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Some studies have begun exploring and defining the use of radiographic imaging for diagnosing Tietze syndrome. This includes computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy, and ultrasound, though these are only case studies and the methods described have yet to be thoroughly investigated. Methods such as plain radiographs, better known as an x-ray, are helpful in the exclusion of other conditions, but not in the diagnosis of Tietze syndrome. Some researchers believe that ultrasound is superior to other available imaging methods, as it can visualize the increased volume, swelling, and structural changes of the costal cartilage. Differential diagnosis
The symptoms of Tietze syndrome can display as a wide variety of conditions, making it difficult to diagnose, especially to physicians unaware of the condition. Due to its presentation, Tietze syndrome can be misdiagnosed as a number of conditions, including myocardial infarction (heart attack), angina pectoris, and neoplasms.Costochondritis is most commonly confused with Tietze syndrome, as they have similar symptoms and can both affect the costochondral and sternocostal joints. Costochondritis is considered a more common condition and is not associated with any swelling to the affected joints, which is the defining distinction between the two. Tietze syndrome commonly affects the 2nd or 3rd rib and typically occurs among a younger age group, while costochondritis affects the 2nd to 5th ribs and has been found to occur in older individuals, usually over the age of 40. | The respiratory infection has also been observed accompanying rheumatoid arthritis which, coupled with leukocytosis, neutrophilia, c-reactive protein (CRP), and elevated erythrocyte sedimentation rate (ESR), suggest an infectious and rheumatoid factor, though the evidence is conflicting. Many theories such as malnutrition, chest trauma, and tuberculosis, were thought to be among the potential causes but have since been disproven or left unsupported. Diagnosis
Diagnosis for Tietze syndrome is primarily a clinical one, though some studies suggest the use of radiologic imaging. Musculoskeletal conditions are estimated to account for 20-50% of non-cardiac related chest pain in the emergency department. Ruling out other conditions, especially potentially life-threatening ones such as myocardial infarction (heart attack) and angina pectoris, is extremely important as they can present similarly to Tietze syndrome. These can usually be ruled out with diagnostic tools such as an electrocardiogram and a physical examination showing reproducible chest wall tenderness, . After eliminating other possible conditions, physical examination is considered the most accurate tool in diagnosing Tietze syndrome. Physical examination consists of gentle pressure to the chest wall with a single finger to identify the location of the discomfort. Swelling and tenderness upon palpation at one or more of the costochondral, sternocostal, or sternoclavicular joints, is a distinctive trait of Tietze syndrome and is considered a positive diagnosis when found.There are some pathological features that can be observed with Tietze syndrome, including degeneration of the costal cartilage, increase in vascularity, and hypertrophic changes (enlarged cells). However, these features can only be identified from a biopsy. | 11
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Implementation of DOTS-Plus requires the capacity to perform drug-susceptibility testing (not routinely available even in developed countries) and the availability of second-line agents, in addition to all the requirements for DOTS. DOTS-Plus is therefore much more resource-expensive than DOTS, and requires much greater commitment from countries wishing to implement it. Community engagement is a new approach that is being initiated alongside the DOTS individualized treatment. By creating a community for health workers to give support to patients and hospital faculty, the DOTS-plus model also incorporates psychological structural support treatments to help accommodate patients to ensure completion of treatment. Treatment with the new strategy is a total duration of 18–24 months.Monthly surveillance until cultures convert to negative is recommended for DOTS-Plus, but not for DOTS. If cultures are positive or symptoms do not resolve after three months of treatment, it is necessary to re-evaluate the patient for drug-resistant disease or nonadherence to drug regimen. If cultures do not convert to negative despite three months of therapy, some physicians may consider admitting the patient to hospital so as to closely monitor therapy. Extra-pulmonary tuberculosis
Tuberculosis not affecting the lungs is called extra-pulmonary tuberculosis. Disease of the central nervous system is specifically excluded from this classification. The United Kingdom and the World Health Organization (WHO) recommendation is 2HREZ/4HR; the US recommendation is 2HREZ/7HR. | There is good evidence from randomised-controlled trials to say that in tuberculous lymphadenitis and in TB of the spine, the six-month regimen is equivalent to the nine-month regimen; the US recommendation is therefore not supported by the evidence.Up to 25% of patients with TB of the lymph nodes (TB lymphadenitis) will get worse on treatment before they get better and this usually happens in the first few months of treatment. A few weeks after starting treatment, lymph nodes often start to enlarge, and previously solid lymph nodes may soften and develop into tuberculous cervical lymphadenitis. This should not be interpreted as failure of therapy and is a common reason for patients (and their physicians) to panic unnecessarily. With patience, two to three months into treatment the lymph nodes start to shrink again and re-aspiration or re-biopsy of the lymph nodes is unnecessary: if repeat microbiological studies are ordered, they will show the continued presence of viable bacteria with the same sensitivity pattern, which further adds to the confusion: physicians inexperienced in the treatment of TB will then often add second-line drugs in the belief that the treatment is not working. In these situations, all that is required is re-assurance. Steroids may be useful in resolving the swelling, especially if it is painful, but they are unnecessary. Additional antibiotics are unnecessary and the treatment regimen does not need to be lengthened.There is no evidence that 6 months regimen is inadequate in treating abdominal TB and there is no additional benefits for 9-month regimen for preventing relapse. | 11
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The National Institute on Drug Abuse determined that marijuana use is "likely to precede use of other licit and illicit substances" and that "adults who reported marijuana use during the first wave of the survey were more likely than adults who did not use marijuana to develop an alcohol use disorder within 3 years; people who used marijuana and already had an alcohol use disorder at the outset were at greater risk of their alcohol use disorder worsening. Marijuana use is also linked to other substance use disorders including nicotine addiction." It also reported that "These findings are consistent with the idea of marijuana as a "gateway drug." However, the majority of people who use marijuana do not go on to use other, "harder" substances. Also, cross-sensitization is not unique to marijuana. Alcohol and nicotine also prime the brain for a heightened response to other drugs and are, like marijuana, also typically used before a person progresses to other, more harmful substances." Research issues
Cannabis research is challenging since the plant is illegal in most countries. Research-grade samples of the drug are difficult to obtain for research purposes, unless granted under authority of national regulatory agencies, such as the US Food and Drug Administration.There are also other difficulties in researching the effects of cannabis. Many people who smoke cannabis also smoke tobacco. This causes confounding factors, where questions arise as to whether the tobacco, the cannabis, or both that have caused a cancer. Another difficulty researchers have is in recruiting people who smoke cannabis into studies. | Benign neonatal sleep myoclonus (BNSM) is the occurrence of myoclonus (jerky movements) during sleep. It is not associated with seizures.BNSM occurs in the first few weeks of life, and usually resolves on its own within the first 3-4 months of life. It often worries parents because it can appear like seizures, but is not. Features that can help distinguish this condition from seizures include: The myoclonic movements only occur during sleep, when baby is woken up the myoclonic movements stop, normal EEG, normal neurological examination, normal developmental examination. The myoclonic jerks occur during non-REM sleep. References
== External links == | 0-1
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Diagnosis
One of, if not the most common form of organic acidemia, methylmalonic acidemia is not apparent at birth as symptoms usually do not present themselves until proteins are added to the infants diet. Because of this, symptoms typically manifest anytime within the first year of life. Due to the severity and rapidity in which this disorder can cause complications when left undiagnosed, screening for methylmalonic acidemia is often included in the newborn screening exam.Because of the inability to properly break down amino acids completely, the byproduct of protein digestion, the compound methylmalonic acid, is found in a disproportionate concentration in the blood and urine of those afflicted. These abnormal levels are used as the main diagnostic criteria for diagnosing the disorder. This disorder is typically determined through the use of a urine analysis or blood panel. The presence of methylmalonic acidemia can also be suspected through the use of a CT or MRI scan or ammonia test, however these tests are by no means specific and require clinical and metabolic/correlation. Elevated levels of ammonia, glycine, and ketone bodies may also be present in the blood and urine. Types
Methylmalonic acidemia has varying diagnoses, treatment requirements and prognoses, which are determined by the specific genetic mutation causing the inherited form of the disorder. | Though currently unclear if this is due to the specific mutation or early detection and treatment, despite complete nonresponse to cobalamin supplements, these individuals appeared to develop a largely benign and near completely asymptomatic version of MMA. Despite consistently showing elevated methylmalonic acid in the blood and urine, these individuals appeared for the large part developmentally normal. Notable cases
Ryan Stallings, a St. Louis infant, was mistakenly diagnosed with ethylene glycol poisoning instead of MMA in 1989, leading to a wrongful murder conviction and life sentence for his mother, Patricia Stallings. See also
Combined malonic and methylmalonic aciduria (CMAMMA)
Isovaleric acidemia
Propionic acidemia
Maple syrup urine disease
Notes
References
Further reading
== External links == | 11
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Reunion helps resolve the lack of self-knowledge.Externally focused theories, in contrast, suggest that reunion is a way for adoptees to overcome social stigma. First proposed by Goffman, the theory has four parts: 1) adoptees perceive the absence of biological ties as distinguishing their adoptive family from others, 2) this understanding is strengthened by experiences where non-adoptees suggest adoptive ties are weaker than blood ties, 3) together, these factors engender, in some adoptees, a sense of social exclusion, and 4) these adoptees react by searching for a blood tie that reinforces their membership in the community. The externally focused rationale for reunion suggests adoptees may be well adjusted and happy within their adoptive families, but will search as an attempt to resolve experiences of social stigma.Some adoptees reject the idea of reunion. It is unclear, though, what differentiates adoptees who search from those who do not. One paper summarizes the research, stating, "...attempts to draw distinctions between the searcher and non-searcher are no more conclusive or generalizable than attempts to substantiate ... differences between adoptees and nonadoptees. "In sum, reunions can bring a variety of issues for adoptees and parents. Nevertheless, most reunion results appear to be positive. In the largest study to date (based on the responses of 1,007 adoptees and relinquishing parents), 90% responded that reunion was a beneficial experience. This does not, however, imply ongoing relationships were formed between adoptee and parent nor that this was the goal. | To do this, the drug was designed to irreversibly inhibit the GABA transaminase, which degrades the GABA substrate. Although the drug was approved for treatment in the United Kingdom in 1989, the authorized use of Vigabatrin by US Food and Drug Administration was delayed twice in the United States before 2009. It was delayed in 1983 because animal trials produced intramyelinic edema, however, the effects were not apparent in human trials so the drug design continued. In 1997, the trials were temporarily suspended because it was linked to peripheral visual field defects in humans. Society and culture
Brand Names
Vigabatrin is sold as Sabril in Canada, Mexico,
and the United Kingdom. The brand name in Denmark is Sabrilex. Sabril was approved in the United States on August 21, 2009 and is marketed in the U.S. by Lundbeck Inc., which acquired Ovation Pharmaceuticals, the U.S. sponsor in March 2009. Generic equivalents
On January 16, 2019, the Food and Drug Administration approved the first generic version of Sabril (vigabatrin) in the United States. References
External links
"Vigabatrin". Drug Information Portal. U.S. National Library of Medicine. | 0-1
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), and another is
M
10
{\displaystyle \mathrm {M} _{10}}
, also almost simple, that functions as a point stabilizer which has
5
{\displaystyle 5}
as its largest prime factor in its group order: 24·32·5 = 2·3·4·5·6 = 8·9·10 = 720. | Aortic rupture is the rupture or breakage of the aorta, the largest artery in the body. Aortic rupture is a rare, extremely dangerous condition. The most common cause is an abdominal aortic aneurysm that has ruptured spontaneously. Aortic rupture is distinct from aortic dissection, which is a tear through the inner wall of the aorta that can block the flow of blood through the aorta to the heart or abdominal organs. An aortic rupture can be classified according to its cause into one of the following main types:
Traumatic aortic rupture
Aortic rupture secondary to an aortic aneurysm
Signs and symptoms
Symptoms
Tearing pain, located in the abdomen, flank, groin, or back
Loss of consciousness
Signs
Low blood pressure from hypovolemic shock
Fast heart rate
Blue discoloration of the skin
Altered mental status
Bruising of the flank, a sign of retroperitoneal bleeding. Death
Causes
The most common cause of aortic rupture is a ruptured aortic aneurysm. Other causes include trauma and iatrogenic (procedure-related) causes. Mechanism
The wall of the aorta is an elastic structure which requires integrity. Rupture results from either loss of wall strength to the point at which systemic pressure is greater than wall strength, or external destruction of the wall of the aorta, by a tumor or traumatic means. The bleeding can be retroperitoneal or intraperitoneal, or the rupture can create an aortocaval (between the aorta and inferior vena cava) or aortoenteric (between the aorta and intestine) fistula. Diagnosis
The condition is often suspected in patients close to death with abdominal trauma or with relevant risk-factors. Diagnosis may be confirmed by ultrasound or X-ray computed tomography (CT) scan. | 0-1
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Related terminology
A woman on her wedding day is usually described as a bride, even after the wedding ceremony, while being described as a wife is also appropriate after the wedding or after the honeymoon. If she is marrying a man, her partner is known as the bridegroom during the wedding, and within the marriage is called her husband. In the older custom, still followed, e. g., by Roman Catholic ritual, the word bride actually means fiancée and applies up to the exchange of matrimonial consent (the actual marriage act); from then on, even while the rest of the very ceremony is ongoing, the woman is a wife, and no longer a bride, and the bridal couple is no longer referred to as such but as the newlywed couple or "newlyweds". "Wife" refers to the institutionalized relation to the other spouse, unlike mother, a term that puts a woman into the context of her children. In some societies, especially historically, a concubine was a woman who was in an ongoing, usually matrimonially oriented relationship with a man who could not be married to her, often because of a difference in social status. The term wife is most commonly applied to a woman in a union sanctioned by law (including religious law), not to a woman in an informal cohabitation relationship, which may be known as a girlfriend, partner, cohabitant, significant other, concubine, mistress etc. | Aortic rupture is the rupture or breakage of the aorta, the largest artery in the body. Aortic rupture is a rare, extremely dangerous condition. The most common cause is an abdominal aortic aneurysm that has ruptured spontaneously. Aortic rupture is distinct from aortic dissection, which is a tear through the inner wall of the aorta that can block the flow of blood through the aorta to the heart or abdominal organs. An aortic rupture can be classified according to its cause into one of the following main types:
Traumatic aortic rupture
Aortic rupture secondary to an aortic aneurysm
Signs and symptoms
Symptoms
Tearing pain, located in the abdomen, flank, groin, or back
Loss of consciousness
Signs
Low blood pressure from hypovolemic shock
Fast heart rate
Blue discoloration of the skin
Altered mental status
Bruising of the flank, a sign of retroperitoneal bleeding. Death
Causes
The most common cause of aortic rupture is a ruptured aortic aneurysm. Other causes include trauma and iatrogenic (procedure-related) causes. Mechanism
The wall of the aorta is an elastic structure which requires integrity. Rupture results from either loss of wall strength to the point at which systemic pressure is greater than wall strength, or external destruction of the wall of the aorta, by a tumor or traumatic means. The bleeding can be retroperitoneal or intraperitoneal, or the rupture can create an aortocaval (between the aorta and inferior vena cava) or aortoenteric (between the aorta and intestine) fistula. Diagnosis
The condition is often suspected in patients close to death with abdominal trauma or with relevant risk-factors. Diagnosis may be confirmed by ultrasound or X-ray computed tomography (CT) scan. | 0-1
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Flibanserin is an analogue of trazodone. History
Trazodone was developed in Italy, in the 1960s, by Angelini Research Laboratories as a second-generation antidepressant. It was developed according to the mental pain hypothesis, which was postulated from studying patients and which proposes that major depression is associated with a decreased pain threshold. In sharp contrast to most other antidepressants available at the time of its development, trazodone showed minimal effects on muscarinic cholinergic receptors. Trazodone was patented and marketed in many countries all over the world. It was approved by the Food and Drug Administration (FDA) in 1981 and was the first non-tricyclic or MAOI antidepressant approved in the US. Society and culture
Generic names
Trazodone is the generic name of the drug and its INN, BAN, and DCF, while trazodone hydrochloride is its USAN, USP, BANM, and JAN. Brand names
Trazodone has been marketed under a large number of brand names throughout the world. Major brand names include Desyrel (worldwide), Donaren (Brazil), Molipaxin (Ireland, United Kingdom), Oleptro (United States), Trazorel (Canada), and Trittico (worldwide). Research
Trazodone may be effective in the treatment of sexual dysfunction, for instance female sexual dysfunction and erectile dysfunction. A 2003 systematic review and meta-analysis found some indication that trazodone may be useful in the treatment of erectile dysfunction. Besides trazodone alone, a combination of trazodone and bupropion (developmental code names and tentative brand names S1P-104, S1P-205, Lorexys, and Orexa) is under development for the treatment of erectile dysfunction and female sexual dysfunction. As of September 2021, it is in phase 2 clinical trials for these indications. | Angel-shaped phalango-epiphyseal dysplasia, also known as peripheral dysostosis, is a rare type of osteochondrodysplasia which is characterized by angel-shaped middle phalanges of the fingers and generalized metaphyseal dysplasia/delayed osseous age. Additional findings include joint hypermobility, hypodontia, and hip osteoarthritis. According to OMIM, 10 cases from multiple families have been described in medical literature. It is thought to be inherited in an autosomal dominant manner. According to ORPHA, 20 cases have been reported. Presentation
The middle phalanges (often those of the 2nd, 3rd and 5th digits of the hands) angel shape is caused by an abnormal development of the epiphysis, metaphysis, and diaphysis of said phalanges; the wings are formed by an abnormal dyaphysis, the angels skirt is from a cone-shaped epiphysis, and the head is formed by an abnormal distal pseudoepophysis. Genetics
This disorder is thought to be caused by autosomal dominant mutations in the GDF5 gene, in chromosome 20. History
This condition was first discovered in 1967, by Bachman et al. when he described a "hereditary peripheral dysostosis" on one woman and 2 of her children. Eponym
This disorders name comes from the fact that Bachman et al. (the researchers who originally described the disorder) and Giedion et al. missed a characteristic feature that the people diagnosed with the disorder shared: a middle phalange that had a striking resemblance to the shape of decorative angels of small size that are often put in Christmas trees. == References == | 0-1
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A two-month course of antibiotics such as ciprofloxacin, levofloxacin and doxycycline after exposure can also prevent infection. If infection occurs, treatment is with antibiotics and possibly antitoxin. The type and number of antibiotics used depend on the type of infection. Antitoxin is recommended for those with widespread infection.A rare disease, human anthrax is most common in Africa and central and southern Asia. It also occurs more regularly in Southern Europe than elsewhere on the continent and is uncommon in Northern Europe and North America. Globally, at least 2,000 cases occur a year, with about two cases a year in the United States. Skin infections represent more than 95% of cases. Without treatment the risk of death from skin anthrax is 23.7%. For intestinal infection the risk of death is 25 to 75%, while respiratory anthrax has a mortality of 50 to 80%, even with treatment. Until the 20th century anthrax infections killed hundreds of thousands of people and animals each year. Anthrax has been developed as a weapon by a number of countries. In herbivorous animals infection occurs when they eat or breathe in the spores while grazing. Animals may become infected by killing and/or eating infected animals. Etymology
The English name comes from anthrax (ἄνθραξ), the Greek word for coal, possibly having Egyptian etymology, because of the characteristic black skin lesions developed by people with a cutaneous anthrax infection. The central black eschar surrounded by vivid red skin has long been recognised as typical of the disease. | Even though there are many known causes of delay, some children will never receive a diagnosis. Investigation
Developmental monitoring is performed during wellness visits to check a childs development. Health authorities encourage parents to monitor their childs development, the CDCs program "Learn the Signs. Act Early" provides materials for a childs development is assessed based on expected milestones for actions like how they play, learn, speak, act and move. Missed milestones may be cause for concern, so the doctor or another specialist may call for a more thorough test or exam to take a closer look, this is usually done by going through Developmental Screening. Developmental Screening is a more involved process. The evaluating professional will ask a parent to complete a research-based questionnaire that asks about a childs development, including language, movement, thinking, behavior, and emotions. Developmental Screening is recommended by the American Academy of Pediatrics (AAP) to all children at 9, 18, and 30 months. The AAP also recommends that all children be screened specifically for autism spectrum disorder (ASD) during regular well-child visits at 18 and 24 months. If a Developmental Screening indicates a delay, the child should then be assessed with a Developmental Evaluation. Developmental Evaluations are performed by a Developmental pediatrician, child psychologist, or other trained provider with the purpose of Identifying and diagnosing developmental delays and conditions. Chromosome microarray and karyotyping to look for trisomy, microdeletions, and duplications. | 0-1
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Some are more comprehensive, such as the Pathogenetic Triad, which proposes and operationalizes three core features (an autistic personality, cognitive compensation, neuropathological burden) that interact to cause autism, and the Intense World Theory, which explains autism through a hyper-active neurobiology that leads to an increased perception, attention, memory, and emotionality. There are also simpler hypotheses that explain only individual parts of the neurobiology or phenotype of autism, such as mind-blindness (a decreased ability for Theory of Mind), the weak central coherence theory, or the extreme male brain and empathising-systemising theory. Evolutionary hypotheses
Research exploring the evolutionary benefits of autism and associated genes has suggested that autistic people may have played a "unique role in technological spheres and understanding of natural systems" in the course of human development. It has been suggested that it may have arisen as "a slight trade off for other traits that are seen as highly advantageous", providing "advantages in tool making and mechanical thinking", with speculation that the condition may "reveal itself to be the result of a balanced polymorphism, like sickle cell anemia, that is advantageous in a certain mixture of genes and disadvantageous in specific combinations".In 2011, a paper in Evolutionary Psychology proposed that autistic traits, including increased abilities for spatial intelligence, concentration and memory, could have been naturally selected to enable self-sufficient foraging in a more (although not completely) solitary environment, referred to as the "Solitary Forager Hypothesis". | Problems with blood cell formation result in some combination of low red blood cells, low platelets, and low white blood cells. Some types have an increase in immature blood cells, called blasts, in the bone marrow or blood. Fibrous dysplasia of bone
Fibrous dysplasia of bone is a disorder where normal bone and marrow is replaced with fibrous tissue, resulting in formation of bone that is weak and prone to expansion. As a result, most complications result from fracture, deformity, functional impairment and pain. Macroscopic scale
Hip dysplasia
Hip dysplasia is an abnormality of the hip joint where the socket portion does not fully cover the ball portion, resulting in an increased risk for joint dislocation. Hip dysplasia may occur at birth or develop in early life. Regardless, it does not typically produce symptoms in babies less than a year old. Occasionally one leg may be shorter than the other. The left hip is more often affected than the right. Complications without treatment can include arthritis, limping, and low back pain. Multicystic dysplastic kidney
Multicystic dysplastic kidney (MCDK) is a condition that results from the malformation of the kidney during fetal development. The kidney consists of irregular cysts of varying sizes. Multicystic dysplastic kidney is a common type of renal cystic disease, and it is a cause of an abdominal mass in infants. Etymology
From Ancient Greek δυσ- dys-, "bad" or "difficult" and πλάσις plasis, "formation". The equivalent surface analysis, in parallel with classical compounds, is dys- + -plasia. See also
Pleomorphism
List of biological development disorders
References
== Further reading == | 0-1
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Signs and symptoms
Bronchiolitis typically presents in children under two years old and is characterized by a constellation of respiratory symptoms that consists of fever, rhinorrhea, cough, wheeze, tachypnea and increased work of breathing such as nasal flaring or grunting that develops over one to three days. Crackles or wheeze are typical findings on listening to the chest with a stethoscope. The child may also experience apnea, or brief pauses in breathing. After the acute illness, it is common for the airways to remain sensitive for several weeks, leading to recurrent cough and wheeze. Some signs of severe disease include:
increased work of breathing (such as use of accessory muscles of respiration, rib & sternal retraction, tracheal tug)
severe chest wall recession (Hoovers sign)
presence of nasal flaring and/or grunting
increased respiratory rate above normal
hypoxia (low oxygen levels)
cyanosis (bluish skin)
lethargy and decreased activity
poor feeding (less than half of usual fluid intake in preceding 24 hours)
history of stopping breathing
Causes
The term usually refers to acute viral bronchiolitis, a common disease in infancy. This is most commonly caused by respiratory syncytial virus (RSV, also known as human pneumovirus). Other agents that cause this illness include human metapneumovirus, influenza, parainfluenza, coronavirus, adenovirus, rhinovirus and mycoplasma. Risk factors
Children are at an increased risk for progression to severe respiratory disease if they have any of the following additional factors:
Preterm infant (gestational age less than 37 weeks)
Younger age at onset of illness (less than 3 months of age)
Congenital heart disease
Immunodeficiency
Chronic lung disease
Neurological disorders
Tobacco smoke exposure
Diagnosis
The diagnosis is typically made by clinical examination. | Guidelines recommend exclusive breastfeeding for infants for the first 6 months of life.Palivizumab, a monoclonal antibody against RSV, can be administered to prevent bronchiolitis to infants less than one year of age that were born very prematurely or that have underlying heart disease or chronic lung disease of prematurity. Passive immunization therapy requires monthly injections during winter. Otherwise healthy premature infants that were born after a gestational age of 29 weeks should not be administered palivizumab as the harms outweigh the benefits. Passive protection through the administration of other novel monoclonal antibodies is also under evaluation.Immunizations for RSV are being developed but none are available currently outside of clinical trials.Tobacco smoke exposure has been shown to increase both the rates of lower respiratory disease in infants, as well as the risk and severity of bronchiolitis. Tobacco smoke lingers in the environment for prolonged periods and on clothing even when smoking outside the home. Guidelines recommend that parents be fully educated on the risks of tobacco smoke exposure on children with bronchiolitis. Management
Treatment of bronchiolitis is usually focused on the hydration and symptoms instead of the infection itself since the infection will run its course and complications are typically from the symptoms themselves. Without active treatment, half of cases will go away in 13 days and 90% in three weeks. Children with severe symptoms, especially poor feeding or dehydration, may be considered for hospital admission. Oxygen saturation under 90%-92% as measured with pulse oximetry is also frequently used as an indicator of need for hospitalization. | 11
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A Coopers hernia is a femoral hernia with two sacs, the first being in the femoral canal, and the second passing through a defect in the superficial fascia and appearing almost immediately beneath the skin. Umbilical
They involve protrusion of intra-abdominal contents through a weakness at the site of passage of the umbilical cord through the abdominal wall. Umbilical hernias in adults are largely acquired, and are more frequent in obese or pregnant women. Abnormal decussation of fibers at the linea alba may be a contributing factor. Incisional
An incisional hernia occurs when the defect is the result of an incompletely healed surgical wound. When these occur in median laparotomy incisions in the linea alba, they are termed ventral hernias. These can be the most frustrating and difficult to treat, as the repair utilizes already attenuated tissue. These occur in about 13% of people at 2 years following surgery. Diaphragmatic
Higher in the abdomen, an (internal) "diaphragmatic hernia" results when part of the stomach or intestine protrudes into the chest cavity through a defect in the diaphragm. A hiatus hernia is a particular variant of this type, in which the normal passageway through which the esophagus meets the stomach (esophageal hiatus) serves as a functional "defect", allowing part of the stomach to (periodically) "herniate" into the chest. | A subsequent group noticed that this mutation is in a region important for modulation by G protein-coupled receptors (GPCRs). GPCR activation leads to inhibition of wild-type CaV2.1 currents. R192Q mutant channel currents are also decreased by GPCR activation, but by a smaller amount. A more recent group has confirmed some of these results by creating a R192Q knock-in mouse. They confirmed that the R192Q mutant activates at more negative potentials and that neurons producing these channels have much larger whole-cell current. This resulted in a much larger quantal content (the number of neurotransmitter packets released per action potential) and generally enhanced neurotransmitter release in R192Q-expressing neurons versus wild-type. Consequently, these mutant mice were more susceptible to cortical-spreading-depression than their wild-type counterparts. The most recent experiments on this mutant, however, have contradicted some of these results. In CaV2.1 knockout neurons transfected with human channels, P/Q-type currents from mutant channels are actually smaller than their wild-type counterpart. They also found a significant decrease in calcium influx during depolarization, leading to decreased quantal content, in mutant versus wild-type expressing neurons. Neurons expressing mutant channels were also less able to mediate inhibitory input and have smaller inhibitory postsynaptic currents through P/Q-type channels. Further testing with this and other mutants is required to determine their end effect on human physiology. FHM2 (ATP1A2)
