page_title
stringlengths 1
91
| page_text
stringlengths 0
34.2k
|
|---|---|
Cephalopelvic disproportion | Cephalopelvic disproportion exists when the capacity of the pelvis is inadequate to allow the fetus to negotiate the birth canal. This may be due to a small pelvis, a nongynecoid pelvic formation, a large fetus, an unfavorable orientation of the fetus, or a combination of these factors. Certain medical conditions may distort pelvic bones, such as rickets or a pelvic fracture, and lead to CPD.
Transverse diagonal measurement has been proposed as a predictive method.
Causes
A large fetus can be one cause of CPD. A large fetus can be caused by gestational diabetes, postterm pregnancy, genetic factors, and multiparity.
The shape of the pelvis can also be a cause of CPD. The pelvis may be too small, or the shape of the pelvis may be malformed. Shorter women are more likely to have CPD as are adolescents.
Diagnosis
Diagnosis of CPD may be made when there is failure to progress, but not all cases of prolonged labour are the result of CPD. Use of ultrasound to measure the size of the fetus in the womb is controversial, as these methods are often inaccurate and may lead to unnecessary caesarian section; a trial of labour is often recommended even if size of the fetus is estimated to be large.Theoretically, pelvimetry may identify cephalo-pelvic disproportion. However, a womans pelvis loosens up before birth (with the help of hormones). A Cochrane review in 2017 found that there was too little evidence to show whether pelvimetry is beneficial and safe when the baby is in cephalic presentation. A review in 2003 came to the conclusion that pelvimetry does not change the management of pregnant women, and recommended that all women should be allowed a trial of labor regardless of pelvimetry results. It considered routine performance of pelvimetry to be a waste of time, a potential liability, and an unnecessary discomfort.
Treatment
In the case of a fetus being too large, some obstetricians recommend induction of labour for earlier delivery. Diagnosis of CPD in active labour will usually result in a Caesarian section.
See also
Trial of labour
References
== External links == |
Porokeratosis | Porokeratosis is a specific disorder of keratinization that is characterized histologically by the presence of a cornoid lamella, a thin column of closely stacked, parakeratotic cells extending through the stratum corneum with a thin or absent granular layer.: 532
Types
Porokeratosis may be divided into the following clinical types:: 532
Plaque-type porokeratosis (also known as "Classic porokeratosis" and "Porokeratosis of Mibelli") is characterized by skin lesions that start as small, brownish papules that slowly enlarge to form irregular, annular, hyperkeratotic or verrucous plaques.: 533 : 566 Sometimes they may show gross overgrowth and even horn-like structures may develop. Skin malignancy, although rare, is reported from all types of porokeratosis. Squamous cell carcinomas have been reported to develop in Mibellis type porokeratosis over partianal areas involving anal mucosa. This was the first report mentioning mucosal malignancy in any form of porokeratosis.
Disseminated superficial porokeratosis is a more generalized processes and involves mainly the extremities in a bilateral, symmetric fashion.: 533 In about 50% of cases, skin lesions only develop in sun-exposed areas, and this is referred to as disseminated superficial actinic porokeratosis: 533
Porokeratosis palmaris et plantaris disseminata is characterized by skin lesions that are superficial, small, relatively uniform, and demarcated by a distinct peripheral ridge of no more than 1mm in height.: 534 : 1668 : 567
Linear porokeratosis is characterized clinically skin lesions are identical to those of classic porokeratosis, including lichenoid papules, annular lesions, hyperkeratotic plaques with central atrophy, and the characteristic peripheral ridge.: 1668 : 567
Punctate porokeratosis is a skin condition associated with either classic porokeratosis or linear porokeratosis types of porokeratosis, and is characterized by multiple, minute, and discrete punctate, hyperkeratotic, seed-like skin lesions surrounded by a thin, raised margin on the palms and soles.: 535 : 1668
Porokeratosis plantaris discreta is a skin condition that occurs in adults, with a 4:1 female preponderance, characterized by a sharply marginated, rubbery, wide-based papules.: 213 It is also known as "Steinbergs lesion". It was characterized in 1970.
Genetics
Linear porokeratosis has been associated with mutations in the PMVK and MVD genes. The PMVK gene encodes the enzyme phosphomevalonate kinase and the MVD gene encodes the enzyme diphosphomevalonate decarboxylase.
Diagnosis
Pathology
Porokeratosis has a characteristic histomorphologic feature known as a cornoid lamella.
Treatment
Dermabrasion
See also
List of cutaneous conditions
List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer
References
External links
Database of rare diseases at Orphanet
NIHs Genetic and Rare Diseases Information Center |
Myopathy | In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. Myopathy means muscle disease (Greek : myo- muscle + patheia -pathy : suffering). This meaning implies that the primary defect is within the muscle, as opposed to the nerves ("neuropathies" or "neurogenic" disorders) or elsewhere (e.g., the brain). Muscle cramps, stiffness, and spasm can also be associated with myopathy.
Capture myopathy can occur in wild or captive animals, such as deer and kangaroos, and leads to morbidity and mortality. It usually occurs as a result of stress and physical exertion during capture and restraint.
Muscular disease can be classified as neuromuscular or musculoskeletal in nature. Some conditions, such as myositis, can be considered both neuromuscular and musculoskeletal.
Signs and symptoms
Common symptoms include muscle weakness, cramps, stiffness, and tetany.
Systemic diseases
Myopathies in systemic disease results from several different disease processes including endocrine, inflammatory, paraneoplastic, infectious, drug- and toxin-induced, critical illness myopathy, metabolic, collagen related, and myopathies with other systemic disorders. Patients with systemic myopathies often present acutely or sub acutely. On the other hand, familial myopathies or dystrophies generally present in a chronic fashion with exceptions of metabolic myopathies where symptoms on occasion can be precipitated acutely. Most of the inflammatory myopathies can have a chance association with malignant lesion; the incidence appears to be specifically increased only in patients with dermatomyositis.There are many types of myopathy. ICD-10 codes are provided here where available.
Inherited forms
(G71.0) Dystrophies (or muscular dystrophies) are a subgroup of myopathies characterized by muscle degeneration and regeneration. Clinically, muscular dystrophies are typically progressive, because the muscles ability to regenerate is eventually lost, leading to progressive weakness, often leading to use of a wheelchair, and eventually death, usually related to respiratory weakness.
