin to treat onchocerciasis. The effect is exacerbated when there are high L. loa microfilarial loads however, and microfilariae can be observed in the urine occasionally. | An induced coma – also known as a medically induced coma (MIC), barbiturate-induced coma, or drug-induced coma – is a temporary coma (a deep state of unconsciousness) brought on by a controlled dose of an anesthetic drug, often a barbiturate such as pentobarbital or thiopental. Barbiturate comas are used to protect the brain during major neurosurgery, as a last line of treatment in certain cases of status epilepticus that have not responded to other treatments, and in refractory intracranial hypertension following traumatic brain injury. Induced coma usually results in significant systemic adverse effects. The patient is likely to completely lose respiratory drive and require mechanical ventilation; gut motility is reduced; hypotension can complicate efforts to maintain cerebral perfusion pressure and often requires the use of vasopressor drugs. Hypokalemia often results. The completely immobile patient is at increased risk of bed sores as well as infection from catheters. Induced coma is a feature of the Milwaukee protocol, a controversial method that is promoted as a means of treating rabies infection in people. Theory
Barbiturates reduce the metabolic rate of brain tissue, as well as the cerebral blood flow. With these reductions, the blood vessels in the brain narrow, resulting in a shrunken brain, and hence lower intracranial pressure. The hope is that, with the swelling relieved, the pressure decreases and some or all brain damage may be averted. | 0-1
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AVA remains the only FDA-licensed human anthrax vaccine in the United States and is produced by Emergent BioSolutions, formerly known as BioPort Corporation in Lansing, Michigan. The principal purchasers of the vaccine in the United States are the Department of Defense and Department of Health and Human Services. Ten million doses of AVA have been purchased for the U.S. Strategic National Stockpile for use in the event of a mass bioterrorist anthrax attack. In 1997, the Clinton administration initiated the Anthrax Vaccine Immunization Program (AVIP), under which active U.S. service personnel were to be immunized with the vaccine. Controversy ensued since vaccination was mandatory and GAO published reports that questioned the safety and efficacy of AVA, causing sometimes serious side effects. A Congressional report also questioned the safety and efficacy of the vaccine and challenged the legality of mandatory inoculations. Mandatory vaccinations were halted in 2004 by a formal legal injunction which made numerous substantive challenges regarding the vaccine and its safety. After reviewing extensive scientific evidence, the FDA determined in 2005 that AVA is safe and effective as licensed for the prevention of anthrax, regardless of the route of exposure. In 2006, the Defense Department announced the reinstatement of mandatory anthrax vaccinations for more than 200,000 troops and defense contractors. The vaccinations are required for most U.S. military units and civilian contractors assigned to homeland bioterrorism defense or deployed in Iraq, Afghanistan or South Korea. | Anthrax vaccines are vaccines to prevent the livestock and human disease anthrax, caused by the bacterium Bacillus anthracis.They have had a prominent place in the history of medicine, from Pasteurs pioneering 19th-century work with cattle (the first effective bacterial vaccine and the second effective vaccine ever) to the controversial late 20th century use of a modern product to protect American troops against the use of anthrax in biological warfare. Human anthrax vaccines were developed by the Soviet Union in the late 1930s and in the US and UK in the 1950s. The current vaccine approved by the U.S. Food and Drug Administration (FDA) was formulated in the 1960s. Currently administered human anthrax vaccines include acellular (USA, UK) and live spore (Russia) varieties. All currently used anthrax vaccines show considerable local and general reactogenicity (erythema, induration, soreness, fever) and serious adverse reactions occur in about 1% of recipients. New third-generation vaccines being researched include recombinant live vaccines and recombinant sub-unit vaccines. Pasteurs vaccine
In the 1870s, the French chemist Louis Pasteur (1822–1895) applied his previous method of immunising chickens against chicken cholera to anthrax, which affected cattle, and thereby aroused widespread interest in combating other diseases with the same approach. In May 1881, Pasteur performed a famous public experiment at Pouilly-le-Fort to demonstrate his concept of vaccination. He prepared two groups of 25 sheep, one goat and several cows. The animals of one group were twice injected, with an interval of 15 days, with an anthrax vaccine prepared by Pasteur; a control group was left unvaccinated. | 11