The second subtype of familial hemiplegic migraine, FHM2, is caused by mutations in the gene ATP1A2 that encodes a Na+/K+-ATPase. This Na+/K+-ATPase is heavily expressed in astrocytes and helps to set and maintain their reversal potential. | 0-1
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A Colles fracture is a type of fracture of the distal forearm in which the broken end of the radius is bent backwards. Symptoms may include pain, swelling, deformity, and bruising. Complications may include damage to the median nerve.It typically occurs as a result of a fall on an outstretched hand. Risk factors include osteoporosis. The diagnosis may be confirmed via X-rays. The tip of the ulna may also be broken.Treatment may include casting or surgery. Surgical reduction and casting is possible in the majority of cases in people over the age of 50. Pain management can be achieved during the reduction with procedural sedation and analgesia or a hematoma block. A year or two may be required for healing to occur.About 15% of people have a Colles fracture at some point in their life. They occur more commonly in young adults and older people than in children and middle-aged adults. Women are more frequently affected than men. The fracture is named after Abraham Colles who described it in 1814. Causes
The fracture is most commonly caused by people falling onto a hard surface and breaking their fall with outstretched hand (FOOSH)–falling with wrists flexed would lead to a Smiths fracture. Originally it was described in elderly and/or post-menopausal women. It usually occurs about three to five centimetres proximal to the radio-carpal joint with posterior and lateral displacement of the distal fragment resulting in the characteristic "dinner fork" or "bayonet" like deformity. | Colles fracture is a common fracture in people with osteoporosis, second only to vertebral fractures. Diagnosis
Diagnosis can be made upon interpretation of anteroposterior and lateral views alone.The classic Colles fracture has the following characteristics:
Transverse fracture of the radius
2.5 cm (0.98 inches) proximal to the radio-carpal joint
dorsal displacement and dorsal angulation, together with radial tiltOther characteristics:
Radial shortening
Loss of ulnar inclination≤
Radial angulation of the wrist
Comminution at the fracture site
Associated fracture of the ulnar styloid process in more than 60% of cases. Classification
The term Colles fracture is classically used to describe a fracture at the distal end of the radius, at its cortico-cancellous junction. However, the term now tends to be used loosely to describe any fracture of the distal radius, with or without involvement of the ulna, that has dorsal displacement of the fracture fragments. Colles himself described it as a fracture that “takes place at about an inch and a half (38mm) above the carpal extremity of the radius” and “the carpus and the base of metacarpus appears to be thrown backward”. The fracture is sometimes referred to as a "dinner fork" or "bayonet" deformity due to the shape of the resultant forearm.Colles fractures can be categorized according to several systems including Frykman, Gartland & Werley, Lidström, Nissen-Lie and the Olders classifications. Treatment
Management depends on the severity of the fracture. An undisplaced fracture may be treated with a cast alone. The cast is applied with the distal fragment in palmar flexion and ulnar deviation. A fracture with mild angulation and displacement may require closed reduction. | 11
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This is important because individuals with Angelman Syndrome who already possess some form of non-verbal communication have a much harder time adapting to changes in a new or existing AAC device because they can communicate their needs much faster nonverbally.Occupational therapists can assist individuals with Angelman syndrome with many other skills as well. Many individuals with Angelman syndrome also have difficulty processing sensory information and responding appropriately to sensory stimuli. Occupational therapists can work together with these individuals to improve their visual perceptual skills and increase their sensory awareness.Those with the syndrome are generally happy and contented people who like human contact and play. People with AS exhibit a profound desire for personal interaction with others. Communication can be difficult at first, but as a child with AS develops, there is a definite character and ability to make themselves understood. People with AS tend to develop strong non-verbal skills to compensate for their limited use of speech. It is widely accepted that their understanding of communication directed to them is much larger than their ability to return conversation. Most affected people will not develop more than 5–10 words, if any at all. Prognosis
The severity of the symptoms associated with Angelman syndrome varies significantly across the population of those affected. Some speech and a greater degree of self-care are possible among the least profoundly affected. Walking and the use of simple sign language may be beyond the reach of the more profoundly affected. | Signs and symptoms
Signs and symptoms of Angelman syndrome and their relative frequency in affected individuals are:
Consistent (100%)
Developmental delay, functionally severe
Speech impairment, no or minimal use of words; receptive and non-verbal communication skills higher than verbal ones
Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs
Behavioral characteristics of the following types: any combination of atypical frequent laughter/smiling; atypically happy demeanor; easily excitable personality, often with hand flapping movements; hypermotoric behavior; short attention span
Frequent (more than 80%)
Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (absolute or relative) by age 2
Seizures, onset usually less than 3 years of age
Abnormal EEG, characteristic pattern with large amplitude slow-spike waves
Associated (20–80%)
Cause
Angelman syndrome is caused by the lack of expression of a gene known as UBE3A during development. This gene is located within a region of chromosome 15 known as 15q11-q13 and is part of the ubiquitin pathway. In fact, UBE3A codes for a very selective E6-AP ubiquitin ligase for which MAPK1, PRMT5, CDK1, CDK4, β-catenin, and UBXD8 have been identified as ubiquitination targetsTypically, a fetus inherits a maternal copy of UBE3A and a paternal copy of UBE3A. In certain areas of the developing brain, the paternal copy of UBE3A is inactivated through a process known as imprinting and the fetus relies on the functioning maternal copy of UBE3A in order to develop normally. In an individual with AS, however, the maternal UBE3A gene is absent or not functioning normally. | 11
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This was the first demonstration that an arthropod could act as a disease vector to transmit an infectious agent to a vertebrate host.In 1957, the first human case was documented in a splenectomized Croatian herdsman. The agent was B. divergens. In 1969, the first case was reported in an immunocompetent individual on Nantucket Island. The agent was B. microti, and the vector was the tick I. scapularis. Equine babesiosis (caused by the protozoan Theileria equi) is also known as piroplasmosis (from the Latin piro, meaning pear + Greek plasma, a thing formed). Other animals
Veterinary treatment of babesiosis does not normally use antibiotics. In livestock and animals, diminazen (Berenil), imidocarb, or trypan blue would be the drugs of choice for treatment of B. canis rossi (dogs in Africa), B. bovis, and B. bigemina (cattle in Southern Africa). In acute cases in cattle, blood transfusion may be carried out. A vaccine is effective against B. canis canis (dogs in the Mediterranean region), but is ineffective against B. c. rossi. B. imitans causes a mild form of the disease that frequently resolves without treatment (dogs in Southeast Asia). References
External links
Center for Global Health (2019-06-25). "Babesiosis". Parasites and Health, DPDx—Laboratory Identification of Parasites of Public Health Concern. Centers for Disease Control & Prevention. Archived from the original on 2013-03-07. Retrieved 2003-10-07. Public domain source from which the first version of this article was derived. Krause, Peter J; et al. (27 January 2021). | This causes the affected portion of the colon to be unable to contract and relax to help push out a bowel movement. The affected portion of the colon remains contracted, making it difficult for stool to pass through. Concern for HD should be raised in a child who has not passed stool during the first 48 hours of life. Milder forms of HD, in which only a small portion of the colon is affected, can present later in childhood as constipation, abdominal pain, and bloating. Similar disorders to HD include anal achalasia and hypoganglionosis. In hypoganglionosis, there is a low number of neural crest cells, so the colon remains contracted. In anal achalasia, the internal anal sphincter remains contracted, making it difficult for stool to pass. However, there is a normal number of neural crest cells present.There are also congenital structural anomalies that can lead to constipation, including anterior displacement of the anus, imperforate anus, strictures, and small left colon syndrome. Anterior displacement of the anus can be diagnosed on physical exam. The disease causes constipation because the inappropriate positioning of the anus which make it difficult to pass a bowel movement. Imperforate anus is an anus that ends in a blind pouch and does not connect to the rest of the persons intestines. Small left colon syndrome is a rare disease in which the left side of the babies colon has a small diameter, which makes it difficult for stool to pass. | 0-1
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Proctitis is an inflammation of the anus and the lining of the rectum, affecting only the last 6 inches of the rectum. Signs and symptoms
A common symptom is a continual urge to have a bowel movement—the rectum could feel full or have constipation. Another is tenderness and mild irritation in the rectum and anal region. A serious symptom is pus and blood in the discharge, accompanied by cramps and pain during the bowel movement. If there is severe bleeding, anemia can result, showing symptoms such as pale skin, irritability, weakness, dizziness, brittle nails, and shortness of breath.Symptoms are ineffectual straining to empty the bowels, diarrhea, rectal bleeding and possible discharge, a feeling of not having adequately emptied the bowels, involuntary spasms and cramping during bowel movements, left-sided abdominal pain, passage of mucus through the rectum, and anorectal pain. Sexually transmitted proctitis
Gonorrhea (Gonococcal proctitis)
This is the most common cause. Strongly associated with anal intercourse. Symptoms include soreness, itching, bloody or pus-like discharge, or diarrhea. Other rectal problems that may be present are anal warts, anal tears, fistulas, and hemorrhoids.Chlamydia (chlamydia proctitis)
Accounts for twenty percent of cases. People may show no symptoms, mild symptoms, or severe symptoms. Mild symptoms include rectal pain with bowel movements, rectal discharge, and cramping. With severe cases, people may have discharge containing blood or pus, severe rectal pain, and diarrhea. Some people have rectal strictures, a narrowing of the rectal passageway. | Other treatments may include mesalamine suppositories, vitamin E, hyperbaric oxygen, or short chain fatty acid enemas; however these treatments are only supported by observational or anecdotal evidence. See also
Paraproctitis
References
External links
eMedicine | 11
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Flushing is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or ears, and generally assumed to reflect emotional stress, such as embarrassment, anger, or romantic stimulation. Flushing is also a cardinal symptom of carcinoid syndrome—the syndrome that results from hormones (often serotonin or histamine) being secreted into systemic circulation. Causes
Sex flush
Commonly referred to as the sex flush, vasocongestion (increased blood flow) of the skin can occur during all four phases of the human sexual response cycle. Studies show that the sex flush occurs in approximately 50–75% of females and 25% of males, yet not consistently. The sex flush tends to occur more often under warmer conditions and may not appear at all under lower temperatures.During the female sex flush, pinkish spots develop under the breasts, then spread to the breasts, torso, face, hands, soles of the feet, and possibly over the entire body. Vasocongestion is also responsible for the darkening of the clitoris and the walls of the vagina during sexual arousal. | EPI results from progressive failure in the exocrine function of the pancreas to provide its digestive enzymes, often in response to a genetic condition or other disease state, resulting in the inability of the animal involved to properly digest food. Signs and symptoms
Loss of pancreatic enzymes leads to maldigestion and malabsorption, which may in turn lead to:
anemia (Vitamin B12, iron, folate deficiency)
bleeding disorders (Vitamin K malabsorption)
edema (hypoalbuminemia)
fatigue
flatulence and abdominal distention (bacterial fermentation of unabsorbed food)
hypocalcemia
metabolic bone disease (Vitamin D deficiency)
neurologic manifestation
steatorrhea
weight loss
Causes
In humans, the most common causes of EPI are chronic pancreatitis and cystic fibrosis, the former a longstanding inflammation of the pancreas altering the organs normal structure and function that can arise as a result of malnutrition, heredity, or (in the Western world especially), behaviour (alcohol use, smoking), and the latter a recessive hereditary disease most common in Europeans and Ashkenazi Jews where the molecular culprit is an altered, CFTR-encoded chloride channel. According to WebMD, "Crohns disease and celiac disease can also lead to EPI in some people". In children, another common cause is Shwachman-Bodian-Diamond syndrome, a rare autosomal recessive genetic disorder resulting from mutation in the SBDS gene. Diagnosis
The three main tests used in considering a diagnosis of EPI are: fecal elastase test, fecal fat test, and a direct pancreatic function test. The latter is a limitedly used test that assesses exocrine function in the pancreas by inserting a tube into the small intestine to collect pancreatic secretions. | 0-1
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The organization of the modules necessary to biosynthesize Vancomycin is shown in Figure 1. In the biosynthesis of Vancomycin, additional modification domains are present, such as the epimerization (E) domain, which isomerizes the amino acid from one stereochemistry to another, and a thioesterase domain (TE) is used as a catalyst for cyclization and releases of the molecule via a thioesterase scission. A set of NRPS enzymes (peptide synthase VpsA, VpsB, and VpsC) are responsible for assembling the heptapeptide. (Figure 2). VpsA codes for modules 1, 2, and 3. VpsB codes for modules 4, 5, and 6, and VpsC codes for module 7. The vancomycin aglycone contains 4 D-amino acids, although the NRPSs only contain 3 epimerization domains. The origin of D-Leu at residue 1 is not known. The three peptide syntheses are located at the start of the region of the bacterial genome linked with antibiotic biosynthesis, and span 27 kb.β-hydroxytyrosine (β-HT) is synthesized prior to incorporation into the heptapeptide backbone. L-tyrosine is activated and loaded on the NRPS VpsD, hydroxylated by OxyD, and released by the thioesterase Vhp. The timing of the chlorination by halogenase VhaA during biosynthesis is currently undetermined, but is proposed to occur before the complete assembly of the heptapeptide.After the linear heptapeptide molecule is synthesized, vancomycin has to undergo further modifications, such as oxidative cross-linking and glycosylation, in trans by distinct enzymes, referred to as tailoring enzymes, to become biologically active (Figure 3). To convert the linear heptapeptide to cross-linked, glycosylated vancomycin, six enzymes, are required. | These guidelines restrict use of vancomycin to these indications:
Treatment of serious infections caused by susceptible organisms resistant to penicillins (methicillin-resistant S. aureus (MRSA) and multidrug-resistant S. epidermidis (MRSE)) or in individuals with serious allergy to penicillins
Treatment of pseudomembranous colitis caused by C. difficile; in particular, in cases of relapse or where the infection is unresponsive to metronidazole treatment (for this indication, vancomycin is given orally, rather than by its typical intravenous route)
For treatment of infections caused by Gram-positive microorganisms in patients with serious allergies to beta-lactam antimicrobials. Antibacterial prophylaxis for endocarditis following certain procedures in penicillin-hypersensitive individuals at high risk
Surgical prophylaxis for major procedures involving implantation of prostheses in institutions with a high rate of MRSA or MRSE
Early in treatment as an empiric antibiotic for possible MRSA infection while waiting for culture identification of the infecting organism
Halting the progression of primary sclerosing cholangitis and preventing symptoms; vancomycin does not cure the patient and success is limited
Treatment of endophthalmitis by intravitreal injection for gram-positive bacteria coverage. It use to prevent the condition, however, is not recommended due to the risk of side effects. Spectrum of susceptibility
Vancomycin is considered a last resort medication for the treatment of sepsis and lower respiratory tract, skin, and bone infections caused by Gram-positive bacteria. | 11
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Another new application of genetic technology is the ability to produce genetically modified mosquitoes that do not transmit malaria, potentially allowing biological control of malaria transmission.In one study, a genetically modified strain of Anopheles stephensi was created that no longer supported malaria transmission, and this resistance was passed down to mosquito offspring.Gene drive is a technique for changing wild populations, for instance to combat or eliminate insects so they cannot transmit diseases (in particular mosquitoes in the cases of malaria, zika, dengue and yellow fever).In December 2020, a review article found that malaria-endemic regions had lower reported COVID-19 case fatality rates on average than regions where malaria was not known to be endemic. Other animals
While there are no animal reservoirs for the strains of malaria that cause human infections, nearly 200 parasitic Plasmodium species have been identified that infect birds, reptiles, and other mammals, and about 30 species naturally infect non-human primates. Some malaria parasites that affect non-human primates (NHP) serve as model organisms for human malarial parasites, such as P. coatneyi (a model for P. falciparum) and P. cynomolgi (P. vivax). Diagnostic techniques used to detect parasites in NHP are similar to those employed for humans. Malaria parasites that infect rodents are widely used as models in research, such as P. berghei. Avian malaria primarily affects species of the order Passeriformes, and poses a substantial threat to birds of Hawaii, the Galapagos, and other archipelagoes. The parasite P. relictum is known to play a role in limiting the distribution and abundance of endemic Hawaiian birds. | To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen. The blockage of the microvasculature causes symptoms such as those in placental malaria. Sequestered red blood cells can breach the blood–brain barrier and cause cerebral malaria. Genetic resistance
According to a 2005 review, due to the high levels of mortality and morbidity caused by malaria—especially the P. falciparum species—it has placed the greatest selective pressure on the human genome in recent history. Several genetic factors provide some resistance to it including sickle cell trait, thalassaemia traits, glucose-6-phosphate dehydrogenase deficiency, and the absence of Duffy antigens on red blood cells.The impact of sickle cell trait on malaria immunity illustrates some evolutionary trade-offs that have occurred because of endemic malaria. Sickle cell trait causes a change in the haemoglobin molecule in the blood. Normally, red blood cells have a very flexible, biconcave shape that allows them to move through narrow capillaries; however, when the modified haemoglobin S molecules are exposed to low amounts of oxygen, or crowd together due to dehydration, they can stick together forming strands that cause the cell to distort into a curved sickle shape. In these strands, the molecule is not as effective in taking or releasing oxygen, and the cell is not flexible enough to circulate freely. | 11
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Symptoms including paranoia, amnesia, cerebellar malfunction, and lethargy can also manifest when undergoing histidine treatment. Future research
Every year, more than 200,000 individuals see their physicians concerning chemosensory problems, and many more taste disturbances are never reported. Due to the large number of persons affected by taste disorders, basic and clinical research are receiving support at different institutions and chemosensory research centers across the country. These taste and smell clinics are focusing their research on better understanding the mechanisms involved in gustatory function and taste disorders such as dysgeusia. For example, the National Institute on Deafness and Other Communication Disorders is looking into the mechanisms underlying the key receptors on taste cells and applying this knowledge to the future of medications and artificial food products. Meanwhile, the Taste and Smell Clinic at the University of Connecticut Health Center is integrating behavioral, neurophysiological, and genetic studies involving stimulus concentrations and intensities in order to better understand taste function. See also
Anosmia
Parosmia
References
External links
Dysgeusia at NIH | Once the loss has progressed to the 2–4 kHz range, there is increased difficulty understanding consonants. Both ears tend to be affected. The impact of presbycusis on communication depends on both the severity of the condition and the communication partner.Older adults with presbycusis often exhibit associated symptoms of social isolation, depression, anxiety, frailty and cognitive decline. The risk of having cognitive impairment increased 7 percent for every 10 dB of hearing loss at baseline. No effect of hearing aids was seen in the Lin Baltimore study. Causes
The aging process has three distinct components: physiologic degeneration, extrinsic damage (nosocusis), and intrinsic damage (sociocusis). These factors are superimposed on a genetic substrate, and may be overshadowed by general age-related susceptibility to diseases and disorders. Hearing loss is only weakly correlated with age. In preindustrial and non-industrial societies, persons retain their hearing into old age. In the Framingham cohort study, only 10% of the variability of hearing with age could be explained by age-related physiologic deterioration. Within family groups, heredity factors were dominant; across family groups, other, presumably sociocusis and nosocusis factors were dominant. Heredity: factors like early aging of the cochlea and susceptibility of the cochlea for drug insults are genetically determined. Oxidative stress
General inflammatory conditions
Sociocusis
Sociocusis is the condition of those who have hearing loss attributed to continuous noise exposures, unrelated to their job or occupation. This exposure to these stimuli is frequent, and are often considered common "background noises" that affect the hearing abilities of individuals. | 0-1
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Since this is difficult to see on the AP (anterior posterior) x-ray view an oblique x-ray of the lumbar spine can usually identify the spondylolysis. If inconclusive a further CT scan can produce a 3-dimensional images to more clearly show the defect although the exam increases the patients radiation dose by at least an order of magnitude than plain x-rays. Bone scintigraphy
Also known as a bone scan, bone scintigraphy involves the injection of a small amount of radioactive tracer into the bloodstream. This tracer decays and emits radioactive energy which can be detected by a special camera. The camera produces a black and white image where areas shown as dark black indicate bone damage of some kind. If there is a black spot in the lumbar vertebrae (e.g. L5) this indicates damage and potentially spondylolysis. If this test is positive, a CT scan is usually ordered to confirm spondylolysis. Computed tomography
Commonly known as a CT Scan or CAT scan, this form of imaging is very similar to x-ray technology but produces many more images than an x-ray does. The multiple images produce cross-sectional views not possible with an x-ray. This allows a physician or radiologist to examine the images from many more angles than an x-ray allows. For this reason the CT scan is much more accurate in detecting spondylolysis than an x-ray. Bone scintigraphy combined with CT scan is considered the gold standard which means that it is best at detecting spondylolysis. | To compensate, the large torque producing global muscles are used to stabilize the spine.In one study, patients are taught to train the co-contraction of deep abdominal muscles and lumbar multifidus in static postures, functional tasks and aerobic activities. This technique was shown to reduce pain and functional disability when compared to other conservative treatments. These results also had a long- term effect in reducing levels of pain and functional disability. This is because motor programming eventually became automatic, and conscious control was no longer needed to contract the deep abdominal muscles during activities. Activity restriction
Activity restriction of spondylolysis is advised for a short period of time once the patient becomes symptomatic, followed by a guided physical therapy program. Once spondylolysis has been diagnosed, treatment often consists of a short rest period of two to three days, followed by a physical therapy program. There should be restriction of heavy lifting, excessive bending, twisting and avoidance of any work, recreational activities or participation in sport that causes stress to the lumbar spine. Activity restriction can help eliminate and control a patients symptoms so they are able to resume their normal activities. Activity restriction is most commonly used in conjunction with other rehabilitation techniques including bracing. Bracing
Acute spondylolysis is most commonly treated through the use of an antilordotic brace (Boston brace) to control and limit spinal movement, and reduce stress on the injured spinal segment. Bracing immobilizes the spine in a flexed position for a short period to allow healing of the bony defect in the pars interarticularis. | 11
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Vaginal lubrication is a naturally produced fluid that lubricates a
vagina. Vaginal lubrication is always present, but production increases significantly near ovulation and during sexual arousal in anticipation of sexual intercourse. Vaginal dryness is the condition in which this lubrication is insufficient, and sometimes artificial lubricants are used to augment it. Without sufficient lubrication, sexual intercourse can be painful. The vaginal lining has no glands, and therefore the vagina must rely on other methods of lubrication. Plasma from vaginal walls due to vascular engorgement is considered to be the chief lubrication source, and the Bartholins glands, located slightly below and to the left and right of the introitus (vaginal opening), also secrete mucus to augment vaginal-wall secretions. Near ovulation, cervical mucus provides additional lubrication. Vaginal discharge
Composition
The lubricating fluid can vary in consistency, texture, taste, color, and odor, depending on sexual arousal, the phase of the menstrual cycle, the presence of an infection, certain drugs, genetic factors, and diet.Vaginal fluid is slightly acidic and can become more acidic with certain sexually transmitted diseases. The normal pH of vaginal fluid is between 3.8 and 4.5, contrasting with male semen which is typically between 7.2 and 7.8 (neutral pH is 7.0).During arousal, vaginal lubrication, also sometimes called "arousal fluid", is produced. This is clear, thin, and slippery. It typically only lasts up to an hour. Colloquially, this is referred to as "getting wet". Production
The human vagina is serviced by nerves that respond to vasoactive intestinal polypeptide (VIP). | As a result, VIP induces an increase in vaginal blood flow accompanied by an increase in vaginal lubrication. The findings suggest that VIP may participate in the control of the local physiological changes observed during sexual arousal: genital vasodilation and increase in vaginal lubrication. Vaginal dryness
Insufficient lubrication or vaginal dryness can cause dyspareunia, which is a type of sexual pain disorder. While vaginal dryness is considered an indicator for sexual arousal disorder, vaginal dryness may also result from insufficient excitement and stimulation or from hormonal changes caused by menopause (potentially causing atrophic vaginitis), pregnancy, or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sexual intimacy. Vaginal dryness can also be a symptom of Sjögren syndrome (SS), a chronic autoimmune disorder in which the body destroys moisture-producing glands. Certain medications, including some over-the-counter antihistamines, as well as life events such as pregnancy, lactation, menopause, aging or diseases such as diabetes, will inhibit lubrication. Medicines with anticholinergic or sympathomimetic effects will dry out the mucosal or "wet" tissues of the vagina. Such medicines include many common drugs for allergenic, cardiovascular, psychiatric, and other medical conditions. Oral contraceptives may also increase or decrease vaginal lubrication. Older women produce less vaginal lubrication and reduced estrogen levels may be associated with increased vaginal dryness. Artificial lubricants
When a woman is experiencing vaginal dryness before sexual activity, sexual intercourse may be uncomfortable or painful for her. | 11
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By standard plate count methods, following sequential dilutions, and growth on agar gel plates, the concentration of viable organisms or CFUs (Colony Forming Units), in a known volume of treated water can be evaluated, allowing the comparative assessment of materials performance.In 1946, Joshua Lederberg and Edward Tatum first described the phenomenon known as bacterial conjugation using E. coli as a model bacterium, and it remains the primary model to study conjugation. E. coli was an integral part of the first experiments to understand phage genetics, and early researchers, such as Seymour Benzer, used E. coli and phage T4 to understand the topography of gene structure. Prior to Benzers research, it was not known whether the gene was a linear structure, or if it had a branching pattern.E. coli was one of the first organisms to have its genome sequenced; the complete genome of E. coli K12 was published by Science in 1997From 2002 to 2010, a team at the Hungarian Academy of Science created a strain of Escherichia coli called MDS42, which is now sold by Scarab Genomics of Madison, WI under the name of "Clean Genome E. coli", where 15% of the genome of the parental strain (E. coli K-12 MG1655) were removed to aid in molecular biology efficiency, removing IS elements, pseudogenes and phages, resulting in better maintenance of plasmid-encoded toxic genes, which are often inactivated by transposons. Biochemistry and replication machinery were not altered. | Succimer, sold under the brand name Chemet among others, is a medication used to treat lead, mercury, and arsenic poisoning. When radiolabeled with technetium-99m, it is used in a number of types of diagnostic testing. A full course is 19 days of medications by mouth. More than two weeks should pass before a second course is given.Common side effects include vomiting, diarrhea, rash, and low blood neutrophil levels. Liver problems and allergic reactions may also occur with use. Whether use during pregnancy is safe for the baby is unclear. Dimercaptosuccinic acid is in the chelating agent family of medications. It works by binding with lead and a number of other heavy metals, allowing them to leave the body in the urine.Dimercaptosuccinic acid has been used medically since the 1950s. It is on the World Health Organizations List of Essential Medicines. In the United States, no generic version was available as of 2015. Medical uses
Dimercaptosuccinic acid is indicated for the treatment of lead poisoning in children with blood level measured above 45 µg/dl. The use of dimercaptosuccinic acid is not approved for prevention of lead poisoning in anticipation of exposure in known lead-contaminated environments. Dimercaptosuccinic acid can cross the blood–brain barrier of mice, but it is not known if this is also the case in humans. Even if dimercaptosuccinic acid cannot reverse the damages done to the central nervous system, it might prevent further deterioration.Dimercaptosuccinic acid facilitates urinary excretion of lead, and with sufficiently aggressive treatment, can reduce lead content in the brain. | 0-1
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Other anti-CD20 monoclonals
The efficacy and success of rituximab has led to some other anti-CD20 monoclonal antibodies being developed:
ocrelizumab, humanized (90%-95% human) B cell-depleting agent. ofatumumab (HuMax-CD20) a fully human B cell-depleting agent. Third-generation anti-CD20s such as obinutuzumab have a glycoengineered Fc fragment (Fc) with enhanced binding to Fc gamma receptors, which increase ADCC (antibody-dependent cellular cytotoxicity). This strategy for enhancing a monoclonal antibodys ability to induce ADCC takes advantage of the fact that the displayed Fc glycan controls the antibodys affinity for Fc receptors. References