(G71.1) Myotonia
Neuromyotonia
(G71.2) The congenital myopathies do not show evidence for either a progressive dystrophic process (i.e., muscle death) or inflammation, but instead characteristic microscopic changes are seen in association with reduced contractile ability of the muscles. Congenital myopathies include, but are not limited to:
(G71.2) nemaline myopathy (characterized by presence of "nemaline rods" in the muscle),
(G71.2) multi/minicore myopathy (characterized by multiple small "cores" or areas of disruption in the muscle fibers),
(G71.2) centronuclear myopathy (or myotubular myopathy) (in which the nuclei are abnormally found in the center of the muscle fibers), a rare muscle wasting disorder
(G71.3) Mitochondrial myopathies, which are due to defects in mitochondria, which provide a critical source of energy for muscle
(G72.3) Familial periodic paralysis
(G72.4) Inflammatory myopathies, which are caused by problems with the immune system attacking components of the muscle, leading to signs of inflammation in the muscle
(G73.6) Metabolic myopathies, which result from defects in biochemical metabolism that primarily affect muscle
(G73.6/E74.0) Glycogen storage diseases, which may affect muscle
(G73.6/E75) Lipid storage disorder
(G72.89) Other myopathies
Brody myopathy
Congenital myopathy with abnormal subcellular organelles
Fingerprint body myopathy
Inclusion body myopathy 2
Megaconial myopathy
Myofibrillar myopathy
Rimmed vacuolar myopathy
Acquired
(G72.0 - G72.2) External substance induced myopathy
(G72.0) Drug-induced myopathy
Glucocorticoid myopathy is caused by this class of steroids increasing the breakdown of the muscle proteins leading to muscle atrophy.
(G72.1) Alcoholic myopathy
(G72.2) Myopathy due to other toxic agents - including atypical myopathy in horses caused by toxins in sycamore seeds and seedlings.
(M33.0-M33.1)
Dermatomyositis produces muscle weakness and skin changes. The skin rash is reddish and most commonly occurs on the face, especially around the eyes, and over the knuckles and elbows. Ragged nail folds with visible capillaries can be present. It can often be treated by drugs like corticosteroids or immunosuppressants. (M33.2)
Polymyositis produces muscle weakness. It can often be treated by drugs like corticosteroids or immunosuppressants.
Inclusion body myositis is a slowly progressive disease that produces weakness of hand grip and straightening of the knees. No effective treatment is known.
(M61) Myositis ossificans
(M62.89) Rhabdomyolysis and (R82.1) myoglobinuriasThe Food and Drug Administration is recommending that physicians restrict prescribing high-dose Simvastatin (Zocor, Merck) to patients, given an increased risk of muscle damage. The FDA drug safety communication stated that physicians should limit using the 80-mg dose unless the patient has already been taking the drug for 12 months and there is no evidence of myopathy.
"Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug," the agency states.
Statin-associated autoimmune myopathy
Myocardium / cardio-myopathy
(I40) Acute myocarditis
(I41) Myocarditis in diseases classified elsewhere
(I42) Cardiomyopathy
(I42.0) Dilated cardiomyopathy
(I42.1) Obstructive hypertrophy cardiomyopathy
(I42.2) Other hypertrophic cardiomyopathy
(I42.3) Endomyocardial (eosinophilic) disease
Eosinophilic myocarditis
Endomyocardial (tropical) fibrosis
Löfflers endocarditis
(I42.4) Endocardial fibroelastosis
(I42.5) Other restrictive cardiomyopathy
(I42.6) Alcoholic cardiomyopathy
(I42.8) Other cardiomyopathies
Arrhythmogenic right ventricular dysplasia
(I43) Cardiomyopathy in diseases classified elsewhere
Differential diagnosis
At birth
None as systemic causes; mainly hereditaryOnset in childhood
Inflammatory myopathies – dermatomyositis, polymyositis (rarely)
Infectious myopathies
Endocrine and metabolic disorders – hypokalemia, hypocalcemia, hypercalcemiaOnset in adulthood
Inflammatory myopathies – polymyositis, dermatomyositis, inclusion body myositis, viral (HIV)
Infectious myopathies
Endocrine myopathies – thyroid, parathyroid, adrenal, pituitary disorders
Toxic myopathies – alcohol, corticosteroids, narcotics, colchicines, chloroquine
Critical illness myopathy
Metabolic myopathies
Paraneoplastic myopathy
Treatments
Because different types of myopathies are caused by many different pathways, there is no single treatment for myopathy. Treatments range from treatment of the symptoms to very specific cause-targeting treatments. Drug therapy, physical therapy, bracing for support, surgery, and massage are all current treatments for a variety of myopathies.
References
External links
GeneReviews/NCBI/NIH/UW entry on Myopathy with Deficiency of ISCU
See http://neuromuscular.wustl.edu/ for medical descriptions. |
Diencephalic syndrome | Diencephalic syndrome, or Russells syndrome, is a rare neurological disorder seen in infants and children and characterised by failure to thrive and severe emaciation despite normal or slightly decreased caloric intake. Classically there is also locomotor hyperactivity and euphoria. Less commonly diencephalic syndrome may involve skin pallor without anaemia, hypoglycaemia, and hypotension. The syndrome is a rare but potentially fatal cause of failure to thrive in children. Failure to thrive presents on average at seven months of age. Of note the syndrome is not associated with developmental delay. There may be associated hydrocephalus.Diencephalic syndrome was first described by Dr. A. Russell in 1951. It is usually caused by a brain tumor such as a low-grade glioma or astrocytoma located in the hypothalamic-optic chiasmatic region. It is not yet understood how diencephalic syndrome causes the effects on appetite and metabolism which are seen, though inappropriately high growth hormone release has been proposed, as has excessive β-lipotropin secretion and overall increased metabolic demand. It is treated with nutritional optimisation while the underlying lesion is treated with chemotherapy, surgery or radiotherapy.
== References == |
Lipoprotein lipase deficiency | Lipoprotein lipase deficiency is a genetic disorder in which a person has a defective gene for lipoprotein lipase, which leads to very high triglycerides, which in turn causes stomach pain and deposits of fat under the skin, and which can lead to problems with the pancreas and liver, which in turn can lead to diabetes. The disorder only occurs if a child acquires the defective gene from both parents (it is autosomal recessive). It is managed by restricting fat in diet to less than 20 g/day.
Signs and symptoms
The disease often presents in infancy with colicky pain, failure to thrive, and other symptoms and signs of the chylomicronemia syndrome. In women the use of estrogens or first pregnancy are also well known trigger factors for initial manifestation of LPLD. At all ages, the most common clinical manifestation is recurrent abdominal pain and acute pancreatitis. The pain may be epigastric, with radiation to the back, or it may be diffuse, with the appearance of an emergent acute abdomen. Other typical symptoms are eruptive xanthomas (in about 50% of patients), lipaemia retinalis and hepatosplenomegaly.
Complications
Patients with LPLD are at high risk of acute pancreatitis, which can be life-threatening, and can lead to chronic pancreatic insufficiency and diabetes.