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Neurological
Three types of brain tumours are associated with TSC:
Giant cell astrocytoma: (grows and blocks the cerebrospinal fluid flow, leading to dilatation of ventricles causing headache and vomiting)
Cortical tubers: after which the disease is named
Subependymal nodules: form in the walls of ventriclesClassic intracranial manifestations of TSC include subependymal nodules and cortical/subcortical tubers.The tubers are typically triangular in configuration, with the apex pointed towards the ventricles, and are thought to represent foci of abnormal neuronal migration. The T2 signal abnormalities may subside in adulthood, but will still be visible on histopathological analysis. On magnetic resonance imaging (MRI), TSC patients can exhibit other signs consistent with abnormal neuron migration such as radial white matter tracts hyperintense on T2WI and heterotopic grey matter.Subependymal nodules are composed of abnormal, swollen glial cells and bizarre multinucleated cells which are indeterminate for glial or neuronal origin. Interposed neural tissue is not present. These nodules have a tendency to calcify as the patient ages. A nodule that markedly enhances and enlarges over time should be considered suspicious for transformation into a subependymal giant cell astrocytoma, which typically develops in the region of the foramen of Monro, in which case it is at risk of developing an obstructive hydrocephalus.A variable degree of ventricular enlargement is seen, either obstructive (e.g. by a subependymal nodule in the region of the foramen of Monro) or idiopathic in nature. Neuropsychiatric
About 90% of people with TSC develop a range of neurodevelopmental, behavioural, psychiatric, and psychosocial difficulties. The "TSC‐associated neuropsychiatric disorders" are abbreviated TAND. | Blood flow is selectively redirected to the myocardium, adrenal glands, and in particular to the brain in a brain-sparing effect.In late stage, the redistribution becomes ineffective, there is decrease in cardiac output, ineffective preload handling and elevation of central venous pressure. This deterioration in circulation may ultimately lead to tricuspid insufficiency and death of the fetus. Peripheral circulatory disturbances also accompany these central circulatory changes. Fetal behavioral changes
Chronic hypoxemia leads to delay in all aspects of CNS maturation. With worsening fetal hypoxemia, there is decline in fetal activity. With further hypoxemia, fetal breathing ceases. Gross body movements and tone decrease further. Fetal heart rate decreases due to spontaneous deceleration due to direct depression of cardiac contractility. This leads to intrauterine fetal death. Risk of later metabolic disease
According to the theory of thrifty phenotype, placental insufficiency triggers epigenetic responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment rich in food it may be more prone to metabolic disorders, such as obesity and type II diabetes. | 0-1
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An early scientific study of mercury poisoning was in 1923–1926 by the German inorganic chemist, Alfred Stock, who himself became poisoned, together with his colleagues, by breathing mercury vapor that was being released by his laboratory equipment—diffusion pumps, float valves, and manometers—all of which contained mercury, and also from mercury that had been accidentally spilt and remained in cracks in the linoleum floor covering. He published a number of papers on mercury poisoning, founded a committee in Berlin to study cases of possible mercury poisoning, and introduced the term micromercurialism. The term Hunter-Russell syndrome derives from a study of mercury poisoning among workers in a seed-packaging factory in Norwich, England in the late 1930s who breathed methylmercury that was being used as a seed disinfectant and pesticide. Outbreaks of methylmercury poisoning occurred in several places in Japan during the 1950s due to industrial discharges of mercury into rivers and coastal waters. The best-known instances were in Minamata and Niigata. In Minamata alone, more than 600 people died due to what became known as Minamata disease. More than 21,000 people filed claims with the Japanese government, of which almost 3000 became certified as having the disease. In 22 documented cases, pregnant women who consumed contaminated fish showed mild or no symptoms but gave birth to infants with severe developmental disabilities. | Hemiballismus
Typically caused by damage to the subthalamic nucleus or nuclei, hemiballismus movements are nonrhythmic, rapid, nonsuppressible, and violent. They usually occur in an isolated body part, such as the proximal arm. Hemifacial spasm