External links
"Rituximab". Drug Information Portal. U.S. National Library of Medicine. "Discovery – Development of Rituximab". National Cancer Institute. 7 March 2014. | Other signs of a basilar skull fracture include CSF otorrhoea (drainage of CSF through the ear). It can have devastating complications in some patients, as the communication between the nasal cavity, the cerebrospinal fluid and the central nervous system can result in severe bacterial infections.CSF rhinorrhoea may be a complication of neurosurgery, such as functional endoscopic sinus surgery, and hypophysectomy (partial or complete removal of the pituitary gland). Non-traumatic
CSF rhinorrhoea may be caused by the growth of certain cancers (such as pituitary adenoma), congenital problems with bones of the skull, or inflammation that damages the bones of the skull. Diagnosis
Radiology
If a patient has clear, colourless liquid leaking from the nose, then radiographs or CT scans may be used to look for a basilar skull fracture. Biochemistry
Measures of CSF components, such as glucose, have been used in the past, but are neither sensitive nor specific. Beta-2 transferrin has a high positive predictive value of CSF rhinorrhoea. It has also been noted to be characterized by unilateral discharge. Treatment
Surgery
Neurosurgery is usually necessary to prevent the spread of infection to the meninges. Minimally invasive techniques tend to have fewer complications compared to open techniques. Conservative management
Conservative management includes watchful waiting, as some minor CSF leaks often stop spontaneously. See also
Beta-2 transferrin
Meningitis
Traumatic head injury
References
== External links == | 0-1
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Hyperchlorhydria, sometimes called chlorhydria, sour stomach or acid stomach, refers to the state in the stomach where gastric acid levels are higher than the reference range. The combining forms of the name (chlor- + hydr-), referring to chlorine and hydrogen, are the same as those in the name of hydrochloric acid, which is the active constituent of gastric acid. In humans, the normal pH is around 1 to 3, which varies throughout the day. The highest basal secretion levels are in the late evening (around 12 A.M. to 3 A.M.). Hyperchlorhydria is usually defined as having a pH less than 2. It has no negative consequences unless other conditions are also present such as gastroesophageal reflux disease (GERD).A cause for hyperchlorhydria is increased Gastrin production
See also
Achlorhydria
Hypochlorhydria
== References == | The arthritis may be "additive" (more joints become inflamed in addition to the primarily affected one) or "migratory" (new joints become inflamed after the initially inflamed site has already improved).Reactive arthritis is an RF-seronegative, HLA-B27-linked arthritis often precipitated by genitourinary or gastrointestinal infections. The most common triggers are intestinal infections (with Salmonella, Shigella or Campylobacter) and sexually transmitted infections (with Chlamydia trachomatis); however, it also can happen after group A streptococcal infections.It most commonly strikes individuals aged 20–40 years of age, is more common in men than in women, and more common in white than in black people. This is owing to the high frequency of the HLA-B27 gene in the white population. It can occur in epidemic form. Patients with HIV have an increased risk of developing reactive arthritis as well. Numerous cases during World Wars I and II focused attention on the triad of arthritis, urethritis, and conjunctivitis (often with additional mucocutaneous lesions), which at that time was also referred to as Fiessenger-Leroy-Reiter syndrome. Signs and symptoms
Because common systems involved include the eye, the urinary system, and the hands and feet, one clinical mnemonic in reactive arthritis is "Cant see, cant pee, cant climb a tree." The classic triad consists of:
Conjunctivitis
Nongonococcal urethritis
Asymmetric oligoarthritis
Symptoms generally appear within 1–3 weeks but can range from 4 to 35 days from the onset of the inciting episode of the disease. The classical presentation of the syndrome starts with urinary symptoms such as burning pain on urination (dysuria) or an increased frequency of urination. | 0-1
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The fibrils are, however, far from innocuous, as they keep the protein homeostasis network engaged, release oligomers, cause the formation of toxic oligomers via secondary nucleation, grow indefinitely spreading from district to district and, in some cases, may be toxic themselves.Calcium dysregulation has been observed to occur early in cells exposed to protein oligomers. These small aggregates can form ion channels through lipid bilayer membranes and activate NMDA and AMPA receptors. Channel formation has been hypothesized to account for calcium dysregulation and mitochondrial dysfunction by allowing indiscriminate leakage of ions across cell membranes. Studies have shown that amyloid deposition is associated with mitochondrial dysfunction and a resulting generation of reactive oxygen species (ROS), which can initiate a signalling pathway leading to apoptosis. There are reports that indicate amyloid polymers (such as those of huntingtin, associated with Huntingtons disease) can induce the polymerization of essential amyloidogenic proteins, which should be deleterious to cells. Also, interaction partners of these essential proteins can also be sequestered.All these mechanisms of toxicity are likely to play a role. In fact, the aggregation of a protein generates a variety of aggregates, all of which are likely to be toxic to some degree. A wide variety of biochemical, physiological and cytological perturbations has been identified following the exposure of cells and animals to such species, independently of their identity. The oligomers have also been reported to interact with a variety of molecular targets. Hence, it is unlikely that there is a unique mechanism of toxicity or a unique cascade of cellular events. | Note that the rate of secondary nucleation is proportional to the mass of aggregates, defined as
M
(
t
)
=
∑
j
=
n
1
∞
j
f
(
t
,
j
)
{\displaystyle M(t)=\sum _{j=n_{1}}^{\infty }jf(t,j)}
. | 11
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Employers may use hearing loss prevention programs to help educate and prevent dangerous levels of exposure to noise. Government organizations set regulations to ensure employees, if following the protocol, should have minimal risk to permanent damage to their hearing.Certain groups are advised to wear ear plugs when working or riding to avoid the risk of tinnitus, caused by overexposure to loud noises such as wind noise for motorcycle riders. Occupationally this includes musicians, DJs, agricultural, and construction workers as they are at a greater risk compared to the general population. Several medicines have ototoxic effects, and can have a cumulative effect that can increase the damage done by noise. If ototoxic medications must be administered, close attention by the physician to prescription details, such as dose and dosage interval, can reduce the damage done. Management
If a specific underlying cause is determined, treating it may lead to improvements. Otherwise, the primary treatment for tinnitus is talk therapy, sound therapy, or hearing aids. There are no effective drugs that treat tinnitus. Psychological
The best supported treatment for tinnitus is a type of counseling called cognitive behavioral therapy (CBT) which can be delivered via the internet or in person. It decreases the amount of stress those with tinnitus feel. These benefits appear to be independent of any effect on depression or anxiety in an individual. Acceptance and commitment therapy (ACT) also shows promise in the treatment of tinnitus. Relaxation techniques may also be useful. | Treatable conditions may include middle ear infection, acoustic neuroma,
concussion, and otosclerosis.Evaluation of tinnitus can include a hearing test (audiogram), measurement of acoustic parameters of the tinnitus like pitch and loudness, and psychological assessment of comorbid conditions like depression, anxiety, and stress that are associated with severity of the tinnitus.One definition of tinnitus, as compared to normal ear noise experience, is lasting five minutes at least twice a week. However, people with tinnitus often experience the noise more frequently than this. Tinnitus can be present constantly or intermittently. Some people with constant tinnitus might not be aware of it all the time, but only for example during the night when there is less environmental noise to mask it. Chronic tinnitus can be defined as tinnitus with duration of six months or more. Audiology
Since most persons with tinnitus also have hearing loss, a pure tone hearing test resulting in an audiogram may help diagnose a cause, though some persons with tinnitus do not have hearing loss. An audiogram may also facilitate fitting of a hearing aid in those cases where hearing loss is significant. The pitch of tinnitus is often in the range of the hearing loss. Psychoacoustics
Acoustic qualification of tinnitus will include measurement of several acoustic parameters like frequency in cases of monotone tinnitus or frequency range and bandwidth in cases of narrow band noise tinnitus, loudness in dB above hearing threshold at the indicated frequency, mixing-point, and minimum masking level. | 11
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In 2001 the FDA announced a new regulatory scheme called SMART (the System to Manage Accutane Related Teratogenicity) that required Roche to provide defined training materials to doctors, and for doctors to sign and return a letter to Roche acknowledging that they had reviewed the training materials, for Roche to then send stickers to doctors, which doctors would have to place on prescriptions they give people after they have confirmed a negative pregnancy test; prescriptions could only be written for 30 days and could not be renewed, thus requiring a new pregnancy test for each prescription.In February 2002, Roches patents for isotretinoin expired, and there are now many other companies selling cheaper generic versions of the drug. On June 29, 2009, Roche Pharmaceuticals, the original creator and distributor of isotretinoin, officially discontinued both the manufacture and distribution of their Accutane brand in the United States due to what the company described as business reasons related to low market share (below 5%), coupled with the high cost of defending personal injury lawsuits brought by some people who took the drug. Generic isotretinoin will remain available in the United States through various manufacturers. Roche USA continues to defend Accutane and claims to have treated over 13 million people since its introduction in 1982. F. Hoffmann-La Roche Ltd. apparently will continue to manufacture and distribute Roaccutane outside of the United States.Among others, actor James Marshall sued Roche over allegedly Accutane-related disease that resulted in removal of his colon. | There are typically language and walking delays, and those affected have very low muscle tone and decreased reflexes. They may have neural tube defects such as lipomyelomeningocele (a form of spina bifida) or may have syringomyelia (a cyst in the spinal cord). Those with the syndrome may also have symptoms of dysautonomia (impairments in the autonomic nervous system), including gastrointestinal dysmotility, contributing to gastroesophageal reflux disease, or neurogenic bladder dysfunction, in which bladder control is limited. Dysautonomia has also led to high pain tolerance and reduced sweating in some patients. Some of those with the syndrome have been found to have an underdeveloped corpus callosum, the main band of white matter that connects the two cerebral hemispheres. Skeletal
Okamoto syndrome patients often have skeletal problems such as scoliosis or hip dysplasia, which can lead to hip dislocation. They may be born with congenital vertebral anomalies; parts of the spine may be fused and fail to segment. There may also be extra vertebrae in the lower back. Some of those affected have been reported to have premature fusion of the skull bones (craniosynostosis), particularly those across the midline and at the front of the skull. This has led to an elongated skull shape known as scaphocephaly as well as a ridge on the forehead known as a metopic ridge. Growth
Those affected may be born with low weight and size and may display stunted growth in childhood, although this symptom has been variable and not in every individual with Okamoto syndrome. | 0-1
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Depression
A few small trials have found benefits in people with depression. Research is based on the facial feedback hypothesis. Premature ejaculation
The drug for the treatment of premature ejaculation has been under development since 7 August 2013, and is in Phase II of the FDA trials. References
External links
BotDB: extensive resources on BoNT structures, inhibitors, kinetics, and literature
Overview of all the structural information available in the PDB for UniProt: P0DPI1 (Botulinum neurotoxin type A) at the PDBe-KB. Overview of all the structural information available in the PDB for UniProt: P10844 (Botulinum neurotoxin type B) at the PDBe-KB. Overview of all the structural information available in the PDB for UniProt: A0A0X1KH89 (Bontoxilysin A) at the PDBe-KB. "OnabotulinumtoxinA". Drug Information Portal. U.S. National Library of Medicine. "RimabotulinumtoxinB". Drug Information Portal. U.S. National Library of Medicine. "AbobotulinumtoxinA". Drug Information Portal. U.S. National Library of Medicine. "AbobotulinumtoxinA Injection". MedlinePlus. "IncobotulinumtoxinA Injection". MedlinePlus. "OnabotulinumtoxinA Injection". MedlinePlus. "PrabotulinumtoxinA-xvfs Injection". MedlinePlus. "RimabotulinumtoxinB Injection". MedlinePlus. | Banki syndrome is a rare disorder in which two or more bones are fused. The symptoms may include: abnormality of the long bone of hand; short fingers or toes; permanent curving of the pinkie finger; fusion of wrist bones. The disorder has been reported in three generations of a single Hungarian family. First described by Z. Banki in a 1965 paper, it has been noted as being similar to Liebenberg syndrome, featuring lunatotriquetral fusion of the lunate bone with the triquetral bone, clinodactyly of the fingers, overall short metacarpals, and thin diaphysis of the longer bones, but unlike Liebenberg, no elbow dysplasia is observed. Sources
== References == | 0-1
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Severe sickle cell crises, in some cases resulting in death, have been associated with the use of filgrastim in patients with sickle cell disorders. Interactions
Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes; this should be considered when interpreting bone-imaging results. Mechanism of action
G-CSF is a colony stimulating factor which has been shown to have minimal direct in vivo or in vitro effects on the production of other haematopoietic cell types. Neupogen (filgrastim) is the name for recombinant methionyl human granulocyte colony stimulating factor (r-metHuG-CSF). Society and culture
Biosimilars
In 2015, Sandozs filgrastim-sndz (trade name Zarxio), obtained the approval of the U.S. Food and Drug Administration (FDA) as a biosimilar. This was the first product to be passed under the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), as part of the Affordable Care Act. Zarxio was approved as a biosimilar, not as an interchangeable product, the FDA notes. And under the BPCI Act, only a biologic that has been approved as an "interchangeable" may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. | Flashing may refer to:
Technology
Firmware#Flashing, overwriting an EEPROM module in a device
BIOS flashing, overwriting a BIOS image
Flashing (cinematography), a technique that desaturates the color so that one sees more in shadowed areas
Flashing (weatherproofing), construction material used to prevent the passage of water around objects
Flash evaporation, causing evaporation by lowering a fluids pressure below its vapour pressure
Flashing light, such as a light bulb or computers cursor
Flash (manufacturing), excess material attached to a moulded product which must usually be removed
Other
Flashing (horse)
Flashing, a 1981 album by Himiko Kikuchi
Exhibitionism, sexual body exposure
Indecent exposure, inappropriate public nudity
Headlight flashing, to alert other drivers
Facing (retail), moving shelved products to the front
See also
Flash (disambiguation) | 0-1
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People who may have had depression include English author Mary Shelley, American-British writer Henry James, and American president Abraham Lincoln. Some well-known contemporary people with possible depression include Canadian songwriter Leonard Cohen and American playwright and novelist Tennessee Williams. Some pioneering psychologists, such as Americans William James and John B. Watson, dealt with their own depression. There has been a continuing discussion of whether neurological disorders and mood disorders may be linked to creativity, a discussion that goes back to Aristotelian times. British literature gives many examples of reflections on depression. English philosopher John Stuart Mill experienced a several-months-long period of what he called "a dull state of nerves", when one is "unsusceptible to enjoyment or pleasurable excitement; one of those moods when what is pleasure at other times, becomes insipid or indifferent". He quoted English poet Samuel Taylor Coleridges "Dejection" as a perfect description of his case: "A grief without a pang, void, dark and drear, / A drowsy, stifled, unimpassioned grief, / Which finds no natural outlet or relief / In word, or sigh, or tear." English writer Samuel Johnson used the term "the black dog" in the 1780s to describe his own depression, and it was subsequently popularized by British Prime Minister Sir Winston Churchill, who also had the disorder. Johann Wolfgang von Goethe in his Faust, Part I, published in 1808, has Mephistopheles assume the form of a black dog, specifically a poodle. Social stigma of major depression is widespread, and contact with mental health services reduces this only slightly. | This may take 24 to 48 hours for it to take effect, and it is not well suited to cases where the impaction needs to be removed immediately due to risk of complications or severe pain. Enemas (such as hyperosmotic saline) and suppositories (such as glycerine suppositories) work by increasing water content and stimulating peristalsis to aid in expulsion, and both work much more quickly than oral laxatives. Because enemas work in 2–15 minutes, they do not allow sufficient time for a large fecal mass to soften. Even if the enema is successful at dislodging the impacted stool, the impacted stool may remain too large to be expelled through the anal canal. Mineral oil enemas can assist by lubricating the stool for easier passage. In cases where enemas fail to remove the impaction, polyethylene glycol can be used to attempt to soften the mass over 24–48 hours, or if immediate removal of the mass is needed, manual disimpaction may be used. Manual disimpaction may be performed by lubricating the anus and using one gloved finger with a scoop-like motion to break up the fecal mass. Most often manual disimpaction is performed without general anaesthesia, although sedation may be used. In more involved procedures, general anaesthesia may be used, although the use of general anaesthesia increases the risk of damage to the anal sphincter. If all other treatments fail, surgery may be necessary. An easier, more comfortable, and more efficient method to enema and manual disimpaction is to use pulsed irrigation evacuation (PIE). | 0-1
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Most people with ASIA scores of A (complete injuries) do not have functional motor recovery, but improvement can occur. Most patients with incomplete injuries recover at least some function. Chances of recovering the ability to walk improve with each AIS grade found at the initial examination; e.g. an ASIA D score confers a better chance of walking than a score of C. The symptoms of incomplete injuries can vary and it is difficult to make an accurate prediction of the outcome. A person with a mild, incomplete injury at the T5 vertebra will have a much better chance of using his or her legs than a person with a severe, complete injury at exactly the same place. Of the incomplete SCI syndromes, Brown-Séquard and central cord syndromes have the best prognosis for recovery and anterior cord syndrome has the worst.People with nontraumatic causes of SCI have been found to be less likely to develop complete injuries and some complications such as pressure sores and deep vein thrombosis, and to have shorter hospital stays. Their scores on functional tests were better than those of people with traumatic SCI upon hospital admission, but when they were tested upon discharge, those with traumatic SCI had improved such that both groups results were the same. In addition to the completeness and level of the injury, age and concurrent health problems affect the extent to which a person with SCI will be able to live independently and to walk. | Aliskiren/hydrochlorothiazide, sold under the brand name Tekturna HCT among others, is a fixed-dose combination medication for the treatment of hypertension (high blood pressure). It contains aliskiren, a renin inhibitor, and hydrochlorothiazide, a diuretic. It is taken by mouth.The most common side effect is diarrhea.Aliskiren/hydrochlorothiazide was approved for medical use in the United States in January 2008, and for use in the European Union in January 2009. Medical uses
Aliskiren/hydrochlorothiazide is indicated for the treatment of essential hypertension in adults. References
External links
"Aliskiren hemifumarate mixture with hydrochlorothiazide". Drug Information Portal. U.S. National Library of Medicine. | 0-1
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This early onset gives the name of this disorder the slightly misleading ending "of childhood". AHC is not exclusively limited to childhood – attacks in some cases become milder after the first ten years of life, but they never completely disappear. Paroxysmal symptoms
AHC patients have exhibited various paroxysmal symptoms which manifest to different degrees in each person. Paroxysmal symptoms include tonic, tonic-clonic, or myoclonic limb movements, dystonic posturing, choreoathetosis, ocular nystagmus, and various other ocular motor abnormalities. Almost half of all people have dystonic symptoms prior to experiencing hemiplegia. These symptoms generally begin before 8 months of age. Ocular motor abnormalities occur early, and these are the most frequent early symptoms of AHC, particularly nystagmus. Almost 1/3 of people with this disorder had episodic ocular motor features within 1–2 days of birth. Many also experienced hemiplegia and dystonia before 3 months of age. A final symptom that may be considered paroxysmal is a temporary change in behavior - some patients will become unreasonable, demanding, and aggressive either before or after an attackNot all patients have all of these symptoms, and it is not known whether they are caused by AHC. Symptoms usually manifest in the first 3 months of the childs life, with an average onset of 2.5 months. Frequently, some of these symptoms will manifest in the neonatal period. These paroxysmal symptoms are often used to help diagnose AHC, since there is no simple test for it.In some cases, EEGs taken during these paroxysmal events were characterized by a generalized background slowing. | There is, however, not yet any conclusive evidence that AHC is fatal or that it shortens life expectancy, but the relatively recent discovery of the disorder makes large data for this type of information unavailable. Treatment for AHC has not been extremely successful, and there is no cure. There are several drugs available for treatment, as well as management strategies for preventing and dealing with hemiplegic attacks. Management strategies
Hemiplegic attacks can be brought on by particular triggers, and management of AHC often centers around avoiding common or known triggers. While triggers vary greatly from person to person, there are also some common ones which are prevalent in many patients. Common triggers include temperature changes, water exposure, bright lights, certain foods, emotional stress, and physical activity. While avoiding triggers may help, it cannot prevent all hemiplegic episodes because many occur without being triggered. Because attacks and other associated symptoms end with sleep, various sedatives can be used to help patients sleep. Flunarizine
The most common drug used to treat AHC is flunarizine. Flunarizine functions by acting as a calcium channel blocker. Other drugs, in order of frequency of use are benzodiazepines, carbamazapine, barbiturates, and valproic acid. Flunarizine is prescribed for the purpose of reducing the severity of AHC attacks and the number of episodes, though it rarely stops attacks altogether. Minimizing the attacks may help reduce damage to the body from hemiplegic attacks and improve long-term outcomes as far as mental and physical disabilities are concerned.Experts differ in their confidence in flunarizines effectiveness. | 11
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However, this is partially explained by the fact that the indication itself, that is, complete DiGeorge syndrome, increases the risk of autoimmune disease. Thymoma-associated multiorgan autoimmunity (TAMA)
A GvHD-like disease called thymoma-associated multiorgan autoimmunity (TAMA) can occur in patients with thymoma. In these patients rather than a donor being a source of pathogenic T cells, the patients own malignant thymus produces self-directed T cells. This is because the malignant thymus is incapable of appropriately educating developing thymocytes to eliminate self-reactive T cells. The result is a disease virtually indistinguishable from GvHD. Mechanism
The pathophysiology of GvHD includes three phases:
The afferent phase: activation of APC (antigen presenting cells)
The efferent phase: activation, proliferation, differentiation and migration of effector cells
The effector phase: target tissue destructionActivation of APC occurs in the first stage of GvHD. Prior to haematopoietic stem cell transplantation, radiation or chemotherapy results in damage and activation of host tissues, especially intestinal mucosa. This allows the microbial products to enter and stimulate pro-inflammatory cytokines such as IL-1 and TNF-α. These proinflammatory cytokines increase the expression of MHC and adhesion molecules on APCs, thereby increasing the ability of APC to present antigen. The second phase is characterized by the activation of effector cells. Activation of donor T-cells further enhances the expression of MHC and adhesion molecules, chemokines and the expansion of CD8 + and CD4 + T-cells and guest B-cells. In the final phase, these effector cells migrate to target organs and mediate tissue damage, resulting in multiorgan failure. | Finally, they had tissue necrosis, which caused deterioration of the epidermis, connective tissue, heart, hepatopancreas, nervous system, and gills. In severe cases, there was congestion of hemal sinuses, two principal empty areas along the digestive tube and vessels. Mass amounts of yeast-like cells compressed nerve fibers and the gill lamellae were destroyed. Mollusks clinical signs vary from scattered spots of brownish discoloration on the mantle tissues to general deterioration of mussel condition. In severe cases, there were black-bodied mussels with a distinct odor and black yeast-cells infected the connective tissues around the gonads and the digestive tract. Cold-blooded vertebrates
Cold-blooded vertebrates exhibited an assortment of clinical signs. Amphibians showed signs of anorexia. Ulcers or nodules in the skin were found, as well as swelling and lesions of internal organs, including the spleen, liver, and kidney. In extreme cases, neurological disorders and multifocal dermatitis (swelling caused by irritation of the fungus) occurred. Fish demonstrated signs of lethargy and disoriented swimming. There were ulcerative lesions, multiple dark foci in the gills, and non-ulcerative dermal masses found. In critical cases, some fish showed a variety of inflammatory responses including the formation of microabscesses. Lesions in the brain and kidneys were also found. These fish had abnormal swimming behavior, bulging eyes, and abdominal swelling. Warm-blooded vertebrates
From birds to equines, Phaeohyphomycosis persists and has a massive range of clinical signs throughout differing species. Poultry and wild birds had neurological disorders and a loss of movement control. | 0-1
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Additional surgeries may be required to correct postsurgical complications such as stenosis of the anastomosis between the native urethra and the graft, urethral fistulas, and posterior displacement of the balanic meatus. Successful masculinizing genitoplasty performed on individuals with grade 3 PAIS often requires multiple surgeries. If feminizing genitoplasty is performed in infancy, the result will need to be refined at puberty through additional surgery. Procedures include clitoral reduction / recession, labiaplasty, repair of the common urogenital sinus, vaginoplasty, and vaginal dilation through non-surgical pressure methods. Clitoral reduction / recession surgery carries with it the risk of necrosis as well as the risk of impairing the sexual function of the genitalia, and thus should not be performed for less severe clitoromegaly. Clitoral surgery should be focused on function rather than appearance, with care being taken to spare the erectile function and innervation of the clitoris. If PAIS presents with a common urogenital sinus, the American Academy of Pediatrics currently recommends that surgery to separate the urethra from the vagina be performed at an early age. As is the case for CAIS, vaginal dilation using pressure dilation methods should be attempted before the surgical creation of a neovagina is considered, and neither should be performed before puberty. Complications of feminizing genitoplasty can include vaginal stenosis, meatal stenosis, vaginourethral fistula, female hypospadias, urinary tract injuries, and recurrent clitoromegaly. | The Court observed that advocates of surgery were more numerous than opponents, alternatives to surgery were not entirely feasible, and surgeries had improved, “making it less likely that sexual sensitivity would be destroyed; and the medical community was improving communication with parents”.The Court determined that a constitutional protection of a right to free development of personality meant that a childs autonomy increases with age, including the development of a gender identity and bodily awareness. It determined that the best interests of the child were protected by allowing the child to determine their own gender identity. The Court determined that genital surgeries should not be conducted on children over the age of five, and that multidisciplinary teams should assess childrens needs on a case-by-case basis. References
External links
androgen at NIH/UW GeneTests | 11
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Methanol is commonly found in methylated spirits, denatured ethyl alcohol, to avoid paying taxes on selling ethanol intended for human consumption. Methylated spirits are sometimes used by alcoholics as a desperate and cheap substitute for regular ethanol alcoholic beverages. Other
Amblyopia: is a category of vision loss or visual impairment that is caused by factors unrelated to refractive errors or coexisting ocular diseases. Amblyopia is the condition when a childs visual systems fail to mature normally because the child either has been born premature, measles, congenital rubella syndrome, vitamin A deficiency, or meningitis. If left untreated during childhood, amblyopia is currently incurable in adulthood because surgical treatment effectiveness changes as a child matures. Consequently, amblyopia is the worlds leading cause of child monocular vision loss, which is the damage or loss of vision in one eye. In the best case scenario, which is very rare, properly treated amblyopia patients can regain 20/40 acuity. Corneal opacification
Degenerative myopia
Diabetic retinopathy: is one of the manifestation microvascular complications of diabetes, which is characterized by blindness or reduced acuity. That is, diabetic retinopathy describes the retinal and vitreous hemorrhages or retinal capillary blockage caused by the increase of A1C, which a measurement of blood glucose or sugar level. In fact, as A1C increases, people tend to be at greater risk of developing diabetic retinopathy than developing other microvascular complications associated with diabetes (e.g. chronic hyperglycemia, diabetic neuropathy, and diabetic nephropathy). Despite the fact that only 8% of adults 40 years and older experience vision-threatening diabetic retinopathy (e.g. | In the late stage, termed mature, myositis ossificans is depicted as an elongated calcific deposit that is aligned with the long-axis of the muscle, exhibits acoustic shadowing, and has no soft tissue mass associated. US may suggest the diagnosis at early stage, but imaging features need to evolve with successive maturation of the lesion and formation of the characteristic late stage changes before they become pathognomonic.The differential diagnosis includes many tumoral and nontumoral pathologies. A main concern is to differentiate early myositis ossificans from malignant soft-tissue tumors, and the latter is suggested by a fast-growing process. If clinical or sonographic findings are dubious and extraosseous sarcoma is suspected, biopsy should be performed. At histology, detection of the typical zonal phenomenon is diagnostic of myositis ossificans, though microscopic findings may be misleading during the early stage. Radiologic diagnosis
The radiological features of myositis ossificans are ‘faint soft tissue calcification within 2–6 weeks, (may have well-defined
bony margins by 8 weeks) separated from periosteum by lucent zone and on CT, the characteristic feature is peripheral ossification’. Management