Diagnosis
Lab tests show massive accumulation of chylomicrons in the plasma and corresponding severe hypertriglyceridemia. Typically, the plasma in a fasting blood sample appears creamy (plasma lactescence).Familial LPL deficiency should be considered in anyone with severe hypertriglyceridemia and the chylomicronemia syndrome. The absence of secondary causes of severe hypertriglyceridemia (like e.g. diabetes, alcohol, estrogen-, glucocorticoid-, antidepressant- or isotretinoin-therapy, certain antihypertensive agents, and paraproteinemic disorders) increases the possibility of LPL deficiency. In this instance besides LPL also other loss-of-function mutations in genes that regulate catabolism of triglyceride-rich lipoproteins (like e.g. ApoC2, ApoA5, LMF-1, GPIHBP-1 and GPD1) should also be consideredThe diagnosis of familial lipoprotein lipase deficiency is finally confirmed by detection of either homozygous or compound heterozygous pathogenic gene variants in LPL with either low or absent lipoprotein lipase enzyme activity.Lipid measurements
· Milky, lipemic plasma revealing severe hyperchylomicronemia;· Severely elevated fasting plasma triglycerides (>2000 mg/dL);LPL enzyme
· Low or absent LPL activity in post-heparin plasma;· LPL mass level reduced or absent in post-heparin plasma;Molecular genetic testing
The LPL gene is located on the short (p) arm of chromosome 8 at position 22. More than 220 mutations in the LPL gene have been found to cause familial lipoprotein lipase deficiency so far.
Treatment
Treatment of LPLD has two different objectives: immediate prevention of pancreatitis attacks and long-term reduction of cardiovascular disease risk. Treatment is mainly based on medical nutrition therapy to maintain plasma triglyceride concentration below 11,3 mmol/L (1000 mg/dL). Maintenance of triglyceride levels below 22,6 mmol/L (2000 mg/dL) prevents in general from recurrent abdominal pain.
Strict low fat diet and avoidance of simple carbohydrates
Restriction of dietary fat to not more than 20 g/day or 15% of the total energy intake is usually sufficient to reduce plasma triglyceride concentration, although many patients report that to be symptom free a limit of less than 10g/day is optimal. Simple carbohydrates should be avoided as well. Medium-chain triglycerides can be used for cooking, because they are absorbed into the portal vein without becoming incorporated into chylomicrons. Fat-soluble vitamins A, D, E, and K, and minerals should be supplemented in patients with recurrent pancreatitis since they often have deficiencies as a result of malabsorption of fat. However, the diet approach is difficult to sustain for many of the patients.
Lipid lowering drugs
Lipid-lowering agents such as fibrates and omega-3-fatty acids can be used to lower TG levels in LPLD; however, those drugs are very often not effective enough to reach treatment goals in LPLD patients. Statins should be considered to lower elevated non-HDL-Cholesterol.
Additional measures are avoidance of agents known to increase endogenous triglyceride levels, such as alcohol, estrogens, diuretics, isotretinoin, antidepressants (e.g. sertraline) and b-adrenergic blocking agents.
Gene therapy
In 2012, the European Commission approved alipogene tiparvovec (Glybera), a gene therapy for adults diagnosed with familial LPLD (confirmed by genetic testing) and having severe or multiple pancreatitis attacks despite dietary fat restrictions. It was the first gene therapy to receive marketing authorization in Europe; it was priced at about $1 million per treatment, and as of 2016, only one person had been treated with it commercially. A total of 31 patients were treated with Glybera, most for free in clinical trials before the drug was taken off the market.
Incidence
The disorder affects about 1 out of 1,000,000 people; however, epidemiological data are limited and there are regional differences due to cofounder effect (e.g. in Canada) or intermarriage.
See also
Primary hyperlipoproteinemia
Familial apoprotein CII deficiency
List of cutaneous conditions
References
Further reading
Gaudet, D; de Wal, J; Tremblay, K; Déry, S; van Deventer, S; Freidig, A; Brisson, D; Méthot, J (June 2010). "Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency". Atherosclerosis. Supplements. 11 (1): 55–60. doi:10.1016/j.atherosclerosissup.2010.03.004. PMID 20427244.
"LPL gene". NIH Genetics Home Reference. February 2015.
Hegele, RA; et al. (August 2014). "The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management". The Lancet. Diabetes & Endocrinology. 2 (8): 655–66. doi:10.1016/S2213-8587(13)70191-8. PMC 4201123. PMID 24731657.
== External links == |
Ventilator-associated pneumonia | Ventilator-associated pneumonia (VAP) is a type of lung infection that occurs in people who are on mechanical ventilation breathing machines in hospitals. As such, VAP typically affects critically ill persons that are in an intensive care unit (ICU) and have been on a mechanical ventilator for at least 48 hours. VAP is a major source of increased illness and death. Persons with VAP have increased lengths of ICU hospitalization and have up to a 20–30% death rate. The diagnosis of VAP varies among hospitals and providers but usually requires a new infiltrate on chest x-ray plus two or more other factors. These factors include temperatures of >38 °C or <36 °C, a white blood cell count of >12 × 109/ml, purulent secretions from the airways in the lung, and/or reduction in gas exchange.A different less studied infection found in mechanically ventilated people is ventilator-associated tracheobronchitis (VAT). As with VAP, tracheobronchial infection can colonise the trachea and travel to the bronchi. VAT may be a risk factor for VAP.
Signs and symptoms
People who are on mechanical ventilation are often sedated and are rarely able to communicate. As such, many of the typical symptoms of pneumonia will either be absent or unable to be obtained. The most important signs are fever or low body temperature, new purulent sputum, and hypoxemia (decreasing amounts of oxygen in the blood). However, these symptoms may be similar for tracheobronchitis.
Cause
Risk factors
Risk factors for VAP include underlying heart or lung disease, neurologic disease, and trauma, as well as modifiable risk factors such as whether the head of the bed is flat (increased risk) or raised, whether the patient had an aspiration event before intubation, and prior antibiotic exposure. As a result of intubation many of the bodys defenses against infections are reduced or impaired; this can result in an ability for microorganisms to enter and cause infection. Patients who are in the ICU for head trauma or other severe neurologic illness, as well as patients who are in the ICU for blunt or penetrating trauma, are at especially high risk of developing VAP. Further, patients hospitalized for blunt trauma are at a higher risk of developing VAP compared to patients with penetrating trauma.Ventilator-associated tracheobronchitis may be a risk factor for VAP, though not all cases of VAT progress to VAP.Recent studies have also linked the overall oral health of a patient to the potential development of VAP; suggesting that bacteria found in plaque can "migrate to the respiratory system."