Hemifacial spasm (HFS) is characterized by involuntary contraction of facial muscles, typically occurring only on one side of the face. Like blepharospasm, the frequency of contractions in hemifacial spasm may range from intermittent to frequent and constant. The unilateral blepharospasm of HFS may interfere with routine tasks such as driving. In addition to medication, patients may respond well to treatment with Botox. HFS may be due to vascular compression of the nerves going to the muscles of the face. For these patients, surgical decompression may be a viable option for the improvement of symptoms. Myoclonus
Myoclonus is defined as a sequence of repeated, often nonrhythmic, brief, shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles. These movements may be asynchronous, in which several muscles contract variably in time, synchronous, in which muscles contract simultaneously, or spreading, in which several muscles contract sequentially. It is characterized by a sudden, unidirectional movement due to muscle contraction, followed by a relaxation period in which the muscle is no longer contracted. However, when this relaxation phase is decreased, as when muscle contractions become faster, a myoclonic tremor results. Myoclonus can often be associated with seizures, delirium, dementia, and other signs of neurological disease and gray matter damage. Stereotypies
Stereotypies are repetitive, rhythmic, simple movements that can be voluntarily suppressed. | 0-1
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Nipple discharge is fluid from the nipple, with or without squeezing the breast. The discharge can be milky, clear, green, purulent, bloody, or faintly yellow. The consistency can be thick, thin, sticky, or watery.Nipple discharge may be normal, such as milk in late pregnancy or after childbirth, and in newborns during the first weeks of life. It may also be normal following squeezing, in women during the reproductive years. It is likely abnormal if it occurs in men, contains blood, is from only one breast, or is associated with a breast lump, swelling, redness or overlying skin changes. Reasons for abnormal discharge include an intraductal papilloma, duct ectasia, blocked milk duct, infected breast (mastitis or breast abscess), breast cancer, certain medications, and conditions that raise prolactin.Milky discharge in a non-pregnant, non-breast feeding women is evaluated differently to other abnormal nipple discharge. Often, the cause can be determined based on symptoms and examination. Blood tests may be done to rule out low thyroid or high prolactin. Other tests may include mammography, breast ultrasound, breast biopsy, or skin biopsy.Treatment depends on the underlying cause. Duct ectasia may be treated with surgical removal of the ducts involved. Infectious causes may require antibiotics or incision and drainage. Nipple discharge is the third most common breast complaint by women, after breast pain and a breast lump. About 3% of breast cancer cases are associated with discharge. Signs and symptoms
Nipple discharge is fluid from the nipple, with or without squeezing the breast. | Arachnoiditis is an inflammatory condition of the arachnoid mater or arachnoid, one of the membranes known as meninges that surround and protect the nerves of the central nervous system, including the brain and spinal cord. The arachnoid can become inflamed because of adverse reactions to chemicals, infection from bacteria or viruses, as the result of direct injury to the spine, chronic compression of spinal nerves, complications from spinal surgery or other invasive spinal procedures, or the accidental intrathecal injection of steroids intended for the epidural space. Inflammation can sometimes lead to the formation of scar tissue and adhesion that can make the spinal nerves "stick" together, a condition where such tissue develops in and between the leptomeninges. The condition is extremely painful, especially when progressing to adhesive arachnoiditis. Another form of the condition is arachnoiditis ossificans, in which the arachnoid becomes ossified, or turns to bone, and is thought to be a late-stage complication of the adhesive form of arachnoiditis. Signs and symptoms
Arachnoid inflammation can lead to many painful and debilitating symptoms which can vary greatly in each case, and not all people experience all symptoms. Chronic pain is common, including neuralgia, while numbness and tingling of the extremities can occur with spinal cord involvement, and bowel, bladder, and sexual functioning can be affected if the lower part of the spinal cord is involved. While arachnoiditis has no consistent pattern of symptoms, it frequently affects the nerves that supply the legs and lower back. | 0-1
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Other conditions
Nicotine replacement therapies should be used cautiously in individuals with the following conditions: severe reactive airway diseases (for nasal spray), chronic nasal disorders such as sinusitis, polyps, rhinitis, or allergy (for nasal spray), diabetes (insulin-dependent), gastrointestinal diseases such as esophagitis, active gastric or peptic ulcer disease, liver problems, hyperthyroidism,pheochromocytoma, phenylketonuria (for lozenges), renal problems, and skin conditions such as psoriasis or dermatitis (for the transdermal patch). Mechanism of action
