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Golfers elbow | Golfers elbow, or medial epicondylitis, is tendinosis of the medial epicondyle on the inside of the elbow. It is in some ways similar to tennis elbow, which affects the outside at the lateral epicondyle.
The anterior forearm contains several muscles that are involved with flexing the digits of the hand, and flexing and pronating the wrist. The tendons of these muscles come together in a common tendinous sheath, which originates from the medial epicondyle of the humerus at the elbow joint. In response to minor injury, this point of insertion becomes inflamed, causing pain.
Causes
The condition is called golfers elbow because in making a golf swing this tendon is stressed, especially if a non-overlapping (baseball style) grip is used; however, many people develop the condition without playing golf. It is also sometimes called pitchers elbow due to the same tendon being stressed by the throwing of objects such as a baseball, but this usage is much less frequent. Other names are climbers elbow and little league elbow: all of the flexors of the fingers and the pronators of the forearm insert at the medial epicondyle of the humerus to include: pronator teres, flexor carpi radialis, flexor carpi ulnaris, flexor digitorum superficialis, and palmaris longus; making this the most common elbow injury for rock climbers, whose sport is grip intensive. The pain is normally caused due to stress on the tendon as a result of the large amount of grip exerted by the digits and torsion of the wrist which is caused by the use and action of the cluster of muscles on the condyle of the ulna. However, more than 90% of cases are not actually from sports-related injuries, but rather from labor-related occupations with forceful repetitive activities (such as construction and plumbing).Epicondylitis is much more common on the lateral side of the elbow (tennis elbow), rather than the medial side. In most cases, its onset is gradual and symptoms often persist for weeks before a person seeks care. In golfers elbow, pain at the medial epicondyle is aggravated by resisted wrist flexion and pronation, which is used to aid diagnosis. Tennis elbow is indicated by the presence of lateral epicondylar pain precipitated by resisted wrist extension.
Diagnosis
To diagnose golfers elbow, clinicians may apply force to the elbow and wrist. If the subject indicates pain or inability to resist on the medial side, golfers elbow may be present. Visual signs and symptoms are used to assist medical diagnosis.Radiography, ultrasound and magnetic resonance imaging (MRI) can be used to assess the structural integrity of the different tissues of the elbow and may assist in making a more accurate diagnosis.
Treatment
Non-specific treatments include:
Non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen, naproxen or aspirin
Heat or ice
A counterforce brace or "elbow strap" to reduce strain at the elbow epicondyle, to limit pain provocation and to protect against further damage.Before anesthetics and steroids are used, conservative treatment with an occupational therapist may be attempted. Before therapy can commence, treatment such as rest, ice, compression and elevation (R.I.C.E.) will typically be used. This will help to decrease the pain and inflammation; rest will alleviate discomfort because golfers elbow is an overuse injury. The subject can use a tennis elbow splint for compression. A pad can be placed anteromedially on the proximal forearm. The splint is made in 30–45 degrees of elbow flexion. A daytime elbow pad also may be useful, by limiting additional trauma to the nerve.Simple analgesic medication has a place, as does more specific treatment with oral anti-inflammatory medications. These will help control pain and any inflammation. A more invasive treatment is the injection into and around the inflamed and tender area of a glucocorticoid (steroid) agent. After causing an initial exacerbation of symptoms lasting 24 to 48 hours, this may produce an improvement of the condition in some five to seven days.
Physical therapy
Therapy includes a variety of exercises for muscle and tendon reconditioning, starting with stretching and gradual strengthening of the flexor-pronator muscles. Strengthening will slowly begin with isometrics and progresses to eccentric exercises helping to extend the range of motion back to where it once was. After the strengthening exercises, it is common for the subject to ice the area.
Surgery
After 6 months if the symptoms do not improve, surgery may be recommended. Surgical debridement or cleaning of the area is one of the most common treatments. The ulnar nerve may also be decompressed surgically. If the appropriate remediation steps are taken – rest, ice, and rehabilitative exercise and stretching – recovery may follow. Few subjects will need to progress to steroid injection, and less than 10% will require surgical intervention. Arthroscopy is not an option for treating golfers elbow.
See also
Radial tunnel syndrome
Repetitive strain injury
Tennis elbow
References
== External links == |
Capillaritis | Capillaritis is where the capillaries, usually of the legs or lungs, are inflamed, allowing blood cells to pass through.It may occur in the lungs as pulmonary capillaritis, or in the skin as pigmented purpuric dermatosis. Capillaritis usually affects otherwise healthy people.
Capillaritis can take many forms but is made up of tiny red or brown dots that may be spread out or in a group forming a red or brown patch on the skin. One variation, Majocchi purpupa, forms concentric rings.Capillaritis is a mild condition not requiring treatment. There is no known cure, however capillaritis can disappear within a few weeks, recur from time to time, or persist for years.
== References == |
Dysmelia | Dysmelia (from the Greek dys (δυσ-), "bad" + mélos (μέλος), "limb" + English suffix -ia) is a congenital disorder of a limb resulting from a disturbance in embryonic development.
Types
Dysmelia can refer to
missing (aplasia) limbs: amelia, oligodactyly, congenital amputation e.g. tibial or radial aplasia
malformation of limbs: shortening (micromelia, rhizomelia or mesomelia), ectrodactyly, phocomelia, meromelia, syndactyly, brachydactyly, club foot
too many limbs: polymelia, polydactyly, polysyndactyly
others: tetraamelia, hemimelia, symbrachydactyly
Occurrence rate
Birth defects involving limbs occur in 1 per 1000.
Causes
Dysmelia can be caused by
Inheritance of abnormal genes, e.g. polydactyly, ectrodactyly or brachydactyly, symptoms of deformed limbs then often occur in combination with other symptoms (syndromes)
external causes during pregnancy (thus not inherited), e.g. via amniotic band syndrome
teratogenic drugs (e.g. thalidomide, which causes phocomelia) or environmental chemicals
ionizing radiation (nuclear weapons, radioiodine, radiation therapy)
infections
metabolic imbalance
Syndromes with dysmelia
References
External links
DysNet: An organisation for people affected by Dysmelia (congenital limb difference)
Reach: Association for Children with Upper Limb Deficiency) |
Arts syndrome | Arts syndrome is a rare metabolic disorder that causes serious neurological problems in males due to a malfunction of the PRPP synthetase 1 enzyme. Arts Syndrome is part of a spectrum of PRPS-1 related disorders with reduced activity of the enzyme that includes Charcot–Marie–Tooth disease and X-linked non-syndromic sensorineural deafness.
Signs and symptoms
Males show more serious symptoms than females affected by this disorder.The symptoms for males are:
Profound sensorineural hearing loss i.e., a complete or almost complete loss of hearing caused by abnormalities in the inner ear.
Weak muscle tone - Hypotonia.
Impaired muscle coordination - Ataxia.
Developmental delay.
Intellectual disability.
Vision loss caused by optic nerve atrophy in early childhood.
Peripheral neuropathy.
Recurrent infections, especially in the respiratory system.
Muscle weakness caused by recurrent infections.Symptoms for females:
Very rarely seen hearing loss that begins in adulthood (age > 20 years) combined with ataxia and neuropathy. Optic atrophy and retinitis pigmentosa observed in some cases too.
Cause
Arts syndrome is caused by a loss of function mutation in the PRPS1 gene. The PRPS1 gene codes for the enzyme phosphoribosyl pyrophosphate synthetase 1 or PRPP synthetase 1. This enzyme is involved in producing purines and pyrimidines which are the building blocks of DNA, RNA, ATP and other molecules. The mutations that cause Arts syndrome replace single amino acids the PRPP synthetase 1 enzyme. The resulting enzyme is unstable. Disruption of purine and pyrimidine production may impair energy storage and transport in cells. Impairment of these processes may have a particularly severe effect on tissues that require a large amount of energy, such as the nervous system, resulting in the neurological problems characteristic of Arts syndrome. The reason for the increased risk of respiratory infections in Arts syndrome is unclear.Novel missense mutation - c.367C>G (p.His123Asp) c.455T→C (p. L152P), c.398A→C (p.Q133P) p. Ile275Thr and p.Gly306Glu
Genetics
Arts syndrome follows an X-linked inheritance. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell sometimes causes features of the disorder; in other cases, these females do not experience any symptoms. In the small number of Arts syndrome cases that have been identified, affected individuals have inherited the mutation from a mother who carries an altered copy of the PRPS1 gene. If the mother is a carrier, the chance of transmitting the PRPS1 mutation in each pregnancy is 50%. Males who inherit the mutation will be affected; females who inherit the mutation will be carriers and may or may not be mildly affected. Males with Arts syndrome do not reproduce.Charcot-Marie-Tooth disease-5, Arts syndrome and X-linked nonsyndromic sensorineural deafness present three clinically distinct but genetically allelic disorders, caused by reduced phosphoribosylpyrophosphate synthetase 1 (PRS1) activity due to PRPS1 mutations. Only three families with CMTX5 and two families Arts syndrome, respectively, have been reported worldwide so far. Thus, evidence is still rare whether these two disorders are separate entities, or rather clusters on a phenotypic continuum of PRPS1-related disease.
Diagnosis
Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance. Sequence analysis of PRPS1, the only gene associated with Arts syndrome, has detected mutations in both kindreds reported to date. Arts syndrome patients were also found to have reduced levels of hypoxanthine levels in urine and uric acid levels in the serum. In vitro, PRS-1 activity was reduced in erythrocytes and fibroblasts.
Treatment
Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in people with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients by replacing purine nucleotides and open new avenues of therapeutic intervention. Other non-clinical treatment options include educational programs tailored to their individual needs. Sensorineural hearing loss has been treated with cochlear implantation with good results. Ataxia and visual impairment from optic atrophy are treated in a routine manner. Routine immunizations against common childhood infections and annual influenza immunization can also help prevent any secondary infections from occurring.Regular neuropsychological, audiologic, and ophthalmologic examinations are also recommended.
Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutation in the family is known.
References
== External links == |
Short-limb skeletal dysplasia with severe combined immunodeficiency | Short-limb skeletal dysplasia with severe combined immunodeficiency is an extremely rare autosomal recessive type of achondroplasia which is characterized by short stature, bowing of the long bones, and generalized metaphyseal abnormalities alongside signs of SCID such as recurrent severe infections, failure to thrive, chronic diarrhea, and a notable absence of T and B lymphocytes. Around 11 cases have been described in medical literature.
== References == |
Clostridial necrotizing enteritis | Clostridial necrotizing enteritis (CNE) is a severe and potentially fatal type of food poisoning caused by a β-toxin of Clostridium perfringens, Type C. It occurs in some developing regions, particularly in New Guinea, where it is known as pig-bel. The disease was also documented in Germany following World War II, where it was called Darmbrand (literally "bowel fire," or bowel necrosis). The toxin is normally inactivated by certain proteolytic enzymes and by normal cooking, but when these protections are impeded by diverse factors, and high protein is consumed, the disease can emerge.
Sporadic and extremely rare cases occur in diabetics. In New Guinea, where people generally have low-protein diets apart from tribal feasts, a number of factors—diet and endemic helminth infections among them—compound to result in pig-bel.
Preterm infants
The majority of preterm infants who develop NEC are generally healthy, feeding well, and growing prior to developing NEC. The most frequent sign of NEC is a sudden change in feeding tolerance, which can be manifest by numerous clinical signs listed below. While gastric residuals are often seen in early NEC, there is no evidence that routine measurement of gastric residual volumes in asymptomatic infants is a useful guide to prevent or detect the onset of NEC, or help to advance feeds. The timing of the onset of symptoms varies and appears to be inversely related to gestational age (GA). There appears to be a bimodal distribution (early versus late onset) based on GA. For example, the median age at onset of NEC in infants with a GA of less than 26 weeks was 23 days (late), and for those with a GA of greater than 31 weeks, the median age at onset was 11 days (early).
Laboratory findings of infants presenting with NEC often include anemia, thrombocytopenia, evidence of disseminated intravascular coagulopathy (DIC), and in 20 percent of cases a positive blood culture.
Signs and symptoms
CNE is a necrotizing inflammation of the small bowel (especially the jejunum but also the ileum). Clinical results may vary from mild diarrhea to a life-threatening sequence of severe abdominal pain, vomiting (often bloody), bloody stool, ulceration of the small intestine with leakage (perforation) into the peritoneal cavity and possible death within a single day due to peritonitis. Many patients exhibit meteorism (swelling of the abdomen due to excess gas) and fever. Fluid can enter the peritoneum.
Sepsis can occur, with one case having 28,500 white blood cells per cubic milliliter.
Causes
All the factors collectively causing CNE are generally only present in the hinterlands of New Guinea and parts of Africa, Latin America, and Asia. These factors include protein deprivation (causing inadequate synthesis of the enzyme trypsin protease, to which the toxin is very sensitive), poor food hygiene, episodic meat feasting, staple diets containing trypsin inhibitors (sweet potatoes), and infection by Ascaris parasites, which secrete a trypsin inhibitor. In New Guinea (origin of the term "pig-bel"), the disease is usually spread through contaminated meat (especially pork) and perhaps by peanuts. CNE was also diagnosed in post-World War II Germany, where it was known as Darmbrand or "bowel fire," and reached epidemic proportions. The causative agents of these CNE cases have since been described as Type C isolates of C. perfringens, which possessed genes for β-toxins and enterotoxins.In developed countries, CNE can also occur in people with diabetes, including children. This form of CNE is extremely rare: to demonstrate its scope, only three such cases have been reported in the United States up to 2002.
Diagnosis
An abdominal x-ray shows multiple dilated loops of small bowel and gas. The abdomen can be tender, distended, and soft. A differential diagnosis can be an intussusception.
Treatment
Treatment involves suppressing the toxin-producing organisms with antibiotics such as penicillin G or metronidazole. About half of seriously ill patients require surgery for perforation, persistent intestinal obstruction, or failure to respond to the antibiotics. An investigational toxoid vaccine has been used successfully in some developing countries but is not available outside of research.
Antibiotic therapy — For all infants with suspected or established NEC, we suggest initiating broad-spectrum antibiotics after obtaining appropriate specimens for culture. The empiric antibiotic regimen should provide broad-spectrum coverage, including coverage for common causes of late-onset neonatal sepsis. The choice is also guided by the local susceptibility patterns (ie, the local antibiogram in a particular neonatal intensive care unit [NICU]).
Acceptable empiric regimens include, but are not limited to, the following .:
•Ampicillin plus gentamicin (or amikacin) plus metronidazole
•Ampicillin plus gentamicin (or amikacin) plus clindamycin
•Ampicillin plus an expanded-spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime, or cefepime) plus metronidazole
•Monotherapy with piperacillin-tazobactam
•Monotherapy with meropenem
Vancomycin should be included in the regimen (ie, replacing ampicillin or added to monotherapy) in centers where there is a high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) or ampicillin-resistant enterococcal infections. Centers with significant gentamicin resistance patterns should consider amikacin in place of gentamicin.
We do not recommend the use of oral aminoglycosides because this treatment can result in the development of resistant bacterial strains, and has not been shown to be more beneficial than standard care.
Other clostridial toxemias
Leukemia patients, cancer chemotherapy recipients and others suffering from suppressed white blood cells (neutropenia) can be afflicted by a similar syndrome, neutropenic enterocolitis, in which the cecum is targeted by Clostridium septicum in much the same way.
In neonatal intensive-care units, the syndrome of neonatal necrotizing enterocolitis may be caused in a similar way by C. perfringens, C. butyricum, and C. difficile, but this has not been proved.
See also
Protein poisoning refers to a different diet-induced phenomenon.
References
== External links == |
Reactive hypoglycemia | Reactive hypoglycemia, postprandial hypoglycemia, or sugar crash is a term describing recurrent episodes of symptomatic hypoglycemia occurring within four hours after a high carbohydrate meal in people with and without diabetes. The term is not necessarily a diagnosis since it requires an evaluation to determine the cause of the hypoglycemia.The condition is related to homeostatic systems used by the body to control the blood sugar level. It is described as a sense of tiredness, lethargy, irritation, or hangover, although the effects can be lessened if a lot of physical activity is undertaken in the first few hours after food consumption.
The alleged mechanism for the feeling of a crash is correlated with an abnormally rapid rise in blood glucose after eating. This normally leads to insulin secretion (known as an insulin spike), which in turn initiates rapid glucose uptake by tissues, either storing it as glycogen or fat, or using it for energy production. The consequent fall in blood glucose is indicated as the reason for the "sugar crash". Another cause might be hysteresis effect of insulin action, i.e., the effect of insulin is still prominent even if both plasma glucose and insulin levels were already low, causing a plasma glucose level eventually much lower than the baseline level.Sugar crashes are not to be confused with the after-effects of consuming large amounts of protein, which produces fatigue akin to a sugar crash, but are instead the result of the body prioritising the digestion of ingested food.The prevalence of this condition is difficult to ascertain because a number of stricter or looser definitions have been used. It is recommended that the term reactive hypoglycemia be reserved for the pattern of postprandial hypoglycemia which meets the Whipple criteria (symptoms correspond to measurably low glucose and are relieved by raising the glucose), and that the term idiopathic postprandial syndrome be used for similar patterns of symptoms where abnormally low glucose levels at the time of symptoms cannot be documented.
To assist in diagnosis, a doctor may order an HbA1c test, which measures the blood sugar average over the two or three months before the test. The more specific 6-hour glucose tolerance test can be used to chart changes in the patients blood sugar levels before ingestion of a special glucose drink and at regular intervals during the six hours following to see if an unusual rise or drop in blood glucose levels occurs.
According to the U.S. National Institutes of Health (NIH), a blood glucose level below 70 mg/dL (3.9 mmol/L) at the time of symptoms followed by relief after eating confirms a diagnosis for reactive hypoglycemia.
Signs and symptoms
Symptoms vary according to individuals hydration level and sensitivity to the rate and/or magnitude of decline of their blood glucose concentration.A crash is usually felt within four hours of heavy carbohydrate consumption. Along with the symptoms of hypoglycemia, symptoms of reactive hypoglycemia include:
The majority of these symptoms, often correlated with feelings of hunger, mimic the effect of inadequate sugar intake as the biology of a crash is similar in itself to the bodys response to low blood sugar levels following periods of glucose deficiency.
Causes
The NIH states: "The causes of most cases of reactive hypoglycemia are still open to debate. Some researchers suggest that certain people may be more sensitive to the body’s normal release of the hormone epinephrine, which causes many of the symptoms of hypoglycemia. Others believe deficiencies in glucagon secretion might lead to reactive hypoglycemia.Several other hormones are responsible for modulating the bodys response to insulin, including cortisol, growth hormone and sex hormones. Untreated or under-treated hormonal disorders such as adrenal insufficiency (see also Addisons disease) or growth hormone deficiency can therefore sometimes cause insulin hypersensitivity, and reactive hypoglycemia.
Stomach bypass surgery or hereditary fructose intolerance are believed to be causes, albeit uncommon, of reactive hypoglycemia. Myo-inositol or 1D-chiro-inositol withdrawal can cause temporary reactive hypoglycemia.There are several kinds of reactive hypoglycemia:
Alimentary hypoglycemia (consequence of dumping syndrome; it occurs in about 15% of people who have had stomach surgery)
Hormonal hypoglycemia (e.g., hypothyroidism)
Helicobacter pylori-induced gastritis (some reports suggest this bacteria may contribute to the occurrence of reactive hypoglycemia)
Congenital enzyme deficiencies (hereditary fructose intolerance, galactosemia, and leucine sensitivity of childhood)
Late hypoglycemia (occult diabetes; characterized by a delay in early insulin release from pancreatic beta-cells, resulting in initial exaggeration of hyperglycemia during a glucose tolerance test)"Idiopathic reactive hypoglycemia" is a term no longer used because researchers now know the underlying causes of reactive hypoglycemia and have the tools to perform the diagnosis and the pathophysiological data explaining the mechanisms.To check if there is real hypoglycemia when symptoms occur, neither an oral glucose tolerance test nor a breakfast test is effective; instead, a hyperglucidic breakfast test or ambulatory glucose testing is the current standard.The body requires a relatively constant input of glucose, a sugar produced upon digestion of carbohydrates, for normal functioning. Glucagon and insulin are among the hormones that ensure a normal range of glucose in the human body. Upon consumption of a meal, blood sugar normally rises, which triggers pancreatic cells to produce insulin. This hormone initiates the absorption of the just-digested blood glucose as glycogen into the liver for metabolism or storage, thereby lowering glucose levels in the blood. In contrast, the hormone glucagon is released by the pancreas as a response to lower than normal blood sugar levels. 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.
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. Suggestions include sugary foods that are quickly digested, such as:
Dried fruit
Soft drinks
Juice
Sugar as sweets, tablets or cubes.The anti-hypertensive class of medication known as calcium channel blockers could be useful for reactive hypoglycemia as inhibition of the calcium channels on beta islet cells can help prevent an overproduction of insulin after a meal is eaten.
Postprandial syndrome
If there is no hypoglycemia at the time of the symptoms, this condition is called idiopathic postprandial syndrome. It might be an "adrenergic postprandial syndrome" — blood glucose levels are normal, but the symptoms are caused through autonomic adrenergic counterregulation. Often, this syndrome is associated with emotional distress and anxious behaviour of the patient. This is often seen in dysautonomic disorders as well. Dietary recommendations for reactive hypoglycemia can help to relieve symptoms of postprandial syndrome.
See also
Spontaneous hypoglycemia
Refeeding syndrome
References
Further reading
Açbay O, Celik AF, Kadioğlu P, Göksel S, Gündoğdu S (1999). "Helicobacter pylori-induced gastritis may contribute to occurrence of postprandial symptomatic hypoglycemia". Dig. Dis. Sci. 44 (9): 1837–42. doi:10.1023/A:1018842606388. PMID 10505722.
External links
Article about hypoglycemia at eMedicine |
Congenital vertebral anomaly | Congenital vertebral anomalies are a collection of malformations of the spine. Most, around 85%, are not clinically significant, but they can cause compression of the spinal cord by deforming the vertebral canal or causing instability. This condition occurs in the womb. Congenital vertebral anomalies include alterations of the shape and number of vertebrae.
Lumbarization and sacralization
Lumbarization is an anomaly in the spine. It is defined by the nonfusion of the first and second segments of the sacrum. The lumbar spine subsequently appears to have six vertebrae or segments, not five. This sixth lumbar vertebra is known as a transitional vertebra. Conversely the sacrum appears to have only four segments instead of its designated five segments. Lumbosacral transitional vertebrae consist of the process of the last lumbar vertebra fusing with the first sacral segment. While only around 10 percent of adults have a spinal abnormality due to genetics, a sixth lumbar vertebra is one of the more common abnormalities.
Sacralization of the fifth lumbar vertebra (or sacralization) is a congenital anomaly, in which the transverse process of the last lumbar vertebra (L5) fuses to the sacrum on one side or both, or to ilium, or both. These anomalies are observed at about 3.5 percent of people, and it is usually bilateral but can be unilateral or incomplete (ipsilateral or contralateral rudimentary facets) as well. Although sacralization may be a cause of low back pain, it is asymptomatic in many cases (especially bilateral type). Low back pain in these cases most likely occurs due to biomechanics. In sacralization, the L5-S1 intervertebral disc may be thin and narrow. This abnormality is found by X-ray.Sacralization of L6 means L6 attaches to S1 via a rudimentary joint. This L6-S1 joint creates additional motion, increasing the potential for motion-related stress and lower back pain/conditions. This condition can usually be treated without surgery, injecting steroid medication at the pseudoarticulation instead. Additionally, if L6 fuses to another vertebra this is increasingly likely to cause lower back pain. The presence of a sixth vertebra in the space where five vertebrae normally reside also decreases the flexibility of the spine and increases the likelihood of injury.
Hemivertebrae
Hemivertebrae are wedge-shaped vertebrae and therefore can cause an angle in the spine (such as kyphosis, scoliosis, and lordosis).
Among the congenital vertebral anomalies, hemivertebrae are the most likely to cause neurologic problems. The most common location is the midthoracic vertebrae, especially the eighth (T8). Neurologic signs result from severe angulation of the spine, narrowing of the spinal canal, instability of the spine, and luxation or fracture of the vertebrae. Signs include rear limb weakness or paralysis, urinary or fecal incontinence, and spinal pain. Most cases of hemivertebrae have no or mild symptoms, so treatment is usually conservative. Severe cases may respond to surgical spinal cord decompression and vertebral stabilization.
Associations
Recognised associations are many and include:
Aicardi syndrome,
cleidocranial dysostosis,
gastroschisis 3,
Gorlin syndrome,
fetal pyelectasis 3,
Jarcho-Levin syndrome,
OEIS complex,
VACTERL association.The probable cause of hemivertebrae is a lack of blood supply causing part of the vertebrae not to form.
Hemivertebrae in dogs are most common in the tail, resulting in a screw shape.
Block vertebrae
Block vertebrae occur when there is improper segmentation of the vertebrae, leading to parts of or the entire vertebrae being fused. The adjacent vertebrae fuse through their intervertebral discs and also through other intervertebral joints so that it can lead to blocking or stretching of the exiting nerve roots from that segment. It may lead to certain neurological problems depending on the severity of the block. It can increase stress on the inferior and the superior intervertebral joints. It can lead to an abnormal angle in the spine, there are certain syndromes associated with block vertebrae; for example, Klippel–Feil syndrome. The sacrum is a normal block vertebra.
Fossil record
Evidence for block vertebrae found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. A block vertebra has been documented in T. rex. This suggests that the basic development pattern of vertebrae goes at least as far back as the most recent common ancestor of archosaurs and mammals. The tyrannosaurs block vertebra was probably caused by a "failure of the resegmentation of the sclerotomes".
Butterfly vertebrae
Butterfly vertebrae have a sagittal cleft through the body of the vertebrae and a funnel shape at the ends. This gives the appearance of a butterfly on an x-ray. It is caused by persistence of the notochord (which usually only remains as the center of the intervertebral disc) during vertebrae formation. There are usually no symptoms. There are also coronal clefts mainly in skeletal dysplasias such as chondrodysplasia punctata. In dogs, butterfly vertebrae occur most often in Bulldogs, Pugs, and Boston Terriers.
Transitional vertebrae
Transitional vertebrae have the characteristics of two types of vertebra. The condition usually involves the vertebral arch or transverse processes. It occurs at the cervicothoracic, thoracolumbar, or lumbosacral junction. For instance, the transverse process of the last cervical vertebra may resemble a rib. A transitional vertebra at the lumbosacral junction can cause arthritis, disk changes, or thecal sac compression. Back pain associated with lumbosacral transitional vertebrae (LSTV) is known as Bertolottis syndrome. One study found that male German Shepherd Dogs with a lumbosacral transitional vertebra are at greater risk for cauda equina syndrome, which can cause rear limb weakness and incontinence.The significance of transitional vertebrae has been questioned by one study finding similar prevalence in the general population as those with low back pain, but more recent study found a large difference.
Spina bifida
Spina bifida is characterized by a midline cleft in the vertebral arch. It usually causes no symptoms in dogs. It is seen most commonly in Bulldogs and Manx cats. In Manx it accompanies a condition known as sacrocaudal dysgenesis that gives these cats their characteristic tailless or stumpy tail appearance. It is inherited in Manx as an autosomal dominant trait.
Associations
Vertebral anomalies is associated with an increased incidence of some other specific anomalies as well, together being called the VACTERL association:
V - Vertebral anomalies
A - Anal atresia
C - Cardiovascular anomalies
T - Tracheoesophageal fistula
E - Esophageal atresia
R - Renal (Kidney) and/or radial anomalies
L - Limb defects
References
== External links == |
Acute panmyelosis with myelofibrosis | Acute panmyelosis with myelofibrosis (APMF) is a poorly defined disorder that arises as either a clonal disorder, or following toxic exposure to the bone marrow.
Signs and symptoms
Tamir Lichaas bone biopsy shows abnormal schmete megakaryocytes, macrocytic erythropoiesis, and defects in neutrophil production and fibrosis of the marrow (myelofibrosis).
Clinically patients present with reduction in the count of all blood cells (pancytopenia), a very few blasts in the peripheral blood and no or little spleen enlargement (splenomegaly).
Cells are usually CD34 positive.
Prognosis and treatment
Median survival is about nine months.Autologous stem cell transplantation has been used in treatment.
Terminology
Controversy remains today whether this disorder is a subtype of acute myeloid leukemia or myelodysplastic syndromes; however, it is currently classified as a form of AML.
See also
List of hematologic conditions
References
See also
Acute myeloid leukemia
Panmyelosis
Myelofibrosis
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Idiopathic hypersomnia | Idiopathic hypersomnia (IH) is a neurological disorder which is characterized primarily by excessive sleep and excessive daytime sleepiness (EDS). The condition typically becomes evident in early adulthood and most patients diagnosed with IH will have had the disorder for many years prior to their diagnosis. As of August 2021, an FDA-approved medication exists for IH, in addition to several off-label treatments (primarily FDA-approved narcolepsy medications).Idiopathic hypersomnia may also be referred to as IH, IHS, or primary hypersomnia and belongs to a group of sleeping disorders known as central hypersomnias, central disorders of hypersomnolence, or hypersomnia of brain origin. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) defines idiopathic hypersomnia as EDS without narcolepsy or the associated features of other sleep disorders. It occurs in the absence of medical problems or sleep disruptions, such as sleep apnea, that can cause secondary hypersomnia.
Signs and symptoms
Individuals with IH share common symptoms like excessive daytime sleepiness, sleep inertia, brain fog, long sleep periods, and others.
Excessive daytime sleepiness, characterized by persistent sleepiness throughout the day and often a general lack of energy—even during the day after apparently adequate or even prolonged nighttime sleep. People with EDS nap repeatedly throughout the day and have strong urges to sleep while driving, working, eating, or conversing with others.
Sleep inertia (also known as sleep drunkenness), characterized by having extreme difficulty waking up and feeling an uncontrollable desire to go back to sleep.
Clouding of consciousness characterized by inattention, thought process abnormalities, comprehension abnormalities, and language abnormalities. These symptoms may affect performance on perception, memory, learning, executive functions, language, constructive abilities, voluntary motor control, attention, and mental speed. Affected individuals can complain of forgetfulness, confusion, or inability to think clearly.
Excessive sleep (9 hours or more over a full 24-hour period), without feeling refreshed after waking. Daytime naps can be up to several hours and are also unrefreshing.Some studies have shown increased frequencies of palpitations, digestive problems, difficulty with body temperature regulation, and other symptoms in patients with IH. Anxiety and depression are frequent, likely as a response to chronic illness. A case series in 2010 found that peripheral vascular symptoms, such as cold hands and feet (e.g., Raynaud Syndrome), were more common in people with IH than in controls.Other autonomic dysfunctional symptoms, such as fainting episodes, dizziness upon arising, headaches (possibly migrainous in quality), food cravings, and impotence may also be correlated with IH. Researchers have found that people reporting IH symptoms report high levels of autonomic dysfunction on par with other conditions of autonomic failure (i.e., MSA and diabetes). As of June 2021, there is no evidence to suggest such symptoms are related to IH in any way.
Causes
Unlike narcolepsy with cataplexy, which has a known cause (autoimmune destruction of hypocretin-producing neurons), the cause of IH is largely unknown. As of 2012, researchers have identified a few abnormalities associated with IH, which with further study may help to clarify the etiology.Destruction of noradrenergic neurons has produced hypersomnia in experimental animal studies, and injury to adrenergic neurons has also been shown to lead to hypersomnia. IH has also been associated with a malfunction of the norepinephrine system and decreased cerebrospinal fluid (CSF) histamine levels.Researchers have recently found an abnormal hypersensitivity to GABA (the major brain chemical responsible for sedation) in a subset of patients with central hypersomnia i.e.: IH, narcolepsy without cataplexy and long sleepers. They have identified a small (500 to 3000 daltons) naturally occurring bioactive substance (most likely a peptide as it is trypsin-sensitive) in the CSF of affected patients. Although this substance requires further identification of its chemical structure, it is currently referred to as a "somnogen" because it has been shown to cause hyper-reactivity of GABAA receptors, which leads to increased sedation or somnolence. In essence, it is as though these patients are chronically sedated with a benzodiazepine (medication which acts through the GABA system) such as Versed or Xanax, even though they do not take these medications.
Diagnosis
Idiopathic hypersomnia lacks a clearly defining biological marker like HLA-DQB1*0602 genotype in narcolepsy. Doctors can more carefully exclude these causes of EDS in order to more correctly diagnose IH. However, "even in the presence of other specific causes of hypersomnia, one should carefully assess the contribution of these etiological factors to the complaint of EDS and when specific treatments of these conditions fail to suppress EDS, the additional diagnosis of IH should be considered."The severity of EDS can be quantified by subjective scales, such as the Epworth Sleepiness Scale and the Stanford Sleepiness Scale, and also by objective tests, like actigraphy, psychomotor vigilance task, maintenance of wakefulness test (MWT), multiple sleep latency test (MSLT) although as per latest research studies, the effectiveness of MSLT has been called into question. Several groups of researchers have found normal MSLT results in patients who otherwise seem to have IH. Therefore, when IH is suspected, researchers suggest appending a 24-hour continuous polysomnography to the standard overnight/MSLT study in order to record total sleep time.The recent studies have also found that reports of sleepiness in IH relate more to mental fatigue rather than physiological sleepiness per se and the subjective scales like ESS, IH symptom diary (IHSD) and PGIC better captures the severity of symptoms consistently.It is also important to note that whereas narcolepsy is strongly associated with the HLA-DQB1*0602 genotype, "HLA typing is of no help in the positive diagnosis of idiopathic hypersomnia." This is "despite some reports that suggest an increase [sic] frequency of HLA Cw2 and DRS in idiopathic hypersomnia subjects."In patients with IH, polysomnography typically shows short sleep latency, increased mean slow wave sleep, and a high mean sleep efficiency. "Latency to REM sleep and percentages of light sleep and REM sleep were normal, compared with normal ranges." Despite this, one study has found increased sleep fragmentation in patients with IH without long sleep time, suggesting multiple possible presentations.Per ICSD-3, five criteria must be met for a diagnosis of IH:
Daytime lapses into sleep or an irrepressible need to sleep on a daily basis, for at least 3 months
Absence of insufficient sleep syndrome
Absence of cataplexy
Absence of other causes of hypersomnia
The presence of positive MSLT tests.The latest ICD 10 defines IH with long sleep time as a neurological disorder that is a rare sleep disorder characterized by prolonged sleep at night and extreme sleepiness during the day. There are no apparent causes. This disorder affects the ability to function. It is of central nervous system origin characterized by prolonged nocturnal sleep and periods of daytime drowsiness. Affected individuals experience difficulty with awakening in the morning and may have associated sleep drunkenness, automatic behaviors, and memory disturbances. This condition differs from narcolepsy in that daytime sleep periods are longer, there is no association with cataplexy, and the multiple sleep latency onset test does not record sleep-onset rapid eye movement sleep.
Management
Since the underlying mechanism is not yet fully understood, treatment efforts have usually focused on symptom management. In August 2021, low-sodium oxybate (Xywav) became the first U.S. FDA-approved treatment for idiopathic hypersomnia.
Wake-promoting medications used in narcolepsy are also commonly used off-label to help manage the excessive daytime sleepiness of IH. CNS stimulants tend to be less effective for IH than they are for narcolepsy and may be less well tolerated.
Stimulants
The main treatment of excessive daytime sleepiness is done through central nervous system stimulants.
Methylphenidate and Dextroamphetamine are most used stimulants to controlled EDS. Increased dopamine release is felt to be the main property explaining wake-promotion from these medications. Insomnia is another common side effect and may require additional treatment.
Non-stimulant wake-promoting medications
Solriamfetol is the first and only dual-acting dopamine and norepinephrine reuptake inhibitor approved by the FDA to improve wakefulness in adults living with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea.Pitolisant, a selective histamine 3 (H3) receptor antagonist/inverse agonist, was approved by FDA during August 2019. It works by increasing the synthesis and release of histamine, a wake-promoting neurotransmitter in the brain.
Modafinil and Armodafinil elevate hypothalamic histamine levels, and they are known to bind to the dopamine transporter, thereby inhibiting dopamine reuptake. Modafinil can cause uncomfortable side effects, including nausea, headache, and a dry mouth for some patients, while other patients report no noticeable improvement even on relatively high dosages. They may also "interact with low-dose contraceptives, potentially reducing efficacy, although the scientific data supporting this claim is weak and rests on poorly documented anecdotes."
Sleep promoting medications
Sodium oxybate is an orphan drug which was designed specifically for the treatment of narcolepsy. Common side effects include nausea, dizziness, and hallucinations. A 2016 study by Leu-Semenescu et al. found sodium oxybate reduced daytime sleepiness in IH to the same degree as in patients with narcolepsy type 1, and the drug improved severe sleep inertia in 71% of the hypersomnia patients. In July 2020, the FDA approved Xywav™ (calcium, magnesium, potassium, and sodium oxybates), an oral solution for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy.
Cognitive Behavioral Therapy
Although behavioral approaches have not been demonstrated to improve clinical markers of IH, cognitive behavioral therapy has been found to potentially reduce depressive symptoms and improve self-efficacy in people with central disorders of hypersomnolence.
Prognosis
IH can profoundly affect work, education, and quality of life due to excessive daytime somnolence. Patients will often need to adapt their lifestyle to avoid situations that might be dangerous while sleepy, such as high risk work, or driving. The risks associated with these activities have been found to be higher for patients with hypersomnias than for those with sleep apnea or severe insomnia.
Epidemiology
Typically, the symptoms of IH begin in adolescence or young adulthood, although they can begin at a later age. After onset, hypersomnia often worsens over several years, but it is often stable by the time of diagnosis and appears to be a lifelong condition. Spontaneous remission is only seen in 10–15% of patients.According to the limited epidemiological data that exists, IH "has more of a female preponderance (1.8/1)." Family cases are frequent, in a range from 25% to 66% without any clear mode of inheritance."IH has long been considered a rare disease, believed to be 10 times less frequent than narcolepsy. The prevalence of narcolepsy (with cataplexy) is estimated between 1/3,300 and 1/5,000. Although the true prevalence of IH is unknown, it is estimated at 1/10,000 to 1/25,000 for the long sleep form and 1/11,000 to 1/100,000 without long sleep. A more precise estimate "is complicated by a lack of clear biologic markers" and a lack of "unambiguous diagnostic criteria."Because of the rarity of IH, research into the condition is limited "Patients are rare, researchers and scientists involved in the field are few and research findings are therefore scarce." "In Europe and in North America there is now a public health concern about helping patients and families affected by these rare diseases. Due to the complexity of the disease, they often experience difficulties to be diagnosed and often face social and professional consequences."
Research
GABA-directed medications
There is ongoing research into the efficacy of gamma aminobutyric acid A (GABAA) receptor antagonists for the treatment of IH. Research findings suggest that the GABA neurotransmitter system plays a significant role in the etiology of primary hypersomnias, such as IH and Narcolepsy Type 2. Given the possible role of hyperactive GABAA receptors in IH, medications that could counteract this activity are being studied to test their potential to improve sleepiness. These currently include clarithromycin and flumazenil.Flumazenil, a GABAA receptor antagonist is approved by the FDA for use in anesthesia reversal and benzodiazepine overdose. Research has shown that flumazenil provides relief for most patients whose CSF contains the unknown "somnogen" that enhances the function of GABAA receptors, making them more susceptible to the sleep-inducing effect of GABA. For one patient, daily administration of flumazenil by sublingual lozenge and topical cream has proven effective for several years. A 2014 case report also showed improvement in IH symptoms after treatment with a continuous subcutaneous flumazenil administration. The patient was treated with a short-term subcutaneous administration through 96-hour continuous low dose (4 mg/day) infusion of flumazenil, followed by a slow-release long term subcutaneous administration through flumazenil implant.Clarithromycin, an antibiotic approved by the FDA for the treatment of infections, was found to return the function of the GABA system to normal in patients with IH. In the pilot study, clarithromycin improved subjective sleepiness in GABA-related hypersomnia. In 2013, a retrospective review evaluating longer-term clarithromycin use showed efficacy in a large percentage of patients with GABA-related hypersomnia.
Transcranial direct-current stimulation (tDCS)
Dr. Ferini-Strambi and his colleagues in Milan, Italy, performed neurologic examinations by applying anodal tDCS by placing one electrode over the left dorsolateral prefrontal cortex, with the cathode over the contralateral orbit over 3 weeks period and found that seven of the eight participants (87.5%) reported improvement in their daytime sleepiness, including for up to two weeks after the end of the study.
Transcranial magnetic stimulation (TMS)
Neural networks that regulate arousal and sleep comprise a bottom-up (from the brainstem to the cortex) pathway and a top-down (corticothalamic) pathway. The bottom-up pathway emerges from the ascending reticular arousal system (ARAS) and activates the cortex via well-characterized thalamic and nonthalamic pathways through cholinergic and aminergic neurotransmission. The bottom-up pathway represents the leverage point for pharmaceutical interventions. It is complemented by a corticothalamic top-down pathway, which appears to be modifiable through noninvasive brain stimulation (NIBS) techniques.
A single case report study indicates that high-frequency repetitive transcranial magnetic stimulation (HF rTMS) over the left dorsolateral prefrontal cortex (DLPFC) might represent an alternative choice for symptom control in narcoleptic patients with cataplexy. rTMS may also exert intrinsic effects on hypersomnia in depressed adolescents.
Mazindol
Mazindol is a stimulant similar to amphetamines that "has been shown to be effective in treating hypersomnia in narcoleptics." However, it is not currently approved in the US.
Selegiline
Selegiline, monoamine oxidase type B (MAO-B) inhibitor works by slowing the breakdown of certain substances in the brain (mostly dopamine, but also serotonin and norepinephrine). It may also be useful, as it is also a metabolic precursor of amphetamine and exerts most of its therapeutic effects through amphetamine metabolism. It is not commonly prescribed for people with narcolepsy because of the high dosage required and potential for severe side effects.
Atomoxetine
Atomoxetine (or reboxetine in Europe) is an adrenergic reuptake inhibitor which increases wakefulness (generally less strongly than the medications which act on dopamine) and which has been argued to have a "clear use in the therapeutic arsenal against narcolepsy and hypersomnia although undocumented by clinical trials."
Ritanserin
Ritanserin is a serotonin antagonist that has "been shown to improve daytime alertness and subjective sleep quality in patients on their usual narcolepsy medications." It is intended as an adjunct (supplement to another main therapeutic agent), and although it is not available in the US, it is available in Europe.
Antidepressants
Antidepressants seems to have some therapeutic effects as they enhance synaptic levels of noradrenaline and serotonin. Further, different medicines are known to augment the activity of one another like as seen in the case of Fluoxetine which augmented the activity of methylphenidate when taken together.
Bupropion, a norepinephrine-dopamine reuptake inhibitor (NDRI), which works by inhibiting the reabsorption of two important brain chemicals – norepinephrine and dopamine, is known to have wake-promoting effects.Fluoxetine, an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class is also known to have mild stimulating effects. It is also known to augment the activity of methylphenidate.
Caffeine
Caffeine is one of the safer nondopaminergic wake-promoting compounds. It is widely used but "has intolerable side effects at high doses (including cardiovascular), and it is generally not efficient enough for patients with hypersomnia or narcolepsy." Although it is commonly used by people with IH or narcolepsy, many people with these disorders report that it has only limited benefit on their sleepiness.
Melatonin
Melatonin is a hormone that the body produces to help regulate sleep. One small study, which used a dose of 2 mg slow-release melatonin at bedtime, found that 50% of participants had “shortened nocturnal sleep duration, decreased sleep drunkenness and relieved daytime sleepiness.” Other studies have shown that melatonin synchronizes the circadian rhythms, and improves the “onset, duration and quality of sleep.”
Levothyroxine
There have been some studies suggesting levothyroxine as a possible treatment for IH, especially for patients with subclinical hypothyroidism. This treatment does carry potential risks (especially for patients without hypothyroidism or subclinical hypothroidism), which include cardiac arrhythmia.
Hypocretin agonists
Hypocretin-1 has been shown to be strongly wake-promoting in animal models, but it does not cross the blood-brain barrier. Suvorexant, a hypocretin receptor antagonist, has been developed to limit the natural effects of hypocretin in patients with insomnia. It is therefore possible that a hypocretin agonist may be similarly developed for the treatment of hypersomnia.
Acetylcholinesterase inhibitor
Antidepressants seems to have some therapeutic effects as they enhance synaptic levels of noradrenaline and serotonin and for same reason enhancing the levels of acetylcholine may have some therapeutic effect. Donepezil showed improvement in one patient by decreasing ESS score from 20 up to 14. Memantine has also shown some positive effect on a patient with narcolepsy.
Levodopa
Levodopa is an amino acid and is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). As per a study of six narcoleptic patients it was found that L-dopa improved vigilance and performance as evaluated by the AVS and the FCRTT, while the capacity to fall asleep rapidly remained unchanged as evaluated by the MSLT. It raises the hypothesis that dopamine may play a role in the physiopathology of excessive daytime sleepiness of this condition.
Carnitine
Carnitine, has also been shown to improve narcolepsy symptoms (including daytime sleepiness) by increasing fatty-acid oxidation. Abnormally low levels of acylcarnitine have been observed in patients with narcolepsy. These same low levels have been associated with primary hypersomnia in general in mouse studies. "Mice with systemic carnitine deficiency exhibit a higher frequency of fragmented wakefulness and rapid eye movement (REM) sleep, and reduced locomotor activity." Administration of acetyl-L-carnitine was shown to improve these symptoms in mice. A subsequent human trial found that narcolepsy patients given L-carnitine spent less total time in daytime sleep than patients who were given placebo.
See also
References
== External links == |
Balanitis plasmacellularis | Balanitis plasmacellularis is a cutaneous condition characterized by a benign inflammatory skin lesion characterized histologically by a plasma cell infiltrate.: 657 A similar condition has been described in women (i.e. "Zoons vulvitis"), although its existence is controversial due to the possibility of diagnostic error in many of the cases that have been reported in the medical literature.It is named for J.J. Zoon, who characterized it in 1952.
See also
Balanitis
Pseudoepitheliomatous keratotic and micaceous balanitis
Skin lesion
List of cutaneous conditions
References
== External links == |
Thyroglossal cyst | A thyroglossal cyst is a fibrous cyst that forms from a persistent thyroglossal duct. Thyroglossal cysts can be defined as an irregular neck mass or a lump which develops from cells and tissues left over after the formation of the thyroid gland during developmental stages.Thyroglossal cysts are the most common cause of midline neck masses and are generally located caudal to (below) the hyoid bone. These neck masses can occur anywhere along the path of the thyroglossal duct, from the base of the tongue to the suprasternal notch. Other common causes of midline neck masses include lymphadenopathy, dermoid cysts, and various odontogenic anomalies.Thyroglossal cysts develop at birth. Many diagnostic procedures may be used to establish the degree of the cyst.
Signs and symptoms
Thyroglossal duct cysts most often present with a palpable asymptomatic midline neck mass usually below [65% of the time] the level of the hyoid bone. The mass on the neck moves during swallowing or on protrusion of the tongue because of its attachment to the tongue via the tract of thyroid descent. Some patients will have neck or throat pain, or dysphagia.The persistent duct or sinus can promote oral secretions, which may cause cysts to become infected. Up to half of thyroglossal cysts are not diagnosed until adult life. The tract can lie dormant for years or even decades, until some kind of stimulus leads to cystic dilation. Infection can sometimes cause the transient appearance of a mass or enlargement of the cyst, at times with periodic recurrences. Spontaneous drainage may also occur. Differential diagnosis are ectopic thyroid, enlarged lymph nodes, dermoid cysts and goiter.Thyroglossal cyst usually presents as a midline neck lump (in the region of the hyoid bone) that is usually painless, smooth and cystic, though if infected, pain can occur. There may be difficulty breathing, dysphagia (difficulty swallowing), or dyspepsia (discomfort in the upper abdomen), especially if the cyst becomes large.The most common location for a thyroglossal cyst is midline or slightly off midline, between the isthmus of the thyroid and the hyoid bone or just above the hyoid bone. A thyroglossal cyst can develop anywhere along a thyroglossal duct, though cysts within the tongue or in the floor of the mouth are rare.A thyroglossal cyst will move upwards with protrusion of the tongue.Thyroglossal cysts are associated with an increased incidence of ectopic thyroid tissue. Occasionally, a lingual thyroid can be seen as a flattened strawberry-like lump at the base of the tongue.
Complications
Infection
An infected thyroglossal duct cyst can occur when it is left untreated for a certain amount of time or simply when a thyroglossal duct cyst hasnt been suspected. The degree of infection can be examined as major rim enhancement has occurred, located inferior to the hyoid bone. Soft tissue swelling occurs, along with airway obstruction and trouble swallowing, due to the rapid enlargement of the cyst. With infections, there can be rare cases where an expression of fluid is projected into the pharynx causing other problems within the neck.
Thyroglossal Fistula
A thyroglossal duct cyst may rupture unexpectedly, resulting in a draining sinus known as a thyroglossal fistula. Thyroglossal fistula can develop when the removal of the cyst has not been fully completed. This is usually noticed when bleeding in the neck occurs, causing swelling and fluid ejection around the original wound of removal.
Thyroglossal duct cyst carcinoma
Rarely (in less than 1% of cases), cancer may be present in a thyroglossal duct cyst. These tumors are generally papillary thyroid carcinomas, arising from the ectopic thyroid tissue within the cyst.
Causes
Thyroglossal Duct Cysts are a birth defect. During embryonic development, the thyroid gland is being formed, beginning at the base of the tongue and moving towards the neck canal, known as the thyroglossal duct. Once the thyroid reaches its final position in the neck, the duct normally disappears. In some individuals, portions of the duct remain behind, leaving small pockets, known as cysts. During a persons life, these cyst pockets can fill with fluids and mucus, enlarging when infected, presenting the thyroglossal cyst.
Embryology
The thyroglossal tract arises from the foramen cecum at the junction of the anterior two-thirds and posterior one-third of the tongue. Any part of the tract can persist, causing a sinus, fistula or cyst. Most fistulae are acquired following rupture or incision of the infected thyroglossal cyst. A thyroglossal cyst is lined by pseudostratified, ciliated columnar epithelium while a thyroglossal fistula is lined by columnar epithelium.
Diagnosis
Diagnosis of a thyroglossal duct cyst requires a medical professional, and is usually done by a physical examination. It is important to identify whether or not the thyroglossal cyst contains any thyroid tissue, as it can define the degree of cyst that is being dealt with.Diagnostic procedures for a thyroglossal cyst include:
Clinical features
Clinical features can be found in the subhyoid portion of the tract and 75% present as midline swellings. The remainder can be found as far lateral as the lateral tip of the hyoid bone.
Typically, the cyst will move upwards on protrusion of the tongue, given its attachment to the embryonic duct, as well as on swallowing, due to attachment of the tract to the foramen caecum.
Treatment
Although generally benign, the cyst must be removed if the patient exhibits difficulty in breathing or swallowing, or if the cyst is infected. Even if these symptoms are not present, the cyst may be removed to eliminate the chance of infection or development of a carcinoma,Thyroid scans and thyroid function studies are ordered preoperatively; this is important to demonstrate that normally functioning thyroid tissue is in its usual area.Surgical management options include the Sistrunk procedure, en bloc central neck dissection, suture-guided transhyoid pharyngotomy, and Koempels supra-hyoid technique. Cystectomy is an inadequate approach.
Sistrunk Procedure
The Sistrunk procedure is the surgical resection of the central portion of the hyoid bone along with a wide core of tissue from the midline area between the hyoid and foramen cecum. It involves excision not only of the cyst but also of the paths tract and branches, and removal of the central portion of the hyoid bone is indicated to ensure complete removal of the tract. The original Sistrunk papers (the "classic" procedure described in 1920, and the "modified" procedure described in 1928) are available on-line with a modern commentary.In general, the procedure consists of three steps:
incision
resection of cyst and hyoid bone
drainage and closureThere are several versions of the Sistrunk procedure, including:
"classic": excision of the center of the hyoid bone along with a thyroglossal duct cyst, removal of one-eighth inch diameter core of tongue muscle superior to the hyoid at a 45 degree angle up to the foramen cecum to include mucosa, removal of one-quarter inch of the center of the hyoid bone, closure of the cut ends of the hyoid bone, and placement of a drain.
modified: dissection through the tongue base but not through the mucosa. The modified Sistrunk procedure is the procedure of choice in both primary and revision cases.
hyoid cartilage division: In cases without mature ossification of the hyoid bone, the non-fused cartilage portion can be divided by monopolar Bovie electro-cauterization or scissors. There were no statistical differences between this modified Sistrunk and the conventional Sistrunk procedure.The procedure is relatively safe. In a study of 35 pediatric patients, Maddalozzo et al. found no major complications, but did observe minor complications (6 patients presented with seroma and 4 patients with local wound infections). A more recent paper analyzed 24 research studies on different treatment complications of thyroglossal cyst, and reported a total minor complications rate of 6% for the Sistrunk operation (classical or modified) and simple cystectomy treatment modalities. The Sistrunk procedure also showed better outcomes concerning the rate of overall recurrence, i.e. has the lowest rate of recurrence.Sistrunk procedure results in a 95% cure rate and 95–100% long-term survival.
Epidemiology
90% of cases are presented in children before the age of 10
70% of neck anomalies are from Thyroglossal cysts
Thyroglossal Duct Cysts are the second most common neck abnormalities after lymphadenopathy
A person can live with a Thyroglossal Duct Cyst without any problems, until a pathology develops.
Approximately 7% of the population has thyroglossal duct remnants
Thyroglossal duct carcinoma occurs in approximately 1 to 2% of Thyroglossal cyst cases.
See also
Cutaneous columnar cyst
Branchial cleft cyst
Cystic hygroma
Preauricular sinus and cyst
Ranula
References
Further reading
Brewis C, Mahadevan M, Bailey CM, Drake DP (2000). "Investigation and treatment of thyroglossal cysts in children". Journal of the Royal Society of Medicine. 93 (1): 18–21. doi:10.1177/014107680009300106. PMC 1288046. PMID 10700841.
http://www.doctoronline.nhs.uk/masterwebsite1Asp/targetpages/testandprocedures/surgery/thyroglo.asp
== External links == |
Aceruloplasminemia | Aceruloplasminemia is a rare autosomal recessive disorder in which the liver can not synthesize the protein ceruloplasmin properly, which is needed to transport copper around the blood. Copper deficiency in the brain results in neurological problems that generally appear in adulthood and worsen over time.
.Aceruloplasminemia has been seen worldwide, but its overall prevalence is unknown. Studies in Japan have estimated that approximately 1 in 2 million adults in this population are affected.Aceruloplasminemia belongs to the group of genetic disorders called neurodegeneration with brain iron accumulation (NBIA).
Signs and symptoms
Patients with aceruloplasminemia develop a variety of movement problems. They may experience dystonia of the head and neck, resulting in repetitive movements and contortions. Other involuntary movements may also occur, such as tremors, chorea, blepharospasms, and grimacing. Affected individuals may also experience ataxia, the lack of coordination of muscle movements. Some develop psychiatric problems and midlife dementia. The type of neurological disruption corresponds to associated regions of iron deposition in the brain and liver.In addition to neurological problems, affected individuals may have diabetes mellitus caused by iron damage to cells in the pancreas that make insulin. This impairs blood sugar regulation and leads to the signs and symptoms of diabetes.Iron accumulation in the tissues and organs results in a corresponding iron deficiency in the blood, leading to anemia. Anemia and diabetes usually occur by the time an affected person is in his or her twenties.Affected individuals also experience retinal degeneration caused by excess iron. The changes result in small opaque spots and areas of atrophy around the edges of the retina. These abnormalities usually do not affect vision but can be observed during an eye examination.
Cause
Aceruloplasminemia is caused by a mutation (a five-base pair insertion in exon 7) in the CP gene, which provides instructions for making a protein called ceruloplasmin, a protein involved in iron transport and processing. Ceruloplasmin helps move iron from the organs and tissues of the body and prepares it for incorporation into a molecule called transferrin, which transports it to red blood cells to help carry oxygen. The CP gene mutation results in the production of ceruloplasmin protein that is unstable or nonfunctional by altering the open reading frame such that the amino acid ligands in the essential carboxyl terminal region are eliminated. When ceruloplasmin is unavailable, transport of iron out of the bodys tissues is impaired. The resulting iron accumulation damages cells in those tissues, leading to neurological dysfunction and other health problems.This condition is inherited in an autosomal recessive pattern, which means both copies of the gene have the mutation. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Diagnosis
Diagnosis of this disorder depends on blood tests demonstrating the absence of serum ceruloplasmin, combined with low serum copper concentration, low serum iron concentration, high serum ferritin concentration, or increased hepatic iron concentration. MRI scans can also confirm a diagnosis; abnormal low intensities can indicate iron accumulation in the brain.
Prevention
Children of affected individuals are obligate carriers for aceruloplasminemia. If the CP mutations has been identified in a related individual, prenatal testing is recommended. Siblings of those affected by the disease are at a 25% of aceruloplasminemia. In asymptomatic siblings, serum concentrations of hemoglobin and hemoglobin A1c should be monitored.To prevent the progression of symptoms of the disease, annual glucose tolerance tests beginning in early teen years to evaluate the onset of diabetes mellitus. Those at risk should avoid taking iron supplements.
Treatment
Treatment includes the use of iron chelating agents (such as desferrioxamine) to lower brain and liver iron stores, and to prevent progression of neurologic symptoms. This, combined with fresh-frozen human plasma (FFP) works effectively in decreasing liver iron content. Repetitive use of FFP can even improve neurologic symptoms. Antioxidants such as vitamin E can be used simultaneously to prevent tissue damage to the liver and pancreas.
See also
Human iron metabolism
Iron overload disorder
References
External links
GeneReviews/NCBI/NIH/UW entry on Aceruloplasminemia
OMIM entries on Aceruloplasminemia |
Pruritic folliculitis of pregnancy | Pruritic folliculitis of pregnancy is a skin condition that occurs in one in 3000 people, about 0.2% of cases, who are in their second to third trimester of pregnancy where the hair follicle becomes inflamed or infected, resulting in a pus filled bump. Some dermatologic conditions aside from pruritic folliculitis during pregnancy include "pruritic urticarial papules and plaques of pregnancy, atopic eruption of pregnancy, pemphigoid gestationis, intrahepatic cholestasis of pregnancy, and pustular psoriasis of pregnancy". This pruritic folliculitis of pregnancy differs from typical pruritic folliculitis; in pregnancy, it is characterized by sterile hair follicles becoming inflamed mainly involving the trunk, contrasting how typical pruritic folliculitis is mainly localized on "the upper back, shoulders, and chest." This condition was first observed after some pregnant individuals showed signs of folliculitis that were different than seen before. The inflammation was thought to be caused by hormonal imbalance, infection from bacteria, fungi, viruses or even an ingrown hair. However, there is no known definitive cause as of yet. These bumps usually begin on the belly and then spread to upper regions of the body as well as the thighs. This condition does not harm the fetus or the mother and usually resolves after delivery of the baby. The rate of incidence could possibly be higher but due to the unknown etiology of the condition, misdiagnosis, and varying levels of severity, it is difficult to differentiate. Pruritic folliculitis of pregnancy is currently classified as atopic eruption of pregnancy (AEP) in a retrospective study done in 2006 that compared this condition to eczema and prurigo of pregnancy, which occurred in 49.7% and 0.8% of cases respectively, with eczema clearly being more frequent. Unlike typical pruritic folliculitis which does not resolve on its own, pruritic folliculitis of pregnancy clears spontaneously on delivery or in postpartum period. Fortunately, pruritic folliculitis of pregnancy has no mortality effects or significant adverse effects on the mother or on the fetus.Currently, there are no treatment guidelines for this condition due to the nature of its unknown etiology but symptom relief is strongly emphasized using non-pharmacological interventions such as warm baths or wearing loose clothing. If itchiness and discomfort persists, benzoyl peroxide, low to mid potency topical steroids, or antihistamines can be tried. Novel treatments have also shown potential in treating case studies of pruritic folliculitis of pregnancy, such as using ultraviolet phototherapy. However, further investigation is still required to study its efficacy and safety in second to third trimester pregnant patients.
History
This condition was first observed in six people in 1981 with many different speculations but no real evidence as to a specific cause. These people had papules starting at various times throughout the second to third trimester with varying severity. Biopsies were taken from these people over a 15 month period in order to examine the composition of these papules. After using H&E, hematoxylin and eosin, to stain the samples, the researchers only found some inflammatory cells like neutrophils, monocytes, lymphocytes, and eosinophils. In four of the samples, immunofluorescence microscopy, where fluorescent antibodies bind to a protein of interest and the expression levels are observed through microscopy, was used but there were no signs of immunoglobulins such as IgG, IgM, IgA or C3 found. Since the first description of this condition, there were very few case reports after, indicating the infrequency of pruritic folliculitis. This was also shown by a prospective study that was conducted in 1994 by Roger et al. that concluded with one individual out of 3,192 pregnant mothers (0.03%) had symptoms which were consistent with the diagnosis of pruritic folliculitis.
Pathophysiology
Folliculitis, by itself, is a common inflammation process of hair follicles in response to infection or damage to the hair follicles. This inflammatory response can be caused by bacteria, fungi, viruses, or simply ingrown hair. However, pruritic folliculitis of pregnancy is different in that it only occurs in pregnant individuals and during the second or third trimester of pregnancy. There is no clear mechanism in how pruritic folliculitis of pregnancy develops. Because this is a rare condition, there is still currently not enough research to study the cause of it. Some research suggest that this condition may be due to hormone level imbalance during pregnancy . Other research indicate that this condition could be due to immunological changes, such as the reduction of T helper 1 immune cells and the increase in T helper 2 immune cells that occur specifically when pregnant. However, there is not enough evidence to clearly support these claims. Although the pathophysiology of pruritic folliculitis of pregnancy is currently unknown, it has not been significantly linked to harm to either mother or baby. Moreover, this condition resolves after pregnancy and does not affect the development of the baby or recovery of the mother after delivery.
Suspected risk factors
There are currently no studies into the etiology behind pruritic folliculitis specifically in pregnancy; however, suspected risk factors include:
Dry skin
Genetics affecting hormone production
Poor personal hygiene
Family history of pruritus in pregnancy
Family history of eczema, hay fever, or asthma
Pruritus while taking contraceptive pill prior to pregnancy
Signs and Symptoms
The signs and symptoms of pruritic folliculitis of pregnancy include: redness of the skin, small red bumps that surrounds a hair follicle, and red bumps that are filled with pus "that usually appear first on the abdomen and may spread to the chest, upper portion of the back, shoulders, arms, and thighs" and it occurs during the second or third trimester of pregnancy. These symptoms are typically "mildly pruritic or asymptomatic" lasting between one week to several months. However, symptoms usually self-relieves spontaneously within one month after birth.
Diagnosis
The diagnosis of pruritic folliculitis of pregnancy is established based on clinical features such as redness of the skin consisting of small red bumps that surrounds a hair follicle and histopathologic features such as immune cells within the pus along with microscopic testing that shows there is no bacteria, microorganism, or other conditions that could cause itchy skin. Diagnosis for pruritic folliculitis of pregnancy requires patients to go through a biopsy, which consists of taking samples from the tissue to evaluate whether their lesions match the physical factors of pruritic folliculitis. Other pregnancy associated skin diseases must be ruled out along side obstetric cholestasis, which is a disorder that affects the liver during pregnancy.There is a great deal of overlap between the following conditions in pregnancy: eczema, prurigo, and pruritic folliculitis. Because of this, they are grouped in a class called atopic eruption of pregnancy. Compared to other pregnancy associated skin conditions, conditions in the class of atopic eruption of pregnancy occurs much earlier.