Microbiology
The microbiologic flora responsible for VAP is different from that of the more common community-acquired pneumonia (CAP). In particular, viruses and fungi are uncommon causes in people who do not have underlying immune deficiencies. Though any microorganism that causes CAP can cause VAP, there are several bacteria which are particularly important causes of VAP because of their resistance to commonly used antibiotics. These bacteria are referred to as multidrug resistant (MDR).
Pseudomonas aeruginosa is the most common MDR Gram-negative bacterium causing VAP. Pseudomonas has natural resistance to many antibiotics and has been known to acquire resistance to every antibiotic except for polymyxin B. Resistance is typically acquired through upregulation or mutation of a variety of efflux pumps which pump antibiotics out of the cell. Resistance may also occur through loss of an outer membrane porin channel (OprD)
Klebsiella pneumoniae has natural resistance to some beta-lactam antibiotics such as ampicillin. Resistance to cephalosporins and aztreonam may arise through induction of a plasmid-based extended spectrum beta-lactamase (ESBL) or plasmid-based ampC-type enzyme
Serratia marcescens has an ampC gene which can be induced by exposure to antibiotics such as cephalosporins. Thus, culture sensitivities may initially indicate appropriate treatment which fails due to bacterial response.
Enterobacter as a group also have an inducible ampC gene. Enterobacter may also develop resistance by acquiring plasmids.
Citrobacter also has an inducible ampC gene.
Stenotrophomonas maltophilia often colonizes people who have tracheal tubes but can also cause pneumonia. It is often resistant to a wide array of antibiotics but is usually sensitive to co-trimoxazole
Acinetobacter are becoming more common and may be resistant to carbapenems such as imipenem and meropenem
Burkholderia cepacia is an important organism in people with cystic fibrosis and is often resistant to multiple antibiotics
Methicillin-resistant Staphylococcus aureus is an increasing cause of VAP. As many as fifty percent of Staphylococcus aureus isolates in the intensive care setting are resistant to methicillin. Resistance is conferred by the mecA gene.
The development of molecular diagnostic techniques is changing the understanding of the microbiology of VAP, with an increasing appreciation of the role of hard to culture bacteria and the change in the lung microbiome. A recent finding has highlighted the presence of Mycoplasma in the lavage of patients with VAP, a finding which was largely absent from ventilated patients without VAP and healthy controls. The Mycoplasma species most commonly identified, Mycoplasma salivarium, was able to impair the antibacterial functions of monocytes and macrophages.
Pathophysiology
It is thought by many, that VAP primarily occurs because the endotracheal or tracheostomy tube allows free passage of bacteria into the lower segments of the lung in a person who often has underlying lung or immune problems. Bacteria travel in small droplets both through the endotracheal tube and around the cuff. Often, bacteria colonize the endotracheal or tracheostomy tube and are embolized into the lungs with each breath. Bacteria may also be brought down into the lungs with procedures such as deep suctioning or bronchoscopy. Another possibility is that the bacteria already exist in the mucus lining the bronchial tree, and are just kept in check by the bodys first line of defenses. Ciliary action of the cells lining the trachea drive the mucus superiorly, leading to a build-up of fluids around the inflated cuff where there is little to no airway clearance. The bacteria can then colonize easily without disturbance and then rise in numbers enough to become infective. The droplets that are driven into the airstream and into the lung fields are lofted by way of Bernoullis principle. There is also a condition called oxidative damage that occurs when concentrations of pure oxygen come into prolonged contact with cells and this damages the cilia of the cells, thus inhibiting their action as part of the bodys first line of defense.
Whether bacteria also travel from the sinuses or the stomach into the lungs is, as of 2005, controversial. However, spread to the lungs from the blood stream or the gut is uncommon.
Once inside the lungs, bacteria then take advantage of any deficiencies in the immune system (such as due to malnutrition or chemotherapy) and multiply. Patients with VAP demonstrate impaired function of key immune cells, including the neutrophil, both in the blood and in the alveolar space, with this impairment being driven by pro-inflammatory molecules such as C5a. These defects in immune function appear to be causally linked to the development of VAP, as they are seen before clinical infection develops. A combination of bacterial damage and consequences of the immune response lead to disruption of gas exchange with resulting symptoms.
Diagnosis
Diagnosis of ventilator-associated pneumonia is difficult and is not standardized. The criteria used for diagnosis of VAP varies by institution, but tends to be a combination of several of the following radiographic, clinical sign, and laboratory evidence:
Temperature greater than 38 °C or less than 36 °C
White blood cell count greater than 12,000/mm3 or less than 4,000/mm3
Purulent secretions, increased secretions, or change in secretions
Positive tracheal cultures or bronchoalveolar lavage cultures
Some sign of respiratory distress, such as shortness of breath, rapid breathing, abnormal breathing sounds when listening with stethoscope
Increased need for oxygen on the ventilator
Chest X-rays: at least two serial x-rays showing sustained or worsening shadowing (infiltrates or consolidations)
Positive cultures that were obtained directly from the lung environment, such as from the trachea or bronchiolesAs an example, some institutions may require one clinical symptoms such as shortness of breath, one clinical sign such as fever, plus evidence on chest xray and in tracheal cultures.There is no gold standard for getting cultures to identify the bacteria, virus, or fungus that is causing the pneumonia, and there are invasive and non-invasive strategies for obtaining the culture sample. One non-invasive strategy collects cultures from the trachea of people with symptoms of VAP. Another is more invasive and advocates a bronchoscopy plus bronchoalveolar lavage (BAL) for people with symptoms of VAP. Both strategies also require a new or enlarging infiltrate on chest x-ray as well as clinical signs/symptoms such as fever and shortness of breath. There is no strong evidence to suggest that an invasive method to collect cultures is more effective than a non-invasive method. In addition, a quantitative approach to assessing the culture (performing a bacterial count of the pathogen that is causing the pneumonia) does not appear to be superior to a qualitative approach (determining the presence of the pathogen). In recent years there has been a focus on rapid diagnostics, allowing for detection of significant levels of pathogens before this becomes apparent on microbial cultures. Several approaches have been used, including using host biomarkers such as IL-1β and IL-8. Alternatively, molecular detection of bacteria has been undertaken, with reports that amplifying the pan-bacterial 16S gene can provide a measure of bacterial load. A trial of biomarker-based exclusion of VAP (VAP-RAPID2) has recently finished recruitment, and results are awaited (https://clinicaltrials.gov/ct2/show/NCT01972425).
Blood cultures may reveal the microorganisms causing VAP, but are often not helpful as they are positive in only 25% of clinical VAP cases. Even in cases with positive blood cultures, the bacteremia may be from a source other than the lung infection.