Nicotine replacement therapy works by reducing cravings due to nicotine addiction. Smoking cigarettes releases high doses of nicotine to the brain in a matter of seconds as opposed to low doses released over a period of minutes to hours by the various forms of nicotine replacement therapy. Nicotine from NRT does not reach as high a concentration in the blood as does nicotine from smoke inhalation due to different absorption methods. NRT relies on systemic venous absorption, whereas nicotine from cigarettes reaches the arterial system. Nicotine replacement products vary in the time it takes for the nicotine to enter the body and the total time nicotine stays in the body. The more quickly a dose of nicotine is delivered and absorbed, the higher the addiction risk. It is possible to become dependent on some NRTs.Nicotine patches are applied to the skin and continuously administer a stable dose of nicotine slowly over 16–24 hours. Nicotine gum, nicotine sprays, nicotine toothpicks, nicotine sublingual tablets, and nicotine lozenges administer nicotine orally with quicker nicotine uptake into the body but lasting a shorter amount of time. | A cigarette delivers an average of 1 mg to 3 mg of the nicotine contained in it. NRT products typically aim to parallel this, but the amount of nicotine absorbed by the user is less than the original dose. Nicotine nasal sprays are formulated in doses of lowest strength, available in 0.5 mg and 1 mg strengths. Nicotine lozenges deliver doses as low as 1 mg up to 4 mg. It is not chewed as the gum would be, and dissolves in approximately 30 minutes. This formulation may be preferred by those individuals who do not find gum chewing to be acceptable. Nicotine gum is available in doses of 2 mg and 4 mg. Using 4 mg nicotine gum versus 2 mg gum increases the likelihood of successful smoking cessation. When using the gum, acidic beverages like soda, coffee, or beer should be avoided fifteen minutes prior and during use because they can impede proper absorption of nicotine.Nicotine inhalers come in 10 mg and 15 mg cartridge strengths and typically deliver around 4 mg in one dose. The inhaler may be preferred in individuals who want to satisfy the hand-to-mouth ritual that smoking provides.Transdermal patches deliver between 5 mg and 52.5 mg of nicotine, which results in plasma levels similar to that of heavy smokers. Combining nicotine patch treatment with a faster nicotine-delivery means, like nicotine gum or spray, improves the likelihood of successful treatment. | 11
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History
Rubinstein–Taybi syndrome was first unofficially mentioned in a French orthopedic medical journal in 1957 by Greek physicians doctors: Michail, Matsoukas, and Theodorou. The medical journal reported a case concerning a seven-year-old boy with radically deviated/arched thumbs, long nose, muscular hypotonia, along with physical and mental underdevelopment. At this point in time the case study mentioned by the Greek physicians was considered to be an anomaly due to the fact that there hadnt been any other reported cases of children with these specific physical and mental characteristics. The doctors accredited with discovering the syndrome and therefore bear its name-sake were unaware of this journal at the time of their discovery. However, it is acknowledged that the 1957 case reported in the French journal of orthopedic medicine is most likely the first reported case of RTS.Dr. Jack Herbert Rubinstein, an American pediatrician reported assessing a three-year-old girl with unusual facial and digital findings in 1958. Similarly, that same year Rubinstein had evaluated another child with similar characteristics, this time a seven-year-old boy. Having sensed a striking similarity between these two unrelated cases Rubinstein tried distributing photos and information concerning these two cases to other clinics in the U.S. from 1959 to 1960. Rubinstein graduated from Harvard Medical School and worked as the director of the Hamilton County Diagnostic Clinic for the Mentally Retarded. | Warthins tumor, also known as papillary cystadenoma lymphomatosum, is a benign cystic tumor of the salivary glands containing abundant lymphocytes and germinal centers (lymph node-like stroma). It is named for pathologist Aldred Scott Warthin, who described two cases in 1929. Signs and symptoms
Warthins tumor primarily affects older individuals (age 60–70 years). There is a slight male predilection according to recent studies. The tumor is slow growing, painless, and usually appears in the tail of the parotid gland near the angle of the mandible. In 5–14% of cases, Warthins tumor is bilateral, but the two masses usually are at different times. Warthins tumor is highly unlikely to become malignant. Locations
The gland most likely affected is the parotid gland. In fact, it is the only tumor virtually restricted to the parotid gland. Warthins tumor is the second most common benign parotid tumor after pleomorphic adenoma, but its prevalence is steadily increasing. Cause