Management/Treatment
There is currently no official treatment guidelines for pruritic folliculitis of pregnancy as its etiology and clinical presentations still require further investigation; however, the goal of treatment is to relieve symptoms without causing harm to the mother or fetus. Non-pharmacological intervention is recommended first before using pharmacological agents to treat symptoms.
Since pruritic folliculitis of pregnancy appears in later stages of pregnancy and self-resolves post-partum, non-pharmacological interventions are recommended first to relieve itching symptoms. These interventions focuses on incorporating lifestyle changes which include: switching to loose-fitting clothes, using emollients, taking warm baths, avoiding harsh soaps, and maintaining good personal hygiene.If itching symptoms still persist, low to mid potency topical corticosteroids and first-generation antihistamines can be considered and may improve appearance of skin lesions. However, they may also not provide complete relief. Commonly used agents to treat pruritic folliculitis of pregnancy include: 10% topical benzoyl peroxide, 1% topical hydrocortisone, first generation H1 receptor blockers such as diphenhydramine or chlorpheniramine, and a short course of systemic corticosteroids such as prednisone.Narrowband ultraviolet B phototherapy has also been explored as a novel treatment option for pruritic folliculitis of pregnancy in one case study. Further investigation that leads to clinical trials is still required to understand the efficacy and safety of this unconventional treatment option.A comprehensive literature review using Medline and Cochrane Database relating to skin disease in pregnancy from 1990-2005 found that pruritic folliculitis of pregnancy has no associated morbidity for the mother or fetus and the condition will go away after pregnancy.An article from American Family Physician in 2007 states pruritic folliculitis of pregnancy has "no identified adverse effects" on pregnancy risks and that pruritic folliculitis of pregnancy can be treated using topical corticosteroids, topical benzoyl peroxide, or ultraviolet B light therapy.
Clinical Studies and Case Reports
There was a case report about a 30 year old women who was in her tenth week of her second pregnancy. She had widespread papulopustular follicular eruption (rash involving hair follicles) mainly affecting her limbs. She was first treated for a bacteria-associated folliculitis, to which she had some symptom relief. However, the continuation of the pruritic folliculitis still persisted. She was later diagnosised with pruritic folliculitis of pregnancy after a histopathologic test was done to confirm sterility and immune cells. She then started "narrowband ultraviolet (UV) B phototherapy at 70% of the minimal erythemal dose with 20% increments using a three times per week treatment schedule" at 11 weeks of her pregnancy. With this treatment, her skin greatly improved after 10 treatments and completely resolved after 20 treatments. She did not have pruritic folliculitis for the remainder of her pregnancy.Treatment, whether it is pharmacological or non-pharmacological, can vary in pregnant individuals with pruritic folliculitis. The patients choice to accept such treatment can vary as well. There have been case reports on resolution of pruritic folliculitis in patients who declined and accepted treatment. There was a case report on a 39-year-old woman who experienced a 2-month long manifestation of pruritic folliculitis during the 27th week of pregnancy. The signs, symptoms, and histology of physical presentation were consistent with pruritic folliculitis. Although benzoyl peroxide was prescribed, the patient declined treatment. Without any treatment, her pruritic folliculitis condition resolved after giving birth. In another case report, a 26 year old woman who was 31 weeks into her pregnancy, reported that these inflamed pustules formed over her upper torso especially around her linea nigra and changed over the course of the last 2 months. The diagnosis was confirmed after laboratory tests showed that there was mainly neutrophils and damaged follicle structures. The symptoms were treated with a 5% topical benzoyl peroxide gel but the pruritic folliculitis completely went away after the first week after delivering the baby.In an effort to establish a possible pathophysiologic mechanism behind pruritic folliculitis of pregnancy, a 2005 case study found pityrosporum yeast in the hair follicles of a pregnant 24 year-old patient. Pityrosporum yeast is typically grouped in hair follicles, leading to an inflammation of the pore causing folliculitis and symptoms of itching. However, it is important to note that this patients pruritic folliculitis lesions did not improve after delivery of the baby. This finding may lead investigators to believe that this patients lesions may not be contributed from the pregnancy, but instead it can be speculated that the reason behind the presence of this patients lesions postpartum is due to hot and humid weather, making her lesions more difficult to heal after giving birth.
See also
Prurigo gestationis
List of cutaneous conditions
Pruritic urticarial papules and plaques of pregnancy (PUPPP) rash
Intrahepatic cholestasis of pregnancy
== References == |
Schmitt Gillenwater Kelly syndrome | Schmitt Gillenwater Kelly syndrome is a rare autosomal dominant congenital disorder consisting of radial hypoplasia, triphalangeal thumbs, hypospadias, and maxillary diastema.
References
== External links == |
Diffuse panbronchiolitis | Diffuse panbronchiolitis (DPB) is an inflammatory lung disease of unknown cause. It is a severe, progressive form of bronchiolitis, an inflammatory condition of the bronchioles (small air passages in the lungs). The term diffuse signifies that lesions appear throughout both lungs, while panbronchiolitis refers to inflammation found in all layers of the respiratory bronchioles (those involved in gas exchange). DPB causes severe inflammation and nodule-like lesions of terminal bronchioles, chronic sinusitis, and intense coughing with large amounts of sputum production.
The disease is believed to occur when there is susceptibility, or a lack of immune system resistance, to DPB-causing bacteria or viruses, caused by several genes that are found predominantly in individuals of East Asian descent. The highest incidence occurs among Japanese people, followed by Koreans. DPB occurs more often in males and usually begins around age 40. It was recognized as a distinct new disease in the early 1960s and was formally named diffuse panbronchiolitis in 1969.
If left untreated, DPB progresses to bronchiectasis, an irreversible lung condition that involves enlargement of the bronchioles, and pooling of mucus in the bronchiolar passages. Daily treatment of DPB with macrolide antibiotics such as erythromycin eases symptoms and increases survival time, but the disease currently has no known cure. The eventual result of DPB can be respiratory failure and heart problems.
Classification
The term "bronchiolitis" generally refers to inflammation of the bronchioles. DPB is classified as a form of "primary bronchiolitis", which means that the underlying cause of bronchiolitis is originating from or is confined to the bronchioles. Along with DPB, additional forms of primary bronchiolitis include bronchiolitis obliterans, follicular bronchiolitis, respiratory bronchiolitis, mineral dust airway disease, and a number of others. Unlike DPB, bronchiolitis that is not considered "primary" would be associated with diseases of the larger airways, such as chronic bronchitis.
Signs and symptoms
Symptoms of DPB include chronic sinusitis (inflamed paranasal sinuses), wheezing, crackles (respiratory sounds made by obstructions such as phlegm and secretions in the lungs), dyspnea (shortness of breath), and a severe cough that yields large amounts of sputum (coughed-up phlegm). There may be pus in the sputum, and affected individuals may have fever. Typical signs of DPB progression include dilation (enlargement) of the bronchiolar passages and hypoxemia (low levels of oxygen in the blood). If DPB is left untreated, bronchiectasis will occur; it is characterized by dilation and thickening of the walls of the bronchioles, inflammatory damage to respiratory and terminal bronchioles, and pooling of mucus in the lungs. DPB is associated with progressive respiratory failure, hypercapnia (increased levels of carbon dioxide in the blood), and can eventually lead to pulmonary hypertension (high blood pressure in the pulmonary vein and artery) and cor pulmonale (dilation of the right ventricle of the heart, or "right heart failure").
Cause
DPB is idiopathic, which means an exact physiological, environmental, or pathogenic cause of the disease is unknown. However, several factors are suspected to be involved with its pathogenesis (the way in which the disease works).The major histocompatibility complex (MHC) is a large genomic region found in most vertebrates that is associated with the immune system. It is located on chromosome 6 in humans. A subset of MHC in humans is human leukocyte antigen (HLA), which controls the antigen-presenting system, as part of adaptive immunity against pathogens such as bacteria and viruses. When human cells are infected by a pathogen, some of them can present parts of the pathogens proteins on their surfaces; this is called "antigen presentation". The infected cells then become targets for types of cytotoxic T-cells, which kill the infected cells so they can be removed from the body.Genetic predisposition for DPB susceptibility has been localized to two HLA haplotypes (a nucleotide or gene sequence difference between paired chromosomes, that is more likely to occur among a common ethnicity or trait) common to people of East Asian descent. HLA-B54 is associated with DPB in the Japanese, while HLA-A11 is associated with the disease in Koreans. Several genes within this region of class I HLA are believed to be responsible for DPB, by allowing increased susceptibility to the disease. The common genetic background and similarities in the HLA profile of affected Japanese and Korean individuals were considered in the search for a DPB gene. It was suggested that a mutation of a suspected disease-susceptibility gene located somewhere between HLA-B and HLA-A had occurred on an ancestral chromosome carrying both HLA-B54 and HLA-A11. Further, it is possible that a number of genetic recombination events around the disease locus (location on a chromosome) could have resulted in the disease being associated with HLA-B54 in the Japanese and HLA-A11 in Koreans. After further study, it was concluded that a DPB susceptibility gene is located near the HLA-B locus at chromosome 6p21.3. Within this area, the search for a genetic cause of the disease has continued.Because many genes belonging to HLA remain unidentified, positional cloning (a method used to identify a specific gene, when only its location on a chromosome is known) has been used to determine that a mucin-like gene is associated with DPB. In addition, diseases caused by identified HLA genes in the DPB-susceptibility region have been investigated. One of these, bare lymphocyte syndrome I (BLS I), exhibits a number of similarities with DPB in those affected, including chronic sinusitis, bronchiolar inflammation and nodules, and the presence of H. influenzae. Also like DPB, BLS I responds favorably to erythromycin therapy by showing a resolution of symptoms. The similarities between these two diseases, the corresponding success with the same mode of treatment, and the fact that the gene responsible for BLS I is located within the DPB-causing area of HLA narrows the establishment of a gene responsible for DPB. Environmental factors such as inhaling toxic fumes and cigarette smoking are not believed to play a role in DPB, and unknown environmental and other non-genetic causes—such as unidentified bacteria or viruses—have not been ruled out.Cystic fibrosis (CF), a progressive multi-system lung disease, has been considered in the search for a genetic cause of DPB. This is for a number of reasons. CF, like DPB, causes severe lung inflammation, abundant mucus production, infection, and shows a genetic predominance among Caucasians of one geographic group to the rarity of others; whereas DPB dominates among East Asians, CF mainly affects individuals of European descent. While no gene has been implicated as the cause of DPB, mutation in a specific gene—much more likely to occur in Europeans—causes CF. This mutation in the CF-causing gene is not a factor in DPB, but a unique polymorphism (variation) in this gene is known to occur in many Asians not necessarily affected by either disease. It is being investigated whether this gene in any state of mutation could contribute to DPB.
Pathophysiology
Inflammation is a normal part of the human immune response, whereby leukocytes (white blood cells), including neutrophils (white blood cells that specialize in causing inflammation), gather, and chemokines (proteins released from certain cells, which activate or elicit a response from other cells) accumulate at any location in the body where bacterial or viral infections occur. Inflammation interferes with the activity of bacteria and viruses, and serves to clear them from the body. In DPB, bacteria such as Haemophilus influenzae and Pseudomonas aeruginosa can cause the proliferation of inflammatory cells into the bronchiolar tissues. However, when neither bacteria are present with DPB, the inflammation continues for an as yet unknown reason. In either circumstance, inflammation in DPB can be so severe that nodules containing inflammatory cells form in the walls of the bronchioles. The presence of inflammation and infection in the airways also results in the production of excess mucus, which must be coughed up as sputum. The combination of inflammation, nodule development, infection, mucus, and frequent cough contributes to the breathing difficulties in DPB.The fact that inflammation in DPB persists with or without the presence of P. aeruginosa and H. influenzae provides a means to determine several mechanisms of DPB pathogenesis. Leukotrienes are eicosanoids, signaling molecules made from essential fatty acids, which play a role in many lung diseases by causing the proliferation of inflammatory cells and excess mucus production in the airways. In DPB and other lung diseases, the predominant mediator of neutrophil-related inflammation is leukotriene B4, which specializes in neutrophil proliferation via chemotaxis (the movement of some types of cells toward or away from certain molecules).Inflammation in DPB is also caused by the chemokine MIP-1alpha and its involvement with CD8+ T cells. Beta defensins, a family of antimicrobial peptides found in the respiratory tract, are responsible for further inflammation in DPB when a pathogen such as P. aeruginosa is present. If present with DPB, the human T-lymphotropic virus, type I, a retrovirus, modifies DPB pathogenesis by infecting T helper cells and altering their effectiveness in recognizing the presence of known or unknown pathogens involved with DPB.
Diagnosis
The diagnosis of DPB requires analysis of the lungs and bronchiolar tissues, which can require a lung biopsy, or the more preferred high resolution computed tomography (HRCT) scan of the lungs. The diagnostic criteria include severe inflammation in all layers of the respiratory bronchioles and lung tissue lesions that appear as nodules within the terminal and respiratory bronchioles in both lungs. The nodules in DPB appear as opaque lumps when viewed on X-rays of the lung, and can cause airway obstruction, which is evaluated by a pulmonary function test, or PFT. Lung X-rays can also reveal dilation of the bronchiolar passages, another sign of DPB. HRCT scans often show blockages of some bronchiolar passages with mucus, which is referred to as the "tree-in-bud" pattern. Hypoxemia, another sign of breathing difficulty, is revealed by measuring the oxygen and carbon dioxide content of the blood, using a blood test called arterial blood gas. Other findings observed with DPB include the proliferation of lymphocytes (white blood cells that fight infection), neutrophils, and foamy histiocytes (tissue macrophages) in the lung lining. Bacteria such as H. influenzae and P. aeruginosa are also detectable, with the latter becoming more prominent as the disease progresses. The white blood, bacterial and other cellular content of the blood can be measured by taking a complete blood count (CBC). Elevated levels of IgG and IgA (classes of immunoglobulins) may be seen, as well as the presence of rheumatoid factor (an indicator of autoimmunity). Hemagglutination, a clumping of red blood cells in response to the presence of antibodies in the blood, may also occur. Neutrophils, beta-defensins, leukotrienes, and chemokines can also be detected in bronchoalveolar lavage fluid injected then removed from the bronchiolar airways of individuals with DPB, for evaluation.
Differential diagnosis
In the differential diagnosis (finding the correct diagnosis between diseases that have overlapping features) of some obstructive lung diseases, DPB is often considered. A number of DPB symptoms resemble those found with other obstructive lung diseases such as asthma, chronic bronchitis, and emphysema. Wheezing, coughing with sputum production, and shortness of breath are common symptoms in such diseases, and obstructive respiratory functional impairment is found on pulmonary function testing. Cystic fibrosis, like DPB, causes severe lung inflammation, excess mucus production, and infection; but DPB does not cause disturbances of the pancreas nor the electrolytes, as does CF, so the two diseases are different and probably unrelated. DPB is distinguished by the presence of lesions that appear on X-rays as nodules in the bronchioles of both lungs; inflammation in all tissue layers of the respiratory bronchioles; and its higher prevalence among individuals with East Asian lineage.DPB and bronchiolitis obliterans are two forms of primary bronchiolitis. Specific overlapping features of both diseases include strong cough with large amounts of often pus-filled sputum; nodules viewable on lung X-rays in the lower bronchi and bronchiolar area; and chronic sinusitis. In DPB, the nodules are more restricted to the respiratory bronchioles, while in OB they are often found in the membranous bronchioles (the initial non-cartilaginous section of the bronchiole, that divides from the tertiary bronchus) up to the secondary bronchus. OB is a bronchiolar disease with worldwide prevalence, while DPB has more localized prevalence, predominantly in Japan. Prior to clinical recognition of DPB in recent years, it was often misdiagnosed as bronchiectasia, COPD, IPF, phthisis miliaris, sarcoidosis or alveolar cell carcinoma.
Treatment
Macrolide antibiotics, such as erythromycin, are an effective treatment for DPB when taken regularly over an extended period of time. Clarithromycin or roxithromycin are also commonly used. The successful results of macrolides in DPB and similar lung diseases stems from managing certain symptoms through immunomodulation (adjusting the immune response), which can be achieved by taking the antibiotics in low doses. Treatment consists of daily oral administration of erythromycin for two to three years, an extended period that has been shown to dramatically improve the effects of DPB. This is apparent when an individual undergoing treatment for DPB, among a number of disease-related remission criteria, has a normal neutrophil count detected in BAL fluid, and blood gas (an arterial blood test that measures the amount of oxygen and carbon dioxide in the blood) readings show that free oxygen in the blood is within the normal range. Allowing a temporary break from erythromycin therapy in these instances has been suggested, to reduce the formation of macrolide-resistant P. aeruginosa. However, DPB symptoms usually return, and treatment would need to be resumed. Although highly effective, erythromycin may not prove successful in all individuals with the disease, particularly if macrolide-resistant P. aeruginosa is present or previously untreated DPB has progressed to the point where respiratory failure is occurring.With erythromycin therapy in DPB, great reduction in bronchiolar inflammation and damage is achieved through suppression of not only neutrophil proliferation, but also lymphocyte activity and obstructive mucus and water secretions in airways. The antibiotic effects of macrolides are not involved in their beneficial effects toward reducing inflammation in DPB. This is evident because the treatment dosage is much too low to fight infection, and in DPB cases with the occurrence of macrolide-resistant P. aeruginosa, erythromycin therapy still reduces inflammation.A number of factors are involved in suppression of inflammation by erythromycin and other macrolides. They are especially effective at inhibiting the proliferation of neutrophils, by diminishing the ability of interleukin 8 and leukotriene B4 to attract them. Macrolides also reduce the efficiency of adhesion molecules that allow neutrophils to stick to bronchiolar tissue linings. Mucus production in the airways is a major culprit in the morbidity and mortality of DPB and other respiratory diseases. The significant reduction of inflammation in DPB attributed to erythromycin therapy also helps to inhibit the production of excess mucus.
Prognosis
Untreated DPB leads to bronchiectasis, respiratory failure, and death. A journal report from 1983 indicated that untreated DPB had a five-year survival rate of 62.1%, while the 10-year survival rate was 33.2%. With erythromycin treatment, individuals with DPB now have a much longer life expectancy due to better management of symptoms, delay of progression, and prevention of associated infections like P. aeruginosa. The 10-year survival rate for treated DPB is about 90%. In DPB cases where treatment has resulted in significant improvement, which sometimes happens after about two years, treatment has been allowed to end for a while. However, individuals allowed to stop treatment during this time are closely monitored. As DPB has been proven to recur, erythromycin therapy must be promptly resumed once disease symptoms begin to reappear. In spite of the improved prognosis when treated, DPB currently has no known cure.
Epidemiology
DPB has its highest prevalence among the Japanese, at 11 per 100,000 population. Korean, Chinese, and Thai individuals with the disease have been reported as well. A genetic predisposition among East Asians is suggested. The disease is more common in males, with the male to female ratio at 1.4–2:1 (or about 5 men to 3 women). The average onset of the disease is around age 40, and two-thirds of those affected are non-smokers, although smoking is not believed to be a cause. The presence of HLA-Bw54 increases the risk of diffuse panbronchiolitis 13.3-fold.In Europe and the Americas, a relatively small number of DPB cases have been reported in Asian immigrants and residents, as well as in individuals of non-Asian ancestry. Misdiagnosis has occurred in the West owing to less recognition of the disease than in Asian countries. Relative to the large number of Asians living in the west, the small number of them thought to be affected by DPB suggests non-genetic factors may play some role in its cause. This rarity seen in Western Asians may also be partly associated with misdiagnosis.
History
In the early 1960s, a relatively new chronic lung disease was being observed and described by physicians in Japan. In 1969, the name "diffuse panbronchiolitis" was introduced to distinguish it from chronic bronchitis, emphysema, alveolitis, and other obstructive lung disease with inflammation. Between 1978 and 1980, the results of a nationwide survey initiated by the Ministry of Health and Welfare of Japan revealed more than 1,000 probable cases of DPB, with 82 histologically confirmed. By the 1980s, it was internationally recognized as a distinct disease of the lungs.Before the 1980s, the prognosis or expected outcome of DPB was poor, especially in cases with superinfection (the emergence of a new viral or bacterial infection, in addition to the currently occurring infection) by P. aeruginosa. DPB continued to have a very high mortality rate before generalized antibiotic treatment and oxygen therapy were beginning to be used routinely in the effort to manage symptoms. Around 1985, when long-term treatment with the antibiotic erythromycin became the standard for managing DPB, the prognosis significantly improved. In 1990, the association of DPB with HLA was initially asserted.
References
== External links == |
Graft-versus-host disease | Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.
White blood cells of the donors immune system which remain within the donated tissue (the graft) recognize the recipient (the host) as foreign (non-self). The white blood cells present within the transplanted tissue then attack the recipients bodys cells, which leads to GvHD. This should not be confused with a transplant rejection, which occurs when the immune system of the transplant recipient rejects the transplanted tissue; GvHD occurs when the donors immune systems white blood cells reject the recipient. The underlying principle (alloimmunity) is the same, but the details and course may differ. GvHD can also occur after a blood transfusion if the blood products used have not been irradiated or treated with an approved pathogen reduction system.
Types
In the clinical setting, graft-versus-host disease is divided into acute and chronic forms, and scored or graded on the basis of the tissue affected and the severity of the reaction.In the classical sense, acute graft-versus-host disease is characterized by selective damage to the liver, skin (rash), mucosa, and the gastrointestinal tract. Newer research indicates that other graft-versus-host disease target organs include the immune system (the hematopoietic system, e.g., the bone marrow and the thymus) itself, and the lungs in the form of immune-mediated pneumonitis. Biomarkers can be used to identify specific causes of GvHD, such as elafin in the skin. Chronic graft-versus-host disease also attacks the above organs, but over its long-term course can also cause damage to the connective tissue and exocrine glands.Mucosal damage to the vagina can result in severe pain and scarring, and appears in both acute and chronic GvHD. This can result in an inability to have sexual intercourse.
Acute
The acute or fulminant form of the disease (aGvHD) is normally observed within the first 10 to 100 days post-transplant, and is a major challenge to transplants owing to associated morbidity and mortality. About one-third to one-half of allogeneic transplant recipients will develop acute GvHD. Its less common in younger patients and in those with closer human leukocyte antigens (HLA) matches between donor and the patient.The first signs are usually a rash, burning, and redness of the skin on the palms and soles. This can spread over the entire body. Other symptoms can include Nausea, vomiting, stomach cramps, diarrhea (watery and sometimes bloody), loss of appetite, jaundice, abdominal pain, and weight loss.Acute GvHD of the GI tract can result in severe intestinal inflammation, sloughing of the mucosal membrane, severe diarrhea, abdominal pain, nausea, and vomiting. This is typically diagnosed via intestinal biopsy. Liver GvHD is measured by the bilirubin level in acute patients. Skin GvHD results in a diffuse red maculopapular rash, sometimes in a lacy pattern.
Acute GvHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of 1 to a high of 4. Patients with grade IV GvHD usually have a poor prognosis. If the GvHD is severe and requires intense immunosuppression involving steroids and additional agents to get under control, the patient may develop severe infections as a result of the immunosuppression and may die of infection. However, a 2016 study found that the prognosis for patients with grade IV GvHD has improved in recent years.
Chronic
The chronic form of graft-versus-host disease (cGvHD) normally begins 90 to 600 days post-transplant. The appearance of moderate to severe cases of cGVHD adversely influences long-term survival.The first symptom of cGvHD is commonly a rash on the palms of the hands or the soles of the feet, and the rash can spread and is usually itchy and dry. In severe cases, the skin may blister and peel, like a bad sunburn. A fever may also develop. Other symptoms of chronic GVHD can include:
Decreased appetite
Diarrhea
Abdominal (belly) cramps
Weight loss
Yellowing of the skin and eyes (jaundice)
Enlarged liver
Bloated abdomen (belly)
Pain in the upper right part of the abdomen (belly)
Increased levels of liver enzymes in the blood (seen on blood tests)
Skin that feels tight
Dry, burning eyes
Dryness or painful sores in the mouth
Burning sensations when eating acidic foods
Bacterial infections
Blockages in the smaller airways of the lungsIn the oral cavity, chronic graft-versus-host disease manifests as lichen planus with a higher risk of malignant transformation to oral squamous cell carcinoma in comparison to the classical oral lichen planus. Oral cancer associated with graft-versus-host disease may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-hematopoietic stem cell transplantation patients.
Causes
Three criteria, known as the Billingham criteria, must be met in order for GvHD to occur.
An immuno-competent graft is administered, with viable and functional immune cells.
The recipient is immunologically different from the donor – histo-incompatible.
The recipient is immunocompromised and therefore cannot destroy or inactivate the transplanted cells.After bone marrow transplantation, T cells present in the graft, either as contaminants or intentionally introduced into the host, attack the tissues of the transplant recipient after perceiving host tissues as antigenically foreign. The T cells produce an excess of cytokines, including TNF-α and interferon-gamma (IFNγ). A wide range of host antigens can initiate graft-versus-host disease, among them the human leukocyte antigens (HLA). However, graft-versus-host disease can occur even when HLA-identical siblings are the donors. HLA-identical siblings or HLA-identical unrelated donors often have genetically different proteins (called minor histocompatibility antigens) that can be presented by major histocompatibility complex (MHC) molecules to the donors T-cells, which see these antigens as foreign and so mount an immune response.Antigens most responsible for graft loss are HLA-DR (first six months), HLA-B (first two years), and HLA-A (long-term survival).While donor T-cells are undesirable as effector cells of graft-versus-host disease, they are valuable for engraftment by preventing the recipients residual immune system from rejecting the bone marrow graft (host-versus-graft). In addition, as bone marrow transplantation is frequently used to treat cancer, mainly leukemias, donor T-cells have proven to have a valuable graft-versus-tumor effect. A great deal of current research on allogeneic bone marrow transplantation involves attempts to separate the undesirable graft-vs-host disease aspects of T-cell physiology from the desirable graft-versus-tumor effect.
Transfusion-associated GvHD
This type of GvHD is associated with transfusion of un-irradiated blood to immunocompromised recipients. It can also occur in situations in which the blood donor is homozygous and the recipient is heterozygous for an HLA haplotype. It is associated with higher mortality (80–90%) due to involvement of bone marrow lymphoid tissue, however the clinical manifestations are similar to GVHD resulting from bone marrow transplantation. Transfusion-associated GvHD is rare in modern medicine. It is almost entirely preventable by controlled irradiation of blood products to inactivate the white blood cells (including lymphocytes) within.
Thymus transplantation
Thymus transplantation may be said to be able to cause a special type of GvHD because the recipients thymocytes would use the donor thymus cells as models when going through the negative selection to recognize self-antigens, and could therefore still mistake own structures in the rest of the body for being non-self. This is a rather indirect GvHD because it is not directly cells in the graft itself that causes it but cells in the graft that make the recipients T cells act like donor T cells. It can be seen as a multiple-organ autoimmunity in xenotransplantation experiments of the thymus between different species. Autoimmune disease is a frequent complication after human allogeneic thymus transplantation, found in 42% of subjects over 1 year post transplantation. 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.
Prevention
DNA-based tissue typing allows for more precise HLA matching between donors and transplant patients, which has been proven to reduce the incidence and severity of GvHD and to increase long-term survival.
The T-cells of umbilical cord blood (UCB) have an inherent immunological immaturity, and the use of UCB stem cells in unrelated donor transplants has a reduced incidence and severity of GvHD.
Methotrexate, cyclosporin and tacrolimus are common drugs used for GvHD prophylaxis. Further research is necessary to evaluate whether mesenchymal stromal cells can also be used for the prophylaxis.
Graft-versus-host disease can largely be avoided by performing a T-cell-depleted bone marrow transplant. However, these types of transplants come at a cost of diminished graft-versus-tumor effect, greater risk of engraftment failure, or cancer relapse, and general immunodeficiency, resulting in a patient more susceptible to viral, bacterial, and fungal infection. In a multi-center study, disease-free survival at 3 years was not different between T cell-depleted and T cell-replete transplants.
Treatment
Intravenously administered glucocorticoids, such as prednisone, are the standard of care in acute GvHD and chronic GVHD. The use of these glucocorticoids is designed to suppress the T-cell-mediated immune onslaught on the host tissues; however, in high doses, this immune-suppression raises the risk of infections and cancer relapse. Therefore, it is desirable to taper off the post-transplant high-level steroid doses to lower levels, at which point the appearance of mild GVHD may be welcome, especially in HLA mis-matched patients, as it is typically associated with a graft-versus-tumor effect.. Cyclosporine and tacrolimus are calcineurin inhibitors. Both substances are structurally different but have the same mechanism of action. Cyclosporin binds to the cytosolic protein Peptidyl-prolyl cis-trans isomerase A (known as cyclophilin), while tacrolimus binds to the cytosolic protein Peptidyl-prolyl cis-trans isomerase FKBP12. These complexes inhibit calcineurin, block dephosphorylation of the transcription factor NFAT of activated T-cells and its translocation into the nucleus. Standard prophylaxis involves the use of cyclosporine for six months with methotrexate. Cyclosporin levels should be maintained above 200 ng/ml.
Other substances that have been studied for GvHD treatment include, for example: sirolimus, pentostatin, etanercept, and alemtuzumab.In August 2017 the US FDA approved ibrutinib to treat chronic GvHD after failure of one or more other systemic treatments.
Clinical research
There are a large number of clinical trials either ongoing or recently completed in the investigation of graft-versus-host disease treatment and prevention.On May 17, 2012, Osiris Therapeutics announced that Canadian health regulators approved Prochymal, its drug for acute graft-versus-host disease in children who have failed to respond to steroid treatment. Prochymal is the first stem cell drug to be approved for a systemic disease.In January 2016, Mesoblast released results of a phase 2 clinical trial on 241 children with acute Graft-versus-host disease, that was not responsive to steroids. The trial was of a mesenchymal stem cell therapy known as remestemcel-L or MSC-100-IV. Survival rate was 82% (vs 39% of controls) for those who showed some improvement after 1 month, and in the long term 72% (vs 18% of controls) for those that showed little effect after 1 month.
HIV elimination
Graft-versus-host disease has been implicated in eliminating several cases of HIV, including The Berlin Patient and 6 others in Spain.
See also
Graft-versus-tumor effect
Immunosuppression
Transplant rejection
References
Further reading
Ferrara JLM, Deeg HJ, Burakoff SJ. Graft-Vs.-Host Disease: Immunology, Pathophysiology, and Treatment. Marcel Dekker, 1990 ISBN 0-8247-9728-0
Polsdorfer, JR Gale Encyclopedia of Medicine: Graft-vs.-host disease
== External links == |
Familial episodic pain syndrome | Familial episodic pain syndrome, also known simply as FEPS, is a group of rare genetic peripheral neuropathies which are characterized by recurrent random episodes of intense pain which occur most often in the upper or lower parts of the body occurring in several members of the same family. They are often triggered by cold temperatures, physical exercise, fatigue, etc. It may or may not get better with age.
Types
This disorder is distributed into three types:
FEPS Type 1
This type of familial episodic pain syndrome is characterized by infancy-onset intense and debilitating upper-body episodic pain. Its caused by mutations in the TRPA1 gene, in chromosome 8. It was first described in 2010 by Kremeyer et al. in 21 affected members from a large 4-generation Colombian family. Transmission is autosomal dominant.
FEPS Type 2
This type of familial episodic pain syndrome is characterized by adult-onset episodic paroxysmal pain in the distal lower limbs (feet). Its caused by mutations in the SCN10A gene, in chromosome 3. It was first described in 2012 by Faber et al in a 2-generation family (a man and his son), the proband developed episodic burning, intense pain in his feet at the age of 57 while his son developed it at the age of 39. Transmission is autosomal dominant.
FEPS Type 3
This type of familial episodic pain syndrome is characterized by childhood-onset intense episodic pain on the lower and sometimes upper extremities, this pain typically lasts days and can be treated with anti-inflammatory medication, the pain episodes tend to lower in severity with age. It is caused by mutations in the SCN11A gene, in chromosome 3. It has been described in 13 and 10 members from two large Chinese families and 12 un-related patients. Transmission is autosomal dominant.
== References == |
Giant-cell reticulohistiocytoma | Giant-cell reticulohistiocytoma (also known as Solitary reticulohistiocytoma and Solitary reticulohistiocytosis) is a cutaneous condition characterized by a solitary skin lesion.
See also
Indeterminate cell histiocytosis
List of cutaneous conditions
== References == |
Gastric volvulus | Gastric volvulus or volvulus of stomach is a twisting of all or part of the stomach by more than 180 degrees with obstruction of the flow of material through the stomach, variable loss of blood supply and possible tissue death. The twisting can occur around the long axis of the stomach: this is called organoaxial or around the axis perpendicular to this, called mesenteroaxial. Obstruction is more likely in organoaxial twisting than with mesenteroaxial while the latter is more associated with ischemia. About one third of the cases are associated with a hiatus hernia. Treatment is surgical.
The classic triad (Borchardts Triad) of gastric volvulus, described by Borchardt in 1904, consists of severe epigastric pain, retching (due to sour taste in mouth) without vomiting, inability to pass a nasogastric tube and reportedly occurs in 70% of cases. Sometimes severe pain at the top of left shoulder, this may be due to internal bleeding irritating the diaphragm upon respiration.
Classification
Organoaxial type
In an organoaxial gastric volvulus, the stomach rotates around an axis that connects the gastroesophageal junction and the pylorus. The antrum rotates in opposite direction to the fundus of the stomach. This is the most common type of gastric volvulus, occurring in approximately 59% of cases, and it is usually associated with diaphragmatic defects. Strangulation and necrosis commonly occur with organoaxial gastric volvulus and have been reported in 5–28% of cases. The key imaging feature of organoaxial volvulus is that the greater curvature is located above the lesser curvature of the stomach.
Mesenteroaxial type
The mesenteroaxial axis bisects the lesser and greater curvatures. The antrum rotates anteriorly and superiorly so that the posterior surface of the stomach lies anteriorly. The rotation is usually incomplete and occurs intermittently. Vascular compromise is uncommon. This cause comprises approximately 29% of cases of gastric volvulus. The key imaging feature of mesenteroaxial volvulus is that the antrum is above the gastroesophageal junction.
Combined type
The combined type of gastric volvulus is a rare form in which the stomach twists mesentericoaxially and organoaxially. This type of gastric volvulus makes up the remainder of cases and is usually observed in patients with chronic volvulus.
Cause
Type 1
Gastric volvulus of unknown cause comprises two thirds of cases and is presumably due to abnormal laxity of the gastrosplenic, gastroduodenal, gastrophrenic, and gastrohepatic ligaments. Type 1 gastric volvulus is more common in adults but has been reported in children.
Type 2
Type 2 gastric volvulus is found in one third of patients and is usually associated with congenital or acquired abnormalities that result in abnormal mobility of the stomach.
Diagnosis
On chest radiography, a retrocardiac, gas-filled viscus may be seen in cases of intrathoracic stomach, which confirms the diagnosis. Plain abdominal radiography reveals a massively distended viscus in the upper abdomen. In organoaxial volvulus, plain films may show a horizontally oriented stomach with a single air-fluid level and a paucity of distal gas. In mesenteroaxial volvulus, plain abdominal radiographic findings include a spherical stomach on supine images and 2 air-fluid levels on erect images, with the antrum positioned superior to the fundus.
Upper GI studies
The diagnosis of gastric volvulus is usually based on barium studies; however, some authors recommend computed tomography (CT) scanning as the imaging modality of choice.
Upper gastrointestinal (GI) contrast radiographic studies (using barium or Gastrografin) are sensitive and specific if performed with the stomach in the "twisted" state and may show an upside-down stomach. Contrast studies have been reported to have a diagnostic yield in 81–84% of patients.
Often performed for an evaluation of acute abdominal pain, a computed tomography (CT) scan can offer immediate diagnosis by showing two bubbles with a transition line. Proponents of CT scanning in the diagnosis of gastric volvulus report several benefits, including:
the ability to rapidly diagnose the condition based on a few coronal reconstructed images,
the ability to detect the presence or absence of gastric pneumatosis and free air,
the detection of predisposing factors (i.e., diaphragmatic or hiatal hernias), and
the exclusion of other abdominal pathology.
Endoscopy
Upper gastrointestinal (GI) endoscopy may be helpful in the diagnosis of gastric volvulus. When this procedure reveals distortion of the gastric anatomy with difficulty intubating the stomach or pylorus, it can be highly suggestive of gastric volvulus. In the late stage of gastric volvulus, strangulation of the blood supply can result in progressive ischemic ulceration or mucosal fissuring.
The nonoperative mortality rate for gastric volvulus is reportedly as high as 80%. Historically, mortality rates of 30–50% have been reported for acute gastric volvulus, with the major cause of death being strangulation, which can lead to necrosis and perforation. With advances in diagnosis and management, the mortality rate from acute gastric volvulus is 15–20% and that for chronic gastric volvulus is 0–13%.
References
External links
Schaefer D, Nikoomenesh P, Moore C (1997). "Gastric volvulus: an old disease process with some new twists". Gastroenterologist. 5 (1): 41–5. PMID 9074918. |
Arterial tortuosity syndrome | Arterial tortuosity syndrome is a rare congenital connective tissue condition disorder characterized by elongation and generalized tortuosity of the major arteries including the aorta. It is associated with hyperextensible skin and hypermobility of joints, however symptoms vary depending on the person. Because ATS is so rare, not much is known about the disease.
Signs and symptoms
Among the signs and symptoms demonstrated, by this condition are the following:
Arachnodactyly
Congenital diaphragmatic hernia
Mental dysfunction
Keratoconus
Aortic regurgitation
Blepharophimosis
Genetics
Arterial tortuosity syndrome exhibits autosomal recessive inheritance, and the responsible gene is located at chromosome 20q13. The gene associated with arterial tortuosity syndrome is SLC2A10 and has no less than 23 mutations in those individuals found to have the aforementioned condition.
Pathophysiology
The mechanism of this condition is apparently controlled by(or due to) the SLC2A10 gene. The molecular genetic pathogenesis finds that SLC2A10 encodes GLUT10(in nuclear membrane, or the endoplasmic reticulum, the later of which GLUT10 transports DHA into).Clinically speaking, according to one review, the condition of tortuosity is seen more with the advance of age.
Diagnosis
In terms of the diagnosis of arterial tortuosity syndrome can be done via genetic testing, as well as the following listed below:
CT
MRI
Echocardiogram
Physical exam(for specific characteristics)
Treatment
The treatment of arterial tortuosity syndrome entails possible surgery for aortic aneurysms, as well as, follow ups which should consist of EGC. The prognosis of this condition has it at about 12% mortality
References
Further reading
Segade, Fernando (16 July 2010). "Glucose transporter 10 and arterial tortuosity syndrome: the vitamin C connection". FEBS Letters. 584 (14): 2990–2994. doi:10.1016/j.febslet.2010.06.011. ISSN 1873-3468. PMID 20547159. S2CID 33856792.Review
Wetzel-Strong, Sarah E; Detter, Matthew R; Marchuk, Douglas A (2017-01-01). "The pathobiology of vascular malformations: insights from human and model organism genetics". The Journal of Pathology. 241 (2): 281–293. doi:10.1002/path.4844. ISSN 1096-9896. PMC 5167654. PMID 27859310.
Albuisson, Juliette; Moceri, Pamela; Flori, Elisabeth; Belli, Emre; Gronier, Céline; Jeunemaitre, Xavier (2017-03-21). "Clinical utility gene card for: Arterial tortuosity syndrome". European Journal of Human Genetics. 23 (10): 1432. doi:10.1038/ejhg.2014.294. ISSN 1018-4813. PMC 4592088. PMID 25604859.
== External links == |
Placenta accreta spectrum | Placenta accreta occurs when all or part of the placenta attaches abnormally to the myometrium (the muscular layer of the uterine wall). Three grades of abnormal placental attachment are defined according to the depth of attachment and invasion into the muscular layers of the uterus:
Accreta – chorionic villi attached to the myometrium, rather than being restricted within the decidua basalis.
Increta – chorionic villi invaded into the myometrium.
Percreta – chorionic villi invaded through the perimetrium (uterine serosa).Because of abnormal attachment to the myometrium, placenta accreta is associated with an increased risk of heavy bleeding at the time of attempted vaginal delivery. The need for transfusion of blood products is frequent, and surgical removal of the uterus (hysterectomy) is sometimes required to control life-threatening bleeding.Rates of placenta accreta are increasing. As of 2016, placenta accreta affects an estimated 1 in 272 pregnancies.
Risk factors
An important risk factor for placenta accreta is placenta previa in the presence of a uterine scar. Placenta previa is an independent risk factor for placenta accreta. Additional reported risk factors for placenta accreta include maternal age and multiparity, other prior uterine surgery, prior uterine curettage, uterine irradiation, endometrial ablation, Asherman syndrome, uterine leiomyomata, uterine anomalies, and smoking.
The condition is increased in incidence by the presence of scar tissue i.e. Ashermans syndrome usually from past uterine surgery, especially from a past dilation and curettage, (which is used for many indications including miscarriage, termination, and postpartum hemorrhage), myomectomy, or caesarean section. A thin decidua can also be a contributing factor to such trophoblastic invasion. Some studies suggest that the rate of incidence is higher when the fetus is female. Other risk factors include low-lying placenta, anterior placenta, congenital or acquired uterine defects (such as uterine septa), leiomyoma, ectopic implantation of placenta (including cornual pregnancy).Pregnant women above 35 years of age who have had a caesarian section and now have a placenta previa overlying the uterine scar have a 40% chance of placenta accreta.
Pathogenesis
The placenta forms an abnormally firm and deep attachment to the uterine wall. There is absence of the decidua basalis and incomplete development of the Nitabuchs layer. There are three forms of placenta accreta, distinguishable by the depth of penetration.
Diagnosis
When the antepartum diagnosis of placenta accreta is made, it is usually based on ultrasound findings in the second or third trimester. Sonographic findings that may be suggestive of placenta accreta include:
Loss of normal hypoechoic retroplacental zone
Multiple vascular lacunae (irregular vascular spaces) within placenta, giving "Swiss cheese" appearance
Blood vessels or placental tissue bridging uterine-placental margin, myometrial-bladder interface, or crossing the uterine serosa
Retroplacental myometrial thickness of <1 mm
Numerous coherent vessels visualized with 3-dimensional power Doppler in basal viewUnfortunately, the diagnosis is not easy and is affected by a significant interobserver variability. In doubtful cases it is possible to perform a nuclear magnetic resonance (MRI) of the pelvis, which has a very good sensitivity and specificity for this disorder. MRI findings associated with placenta accreta include dark T2 bands, bulging of the uterus, and loss of the dark T2 interface.Although there are isolated case reports of placenta accreta being diagnosed in the first trimester or at the time of abortion <20 weeks gestational age, the predictive value of first-trimester ultrasound for this diagnosis remains unknown. Women with a placenta previa or "low-lying placenta" overlying a uterine scar early in pregnancy should undergo follow-up imaging in the third trimester with attention to the potential presence of placenta accreta.
Complications
Damage to local organs (e.g., bowel, bladder, uterus and neurovascular structures in the retroperitoneum and lateral pelvic sidewalls from placental implantation and its removal;
Postoperative bleeding requiring repeated surgery;
Amniotic fluid embolism;
Complications (such as dilutional coagulopathy, consumptive coagulopathy, acute transfusion reactions, transfusion-associated lung injury, acute respiratory distress syndrome, and electrolyte abnormalities) caused by transfusion of large volumes of blood products, crystalloids, and other volume expanders;
Postoperative thromboembolism, infection, multisystem organ failure, and maternal death.The exact incidence of maternal mortality related to placenta accreta and its complications is unknown, but it is significant, especially if the urinary bladder is involved
Treatment
Treatment may be delivery by caesarean section and abdominal hysterectomy if placenta accreta is diagnosed before birth. Oxytocin and antibiotics are used for post-surgical management. When there is partially separated placenta with focal accreta, best option is removal of placenta. If it is important to save the womans uterus (for future pregnancies) then resection around the placenta may be successful. Conservative treatment can also be uterus sparing but may not be as successful and has a higher risk of complications.
Techniques include:
Leaving the placenta in the uterus and curettage of uterus. Methotrexate has been used in this case.
Intrauterine balloon catheterisation to compress blood vessels
Embolisation of pelvic vessels
Internal iliac artery ligation
Bilateral uterine artery ligationIn cases where there is invasion of placental tissue and blood vessels into the bladder, it is treated in similar manner to abdominal pregnancy and manual placental removal is avoided. However, this may eventually need hysterectomy and/or partial cystectomy.If the patient decides to proceed with a vaginal delivery, blood products for transfusion and an anesthesiologist are kept ready at delivery.
Epidemiology
The reported incidence of placenta accreta has increased from approximately 0.8 per 1000 deliveries in the 1980s to 3 per 1000 deliveries in the past decade.
Incidence has been increasing with increased rates of caesarean deliveries, with rates of 1 in 4,027 pregnancies in the 1970s, 1 in 2,510 in the 1980s, and 1 in 533 for 1982–2002. In 2002, ACOG estimated that incidence has increased 10-fold over the past 50 years. The risk of placenta accreta in future deliveries after caesarian section is 0.4-0.8%. For patients with placenta previa, risk increases with number of previous caesarean sections, with rates of 3%, 11%, 40%, 61%, and 67% for the first, second, third, fourth, and fifth or greater number of caesarean sections.
References
External links
National Accreta Foundation |
Entoptic phenomenon | Entoptic phenomena (from Ancient Greek ἐντός (entós) within, and ὀπτικός (optikós) visual) are visual effects whose source is within the human eye itself. (Occasionally, these are called entopic phenomena, which is probably a typographical mistake.)
In Helmholtzs words: "Under suitable conditions light falling on the eye may render visible certain objects within the eye itself. These perceptions are called entoptical."
Overview
Entoptic images have a physical basis in the image cast upon the retina. Hence, they are different from optical illusions, which are caused by the visual system and characterized by a visual percept that (loosely said) appears to differ from reality. Because entoptic images are caused by phenomena within the observers own eye, they share one feature with optical illusions and hallucinations: the observer cannot share a direct and specific view of the phenomenon with others.
Helmholtz[1] commented on entoptic phenomena which could be seen easily by some observers, but could not be seen at all by others. This variance is not surprising because the specific aspects of the eye that produce these images are unique to each individual. Because of the variation between individuals, and the inability for two observers to share a nearly identical stimulus, these phenomena are unlike most visual sensations. They are also unlike most optical illusions which are produced by viewing a common stimulus. Yet, there is enough commonality between the main entoptic phenomena that their physical origin is now well understood.
Examples
Some examples of entoptical effects include:
Floaters or muscae volitantes are slowly drifting blobs of varying size, shape, and transparency, which are particularly noticeable when viewing a bright, featureless background (such as the sky) or a point source of diffuse light very close to the eye. They are shadow images of objects floating in liquid between the retina and the jelly inside the eye (the vitreous) or in the vitreous humor itself. They are visible because they move; if they were pinned to retina by the vitreous or fixed within the vitreous they would be as invisible as ordinary viewing of any stationary object, such as the retinal blood vessels (see Purkinje tree below). Some may be individual red blood cells swollen due to osmotic pressure. Others may be chains of red blood cells stuck together; diffraction patterns can be seen around these.[2] Others may be "coagula of the proteins of the vitreous gel, to embryonic remnants, or the condensation round the walls of Cloquets canal" that exist in pockets of liquid within the vitreous.[3] The first two sort of floaters may collect over the fovea (the center of vision), and therefore be more visible, when a person is lying on his or her back looking upwards.
Blue field entoptic phenomenon has the appearance of tiny bright dots moving rapidly along squiggly lines in the visual field. It is much more noticeable when viewed against a field of pure blue light and is caused by white blood cells moving in the capillaries in front of the retina. White cells are larger than red blood cells and can be larger than the diameter of a capillary, so must deform to fit. As a large, deformed white blood cell goes through a capillary, a space opens up in front of it and red blood cells pile up behind. This makes the dots of light appear slightly elongated with dark tails.[4][5]
Haidingers brush is a very subtle bowtie or hourglass shaped pattern that is seen when viewing a field with a component of blue light that is plane or circularly polarized. Its easier to see if the polarisation is rotating with respect to the observers eye, although some observers can see it in the natural polarisation of sky light. If the light is all blue, it will appear as a dark shadow; if the light is full spectrum, it will appear yellow. It is due to the preferential absorption of blue polarized light by pigment molecules in the fovea.[6][7]
Purkinje images are the reflections from the anterior and posterior surfaces of the cornea and the anterior and posterior surfaces of the lens. Although these first four reflections are not entoptic—they are seen by others who are looking at someone’s eye— Becker[8] described how light can reflect from the posterior surface of the lens and then again from the anterior surface of the cornea to focus a second image on the retina, this one much fainter and inverted. Tscherning[9] referred to this as the sixth image (the fifth image is formed by reflections from the anterior surfaces of the lens and cornea to form an image too far in front of the retina to be visible) and noted it was much fainter and best seen with a relaxed emmetropic eye. To see it, one must be in a dark room, with one eye closed; one must look straight ahead while moving a light back and forth in the field of the open eye. Then one should see the sixth Purkinje as a dimmer image moving in the opposite direction.
The Purkinje tree is an image of the retinal blood vessels in ones own eye, first described by Purkyně in 1823.[10] It can be seen by shining the beam of a small bright light through the pupil from the periphery of a subjects vision. This results in an image of the light being focused on the periphery of the retina. Light from this spot then casts shadows of the blood vessels (which lie on top of the retina) onto unadapted portions of the retina. Normally the image of the retinal blood vessels is invisible because of adaptation. Unless the light moves, the image disappears within a second or so. If the light is moved at about 1 Hz, adaptation is defeated, and a clear image can be seen indefinitely. The vascular figure is often seen by patients during an ophthalmic examination when the examiner is using an ophthalmoscope. Another way in which the shadows of blood vessels may be seen is by holding a bright light against the eyelid at the corner of the eye. The light penetrates the eye and casts a shadow on the blood vessels as described previously. The light must be jiggled to defeat adaptation. Viewing in both cases is improved in a dark room while looking at a featureless background. This topic is discussed in more detail by Helmholtz.
Purkinjes blue arcs are associated with the activity of the nerves sending signals from where a spot of light is focussed on the retina near the fovea to the optic disk. To see it, one needs to look at the right edge of a small red light in a dark room with the right eye (left eye closed) after dark-adapting for about 30 seconds; one should see two faint blue arcs starting at the light and heading towards the blind spot. When one looks at the left edge, one will see a faint blue spike going from the light to the right.[11]
A phosphene is the perception of light without light actually entering the eye, for instance caused by pressure applied to the closed eyes.A phenomenon that could be entoptical if the eyelashes are considered to be part of the eye is seeing light diffracted through the eyelashes. The phenomenon appears as one or more light disks crossed by dark blurry lines (the shadows of the lashes), each having fringes of spectral colour. The disk shape is given by the circular aperture of the pupil.
See also
References
Sources
Jan E. Purkyně, 1823: Beiträge zur Kenntniss des Sehens in subjectiver Hinsicht in Beobachtungen und Versuche zur Physiologie der Sinne, In Commission der J.G. Calveschen Buchhandlung, Prag.
H. von Helmholtz, Handbuch der Physiologischen Optik, published as "Helmholtzs Treatise on Physiological Optics, Translated from the Third German Edition," ed. James P. C. Southall; 1925; The Optical Society of America.
Leonard Zusne, 1990: Anomalistic Psychology: A Study of Magical Thinking; Lea; ISBN 0-8058-0508-7 [12]
Becker, O., 1860, “Über Wahrnehmung eines Reflexbildes im eigenen Auge [About perception of a reflected image in your own eye],” Wiener Medizinische Wochenschrift, pp. 670 672 & 684 688.
M. Tscherning, 1920, Physiologic Optics; Third Edition, (English translation by C. Weiland). Philadelphia: Keystone Publishing Co. pp. 55–56.
White, Harvey E., and Levatin, Paul, 1962, "Floaters in the eye," Scientific American, Vol. 206, No. 6, June, 1962, pp. 199 127.
Duke Elder, W. S. (ed.), 1962, System of Ophthalmology, Volume 7, The Foundations of Ophthalmology: heredity pathology diagnosis and therapeutics, St. Louis, The C.V. Mosby Company. p450.
Snodderly, D.M., Weinhaus, R.S., & Choi, J.C. (1992). Neural-vascular relationships in central retina of Macaque monkeys (Macaca fascicularis). Journal of Neuroscience, 12(4), 1169-1193. Available online at: http://www.jneurosci.org/cgi/reprint/12/4/1169.pdf.
Sinclair, S.H., Azar-Cavanagh, M., Soper, K.A., Tuma, R.F., & Mayrovitz, H.N. (1989). Investigation of the source of the blue field entoptic phenomenon. Investigative Ophthalmology & Visual Science, 30(4), 668-673. Available online at: http://www.iovs.org/.
Giles Skey Brindley, Physiology of the Retina and Visual Pathway, 2nd ed. (Edward Arnold Ltd., London, 1970), pp. 140–141.
Bill Reid, “Haidingers brush,” Physics Teacher, Vol. 28, p. 598 (Dec. 1990).
Walker, J., 1984, “How to stop a spinning object by humming and perceive curious blue arcs around the light,” Scientific American, February, Vol. 250, No. 2, pp. 136 138, 140, 141, 143, 144, 148.
External links
Entoptic+Vision at the US National Library of Medicine Medical Subject Headings (MeSH)
Picture of the entoptic phenomenon: Vitreous Floaters (PDF file, requires an Acrobat Reader or plugin)
Diagram of entoptic subjective visual phenomena
Video describing history and science of first entoptic viewing technique
Video describing history and science of second entoptic viewing technique
The Relation Between Migraine, Typical Migraine Aura and “Visual Snow” |
Fluorosis | Fluorosis may refer to:
Dental fluorosis, a disturbance of dental enamel caused by excessive exposure to high concentrations of fluoride during tooth development.
Skeletal fluorosis, a bone disease caused by excessive accumulation of fluoride in the bones
Fluoride toxicity, elevated levels of the fluoride ion in the body |
Weill–Marchesani syndrome | Weill–Marchesani syndrome is a rare genetic disorder characterized by short stature; an unusually short, broad head (brachycephaly) and other facial abnormalities; hand defects, including unusually short fingers (brachydactyly); and distinctive eye (ocular) abnormalities. It was named after ophthalmologists Georges Weill (1866–1952) and Oswald Marchesani (1900–1952) who first described it in 1932 and 1939, respectively.
The eye manifestations typically include unusually small, round lenses of the eyes (microspherophakia), which may be prone to dislocating (ectopia lentis), as well as other ocular defects. Due to such abnormalities, affected individuals may have varying degrees of visual impairment, ranging from nearsightedness myopia to blindness. Weill–Marchesani syndrome may have autosomal recessive inheritance involving the ADAMTS10 gene, or autosomal dominant inheritance involving the FBN1 gene. In some cases there is no association with either of these genes.
Diagnosis
Diagnosis is made when several characteristic clinical signs are observed. There is no single test to confirm the presence of Weill–Marchesani syndrome. Exploring family history or examining other family members may prove helpful in confirming this diagnosis.
Treatment
Eye surgery has been documented to help those with ocular diseases, such as some forms of glaucoma.
Prognosis
However, long term medical management of glaucoma has not proven to be successful for patients with Weill–Marchesani syndrome. Physical therapy and orthopedic treatments are generally prescribed for problems stemming from mobility from this connective tissue disorder. However, this disorder has no cure, and generally, treatments are given to improve quality of life.
See also
ADAMTS17
LTBP2
References
External links
GeneReviews/NCBI/NIH/UW entry on Weill-Marchesani Syndrome |
Granular myringitis | Granular myringitis is a long term condition in which there is inflammation of the tympanic membrane in the ear and formation of granulation tissue within the tympanic membrane. It is a type of otitis externa.Without treatment it can lead to narrowing of the ear canal. A number of treatment options exist including putting vinegar in the ear, using antibiotic drops, and surgery.
== References == |
Early childhood caries | Early childhood caries (ECC), formerly known as nursing bottle caries, baby bottle tooth decay, night bottle mouth and night bottle caries, is a disease that affects teeth in children aged between birth and 71 months. ECC is characterized by the presence of 1 or more decayed (noncavitated or cavitated lesions), missing (due to caries), or filled tooth surfaces in any primary tooth. ECC has been shown to be a very common, transmissible bacterial infection, usually passed from the primary caregiver to the child. The main bacteria responsible for dental caries are Streptococcus mutans (S. mutans) and Lactobacillus. There is also evidence that supports that those who are in lower socioeconomic populations are at greater risk of developing ECC.
Aetiology
Early childhood caries (ECC) is a multi-factorial disease, referring to various risk factors that inter-relate to increase risk of developing the disease. These risk factors include but not limits to, cariogenic bacteria, diet practices and socioeconomic factors. Normally after 6 months, deciduous teeth begin to erupt means, they are susceptible to tooth decay or dental caries. In some unfortunate cases, infants and young children have experienced severe tooth decay called ECC. This can result in the child experiencing severe pain, extensive dental restorations or extractions. The good news is that ECC is preventable, however, still remains a large burden particularly towards health care expenditure.
Microbial factors
The primary cariogenic bacteria involved in ECC are S. mutans and Lactobacillus. The oral flora in an infant oral cavity is not colonised with normal oral flora until the eruption of the primary dentition at approximately 6 to 30 months of age. The colonisation of S. Mutans from mother to infant is well documented. Over time this combination of food debris and bacteria form a biofilm on the tooth surface called plaque. In plaque, the cariogenic microorganisms are those that produce lactic acid as a by-product from fermentable carbohydrates. Examples of these fermentable carbohydrates include fructose, sucrose and glucose. Cariogenic bacteria thrive on these sugars and help them to weaken the adjacent tooth surface. A poor oral care routine and a diet that is high in fermentable carbohydrates favour acidic attack in the oral cavity. This prolonged acidic exposure allows the net loss of minerals from the tooth. This diminishes the strength of the tooth and is called demineralisation. For the outer layer of the tooth (enamel) to reach cavitation, there is a breakdown of the enamel matrix that allows the influx of the cariogenic bacteria. As cavitation progresses into dentine, the dental caries is classified severe, this causes ECC.
Dietary factors
Diet plays a key role in the process of dental caries. The type of foods along with the frequency at which they are consumed can determine the risk it puts for also developing carious lesions. With new products being put on supermarket shelves with irresistible prices, this can largely influence what people buy. It is common for infants and young children to frequently consume fermentable carbohydrates, in the form of liquids. The consumption of liquids containing fermentable carbohydrate, include drinks such as: juice, breast milk, formula, soda. These consumables all have the potential to increase the risk of dental caries due to prolonged contact between sugars in the liquid and cariogenic bacteria on the tooth surface.
Recent research has shown that breastfeeding does not increase caries risk up to 12 months of age. Poor feeding practices without appropriate preventive measures can lead to a distinctive pattern of caries in susceptible infants and toddlers commonly known as baby bottle tooth decay or ECC. Frequent and long duration bottle feeding, especially at night, is associated with ECC. This finding can be attributed to the fact that there is less salivary flow at night and hence less capacity for buffering and remineralisation. Each time a child drinks these liquids, acids attack for 20 minutes or longer. A parents education and health awareness has a major influence on the caries experience of their child - feeding practices, dietary habits and food choices.
Socioeconomic factors
Dental caries still today, remains the most prevalent disease worldwide. This means the disease is highly preventable, yet it is still burdening millions of children and into adulthood with pain and potentially lower quality of life. There are several studies by Locker and Mota-Veloso reporting that there is a two-way relationship that exists between dental caries and levels of education, household income that effect quality of life and social positioning. Locker suggested that the relationship between oral disease and health-related quality of life outcomes can be mediated by personal and environmental variables. Previous studies have also mentioned that the rate of ECC has decreased. However, these results can tend to dis-include communities where equity still exists. More health promotion initiatives and policy-making that collaborate directly with the community to increase meeting their needs, should be implemented.While the primary aetiology is due to microbial factors, it is also largely influenced by the social, behavioral and economic determinants in which children are surrounded by. such factors include living in a low income earning family that may not have the budget to afford visiting a dental clinic. Secondly, having limited access to healthcare and education where important messages about the consumption of carcinogenic foods are not being transferred to children or their parents. Distribution of budget should be made to reach rural and remote communities to implement health promotion strategies to increase awareness about diet and oral hygiene.
The education, occupation and income of families also greatly affects the quality of life. Children greatly rely on their parents or guardians for help concerning their health and well-being. Studies have shown that families of lower socioeconomic status are less likely to regularly attend the dentist and access preventive dental resources. ECC also has an accumulative effect for those that live in rural areas.
Prevention
Early childhood caries can be prevented through the combination of the following: adhering to a healthy nutritional diet, optimal plaque removal, use of fluoridation on the tooth surface once erupted, care taken by the mother during the pre-natal and peri-natal period and regular dental visits. The following are recommendations to help prevent ECC.
Adequate diet
Dietary habits and the presence of cariogenic bacteria within the oral cavity are an important factor in the risk of ECC. ECC is commonly caused by bottle feeding, frequent snacking and a high sugar diet
In regards to preventing ECC through bottle feeding, it is fundamental not to allow the child to sleep using ‘sippy cups’ or bottles as this is a large factor contributing to baby bottle decay/caries. This is highly encouraged as it prevents continuous exposure to non-milk extrinsic sugars and therefore the potential progression of caries – this means the oral cavity can return to a neutral pH and therefore decreased acidity. These researches also suggest trying to introduce cups to children as they approach their first birthday and to reduce the use of a bottle.
A low-sugar and high nutritional diet is recommended for both the mother and the child especially during breastfeeding, and it is also recommended to avoid frequent snackingA 2019 Cochrane review concluded that there is a 15% drop in risk of developing ECC, when mother with infants or pregnant women were given advice on a healthy child diet and feeding practices. Consequently, resulting in less decay for the child.
Optimal plaque removal
On eruption of the first primary tooth in a child, tooth brushing and cleaning should be performed by an adult. This is important as the plaque that attaches to the surface of the tooth has bacteria that have the ability to cause caries (decay) on the tooth surface.
It is recommended to brush childrens teeth using a soft bristled, age and size appropriate toothbrush and age appropriate toothpaste twice daily, however children below the age of two usually dont require toothpaste. These researches also suggest that it is suitable to brush childrens teeth until they reach the approximate age of 6; where they will begin to learn adequate dexterity and cognition needed for adequate brushing by themselves. It is encouraged to watch children brushing their teeth until they are competently able to brush appropriately alone.
Fluoride
Fluoride is a natural mineral that naturally occurs throughout the world – it is also the active ingredient of many toothpastes specifically for its remineralizing effects on enamel, often repairing the tooth surface and reducing the risk of caries.
The use of fluoridated toothpaste is highly recommended by dental professionals; whereby studies suggest that the correct daily use of fluoride on the dentition of children has a high caries-preventive effect and therefore prevents has potential to prevent ECC. However, it is important to use fluoridated toothpastes correctly; children below the age of two do not usually require toothpaste unless they are already at a high risk of ECC as diagnosed by a dental professional, and therefore it is recommended to use a small sized ‘smear’ of toothpaste to incorporate fluoride, with caution removing the toothpaste from within the mouth and not allowing the child to swallow the substances.
Pre-natal and peri-natal period
Prevention of early childhood caries begins before the baby is born; women are advised to maintain a well-balanced diet of high nutritional value, especially during the third trimester and within the infants first year of life. This is since enamel undergoes maturation; if the diet is not sufficient, a common condition that may occur is enamel hypoplasia.