Since myositis ossificians is more common in those with bleeding disorders, the formation of bone in soft tissue is thought to be associated with haematoma formation. As the calcifications will typically resolve after a period of time, non-surgical treatment is encouraged to minimize the unpleasant symptoms and maximize the function of the affected limb.Following a skeletal muscle injury, the affected limb should be immobilized with bed rest, ice therapy, compression, and elevation of the affected limb. | 0-1
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Palonosetron, sold under the brand name Aloxi, is used for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is a 5-HT3 antagonist.Palonosetron is administered intravenously, or as a single oral capsule. It has a longer duration of action than other 5-HT3 antagonists. The oral formulation was approved on August 22, 2008, for prevention of acute CINV alone, as a large clinical trial did not show oral administration to be as effective as intravenous use against delayed CINV. It is on the World Health Organizations List of Essential Medicines.The oral combination netupitant/palonosetron is approved for both acute and delayed CINV. Adverse effects
The most common adverse effects are headache, which occurs in 4–11% of patients, and constipation in up to 6% of patients. In less than 1% of patients, other gastrointestinal disorders occur, as well as sleeplessness, first- and second-degree atrioventricular block, muscle pain and shortness of breath. Palonosetron is similarly well tolerated as other 5-HT3 antagonists, and slightly less than placebo. Interactions
Palonosetron does not relevantly inhibit or induce cytochrome P450 liver enzymes. There are case reports about serotonin syndrome when the drug is combined with serotonergic substances such as selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), two common types of antidepressants. Pharmacology
Mechanism of action
Palonosetron is a 5-HT3 antagonist, commonly known as a setron. These drugs act by blocking serotonin from binding to the 5-HT3 receptor. Pharmacokinetics
Orally taken palonosetron is absorbed well from the gut and has a bioavailability of 97%. | These results show that it is clinically productive to target speech production, phonological awareness, letter knowledge, spelling, and reading all at once. This is particularly important since children with DVD/CAS often have continuous problems with reading and spelling, even if their production of speech improves. See also
Apraxia
Apraxia of speech
Developmental coordination disorder
Dysarthria
FOXP2 and human evolution
KE family
Origin of speech
Speech and language impairment
References
== External links == | 0-1
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This has been conjectured as a mechanism for high-dose effects on seizures in the study.Clonazepam is a 2-chlorinated derivative of nitrazepam, which increases its potency due to electron-attracting effect of the halogen in the ortho-position. Pharmacokinetics
Clonazepam is lipid-soluble, rapidly crosses the blood–brain barrier, and penetrates the placenta. It is extensively metabolised into pharmacologically inactive metabolites, with only 2% of the unchanged drug excreted in the urine. Clonazepam is metabolized extensively via nitroreduction by cytochrome P450 enzymes, including CYP3A4. Erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, cimetidine, and grapefruit juice are inhibitors of CYP3A4 and can affect the metabolism of benzodiazepines. It has an elimination half-life of 19–60 hours. Peak blood concentrations of 6.5–13.5 ng/mL were usually reached within 1–2 hours following a single 2 mg oral dose of micronized clonazepam in healthy adults. In some individuals, however, peak blood concentrations were reached at 4–8 hours.Clonazepam passes rapidly into the central nervous system, with levels in the brain corresponding with levels of unbound clonazepam in the blood serum. Clonazepam plasma levels are very unreliable amongst patients. Plasma levels of clonazepam can vary as much as tenfold between different patients.Clonazepam has plasma protein binding of 85%. Clonazepam passes through the blood–brain barrier easily, with blood and brain levels corresponding equally with each other. The metabolites of clonazepam include 7-aminoclonazepam, 7-acetaminoclonazepam and 3-hydroxy clonazepam. These metabolites are excreted by the kidney.It is effective for 6–8 hours in children, and 6–12 in adults. | One-third of individuals treated with benzodiazepines for longer than four weeks develop a dependence on the drug and experience a withdrawal syndrome upon dose reduction. High dosage and long-term use increase the risk and severity of dependence and withdrawal symptoms. Withdrawal seizures and psychosis can occur in severe cases of withdrawal, and anxiety and insomnia can occur in less severe cases of withdrawal. A gradual reduction in dosage reduces the severity of the benzodiazepine withdrawal syndrome. Due to the risks of tolerance and withdrawal seizures, clonazepam is generally not recommended for the long-term management of epilepsies. Increasing the dose can overcome the effects of tolerance, but tolerance to the higher dose may occur and adverse effects may intensify. The mechanism of tolerance includes receptor desensitization, down regulation, receptor decoupling, and alterations in subunit composition and in gene transcription coding.Tolerance to the anticonvulsant effects of clonazepam occurs in both animals and humans. In humans, tolerance to the anticonvulsant effects of clonazepam occurs frequently. Chronic use of benzodiazepines can lead to the development of tolerance with a decrease of benzodiazepine binding sites. The degree of tolerance is more pronounced with clonazepam than with chlordiazepoxide. In general, short-term therapy is more effective than long-term therapy with clonazepam for the treatment of epilepsy. | 11
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Diagnosis
Diagnosis is made through a combination of patient history, neurological examination, and medical imaging. Magnetic resonance imaging (MRI) is considered the preferred imaging modality for Chiari malformation. The MRI visualizes neural tissue such as the cerebellar tonsils and spinal cord as well as bone and other soft tissues. CT and CT myelography are other options and were used prior to the advent of MRI, unfortunately the resolution of CT based modalities do not characterize syringomyelia and other neural abnormalities as well.By convention, the cerebellar tonsil position is measured relative to the basion-opisthion line, using sagittal T1 MRI images or sagittal CT images. The selected cutoff distance for abnormal tonsil position is somewhat arbitrary, as not every person will be symptomatic at a certain amount of tonsil displacement, and the probability of symptoms and syrinx increases with greater displacement; however, greater than 5 mm is the most frequently cited cutoff number, though some consider 3–5 mm to be "borderline,"; pathological signs and syrinx may occur beyond that distance. One study showed little difference in cerebellar tonsil position between standard recumbent MRI and upright MRI for patients without a history of whiplash injury. Neuroradiological investigation is used to first rule out any intracranial condition that could be responsible for tonsillar herniation. Neuroradiological diagnostics evaluate the severity of crowding of the neural structures within the posterior cranial fossa and their pressure against the foramen magnum. | Weak crying
Facial weakness
Aspiration
Headaches aggravated by Valsalva maneuvers, such as yawning, laughing, crying, coughing, sneezing or straining, bending over, or getting up suddenly
Tinnitus (ringing in the ears)
Lhermittes sign (electrical sensation that runs down the back and into the limbs)
Vertigo (dizziness)
Nausea
Schmahmann syndrome
Nystagmus (irregular eye movements; typically, so-called "downbeat nystagmus")
Facial pain
Muscle weakness
Impaired gag reflex
Dysphagia (difficulty swallowing)
Restless leg syndrome
Sleep apnea
Sleep disorders
Impaired coordination
Severe cases may develop all the symptoms and signs of a bulbar palsy
Paralysis due to pressure at the cervico-medullary junction may progress in a so-called "clockwise" fashion, affecting the right arm, then the right leg, then the left leg, and finally the left arm; or the opposite way around. Papilledema on fundoscopic exam due to Increased intracranial pressure
Pupillary dilation
Dysautonomia: tachycardia (rapid heart), syncope (fainting), polydipsia (extreme thirst), chronic fatigue
Apnea: Sudden pause of breathing, usually during sleep. Opisthotonos: Spasm of the head which causes head to arch backwards. More common in infants than adults. StridorThe blockage of cerebrospinal fluid (CSF) flow may also cause a syrinx to form, eventually leading to syringomyelia. Central cord symptoms such as hand weakness, dissociated sensory loss, and, in severe cases, paralysis may occur. Syringomyelia
Syringomyelia is a chronic progressive degenerative disorder characterized by a fluid-filled cyst located in the spinal cord. Its symptoms include pain, weakness, numbness, and stiffness in the back, shoulders, arms or legs. Other symptoms include headaches, the inability to feel changes in the temperature, sweating, sexual dysfunction, and loss of bowel and bladder control. | 11
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Whether or not there is any conscious awareness with a patients vegetative state is a prominent issue. Three completely different aspects of this should be distinguished. First, some patients can be conscious simply because they are misdiagnosed (see above). In fact, they are not in vegetative states. Second, sometimes a patient was correctly diagnosed but is then examined during the early stages of recovery. Third, perhaps some day the notion itself of vegetative states will change so to include elements of conscious awareness. Inability to disentangle these three example cases causes confusion. An example of such confusion is the response to an experiment using functional magnetic resonance imaging which revealed that a woman diagnosed with PVS was able to activate predictable portions of her brain in response to the testers requests that she imagine herself playing tennis or moving from room to room in her house. The brain activity in response to these instructions was indistinguishable from those of healthy patients.In 2010, Martin Monti and fellow researchers, working at the MRC Cognition and Brain Sciences Unit at the University of Cambridge, reported in an article in the New England Journal of Medicine that some patients in persistent vegetative states responded to verbal instructions by displaying different patterns of brain activity on fMRI scans. Five out of a total of 54 diagnosed patients were apparently able to respond when instructed to think about one of two different physical activities. | One of these five was also able to "answer" yes or no questions, again by imagining one of these two activities. It is unclear, however, whether the fact that portions of the patients brains light up on fMRI could help these patients assume their own medical decision making.In November 2011, a publication in The Lancet presented bedside EEG apparatus and indicated that its signal could be used to detect awareness in three of 16 patients diagnosed in the vegetative state. Treatment
Currently no treatment for vegetative state exists that would satisfy the efficacy criteria of evidence-based medicine. Several methods have been proposed which can roughly be subdivided into four categories: pharmacological methods, surgery, physical therapy, and various stimulation techniques. Pharmacological therapy mainly uses activating substances such as tricyclic antidepressants or methylphenidate. Mixed results have been reported using dopaminergic drugs such as amantadine and bromocriptine and stimulants such as dextroamphetamine. Surgical methods such as deep brain stimulation are used less frequently due to the invasiveness of the procedures. Stimulation techniques include sensory stimulation, sensory regulation, music and musicokinetic therapy, social-tactile interaction, and cortical stimulation. Zolpidem
There is limited evidence that the hypnotic drug zolpidem has an effect. The results of the few scientific studies that have been published so far on the effectiveness of zolpidem have been contradictory. Epidemiology
In the United States, it is estimated that there may be between 15,000 and 40,000 patients who are in a persistent vegetative state, but due to poor nursing home records exact figures are hard to determine. | 11
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Cerebral areas most susceptible to ischemic damage include the speech and motor cortices, leading to contralateral paralysis, speech, and comprehension loss. Severe or prolonged strokes may terminate in coma or brain death. Therefore, the diagnosis and treatment of ischemic stroke are time-dependent. Diagnosis
There are several methods of diagnosing arterial occlusion, ranging from straightforward setups like exercise testing, to advanced scanning equipment such as ultrasonic duplex scanning or Multi-Detector Coronary Tomography (MDCT) angiography. Exercise Testing
Exercise testing is a simplistic, non-invasive method of diagnosing intermittent claudication. Blood pressure measurements at the suspected area can be taken before and after exercise, as some symptoms only appear during strenuous activity. Commonly, a treadmill setting at 2 mph with a 12-degree slope is utilized. Subjects are asked to walk on the treadmill for a maximum of 5 minutes or until moderate pain is felt. The time to pain or maximal walking duration is recorded and compared with baselines. Healthy individuals maintain systolic blood pressures at a normal range. Once exercise becomes more intense, there may be a temporary fall in systolic pressure, which quickly returns to normal with rest. However, those with intermittent claudication struggle to maintain standard values of systolic pressure, while recovery back to baseline is prolonged. Ultrasonic Duplex Testing
Ultrasonic duplex scanning was developed to primarily determine the extent of atherosclerosis in carotid arteries. Since then, its application has widened to include arteries in the limbs. The technique utilizes high-frequency sound waves for visualization of flow direction and velocity within the arteries in an area of interest. | Hypertension can also be caused by endocrine conditions, such as Cushings syndrome, hyperthyroidism, hypothyroidism, acromegaly, Conns syndrome or hyperaldosteronism, renal artery stenosis (from atherosclerosis or fibromuscular dysplasia), hyperparathyroidism, and pheochromocytoma. Other causes of secondary hypertension include obesity, sleep apnea, pregnancy, coarctation of the aorta, excessive eating of liquorice, excessive drinking of alcohol, certain prescription medicines, herbal remedies, and stimulants such as coffee, cocaine and methamphetamine. Arsenic exposure through drinking water has been shown to correlate with elevated blood pressure. Depression was also linked to hypertension. Loneliness is also a risk factor.A 2018 review found that any alcohol increased blood pressure in males while over one or two drinks increased the risk in females. Pathophysiology
In most people with established essential hypertension, increased resistance to blood flow (total peripheral resistance) accounts for the high pressure while cardiac output remains normal. There is evidence that some younger people with prehypertension or borderline hypertension have high cardiac output, an elevated heart rate and normal peripheral resistance, termed hyperkinetic borderline hypertension. These individuals develop the typical features of established essential hypertension in later life as their cardiac output falls and peripheral resistance rises with age. Whether this pattern is typical of all people who ultimately develop hypertension is disputed. The increased peripheral resistance in established hypertension is mainly attributable to structural narrowing of small arteries and arterioles, although a reduction in the number or density of capillaries may also contribute.It is not clear whether or not vasoconstriction of arteriolar blood vessels plays a role in hypertension. | 0-1
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One of these five was also able to "answer" yes or no questions, again by imagining one of these two activities. It is unclear, however, whether the fact that portions of the patients brains light up on fMRI could help these patients assume their own medical decision making.In November 2011, a publication in The Lancet presented bedside EEG apparatus and indicated that its signal could be used to detect awareness in three of 16 patients diagnosed in the vegetative state. Treatment
Currently no treatment for vegetative state exists that would satisfy the efficacy criteria of evidence-based medicine. Several methods have been proposed which can roughly be subdivided into four categories: pharmacological methods, surgery, physical therapy, and various stimulation techniques. Pharmacological therapy mainly uses activating substances such as tricyclic antidepressants or methylphenidate. Mixed results have been reported using dopaminergic drugs such as amantadine and bromocriptine and stimulants such as dextroamphetamine. Surgical methods such as deep brain stimulation are used less frequently due to the invasiveness of the procedures. Stimulation techniques include sensory stimulation, sensory regulation, music and musicokinetic therapy, social-tactile interaction, and cortical stimulation. Zolpidem
There is limited evidence that the hypnotic drug zolpidem has an effect. The results of the few scientific studies that have been published so far on the effectiveness of zolpidem have been contradictory. Epidemiology
In the United States, it is estimated that there may be between 15,000 and 40,000 patients who are in a persistent vegetative state, but due to poor nursing home records exact figures are hard to determine. | In the US, courts have required petitions before termination of life support that demonstrate that any recovery of cognitive functions above a vegetative state is assessed as impossible by authoritative medical opinion. In England, Wales and Scotland, the legal precedent for withdrawal of clinically assisted nutrition and hydration in cases of patients in a PVS was set in 1993 in the case of Tony Bland, who sustained catastrophic anoxic brain injury in the 1989 Hillsborough disaster. An application to the Court of Protection is no longer required before nutrition and hydration can be withdrawn or withheld from PVS (or minimally conscious – MCS) patients.This legal grey area has led to vocal advocates that those in PVS should be allowed to die. Others are equally determined that, if recovery is at all possible, care should continue. The existence of a small number of diagnosed PVS cases that have eventually resulted in improvement makes defining recovery as "impossible" particularly difficult in a legal sense. This legal and ethical issue raises questions about autonomy, quality of life, appropriate use of resources, the wishes of family members, and professional responsibilities. Signs and symptoms
Most PVS patients are unresponsive to external stimuli and their conditions are associated with different levels of consciousness. Some level of consciousness means a person can still respond, in varying degrees, to stimulation. A person in a coma, however, cannot. | 11
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In APS patients, the most common venous event is deep vein thrombosis of the lower extremities, and the most common arterial event is stroke. In pregnant person affected by APS, there is an increased risk of recurrent miscarriage, intrauterine growth restriction, and preterm birth. A frequent cause of such complications is placental infarctions. In some cases, APS seems to be the leading cause of intellectual and/or developmental disabilities in the newborn, due to an aPL-induced inhibition of trophoblast differentiation. The antiphospholipid syndrome is responsible for most of the miscarriages in later trimesters seen in concomitant systemic lupus erythematosus and pregnancy.Other common findings, although not part of the APS classification criteria, are low platelet count, heart valve disease, and livedo reticularis. There are also associations between antiphospholipid antibodies and different neurologic manifestations including headache, migraine, epilepsy, and dementia. Some studies have shown the presence of antiphospholipid antibodies in the blood and spinal fluid of patients with psychological symptoms. Cancer is also observed to comorbid in patients with APS. Risk factors
Risk factors for developing antiphospholipid syndrome include:
Genetic Markers: HLA-DR4, HLA-DR7, and HLA-DRw53
Race: Blacks, Hispanics, Asians, and Native Americans
Pathogenesis
Antiphospholipid syndrome is an autoimmune disease, in which "antiphospholipid antibodies" (anticardiolipin antibodies and lupus anticoagulant) react against proteins that bind to anionic phospholipids on plasma membranes. Like many autoimmune diseases, it is more common in women than in men. The exact cause is not known, but activation of the system of coagulation is evident. | Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia. Although the exact etiology of APS is still not clear, genetics is believed to play a key role in the development of the disease. The diagnostic criteria require one clinical event (i.e. thrombosis or pregnancy complication) and two positive blood test results spaced at least three months apart that detect lupus anticoagulant, anti-apolipoprotein antibodies, or anti-cardiolipin antibodies.Antiphospholipid syndrome can be primary or secondary. Primary antiphospholipid syndrome occurs in the absence of any other related disease. Secondary antiphospholipid syndrome occurs with other autoimmune diseases, such as systemic lupus erythematosus. In rare cases, APS leads to rapid organ failure due to generalised thrombosis; this is termed "catastrophic antiphospholipid syndrome" (CAPS or Asherson syndrome) and is associated with a high risk of death. Antiphospholipid syndrome often requires treatment with anticoagulant medication such as heparin to reduce the risk of further episodes of thrombosis and improve the prognosis of pregnancy. Warfarin (brand name Coumadin) is not used during pregnancy because it can cross the placenta, unlike heparin, and is teratogenic. Signs and symptoms
The presence of antiphospholipid antibodies (aPL) in the absence of blood clots or pregnancy-related complications does not indicate APS (see below for the diagnosis of APS). Antiphospholipid syndrome can cause arterial or venous blood clots, in any organ system, or pregnancy-related complications. | 11
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Therefore, the goal of treatment of Bennett fracture should be to achieve the most precise reduction possible, whether by the CRPP or the ORIF approach. Nomenclature
The Bennett fracture is named after Edward Hallaran Bennett, Professor of Surgery (1837–1907) at Trinity College of the University of Dublin, who described it in 1882. Bennett said his fracture "passed obliquely across the base of the bone, detaching the greater part of the articular surface, and the separated fragment was very large and the deformity that resulted there-from seemed more a dorsal subluxation of the first metacarpal". See also
Rolando fracture
Boxers fracture
Gamekeepers thumb
References
External links
Bennett fracture at Who Named It? | Facial weakness is a medical sign associated with a variety of medical conditions.Some specific conditions associated with facial weakness include:
Stroke
Neurofibromatosis
Bells palsy
Ramsay Hunt syndrome
Spontaneous cerebrospinal fluid leak
Myasthenia gravis
See also
Acute facial nerve paralysis
Facioscapulohumeral muscular dystrophy
References
External links
Differential diagnosis
Diagram of appearance in stroke | 0-1
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They are registered to the IRS under the name Superior Mesenteric Artery Syndrome Research, Awareness and Support, but also work under the DBA of SMAS Patient Assistance. See also
References
== External links == | Vanishing bile duct syndrome is a loose collection of diseases which leads to the injury to hepatic bile ducts and eventual ductopenia. Signs and symptoms
The presentation is dependent upon the underlying cause. The course can be rapid or chronic. Fatigue
Anorexia
Abdominal pain
Weight loss
Pruritus
Hyperlipidemia
Malabsorption
Fat-soluble vitamin deficiencies
Elevated alkaline phosphatase
Elevated gamma-glutamyltransferase
Elevated conjugated bilirubin
Cause
Congenital
In fetal and neonatal life the ductal plates are remodeled. The malformations can be atretic or fibrocystic. Atretic causes
Intrahepatic bile duct atresia (Alagille syndrome) (ALGS2 MIM:610205 and ALGS1 MIM:118450)
Extrahepatic bile duct atresia
Fibrocystic causes
Autosomal recessive polycystic kidney disease
Congential hepatic fibrosis
Carolis disease
Von Meyenburg complex
Chromosomal associations
Trisomy 17, 18 and 21
Genetic associations
Cystic fibrosis
Alpha 1 antitrypsin deficiency
Trihydroxycoprostanic acidemia
Bylers disease
Immunologic associations
Bile duct injury and loss can result from autoimmune destruction. T cells recognize biliary epithelial cell antigens causing injury and eventual atresia. Other causes
Primary biliary cirrhosis
Primary sclerosing cholangitis
Hodgkins lymphoma
Chronic graft-versus-host disease
Drugs(chlorpromazine)/Toxins
Ischemia
Diagnosis
Treatment
Treatment is dependent upon the underlying cause. Treatment is supportive as it is not possible to induce regrowth of lost ducts. Medical therapies
Ursodeoxycholic acid
Immunosuppression
General consensus is that more studies are needed before this can be considered
Organ transplant
References
External links
Uptodate:Hepatic ductopenia and vanishing bile duct syndrome | 0-1
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Presence of infection indicates cholecystitis. Surgery
It is unclear whether those experiencing a gallstone attack should receive surgical treatment or not. The scientific basis to assess whether surgery outperformed other treatment was insufficient and better studies were needed as of a SBU report in 2017. Treatment of biliary colic is dictated by the underlying cause. The presence of gallstones, usually visualized by ultrasound, generally necessitates a surgical treatment (removal of the gall bladder, typically via laparoscopy). Removal of the gallbladder with surgery, known as a cholecystectomy, is the definitive surgical treatment for biliary colic. A 2013 Cochrane review found tentative evidence to suggest that early gallbladder removal may be better than delayed removal. Early laparoscopic cholecystectomy happens within 72 hours of diagnosis. In a Cochrane review that evaluated receiving early versus delayed surgery, they found that 23% of those who waited on average 4 months ended up in hospital for complications, compared to none with early intervention with surgery. Early intervention has other advantages including a reduced number of visits to the emergency department, fewer conversions to open surgery, less operating time required, and reduced time in hospital postoperatively. The Swedish agency SBU estimated in 2017 that increasing acute phase surgeries could free multiple in-hospital days per patient and would additionally spare pain and suffering in wait of receiving an operation. | Remnant hyperlipidemia occurs as a result of abnormal function of the ApoE receptor, which is normally required for clearance of chylomicron remnants and IDL from the circulation. The receptor defect causes levels of chylomicron remnants and IDL to be higher than normal in the blood stream. The receptor defect is an autosomal recessive mutation or polymorphism. Type IV
Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population.This form is due to high triglyceride level. Other lipoprotein levels are normal or increased a little.Treatment include diet control, fibrates and niacins. Statins are not better than fibrates when lowering triglyceride levels. Type V
Hyperlipoproteinemia type V, also known as mixed hyperlipoproteinemia familial or mixed hyperlipidemia, is very similar to type I, but with high VLDL in addition to chylomicrons. It is also associated with glucose intolerance and hyperuricemia.In medicine, combined hyperlipidemia (or -aemia) (also known as "multiple-type hyperlipoproteinemia") is a commonly occurring form of hypercholesterolemia (elevated cholesterol levels) characterized by increased LDL and triglyceride concentrations, often accompanied by decreased HDL. On lipoprotein electrophoresis (a test now rarely performed) it shows as a hyperlipoproteinemia type IIB. It is the most common inherited lipid disorder, occurring in about one in 200 persons. In fact, almost one in five individuals who develop coronary heart disease before the age of 60 has this disorder. The elevated triglyceride levels (>5 mmol/L) are generally due to an increase in very low density lipoprotein (VLDL), a class of lipoprotein prone to cause atherosclerosis. | 0-1
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Genetic testing is usually carried out using a blood sample, and MLPA is one of more frequently used genetic testing techniques, as it also allows establishing the number of SMN2 gene copies, which has clinical importance.Symptomatically, SMA can be diagnosed with a degree of certainty only in children with the acute form who manifest a progressive illness with paradoxical breathing, bilateral low muscle tone and absent tendon reflexes. Early diagnosis
Early diagnosis of SMA, at the asymptomatic stage of the disease, allows for
Preimplantation testing
Preimplantation genetic diagnosis can be used to screen for SMA-affected embryos during in-vitro fertilisation. Prenatal testing
Prenatal testing for SMA is possible through chorionic villus sampling, cell-free fetal DNA analysis and other methods. Newborn screening
Routine newborn screening for SMA is becoming increasingly commonplace in developed countries, given the availability of causative treatments that are most effective at the asymptomatic stage of the disease. In 2018, newborn screening for SMA was added to the US list of recommended newborn screening tests and as of April 2020 it has been adopted in 39 US states. As of May 2021, SMA newborn screening has been implemented in Taiwan and is in the course of implementation in Australia, Belgium, Canada, France, Germany, Netherlands, Poland, Serbia and Slovenia. Additionally, pilot projects are being conducted in Australia, China, Italy, and Japan. Carrier testing
Those at risk of being carriers of SMN1 deletion, and thus at risk of having offspring affected by SMA, can undergo carrier analysis using a blood or saliva sample. | Its development was discontinued in 2018 in view of competition from nusinersen and underwhelming data from an open-label extension trial.Of clinically studied compounds which did not show efficacy, thyrotropin-releasing hormone (TRH) held some promise in an open-label uncontrolled clinical trial but did not prove effective in a subsequent double-blind placebo-controlled trial. Riluzole, a drug that offers limited clinical benefit in amyotrophic lateral sclerosis, was proposed to be similarly tested in SMA; however, a 2008–2010 trial in SMA types 2 and 3 was stopped early due to the lack of satisfactory results. Other compounds that displayed some neuroprotective effect in in vitro research but never moved on to in vivo studies include β-lactam antibiotics (e.g., ceftriaxone) and follistatin. Muscle restoration
This approach aims to counter the effect of SMA by targeting the muscle tissue instead of neurons. Reldesemtiv (CK-2127107, CK-107) is a skeletal troponin activator developed by Cytokinetics in cooperation with Astellas. The drug aims at increasing muscle reactivity despite lowered neural signalling. The molecule showed some success in phase II clinical trial in adolescent and adults with SMA types 2, 3, and 4. Apitegromab (SRK-015) is monoclonal antibody that blocks the activation of the skeletal muscle protein myostatin, thereby promoting muscle tissue growth. As of 2021, the molecule showed success as an experimental add-on treatment in paediatric and adult patients treated with nusinersen. GYM329 (RO7204239), developed by Hoffman-La Roche, works similarly to apitegromab by blocking myostatin activation. As of 2022, it is undergoing clinical development in non-ambulant children with SMA aged 2–10, combined with risdiplam. | 11
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In cases of respiratory acidosis, the infused bicarbonate ion drives the carbonic acid/bicarbonate buffer of plasma to the left, and thus raises the pH. For this reason, sodium bicarbonate is used in medically supervised cardiopulmonary resuscitation. Infusion of bicarbonate is indicated only when the blood pH is markedly low (< 7.1–7.0).HCO3− is used for treatment of hyperkalemia, as it will drive K+ back into cells during periods of acidosis. Since sodium bicarbonate can cause alkalosis, it is sometimes used to treat aspirin overdoses. Aspirin requires an acidic environment for proper absorption, and a basic environment will diminish aspirin absorption in cases of overdose. Sodium bicarbonate has also been used in the treatment of tricyclic antidepressant overdose. It can also be applied topically as a paste, with three parts baking soda to one part water, to relieve some kinds of insect bites and stings (as well as accompanying swelling).Some alternative practitioners, such as Tullio Simoncini, have promoted baking soda as a cancer cure, which the American Cancer Society has warned against due to both its unproven effectiveness and potential danger in use. Edzard Ernst has called the promotion of sodium bicarbonate as a cancer cure "one of the more sickening alternative cancer scams I have seen for a long time".Sodium bicarbonate can be added to local anesthetics, to speed up the onset of their effects and make their injection less painful. It is also a component of Moffetts solution, used in nasal surgery.It has been proposed that acidic diets weaken bones. | Female infants may have leukorrhea for a short time after birth due to their in-uterine exposure to estrogen. Inflammatory leukorrhea
It may also result from inflammation or congestion of the vaginal mucosa. In cases where it is yellowish or gives off an odor, a doctor should be consulted since it could be a sign of several disease processes, including an organic bacterial infection (aerobic vaginitis) or STD.After delivery, leukorrhea accompanied by backache and foul-smelling lochia (post-partum vaginal discharge, containing blood, mucus, and placental tissue) may suggest the failure of involution (the uterus returning to pre-pregnancy size) due to infection. A number of investigation such as wet smear, Gram stain, culture, pap smear and biopsy are suggested to diagnose the condition. Parasitic leukorrhea