Its cause is unknown, but there is a strong association with cigarette smoking. Smokers are at 8 times greater risk of developing Warthins tumor than the general population. Diagnosis
The appearance of this tumor under the microscope is unique. There are cystic spaces surrounded by two uniform rows of oncocytes, which are epithelial cells with abundant, granular, eosinophilic cytoplasm. The cystic spaces have epithelium referred to as papillary infoldings that protrude into them. Additionally, the epithelium has lymphoid stroma with germinal center formation.The differential diagnosis includes sebaceous lymphadenoma and oncocytoma. Treatment
Most of these tumors are treated with surgical removal called parotidectomy. | 0-1
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The trial measured how many subjects experienced complete or partial shrinkage (by a certain amount) of their tumors during treatment (overall response rate). For subjects harboring a PDGFRA exon 18 mutation, the overall response rate was 84%, with 7% having a complete response and 77% having a partial response. For the subgroup of subjects with PDGFRA D842V mutations, the overall response rate was 89%, with 8% having a complete response and 82% having a partial response. While the median duration of response was not reached, 61% of the responding subjects with exon 18 mutations had a response lasting six months or longer (31% of subjects with an ongoing response were followed for less than six months).The FDA approved avapritinib based on evidence from one clinical trial (NCT02508532) of 204 subjects with GIST. The trial was conducted at 17 sites in the United States, Europe and Asia.Avapritinib showed a median PFS of 4.2 months compared to 5.6 months for regorafenib. The difference in median PFS between the avapritinib and regorafenib groups was not statistically significant. The overall response rate was 17 percent for the avapritinib group and 7 percent for the regorafenib group. The VOYAGER trial evaluated the efficacy and safety of avapritinib (N=240) versus regorafenib (N=236) in patients with third- or fourth-line GIST.Avapritinib was approved for medical use in the European Union in September 2020.Ayvakit was granted approval for advanced systemic mastocytosis by the FDA on June 16th 2021. References
Further reading
Wu CP, Lusvarghi S, Wang JC, et al. (July 2019). | Avapritinib, sold under the brand name Ayvakit among others, is a medication used for the treatment of advanced systemic mastocytosis and for the treatment of tumors due to one specific rare mutation: it is specifically intended for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) that harbor a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation.Common side effects include edema (swelling), nausea, fatigue/asthenia (abnormal physical weakness or lack of energy), cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation (secretion of tears), abdominal pain, constipation, rash and dizziness.Avapritinib is a kinase inhibitor. Medical uses
Avapritinib is indicated for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring the platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations.Avapritinib is also indicated for the treatment of adults with advanced systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia (MCL). History
The U.S. Food and Drug Administration (FDA) approved avapritinib in January 2020. The application for avapritinib was granted fast track designation, breakthrough therapy designation, and orphan drug designation. The FDA granted approval of Ayvakit to Blueprint Medicines Corporation.Avapritinib was approved based on the results from the Phase I NAVIGATOR clinical trial involving 43 subjects with GIST harboring a PDGFRA exon 18 mutation, including 38 subjects with PDGFRA D842V mutation. Subjects received avapritinib 300 mg or 400 mg orally once daily until disease progression or they experienced unacceptable toxicity. The recommended dose was determined to be 300 mg once daily. | 11
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People with more severe haemophilia experience more severe and more frequent bleeds, while people with mild haemophilia usually experience more minor symptoms except after surgery or serious trauma. In cases of moderate haemophilia symptoms are variable which manifest along a spectrum between severe and mild forms.In both haemophilia A and B, there is spontaneous bleeding but a normal bleeding time, normal prothrombin time, normal thrombin time, but prolonged partial thromboplastin time. Internal bleeding is common in people with severe haemophilia and some individuals with moderate haemophilia. The most characteristic type of internal bleed is a joint bleed where blood enters into the joint spaces. This is most common with severe haemophiliacs and can occur spontaneously (without evident trauma). If not treated promptly, joint bleeds can lead to