Enamel hypoplasia is a developmental defect of enamel that occurs during tooth development, mainly pre-natally or during early childhood. Teeth affected by enamel hypoplasia are commonly at a higher risk of caries since there is an increased loss of minerals and therefore the tooth surface is able to breakdown more easily than in comparison to a non-hypoplastic tooth. It is therefore suggested to the mother to maintain a healthy diet since evidence suggests malnourishment during the perinatal period increases the risk of hypoplastic teeth in an infant.
Dental visits
It is recommended to parents and caregivers to take their children to a dental professional for examination as soon as the first few teeth start to erupt into the oral cavity. The dental professional will assess all the present dentition for early carious demineralization and may provide recommendations to the parents or caregivers the best way to prevent ECC and what actions to take.
Studies suggest that children who have attended visits within the first few years of life (an early preventive dental visit) potentially experience less dental related issues and incur lower dental related costs throughout their lives.
Treatment
The current standard of care for Severe Early Childhood Caries includes restoration and extraction of carious teeth and, where possible, includes early intervention which includes application of topical fluoride, oral hygiene instructions and education.
The initial visit is important as it allows dental professionals to flag unfavourable behaviour or eating habits. This will also allow dental clinician, working in a collaborative team, to perform diagnostic testing to determine the rate and progression of the disease. This is done by performing risk assessment based on the childs age, as well as the social, behavioural, and medical history of the child. Children at low risk may not need any restorative therapy, and frequent visits should be made to detect possible early lesions. Children at moderate risk may require restoration of progressing and cavitated lesions, while white spot and enamel proximal lesions should be treated by preventive techniques and monitored for progression. Children at high risk, however, may require earlier restorative intervention of enamel proximal lesions, as well as intervention of progressing and cavitated lesions to minimize continual caries development. As Early Childhood Caries occurs in children under the age of 5, restorative treatment is conventionally performed under general anesthetic to prevent a traumatic experience for the child. Still, the literature shows a high rate of caries relapse after treatment under general anesthesia, sometimes as early as 6 months after treatment was rendered.Dental professionals now have a safe, inexpensive, and less invasive option to manage Early Childhood Caries: Silver Diamine Fluoride (SDF) is a liquid containing silver and fluoride that can be brushed on teeth to stop decay, relieve sensitivity, and prevent cavities from getting worse. Silver kills the bacteria that cause tooth decay and fluoride helps strengthen the tooth. SDF is applied directly to the area of decay without first having to drill the tooth. SDF is an inexpensive option that is simple to apply; however, although it stops the decay from progressing, it does not fill the cavity, and the tooth may still need to be restored with a filling or crown. After treatment with SDF, arrested decay will become black, but a dental provider can cover the treated area with a white filling material if needed. This may be less of a problem in baby teeth, which will be lost as the child ages, than for permanent teeth. Even so, because applying SDF is quick, it may be especially helpful for young children and other patients who have trouble sitting still during dental treatments, avoiding the need for sedation or general anesthesia. However, the use of SDF remains controversial and more good quality research is needed to be conclusive on its effectiveness, its need and its adverse effects on early caries and childrens health especially for those in developed countries. This is particularly important in light of the FDA warnings about using general anesthetics and sedation in young children. The American Dental Association recognizes SDF as an effective approach to conservatively manage dental decay.Depending on the level of cavitation of the teeth, different types of restorations may be employed. Stainless steel (preformed) crowns are pre-fabricated crown forms which can be adapted to individual primary molars and cemented in place to provide a definitive restoration or can be fitted using the Hall Technique. They have been indicated for the restoration of primary and permanent teeth with caries where a normal filling may not last.
Another approach of treating dental caries in young children is Atraumatic Restorative Treatment (ART). The ART is a procedure based on removing carious tooth tissues using hand instruments alone and restoring the cavity with an adhesive restorative material. This is useful to prevent trauma and requires less chair time for the young patients. This is used in cases where the teeth are being maintained in the mouth to maintain space for the future teeth to come through. Low quality evidence indicates that ART may have a higher risk of filling failure when compared to usual care. Despite the potential for filling failure, ART is still recommended for children when access to electricity, drills, dentists, or other dental resources are limited.
References
16.Maternal Perception about Early Childhood Caries in Nigeria in Kalipeni, E.; Iwelunmor, J.; Grigsby-Toussaint, D.; and Moise, I. K. (eds.) (In Press, June 2018). Public Health, Disease and Development in Africa. London: Routledge Publishers.
External links
American Academy of Pediatric Dentistry
American Dental Association ADA page on early childhood tooth decay
Columbia Center Comparison of Dental Surgery versus Caries Suppression with other treatments
Childrens Dental Health Project |
Trichoepithelioma | Trichoepithelioma is a neoplasm of the adnexa of the skin. Its appearance is similar to basal cell carcinoma.
One form has been mapped to chromosome 9p21.
Types
Trichoepitheliomas may be divided into the following types:: 672
Multiple familial trichoepithelioma
Solitary trichoepithelioma
Desmoplastic trichoepithelioma
Pathology
Trichoepitheliomas consists of nests of basaloid cells, with palisading. They lack the myxoid stroma and artefactual clefting seen in basal cell carcinoma. Mitoses are uncommon when compared to basal cell carcinoma.
Diagnosis
Trichoepiteliomas often contain Merkel cells; an immunostain for CK20 can be used to demonstrate this.
See also
Trichoblastoma
Pilomatricoma
CYLD cutaneous syndrome
List of cutaneous conditions
List of cutaneous neoplasms associated with systemic syndromes
References
== External links == |
Littoral cell angioma | Littoral cell angioma, abbreviated LCA, and formally known as littoral cell angioma of the spleen, is a benign tumour of the spleen that arises from the cells that line the red pulp.
Symptoms
LCAs most often are not clinically detectable. On occasion, their first presentation may be with splenic rupture.Most patients show no symptoms and the tumours are found incidentally.
Diagnosis
Littoral cell angiomas show in CT scans. They are diagnosed by pathologists by taking a sample of the tumour via Fine Needle Aspiration or Core Needle Aspiration or from a splenectomy. Histologically, they have anastoming small vascular channels and cystic spaces with papillary projections.
Treatment
The treatment for a littoral cell angioma is a splenectomy.
See also
Vascular tumor
References
External links
Micrograph of a LCA (webpathology.com). |
Gastroesophageal varices | Gastroesophageal varices may refer to:
Esophageal varices, dilated sub-mucosal veins in esophagus
Gastric varices, dilated submucosal veins in the stomach |
Hypereosinophilic syndrome | Hypereosinophilic syndrome is a disease characterized by a persistently elevated eosinophil count (≥ 1500 eosinophils/mm³) in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow.HES is a diagnosis of exclusion, after clonal eosinophilia (such as FIP1L1-PDGFRA-fusion induced hypereosinophelia and leukemia) and reactive eosinophilia (in response to infection, autoimmune disease, atopy, hypoadrenalism, tropical eosinophilia, or cancer) have been ruled out.There are some associations with chronic eosinophilic leukemia as it shows similar characteristics and genetic defects.
If left untreated, HES is progressive and fatal. It is treated with glucocorticoids such as prednisone. The addition of the monoclonal antibody mepolizumab may reduce the dose of glucocorticoids.
Signs and symptoms
As HES affects many organs at the same time, symptoms may be numerous. Some possible symptoms a patient may present with include:
Cardiomyopathy
Skin lesions
Thromboembolic disease
Pulmonary disease
Neuropathy
Hepatosplenomegaly
Reduced ventricular size
Atopic eczema
Diagnosis
Numerous techniques are used to diagnose hypereosinophilic syndrome, of which the most important is blood testing. In HES, the eosinophil count is greater than 1.5 × 109/L. On some smears the eosinophils may appear normal in appearance, but morphologic abnormalities, such as a lowering of granule numbers and size, can be observed. Roughly 50% of patients with HES also have anaemia.Secondly, various imaging and diagnostic technological methods are utilised to detect defects to the heart and other organs, such as valvular dysfunction and arrhythmias by usage of echocardiography. Chest radiographs may indicate pleural effusions and/or fibrosis, and neurological tests such as CT scans can show strokes and increased cerebrospinal fluid pressure.A proportion of patients have a mutation involving the PDGFRA and FIP1L1 genes on the fourth chromosome, leading to a tyrosine kinase fusion protein. Testing for this mutation is now routine practice, as its presence indicates response to imatinib, a tyrosine kinase inhibitor.
Treatment
Treatment primarily consists of reducing eosinophil levels and preventing further damage to organs. Corticosteroids, such as prednisone, are good for reducing eosinophil levels and antineoplastics are useful for slowing eosinophil production. Surgical therapy is rarely utilised, however splenectomy can reduce the pain due to spleen enlargement. If damage to the heart (in particular the valves), then prosthetic valves can replace the current organic ones. Follow-up care is vital for the survival of the patient, as such the patient should be checked for any signs of deterioration regularly. After promising results in drug trials (95% efficiency in reducing blood eosinophil count to acceptable levels) it is hoped that in the future hypereosinophilic syndrome, and diseases related to eosinophils such as asthma and eosinophilic granulomatosis with polyangiitis, may be treated with the monoclonal antibody mepolizumab currently being developed to treat the disease. If this becomes successful, it may be possible for corticosteroids to be eradicated and thus reduce the amount of side effects encountered.
Epidemiology
The European Medicines Agency (EMA) estimated the prevalence of HES at the time of granting orphan drug designation for HES in 2004 at 1.5 in 100,000 people, corresponding to a current prevalence of about 8,000 in the EU, 5,000 in the U.S., and 2,000 in Japan.Patients who lack chronic heart failure and those who respond well to prednisone or a similar drug have a good prognosis. However, the mortality rate rises in patients with anaemia, chromosomal abnormalities or a very high white blood cell count.
History
Hypereosinophilic syndrome was first described as a distinct entity by Hardy and Anderson in 1968.
References
External links
Hypereosinophilic Syndrome on patient.info
Hypereosinophilic Syndrome on eMedicine |
Brachymetatarsia | Brachymetatarsia is a condition in which there is one or more abnormally short or overlapping toe bones (metatarsals). This condition may result due to a congenital defect or it may be an acquired condition. It most frequently involves the fourth metatarsal. If it involves the first metatarsal, the condition is known as Mortons syndrome. Treatment is via a number of differing surgical procedures.
Diagnosis
Differential diagnosis
Congenital causes include: Aarskog syndrome, Turner syndrome, Albrights hereditary osteodystrophy, maternal ingestion of thalidomide during pregnancy and Apert syndrome. Can be caused by a trauma, although the exact mechanism is not known.
Treatment
Symptoms may be treated by wearing wider shoes to relieve pressure, or patient can wear padding around the toes. Surgery is also an option, if the pain and discomfort cannot be treated, or for cosmetic reasons. In this procedure, the short metatarsal is typically cut and a piece of bone is grafted between the two ends. In some cases an external fixator may be attached to the metatarsal with pins. Within the external fixator is an adjustable screw that must be turned (per doctors orders) to lengthen the gap between bone segments, so the bone will regrow to the appropriate shape.Following surgery, crutches or a knee scooter should be used to keep all weight off the surgically repaired foot for 3 months. After this period, orthopedic shoes or boots may be used.
Epidemiology
Brachymetatarsia is found to occur more frequently in women than men. Brachymetatarsia affecting the first metatarsal of the foot is the most common type of brachymetatarsia, with approximately 22% of the population being affected by it.
== References == |
Swan neck deformity | Swan neck deformity is a deformed position of the finger, in which the joint closest to the fingertip is permanently bent toward the palm while the nearest joint to the palm is bent away from it (DIP flexion with PIP hyperextension). It is commonly caused by injury, hypermobility or inflammatory conditions like rheumatoid arthritis or sometimes familial (congenital, like Ehlers–Danlos syndrome).
Pathophysiology
Swan neck deformity has many of possible causes arising from the DIP, PIP, or even the MCP joints. In all cases, there is a stretching of the volar plate at the PIP joint to allow hyperextension, plus some damage to the attachment of the extensor tendon to the base of the distal phalanx that produces a hyperflexed mallet finger. Duck bill deformity is a similar condition affecting the thumb (which cannot have true swan neck deformity because it does not have enough joints).
Diagnosis
Diagnosis of swan neck deformity is mainly clinical. MRI of the hand may suggest volar plate attenuation of PIP and extensor tendon damage for DIP Genetic screening tests such as for CMT disease may also be indicated.
Treatment
Splinting for fingers. Passive stretching and clearing the deformity.
References
External links
Swan neck deformity at Wheeless Textbook of Orthopedics, a technical review of the condition
Rheumatoid arthritis: Image showing deformities |
Angelman syndrome | Angelman syndrome or Angelmans syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no functional speech, balance and movement problems, seizures, and sleep problems. Children usually have a happy personality and have a particular interest in water. The symptoms generally become noticeable by one year of age.Angelman syndrome is due to a lack of function of part of chromosome 15, typically due to a new mutation rather than one inherited from a persons parents. Most of the time, it is due to a deletion or mutation of the UBE3A gene on that chromosome. Occasionally, it is due to inheriting two copies of chromosome 15 from a persons father and none from their mother (paternal uniparental disomy). As the fathers versions are inactivated by a process known as genomic imprinting, no functional version of the gene remains. Diagnosis is based on symptoms and possibly genetic testing.No cure is available. Treatment is generally supportive in nature. Anti-seizure medications are used in those with seizures. Physical therapy and bracing may help with walking. Those affected have a nearly normal life expectancy.AS affects 1 in 12,000 to 20,000 people. Males and females are affected with equal frequency. It is named after British pediatrician Harry Angelman, who first described the syndrome in 1965. An older term, happy puppet syndrome, is generally considered pejorative. Prader–Willi syndrome is a separate condition, caused by a similar loss of the fathers chromosome 15.
Signs and symptoms
Signs and symptoms of Angelman syndrome and their relative frequency in affected individuals are:
Consistent (100%)
Developmental delay, functionally severe
Speech impairment, no or minimal use of words; receptive and non-verbal communication skills higher than verbal ones
Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs
Behavioral characteristics of the following types: any combination of atypical frequent laughter/smiling; atypically happy demeanor; easily excitable personality, often with hand flapping movements; hypermotoric behavior; short attention span
Frequent (more than 80%)
Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (absolute or relative) by age 2
Seizures, onset usually less than 3 years of age
Abnormal EEG, characteristic pattern with large amplitude slow-spike waves
Associated (20–80%)
Cause
Angelman syndrome is caused by the lack of expression of a gene known as UBE3A during development. This gene is located within a region of chromosome 15 known as 15q11-q13 and is part of the ubiquitin pathway. In fact, UBE3A codes for a very selective E6-AP ubiquitin ligase for which MAPK1, PRMT5, CDK1, CDK4, β-catenin, and UBXD8 have been identified as ubiquitination targetsTypically, a fetus inherits a maternal copy of UBE3A and a paternal copy of UBE3A. In certain areas of the developing brain, the paternal copy of UBE3A is inactivated through a process known as imprinting and the fetus relies on the functioning maternal copy of UBE3A in order to develop normally. In an individual with AS, however, the maternal UBE3A gene is absent or not functioning normally. This can be due to genetic errors such as the deletion or mutation of a segment of chromosome 15, uniparental disomy, or translocation. While Angelman syndrome can be caused by a single mutation in the UBE3A gene, the most common genetic defect leading to Angelman syndrome is a 5- to 7-Mb (megabase) maternal deletion in chromosomal region 15q11.2-q13.Specifically, the paternal copy of UBE3A is known to be imprinted within the hippocampus, cortex, thalamus, olfactory bulb, and cerebellum. Therefore, in these areas of the brain, a functioning maternal copy of UBE3A is essential for proper development.Region 15q11-13 is implicated in both Angelman syndrome and Prader–Willi syndrome (PWS). While AS results from mutation, loss or abnormal imprinting involving the UBE3A gene within this region on the maternal chromosome, loss of a different cluster of genes within the same region on the paternal chromosome causes PWS.The methylation test that is performed for Angelman syndrome looks for methylation on the genes neighbor SNRPN, which is silenced by methylation on the maternal copy of the gene.
Neurophysiology
The electroencephalogram (EEG) in AS is usually abnormal, more so than clinically expected. This EEG facilitates the differential diagnosis of AS, but is not pathognomonic. Three distinct interictal patterns are seen in these patients. The most common pattern is a very large amplitude 2–3 Hz rhythm most prominent in prefrontal leads. Next most common is a symmetrical 4–6 Hz high voltage rhythm. The third pattern, 3–6 Hz activity punctuated by spikes and sharp waves in occipital leads, is associated with eye closure. Paroxysms of laughter have no relation to the EEG, ruling out this feature as a gelastic phenomenon.EEG anomalies may be used as a quantitative biomarkers to "chart progression of AS and as clinical outcome measures". Slow delta activity (~3 Hz) is greatly increased in AS relative to typically developing children, yet more pronounced in children with partial 15q deletions as opposed to those with etiologies principally affecting UBE3A. Theta activity (~5 Hz) is much greater in children with partial 15q deletions. Thus, delta activity appears to be chiefly reflective of UBE3A dysfunction with some modulation from other 15q genes, whereas theta activity may be an electrophysiological readout of genes beyond UBE3A such as GABRA5, GABRB3, and GABRG3. Future clinical trials in AS might exploit the foregoing by using EEG as a readout of drug target engagement.It appears that the neurons of people with Angelman syndrome are formed correctly, but they cannot function properly.
Diagnosis
The diagnosis of Angelman syndrome is based on:
A history of delayed motor milestones and then later a delay in general development, especially of speech
Unusual movements including fine tremors, jerky limb movements, hand flapping and a wide-based, stiff-legged gait.
Characteristic facial appearance (but not in all cases).
A history of epilepsy and an abnormal EEG tracing.
A happy disposition with frequent laughter
A deletion or inactivity on chromosome 15 by array comparative genomic hybridization (aCGH) or by BACs-on-Beads technology.Diagnostic criteria for the disorder were initially established in 1995 in collaboration with the Angelman syndrome Foundation (US); these criteria underwent revision in 2005.Seizures are a consequence, but so is excessive laughter, which is a major hindrance to early diagnosis.
Differential diagnosis
Other conditions that can appear similar include:
Autism spectrum
Cerebral palsy
Rett syndrome
Mowat–Wilson syndrome
Adenylosuccinate lyase deficiency
Pitt–Hopkins syndrome
Phelan–McDermid syndrome
Prader–Willi syndrome
Treatment
There is currently no cure available. The epilepsy can be controlled by the use of one or more types of anticonvulsant medications. However, there are difficulties in ascertaining the levels and types of anticonvulsant medications needed to establish control, because people with AS often have multiple types of seizures. Many families use melatonin to promote sleep in a condition which often affects sleep patterns. Many individuals with Angelman syndrome sleep for a maximum of five hours at any one time. Mild laxatives are also used frequently to encourage regular bowel movements. Early intervention with physiotherapy is sometimes used to encourage joint mobility and prevent stiffening of the joints. Speech and Language Therapy is commonly employed to assist individuals with Angelman syndrome and their communication issues.Occupational therapists can contribute to the development and augmentation of non-verbal communication skills by addressing the foundational skills such as finger isolation, motor planning, hand-eye coordination, spatial awareness, and refining gestures. This is important because individuals with Angelman Syndrome who already possess some form of non-verbal communication have a much harder time adapting to changes in a new or existing AAC device because they can communicate their needs much faster nonverbally.Occupational therapists can assist individuals with Angelman syndrome with many other skills as well. Many individuals with Angelman syndrome also have difficulty processing sensory information and responding appropriately to sensory stimuli. Occupational therapists can work together with these individuals to improve their visual perceptual skills and increase their sensory awareness.Those with the syndrome are generally happy and contented people who like human contact and play. People with AS exhibit a profound desire for personal interaction with others. Communication can be difficult at first, but as a child with AS develops, there is a definite character and ability to make themselves understood. People with AS tend to develop strong non-verbal skills to compensate for their limited use of speech. It is widely accepted that their understanding of communication directed to them is much larger than their ability to return conversation. Most affected people will not develop more than 5–10 words, if any at all.
Prognosis
The severity of the symptoms associated with Angelman syndrome varies significantly across the population of those affected. Some speech and a greater degree of self-care are possible among the least profoundly affected. Walking and the use of simple sign language may be beyond the reach of the more profoundly affected. Early and continued participation in physical, occupational (related to the development of fine-motor control skills), and communication (speech) therapies are believed to significantly improve the prognosis (in the areas of cognition and communication) of individuals affected by AS. Further, the specific genetic mechanism underlying the condition is thought to correlate to the general prognosis of the affected person. On one end of the spectrum, a mutation to the UBE3A gene is thought to correlate to the least affected, whereas larger deletions on chromosome 15 are thought to correspond to the most affected.The clinical features of Angelman syndrome alter with age. As adulthood approaches, hyperactivity and poor sleep patterns improve. The seizures decrease in frequency and often cease altogether and the EEG abnormalities are less obvious. Medication is typically advisable to those with seizure disorders. Often overlooked is the contribution of the poor sleep patterns to the frequency and/or severity of the seizures. Medication may be worthwhile to help deal with this issue and improve the prognosis with respect to seizures and sleep. Also noteworthy are the reports that the frequency and severity of seizures temporarily escalate in pubescent Angelman syndrome girls, but do not seem to affect long-term health.The facial features remain recognizable with age, but many adults with AS look remarkably youthful for their age.Puberty and menstruation begin at around the average age. Sexual development is thought to be unaffected, as evidenced by a single reported case of a woman with Angelman syndrome conceiving a female child who also had Angelman syndrome.The majority of those with AS achieve continence by day and some by night. Angelman syndrome is not a degenerative syndrome, and thus people with AS may improve their living skills with support.Dressing skills are variable and usually limited to items of clothing without buttons or zippers. Most adults can eat with a knife or spoon and fork, and can learn to perform simple household tasks. Particular problems which have arisen in adults are a tendency to obesity (more in females), and worsening of scoliosis if it is present. The affectionate nature may also persist into adult life where it can pose a problem socially, but this problem is not insurmountable. People with Angelman syndrome appear to have a reduced but near-normal life expectancy, dying on average 10 to 15 years earlier than the general population.
Epidemiology
Though the prevalence of Angelman syndrome is not precisely known, there are some estimates. The best data available are from studies of school age children, ages 6–13 years, living in Sweden and from Denmark where the diagnosis of AS children in medical clinics was compared to an 8-year period of about 45,000 births. The Swedish study showed an AS prevalence of about 1/20,000 and the Danish study showed a minimum AS prevalence of about 1/10,000.
History
Harry Angelman, a pediatrician working in Warrington, England, first reported three children with this condition in 1965. Angelman later described his choice of the title "Puppet Children" to describe these cases as being related to an oil painting he had seen while vacationing in Italy:
The history of medicine is full of interesting stories about the discovery of illnesses. The saga of Angelmans syndrome is one such story. It was purely by chance that nearly thirty years ago (e.g. [sic], circa 1964) three handicapped children were admitted at various times to my childrens ward in England. They had a variety of disabilities and although at first sight they seemed to be suffering from different conditions I felt that there was a common cause for their illness. The diagnosis was purely a clinical one because in spite of technical investigations which today are more refined I was unable to establish scientific proof that the three children all had the same handicap. In view of this I hesitated to write about them in the medical journals. However, when on holiday in Italy I happened to see an oil painting in the Castelvecchio Museum in Verona called ... a Boy with a Puppet. The boys laughing face and the fact that my patients exhibited jerky movements gave me the idea of writing an article about the three children with a title of Puppet Children. It was not a name that pleased all parents but it served as a means of combining the three little patients into a single group. Later the name was changed to Angelman syndrome. This article was published in 1965 and after some initial interest lay almost forgotten until the early eighties.
Case reports from the United States first began appearing in the medical literature in the early 1980s. In 1987, it was first noted that around half of the children with AS have a small piece of chromosome 15 missing (chromosome 15q partial deletion).
Society and culture
Many poems in Richard Prices poetry collections Hand Held (1997), Lucky Day (2005), and Small World (2012) reflect on the disability of the poets daughter, who has Angelman syndrome. In the 2011 Philippine drama series Budoy, the titular character and main protagonist Budoy Maniego (played by Filipino actor Gerald Anderson) is diagnosed with Angelman syndrome.
References
External links
Angelman syndrome at Curlie
GeneReviews/NCBI/NIH/UW entry on Angelman syndrome |
Floating–Harbor syndrome | Floating–Harbor syndrome, also known as Pelletier–Leisti syndrome, is a rare disease with fewer than 50 cases described in the literature. It is usually diagnosed in early childhood and is characterized by the triad of proportionate short stature with delayed bone age, characteristic facial appearance, and delayed speech development. Although its cause is unknown, it is thought to result from genetic mutation, and diagnosis is established by the presence of a heterozygous SRCAP mutation in those with clinical findings of FHS.
Signs and symptoms
Below are the common clinical features of those diagnosed with Floating–Harbor syndrome. Patients will show varying degrees of some or all FHS symptoms. Facial abnormalities are the most defining aspects of those diagnosed with this disease.
Cardinal facial features
Triangular face
Deep-set eyes
Short philtrum
Wide mouth with a thin vermilion border of the upper lip
Long nose with a narrow bridge and broad, bulbous base
Low-set ears
Voice quality and language
Dysarthria and verbal dyspraxia with phoneme imprecision
Hypernasality
High-pitched voices
Severe receptive and expressive language impairment across all domains of function
Bodily features
Significant delay in bone age (-2 SD or greater) with normalization between 6–12 years old
Skeletal anomalies: brachydactyly, broad fingertips or clubbing, clinodactyly, short thumbs, prominent joints, clavicle abnormalities
Short adult stature: for females, maximum height was at the 20th percentile; for males, the maximum height was at the 25th percentile, though male height varied more widelyThe differential diagnosis of broad thumbs includes Rubinstein-taybi syndrome, where they are a cardinal feature. FHS is also in the differential, which logically agrees with the thought that the disease is a result of a mutation in SRCAP, as this gene interacts with CBP.
Behavior
Tantrums during infancy
Attention deficit-hyperactivity disorder (ADHD) during school years: impulsivity, inattention, restlessness
Unpredictable, aggressive outbursts
Autistic spectrum disorder (one case)
Asperger syndrome (one case)
Obsessive compulsive disorder (two cases)
Other observations
Intellectual disability: in all cases each individual showed a varying degree of intellectual impairment and learning disability, ranging from borderline normal to moderate intellectual disability
Early entry into puberty is shown in some girls, leading to menorrhagia and irregular periods
Dental problems (caries, malocclusion, dysplastic, small teeth)
Visual impairment
Mechanism
The cause of this condition is unknown but evidence of familial inheritance and sporadic genetic mutation has been linked to cases of FHS. Two possibly familial cases have been reported—one in a mother and son, and the other in a mother and daughter. This suggests an autosomal dominant inheritance but additional cases need to be investigated to establish this. Another report has suggested that the inheritance may be autosomal recessive. In all of these cases, however, the mothers and children were not similarly affected, suggesting a variable clinical expression of the syndrome.In a study published by the American Journal of Human Genetics in 2012, exome sequencing was used to investigate a group of unrelated individuals with classic features of FHS and identified heterozygous mutations in SRCAP as causative of this disorder. Each reported mutation was truncating (nonsense or frameshift) and occurred between codons 2,407 and 2,517 in exon 34, resulting in the loss of three C-terminal AT-hook motifs. SRCAP encodes a SNF2-related chromatin-remodeling ATPase that is a coactivator for CREB-binding protein (or CBP), which is the major cause of Rubinstein–Taybi syndrome. This disrupted interaction between the proteins most likely explains the clinical overlap between FHS and RTS.
SRCAP has been shown to transduce signals of nuclear (steroid) hormone receptors and Notch pathways, showing that it plays diverse roles in gene expression.
SRCAP contains several functional domains (SNF2 like ATPase, an N-terminal HSA domain, and three C-terminal AT-hook DNA-binding motifs).
The CBP interaction domain of SRCAP is located centrally.Thus, the mechanism of disease in FHS is suspected to be dominant-negative (or antimorphic) due to the mutation in the final exon that results in the loss of the major transactivation function of SRCAP (or loss of one or more critical domains). All of the patients that carried the mutation also had obvious physical symptoms (i.e., prominent nose, delayed bone age, and short stature). Those who tested negative for the mutation often had dysmorphic facial features distinct from classical FHS, as well as a formal diagnosis of autism.
Drawbacks to findings
From the same group, three individuals whose phenotype most closely resembled FHS carried no mutation on the SRCAP gene. Though these findings are a large step in determining the underlying cause of FHS and widely accepted, others would claim molecular diagnosis is not always successful and the mutation is not a mandatory feature for the diagnosis of FHS.
Diagnosis
Until recently, doctors have diagnosed patients with FHS based on clinical observations and how well they fit the disease description, usually occurring in early childhood. Molecular genetic testing is also used now to test for genetic mutations. By performing a sequence analysis test of select exons, mutations can be detected in exon 34 of the SRCAP gene. This mutation has been observed in 19 patients to date.
In most cases, if the patient shows classic facial features of FHS, the molecular testing will show a mutation on the SRCAP gene.
Differential diagnosis
FHS shares some common features with Rubinstein–Taybi (due to overlapping effects of mutations on SRCAP), however cranial and hand anomalies are distinctive: broad thumbs, narrow palate, and microcephaly are absent in Floating-Harbor Syndrome. One child in the UK has a diagnosis of microcephaly alongside Floating–Harbor syndrome.
Management
There are no cures for FHS. Close monitoring of growth in the first few years is essential, as well as annual general health screening and tests listed below. An FHS diagnosis will affect the individual and those there to support them.Managing symptoms and features of FHS involves maintaining a close watch on the patients physical as well as mental health. This would include:
Sequencing of SRCAP exons 31–34 in all suspected cases
Complete assessments of auditory and visual systems
Renal and urinary tract ultrasound
Orthopedic assessment of hip dysplasia and clavicle abnormalities
Neurologic assessment if there is a suspicion of seizures
Dental hygiene to prevent cavities and to monitor for malocclusion
Evaluation for growth hormone deficiency at baseline, to be repeated if loss of growth velocity occurs
Monitoring of bone age and pubertal timing in case of precocious puberty
Psychoeducational assessments corrected for deficiencies in expressive language and sensory issues
Monitoring of behavioral disturbances and provision of early intervention
Counseling for families regarding recurrence risk and the offspring of individuals with FHSSpecial education programs and vocational training to address developmental disabilities are highly recommended, as well as communication rehabilitation with sign language or alternative means of communication. Behavior management strategies could also include referrals to behavior specialists or psychologists for help. For those concerned, genetic counseling can be sought for issues related to testing of at-risk relatives.
History
The first identified instances occurred in 1973 at the Boston Floating Hospital, and in 1975 at Harbor General Hospital in Torrance, California. The name Floating–Harbor syndrome was coined by Robinson et al. in 1988. Since then approximately 40 more cases have been described.The first case recorded was that of a 5-year-old boy. In a 32-year follow up done in 2006, the patient was in good overall health, had never been hospitalized, and had been employed for the past 15 years. His mother stated he had a very good memory, was gregarious, had a temper, and at times was stubborn. Changes in the patients facial configuration and body could be attributed to age and familial history (i.e., the patient shows signs of arthritis and hypertension). Still present were the low hairline, broad tip of the nose, short nasal labial distance, depressed columella, thin lips, and posteriorly positioned ears, as well as short stature and mild to moderate retardation.
Recent research
In a study published in 2012 in the Journal of Pediatric Endocrinology, a group of scientists reported the long-term effects of a patient diagnosed with FHS undergoing growth hormone therapy from the age of 3.5 years to 9 years old. While the GH seemed to work initially, the patients growth after the first couple years slowed significantly and the patient reached a stable height far below the target or standard height. The results on GH therapy remain inconclusive.Recent research mostly centers around the search and confirmation of the gene responsible for FHS. As discussed in the mechanisms section, though the mutation of SRCAP is a widely accepted indicator of a patient diagnosed with FHS, it is not the cause in every case.
References
External links
OMIM entry on Floating–Harbor syndrome and SRCAP
GeneReview/UW/NCBI/NIH entry on Floating–Harbor syndrome |
Recurrent miscarriage | Recurrent miscarriage is three or more consecutive pregnancy losses. In contrast, infertility is the inability to conceive. In many cases the cause of RPL is unknown. After three or more losses, a thorough evaluation is recommended by American Society of Reproductive Medicine. About 1% of couples trying to have children are affected by recurrent miscarriage.
Causes
There are various causes for recurrent miscarriage, and some can be treated. Some couples never have a cause identified, often after extensive investigations. About 50–75% of cases of recurrent miscarriage are unexplained.
Chromosomal disorders
A balanced translocation or Robertsonian translocation in one of the partners leads to unviable fetuses that are miscarried. This explains why a karyogram is often performed in both partners if a woman has experienced repeated miscarriages.Aneuploidy may be a cause of a random spontaneous as well as recurrent pregnancy loss. Aneuploidy is more common with advanced reproductive age reflecting decreased germ cell quality.Larger chromosomal disorders are generally detected on karyotype. In couples where a miscarried embryo has an abnormal karyotype, 76% of subsequent miscarried embryos have shown abnormal karyotypes as well. On the other hand, this group of couples have a better long-term live birth rate than those where miscarried embryos have normal karyotype.
Lifestyle factors
While lifestyle factors have been associated with increased risk for miscarriage in general, and are usually not listed as specific causes for RPL, every effort should be made to address these issues in patients with RPL. Of specific concern are chronic exposures to toxins including smoking, alcohol, and drugs.
Anatomical conditions
Fifteen percent of women who have experienced three or more recurring miscarriages have some anatomical reason for the inability to complete the pregnancy. The structure of the uterus has an effect on the ability to carry a child to term. Anatomical differences are common and can be congenital.
Cervical conditions
In the second trimester a weak cervix can become a recurrent problem. Such cervical incompetence leads to premature pregnancy loss resulting in miscarriages or preterm deliveries. It has been estimated that cervical insufficiency is a cause in about 8% of women with second trimester recurrent miscarriages.
Endocrine disorders
Women with hypothyroidism are at increased risk for pregnancy losses. Unrecognized or poorly treated diabetes mellitus leads to increased miscarriages. Women with polycystic ovary syndrome also have higher loss rates possibly related to hyperinsulinemia or excess androgens. Inadequate production of progesterone in the luteal phase may set the stage for RPL (see below).
Thrombophilia
An important example is the possible increased risk of miscarriage in women with thrombophilia (propensity for blood clots). The most common problem is the factor V Leiden and prothrombin G20210A mutation. Some preliminary studies suggest that anticoagulant medication may improve the chances of carrying pregnancy to term but these studies need to be confirmed before they are adopted in clinical practice. Note that many women with thrombophilia go through one or more pregnancies with no difficulties, while others may have pregnancy complications. Thrombophilia may explain up to 49–65% of recurrent miscarriages.
Immune factors
A common feature of immune factors in causing recurrent pregnancy loss appears to be a decreased maternal immune tolerance towards the fetus.
Antiphospholipid syndrome
The antiphospholipid syndrome is an autoimmune disease that is a common cause of recurrent pregnancy loss. Around 15% of the women who have recurrent miscarriages have high levels of antiphospholipid antibodies. Women who have had more than one miscarriage in the first trimester, or a miscarriage in the second trimester, may have their blood tested for antibodies, to determine if they have antiphospholipid syndrome. Women diagnosed with antiphospholipid syndrome generally take aspirin or heparin in subsequent pregnancies, but questions remain due to the lack of high quality trials.
Thyroid antibodies
Anti-thyroid autoantibodies are associated with an increased risk of recurrent miscarriage with an odds ratio of 2.3 with a 95% confidence interval of 1.5–3.5.
Increased uterine NK cells
Natural killer cells, a type of white blood cell, are present in uterine tissue. High levels of these cells may be linked to RPL but high numbers or the presence of these cells is not a predictor of pregnancy loss in women who have not have had a miscarriage.
Parental HLA sharing
Earlier studies that perhaps paternal sharing of HLA genes would be associated with increased pregnancy loss have not been confirmed.
Male-specific minor histocompatibility
Immunization of mothers against male-specific minor histocompatibility (H-Y) antigens has a pathogenic role in many cases of secondary recurrent miscarriage, that is, recurrent miscarriage in pregnancies succeeding a previous live birth. An example of this effect is that the male:female ratio of children born prior and subsequent to secondary recurrent miscarriage is 1.49 and 0.76 respectively.
Ovarian factors
Luteal phase defect
The issue of a luteal phase defect is complex. The theory behind the concept suggests that an inadequate amount of progesterone is produced by the corpus luteum to maintain the early pregnancy. Assessment of this situation was traditionally carried out by an endometrial biopsy, however recent studies have not confirmed that such assessment is valid. Studies about the value of progesterone supplementation remain deficient, however, such supplementation is commonly carried out on an empirical basis.
Infection
Infections are estimated to be responsible for between 0.5 and 5% of cases with recurrent miscarriage. The main suspected pathogens are mycoplasma, ureaplasma, Chlamydia trachomatis, Listeria monocytogenes, and herpes simplex virus. An infectious evaluation may be warranted in people with immunodeficiency, or with signs of chronic endometritis/cervicitis on examination. Otherwise, there is no evidence that routine infectious evaluation is appropriate or productive.Chronic endometritis (CE) due to common bacteria has been found to be prevalent in some women with a history of recurrent miscarriage. One study found that 71 percent of women who tested positive for this condition were successfully treated by an antibiogram-based antibiotic treatment. 78.4 percent of these women subsequently became pregnant in the year following treatment. The study concludes that "CE is frequent in women with recurrent miscarriages," and that "antibiotic treatment seems to be associated with an improved reproductive outcome." The authors also conclude, "that hysteroscopy should be a part of the diagnostic workup of infertile women complaining of unexplained recurrent miscarriage." Despite challenges in diagnosing chronic endometritis, often done by identifying plasma cells within the lining of the womb, a recent study identified women with chronic endometritis were more likely to have a miscarriage than women without.
Assessment
Transvaginal ultrasonography has become the primary method of assessment of the health of an early pregnancy.
In non-pregnant patients who are evaluated for recurrent pregnancy loss the following tests are usually performed.
Parental chromosome testing (karyogram) is generally recommended after 2 or 3 pregnancy losses. Blood tests for thrombophilia, ovarian function, thyroid function and diabetes are performed.
Treatment
If the likely cause of recurrent pregnancy loss can be determined treatment is to be directed accordingly. In pregnant women with a history of recurrent miscarriage, anticoagulants seem to increase the live birth rate among those with antiphospholipid syndrome and perhaps those with congenital thrombophilia but not in those with unexplained recurrent miscarriage. One study found that in many women with chronic endometritis, "fertility was restored after appropriate antibiotic treatment."There are currently no treatments for women with unexplained recurrent pregnancy loss. The majority of patients are counseled to try to conceive again, and chances are about 60% that the next pregnancy is successful without treatment. However, each additional loss worsens the prognostic for a successful pregnancy and increases the psychological and physical risks to the mother. Aspirin has no effect in preventing recurrent miscarriage in women with unexplained recurrent pregnancy loss. Immunotherapy has not been found to help. There is currently one drug in development, NT100, which is in clinical trials for the treatment of unexplained recurrent miscarriage. The study investigates the role of NT100 in improving maternal-fetal tolerance for women with unexplained recurrent miscarriage.In certain chromosomal situations, while treatment may not be available, in vitro fertilization with preimplantation genetic diagnosis may be able to identify embryos with a reduced risk of another pregnancy loss which then would be transferred. However, in vitro fertilization does not improve maternal-fetal tolerance imbalances.Close surveillance during pregnancy is generally recommended for pregnant patients with a history of recurrent pregnancy loss. Even with appropriate and correct treatment another pregnancy loss may occur as each pregnancy develops its own risks and problems.
Psychological effects of miscarriages
There is significant, and often unrecognized, psychological and psychiatric trauma for the mother – for many, miscarriage represents the loss of a future child, of motherhood, and engenders doubts regarding her ability to procreate."There is tremendous psychological impact of recurrent miscarriage. Psychological support in the form of frequent discussions and sympathetic counseling are crucial to the successful evaluation and treatment of the anxious couple. When no etiologic factor is identified, no treatment started at 60% to 80% fetal salvage rate still may be expected. Therefore, couples with unexplained recurrent miscarriage should be offered appropriate emotional support and reassurance."
Association with later disease
Recurrent miscarriage in itself is associated with later development of coronary artery disease with an odds ratio of approximately 2, increased risk of ovarian cancer, increased risk of cardiovascular complications, and an increased risk of all-cause mortality of 44%, 86%, and 150% for women with a history of 1, 2, or 3 miscarriages, respectively.Women with a history of recurrent miscarriage are at risk of developing preeclampsia in later pregnancies.
References
Bibliography
Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
== External links == |
Dandy–Walker malformation | Dandy–Walker malformation (DWM), also known as Dandy–Walker syndrome (DWS), is a rare congenital brain malformation in which the part joining the two hemispheres of the cerebellum (the cerebellar vermis) does not fully form, and the fourth ventricle and space behind the cerebellum (the posterior fossa) are enlarged with cerebrospinal fluid. Most of those affected develop hydrocephalus within the first year of life, which can present as increasing head size, vomiting, excessive sleepiness, irritability, downward deviation of the eyes and seizures. Other, less common symptoms are generally associated with comorbid genetic conditions and can include congenital heart defects, eye abnormalities, intellectual disability, congenital tumours, other brain defects such as agenesis of the corpus callosum, skeletal abnormalities, an occipital encephalocele or underdeveloped genitalia or kidneys. It is sometimes discovered in adolescents or adults due to mental health problems.DWM is usually caused by a ciliopathic or chromosomal genetic condition, though the causative condition is only identified in around half of those diagnosed before birth and a third of those diagnosed after birth. The mechanism involves impaired cell migration and division affecting the long period of development of the cerebellar vermis. The mechanism by which hydrocephalus occurs in DWM is not yet fully understood. The condition is diagnosed by MRI or, less commonly, prenatal ultrasound. There are other malformations that can strongly resemble DWM, and disagreement exists around the criteria and classifications used for the malformation.Treatment for most involves the implantation of a cerebral shunt in infancy. This is usually inserted in the posterior fossa, but a shunt in the lateral ventricles may be used instead or in conjunction. Endoscopic third ventriculostomy (ETV) is a less invasive option for patients older than 1 year. Posterior fossa shunts are most effective (80% of the time) but carry the highest risk of complications, while ETV is least effective but has the least risk of complications. The mortality rate is roughly 15%, mostly due to complications from hydrocephalus or its treatment, which can include subdural haematomas or infection. The prognosis after successful hydrocephalus treatment is usually good but depends on any associated condition and its symptoms. Those without hydrocephalus are treated based on any associated symptoms or condition.The prevalence of DWM is estimated at between 1 in 25,000 to 1 in 50,000. DWM is the cause of around 4.3% of cases of congenital hydrocephalus and 2.5% of all cases of hydrocephalus. At least 21% of those with DWM have a sibling with the malformation, and at least 16% have a parent with the malformation. The malformation was first described by English surgeon John Bland-Sutton in 1887, though it was named by German psychiatrist Clemens Ernst Benda in 1954 after American neurosurgeons Walter Dandy and Arthur Earl Walker, who described it in 1914 and 1942, respectively.
Signs and symptoms
Hydrocephalus
The most frequent and prominent symptoms of DWM are those associated with hydrocephalus in the postnatal period. Hydrocephalus occurs in an estimated 80% of patients with classic DWM. This usually presents within the first year of life (85% of the time), most often within the first 3 months. Signs of hydrocephalus in infants include increasing head size, vomiting, excessive sleepiness, irritability, downward deviation of the eyes (known as "sunsetting eyes") and seizures. In contrast to classic DWM, only around 30% of those with Dandy–Walker variant (DWV), in which the posterior fossa is not enlarged, have hydrocephalus.
Neurological
Despite the hypoplastic cerebellar vermis, just over half of individuals with DWM (between 27% and 84%) do not appear to have significant intellectual disability or developmental delay. However, many of the genetic conditions associated with DWM can present with developmental delay and other brain anomalies. Agenesis of the corpus callosum has been found in between 5% and 17% of those with DWM. This does not seem to result in intellectual disability on its own, however. Other brain abnormalities known to be sometimes associated with DWM include grey matter heterotopia, pachygyria (fewer ridges in the brain), lissencephaly (shallower ridges), polymicrogyria, holoprosencephaly and schizencephaly. Individuals with these features tend to have developmental delay or seizures. Those without any other central nervous system abnormalities tend to have normal or close-to-normal intellectual development. A 2003 review found that moderate-to-severe intellectual disability and non-DWM brain abnormalities were only present in those with the most severe cerebellar vermis malformations (less than two fissures/three lobules in the vermis), and these comprised 16% of their sample. Hydrocephalus also affected all of these patients.In Dandy–Walker variant (DWV) and mega cisterna magna specifically, which are less severe malformations, there appears to be an increased rate of psychotic spectrum disorders such as schizophrenia, bipolar disorder, mania or catatonia.
Associated anomalies
A 2017 review found the following associations in patients with DWS (usually from an associated genetic condition or abnormality):
27% of patients had a congenital heart defect. These included patent ductus arteriosus, coarctation of the aorta, ventricular septal defect and atrial septal defect. In 2.7% of patients, heart failure was reported.
24% of patients had at least one ocular abnormality. These included cataracts, small eyes (microphthalmia), chorioretinal dysplasia/atrophy, optic nerve dysplasia/atrophy, a small cornea (microcornea) or corneal opacity (leukoma), short-sightedness (myopia) and coloboma (a hole in an eye structure).
16% of patients were diagnosed with a mental or behavioural disorder, with 6.4% also having a learning disability. 5.3% had either bipolar disorder or a psychotic spectrum disorder, and 2.1% had ADHD. Slightly more of these were found in Dandy–Walker variant (DWV) than in classic DWM, despite DWV being less common, at only around 20% of DWS diagnoses.
Around 12% of patients had cancers or tumours arising from congenital genetic abnormalities. The most common were neurocutaneous melanosis (5.9%), hemangiomas (4.8%, including those with PHACE syndrome) and Wilms tumour (4.4%). 3.2% of patients had congenital melanocytic nevi, and 2.1% had tongue hamartoma. The melanocytic tumours in these cases are thought to relate to the same genetic errors in the development of the embryonic neural tube that lead to the DWM, since the subsequent embryonic neural crest gives rise to melanocytes, among other cells.
10% of patients had endocrine or metabolic disorders, and 2.7% had excessive hair growth (hypertrichosis).
9% of patients (almost all with classic DWM) had musculoskeletal abnormalities, which included scoliosis or kyphoscoliosis and arthrogryposis.
5.9% of patients had underdeveloped reproductive organs, such as hypoplastic genitalia or undescended testicles (cryptorchidism).
5.3% of patients had underdeveloped or polycystic kidneys.Occipital encephalocele may occur in DWM. This has generally been found at rates between 6 and 8%. It has been suggested to occur to compensate for the increased pressure in the posterior fossa during foetal life.Syringomyelia occasionally occurs with DWM, though it is not certain how often. One review reported an occurrence of 4.3% in a sample. This may be due to herniation of the bottom of the cyst through the foramen magnum (a similar mechanism to Chiari malformation). Alternatively, it may be a result of hydrocephalus, in which it forms as a "fifth ventricle" due to an enlarged central canal.Rarely, spina bifida has been found with DWM. When it is present, it is usually spina bifida occulta.
Cause
DWM is caused by any disruption to embryonic development that affects the formation of the cerebellar vermis. This is usually a genetic mutation that results in impaired cell migration and division. A large number of genetic conditions can result in the anomaly. In a large portion of DWM cases, the condition is identified in the person affected, however in most cases the cause is not identified. At least 21% of those with DWM have a sibling with the malformation, and at least 16% have a parent with the malformation.
Ciliopathic genetic conditions
A genetic condition is identified in around 33% of those diagnosed with DWM after birth. In a 2017 review, 4.3% were found to have PHACE syndrome, a condition involving brain, cardiovascular and eye abnormalities, while 2.3% had Joubert syndrome, a condition involving neurological and sometimes eye and kidney abnormalities. Anywhere from 21% to 81% of those with PHACE syndrome have DWM. Other comorbid genetic conditions that were found included oculocerebrocutaneous syndrome, oral-facial-digital syndrome, Coffin–Siris syndrome, Meckel–Gruber syndrome type 7 and Kallmann syndrome, among many others. DWM has also been associated with 3C syndrome, Rubinstein–Taybi syndrome, Marden–Walker syndrome, Sheldon–Hall syndrome, Shah–Waardenburg syndrome, Fryns syndrome,< Walker–Warburg syndrome, Fukuyama congenital muscular dystrophy, Ellis–van Creveld syndrome, Fraser syndrome, Aicardi syndrome, Cornelia de Lange syndrome,< Klippel–Feil syndrome and acrocallosal syndrome, among others. Many of these disorders are classified as ciliopathies, genetic disorders that affect the cellular primary cilia, thin cell projections made from microtubules that are believed to be crucial in signalling embryonic cell division and migration. DWM is one of the single largest predictors of a ciliopathic genetic disease.Other genes that have been linked to DWM include ZIC1, ZIC4, FOXC1, FGF17, LAMC1 and NID1.
Chromosomal abnormalities
In those who are diagnosed with DWM before birth on ultrasound, up to half are found to have a chromosomal abnormality, with the most common being Edwards syndrome (trisomy 18), at roughly 26% of prenatal DWM cases. 6.5% of those diagnosed with DWM after birth also have Edwards syndrome. Other chromosomal abnormalities that can lead to DWM include triploidy, Patau syndrome (trisomy 13), trisomy 9 and partial 3q deletion or duplication. The 3q24 region contains the ZIC1 and ZIC4 genes, known to be associated with DWM.
External toxins
Warfarin use during pregnancy has been known to lead to systemic defects in the fetus, including ocular dysgenesis, microcephaly, agenesis of the corpus callosum, skeletal abnormalities and heart defects. In 1985, it was also linked to DWM.
Pathophysiology
The cerebellum begins forming at the fifth week of embryonic development. It differentiates at the top of the metencephalon, while the pons (in the brainstem) differentiates at the bottom, separated by the fourth ventricle. The cerebellar hemispheres form from the rhombic lips on the forward surface of the fourth ventricle, which expand and roll over to fuse in the midline to form the cerebellar vermis by the 15th week. If this process does not complete, the cerebellar vermis will not form fully. This long period of development of the cerebellar vermis makes it particularly vulnerable to disruptions.In DWM, the fourth ventricle opens up into and is continuous with almost the entire posterior fossa subarachnoid space.
Pathophysiology of hydrocephalus
The reason why hydrocephalus occurs in DWM is not yet fully understood. The earliest authors had put it down it to blockage or narrowing of the foramina of Magendie and Luschka, the two apertures in the fourth ventricle that allow cerebrospinal fluid (CSF) to escape into the subarachnoid space of the posterior fossa. However, later studies found that these foramina are usually open in DWM. Hydrocephalus is also usually (80% of the time) not present at birth in those with DWM.The impairment to CSF flow may lie beyond the outlets of the fourth ventricle. Theories of abnormal development or inflammation of the arachnoid mater in the posterior fossa have been put forward. The arachnoid mater contains granulations necessary to return CSF from the subarachnoid spaces to the dural veins and circulation. Excisions of the cyst in DWM have not been able to show whether impaired arachnoid absorption is involved, since the subarachnoid space always takes days to weeks to fill up following excision.Aqueductal stenosis (narrowing of the passage between the third and fourth ventricles) does not seem to be a factor in DWM. It is usually open, and shunts placed in the posterior fossa cyst almost always drain all above ventricles. When it is present, it may be the result of compression from a herniated vermis or cyst or an associated developmental abnormality.It is known that once hydrocephalus has started, the compression by the posterior fossa cyst against the venous passages in the arachnoid mater is involved in the worsening pathology.
Diagnosis
Dandy–Walker malformation is diagnosed based on the characteristic neuroimaging findings. It can be diagnosed prenatally on ultrasound as early as 14 weeks of gestation, although it is usually diagnosed postnatally by MRI. It is diagnosed within the first year of life 41% of the time, normally due to increasing signs of hydrocephalus, but 28% of the time it is discovered in adolescence or adulthood due to mental health problems, such as psychosis or mood disorder.
Criteria and classification
The precise diagnostic criteria and classification systems of DWM are not agreed upon, and significant dispute exists as to which terms or criteria should be used. The core criteria of DWM are hypoplasia of the cerebellar vermis and an enlarged fourth ventricle and posterior fossa (the space behind the cerebellum), though the specific degree of hypoplasia or cystic enlargement for diagnosis of DWM is not agreed upon. Additionally, there are several similar conditions which have at various times been grouped with DWM on a continuum by some authors and separated as distinct by others, further complicating diagnosis.In 1976, Harwood-Nash and Fitz proposed the term Dandy–Walker variant (DWV) for a malformation in which the posterior fossa is not enlarged but the cerebellar vermis is hypoplastic. In 1989, Barkovich et al. proposed the term Dandy–Walker complex (DWC) to include classic DWM and DWV (under type A) plus a third malformation (under type B) in which the cerebellar vermis remains large enough to sit between the fourth ventricle and the cisterna magna beneath it, and instead it is mostly the cisterna magna that is enlarged. In this type, the hypoplasia of the cerebellar vermis does not reach past the horizontal midline of the fourth ventricle, and the posterior fossa is also not as large. The authors noted that this form would previously have been classified as simply mega–cisterna magna. In 1999, Calabró et al. first used the phrase Dandy–Walker continuum when referring to proposals that a condition known as Blakes pouch cyst falls under the umbrella of the Dandy–Walker complex proposed by Barkovich. Later authors would put these terms and systems under intense scrutiny and state that they added considerable confusion to the diagnosis of DWM. However, they remain commonly used.In 2011, Spennato et al. came up with a set of criteria based on Klein et al. (2003) that they considered necessary for diagnosis of DWM:
The lower portion of the cerebellar vermis is absent to varying degrees (three quarters, one half or one quarter missing).
The posterior fossa (the space behind the cerebellum) is enlarged, and its cerebrospinal fluid flow is continuous with that of the fourth ventricle.
The rest of the cerebellar vermis is hypoplastic and is pushed upwards and rotated forwards due to the enlarged posterior fossa.
The cerebellar hemispheres are pushed forwards and to the side by the enlarged posterior fossa.
The angle at the centre of the cerebellar vermis (representing the location of the fastigial nucleus) is large, giving a flattened appearance to the bottom of the vermis, or the fastigial nucleus is absent entirely.
The confluence of sinuses, part of the drainage system located at the far rear of the occipital lobe, is elevated due to the enlarged posterior fossa. (The adjacent cerebellar tentorium is also elevated.)Due to the inconsistency of the presence of hydrocephalus in DWM, Spennato and Klein suggested that it should not be considered a criterion for DWM. Kleins criteria differed from Spennatos mainly in that it required no apparent cerebellar hemisphere hypoplasia, but it may also have required the vermis to touch the tentorium or an absence of brainstem abnormalities.
Methods
DWM can be observed prenatally on ultrasound as early as 14 weeks of gestation, though an MRI scan is the most useful method for diagnosis. MRI can delineate the shape and extent of the malformation as well as assessing additional areas for malformations such as the cerebellar hemispheres, cerebral aqueduct or corpus callosum. Cardiac-gated phase-contrast MRI can observe the flow of cerebrospinal fluid (CSF) during systole and diastole of the heart. In true DWM, this will find a flow from the cerebral aqueduct to the posterior fossa and no flow between the cisterna magna and the space behind the cervical spinal cord.CT may also be used if MRI is unavailable, but it provides less detail. Klein et al. (2003) suggested that a suspected diagnosis based on CT or ultrasound should not be confirmed until an MRI is performed, due to the large number of conditions that can present highly similarly and confound diagnosis.
Differential diagnosis
DWM has a large number of conditions that can present highly similarly on imaging and confound diagnosis.
Blakes pouch cyst
Blakes pouch cyst (BPC), or persistent Blakes pouch, is a condition that arises when Blakes pouch, an invagination in the fourth ventricle that ruptures at around 4 months of gestation to form the foramen of Magendie (medial aperture), fails to rupture. This can lead to a dilated fourth ventricle and subsequent hydrocephalus of all four ventricles.In a Blakes pouch cyst, unlike in DWM:
The cerebellum is not hypoplastic, though it may be compressed by the enlarged posterior fossa (mass effect).
The posterior fossa is not enlarged.
The cerebellar tentorium/confluence of sinuses is not raised.
Hydrocephalus, when it occurs, involves all four ventricles.Some authors, however, consider Blakes pouch cyst part of a continuum with DWM (the "Dandy–Walker continuum").
Mega cisterna magna
Mega cisterna magna is a condition in which the cisterna magna, the subarachnoid cistern below the fourth ventricle, is enlarged. It has been proposed to be due to a delayed rupture of Blakes pouch rather than a failed rupture.In mega cisterna magna, unlike in DWM:
The cerebellum is not usually hypoplastic.
The fourth ventricle is of relatively normal shape.
Hydrocephalus is uncommon.There is debate as to whether this malformation is distinct from DWM or forms part of the "Dandy–Walker continuum".
Posterior fossa arachnoid cyst
An arachnoid cyst is a collection of cerebrospinal fluid (CSF) in the arachnoid mater. 10% of these occur in the posterior fossa.In a posterior fossa arachnoid cyst, unlike in DWM:
The cyst is clearly localised in a specific location separate from the fourth ventricle outlets.
The cerebellum is not hypoplastic, though it may be compressed by the cyst (mass effect).
The CSF flow in the cyst is not continuous with that of the fourth ventricle.
Hydrocephalus, if it occurs, is due to the cyst pressing on the cerebellum and compressing the cerebral aqueduct or fourth ventricle outlets.
Treatment
The main immediate goal of treatment is the control of hydrocephalus and the enlarged posterior fossa cyst, as these can lead to increased intracranial pressure and brain damage. A minority of those affected do not develop hydrocephalus and are treated based on any associated symptoms or condition.
Hydrocephalus/cyst
For hydrocephalus or the posterior fossa cyst, shunts are the mainstay of treatment. However, those with DWM have a higher rate of shunt-related complications than other patients with hydrocephalus (mainly due to the unconventional anatomy). One explanation for a failure of a shunt to reduce intracranial pressure in DWM has been that the cyst may herniate into the foramen magnum and form a scarring adhesion at the cervical junction, preventing it from shrinking again. If this occurs, a suboccipital decompression with duraplasty may be attempted.In DWM, it is not agreed whether a shunt should be placed in the fourth ventricle (a cystoperitoneal shunt, or CP shunt), the lateral ventricles (a ventriculoperitoneal shunt, or VP shunt) or both, due to conflicting studies on whether the cerebral aqueduct is affected by the malformation. However, a CP shunt almost always drains both the fourth and lateral ventricles in DWM, and according to strict definitions of the malformation, the aqueduct should be assumed open, though imaging is important to confirm this. Many authors therefore recommend the CP shunt as the logical option. However, it is associated with a high rate of complications, including shifting and overdrainage. Overdrainage can lead to subdural haematomas, a tethered spinal cord, due to scarring, or downward herniation of the cerebral hemispheres. Spennato et al. therefore recommend a flow-regulating or anti-syphon valve. On the other hand, VP shunts have a lower rate of complications than CP shunts and are recommended initially by some. However, they are less effective in DWM, and the elevated position of the tentorium should be considered before installing a VP shunt.In patients older than 1 year, endoscopic third ventriculostomy (ETV) may be considered as the first-line treatment. This less invasive procedure creates an artificial hole in the third ventricle to allow CSF to bypass any obstruction. It cannot be used on those with brain abnormalities such as agenesis of the corpus callosum, due to the risk of CSF escaping to other brain areas. A compressed brainstem is not a contraindication, however. ETV has a more modest success rate than shunts, as the hole often closes over. It is more likely to fail in younger patients (below 1 year), and its effects on the developing brain are not yet known. Cysts posterior to the cerebellum, presenting in children younger than 5 years, have been labeled developmental retrocerebellar cysts under a new classification in relation to the proposed neuroendoscopic management.Previously, craniotomy of the posterior fossa and excision of the cystic membrane was used, which was often unsuccessful in preventing cyst reformation and carried a degree of mortality. This may still be reserved for patients with repeated shunt failures/infections.
Other
Treatments for any other symptoms are generally focussed on the specific condition involved and may include supported education, physical therapy or other services. Genetic counselling may be offered to parents for future conceptions.
Prognosis
The prognosis is first and foremost dependent on the early and successful treatment of hydrocephalus, if present. The other significant factor affecting prognosis is the presence of a comorbid genetic condition or brain anomaly.Mortality rates from DWM are roughly 15%. In a study of Dandy–Walker variant (DWV), a mortality rate of 12.5% was observed. The most common cause of death is complications from hydrocephalus or its treatment. Untreated hydrocephalus can lead to increased intracranial pressure and brain damage. Shunts used to treat DWM have a moderate-to-good success rate, but they have a higher-than-average failure rate, which can result in failure to reduce the intracranial pressure or infection, such as meningitis. Complications from overdrainage such as subdural haematomas are also possible and can lead to mortality. Shunts in the fourth ventricle (cystoperitoneal shunts, or CP shunts) have a generally high rate of successful cyst and ventricle size reduction, especially in the cyst (at least 80%). With a shunt in the lateral ventricles (ventriculoperitoneal shunt, or VP shunt), studies have generally found a roughly 50% successful cyst size reduction rate, with successful ventricle size reduction roughly two thirds of the time.Other systemic or genetic conditions are often present with DWM, and each have their own significant effect on prognosis.
Epidemiology
The prevalence of DWM is estimated at between 1 in 25,000 to 1 in 50,000. DWM is the cause of around 4.3% of cases of congenital hydrocephalus and 2.5% of all cases of hydrocephalus.A 2017 review found that most patients (65%) were diagnosed with either "Dandy–Walker malformation" or "Dandy–Walker syndrome", while 20% were diagnosed with "Dandy–Walker variant" and 1.1% with "mega cisterna magna".
History
The malformation was first described in 1887 by English surgeon John Bland-Sutton as hypoplasia of the cerebellar vermis, an enlarged posterior fossa and hydrocephalus. In 1914, American neurosurgeon Walter Dandy and American paediatrician Kenneth Blackfan described the malformation as partial or complete absence of the cerebellar vermis, an enlarged fourth ventricle and hydrocephalus. In 1942, American physician John K. Taggart and Canadian–American neurosurgeon Arthur Earl Walker detailed the phenomenon extensively, ascribing the potential cause as underdevelopment of the foramina of Luschka and Magendie, now no longer believed to be significant.The term Dandy–Walker syndrome (DWS) was introduced by German psychiatrist Clemens Ernst Benda in 1954; he also used the term Dandy–Walker malformation once. In 1976, Harwood-Nash and Fitz proposed the term Dandy–Walker variant (DWV) for a malformation in which the posterior fossa is not enlarged but the cerebellar vermis is hypoplastic. In 1989, Barkovich et al. proposed the term Dandy–Walker complex (DWC) to include classic DWM and DWV (under type A) plus a third malformation (under type B) in which the cerebellar vermis remains large enough to sit between the fourth |
Dandy–Walker malformation | ventricle and the cisterna magna, and instead it is mostly the cisterna magna that is enlarged (sometimes diagnosed as "mega cisterna magna"). In 1999, Calabró et al. first used the phrase Dandy–Walker continuum when referring to proposals that a condition known as Blakes pouch cyst falls under the umbrella of the Dandy–Walker complex proposed by Barkovich. These additional terms are mostly discouraged by modern authors due to additional confusion and complexity to the diagnosis of DWM.