Leukorrhea is also caused by trichomonads, a group of parasitic protozoan, specifically Trichomonas vaginalis. Common symptoms of this disease are burning sensation, itching and discharge of frothy substance, thick, white or yellow mucous. Treatment
Leukorrhea may be caused by sexually transmitted diseases; therefore, treating the STD will help treat the leukorrhea. Treatment may include antibiotics, such as metronidazole. Other antibiotics common for the treatment of STIs include clindamycin or tinidazole. References
== External links == | 0-1
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In the early stages of malaria, the parasite can cause infected red cells to sickle, and so they are removed from circulation sooner. This reduces the frequency with which malaria parasites complete their life cycle in the cell. Individuals who are homozygous (with two copies of the abnormal haemoglobin beta allele) have sickle-cell anaemia, while those who are heterozygous (with one abnormal allele and one normal allele) experience resistance to malaria without severe anaemia. Although the shorter life expectancy for those with the homozygous condition would tend to disfavour the traits survival, the trait is preserved in malaria-prone regions because of the benefits provided by the heterozygous form. Liver dysfunction
Liver dysfunction as a result of malaria is uncommon and usually only occurs in those with another liver condition such as viral hepatitis or chronic liver disease. The syndrome is sometimes called malarial hepatitis. While it has been considered a rare occurrence, malarial hepatopathy has seen an increase, particularly in Southeast Asia and India. Liver compromise in people with malaria correlates with a greater likelihood of complications and death. Diagnosis
Due to the non-specific nature of malaria symptoms, diagnosis is typically suspected based on symptoms and travel history, then confirmed with a parasitological test. In areas where malaria is common, the World Health Organization (WHO) recommends clinicians suspect malaria in any person who reports having fevers, or who has a current temperature above 37.5 °C without any other obvious cause. | Artemether-lumefantrine (six-dose regimen) is more effective than the artemether-lumefantrine (four-dose regimen) or other regimens not containing artemisinin derivatives in treating falciparum malaria. Another recommended combination is dihydroartemisinin and piperaquine. Artemisinin-naphthoquine combination therapy showed promising results in treating falciparum malaria. However, more research is needed to establish its efficacy as a reliable treatment. Artesunate plus mefloquine performs better than mefloquine alone in treating uncomplicated falciparum malaria in low transmission settings. Atovaquone-proguanil is effective against uncomplicated falciparum with a possible failure rate of 5% to 10%; the addition of artesunate may reduce failure rate. Azithromycin monotherapy or combination therapy has not shown effectiveness in treating plasmodium or vivax malaria. Amodiaquine plus sulfadoxine-pyrimethamine may achieve less treatment failures when compared to sulfadoxine-pyrimethamine alone in uncomplicated falciparum malaria. There is insufficient data on chlorproguanil-dapsone in treating uncomplicated falciparum malaria. The addition of primaquine with artemisinin-based combination therapy for falciparum malaria reduces its transmission at day 3-4 and day 8 of infection. Sulfadoxine-pyrimethamine plus artesunate is better than sulfadoxine-pyrimethamine plus amodiaquine in controlling treatment failure at day 28. However, the latter is better than the former in reducing gametocytes in blood at day 7.Infection with P. vivax, P. ovale or P. malariae usually does not require hospitalisation. | 11
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One theorized reason for the increase in epidemiological estimates is that a substantial minority of individuals with the genetic markers of WS syndrome lack the characteristic facial features or the diminished intelligence considered to be diagnostic of the syndrome, and often are not immediately recognized as having the syndrome. History
Williams syndrome was first described by J. C. P. Williams and his colleagues, who wrote in 1961 of four patients with supravalvular aortic stenosis, mental disability, and facial features including a broad forehead, large chin, low-set, "drooping" cheeks, widely spaced eyes, and wide-set mouth. A year after this report, German physician A. J. Beuren described three new patients with the same presentation. This led to the syndromes full original name, Williams-Beuren syndrome, which is still used in some medical publications. From 1964 to 1975, small research reports broadened medical knowledge of this syndromes cardiovascular problems. Then in 1975, K. Jones and D. Smith conducted a large-scale report on numerous patients with WS, ranging in age from infancy to adulthood, and described the behavioral and observable physical symptoms in greater detail than previously recorded. Society and culture
The adjective "elfin" may have originated to describe the facial features of people with WS; before its scientific cause was understood, people believed that individuals with the syndrome, who have exceptionally charming and kind personalities, had extraordinary, even magical, powers. | Dykens and Rosner (1999) found that 100% of those with Williams syndrome were kind-spirited, 90% sought the company of others, 87% empathize with others pain, 84% are caring, 83% are unselfish/forgiving, 75% never go unnoticed in a group, and 75% are happy when others do well. Infants with Williams syndrome make normal and frequent eye contact, and young children with Williams will often approach and hug strangers. People affected by Williams syndrome typically have high empathy, showing relative strength in reading peoples eyes to gauge intentions, emotions, and mental states. The level of friendliness observed in people with Williams is often inappropriate for the social setting, however, and teens and adults with Williams syndrome often experience social isolation, frustration, and loneliness despite their clear desire to connect to other people.While these children often came off as happy due to their sociable nature, often there are internal drawbacks to the way they act. 76–86% of these children were reported as believing that they either had few friends or problems with their friends. This is possibly due to the fact that although they are very friendly to strangers and love meeting new people, they may have trouble interacting on a deeper level. 73–93% were reported as unreserved with strangers, 67% highly sensitive to rejection, 65% susceptible to teasing, and the statistic for exploitation and abuse was unavailable. There are external problems as well. | 11
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General relativity does not address the nature of time for extremely small intervals where quantum mechanics holds. At this time, there is no generally accepted theory of quantum general relativity.Time is one of the seven fundamental physical quantities in both the International System of Units (SI) and International System of Quantities. The SI base unit of time is the second, which is defined by measuring the electronic transition frequency of caesium atoms. Time is used to define other quantities, such as velocity, so defining time in terms of such quantities would result in circularity of definition. An operational definition of time, wherein one says that observing a certain number of repetitions of one or another standard cyclical event (such as the passage of a free-swinging pendulum) constitutes one standard unit such as the second, is highly useful in the conduct of both advanced experiments and everyday affairs of life. To describe observations of an event, a location (position in space) and time are typically noted. The operational definition of time does not address what the fundamental nature of it is. It does not address why events can happen forward and backward in space, whereas events only happen in the forward progress of time. Investigations into the relationship between space and time led physicists to define the spacetime continuum. General relativity is the primary framework for understanding how spacetime works. | Tendinopathy, a type of tendon disorder that results in pain, swelling, and impaired function. The pain is typically worse with movement. It most commonly occurs around the shoulder (rotator cuff tendinitis, biceps tendinitis), elbow (tennis elbow, golfers elbow), wrist, hip, knee (jumpers knee, popliteus tendinopathy), or ankle (Achilles tendinitis).Causes may include an injury or repetitive activities. Less common causes include infection, arthritis, gout, thyroid disease, diabetes and the use of Quinolone_antibiotic medicines. Groups at risk include people who do manual labor, musicians, and athletes. Diagnosis is typically based on symptoms, examination, and occasionally medical imaging. A few weeks following an injury little inflammation remains, with the underlying problem related to weak or disrupted tendon fibrils.Treatment may include rest, NSAIDs, splinting, and physiotherapy. Less commonly steroid injections or surgery may be done. About 80% of patients recover completely within six months. Tendinopathy is relatively common. Older people are more commonly affected. It results in a large amount of missed work. Signs and symptoms
Symptoms include tenderness on palpation, swelling, and pain, often when exercising or with a specific movement. Cause
Causes may include an injury or repetitive activities. Groups at risk include people who do manual labor, musicians, and athletes. Less common causes include infection, arthritis, gout, thyroid disease, and diabetes. Despite the injury of the tendon, there are roads to healing which includes rehabilitation therapy and/or surgery. Obesity, or more specifically, adiposity or fatness, has also been linked to an increasing incidence of tendinopathy.Quinolone antibiotics are associated with increased risk of tendinitis and tendon rupture. | 0-1
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However, genetic and family studies have demonstrated that the presence of Darwins tubercle may be more likely to be influenced by ones environment or developmental accidents than it is by genetics alone. There is no clear argument for whether the trait has significance in sexual dimorphism studies or age related studies. In some studies, there is clear data that Darwins tubercle is not associated with sex. In contrast, others indicate that there is a correlation with sexual dimorphism between men and women, where men tend to have the tubercle more than women in some populations. Two studies indicate that older men tend to have greater expression of Darwins tubercle than do older women. See also
Human vestigiality
References
== External links == | CFTR potentiator VRT-532 increased ARSB expression and activity in cystic fibrosis cells to the level in the normal bronchial epithelial cells. Role in malignancy
ARSB has been studied in a variety of cancers. Cultured normal mammary epithelial and myoepithelial cells had significantly higher ARSB activity than cultured malignant mammary cells. Immunohistochemistry in the colon showed decreased membrane ARSB staining in colon cancer compared to normal colon, as well as in higher grade malignancies. ARSB activity was lower in malignant than normal prostate tissue, and immunostaining of prostate tissue microarrays showed not only decreasing ARSB staining in prostate cancer tissue of a higher Gleason score, but also lower staining in patients with recurrent compared to non-recurrent cancer. ARSB staining was a greater predictor of recurrence than Prostate-specific antigen (PSA) test, indicating possible future role of ARSB as a prognostic biomarker of prostate cancer. Further evidence of ARSB as a tumor suppressor was determined by molecular studies in cell cultures where ARSB was silenced by siRNA. The studies showed that decrease of ARSB leads to increase in free galectin-3, which attaches more strongly to less sulfated chondroitin 4-sulfate. Galectin-3 then acts on transcription factors AP-1 to increase expression of chondroitin sulfate proteoglycan versican and SP-1 to increase expression of WNT9A. Another mechanism by which reduced ARSB is associated with carcinogenesis is through increased binding of SHP2 to more sulfated chondroitin 4-sulfate, which leads to increased phosphorylation of p38 and MITF with subsequently increased expression of GPNMB. | 0-1
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Christian missionaries in Africa were among the first to object to FGM, but Christian communities in Africa do practise it. In 2013 UNICEF identified 19 African countries in which at least 10 percent of Christian women and girls aged 15 to 49 had undergone FGM; in Niger, 55 percent of Christian women and girls had experienced it, compared with two percent of their Muslim counterparts. The only Jewish group known to have practised it is the Beta Israel of Ethiopia. Judaism requires male circumcision but does not allow FGM. FGM is also practised by animist groups, particularly in Guinea and Mali. History
Antiquity
The practices origins are unknown. Gerry Mackie has suggested that, because FGMs east–west, north–south distribution in Africa meets in Sudan, infibulation may have begun there with the Meroite civilization (c. 800 BCE – c. 350 CE), before the rise of Islam, to increase confidence in paternity. According to historian Mary Knight, Spell 1117 (c. 1991–1786 BCE) of the Ancient Egyptian Coffin Texts may refer in hieroglyphs to an uncircumcised girl (mt):
The spell was found on the sarcophagus of Sit-hedjhotep, now in the Egyptian Museum, and dates to Egypts Middle Kingdom. (Paul F. ORourke argues that mt probably refers instead to a menstruating woman.) The proposed circumcision of an Egyptian girl, Tathemis, is also mentioned on a Greek papyrus, from 163 BCE, in the British Museum: "Sometime after this, Nephoris [Tathemiss mother] defrauded me, being anxious that it was time for Tathemis to be circumcised, as is the custom among the Egyptians. | Opposition and legal status
Colonial opposition in Kenya
Protestant missionaries in British East Africa (present-day Kenya) began campaigning against FGM in the early 20th century, when Dr. John Arthur joined the Church of Scotland Mission (CSM) in Kikuyu. An important ethnic marker, the practice was known by the Kikuyu, the countrys main ethnic group, as irua for both girls and boys. It involved excision (Type II) for girls and removal of the foreskin for boys. Unexcised Kikuyu women (irugu) were outcasts.Jomo Kenyatta, general secretary of the Kikuyu Central Association and later Kenyas first prime minister, wrote in 1938 that, for the Kikuyu, the institution of FGM was the "conditio sine qua non of the whole teaching of tribal law, religion and morality". No proper Kikuyu man or woman would marry or have sexual relations with someone who was not circumcised, he wrote. A womans responsibilities toward the tribe began with her initiation. Her age and place within tribal history were traced to that day, and the group of girls with whom she was cut was named according to current events, an oral tradition that allowed the Kikuyu to track people and events going back hundreds of years. Beginning with the CSM in 1925, several missionary churches declared that FGM was prohibited for African Christians; the CSM announced that Africans practising it would be excommunicated, which resulted in hundreds leaving or being expelled. | 11
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Arsenic trioxide, sold under the brand name Trisenox among others, is an inorganic compound and medication. As an industrial chemical, whose major uses include in the manufacture of wood preservatives, pesticides, and glass. As a medication, it is used to treat a type of cancer known as acute promyelocytic leukemia. For this use it is given by injection into a vein.Common side effects include vomiting, diarrhea, swelling, shortness of breath, and headaches. Severe side effects may include APL differentiation syndrome and heart problems. Use during pregnancy or breastfeeding may harm the baby. Arsenic trioxide has the formula As2O3. Its mechanism in treating cancer is not entirely clear.Arsenic trioxide was approved for medical use in the United States in 2000. It is on the World Health Organizations List of Essential Medicines. Approximately 50,000 tonnes are produced a year. Due to its toxicity, a number of countries have regulations around its manufacture and sale. Uses
Medical
Arsenic trioxide is used to treat a type of cancer known as acute promyelocytic leukemia (APL). It may be used both in cases that are unresponsive to other agents, such as all-trans retinoic acid (ATRA) or as part of the initial treatment of newly diagnosed cases. This initial treatment may include combination therapy of arsenic trioxide with all-trans retinoic acid (ATRA).Effectiveness appears similar to Realgar/Indigo naturalis, which can be taken by mouth and is less expensive but is less available.In the 1970s, Chinese researcher Zhang Tingdong and colleagues discovered this use. It was approved for leukemia treatment in the United States in 2000. | Properties and reactions
Arsenic trioxide is an amphoteric oxide, and its aqueous solutions are weakly acidic. Thus, it dissolves readily in alkaline solutions to give arsenites. It is less soluble in acids, although it will dissolve in hydrochloric acid.With anhydrous HF and HCl, it gives AsF3 and the trichloride:
As2O3 + 6 HX → 2 AsX3 + 3 H2O (X = F, Cl)Only with strong oxidizing agents such as ozone, hydrogen peroxide, and nitric acid does it yield arsenic pentoxide, As2O5 or its corresponding acid:
2 HNO3 + As2O3 + 2 H2O → 2 H3AsO4 + N2O3In terms of its resistance to oxidation, arsenic trioxide differs from phosphorus trioxide, which readily combusts to phosphorus pentoxide. Reduction gives elemental arsenic or arsine (AsH3) depending on conditions:
As2O3 + 6 Zn + 12 HNO3 → 2 AsH3 + 6 Zn(NO3)2 + 3 H2OThis reaction is used in the Marsh test. Structure
In the liquid and gas phase below 800 °C, arsenic trioxide has the formula As4O6 and is isostructural with P4O6. Above 800 °C As4O6 significantly dissociates into molecular As2O3, which adopts the same structure as N2O3. Three forms (polymorphs) are known in the solid state: a high temperature ( > 110 °C) cubic As4O6, containing molecular As4O6, and two related polymeric forms. The polymers, which both crystallize as monoclinic crystals, feature sheets of pyramidal AsO3 units that share O atoms. Society and culture
Environmental effects
Smelting and related ore processing often generate arsenic trioxide, which poses a risk to the environment. | 11
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Nerve injury is an injury to nervous tissue. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve fiber injury and whether there is continuity of the nerve. Usually, however, peripheral nerve injuries are classified in five stages, based on the extent of damage to both the nerve and the surrounding connective tissue, since supporting glial cells may be involved.Unlike in the central nervous system, neuroregeneration in the peripheral nervous system is possible. The processes that occur in peripheral regeneration can be divided into the following major events: Wallerian degeneration, axon regeneration/growth, and reinnervation of nervous tissue. The events that occur in peripheral regeneration occur with respect to the axis of the nerve injury. The proximal stump refers to the end of the injured neuron that is still attached to the neuron cell body; it is the part that regenerates. The distal stump refers to the end of the injured neuron that is still attached to the end of the axon; it is the part of the neuron that will degenerate, but the stump remains capable of regenerating its axons. The study of peripheral nerve injury began during the American Civil War and greatly expanded during modern medicine with such advances as use of growth-promoting molecules. Types
To assess the location and severity of a peripheral nerve injury, clinical assessment is commonly combined with electrodiagnostic tests. | CNTF has numerous trophic roles in motor neurons in the peripheral nervous system including the prevention of atrophy of dennervated tissue and the prevention of degeneration and death of motor neurons after nerve injury. (frostick) In sciatic motor neurons both CNTF receptor mRNA expression and CNTF receptor is increased after injury for a prolonged time frame compared to the short time frame in the central nervous system suggesting a role for CNTF in nerve regeneration.Insulin-like growth factors (IGFs) have been shown to increase the rate of peripheral nervous system axon regeneration. IGF-I and IGF-II mRNA levels are significantly increased distal to the site of crush injury in rat sciatic nerves. At the site of nerve repair, locally delivered IGF-I can significantly increase the rate of axon regeneration within a nerve graft and help expedite functional recovery of a paralyzed muscle. Role of neurite-promoting factors
Neurite promoting factors include many extracellular matrix proteins produced by Schwann cells at the distal stump including fibronectin and laminin. Fibronectin are components of the basal lamina and promote neurite growth and adhesion of the growth cone to the basal lamina. In regenerating neural cells, neurite promoting factors play a role in adhesion of the axon and include neural cell adhesion molecule (N-CAM) and N-cadherin. Treatment
Unless otherwise demonstrated, nerve injuries are commonly irreversible, and therefore complete treatment is rather difficult, though still possible and hence lifelong management of disabilities arising due to nerve injuries is necessary. Nerve regeneration therapies
Electrical stimulation can promote nerve regeneration. | 11
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Dosage and administration
For infusion
Treprostinil may be administered as a continuous subcutaneous infusion or continuous intravenous infusion via a small infusion pump that the patient must wear at all times. Treprostinil can be given subcutaneously by continuous infusion using an infusion set connected to an infusion pump, but also may be given intravenously via a central venous catheter if the patient is unable to tolerate subcutaneous administration because of severe site pain or reaction. Remodulin is supplied in 20 mL vials, containing treprostinil in concentrations of 1 mg/mL, 2.5 mg/mL, 5 mg/mL, and 10 mg/mL. Treprostinil can be administered subcutaneously as supplied. It must be diluted for intravenous infusion with either sterile water or a 0.9% sodium chloride solution prior to administration. The infusion rate is normally initiated at 1.25 ng/kg/min for new patients, but may be reduced to 0.625 ng/kg/min if the normal rate provokes unwanted side effects in the patient. The infusion rate of treprostinil should be increased no more than 1.25 ng/kg/min per week for the first month, then 2.5 ng/kg/min per week for the remaining duration of infusion. The infusion rate should ideally be high enough to improve symptoms of pulmonary hypertension, while minimizing unpleasant side effects (headache, nausea, emesis, restlessness, anxiety and infusion site pain or reaction). Dosage adjustments may be undertaken more often if tolerated. There is little experience with doses >40 ng/kg/min. Abrupt cessation of infusion should be avoided. Restarting a Remodulin infusion within a few hours after an interruption can be done using the same dose rate. | Treprostinil, sold under the brand names Remodulin for infusion, Orenitram for oral, and Tyvaso for inhalation, is a vasodilator that is used for the treatment of pulmonary arterial hypertension. Treprostinil is a synthetic analog of prostacyclin (PGI2). Treprostinil was approved for use in the United States in May 2002.The drug can be given in various forms: IV, subcutaneous injection, oral inhalation, as well as oral extended-release tablets. The subcutaneous administration tends to be very painful. Medical uses
Treprostinil is indicated for the treatment of pulmonary arterial hypertension in people with NYHA Class II-IV symptoms to diminish symptoms associated with exercise. It may be administered as a continuous subcutaneous infusion or continuous intravenous infusion; however, because of the risks associated with chronic indwelling central venous catheters, including serious blood stream infections, continuous intravenous infusion should be reserved for patients who are intolerant of the subcutaneous route, or in whom these risks are considered warranted. This medication is also available in inhaled and tablet forms. In people with pulmonary arterial hypertension requiring transition from epoprostenol sodium (Flolan), treprostinil is indicated to diminish the rate of clinical deterioration. The risks and benefits of each drug should be carefully considered prior to transition. Treprostinil therapy may be effective in treating Degos disease. Adverse effects
Since treprostinil is a vasodilator, its antihypertensive effect may be compounded by other medications that affect the blood pressure, including calcium channel blockers, diuretics, and other vasodilating agents. | 11
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This disease caused the affected animals to "lie down, bite at their feet and legs, rub their backs against posts, fail to thrive, stop feeding and finally become lame". The disease was also observed to have the long incubation period that is a key characteristic of transmissible spongiform encephalopathies (TSEs). Although the cause of scrapie was not known back then, it is probably the first transmissible spongiform encephalopathy to be recorded. In the 1950s, Carleton Gajdusek began research which eventually showed that kuru could be transmitted to chimpanzees by what was possibly a new infectious agent, work for which he eventually won the 1976 Nobel prize. During the 1960s, two London-based researchers, radiation biologist Tikvah Alper and biophysicist John Stanley Griffith, developed the hypothesis that the transmissible spongiform encephalopathies are caused by an infectious agent consisting solely of proteins. Earlier investigations by E.J. Field into scrapie and kuru had found evidence for the transfer of pathologically inert polysaccharides that only become infectious post-transfer, in the new host. Alper and Griffith wanted to account for the discovery that the mysterious infectious agent causing the diseases scrapie and Creutzfeldt–Jakob disease resisted ionizing radiation. | Most of them come with the complaints of "drops" and become extremely anxious about it and see it as loss of "male power". It is often related with obsessive ruminations and somatoform symptoms. Others see it as a distinct clinical entity which is less culture-bound than these critics assert, and describe it as one form of a syndrome of "semen-loss anxiety" which also occurs in other Eastern cultures as jiryan and shen-kuei, as well as in Western cultures. Chlamydia infection might also be related to it because of similar symptoms in case of infection of the urethra (urethritis), which is usually symptomatic, causing a white discharge from the penis with or without pain on urinating (dysuria). See also
Cross-cultural psychiatry
Koro
Shenkui
References
== External links == | 0-1
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Epilepsy is considered a sign of spiritual gifts among the Hmong people.Sickness confers the social legitimization of certain benefits, such as illness benefits, work avoidance, and being looked after by others. The person who is sick takes on a social role called the sick role. A person who responds to a dreaded disease, such as cancer, in a culturally acceptable fashion may be publicly and privately honored with higher social status. In return for these benefits, the sick person is obligated to seek treatment and work to become well once more. As a comparison, consider pregnancy, which is not interpreted as a disease or sickness, even if the mother and baby may both benefit from medical care. Most religions grant exceptions from religious duties to people who are sick. For example, one whose life would be endangered by fasting on Yom Kippur or during Ramadan is exempted from the requirement, or even forbidden from participating. People who are sick are also exempted from social duties. For example, ill health is the only socially acceptable reason for an American to refuse an invitation to the White House.The identification of a condition as a disease, rather than as simply a variation of human structure or function, can have significant social or economic implications. The controversial recognition of diseases such as repetitive stress injury (RSI) and post-traumatic stress disorder (PTSD) has had a number of positive and negative effects on the financial and other responsibilities of governments, corporations, and institutions towards individuals, as well as on the individuals themselves. | It has also been studied as an adjuvant in two other trials in people with schizophrenia, around fifty people overall, and did not appear to have an effect.There have been some trials to see if cyproheptadine could reduce sexual dysfunction caused by SSRI and antipsychotic medications.Cyproheptadine has been studied for the treatment of posttraumatic stress disorder. Veterinary use
Cyproheptadine is used in cats as an appetite stimulant: 1371 and as an adjunct in the treatment of asthma. Possible adverse effects include excitement and aggressive behavior. The elimination half-life of cyproheptadine in cats is 12 hours.Cyproheptadine is a second line treatment for pituitary pars intermedia dysfunction in horses. == References == | 0-1
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Knockout models for CDKN1C in mice do exist; in fact, many of the affected offspring exhibit fetal and neonatal lethality and have most of the features related to Beckwith-Weidemann Syndrome. Diagnosis
Management
Abdominal wall defects are common in newborns with BWS and may require surgical treatment. These defects can range in severity from omphalocele (most serious) to umbilical hernia and diastasis recti (least serious). An omphalocele is a congenital malformation in which a newborns intestines, and sometimes other abdominal organs, protrude out of the abdomen through the umbilicus. Newborns with an omphalocele typically require surgery to place the abdominal contents back into the abdomen in order to prevent serious infection or shock. An umbilical hernia is also a defect in which abdominal contents come through weak abdominal wall muscle at the umbilicus. In general, newborns with umbilical hernias do not require treatment because often these hernias spontaneously close by age four. If, after this time, a hernia is still present, surgery may be recommended. Diastasis recti is a separation of the left and right sides of the rectus abdominis muscle that are normally joined. Children with diastasis recti usually require no treatment because the condition resolves as the child grows.Neonatal hypoglycemia, low blood glucose in the first month of life, occurs in about half of children with BWS. Most of these hypoglycemic newborns are asymptomatic and have a normal blood glucose level within days. However, untreated persistent hypoglycemia can lead to permanent brain damage. | Myopericarditis is a combination of both myocarditis and pericarditis appearing in a single individual, namely inflammation of both the pericardium and the heart muscle. It can involve the presence of fluid in the heart. Risk factors
The appearance of myopericarditis is associated with infections such as acute tonsillitis, pneumonia, and gastroenteritis.Smallpox vaccination has been a known risk factor for myocarditis and pericarditis since the 1950s. In 1983, an incidence of myocarditis of 1 per 10 000 was reported among Finnish military personnel. Among US military service members vaccinated between December 2002 and March 2003 with Dryvax smallpox vaccine 18 cases of probable myopericarditis were reported, which was an incidence of 7.8 per 100 000 over 30 days.A meta-review from 2022 shows that the overall risk for myopericarditis after receiving a COVID-19 vaccine is low. In addition, the incidence of myopericarditis is significantly higher with a smallpox vaccination in comparison with a COVID-19 vaccination. The ACAM2000 smallpox vaccine has been known to cause myopericarditis in some people. Etymology
When ventricular function is normal, the term myopericarditis is used. Cases with impaired function are labeled perimyocarditis, though the two terms are often used interchangeably. Both will be reflected on an ECG.In a different naming scheme, inflammation that is predominantly pericarditis with some myocardial involvement is called myopericarditis, while predominant myocarditis with some pericardial involvement is called perimyocarditis. == References == | 0-1
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5 in C major (revised version), Op. 135 (1952–53)
Sergei Rachmaninoff
Piano Sonata No. 2 in B-flat minor, Op. 36 (1913, revised in 1931)
Sonata for Cello and Piano in G minor, Op. 19 (1901)
Alexander Scriabin
Piano Sonata No. 2 (Sonata-Fantasy)
Piano Sonata No. 3
Piano Sonata No. 4
Piano Sonata No. 5
Piano Sonata No. 6
Piano Sonata No. 7 "White Mass"
Piano Sonata No. 8
Piano Sonata No. 9 "Black Mass"
Piano Sonata No. 10
Kaikhosru Shapurji Sorabji
Piano Sonata No. 0
Piano Sonata No. 1
Piano Sonata No. 2
Piano Sonata No. 3
Piano Sonata No. 4
Piano Sonata No. 5 "Opus Archimagicum"
Igor Stravinsky
Sonata for Two Pianos (1943)
Eugène Ysaÿe
Six Sonatas for solo violin (1923)
References
Sources
== Further reading == | The arthritis may be "additive" (more joints become inflamed in addition to the primarily affected one) or "migratory" (new joints become inflamed after the initially inflamed site has already improved).Reactive arthritis is an RF-seronegative, HLA-B27-linked arthritis often precipitated by genitourinary or gastrointestinal infections. The most common triggers are intestinal infections (with Salmonella, Shigella or Campylobacter) and sexually transmitted infections (with Chlamydia trachomatis); however, it also can happen after group A streptococcal infections.It most commonly strikes individuals aged 20–40 years of age, is more common in men than in women, and more common in white than in black people. This is owing to the high frequency of the HLA-B27 gene in the white population. It can occur in epidemic form. Patients with HIV have an increased risk of developing reactive arthritis as well. Numerous cases during World Wars I and II focused attention on the triad of arthritis, urethritis, and conjunctivitis (often with additional mucocutaneous lesions), which at that time was also referred to as Fiessenger-Leroy-Reiter syndrome. Signs and symptoms