permanent joint damage and disfigurement. Bleeding into soft tissues such as muscles and subcutaneous tissues is less severe but can lead to damage and requires treatment.Children with mild to moderate haemophilia may not have any signs or symptoms at birth, especially if they do not undergo circumcision. Their first symptoms are often frequent and large bruises and haematomas from frequent bumps and falls as they learn to walk. Swelling and bruising from bleeding in the joints, soft tissue, and muscles may also occur. Children with mild haemophilia may not have noticeable symptoms for many years. Often, the first sign in very mild haemophiliacs is heavy bleeding from a dental procedure, an accident, or surgery. | transplantation of stem cells derived another individual) has given better disease-free survival results than autologous transplantation and, based on recent uncontrolled studies, should be considered in DS-AMKL cases that have relapsed after their first chemotherapy-induced complete remission. Prognosis
The 5-year event free survival, disease-free survival, and overall survival rate in the phase 3 clinical study in DS-AMKL were 79, 89, 84 percent, respectively. Other studies that use a treatment regimen similar to that used in the phase 3 clinical study report overall survival rates of ~80% and long-term survivals of 74-91%. However, DS-AMKL patients who relapse following chemotherapy have a far poorer outlook with 3 year overall survival rate in one study of only 26%. There also appears to be little role for stem cell transplantation in DS-AMKL given the success of initial chemotherapy and the relatively poor results in DS-AMKL patients given this transplantation. Non-DS-AMKL
Pathophysiology
The most common genetic abnormality occurring in non-Down-AMKL is a nonreciprocal translocation between the short or p arm at position 13 on chromosome 1 (i.e. 1p13) and the p arm at position 13 on chromosome 22 (i.e. 22p13). Nonreciprocal translocations are exchanges of genes between two chromosomes that are not homologs, i.e. that are not maternal and paternal copies of the same chromosome. This particular translocation, designated t(1;22)(p13;q13), occurs mainly in infants but also is seen in children up to the age of 7 years with non-DS-AMKL. This translocation involves the RBM15 gene on chromosome 1 and the MKL1 gene (also termed MRTFA) on chromosome 22 to create a RBM15-MKL1 fusion gene. | 0-1
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Haemophilia, or hemophilia (from Ancient Greek αἷμα (haîma) blood, and φιλία (philía) love of), is a mostly inherited genetic disorder that impairs the bodys ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a longer time after an injury, easy bruising, and an increased risk of bleeding inside joints or the brain. Those with a mild case of the disease may have symptoms only after an accident or during surgery. Bleeding into a joint can result in permanent damage while bleeding in the brain can result in long term headaches, seizures, or a decreased level of consciousness.There are two main types of haemophilia: haemophilia A, which occurs due to low amounts of clotting factor VIII, and haemophilia B, which occurs due to low levels of clotting factor IX. They are typically inherited from ones parents through an X chromosome carrying a nonfunctional gene. Rarely a new mutation may occur during early development or haemophilia may develop later in life due to antibodies forming against a clotting factor. Other types include haemophilia C, which occurs due to low levels of factor XI, Von Willebrand disease, which occur due to low level of a substance called von Willebrand factor in their blood, and parahaemophilia, which occurs due to low levels of factor V. Acquired haemophilia is associated with cancers, autoimmune disorders, and pregnancy. | When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group had a normal index joint-structure on MRI. Preventative treatment, however, resulted in average costs of $300,000 per year. The author of an editorial published in the same issue of the NEJM supports the idea that prophylactic treatment not only is more effective than on demand treatment but also suggests that starting after the first serious joint-related haemorrhage may be more cost effective than waiting until the fixed age to begin. Most haemophiliacs in third world countries have limited or no access to commercial blood clotting factor products. Other
Desmopressin (DDAVP) may be used in those with mild haemophilia A. Tranexamic acid or epsilon aminocaproic acid may be given along with clotting factors to prevent breakdown of clots.Pain medicines, steroids, and physical therapy may be used to reduce pain and swelling in an affected joint. In those with severe hemophilia A already receiving FVIII, emicizumab may provide some benefit. Different treatments are used to help those with an acquired form of hemophilia in addition to the normal clotting factors. Often the most effective treatment is corticosteroids which remove the auto-antibodies in half of people. As a secondary route of treatment, cyclophosphamide and cyclosporine are used and are proven effective for those who did not respond to the steroid treatments. | 11