References
This article incorporates public domain material from the United States Government document: "Dandy-Walker Syndrome Information Page".
Further reading
Metry Phaces article in the Journal of Pediatrics, July 2001
E-medicine webpage definition
Dandy–Walker Malformation article from Pan Arab Journal of Neurosurgery
== External links == |
Clubfoot | Clubfoot is a birth defect where one or both feet are rotated inward and downward. Congenital clubfoot, is the most common congenital malformation of the foot with an incidence of 1 per 1000 births. In approximately 50% of cases, clubfoot affects both feet, but it can present unilaterally causing one leg or foot to be shorter than the other. Most of the time, it is not associated with other problems. Without appropriate treatment, the foot deformity will persist and lead to pain and impaired ability to walk, which can have a dramatic impact on the quality of life.The exact cause is usually not identified. Both genetic and environmental factors are believed to be involved. There are two main types of congenital clubfoot: idiopathic (80% of cases) and secondary clubfoot (20% of cases). The idiopathic congenital clubfoot is a multifactorial condition that includes environmental, vascular, positional, and genetic factors. There appears to be hereditary component for this birth defect given that the risk of developing congenital clubfoot is 25% when a first-degree relative is affected. In addition, if one identical twin is affected, there is a 33% chance the other one will be as well. The underlying mechanism involves disruption of the muscles or connective tissue of the lower leg, leading to joint contracture. Other abnormalities are associated 20% of the time, with the most common being distal arthrogryposis and myelomeningocele. The diagnosis may be made at birth by physical examination or before birth during an ultrasound exam.The most common initial treatment is the Ponseti method, which is divided into two phases: 1) correcting of foot position and 2) casting at repeated weekly intervals. If the clubfoot deformity does not improve by the end of the casting phase, an Achilles tendon tenotomy can be performed. The procedure consists of a small posterior skin incision through which the tendon cut is made. In order to maintain the correct position of the foot, it is necessary to wear an orthopedic brace until 5 years of age.Initially, the brace is worn nearly continuously and then just at night. In about 20% of cases, further surgery is required. Treatment can be carried out by a range of healthcare providers and can generally be achieved in the developing world with few resources.Clubfoot occurs in 1 to 4 of every 1,000 live births, making it one of the most common birth defects affecting the legs. About 80% of cases occur in developing countries where there is limited access to care. Clubfoot is more common in firstborn children and males. It is more common among Māori people, and less common among Chinese people.
Epidemiology
Birth prevalence of clubfoot varies between 0.51 and 2.03/1,000 live births in Low to middle income countries. It is one of the most common birth defects affecting the legs. Clubfoot is more common in firstborn children and males, who are twice as likely to be affected as females. It is more common among Māori people, and less common among Chinese people.Clubfoot disproportionally affects those in low and middle-income countries (LMICs). About 80% of those with clubfoot, or approximately 100,000 children per year as of 2018, are born in LMICs.
History
Pharaohs Siptah and Tutankhamun had clubfoot, and the condition appeared in Egyptian paintings. Indian texts (c. 1000 BC) and Hippocrates (c. 400 BC) described treatment. In 1823, Delpech presented another way to treat patient with clubfoot. This new way was tenotomy, which means the cut of the Achilles tendon in those patients. As a surgical procedure it had its complications like infections.
Signs and symptoms
In clubfoot, feet are rotated inward and downward. The affected foot and leg may be smaller than the other, while in about half of cases, clubfoot affects both feet. Most of the time clubfoot is not associated with other problems.Clubfoot can be diagnosed by ultrasound of the fetus in more than 60% of cases. The earliest week of gestation in which the condition is diagnosed with a high degree of confidence was the 12th and the latest was the 32nd. Not all patients were diagnosed at an early stage. In 29% of fetuses the first ultrasound examination failed to detect the deformity which subsequently became obvious at a later examination. Clubfoot was diagnosed between 12 and 23 weeks of gestation in 86% of children and between 24 and 32 weeks of gestation in the remaining 14%.Without treatment the foot remains deformed and people walk on the sides or tops of their feet, which can cause calluses, foot infections, trouble fitting into shoes, pain, difficulty walking, and disability.
Causes
Hypotheses about the precise cause of clubfoot vary. However, research has found that genetics, environmental factors or a combination of both are associated with this condition. Evidence suggests that the etiology of clubfoot is most likely multifactorial. A meta-analysis and systematic review found that the most clinically relevant risk factors for clubfoot were family history, paternal and maternal smoking, birthing parent obesity, gestational diabetes, amniocentesis, and the use of selective serotonin re-uptake inhibitors (SSRIS). Many findings agree that "it is likely there is more than one different cause and at least in some cases the phenotype may occur as a result of a threshold effect of different factors acting together." The most commonly associated conditions are distal arthrogryposis or myelomeningocele. The factors contributing to the development of clubfoot can be categorized as extrinsic and intrinsic factors.Extrinsic Factors
Factors that can influence the positioning of the fetal foot in uteru include oligohydramnios, breech presentation, Müllerian anomalies, multiple gestation, amniotic band sequence, or amniocentesis at <15 weeks of gestation. In cases that impede normal growth and position for longstanding period of times, clubfoot can be accompanied with other deformations and may be associated with developmental hip dysplasia. The theory of fetal growth arrest was proposed by Von Volkmann in 1863, and has been verified by other authors since. According to this theory, intrinsic errors or environmental insults during gestation prevents the correction of a equinovarus to pronated foot. Other researchers hypothesize that clubfoot may derive from external insults during gestation. For example, a research study found an alarming high incidence of club foot and limb contractures associated with iatrogenic amniotic leakage cause by early amniocentesis between the 11th and 12th week of gestation.Intrinsic Factors
Chromosomal abnormalities found in 30% and 2% of complex clubfoot and isolated clubfoot respectively. These include trisomy 18, 13, 21, sex chromosome abnormalities, micro-deletions and duplications.
Genetic Syndromes: Larsen, Gordon, Pierre-Robin, Meckel-Gruber, Roberts, Smith-Lemli-Opitz, TARP (Talipes equinovarus, Atrial septal defect, Robin sequence, Persistence of left superior vena cava).
Skeletal Dysplasias: Ellis van Creveld syndrome, diastrophic dysplasia, chondrodysplasia punctata, camptomelic dysplasia, atelosteogenesis, and mesomelic dysplasia.
Neuromuscular and Neurologic abnormalities: arthrogryposis multiplex congenita, myotonic dystrophy, spinal muscular atrophy, neural tube defects, holoprosencephaly, and hydranencephaly.
Genetics
Clubfoot can be diagnosed prenatally as early as 13 weeks of gestation via ultrasound. According to the Society of Maternal-Fetal Medicine, a diagnostic testing for genetic causes is recommended when clubfoot is diagnoses prenatally. If prenatal screening is suspicious for aneuploidy, karyotype analysis or chromosomal microarray (CMA) may be performed. However, if patients decline diagnostic testing, Cell-Free DNA is another screening option to identify high-risk pregnancies for aneuploidy and it is not diagnostic. The incidence of chromosomal abnormalities in fetuses with prenatal diagnosis of clubfoot is relatively low. Overall, fetal ultrasound should be performed with a prenatal diagnosis of clubfoot in order to classify the condition as either complex or isolated because of the significant differences in rates of chromosomal abnormalities and outcomes between these two groups.If one identical twin is affected, there is a 33% chance the other one will be as well.Mutations in genes involved in muscle development are risk factors for clubfoot, specifically those encoding the muscle contractile complex (MYH3, TPM2, TNNT3, TNNI2 and MYH8). These can cause congenital contractures, including clubfoot, in distal arthrogryposis (DA) syndromes. Clubfoot can also be present in people with genetic conditions such as Loeys–Dietz syndrome and Ehlers-Danlos syndrome.Genetic mapping and the development of models of the disease have improved understanding of developmental processes. Its inheritance pattern is explained as a heterogenous disorder using a polygenic threshold model. The PITX1-TBX4 transcriptional pathway has become key to the study of clubfoot. PITX1 and TBX4 are uniquely expressed in the hind limb.
Diagnosis
Clubfoot is diagnosed through physical examination. Typically, babies are examined from head-to-toe shortly after they are born. There are four components of the clubfoot deformity:
Factors used to assess severity include the stiffness of the deformity (how much it can be corrected by manually manipulating the foot), the presence of skin creases at the arch and heel, and poor muscle consistency.
Sometimes, it is possible to detect clubfoot before birth using ultrasound. Prenatal diagnosis by ultrasound can allow parents to learn more about this condition and plan ahead for treatment after their baby is born.More testing and imaging is typically not needed, unless there is concern for other associated conditions.
Treatment
Treatment is usually with some combination of the Ponseti method and French method. The Ponseti method involves a combination of casting, Achilles tendon release, and bracing. It is widely used and highly effective under the age of two. The French method involves realignment, taping, and long-term home exercises and night splinting. It is also effective but outcomes vary and rely on heavy involvement of caregivers. Generally, the Ponseti method is preferred. Another technique, the Kite method, does not appear to be as effective. In about 20% of cases, additional surgery is required after initial treatment.
Ponseti method
The Ponseti method corrects clubfoot over the course of several stages.
Serial casting: First, the foot is manually manipulated into an improved position and held in place with a long leg cast which extends from the toes up to the thigh. After a week this cast is removed, the foot is re-manipulated, and placed into a new cast. This process repeats and the foot is gradually reshaped over the course of 4-6 serial casts, although some feet may require additional casts.
The goal of the initial cast is to align the forefoot with the hindfoot. Ponseti describes the forefoot as pronated in relation to the hindfoot, so supinating the forefoot and elevating the first metatarsal improves this alignment.
Subsequent casts are applied after stretching the foot with a focus on abducting the forefoot with lateral pressure at the talus, to bring the navicular laterally and improve the alignment of the talonavicular joint. In contrast to the Kite method of casting, it is important to avoid constraining the calcanocuboid joint. With each additional cast, the abduction is increased and this moves the hindfoot from varus into valgus. It is important to leave the ankle in equinus until the forefoot and hindfoot are corrected.
The final stage of casting is to correct the equinus. After fully abducting the forefoot with spontaneous correction of the hindfoot, an attempt is made to bring the ankle up and into dorsiflexion. The foot must have the ability to dorsiflex to at least 10 degrees past 0 (neutral, or L position), although 15 degrees or more is better and preferred. If the foot can not dorsiflex enough, the brace will not work/be tolerated. If it is determined the foot can not dorsiflex at least 10 degrees, the Achilles Tenotomy surgical procedure is performed.
Achilles tendon release: At the end of the serial casting, most children have corrected cavus, adductus and varus deformities, but continue to have equinus deformity. To correct this, a procedure called an Achilles tendon release (commonly called Achilles tenotomy) is performed. Before the procedure, many centers place the child under sedation or monitored anesthesia care, although Ponseti recommended using local anesthetic alone. Next, the area around the heel is cleansed and numbed, and a small scalpel is used to cut the Achilles tendon. The incision is small so there is minimal bleeding and no need for stitches. The skin is covered with a small dressing, and the foot is placed into a final long leg cast in a fully corrected position. This cast is typically left in place for three weeks. During this time, the Achilles tendon will regrow in a lengthened position.
Bracing: After successful correction is achieved through serial casting and Achilles tenotomy, the foot must be kept in a brace to prevent it from returning to the deformed position over the first few years of a childs life. The brace is made up of two shoes or boots that are connected to each other by a bar that is bent under the shoes at 10-15 degrees, or curved to create 10-15 degrees dorsiflexion. This device is also called a foot abduction brace (FAB) or more generally boots and bar (BnB). At first, the brace is worn full-time (23 hours per day) on both feet, regardless of whether the clubfoot affects one or two feet. After 3 months of 23/7 wear, the brace is worn less frequently by gradually reducing hours a couple at a time, every couple months so that hours are down to 12-14 per day at or around a year old. From this point on until at least 4–5 years, or even longer (6–9 years if needed), the brace is worn mostly while sleeping at night and during naps (12–14 hours per day). Bracing is essential in preventing recurrence of the deformity and is a major determinant of a childs long-term outcome.The Ponseti method is highly effective with short-term success rates of 90%. However, anywhere from 14% to 41% of children experience a recurrence of the deformity. The most common reason for this is inadequate adherence to bracing, such as not wearing the brace properly, not keeping it on for the recommended length of time, or not using it every day. Children who do not follow proper bracing protocol have up to seven times higher recurrence rates than those who follow bracing protocol, as the muscles around the foot can pull it back into the abnormal position. Low parental education level and failure to understand the importance of bracing is a major contributor to non-adherence. Relapses are managed by repeating the casting process. Relapsed feet may also require additional, more extensive surgeries and have a reduced chance of achieving subsequent correction.Another reason for recurrence is a congenital muscle imbalance between the muscles that invert the ankle (tibialis posterior and tibialis anterior muscles) and the muscles that evert the ankle (peroneal muscles). This imbalance is present in approximately 20% of infants successfully treated with the Ponseti casting method, and makes them more prone to recurrence. This relapse is usually treated with Ponseti casting and can be done multiple times before resorting to surgery. If after all non-surgical casting and bracing options have been exhausted, and when the child is over four years of age (many doctors prefer to wait until after seven years old), this can be addressed with a surgery to transfer the tibialis anterior tendon from its medial attachment (on the navicula) to a more lateral position (on the lateral cuneiform). The surgery requires general anesthesia and subsequent casting while the tendon heals, but it is a relatively minor surgery that re-balances the muscles of the foot without disturbing any joints.
French method
The French method is a conservative, non-operative method of clubfoot treatment that involves daily physical therapy for the first two months followed by thrice-weekly physical therapy for the next four months and continued home exercises following the conclusion of formal physical therapy. During each physical therapy session the feet are manipulated, stretched, then taped to maintain any gains made to the feets range of motion. Exercises may focus on strengthening the peroneal muscles, which is thought to contribute to long-term correction. After the two month mark, the frequency of physical therapy sessions can be weaned down to three times a week instead of daily, until the child reaches six months. After the conclusion of the physical therapy program, caregivers must continue performing exercises at home and splinting at night in order to maintain long-term correction.
Compared to the Ponseti method which uses rigid casts and braces, the French method uses tape which allows for some motion in the feet. Despite its goal to avoid surgery, the success rate varies and surgery may still be necessary. The Ponseti method is generally preferred over the French method.
Surgery
If non-operative treatments are unsuccessful or achieve incomplete correction of the deformity, surgery is sometimes needed. Surgery was more common prior to the widespread acceptance of the Ponseti method. The extent of surgery depends on the severity of the deformity. Usually, surgery is done at 9 to 12 months of age and the goal is to correct all the components of the clubfoot deformity at the time of surgery.
For feet with the typical components of deformity (cavus, forefoot adductus, hindfoot varus, and ankle equinus), the typical procedure is a Posteromedial Release (PMR) surgery. This is done through an incision across the medial side of the foot and ankle, that extends posteriorly, and sometimes around to the lateral side of the foot. In this procedure, it is typically necessary to release (cut) or lengthen the plantar fascia, several tendons, and joint capsules/ligaments. Typically, the important structures are exposed and then sequentially released until the foot can be brought to an appropriate plantigrade position. Specifically, it is important to bring the ankle to neutral, the heel into neutral, the midfoot aligned with the hindfoot (navicula aligned with the talus, and the cuboid aligned with the calcaneus). Once these joints can be aligned, thin wires are usually placed across these joints to hold them in the corrected position. These wires are temporary and left out through the skin for removal after 3–4 weeks. Once the joints are aligned, tendons (typically the Achilles, posterior tibialis, and flexor halluces longus) are repaired at an appropriate length. The incision (or incisions) are closed with dissolvable sutures. The foot is then casted in the corrected position for 6–8 weeks. It is common to do a cast change with anesthesia after 3–4 weeks, so that pins can be removed and a mold can be made to fabricate a custom AFO brace. The new cast is left in place until the AFO is available. When the cast is removed, the AFO is worn to prevent the foot from returning to the old position.For feet with partial correction of deformity with non-operative treatment, surgery may be less extensive and may involve only the posterior part of the foot and ankle. This might be called a posterior release. This is done through a smaller incision and may involve releasing only the posterior capsule of the ankle and subtalar joints, along with lengthening the Achilles tendon.
Surgery leaves residual scar tissue and typically there is more stiffness and weakness than with nonsurgical treatment. As the foot grows, there is potential for asymmetric growth that can result in recurrence of foot deformity that can affect the forefoot, midfoot, or hindfoot. Many patients do fine, but some require orthotics or additional surgeries. Long-term studies of adults with post-surgical clubfeet, especially those needing multiple surgeries, show that they may not fare as well in the long term. Some people may require additional surgeries as they age, though there is some dispute as to the effectiveness of such surgeries, in light of the prevalence of scar tissue present from earlier surgeries.
Developing world
Despite effective treatments, children in LMICs face many barriers such as limited access to equipment (specifically casting materials and abduction braces), shortages of healthcare professionals, and low education levels and socioeconomic status amongst caregivers and families. These factors make it difficult to detect and diagnose children with clubfoot, connect them to care, and train their caregivers to follow the proper treatment and return for follow-up visits. It is estimated that only 15% of those diagnosed with clubfoot receive treatment.In an effort to reduce the burden of clubfoot in LMICs, there have been initiatives to improve early diagnosis, organize high-volume Ponseti casting centers, utilize mid-level practitioners and non-physician health workers, engage families in care, and provide local follow-up in the persons community.
Cultural references
Hippolyte Tautain, the stableman at the Lion DOr public house in the 1856 novel Madame Bovary by Gustave Flaubert, has clubfoot. Charles Bovary tries to correct it, but the procedure is unsuccessful, and Tautain must have an amputation.
Philip Carey, the main character of the 1915 novel Of Human Bondage by W. Somerset Maugham, has clubfoot. It is a central theme of the work.
Velma, a character in the 1941 film High Sierra, has clubfoot. It is successfully treated with surgery.
Gimpy, a coworker of the main character in the 1959 science fiction short story "Flowers for Algernon" by Daniel Keyes, has clubfoot.
Kashiwagi, a character in the 1956 novel The Temple of the Golden Pavilion by Yukio Mishima, has clubfoot. It parallels the main character, Mizoguchi, who has a stutter.
Johnson, a character in the 1965 short story "The Lame Shall Enter First" by Flannery OConnor, has clubfoot. It is a major symbol in the story.
The main character of the 1974 science fiction novel The Bladerunner by Alan E. Nourse has clubfoot.
The main character of the 1985 novel Perfume: The Story of a Murderer by Patrick Süskind, has clubfoot. It causes a limp.
Senji, a character in the 1987 to 1991 fantasy book series The Mallorean by David Eddings, has clubfoot.
Kwai Geuk-Chat, a character in the 1993 film Once Upon a Time in China III, which is part of the 1991 to 1997 Once Upon a Time in China series, has clubfoot. He is nicknamed "Clubfoot Seven Chiu-Tsat" – "Clubfoot" because of his foot, and "Seven Chiu-Tsat" because he is the seventh member of the character Chiu Tin-baks apprentices, disciples, and henchmen.
Mordred, King of Dumonia, a character in the 1995 to 1997 historical fantasy book series The Warlord Chronicles by Bernard Cornwell, has clubfoot. It is often used as a symbol for his weakness as a ruler.
Charlie Wilcox, the main character of the 2000 childrens book of the same name by Sharon McKay, has clubfoot.
Vulcan the blacksmith, a character in the 2001 novel The Secrets of Vesuvius, which is part of the 2001 to 2009 historical fiction series The Roman Mysteries by Caroline Lawrence, has clubfoot.
Princess Matilda, the main character of Handbook for Dragon Slayers by Merrie Haskell, a 2013 novel published by HarperCollins, has a clubfoot.
Ada, the main character of the 2016 childrens book The War That Saved My Life by Kimberly Brubaker Bradley, has clubfoot. Her mother emotionally and physically abuses her because of it.
References
== External links == |
Hypoplastic left heart syndrome | Hypoplastic left heart syndrome (HLHS) is a rare congenital heart defect in which the left side of the heart is severely underdeveloped and incapable of supporting the systemic circulation. It is estimated to account for 2-3% of all congenital heart disease. Early signs and symptoms include poor feeding, cyanosis, and diminished pulse in the extremities. The etiology is believed to be multifactorial resulting from a combination of genetic mutations and defects resulting in altered blood flow in the heart.Several structures can be affected including the left ventricle, aorta, aortic valve, or mitral valve all resulting in decreased systemic blood flow.Diagnosis can occur prenatally via ultrasound or shortly after birth via echocardiography. Initial management is geared to maintaining patency of the ductus arteriosus - a connection between the pulmonary artery and the aorta that closes shortly after birth.Patient subsequently undergoes a three-stage palliative repair over the next few years of life. The Norwood procedure is typically done within a few days of birth. The Glenn procedure is typically performed at three to six months of age. Finally the Fontan procedure is done sometime between the age of two and five years of age.
If left untreated patients with HLHS die within the first weeks of life while 70% of those that undergo three-staged palliative surgery reach adulthood. After surgery children with HLHS typically experience neurodevelopmental as well as motor delay and are at an increased risk of heart failure as adults.
Epidemiology
HLHS occurs in an estimated 1 out of 3,841 live births in the United States, or an estimated total of 1,025 live births per year in the US. Overall, it is estimated to make up 2-3% of all cases of congenital heart disease, and is the most common single-ventricle defect. It is thought to be more common in male infants, 1.5 times as common as in female infants. A recent systematic review found a slight decrease in prevalence of HLHS from 0.689/1000 in 1995 -1999, to 0.475/1000 in 2010 - 2017. This is thought to be due to improvements in prenatal detection and prenatal counseling and subsequent pregnancy.
Signs and symptoms
Closing of the ductus arteriosus in a heart that is severely underdeveloped on the left results in cyanosis and respiratory distress which can progress to cardiogenic shock and death. Early symptoms might include poor feeding or cyanosis that does not respond to oxygen administration. Peripheral pulses may be weak and extremities cool to the touch.HLHS often co-occurs with low birth weight and premature birth.In neonates with a small atrial septal defect, termed "restrictive", there is inadequate mixing of oxygenated and deoxygenated blood. These neonates quickly decompensate and develop acidosis and cyanosis.On EKG, right axis deviation and right ventricular hypertrophy are common, but not indicative of HLHS. Chest x-ray may show a large heart (cardiomegaly) or increased pulmonary vasculature. Neonates with HLHS do not typically have a heart murmur, but in some cases, a pulmonary flow murmur or tricuspid regurgitation murmur may be audible.Co-occurring tricuspid regurgitation or right ventricular dysfunction can cause hepatomegaly to develop.
Pathogenesis
The majority of HLHS cases are sporadic meaning they arise in patients with no family history of HLHS. Some cases may have a genetic component, as HLHS has been shown to be heritable and associated with specific gene mutations. Possible contributing factors may include intrauterine infarction, infectious changes, and a selective left ventricular cardiomyopathy.
Genetics
Genetic loci associated with HLHS include GJA1 (connexin 43), HAND1, NKX2.5, 10q22, and 6q23. There is a slight risk of recurrence in future pregnancies, estimated to be 2-4%, which increases to 25% in families with two affected children. This is thought to be mediated by genetic mutations with incomplete penetrance.HLHS is also associated with several genetic syndromes, including trisomy 13 (Patau syndrome), trisomy 18 (Edwards syndrome), partial trisomy 9, Turners syndrome (XO), Jacobsen syndrome (11q deletion syndrome), Holt-Oram syndrome, and Smith-Lemli-Opitz syndrome.
Altered Blood Flow
A popular theory termed the "no flow, no grow" hypothesis suggest that primary anatomic defects of the aortic and mitral valves lead to malformations of the left ventricle and its outflow tract. These primary defects can be divided into those that lead to outflow tract obstruction or reduced left ventricular filling. Outflow tract obstruction leads to left ventricular hypertrophy and reduction in the left ventricular lumen. One example of this would be in the case of aortic stenosis. Aortic stenosis that occurs during fetal development results in added stress on the left ventricle in utero. This can eventually lead to decreased perfusion through the left ventricle which is believed to inhibit ventricular growth.
Pathophysiology
At birth, the ductus arteriosus is still open, and there is higher than normal resistance to blood flow in the lungs. This allows for adequate oxygenation via mixing between the atria and a normal appearance at birth. When the ductus begins to close and pulmonary vascular resistance decreases, blood flow through the ductus is restricted and flow to the lungs is increased.In typical anatomy, the left side of the heart receives oxygen-rich blood from the lungs and pumps it to the rest of the body. Patients with HLHS can have a number of cardiac malformations that ultimately lead to a diminutive left ventricle that is unable to supply sufficient blood flow to the rest of the body. There are three main anatomic variants of the disease differentiated by either stenosis or atresia of the aortic and mitral valve.Mitral atresia and aortic atresia (MA-AA) subtype is the most severe form of HLHS resulting in no blood flow entering the left ventricle at all resulting in no possibility of left ventricular output. In the mitral stenosis and aortic atresia (MS-AA) subtype blood is able to fill the left ventricle, however it is unable to be supplied to the systemic circulation via the hypoplastic ascending aorta. Lastly, the mildest form is the mitral stenosis and aortic stenosis (MS-AS) subtype. In these patients although the left ventricle is able to supply some blood flow to the rest of the body the overall left ventricular systemic output remains inadequate.In all of these cases blood is unable to be pumped to the rest of the body by the left ventricle. The neonate is reliant on blood flowing through an atrial septal defect to mix oxygenated and deoxygenated blood, and on a patent ductus arteriosus to allow blood to reach the aorta and the systemic circulation via the right ventricle. This is what defines HLHS as a "single ventricle" defect.Due to the underdevelopment of the left side of the heart in utero, the increased afterload causes hypertension of the left atrium, pulmonary edema, and therefore lung damage to the fetus before birth.
Diagnosis
Hypoplastic left heart syndrome can be diagnosed prenatally or after birth via echocardiography. Typical findings include a small left ventricle and aorta, abnormalities of the mitral and aortic valves, retrograde flow in the transverse arch of the aorta, and left-to-right flow between the atria. It is often recognized during the second trimester of pregnancy, between 18 and 24 weeks gestation.
Management
Medical
Without life-prolonging interventions, HLHS is fatal, but with intervention, an infant may survive. A cardiothoracic surgeon may perform a series of operations or a full heart transplant. While surgical intervention has emerged as the standard of care in the United States, other national health systems, notably in France, approach diagnosis of HLHS in a more conservative manner, with an emphasis on termination of pregnancy or compassionate care after delivery.Before surgery, the ductus must be kept open to allow blood-flow using medication containing prostaglandin. Air with less oxygen than normal is used for infants with hypoplastic left heart syndrome. These low oxygen levels increases the pulmonary vascular resistance (PVR) and thus improve blood flow to the rest of the body due to the greater pressure difference between the lungs and body. Achieving oxygen levels below atmosphere requires the use of inhaled nitrogen. Nitric oxide is a potent pulmonary vasodilator, and thus reduces PVR and improves venous return. Any factor that increases PVR will impede right sided flow.
Surgical
Surgical operations to assist with hypoplastic left heart are complex and need to be individualized for each patient. A cardiologist must assess all medical and surgical options on a case-by-case basis.Currently, infants undergo either the staged reconstructive surgery (Norwood or Sano procedure within a few days of birth, Glenn or Hemi-Fontan procedure at 3 to 6 months of age, and the Fontan procedure at 1 1/2 to 5 years of age) or cardiac transplantation. Current expectations are that 70% of those with HLHS may reach adulthood. Many studies show that the higher the volume (number of surgeries performed) at a hospital, the lower the mortality (death) rate. Factors that increase an infants risk include lower birth weight, additional congenital anomalies, a genetic syndrome or those with a highly restrictive atrial septum. For patients without these additional risk factors, 5 year survival now approaches 80%. Studies show that about 75% of those children who survive surgery show developmental delays in one or more areas, such as motor, cognitive, or language impairments, with about a third of single-ventricle children without a genetic syndrome having significant impairments. Current research focuses on charting the connections between neurodevelopment injuries, surgical and intensive care procedures, and genetic susceptibility with the goal of modifying interventions that impair neurodevelopmental and psychosocial outcomes. An alternative to the traditional Norwood is the Hybrid procedure.Some physicians offer compassionate care, instead of the surgeries, which results in the childs death, usually within 2 weeks of birth. Compassionate care is overseen by a physician, and may be carried out either in the hospital or at home. However, due to the vast improvement of surgical intervention, with many hospitals achieving over 90% survival, there is debate on whether or not compassionate care should still be offered to families. A study in 2003 concluded that a selection of physicians who are experts in the care of children with HLHS were evenly split when asked what they would do if their own children were born with HLHS, with 1/3 stating that they would choose surgery, 1/3 stating that they would choose palliative (compassionate) treatment without surgery, and 1/3 stating that they are uncertain which choice they would make.The three-stage procedure is a palliative procedure (not a cure), as the childs circulation is made to work with only two of the hearts four chambers.
Norwood procedure
The first step is the Norwood procedure. In this procedure, the right ventricle is used to pump blood into the systemic circulation. Since the right ventricle is no longer directly pumping blood to the lungs, a shunt is required in order to pass deoxygenated blood through the lungs. Either the subclavian artery can be connected to the pulmonary circulation (Blalock-Taussig shunt), or a shunt is made directly from the right ventricle to the pulmonary circulation (Sano shunt). The narrow aorta is enlarged using a patch to improve blood flow to the body.During this time the baby may be medically fragile and have feeding problems because the heart is working very hard. There is a considerable degree of venous mixing in the right ventricle, leading to lower oxygenation saturation. In addition, both the Blalock-Taussig and the Sano shunts expose the lungs to systemic arterial pressures, leading to long-term pulmonary hypertension and eventually heart failure.
Hybrid procedure
The Hybrid procedure may be used in place of the Norwood. The Hybrid procedure does not necessitate the use of heart-lung bypass or performing a sternotomy. Instead of a six-hour surgery, the Hybrid typically takes one to two hours. In this procedure, a stent is placed in the ductus arteriosus to maintain its patency, and bands are placed over both the left and right pulmonary artery branches to limit pressure and over-circulation to the lungs. Outcomes with the Hybrid approach are comparable to those with the Norwood.
Glenn procedure
The second stage—the bidirectional Glenn or Hemi-Fontan (see also Kawashima procedure)—relieves some of the problems introduced by Stage I palliation. In this operation, the superior vena cava is ligated from the heart and connected to the pulmonary circulation. At this time, the Blalock-Taussig or Sano shunt is taken down. The lungs are no longer exposed to systemic arterial pressures, but much lower venous pressures. Although venous blood from the upper half of the body is no longer mixing with oxygenated blood in the right ventricle, there is still venous mixing from the lower half of the body, leading to some degree of oxygen desaturation.
Fontan procedure
The final procedure, the Fontan procedure, completes the repair of the hypoplastic left heart. Although there are several variations, the functional effect is to redirect venous blood from the lower body (through the inferior vena cava) away from the right atrium to the pulmonary artery. This should eliminate any mixing of oxygenated and deoxygenated blood in the right ventricle. The right ventricle performs the traditional job of the left, supplying the body with oxygenated blood, while the passive systemic venous pressure performs the traditional job of the right, passing deoxygenated blood to the lungs.
Fetal surgery
Interventions performed during fetal development are under investigation. In fetuses with hypoplastic left ventricles and an intact interatrial septum, percutaneous atrial septostomy has been attempted.
Prognosis
95% of untreated infants with HLHS die in the first weeks of life.Early survival has improved since the introduction of the Norwood procedure. Since there are no long-term studies of HLHS adults, statistics are usually derived from post-Fontan patients; it is estimated that 70% of HLHS patients may reach adulthood.Prognosis is dependent upon the health of the child, as there is an increased demand on respiratory and heart rate in infants during common childhood illnesses. This fragile population has little cardiac reserve to accommodate these demands and provide hemodynamic stability during illnesses.Children with HLHS and other comparable single-ventricle conditions, as a group, have poorer neurodevelopmental outcomes than their healthy peers. Deficits in language, executive functioning, and higher rates of anxiety and depression disorders have been demonstrated. Some of these outcomes may be a consequence of genetic factors associated with HLHS, and others may be modifiable through changes to procedures and to the healthcare environment. There is an emerging clinical consensus around the importance of continuous neurodevelopmental surveillance from the earliest years into adulthood. Additionally, a recent meta-analysis comparing twenty-two studies showed that 64.7% of the studies reported delayed motor development in children with single ventricle physiologies, such as hypoplastic left heart syndrome.As is true for patients with other types of heart defects involving malformed valves, HLHS patients run a high risk of endocarditis, and must be monitored by a cardiologist for the rest of their lives to check on their heart function.Heart transplantation may be indicated, typically after Fontan completion. One multi-center study (of patients undergoing the Fontan from 1993 to 2001) reported a 76% 1-year survival rate in patients who survived to transplant.
Future of stem cell therapies
A systematic review found 23 articles, published since 2010, as well as nine relevant clinical trials related to congenital heart disease and recent advances in stem cell therapies. Pre-clinical research has focused on several types of stem cells including: mesenchymal stem cells (MSCs), autologous umbilical cord blood cells, c-kit+ cardiac stem cells, and neonatal thymus mesenchymal stem cells. These cell types have shown the ability to differentiate into cardiac tissue making them ideal for cardiac regenerative therapy. The first use of autologous umbilical cord blood cells was done at the Mayo Clinic in 2015 and was found to increase right ventricular function in the patient after their procedure. The first use of cardiac progenitor cells occurred in the Transcoronary Infusion of Cardiac Progenitor Cells in Patients with Single-Ventricle Physiology (TICAP) Trail of 2011.
Ongoing trials
There are several ongoing studies testing the feasibility and efficacy of stem cell therapies for single ventricle diseases such as HLHS. These trials focus on what are the most effective stem cells, what is the best timing in the 3-stage repair, and what is the optimal delivery method.
Phase IIb trial testing the efficacy of intramyocardial injections umbilical cord blood cells during Stage II (Glenn) repair.
Phase I trial testing the efficacy of autologous cord blood cell infusion during Stage 1 (Norwood) repair within two-to-three days of birth.
The ELPIS trial is a phase I/IIb open pilot testing the efficacy and safety of intramyocardial donor human mesenchymal stem cell injections in patients during Stage 2 (Glenn) and Stage 3 (Fontan) repairs.
Phase I trial testing the efficacy of umbilical cord blood intramyocardial injections during Stage 2 (Glenn) repair.
The PERSEUS study is a phase II trial testing the efficacy of intracoronary infusions of cardiac progenitor cells and evaluating function 3-months post-treatment.
APOLLON study is a phase III clinical trial testing the efficacy and safety of intracoronary injections of autologous cardiac stem cells during Stage 2 (Glenn) or Stage 3 (Fontan) repair.
CHILD Study is a phase I clinical trial testing the feasibility and safety of intramyocardial injections of c-kit+ cells during Stage 2 (Glenn) repair.It is important to keep in mind that patients with HLHS are at increased risk of developing heart failure as adults. It remains unknown if these potential therapies would reduce the future risk of heart failure in these patients.
References
External links
Hypoplastic left heart syndrome Archived 2013-03-14 at the Wayback Machine information for parents. |
Keratolysis exfoliativa | Keratolysis exfoliativa (also known as "lamellar dyshidrosis", "recurrent focal palmar peeling", "recurrent palmar peeling": 212 ) is a sometimes harmless, sometimes painful skin condition that can affect the focal surface of the fingers and/or the palm or soles of the feet. It is often misdiagnosed as chronic contact dermatitis or psoriasis. It is characterized by dry skin and superficial, air-filled blisters. These blisters can be peeled off very easily and will leave reddish, tender areas. The loss of this corneal layer of the skin, which protects the underlying layers, leaves the skin more vulnerable to dryness and cracking.
Causes
Keratolysis exfoliativa normally appears during warm weather. Due to excessive sweating and friction, in for example athletic shoes, the skin can start to exfoliate. Other factors that can cause exfoliation are detergents and solvents.
Another very common cause has been reported from salt water fishermen, who often suffer from these symptoms. It is not sure whether it is from the salt water or whether it is from some bacteria from fish.
Treatment
Normally, exfoliation is restricted to a particular area and normal skin will replace the exfoliated parts, so no treatment is needed. Since keratolysis exfoliativa is caused by friction, detergents, and solvents, these factors should be avoided. Creams, especially those with silicone and lactic acid are also helpful. In severe cases, photochemotherapy is an option.
Prognosis
In most cases exfoliation resolves spontaneously and no lasting damage is seen. However, some patients experience cracking and even bleeding in extreme cases.
See also
Acrokeratoelastoidosis of Costa
Peeling skin syndrome
List of cutaneous conditions
References
External links
[1] |
Sycosis | Sycosis is an inflammation of hair follicles, especially of the beard area, and generally classified as papulopustular and chronic.
Types
Types include:
Sycosis barbae
Lupoid sycosis
Tinea sycosis
Herpetic sycosis
== References == |
Regional odontodysplasia | Regional odontodysplasia is an uncommon developmental abnormality of teeth, usually localized to a certain area of the mouth. The condition is nonhereditary. There is no predilection for race, but females are more likely to get regional odontodysplasia. The enamel, dentin, and pulp of teeth are affected, to the extent that the affected teeth do not develop properly. These teeth are very brittle. On radiographs the teeth appear more radiolucent than normal, so they are often described as "ghost teeth". Most cases are considered idiopathic, but some cases are associated with syndromes, growth abnormalities, neural disorders, and vascular malformations.
Permanent teeth usually show effects of regional odontodysplasia if the deciduous tooth was affected. Many of these teeth do not erupt, and those that do have an increased risk of caries and periapical inflammation.
Treatment and prognosis
Treatment and prognosis are usually based upon keeping these teeth and preserving the alveolus. For erupted teeth, endodontics is an option if the tooth is devitalized and restorable. For unerupted teeth, function can be restored with a removable partial denture until all major growth has been completed and a final restoration can be placed.
References
== External links == |
Median nerve | The median nerve is a nerve in humans and other animals in the upper limb. It is one of the five main nerves originating from the brachial plexus.
The median nerve originates from the lateral and medial cords of the brachial plexus, and has contributions from ventral roots of C5-C7 (lateral cord) and C8 and T1 (medial cord).The median nerve is the only nerve that passes through the carpal tunnel. Carpal tunnel syndrome is the disability that results from the median nerve being pressed in the carpal tunnel.
Structure
The median nerve arises from the branches from lateral and medial cords of the brachial plexus, courses through the anterior part of arm, forearm, and hand, and terminates by supplying the muscles of the hand.
Arm
After receiving inputs from both the lateral and medial cords of the brachial plexus, the median nerve enters the arm from the axilla at the inferior margin of the teres major muscle. It then passes vertically down and courses lateral to the brachial artery between biceps brachii (above) and brachialis (below). At first, it is lateral to the artery and lies anterior to the shoulder joint; it then crosses anteriorly to run medial to the artery in the distal arm and into the cubital fossa. Inside the cubital fossa, the median nerve passes medial to the brachial artery. The median nerve gives off an articular branch to the elbow joint. A branch to pronator teres muscle arise from the median nerve immediately above the elbow joint.
Forearm
The median nerve continues in the cubital fossa medial to the brachial artery and passes between the two heads of the pronator teres, deep to the bicipital aponeurosis (aponeurosis of biceps) and superficial the brachialis muscle. It crosses the ulnar artery (branch of brachial artery) while being separated by the deep head of the pronator teres. It then travels between the flexor digitorum superficialis (above) and flexor digitorum profundus (below). The median nerve is accompanied by the median artery (a branch of anterior interosseous artery) during this course. Then, about 5 cm above the flexor retinaculum (wrist), it emerges between the flexor digitorum superficialis (medially) and the flexor carpi radialis (laterally) into the hand.The main trunk of the median nerve innervates the superficial and deep groups of the muscles in the anterior compartment of the forearm with the exception of flexor carpi ulnaris. The median nerve does this by giving off two branches as it courses through the forearm:
Muscular branches are given off in the cubital fossa to supply flexor carpi radialis, palmaris longus, and flexor digitorum superficialis.
The anterior interosseous branch is given off in the upper part of the forearm, courses with the anterior interosseous artery and innervates flexor pollicis longus and the lateral half of flexor digitorum profundus (the ulnar half is supplied by ulnar nerve, as is the flexor carpi ulnaris muscle). It ends with its innervation of pronator quadratus. In addition to its supply to muscles, this nerve also supplies the distal radioulnar joint and wrist joint.The median nerve also gives off sensory and other branches in the forearm. The palmar cutaneous branch of the median nerve arises at the distal part of the forearm. It supplies sensory innervation to the thenar eminence of the palm and the central palm. Articular branches are given to the elbow joint and proximal radioulnar joint. Vascular branches supply the radial and ulnar arteries. Meanwhile, a communicating branch is given to the ulnar nerve.
Hand
The median nerve enters the hand through the carpal tunnel, deep to the flexor retinaculum along with the tendons of flexor digitorum superficialis, flexor digitorum profundus, and flexor pollicis longus. From there, it is divided into recurrent muscular branch and digital cutaneous branch:
The muscular branch (also known as recurrent branch) supplies the thenar muscles (opponens pollicis, abductor pollicis brevis, and superficial part of flexor pollicis brevis)
Digital cutaneous to the proper palmar digital branch and the common palmar digital branch: The proper palmar digital branch gives out three digital branches to the lateral one and a half digits (two digital branches to the thumb, one digital branch to the lateral side of the index finger). The digital branch to the index finger also supplies the first lumbrical. The common palmar digital branch divides further into two branches. Both the medial and lateral branches supply the second and third interdigital clefts with adjoining index, middle, and lateral half of ring finger. The lateral branch also supplies the second lumbrical.
Variation
The naturally occurring anomalies of the median nerve are:
Bifurcation of the median nerve typically occurs after the nerve exits the carpal tunnel; however, in a small percentage (5-10%) of individuals, the median nerve bifurcates more proximal in the carpal tunnel, wrist, or forearm.
During gestation, a median artery that serves the hand retracts. However, in some individuals, the median artery does not retract and follows the course next to the median nerve into the hand.
Martin-Gruber anastomoses can occur when branches of the median nerve cross-over in the forearm and merge with the ulnar nerve to innervate portions of the forehand.
Riche-Cannieu anastomosis can occur when a connection exists between recurrent branch of the median nerve and deep branch of the ulnar nerve of the hand.
Function
The median nerve is the main nerve of the front of the forearm. It supplies the muscles of the front of the forearm and muscles of the thenar eminence, thus controlling the coarse movements of the hand. Therefore, it is also called "labourers nerve".
Arm
The median nerve has no voluntary motor or cutaneous function in the brachium. It gives vascular branches to the wall of the brachial artery. These vascular branches carry sympathetic fibers.
Forearm
It innervates all of the flexors in the forearm, except flexor carpi ulnaris and that part of flexor digitorum profundus that supplies the fourth and fifth digits. The latter two muscles are supplied by the ulnar nerve (specifically the muscular branches of ulnar nerve).
The main portion of the median nerve supplies these muscles:
Superficial group:
Pronator teres
Flexor carpi radialis
Palmaris longusIntermediate group:
Flexor digitorum superficialis muscleThe anterior interosseus branch of the median nerve supplies these muscles:
Deep group:
Flexor digitorum profundus (only the lateral half)
Flexor pollicis longus
Pronator quadratus
Hand
In the hand, the median nerve supplies motor innervation to the first and second lumbrical muscles. It also supplies the muscles of the thenar eminence by a recurrent thenar branch. The rest of the intrinsic muscles of the hand are supplied by the ulnar nerve.
The median nerve innervates the skin of the palmar (volar) side of the index finger, thumb, middle finger, and half the ring finger, and the nail bed. The radial aspect of the palm is supplied by the palmar cutaneous branch of the median nerve, which leaves the nerve proximal to the wrist creases. This palmar cutaneous branch travels in a separate fascial groove adjacent to the flexor carpi radialis and then superficial to the flexor retinaculum. It is, therefore, spared in carpal tunnel syndrome.
Clinical significance
Injury
Injury of median nerve at different levels causes different syndromes with varying motor and sensory deficits.
At the shoulder
Injury can occur at the brachial plexusAbove the elbow
Common mechanism of injury: A supracondylar humerus fracture
Motor deficit:
Loss of pronation of forearm, weakness in flexion of the hand at the wrist, loss of flexion of radial half of digits and thumb, loss of abduction and opposition of thumb.
Presence of an ape hand deformity when the hand is at rest, due to an hyperextension of index finger and thumb, and an adducted thumb
Presence of benediction sign when attempting to form a fist, due to loss of flexion of radial half of digits
Sensory deficit: Loss of sensation in lateral 3+1⁄2 digits including their nail beds, and the thenar areaAt the elbow
Entrapment at the level of the elbow or the proximal forearm could be due to the pronator teres syndrome.Within the proximal forearm: Anterior interosseous syndrome
Injury to the anterior interosseous branch in the forearm causes the anterior interosseous syndrome
Common mechanisms: Tight cast, forearm bone fracture
Motor deficit: Loss of pronation of forearm, loss of flexion of radial half of digits and thumb
Sensory deficit: NoneAt the wrist
Common mechanism: Wrist laceration
Motor deficit:
Weakness in flexion of radial half of digits and thumb, loss of abduction and opposition of thumb
Presence of an ape hand deformity when the hand is at rest may be likely, due to an hyperextension of index finger and thumb, and an adducted thumb. Nevertheless, an ape hand deformity is not a requirement for a carpal tunnel syndrome diagnosis.
Presence of a benediction sign when attempting to form a fist, due to weakness in flexion of radial half of digits
Sensory deficit: Loss of sensation in lateral 3+1⁄2 digits including their nail beds, and the thenar areaWithin the wrist: Carpal tunnel syndrome
Common mechanism: Carpal tunnel syndrome, an injury by compression in the carpal tunnel, without transection of the median nerve, due to overuse by activities such as keyboard typing and cooking
Motor deficit:
Weakness in flexion of radial half of digits and thumb, weakness in abduction and opposition of thumb
Presence of an ape hand deformity or when attempting to form a fist, the benediction sign, due to compression of the median nerve, as opposed to complete median nerve palsy
Sensory deficit: Numbness and tingling in lateral 3+1⁄2 digits including their nail beds, but excluding the thenar eminence which is supplied by the palmar cutaneous branch of the median nerve Unlike in wrist laceration, sensation still occurs in the area of the central palm. Sensation is not lost because the palmar cutaneous branch runs above the flexor retinaculum, and is not affected in compression in carpal tunnel syndrome.
Additional images
See also
References
This article incorporates text in the public domain from page 938 of the 20th edition of Grays Anatomy (1918)
External links
Median nerve at the Duke University Health Systems Orthopedics program
Median+Nerve at the US National Library of Medicine Medical Subject Headings (MeSH)
Hand kinesiology at the University of Kansas Medical Center
Atlas image: hand_plexus at the University of Michigan Health System - "Axilla, dissection, anterior view" |
Diversion colitis | Diversion colitis is an inflammation of the colon which can occur as a complication of ileostomy or colostomy, where symptoms may occur between one month and three years following surgery. It also occurs frequently in a neovagina created by colovaginoplasty, with varying delay after the original procedure. Despite the presence of a variable degree of inflammation the most suggestive histological feature remains the prominent lymphoid aggregates.
Symptoms and signs
People may be asymptomatic but common symptoms are abdominal discomfort, anorectal pain, mucous discharge and rectal bleeding that develops from the inflamed mucosa of the distal, unused colon.
Diagnosis
Diagnosis is aided by knowing the full clinical history.
Treatment
In many milder cases after ileostomy or colostomy, diversion colitis is left untreated and disappears naturally. Possible pharmacologic treatments include short-chain fatty acid irrigation, steroid enemas and mesalazine. For surgical candidates, reanastomosis is a reversal procedure carried out to restore bowel continuity that effectively halts the symptoms of diversion colitis.
== References == |
Orthorexia nervosa | Orthorexia nervosa (also known as orthorexia) (ON) is a proposed eating disorder characterized by an excessive preoccupation with eating healthy food. The term was introduced in 1997 by American physician Steven Bratman, M.D. He suggested that some peoples dietary restrictions intended to promote health may paradoxically lead to unhealthy consequences, such as social isolation, anxiety, loss of ability to eat in a natural, intuitive manner, reduced interest in the full range of other healthy human activities, and, in rare cases, severe malnutrition or even death.In 2009, Ursula Philpot, chair of the British Dietetic Association and senior lecturer at Leeds Metropolitan University, described people with orthorexia nervosa as being "solely concerned with the quality of the food they put in their bodies, refining and restricting their diets according to their personal understanding of which foods are truly pure." This differs from other eating disorders, such as anorexia nervosa and bulimia nervosa, where those affected focus on the quantity of food eaten.Orthorexia nervosa also differs from anorexia nervosa in that it does not disproportionally affect one gender. Studies have found that orthorexia nervosa is equally found in both men and women with no significant gender differences at all. Furthermore, research has found significant positive correlations between ON and both narcissism and perfectionism, but no significant correlation between ON and self esteem. This shows that high-ON individuals likely take pride over their healthy eating habits over others and that is the driving force behind their orthorexia as opposed to body image like anorexia.
Orthorexia nervosa is not recognized as an eating disorder by the American Psychiatric Association, and so is not mentioned as an official diagnosis in the widely used Diagnostic and Statistical Manual of Mental Disorders (DSM).
Signs and symptoms
Symptoms of orthorexia nervosa include "obsessive focus on food choice, planning, purchase, preparation, and consumption; food regarded primarily as source of health rather than pleasure; distress or disgust when in proximity to prohibited foods; exaggerated faith that inclusion or elimination of particular kinds of food can prevent or cure disease or affect daily well-being; periodic shifts in dietary beliefs while other processes persist unchanged; moral judgment of others based on dietary choices; body image distortion around sense of physical "impurity" rather than weight; persistent belief that dietary practices are health-promoting despite evidence of malnutrition."
Cause
There has been no investigation into whether there may be a biological cause specific to orthorexia nervosa. It may be a food-centered manifestation of obsessive-compulsive disorder, which has a lot to do with control.
Diagnosis
In 2016, formal criteria for orthorexia were proposed in the peer-reviewed journal Eating Behaviors by Thom Dunn and Steven Bratman. These criteria are as follows:
Criterion A. Obsessive focus on "healthy" eating, as defined by a dietary theory or set of beliefs whose specific details may vary; marked by exaggerated emotional distress in relationship to food choices perceived as unhealthy; weight loss may ensue, but this is conceptualized as an aspect of ideal health rather than as the primary goal. As evidenced by the following:
Compulsive behavior and/or mental preoccupation regarding affirmative and restrictive dietary practices believed by the individual to promote optimum health. (Footnotes to this criteria add: Dietary practices may include use of concentrated "food supplements." Exercise performance and/or fit body image may be regarded as an aspect or indicator of health.)
Violation of self-imposed dietary rules causes exaggerated fear of disease, sense of personal impurity and/or negative physical sensations, accompanied by anxiety and shame.
Dietary restrictions escalate over time, and may come to include elimination of entire food groups and involve progressively more frequent and/or severe "cleanses" (partial fasts) regarded as purifying or detoxifying. This escalation commonly leads to weight loss, but the desire to lose weight is absent, hidden or subordinated to ideation about healthy food.Criterion B. The compulsive behavior and mental preoccupation becomes clinically impairing by any of the following:
Malnutrition, severe weight loss or other medical complications from restricted diet
Intrapersonal distress or impairment of social, academic or vocational functioning secondary to beliefs or behaviors about healthy diet
Positive body image, self-worth, identity and/or satisfaction excessively dependent on compliance with self-defined "healthy" eating behavior.A diagnostic questionnaire has been developed for orthorexia sufferers, similar to questionnaires for other eating disorders, named the ORTO-15. However, Dunn and Bratman critique this survey tool as lacking appropriate internal and external validation.
Epidemiology
Results across scientific findings have yet to find a definitive conclusion to support whether nutrition students and professionals are at higher risk than other population subgroups, due to differing results in the research literature. There are only a few notable scientific works that, in an attempt to explore the breadth and depth of the still vaguely-understood illness, have tried to identify which groups in society are most vulnerable to its onset. This includes a 2008 German study, which based its research on the widespread suspicion that the most nutritionally-informed, such as university nutrition students, are a potential high-risk group for eating disorders, due to a substantial accumulation of knowledge on food and its relationship to health; the idea being that the more one knows about health, the more likely an unhealthy fixation about being healthy can develop. This study also inferred that orthorexic tendencies may even fuel a desire to study the science, indicating that many within this field might suffer from the disorder before commencing the course. However the results found that the students in the study, upon initial embarkation of their degree, did not have higher orthorexic values than other non-nutrition university students, and thus the report concluded that further research is needed to clarify the relationship between food-education and the onset of ON.Similarly, in a Portuguese study on nutrition tertiary students, the participants orthorexic scores (according to the ORTO-15 diagnostic questionnaire) actually decreased as they progressed through their course, as well as the overall risk of developing an eating disorder being an insignificant 4.2 percent. The participants also answered questionnaires to provide insight into their eating behaviours and attitudes, and despite this study finding that nutrition and health-science students tend to have more restrictive eating behaviours, these studies however found no evidence to support that these students have "more disturbed or disordered eating patterns than other students" These two aforementioned studies conclude that the more understanding of food one has is not necessarily a risk factor for ON, explaining that the data gathered suggests dietetics professionals are not at significant risk of it.
However, these epidemiologic studies have been critiqued as using a fundamentally flawed survey tool that inflates prevalence rates. Scholars have questioned both the reliability and validity of the ORTO-15.Most scientific findings tend to agree, however, young adults and adolescents are extremely susceptible to developing eating disorders. One study found that there was no relationship between BOT score and college major, which may indicate the prevalence of mental health issues and eating disorders on college campuses and that health and science majors are no longer the only ones affected More studies have also been conducted on the link between increased Instagram use and Orthorexia nervosa. The social media based healthy community has recently grown in popularity especially on platforms such as Instagram. The hashtag #food is one of the top 25 most popular hashtags on Instagram. A study that investigated this relationship found that increased use of Instagram correlated between symptoms of ON with no other social media platform having the same effect. With young adults and adolescents making up the majority of social media users, exposure to this type of content can lead to developing unhealthy behavior.
History
In a 1997 article in the magazine Yoga Journal, the American physician Steven Bratman coined the term "orthorexia nervosa" from the Greek ορθο- (ortho, "right" or "correct"), and όρεξις (orexis, "appetite"), literally meaning correct appetite, but in practice meaning correct diet. The term is modeled on anorexia, literally meaning "without appetite", as used in the definition of the condition anorexia nervosa. (In both terms, "nervosa" indicates an unhealthy psychological state.) Bratman described orthorexia as an unhealthy fixation with what the individual considers to be healthy eating. Beliefs about what constitutes healthy eating commonly originate in one or another dietary theory such as raw foods veganism or macrobiotics, but are then taken to extremes, leading to disordered eating patterns and psychological and/or physical impairment. Bratman based this proposed condition on his personal experiences in the 1970s, as well as behaviors he observed among his patients in the 1990s. In 2000, Bratman, with David Knight, authored the book Health Food Junkies, which further expanded on the subject.Following the publication of the book, in 2004 a team of Italian researchers from La Sapienza University of Rome, published the first empirical study attempting to develop a tool to measure the prevalence of orthorexia, known as the ORTO-15.In 2015, responding to news articles in which the term orthorexia is applied to people who merely follow a non-mainstream theory of healthy eating, Bratman specified the following: "A theory may be conventional or unconventional, extreme or lax, sensible or totally wacky, but, regardless of the details, followers of the theory do not necessarily have orthorexia. They are simply adherents of a dietary theory. The term orthorexia only applies when an eating disorder develops around that theory." Bratman elsewhere clarifies that with a few exceptions, most common theories of healthy eating are followed safely by the majority of their adherents; however, "for some people, going down the path of a restrictive diet in search of health may escalate into dietary perfectionism." Karin Kratina, PhD, writing for the National Eating Disorders Association, summarizes this process as follows: "Eventually food choices become so restrictive, in both variety and calories, that health suffers – an ironic twist for a person so completely dedicated to healthy eating."Although orthorexia is not recognized as a mental disorder by the American Psychiatric Association, and it is not listed in the DSM-5, as of January 2016, four case reports and more than 40 other articles on the subject have been published in a variety of peer-reviewed journals internationally. According to a study published in 2011, two-thirds of a sample of 111 Dutch-speaking eating disorder specialists felt they had observed the syndrome in their clinical practice.According to the Macmillan English Dictionary, the word is entering the English lexicon. The concept of orthorexia as a newly developing eating disorder has attracted significant media attention in the 21st century.
Orthorexia and other disorders
Orthorexia differs from anorexia and bulimia in its relationship to food. Instead of focusing on food intake in an attempt to lose weight and eat less, orthorexia is an "obsession about the quality of food intake" and is fueled by a feeling of achieving perfection and purity by only consuming "healthy" foods.Orthorexic behaviors can often lead to malnutrition and weight loss, and it is often associated with anorexia nervosa. Studies have also shown that obsessive-compulsive tendencies are linked to the development of orthorexia, and some researchers suggest that orthorexia should be diagnosed as OCD because it is driven by an obsession for attaining a perfect diet.
See also
Notes
== References == |
Caffeine-induced sleep disorder | Caffeine-induced sleep disorder is a psychiatric disorder that results from overconsumption of the stimulant caffeine. Caffeine is one of the most widely consumed psychoactive drugs: almost 90% of Americans in a survey consume some type of caffeine each day. "When caffeine is consumed immediately before bedtime or .... throughout the day, sleep onset may be delayed, total sleep time reduced, normal stages of sleep altered, and the quality of sleep decreased." Caffeine reduces slow-wave sleep in the early part of the sleep cycle and can reduce rapid eye movement sleep later in the cycle. Caffeine increases episodes of wakefulness, and high doses in the late evening can increase sleep onset latency. In elderly people, there is an association between use of medication containing caffeine and difficulty in falling asleep.The specific criteria for this disorder in the fourth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) include that there must be a significant inability to sleep which is caused entirely by the physiological effects of caffeine as proven by an examination; if sleeping issues can be accounted for due to a breathing-related sleep disorder, narcolepsy, a circadian rhythm sleep disorder or a mental disorder, then caffeine-induced sleep disorder is not the cause. This condition causes a notable impairment in functioning. The ICD-10 criteria for the principally same disorder is F15:982.
Caffeine and age
Most studies now, find that there is relatively no association between caffeine and its effects on sleep for infants. There was very little difference between mothers who had high caffeine consumption during pregnancy as opposed to mothers who did not have high consumption of caffeine during their pregnancy.Caffeine in younger children has been found to shorten their sleep duration and increase daytime sleepiness. One study, which looked at children ages six to ten years of age, found that those who consistently consumed caffeine lost about 15 minutes of sleep each night. In most cases where younger children are drinking high amounts of caffeine, parents usually buy their children soft drinks, iced tea, or energy drinks without realizing the amount of caffeine these drinks contain or the implications they have on their children.30% of adolescent adults in a survey were found to consume caffeine daily. Individuals with higher caffeine consumption, tended to feel an increase in wakefulness after sleep onset, shorter sleep durations, and longer daytime sleep. Those who consumed high amounts of caffeine daily, were found to be 1.9 times more likely to have difficulty sleeping and 1.8 times more likely to feel sleepy in the morning compared to those who consume almost no caffeine. Individuals with higher caffeine consumption felt an increase in wakefulness after sleep onset, shorter sleep durations, and longer daytime sleep. The higher consumption time for adolescent adults tends to be on the weekends, while the lowest consumption is midweek. This is assumed to be from greater social opportunities among adolescence.
Mechanism of caffeine
Caffeine is an adenosine receptor antagonist. This means that caffeine mainly works by occupying adenosine receptors in the brain, specifically, receptors that influence sleep, arousal, and cognition. Once it is in the body, caffeine will persist for several hours, and takes about six hours for one half of the caffeine consumed to be eliminated. When caffeine reaches the brain, it increases the secretion of norepinephrine which is related to the "fight or flight" response. The rise in norepinephrine levels increases activity of neurons in areas of the brain and the symptoms resemble those of a panic attack.The half-life of caffeine is roughly 3–4 hours in healthy adults, however, it is dependent on a variety of variables such as age, liver function, medications, level of enzymes, pregnancy. This short half-life has been found to help out daytime functioning, but increase the side effect of sleep problems. So, while caffeine has the potential to increase performance, it comes at a cost of sleep deprivation which in its own way can counter the main point of caffeine. Sleep deprivation alone can cause a variety of problems associated with cognitive control and functions. This can include reduced alertness, attention, vigilance, speed of motor functions.Though caffeine can be shown to decrease the quality of sleep, there is no evidence that caffeine affects all people the same way. In fact, some people report no sleep problems despite regularly consuming caffeine. Regular intake of caffeine may be normal for a person so it is understandable how they may still get satisfactory sleep. This finding shows that caffeine interferes with a modulatory mechanism in sleep regulation rather than a fundamental sleep regulatory brain circuit. Ultimately, regular sleep habits are important in overall quality and timing of sleep.
Caffeine consumption
Overconsumption
Although the maximum daily consumption of caffeine varies with consideration of couple of aspects such as sex, age, race, physical activity and smoking, excessive ingestion of caffeine can lead to a state of intoxication. This period of intoxication is characterized by restlessness, agitation, excitement, rambling thought or speech, and even insomnia. Even doses of caffeine relating to just one cup of coffee can increase sleep latency and decrease the quality of sleep especially in non-REM deep sleep. A dose of caffeine taken in the morning can have these effects the following night, so one of the main practices of sleep hygiene a person can do is to cease the consumption of caffeine.
Moderation
Keeping in mind that caffeine content in beverages and food varies and that some individuals are more sensitive to caffeine consumption than others are, moderation of caffeine is key. Between 200 and 300 mg of caffeine is considered "moderate" for most adults. While children can consume caffeine, it is advised to refrain children and adolescents from consuming caffeine due to their growing brains and to allow them to develop healthy sleep patterns.
Consequences of sleep disruption
Normal healthy sleep is described as having sufficient duration, quality, timing, regulation, and the absence of sleep disturbances or disorders. Even though the suggested amounts of sleep is relatively well known, there are increasing high numbers in the lack of healthy and good quality sleep.Risk factors of sleep can range across many different arrays such as environmental, lifestyle, psychosocial, sleep disorders, or medical conditions. These are all circumstances which put individuals at risk for sleep disruption. Environmental risk factors for sleep disruption can include living in an area where there is excessive noise such as near an interstate, keeping an individual up later than normal. A lifestyle risk factor would include drinking alcohol, drug abuse, or a late shift at work. Psychosocial risk factors include being a caregiver for someone who needs constant attention, parents of young children, anxiety, worry, or stress, etc.Sleep plays an essential part in brain functions and has crucial implications across almost all body systems. Numerous studies have shown caffeine consumption to heavily disrupt sleep patterns. This can lead to other implications such as lengthening the onset of sleep latency and decrease the efficiency and duration of sleep. Disruption of sleep also affects pressure for sleep and lowers electroencephalogram power in the frontal, central, and parietal regions of the brain. Short-term consequences of sleep disruption include: an increase in stress, emotional distress, mood and other mental health problems, cognition, memory, and performance deficits as well as an increase in behavioral problems in normally heathy individuals. Long-term consequences of sleep disruption include: cardiovascular problems such as cardiovascular disease, hypertension, higher concentration of fats in the body, weight issues such as metabolic syndrome, increased likelihood of cancer, and gastrointestinal disorders.