Because common systems involved include the eye, the urinary system, and the hands and feet, one clinical mnemonic in reactive arthritis is "Cant see, cant pee, cant climb a tree." The classic triad consists of:
Conjunctivitis
Nongonococcal urethritis
Asymmetric oligoarthritis
Symptoms generally appear within 1–3 weeks but can range from 4 to 35 days from the onset of the inciting episode of the disease. The classical presentation of the syndrome starts with urinary symptoms such as burning pain on urination (dysuria) or an increased frequency of urination. | 0-1
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The onyongnyong virus (ONNV) was first isolated by researchers at the Uganda Virus Research Institute in Entebbe, Uganda, during a large outbreak of a disease in 1959 that resembled dengue fever. ONNV is a togavirus (family Togaviridae), genus Alphavirus, is closely related to the chikungunya and Igbo Ora viruses, and is a member of the Semliki Forest antigenic complex. The name was given to the disease by the Acholi tribe during the 1959 outbreak. The name comes from the Nilotic language of Uganda and Sudan and means “weakening of the joints". The virus can infect humans and may cause disease. Signs and symptoms
Common symptoms of infection with the virus are polyarthritis, rash and fever. Other symptoms include eye pain, chest pain, lymphadenitis and lethargy. The disease is self-limiting. No fatalities due to infection are known. Cause
Strains
ONNV has at least three major subtypes, or strains, the genomic sequences of which are currently available on genome databases. Transmission
ONNV is transmitted by bites from an infected mosquito. It is the only virus whose primary vectors are anopheline mosquitoes (Anopheles funestus and Anopheles gambiae). Epidemiology
There have been two epidemics of o’nyong’nyong fever. The first occurred from 1959 to 1962, spreading from Uganda to Kenya, Tanzania, Zaire (Democratic Republic of the Congo), Malawi and Mozambique, and affecting over two million people, one of the largest arbovirus epidemics ever recorded. | Statistics
Many of those affected during a thunderstorm asthma outbreak may have never experienced an asthma attack before.It has been found 95% of those that were affected by thunderstorm asthma had a history of hayfever, and 96% of those people had tested positive to grass pollen allergies, particularly rye grass. A rye grass pollen grain can hold up to 700 tiny starch granules, measuring 0.6 to 2.5 μm, small enough to reach the lower airways in the lung. Prevention
Patients with a history of grass allergies should be tested for asthma and treated for the grass allergies and asthma if also present. Patients with known asthma should be treated and counseled on the importance of adherence to preventative medication protocols. Preventative treatment found useful for severe asthma includes Allergen immunotherapy (AIT) particularly sublingual immunotherapy (SLIT). Significant events
6 July 1983 (1983-07-06) – 7 July 1983 (1983-07-07): Birmingham, England
8 November 1987 (1987-11-08): Melbourne, Australia
29 November 1989 (1989-11-29) – 30 November 1989 (1989-11-30): Melbourne, Australia
24 July 1994 (1994-07-24) – 25 July 1994 (1994-07-25): London, England
30 October 1997 (1997-10-30): Wagga Wagga, Australia
4 June 2004 (2004-06-04): Naples, Italy
25 November 2010 (2010-11-25): Melbourne, Australia
2 November 2013 (2013-11-02): Ahvaz, Iran
21 November 2016 (2016-11-21): Melbourne, Australia
1 December 2016 (2016-12-01): Kuwait and Riyadh, Saudi Arabia
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That is the bad news.... There is a deeper illness that drives depression and the symptoms of mood. We can call this deeper illness something else, or invent a neologism, but we need to get the discussion off depression and onto this deeper disorder in the brain and body. That is the point. In eliminating the nervous breakdown, psychiatry has come close to having its own nervous breakdown. Nerves stand at the core of common mental illness, no matter how much we try to forget them. "Nervous breakdown" is a pseudo-medical term to describe a wealth of stress-related feelings and they are often made worse by the belief that there is a real phenomenon called "nervous breakdown". Classifications
There are currently two widely established systems that classify mental disorders:
ICD-11 Chapter 06: Mental, behavioural or neurodevelopmental disorders, part of the International Classification of Diseases produced by the WHO (in effect since 1 January 2022). Diagnostic and Statistical Manual of Mental Disorders (DSM-5) produced by the APA since 1952.Both of these list categories of disorder and provide standardized criteria for diagnosis. They have deliberately converged their codes in recent revisions so that the manuals are often broadly comparable, although significant differences remain. Other classification schemes may be used in non-western cultures, for example, the Chinese Classification of Mental Disorders, and other manuals may be used by those of alternative theoretical persuasions, such as the Psychodynamic Diagnostic Manual. In general, mental disorders are classified separately from neurological disorders, learning disabilities or intellectual disability. | Although "nervous breakdown" is not rigorously defined, surveys of laypersons suggest that the term refers to a specific acute time-limited reactive disorder, involving symptoms such as anxiety or depression, usually precipitated by external stressors. Many health experts today refer to a nervous breakdown as a mental health crisis. Nervous illness
Additionally to the concept of mental disorder, some people have argued for a return to the old-fashioned concept of nervous illness. In How Everyone Became Depressed: The Rise and Fall of the Nervous Breakdown (2013), Edward Shorter, a professor of psychiatry and the history of medicine, says:
About half of them are depressed. Or at least that is the diagnosis that they got when they were put on antidepressants. ... They go to work but they are unhappy and uncomfortable; they are somewhat anxious; they are tired; they have various physical pains—and they tend to obsess about the whole business. There is a term for what they have, and it is a good old-fashioned term that has gone out of use. They have nerves or a nervous illness. It is an illness not just of mind or brain, but a disorder of the entire body. ... We have a package here of five symptoms—mild depression, some anxiety, fatigue, somatic pains, and obsessive thinking. ... We have had nervous illness for centuries. When you are too nervous to function ... it is a nervous breakdown. But that term has vanished from medicine, although not from the way we speak.... The nervous patients of yesteryear are the depressives of today. | 11
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These documents have been updated as research is published. In the US, Recommended Dietary Allowances (RDAs) were first set in 1941 by the Food and Nutrition Board of the National Academy of Sciences. There were periodic updates, culminating in the Dietary Reference Intakes. Updated in 2016, the US Food and Drug Administration published a set of tables that define Estimated Average Requirements (EARs) and (RDAs). RDAs are higher to cover people with higher than average needs. Together, these are part of Dietary Reference Intakes. For a few vitamins, there is not sufficient information to set EARs and RDAs. For these, an Adequate Intake is shown, based on an assumption that what healthy people consume is sufficient. Countries do not always agree on the amounts of vitamins needed to safeguard against deficiency. For example, for vitamin C, the RDAs for women for Japan, the European Union (called Population Reference Intakes) and the US are 100, 95 and 75 mg/day, respectively. India sets its recommendation at 40 mg/day. Individual vitamin deficiencies
Water-soluble vitamins
|-abc 0.54jdb
Fat-soluble vitamins
Prevention
Food fortification
Food fortification is the process of adding micronutrients (essential trace elements and vitamins) to food as a public health policy which aims to reduce the number of people with dietary deficiencies within a population. Staple foods of a region can lack particular nutrients due to the soil of the region or from inherent inadequacy of a normal diet. | Genzyme maintains higher prices for orphan drugs—most often paid for by insurers—in order to remain financially sustainable. References
External links
"Eliglustat". Drug Information Portal. U.S. National Library of Medicine. | 0-1
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Moreover, a third of the remaining chronic cases will usually remit during follow-up observation, and another third will end up with only mild thrombocytopenia (defined as a platelet count above 50,000). A number of immune related genes and polymorphisms have been identified as influencing predisposition to ITP, with FCGR3a-V158 allele and KIRDS2/DL2 increasing susceptibility and KIR2DS5 shown to be protective.ITP is usually chronic in adults and the probability of durable remission is 20–40 percent. The male to female ratio in the adult group varies from 1:1.2 to 1.7 in most age ranges (childhood cases are roughly equal for both sexes) and the median age of adults at the diagnosis is 56–60. The ratio between male and female adult cases tends to widen with age. In the United States, the adult chronic population is thought to be approximately 60,000—with women outnumbering men approximately 2 to 1, which has resulted in ITP being designated an orphan disease.The mortality rate due to chronic ITP varies but tends to be higher relative to the general population for any age range. In a study conducted in Great Britain, it was noted that ITP causes an approximately 60 percent higher rate of mortality compared to sex- and age-matched subjects without ITP. This increased risk of death with ITP is largely concentrated in the middle-aged and elderly. Ninety-six percent of reported ITP-related deaths were individuals 45 years or older. No significant difference was noted in the rate of survival between males and females. | Platelets were unknown at the time. The name "Werlhofs disease" was used more widely before the current descriptive name became more popular. Platelets were described in the early 19th century, and in the 1880s several investigators linked the purpura with abnormalities in the platelet count. The first report of a successful therapy for ITP was in 1916, when a young Polish medical student, Paul Kaznelson, described a female patients response to a splenectomy. Splenectomy remained a first-line remedy until the introduction of steroid therapy in the 1950s. References
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Electrically, the nerve shows rapid and complete degeneration, with loss of voluntary motor units. Regeneration of the motor end plates will occur, as long as the endoneural tubules are intact.Axonotmesis involves the interruption of the axon and its covering of myelin, but with preservation of the connective tissue framework of the nerve (the encapsulating tissue, the epineurium and perineurium, are preserved). Because axonal continuity is lost, Wallerian degeneration occurs. Electromyography (EMG) performed 2 to 4 weeks later shows fibrillations and denervation potentials in musculature distal to the injury site. Loss in both motor and sensory spines is more complete with axonotmesis than with neurapraxia, and recovery occurs only through regenerations of the axons, a process requiring time. Axonotmesis is usually the result of a more severe crush or contusion than neurapraxia, but can also occur when the nerve is stretched (without damage to the epineurium). There is usually an element of retrograde proximal degeneration of the axon, and for regeneration to occur, this loss must first be overcome. The regeneration fibers must cross the injury site and regeneration through the proximal or retrograde area of degeneration may require several weeks. Then the neuritis tip progresses down the distal site, such as the wrist or hand. Proximal lesion may grow distally as fast as 2 to 3 mm per day and distal lesion as slowly as 1.5 mm per day. Regeneration occurs over weeks to years. Neurotmesis
Neurotmesis is the most severe lesion with no potential of full recovery. It occurs on severe contusion, stretch, or laceration. | They not only have a role in phagocytosis of myelin, but they also have a role in recruitment of macrophages to continue the phagocytosis of myelin. The phagocytic role of Schwann cells has been investigated by studying the expression of molecules in Schwann cells that are typically specific to inflammatory macrophages. Expression of one such molecule MAC-2, a galactose-specific lectin, is observed in not only degenerating nerves that are macrophage-rich but also degenerating nerves that are macrophage-scarce and Schwann cell-rich. Furthermore, the effects of MAC-2 in degenerating nerves are associated with myelin phagocytosis. There was a positive correlation between the amount of MAC-2 expression and the extent of myelin phagocytosis. A deficiency in MAC-2 expression can even cause inhibition of myelin removal from injury sites.Schwann cells are active in demyelination of injured nerves before macrophages are even present at the site of nerve injury. Electron microscopy and immunohistochemical staining analysis of teased nerve fibers shows that before macrophages arrive at the injury site, myelin is fragmented and myelin debris and lipid droplets are found in the cytoplasm of Schwann cells, indicating phagocytic activity before macrophages arrive.Schwann cell activity includes recruitment of macrophages to the injury site. Monocyte chemoattractant protein (MCP-1) plays a role in recruiting monocytes/macrophages. In tellurium-induced demylenation with no axon degeneration, nerve crush with axon degeneration, and nerve transection with axon degeneration an increase in MCP-1 mRNA expression followed by an increase in macrophage recruitment occurred. In addition varying levels of MCP-1 mRNA expression also had an effect. | 11
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So the patient can in fact have his or her medication with food as long as the meal does not contain fat or oils (e.g., a cup of black coffee or toast with jam and no butter). Taking the medicines with food also helps ease the nausea that many patients feel when taking the medicines on an empty stomach. The effect of food on the absorption of INH is not clear: two studies have shown reduced absorption with food but one study showed no difference. There is a small effect of food on the absorption of PZA and of EMB that is probably not clinically important.It is possible to test urine for isoniazid and rifampicin levels to check for compliance. The interpretation of urine analysis is based on the fact that isoniazid has a longer half-life than rifampicin:
urine positive for isoniazid and rifampicin – patient probably fully compliant
urine positive for isoniazid only – patient has taken his medication in the last few days preceding the clinic appointment, but had not yet taken a dose that day. urine positive for rifampicin only – patient has omitted to take his medication the preceding few days, but did take it just before coming to clinic. urine negative for both isoniazid and rifampicin – patient has not taken either medicine for a number of daysIn countries where doctors are unable to compel patients to take their treatment (e.g., the UK), some say that urine testing only results in unhelpful confrontations with patients and does not help increase compliance. | Located in India and Cambodia, Operation ASHA focuses on the development of "e-Compliance," which is a verification and SMS text messaging system where patients can use their fingerprints to access their medical records and be reminded daily via text when to take their medication. According to Operation ASHA, the e-Compliance treatment successive rate is 85%. Treatment failure
Patients who fail treatment must be distinguished from patients who relapse. Patients who responded to treatment and appeared to be cured after completing a course of TB treatment are not classed as treatment failures, but as relapses and are discussed in a separate section below. Patients are said to have failed treatment if they
fail to respond to treatment (cough and sputum production persisting throughout the whole of treatment), or
only experience a transient response to treatment (the patient gets better at first, but then get worse again, all the while on treatment).It is very uncommon for patients not to respond to TB treatment at all (even transiently), because this implies resistance at base-line to all of the drugs in the regimen. Patients who fail to get any response at all while on treatment should first of all be questioned very closely about whether or not they have been taking their medicines, and perhaps even be admitted to hospital to be observed taking their treatment. Blood or urine samples may be taken to check for malabsorption of TB drugs. | 11
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Patients with metastatic EMPD only survive for a median of 1.5 years, and have a 7% 5-year survival rate. Prognosis
Prognosis is generally good, but factors such as depth of invasion and duration of disease need to be considered. In primary EMPD, if invasion of the underlying tissue is non-existent or even minimal, treatment options are more likely to be effective, however, if there are signs that the disease has metastasised, the prognosis is usually poor. Epidemiology
EMPD is most prevalent in Caucasian women and Asian men over the age of 60. The invasive form occurs in 5–25% of all EMPD patients and 17–30% of the cases involve an underlying adenocarcinoma. 10-20% of EMPD is of the secondary form. Approximately 10% of patients develop invasive adenocarcinoma that may progress to metastatic disease.The disease affects regions that are rich in apocrine secretions. 65% EMPD occurs at the vulva, followed by 15% at perianal areas and 14% at the male genitalia. In terms of the vulva, the labia majora is the site that is most often involved, followed by labia minora, clitoris and perineum. EMPD originating at the vulva can spread to the upper vaginal mucosa and cervix. Other areas where EMPD can be found, although very rarely, include: the axillae, eyelids, external auditory canal, umbilical region, trunk and extremities. History
The first case of Pagets disease was described by James Paget in 1874. | Extramammary Pagets Disease (EMPD) is a rare and slow-growing malignancy which occurs within the epithelium and accounts for 6.5% of all Pagets disease. The clinical presentation of this disease is similar to the characteristics of mammary Pagets disease (MPD). However, unlike MPD, which occurs in large lactiferous ducts and then extends into the epidermis, EMPD originates in glandular regions rich in apocrine secretions outside the mammary glands. EMPD incidence is increasing by 3.2% every year, affecting hormonally-targeted tissues such as the vulva and scrotum. In women, 81.3% of EMPD cases are related to the vulva, while for men, 43.2% of the manifestations present at the scrotum.The disease can be classified as being either primary or secondary depending on the presence or absence of associated malignancies. EMPD presents with typical symptoms such as scaly, erythematous, eczematous lesions accompanied by itchiness. In addition to this, 10% of patients are often asymptomatic. As a consequence, EMPD has high rates of misdiagnoses and delayed diagnoses. There are a variety of treatment options available, but most are unsuccessful. If caught early and treated, prognosis is generally good. Presentation
Patients with EMPD present with typical symptoms, similar to MPD, such as severe itchiness (also called pruritus), rash, plaque formation, burning sensation, pain and tenderness. These symptoms are often confused for dermatitis or eczema. 10% of patients are asymptomatic resulting in delayed diagnosis. In rare cases bleeding can also be seen. Disease of the vulva
Vulvar Pagets disease affect women and presents as erythematous (red), eczematous lesions. | 11
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The solution to this enormous problem is for the child to encase themself within a thick psychological cocoon of denial and fantasy that creates a false reality in which they believe that they are living in a loving and caring family. The first way that the child protects themself is by using the greatest reality-altering defense that humans have at their disposal, which is the defense of dissociation. The dissociative defense mechanism is seen in adults who have suffered a life-threatening trauma, and dissociation prevents them from fully realizing what has happened. In children, the same defense protects the child by forcing intolerable memories of neglect, abuse, or total indifference that they suffered at the hands of their parents into their unconscious, where these memories will not disturb the childs illusion that they live in a safe and loving family. The dissociative defense is the basis of what is commonly called denial. The more frequent the abuse, the more frequently dissociation is required and the larger and larger the number of intolerable memories are forced into the unconscious. Once lodged in their unconscious, the child cannot remember the horrifying incidents that they previously experienced. Splitting defense
The child not only dissociates memories of the abusive parent, but also memories of themselves in those anxiety-filled encounters with the rejecting parent. Their memory of themselves in these situations is one of being a frightened, impotent, and vulnerable child who is overwhelmed and deeply ashamed because they are unable to protect themselves when confronted by the aggressive parent. | It was noted that in this case, however, the police were perceived to have acted with little care for the hostages safety, providing an alternative reason for their unwillingness to testify. Stockholm syndrome is paradoxical because the sympathetic sentiments that captives feel towards their captors are the opposite of the fear and disdain which an onlooker might feel towards the captors. There are four key components that characterize Stockholm syndrome:
A hostages development of positive feelings towards the captor
No previous relationship between hostage and captor
A refusal by hostages to cooperate with police and other government authorities
A hostages belief in the humanity of the captor, ceasing to perceive them as a threat, when the victim holds the same values as the aggressor.The term "Stockholm syndrome" has also been used to describe the reactions of some abuse victims beyond the context of kidnappings or hostage-taking. Actions and attitudes similar to those with Stockholm syndrome have also been found in victims of sexual abuse, human trafficking, extremism, terrorism, economic oppression, financial repression, political repression and religious persecution. This is because Stockholm syndrome can be argued as "another method of coping with the stress and danger...similar to some forms of coping in that the participants do not directly address the problem but find a way to cope with the situation by identifying with the aggressor. Coping mechanisms such as these can have a large impact on PTSD. "Helsinki syndrome is a term sometimes used incorrectly instead of Stockholm syndrome. The confusion is often deliberate and used for ironic effect. | 11
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There are several possible mechanisms, including the inhibition of CYP3A4-mediated metabolism.As calcium channel blocker, nifedipine has a risk of causing gingival hyperplasia
Overdose
A number of persons have developed toxicity due to acute overdosage with nifedipine, either accidentally or intentionally, and via either oral or parenteral administration. The adverse effects include lethargy, bradycardia, marked hypotension and loss of consciousness. The drug may be quantified in blood or plasma to confirm a diagnosis of poisoning, or to assist in a medicolegal investigation following death. Analytical methods usually involve gas or liquid chromatography and specimen concentrations are usually in the 100-1000 μg/L range. [1]
Mechanism of action
Nifedipine is a calcium channel blocker. Although nifedipine and other dihydropyridines are commonly regarded as specific to the L-type calcium channel, they also possess nonspecific activity towards other voltage-dependent calcium channels.Nifedipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid. History
Nifedipine (initially BAY a1040, then Adalat) was developed by the German pharmaceutical company Bayer, with most initial studies being performed in the early 1970s.The use of nifedipine and related calcium channel antagonists was much reduced in response to 1995 trials that mortality was increased in patients with coronary artery disease who took nifedipine. This study was a meta-analysis, and demonstrated harm mainly in short-acting forms of nifedipine (that could cause large fluctuations in blood pressure) and at high doses of 80 mg a day and more. Adalat was the first German pharmaceutical to be awarded the highly prestigious Prix Galien in 1980. | In the same year, Ahmed Hegazy submitted his invention (in collaboration with Klaus-Dieter Rämsch) of an extended release, solid medicinal preparation of nifedipine to the German Patent Office in Munich, patenting the “use of nifedipine crystals with a specific surface area of 1-4 m2/g for the production of solid medicinal formulations for achieving long-lasting blood levels for the oral treatment of hypertension by administration 1 to 2 times”, an invention that became known as Adalat retard from Bayer (see letter Dr Schauerte). In that formulation, the active ingredient is released over a period of up to 36 hours. With the increasing incidence of heart disease in that period—heart failure became the first cause of death in West Germany—and the new formulation, the medication replaced Aspirine in the 1990s as the biggest single product of Bayer. As Alexander Mey noted, "[d]iese Maßnahmen führten dazu, dass der Umsatz im Jahr 2000 auf 1,7 Mrd. US-$ stieg, obwohl das Präparat bereits ein Vierteljahrhundert am Markt war." On 14 October 1991, Hegazy was awarded the Otto Bayer Medal—no relation to the company founder—for his work solubilizing poorly soluble active ingredients such as nifedipine, a prize, that the Bayer Group has been using to honor excellent research since 1984. By 2020, 528 researchers had received the award. A 1995 US lawsuit, in which Hegazy defended his patent, found that Pfizers Procardia XL product was also based on his European patent No. 0047899, United States Patent 5264446. | 11
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The most simple form of treatment is therefore reassurance that the condition does not represent a serious disease, which may act to alleviate contributing stress.Sleep hygiene education should be provided by the clinician, as well as a clear and short explanation of bruxism (definition, causes and treatment options). Relaxation and tension-reduction have not been found to reduce bruxism symptoms, but have given patients a sense of well-being. One study has reported less grinding and reduction of EMG activity after hypnotherapy.Other interventions include relaxation techniques, stress management, behavioural modification, habit reversal and hypnosis (self hypnosis or with a hypnotherapist). Cognitive behavioral therapy has been recommended by some for treatment of bruxism. In many cases awake bruxism can be reduced by using reminder techniques. Combined with a protocol sheet this can also help to evaluate in which situations bruxism is most prevalent. Medication
Many different medications have been used to treat bruxism, including benzodiazepines, anticonvulsants, beta blockers, dopamine agents, antidepressants, muscle relaxants, and others. However, there is little, if any, evidence for their respective and comparative efficacies with each other and when compared to a placebo. A multiyear systematic review to investigate the evidence for drug treatments in sleep bruxism published in 2014 (Pharmacotherapy for Sleep Bruxism. Macedo, et al.) found "insufficient evidence on the effectiveness of pharmacotherapy for the treatment of sleep bruxism. | Spindle cell lipoma is an asymptomatic, slow-growing subcutaneous tumor that has a predilection for the posterior back, neck, and shoulders of older men. : 625
See also
Intradermal spindle cell lipoma
List of cutaneous conditions
References
== External links == | 0-1
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Nuclear atypia, in which the nuclei of cells varies in size, any may be increased in size relative to the cytoplasm, shape, and may stain more intensely. There may also be more prominent nucleoli. Increased number of cells seen undergoing mitosis, including both normal and abnormal mitoses. Abnormal mitosis may be abnormally located, e.g. occurring in suprabasal cells (cell layers more superficial to the basal cell layer) or of abnormal form, e.g. "tri-radiate mitoses" (a cell splitting into 3 daughter cells rather than only 2)
Loss the normal organization of the epithelial layers. The distinction between the epithelial layers may be lost. Normally stratified squamous epithelium shows progressive changes in the form of cells from the basal to the superficial layers, with cells becoming more flat ("squames") towards the surface as a continuous maturation process. In dysplastic epithelium, cells may become vertically orientated rather than becoming flat towards the surface. There may be abnormal keratinization, where keratin is formed below the normal keratin layer. This can occur in individual cells or groups of cells, forming an intraepithelial keratin pearl. There may be an increase in the number of basal cells, and they may lose their cellular orientation (losing their polarity and long axis). Alteration of the normal epithelial-connective tissue architecture - the rete pegs may become "drop shaped". wider at their base than more superficially.Generally, dysplasia is subjectively graded by pathologists into mild, moderate or severe dysplasia. This requires experience as it is a difficult skill to learn. | Angina
GTN is useful in decreasing angina attacks, perhaps more so than reversing angina once started, by supplementing blood concentrations of NO, also called endothelium-derived relaxing factor, before the structure of NO as the responsible agent was known. This led to the development of transdermal patches of glyceryl trinitrate, providing 24-hour release. However, the effectiveness of glyceryl trinitrate is limited by development of tolerance/tachyphylaxis within 2–3 weeks of sustained use. Continuous administration and absorption (such as provided by daily pills and especially skin patches) accelerate onset of tolerance and limit the usefulness of the agent. Thus, glyceryl trinitrate works best when used only in short-term, pulse dosing. Glyceryl trinitrate is useful for myocardial infarction (heart attack) and pulmonary edema, again working best if used quickly, within a few minutes of symptom onset, as a pulse dose.It may also be given as a sublingual or buccal dose in the form of a tablet placed under the tongue or a spray into the mouth for the treatment of an angina attack. Other uses
Tentative evidence indicates efficacy of glyceryl trinitrate in the treatment of various tendinopathies, both in pain management and acceleration of soft tissue repair.GTN is also used in the treatment of anal fissures, though usually at a much lower concentration than that used for angina treatment.GTN has been used to decrease pain associated with dysmenorrhea.GTN was once researched for the prevention and treatment of osteoporosis; however, the researcher Sophie Jamal was found to have falsified the findings, sparking one of the largest scientific misconduct cases in Canada. | 0-1
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Risk factors
Identified risk factors for plantar fasciitis include excessive running, standing on hard surfaces for prolonged periods, high arches of the feet, the presence of a leg length inequality, and flat feet. The tendency of flat feet to excessively roll inward during walking or running makes them more susceptible to plantar fasciitis. Obesity is seen in 70% of individuals who present with plantar fasciitis and is an independent risk factor.Plantar fasciitis is commonly a result of some biomechanical imbalance that causes an increased amount of tension placed along the plantar fascia.Studies consistently find a strong association between increased body mass index and plantar fasciitis in the non-athletic population. This association between weight and plantar fasciitis is not present in the athletic population. Achilles tendon tightness and inappropriate footwear have also been identified as significant risk factors. Pathophysiology
The cause of plantar fasciitis is poorly understood and appears to have several contributing factors. The plantar fascia is a thick fibrous band of connective tissue that originates from the medial tubercle and anterior aspect of the heel bone. From there, the fascia extends along the sole of the foot before inserting at the base of the toes and supports the arch of the foot.Plantar fasciitis is a non-inflammatory condition of the plantar fascia. | Differential diagnosis
The differential diagnosis for heel pain is extensive and includes pathological entities including, but not limited to, the following: calcaneal stress fracture, septic arthritis, calcaneal bursitis, osteoarthritis, spinal stenosis involving the nerve roots of lumbar spinal nerve 5 (L5) or sacral spinal nerve 1 (S1), calcaneal fat pad syndrome, metastasized cancers from elsewhere in the body, hypothyroidism, gout, seronegative spondyloparthopathies such as reactive arthritis, ankylosing spondylitis, or rheumatoid arthritis (more likely if pain is present in both heels), plantar fascia rupture, and compression neuropathies such as tarsal tunnel syndrome or impingement of the medial calcaneal nerve.A determination about a diagnosis of plantar fasciitis can usually be made based on a persons medical history and physical examination. When a physician suspects a fracture, infection, or some other serious underlying condition, they may order an X-ray to investigate. X-rays are unnecessary to screen for plantar fasciitis for people who stand or walk a lot at work unless imaging is otherwise indicated. Treatment