Prevention
Prevention of VAP involves limiting exposure to resistant bacteria, discontinuing mechanical ventilation as soon as possible, and a variety of strategies to limit infection while intubated. Resistant bacteria are spread in much the same ways as any communicable disease. Proper hand washing, sterile technique for invasive procedures, and isolation of individuals with known resistant organisms are all mandatory for effective infection control. A variety of aggressive weaning protocols to limit the amount of time a person spends intubated have been proposed. One important aspect is limiting the amount of sedation that a ventilated person receives.
Weak evidence suggests that raising the head of the bed to at least 30 degrees may help prevent VAP, however further research is required to understand the risks associated with this. Antiseptic mouthwashes (in particular associated with toothbrushing) such as chlorhexidine may also reduce the risk of VAP, although the evidence is mainly restricted to those who have undergone cardiac surgery.American and Canadian guidelines strongly recommend the use of subglottic secretion drainage (SSD). Special tracheal tubes with an incorporated suction lumen as the EVAC tracheal tube form Covidien / Mallinckrodt can be used for that reason. New cuff technology based on polyurethane material in combination with subglottic drainage (SealGuard Evac tracheal tube from Covidien / Mallinckrodt) showed significant delay in early and late onset of VAP.There is little evidence that the use of silver-coated endotracheal tubes reduces the incidence of VAP in the first ten days of ventilation. There is tentative evidence that the use of probiotics may reduced the likelihood of getting VAP, however it is unclear if probiotics affect ICU or in-hospital death.
Treatment
Treatment of VAP should be matched to known causative bacteria. However, when VAP is first suspected, the bacteria causing infection is typically not known and broad-spectrum antibiotics are given (empiric therapy) until the particular bacterium and its sensitivities are determined. Empiric antibiotics should take into account both the risk factors a particular individual has for resistant bacteria as well as the local prevalence of resistant microorganisms. If a person has previously had episodes of pneumonia, information may be available about prior causative bacteria. The choice of initial therapy is therefore entirely dependent on knowledge of local flora and will vary from hospital to hospital. Treatment of VAP with a single antibiotic has been reported to result in similar outcomes as with a combination of more than one antibiotics, in terms of cure rates, duration of ICU stay, mortality and adverse effects.Risk factors for infection with an MDR strain include ventilation for more than five days, recent hospitalization (last 90 days), residence in a nursing home, treatment in a hemodialysis clinic, and prior antibiotic use (last 90 days).
Possible empirical therapy combinations include (but are not limited to):
vancomycin/linezolid and ciprofloxacin,
cefepime and gentamicin/amikacin/tobramycin
vancomycin/linezolid and ceftazidime
Ureidopenicillin plus β-lactamase inhibitor such as piperacillin/tazobactam or ticarcillin/clavulanate
a carbapenem (e.g., imipenem or meropenem)Therapy is typically changed once the causative bacteria are known and continued until symptoms resolve (often 7 to 14 days). For patients with VAP not caused by nonfermenting Gram-negative bacilli (like Acinetobacter, Pseudomonas aeruginosa) the available evidence seems to support the use of short-course antimicrobial treatments (< or =10 days).People who do not have risk factors for MDR organisms may be treated differently depending on local knowledge of prevalent bacteria. Appropriate antibiotics may include ceftriaxone, ciprofloxacin, levofloxacin, or ampicillin/sulbactam.
As of 2005, there is ongoing research into inhaled antibiotics as an adjunct to conventional therapy. Tobramycin and polymyxin B are commonly used in certain centres but there is no clinical evidence to support their use.
Prognosis
VAP occurring early after intubation typically involves fewer resistant organisms and is thus associated with a more favorable outcome. Because respiratory failure requiring mechanical ventilation is itself associated with a high mortality, determination of the exact contribution of VAP to mortality has been difficult. As of 2006, estimates range from 33% to 50% death in patients who develop VAP. Mortality is more likely when VAP is associated with certain microorganisms (Pseudomonas, Acinetobacter), blood stream infections, and ineffective initial antibiotics. VAP is especially common in people who have acute respiratory distress syndrome (ARDS).
Epidemiology
Between 8 and 28% of patients receiving mechanical ventilation are affected by VAP. VAP can develop at any time during ventilation, but occurs most often in the first week of mechanical ventilation. There is some evidence for gender differences in the course of VAP: men have been found to get VAP more often, but women are more likely to die after contracting VAP. Recent reports indicate that patients with Coronavirus disease 2019 who require mechanical ventilation in an Intensive care unit are at increased risk of ventilator-associated pneumonia, compared to patients without COVID-19 ventilated in the same unit and patients who had viral pneumonitis arising from viruses other than SARS-CoV-2. Why this increased susceptibility should be present remains uncertain, as the noted reports adjusted for duration of ventilation, it is likely that the increased susceptibility relates impaired innate immunity in the lungs. However several observational studies have identified the use of glucocorticoids as a factor associated with increased risk of VAP and other Hospital-acquired infections.
References
Further reading
== External links == |
Diphallia | Diphallia, penile duplication (PD), diphallic terata, or diphallasparatus, is an extremely rare developmental abnormality in which a male is born with two penises. The first reported case was by Johannes Jacob Wecker in 1609. Its occurrence is 1 in 5.5 million boys in the United States.When diphallia is present, it is usually accompanied by renal, vertebral, hindgut, anorectal or other congenital anomalies. There is also a higher risk of spina bifida. Infants born with PD and its related conditions have a higher death rate from various infections associated with their more complex renal or colorectal systems.
It is thought diphallia occurs in the fetus between the 23rd and 25th days of gestation when an injury, chemical stress, or malfunctioning homeobox genes hamper proper function of the caudal cell mass of the fetal mesoderm as the urogenital sinus separates from the genital tubercle and rectum to form the penis.
The first case was reported by Wecker in Bologna, Italy, in 1609, and since then, about one hundred cases have been reported. This condition has existed in humans since ancient times. The two external genitalia may vary in size and shape, either lying beside each other in a sagittal plane or one above the other in a frontal plane.According to Schneider classification in 1928, double penis is classified into three groups: (a) glans diphallia, (b) bifid diphallia and (c) complete diphallia or double penis. According to Vilanora and Raventos, in 1954, a fourth group called pseudodiphallia is added.The current widely accepted classification, introduced by Aleem in 1972, classifies double penis into two groups: true diphallia and bifid phallus. True diphallia is caused by cleavage of pubic tubercle; bifid phallus is caused by separation of pubic tubercle. Each of these two groups is further subdivided into partial or complete. True diphallia is where each phallus has two corpora cavernosa and a single corpus spongiosum containing a urethra. True diphallia can be either complete with both penises similar in size, or partial when one of the phallia is smaller in size or immature, though structurally same as the larger phallus. In bifid phallus, each phallus has only one corpus cavernosum and one corpus spongiosum containing a urethra. Separation of penises down to the base of the penile shaft is complete bifid, whereas to glans is partial bifid. For complete bifid phallus associated with anomalies, the anterior urethra is absent from each penis and the prostatic urethra is situated in the skin between the two penises. In partial bifid phallus, the duplication of urethra, corpora cavernous and corpus spongiosum in one penis is incomplete, and there is only a corpus cavernosum and a spongiosum surrounding the functioning urethra in the other penis.