References
Further reading
Broderick P, Benjamin AB (December 2004). "Caffeine and psychiatric symptoms: a review". J Okla State Med Assoc. 97 (12): 538–42. PMID 15732884.
== External links == |
Patella | The patella, also known as the kneecap, is a flat, rounded triangular bone which articulates with the femur (thigh bone) and covers and protects the anterior articular surface of the knee joint. The patella is found in many tetrapods, such as mice, cats, birds and dogs, but not in whales, or most reptiles.
In humans, the patella is the largest sesamoid bone (i.e., embedded within a tendon or a muscle) in the body. Babies are born with a patella of soft cartilage which begins to ossify into bone at about four years of age.
Structure
The patella is a sesamoid bone roughly triangular in shape, with the apex of the patella facing downwards. The apex is the most inferior (lowest) part of the patella. It is pointed in shape, and gives attachment to the patellar ligament.
The front and back surfaces are joined by a thin margin and towards centre by a thicker margin. The tendon of the quadriceps femoris muscle attaches to the base of the patella., with the vastus intermedius muscle attaching to the base itself, and the vastus lateralis and vastus medialis are attached to outer lateral and medial borders of patella respectively.
The upper third of the front of the patella is coarse, flattened, and rough, and serves for the attachment of the tendon of the quadriceps and often has exostoses. The middle third has numerous vascular canaliculi. The lower third culminates in the apex which serves as the origin of the patellar ligament. The posterior surface is divided into two parts.
The upper three-quarters of the patella articulates with the femur and is subdivided into a medial and a lateral facet by a vertical ledge which varies in shape.
In the adult the articular surface is about 12 cm2 (1.9 sq in) and covered by cartilage, which can reach a maximal thickness of 6 mm (0.24 in) in the centre at about 30 years of age. Owing to the great stress on the patellofemoral joint during resisted knee flexion, the articular cartilage of the patella is among the thickest in the human body.
The lower part of the posterior surface has vascular canaliculi filled and is filled by fatty tissue, the infrapatellar fat pad.
Variation
Emarginations (i.e. patella emarginata, a "missing piece") are common laterally on the proximal edge. Bipartite patellas are the result of an ossification of a second cartilaginous layer at the location of an emargination. Previously, bipartite patellas were explained as the failure of several ossification centres to fuse, but this idea has been rejected. Partite patellas occur almost exclusively in men. Tripartite and even multipartite patellas occur.
The upper three-quarters of the patella articulates with the femur and is subdivided into a medial and a lateral facet by a vertical ledge which varies in shape. Four main types of articular surface can be distinguished:
Most commonly the medial articular surface is smaller than the lateral.
Sometimes both articular surfaces are virtually equal in size.
Occasionally, the medial surface is hypoplastic or
the central ledge is only indicated.
Development
In the patella an ossification centre develops at the age of 3–6 years. The patella originates from two centres of ossification which unite when fully formed.
Function
The primary functional role of the patella is knee extension. The patella increases the leverage that the quadriceps tendon can exert on the femur by increasing the angle at which it acts.
The patella is attached to the tendon of the quadriceps femoris muscle, which contracts to extend/straighten the knee. The patella is stabilized by the insertion of the horizontal fibres of vastus medialis and by the prominence of the lateral femoral condyle, which discourages lateral dislocation during flexion. The retinacular fibres of the patella also stabilize it during exercise.
Clinical significance
Dislocation
Patellar dislocations occur with significant regularity, particularly in young female athletes. It involves the patella sliding out of its position on the knee, most often laterally, and may be associated with extremely intense pain and swelling. The patella can be tracked back into the groove with an extension of the knee, and therefore sometimes returns into the proper position on its own.
Vertical alignment
A patella alta is a high-riding (superiorly aligned) patella. An attenuated patella alta is an unusually small patella that develops out of and above the joint.
A patella baja is a low-riding patella. A long-standing patella baja may result in extensor dysfunction.
The Insall-Salvati ratio helps to indicate patella baja on lateral X-rays, and is calculated as the patellar tendon length divided by the patellar bone length. An Insall-Salvati ratio of < 0.8 indicates patella baja.
Fracture
The kneecap is prone to injury because of its particularly exposed location, and fractures of the patella commonly occur as a consequence of direct trauma onto the knee. These fractures usually cause swelling and pain in the region, bleeding into the joint (hemarthrosis), and an inability to extend the knee. Patella fractures are usually treated with surgery, unless the damage is minimal and the extensor mechanism is intact.
Exostosis
An exostosis is the formation of new bone onto a bone, as a result of excess calcium formation. This can be the cause of chronic pain when formed on the patella.
In animals
The patella is found in placental mammals and birds; most marsupials have only rudimentary, non-ossified patellae although a few species possess a bony patella. A patella is also present in the living monotremes, the platypus and the echidna. In more primitive tetrapods, including living amphibians and most reptiles (except some Lepidosaurs), the muscle tendons from the upper leg are attached directly to the tibia, and a patella is not present. In 2017 it was discovered that frogs have kneecaps, contrary to what was thought. This raises the possibility that the kneecap arose 350 million years ago when tetrapods first appeared, but that it disappeared in some animals.
Etymology
The word patella originated in the late 17th century from the diminutive form of Latin patina or patena or paten, meaning shallow dish.
See also
Patellar reflex
Knee pain
Osteoarthritis
Lateral retinaculum
Lateral release
References
== External links == |
Epidermis | The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water released from the body into the atmosphere through transepidermal water loss.The epidermis is composed of multiple layers of flattened cells that overlie a base layer (stratum basale) composed of columnar cells arranged perpendicularly. The layers of cells develop from stem cells in the basal layer. The human epidermis is a familiar example of epithelium, particularly a stratified squamous epithelium.
The word epidermis is derived through Latin from Ancient Greek epidermis, itself from Ancient Greek epi over, upon and from Ancient Greek derma skin. Something related to or part of the epidermis is termed epidermal.
Structure
Cellular components
The epidermis primarily consists of keratinocytes (proliferating basal and differentiated suprabasal), which comprise 90% of its cells, but also contains melanocytes, Langerhans cells, Merkel cells,: 2–3 and inflammatory cells. Epidermal thickenings called Rete ridges (or rete pegs) extend downward between dermal papillae.Blood capillaries are found beneath the epidermis, and are linked to an arteriole and a venule.
The epidermis itself has no blood supply and is nourished almost exclusively by diffused oxygen from the surrounding air. Cellular mechanisms for regulating water and sodium levels (ENaCs) are found in all layers of the epidermis.
Cell junctions
Epidermal cells are tightly interconnected to serve as a tight barrier against the exterior environment. The junctions between the epidermal cells are of the adherens junction type, formed by transmembrane proteins called cadherins. Inside the cell, the cadherins are linked to actin filaments. In immunofluorescence microscopy, the actin filament network appears as a thick border surrounding the cells, although the actin filaments are actually located inside the cell and run parallel to the cell membrane. Because of the proximity of the neighboring cells and tightness of the junctions, the actin immunofluorescence appears as a border between cells.
Layers
The epidermis is composed of 4 or 5 layers, depending on the region of skin being considered. Those layers in descending order are:
cornified layer (stratum corneum)
Composed of 10 to 30 layers of polyhedral, anucleated corneocytes (final step of keratinocyte differentiation), with the palms and soles having the most layers. Corneocytes contain a protein envelope (cornified envelope proteins) underneath the plasma membrane, are filled with water-retaining keratin proteins, attached together through corneodesmosomes and surrounded in the extracellular space by stacked layers of lipids. Most of the barrier functions of the epidermis localize to this layer.
clear/translucent layer (stratum lucidum, only in palms and soles)
This narrow layer is found only on the palms and soles. The epidermis of these two areas is known as "thick skin" because with this extra layer, the skin has 5 epidermal layers instead of 4.
granular layer (stratum granulosum)
Keratinocytes lose their nuclei and their cytoplasm appears granular. Lipids, contained into those keratinocytes within lamellar bodies, are released into the extracellular space through exocytosis to form a lipid barrier that prevents water loss from the body as well as entry of foreign substances. Those polar lipids are then converted into non-polar lipids and arranged parallel to the cell surface. For example glycosphingolipids become ceramides and phospholipids become free fatty acids.
spinous layer (stratum spinosum)
Keratinocytes become connected through desmosomes and produce lamellar bodies, from within the Golgi, enriched in polar lipids, glycosphingolipids, free sterols, phospholipids and catabolic enzymes. Langerhans cells, immunologically active cells, are located in the middle of this layer.
basal/germinal layer (stratum basale/germinativum)
Composed mainly of proliferating and non-proliferating keratinocytes, attached to the basement membrane by hemidesmosomes. Melanocytes are present, connected to numerous keratinocytes in this and other strata through dendrites. Merkel cells are also found in the stratum basale with large numbers in touch-sensitive sites such as the fingertips and lips. They are closely associated with cutaneous nerves and seem to be involved in light touch sensation.
Malpighian layer (stratum malpighi)
This is both the stratum basale and stratum spinosum.The epidermis is separated from the dermis, its underlying tissue, by a basement membrane.
Cellular kinetics
Cell division
As a stratified squamous epithelium, the epidermis is maintained by cell division within the stratum basale. Differentiating cells delaminate from the basement membrane and are displaced outward through the epidermal layers, undergoing multiple stages of differentiation until, in the stratum corneum, losing their nucleus and fusing to squamous sheets, which are eventually shed from the surface (desquamation). Differentiated keratinocytes secrete keratin proteins, which contribute to the formation of an extracellular matrix that is an integral part of the skin barrier function. In normal skin, the rate of keratinocyte production equals the rate of loss, taking about two weeks for a cell to journey from the stratum basale to the top of the stratum granulosum, and an additional four weeks to cross the stratum corneum. The entire epidermis is replaced by new cell growth over a period of about 48 days.
Calcium concentration
Keratinocyte differentiation throughout the epidermis is in part mediated by a calcium gradient, increasing from the stratum basale until the outer stratum granulosum, where it reaches its maximum, and decreasing in the stratum corneum. Calcium concentration in the stratum corneum is very low in part because those relatively dry cells are not able to dissolve the ions. This calcium gradient parallels keratinocyte differentiation and as such is considered a key regulator in the formation of the epidermal layers.Elevation of extracellular calcium concentrations induces an increase in intracellular free calcium concentrations. Part of that intracellular increase comes from calcium released from intracellular stores and another part comes from transmembrane calcium influx, through both calcium-sensitive chloride channels and voltage-independent cation channels permeable to calcium. Moreover, it has been suggested that an extracellular calcium-sensing receptor (CaSR) also contributes to the rise in intracellular calcium concentration.
Development
Epidermal organogenesis, the formation of the epidermis, begins in the cells covering the embryo after neurulation, the formation of the central nervous system. In most vertebrates, this original one-layered structure quickly transforms into a two-layered tissue; a temporary outer layer, the periderm, which is disposed once the inner basal layer or stratum germinativum has formed.This inner layer is a germinal epithelium that gives rise to all epidermal cells. It divides to form the outer spinous layer (stratum spinosum). The cells of these two layers, together called the Malpighian layer(s) after Marcello Malpighi, divide to form the superficial granular layer (Stratum granulosum) of the epidermis.The cells in the stratum granulosum do not divide, but instead form skin cells called keratinocytes from the granules of keratin. These skin cells finally become the cornified layer (stratum corneum), the outermost epidermal layer, where the cells become flattened sacks with their nuclei located at one end of the cell. After birth these outermost cells are replaced by new cells from the stratum granulosum and throughout life they are shed at a rate of 30 - 90 milligrams of skin flakes every hour, or 0.720 - 2.16 grams per day.Epidermal development is a product of several growth factors, two of which are:
Transforming growth factor Alpha (TGFα) is an autocrine growth factor by which basal cells stimulate their own division.
Keratinocyte growth factor (KGF or FGF7) is a paracrine growth factor produced by the underlying dermal fibroblasts in which the proliferation of basal cells is regulated.
Function
Barrier
The epidermis serves as a barrier to protect the body against microbial pathogens, oxidant stress (UV light), and chemical compounds, and provides mechanical resistance to minor injury. Most of this barrier role is played by the stratum corneum.
CharacteristicsPhysical barrier: Epidermal keratinocytes are tightly linked by cell–cell junctions associated to cytoskeletal proteins, giving the epidermis its mechanical strength.
Chemical barrier: Highly organized lipids, acids, hydrolytic enzymes, and antimicrobial peptides inhibit passage of external chemicals and pathogens into the body.
Immunologically active barrier: The humoral and cellular constituents of the immune system found in the epidermis actively combat infection.
Water content of the stratum corneum drops towards the surface, creating hostile conditions for pathogenic microorganism growth.
An acidic pH (around 5.0) and low amounts of water make the epidermis hostile to many microorganic pathogens.
Non-pathogenic microorganisms on the surface of the epidermis help defend against pathogens by competing for food, limiting its availability, and producing chemical secretions that inhibit the growth of pathogenic microbiota.PermeabilityPsychological stress, through an increase in glucocorticoids, compromises the stratum corneum and thus the barrier function.
Sudden and large shifts in humidity alter stratum corneum hydration in a way that could allow entry of pathogenic microorganisms.
Skin hydration
The ability of the skin to hold water is primarily due to the stratum corneum and is critical for maintaining healthy skin. Skin hydration is quantified using corneometry. Lipids arranged through a gradient and in an organized manner between the cells of the stratum corneum form a barrier to transepidermal water loss.
Skin color
The amount and distribution of melanin pigment in the epidermis is the main reason for variation in skin color in Homo sapiens. Melanin is found in the small melanosomes, particles formed in melanocytes from where they are transferred to the surrounding keratinocytes. The size, number, and arrangement of the melanosomes vary between racial groups, but while the number of melanocytes can vary between different body regions, their numbers remain the same in individual body regions in all human beings. In white and Asian skin the melanosomes are packed in "aggregates", but in black skin they are larger and distributed more evenly. The number of melanosomes in the keratinocytes increases with UV radiation exposure, while their distribution remain largely unaffected.
Clinical significance
Laboratory culture of keratinocytes to form a 3D structure (artificial skin) recapitulating most of the properties of the epidermis is routinely used as a tool for drug development and testing.
Hyperplasia
Epidermal hyperplasia (thickening resulting from cell proliferation) has various forms:
Acanthosis is diffuse epidermal hyperplasia (thickening of the skin, and not to be confused with acanthocytes). It implies increased thickness of the Malpighian layer (stratum basale and stratum spinosum). Acanthosis nigricans is a black, poorly defined, velvety hyperpigmented acanthosis, usually observed in the back of neck, axilla, and other folded regions of the skin.
Focal epithelial hyperplasia (Hecks disease) is an asymptomatic, benign neoplastic condition characterized by multiple white to pinkish papules that occur diffusely in the oral cavity.: 411
Pseudoepitheliomatous hyperplasia (PEH) is a benign condition characterized by hyperplasia of the epidermis and epithelium of skin appendages, with irregular squamous strands extending down into the dermis, and closely simulating squamous cell carcinoma (SCC).
In contract, hyperkeratosis is a thickening of the stratum corneum, and is not necessarily due to hyperplasia.
Additional images
See also
Skin repair
== References == |
Onychoatrophy | Onychoatrophy is a faulty underdevelopment of the nail that may be congenital or acquired, in which the nail is thinned and smaller.: 784
== References == |
Junctional epidermolysis bullosa | Junctional epidermolysis bullosa may refer to:
Junctional epidermolysis bullosa (medicine)
Junctional epidermolysis bullosa (veterinary medicine) |
Sabinas brittle hair syndrome | Sabinas brittle hair syndrome, also called Sabinas syndrome or brittle hair-mental deficit syndrome, is an autosomal recessive congenital disorder affecting the integumentary system.
Signs and symptoms
Symptoms include brittle hair, mild mental retardation and nail dysplasia. The syndrome was first observed in Sabinas, a small community in northern Mexico.
The principal biochemical features of the illness are reduced hair cystine levels, increased copper/zinc ratio, and presence of arginosuccinic acid in the blood and urine.The key finding is brittle hair with low sulfur content, but alternating dark and light bands under polarizing microscopy, trichoschisis, and absent or defective cuticle are additional important clues for the diagnosis of trichothiodystrophy. Review of literature reveals extensive associated findings in trichothiodystrophy. Amino acid analyses of control hair when compared with those of patients with the Sabinas syndrome showed very striking differences with regard to content of sulphur amino acids. As in previous descriptions of amino acid abnormalities in the trichorrhexis nodosa of arginosuccinicaciduria, there were increases in lysine, aspartic acid, alanine, leucine, isoleucine, and tyrosine.
Trichothiodystrophy represents a central pathologic feature of a specific hair dysplasia associated with several disorders in organs derived from ectoderm and neuroectoderm. Trichothiodystrophy or TTD is a heterogeneous group of autosomal recessive disorders, characterized by abnormally sulfur deficient brittle hair and accompanied by ichthyosis and other manifestations.
Patients with trichothiodystrophy should have a thorough evaluation for other associated manifestations, including investigation of photosensitivity and DNA repair defects. Because the disease appears to be inherited in an autosomal recessive pattern, detection of low-sulfur brittle hair syndrome is also important for genetic counseling.
Genetics
Sabinas brittle hair syndrome is inherited as an autosomal recessive genetic trait.In a study by Howell et al. patients were located and studied by means of complete histories and physical examinations, analyses of serum trace metals, ceruloplasmin concentration, urine and serum amino acids, and routine metabolic urine screens. In addition, serum and urine luteinizing hormone (LH) and follicle-stimulating hormone (FSH) values were determined, and were interpreted in conjunction with total plasma estrogen, estradiol, and testosterone levels. Close examination demonstrated the scalp hairs were very brittle, coarse, wiry in texture, and broke off quite easily with mechanical trauma such as combing and brushing. Some hairs could be visualized in their follicles, which were broken off at the skin line. Most patients had accompanying hyperkeratosis (thickening of the skin) of moderate degree on exposed surfaces. Maxillary hypoplasia (midfacial retrusion) was significant in many patients. The brittle, short hair, reduced eyelashes, crowded teeth, and dull appearance created a characteristic facial appearance. Post-pubertal patients had development of secondary sexual characteristics consistent with their age, except for sparse pubic escutcheons. All cases studied demonstrated some degree of mental deficiency; I.Q.s ranged between 50 and 60. A deficiency in eye–hand coordination was also noted.
Diagnosis
The easiest way to test for this condition is through genetic testing. Several methods can be used for genetic testing that can help identity this condition,
Molecular genetic tests (or gene tests) study single genes or short lengths of DNA to identify mutations and variations that can help lead to a genetic disorder.
Chromosomal genetic tests help investigate whole chromosomes or long lengths of DNA to see if there are bigger genetic changes, for example, an extra copy of a chromosome that can help cause a genetic condition.
Biochemical genetic tests study the activity level and amount level of proteins; abnormalities in either can indicate changes to the DNA and result in a genetic disorder.
Management
Although there has been no conclusive evidence on medications to manage the disorder, many organizations help with several aspects on living with the chronic condition, not only for the affected but also for the loved ones around them. With services like Global Genes helping contribute to this.
References
Further reading
Itin P., Pittelkow M., Trichothiodystrophy: Review of sulfur-deficient brittle hair syndromes and association with the ectodermal dysplasias[1]. Journal of the American Academy of Dermatology, Volume 22, Issue 5, Pages 705–717
Rare Disorders: All you need to know. Trichothiodystrophy[2]. Copyright © 2005 Rare-Disorders.com
Sabinas brittle hair syndrome is a form of nonphotosensitive trichothiodystrophy; Brittle hair and mental deficit at NIHs Office of Rare Diseases
== External links == |
Ischemic hepatitis | Ischemic hepatitis, also known as shock liver, is a condition defined as an acute liver injury caused by insufficient blood flow (and consequently insufficient oxygen delivery) to the liver. The decreased blood flow (perfusion) to the liver is usually due to shock or low blood pressure. However, local causes involving the hepatic artery that supplies oxygen to the liver, such as a blood clot in the hepatic artery, can also cause ischemic hepatitis.
Signs and symptoms
People who develop ischemic hepatitis may have weakness, fatigue, mental confusion, and low urine production (oliguria). A small percentage of affected people may develop hepatic coma. Yellow discoloration of the skin (jaundice) can occur, but is rare and temporary, as is actual loss of function of the liver.
Cause
Ischemic hepatitis can be caused by a number of reasons (that lead to low blood pressure) including:
Abnormal heart rhythm
Heart failure
Infection
Hypovolemic shock (e.g., due to profuse bleeding)
Blood clots (hepatic artery after surgery)
Mechanism
The mechanism of ischemic hepatitis depends on the etiopathogenetic origin, be it a cardiomyopathy, cardiac tamponade, trauma, or bleeding. Usually ischemic hepatitis reveals itself after a hypotensive event with increased levels of aminotransferases. Because of this, hypotension is thought to be one of the primary insults leading to ischemic hepatitis.
Diagnosis
Blood testing usually shows high levels of the liver transaminase enzymes, AST and ALT, which may exceed 10,000 U/L. It has been found that those who suffer from ischemic hepatitis had significant cardiac disease as well.As a measure of precaution, paracetamol levels and a toxicology screening should be completed to evaluate for possible toxin-mediated injury; it is also imperative to be able to exclude the possibility of acute viral hepatitis.
Related conditions
Ischemic hepatitis is related to another condition called congestive hepatopathy. Congestive hepatopathy includes a number of liver disorders that occur in right-sided heart failure. The medical term congestive hepatopathy is used, however, the term cardiac cirrhosis is convention. These two entities can coexist in an affected individual.
Treatment
The treatment of ischemic hepatitis is as follows:
See also
Elevated transaminases
References
Further reading
Kirk, Allan D.; Knechtle, Stuart J.; Larsen, Christian P.; Madsen, Joren C.; Pearson, Thomas C.; Webber, Steven A. (2014-07-21). Textbook of Organ Transplantation Set. John Wiley & Sons. ISBN 9781118889626.
Irwin, Richard S.; Rippe, James M. (2012-03-28). Manual of Intensive Care Medicine. Lippincott Williams & Wilkins. ISBN 9781451149074.
== External links == |
Intravascular papillary endothelial hyperplasia | Intravascular papillary endothelial hyperplasia is a rare, benign tumor. It may mimic an angiosarcoma, with lesions that are red or purplish 5-mm to 5-cm papules and deep nodules on the head, neck, or upper extremities.: 592
Pathology
Histopathology Images
See also
List of cutaneous conditions
References
== External links == |
Choroideremia | Choroideremia (; CHM) is a rare, X-linked recessive form of hereditary retinal degeneration that affects roughly 1 in 50,000 males. The disease causes a gradual loss of vision, starting with childhood night blindness, followed by peripheral vision loss and progressing to loss of central vision later in life. Progression continues throughout the individuals life, but both the rate of change and the degree of visual loss are variable among those affected, even within the same family.Choroideremia is caused by a loss-of-function mutation in the CHM gene which encodes Rab escort protein 1 (REP1), a protein involved in lipid modification of Rab proteins. While the complete mechanism of disease is not fully understood, the lack of a functional protein in the retina results in cell death and the gradual deterioration of the retinal pigment epithelium (RPE), photoreceptors and the choroid.As of 2019, there is no treatment for choroideremia; however, retinal gene therapy clinical trials have demonstrated a possible treatment.
Presentation
Since the CHM gene is located on the X chromosome, symptoms are seen almost exclusively in men. While there are a few exceptions, female carriers have a noticeable lack of pigmentation in the RPE but do not experience any symptoms. Female carriers have a 50% chance of having either an affected son or a carrier daughter, while a male with choroideremia will have all carrier daughters and unaffected sons.
Even though the disease progression can vary significantly, there are general trends. The first symptom many individuals with choroideremia notice is a significant loss of night vision, which begins in youth. Peripheral vision loss occurs gradually, starting as a ring of vision loss, and continuing on to "tunnel vision" in adulthood. Individuals with choroideremia tend to maintain good visual acuity into their 40s, but eventually lose all sight at some point in the 50–70 age range. A study of 115 individuals with choroideremia found that 84% of patients under the age of 60 had a visual acuity of 20/40 or better, while 33% of patients over 60 years old had a visual acuity of 20/200 or worse. The most severe visual acuity impairment (only being able to count fingers or worse) did not occur until the seventh decade of life. The same study found the mean rate of visual acuity loss to be about 0.09 logMAR per 5 years, which is roughly 1 row on a Snellen chart.
Diagnosis
A diagnosis of choroideremia can be made based on family history, symptoms and the characteristic appearance of the fundus. However, choroideremia shares several clinical features with retinitis pigmentosa, a similar but broader group of retinal degenerative diseases, making a specific diagnosis difficult without genetic testing. Because of this choroideremia is often initially misdiagnosed as retinitis pigmentosa. A variety of different genetic testing techniques can be used to make a differential diagnosis.
Management
While nothing currently can be done to stop or reverse the retinal degeneration, there are steps that can be taken to slow the rate of vision loss. UV-blocking sunglasses for outdoors, appropriate dietary intake of fresh fruit and leafy green vegetables, antioxidant vitamin supplements, and regular intake of dietary omega-3 very-long-chain fatty acids are all recommended. One study found that a dietary supplement of lutein increases macular pigment levels in patients with choroideremia. Over a long period of time, these elevated levels of pigmentation "could" slow retinal degeneration. Additional interventions that may be needed include surgical correction of retinal detachment and cataracts, low vision services, and counseling to help cope with depression, loss of independence, and anxiety over job loss.
Gene therapy
Gene therapy is currently not a treatment option, however human clinical trials for both choroideremia and Lebers congenital amaurosis (LCA) have produced somewhat promising results.Clinical trials of gene therapy for patients with LCA began in 2008 at three different sites. In general, these studies found the therapy to be safe, somewhat effective, and promising as a future treatment for similar retinal diseases.
In 2011, the first gene therapy treatment for choroideremia was administered. The surgery was performed by Robert MacLaren, Professor of Ophthalmology at the University of Oxford and leader of the Clinical Ophthalmology Research Group at the Nuffield Laboratory of Ophthalmology (NLO). In the study, 2 doses of the AAV.REP1 vector were injected subretinally in 12 patients with choroideremia. There study had 2 objectives:
to assess the safety and tolerability of the AAV.REP1 vector
to observe the therapeutic benefit, or slowing of the retinal degeneration, of the gene therapy during the study and at a 24-month post-treatment time pointDespite retinal detachment caused by the injection, the study observed initial improved rod and cone function, warranting further study.
In 2016, researchers were optimistic that the positive results of 32 choroideremia patients treated over four and a half years with gene therapy in four countries could be long-lasting.
Preimplantation genetic diagnosis
For women who carry a mutation in the CHM gene, preimplantation genetic diagnosis can be used during the in-vitro fertilization process to select unaffected embryos to implant. This process call be applied to any monogenic disease.
Other potential therapies
While choroideremia is an ideal candidate for gene therapy there are other potential therapies that could restore vision after it has been lost later in life. Foremost of these is stem cell therapy. A clinical trial published in 2014 found that a subretinal injection of human embryonic stem cells in patients with age-related macular degeneration and Stargardt disease was safe and improved vision in most patients. Out of 18 patients, vision improved in 10, improved or remained the same in 7, and decreased in 1 patient, while no improvement was seen in the untreated eyes. The study found "no evidence of adverse proliferation, rejection, or serious ocular or systemic safety issues related to the transplanted tissue." A 2015 study used CRISPR/Cas9 to repair mutations in patient-derived induced pluripotent stem cells that cause X-linked retinitis pigmentosa. This study suggests that a patients own repaired cells could be used for therapy, reducing the risk of immune rejection and ethical issues that come with the use of embryonic stem cells.
Research
History
Choroideremia was first described in 1872 by an Austrian ophthalmologist, Ludwig Mauthner. Initially, the condition was thought to be a developmental disorder which caused the absence of a majority of the choroid (hence the probable use of the ancient Greek suffix “eremia,” meaning barren land or desert). After several decades, the non-progressive nature of the disease was called into doubt, eventually being rejected by Paymerer et al. in 1960. The CHM gene was identified and cloned in 1990 by Frans P.M. Cremers.
Basic research
In many inherited retinal diseases the protein affected by the mutation is directly involved in the light sensing function of the eye, however this is not the case in choroideremia. REP1 assists the prenylation of Rab G-proteins by binding and presenting them to the Rab geranylgeranyltransferase subunit. REP1 also escorts prenylated Rabs through the cytoplasm by binding the hydrophobic prenyl groups and carrying them to a specific destination membrane.In healthy individuals, REP1 is found throughout all of the cells of the body, however patients with choroideremia only experience vision loss, and not broader, systemic symptoms (with the exception of a study that found crystals and fatty acid abnormalities in leukocytes). REP2, a protein that is 75% identical and 90% similar to REP1, is able to significantly compensate for the loss of REP1 outside the eye. It is thought that REP2 is not able to fully compensate for the loss of REP1 in the retina. RAB27A, a Rab that has essential functions in the retina, has been shown to be preferentially prenylated by REP1. Additionally, the Rab27a-REP1 and Rab27a-REP2 complexes have different affinities for the Rab geranylgeranyltransferase enzyme, possibly explaining REP2s inability to fully compensate for REP1 in the retina.
Culture
A number of individuals in public roles are living with choroidermia, and some have been involved in fundraising efforts for the disease. The former UK Labour Member of Parliament Siôn Simon is a known to have the condition. Comic and activist E.J. Scott, partner of Daredevil actress Deborah Ann Woll, also has choroideremia, and is involved in regular fundraising efforts.
References
Further reading
Danny Boren, 2015, "First U.S. Gene Therapy Clinical Trial to treat Choroideremia initiated in Philadelphia," Choroideremia Research Foundation (online), Press Release Summary, January 20, 2015, see [10] Archived 2015-09-21 at the Wayback Machine, accessed 23 April 2015.
Cory MacDonald, 2015, "Nightstar Receives U.S. and European Orphan Drug Designation for Gene Therapy to Treat Choroideremia," Choroideremia Research Foundation (online), Press Release Summary, March 24, 2015 (release date, January 11), see [11], accessed 23 April 2015.
FFB, 2015, "U.S. Human Study for Choroideremia Gene Therapy Launched by Spark Therapeutics," Foundation Fighting Blindness (online), January 27, 2015, see [12], accessed 23 April 2015.
NLO, 2014, "First Results of Choroideremia Gene Therapy Trial (2014)," Nuffield Laboratory of Ophthalmology (online), Press Release, undated, see [13], accessed 23 April 2015.
External links
Genetic testing for Choroideremia.
Choroideremia Research Foundation is an international not-for-profit organization dedicated to supporting the Choroideremia community |
Cor bovinum | Cor bovinum or cor bovis refers to a massive hypertrophy of the left ventricle of the heart due to volume overload, usually in earlier times in the context of tertiary syphilis but currently more often due to chronic aortic regurgitation, hypertensive and ischaemic heart disease.
Pathophysiology
Due to Syphilitic aortitis (a complication of tertiary syphilis) the aortic valve ring becomes dilated. The free margins of valve cusps no longer approximate leading to aortic valve insufficiency. As blood regurgitates into the left ventricle between each systole, volume overload ensues and the ventricular wall hypertrophies in an attempt to maintain cardiac output and blood pressure. The massive ventricle can lead to a heart weighing over 1000 grams (the weight of a normal heart is about 350 grams), referred to as cor bovinum (Latin for cows heart).Fluri and Gebbers define cor bovinum as a heart exceeding 500 g in weight. Looking through autopsies on Internal Medicine patients at the Kantonsspital Luzern, they found 415 cases out of 1181 autopsies in the two periods 1978-81 and 1997-2000. Cor bovinum was found in 25.3% of cases in the earlier period, with mean age at death 67.7 years, and in the later period 20.6% with mean age 74.3 years. The male female ratio was 4:1. "In 93% of all patients with CB, we found coronary atherosclerosis as a sign of high blood pressure and in 79% a COPD."
In 84% of cases the cause of death was directly related to the cor bovinum, but in 37% the cause of death was still unclear. They concluded that cor bovinum was a decreasing but still frequent autopsy finding. High blood pressure, COPD and male sex were the main risk factors. The decreasing incidence was ascribed to improved medical management: they mention treatments for high blood pressure and coronary artery disease, which suggests that "COPD" in their abstract refers to the latter.
Diagnosis
Terminology
A Medline search in January 2008 of articles published since 1950 revealed seven articles on "cor bovinum" (in the earlier part of this period only the titles could be searched), of which only one was in English. A search for dictionary-reported synonyms revealed no mention of "bucardia," and all 101 articles mentioning "ox heart" related to oxen.
See also
Cardiomegaly
Left ventricular hypertrophy
Syphilitic aortitis
Ventricular hypertrophy
== References == |
Recurrent pyogenic cholangitis | Recurrent pyogenic cholangitis (RPC), also known as Hong Kong disease, Oriental cholangitis, and Oriental infestational cholangitis, is a chronic infection characterized by recurrent bouts of bacterial cholangitis with primary hepatolithiasis. It is exclusive to people who live or have lived in southeast Asia.
Presentation
Presentation can be atypical and without pain or fever, especially in the elderly. Positive symptoms include biliary colic, acute pancreatitis, obstructive jaundice and less commonly, liver enlargement and abnormal liver function tests. Additional complications in the acute setting include ascending cholangitis, gallbladder empyema, clotting within the hepatic and portal veins, sepsis and death.Chronic biliary obstruction may cause jaundice, itchiness, liver abscesses, and cirrhosis, particularly at the left lobe segment 3, and can eventually lead to intraductal papillary mucinous neoplasm or cholangiocarcinoma.
Pathogenesis
With RPC, the gallstones found within the biliary system are made of calcium bilirubinate or pigmented calcium. Calcium bilirubinate stones are prevalent in Asia and very rare in Europe and the United States. They tend to be friable concretions of various shapes and sizes within the biliary tree, and their associated bile is often muddy in consistency and contains numerous fine particles of calcium bilirubinate as well. This differs greatly from cholesterol stones, which are common in Europe and the United States. The formation of calcium bilirubinate stones in RPC has been attributed to a high incidence of infection with Escherichia coli in bile. In humans, the majority of bilirubin is excreted in the bile as bilirubin glucuronide.Hepatolithiasis is associated with Clonorchis sinensis and Ascaris lumbricoides infestation of the liver. This theory is based on high incidence of dead parasites or ova within stone in autopsy findings.
Diagnosis
The diagnosis can be suspected by imaging, with typical characteristics centering around appearance of the liver, typically with CT, ultrasound or MRI. Traits that raise suspicion for the infection include intra- and extra- hepatic dilatation and strictures with intraductal pigmented stones, usually in the absence of gallstones and with regions of segmental liver atrophy, particularly the lateral aspect of the left hepatic lobe. There is also reduced arborization of peripheral ducts. Approximately 5% of chronic infections go on to develop cholangiocarcinoma.Pathogenic bacteria responsible for the infection include E. coli, Klebsiella, Pseudomonas, and Proteus species. Anaerobes are a less frequent cause, and a culture positive for multiple strains can be common. When related to Clonorchis sinensis, definitive diagnosis is by identification of eggs by microscopic demonstration in faeces or in duodenal aspirate, but other sophisticated methods have been developed, such as ELISA, which has become the most important clinical technique. Diagnosis by detecting DNAs from eggs in faeces are also developed using PCR, real-time PCR, and LAMP, which are highly sensitive and specific.
Treatment
The treatment of RPC involves management of sepsis during episodes of cholangitis with antibiotics, abscess drainage, and blood pressure support. With resistant infection, a surgical hepatectomy or hepaticocutaneousjejunostomy can be performed. Lifelong surveillance for malignancy is also usually necessary.
See also
Cholangitis
Cholecystitis
Clonorchiasis
Clonorchis sinensis
Hepaticojejunostomy
Cirrhosis
References
== External links == |
Pulled hamstring | Straining of the hamstring, also known as a pulled hamstring, is defined as an excessive stretch or tear of muscle fibers and related tissues. Hamstring injuries are common in athletes participating in many sports. Track and field athletes are particularly at risk, as hamstring injuries have been estimated to make up 29% of all injuries in sprinters.
Hamstring injuries can also come with a hip injury from sprinting. Symptoms for a hip injury are pain, aching and discomfort while running or any physical exercise.
The biceps femoris long head is at the most risk for injury, possibly due to its reduced moment of knee and hip flexion as compared to the medial hamstrings.
Causes of hamstring strain
The muscle group is prone to injuries due to the explosive nature of movement in sports and thus causing overload and overstretching of the hamstring musculature.
The other causes may be:
Previous injury
Poor muscle strength
Poor flexibility
Inadequate warm-up
Fatigue
Imbalance
OveruseThis condition is most commonly seen in:
Athletes involved in soccer, baseball, football, rugby
Dancers and water skiers
Sports involving cross-country skiing, downhill skiing, judo, cricket, and bull riding
Diagnosis
Grades
Grade 1
Sensation of cramp or tightness and a slight feeling of pain when the muscles are stretched or contracted.
Grade 2
With a grade two hamstring strain there is immediate pain which is more severe than the pain of a grade one injury. It is confirmed by pain on stretch, swelling and contraction of the muscle.
Grade 3
A grade three hamstring strain is a severe injury. There is an immediate burning or stabbing pain and the individual is unable to walk without pain. The muscle is completely torn and there may be a large lump of muscle tissue above a depression where the tear is.
After a few days with grade two and three injuries, a large bruise may appear below the injury site caused by the bleeding within the tissues.
Treatment
Recommended treatment for this injury consists of the RICE protocol — rest, ice, compression and elevation. The RICE method is primarily used to reduce bleeding and damage within the muscle tissue. Lower grade strains can easily become worse if the hamstring is not rested properly. Complete ruptures require surgical repair and rehabilitation.
Initial treatment of the injury, regardless of the severity of the strain, is the same. Within the first five days, the hamstring is rested in an elevated position with an ice pack applied for twenty minutes every two hours. A compression bandage is applied to limit bleeding and swelling in the tissues. After five days of rest, active rehabilitation begins.
Epidemiology
An academic study found that the most common and prevalent musculoskeletal injury in the world is a hamstring strain. The study further explains that hamstring strains represented 15% of all injuries per club per season also had a 34% chance of recurrence. Another study showed that a previous hamstring injury is one of the most cited risks for future injury, with as many as one-third of active individuals experiencing a re-injury within 2 weeks of returning to activity.
A meta-analysis article showed evidence that a history of hamstring injury and being of older age were associated with increased risk of hamstring strains. One study found that men and master athletes (athletes older than forty) were at an increased risk of hamstring strains compared with women and younger athletes. Women were approximately 3 times more likely to develop hamstring strain than males with the majority of these being non-sporting scenarios. Similarly the average age of non-sporting hamstring strains are from the ages of 40–60. Many of these non-sporting injuries are sustained during road traffic accidents, slipping, and falling. These results also show that hamstring strains account for 50% of muscle injuries received by sprinters and are the most common injury in hurdling. One explanation is that older active individuals may be at greater risk due to lower levels of eccentric knee flexor strength compared with their younger counterparts. However, it is unclear whether flexibility serves as a risk factor; this topic should be researched in the future to further understand the relationship between flexibility and risk of injury. Muscle weakness has also been an implication as a predisposing factor for both primary and recurring hamstring strain injuries. Over a 10-year study more than 51.3% of hamstring strains occurred during the preseason of athletics. In another study, that analyzed 25 NCAA sports over four years, it was clearly shown that hamstring strain rates are higher in the preseason. The factors that are being implicated in this trend are the relative deterioration and muscle weakness that occur during the off-season.The hamstrings undergo a complex dynamic process during gait, making it unsurprising that they are frequently injured. They must first contract concentrically during the end of the stance phase in order to bend the knee and allow the foot (along with dorsiflexion at the ankle) to clear the ground. At the end of the swing phase, the hamstrings must eccentrically contract while applying a braking moment to knee extension, then immediately change functions to again concentrically contract and produce hip extension. Studies have shown that "the hamstring group reaches peak elongation and acts eccentrically at the hip and knee during the late swing phases of running" and that "the hamstrings are most active and develop the greatest torques at the hip and knee during the late swing through midstance phase of running." Thus, the hamstrings reach their maximum length while attempting to forcefully contract eccentrically and switch functions to immediately produce a concentric contraction, which makes the terminal part of swing phase the most vulnerable for injury.
There have been many other proposed predisposing factors to injury. These include muscle weakness, muscle imbalance, poor flexibility, fatigue, inadequate warm up, poor neuromuscular control, and poor running technique. One of the few predisposing factors that most researchers agree upon however is previous hamstring injury. Brokett et al. (2004) stated that "the athletes most at risk of a hamstring strain are those with a previous history of such injury" and noted that 34% of the hamstring injuries were recurrences." Cameron et al. also found that 34% of injuries recur in the same season. Arnason et al. generalized these numbers, saying that previous injury was in itself an independent risk factor for re-injury.
References
External links
Hamstring Injuries |
Hereditary diffuse leukoencephalopathy with spheroids | Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare adult onset autosomal dominant disorder characterized by cerebral white matter degeneration with demyelination and axonal spheroids leading to progressive cognitive and motor dysfunction. Spheroids are axonal swellings with discontinuous or absence of myelin sheaths. It is believed that the disease arises from primary microglial dysfunction that leads to secondary disruption of axonal integrity, neuroaxonal damage, and focal axonal spheroids leading to demyelination. Spheroids in HDLS resemble to some extent those produced by shear stress in a closed head injury with damage to axons, causing them to swell due to blockage of axoplasmic transport. In addition to trauma, axonal spheroids can be found in aged brain, stroke, and in other degenerative diseases. In HDLS, it is uncertain whether demyelination occurs prior to the axonal spheroids or what triggers neurodegeneration after apparently normal brain and white matter development, although genetic deficits suggest that demyelination and axonal pathology may be secondary to microglial dysfunction. The clinical syndrome in patients with HDLS is not specific and it can be mistaken for Alzheimers disease, frontotemporal dementia, atypical Parkinsonism, multiple sclerosis, or corticobasal degeneration.
Symptoms
With symptoms of personality changes, behavioral changes, dementia, depression, and epilepsy, HDLS has been commonly misdiagnosed for a number of other diseases. Dementia or frontotemporal behavioral changes, for example, have commonly steered some clinicians to mistakenly consider diagnoses such as Alzheimers disease, frontotemporal dementia or atypical Parkinsonism. The presence of white matter changes has led to misdiagnosis of multiple sclerosis. HDLS commonly manifests with neuropsychiatric symptoms, progressing to dementia, and after a few years shows motor dysfunction. Eventually patients become reliant on wheelchairs.White matter degeneration is associated with and makes differential diagnoses out of other adult onset leukodystrophies such as metachromatic leukodystrophy (MLD), Krabbe disease (globoid cell leukodystrophy), and X-linked adrenoleukodystrophy (X-ADL).
Neuropsychiatric symptoms
Many neuropsychiatric symptoms have been identified in clinical studies of HDLS patients. These include severe depression and anxiety that have been identified in about 70% of HDLS families, verging on suicidal tendencies and substance abuse such as alcoholism. Additionally, patients may exhibit disorientation, confusion, agitation, irritability, aggressiveness, an altered mental state, the loss of the ability to execute learned movements (apraxia), or the inability to speak (mutism).
Motor impairment
Persons with HDLS can develop tremors, decreased body movement, unsteadiness (Parkinsonism, muscles on one side of the body in constant contraction (spastic hemiparesis), impairment in motor and sensory function in the lower extremities (paraparesis), paralysis resulting in partial or total loss of all extremities and torso (tetraparesis), and the lack of voluntary coordination of muscle movements (ataxia).
Causes
The cause of HDLS in most families is mutation in the colony stimulating factor 1 receptor (CSF1R), a growth factor for microglia and monocyte/macrophages, suggesting that microglial dysfunction may be primary in HDLS.The mutations are concentrated in tyrosine kinase domain (TKD) of the protein. Mutations were mainly found in exons 12-22 of the intracellular TKD, including 10 missense mutations that have a single nucleotide deletion and a single codon deletion that consists of a triplet of nucleotides that have been removed causing a whole amino acid to not be coded. Additionally, three splice site mutations were identified that caused an in-frame deletion of an exon, an expressed nucleotide sequence, leading to the removal of more than 40 amino acids in the TKD.This determination has based upon genetic studies of 14 HDLS families confirming mutations in this gene. The CSF1 receptor protein primarily functions in regulation, survival, proliferation, and differentiation of microglial cells. The mechanism of microglial dysfunction due to mutations in CSF1R to the myelin loss and axonal spheroid formation remains unknown. Further research is needed to better understand disease pathogenesis.
Pathology
In HDLS, there is enlargement of the lateral ventricles and marked thinning or weakening of cerebral white matter. The loss of white matter is caused by myelin loss. These changes are associated with diffuse gliosis, moderate loss of axons and many axonal spheroids.Activated or ameboid microglia and macrophages that contain myelin debris, lipid droplets and brown autofluorescent pigment granules are found in the areas with demyelination and axonal spheroids. In severely degenerated areas there are many large, reactive astrocytes filled with glial fibrils.In autopsy cases, it has been shown that white matter abnormalities are relatively confined to the cerebrum while avoiding the cerebellum and many of the major fiber tracts of the nervous system. The exception is the corticospinal tracts(pyramidal tracts) in the brainstem and sometimes spinal cord.The brain pathology of HDLS resembles that of Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy).
Diagnosis
Research as of 2012 includes investigations of microglial function. This work would further clarify whether the disease is primarily a defect in microglia function. For such a study, microglial cells from HDLS kindred can be cultured from autopsy brain and analyzed in comparison to normal microglial cells on the basis of differences in mutation occurrences and growth factor expression.
Differential diagnosis
Related disorders in the same disease spectrum as HDLS include Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy), and a type of leukodystrophy with pigment-filled macrophages called pigmentary orthochromatic leukodystrophy (POLD). In addition to white matter disease, Nasu-Hakola causes bone cysts. It is caused by mutations in the genes involved in the same colony stimulating factor (CSF) signaling pathway cascade as identified in HDLS.Nasu-Hakola disease appears to be caused by mutations in the TYRO protein tyrosine kinase-binding protein (TYROBP - also known as DAP12) or the triggering receptor expressed on myeloid cells 2 (TREM2) protein. While different gene mutations occur within the pathway for Nasu-Hakola and HDLS, both are characterized by white matter degeneration with axonal spheroids. Current researchers in the field believe that more in depth analysis and comparison of the two genetic abnormalities in these disorders could lead to a better understanding of the disease mechanisms in these rare disorders. POLD exhibits noninflammatory demyelination of axons with initial symptoms of euphoria, apathy, headache, and executive dysfunction. While HDLS is autosomal dominant, some families with POLD have features that suggest autosomal recessive inheritance. Nevertheless, POLD has recently been shown to have the same genetic basis as HDLS.
Clinical and genealogic studies
To gain a better understanding of the disease, researchers have retrospectively reviewed medical records of probands and others who were assessed through clinical examinations or questionnaires. Blood samples are collected from the families of the probands for genetic testing. These family members are assessed using their standard medical history, on their progression of Parkinsons like symptoms (Unified Parkinsons Disease Rating Scale), and on their progression of cognitive impairment such as dementia (Folstein Test).
Neuroimaging
Standard MRI scans have been performed on 1.5 Tesla scanners with 5 mm thickness and 5 mm spacing to screen for white matter lesions in identified families. If signal intensities of the MRI scans are higher in white matter regions than in grey matter regions, the patient is considered to be at risk for HDLS, although a number of other disorders can also produce white matter changes and the findings are not diagnostic without genetic testing or pathologic confirmation.
Pathology
Tissue sections from brain biopsies or autopsy brains are commonly embedded in paraffin from which sections are cut an mounted on glass slides for histologic studies. Special stains for myelin and axonal pathology show the abnormal changes that are characteristic of HDLS are identified in white matter of the neocortex, basal ganglia, thalamus, midbrain, pons and spinal cord. In addition to routine histologic methods (H&E staining), samples are evaluated with immunohistochemistry for ubiquitin, amyloid precursor protein, and neurofilament to characterize axonal changes and myelin basic protein for myelin pathology. Immunohistochemical stains for microglia (CD68 or HLA-DR) and astrocytes (GFAP) are also helpful techniques to characterize white matter pathology. With a similar pathology to POLD, HDLS is commonly grouped as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) so as to give these individually under-recognized conditions heightened attention.
Classification
HDLS falls under the category of brain white matter diseases called leukoencephalopathies that are characterized by some degree of white matter dysfunction. HDLS has white matter lesions with abnormalities in myelin sheath around axons, where the causative influences are being continually explored based upon recent genetic findings. Studies by Sundal and colleagues from Sweden showed that a risk allele in Caucasians may be causative because cases identified have thus far been among large Caucasian families.
Management
Epidemiology
An average clinical profile from published studies shows that the median onset age for HDLS patients is 44.3 years with a mean disease duration of 5.8 years and mean age of death at 53.2 years. As of 2012, there have been around 15 cases identified with at least 11 sporadic cases of HDLS. HDLS cases have been located in Germany, Norway, Sweden, and the United States, showing an international distribution focusing between Northern Europe and the United States.Through the study of numerous kindred, it was found that the disease did not occur among just males or females, but rather was evenly distributed indicative of an autosomal rather than a sex-linked genetic disorder. It was also observed that the HDLS cases did not skip generations as it would occur with a recessive inheritance, and as such has been labeled autosomal dominant.
History
This disease was first described in 1984 by Axelsson et al. in a large Swedish pedigree. It is a disorder better known to neuropathologists than clinicians. A neuropathologist with an interest in HDLS, Dr. Dennis W. Dickson, has identified a number of cases from neuropathology study of brains submitted for investigation of familial adult-onset dementia and movement disorders in New York and later in Florida. Recognition of the importance of this disorder as a cause of adult onset dementia and movement disorders was further heightened in 1997 at the Mayo Clinic when Dr. Zbigniew K. Wszolek identified a family with HDLS that was initially thought to be due to another disease process (FTDP-17), but only an autopsy of one and then other family members revealed it to be HDLS. Wszolek established an international consortium in 2005 to identify other families and to collect DNA or brain samples from family members for neuropathologic confirmation and genetic research at the Mayo Clinic in Florida.
See also
Neurodegeneration
Leukoencephalopathy with vanishing white matter
Microcephaly
References
== External links == |
Alopecia universalis | Alopecia universalis (AU), also known as alopecia areata universalis, is a medical condition involving the loss of all body hair, including eyebrows, eyelashes, chest hair, armpit hair, and pubic hair. It is the most severe form of alopecia areata. People with the disease are usually healthy and have no other symptoms and a normal life expectancy.
Causes
Alopecia universalis can occur at any age, and is currently believed to be an autoimmune disorder, in which a persons immune system attacks the hair follicles. Genetic factors may contribute to AU, as about 20% of those affected have a family member with alopecia.
Treatment
Many treatments have been explored, including immunomodulatory agents such as imiquimod. Tofacitinib citrate may also have benefits. In June 2014, a 25-year-old man with almost no hair on his body was reported to have grown full head of hair, as well as eyebrows, eyelashes, and facial, armpit, and other hair, following eight months of treatment.Contact immunotherapy involves the use of contact allergens, such as diphencyprone and squaric acid dibutylester, to induce an immune response that is thought to oppose the action of cells causing hair loss. A review that combined and analyzed the findings of 45 studies comprising 2,227 patients showed any hair regrowth in 54.5% and complete hair regrowth in 24.9% of patients with AT and AU using contact immunotherapy. In addition to its helpful effects in treating AU, it can have side effects that can be very serious, such as severe dermatitis.Topical and intralesional corticosteroids, such as clobetasol propionate, have also shown to be an effective treatment for AT and AU patients. A controlled study comprising 28 patients found positive terminal hair growth in eight of the patients (28.5%) using a 0.05% clobetasol propionate ointment. This is very similar to the results obtained from immunotherapy treatment trials. Additionally, studies suggest that intralesional applications are much more effective than topical applications of steroids. However, the main side effect is increased risk of cutaneous atrophy at the site of treatment; folliculitis is also an occasional complication.Janus kinase inhibitors, previously used in the treatment of cancer and other diseases, such as arthritis, have successfully shown to be effective in the initial trials of treatment for alopecia patients. Multiple cases of treatments have been successful, one of them being of a 22-year-old man with a history of AU and atopic dermatitis (AD). This man was treated with JAK inhibitor tofacitinib, and after ten months, he experienced hair regrowth on all of his affected body parts and subsequent improvement of his AD. Current research and findings suggest that systemic JAK inhibitors eliminate and prevent the development of AA, while topical JAK inhibitors promote hair regrowth and reverse the established disease. Many clinical trials are ongoing involving JAK inhibitors such as ruxolitinib and tofacitinib.
See also
Alopecia areata
Alopecia totalis
References
== External links == |
Fibrolamellar hepatocellular carcinoma | Fibrolamellar hepatocellular carcinoma (FHCC) is a rare form of hepatocellular carcinoma (HCC) that typically affects young adults and is characterized, under the microscope, by laminated fibrous layers interspersed between the tumour cells. Approximately 200 new cases are diagnosed worldwide each year.
Cause
A recent study showed the presence of the DNAJB1-PRKACA chimeric transcript (resulting from a 400kb somatic deletion on chromosome 19) in 100% of the FHCCs examined (15/15) This gene fusion has been confirmed in a second study.
Pathology
The histopathology of FHCC is characterized by laminated fibrous layers, interspersed between the tumor cells. Cytologically, the tumor cells have a low nuclear to cytoplasmic ratio with abundant eosinophilic cytoplasm. Tumors are non-encapsulated, but well circumscribed, when compared to conventional HCC (which typically has an invasive border).
Diagnosis
Due to lack of symptoms, until the tumor is sizable, this form of cancer is often advanced when diagnosed. Symptoms include vague abdominal pain, nausea, abdominal fullness, malaise and weight loss. They may also include a palpable liver mass. Other presentations include jaundice, ascites, fulminant liver failure, encephalopathy, gynecomastia (males only), thrombophlebitis of the lower limbs, recurrent deep vein thrombosis, anemia and hypoglycemia.The usual markers for liver disease – aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase – are often normal or only slightly elevated. FHCC often does not produce alpha fetoprotein (AFP), a widely used marker for conventional hepatocellular carcinoma. It is associated with elevated neurotensin levels.Diagnosis is normally made by imaging (ultrasound, CT or MRI) and biopsy
Treatment
In FHCC, plasma neurotensin and serum vitamin B12 binding globulin are commonly increased and are useful in monitoring the disease and detecting recurrence.FHCC can often be surgically removed. Liver resection is the optimal treatment and may need to be performed more than once, since this disease has a very high recurrence rate. Due to such recurrence, periodic follow-up medical imaging (CT or MRI) is necessary.As the tumor is quite rare, there is no standard chemotherapy regimen. Radiotherapy has been used but data is limited concerning its use. The survival rate for fibrolamellar HCC largely depends on whether (and to what degree) the cancer has metastasized, i.e. spread to the lymph nodes or other organs. Distant spread (metastases), significantly reduces the median survival rate. Five-year survival rates vary between 40–90%.
Epidemiology
FHCC accounts for 1–10% of primary liver cancers. It typically has a young age at presentation (20–40 years: mean age ~27 years) when compared to conventional HCC. Unlike the more common HCC, patients most often do not have coexistent liver disease such as cirrhosis.
History
This disease was first described by Hugh Edmondson in a 14-year-old female with no underlying liver disease. The name fibrolamellar hepatocellular carcinoma was coined by Craig et al. in 1980. It was not recognised as a distinct form of cancer by the WHO until 2010.
Additional images
References
== External links == |
Urticaria pigmentosa | Urticaria pigmentosa (also known as generalized eruption of cutaneous mastocytosis (childhood type): 616
) is the most common form of cutaneous mastocytosis. It is a rare disease caused by excessive numbers of mast cells in the skin that produce hives or lesions on the skin when irritated.
Signs and symptoms
Urticaria pigmentosa is characterized by excessive amounts of mast cells in the skin. Red or brown spots are often seen on the skin, typically around the chest, forehead, and back. These mast cells, when irritated (e.g. by rubbing the skin, heat exposure), produce too much histamine, triggering an allergic reaction that leads to hives localized to the area of irritation, sometimes referred to as Dariers sign. Severe itching usually follows, and scratching the area only serves to further symptoms. Symptoms can be mild (flushing and hives that require no treatment), moderate (diarrhea, tachycardia, nausea/vomiting, headache, and fainting), or life-threatening (vascular collapse requiring emergency treatment and hospitalization).
Cause
The majority of urticaria pigmentosa cases are caused by a point mutation at amino acid 816 of the proto-oncogene c-kit. c-kit is a transmembrane protein which, when bound to Mast Cell Growth Factor (MCGF), signals the cell to divide. Mutations in position 816 of c-kit can result in a constant division signal being sent to the mast cells, resulting in abnormal proliferation. Different mutations have been linked to different onset times of the disease.
For example, the Asp816Phe and Asp816Val mutations (the aspartate normally at position 816 in the c-kit protein has been replaced with phenylalanine or valine respectively) have been associated with early manifestation of the disease (mean age of onset: 1.3 and 5.9 months respectively).
The c-kit gene is encoded on the q12 locus of chromosome 4.
Irritants
Several factors can worsen the symptoms of urticaria pigmentosa:
Emotional stress
Physical stimuli such as heat, friction, and excessive exercise
Bacterial toxins
Venom
Eye drops containing dextran
NSAIDs
Alcohol
MorphineThe classification of NSAIDs can be disputed. Aspirin, for example, causes the mast cells to degranulate, releasing histamines and causing symptoms to flare. However, daily intake of 81 mg aspirin may keep the mast cells degranulated. Thus, while symptoms may be worsened at first, they can get better as the mast cells are unable to recharge with histamine.
Diagnosis
The disease is most often diagnosed as an infant, when parents take their baby in for what appears to be bug bites. The bug bites are actually the clumps of mast cells. Doctors can confirm the presence of mast cells by rubbing the babys skin. If hives appear, it most likely signifies the presence of urticaria pigmentosa.
Treatments
There are no permanent cures for urticaria pigmentosa. However, treatments are possible. Most treatments for mastocytosis can be used to treat urticaria pigmentosa. Many common anti-allergy medications are useful because they reduce the mast cells ability to react to histamine.At least one clinical study suggested that nifedipine, a calcium channel blocker used to treat high blood pressure, may reduce mast cell degranulation in patients with urticaria pigmentosa. A 1984 study by Fairly et al. included a patient with symptomatic urticaria pigmentosa who responded to nifedipine at dose of 10 mg po tid. However, nifedipine has never been approved by the FDA for treatment of urticaria pigmentosa.
Another mast cell stabilizer Gastrocrom, a form of cromoglicic acid has also been used to reduce mast cell degranulation.
Epidemiology
Urticaria pigmentosa is a rare disease, affecting fewer than 200,000 people in the United States.
See also
Urticaria
Dermatographic urticaria
Generalized eruption of cutaneous mastocytosis (adult type)
References
Further reading
Alto WA, Clarcq L (June 1999). "Cutaneous and systemic manifestations of mastocytosis". Am Fam Physician. 59 (11): 3047–54, 3059–60. PMID 10392589.
== External links == |
Pipecolic acidemia | Pipecolic acidemia is a very rare autosomal recessive metabolic disorder that is caused by a peroxisomal defect.
Pipecolic acidemia can also be an associated component of Refsum disease with increased pipecolic acidemia (RDPA), as well as other peroxisomal disorders, including both infantile and adult Refsum disease, and Zellweger syndrome.The disorder is characterized by an increase in pipecolic acid levels in the blood, leading to neuropathy and hepatomegaly.
See also
AASDHPPT
PHYH
References
== External links == |
Breast hypertrophy | Breast hypertrophy is a rare medical condition of the breast connective tissues in which the breasts become excessively large. The condition is often divided based on the severity into two types, macromastia and gigantomastia. Hypertrophy of the breast tissues may be caused by increased histologic sensitivity to certain hormones such as female sex hormones, prolactin, and growth factors. Breast hypertrophy is a benign progressive enlargement, which can occur in both breasts (bilateral) or only in one breast (unilateral). It was first scientifically described in 1648.
Description and types
The indication is an excess breast weight that exceeds approximately 3% of the total body weight. There are varying definitions of what is considered to be excessive breast tissue, that is the expected breast tissue plus extraordinary breast tissue, ranging from as little as 0.6 kilograms (1.3 lb) up to 2.5 kilograms (5.5 lb) with most physicians defining macromastia as excessive tissue of over 1.5 kilograms (3.3 lb). Some resources distinguish between macromastia (Greek, macro: large, mastos: breast), where excessive tissue is less than 2.5 kg, and gigantomastia (Greek, gigantikos: giant), where excessive tissue is more than 2.5 kg. The enlargement can cause muscular discomfort and over-stretching of the skin envelope, which can lead in some cases to ulceration.Hypertrophy of the breast can affect the breasts equally, but usually affects one breast more than the other, thereby causing asymmetry, when one breast is larger than the other. The condition can also individually affect the nipples and areola instead of or in addition to the entire breast. The effect can produce a minor size variation to an extremely large breast asymmetry. Breast hypertrophy is classified in one of five ways: as either pubertal (virginal hypertrophy), gestational (gravid macromastia), in adult women without any obvious cause, associated with penicillamine therapy, and associated with extreme obesity. Many definitions of macromastia and gigantomastia are based on the term of "excessive breast tissue", and are therefore somewhat arbitrary.
A total of 115 cases of breast hypertrophy had been reported in the literature as of 2008.
Virginal breast hypertrophy
When gigantomastia occurs in young women during puberty, the medical condition is known as juvenile macromastia or juvenile gigantomastia and sometimes as virginal breast hypertrophy or virginal mammary hypertrophy. Along with the excessive breast size, other symptoms include red, itchy lesions and pain in the breasts. A diagnosis is made when an adolescents breasts grow rapidly and achieve great weight, usually soon after her first menstrual period. Some doctors suggest that the rapid breast development occurs before the onset of menstruation.Some women with virginal breast hypertrophy experience breast growth at a steady rate for several years, after which the breasts rapidly develop exceeding normal growth. Some adolescent females experience minimal or negligible breast growth until their breasts suddenly grow very rapidly in a short period of time. This may cause considerable physical discomfort. Women with VBH often experience an excessive growth of their nipples as well. In severe cases of VBH, hypertrophy of the clitoris occurs.At the onset of puberty, some females with who have experienced little or no breast development can reportedly reach three or more cup sizes within a few days (see below).As of 1992, 70 cases of virginal breast hypertrophy had been reported.
Gestational breast hypertrophy
This same effect can also occur at the onset of pregnancy or between the 16th to 20th week of gestation. When the swelling in the connective tissue occurs after birth, it can negatively impact long term milk supply. The swelling increases with each subsequent pregnancy.
The extremely rapid growth of the breasts can result in intense heat. The womans breasts can generate extraordinary discomfort, turning feverish, red, itchy, and even causing the skin to peel. The swelling can suppress the milk supply, pinching off the milk ducts, and leading to mastitis.Gestational gigantomastia is estimated to in 1 out of every 28,000 to 100,000 pregnancies.Breast size in women with gestational breast hypertrophy typically reverts to approximately pre-pregnancy size or near it after pregnancy and cessation of breastfeeding. This is not always the case however and in some only partial reduction in breast size may occur, necessitating surgical breast reduction.
Other types of breast hypertrophy
Only 15% of cases of breast hypertrophy are unrelated to puberty or pregnancy. Other types and causes of breast hypertrophy include idiopathic, drug-induced (e.g., penicillamine, cyclosporine, bucillamine), autoimmunity-associated, tumors, and syndromes. Two case reports of prepubertal breast hypertrophy, both in infants, have been reported.