Non-surgical
About 90% of plantar fasciitis cases improve within six months with conservative treatment, and within a year regardless of treatment.The recommended first treatment is a 4-6 week course which combines three elements: daily stretching, daily foot taping (using a special tape around the foot for supporting the arch) and individually tailored education on choosing footwear and other ways of managing the condition.If plantar fasciitis fails to respond to conservative treatment for at least three months, then extracorporeal shockwave therapy (ESWT) may be considered. | 11
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However, with almost universal use of ultrasound in the developed world, many cases are now detected during pregnancy, giving the opportunity to deliver the baby before this catastrophic rupture of the membranes occurs. Vasa previa is diagnosed with ultrasound when echolucent linear or tubular structures are found overlying the cervix or in close proximity to it. Transvaginal ultrasound is the preferred modality. Color, power and pulsed wave Doppler should be used to confirm that the structures are fetal vessels. The vessels will demonstrate a fetal arterial or venous waveform. Alkali denaturation test detects the presence of fetal hemoglobin in vaginal blood, as fetal hemoglobin is resistant to denaturation in presence of 1% NaOH. Tests such as the Ogita Test, Apt test or Londersloot test were previously used to attempt to detect fetal blood in the vaginal blood, to help make the diagnosis. These tests are no longer widely used in the US, but are sometimes used in other parts of the world. Also detection of fetal hemoglobin in vaginal bleeding is diagnostic. Treatment
It is recommended that women with vasa previa should deliver through elective cesarean prior to rupture of the membranes. Given the timing of membrane rupture is difficult to predict, elective cesarean delivery at 35–36 weeks is recommended. This gestational age gives a reasonable balance between the risk of death and that of prematurity. Several authorities have recommended hospital admission about 32 weeks. This is to give the patient proximity to the operating room for emergency delivery should the membranes rupture. | There are three types of vasa previa. Types 1 and 2 were described by Catanzarite et al. In Type 1, there is a velamentous insertion with vessels running over the cervix. In Type 2, unprotected vessels run between lobes of a bilobed or succenturiate lobed placenta. In Type 3, a portion of the placenta overlying the cervix undergoes atrophy. In this type, there is a normal placental cord insertion and the placenta has only one lobe. However, vessels at a margin of the placenta are exposed. Risk factors
Vasa previa is seen more commonly with velamentous insertion of the umbilical cord, accessory placental lobes (succenturiate or bilobate placenta), multiple gestation, and in vitro fertilisation pregnancy. In IVF pregnancies, incidence as high as one in 300 has been reported. The reasons for this association are not clear, but disturbed orientation of the blastocyst at implantation, vanishing embryos and the increased frequency of placental morphological variations in IVF pregnancies have all been postulated. Diagnosis
The classic triad of the vasa praevia is: membrane rupture, painless vaginal bleeding and fetal bradycardia or fetal death. Prior to the advent of ultrasound, this diagnosis was most often made after a stillbirth or neonatal death in which the mother had ruptured her membranes, had some bleeding, and delivered an exsanguinated baby. In these cases, examination of the placenta and membranes after delivery would show evidence of a velamentous cord insertion with rupture of the vessels. | 11
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acoustic trauma
presbycusis (age-associated hearing loss)
Ménières disease
endolymphatic hydrops
superior canal dehiscence
acoustic neuroma
mercury or lead poisoning
ototoxic medications
neurologic disorders:
Arnold–Chiari malformation
multiple sclerosis
head injury
giant cell arteritis
temporomandibular joint dysfunction
metabolic disorders:
vitamin B12 deficiency
iron deficiency anemia
psychiatric disorders
depression
anxiety disorders
other factors:
vasculitis
Some psychedelic drugs can produce temporary tinnitus-like symptoms as a side effect
5-MeO-DET
diisopropyltryptamine (DiPT)
benzodiazepine withdrawal
intracranial hyper or hypotension caused by, for example, encephalitis or a cerebrospinal fluid leak
Objective tinnitus
Objective tinnitus can be detected by other people and is sometimes caused by an involuntary twitching of a muscle or a group of muscles (myoclonus) or by a vascular condition. In some cases, tinnitus is generated by muscle spasms around the middle ear.Spontaneous otoacoustic emissions (SOAEs), which are faint high-frequency tones that are produced in the inner ear and can be measured in the ear canal with a sensitive microphone, may also cause tinnitus. About 8% of those with SOAEs and tinnitus have SOAE-linked tinnitus, while the percentage of all cases of tinnitus caused by SOAEs is estimated at 4%. Pediatric tinnitus
Children may be subject to pulsatile or continuous tinnitus. With pulsatile tinnitus involving anomalies and variants of the vascular parts. While continuous affecting the middle/inner ear structures. CT scans are able to check for integrity of the structures, and MR scans can evaluate the nerves and potential masses or malformations. Early diagnosis can prevent long term impairments to development, imaging and categorizing whether it nonpulsatile or pulsatile tinnitus help create an efficient diagnosis. Pulsatile tinnitus
Some people experience a sound that beats in time with their pulse, known as pulsatile tinnitus or vascular tinnitus. | These questionnaires measure the degree of psychological distress and handicap associated with tinnitus, including effects on hearing, lifestyle, health and emotional functioning. A broader assessment of general functioning, such as levels of anxiety, depression, stress, life stressors and sleep difficulties, is also important in the assessment of tinnitus due to higher risk of negative well-being across these areas, which may be affected by or exacerbate the tinnitus symptoms for the individual. Overall, current assessment measures are aimed to identify individual levels of distress and interference, coping responses and perceptions of tinnitus to inform treatment and monitor progress. However, wide variability, inconsistencies and lack of consensus regarding assessment methodology are evidenced in the literature, limiting comparison of treatment effectiveness. Developed to guide diagnosis or classify severity, most tinnitus questionnaires have been shown to be treatment-sensitive outcome measures. Pulsatile tinnitus
If the examination reveals a bruit (sound due to turbulent blood flow), imaging studies such as transcranial doppler (TCD) or magnetic resonance angiography (MRA) should be performed. Differential diagnosis
Other potential sources of the sounds normally associated with tinnitus should be ruled out. For instance, two recognized sources of high-pitched sounds might be electromagnetic fields common in modern wiring and various sound signal transmissions. A common and often misdiagnosed condition that mimics tinnitus is radio frequency (RF) hearing, in which subjects have been tested and found to hear high-pitched transmission frequencies that sound similar to tinnitus. Prevention
Prolonged exposure to loud sound or noise levels can lead to tinnitus. Custom made ear plugs or other measures can help with prevention. | 11
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Diagnosis
Diagnosis is confirmed via biopsy of the tissue or tissues suspected to be affected by SCC. For the skin, look under skin biopsy. The pathological appearance of a squamous cell cancer varies with the depth of the biopsy. For that reason, a biopsy including the subcutaneous tissue and basilar epithelium, to the surface is necessary for correct diagnosis. The performance of a shave biopsy (see skin biopsy) might not acquire enough information for a diagnosis. An inadequate biopsy might be read as actinic keratosis with follicular involvement. A deeper biopsy down to the dermis or subcutaneous tissue might reveal the true cancer. An excision biopsy is ideal, but not practical in most cases. An incisional or punch biopsy is preferred. A shave biopsy is least ideal, especially if only the superficial portion is acquired. Characteristics
Histopathologically, the epidermis in SCC in situ (Bowens disease) will show hyperkeratosis and parakeratosis. There will also be marked acanthosis with elongation and thickening of the rete ridges. These changes will overly keratinocytic cells which are often highly atypical and may in fact have a more unusual appearance than invasive SCC. The atypia spans the full thickness of the epidermis, with the keratinocytes demonstrating intense mitotic activity, pleomorphism, and greatly enlarged nuclei. They will also show a loss of maturity and polarity, giving the epidermis a disordered or "windblown" appearance.Two types of multinucleated cells may be seen: the first will present as a multinucleated giant cell, and the second will appear as a dyskeratotic cell engulfed in the cytoplasm of a keratinocyte. | When it does metastasize, the most common involved organs are the lungs, brain, bone and other skin locations.One study found squamous cell carcinoma of the penis had a much greater rate of mortality than some other forms of squamous cell carcinoma, that is, about 23%, although this relatively high mortality rate may be associated with possibly latent diagnosis of the disease due to patients avoiding genital exams until the symptoms are debilitating, or refusal to submit to a possibly scarring operation upon the genitalia. Squamous cell carcinoma occurring in the organ transplant population is also associated with a higher risk of mortality. Epidemiology
The incidence of squamous cell carcinoma continues to rise around the world. A recent study estimated that there are between 180,000 and 400,000 cases of SCC in the United States in 2013. Risk factors for squamous cell carcinoma varies with age, gender, race, geography, and genetics. The incidence of SCC increases with age and the peak incidence is usually around 60 years old. Males are affected with SCC at a ratio of 2:1 in comparison to females. Caucasians are more likely to be affected, especially those with fair skin or those chronically exposed to UV radiation.Squamous cell carcinoma of the skin can be found on all areas of the body but is most common on frequently sun-exposed areas, such as the face, legs and arms. Solid organ transplant recipients (heart, lung, liver, pancreas, among others) are also at a heightened risk of developing aggressive, high-risk SCC. | 11
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This ANA test was easier to perform and led not only to a definitive diagnosis of lupus but also many other related diseases. This discovery led to the understanding of what is now known as autoimmune diseases.To ensure that the person has lupus and not another autoimmune disease, the American College of Rheumatology (ACR) established a list of clinical and immunologic criteria that, in any combination, point to SLE. The criteria include symptoms that the person can identify (e.g. pain) and things that a physician can detect in a physical examination and through laboratory test results. The list was originally compiled in 1971, initially revised in 1982, and further revised and improved in 2009.Medical historians have theorized that people with porphyria (a disease that shares many symptoms with SLE) generated folklore stories of vampires and werewolves, due to the photosensitivity, scarring, hair growth, and porphyrin brownish-red stained teeth in severe recessive forms of porphyria (or combinations of the disorder, known as dual, homozygous, or compound heterozygous porphyrias).Useful medication for the disease was first found in 1894 when quinine was first reported as an effective therapy. Four years later, the use of salicylates in conjunction with quinine was noted to be of still greater benefit. This was the best available treatment until the middle of the twentieth century when Hench discovered the efficacy of corticosteroids in the treatment of SLE. Research
A study called BLISS-76 tested the drug belimumab, a fully human monoclonal anti-BAFF (or anti-BLyS) antibody. | A bifid rib is a congenital abnormality of the rib cage and associated muscles and nerves which occurs in about 1.2% of humans. Bifid ribs occur in up to 8.4% of Samoans. The sternal end of the rib is cleaved into two. It is usually unilateral. Bifid ribs are usually asymptomatic, and are often discovered incidentally by chest X-ray. Effects of this neuroskeletal anomaly can include respiratory difficulties, neurological difficulties, limitations, and limited energy from the stress of needing to compensate for the neurophysiological difficulties. An unstable bifid rib may lead to slipping rib syndrome.Another association is with odontogenic keratocysts of the jaw, which may behave aggressively and have a high propensity to recur when treated with simple enucleation and curettage. When seen together, the patient is likely to have nevoid basal-cell carcinoma syndrome (Gorlin-Goltz syndrome). See also
List of radiographic findings associated with cutaneous conditions
== References == | 0-1
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{\displaystyle (x,y,z)=((R+P\sin v)\cos u,(R+P\sin v)\sin u,P\cos v).} If R and P in the above flat torus parametrization form a unit vector (R, P) = (cos(η), sin(η)) then u, v, and 0 < η < π/2 parameterize the unit 3-sphere as Hopf coordinates. In particular, for certain very specific choices of a square flat torus in the 3-sphere S3, where η = π/4 above, the torus will partition the 3-sphere into two congruent solid tori subsets with the aforesaid flat torus surface as their common boundary. | A simple 4-dimensional Euclidean embedding of a rectangular flat torus (more general than the square one) is as follows:
(
x
,
y
,
z
,
w
)
=
(
R
cos
u
,
R
sin
u
,
P
cos
v
,
P
sin
v
)
{\displaystyle (x,y,z,w)=(R\cos u,R\sin u,P\cos v,P\sin v)}
where R and P are positive constants determining the aspect ratio. | 11
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Avoiding eating meals or snacks composed entirely of carbohydrates; simultaneously ingest fats and proteins, which have slower rates of absorption;
Consistently choosing longer lasting, complex carbohydrates to prevent rapid blood-sugar dips in the event that one does consume a disproportionately large amount of carbohydrates with a meal;
Monitoring any effects medication may have on symptoms.Low-carbohydrate diet and/or frequent small meals is the first treatment of this condition. The first important point is to add small meals at the middle of the morning and of the afternoon, when glycemia would start to decrease. If adequate composition of the meal is found, the fall in blood glucose is thus prevented. Patients should avoid rapidly absorbed sugars and thus avoid popular soft drinks rich in glucose or sucrose. They should also be cautious with drinks associating sugar and alcohol, mainly in the fasting state.As it is a short-term ailment, a sugar crash that was not caused by injecting too much insulin does not usually require medical intervention in most people. The most important factors to consider when addressing this issue are the composition and timing of foods.Acute (short-term) low blood sugar symptoms are best treated by consuming small amounts of sweet foods, so as to regain balance in the bodys carbohydrate metabolism. | Glucagon initiates uptake of the stored glycogen in the liver into the bloodstream so as to increase glucose levels in the blood. Sporadic, high-carbohydrate snacks and meals are deemed the specific causes of sugar crashes. The “crash” one feels is due to the rapid increase and subsequent decline of blood sugar in the body system as one begins and ceases consumption of high-sugar foods. More insulin than is actually needed is produced in response to the large, rapid ingestion of sugary foods. Treatment
Reactive hypoglycemia can usually be relieved by dietary changes:
Avoiding or limiting sugar intake, including candy, sweet desserts, fruit juice, and drinks with added sugar. Eating only small amounts of starchy foods, including potatoes, pasta, breakfast cereals, and rice. Eating a variety of foods, including:
eggs, nuts, dairy products, tofu, beans, lentils, meat, poultry, fish, or other sources of protein with every meal or snack,
whole-grain carbohydrates, such as eating whole wheat bread instead of white bread, and
more fruits and vegetables (but not fruit juice), with 5 A Day being a recommended goal for most people. Eating more high-fiber foods, such as lentils, beans, pulses (legumes), leafy greens, and most fruits and vegetables.Other tips to prevent sugar crashes include:
Exercising regularly, as exercise increases cellular sugar uptake, which decreases excessive insulin release. | 11
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Kidney disease reduces 1,25-hydroxyvitamin D formation, leading to a deficiency of the effects of vitamin D.Intestinal conditions that result in malabsorption of nutrients may also contribute to vitamin D deficiency by decreasing the amount of vitamin D absorbed via diet. In addition, a vitamin D deficiency may lead to decreased absorption of calcium by the intestines, resulting in increased production of osteoclasts that may break down a persons bone matrix. In states of hypocalcemia, calcium will leave the bones and may give rise to secondary hyperparathyroidism, which is a response by the body to increase serum calcium levels. The body does this by increasing uptake of calcium by the kidneys and continuing to take calcium away from the bones. If prolonged, this may lead to osteoporosis in adults and rickets in children. Diagnosis
The serum concentration of calcifediol, also called 25-hydroxyvitamin D (abbreviated 25(OH)D), is typically used to determine vitamin D status. Most vitamin D is converted to 25(OH)D in the serum, giving an accurate picture of vitamin D status. The level of serum 1,25(OH)D is not usually used to determine vitamin D status because it often is regulated by other hormones in the body such as parathyroid hormone. The levels of 1,25(OH)D can remain normal even when a person may be vitamin D deficient. Serum level of 25(OH)D is the laboratory test ordered to indicate whether or not a person has vitamin D deficiency or insufficiency. | Acute zonal occult outer retinopathy (AZOOR) is an inflammatory retinopathy in the category of white dot syndromes typified by acute loss of one or more zones of outer retinal function associated with photopsia, minimal funduscopic changes and abnormal electroretinography findings.This retinal disease was first described by Donald Gass in 1992. Relatively little is known about the condition. Risk factors
Caucasian females in their mid-thirties appear to be most susceptible but the disease may affect anyone regardless of age, sex or race. Pathophysiology
The disease mechanism is unknown but it is believed that it may be caused by a virus, or an auto immune response. References
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Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used by mouth or intravenously. It typically begins working within an hour.Common side effects include heartburn and a rash. Compared to other NSAIDs, it may have other side effects such as gastrointestinal bleeding. It increases the risk of heart failure, kidney failure, and liver failure. At low doses, it does not appear to increase the risk of heart attack; however, at higher doses it may. Ibuprofen can also worsen asthma. While it is unclear whether it is safe in early pregnancy, it appears to be harmful in later pregnancy and therefore is not recommended. Like other NSAIDs, it works by inhibiting the production of prostaglandins by decreasing the activity of the enzyme cyclooxygenase (COX). Ibuprofen is a weaker anti-inflammatory agent than other NSAIDs.Ibuprofen was discovered in 1961 by Stewart Adams and John Nicholson while working at Boots UK Limited and initially marketed as Brufen. It is available under a number of trade names, including Nurofen, Advil and Motrin. Ibuprofen was first marketed in 1969 in the United Kingdom and in 1974 in the United States. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. | In 2020, it was the 38th most commonly prescribed medication in the United States, with more than 16 million prescriptions. Medical uses
Ibuprofen is used primarily to treat fever (including post-vaccination fever), mild to moderate pain (including pain relief after surgery), painful menstruation, osteoarthritis, dental pain, headaches, and pain from kidney stones. About 60% of people respond to any nonsteroidal anti-inflammatory drug; those who do not respond well to a particular one may respond to another.It is used for inflammatory diseases such as juvenile idiopathic arthritis and rheumatoid arthritis. It is also used for pericarditis and patent ductus arteriosus.If a patient is self-treating with over-the-counter Ibuprofen, it should not be taken for more than 10 days, unless the patient has spoken with their doctor. Lysine
In some countries, ibuprofen lysine (the lysine salt of ibuprofen, sometimes called "ibuprofen lysinate") is licensed for treatment of the same conditions as ibuprofen; the lysine salt is used because it is more water-soluble.Ibuprofen lysine is sold for rapid pain relief; given in form of a lysine salt, absorption is much quicker (35 minutes compared to 90–120 minutes). | 11
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Loose anagen syndrome hairs at the occipital scalp can be knotted easily when theres movement of those hairs against the pillow at night.There are 3 different types of loose anagen hair syndrome. Loose anagen syndrome type A is when the hair of the patient appears to be fine and thinly distributed. Patients with type A loose anagen syndrome experience a decrease in the density of their hairs. Patients diagnosed with type B loose anagen hair syndrome tend to have hair that is difficult to manage and has a disordered, unruly appearance. Type C loose anagen syndrome is when the hair sheds but the appearance of their hair appears to be normal. Loose anagen syndrome type A and B are more prevalent in children. Loose anagen hair syndrome type C is most frequently seen in adults. There is not specific treatment for each type of loose anagen syndrome. It is also unknown as to how each type is developed. Differential diagnosis
Loose Anagen Syndrome can commonly be misdiagnosed for other skin and hair disorders such as short anagen syndrome, alopecia areata, telogen effluvium, trichotillomania and toxic ingestion. Similar symptoms and signs appear in these conditions, however there are different aspects that distinguish each one from another. Short anagen syndrome and loose anagen syndrome are similar as both conditions lead to the inability to grow long hair and patients rarely need to get their hair cut. | Minoxidil can be used as it enriches the cells of the hair by heightening the blood supply of local cutaneous. From this, there is intensified DNA synthesis occurring in both follicular keratinocytes and non-follicular, as well as an increase in cell multiplication. The degree of hair shedding is reduced with the use of minoxidil. 7 in 11 loose anagen hair syndrome patients find visible improvement after using minoxidil lotion. Treatment involving the maintenance of nutrients within the patient and biotin have not made any noted impacts to the improvement of loose anagen hair syndrome. Management
For children, changes to their lifestyle and daily routine are altered and improved to reduce trauma to hair. This includes modifications in hair maintenance such as different washing, styling and combing techniques are adapted, as an attempt to minimise trauma to loose anagen syndrome hairs. Young girls are also recommended to avoid activities such as extreme braiding. Caring for hair gently will minimise the amount of loosely anchored hairs being removed from scalp. History
The first published report on loose anagen syndrome was made in 1986 by Nodl and then by Zaun. Loose anagen syndrome was originally referred to as ‘syndrome of loosely attached hair in childhood’. The name ‘loose anagen syndrome’ was first adapted in 1989 by Price, Gummer, Hamm and Traupe in American literature. Early literature on loose anagen syndrome all reported identical findings. The genetic aspects and potential mechanisms for the cause of loose anagen syndrome was first discovered in 1992 by Baden, Kvedar and Magro. | 11
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However, a novel oral formulation of OHPC (developmental code name LPCN-1107) is under development and has been found to be effective, though it required administration twice a day in a clinical study.A depot effect occurs when OHPC is injected intramuscularly or subcutaneously, such that the medication has a prolonged duration of action. Following a single intramuscular injection of 1,000 mg OHPC in five women with endometrial cancer, peak levels of OHPC were 27.8 ± 5.3 ng/mL and the time to peak concentrations was 4.6 ± 1.7 (3–7) days. Following 13 weeks of continuous administration of 1,000 mg OHPC per week, trough levels of OHPC were 60.0 ± 14 ng/mL. The pharmacokinetic parameters of 250 mg OHPC once per week by intramuscular injection have also been studied in pregnant women with singleton and multiple (twin and triplet) gestation. Steady state levels of the medication are achieved within 4 to 12 weeks of administration in pregnant women. The duration of clinical biological effect of OHPC by intramuscular injection has also been studied in women. A single intramuscular injection of 65 to 500 mg OHPC in oil solution has been found to have a duration of action of 5 to 21 days in terms of effect in the uterus and on body temperature in women.OHPC has been found to possess similar pharmacokinetics, including peak levels, time to peak levels, area-under-the-curve levels (i.e., total exposure), and elimination half-life, with administration via intramuscular injection or subcutaneous autoinjection. | The rabies vaccine is a vaccine used to prevent rabies. There are a number of rabies vaccines available that are both safe and effective. They can be used to prevent rabies before, and, for a period of time, after exposure to the rabies virus, which is commonly caused by a dog bite or a bat bite.Doses are usually given by injection into the skin or muscle. After exposure, the vaccination is typically used along with rabies immunoglobulin. It is recommended that those who are at high risk of exposure be vaccinated before potential exposure. Rabies vaccines are effective in humans and other animals, and vaccinating dogs is very effective in preventing the spread of rabies to humans. A long-lasting immunity to the virus develops after a full course of treatment.Rabies vaccines may be used safely by all age groups. About 35 to 45 percent of people develop a brief period of redness and pain at the injection site, and 5 to 15 percent of people may experience fever, headaches, or nausea. After exposure to rabies, there is no contraindication to its use, because the untreated virus is overwhelmingly fatal.The first rabies vaccine was introduced in 1885 and was followed by an improved version in 1908. Millions of people globally are vaccinated against the virus. It is on the World Health Organizations List of Essential Medicines. Medical uses
Before exposure
The World Health Organization (WHO) recommends vaccinating those who are at high risk of the disease, such as children who live in areas where it is common. | 0-1
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Diagnosis
On funduscopic eye examination, the retinal vessels in early Coats disease appear tortuous and dilated, mainly confined to the peripheral and temporal portions of retina. In moderate to severe Coats disease, massive retinal detachment and hemorrhage from the abnormal vessels may be seen. Imaging findings
Imaging studies such as ultrasonography (US), Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) can aid diagnosis. On ultrasound, Coats disease appears as a hyperechoic mass in the posterior vitreous without posterior acoustic shadowing; vitreous and subretinal hemorrhage may often be observed.On CT, the globe appears hyperdense compared to normal vitreous due to the proteinaceous exudate, which may obliterate the vitreous space in advanced disease. The anterior margin of the subretinal exudate enhances with contrast. Since the retina is fixed posteriorly at the optic disc, this enhancement has a V-shaped configuration.On MRI, the subretinal exudate shows high signal intensity on both T1- and T2-weighted images. The exudate may appear heterogeneous if hemorrhage or fibrosis is present. The subretinal space does not enhance with gadolinium contrast. Mild to moderate linear enhancement may be seen between the exudate and the remaining vitreous. The exudate shows a large peak at 1–1.6 ppm on proton MR spectroscopy. Pathologic findings
Grossly, retinal detachment and yellowish subretinal exudate containing cholesterol crystals are commonly seen. Microscopically, the wall of retinal vessels may be thickened in some cases, while in other cases the wall may be thinned with irregular dilatation of the lumen. The subretinal exudate consists of cholesterol crystals, macrophages laden with cholesterol and pigment, erythrocytes, and hemosiderin. | A granulomatous reaction, induced by the exudate, may be seen with the retina. Portions of the retina may develop gliosis as a response to injury. Treatment
In the early stages, there are a few treatment options. Laser surgery or cryotherapy (freezing) can be used to destroy the abnormal blood vessels, thus halting progression of the disease. However, if the leaking blood vessels are clustered around the optic nerve, this treatment is not recommended as accidental damage to the nerve itself can result in permanent blindness. Although Coats disease tends to progress to visual loss, it may stop progressing on its own, either temporarily or permanently. Cases have been documented in which the condition even reverses itself. However, once total retinal detachment occurs, sight loss is permanent in most cases. Removal of the eye (enucleation) is an option if pain or further complications arise. History
Coats disease is named after George Coats. References
External links
GeneReviews/NIH/NCBI/UW entry on NDP-Related Retinopathies
http://www.orpha.net/data/patho/GB/uk-Coats.pdf | 11
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This was present at four weeks for all infants ≤30 weeks gestation and at 8 weeks for infants ≤27 weeks gestation.To date, studies of r-EPO use in premature infants have had mixed results. Ohls et al. examined the use of early r-EPO plus iron and found no short-term benefits in two groups of infants (172 infants less than 1000 g and 118 infants 1000–1250 g). All r-EPO treated infants received 400 U/g three times a week until they reached 35 weeks gestational age. The use of r-EPO did not decrease the average number of transfusions in the infants born at less than 1000 g, or the percentage of infants in the 1000 to 1250 group. A multi-center European trial studied early versus late r-EPO in 219 infants with birth weights between 500 and 999 g. An r-EPO close of 750 U/kg/week was given to infants in both the early (1–9 weeks) and late (4–10 weeks) groups. The two r-EPO groups were compared to a control group who did not receive r-EPO. Infants in all three groups received 3 to 9 mg/kg of enteral iron. These investigators reported a slight decrease in transfusion and donor exposures in the early r-EPO group (1–9 weeks): 13% early, 11% late and 4% control group. It is likely that only a carefully selected subpopulation of infants may benefit from its use. | However, in premature infants the decline in Hb may be associated with abnormal clinical signs severe enough to prompt transfusions. Treatment
Transfusion
AOP is usually treated by blood transfusion but the indications for this are still unclear. Blood transfusions have both infectious and non-infectious risks associated with them. Also, blood transfusions are costly and may add to parental anxiety. The best treatment for AOP is prevention of worsening of anemia by minimizing the amount of blood drawn from the infant (ie, anemia from phlebotomy). It is found that since blood loss attributable to laboratory testing is the primary cause of anemia among preterm infants during the first weeks of life, it would be useful to quantify blood loss attributable to phlebotomy overdraw (ie, blood collected in excess than what is strictly required for the requested lab tests). Lin and colleagues performed a study to see when and if phlebotomy overdraw was actually a significant problem. They recorded all of the data that could be of influence such as the test performed, the blood collection container used, the infants location (neonatal intensive care unit (NICU) and intermediate intensive care unit), the infant’s weight sampling and the phlebotomist’s level of experience, work shift, and clinical role. Infants were classified by weight into 3 groups: <1 kg, 1 to 2 kg, and >2 kg. The volume of blood removed was calculated by subtracting the weight of the empty collection container from that of the container filled with blood. | 11
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In a longitudinal natural history study, nearly 20% of the patients died. For those classified into type C, they may have mild hepatosplenomegaly, but their central nervous system is profoundly affected. Niemann–Pick disease, SMPD1-associated, which includes types A and BNiemann–Pick disease type A: classic infantile
Niemann–Pick disease type B: visceralNiemann–Pick disease, type C: subacute/juvenile, includes types C1 (95% of type C) and C2. Type C is the most common form of the disease Type C2 is a rare form of the disease.Niemann–Pick disease type D (or Nova Scotia form) is now believed to be the same condition as Niemann–Pick disease type C. Two poorly characterized forms of Niemann–Pick disease have also been described as types E and F.