Notable clinical cases
Diphallia is usually accompanied by systemic anomalies; their extent varies, ranging from no associated anomaly to multiple anomalies including urogenital, gastrointestinal and musculoskeletal systems. Penile duplication also varies from a single penis with double glans to complete double penises. The meatus may be normal at tip of glans, hypospadiac, or epispadiac; the scrotum may be normal or bifid. True diphallia is more likely accompanied with associated anomalies and malformations compared with bifid phallus. Infants born with diphallia have higher death rate due to infections associated with anomalies.
Complete true diphallia with associated anomalies
A two-day-old male newborn, associated with complex genitourinary and ano-rectal malformation. He had imperforated anus, hypospadias, bifid scrotum, meatuses on both glandes, two bladders and two colons, and had normal testes, kidneys and ureters.
Partial true diphallia or pseudodiphallia, without associated anomalies
Partial true diphallia corresponds to pseudodiphallia. Pseudodiphallia is formed from erectile tissue only, undifferentiated and non-functional. It is independent of the normal penis and can be removed surgically without problem. This rare case was reported, based on the age of the 83-year-old man when diphallia was only detected then when he was hospitalised, and also because of the absence of other anatomical malformations. The small, immature and nonfunctional penis protruded on one side of the large, normal penis. The secondary penis had glans but without urinary meatus.
Complete bifid diphallia with associated anomalies
A 12-year-old boy, associated with bifid scrotum, epispadia and pubic symphysis diastasis. He had two separate penises, similar in size and shape, each penis had an epispadia urethral meatus. He had bifid scrotum, one testicle on each side of the scrotum. A bowel loop-like structure was over the pubis region. This structure had no communication with any other structures. He had a single normal bladder and ureter.
Partial bifid diphallia without associated anomalies
A 15-year-old boy, apart from having two penises, had normal external genitalia. His two testicles were within normal scrotum and normally positioned. He had two unequal sized glans at tip of a thick penile shaft, and only urinated through the larger glans. He had a patent anus, one bladder, one normal urethra, normal gastrointestinal and genitourinary systems.
Cause
Cause of diphallia is unknown, and also because its associated anomalies vary largely, it is impossible to give a simple, single explanation of its cause. But it is thought to have started from duplication of cloacal membrane in early embryonic development stages in the fetus, between third and sixth week of gestation, because normal development of cloacal folds in the fetus is complete between this time.Normal development of penis occurs with the fusion of cloacal tubercles at anterior end of urogenital sinus. Mesenchyme migrate around cloacal membrane, proliferate and expand around cloacal plate, forming a pair of cloacal folds that fuse to form genital tubercle which develops into penis. If cloacal membrane is doubled, mesenchyme will migrate and surround both cloacal membranes, leading to the formation of two pairs of cloacal folds around two cloacal membranes, resulting in formation of two genital tubercles and thus two penises. The concept of caudal duplication syndrome is used to explain the symptoms of diphallia with associated complex anomalies in lower abdomen and urinary tract. Further, as mesenchyme migrate from more than one area, failure in migration and in the fusion of mesoderm results in formation of two genital tubercles and double penises, as well as producing associated anomalies such as double bladders, double urethra, double colons and imperforated anus. Failure in proper fusion of urethral folds results in hypospadias. Failure in mesoderm cell migration results in epispadia.Diphallia is a rare abnormal external genitalia. The cause is uncertain, but most scientists agree that diphallia is a defect of genital tubercle, and occurs at about week three of gestation, when caudal cell mass of mesoderm is affected by various external environmental factors including drugs, infections and malfunctioning homeobox genes.
Treatment
Treatment is a case-by-case analysis taking into account considerations for medical and ethical reasons, and involves surgical excision of the non-functioning penis.
See also
Bifid penis
Supernumerary body part
Polyorchidism
Penile agenesis
Uterus didelphys
Vaginal septum
References
Notes
A scientific paper of triphallia (three penises) in a marine snail was reported.(Castillo, Viviana M; Brown, Donald I (2012). "One Case of Triphallia in the Marine Snail Echinolittorina peruviana (Caenogastropoda: Littorinidae)". International Journal of Morphology. 30 (3): 791–796. doi:10.4067/S0717-95022012000300003.)
In 2021, the first known case of a human with triphallia was recorded in Iraq.("Triphallia: First Human Case of Baby Born With Three Male Genitalia Reported". 3 April 2021.)
Further reading
Chadha R, Bagga D, Gupta S, Mahajan JK. (July 2001). "Complete diphallia associated with features of covered exstrophy." 36 (7): E12, W.B. Saunders Company. National Center for Biotechnology Information, US National Library of Medicine, National Institutes of Health
== External links == |
Fat necrosis | Fat necrosis is a form of necrosis characterized by the action upon fat by digestive enzymes.In fat necrosis the enzyme lipase releases fatty acids from triglycerides. The fatty acids then complex with calcium to form soaps. These soaps appear as white chalky deposits.It is usually associated with trauma of the pancreas or acute pancreatitis. It can also occur in the breast, the salivary glands and neonates after a traumatic delivery.
Signs and symptoms
Signs and symptoms of fat necrosis are presented below:
masses that seem to be irregular beneath the skin, by touch these should feel smooth and rounded.