Causes
The underlying cause of the rapidly growing breast connective tissue, resulting in gigantic proportions, has not been well elucidated. However, proposed factors have included increased levels/expression of or heightened sensitivity to certain hormones (e.g., estrogen, progesterone, and prolactin) and/or growth factors (e.g., hepatocyte growth factor, insulin-like growth factor 1, and epidermal growth factor) in the breasts. Macromastic breasts are reported to be composed mainly of adipose and fibrous tissue, while glandular tissue remains essentially stable.Macromastia occurs in approximately half of women with aromatase excess syndrome (a condition of hyperestrogenism). Hyperprolactinemia has been reported as a cause of some cases of macromastia. Macromastia has also been associated with hypercalcemia (which is thought to be due to excessive production of parathyroid hormone-related protein) and, rarely, systemic lupus erythematosus and pseudoangiomatous stromal hyperplasia. It is also notable that approximately two-thirds of women with macromastia are obese. Aside from aromatase (as in aromatase excess syndrome), at least two other genetic mutations (one in PTEN) have been implicated in causing macromastia.A handful of drugs have been associated with gigantomastia, including penicillamine, bucillamine, neothetazone, ciclosporin, indinavir, and prednisolone.
Treatment
Medical treatment has not proven consistently effective. Medical regimens have included tamoxifen, progesterone, bromocriptine, the gonadotropin-releasing hormone agonist leuprorelin, and testosterone. Gestational macromastia has been treated with breast reduction drugs alone without surgery. Surgical therapy includes reduction mammaplasty and mastectomy. However, breast reduction is not clinically indicated unless at least 1.8 kg (4 lb) of tissue per breast needs to be removed. In the majority of cases of macromastia, surgery is medically unnecessary, depending on body height. Topical treatment includes regimens of ice to cool the breasts.Treatment of hyperprolactinemia-associated macromastia with D2 receptor agonists such as bromocriptine and cabergoline has been found to be effective in some, but not all cases. Danazol, an antiestrogen and weak androgen, has also been found to be effective in the treatment of macromastia.When hypertrophy occurs in adolescence, noninvasive treatments, including pharmaceutical treatment, hormone therapy, and steroid use are not usually recommended due to known and unknown side effects. Once breast growth rate has stabilized, breast reduction may be an appropriate choice. In some instances after aggressive or surgical treatment, the breast may continue to grow or re-grow, a complete mastectomy may be recommended as a last resort.
Pregnancy is recognized as the second most common reason for hypertrophy. When secondary to pregnancy, it may resolve itself without treatment after the pregnancy ends.
Society and culture
Difficulties
Extremely large breasts are a source of considerable attention. Some women try to hide or mask their breasts with special clothing, including minimizing bras. Women with this condition may be subject to psychological problems due to unwanted attention or harassment. Depression is common in those affected.
In the case of a 12-year-old Japanese girl reported in 1993, her "massively enlarged" breasts caused her "intense psychological problems, incapacitating her in school activities and social relations". Actress Soleil Moon Frye, who starred as a child in the sitcom Punky Brewster, reported in an interview with People magazine that boys taunted her, calling her "Hey, Punky Boobster!". It affected her professional and social life negatively. "People started to think of me as a bimbo", she said in the interview. "I couldnt sit up straight without people looking at me like I was a prostitute", Frye said.Finding large bra-sizes and styles that fit is challenging. Also, larger bras are more costly, challenging to find, and unflattering to the wearer. Ill-fitting bras with narrow straps can cause chronic irritation, redness, and indentations in the shoulders. Skin rashes under the breasts are common, particularly during warm weather. Heavy breasts may cause headaches, neck pain, upper and lower back pain, and numbness or tingling in the fingers. There is a possible connection between macromastia and carpal-tunnel-syndrome.
Medical insurance coverage
Insurance companies in the United States typically require the physician to provide evidence that a womans large breasts cause headaches or back and neck pain before they will pay for reduction mammoplasty. Insurance companies also mandate a woman who is overweight, which is often the case with gigantomastia, to first lose a certain amount of weight. They also commonly require the patient to try alternative treatments like physical therapy for a year or more.
Reported instances
Gigantomastia
One early and extreme case study of gigantomastia dates to 1670. The patient died four months after the onset of enlargement. One breast removed after the womans death weighed 29 kg (64 lb).
On April 17, 1848, a 42-year-old woman named Lu-shi was treated for hypertrophy in a Chinese hospital. She was treated by a missionary physician. On December 24, 1849, the left breast, measuring 67 cm (26.5 in) in circumference, and weighing 2.7 kg (6 lb), was removed in a procedure lasting three and a half minutes. The right breast was removed one month later. It measured 61 cm (24 in) in circumference and weighed 2.5 kg (5.5 lb).In 2005, a woman reported that her breasts grew at puberty from nothing to a C cup in one month. When she became pregnant for the first time, her breasts increased two cup sizes in a few days. Immediately after her first birth, her breasts grew three cup sizes. After her second child was born, her breasts increased six cup sizes. After her third childbirth, they grew 10 cup sizes, and after her fourth child was born, they grew nine cup sizes. In this instance, the swelling abated about 10 days after childbirth, but her bra cup size remained E to a G for the next year. About one year postpartum, her breasts rapidly atrophied to AA cup size.One of the most severe cases of macromastia was reported from Ilorin in Nigeria. In 2007, Dr Ganiyu Adebisi Rahman and his colleagues reported the case of a 26-year-old woman who presented with massive swelling of her breasts and bilateral axillary swellings of 6 years duration. Dr Rahman led a team of surgeons in Ilorin to perform a total bilateral excision of the hypertrophied axillary breasts, and bilateral breast amputation with composite nipple-areola complex graft of the normally located breasts. The total weight of the breast tissues removed was 44.8 kilograms.Another extreme case was observed in 2008 in Maria Vittoria Hospital in Turin, Italy, where the amount removed from both breasts was 17.2 kg (38 lb). The growth occurred during puberty making it a case of juvenile gigantomastia, but the patient did not seek treatment until the age of 29. Another extreme case was observed on August 28, 2003, when a 24-year-old woman was admitted to the Clinical Center Skopje in Macedonia with gigantomastia of pregnancy and the amount later removed from both breasts was 15 kg (33 lb) in total. A second case in Macedonia was reported when the breasts of a 30-year-old woman from a remote mountain village in eastern Macedonia suddenly grew to more than 30 kilograms (66 lb) total.As the disorder becomes more widely known, media reports have increased. French Canadian Isabelle Lanthier appeared on Montel Williams talk show where she told how her chest grew from 86 cm (34 in) to 133 cm (52.5 in) in five months during her pregnancy. At their largest, one breast weighed 6.8 kg (15 lb) and the other 5.4 kg (12 lb). Her husband custom-made a special bra to support her breasts.In 2007, a Chilean TV station covered the story of 32-year-old Yasna Galleguillos from Antofagasta, who experienced ongoing back pain, making everyday tasks very difficult to perform. She underwent breast reduction surgery to relieve her pain. Surgeons removed 4.25 kilograms (9.4 lb) from one breast and 3.33 kilograms (7.3 lb) from the other breast.On October 29, 2009, the Philippine television network GMA News and Public Affairs, producers of Wish Ko Lang ("Just My Wish") hosted by Vicky Morales, profiled the story of Pilma Cabrijas, a 30-year-old woman affected by gigantomastia. The woman was told by a folk healer that her condition may have been caused by a curse. The measured bust circumference without appropriate bra support was 160 cm (63 in). The weight of her breasts was not reported in detail, but seemed to weigh "as much as two children." She had breast reduction surgery performed, but her breasts regrew. The producers of Wish Ko Lang paid for additional surgery.
Virginal breast hypertrophy
In 1993, the Japanese journal Surgery Today reported on the case of a 12-year-old girl. Only 152 centimetres (60 in) tall and weighing 43 kilograms (95 lb), her breasts began to develop at age 11 before the onset of menstruation. Over the next eight months, both breasts grew abnormally large, and physicians treating her found that her physiological development was normal except for her breasts. The weight produced by their symmetrical and massive enlargement resulted in marked curvature of the spine. Lab tests of her blood for hormones and biochemical substances showed normal values, though tests revealed that it might have been caused by hypersensitivity to estrogen. She underwent a bilateral reduction mammoplasty. Surgeons removed 2 kilograms (4.4 lb) of tissue from her right breast and 1.9 kilograms (4.2 lb) from her left breast. She was administered tamoxifen afterward to suppress breast regrowth.A more severe case of virginal breast hypertrophy of an 11-year-old girl was reported in 2008. The breasts had begun to grow rapidly at puberty and had reached the point of causing physical impairment and respiratory compromise after one year. The skin was intact without any ulcerations. Blood chemistry and endocrine investigation was normal. A bilateral reduction mammaplasty with free nipple grafts was performed. Six kg of the right breast and 6.5 kg of the left breast were removed, resulting in a removal of 12.5 kg of tissue in all (24% of the total body weight).
See also
Mammoplasia
Norma Stitz
References
Further reading
Touraine, P. (2005). "Breast Inflammatory Gigantomastia in a Context of Immune-Mediated Diseases". Journal of Clinical Endocrinology & Metabolism. 90 (9): 5287–5294. doi:10.1210/jc.2005-0642. PMID 15972574.
Oladele, AO; Olabanji, JK; Alabi, GH (2007). "Reduction mammoplasty: The experience in Ile-Ife, Nigeria". Nigerian Journal of Medicine. 16 (3): 261–267. PMID 17937167.
Netscher, David T.; Mosharrafa, ALI M.; Laucirica, Rodolfo (1996). "Massive Asymmetric Virginal Breast Hypertrophy". Southern Medical Journal. 89 (4): 434–7. doi:10.1097/00007611-199604000-00019. PMID 8614890.
U.S.A. Library of Congress - Healthy Breasts: A Primer
John Blair Deaver (1917). The Breast: Its Anomalies, Its Diseases, and Their Treatment. P. Blakistons Son & Co. p. 102.
Joseph, Jacques (1987). Rhinoplasty and facial plastic surgery with a supplement on mammaplasty and other operations in the field of plastic surgery of the body: an atlas and textbook. Phoenix: Columella Press. p. 755. ISBN 0-9605972-1-2.
Plummer, Samuel C.; Bump, Warner S. (1927). "Massive Hypertrophy of the Breasts". Annals of Surgery. 85 (1): 61–6. doi:10.1097/00000658-192701000-00008. PMC 1399262. PMID 17865606.
Warren, John Collins (1900). The International text-book of surgery. Vol. II. Saunders. p. 234.
Erichsen, John Eric (1885). The Science and art of surgery. Vol. II. H. C. Leas Son & Company. pp. 693–694.
Ochsner, Albert John (1921). Surgical Diagnosis and Treatment: By American Authors. Lea & Febiger. p. 147.
External links
Media related to Hypertrophy of breast at Wikimedia Commons |
Currarino syndrome | Currarino syndrome is an inherited congenital disorder where either the sacrum (the fused vertebrae forming the back of the pelvis) is not formed properly, or there is a mass in the presacral space in front of the sacrum, and there are malformations of the anus or rectum. It occurs in approximately 1 in 100,000 people.Anterior sacral meningocele is the most common presacral mass in patients with Currarino syndrome, occurring in 60% of cases. Its presence may significantly affect the surgical management of these patients. Other potential presacral masses include presacral teratoma and enteric cyst. Presacral teratoma usually is considered to be a variant of sacrococcygeal teratoma. However, the presacral teratoma that is characteristic of the Currarino syndrome may be a distinct kind.
Genetics
The disorder is an autosomal dominant genetic trait caused by a mutation in the HLXB9 homeobox gene. In 2000 the first large series of Currarino cases was genetically screened for HLXB9 mutations, and it was shown that the gene is specifically causative for the syndrome, but not for other forms of sacral agenesis. The study was published in the American Journal of Human Genetics.
Diagnosis
Diagnosis of Currarino syndrome is usually clinical, detecting all three elements of the triad. However, genetic testing is often used as the confirmation of diagnosis and genetic analysis of patients family members.
Treatment
Surgery of an anterior myelomeningocele is only indicated in the rare case in which the space-occupying aspect is expected to cause constipation or problems during pregnancy or delivery. Fistulas between the spinal canal and colon have to be operated on directly.Early diagnosis and multidisciplinary assessment is recommended to plan adequate treatment.By accurate evaluation, the correct surgical management, including neurosurgery, can be performed in a single-stage approach.The management of Currarino syndrome is similar to the usual management of anorectal malformation (ARM) regarding the surgical approach and probably the prognosis, which mainly depends on degree of associated sacral dysplasia.Neurosurgeons are involved in the surgical treatment of anterior meningoceles, which are often associated with this condition. The accepted surgical treatment is an anterior or posterior or a staged anterior-posterior resection of the presacral mass and obliteration of the anterior meningocele.
Posterior approach
A posterior procedure via lumbar and sacral partial laminectomy-laminoplasty and transdural ligation of the neck of the meningocele is used for anterior sacral meningoceles; alternatively, tumor excision is used for other types of presacral lesions.Endoscopic or endoscope-assisted surgery via a posterior sacral route can be feasible for treatment of some patients with anterior sacral meningocele. Anterior meningocele pouch associated with Currarino syndrome will regresses over time following transdural ligation of its neck.
See also
Imperforate anus
References
currarino_syndrome_treatment [Operative Neurosurgery]
== External links == |
Gastrojejunocolic fistula | A gastrojejunocolic fistula is a disorder of the human gastrointestinal tract. It may form between the transverse colon and the upper jejunum after a Billroth II surgical procedure. (The Billroth procedure attaches the jejunum to the remainder of the stomach.) Fecal matter thereby passes improperly from the colon to the stomach, and causes halitosis.Patients may present with diarrhea, weight loss and halitosis as a result of fecal matter passing through the fistula from the colon into the stomach.
== References == |
Fixed drug reaction | Fixed drug reactions, are common and so named because they recur at the same site with each exposure to a particular medication. Medications inducing fixed drug eruptions are usually those taken intermittently.
Signs and symptoms
A painful and itchy reddish/purple patch of skin that occurs in the same location with repeated exposures to the culprit drug is the classic presentation of a fixed drug reaction. The lips, genitals, and hands are often involved.
Cause
Medications that are commonly implicated as a cause of fixed drug eruptions include the following:
Cetirizine
Ciprofloxacin
Clarithromycin
Cotrimoxazole
Doxycycline
Fluconazole
NSAIDs (e.g., ibuprofen, etoricoxib, naproxen)
Phenytoin
Pseudoephedrine
Trimethoprim
See also
Drug eruption
List of cutaneous conditions
List of human leukocyte antigen alleles associated with cutaneous conditions
Stevens–Johnson syndrome
References
== External links == |
Lymphangioma circumscriptum | Superficial lymphatic malformation is a congenital malformation of the superficial lymphatics, presenting as groups of deep-seated, vesicle-like papules resembling frog spawn, at birth or shortly thereafter. Lymphangioma circumscriptum is the most common congenital lymphatic malformation. It is a benign condition and treatment is not required if the person who has it does not have symptoms from it.
Signs and symptoms
Lymphangioma circumscriptum is characterized by a rash on the skin featuring clear vesicles. The rash may be painful and is sometimes itchy. The vesicles often leak lymph and may bleed. The rash may appear similar to warts if the vesicles frequently break open.
Diagnosis
A biopsy of the affected skin and histological examination under the microscope is necessary to diagnose lymphangioma circumscriptum.
Differential diagnosis
Several other conditions may mimic lymphangioma circumscriptum. These conditions include infections such as an outbreak of herpes simplex, herpes simplex vegetans, molluscum contagiosum, verruca vulgaris, and condyloma acuminatum. Similarly, benign and cancerous non-infectious conditions may also present in a similar manner and include conditions such as angiokeratoma, dermatitis herpetiformis, hemangioma, epidermal nevus, lymphangiectasia, melanoma, angiosarcoma, and metastatic carcinomas.
Treatment
The condition is benign and does not require treatment if the affected person does not have symptoms. Lymphangioma circumscriptum is often treated when it causes troubling symptoms to the affected person (itching, pain) or due to concerns about its cosmetic appearance. Surgical removal (excision) of the affected layers of skin is the most common and effective treatment. Treatment with ablative carbon dioxide lasers is a less invasive method that can be used to improve the appearance of lymphangioma circumscriptum. These laser treatments require local anesthesia and may cause significant wounds.
See also
Lymphangioma
Skin lesion
List of cutaneous conditions
References
== External links == |
Oxycephaly | Oxycephaly is a type of cephalic disorder where the top of the skull is pointed or conical due to premature closure of the coronal suture plus any other suture, like the lambdoid, or it may be used to describe the premature fusion of all sutures. It should be differentiated from Crouzon syndrome. Oxycephaly is the most severe of the craniosynostoses.
Presentation
Common associations
It may be associated with:
8th cranial nerve lesion
Optic nerve compression
Intellectual disability
Syndactyly
Diagnosis
Treatment
See also
Acrocephalosyndactylia
References
Further reading
NINDS Overview
Ebenezer, Roy (1960). "Craniostenosis or oxycephaly". Indian Journal of Ophthalmology. 8 (3): 77–80. ISSN 0301-4738. PMID 13819157.
== External links == |
Isodicentric 15 | Isodicentric 15, also called marker chromosome 15 syndrome, idic(15), partial tetrasomy 15q, or inverted duplication 15 (inv dup 15), is a chromosome abnormality in which a child is born with extra genetic material from chromosome 15. People with idic(15) are typically born with 47 chromosomes in their body cells, instead of the normal 46. The extra chromosome, which is classified as a small supernumerary marker chromosome, is made up of a piece of chromosome 15 that has been duplicated end-to-end like a mirror image. It is the presence of this extra genetic material that is thought to account for the symptoms seen in some people with idic(15). Individuals with idic(15) have a total of four copies of this chromosome 15 region instead of the usual two copies (1 copy each on the maternal and paternal chromosomes).
The syndrome is also often referred to by the term Chromosome 15q11.2-q13.1 Duplication Syndrome, shortened to Dup15q Syndrome, or marker chromosome 15 syndrome (mainly in the United States). Dup15q Syndrome includes both idic(15) and interstitial 15q11.2-q13.1, another type of duplication that causes similar clinical traits.
The extra chromosome is occasionally found in the mosaic state, i.e. some of the cells carry the marker chromosome. However, mostly because of the markers instability and tendency to be lost during cell division (mitosis), some cells are completely normal with 46 chromosomes. Occasionally, cells may have more than one idic(15), resulting in 48 or 49 chromosomes in all or some of their cells. A similar clinical picture albeit to a milder degree could be expected in individuals that have the extra chromosome 15 material as an interstitial duplication (when the extra piece of chromosome 15 is included within the long arm of one of the two copies of chromosome 15, rather than as a small extra marker chromosome) - often abbreviated to int dup(15); the individual thus having 46 chromosomes.
Signs and symptoms
The severity of symptoms of idic(15) vary greatly between individuals. Individuals with idic(15) usually have delays in language development and motor skills such as walking or sitting up. Other traits may include low muscle tone (hypotonia), seizures (>50%), short stature, and intellectual disability. Distinctive facial features associated with idic(15) - where present at all - are usually very subtle but may include epicanthal folds (skin folds at the inner corners of one or both eyes), downward slanting palpebral fissures, broad forehead, a flattened nasal bridge, button nose, and a high arched palate (roof of the mouth). Some individuals show other signs that can often be associated with chromosomal conditions, such as pectus excavatum, or a unilateral or bilateral single transverse palmar crease. Many individuals with idic(15) display features of autism, such as problems with communication and social interactions, obsessional interests (often with interactive mechanisms like wheels, doors or switches), unpredictable sleep cycles (and a reduced need for sleep), and repetitive and stereotyped behaviors (e.g., lining up toys, playing with a toy in the same manner over and over again, hand flapping, rocking back and forth). Sensory processing is often affected, especially the vestibular system. A high pain threshold is often observed. If speech develops, it is often echolalic but some individuals do grasp some language. With a severely affected person there may be an inability to walk or talk.
Genetics
Generally, idic(15) is not inherited; it is said to appear de novo, in one member of the family, by chance. In most cases, the abnormal chromosome is generated in the mothers germ cells: the oocytes. This finding is due to ascertainment bias; cases with maternally derived idic(15) usually have clinical findings and attract attention, but those with paternally derived idic(15) usually do not. Thus, diagnosed cases are usually patients where the duplicated material is derived from the mothers egg cell rather than the fathers sperm cell.People with idic(15) have extra genetic material that has developed from chromosome 15. The material usually exists as a little extra chromosome 15; sometimes called a marker chromosome or an extra structurally abnormal chromosome (ESAC). The marker usually exists as an isodicentric chromosome; i.e. 2 copies of a specific part of the long arm of chromosome 15q11.2-q13.1 that is mirrored and doubled, with 2 centromeres and 2 DNA satellites. The smallest markers appear to be harmless and they may go undetected. However, if they are large enough to contain a number of important genes, they may result in "idic(15) syndrome" which is characterized by learning disabilities, autism and other neurological symptoms. One of the regions responsible for the symptoms of idic(15) syndrome is the critical PWS/AS-region named after the Prader-Willi and/or Angelman syndromes.
Isodicentric chromosome 15 and autism
For more than 12 years, scientists have noticed that some individuals with autism also have idic(15). In fact, idic(15) is the most frequently identified chromosome problem in individuals with autism. (A chromosome anomaly involves extra or missing chromosomal material, not changes within the genes such as Fragile X syndrome). It is suggested that the co-occurrence of autism and idic(15) is not by chance. There may be a gene or genes in the 15q11-q13 region that is/are related to the development of autism in some individuals.Genetic research studies of individuals without chromosome anomalies also support this idea that an autism-related gene may be present in 15q11.2-q13.1 Specifically, research studies found that certain DNA markers from the (15q1.2-q13.1) region were found more often in individuals with autism than in individuals without autism. Although these DNA markers are too small to be genes, they suggest that researchers may be getting close to finding an autism gene in this region.A recent study reported the introduction of two extra copies of just a single gene present in the 15q11.2-q13.1 region, Ube3a, into mice to model the gene copy number expressed in the brain in idic(15). These mice displayed autism-related behavioral deficits including impaired social interaction, reduced ultrasonic vocal communication, and increased repetitive behavior (self-grooming).
Diagnosis
The extra chromosome in people with idic(15) can be easily detected through chromosome analysis (karyotyping). Additional tests are usually required. FISH (Fluorescent in situ hybridization) is used to confirm the diagnosis by distinguishing idic(15) from other supernumerary marker chromosomes. Array CGH can be used to determine the gene content and magnitude of copy number variation so that the clinical picture can be foreseen.
Interstitial duplications of chromosome 15 can be more difficult to detect on a routine chromosome analysis but are clearly identifiable using a 15q FISH study. Families should always discuss the results of chromosome and FISH studies with a genetic counselor or other genetics professionals to ensure accurate interpretation.
Screening
In general, idic(15) occurs de novo but the parents must be karyotyped to make sure it is not inherited, mostly because this will affect the course of genetic counseling given to the family. If the abnormality is found prenatally and one of the parents harbour the marker, the child has a chance of not carrying the mutation. Further tests should however be done to prove the marker has not been rearranged while being inherited. This information is also necessary for counseling of future pregnancies. Each family is unique and should therefore be handled individually.
Management
At the present time, there is no specific treatment that can undo any chromosomal abnormality, nor the genetic pattern seen in people with idic(15). The extra chromosomal material in those affected was present at or shortly after conception, and its effects on brain development began taking place long before the child was born. Therapies are available to help address many of the symptoms associated with idic(15). Physical, occupational, and speech therapies along with special education techniques can stimulate children with idic(15) to develop to their full potential.In terms of medical management of the symptoms associated with Chromosome 15q11.2-q13.1 Duplication Syndrome, families should be aware that individuals with chromosome 15 duplications may tolerate medications differently and may be more sensitive to side effects for some classes of medications, such as the serotonin reuptake inhibitor type medications (SSRI).
Thus, these should be used with caution and any new medication should be instituted in a controlled setting, with slow titration of levels and with a clear endpoint as to what the expected outcome for treatment is.There is an increased risk of sudden, unexpected death among children and adults with this syndrome. The full cause is not yet understood but it is generally attributed to SUDEP (Sudden Unexplained Death in Epilepsy).
Epidemiology
About half of all marker chromosomes are idic(15) but idic(15) in itself is one of the rare chromosome abnormalities. Incidence at birth appears to be 1 in 30,000 with a sex ratio of almost 1:1; however, since dysmorphic features are absent or subtle and major malformations are rare, chromosome analysis may not be thought to be indicated, and some individuals, particularly in the older age groups, probably remain undiagnosed. There are organizations for families with idic(15) children that offer extensive information and support.
Research
Patients with idic(15) and int dup(15) often feature a distinctive electroencephalography (EEG) signature or biomarker in the form of high amplitude spontaneous beta frequency (12–30 Hz) oscillations. This EEG signature was first noted as a qualitative pattern in clinical EEG readings and was later described quantitatively by researchers at the University of California, Los Angeles and their collaborators within the network of national Dup15q clinics. This group of researchers found that beta activity in children with Dup15q syndrome is significantly greater than that observed in (1) healthy, typically developing children of the same age and (2) children of the same age and IQ with autism not caused by a known genetic disorder (i.e., nonsyndromic ASD). The EEG signature appears almost identical to beta oscillations induced by benzodiazepine drugs that modulate GABAA receptors, suggesting that the signature is driven by overexpression of duplicated GABAA receptor genes GABRA5, GABRB3, and GABRG3 found on 15q11.2-q13.1. Treatment monitoring and identification of molecular disease mechanisms may be facilitated by this biomarker.
See also
marker chromosome 15 syndrome
References
== External links == |
Acquired generalized lipodystrophy | Acquired generalized lipodystrophy (also known as "Lawrence syndrome," and "Lawrence–Seip syndrome", abbreviation: AGL) is a rare skin condition that appears during childhood or adolescence, characterized by fat loss affecting large areas of the body, particularly the face, arms, and legs.: 496 There are 4 types of lipodystrophy based on its onset and areas affected: acquired or inherited (congenital or familial), and generalized or partial. Both acquired or inherited lipodystrophy present as loss of adipose tissues. The near-total loss of subcutaneous adipose tissue is termed generalized lipodystrophy while the selective loss of adipose tissues is denoted as partial lipodystrophy. Thus, as the name suggests, AGL is a near-total deficiency of adipose tissues in the body that is developed later in life. It is an extremely rare disease that only about 100 cases are reported worldwide. There are three main etiologies of AGL suspected: autoimmune, panniculitis-associated, or idiopathic. After its onset, the disease progresses over a few days, weeks, months, or even in years. Clinical presentations of AGL are similar to other lipodystrophies, including metabolic complications and hypoleptinemia. Treatments are also similar and mainly supportive for symptomatic alleviation. Although HIV- or drug-induced lipodystrophy are a type of acquired lipodystrophy, its origin is very specific and distinct hence is usually not discussed with AGL (see HIV-Associated Lipodystrophy).
Symptoms
The clinical presentation is similar to people with congenital lipodystrophy: the only difference is that AGL patients are born with normal fat distribution and symptoms develop in childhood and adolescence years and rarely begins after 30 years of age. Females are more often affected than males, with ratio being 3:1.The hallmark characteristics are widespread loss of subcutaneous fat, ectopic fat deposition, leptin deficiency, and severe metabolic abnormalities such as insulin resistance. Subcutaneous fat loss in AGL patients are visible in all parts of the body. AGL mostly affects face and the extremities and may look sunken or swollen in the eyes. However, the degree and location of severity may vary by person. Especially, intra-abdominal fat loss is variable. As subcutaneous fat is lost, affected areas show prominent structures of veins and muscle. Those with panniculitis-associated AGL may present erythematous nodules.Metabolic complications include insulin resistance, high metabolic rate, and uncontrolled lipid levels such as hypertriglyceridemia, low HDL, and high LDL. Patients may develop diabetes mellitus secondary to insulin resistance.
Recent case reports revealed that lymphoma is present in some patients but its prevalence is not known at this time.
Cause
There is no known cause for this disease; however, three origins of AGL are generally suspected: panniculitis-associated, autoimmune-associated, and idiopathic AGLs. Triggers may include infections that aggravate the panniculitis, or any disease state that can induce autoimmunity. Overlap between panniculitis and autoimmune types also exists. Another theory suggest that AGL is an autoimmune disease itself, as panniculitis can be described as an autoimmune disease, however its triggering factors remains to be unknown. Underlying genetic factor may be associated; however neither confirmed nor rejected.
Panniculitis-associated AGL
About 25% of previously reported AGL is associated with panniculitis. Panniculitis is an inflammatory nodules of the subcutaneous fat, and in this type of AGL, adipose destruction originates locally at the infection or inflammation site and develops into generalized lipodystrophy.
Autoimmune-associated AGL
AGL with autoimmune origin is responsible for about 25% of all AGL reports. Those with autoimmune origin stems from other autoimmune diseases, most commonly with juvenile dermatomyositis and autoimmune hepatitis, but also occurs with rheumatoid arthritis, systemic lupus erythematosus, and Sjogren syndrome.
Idiopathic AGL
Although idiopathic AGL accounts for about 50% of all AGL, it can vary in its origin and it is unclear how it develops.No known preventive measurement has been reported.
Mechanism
The exact pathophysiologic mechanism is mostly unknown; however, each of three main origins, autoimmune, panniculitis, or idiopathic, may have different mechanisms of pathogenesis.Normally, adipose tissues contain adipocytes to store fat for energy during fasting period and release leptin to regulate homeostasis of energy and sensitize insulin. In AGL patients, adipose tissues are insufficient and leads to fat deposition in non-adipose tissues, such as muscle or liver, resulting in hypertriglyceridemia. Continuous elevation in triglyceride levels further contributes to metabolic problems including insulin resistance. As the level of leptin in the body is proportional to the amount of adipose tissue present, AGL patients also have a deficiency of leptin which contributes to excessive eating and worsens the metabolic syndrome.In a few patients with AGL, the presence of antibodies against adipocyte has been identified.
Diagnosis
Diagnosis is made comprehensively, together with visual observation, body fat assessment, a review of lab panels consisting of A1c, glucose, lipid, and patient history.
Caliper measurements of skinfold thickness is recommended to quantify fat loss as a supportive information. In this measurement, skinfold thickness of less than 10mm for men and 22mm for women at the anterior thigh is suggestive cutoff for the diagnosis of lipodystrophy. Less commonly, biphotonic absorptiometry and magnetic resonance imaging (MRI) can be done for the measurement of body fat.Other forms of insulin resistance may be assessed for differential diagnosis. Resistance to conventional therapy for hyperglycemia and hypertriglyceridemia serves as an indication for lipodystrophy. Specifically, the diagnosis is strongly considered for those requiring ≥200 units/day of insulin and persistent elevation of ≥250 mg/dl of triglyceride levels.The use of leptin levels should be carefully approached. While low leptin levels are helpful for making the diagnosis, they are not specific for the lipodystrophy. High leptin levels can help excluding the possible lipodystrophy, but there is no well-established standardized leptin ranges.
Treatment
Initial and general approach for AGL patients are to treat the metabolic complications such as leptin-replacement therapy and/or to control the abnormal levels of lipids or glucose levels. Anti-diabetic medications such as insulin, metformin, or thiazolidinediones are used for insulin-resistance or high glucose levels, or statins or fibrates are used for hyperlipidemia. If symptoms persist, metreleptin can be prescribed.
Metreleptin (MYALEPT) is a recombinant human leptin analog and was approved by FDA in 2014 for generalized lipodystrophy as an adjunct therapy to diet to treat the complication of leptin deficiency. It is the only drug option approved for generalized lipodystrophy-related symptoms and is not intended to use for patients with HIV-related lipodystrophy or complications of partial lipodystrophy. Although it is a recombinant human leptin analog, it is not completely the same as natural leptin as it is produced in e. coli and has added methionine residues at is amino terminus. It works by binding to the human leptin receptor, ObR, and activates the receptor. The receptor belongs to the Class I cytokine family and signals the JAK/STAT pathway. It is available as 11.3 mg powder in a vial for subcutaneous injection upon reconstitution and needs to be protected from the light. For treatment, patients and their doctors need to be enrolled and certified in the Myalept Risk Evaluation and Mitigation Strategy (REMS) Program because people on this treatment has a risk of developing anti-metreleptin antibodies that decrease the effectiveness of metreleptin, and increased risk of lymphoma. Clinical study with GL patients who took metreleptin had increased insulin sensitivity, as indicated by decreased HbA1c and fasting glucose level, and reduced caloric intake as well as fasting triglyceride levels.Plasmapheresis was previously an option for lowering extremely high triglyceride levels for preventing pancreatitis and painful xanthoma, but its use has been decreased after the approval of metreleptin.Cosmetic treatments, such as facial reconstruction or implants, can be done to replace adipose tissues.
Lifestyle modifications are also recommended, including changes into less fat diet and exercise.
The prognosis of the disease is unknown as of December, 2017.
Recent research
Many researches for the treatment of lipodystrophy focus on the safety and efficacy of leptin replacement therapy and the outlook is positive in many studies.
According to a prospective, open-label clinical study at the NIH, metreleptin decreased the fasting glucose level from 180 mg/dL to 121 mg/dL, HbA1c from 8.4% to 6.4%, total cholesterol from 214 mg/dL to 146 mg/dL, and triglycerides from 467 (200-847)mg/dL to 180 (106-312)mg/dL after 12 months of use (p<0.001). Patients also had decreased use of anti-diabetic medications, lipid-lowering medications, and insulin (p<0.001). In other clinical reports studying 3 patients diagnosed with AGL accompanied by hypoleptinemia, uncontrolled diabetes, and hypertriglyceridemia who were treated with metreleptin for 12–168 weeks, patients had great reduction in HbA1c, from 10.9% to 5.8%, and had normalized serum triglycerides with a mean decline of 90%. Patients reported improved quality of life and reduced need for other medications without significant adverse effects.One research published in 2017 reported a middle-aged patient developed AGL after treatment and recovery for autoimmune thrombocytopenia that included immunoglobulin therapy and prednisone, which suggests the autoimmune trigger may contribute to the development of AGL.
Other researches focus on genetics of lipodystrophy; however its relevance to acquired generalized lipodystrophy has not been confirmed so far. One clinical report published in July 2017 stated two brothers with juvenile-onset generalized lipodystrophy was due to lamin C-specific mutation but it is unknown at this point if this will fall into acquired or familial lipodystrophy.There have been many published case reports. Meta-analysis of published case reports published within the decade will be very helpful in establishing patient demographic, etiologies, and prognosis of the diagnosis.
See also
Lipodystrophy
List of cutaneous conditions
HIV-associated lipodystrophy
References
== External links == |
Hereditary pancreatitis | Hereditary pancreatitis (HP) is an inflammation of the pancreas due to genetic causes. It was first described in 1952 by Comfort and Steinberg but it was not until 1996 that Whitcomb et al isolated the first responsible mutation in the trypsinogen gene (PRSS1) on the long arm of chromosome seven (7q35).
The term "hereditary pancreatitis" is used when a genetic biomarker is identified, and "familial pancreatitis" otherwise.
Presentation
HP is characterised by attacks of epigastric pain, which are often associated with nausea and vomiting. Symptoms may start shortly after birth but onset varies periodically, with some patients not exhibiting symptoms until adulthood. There is usually progression to chronic pancreatitis with endocrine and exocrine failure and a mortally increased risk of pancreatic cancer. Lifetime risk of cancer has been variously calculated as 35–54% to the age of 75 years and screening for early pancreatic cancer is being offered to HP sufferers on a scientific basis. Some patients may choose to have their pancreas surgically removed to prevent pancreatic cancer from developing in the future.The epidemiology of HP follows a similar pattern to alcohol-associated chronic pancreatitis, but there are important differences. For example, HP typically has an earlier age of pancreatitis onset; although malabsorption and diabetes mellitus occur at a later stage in the disease progression.
Genetics
The vast majority of the cases of HP are caused by substitutions, at base 365 (c.365G>A) and base 86 of the cDNA (c.86A>T) on the PRSS1 gene. The nucleotide substitutions were discovered in the late 1990s by classical linkage analysis and are now known as p.R122H and p.N29I respectively, according to the amino acid substitution and position in the protein sequence.
These mutations are rarely identified in general screens of patients with idiopathic disease and the phenotype of p.R122H and p.N29I is now well characterised with the p.A16V mutation recently characterised for the first time. There are many other rare mutations or polymorphisms of PRSS1 which remain less well understood and not all HP families have had the responsible genetic mutation identified.
The mechanism by which these genetic mutations cause pancreatitis is not yet known; but is likely to be the result of increased autoactivation or reduced deactivation of trypsinogen. However, a novel mechanism has recently been identified in a p.R116C kindred.
Diagnosis
Families are defined as having HP, if the phenotype is consistent with highly penetrant autosomal dominant inheritance. In simple terms, this would require two or more first degree relatives (or three or more second degree relatives) to have unexplained recurrent-acute or chronic pancreatitis in two or more generations. It is an autosomal dominant disease with penetrance that is generally accepted to be ≈80%.
Management
Treatment of HP resemble that of chronic pancreatitis of other causes. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction.(PMC1774562)
Prognosis
A 2009 study which followed 189 patients found no excess mortality despite the increased risk of pancreatic cancer.
References
== External links == |
Tooth impaction | An impacted tooth is one that fails to erupt into the dental arch within the expected developmental window.
Because impacted teeth do not erupt, they are retained throughout the individuals lifetime unless extracted or exposed surgically. Teeth may become impacted because of adjacent teeth, dense overlying bone, excessive soft tissue or a genetic abnormality. Most often, the cause of impaction is inadequate arch length and space in which to erupt. That is the total length of the alveolar arch is smaller than the tooth arch (the combined mesiodistal width of each tooth). The wisdom teeth (third molars) are frequently impacted because they are the last teeth to erupt in the oral cavity. Mandibular third molars are more commonly impacted than their maxillary counterparts.
Some dentists believe that impacted teeth should be removed except, in certain cases, canine teeth: canines may just remain buried and give no further problems, thus not requiring surgical intervention. However, removal of asymptomatic, pathology-free, impacted teeth isnt a medical consensus: watchful monitoring may be a more prudent and cost-effective strategy and make the future placement of a dental implant through such impacted tooth a feasible approach.
Classification
Classifications enable the oral surgeon to determine the difficulty in removal of the impacted tooth. The primary factor determining the difficulty is accessibility, which is determined by adjacent teeth or other structures that impair access or delivery pathway. The majority of classification schemes are based on analysis on a radiograph. The most frequently considered factors are discussed below.
Angulation of tooth
Most commonly used classification system with respect to treatment planning. Depending on the angulation the tooth might be classified as:
Mesioangular
Horizontal
Vertical
Distoangular
Palatal
Buccal
Lingual
Relationship of tooth to anterior border of ramus
This type of classification is based on the amount of impacted tooth that is covered with the mandibular ramus. It is known as the Pell and Gregory classification, classes 1, 2, and 3.
Relationship of tooth to occlusal plane
The depth of the impacted tooth compared with the adjacent second molar gives the basis for this type of classification. This was also given by Pell and Gregory and is called as Pell and Gregory A, B and C classification.
Relationship to occlusal plane Class A-C
Complications
Erupted teeth that are adjacent to impacted teeth are predisposed to periodontal disease. Since the most difficult tooth surface to be cleaned is the distal surface of the last tooth, in the presence of an impacted tooth there is always gingival inflammation around the second molar that is invariably present. Even this minor amount of inflammation can provide bacteria access to a larger portion of the root surface that results in early formation of periodontitis compromising the tooth.
Even in situations in which no obvious communication exists between the mouth and the impacted third molar there may be enough communication to initiate dental caries (tooth decay).
Pericoronitis
Pericoronitis is an infection of the soft tissue that covers the crown of an impacted tooth and is usually caused by the normal oral microbiota. For most people there exists a balance between the host defenses and the oral micriobiota but if the host defenses are compromised like during minor illness such as influenza or an upper respiratory tract infection, pericoronitis results. Another common cause is entrapment of food beneath the gum flap (also called an operculum). Pericoronitis can present as a mild infection or severe infection. In its mildest form it is just a localized tissue swelling and soreness whereas in severe forms the swelling is slightly larger even sometimes creating trismus (difficulty opening the mouth).
Occasionally, an impacted tooth causes sufficient pressure on the roots of adjacent teeth causing it to resorb.
An impacted tooth occupies space that is usually filled with bone. This weakens that area of bone and renders the jaw more susceptible to fracture.
When impacted teeth are retained completely within the alveolar process, the associated follicular sac is also retained along with it. Though in most persons the dental follicle maintains its original size sometimes it may undergo cystic degeneration and become a dentigerous cyst or a keratocyst.
Symptoms
Most commonly the individual complains of food getting lodged beneath the gums and a soreness that is usually confused with throat infections. In slightly milder forms a swelling is visible and mouth opening becomes difficult in severe cases. Pain is invariably present.
Management
Impacted teeth might be extracted or left alone, depending on the dentist (and the health authoritys guidelines in that country) and the situation. Extraction might be contraindicated and might be simple or surgical, often depending on the location of the teeth.
In some cases, for aesthetic purposes, a surgeon may wish to expose the canine. This may be achieved through open or closed exposure. Studies show no advantage of one method over another. Laser can be used to uncover superficially impacted teeth with no bleeding and quick recovery
References
See also
Impacted wisdom teeth |
Gestational pemphigoid | Gestational pemphigoid (GP) is a rare autoimmune variant of the skin disease bullous pemphigoid, and first appears in pregnancy. It presents with tense blisters, small bumps, hives and intense itching, usually starting around the navel before spreading to limbs in mid-pregnancy or shortly after delivery. The head, face and mouth are not usually affected.It may flare after delivery before resolving around three to six months after the pregnancy. It can be triggered by subsequent pregnancies, menstrual periods and oral contraceptive pill. A molar pregnancy and choriocarcinoma can provoke it. In some people, it persists long-term. It is associated with premature delivery of a small baby, a few who may be born with blisters and urticaria, which generally resolves within six weeks. It does not spread from one person to another, and does not run in families.Diagnosis is by visulaization, biopsy and immunofluorescence. It can resemble pruritic urticarial papules and plaques of pregnancy, erythema multiforme, drug reactions and blistering scabies.Around 1 in 20,000 to 50,000 pregnancies are affected. It was originally called herpes gestationis because of the blistering appearance, although it is not associated with the herpes virus.
Signs and symptoms
Diagnosis of GP becomes clear when skin lesions progress to tense blisters during the second or third trimester. The face and mucous membranes are usually spared. GP typically starts as a blistering rash in the navel area and then spreads over the entire body. It is sometimes accompanied by raised, hot, painful welts called plaques. After one to two weeks, large, tense blisters typically develop on the red plaques, containing clear or blood-stained fluid. GP creates a histamine response that causes extreme relentless itching (pruritus). GP is characterized by flaring and remission during the gestational and sometimes post partum period. Usually after delivery, lesions will heal within months, but may reoccur during menstruation.
Causes
Pathogenically, it is a type II hypersensitivity reaction where circulating complement-fixing IgG antibodies bind to an antigen (a 180-kDa protein, BP-180) in the hemidesmosomes (attach basal cells of epidermis to the basal lamina and hence to dermis) of the dermoepidermal junction, leading to blister formation as loss of hemidesmosomes causes the epidermis to separate from dermis. The immune response is even more highly restricted to the NC16A domain. The primary site of autoimmunity seems not to be the skin, but the placenta, as antibodies bind not only to the basement membrane zone of the epidermis, but also to that of chorionic and amniotic epithelia. Aberrant expression of MHC class II molecules on the chorionic villi suggests an allogenic immune reaction to a placental matrix antigen, thought to be of paternal origin. Recently, both IgA22 and IgE24 antibodies to either BP180 or BP230 have also been detected in pemphigoid gestationis.
Risk
Pregnant women with GP should be monitored for conditions that may affect the fetus, including, but not limited to, low or decreasing volume of amniotic fluid, preterm labor, and intrauterine growth retardation. Onset of GP in the first or second trimester and presence of blisters may lead to adverse pregnancy outcomes including decreased gestational age at delivery, preterm birth, and low birth weight children. Such pregnancies should be considered high risk and appropriate obstetric care should be provided. Systemic corticosteroid treatment, in contrast, does not substantially affect pregnancy outcomes, and its use for GP in pregnant women is justified. GP typically reoccurs in subsequent pregnancies. Passive transfer of the mother’s antibodies to the fetus causes some (about 10%) newborns to develop mild skin lesions, but these typically will resolve within weeks of parturition.
Diagnosis
Differential diagnosis
GP often is confused with pruritic urticarial papules and plaques of pregnancy (PUPPP), especially if it occurs in a first pregnancy. PUPPP typically begins in stretch mark areas of the abdomen and usually ends within two weeks after delivery. PUPPP is not an autoimmune disease.Diagnosing GP is done by biopsy using direct immunofluorescence, appearance, and blood studies.
Treatment
The most accepted way to treat GP is with the use of corticosteroids, i.e. prednisone; and/or topical steroids, i.e. clobetasol and betamethasone. Suppressing the immune system with corticosteroids helps by decreasing the number of antibodies attacking the skin. Treating GP can be difficult and can take several months. Some cases of GP persist for many years. In the post partum period, if necessary, the full range of immunosuppressive treatment may be administered for cases unresponsive to corticosteroid treatments, such as tetracyclines, nicotinamide, cyclophosphamide, ciclosporin, goserelin, azathioprine, dapsone, rituximumab, or plasmaphoresis, or intravenous immunoglobulin may sometimes be considered when the symptoms are severe.There is no cure for GP. Women who have GP are considered in remission if they are no longer blistering. Remission can last indefinitely, or until a subsequent pregnancy. GP usually occurs in subsequent pregnancies; however, it often seems more manageable because it is anticipated.
See also
Bullous pemphigoid
Cicatricial pemphigoid
List of target antigens in pemphigoid
List of immunofluorescence findings for autoimmune bullous conditions
References
== External links == |
Ulnar neuropathy | Ulnar neuropathy is a disorder involving the ulnar nerve. Ulnar neuropathy may be caused by entrapment of the ulnar nerve with resultant numbness and tingling. It may also cause weakness or and paralysis of the muscles supplied by the nerve.
Signs and symptoms
In terms of the signs/symptoms of ulnar neuropathy trauma and pressure to the arm and wrist, especially the elbow, the medial side of the wrist, and other sites close to the course of the ulnar nerve are of interest in this condition. Many people complain of sensory changes in the fourth and fifth digits. Rarely, an individual actually notices that the unusual sensations are mainly in the medial side of the ring finger (fourth digit). Sometimes the third digit is also involved, especially on the ulnar (medial) side. The sensory changes can be a feeling of numbness or a tingling, pain rarely occurs in the hand. Complaints of pain tend to be more common in the arm, up to and including the elbow area, which is probably the most common site of pain in an ulnar neuropathy.
Causes
Among the causes of ulnar neuropathy are the following-
Much more commonly, ulnar neuropathy is caused by overuse of the triceps muscle and repetitive stress combined with poor ergonomics. Overused and hypertonic triceps muscle causes inflammation in the tendon and adhesions with the connective tissue surrounding that tendon and muscle. These in turn impinge on or trap the ulnar nerve. Ulnar neuropathy resulting from repetitive stress is amenable to massage and can usually be fully reversed without cortisone or surgery.
Center for Occupational and Environmental Neurology, Baltimore, MD has this to say:
“Repetitive Strain Injuries (RSI) refers to many different diagnoses of the neck/shoulder, arm, and wrist/hand area usually associated with work-related ergonomic stressors. Other terms used for Repetitive Strain Injuries are overuse syndrome, musculoskeletal disorders, and cumulative trauma disorders. Some of the more common conditions under these headings include:
Cubital Tunnel Syndrome-compression of the ulnar nerve in the cubital tunnel at the elbow.”
Pathophysiology
In regards to the pathophysiology of ulnar neuropathy:the axon, and myelin can be affected. Within the axon, fascicles to individual muscles could be involved, with subsequent motor unit loss and amplitude decrease. Conduction block means impaired transmission via a part of the nerve. Conduction block can mean myelin damage to the involved area, slowing of conduction or significant spreading out of the temporal profile of the response with axonal integrity is a hallmark of demyelination.
Diagnosis
Among the diagnostic procedures done to determine if the individual has ulnar neuropathy are (but may not be limited to the following):
Nerve conduction exam/study (Nerve Conduction Velocity is a measurements made in a nerve conduction exam)
Physical exam
Medical history
X-ray
CBC
Urinalysis
MRI
Ultrasound
Histology studyUlnar nerve neuropathy at the elbow or the wrist can be assessed by testing for a positive Froments sign. Little finger abduction and adduction can be tested as well.
Treatment
Treatment for ulnar neuropathy can entail:
NSAID (non-steroidal anti-inflammatory) medicines. there is also the option of a cortisone injection. Another possible option is splinting, to secure the elbow, a conservative procedure endorsed by some. In cases where surgery is needed, cubital tunnel release, where the ligament of the cubital tunnel is cut, thereby alleviating pressure on nerve can be performed.Treatment for the common occurrence of ulnar neuropathy resulting from overuse, with no fractures or structural abnormalities, is treatment massage, ice, and anti-inflammatories. Specifically, deep tissue massage to the triceps, myofascial release for the upper arm connective tissue, and cross-fiber friction to the triceps tendon.
Prognosis
In terms of the prognosis of ulnar neuropathy early decompression of the nerve sees a return to normal ability (function), which should be immediate. Severe cubital tunnel syndrome tends to have a faster recovery process in individuals below the age of 70, as opposed to those above such an age. Finally, revisional surgery for cubital tunnel syndrome does not result well for those individuals over 50 years of age.
References
Further reading
"NIOSHTIC-2 Publications Search - 20045060 - Do comorbid ulnar symptoms or ulnar neuropathy affect the prognosis of workers with carpal tunnel syndrome?". www.cdc.gov. Retrieved 2016-07-22.
Yoon, Joon Shik; Walker, Francis O.; Cartwright, Michael S. (1 February 2010). "Ulnar Neuropathy With Normal Electrodiagnosis and Abnormal Nerve Ultrasound". Archives of Physical Medicine and Rehabilitation. 91 (2): 318–320. doi:10.1016/j.apmr.2009.10.010. ISSN 0003-9993. PMC 2892824. PMID 20159139.
Warner, Mark A.; Warner, David O.; Matsumoto, Joseph Y.; Harper, Michel C.; Schroeder, Darrell R.; Maxson, Pamela M. (1 January 1999). "Ulnar Neuropathy in Surgical Patients". The Journal of the American Society of Anesthesiologists. 90 (1): 54–59. doi:10.1097/00000542-199901000-00009. ISSN 0003-3022. PMID 9915312. Retrieved 23 July 2016.
== External links == |
Hepatotoxicity | Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.
The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses (e.g. paracetamol) and sometimes even when introduced within therapeutic ranges (e.g. halothane), may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., microcystins), and herbal remedies (two prominent examples being kava, mechanism unknown, and comfrey, through its pyrrolizidine alkaloid content) can also induce hepatotoxicity. Chemicals that cause liver injury are called hepatotoxins.
More than 900 drugs have been implicated in causing liver injury (see LiverTox, external link, below) and it is the most common reason for a drug to be withdrawn from the market. Hepatotoxicity and drug-induced liver injury also account for a substantial number of compound failures, highlighting the need for toxicity prediction models (e.g. DTI), and drug screening assays, such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process. Chemicals often cause subclinical injury to the liver, which manifests only as abnormal liver enzyme tests.
Drug-induced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures.
Causes
Adverse drug reactions are classified as type A (intrinsic or pharmacological) or type B (idiosyncratic). Type A drug reaction accounts for 80% of all toxicities.Drugs or toxins that have a pharmacological (type A) hepatotoxicity are those that have predictable dose-response curves (higher concentrations cause more liver damage) and well characterized mechanisms of toxicity, such as directly damaging liver tissue or blocking a metabolic process. As in the case of paracetamol overdose, this type of injury occurs shortly after some threshold for toxicity is reached. Carbon tetrachloride is commonly used to induce acute type A liver injury in animal models.
Idiosyncratic (type B) injury occurs without warning, when agents cause non-predictable hepatotoxicity in susceptible individuals, which is not related to dose and has a variable latency period. This type of injury does not have a clear dose-response nor temporal relationship, and most often does not have predictive models. Idiosyncratic hepatotoxicity has led to the withdrawal of several drugs from market even after rigorous clinical testing as part of the FDA approval process; Troglitazone (Rezulin) and trovafloxacin (Trovan) are two prime examples of idiosyncratic hepatotoxins pulled from market.
The herb kava has caused a number of cases of idiosyncratic liver injury, ranging everywhere from asymptomatic to fatal.
Oral use of the antifungal ketoconazole has been associated with hepatic toxicity, including some fatalities; however, such effects appear to be limited to doses taken over a period longer than 7 days.
Paracetamol
Paracetamol also known as acetaminophen, and by the brand names of Tylenol and Panadol, is usually well-tolerated in prescribed dose, but overdose is the most common cause of drug-induced liver disease and acute liver failure worldwide. Damage to the liver is not due to the drug itself but to a toxic metabolite (N-acetyl-p-benzoquinone imine (NAPQI)) produced by cytochrome P-450 enzymes in the liver. In normal circumstances, this metabolite is detoxified by conjugating with glutathione in phase 2 reaction. In an overdose, a large amount of NAPQI is generated, which overwhelms the detoxification process and leads to liver cell damage. Nitric oxide also plays a role in inducing toxicity. The risk of liver injury is influenced by several factors including the dose ingested, concurrent alcohol or other drug intake, interval between ingestion and antidote, etc. The dose toxic to the liver is quite variable from person to person and is often thought to be lower in chronic alcoholics. Measurement of blood level is important in assessing prognosis, higher levels predicting a worse prognosis. Administration of Acetylcysteine, a precursor of glutathione, can limit the severity of the liver damage by capturing the toxic NAPQI. Those that develop acute liver failure can still recover spontaneously, but may require transplantation if poor prognostic signs such as encephalopathy or coagulopathy is present (see Kings College Criteria).
Nonsteroidal anti-inflammatory drugs
Although individual analgesics rarely induce liver damage due to their widespread use, NSAIDs have emerged as a major group of drugs exhibiting hepatotoxicity. Both dose-dependent and idiosyncratic reactions have been documented. Aspirin and phenylbutazone are associated with intrinsic hepatotoxicity; idiosyncratic reaction has been associated with ibuprofen, sulindac, phenylbutazone, piroxicam, diclofenac and indomethacin.
Glucocorticoids
Glucocorticoids are so named due to their effect on the carbohydrate mechanism. They promote glycogen storage in the liver. An enlarged liver is a rare side-effect of long-term steroid use in children. The classical effect of prolonged use both in adult and paediatric population is steatosis.
Isoniazid
Isoniazide (INH) is one of the most commonly used drugs for tuberculosis; it is associated with mild elevation of liver enzymes in up to 20% of patients and severe hepatotoxicity in 1-2% of patients.
Other hydrazine derivative drugs
There are also cases where other hydrazine derivative drugs, such as the MAOI antidepressant iproniazid, are associated with liver damage. Phenelzine has been associated with abnormal liver tests. Toxic effects can develop from antibiotics.
Natural products
Examples include alpha-Amanitin containing mushrooms, kava, and aflatoxin producing molds. Pyrrolizidine alkaloids, which occur in some plants, can be toxic. Green tea extract is a growing cause of liver failure due to its inclusion in more products.
Alternative remedies
Examples include: Ackee fruit, Bajiaolian, Camphor, Copaltra, Cycasin, Garcinia, Kava leaves, pyrrolizidine alkaloids, Horse chestnut leaves, Valerian, Comfrey. Chinese herbal remedies: Jin Bu Huan, Ephedra, Shou Wu Pian, Bai Xian Pi.
Industrial toxin
Examples include arsenic, carbon tetrachloride, and vinyl chloride.
Mechanism
Drugs continue to be taken off the market due to late discovery of hepatotoxicity. Due to its unique metabolism and close relationship with the gastrointestinal tract, the liver is susceptible to injury from drugs and other substances. 75% of blood coming to the liver arrives directly from gastrointestinal organs and the spleen via portal veins that bring drugs and xenobiotics in near-undiluted form. Several mechanisms are responsible for either inducing hepatic injury or worsening the damage process.
Many chemicals damage mitochondria, an intracellular organelle that produces energy. Its dysfunction releases excessive amount of oxidants that, in turn, injure hepatic cells. Activation of some enzymes in the cytochrome P-450 system such as CYP2E1 also lead to oxidative stress. Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside the liver. This promotes further liver damage. Non-parenchymal cells such as Kupffer cells, collagen-producing stellate cells, and leukocytes (i.e. neutrophil and monocyte) also have a role in the mechanism.
Drug metabolism in liver
The human body subjects most, but not all, compounds to various chemical processes (i.e. metabolism) to make them suitable for elimination. This involves chemical transformations to (a) reduce fat solubility and (b) to change biological activity. Although almost all tissues in the body have some ability to metabolize chemicals, smooth endoplasmic reticulum in the liver is the principal "metabolic clearing house" for both endogenous chemicals (e.g., cholesterol, steroid hormones, fatty acids, proteins) and exogenous substances (e.g., drugs, alcohol). The central role played by liver in the clearance and transformation of chemicals makes it susceptible to drug-induced injury.
Drug metabolism is usually divided into two phases: phase 1 and phase 2. Phase 1 reaction is generally speaking to prepare a drug for phase 2. However, many compounds can be metabolized by phase 2 directly or be excreted without any phase 2 reactions occurring. Phase 1 reaction involves oxidation, reduction, hydrolysis, hydration and many other rare chemical reactions. These processes tend to increase water solubility of the drug and can generate metabolites that are more chemically active and/or potentially toxic. Most of phase 2 reactions take place in cytosol and involve conjugation with endogenous compounds via transferase enzymes. Phase 1 are typically more suitable for elimination.
A group of enzymes located in the endoplasmic reticulum, known as cytochrome P-450, is the most important family of metabolizing enzymes in the liver. Cytochrome P-450 is not a single enzyme, but rather consists of a closely related family of 50 isoforms; six of them metabolize 90% of drugs. There is a tremendous diversity of individual P-450 gene products, and this heterogeneity allows the liver to perform oxidation on a vast array of chemicals (including most drugs) in phase 1. Three important characteristics of the P-450 system have roles in drug-induced toxicity:
1. Genetic diversity:Each of the P-450 proteins is unique and accounts (to some extent) for the variation in drug metabolism between individuals. Genetic variations (polymorphism) in P-450 metabolism should be considered when patients exhibit unusual sensitivity or resistance to drug effects at normal doses. Such polymorphism is also responsible for variable drug response among patients of differing ethnic backgrounds.
2. Change in enzyme activity:Many substances can influence the P-450 enzyme mechanism. Drugs interact with the enzyme family in several ways. Drugs that modify cytochrome P-450 enzyme are referred to as either inhibitors or inducers. Enzyme inhibitors block the metabolic activity of one or several P-450 enzymes. This effect usually occurs immediately. On the other hand, inducers increase P-450 activity by increasing enzyme production, or, in the case of CYP2E1, preventing degradation in the proteasome. There is usually a delay before enzyme activity increases.
3. Competitive inhibition:Some drugs may share the same P-450 specificity and thus competitively block their biotransformation. This may lead to accumulation of drugs metabolized by the enzyme. This type of drug interaction may also reduce the rate of generation of toxic metabolites.
Patterns of injury
Chemicals produce a wide variety of clinical and pathological hepatic injury. Biochemical markers (e.g. alanine transferase, alkaline phosphatase and bilirubin) are often used to indicate liver damage. Liver injury is defined as a rise in either (a) ALT level more than three times of upper limit of normal (ULN), (b) ALP level more than twice ULN, or (c) total bilirubin level more than twice ULN when associated with increased ALT or ALP. Liver damage is further characterized into hepatocellular (predominantly initial Alanine transferase elevation) and cholestatic (initial alkaline phosphatase rise) types. However they are not mutually exclusive and mixed types of injuries are often encountered.
Specific histo-pathological patterns of liver injury from drug-induced damage are discussed below.
Zonal Necrosis
This is the most common type of drug-induced liver cell necrosis where the injury is largely confined to a particular zone of the liver lobule. It may manifest as a very high level of ALT and severe disturbance of liver function leading to acute liver failure.
Causes include:
Paracetamol, carbon tetrachloride
Hepatitis
In this pattern, hepatocellular necrosis is associated with infiltration of inflammatory cells. There can be three types of drug-induced hepatitis. (A) viral hepatitis is the most common, where histological features are similar to acute viral hepatitis. (B) in focal or non-specific hepatitis, scattered foci of cell necrosis may accompany lymphocytic infiltration. (C) chronic hepatitis is very similar to autoimmune hepatitis clinically, serologically, and histologically.
Causes:
(a) Viral hepatitis: Halothane, isoniazid, phenytoin
(b) Focal hepatitis: Aspirin
(c) Chronic hepatitis: Methyldopa, diclofenac
Cholestasis
Liver injury leads to impairment of bile flow and cases are predominated by itching and jaundice. Histology may show inflammation (cholestatic hepatitis) or it can be bland (without any parenchymal inflammation). On rare occasions, it can produce features similar to primary biliary cirrhosis due to progressive destruction of small bile ducts (vanishing duct syndrome).
Causes:
(a) Bland: Oral contraceptive pills, anabolic steroid, androgens
(b) Inflammatory: Allopurinol, co-amoxiclav, carbamazepine
(c) Ductal: Chlorpromazine, flucloxacillin
Steatosis
Hepatotoxicity may manifest as triglyceride accumulation, which leads to either small-droplet (microvesicular) or large-droplet (macrovesicular) fatty liver. There is a separate type of steatosis by which phospholipid accumulation leads to a pattern similar to the diseases with inherited phospholipid metabolism defects (e.g., Tay–Sachs disease)
Causes:
(a) Microvesicular: Aspirin (Reyes syndrome), ketoprofen, tetracycline (especially if expired)
(b) Macrovesicular: Acetaminophen, methotrexate
(c) Phospholipidosis: Amiodarone, total parenteral nutrition
(d) Antiviral: nucleoside analogues
(e) Corticosteroid
(f) Hormonal: Tamoxifen
Granuloma
Drug-induced hepatic granulomas are usually associated with granulomas in other tissues and patients typically have features of systemic vasculitis and hypersensitivity. More than 50 drugs have been implicated.
Causes:
Allopurinol, phenytoin, isoniazid, quinine, penicillin, quinidine
Vascular lesions
These result from injury to the vascular endothelium.
Causes:
Venoocclusive disease: Chemotherapeutic agents, bush tea
Peliosis hepatis: Anabolic steroids
Hepatic vein thrombosis: Oral contraceptives
Neoplasm
Neoplasms have been described with prolonged exposure to some medications or toxins. Hepatocellular carcinoma, angiosarcoma, and liver adenomas are the ones usually reported.