Treatment
No specific treatment is known for type A, but symptoms are treated.In adult patients with type B, physicians try to keep cholesterol levels down to normal levels. If statins are used, they monitor liver function. If the spleen is enlarged and platelet levels low, acute episodes of bleeding may require transfusions of blood products. If they have symptoms of interstitial lung disease, they may need oxygen.Anecdotally, organ transplant has been attempted with limited success. Future prospects include enzyme replacement and gene therapy. Bone marrow transplant has been tried for type B.In January 2009, Actelion announced the drug miglustat (Zavesca) had been approved in the European Union for the treatment of progressive neurological manifestations in adult patients and pediatric patients with NPC. The drug is available to patients in the United States on an experimental basis. | In March 2010, the FDA requested additional preclinical and clinical information regarding Zavesca from Actelion before making a final decision on approving the drug in the United States for NPC.Olipudase alfa (Xenpozyme) was approved for medical use in Japan in March 2022. Prognosis
Highly variable, infantile neurovisceral Niemann Pick disease (Type A ASMD) is usually fatal before 3 years of age. In Type B ASMD mortality before adulthood is common. But many patients live well into adulthood and may reach a normal lifespan. Diagnoses have been made in the 7th decade of life. Type C is an entirely different disorder, which also has a highly variable prognosis. Incidence
The incidence among Ashkenazi Jews is estimated to be about one in 40,000 for type A of Niemann–Pick disease. The incidence of both Niemann–Pick disease types A and B in all other populations is estimated to be one in 250,000. The incidence of Niemann–Pick disease type C is estimated to be one in 150,000. History
Albert Niemann published the first description of what now is known as Niemann–Pick disease, type A, in 1914. Ludwig Pick described the pathology of the disease in a series of papers in the 1930s.In 1961, the classification of Niemann–Pick disease into types A, B, and C was introduced, and also contained a type D, called the "Nova Scotian type". Genetic studies showed that type D is caused by the same gene as type C1, and the type D designation is no longer used. | 11
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There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible. Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin, gemcitabine as a single agent, or gemcitabine plus cisplatin, irinotecan, or capecitabine. A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in people with advanced cholangiocarcinoma. Radiation therapy appears to prolong survival in people with resected extrahepatic cholangiocarcinoma, and the few reports of its use in unresectable cholangiocarcinoma appear to show improved survival, but numbers are small.Infigratinib (Truseltiq) is a tyrosine kinase inhibitor of fibroblast growth factor receptor (FGFR) that was approved for medical use in the United States in May 2021. It is indicated for the treatment of people with previously treated locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.Pemigatinib (Pemazyre) is a kinase inhibitor of fibroblast growth factor receptor 2 (FGFR2) that was approved for medical use in the United States in April 2020. It is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. Ivodesinib (Tibsovo) is a small molecule inhibitor of isocitrate dehydrogenase 1. | A cholangiocarcinoma occurring at the junction where the left and right hepatic ducts meet to form the common hepatic duct may be referred to eponymously as a Klatskin tumor.Although cholangiocarcinoma is known to have the histological and molecular features of an adenocarcinoma of epithelial cells lining the biliary tract, the actual cell of origin is unknown. Recent evidence has suggested that the initial transformed cell that generates the primary tumor may arise from a pluripotent hepatic stem cell. Cholangiocarcinoma is thought to develop through a series of stages – from early hyperplasia and metaplasia, through dysplasia, to the development of frank carcinoma – in a process similar to that seen in the development of colon cancer. Chronic inflammation and obstruction of the bile ducts, and the resulting impaired bile flow, are thought to play a role in this progression.Histologically, cholangiocarcinomas may vary from undifferentiated to well-differentiated. They are often surrounded by a brisk fibrotic or desmoplastic tissue response; in the presence of extensive fibrosis, it can be difficult to distinguish well-differentiated cholangiocarcinoma from normal reactive epithelium. There is no entirely specific immunohistochemical stain that can distinguish malignant from benign biliary ductal tissue, although staining for cytokeratins, carcinoembryonic antigen, and mucins may aid in diagnosis. Most tumors (>90%) are adenocarcinomas. Diagnosis
Blood tests
There are no specific blood tests that can diagnose cholangiocarcinoma by themselves. Serum levels of carcinoembryonic antigen (CEA) and CA19-9 are often elevated, but are not sensitive or specific enough to be used as a general screening tool. | 11
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Cachexia is considered the immediate cause of death of many people with cancer, estimated between 22 and 40%. History
The word "cachexia" is derived from the Greek words "Kakos" (bad) and "hexis" (condition). English ophthalmologist John Zachariah Laurence was the first to use the phrase "cancerous cachexia", doing so in 1858. He applied the phrase to the chronic wasting associated with malignancy. It was not until 2011 that the term "cancer-associated cachexia" was given a formal definition, with a publication by Kenneth Fearon. Fearon defined it as "a multifactorial syndrome characterized by ongoing loss of skeletal muscle (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment". Research
Several medications are under investigation or have been previously trialed for use in cachexia but are currently not in widespread clinical use:
Thalidomide
Cytokine antagonists
Cannabinoids
Omega-3 fatty acids, including eicosapentaenoic acid (EPA)
Non-steroidal anti-inflammatory drugs
Prokinetics
Ghrelin and ghrelin receptor agonist
Anabolic catabolic transforming agents such as MT-102
Selective androgen receptor modulators
Cyproheptadine
HydrazineMedical marijuana has been allowed for the treatment of cachexia in some US states, such as Illinois, Maryland, Delaware, Nevada, Michigan, Washington, Oregon, California, Colorado, New Mexico, Arizona, Vermont, New Jersey, Rhode Island, Maine, and New York Hawaii and Connecticut. Multimodal therapy
Despite the extensive investigation into single therapeutic targets for cachexia, the most effective treatments use multi-targeted therapies. In Europe, a combination of non-drug approaches including physical training, nutritional counseling, and psychotherapeutic intervention are used in belief this approach may be more effective than monotherapy. | Administration of anti-inflammatory drugs showed efficacy and safety in the treatment of people with advanced cancer cachexia. See also
Sarcopenia
Muscle atrophy
Marasmus
Cancer
Progressive disease
Journal of Cachexia, Sarcopenia and Muscle
References
== External links == | 11
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Alpha 1-antitrypsin deficiency was documented in one case, interferon-alpha therapy in another case. Similar cases of granulomatous mastitis were reported in IgG4-related disease though the exact relationship to IGM remains to be elucidated. Other contributing factors of IGM were investigated such as oral contraceptives usage. Many cases were reported after use of prolactin elevating medications such as antipsychotics.Elevated prolactin levels have the direct effects of increasing secretory activity of breast lobules, maintaining tight junctions of the ductal epithelium, preventing involution of the breast gland after weaning and are known to stimulate the immune system, contributing to both physiological and pathological granulomatous lesions and non-caseating granulomas. PRL is also secreted locally in the breast and local secretion by lymphocytes may be enhanced during inflammatory reactions. Autoimmune reaction to extravasated fat and protein rich luminal fluid (denaturized milk) resulting from the secretory activity is assumed to be one of the triggers of IGM. Several other hormones can contribute to PRL signaling in the breast gland, high levels of insulin caused for example by peripheral insulin resistance (resulting from pregnancy, gestational diabetes or developing diabetes mellitus type 2) will enhance the galactogenic and antiapoptotic effects of PRL and growth hormone by acting synergistically with IGF-1. Microbiology
The presence of Corynebacterium in granulomatous mastitis was first reported in 1996. Since then multiple reports have confirmed the presence of this genus in granulomatous mastitis. The most commonly isolated species is Corynebacterium kroppenstedtii. A selective medium for the isolation of this species has been described. | Chemistry
Zileuton is an active oral inhibitor of the enzyme 5-lipoxygenase, which forms leukotrienes, 5-hydroxyeicosatetraenoic acid, and 5-oxo-eicosatetraenoic acid from arachidonic acid. The chemical name of zileuton is (±)-1-(1-Benzo[b]thien-2-ylethyl)-l-hydroxyurea.The molecular formula of zileuton is C11H12N2O2S with a molecular weight of 236.29. The formulation from the manufacturer is a racemic mixture of R(+) and S(-) enantiomers. Pharmacokinetics
Following oral administration zileuton is rapidly absorbed with a mean time to peak blood serum concentration of 1.7 hours and an average half-life elimination of 2.5 hours. Blood plasma concentrations are proportional to dose, whereas the absolute bioavailability is unknown. The apparent volume of distribution of zileuton is approximately 1.2 L/kg. Zileuton is 93% bound to plasma proteins, primarily to albumin, with minor binding to alpha-1-acid glycoprotein. Elimination of zileuton is primarily through metabolites in the urine (~95%) with the feces accounting for the next largest amount (~2%). The drug is metabolized by the cytochrome P450 enzymes: CYP1A2, 2C9, and 3A4. Adverse effects
The most common adverse reactions reported by patients treated with Zyflo CR were sinusitis (6.5%), nausea (5%), and pharyngolaryngeal pain (5%) vs. placebo, 4%, 1.5%, and 4% respectively. Interactions
Drug interactions
Zileuton is a minor substrate of CYP1A2, 2C8/9, 3A4, and a weak inhibitor of CYP 1A2. The drug has been shown to increase the serum concentration or effects of theophylline, propranolol, and warfarin, although significant increase in prothrombin time is not obvious. It is advised that the doses of each medication be monitored and/or reduced accordingly. | 0-1
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Recurrent aphthous ulcers are common; however, it is not clear whether this is due to Crohns disease or simply that they are common in the general population. Other findings may include diffuse or nodular swelling of the mouth, a cobblestone appearance inside the mouth, granulomatous ulcers, or pyostomatitis vegetans. Medications that are commonly prescribed to treat CD, such as anti-inflammatory and sulfa-containing drugs, may cause lichenoid drug reactions in the mouth. Fungal infection such as candidiasis is also common due to the immunosuppression required in the treatment of the disease. Signs of anemia such as pallor and angular cheilitis or glossitis are also common due to nutritional malabsorption.People with Crohns disease are also susceptible to Angular Stomatitis, an inflammation of the corners of the mouth, and Pyostomatitis Vegetans. Systemic
Like many other chronic, inflammatory diseases, Crohns disease can cause a variety of systemic symptoms. Among children, growth failure is common. Many children are first diagnosed with Crohns disease based on inability to maintain growth. As it may manifest at the time of the growth spurt in puberty, up to 30% of children with Crohns disease may have retardation of growth. Fever may also be present, though fevers greater than 38.5 °C (101.3 °F) are uncommon unless there is a complication such as an abscess. Among older individuals, Crohns disease may manifest as weight loss, usually related to decreased food intake, since individuals with intestinal symptoms from Crohns disease often feel better when they do not eat and might lose their appetite. | Black heel and palm is a skin condition characterized by a sudden shower of minute, black, punctate macules occurring most often on the posterior edge of the plantar surface of one or both heels. : 43
See also
Skin lesion
List of cutaneous conditions
== References == | 0-1
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Control and Prevention
Characteristics of Tin for Industrial Uses
Tin oxide metals are used for their variable valence state and positive charge deficit from their oxygen vacancy. When heated to temperatures above 2602 °C or 2875 K, tin oxides start to boil and produce fumes. For example, tin forms Sn2when heated in oxygenated environments; also called feebly acid. Tin oxide is known for being a good catalyst in solid photochemical reactions (photocatalysis) and electric production from light (photoelectrocatalysis). The energy produced form splitting water in photoelectrocatalysis is used for the creation of dehydrated dyes.Tin is found in nature as an off-white or gray crystal mineral called cassiterite. The corrosion resistant metal is harvested primarily in Malaya, Bolivia, Indonesia, Zaire, thailand, and Nigeria. Traditionally, tin was used to create containers; however, since the increase use of plastics and aluminum its no longer common. There are two allotropic forms of tin, depending on the temperature. A variety of tin alloys morphologies exist including the following metals: soft solder, fusible, pewter, bronze, Babbit, White, and phosphor bronze metal. Tin oxide metals are corrosive resistant which is important in industrial uses. Industrial Applications of Tin oxides
Stannous oxide (SnO)
Stannous oxide (SnO) is used for manufacturing glass materials, like ceramics. The compound is insoluble in water and takes the form of a brow-black powder or blue-black crystalline solid. It is labeled as both an irritant and health hazard in the chemical safety sections of safety data sheets. | Stannosis is an occupational, non-fibrotic pneumoconiosis caused by chronic exposure and inhalation of tin. Pneumoconiosis is essentially when inorganic dust is found on the lung tissue; in this case, caused by tin oxide minerals. Dust particles and fumes from tin industries, stannous oxide (SnO) and stannic oxide (SnO2), are specific to stannosis diagnoses. Hazardous occupations such as, tinning, tin-working, and smelting are where most cases of stannosis are documented. When melted tin ions are inhaled as a fume, the tin oxides deposit onto the lung nodules and immune response cells. If a worker is exposed to tin oxides over multiple events for an extended time, they are at risk of developing stannosis. Toxicology and Physiology
Workers with acute exposures, short duration with varying dose concentrations, to tin oxides develop a mild irritation on the eyes, skin, and mucous membranes. When the inorganic metal materials are inhaled, the body activates the immune system and sends macrophages to the lungs. The macrophages try removing xenobiotic particles; however, stannous and stannic oxide interfere with the cells function. Tin deposition on lung nodules becomes apparent after X-ray imaging, although the stannosis does not appear to damage the lung tissues. Since the macrophages are laden with tin oxides but little to no fibrosis, stannosis is classified as a non-fibrotic pneumoniosis. Stannosis is an rare disease with only case-by-case appearances throughout history. Therefore, a diagnostic treatment plan has not yet been created by health officials. | 11
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These alterations can include: a sense that self or the world is unreal (depersonalization and derealization), a loss of memory (amnesia), forgetting identity or assuming a new self (fugue), and separate streams of consciousness, identity and self (dissociative identity disorder, formerly termed multiple personality disorder) and complex post-traumatic stress disorder. Although some dissociative disruptions involve amnesia, other dissociative events do not. Dissociative disorders are typically experienced as startling, autonomous intrusions into the persons usual ways of responding or functioning. Due to their unexpected and largely inexplicable nature, they tend to be quite unsettling. Dissociative disorders are sometimes triggered by trauma, but may be preceded only by stress, psychoactive substances, or no identifiable trigger at all. The ICD-10 classifies conversion disorder as a dissociative disorder. The Diagnostic and Statistical Manual of Mental Disorders groups all dissociative disorders into a single category and recognizes dissociation as a symptom of acute stress disorder, posttraumatic stress disorder, and borderline personality disorder.Misdiagnosis is common among people who display symptoms of dissociative disorders, with an average of seven years to receive proper diagnosis and treatment. Research is ongoing into etiologies, symptomology, and valid and reliable diagnostic tools. In the general population, dissociative experiences that are not clinically significant are highly prevalent with 60% to 65% of the respondents indicating that they have had some dissociative experiences. Diagnostic and Statistical Manual of Mental Disorders
Diagnoses listed under the DSM-5 are dissociative identity disorder, dissociative amnesia, depersonalization/derealization disorder, other specified dissociative disorder and unspecified dissociative disorder. | This is intended to reduce the incidence and severity of menopausal symptoms such as hot flushes and decreased bone mineral density that are secondary to estrogen deficiency. Pharmacokinetics
A single 40-mg oral dose of relugolix has been found to result in peak levels of relugolix of 29 ng/mL (47 nmol/L) after 1.5 hours. Steady-state levels are reached within 7 days with 40 mg/day relugolix administration. There is an approximate 2-fold accumulation of relugolix by 2 weeks of continuous administration. Food diminishes the oral bioavailability of relugolix by about 50%.Relugolix is a substrate for P-glycoprotein, which may have a limiting effect on its absorption and distribution. The plasma protein binding of relugolix is approximately 68 to 71% over a concentration range of 0.05 to 5 μg/mL.Relugolix is not a substrate for CYP3A4. The elimination half-life of relugolix is 36 to 65 hours across a dosage range of 20 to 180 mg/day. There is moderate to high interindividual variability in systemic exposure to relugolix.Relugolix is excreted mainly in feces (83%) and to a small degree in urine (4%). Only about 6% of a dose of relugolix is excreted unchanged. Chemistry
Relugolix is a non-peptide, small-molecule compound, and is structurally distinct from GnRH analogues. It is an N-phenylurea derivative. History
Relugolix was first described in 2004. It superseded sufugolix (developmental code name TAK-013), which was developed by the same researchers. Relugolix was approved for the treatment of uterine fibroids in Japan on 8 January 2019. | 0-1
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Tinea manuum is a fungal infection of the hand, mostly a type of dermatophytosis, often part of two feet-one hand syndrome. There is diffuse scaling on the palms or back of usually one hand and the palmer creases appear more prominent. When both hands are affected, the rash looks different on each hand, with palmer creases appearing whitish if the infection has been present for a long time. It can be itchy and look slightly raised. Nails may also be affected.The most common cause is Trichophyton rubrum. The infection can result from touching another area of the body with a fungal infection such as athletes foot or fungal infection of groin, contact with an infected person or animal, or from contact with soil or contaminated towels. Risk factors include diabetes, high blood pressure, weak immune system, humid surroundings, excessive sweating, recurrent hand trauma and cracks in feet. Pet owners and farmworkers are also at higher risk. Machine operators, mechanics, gas/electricity workers and people who work with chemicals have also been reported to be at greater risk.Diagnosis is by visualization, direct microscopy and culture. Psoriasis of the palms, pompholyx and contact dermatitis may appear similar. Treatment is usually with long-term topical antifungal medications. If not resolving, terbinafine or itraconazole taken by mouth might be options.It occurs worldwide. | Prevention
Prevention is focussed on hygiene such as washing hands, avoiding scratching the feet or touching fungal toe infections. Epidemiology
Tinea manuum is most common in young adult males. Dermatophyte infections occur in up to a quarter of the worlds population, of which the hands and feet are most commonly involved. It occurs worldwide. One large study revealed around 84% of tinea manuum was associated with athletes foot, of which 80% admitted scratching their feet, and 60% were male,
See also
List of cutaneous conditions
References
== External links == | 11
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One classification distinguishes "common simple aphthae", accounting for 95% of cases, with 3–6 attacks per year, rapid healing, minimal pain and restriction of ulceration to the mouth; and "complex aphthae", accounting for 5% of cases, where ulcers may be present on the genital mucosa in addition to mouth, healing is slower and pain is more severe. A more common method of classifying aphthous stomatitis is into three variants, distinguished by the size, number and location of the lesions, the healing time of individual ulcers and whether a scar is left after healing (see below). Minor aphthous ulceration
This is the most common type of aphthous stomatitis, accounting for about 80–85% of all cases. This subtype is termed minor aphthous ulceration (MiAU), or minor recurrent aphthous stomatitis (MiRAS). The lesions themselves may be referred to as minor aphthae or minor aphthous ulcers. These lesions are generally less than 10 mm in diameter (usually about 2–3 mm), and affect non-keratinized mucosal surfaces (i.e. the labial and buccal mucosa, lateral borders of the tongue and the floor of the mouth). Usually several ulcers appear at the same time, but single ulcers are possible. Healing usually takes seven to ten days and leaves no scar. Between episodes of ulceration, there is usually an ulcer-free period of variable length. Major aphthous ulceration
This subtype makes up about 10% of all cases of aphthous stomatitis. It is termed major aphthous ulceration (MaAU) or major recurrent aphthous stomatitis (MaRAS). | Regarding chronic subdural hematoma (CSDH) surgery, a postoperative volume of pneumocephalus greater than 15mL puts a patient at increased risk of CSDH recurrence; in fact, for every milliliter of air entering the cranial cavity after CSDH evacuation, the recurrence risk increases by 4%. Efforts are made by neurosurgeons to reduce pneumocephalus volume during surgery, and thus, subsequent brain shift. Additional images
Footnotes
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This is seen as a PR interval greater than 200 ms in length on the surface ECG. It is usually an incidental finding on a routine ECG.First-degree heart block does not require any particular investigations except for electrolyte and drug screens, especially if an overdose is suspected. Treatment
The management includes identifying and correcting electrolyte imbalances and withholding any offending medications. This condition does not require admission unless there is an associated myocardial infarction. Even though it usually does not progress to higher forms of heart block, it may require outpatient follow-up and monitoring of the ECG, especially if there is a comorbid bundle branch block. If there is a need for treatment of an unrelated condition, care should be taken not to introduce any medication that may slow AV conduction. If this is not feasible, clinicians should be very cautious when introducing any drug that may slow conduction; and regular monitoring of the ECG is indicated. Prognosis
Isolated first-degree heart block has no direct clinical consequences. There are no symptoms or signs associated with it. It was originally thought of as having a benign prognosis. In the Framingham Heart Study, however, the presence of a prolonged PR interval or first degree AV block doubled the risk of developing atrial fibrillation, tripled the risk of requiring an artificial pacemaker, and was associated with a small increase in mortality. | This risk was proportional to the degree of PR prolongation.A subset of individuals with the triad of first-degree heart block, right bundle branch block, and either left anterior fascicular block or left posterior fascicular block (known as trifascicular block) may be at an increased risk of progression to complete heart block. See also
Atrioventricular block
Second-degree atrioventricular block
Third-degree atrioventricular block
References
== External links == | 11
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Side effects
Side effects are similar to other angiotensin II receptor antagonists and include tachycardia and bradycardia (fast or slow heartbeat), hypotension (low blood pressure) and edema (swelling of arms, legs, lips, tongue, or throat, the latter leading to breathing problems). Allergic reactions may also occur. Interactions
Due to its mechanism of action, telmisartan increases blood potassium levels. Combination with potassium preparations or potassium-sparing diuretics could cause hyperkalaemia (excessive potassium levels). Combination with NSAIDs, especially in patients with impaired kidney function, has a risk of causing (usually reversible) kidney failure. Pharmacology
Mechanism of action
Telmisartan is an angiotensin II receptor blocker that shows high affinity for the angiotensin II receptor type 1 (AT1), with a binding affinity 3000 times greater for AT1 than AT2. In addition to blocking the renin–angiotensin system, telmisartan acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPAR-γ), a central regulator of insulin and glucose metabolism. It is believed that telmisartans dual mode of action may provide protective benefits against the vascular and renal damage caused by diabetes and cardiovascular disease (CVD).Telmisartans activity at the peroxisome proliferator-activated receptor delta (PPAR-δ) receptor has prompted speculation around its potential as a sport doping agent as an alternative to GW 501516. Telmisartan activates PPAR-δ receptors in several tissues.Also, telmisartan has a PPAR-γ agonist activity. : 171
Pharmacokinetics
The substance is quickly but to varying degrees absorbed from the gut. The average bioavailability is about 50% (42–100%). Food intake has no clinically relevant influence on the kinetics of telmisartan. | Apparent mineralocorticoid excess is an autosomal recessive disorder causing hypertension (high blood pressure), hypernatremia (increased blood sodium concentration) and hypokalemia (decreased blood potassium concentration). It results from mutations in the HSD11B2 gene, which encodes the kidney isozyme of 11β-hydroxysteroid dehydrogenase type 2. In an unaffected individual, this isozyme inactivates circulating cortisol to the less active metabolite cortisone. The inactivating mutation leads to elevated local concentrations of cortisol in the aldosterone sensitive tissues like the kidney. Cortisol at high concentrations can cross-react and activate the mineralocorticoid receptor due to the non-selectivity of the receptor, leading to aldosterone-like effects in the kidney. This is what causes the hypokalemia, hypertension, and hypernatremia associated with the syndrome. Patients often present with severe hypertension and end-organ changes associated with it like left ventricular hypertrophy, retinal, renal and neurological vascular changes along with growth retardation and failure to thrive. In serum both aldosterone and renin levels are low. Signs and symptoms
This disorder presents similarly to hyperaldosteronism, leading to feedback inhibition of aldosterone. Common symptoms include hypertension, hypokalemia, metabolic alkalosis, and low plasma renin activity.DOC excess syndrome is an excessive secretion of 21-hydroxyprogesterone also called 11-Deoxycorticosterone from adrenal glands and may cause mineralocorticoid hypertension. Genetics
AME is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder 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 disorder. | 0-1
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Sotorasib, sold under the brand names Lumakras and Lumykras, is an anti-cancer medication used to treat non-small-cell lung cancer (NSCLC). It targets a specific mutation, G12C, in the protein K-Ras encoded by gene KRAS which is responsible for various forms of cancer.The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage and cough.Sotorasib is an inhibitor of the RAS GTPase family.Sotorasib is the first approved targeted therapy for tumors with any KRAS mutation, which accounts for approximately 25% of mutations in non-small cell lung cancers. KRAS G12C mutations occur in about 13% of patients with non-small cell lung cancers. Sotorasib was approved for medical use in the United States in May 2021, and in the European Union in January 2022. Medical uses
Sotorasib is indicated for the treatment of adults with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. Clinical development
Sotorasib is being developed by Amgen. Phase I clinical trials were completed in 2020. In December 2019, it was approved to begin Phase II clinical trials.Because the G12C KRAS mutation is relatively common in some cancer types, 14% of non-small-cell lung cancer adenocarcinoma patients and 5% of colorectal cancer patients, and sotorasib is the first drug candidate to target this mutation, there have been high expectations for the drug. | Legal status
In November 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Lumykras, intended for the treatment of people with KRAS G12C mutation non-small cell lung cancer (NSCLC). The applicant for this medicinal product is Amgen Europe B.V. Sotorasib was approved for medical use in the European Union in January 2022. Names
Sotorasib is the recommended international nonproprietary name (INN). References
Further reading
Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, et al. (September 2020). "KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors". N Engl J Med. 383 (13): 1207–17. doi:10.1056/NEJMoa1917239. PMC 7571518. PMID 32955176. Lanman BA, Allen JR, Allen JG, Amegadzie AK, Ashton KS, Booker SK, et al. (January 2020). "Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors". J Med Chem. 63 (1): 52–65. doi:10.1021/acs.jmedchem.9b01180. PMID 31820981. External links
"Sotorasib". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03600883 for "A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)" at ClinicalTrials.gov | 11
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It occurs most often around 1.5 years after treatment and results in irreversible and severe vision loss, which may also be associated with damage to the retina (radiation retinopathy). This is thought to be due to damage to dividing glial and vascular endothelial cells. RON can present with transient visual loss followed by acute painless visual loss in one or both eyes several weeks later. The risk of RON is significantly increased with radiation doses over 50 Gy. Optic neuritis
Optic neuritis is inflammation of the optic nerve, which is associated with swelling and destruction of the myelin sheath covering the optic nerve. Young adults, usually females, are most commonly affected. Symptoms of optic neuritis in the affected eye include pain on eye movement, sudden loss of vision, and decrease in color vision (especially reds). Optic neuritis, when combined with the presence of multiple demyelinating white matter brain lesions on MRI, is suspicious for multiple sclerosis. Several causes and clinical courses are possible for the optic neuritis. It can be classified in:
Single isolated optic neuritis (SION)
relapsing isolated optic neuritis (RION)
chronic relapsing inflammatory optic neuropathy (CRION)
the neuromyelitis optica (NMO) spectrum disorder
multiple sclerosis associated optic neuritis (MSON)
unclassified optic neuritis (UCON) forms.Medical examination of the optic nerve with an ophthalmoscope may reveal a swollen optic nerve, but the nerve may also appear normal. Presence of an afferent pupillary defect, decreased color vision, and visual field loss (often central) are suggestive of optic neuritis. Recovery of visual function is expected within 10 weeks. | The resection of the ileum leads to a malabsorption of vitamin B12, bile acids and the fat soluble vitamins A, D, E and K. Loss of the distal ileum also leads to loss of inhibitory hormones; leading to gastric hypersecretion, intestinal hypermotility (decreases in the intestinal transit time) leading to secretory diarrhea and macronutrient, micronutrient, vitamin and mineral deficiencies. Loss of the ileocecal valve leads to small intestinal bacterial overgrowth(SIBO) as bacterial flora normally found in the large intestines migrate proximally and colonize the small intestines leading to further malabsorption. SIBO leads to malabsorption as the bacteria colonizing the small intestine metabolize nutrients, directly competing with the intestinal absorption of nutrients. The bacteria colonizing the small intestines in SIBO may also cause bile acid deconjugation leading to malabsorption of lipids.In a process called intestinal adaptation, physiological changes to the remaining portion of the small intestine occur to increase its absorptive capacity. These changes usually take place over 1-2 years. These changes include:
Enlargement (increased diameter) and lengthening of the villi found in the lining
Increase in the diameter of the small intestine
Slow down in peristalsis or movement of food through the small intestine (an increase in the transit time) to increase the time available for nutrient absorptionOsteoporosis is a very common comorbidity in people with short bowel syndrome who are on parenteral nutrition, with an estimated prevalence of 57-67%. The contributing factors to the osteoporosis include malnutrition, vitamin D deficiency due to malabsorption and vitamin D deficiency due to scarce sunlight exposure due to chronic disability. | 0-1
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Mercury poisoning is a type of metal poisoning due to exposure to mercury. Symptoms depend upon the type, dose, method, and duration of exposure. They may include muscle weakness, poor coordination, numbness in the hands and feet, skin rashes, anxiety, memory problems, trouble speaking, trouble hearing, or trouble seeing. High-level exposure to methylmercury is known as Minamata disease. Methylmercury exposure in children may result in acrodynia (pink disease) in which the skin becomes pink and peels. Long-term complications may include kidney problems and decreased intelligence. The effects of long-term low-dose exposure to methylmercury are unclear.Forms of mercury exposure include metal, vapor, salt, and organic compound. Most exposure is from eating fish, amalgam-based dental fillings, or exposure at a workplace. In fish, those higher up in the food chain generally have higher levels of mercury, a process known as biomagnification. Less commonly, poisoning may occur as a method of attempted suicide. Human activities that release mercury into the environment include the burning of coal and mining of gold. Tests of the blood, urine, and hair for mercury are available but do not relate well to the amount in the body.Prevention includes eating a diet low in mercury, removing mercury from medical and other devices, proper disposal of mercury, and not mining further mercury. In those with acute poisoning from inorganic mercury salts, chelation with either dimercaptosuccinic acid (DMSA) or dimercaptopropane sulfonate (DMPS) appears to improve outcomes if given within a few hours of exposure. Chelation for those with long-term exposure is of unclear benefit. | His treatment was to order the lower deck gun ports to be opened, when it was safe to do so; sleeping on the orlop was forbidden; and no men slept in the lower deck if they were at all symptomatic. Windsails were set to channel fresh air into the lower decks day and night. Historically, gold-mercury amalgam was widely used in gilding, applied to the object and then heated to vaporize the mercury and deposit the gold, leading to numerous casualties among the workers. It is estimated that during the construction of Saint Isaacs Cathedral alone, 60 men died from the gilding of the main dome. For years, including the early part of his presidency, Abraham Lincoln took a common medicine of his time called "blue mass", which contained significant amounts of mercury. On September 5, 1920, silent movie actress Olive Thomas ingested mercury capsules dissolved in an alcoholic solution at the Hotel Ritz in Paris. There is still controversy over whether it was suicide, or whether she consumed the external preparation by mistake. Her husband, Jack Pickford (the brother of Mary Pickford), had syphilis, and the mercury was used as a treatment of the venereal disease at the time. She died a few days later at the American Hospital in Neuilly. | 11
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Some tumors secrete more than one hormone, the most common combination being GH and prolactin, which present as unexpected bone growth and unexpected lactation (in both men and women).A patient with pituitary adenoma may present with visual field defects, classically bitemporal hemianopsia. It arises from the compression of the optic nerve by the tumor. The specific area of the visual pathway at which compression by these tumours occurs is at the optic chiasma. The anatomy of this structure causes pressure on it to produce a defect in the temporal visual field on both sides, a condition called bitemporal hemianopsia. If originating superior to the optic chiasm, more commonly in a craniopharyngioma of the pituitary stalk, the visual field defect will first appear as bitemporal inferior quadrantanopia, if originating inferior to the optic chiasm the visual field defect will first appear as bitemporal superior quadrantanopia. Lateral expansion of a pituitary adenoma can also compress the abducens nerve, causing a lateral rectus palsy.Also, a pituitary adenoma can cause symptoms of increased intracranial pressure. Prolactinomas often start to give symptoms especially during pregnancy, when the increased hormone level estrogen can increase the tumors growth rate.Various types of headaches are common in patients with pituitary adenomas. The adenoma may be the prime causative factor behind the headache or may serve to exacerbate a headache caused by other factors. | This means the defective gene responsible for the disorder is located on an autosome (chromosome 8 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. DNA repair
RECQL4 has a crucial role in DNA end resection that is the initial step required for homologous recombination (HR)-dependent double-strand break repair. When RECQL4 is depleted, HR-mediated repair and 5’ end resection are severely reduced in vivo. RECQL4 also appears to be necessary for other forms of DNA repair including non-homologous end joining, nucleotide excision repair and base excision repair. The association of deficient RECQL4-mediated DNA repair with accelerated aging is consistent with the DNA damage theory of aging. Diagnosis
Management
History
The condition was originally described by August von Rothmund (1830–1906) in 1868. Matthew Sydney Thomson (1894–1969) published further descriptions in 1936. See also
Poikiloderma vasculare atrophicans
List of cutaneous conditions
List of radiographic findings associated with cutaneous conditions
References
External links
GeneReviews/NCBI/NIH/UW entry on Rothmund-Thomson Syndrome
Poikiloderma of Rothmund-Thomson at NIHs Office of Rare Diseases | 0-1
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Since it was not understood that these different presentations were all caused by the same set of mutations in the androgen receptor gene, a unique name was given to each new combination of symptoms, resulting in a complicated stratification of seemingly disparate disorders.Over the last 60 years, as reports of strikingly different phenotypes were reported to occur even among members of the same family, and as steady progress was made towards the understanding of the underlying molecular pathogenesis of AIS, these disorders were found to be different phenotypic expressions of one syndrome caused by molecular defects in the androgen receptor gene.AIS is now the accepted terminology for the syndromes resulting from unresponsiveness of the target cell to the action of androgenic hormones. CAIS encompasses the phenotypes previously described by "testicular feminization", Morris syndrome, and Goldberg-Maxwell syndrome; PAIS includes Reifenstein syndrome, Gilbert-Dreyfus syndrome, Lubs syndrome, "incomplete testicular feminization", and Rosewater syndrome; and MAIS includes Aimans syndrome.The more virilized phenotypes of AIS have sometimes been described as "undervirilized male syndrome", "infertile male syndrome", "undervirilized fertile male syndrome", etc., before evidence was reported that these conditions were caused by mutations in the AR gene. These diagnoses were used to describe a variety of mild defects in virilization; as a result, the phenotypes of some men who have been diagnosed as such are better described by PAIS (e.g. micropenis, hypospadias, and undescended testes), while others are better described by MAIS (e.g. isolated male infertility or gynecomastia). | In men, disease states are associated with extremes in polyglutamine tract length; prostate cancer, hepatocellular carcinoma, and intellectual disability are associated with too few repetitions, while spinal and bulbar muscular atrophy (SBMA) is associated with a CAG repetition length of 40 or more. Some studies indicate that the length of the polyglutamine tract is inversely correlated with transcriptional activity in the AR protein, and that longer polyglutamine tracts may be associated with male infertility and undermasculinized genitalia in men. However, other studies have indicated no such correlation exists. A comprehensive meta-analysis of the subject published in 2007 supports the existence of the correlation, and concluded these discrepancies could be resolved when sample size and study design are taken into account. Some studies suggest longer polyglycine tract lengths are also associated with genital masculinization defects in men. Other studies find no such association. AR mutations
As of 2010, over 400 AR mutations have been reported in the AR mutation database, and the number continues to grow. Inheritance is typically maternal and follows an X-linked recessive pattern; individuals with a 46,XY karyotype always express the mutant gene since they have only one X chromosome, whereas 46,XX carriers are minimally affected. About 30% of the time, the AR mutation is a spontaneous result, and is not inherited. Such de novo mutations are the result of a germ cell mutation or germ cell mosaicism in the gonads of one of the parents, or a mutation in the fertilized egg itself. | 11
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