tenderness in areas with masses
skin tethering
dimpling
nipple retraction
Causes
Fat necrosis occurs primarily in the breast and pancreas. Breast lesions are mostly caused by adipose tissue trauma or post-surgical complications (e.g. hypoxia). Pancreatic lesions arise as a result of the pathological release of pancreatic enzymes which digest surrounding adipose tissue. Fat necrosis is also a feature of some diseases that cause inflammation of subcutaneous fat (panniculitis). Examples of causes include but are not limited to:
Breast trauma (e.g. seat belt injury from a car accident)
Breast surgery
Fine needle aspiration biopsy and cytology (FNAB, FNAC)
Radiotherapy
Lumpectomy
Reduction mammoplasty
Breast reconstruction
Pancreatic disease
Acute pancreatitis
Pancreatic cancer
Pancreatic injury
Some forms of panniculitis
Subcutaneous fat necrosis of the newborn
Weber–Christian disease
Polyarteritis nodosa
Pathophysiology
Fat necrosis is the pattern of damage associated with the destruction of adipose tissue by trauma, hypoxia, or lipase digestion (e.g. pancreatitis). In the classic case of fat necrosis in severe acute pancreatitis, the necrosis arises because adipocytes in the peritoneum are broken and digested by inappropriately activated pancreatic enzymes. Stored triglycerides in the adipocytes are released and split by pancreatic lipases into fatty acids and glycerol molecules. The resultant fatty acids react with extracellular calcium to make calcium soaps (i.e. fatty acid salts) that give fat necrosis its characteristic chalky-white appearance. Fat necrosis is an example of dystrophic calcification because the calcification occurs at normal serum calcium levels.Besides pancreatitis, fat necrosis is also associated with conditions such as pancreatic carcinoma and pancreatic trauma. Although the peripancreatic region is the most commonly affected site in pancreatic disease (due to direct contact with enzymes), associated fat necrosis can occur around the body in subcutaneous tissue, hand and foot joints, and bone marrow. These extrapancreatic complications are known as pancreatic panniculitis.Beyond saponification and calcification, fat necrosis concludes with fibrosis and the formation of grey-yellow scar tissue. It is also possible for calcification to occur around the edges of a fatty necrotic lesion, enclosing the fat in a cyst. These "oil cysts" may persist for months to years without undergoing fibrosis. This is often the case in breast fat necrosis, where the underlying oil cysts can be visualised using sonography, X-Ray, CT, or MRI.
Diagnosis
Although fat necrosis can be diagnosed through a routine checkup with a physician, called a physical, a patient can also perform a physical checkup on themselves. For additional diagnosis, a physician would request one or more of the following scans or tests.
CT scan
Mammography test
Sonography test
MRI test
Management
When fat necrosis is being felt by a physician or patient, it may feel larger, smaller, unchanged, or not felt at all (resolved). Fat necrosis usually does not require surgery, it usually requires a patient to meet with their physician and as long as the pain is not present there is nothing to be concerned about unless the patient is concerned about cosmetic abnormalities. However, if pain is present surgery is a form of treatment a patient can consider.
To keep track of benign fat necrosis a yearly mammogram is taken in order to observe it.
However, if fat necrosis consists of oily fluid a physician will go in with a needle to remove this liquid, which may be causing discomfort. Excision may be needed if the mass becomes solid or causes a cosmetic abnormality.
Prognosis
Although getting diagnosed with fat necrosis of any kind can be a great cause for concern, as most individuals may mistake it for a malignant tumor. Fat necrosis of the breast is a prognosis that is benign and does not increase an individuals risk for various cancers. An individuals life expectancy does not decrease with this diagnosis.
Epidemiology
Fat necrosis in the breast occurs around 0.6%, this represents 2.75% of lesions that end up being benign. However, 0.8% of fat necrosis occurs from tumors of the breast, 1% - 9% occurs in breast reduction surgery. Individuals that are high risk include women around the age of 50yrs along with pendulous breasts.
See also
Caseous necrosis
Coagulative necrosis
Liquefactive necrosis
Myospherulosis
Necrosis
References
External links
Fat Necrosis of the breast |
Visceral gout | Visceral gout is a disease of birds in which kidney failure causes a build-up of urates in the internal organs, leaving a chalky white coating on them. Symptoms include anorexia and emaciation.
It is a problem common to caged birds. Vultures are particularly sensitive to poisoning by diclofenac, which leads to kidney failure, visceral gout, and death.
Threat to vultures
The collapse of the vulture population in India and Pakistan, to about a twentieth of their original numbers, has been caused by diclofenac, which is a non-steroidal anti-inflammatory drug (NSAID). Diclofenac is given to working and ill farm cattle to reduce pain so that they can work on the land for longer. Farmers leave dead farm animals out in the open for the vultures to tidy up, and the vultures then feed from the carcasses of the cattle that die, and are poisoned by the diclofenac contained in the flesh they eat.
Vultures are now not present in large enough numbers to tidy up all the dead animals. Instead, dead animals are now likely to rot in the open and be partly eaten by rats or wild dogs or other pests, causing major concern and human health hazards including risks of rabies.
Meloxicam (another NSAID) has been found to be harmless to vultures and should prove an acceptable alternative to diclofenac. The Government of India has banned diclofenac, but it continues to be sold over a year later and is still a problem in other parts of the World.
References
Visceral gout in caged birds
"Indias Vultures Fall Prey to a Drug in the Cattle They Feed On", New York Times, Amelia Gentleman, March 28, 2006.
NSAID effects on vultures (BBC website) |
Trisomy | A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an abnormal number of chromosomes).
Description and causes
Most organisms that reproduce sexually have pairs of chromosomes in each cell, with one chromosome inherited from each parent. In such organisms, a process called meiosis creates cells called gametes (eggs or sperm) that have only one set of chromosomes. The number of chromosomes is different for different species. Humans have 46 chromosomes (i.e. 23 pairs of chromosomes). Human gametes have only 23 chromosomes.
If the chromosome pairs fail to separate properly during cell division, the egg or sperm may end up with a second copy of one of the chromosomes. (See non-disjunction.) If such a gamete results in fertilization and an embryo, the resulting embryo may also have an entire copy of the extra chromosome.
Terminology
The number of chromosomes in the cell where trisomy occurs is represented as, for example, 2n+1 if one chromosome shows trisomy, 2n+1+1 if two show trisomy, etc.
"Full trisomy", also called "primary trisomy", means that an entire extra chromosome has been copied.
"Partial trisomy" means that there is an extra copy of part of a chromosome.
"Secondary trisomy" - the extra chromosome has quadruplicated arms (the arms are identical; it is an "isochromosome").
"Tertiary trisomy" - the extra chromosome is made up of copies of arms from two other chromosomes.Trisomies are sometimes characterised as "autosomal trisomies" (trisomies of the non-sex chromosomes) and "sex-chromosome trisomies." Autosomal trisomies are described by referencing the specific chromosome that has an extra copy. Thus, for example, the presence of an extra chromosome 21, which is found in Down syndrome, is called trisomy 21.
Human trisomy
Trisomies can occur with any chromosome, but often result in miscarriage, rather than live birth. For example, Trisomy 16 is the most common trisomy in human pregnancies, occurring in more than 1% of pregnancies; only those pregnancies in which some normal cells occur in addition to the trisomic cells, or mosaic trisomy 16, survive. This condition, however, usually results in spontaneous miscarriage in the first trimester.
The most common types of autosomal trisomy that survive to birth in humans are:
Trisomy 21 (Down syndrome)
Trisomy 18 (Edwards syndrome)
Trisomy 13 (Patau syndrome)
Trisomy 9
Trisomy 8 (Warkany syndrome 2)Of these, Trisomy 21 and Trisomy 18 are the most common. In rare cases, a fetus with Trisomy 13 can survive, giving rise to Patau syndrome. Autosomal trisomy can be associated with birth defects, intellectual disability and shortened life expectancy.