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The size of the tubercle varies and it is not always located on the intertrochanteric crest and that also adjacent areas can be part of the quadrate tubercle, such as the posterior surface of the greater trochanter or the neck of the femur. In a small anatomical study it was shown that the epiphyseal line passes directly through the quadrate tubercle. Body
The body of the femur (or shaft) is large, thick and almost cylindrical in form. It is a little broader above than in the center, broadest and somewhat flattened from before backward below. It is slightly arched, so as to be convex in front, and concave behind, where it is strengthened by a prominent longitudinal ridge, the linea aspera which diverges proximally and distal as the medial and lateral ridge. Proximally the lateral ridge of the linea aspera becomes the gluteal tuberosity while the medial ridge continues as the pectineal line. Besides the linea aspera the shaft has two other bordes; a lateral and medial border. These three bordes separates the shaft into three surfaces: One anterior, one medial and one lateral. Due to the vast musculature of the thigh the shaft can not be palpated.The third trochanter is a bony projection occasionally present on the proximal femur near the superior border of the gluteal tuberosity. When present, it is oblong, rounded, or conical in shape and sometimes continuous with the gluteal ridge. | Fungal keratitis is a fungal infection of the cornea, which can lead to blindness. It generally presents with a red, painful eye and blurred vision. There is also increased sensitivity to light, and excessive tears or discharge.It is caused by fungal organisms such as Fusarium, Aspergillus or Candida.Fungal keratitis has a worldwide distribution, but is more common in the tropics. Around 1 million people become blind every year due to fungal keratitis. Theodor Leber first described a case of fungal keratitis caused by Aspergillus in 1879. Signs and symptoms
The symptoms of fungal keratitis typically emerge over 5-10 days and present with a painful eye, blurred vision, and redness of eye. There is increased sensitivity to light, and excessive tears or discharge. The symptoms are markedly less as compared to a similar bacterial ulcer. Symptoms may be noted to persist after contact lenses are removed, or following antibiotic treatment.Signs: The eyelids and adnexa involved shows edema and redness, conjunctiva is chemosed. Ulcer may be present. It is a dry looking corneal ulcer with satellite lesions in the surrounding cornea. Usually associated with fungal ulcer is hypopyon, which is mostly white fluffy in appearance. Rarely, it may extend to the posterior segment to cause endophthalmitis in later stages, leading to the destruction of the eye. (Note: Fungal endophthalmitis is extremely rare)
Causes
Fungal keratitis has been reported to be caused by more than 70 different fungi, of which Fusarium, Aspergillus and Candida are responsible for 95% of cases.A. | 0-1
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Secondary lactation failure: milk production that is low due to preventable factors, such as formula supplementation, poor milk transfer by the baby, or unrelieved breast engorgement. Chronic low milk supply is estimated to be experienced by 10-15% of women. Breast pain
Pain often interferes with successful breastfeeding. It is cited as the second most common cause for the abandonment of exclusive breastfeeding after perceived low milk supply. Inverted nipples
Inverted or retracted nipples sometimes make attachment to the breast difficult. These mothers need additional support to feed their babies. Treatment is started after the birth of the baby. The nipple is manually stretched out several times a day. A pump or a plastic syringe is used to draw out the nipple and the baby is then put to the breast. Engorgement
Breast engorgement is the sense of breast fullness experienced by most women within 36 hours of delivery. Normally, this is a painless sensation of "heaviness". Breastfeeding on demand is the primary way of preventing painful engorgement. When the breast overfills with milk it becomes painful. Engorgement comes from not getting enough milk from the breast. It happens about 3 to 7 days after delivery and occurs more often in first time mothers. The increased blood supply, the accumulated milk and the swelling all contribute to the painful engorgement. Engorgement may affect the areola, the periphery of the breast or the entire breast, and may interfere with breastfeeding both from the pain and also from the distortion of the normal shape of the areola/nipple. | According to the American Academy of Pediatrics 2006 Redbook: Women with tuberculosis who have been treated appropriately for 2 or more weeks and who are not considered contagious may breastfeed. Women with tuberculosis disease suspected of being contagious should refrain from breastfeeding or any other close contact with the infant because of potential transmission through respiratory tract droplets (see Tuberculosis, p 678). Mycobacterium tuberculosis rarely causes mastitis or a breast abscess, but if a breast abscess caused by M. tuberculosis is present, breastfeeding should be discontinued until the mother no longer is contagious. In areas where BCG vaccination is the standard of care, the WHO provides treatment recommendations and advises mothers to continue breastfeeding. TBC may be congenital, or perinatally acquired through airborne droplet spread. HIV