Causes:
Vinyl chloride, combined oral contraceptive pill, anabolic steroid, arsenic, thorotrast
Diagnosis
This remains a challenge in clinical practice due to a lack of reliable markers. Many other conditions lead to similar clinical as well as pathological pictures. To diagnose hepatotoxicity, a causal relationship between the use of the toxin or drug and subsequent liver damage has to be established, but might be difficult, especially when idiosyncratic reaction is suspected. Simultaneous use of multiple drugs may add to the complexity. As in acetaminophen toxicity, well established, dose-dependent, pharmacological hepatotoxicity is easier to spot. Several clinical scales such as CIOMS/RUCAM scale and Maria and Victorino criteria have been proposed to establish causal relationship between offending drug and liver damage. CIOMS/RUCAM scale involves a scoring system that categorizes the suspicion into "definite or highly probable" (score > 8), "probable" (score 6–8), "possible" (score 3–5), "unlikely" (score 1–2) and "excluded" (score ≤ 0). In clinical practice, physicians put more emphasis on the presence or absence of similarity between the biochemical profile of the patient and known biochemical profile of the suspected toxicity (e.g., cholestatic damage in amoxycillin-clauvonic acid ).
Treatment
In most cases, liver function will return to normal if the offending drug is stopped early. Additionally, the patient may require supportive treatment. In acetaminophen toxicity, however, the initial insult can be fatal. Fulminant hepatic failure from drug-induced hepatotoxicity may require liver transplantation. In the past, glucocorticoids in allergic features and ursodeoxycholic acid in cholestatic cases had been used, but there is no good evidence to support their effectiveness.
Prognosis
An elevation in serum bilirubin level of more than 2 times ULN with associated transaminase rise is an ominous sign. This indicates severe hepatotoxicity and is likely to lead to mortality in 10% to 15% of patients, especially if the offending drug is not stopped (Hys Law). This is because it requires significant damage to the liver to impair bilirubin excretion, hence minor impairment (in the absence of biliary obstruction or Gilbert syndrome) would not lead to jaundice. Other poor predictors of outcome are old age, female sex, high AST.
Drugs withdrawn
The following therapeutic drugs were withdrawn from the market primarily because of hepatotoxicity: Troglitazone, bromfenac, trovafloxacin, ebrotidine, nimesulide, nefazodone, ximelagatran and pemoline.
See also
Hepatoprotection
Reyes syndrome
Notes
References
Friedman, Scott E.; Grendell, James H.; McQuaid, Kenneth R. (2003). Current diagnosis & treatment in gastroenterology. New York: Lang Medical Books/McGraw-Hill. pp. 664–679. ISBN 978-0-8385-1551-8.
Dixit, Vaibhav A. (2019). "A simple model to solve a complex drug toxicity problem". Toxicology,Research. 8 (2):157171. doi:10.1039/C8TX00261D. PMC 6417485. PMID 30997019.
Ostapowicz G, Fontana RJ, Schiødt FV, et al. (2002). "Results of a prospective study of acute liver failure at 17 tertiary care centres in the United States". Ann. Intern. Med. 137 (12).947–54. doi:10.7326/0003-4819-1371220021217000007. PMID 12484709. S2CID 11390513.
Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK (1998). "Adverse drug reactions". BMJ. 316 (7140):12958. doi:10.1136/bmj.316.7140.1295. PMC 1113033. PMID 9554902.
Manov I, Motanis H, Frumin I, Iancu TC (2006). "Hepatotoxicity of anti-inflammatory and analgesic drugs: ultrastructural aspects". Acta Pharmacol. Sin. 27 (3): 259–72. doi:10.1111/j.1745-7254.2006.00278.x. PMID 16490160. S2CID 26874901.
Alpers DH, Sabesin SM (1982). Schiff L; Schiff ER (eds.). Diseases of the liver. Philadelphia: JB Lippincott. pp. 813–45
Chalasani, Naga P.; Hayashi, Paul H.; Bonkovsky, Herbert L.; Navarro, Victor J.; Lee, William M.; Fontana, Robert J.; Practice Parameters Committee of the American College of Gastroenterology (2014). "ACG Clinical Guideline: The Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury". The American Journal of Gastroenterology. 109 (7):950966. doi:10.1038/ajg.2014.131. PMID 24935270. S2CID 2417493
Patel T, Roberts LR, Jones BA, Gores GJ (1998). "Dysregulation of apoptosis as a mechanism of liver disease: an overview". Semin. Liver Dis. 18 (2): 105–14. doi:10.1055/s-2007-1007147. PMID 9606808
Mumoli N, Cei M, Cosimi A (2006). "Drug-related hepatotoxicity". N. Engl. J. Med. 354 (20):21913,author,reply21913. doi:10.1056/NEJMc060733. PMID 16710915
Bénichou C (1990). "Criteria of drug-induced liver disorders. Report of an international consensus meeting". J. Hepatol. 11 (2): 272–6. doi:10.1016/0168-8278(90)90124-A. PMID 2254635
Blazka ME, Wilmer JL, Holladay SD, Wilson RE, Luster MI. (1995) Role of pro‑inflammatory cytokines in acetaminophen hepatotoxicity. Toxicol Appl Pharmacol 1995;133:43‑52
Yadav V, Rai R, Yadav A, Pahuja M, Solanki S, et al. (2012) Evaluation of antibacterial activity of Callicarpa macrophylla Vahl. stem extracts
Siddiqui H (1993) Safety of herbal drugs-an overview. Drugs News Views
Kumar A, Rohal A, Chakraborty S, Tiwari R, Latheef SK, et al. (2013) Ocimum sanctum (Tulsi): a miracle herb and boon to medical science Review. Int J Agron Plant Prod 4: 589
Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, et al. (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4:1
Singh N, Verma P, Pandey BR, Bhalla M (2012) Therapeutic potential of Ocimum sanctum in prevention and treatment of cancer and exposure to radiation: An overview. Int J Pharmacist Sci Drug Res 4: 97–104.
Mondal S, Mirdha BR, Mahapatra SC (2009) The science behind sacredness of Tulsi (Ocimum sanctum Linn.). Indian J Physiol Pharmacol 53: 291–306.
Devra D, Mathur KC, Agrawal RP, Bhadu I, Goyal S, et al. (2012) Effect of Tulsi (Ocimum sanctum Linn.) on Clinical and Biochemical Parameters of Metabolic Syndrome. J Nat Remedies 12: 63-67
Ahmad I, Beg AZ (2001) Antimicrobial and phytochemical studies on 45 Indian medicinal plants against multi-drug resistant human pathogens. Ethnopharmacol 74: 113–123.
Amadi J, Salami S, Eze C (2010) Antifungal properties and phytochemical screening of extracts of African basil (Ocimum gratissimum L.). Agr Biol J North America 1: 163–166.
Ponnusam Y, Louis T, Madhavachandran V, Kumar S, Thoprani N, et al. (2015) Antioxidant Activity of The Ancient Herb, Holy Basil in CCl4-Induced Liver Injury in Rats. Ayurvedic 2: 34–38.
Ravi V, Parida S, Desai A, Chandramukhi A, Devi MG, et al. (1997) Correlation of tumor necrosis factor levels in the serum and cerebrospinal fluid with clinical outcome in Japanese encephalitis patients. J Med Virol 51: 132–136.
Kumari P, Yadav P, Verma PR, Kumar, Arya, Kumar S, et al. (2013) A review on wound healing properties of Indian medicinal plants. Ind J Fund Appl Life Sci 3: 220–232.
Kumar A, Agarwal K, Maurya AK, Shanker K, Bushra U, et al. (2015) Pharmacological and phytochemical evaluation of Ocimum sanctum root extracts for its anti-inflammatory, analgesic and antipyretic activities. Pharmacogn Mag 11: S217.
Ranjana T, Tripathi V (2015) Therapeutic effect of tulsi (Ocimum sanctum Linn) in general and oral health. Ayurlog: National Journal of Research in Ayurveda Science 3: 1–12.
Suanarunsawat T, Ayutthaya WDN, Thirawarapan S, Poungshompoo S (2014) Anti-oxidative, anti-hyperglycemic and lipid-lowering effects of aqueous extracts of Ocimum sanctum L. leaves in diabetic rats. Food Nutr Sci 5: 801–811.
Talekar, Y. P., Das, B., Paul, T., Talekar, D. Y., Apte 1, K. G., & Parab, P. B. (2012). Evaluation of hepatoprotective Potential of Aqueous and Ethanolic Extract of Ocimum sanctum Linn. In Wistar Rats. Asian Journal of Pharmaceutical and Clinical Research, 5(4), 141–145.
Singh V, Kumar R.(2017).Study of Phytochemical Analysis and Antioxidant Activity of Allium sativum of Bundelkhand Region. International Journal of Life Sciences Scientific Research. 3(6):1451-1458.
Raaman N.(2006). Phytochemical Techniques. New India Publishing Agency, New Delhi, 19–24.
Tiwari P, Kumar B, Kaur M, Kaur G, Kaur H.(2011). Phytochemical screening and Extraction: A Review. Internationale Pharmaceutica Sciencia. 1(1):98-106.
Auwal MS, Saka S, Mairiga IA, Sanda KA, Shuaibu A and Ibrahim A.(2014) Preliminary phytochemical and elemental analysis of aqueous and fractionated pod extracts of Acacia nilotica (Thorn mimosa). Veterinary Research Forum.5(2):95-100.
Sadasivam S, Manickam A, Biochemical methods.(2005). Edn 3, New Age International Limited, Publishers, New Delhi. 1–4.
Basumatary AR.(2016).Preliminary Phytochemical Screening of some compounds from plant stem bark extracts of Tabernaemontana divaricata Linn. used by Bodo Community at Kokrajhar District, Assam, India. Archives of Applied Science Research.8(8):47-52
Silva GO, Abeysundara AT, Aponso MM.(2017). Extraction methods, qualitative and quantitative techniques for screening of phytochemicals from plants. American Journal of Essential Oils and Natural Products.5(2):29-32
Jagessar RC.(2017). Phytochemical screening and chromatographic profile of the ethanolic and aqueous extract of Passiflora edulis and Vicia faba L. (Fabaceae). Journal of Pharmacognosy and Phytochemistry.6(6):1714-1721
Gul R, Jan SU, Syed F, Sherani F, Nusrat Jahan.(2017).Preliminary Phytochemical Screening, Quantitative Analysis of Alkaloids, and Antioxidant Activity of Crude Plant Extracts |
Hepatotoxicity | from Ephedra intermedia Indigenous to Balochistan. The Scientific World Journal.1-7
Rubin, E., Hutter, F., Proper, H. (1963). Cell proliferation and fiber formation in chronic carbon tetrachloride intoxication. A morphologic and chemical study. American Journal of Pathology 42, 715.
Recnagal, R. (1983). Carbon tetrachloride hepatotoxicity, status quo and future prospects. Trends in Pharmacological Science 4, 129–131.
Slater, T.F. (1978). Biochemical Studies on Liver Injury. Academic Press, New York, pp. 1–44.
Reitman, S., Frankel, S. (1957). A colorimetric method for the determination of serum glutamate oxaloacetate transaminases. American Journal of Clinical Pathology 28, 56–63.
Malloy, H.T., Evelyn, K.A. (1937). The determination of bilirubin with the photometric colorimeter. Journal of Biological Chemistry 119, 481–490.
Kind, P.R.N., Kings, E.J. (1976). Determination of serum bilirubin. Journal Clinical Pathology 7, 322–330.
Brand-Williams, W.; Cuvelier, M.E.; Berset, C. (1995). Use of a free radical method to evaluate antioxidant activity. LWT—Food Sci. Technol. 28, 25–30.
Shah, N.A.; Khan, M.R.; Ahmad, B.; Noureen, F.; Rashid, U.; Khan, R.A. (2013) Investigation on flavonoid composition and anti-free radical potential of Sida cordata. BMC Complement. Altern. Med, 13, 276.
Zengin, G.; Aktumsek, A.; Guler, G.O.; Cakmak, Y.S.; Yildiztugay, E. (2011). Antioxidant properties of methanolic extract and fatty acid composition of Centaurea urvillei DC. Subsp. Hayekiana Wagenitz. Rec. Nat. Prod., 5, 123–132.
Mitsuda, H.; Yasumoto, K.; Iwami, K. (1966). Antioxidative action of indole compounds during the autooxidation of linoleic acid. Nippon Eiyo Shokuryo Gakkaishi, 19, 210–214
Baccanari, D.; Phillips, A.; Smith, S.; Sinski, D.; Burchall, J. (1975-12-02). "Purification and properties of Escherichia coli dihydrofolate reductase". Biochemistry. 14 (24): 5267–5273. doi:10.1021/bi00695a006. ISSN 0006-2960. PMID 46.
External links
LiverTox at the United States National Library of Medicine |
Cardiac asthma | Cardiac asthma is the medical condition of intermittent wheezing, coughing, and shortness of breath that is associated with underlying congestive heart failure (CHF). Symptoms of cardiac asthma are related to the hearts inability to effectively and efficiently pump blood in a CHF patient. This can lead to accumulation of fluid in and around the lungs (pulmonary congestion), disrupting the lungs ability to oxygenate blood.Cardiac asthma carries similar symptoms to bronchial asthma, but is differentiated by lacking inflammatory origin. Because of the similarity in symptoms, diagnosis of cardiac versus bronchial asthma relies on full cardiac workup and pulmonary function testing.Treatment is centered on improving cardiac function, maintaining blood oxygen saturation levels, and stabilizing total body water volume and distribution.
Signs and symptoms
The most common findings of cardiac asthma are the presence of wheeze, cough, or shortness of breath (predominantly occurring at night or when laying down) in a patient that possesses signs of congestive heart failure.Additional findings consist of production of frothy or watery sputum and presence of water in the lungs that can be heard via stethoscope. In severe cases, a patient can experience multiple night time episodes of breathlessness, changes in skin coloration, and episodes of bloody sputum.
Pathophysiology
The underlying causes for cardiac asthma stem from the eventual back up of fluid into the pulmonary vasculature as a result of the hearts, particularly left sided, inability to effectively and efficiently pump blood. The accumulation of fluid in the heart creates a higher than normal pressure system that places increasing pressure demands on the pulmonary venous system in order for appropriate oxygenation of blood to occur. This results in what is called pulmonary venous hypertension (PVH), and results in distention and recruitment of pulmonary capillaries to help distribute the increased pressure gradient. At the capillary, there is a microvascular barrier that helps regulate fluid status via molecular pressure forces such as forces that push outward from vessels and pressures that pull or attract into vessels. With increasing PVH, pressure outward overcomes pressure inward, and fluid is distributed to the lung interstitium, preserving oxygen exchange at the capillary. Fluid is transported to the hilum and pleural space, and removed via the lymphatic system. At first, the body is capable of handling excess water. Later, the capillary vasculature is overwhelmed by increased pressure and fluid backs up into the alveolar sac, resulting in pulmonary edema and decreased oxygenation capability. Additionally, increased pressure demands on capillary vasculature result in increases in vascular tone to include remodeling of pre-capillary vessels such as medial wall hypertrophic changes. Overtime, the remodeling efforts of the vessels can progress to hyperplastic changes of the vessels wall construction, and results in increased pulmonary vascular resistance.There is ongoing interest into establishing connections of cardiac asthma to abnormalities in bronchiole anatomy. Current evaluation has proposed multiple mechanisms for increased airway resistance, and focus is on four alternate explanations:
Bronchoconstriction as a result of pulmonary edema.
Intrathoracic space competition from heart enlargement and pulmonary edema (complications of CHF) that compress airway construction and bronchioles.
Bronchial obstruction secondary to intraluminal edema.
Bronchial mucosa edema.
Diagnosis
The diagnosis of cardiac asthma is accomplished through workup of congestive heart failure, complete with:
Evaluation of current symptoms with specific consideration of chronological progression or worsening.
Past Medical History screen with consideration for conditions that predispose to heart failure, such as prior heart attack, history of coronary revascularization, high blood pressure, or diabetes (heart).
Physical Exam with emphasis on listening for abnormalities of heart sound, abnormalities of lung sound, or presence of increased fluid retention in neck or in extremities.
Laboratory Evaluation with specific interest in B-type natriuretic peptide levels.
Electrocardiography to evaluate for irregularities in heart rhythm.
Chest Radiograph to evaluate for presence of lung congestion or increased heart size.
Echocardiography to evaluate heart function. Echocardiography is the preferred choice for diagnosis of heart failure in patients.As well as evaluation of lung function via:
Pulmonary function testing (PFT) complete with bronchoprovocation testing. PFTs represent the preferred method for evaluating for bronchial asthma.
Management
Treatment of asthma symptoms in CHF patients is directed towards optimizing the patients cardiovascular status and correcting potential oxygen deficit. Current recommendations in acute asthma symptoms are utilization of diuretics such as furosemide, venodilators such as nitroglycerin, and morphine. The initial strategy should focus on decreasing patient fluid retention with diuretic therapy, thereby decreasing cardiac preload and overall fluid load in pulmonary circuit (pulmonary congestion). Next, if aggressive diuresis is not adequately correcting symptoms, venodilators can be used to distribute blood and fluid to the venous system, thereby decreasing cardiac preload and left heart pressures contributing to pulmonary congestion. Lastly, morphine can be utilized for assistance in improving ease of breathing through a presumed mechanism similar to venodilation, as well as reducing patient anxiety. Additionally, applications of supplemental oxygen and repositioning to upright or standing positions in events of low blood oxygen saturation and difficulty breathing can be utilized as needed.Chronic management of cardiac asthma is directed at optimizing therapy of heart failure. Current recommendations can be found at its respective page (congestive heart failure).There is importance of distinguishing whether asthma is of bronchial or cardiac origin because management of bronchial asthma is primarily centered on utilization of inhalers, such as bronchodilators and corticosteroids. At this point in time, there has been limited evidence of improvement of cardiac asthma symptoms with utilization of inhalers.
See also
Dyspnea
Trepopnea
References
== External links == |
Hwabyeong | Hwabyeong or Hwapyŏng (hangul: 화병, hanja: 火病) is a Korean somatization disorder, a mental illness which arises when people are unable to confront their anger as a result of conditions which they perceive to be unfair. Hwabyeong is known as a Korean culture-bound syndrome.
Hwabyeong is a colloquial name, and it refers to the etiology of the disorder rather than its symptoms or apparent characteristics. In one survey, 4.1% of the general population in a rural area in Korea were reported as having hwabyeong. Hwabyeong is similar to Amuk.
The word hwabyeong is composed of hwa (the Sino-Korean word 火 for "fire" which can also contextually mean "anger") and byeong (the Sino-Korean word 病 for "syndrome" or "illness"). It may also be called ulhwabyeong (鬱火病), literally "depression anger illness".
Symptoms
Physical symptoms include:
palpitations
anorexia
dry mouth
insomnia
thoracic/chest pressure
respiratory difficulties
epigastric mass
headache
a whole-body sensation of heat (distinct from heat intolerance, a symptom of hyperthyroidism)Psychological symptoms include:
being easily startled
externalization of anger, also known in Korean as "bun" (憤, "eruption of anger"), a Korean culture-related sentiment related to social unfairness
generally sad mood
frequent sighing
a feeling of "eok-ul" (抑鬱, [feeling of] unfairness)
being easily agitated
feelings of guilt
feelings of impending doomDiagnosed patients may also have a medical history of prior major depressive disorder, dysthymic disorder, anxiety disorders, somatoform disorders, or adjustment disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria.Diagnosed patients are most likely to be middle-aged, post-menopausal women with low socio-economic status.
Causes
Underlying causes may include:
amuk
prior instances of major depressive disorder
prior instances of anxiety disorder
prior instances of adjustment disorder
prior instances of other somatoform disorders
repression of feelings of anger/resentment arising from past eventsTriggering causes are typically external events, including:
familial stressors, e.g. spousal infidelity or conflict with in-laws
witnessing acts/actions/phenomena that conflict with ones own moral and/or ethical principlesThe syndrome itself is believed to be the result of the continued repression of feelings of anger without addressing their source. In holistic medicine the containment of anger in hwabyung disturbs the balance of the five bodily elements, resulting in the development of psychosomatic symptoms such as panic, insomnia, and depression after a long period of repressed feelings.
It is possible that hormonal imbalances such as those around the time of menopause may also be an underlying cause of hwabyung in middle-aged women, the most often-diagnosed demographic.
Treatment
Western doctors are more likely to diagnose it as a kind of stress or depression. The Diagnostic and Statistical Manual of Mental Disorders currently lists hwabyeong among its culture-bound illnesses. Outside of Korea, informally hwabyeong may be mistaken as a reference to a psychological profile marked by a short temper, or explosive, generally bellicose behavior. To the contrary, hwabyeong is a traditional psychological term used to refer to a condition characterized by passive suffering, is roughly comparable to depression, and is typically associated with older women. It is important that when diagnosing Hwabyeong, the culture of the patient is well understood. Since Hwabyeong can often be misdiagnosed as depression, the symptoms and culture need to be clearly and thoroughly looked into. Once Hwabyeong has been diagnosed, past treatments need to be reviewed. The treatments for the patient can then be a combination of pharmacological, and therapy-based interventions.
The treatment methods used to combat hwabyung include psychotherapy, drug treatment, family therapy, and community approaches. To be more successful psychiatrists might need to incorporate the teachings from traditional and religious healing methods or the use of han-puri, which is the sentiment of resolving, loosening, unraveling and appeasing negative emotions with positive ones. One example of hann-puri would be a mother who has suffered from poverty, less education, a violent husband, or a harsh mother-in-law, can be solved many years later by the success of her son for which she had endured hardships and sacrifices.
See also
Ataque de nervios
Anger
Repression
References
Further reading
Examining Anger in Culture-Bound Syndromes Psychiatric Times
Korean Womens Causal Perceptions of Hwabyung
Hwabyung: the construction of a Korean popular illness among Korean elderly immigrant women in the United States
Symptoms of Hwabyeong (in Korean)
Sung Kil Min, Shin-Young Suh, Ki-Jun Song (2009). Symptoms to use for Diagnostic Criteria of Hwa-Byung, an Anger Syndrome. Psychiatry Investig. 2009 March; 6(1): 7–12. Published online 2009 March 31.doi: 10.4306/pi.2009.6.1.7
Hwa-byung: Culture-related Syndrome
Hwabyung in Korea: Culture and Dynamic Analysis |
Hypercementosis | Hypercementosis is an idiopathic, non-neoplastic condition characterized by the excessive buildup of normal cementum (calcified tissue) on the roots of one or more teeth. A thicker layer of cementum can give the tooth an enlarged appearance, which mainly occurs at the apex or apices of the tooth.
Signs and symptoms
It is experienced as an uncomfortable sensation in the tooth, followed by an aching pain.It may be shown on radiographs as a radiopaque (or lighter) mass at each root apex.
Cause
Can be caused by many things. A way to remember the causes is "PIG ON TAP"Local factors-
Occlusal Trauma
Trauma
Non-functional tooth
Unopposed tooth (and impacted teeth, embedded teeth, teeth without antagonists)Systemic factors-
Idiopathic
Pituitary Gigantism
Pagets Disease
Acromegaly
Periapical granuloma
Arthritis
Calcinosis
Rheumatic feverIt may be one of the complications of Pagets disease of bone in the form of generalized hypercementosis.
It may also be a compensatory mechanism in response to attrition to increase occlusal tooth height.
Complications
Such deposits form bulbous enlargements on the roots and may interfere with extractions, especially if adjacent teeth become fused (concrescence). It may also result in pulpal necrosis by blocking blood supply via the apical foramen.
References
== External links == |
Prurigo pigmentosa | Prurigo pigmentosa is a rare skin condition of unknown cause, characterized by the sudden onset of erythematous papules that leave a reticulated hyperpigmentation when they heal.: 57 The condition has been associated with a strict ketogenic diet in case reports in the medical literature. It was first reported by Masaharu Nagashima in 1978. Research has shown that it may be caused by gut bacteria dysbiosis as a result of ketosis.
See also
Pruritus
Skin lesion
Masaharu Nagashima
References
== External links == |
T-cell acute lymphoblastic leukemia | T-cell acute lymphoblastic leukemia may refer to:
T-lymphoblastic leukemia/lymphoma, a form of lymphoid leukemia and lymphoma
Adult T-cell leukemia/lymphoma, a rare cancer of the immune systems own T-cells |
Eosinophilic cystitis | Eosinophilic cystitis is a rare condition where eosinophiles are present in the bladder wall. Signs and symptoms are similar to a bladder infection. Its cause is not entirely clear; however, may be linked to food allergies, infections, and medications among others.
Management
Treatment involves avoiding the trigger if that can be determined.
Prognosis
Long term outcomes in children are generally good.
== References == |
Diastrophic dysplasia | Diastrophic dysplasia is an autosomal recessive dysplasia which affects cartilage and bone development. ("Diastrophism" is a general word referring to a twisting.) Diastrophic dysplasia is due to mutations in the SLC26A2 gene.
Affected individuals have short stature with very short arms and legs and joint problems that restrict mobility.
Signs and symptoms
This condition is also characterized by an unusual clubfoot with twisting of the metatarsals, inward- and upward-turning foot, tarsus varus and inversion adducted appearances. Furthermore, they classically present with scoliosis (progressive curvature of the spine) and unusually positioned thumbs (hitchhikers thumbs). About half of infants with diastrophic dysplasia are born with an opening in the roof of the mouth called a cleft palate. Swelling of the external ears is also common in newborns and can lead to thickened, deformed ears.
The signs and symptoms of diastrophic dysplasia are similar to those of another skeletal disorder called atelosteogenesis, type 2; however diastrophic dysplasia tends to be less severe.
Genetic
It is one of a spectrum of skeletal disorders caused by mutations in the SLC26A2 gene. The protein encoded by this gene is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, but in adulthood this tissue continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of diastrophic dysplasia.
This condition is an autosomal recessive disorder, meaning that the defective gene is located on an autosome, and both parents must carry one copy of the defective gene in order to have a child born with the disorder. The parents of a child with an autosomal recessive disorder are usually not affected by the disorder.
Prevalence
Diastrophic dysplasia affects about one in 500,000 births, however; in Finland, this disorder is more common, with about in 1 in 33,000 births being affected by the disorder.
See also
Achondrogenesis type 1B
References
This article incorporates some public domain text from The U.S. National Library of Medicine
External links
GeneReviews/NCBI/NIH/UW entry on Diastrophic Dysplasia |
Craniotabes | Craniotabes is softening or thinning of the skull in infants and children, which may be normally present in newborns. It is seen mostly in the occipital and parietal bones. The bones are soft, and when pressure is applied they will collapse underneath it. When the pressure is relieved, the bones will usually snap back into place.
Causes
Any condition that affects bone growth, most notably rickets (from vitamin D deficiency), marasmus, syphilis, or thalassemia, can cause craniotabes if present during a time of rapid skull growth (most especially during gestation and infancy). It can be a "normal" feature in premature infants. It is the first sign in children and infants with rickets.
Diagnosis
Physical examination
Management
Management of craniotabes depends on the cause. The majority of craniotabes occurs in term infants and can be a normal finding.
Commonly, craniotabes results from the position of the head inside the uterus weeks prior to delivery. Calcium and Vitamin D levels should be obtained to rule out rickets, and in mothers who have prenatal labs concerning for T. pallidum infection, neonates should be evaluated for congenital syphilis.
Etymology
The term (cranio- + tabes) is derived from the Latin words cranium for skull and tabes for wasting.
References
== External links == |
Byssinosis | Byssinosis is an occupational lung disease caused by inhalation of cotton or jute dust in inadequately ventilated working environments and can develop over time with repeated exposure. Byssinosis commonly occurs in textile workers who are employed in yarn and fabric manufacture industries. It is now thought that the cotton dust directly causes the disease and some believe that the causative agents are endotoxins that come from the cell walls of gram-negative bacteria that grow on the cotton. Although bacterial endotoxin is a likely cause, the absence of similar symptoms in workers in other industries exposed to endotoxins makes this uncertain. Current smokers are also at risk for developing byssinosis or having complications relating to byssinosis.Of the 81 byssinosis-related fatalities reported in the United States between 1990 and 1999, 48% included an occupation in the yarn, thread, and fabric industry on their death certificate. This disease often occurred in the times of the Industrial Revolution. Most commonly young girls working in mills or other textile factories would be affected by this disease. In the United States, from 1996 to 2005, North Carolina accounted for about 37% of all deaths caused by byssinosis, with 31, followed by South Carolina (8) and Georgia (7).There is a lack of information regarding the prevalence and impact of byssinosis in low and middle income countries (LMIC) despite the fact that of the 25 million tons of cotton produced worldwide, about two thirds of this production comes from LMICs like India, Pakistan, and China. Many textile mills and fiber producing factories located in LMICs have high rates of chronic respiratory disease caused by byssinosis.The term "brown lung" is a misnomer, as the lungs of affected individuals are not brown. Byssinosis is also referred to as cotton workers lung, mill fever, brown lung disease, and Monday fever.
History
In 1971, the Occupational Safety and Health Administration (OSHA) set a permissible exposure limit (PEL) of 1-mg/m3 (total dust) for cotton dust in work places. Later in the 1978 OSHA developed the Cotton Dust Standard which aimed to prevent occupational respiratory disease, such as byssinosis, through medical monitoring of employees. The PEL of cotton dust was set to 0.2 mg/m3 of airborne dust. This was considered the lowest level that could be measured by the vertical elutriator cotton dust sampler.OSHA regulators hoped that the Cotton Dust Standard Act would help decrease the impact of dust exposure of employees and reduce occupational respiratory diseases. However, a NISOH sponsored committee remained apprehensive about this standard as an earlier study conducted by NIOSH found that byssinosis diagnoses were brought on by cotton dust levels as low as 0.1 mg/m3 meaning that there is still a risk for the development of byssinosis for cotton dust exposure under the PEL. Today, NIOSH has set a recommended exposure limit (REL) of cotton dust to less than 0.2 mg/m3 for up to a 10-hour workday.
Symptoms
Symptoms of byssinosis can include:
Cough with sputum
Dyspnea
Breathing difficulties
Chest tightness
Wheezing
CoughPatients can develop these symptoms after a few hours of exposure at minimum. For this reason, patients who develop and report these symptoms, and subsequently byssinosis, are one of the reasons why the term Monday Fever exists. Byssinosis can become chronic in a patient if they are continually exposed to cotton, jute, or yarn dust over time. Byssinosis can be misdiagnosed as COPD, or asthma however the difference in these lung diseases and byssinosis comes from the etiology. Byssinosis can ultimately result in narrowing of the airways, lung scarring and death from infection or respiratory failure. Extended exposure to cotton or jute dust can lead to impaired lung function and further respiratory complications. Patients may require oxygen to assist with breathing and may also have difficulty exercising.
Diagnosis
It can be difficult to accurately diagnose a patient with byssinosis due to symptoms that are similar to other respiratory diseases such as chronic obstructive pulmonary diseases (COPD), asthma, or bronchitis. Byssinosis can be misdiagnosed as other pneumoconioses therefore a chest x-ray and/or lung function test is needed to accurately diagnose a patient who may have byssinosis. The main distinction of byssinosis from other respiratory diseases comes from the initial exposure. Patients who have byssinosis have typically been exposed to cotton or just dust for an extended period of time and experience symptoms of chest tightness and coughing.Patient history should reveal exposure to cotton, flax, hemp, or jute dust. Measurable change in lung function before and after working shifts is key to diagnosis. Patients with byssinosis show a significant drop in FEV1 over the course of work shift.
Chest radiographs show areas of opacity due to fibrosis of the pulmonary parenchyma.Another form of diagnosis is observing patient symptoms throughout their work shift. Patients with byssinosis due to dust inhalation will experience adverse symptoms when they being their work shift on Monday which is where the term Monday Fever comes in.
Treatment
There is currently no official form of diagnosing an individual with byssinosis. Affected workers should be offered alternative employment. Employers in the manufacturing and textile industry should take preventative measures to ensure workers are not exposed to excessive dust and cotton during their work shifts as this is the main cause of byssinosis exposure. Continued exposure leads to development of persistent symptoms and progressive decline in FEV1. Dust control measures can also help reduce the risk of textile workers developing byssinosis.Educational content aimed to raise awareness about byssinosis and other occupational lung diseases can be useful to inform workers and managers in textile industry as well as unions, and other health professionals. Educational content should be based on signs and symptoms of byssinosis as well as other diagnostic measures.
See also
Cotton Production
Textile manufacturing
Respiratory Diseases
LCIM
Notes and References
Notes
References
Further reading
Snyder, Rachel Louise (2007). Fugitive Denim: A Moving Story of People and Pants in the Borderless World of Global Trade. W. W. Norton. ISBN 978-0-393-06180-2.
External links
Byssinosis: MedlinePlus Medical Encyclopedia (NIH)
Work-Related Lung Disease Surveillance System (eWoRLD): Work-Related Respiratory Diseases | CDC/NIOSH |
Functional symptom | A functional symptom is a medical symptom with no known physical cause. In other words, there is no structural or pathologically defined disease to explain the symptom. The use of the term functional symptom does not assume psychogenesis, only that the body is not functioning as expected. Functional symptoms are increasingly viewed within a framework in which biological, psychological, interpersonal and healthcare factors should all be considered to be relevant for determining the aetiology and treatment plans.Historically, there has often been fierce debate about whether certain problems are predominantly related to an abnormality of structure (disease) or are psychosomatic in nature, and what are at one stage posited to be functional symptoms are sometimes later reclassified as organic, as investigative techniques improve. It is well established that psychosomatic symptoms are a real phenomenon, so this potential explanation is often plausible, however the commonality of a range of psychological symptoms and functional weakness does not imply that one causes the other. For example, symptoms associated with migraine, epilepsy, schizophrenia, multiple sclerosis, stomach ulcers, chronic fatigue syndrome, Lyme disease and many other conditions have all tended historically at first to be explained largely as physical manifestations of the patients psychological state of mind; until such time as new physiological knowledge is eventually gained. Another specific example is functional constipation, which may have psychological or psychiatric causes. However, one type of apparently functional constipation, anismus, may have a neurological (physical) basis.
Whilst misdiagnosis of functional symptoms does occur, in neurology, for example, this appears to occur no more frequently than of other neurological or psychiatric syndromes. However, in order to be quantified, misdiagnosis has to be recognized as such, which can be problematic in such a challenging field as medicine.
A common trend is to see functional symptoms and syndromes such as fibromyalgia, irritable bowel syndrome and functional neurological symptoms such as functional weakness as symptoms in which both biological and psychological factors are relevant, without one necessarily being dominant.
Weakness
Functional weakness is weakness of an arm or leg without evidence of damage or a disease of the nervous system. Patients with functional weakness experience symptoms of limb weakness which can be disabling and frightening such as problems walking or a heaviness down one side, dropping things or a feeling that a limb just doesnt feel normal or part of them. Functional weakness may also be described as functional neurological symptom disorder (FNsD), Functional Neurological Disorder (FND) or functional neurological symptoms. If the symptoms are caused by a psychological trigger, it may be diagnosed as dissociative motor disorder or conversion disorder (CD).
To the patient and the doctor it often looks as if there has been a stroke or have symptoms of multiple sclerosis. However, unlike these conditions, with functional weakness there is no permanent damage to the nervous system which means that it can get better or even go away completely.
The diagnosis should usually be made by a consultant neurologist so that other neurological causes can be excluded. The diagnosis should be made on the basis of positive features in the history and the examination (such as Hoovers sign). It is dangerous to make the diagnosis simply because tests are normal. Neurologists usually diagnose wrongly about 5% of the time (which is the same for many other conditions.)
The most effective treatment is physiotherapy, however it is also helpful for patients to understand the diagnosis, and some may find CBT helps them to cope with the emotions associated with being unwell. For those with conversion disorder, psychological therapy is key to their treatment as it is emotional or psychological factors which are causing their symptoms.
Giveway weakness
Giveway weakness (also "give-away weakness", "collapsing weakness", etc.) refers to a symptom where a patients arm, leg, can initially provide resistance against an examiners touch, but then suddenly "gives way" and provides no further muscular resistance.
See also
Functional disorder
Functional neurological symptom disorder
Idiopathy
References
External links
Functional somatic symptoms and syndromes
Engagement in psychological treatment for functional neurological symptoms--Barriers and solutions
Chronic multiple functional somatic symptoms
Functional symptoms in inflammatory bowel disease and their potential influence in misclassification of clinical status |
Conjunctivochalasis | Conjunctivochalasis, also known as Mechanical Dry Eye (MDE), is a common eye surface condition characterized by the presence of excess folds of the conjunctiva located between the globe of the eye and the eyelid margin.
Symptoms
Symptoms range from dry eye, epiphora and irritation to localized pain, foreign body sensation, subconjunctival hemorrhage and ulceration. Symptoms are often made worse by vigorous blinking.
Causes
Most Conjunctivochalasis is thought to be caused by both a gradual thinning and stretching of the conjunctiva that accompanies age and a loss of adhesion between the conjunctiva and underlying sclera as the result of dissolution of Tenons capsule. The resulting loose, excess conjunctiva may mechanically irritate the eye and disrupt the tear film and its outflow, leading to dry eye and excess tearing. A correlation may also exist between inflammation in the eye and conjunctivochalasis, though it is unclear whether this correlation is causal. Conjunctivochalasis may be associated with previous surgery, blepharitis, meibomian gland disorder (MGD), Ehlers-Danlos Syndrome and aqueous tear deficiency.
Diagnosis
Because the disorder often occurs in people with typical dry eye symptoms, it can be difficult to readily distinguish the discomfort caused by the dry eye from that directly related to the redundant conjunctiva.
Mechanical dry eye should not be confused with aqueous tear deficiency dry eye or delayed tear clearance. Mechanical dry eye patients complain of blurry vision and pain that tend to be worse when looking down such as while reading. Dryness in aqueous tear deficiency dry eye patients tends to be worse as the day progresses due to progressive exposure. Frequent blinking exacerbates mechanical dry eye symptoms, while increasing blinking improves symptoms of aqueous tear deficiency dry eye.
Diagnosis can be further made under a slit lamp upon the observation of redundant conjunctival folds. These folds can be made more apparent by staining with fluorescein dye and by applying gentle upward pressure with a finger to the eyeball through the lower lid. In pure aqueous tear deficiency dry eye patients, fluorescein stains in the interpalpebral exposure zone. In mechanical dry eye patients, fluorescein staining can be seen by pulling down the lower lid spread to the non-exposure zone. A tear-clearance test can also detect irregularities in the tear film.Diagnosis can also be made by measuring the replenishment of the tear meniscus. The test can be done as follows: Apply 5 μl of fluorescein to the base of the inferior fornix, maximally deplete the lower tear meniscus by a capillary tube or Weckcel sponge, and then monitor the recovery of the tear meniscus height with or without blinking. Patients with mechanical dry eye detectable within 3–8 seconds without blinking or within 0.5-1.5 seconds with blinking.
Treatment
Mild Conjunctivochalasis can be asymptomatic and in such cases does not require treatment. Lubricating eye drops may be tried but are often ineffective.If discomfort persists after standard dry eye treatment and anti-inflammatory therapy, surgery may be undertaken to remove the conjunctival folds and restore a smooth tear film. This conjunctivoplasty surgery to correct Conjunctivochalasis typically involves resection of an ellipse-shaped segment of conjunctiva just inferior to the lower lid margin, and is usually followed either by suturing or amniotic membrane graft transplantation to close the wound.Further techniques have been developed such as the Reservoir Restoration which aim to replace the degenerated Tenon’s, deepen the inferior fornix to restore the normal anatomy and physiology, and facilitate restoration of the normal tear film. In this surgical procedure, a crescent-shaped area of the conjunctiva is recessed along a limbal peritomy with a maximum anterior-posterior width no more than 3 mm. Diseased and dissolved Tenon’s are undermined leaving a large bare scleral defect. Cryopreserved amniotic membrane is slid over the scleral bed with fibrin glue and tucked under the conjunctiva to recreate the fornix. Immediately postop, the surgeon should note an improved anatomical definition and deepening of the inferior fornix.
References
== External links == |
Candidiasis | Candidiasis is a fungal infection due to any type of Candida (a type of yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth and throat. Other symptoms may include soreness and problems swallowing. When it affects the vagina, it may be referred to as a yeast infection or thrush. Signs and symptoms include genital itching, burning, and sometimes a white "cottage cheese-like" discharge from the vagina. Yeast infections of the penis are less common and typically present with an itchy rash. Very rarely, yeast infections may become invasive, spreading to other parts of the body. This may result in fevers along with other symptoms depending on the parts involved.More than 20 types of Candida can cause infection with Candida albicans being the most common. Infections of the mouth are most common among children less than one month old, the elderly, and those with weak immune systems. Conditions that result in a weak immune system include HIV/AIDS, the medications used after organ transplantation, diabetes, and the use of corticosteroids. Other risks include dentures, following antibiotic therapy, and breastfeeding. Vaginal infections occur more commonly during pregnancy, in those with weak immune systems, and following antibiotic use. Individuals at risk for invasive candidiasis include low birth weight babies, people recovering from surgery, people admitted to intensive care units, and those with an otherwise compromised immune system.Efforts to prevent infections of the mouth include the use of chlorhexidine mouthwash in those with poor immune function and washing out the mouth following the use of inhaled steroids. Little evidence supports probiotics for either prevention or treatment, even among those with frequent vaginal infections. For infections of the mouth, treatment with topical clotrimazole or nystatin is usually effective. Oral or intravenous fluconazole, itraconazole, or amphotericin B may be used if these do not work. A number of topical antifungal medications may be used for vaginal infections, including clotrimazole. In those with widespread disease, an echinocandin such as caspofungin or micafungin is used. A number of weeks of intravenous amphotericin B may be used as an alternative. In certain groups at very high risk, antifungal medications may be used preventatively.Infections of the mouth occur in about 6% of babies less than a month old. About 20% of those receiving chemotherapy for cancer and 20% of those with AIDS also develop the disease. About three-quarters of women have at least one yeast infection at some time during their lives. Widespread disease is rare except in those who have risk factors.
Signs and symptoms
Signs and symptoms of candidiasis vary depending on the area affected. Most candidal infections result in minimal complications such as redness, itching, and discomfort, though complications may be severe or even fatal if left untreated in certain populations. In healthy (immunocompetent) persons, candidiasis is usually a localized infection of the skin, fingernails or toenails (onychomycosis), or mucosal membranes, including the oral cavity and pharynx (thrush), esophagus, and the genitalia (vagina, penis, etc.); less commonly in healthy individuals, the gastrointestinal tract, urinary tract, and respiratory tract are sites of candida infection.
In immunocompromised individuals, Candida infections in the esophagus occur more frequently than in healthy individuals and have a higher potential of becoming systemic, causing a much more serious condition, a fungemia called candidemia. Symptoms of esophageal candidiasis include difficulty swallowing, painful swallowing, abdominal pain, nausea, and vomiting.
Mouth
Infection in the mouth is characterized by white discolorations in the tongue, around the mouth, and throat. Irritation may also occur, causing discomfort when swallowing.Thrush is commonly seen in infants. It is not considered abnormal in infants unless it lasts longer than a few weeks.
Genitals
Infection of the vagina or vulva may cause severe itching, burning, soreness, irritation, and a whitish or whitish-gray cottage cheese-like discharge. Symptoms of infection of the male genitalia (balanitis thrush) include red skin around the head of the penis, swelling, irritation, itchiness and soreness of the head of the penis, thick, lumpy discharge under the foreskin, unpleasant odour, difficulty retracting the foreskin (phimosis), and pain when passing urine or during sex.
Skin
Signs and symptoms of candidiasis in the skin include itching, irritation, and chafing or broken skin.
Invasive infection
Common symptoms of gastrointestinal candidiasis in healthy individuals are anal itching, belching, bloating, indigestion, nausea, diarrhea, gas, intestinal cramps, vomiting, and gastric ulcers. Perianal candidiasis can cause anal itching; the lesion can be red, papular, or ulcerative in appearance, and it is not considered to be a sexually transmissible disease. Abnormal proliferation of the candida in the gut may lead to dysbiosis. While it is not yet clear, this alteration may be the source of symptoms generally described as the irritable bowel syndrome, and other gastrointestinal diseases.
Causes
Candida yeasts are generally present in healthy humans, frequently part of the human bodys normal oral and intestinal flora, and particularly on the skin; however, their growth is normally limited by the human immune system and by competition of other microorganisms, such as bacteria occupying the same locations in the human body.Candida requires moisture for growth, notably on the skin. For example, wearing wet swimwear for long periods of time is believed to be a risk factor. Candida can also cause diaper rashes in babies. In extreme cases, superficial infections of the skin or mucous membranes may enter the bloodstream and cause systemic Candida infections.Factors that increase the risk of candidiasis include HIV/AIDS, mononucleosis, cancer treatments, steroids, stress, antibiotic usage, diabetes, and nutrient deficiency. Hormone replacement therapy and infertility treatments may also be predisposing factors. Use of inhaled corticosteroids increases risk of candidiasis of the mouth. Inhaled corticosteroids with other risk factors such as antibiotics, oral glucocorticoids, not rinsing mouth after use of inhaled corticosteroids or high dose of inhaled corticosteroids put people at even higher risk. Treatment with antibiotics can lead to eliminating the yeasts natural competitors for resources in the oral and intestinal flora, thereby increasing the severity of the condition. A weakened or undeveloped immune system or metabolic illnesses are significant predisposing factors of candidiasis. Almost 15% of people with weakened immune systems develop a systemic illness caused by Candida species. Diets high in simple carbohydrates have been found to affect rates of oral candidiases.C. albicans was isolated from the vaginas of 19% of apparently healthy people, i.e., those who experienced few or no symptoms of infection. External use of detergents or douches or internal disturbances (hormonal or physiological) can perturb the normal vaginal flora, consisting of lactic acid bacteria, such as lactobacilli, and result in an overgrowth of Candida cells, causing symptoms of infection, such as local inflammation. Pregnancy and the use of oral contraceptives have been reported as risk factors. Diabetes mellitus and the use of antibiotics are also linked to increased rates of yeast infections.In penile candidiasis, the causes include sexual intercourse with an infected individual, low immunity, antibiotics, and diabetes. Male genital yeast infections are less common, but a yeast infection on the penis caused from direct contact via sexual intercourse with an infected partner is not uncommon.Breast-feeding mothers may also develop candidiasis on and around the nipple as a result of moisture created by excessive milk-production.Vaginal candidiasis can cause congenital candidiasis in newborns.
Diagnosis
In oral candidiasis, simply inspecting the persons mouth for white patches and irritation may make the diagnosis. A sample of the infected area may also be taken to determine what organism is causing the infection.Symptoms of vaginal candidiasis are also present in the more common bacterial vaginosis; aerobic vaginitis is distinct and should be excluded in the differential diagnosis. In a 2002 study, only 33% of women who were self-treating for a yeast infection actually had such an infection, while most had either bacterial vaginosis or a mixed-type infection.Diagnosis of a yeast infection is done either via microscopic examination or culturing. For identification by light microscopy, a scraping or swab of the affected area is placed on a microscope slide. A single drop of 10% potassium hydroxide (KOH) solution is then added to the specimen. The KOH dissolves the skin cells, but leaves the Candida cells intact, permitting visualization of pseudohyphae and budding yeast cells typical of many Candida species.For the culturing method, a sterile swab is rubbed on the infected skin surface. The swab is then streaked on a culture medium. The culture is incubated at 37 °C (98.6 °F) for several days, to allow development of yeast or bacterial colonies. The characteristics (such as morphology and colour) of the colonies may allow initial diagnosis of the organism causing disease symptoms.
Respiratory, gastrointestinal, and esophageal candidiasis require an endoscopy to diagnose. For gastrointestinal candidiasis, it is necessary to obtain a 3–5 milliliter sample of fluid from the duodenum for fungal culture. The diagnosis of gastrointestinal candidiasis is based upon the culture containing in excess of 1,000 colony-forming units per milliliter.
Classification
Candidiasis may be divided into these types:
Mucosal candidiasis
Oral candidiasis (thrush, oropharyngeal candidiasis)Pseudomembranous candidiasis
Erythematous candidiasis
Hyperplastic candidiasis
Denture-related stomatitis — Candida organisms are involved in about 90% of cases
Angular cheilitis — Candida species are responsible for about 20% of cases, mixed infection of C. albicans and Staphylococcus aureus for about 60% of cases.
Median rhomboid glossitis
Candidal vulvovaginitis (vaginal yeast infection)
Candidal balanitis — infection of the glans penis, almost exclusively occurring in uncircumcised males
Esophageal candidiasis (candidal esophagitis)
Gastrointestinal candidiasis
Respiratory candidiasis
Cutaneous candidiasis
Candidal folliculitis
Candidal intertrigo
Candidal paronychia
Perianal candidiasis, may present as pruritus ani: 309
Candidid
Chronic mucocutaneous candidiasis
Congenital cutaneous candidiasis
Diaper candidiasis: an infection of a childs diaper area: 309
Erosio interdigitalis blastomycetica
Candidal onychomycosis (nail infection) caused by Candida
Systemic candidiasisCandidemia, a form of fungemia which may lead to sepsis
Invasive candidiasis (disseminated candidiasis) — organ infection by Candida
Chronic systemic candidiasis (hepatosplenic candidiasis) — sometimes arises during recovery from neutropenia
Antibiotic candidiasis (iatrogenic candidiasis)
Prevention
A diet that supports the immune system and is not high in simple carbohydrates contributes to a healthy balance of the oral and intestinal flora. While yeast infections are associated with diabetes, the level of blood sugar control may not affect the risk. Wearing cotton underwear may help to reduce the risk of developing skin and vaginal yeast infections, along with not wearing wet clothes for long periods of time. For women who experience recurrent yeast infections, there is limited evidence that oral or intravaginal probiotics help to prevent future infections. This includes either as pills or as yogurt.Oral hygiene can help prevent oral candidiasis when people have a weakened immune system. For people undergoing cancer treatment, chlorhexidine mouthwash can prevent or reduce thrush. People who use inhaled corticosteroids can reduce the risk of developing oral candidiasis by rinsing the mouth with water or mouthwash after using the inhaler. People with dentures should also disinfect their dentures regularly to prevent oral candidiasis.
Treatment
Candidiasis is treated with antifungal medications; these include clotrimazole, nystatin, fluconazole, voriconazole, amphotericin B, and echinocandins. Intravenous fluconazole or an intravenous echinocandin such as caspofungin are commonly used to treat immunocompromised or critically ill individuals.The 2016 revision of the clinical practice guideline for the management of candidiasis lists a large number of specific treatment regimens for Candida infections that involve different Candida species, forms of antifungal drug resistance, immune statuses, and infection localization and severity. Gastrointestinal candidiasis in immunocompetent individuals is treated with 100–200 mg fluconazole per day for 2–3 weeks.
Localized infection
Mouth and throat candidiasis are treated with antifungal medication. Oral candidiasis usually responds to topical treatments; otherwise, systemic antifungal medication may be needed for oral infections. Candidal skin infections in the skin folds (candidal intertrigo) typically respond well to topical antifungal treatments (e.g., nystatin or miconazole). For breastfeeding mothers topical miconazole is the most effective treatment for treating candidiasis on the breasts. Gentian violet can be used for thrush in breastfeeding babies. Systemic treatment with antifungals by mouth is reserved for severe cases or if treatment with topical therapy is unsuccessful. Candida esophagitis may be treated orally or intravenously; for severe or azole-resistant esophageal candidiasis, treatment with amphotericin B may be necessary.Vaginal yeast infections are typically treated with topical antifungal agents. Penile yeast infections are also treated with antifungal agents, but while an internal treatment may be used (such as a pessary) for vaginal yeast infections, only external treatments – such as a cream – can be recommended for penile treatment. A one-time dose of fluconazole by mouth is 90% effective in treating a vaginal yeast infection. For severe nonrecurring cases, several doses of fluconazole is recommended. Local treatment may include vaginal suppositories or medicated douches. Other types of yeast infections require different dosing. C. albicans can develop resistance to fluconazole, this being more of an issue in those with HIV/AIDS who are often treated with multiple courses of fluconazole for recurrent oral infections.For vaginal yeast infection in pregnancy, topical imidazole or triazole antifungals are considered the therapy of choice owing to available safety data. Systemic absorption of these topical formulations is minimal, posing little risk of transplacental transfer. In vaginal yeast infection in pregnancy, treatment with topical azole antifungals is recommended for seven days instead of a shorter duration.For vaginal yeast infections, many complementary treatments are proposed, however a number have side effects. No benefit from probiotics has been found for active infections.
Blood infection
Treatment typically consists of oral or intravenous antifungal medications. In candidal infections of the blood, intravenous fluconazole or an echinocandin such as caspofungin may be used. Amphotericin B is another option.
Prognosis
Among individuals being treated in intensive care units, the mortality rate is about 30–50% when systemic candidiasis develops.
Epidemiology
Oral candidiasis is the most common fungal infection of the mouth, and it also represents the most common opportunistic oral infection in humans. Infections of the mouth occur in about 6% of babies less than a month old. About 20% of those receiving chemotherapy for cancer and 20% of those with AIDS also develop the disease.It is estimated that 20% of women may be asymptomatically colonized by vaginal yeast. In the United States there are approximately 1.4 million doctor office visits every year for candidiasis. About three-quarters of women have at least one yeast infection at some time during their lives.Esophageal candidiasis is the most common esophageal infection in persons with AIDS and accounts for about 50% of all esophageal infections, often coexisting with other esophageal diseases. About two-thirds of people with AIDS and esophageal candidiasis also have oral candidiasis.Candidal sepsis is rare. Candida is the fourth most common cause of bloodstream infections among hospital patients in the United States. The incidence of bloodstream candida in intensive care units varies widely between countries.
History
Descriptions of what sounds like oral thrush go back to the time of Hippocrates circa 460–370 BCE.The first description of a fungus as the causative agent of an oropharyngeal and oesophageal candidosis was by Bernhard von Langenbeck in 1839.Vulvovaginal candidiasis was first described in 1849 by Wilkinson. In 1875, Haussmann demonstrated the causative organism in both vulvovaginal and oral candidiasis is the same.With the advent of antibiotics following World War II, the rates of candidiasis increased. The rates then decreased in the 1950s following the development of nystatin.The colloquial term "thrush" refers to the resemblance of the white flecks present in some forms of candidiasis (e.g., pseudomembranous candidiasis) with the breast of the bird of the same name. The term candidosis is largely used in British English, and candidiasis in American English. Candida is also pronounced differently; in American English, the stress is on the "i", whereas in British English the stress is on the first syllable.The genus Candida and species C. albicans were described by botanist Christine Marie Berkhout in her doctoral thesis at the University of Utrecht in 1923. Over the years, the classification of the genera and species has evolved. Obsolete names for this genus include Mycotorula and Torulopsis. The species has also been known in the past as Monilia albicans and Oidium albicans. The current classification is nomen conservandum, which means the name is authorized for use by the International Botanical Congress (IBC).The genus Candida includes about 150 different species. However, only a few are known to cause human infections. C. albicans is the most significant pathogenic species. Other species pathogenic in humans include C. auris, C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, C. dubliniensis, and C. lusitaniae.
The name Candida was proposed by Berkhout. It is from the Latin word toga candida, referring to the white toga (robe) worn by candidates for the Senate of the ancient Roman republic. The specific epithet albicans also comes from Latin, albicare meaning "to whiten". These names refer to the generally white appearance of Candida species when cultured.
Alternative medicine
A 2005 publication noted that "a large pseudoscientific cult" has developed around the topic of Candida, with claims stating that up to one in three people are affected by yeast-related illness, particularly a condition called "Candidiasis hypersensitivity". Some practitioners of alternative medicine have promoted these purported conditions and sold dietary supplements as supposed cures; a number of them have been prosecuted. In 1990, alternative health vendor Natures Way signed an FTC consent agreement not to misrepresent in advertising any self-diagnostic test concerning yeast conditions or to make any unsubstantiated representation concerning any food or supplements ability to control yeast conditions, with a fine of $30,000 payable to the National Institutes of Health for research in genuine candidiasis.
Research
High level Candida colonization is linked to several diseases of the gastrointestinal tract including Crohns disease.There has been an increase in resistance to antifungals worldwide over the past 30–40 years.
References
External links
Candidiasis at Curlie
"Yeast Infections". MedlinePlus. U.S. National Library of Medicine. |
Cat-scratch disease | Cat-scratch disease (CSD) or felinosis is an infectious disease that most often results from a scratch or bite of a cat. Symptoms typically include a non-painful bump or blister at the site of injury and painful and swollen lymph nodes. People may feel tired, have a headache, or a fever. Symptoms typically begin within 3–14 days following infection.Cat-scratch disease is caused by the bacterium Bartonella henselae which is believed to be spread by the cats saliva. Young cats pose a greater risk than older cats. Occasionally dog scratches or bites may be involved. Diagnosis is generally based on symptoms. Confirmation is possible by blood tests.The primary treatment is supportive. Antibiotics speed healing and are recommended in those with severe disease or immune problems. Recovery typically occurs within 4 months but can require a year. About 1 in 10,000 people are affected. It is more common in children.
Signs and symptoms
Cat-scratch disease commonly presents as tender, swollen lymph nodes near the site of the inoculating bite or scratch or on the neck, and is usually limited to one side. This condition is referred to as regional lymphadenopathy and occurs 1–3 weeks after inoculation. Lymphadenopathy most commonly occurs in the axilla, arms, neck, or jaw, but may also occur near the groin or around the ear. A vesicle or an erythematous papule may form at the site of initial infection.Most people also develop systemic symptoms such as malaise, decreased appetite, and aches. Other associated complaints include headache, chills, muscular pains, joint pains, arthritis, backache, and abdominal pain. It may take 7 to 14 days, or as long as two months, for symptoms to appear. Most cases are benign and self-limiting, but lymphadenopathy may persist for several months after other symptoms disappear. The disease usually resolves spontaneously, with or without treatment, in one month.
In rare situations, CSD can lead to the development of serious neurologic or cardiac sequelae such as meningoencephalitis, encephalopathy, seizures, or endocarditis. Endocarditis associated with Bartonella infection has a particularly high mortality. Parinauds oculoglandular syndrome is the most common ocular manifestation of CSD, and is a granulomatous conjunctivitis with concurrent swelling of the lymph node near the ear. Optic neuritis or neuroretinitis is one of the atypical presentations.People who are immunocompromised are susceptible to other conditions associated with B. henselae and B. quintana, such as bacillary angiomatosis or bacillary peliosis. Bacillary angiomatosis is primarily a vascular skin lesion that may extend to bone or be present in other areas of the body. In the typical scenario, the patient has HIV or another cause of severe immune dysfunction. Bacillary peliosis is caused by B. henselae that most often affects people with HIV and other conditions causing severe immune compromise. The liver and spleen are primarily affected, with findings of blood-filled cystic spaces on pathology.
Cause
Bartonella henselae is a fastidious, intracellular, Gram-negative bacterium.
Transmission
The cat was recognized as the natural reservoir of the disease in 1950 by Robert Debré. Kittens are more likely to carry the bacteria in their blood, so may be more likely to transmit the disease than adult cats. However, fleas serve as a vector for transmission of B. henselae among cats, and viable B. henselae are excreted in the feces of Ctenocephalides felis, the cat flea. Cats could be infected with B. henselae through intradermal inoculation using flea feces containing B. henselae.As a consequence, a likely means of transmission of B. henselae from cats to humans may be inoculation with flea feces containing B. henselae through a contaminated cat scratch wound or by cat saliva transmitted in a bite. Ticks can also act as vectors and occasionally transmit the bacteria to humans. Combined clinical and PCR-based research has shown that other organisms can transmit Bartonella, including spiders. Cryptic Bartonella infection may be a much larger problem than previously thought, constituting an unrecognized occupational health hazard of veterinarians.
Diagnosis
The best diagnostic method available is polymerase chain reaction, which has a sensitivity of 43-76% and a specificity (in one study) of 100%. The Warthin–Starry stain can be helpful to show the presence of B. henselae, but is often difficult to interpret. B. henselae is difficult to culture and can take 2–6 weeks to incubate.
Histology
Cat-scratch disease is characterized by granulomatous inflammation on histological examination of the lymph nodes. Under the microscope, the skin lesion demonstrates a circumscribed focus of necrosis, surrounded by histiocytes, often accompanied by multinucleated giant cells, lymphocytes, and eosinophils. The regional lymph nodes demonstrate follicular hyperplasia with central stellate necrosis with neutrophils, surrounded by palisading histiocytes (suppurative granulomas) and sinuses packed with monocytoid B cells, usually without perifollicular and intrafollicular epithelioid cells. This pattern, although typical, is only present in a minority of cases.
Prevention
Cat-scratch disease can be primarily prevented by taking effective flea control measures; since cats are mostly exposed to fleas when they are outside, keeping cats inside can help prevent infestation. Strictly-indoor cats without exposure to indoor-outdoor animals are generally at negligible risk of infestation. Cats which are carrying the bacterium, B. henselae, are asymptomatic, thus thoroughly washing hands after handling a cat or cat feces is an important factor in preventing potential cat-scratch disease transmission from possibly infected cats to humans.
Treatment
Most healthy people clear the infection without treatment, but in 5 to 14% of individuals, the organisms disseminate and infect the liver, spleen, eye, or central nervous system. Although some experts recommend not treating typical CSD in immunocompetent people with mild to moderate illness, treatment of all people with antimicrobial agents (Grade 2B) is suggested due to the probability of disseminated disease. The preferred antibiotic for treatment is azithromycin, since this agent is the only one studied in a randomized controlled study.Azithromycin is preferentially used in pregnancy to avoid the teratogenic side effects of doxycycline. However, doxycycline is preferred to treat B. henselae infections with optic neuritis due to its ability to adequately penetrate the tissues of the eye and central nervous system.
Epidemiology
Cat-scratch disease has a worldwide distribution, but it is a nonreportable disease in humans, so public health data on this disease are inadequate. Geographical location, present season, and variables associated with cats (such as exposure and degree of flea infestation) all play a factor in the prevalence of CSD within a population. In warmer climates, the CSD is more prevalent during the fall and winter, which may be attributed to the breeding season for adult cats, which allows for the birth of kittens. B henselae, the bacterium responsible for causing CSD, is more prevalent in younger cats (less than one year old) than it is in adult cats.To determine recent incidence of CSD in the United States, the Truven Health MarketScan Commercial Claims and Encounters database was analyzed in a case control study from 2005 to 2013. The database consisted of healthcare insurance claims for employees, their spouses, and their dependents. All participants were under 65 years of age, from all 50 states. The length of the study period was 9 years and was based on 280,522,578 person-years; factors such as year, length of insurance coverage, region, age, and sex were used to calculate the person-years incidence rate to eliminate confounding variables among the entire study population.A total of 13,273 subjects were diagnosed with CSD, and both in- and outpatient cases were analyzed. The study revealed an incidence rate of 4.5/100,000 outpatient cases of cat-scratch disease. For inpatient cases, the incidence rate was much lower at 0.19/100,000 population. Incidence of CSD was highest in 2005 among outpatient cases and then slowly declined. The Southern states had the most significant decrease of incidence over time. Mountain regions have the lowest incidence of this disease because fleas are not commonly found in these areas.Distribution of CSD among children aged 5–9 was of the highest incidence in the analyzed database, followed by women aged 60–64. Incidence among females was higher than that among males in all age groups. According to data on social trends, women are more likely to own a cat over men; which supports higher incidence rates of this disease in women. Risk of contracting CSD increases as the number of cats residing in the home increases. The number of pet cats in the United States is estimated to be 57 million. Due to the large population of cats residing in the United States, the ability of this disease to continue to infect humans is vast. Laboratory diagnosis of CSD has improved in recent years, which may support an increase in incidence of the disease in future populations.
Outbreaks
Historically, the number of reported cases of CSD has been low, there has been a significant increase in reports in urban and suburban areas in the northeast region of United States. An example of the increased incidence can be found in Essex County, New Jersey. In 2016, there were 6 reported cases. In 2017, there were 51 reported cases. In 2018, there were 263 reported cases. Based on preliminary data, it is expected that there will be over 1,000 reported cases of CSD in Essex County, New Jersey. Although usually treated with antibiotics and minimal long-term effects, there have been 3 reported case of tachycardia more than one year after exposure. Pathologists believe that the increased incidence of CSD is due to cat owners neglecting to vaccinate their cats.
History
Symptoms similar to CSD were first described by Henri Parinaud in 1889, and the clinical syndrome was first described in 1950 by Robert Debré. In 1983, the Warthin-Starry silver stain was used to discover a Gram-negative bacillus which was named Afipia felis in 1991 after it was successfully cultured and isolated. The causative organism of CSD was originally believed to be Afipia felis, but this was disproved by immunological studies in the 1990s demonstrating that people with cat-scratch fever developed antibodies to two other organisms, B. henselae (originally known as Rochalimea henselae before the genera Bartonella and Rochalimea were combined) and B. clarridgeiae, which is a rod-shaped Gram-negative bacterium.
References
External links
https://www.cdc.gov/bartonella/cat-scratch/index.html
DermNet bacterial/catscratchCat Scratch Disease on National Organization for Rare Disorders site |
Pericoronitis | Pericoronitis is inflammation of the soft tissues surrounding the crown of a partially erupted tooth, including the gingiva (gums) and the dental follicle. The soft tissue covering a partially erupted tooth is known as an operculum, an area which can be difficult to access with normal oral hygiene methods. The hyponym operculitis technically refers to inflammation of the operculum alone.
Pericoronitis is caused by an accumulation of bacteria and debris beneath the operculum, or by mechanical trauma (e.g. biting the operculum with the opposing tooth). Pericoronitis is often associated with partially erupted and impacted mandibular third molars (lower wisdom teeth), often occurring at the age of wisdom tooth eruption (15-26). Other common causes of similar pain from the third molar region are food impaction causing periodontal pain, pulpitis from dental caries (tooth decay), and acute myofascial pain in temporomandibular joint disorder.
Pericoronitis is classified into chronic and acute. Chronic pericoronitis can present with no or only mild symptoms and long remissions between any escalations to acute pericoronitis. Acute pericoronitis is associated with a wide range of symptoms including severe pain, swelling and fever. Sometimes there is an associated pericoronal abscess (an accumulation of pus). This infection can spread to the cheeks, orbits/periorbits, and other parts of the face or neck, and occasionally can lead to airway compromise (e.g. Ludwigs angina) requiring emergency hospital treatment. The treatment of pericoronitis is through pain management and by resolving the inflammation. The inflammation can be resolved by flushing the debris or infection from the pericoronal tissues or by removing the associated tooth or operculum. Retaining the tooth requires improved oral hygiene in the area to prevent further acute pericoronitis episodes. Tooth removal is often indicated in cases of recurrent pericoronitis. The term is from the Greek peri, "around", Latin corona "crown" and -itis, "inflammation".
Classification
The definition of pericoronitis is inflammation in the soft tissues surrounding the crown of a tooth. This encompasses a wide spectrum of severity, making no distinction to the extent of the inflammation into adjacent tissues or whether there is associated active infection (pericoronal infection caused by micro-organisms sometimes leading to a pus filled pericoronal abscess or cellulitis).
Typically cases involve acute pericoronitis of lower third molar teeth. During "teething" in young children, pericoronitis can occur immediately preceding eruption of the deciduous teeth (baby or milk teeth).
The International Classification of Diseases entry for pericoronitis lists acute and chronic forms.
Acute
Acute pericoronitis (i.e. sudden onset and short lived, but significant, symptoms) is defined as "varying degrees of inflammatory involvement of the pericoronal flap and adjacent structures, as well as by systemic complications." Systemic complications refers to signs and symptoms occurring outside of the mouth, such as fever, malaise or swollen lymph nodes in the neck.
Chronic
Pericoronitis may also be chronic or recurrent, with repeated episodes of acute pericoronitis occurring periodically. Chronic pericoronitis may cause few if any symptoms, but some signs are usually visible when the mouth is examined.
Signs and symptoms
The signs and symptoms of pericoronitis depend upon the severity, and are variable:
Pain, which gets worse as the condition develops and becomes severe. The pain may be throbbing and radiate to the ear, throat, temporomandibular joint, posterior submandibular region and floor of the mouth. There may also be pain when biting. Sometimes the pain disturbs sleep.
Tenderness, erythema (redness) and edema (swelling) of the tissues around the involved tooth, which is usually partially erupted into the mouth. The operculum is characteristically very painful when pressure is applied.
Halitosis resulting from the bacteria putrefaction of proteins in this environment releasing malodorous volatile sulfur compounds.
Bad taste or sour taste in the mouth from exudation of pus.
Intra-oral halitosis.
Formation of pus, which can be seen exuding from beneath the operculum (i.e. a pericoronal abscess), especially when pressure is applied to the operculum.
Signs of trauma on the operculum, such as indentations of the cusps of the upper teeth, or ulceration. Rarely, the soft tissue around the crown of the involved tooth may show a similar appearance to necrotizing ulcerative gingivitis.
Trismus (difficulty opening the mouth). resulting from inflammation/infection of the muscles of mastication.
Dysphagia (difficulty swallowing).
Cervical lymphadenitis (inflammation and swelling of the lymph nodes in the neck), especially of the submandibular nodes.
Facial swelling, and rubor, often of the cheek that overlies the angle of the jaw.
Pyrexia (fever).
Leukocytosis (increased white blood cell count).
Malaise (general feeling of being unwell).
Loss of appetite.
The radiographic appearance of the local bone can become more radiopaque in chronic pericoronitis.
Causes
Pericoronitis occurs because the operculum (the soft tissue directly overlying the partially erupted tooth) creates a "plaque stagnation area", which can accumulate food debris and micro-organisms (particularly plaque). This leads to an inflammatory response in the adjacent soft tissues.Sometimes pericoronal infection can spread into adjacent potential spaces (including the sublingual space, submandibular space, parapharyngeal space, pterygomandibular space, infratemporal space, submasseteric space and buccal space) to areas of the neck or face resulting in facial swelling, or even airway compromise (called Ludwigs angina).
Bacteria
Inadequate cleaning of the operculum space allows stagnation of bacteria and any accumulated debris. This can be a result of poor access due to limited room in the case of the 3rd molars.
Pericoronal infection is normally caused by a mixture of bacterial species present in the mouth, such as Streptococci and particularly various anaerobic species.
This can result in abscess formation. Left untreated, the abscess can spontaneously drain into the mouth from beneath the operculum. In chronic pericoronitis, drainage may happen through an approximal sinus tract.
The chronically inflamed soft tissues around the tooth may give few if any symptoms. This can suddenly become symptomatic if new debris becomes trapped or if the host immune system becomes compromised and fails to keep the chronic infection in check (e.g. during influenza or upper respiratory tract infections, or a period of stress).
Tooth position
When an opposing tooth bites into the operculum, it can initiate or exacerbate pericoronitis resulting in a spiraling cycle of inflammation and trauma.
Over-eruption of the opposing tooth into the unoccupied space left by the stalled eruption of a tooth is a risk factor to operculum trauma from biting.
Teeth that fail to erupt completely (commonly the lower mandibular third molars) are often the result of limited space for eruption, or a non-ideal angle of tooth eruption causing tooth impaction.
The presence of supernumerary teeth (extra teeth) makes pericoronitis more likely.
Diagnosis
The presence of dental plaque or infection beneath an inflamed operculum without other obvious causes of pain will often lead to a pericoronitis diagnosis; therefore, elimination of other pain and inflammation causes is essential. For pericoronal infection to occur, the affected tooth must be exposed to the oral cavity, which can be difficult to detect if the exposure is hidden beneath thick tissue or behind an adjacent tooth. Severe swelling and restricted mouth opening may limit examination of the area. Radiographs can be used to rule out other causes of pain and to properly assess the prognosis for further eruption of the affected tooth.Sometimes a "migratory abscess" of the buccal sulcus occurs with pericoronal infection, where pus from the lower third molar region tracks forwards in the submucosal plane, between the body of the mandible and the attachment of the buccinator muscle to the mandible. In this scenario, pus may spontaneously discharge via an intra-oral sinus located over the mandibular second or first molar, or even the second premolar.
Similar causes of pain, some which can occur in conjunction with pericoronitis may include:
Dental caries (tooth decay) of the wisdom tooth and of the distal surface of the second molar is common. Tooth decay may cause pulpitis (toothache) to occur in the same region, and this may cause pulp necrosis and the formation of a periapical abscess associated with either tooth.
Food can also become stuck between the wisdom tooth and the tooth in front, termed food packing, and cause acute inflammation in a periodontal pocket when the bacteria become trapped. A periodontal abscess may even form by this mechanism.
Pain associated with temporomandibular joint disorder and myofascial pain also often occurs in the same region as pericoronitis. J are easily missed diagnoses in the presence of mild and chronic pericoronitis, and the latter may not be contributing greatly to the individuals pain (see table).It is rare for pericoronitis to occur in association with both lower third molars at the same time, despite the fact that many young people will have both lower wisdom teeth partially erupted. Therefore, bilateral pain from the lower third molar region is unlikely to be caused by pericoronitis and more likely to be muscular in origin.
Prevention
Prevention of pericoronitis can be achieved by removing impacted third molars before they erupt into the mouth, or through preemptive operculectomy. A treatment controversy exists about the necessity and timing of the removal of asymptomatic, disease-free impacted wisdom teeth which prevents pericoronitis. Proponents of early extraction cite the cumulative risk for extraction over time, the high probability that wisdom teeth will eventually decay or develop gum disease and costs of monitoring to retained wisdom teeth. Advocates for retaining wisdom teeth cite the risk and costs of unnecessary operations and the ability to monitor the disease through clinical exam and radiographs.
Management
Since pericoronitis is a result of inflammation of the pericoronal tissues of a partially erupted tooth, management can include applying pain management gels for the mouth consisting of Lignocaine, a numbing agent. Definitive treatment can only be through preventing the source of inflammation. This is either through improved oral hygiene or by removal of the plaque stagnation areas through tooth extraction or gingival resection, which can be done with diode lasers atraumatically. Often acute symptoms of pericoronitis are treated before the underlying cause is addressed.
Acute pericoronitis
When possible, immediate definitive treatment of acute pericoronitis is recommended because surgical treatment has been shown to resolve the spread of the infection and pain, with a quicker return of function. Also immediate treatment avoids overuse of antibiotics (preventing antibiotic resistance).
However, surgery is sometimes delayed in an area of acute infection, with the help of pain relief and antibiotics, for the following reasons:
Reduces the risk of causing an infected surgical site with delayed healing (e.g. osteomyelitis or cellulitis).
Avoids reduced efficiency of local anesthetics caused by the acidic environment of infected tissues.
Resolves the limited mouth opening, making oral surgery easier.
Patients may better cope with the dental treatment when free from pain.
Allows for adequate planning with correctly allocated procedure time.Firstly, the area underneath the operculum is gently irrigated to remove debris and inflammatory exudate. Often warm saline is used but other solutions may contain hydrogen peroxide, chlorhexidine or other antiseptics. Irrigation may be assisted in conjunction with Debridement (removal of plaque, calculus and food debris) with periodontal instruments. Irrigation may be enough to relieve any associated pericoronal abscess; otherwise a small incision can be made to allow drainage.
Smoothing an opposing tooth which bites into the affected operculum can eliminate this source of trauma.Home care may involve regular use of warm salt water mouthwashes/mouth baths. A randomized clinical trial found green tea mouth rinse effective in controlling pain and trismus in acute cases of pericoronitis.Following treatment, if there are systemic signs and symptoms, such as facial or neck swelling, cervical lymphadenitis, fever or malaise, a course of oral antibiotics is often prescribed,. Common antibiotics used are from the β-lactam antibiotic group, clindamycin and metronidazole.If there is dysphagia or dyspnoea (difficulty swallowing or breathing), then this usually means there is a severe infection and an emergency admission to hospital is appropriate so that intravenous medications and fluids can be administered and the threat to the airway monitored. Sometimes semi-emergency surgery may be arranged to drain a swelling that is threatening the airway.
Definitive treatment
If the tooth will not continue to erupt completely, definitive treatment involves either sustained oral hygiene improvements or removal of the offending tooth or operculum. The latter surgical treatment options are usually chosen in the case of impacted teeth with no further eruption potential, or in the case of recurrent episodes of acute pericoronitis despite oral hygiene instruction.
Oral hygiene
In some cases, removal of the tooth may not be necessary with meticulous oral hygiene to prevent buildup of plaque in the area. Long term maintenance is needed to keep the operculum clean in order to prevent further acute episodes of inflammation. A variety of specialized oral hygiene methods are available to deal with hard to reach areas of the mouth, including small headed tooth brushes, interdental brushes, electronic irrigators and dental floss.
Operculectomy
This is a minor surgical procedure where the affected soft tissue covering and surrounding the tooth is removed. This leaves an area that is easy to keep clean, preventing plaque buildup and subsequent inflammation. Sometimes operculectomy is not an effective treatment. Typically operculectomy is done with a surgical scalpel, electrocautery, with lasers or, historically, with caustic agents (trichloracetic acid)
Tooth extraction
Removal of the associated tooth will eliminate the plaque stagnation area, and thus eliminate any further episodes of pericoronitis. Removal is indicated when the involved tooth will not erupt any further due to impaction or ankylosis; if extensive work would be required to restore structural damage; or to allow improved oral hygiene. Sometimes the opposing tooth is also extracted if no longer required.Extraction of teeth which are involved in pericoronitis carries a higher risk of dry socket, a painful complication which results in delayed healing.
Prognosis
Once the plaque stagnation area is removed either through further complete tooth eruption or tooth removal then pericoronitis will likely never return. A non-impacted tooth may continue to erupt, reaching a position which eliminates the operculum. A transient and mild pericoronal inflammation often continues while this tooth eruption completes. With adequate space for sustained improved oral hygiene methods, pericoronitis may never return. However, when relying on just oral hygiene for impacted and partially erupted teeth, chronic pericoronitis with occasional acute exacerbation can be expected.
Dental infections such as a pericoronal abscess can develop into sepsis and be life-threatening in persons who have neutropenia. Even in people with normal immune function, pericoronitis may cause a spreading infection into the potential spaces of the head and neck. Rarely, the spread of infection from pericoronitis may compress the airway and require hospital treatment (e.g. Ludwigs angina), although the majority of cases of pericoronitis are localized to the tooth. Other potential complications of a spreading pericoronal abscess include peritonsillar abscess formation or cellulitis.Chronic pericoronitis may be the etiology for the development of paradental cyst, an inflammatory odontogenic cyst.
Epidemiology
Pericoronitis usually occurs in young adults, around the time when wisdom teeth are erupting into the mouth. If the individual has reached their twenties without any attack of pericoronitis, it becomes substantially less likely one will occur thereafter.
References
20. Professional Dental University education, both Cosmetic Dentists, Dr. David Nguyen and Dr. Benjamin Golik (2009). Pericoronitis dentist.
== External links == |
Oculocutaneous albinism | Oculocutaneous albinism is a form of albinism involving the eyes (oculo-), the skin (-cutaneous), and the hair.
Overall, an estimated 1 in 20,000 people worldwide are born with oculocutaneous albinism. OCA is caused by mutations in several genes that control the synthesis of melanin within the melanocytes.
Seven types of oculocutaneous albinism have been described, all caused by a disruption of melanin synthesis and all autosomal recessive disorders.: 864 Oculocutaneous albinism is also found in non-human animals.
Types
The following types of oculocutaneous albinism have been identified in humans.
See also
Piebaldism
List of skin conditions
List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer
References
External links
Oculocutaneous albinism information at RareDiseases.org
NCBI Genetic Testing Registry |
Hyperlipidemia | Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.Lipids (water-insoluble molecules) are transported in a protein capsule. The size of that capsule, or lipoprotein, determines its density. The lipoprotein density and type of apolipoproteins it contains determines the fate of the particle and its influence on metabolism.
Hyperlipidemias are divided into primary and secondary subtypes. Primary hyperlipidemia is usually due to genetic causes (such as a mutation in a receptor protein), while secondary hyperlipidemia arises due to other underlying causes such as diabetes. Lipid and lipoprotein abnormalities are common in the general population and are regarded as modifiable risk factors for cardiovascular disease due to their influence on atherosclerosis. In addition, some forms may predispose to acute pancreatitis.
Classification
Hyperlipidemias may basically be classified as either familial (also called primary) when caused by specific genetic abnormalities or acquired (also called secondary) when resulting from another underlying disorder that leads to alterations in plasma lipid and lipoprotein metabolism. Also, hyperlipidemia may be idiopathic, that is, without a known cause.Hyperlipidemias are also classified according to which types of lipids are elevated, that is hypercholesterolemia, hypertriglyceridemia or both in combined hyperlipidemia. Elevated levels of Lipoprotein(a) may also be classified as a form of hyperlipidemia.
Familial (primary)
Familial hyperlipidemias are classified according to the Fredrickson classification, which is based on the pattern of lipoproteins on electrophoresis or ultracentrifugation. It was later adopted by the World Health Organization (WHO). It does not directly account for HDL, and it does not distinguish among the different genes that may be partially responsible for some of these conditions.
Type I
Type I hyperlipoproteinemia exists in several forms:
Lipoprotein lipase deficiency (type Ia), due to a deficiency of lipoprotein lipase (LPL) or altered apolipoprotein C2, resulting in elevated chylomicrons, the particles that transfer fatty acids from the digestive tract to the liver
Familial apoprotein CII deficiency (type Ib), a condition caused by a lack of lipoprotein lipase activator.: 533
Chylomicronemia due to circulating inhibitor of lipoprotein lipase (type Ic)Type I hyperlipoproteinemia usually presents in childhood with eruptive xanthomata and abdominal colic. Complications include retinal vein occlusion, acute pancreatitis, steatosis, and organomegaly, and lipemia retinalis.
Type II
Hyperlipoproteinemia type II is further classified into types IIa and IIb, depending mainly on whether elevation in the triglyceride level occurs in addition to LDL cholesterol.
Type IIa
This may be sporadic (due to dietary factors), polygenic, or truly familial as a result of a mutation either in the LDL receptor gene on chromosome 19 (0.2% of the population) or the ApoB gene (0.2%). The familial form is characterized by tendon xanthoma, xanthelasma, and premature cardiovascular disease. The incidence of this disease is about one in 500 for heterozygotes, and one in 1,000,000 for homozygotes.HLPIIa is a rare genetic disorder characterized by increased levels of LDL cholesterol in the blood due to the lack of uptake (no Apo B receptors) of LDL particles. This pathology, however, is the second-most common disorder of the various hyperlipoproteinemias, with individuals with a heterozygotic predisposition of one in every 500 and individuals with homozygotic predisposition of one in every million. These individuals may present with a unique set of physical characteristics such as xanthelasmas (yellow deposits of fat underneath the skin often presenting in the nasal portion of the eye), tendon and tuberous xanthomas, arcus juvenilis (the graying of the eye often characterized in older individuals), arterial bruits, claudication, and of course atherosclerosis. Laboratory findings for these individuals are significant for total serum cholesterol levels two to three times greater than normal, as well as increased LDL cholesterol, but their triglycerides and VLDL values fall in the normal ranges.To manage persons with HLPIIa, drastic measures may need to be taken, especially if their HDL cholesterol levels are less than 30 mg/dL and their LDL levels are greater than 160 mg/dL. A proper diet for these individuals requires a decrease in total fat to less than 30% of total calories with a ratio of monounsaturated:polyunsaturated:saturated fat of 1:1:1. Cholesterol should be reduced to less than 300 mg/day, thus the avoidance of animal products and to increase fiber intake to more than 20 g/day with 6g of soluble fiber/day. Exercise should be promoted, as it can increase HDL. The overall prognosis for these individuals is in the worst-case scenario if uncontrolled and untreated individuals may die before the age of 20, but if one seeks a prudent diet with correct medical intervention, the individual may see an increased incidence of xanthomas with each decade, and Achilles tendinitis and accelerated atherosclerosis will occur.
Type IIb
The high VLDL levels are due to overproduction of substrates, including triglycerides, acetyl-CoA, and an increase in B-100 synthesis. They may also be caused by the decreased clearance of LDL. Prevalence in the population is 10%.
Familial combined hyperlipoproteinemia (FCH)
Lysosomal acid lipase deficiency (often called Cholesteryl ester storage disease)
Secondary combined hyperlipoproteinemia (usually in the context of metabolic syndrome, for which it is a diagnostic criterion)
Type III
This form is due to high chylomicrons and IDL (intermediate density lipoprotein). Also known as broad beta disease or dysbetalipoproteinemia, the most common cause for this form is the presence of ApoE E2/E2 genotype. It is due to cholesterol-rich VLDL (β-VLDL). Its prevalence has been estimated to be approximately 1 in 10,000.It is associated with hypercholesterolemia (typically 8–12 mmol/L), hypertriglyceridemia (typically 5–20 mmol/L), a normal ApoB concentration, and two types of skin signs (palmar xanthomata or orange discoloration of skin creases, and tuberoeruptive xanthomata on the elbows and knees). It is characterized by the early onset of cardiovascular disease and peripheral vascular disease. 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.
Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to decrease free fatty acid production.
Statin drugs, especially the synthetic statins (atorvastatin and rosuvastatin) can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression.
Unclassified familial forms
These unclassified forms are extremely rare:
Hyperalphalipoproteinemia
Polygenic hypercholesterolemia
Acquired (secondary)
Acquired hyperlipidemias (also called secondary dyslipoproteinemias) often mimic primary forms of hyperlipidemia and can have similar consequences. They may result in increased risk of premature atherosclerosis or, when associated with marked hypertriglyceridemia, may lead to pancreatitis and other complications of the chylomicronemia syndrome. The most common causes of acquired hyperlipidemia are:
Diabetes mellitus
Use of drugs such as thiazide diuretics, beta blockers, and estrogensOther conditions leading to acquired hyperlipidemia include:
Hypothyroidism
Kidney failure
Nephrotic syndrome
Alcohol consumption
Some rare endocrine disorders and metabolic disordersTreatment of the underlying condition, when possible, or discontinuation of the offending drugs usually leads to an improvement in the hyperlipidemia.
Another acquired cause of hyperlipidemia, although not always included in this category, is postprandial hyperlipidemia, a normal increase following ingestion of food.
Presentation
Relation to cardiovascular disease
Hyperlipidemia predisposes a person to atherosclerosis. Atherosclerosis is the accumulation of lipids, cholesterol, calcium, fibrous plaques within the walls of arteries. This accumulation narrows the blood vessel and reduces blood flow and oxygen to muscles of the heart. Over time fatty deposits can build up, hardening and narrowing the arteries until organs and tissues dont receive enough blood to properly function. If arteries that supply the heart with blood are affected, a person might have angina (chest pain). Complete blockage of the artery causes infarction of the myocardial cells, also known as heart attack. Fatty buildup in the arteries can also lead to stroke, if a blood clot blocks blood flow to the brain.
Screening
Adults 20 years and older should have the cholesterol checked every four to six years. Serum level of Low Density Lipoproteins (LDL) cholesterol, High Density Lipoproteins (HDL) Cholesterol, and triglycerides are commonly tested in primary care setting using a lipid panel. Quantitative levels of lipoproteins and triglycerides contribute toward cardiovascular disease risk stratification via models/calculators such as Framingham Risk Score, ACC/AHA Atherosclerotic Cardiovascular Disease Risk Estimator, and/or Reynolds Risk Scores. These models/calculators may also take into account of family history (heart disease and/or high blood cholesterol), age, gender, Body-Mass-Index, medical history (diabetes, high cholesterol, heart disease), high sensitivity CRP levels, coronary artery calcium score, and ankle-brachial index. The cardiovascular stratification further determines what medical intervention may be necessary to decrease the risk of future cardiovascular disease.
Total cholesterol
The combined quantity of LDL and HDL. A total cholesterol of higher than 240 mg/dL is abnormal, but medical intervention is determined by the breakdown of LDL and HDL levels.
LDL cholesterol
LDL, commonly known as "bad cholesterol", is associated with increased risk of cardiovascular disease. LDL cholesterol transports cholesterol particles throughout the body, and can build up in the walls of the arteries, making them hard and narrow. LDL cholesterol is produced naturally by the body, but eating a diet high in saturated fat, trans fats, and cholesterol can increase LDL levels. Elevated LDL levels are associated with diabetes, hypertension, hypertriglyceridemia, and atherosclerosis. In a fasting lipid panel, a LDL greater than 160 mg/dL is abnormal.
HDL cholesterol
HDL, also known as "good cholesterol", is associated with decreased risk of cardiovascular disease. HDL cholesterol carries cholesterol from other parts of the body back to the liver and then removes the cholesterol from the body. It can be affected by acquired or genetic factors, including tobacco use, obesity, inactivity, hypertriglyceridemia, diabetes, high carbohydrate diet, medication side effects (beta-blockers, androgenic steroids, corticosteroids, progestogens, thiazide diuretics, retinoic acid derivatives, oral estrogens, etc.) and genetic abnormalities (mutations ApoA-I, LCAT, ABC1). Low level is defined as less than 40 mg/dL.
Triglycerides
Triglyceride level is an independent risk factor for cardiovascular disease and/or metabolic syndrome. Food intake prior to testing may cause elevated levels, up to 20%. Normal level is defined as less than 150 mg/dL. Borderline high is defined as 150 to 199 mg/dL. High level is between 200 and 499 mg/dL. Greater than 500 mg/dL is defined as very high, and is associated with pancreatitis and requires medical treatment.
Screening age
Health organizations does not have a consensus on the age to begin screening for hyperlipidemia. The CDC recommends cholesterol screenings once between ages 9 and 11, once again between 17 and 21, and every 4 to 6 years in adulthood. Doctors may recommend more frequent screenings for people with a family history of early heart attacks, heart disease, or if a child has obesity or diabetes. USPSTF recommends men older than 35 and women older than 45 to be screened. NCE-ATP III recommends all adults older than 20 to be screened as it may lead potential lifestyle modification that can reduce risks of other diseases. However, screening should be done for those with known CHD or risk-equivalent conditions (e.g. Acute Coronary Syndrome, history of heart attacks, Stable or Unstable angina, Transient ischemic attacks, Peripheral arterial disease of atherosclerotic origins, coronary or other arterial revascularization).
Screening frequency
Adults 20 years and older should have the cholesterol checked every four to six years, and most screening guidelines recommends testing every 5 years. USPSTF recommends increased frequency for people with elevated risk of CHD, which may be determined using cardiovascular disease risk scores.
Management
Management of hyperlipidemia includes maintenance of a normal body weight, increased physical activity, and decreased consumption of refined carbohydrates and simple sugars. Prescription drugs may be used to treat some people having significant risk factors, such as cardiovascular disease, LDL cholesterol greater than 190 mg/dL or diabetes. Common medication therapy is a statin.
HMG-CoA reductase inhibitors
Competitive inhibitors of HMG-CoA reductase, such as lovastatin, atorvastatin, fluvastatin, pravastatin, simvastatin, rosuvastatin, and pitavastatin, inhibit the synthesis of mevalonate, a precursor molecule to cholesterol. This medication class is especially effective at decreasing elevated LDL cholesterol. Major side effects include elevated transaminases and myopathy.
Fibric acid derivatives
Fibric acid derivatives, such as gemfibrozil and fenofibrate, function by increasing the lipolysis in adipose tissue via activation of peroxisome proliferator-activated receptor-α. They decrease VLDL – very low density lipoprotein – and LDL in some people. Major side effects include rashes, GI upset, myopathy, or increased transaminases.
Niacin
Niacin, or vitamin B3 has a mechanism of action that is poorly understood, however it has been shown to decrease LDL cholesterol and triglycerides, and increase HDL cholesterol. The most common side effect is flushing secondary to skin vasodilation. This effect is mediated by prostaglandins and can be decreased by taking concurrent aspirin.
Bile acid binding resins
Bile acid binding resins, such as colestipol, cholestyramine, and colesevelam, function by binding bile acids, increasing their excretion. They are useful for decreasing LDL cholesterol. The most common side effects include bloating and diarrhea.
Sterol absorption inhibitors
Inhibitors of intestinal sterol absorption, such as ezetimibe, function by decreasing the absorption of cholesterol in the GI tract by targeting NPC1L1, a transport protein in the gastrointestinal wall. This results in decreased LDL cholesterol.
Prevention
Quitting smoking, lowering intake of saturated fat and alcohol, losing excess body weight, and eating a low-salt diet that emphasizes fruits, vegetables, and whole grains can help reduce blood cholesterol.
See also
List of xanthoma variants associated with hyperlipoproteinemia subtypes
Combined hyperlipidemia
References
== External links == |
Lipedematous alopecia | Lipedematous alopecia is a disorder characterized by a thick boggy scalp and hair loss.
See also
Hot comb alopecia
List of cutaneous conditions
== References == |
Corneal dystrophy | Corneal dystrophy is a group of rare hereditary disorders characterised by bilateral abnormal deposition of substances in the transparent front part of the eye called the cornea.
Signs and symptoms
Corneal dystrophy may not significantly affect vision in the early stages. However, it does require proper evaluation and treatment for restoration of optimal vision. Corneal dystrophies usually manifest themselves during the first or second decade but sometimes later. It appears as grayish white lines, circles, or clouding of the cornea. Corneal dystrophy can also have a crystalline appearance.There are over 20 corneal dystrophies that affect all parts of the cornea. These diseases share many traits:
They are usually inherited.
They affect the right and left eyes equally.
They are not caused by outside factors, such as injury or diet.
Most progress gradually.
Most usually begin in one of the five corneal layers and may later spread to nearby layers.
Most do not affect other parts of the body, nor are they related to diseases affecting other parts of the eye or body.
Most can occur in otherwise totally healthy people, male or female.Corneal dystrophies affect vision in widely differing ways. Some cause severe visual impairment, while a few cause no vision problems and are diagnosed during a specialized eye examination by an ophthalmologist. Other dystrophies may cause repeated episodes of pain without leading to permanent loss of vision.
Genetics
Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Mutations in TGFBI which encodes transforming growth factor beta induced cause several forms of corneal dystrophies including granular corneal dystrophy, lattice corneal dystrophy, epithelial basement membrane dystrophy, Reis-Bucklers corneal dystrophy, and Thiel–Behnke dystrophy.Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or rarely X-linked recessive Mendelian mode of inheritance:
Pathophysiology
A corneal dystrophy can be caused by an accumulation of extraneous material in the cornea, including lipids and cholesterol crystals.
Diagnosis
Diagnosis can be established on clinical grounds and this may be enhanced with studies on surgically excised corneal tissue and in some cases with molecular genetic analyses. As clinical manifestations widely vary with the different entities, corneal dystrophies should be suspected when corneal transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and especially in the presence of a positive family history or in the offspring of consanguineous parents.Superficial corneal dystrophies – Meesmann dystrophy is characterized by distinct tiny bubble-like, punctate opacities that form in the central corneal epithelium and to a lesser extent in the peripheral cornea of both eyes during infancy that persists throughout life. Symmetrical reticular opacities form in the superficial central cornea of both eyes at about 4–5 years of age in Reis-Bücklers corneal dystrophy. Patient remains asymptomatic until epithelial erosions precipitate acute episodes of ocular hyperemia, pain, and photophobia. Visual acuity eventually becomes reduced during the second and third decades of life following a progressive superficial haze and an irregular corneal surface. In Thiel–Behnke dystrophy, sub-epithelial corneal opacities form a honeycomb-shaped pattern in the superficial cornea. Multiple prominent gelatinous mulberry-shaped nodules form beneath the corneal epithelium during the first decade of life in gelatinous drop-like corneal dystrophy which cause photophobia, tearing, corneal foreign body sensation and severe progressive loss of vision. Lisch epithelial corneal dystrophy is characterized by feather shaped opacities and microcysts in the corneal epithelium that are arranged in a band-shaped and sometimes whorled pattern. Painless blurred vision sometimes begins after sixty years of life.Corneal stromal dystrophies – Macular corneal dystrophy is manifested by a progressive dense cloudiness of the entire corneal stroma that usually first appears during adolescence and eventually causing severe visual impairment. In granular corneal dystrophy multiple small white discrete irregular spots that resemble bread crumbs or snowflakes become apparent beneath Bowman zone in the superficial central corneal stroma. They initially appear within the first decade of life. Visual acuity is more or less normal. Lattice dystrophy starts as fine branching linear opacities in Bowmans layer in the central area and spreads to the periphery. Recurrent corneal erosions may occur. The hallmark of Schnyder corneal dystrophy is the accumulation of crystals within the corneal stroma which cause corneal clouding typically in a ring-shaped fashion.Posterior corneal dystrophies – Fuchs corneal dystrophy presents during the fifth or sixth decade of life. The characteristic clinical findings are excrescences on a thickened Descemet membrane (cornea guttae), generalized corneal edema and decreased visual acuity. In advanced cases, abnormalities are found in all the layers of the cornea. In posterior polymorphous corneal dystrophy small vesicles appear at the level of Descemet membrane. Most patients remain asymptomatic and corneal edema is usually absent. Congenital hereditary endothelial corneal dystrophy is characterized by a diffuse ground-glass appearance of both corneas and markedly thickened (2–3 times thicker than normal) corneas from birth or infancy.
Differential diagnosis
Main differential diagnosis include various causes of monoclonal gammopathy, lecithin-cholesterol-acyltransferase deficiency, Fabry disease, cystinosis, tyrosine transaminase deficiency, systemic lysosomal storage diseases, and several skin diseases (X-linked ichthyosis, keratosis follicularis spinolosa decalvans).
Historically, an accumulation of small gray variable shaped punctate opacities of variable shape in the central deep corneal stroma immediately anterior to Descemet membrane were designated deep filiform dystrophy and cornea farinata because of their resemblance to commas, circles, lines, threads (filiform), flour (farina) or dots. These abnormalities are now known to accompany X-linked ichthyosis, steroid sulfatase deficiency, caused by steroid sulfatase gene mutations and are currently usually not included under the rubric of the corneal dystrophies.In the past, the designation vortex corneal dystrophy (corneal verticillata) was applied to a corneal disorder characterized by the presence of innumerable tiny brown spots arranged in curved whirlpool-like lines in the superficial cornea. An autosomal dominant mode of transmission was initially suspected, but later it was realized that these individuals were affected hemizygous males and asymptomatic female carriers of an X-linked systemic metabolic disease caused by a deficiency of α-galactosidase, known as Fabry disease.
Classification
Corneal dystrophies were commonly subdivided depending on its specific location within the cornea into anterior, stromal, or posterior according to the layer of the cornea affected by the dystrophy.In 2015 the ICD3 classification was published. and has classified disease into four groups as follows:
Epithelial and subepithelial dystrophies
Epithelial basement membrane dystrophy
Epithelial recurrent erosion dystrophies (Franceschetti corneal dystrophy, Dystrophia Smolandiensis, and Dystrophia Helsinglandica)
Subepithelial mucinous corneal dystrophy
Meesmann corneal dystrophy
Lisch epithelial corneal dystrophy
Gelatinous drop-like corneal dystrophy
Bowman Layer dystrophies
Reis–Bücklers corneal dystrophy
Thiel–Behnke corneal dystrophy
Stromal dystrophies-
TGFB1 corneal dystrophies
Lattice corneal dystrophy, type 1 variants (III, IIIA, I/IIIA, IV) of lattice corneal dystrophy
Granular corneal dystrophy, type 1
Granular corneal dystrophy, type 2
Stromal dystrophies
Macular corneal dystrophy
Schnyder crystalline corneal dystrophy
Congenital stromal corneal dystrophy
Fleck corneal dystrophy
Posterior amorphous corneal dystrophy
Central cloudy dystrophy of François
Pre-Descemet corneal dystrophy
Endothelial dystrophies
Fuchs dystrophy
Posterior polymorphous corneal dystrophy
Congenital hereditary endothelial dystrophy
X-linked endothelial corneal dystrophyThe following (now historic) classification was by Klintworth:Superficial dystrophies:
Epithelial basement membrane dystrophy
Meesmann juvenile epithelial corneal dystrophy
Gelatinous drop-like corneal dystrophy
Lisch epithelial corneal dystrophy
Subepithelial mucinous corneal dystrophy
Reis-Bucklers corneal dystrophy
Thiel–Behnke dystrophyStromal dystrophies:
Lattice corneal dystrophy
Granular corneal dystrophy
Macular corneal dystrophy
Schnyder crystalline corneal dystrophy
Congenital stromal corneal dystrophy
Fleck corneal dystrophyPosterior dystrophies:
Fuchs dystrophy
Posterior polymorphous corneal dystrophy
Congenital hereditary endothelial dystrophy
Treatment
Early stages may be asymptomatic and may not require any intervention. Initial treatment may include hypertonic eyedrops and ointment to reduce the corneal edema and may offer symptomatic improvement prior to surgical intervention.Suboptimal vision caused by corneal dystrophy may be helped with scleral contact lenses but eventually usually requires surgical intervention in the form of corneal transplantation. Penetrating keratoplasty, a common type of corneal transplantation, is commonly performed for extensive corneal dystrophy.With penetrating keratoplasty (corneal transplant), the long-term results are good to excellent. Recent surgical improvements have been made which have increased the success rate for this procedure. However, recurrence of the disease in the donor graft may happen. Superficial corneal dystrophies do not need a penetrating keratoplasty as the deeper corneal tissue is unaffected, therefore a lamellar keratoplasty may be used instead.Phototherapeutic keratectomy (PTK) can be used to excise or ablate the abnormal corneal tissue. Patients with superficial corneal opacities are suitable candidates for this procedure.
See also
Recurrent corneal erosion
Keratoconus
Keratoglobus
Corneal dystrophies in dogs
Dyskeratosis corneal and photophobia in XLPDR
== References == |
Chronic diarrhea of infancy | Chronic diarrhea (alternate spelling: diarrhoea) of infancy, also called toddlers diarrhea, is a common condition typically affecting up to 1.7 billion children between ages 6–30 months worldwide every year, usually resolving by age 4. According to the World Health Organization (WHO), diarrheal disease is the second greatest cause of death in children 5 years and younger. Diarrheal disease takes the lives of 525,000 or more children per year. Diarrhea is characterized as the condition of passing of three or more loose or watery bowel movements within a day sometimes with undigested food visible. Diarrhea is separated into three clinical categories; acute diarrhea may last multiple hours or days, acute bloody diarrhea, also known as dysentery, and finally, chronic or persistent diarrhea which lasts 2–4 weeks or more. There is normal growth with no evidence of malnutrition in the child experiencing persistent diarrhea. In chronic diarrhea there is no evidence of blood in the stool and there is no sign of infection. The condition may be related to irritable bowel syndrome. There are various tests that can be performed to rule out other causes of diarrhea that dont fall under the chronic criteria, including blood test, colonoscopy, and even genetic testing. Most acute or severe cases of diarrhea have treatment guidelines revolving around prescription or non prescription (also known as over the counter or OTC) medications based on the cause, but the treatment protocols for chronic diarrhea focus on replenishing the body with lost fluids and electrolytes, because there typically isnt a treatable cause.
Signs and Symptoms
Toddlers diarrhea is characterized by three or more watery stools per day that persist for 2–4 weeks or more. Newborns and infants may normally have soft and frequent stools; however, any noticeable changes in stool frequency or form (i.e. watery) can indicate toddlers diarrhea. Other symptoms may include chills, fever, abdominal pain or cramping, nausea, and/or vomiting. Undigested food and/or mucus may also be observed in stools. More serious symptoms may include bloody stools, weight loss, greasy stools, and/or severe abdominal pain.Aside from these signs and symptoms, infants and children present as healthy individuals with appropriate weight gain (considering sufficient calorie intake), active lifestyles, and normal appetites.
Complications
Possible complications associated with toddlers diarrhea include malabsorption and dehydration.Malabsorption affects the small intestine and results in the impaired absorption of important nutrients from an infant or childs diet, leading to malnutrition. Malabsorption is indicated by symptoms of bloating, appetite changes, weight loss, and/or gas.Dehydration occurs when there is not enough fluid intake to compensate for increased loss of fluid and electrolytes that may result from chronic diarrhea. Dehydration is indicated by symptoms of thirst, absence of tears when crying, infrequent urination, dry mouth, and/or decreased energy.
Cause
Diarrhea happens when the amount of fluids absorbed in the intestine does not match the amount secreted. The imbalance can be achieved in two ways: an excess of secretion or a lack of absorption. Thus, diarrhea can be categorized into secretory diarrhea, an excess of secretion, or osmotic diarrhea which is a lack of absorption. Usually both categories are present in chronic diarrhea of infants.Secretory diarrhea can be caused by either infectious or non-infectious agents. Infectious agents include bacteria, viruses, and protozoans while non-infectious agents can be hormones, neurotransmitters, cytokines, and others. Osmotic diarrhea occurs when nutrients that are not absorbed exists in the intestines, typically due to damage to the intestines. The nutrients that are unable to be absorbed in the intestines draws water to itself.Some factors that lead to chronic diarrhea of infancy:
Underdeveloped digestive system, nutrients do not spend adequate time in the digestive tract for water to be absorbed which leads to diarrhea.
Imbalanced Diet - a diet that has excess fiber and/or a lack of fat, fat can slow down the digestion process and prolong the amount of time nutrients spend in the tract which increases absorption. Fiber can lead to diarrhea because it shortens the amount of time food spends in the intestines, decreasing absorption.
Inability to absorb carbohydratesThe specific source of chronic diarrhea typically depends on the age of the infant/child. Diarrhea is uncommon for newborns; consequently, its presence in newborns could indicate a congenital disorder which would need hospitalization. Rare causes of chronic diarrhea in young children include a group of genetic mutations known as "congenital diarrhea and enteropathies" (CODEs). This group of genetic disorders usually presents in the first weeks of birth as severe and debilitating diarrhea and can lead to malabsorption, growth failure, and difficulty feeding. CODEs are rare genetic changes to a single gene that affects the lining of the intestine or changes to the immune system that also affects the cell function of important nutrient and electrolyte transporters in the intestine such as Cl−/HCO3− mutation.Otherwise, socioeconomic factors and access to treatment/healthcare play a significant part in developing chronic diarrhea as an infant. For instance, leading causes of chronic diarrhea in developing countries are infections of the intestine. In developed countries, chronic diarrhea has a diverse range of causes such as chronic infection of the intestines, autoimmune enteropathy, and inability to absorb nutrients via celiac disease, food sensitivities, etc.From age 0–30 days, typical causes are:
Abetalipoproteinemia, a condition caused by a genetic mutation that creates abnormal absorption of fats and some vitamins.
Acrodermatitis enteropathica, a condition in which the intestine cannot absorb zinc.
Autoimmune enteropathy, a rare condition in which the intestines are perceived as a foreign threat by the immune system and are attacked leading to irritation and inflammation.
Microvillous inclusion disease, a condition caused by a genetic mutation leading to severe diarrhea because intestinal cells did not have normal development and thus the intestines are not able to absorb nutrients properly.
Congenital chloride diarrhea, a lifelong condition caused by a genetic mutation that leads to diarrhea with a high concentration of chloride.
Congenital sodium diarrhea, a genetic disorder caused by mutations in electrolyte transporters that disrupt the transport of Na+ across the intestine and results in high levels of Na+ greater than 145 mM in the stool.
Congenital short-bowel syndrome, a condition in which a portion of the small intestine is absent or not functioning properly leading to decreased absorption of both fluids and nutrients.
Congenital lactase deficiency, a condition caused by a genetic mutation in which the body cannot digest lactose properly.
Glucose-galactose malabsorption, a genetic disorder caused by changes in a protein critical for the transport of glucose and galactose across the intestine which leads to impaired glucose/galactose absorption, dehydration, and severe diarrhea in young children. Typically, the severe diarrhea improves with a diet low in glucose/galactose and the tolerability to glucose/galactose improves with age.
Hirschsprungs disease (HSCR), a gut motility disorder characterized by a lack of nerve cells in the large intestine which are needed to move the stool through the digestive tract. In infants, HSCR typically presents when a newborn is unable to pass the first feces, or meconium within 48 hours of birth. Other symptoms include blockage of the intestine, fever, rapid release of stool and flatulence upon rectal examination, and may present with diarrhea in infants.
Intestinal pseudo-obstruction (IPO), a gut motility disorder characterized by the inability to contract intestinal walls with symptoms similar to intestinal obstruction but lack a distinguishable cause of obstruction. Signs and symptoms include abdominal pain, dilated or enlarged bowel, constipation and may include diarrhea. Although rare in infants, IPO is a type of congenital disorder that may present with diarrhea in infants.
Primary bile acid malabsorption, a gut defect in the reabsorption of bile acids in the small intestine which results in increased levels of bile acids in the colon leading to watery diarrhea and bloating.
Chronic infection of C. difficile, G. lamblia
C. difficile - bacteria that can be the source of diarrhea.
G. lamblia - a parasite that can be the source diarrhea.From 1–12 months, typical causes of chronic diarrhea are the following:
Acrodermatitis enteropathica, a condition in which the intestine cannot absorb zinc.
Cystic fibrosis, a condition caused by a genetic mutation that can lead to injury to the bodys organs including the lungs and those in the digestive system.
Apple juice and pear nectar, the digestive tract of children have difficulty absorbing significant quantities of sugars and carbohydrates which certain fruit juices can have.
Celiac Disease, a disorder in which there is an immune response to eating gluten which can eventually cause damage to the small intestine over time and impedes absorption.
Food allergy.Most instances of chronic diarrhea in infancy are caused by infectious and post infectious disease of the intestine as well as food sensitivities or allergies.
Diagnosis
Diagnosis of toddlers diarrhea involves the evaluation of history of present illness, any relevant past medical history, and physical examination to determine any causative factors to inform treatment regimens and further recommendations.Evaluation of history of present illness includes:
Stool characterization (i.e. appearance, consistency, frequency, etc.)
Time frame and duration (important for differentiation between acute and chronic diarrhea)
Food/drink allergies or restrictions (e.g. lactose intolerance)
Medications, especially antibiotics
Infection exposure (e.g. travel)Evaluation of past medical history includes:
Family history
Conditions such as inflammatory bowel disease, cystic fibrosis, and celiac diseasePhysical examination involves:
Abdominal examination (tenderness, distention, and/or bowel sounds)
Genital examination (rashes, anal fissures, and/or ulcerative lesions)
General assessment and vital signs (any signs of dehydration such as tachycardia and low blood pressure)
Examination of extremities and head (any signs of dehydration such as dry mucous membranes and skin turgor)
Diagnostic Tests
The following tests can also be performed to assist in the diagnosis of toddlers diarrhea and evaluation of any associated complications/underlying conditions:
Stool tests provide further information about bleeding, infectious agents, and/or anatomical problems.
Blood tests allow assessment of inflammatory markers and/or other criterion for causative diseases.
X-rays provide evaluations of any problems that may originate in the gastrointestinal tract/liver/etc.
Upper endoscopy or colonoscopy allows visualization of the gastrointestinal tract to assess location of inflammation.
Breath hydrogen tests are utilized to determine lactose, fructose, and/or sucrose intolerance. Small intestinal bacterial overgrowth (SIBO) may also be indicated by this test.
Genetic Testing
Most commonly, chronic diarrhea in infants and children are classified as acquired diarrhea, identified with the general diagnostic tests mentioned above. The other classification of chronic diarrhea, congenital diarrheas and enteropathies (CODEs), are rare diagnoses of exclusion. With recent advances in genome sequencing, the addition of targeted genetic testing to diagnostic algorithms has been proposed to allow faster diagnoses and earlier treatment of CODEs. While certain genes and mutations have been associated with various CODEs, further research and studies are necessary to support the role of diagnostic genetic testing.
Treatment
According to doctors of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), treating the cause of chronic diarrhea in infants is primarily through diet (e.g. avoiding foods their bodies dont tolerate such as gluten, lactose, fructose, and sucrose). Dietary fiber and fat can be increased and fluid intake, especially fruit juice intake, decreased. With these considerations, NIDDK doctors recommend that children consume a normal balanced diet based on their age to avoid malnutrition or growth restriction.Non-prescription medications such as loperamide are not recommended by the Centers for Disease Control and Prevention for children below 6 years of age as they dont address the underlying cause of the condition. According to Benjamin Ortiz, M.D., a pediatrician in the Food and Drug Administrations Office of Pediatric Therapeutics, bismuth subsalicylate is not recommended in children below 12 years of age because its contents, including magnesium, aluminum, and bismuth, are not readily cleared from their bodies, making them more susceptible to harm.Studies have shown that certain probiotic preparations such as Lactobacillus rhamnosus (a bacterium) and Saccharomyces boulardii (a yeast) may be effective at reducing the duration and severity of diarrhea in acute settings as a result of gastroenteritis, while other studies have found that the use of probiotics doesnt have an effect on the length of diarrhea in toddlers.While treatments for chronic diarrhea of infancy arent clear cut, it is crucial to address the complications of dehydration that may arise from chronic diarrhea with the American Academy of Pediatrics (AAP) guidelines recommendation of oral rehydration therapy (ORT). Oral rehydration solution (ORS), recommended by both AAP and the World Health Organization (WHO), must be composed of 50-90mEq/L sodium and 2% glucose or other complex carbohydrates. ORS is easily found in the US because it is available without a prescription. The typical amount of ORS administered is 50mL/kg over a 4-hour time period for mild dehydration and 100mL/kg over a 4-hour time period for moderate dehydration with an extra 10mL/kg for every loose stool. Repeat this administration regimen for as long as the signs and symptoms of dehydration continue. It is important to take measures early on to maintain hydration. Along with ORT, WHO recommends a 10-14 day course of 20 mg zinc tablet supplementation, stating it will shorten the length of diarrhea and potentially improving harmful outcomes.The NIDDK recommends a visit to the doctor when a child experiences stools containing pus or blood (black, tarry, or coffee ground-like appearance), signs of dehydration, diarrhea longer than 24 hours, or a fever of 102 degrees or more.
Epidemiology
Diarrheal illness in children accounts for 1.5 to 2.5 million deaths per year worldwide. It is responsible for the secondary cause of mortality among children less than 5 years of age surpassing the combined childhood deaths from malaria, measles, and AIDS. In 2009, the World Health Organization (WHO)/United Nations International Childrens Emergency Fund (UNICEF) reported 2.5 billion cases of diarrhea in children less than 5 years old. More than half of the cases occurred in Africa and South Asia. It is estimated that Africa and South Asia comprise more than 80% of deaths from diarrhea in children. In fact, about 75% of the childhood deaths from diarrhea come from only 15 countries. According to the World Health Organization (WHO), the proportion of deaths attributable to diarrheal illness among children less than 5 years of age was 13.2% in 2002. Half of these childhood deaths were due to chronic diarrheal causes.Worldwide, studies estimate that diarrheal illness affects 3 to 20% of children under the age of 5 with an incidence of 2.7 episodes of diarrhea per child-year. Developing nations experience higher burden of disease and mortality from chronic diarrhea in children compared to developed nations. In the United States, it is reported that 15 to 20% of young children have an episode of acute diarrhea each year. Compared to worldwide estimates, the United States has a lower incidence rate of chronic diarrhea in young children reported at 0.18 episodes per child year. In pediatrics, diarrhea is a common complaint making up 9% of U.S. hospital visits for children less than 5 years old. In contrast to resource-poor nations, resource-rich nations such as the United States experience less chronic diarrhea severity. In the United States, approximately a quarter of chronic diarrhea cases in young children seek medical care and less than 1% of cases are hospitalized.
== References == |
Orofaciodigital syndrome | Orofaciodigital syndrome or oral-facial-digital syndrome is a group of at least 13 related conditions that affect the development of the mouth, facial features, and digits in between 1 in 50,000 to 250,000 newborns with the majority of cases being type I (Papillon-League-Psaume syndrome).
Type
The different types are:s
Type I, Papillon-League-Psaume syndrome
Type II, Mohr syndrome
Type III, Sugarman syndrome
Type IV, Baraitser-Burn syndrome
Type V, Thurston syndrome
Type VI, Varadi-Papp syndrome
Type VII, Whelan syndrome
Type VIII, Oral-facial-digital syndrome, Edwards type (not to be confused with Edwards syndrome)
Type IX, OFD syndrome with retinal abnormalities
Type X, OFD with fibular aplasia
Type XI, Gabrielli syndrome
References
== External links == |
Parathyroid carcinoma | Parathyroid carcinoma is a rare cancer resulting in parathyroid adenoma to carcinoma progression. It forms in tissues of one or more of the parathyroid glands (four pea-sized glands in the neck that make parathyroid hormone (PTH). PTH helps the body maintain normal levels of serum calcium by promoting calcium reabsorption from bone. It is antagonized by the hormone calcitonin, which prompts calcium storage.).
It is rare, and much less common than parathyroid adenoma.
It can be difficult to excise.
Signs and symptoms
Most patients experience moderate to severe hypercalcemia and high parathyroid hormone levels. A large mass in the neck is often seen, and kidney and bone abnormalities are common.
Risk factors
Parathyroid cancer occurs in midlife at the same rate in men and women.Conditions that appear to result in an increased risk of parathyroid cancer include multiple endocrine neoplasia type 1, autosomal dominant familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumor syndrome (which also is hereditary). Parathyroid cancer has also been associated with external radiation exposure, but, most reports describe an association between radiation and the more common parathyroid adenoma.
Diagnosis
On Sestamibi parathyroid scan, intense radioactivity greater than submandibular gland on delayed image, no washout between early and delayed images, and high concentration of parathyroid hormone concentration in blood in those who age more than 40 years is suggestive of parathyroid carcinoma. Some authors suggest high levels of HCG as a marker for parathyroid carcinoma in the right context. However, other thyroid diseases such as multinodular goitre, Hashimoto thyroiditis, thyroid adenoma, and thyroid carcinoma also retains the radiotracer because of high metabolic nature of these diseases. Thus, the final diagnosis always requires pathological examination of the tissue in question.
Treatment
Parathyroid carcinoma is sometimes diagnosed during surgery for primary hyperparathyroidism. If the surgeon suspects carcinoma based on severity or invasion of surrounding tissues by a firm parathyroid tumor, aggressive excision is performed, including the thyroid and surrounding tissues as necessary.Agents such as calcimimetics (for example, cinacalcet) are used to mimic calcium and are able to activate the parathyroid calcium-sensing receptor (making the parathyroid gland "think" we have more calcium than we actually do), therefore lowering the calcium level, in an attempt to decrease the hypercalcemia.
References
External links
Parathyroid cancer entry in the public domain NCI Dictionary of Cancer Terms
Parathyroid Carcinoma (Medscape eMedicine)
Cancer Management Handbook: Thyroid and Parathyroid Cancers
This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms". |
Shoulder impingement syndrome | Shoulder impingement syndrome is a syndrome involving tendonitis (inflammation of tendons) of the rotator cuff muscles as they pass through the subacromial space, the passage beneath the acromion. It is particularly associated with tendonitis of the supraspinatus muscle. This can result in pain, weakness, and loss of movement at the shoulder.
Signs and symptoms
The most common symptoms in impingement syndrome are pain, weakness and a loss of movement at the affected shoulder. The pain is often worsened by shoulder overhead movement and may occur at night, especially when lying on the affected shoulder. The onset of the pain may be acute if due to an injury or insidious if due to a gradual process such as an osteoarthritic spur. The pain has been described as dull rather than sharp, and lingers for long periods of time, making it hard to fall asleep. Other symptoms can include a grinding or popping sensation during movement of the shoulder.The range of motion at the shoulder may be limited by pain. A painful arc of movement may be present during forward elevation of the arm from 60° to 120°. Passive movement at the shoulder will appear painful when a downward force is applied at the acromion but the pain will ease once the force is removed.
Causes
When the arm is raised, the subacromial space (gap between the anterior edge of the acromion and the head of the humerus) narrows; the supraspinatus muscle tendon passes through this space. Anything that causes further narrowing has the tendency to impinge the tendon and cause an inflammatory response, resulting in impingement syndrome. Such causes can be bony structures such as subacromial spurs (bony projections from the acromion), osteoarthritic spurs on the acromioclavicular joint, and variations in the shape of the acromion. Thickening or calcification of the coracoacromial ligament can also cause impingement. Loss of function of the rotator cuff muscles, due to injury or loss of strength, may cause the humerus to move superiorly, resulting in impingement. Inflammation and subsequent thickening of the subacromial bursa may also cause impingement.Weight training exercises where the arms are elevated above shoulder height but in an internally rotated position such as the upright row have been suggested as a cause of subacromial impingement. Another common cause of Impingement syndrome is restrictions in the range movement of the scapulo-thoracic surfaces. Commonly, one or more ribs between rib 2 and rib 7/8 on the side of the impingement may jut out slightly and/or feel hard when the person springs on it or them. When this occurs, the scapula is raised and anteverted (angled forwards). This in turn pushes the acromion and the humeral head out of its usual anatomical position placing pressure downwards at the head of the humerus at the position of the nerve thus causing the impingement syndrome. This is visibly demonstrated by a slightly raised and protracted shoulder girdle. Note: the humerus anteverts in this position causing a more protrusive section of the humerus to press upwards towards the acromion.
Mechanism
The scapula plays an important role in shoulder impingement syndrome. It is a wide, flat bone lying on the posterior thoracic wall that provides an attachment for three different groups of muscles. The intrinsic muscles of the scapula include the muscles of the rotator cuff- the subscapularis, infraspinatus, teres minor and supraspinatus. These muscles attach to the surface of the scapula and are responsible for the internal and external rotation of the glenohumeral joint, along with humeral abduction. The extrinsic muscles include the biceps, triceps, and deltoid muscles and attach to the coracoid process and supraglenoid tubercle of the scapula, infraglenoid tubercle of the scapula, and spine of the scapula. These muscles are responsible for several actions of the glenohumeral joint. The third group, which is mainly responsible for stabilization and rotation of the scapula, consists of the trapezius, serratus anterior, levator scapulae, and rhomboid muscles and attach to the medial, superior, and inferior borders of the scapula. Each of these muscles has its own role in shoulder function and must be in balance with the others in order to avoid shoulder pathology.
Abnormal scapular function is called scapular dyskinesis. One action the scapula performs during a throwing or serving motion is elevation of the acromion process in order to avoid impingement of the rotator cuff tendons. If the scapula fails to properly elevate the acromion, impingement may occur during the cocking and acceleration phase of an overhead activity. The two muscles most commonly inhibited during this first part of an overhead motion are the serratus anterior and the lower trapezius. These two muscles act as a force couple within the glenohumeral joint to properly elevate the acromion process, and if a muscle imbalance exists, shoulder impingement may develop.
The scapula may also be misplaced if a rib deep to it is not moving correctly. Often in the case of Shoulder impingement syndrome, the scapula may be anteverted such that the shoulder on the affected side appears protracted. The ribs that may cause such an anteversion of the scapula include ribs 2–8.
Diagnosis
Impingement syndrome can be diagnosed by a targeted medical history and physical examination, but it has also been argued that at least medical imaging (generally X-ray initially) and/or response to local anesthetic injection is necessary for workup.
On physical exam, the physician may twist or elevate the patients arm to test for reproducible pain (the Neer sign and Hawkins-Kennedy test). These tests help localize the pathology to the rotator cuff; however, they are not specific for impingement. Neer sign may also be seen with subacromial bursitis.
Response to local anesthetic
The physician may inject lidocaine (usually combined with a steroid) into the bursa, and if there is an improved range of motion and decrease in pain, this is considered a positive "Impingement Test". It not only supports the diagnosis for impingement syndrome, but it is also therapeutic.
Imaging
Plain x-rays of the shoulder can be used to detect some joint pathology and variations in the bones, including acromioclavicular arthritis, variations in the acromion, and calcification. However, x-rays do not allow visualization of soft tissue and thus hold a low diagnostic value. Ultrasonography, arthrography and MRI can be used to detect rotator cuff muscle pathology. MRI is the best imaging test prior to arthroscopic surgery. Due to lack of understanding of the pathoaetiology, and lack of diagnostic accuracy in the assessment process by many physicians, several opinions are recommended before intervention.
Treatment
Impingement syndrome is usually treated conservatively, but sometimes it is treated with arthroscopic surgery or open surgery. Conservative treatment includes rest, cessation of painful activity, and physical therapy. Physical therapy treatments would typically focus at maintaining range of movement, improving posture, strengthening shoulder muscles, and reduction of pain. NSAIDs and ice packs may be used for pain relief.Therapeutic exercises might be favorable intervention compared to passive treatment approaches, electrotherapy and placebo. A recent meta-analysis done on rotator cuff tendinopathy has shown that nearly all types of active resistance training programs were proven to be effective in improving pain and shoulder function with no significant differences among the different exercise types, further cementing the favorability of a more active intervention over passive modalities when it comes to rotator cuff issues. Exercises may help to regain the scapulo-humeral rhythm and scapular control which may reduce pain.
Steroids
Therapeutic injections of corticosteroid and local anaesthetic may be used for persistent impingement syndrome. The total number of injections is generally limited to three due to possible side effects from the corticosteroid. A 2017 review found corticosteroid injections only give small and transient pain relief.
Surgery
A number of surgical interventions are available, depending on the nature and location of the pathology. Surgery may be done arthroscopically or as open surgery. The impinging structures may be removed in surgery, and the subacromial space may be widened by resection of the distal clavicle and excision of osteophytes on the under-surface of the acromioclavicular joint. Damaged rotator cuff muscles can be surgically repaired.
A 2019 review found that the evidence does not support decompression surgery in those with more than 3 months of shoulder pain without a history of trauma. A recent metaanalysis has further supported that early SIS would likely benefit from non-operative treatment modalities and surgical open decompression should be considered only with chronic presentation.
History
Impingement syndrome was reported in 1852. Impingement of the shoulder was previously thought to be precipitated by shoulder abduction and surgical intervention focused on lateral or total acromionectomy. In 1972, Charles Neer proposed that impingement was due to the anterior third of the acromion and the coracoacromial ligament and suggested surgery should be focused on these areas. The role of anteriorinferior aspect of the acromion in impingement syndrome and excision of parts of the anteriorinferior acromion has become a pivotal part of the surgical treatment of the syndrome.
Criticism
Subacromial impingement is not free of criticism. First, the identification of acromion type shows poor intra- and inter-observer reliability. Second, a computerized three-dimensional study failed to support impingement by any portion of the acromion on the rotator cuff tendons in different shoulder positions. Third, most partial-thickness cuff tears do not occur on bursal surface fibers, where mechanical abrasion from the acromion does occur. Fourth, it has been suggested that bursal surface cuff tears could be responsible for subacromial spurs and not the opposite. And finally, there is growing evidence that routine acromioplasty may not be required for successful rotator cuff repair, which would be an unexpected finding if acromial shape had a major role in generating tendon lesions. In summary, despite being a popular theory, the bulk of evidence suggest that subacromial impingement probably does not play a dominant role in many cases of rotator cuff disease.
See also
Milwaukee shoulder syndrome
References
== External links == |
Congenital lip pit | A congenital lip pit or lip sinus is a congenital disorder characterized by the presence of pits and possibly associated fistulas in the lips. They are often hereditary, and may occur alone or in association with cleft lip and palate, termed Van der Woude syndrome.
Diagnosis
Classification
They are divided into three types based on their location:
commissural pits, which are small pits near the labial commissure of the mouth,
a pit in the upper lip, in which case it may be called a midline sinus of the upper lip, and
pits in the lower lip, in which case it may be called a congenital sinus of the lower lip.In some cases commissural pits have been reported in combination with preauricaluar pits, which are near the ear.
Treatment
Lip pits do not usually require any treatment, although in some reported cases surgical excision has been used or if associated with a draining sinus tract.
See also
Skin dimple
References
== External links == |
Subsets and Splits
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