Research published in the Lancet has highlighted a lower risk of HIV transmission with exclusive breastfeeding by HIV positive mothers (4% risk), compared to mixed feeding (10-40% risk). Research on the timing of HIV transmission in 2000 revealed that a "substantial transmission occurs early during breastfeeding," concluding that 75% of all breast milk transmission had occurred within the first 6 months during a randomized control trial in Kenya. This research is of particular importance in developing countries where infant formula is not widely available or safe to prepare. In fact, the World Health Organization recommended breastfeeding in 1987 and 1992 for seropositive and seronegative women in areas where malnutrition and infectious diseases are the major cause of infant mortality. | 11
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Salagen, a manufactured form of pilocarpine, can be used to help produce tears, as well as saliva in the mouth and intestines. It is derived from the jaborandi plant. Vaginal dryness
In women with Sjögrens syndrome, vaginal dryness, vulvodynia and dyspareunia (painful sexual intercourse) are often reported; personal lubricants are recommended to help lessen irritation or pain that may result from dryness in the vaginal and vulval areas. Musculoskeletal
Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed, and sometimes intravenous immunoglobulins. Also, disease-modifying antirheumatic drugs such as methotrexate may be helpful. Hydroxychloroquine (Plaquenil) is another option and is generally considered safer than methotrexate. However, these prescribed drugs have a range of side effects such as nausea, loss of appetite, dizziness, hair loss, stomach aches/cramps, headache, liver toxicity and increased risk of infections. Also, those who take drugs to suppress the immune system are more likely to develop cancer later. Systemic
For systemic symptoms, including fatigue, joint pain, myositis and neuropathy, biologic immunosuppressant drugs such as rituximab and belimumab that work via B-cell pathology are often used and have less toxic profiles than traditional immunosuppressive regimens. Dental care
Preventive dental treatment is also necessary (and often overlooked by the patient), as the lack of saliva associated with xerostomia creates an ideal environment for the proliferation of bacteria that cause cavities. Treatments include at-home topical fluoride application to strengthen tooth enamel and frequent teeth cleanings by a dental hygienist. | For example, rifampicin reduced the AUC by 60% in a study.Upadacitinib seems to be a weak inducer of CYP3A4, as it lowers concentrations of other substrates of this enzyme (such as the midazolam AUC by 26%). It has no effect on substrates of CYP1A2, CYP2B6, CYP2C9, CYP2C19 or CYP2D6. Side effects
Common side effects are upper respiratory tract infections such as common cold and sinus infections (13.5% of patients in studies), nausea (3.5%), cough (2.2%), fever, and increased liver enzymes. Serious side effects include infections, including life-threatening ones, such as pneumonia, cellulitis, tuberculosis, as well as shingles and other herpes infections. Pharmacology
Mechanism of action
The Janus kinases (JAKs) are a family of cytoplasmic tyrosine kinases whose function is to transduce cytokine-mediated signals via the JAK-STAT pathway. There are four JAK subtypes, each of which has overlapping receptor responsibilities. Inhibitors of this enzyme family (jakinibs) have shown efficacy in treating certain inflammatory and autoimmune diseases such as rheumatoid arthritis and Crohns disease. However, the first generation of these drugs, tofacitinib and ruxolitinib, lacked subtype selectivity, affecting JAK1/JAK3 and JAK1/JAK2 respectively. This has led to dose-limiting side effects in this otherwise promising class of drugs. Upadacitinib is a second generation Janus kinase inhibitor that is selective for the JAK1 subtype of this enzyme over the JAK2 (74-fold), JAK3 (58-fold) and tyrosine kinase 2 subtypes. Pharmacokinetics
After oral intake, upadacitinib reaches highest concentrations in the blood plasma after two to four hours. A fatty meal has no clinically relevant effect on its resorption. | 0-1
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