Trisomy of sex chromosomes can also occur and include:
XXX (Triple X syndrome)
XXY (Klinefelter syndrome)
XYYCompared to trisomy of the autosomal chromosomes, trisomy of the sex chromosomes normally has less severe consequences. Individuals may show few or no symptoms and have a normal life expectancy.
See also
Chromosome abnormalities
Aneuploidy
Karyotype
Sexual reproduction
Monosomy
References
== External links == |
Drug-induced gingival enlargement | Drug-induced gingival enlargement (DIGE), also referred to as drug-induced gingival hyperplasia (DIGH) or drug-induced gingival overgrowth (DIGO), is a side effect of many systemic medications for which the Gingervae are not the target receptor. It is normally resultant of medications including immunoregulators, calcium channel blockers and anticonvulsants. When allowed to progress assisted by routinely poor oral hygiene, DIGE can lead to pain and disfigurement, however there are great variations in its presentation and severity dependent on the case. It is suggested that enlargement is aided by genetic predispositions, tending to occur more frequently in the papillae of the anterior Gingivae in younger age groups.
Class of drugs
The main classes of drugs that result in gingivlal hyperplasia are as follows.
Anticonvulsants
Anticonvulsant agents, such as phenytoin, are associated with common forms of gingival overgrowth. It is caused by the increase of metabolites from the break down of anticonvulsants in the body. It should also be noted that concurrent usage of different anticonvulsants in children has resulted in accumulative gingival enlargement.
Immunosuppressive drugs
Immunoregulators are often prescribed to patients who have organ transplantations and/or some autoimmune diseases. Common immunosuppressive drugs linked to gingival hyperplasia are cyclosporin and tacrolimnus.The most frequently used immunosuppressive drug is cyclosporin, which is commonly prescribed after an organ transplant. Nearly 53% of patients taking cyclosporin after renal transplants presented with gingival growth. Inflammation from bacterial overgrowth in the gingiva and cyclosporins main metabolite, hydroxyciclosporin, stimulate production of collagen, while simultaneously inhibiting collagen breakdown — leading to a net increase in production of gingival tissues. Tacrolimus, on the other hand, is less toxic than cyclosporin, causing less severe gingival overgrowth, hepatic and renal toxicity.
Management
If gingival overgrowth becomes a legitimate concern, initial management would be proper oral hygiene habits as it is the least invasive option to alleviate overgrowth. Otherwise, it may also be advisable to cease medication, although this should only be done with the patients’ medical practitioners’ consent, and complete resorption may still take up to 8 weeks. In cases where medication cannot be paused, patients’ medical practitioners or consultants should be consulted to discuss treatment options. Replacement drugs may be suggested. For example, vigabatrin may substitute phenytoin as anticonvulsant. However, this method may be ineffective for long-standing overgrowth. Another option is the surgical removal of excess tissue via gingivectomy. This method is widely successful, although recurrence has been reported for certain drugs. Nonetheless, the procedure is associated with risk of hemorrhage in the highly inflamed and vascularized gingiva. As such, CO2 laser or ND:YAG laser has been suggested for accurate, cauterized, and sterilized incisions. Other nonsurgical interventions such as fast mimicking diet regime and nonsurgical periodontal therapy has also been suggested for alleviating gingival overgrowth, thus reducing the need for surgical intervention. However, they could not prevent or fully resolve gingival overgrowth alone.
== References == |
Mal de debarquement | Mal de debarquement (or mal de débarquement) syndrome (MdDS, or common name disembarkment syndrome) is a neurological condition usually occurring after a cruise, aircraft flight, or other sustained motion event. The phrase "mal de débarquement" is French and translates to "illness of disembarkment".
MdDS is typically diagnosed by a neurologist or an ear nose and throat specialist when a person reports a persistent rocking, swaying, or bobbing feeling (though they are not necessarily rocking). This usually follows a cruise or other motion experience. Because most vestibular testing proves to be negative, doctors may be baffled as they attempt to diagnose the syndrome. A major diagnostic indicator is that most patients feel better while driving or riding in a car, i.e, while in passive motion. MdDS is unexplained by structural brain or inner ear pathology and most often corresponds with a motion trigger, although it can occur spontaneously. This differs from the very common condition of "land sickness" that most people feel for a short time after a motion event such as a boat cruise, aircraft ride, or even a treadmill routine which may only last minutes to a few hours. The syndrome has recently received increased attention due to the number of people presenting with the condition, and more scientific research has commenced in determining what triggers MdDS and how to cure it.
Symptoms
Common symptoms most frequently reported include a persistent sensation of motion usually described as rocking, swaying, or bobbing, disequilibrium with difficulty maintaining balance; it is seldom accompanied by a true spinning vertigo. Chronically fatigued, sufferers can become fatigued quickly with minimal exertion and some might experience neck and back pain. Other symptoms include the feeling of pressure in the brain, mostly around the frontal lobe area, headaches and/or migraine headaches, ophthalmodynia periodica (ice pick stabbing headaches in the early stages of MdDs), ear pain, ear fullness and possibly tinnitus.Fluctuations in weather also affect sufferers, in particularly hot weather and barometric pressure changes. Many have photo-sensitivity and find it more difficult to walk in the dark as well as other sensitivities to strong smells including chemical smells. Cognitive impairment ("brain fog") includes an inability to recall words, short term memory loss, an inability to multi-task, misspelling and mispronunciation of words, difficulty in concentrating. Many MdDS sufferers report they are unable to use a computer for any length of time due to the visual over-stimulation, and some are even unable to watch television.Symptoms can be increased by stress, lack of sleep, crowds, flickering lights, loud sounds, fast or sudden movements, enclosed areas and visual intolerance of busy patterns and scrolling movement.MdDS sufferers may have hypersomnia and can sleep up to 12 or more hours a day, depending on their symptom levels. Research reveals MdDS is not migraine-related and many sufferers have never had migraine symptoms prior to the onset of the disorder. However, for some MdDS sufferers there maybe have been a correlation between migraine and some pathophysiological overlap or even some other precipitating illness.The condition may be masked by a return to motion such as in a car, train, plane, or boat; however, once the motion ceases, the symptoms rebound or return, often at much higher levels than when the journey first commenced.The symptoms of MdDS may be extremely debilitating and fluctuate high and low on a daily basis; it greatly affects the daily life and working capacity of sufferers with many having to relinquish work; it also limits most other daily and social activities. Sufferers can have low quality of life in both the physical and emotional realms, comparable to people who have multiple sclerosis with many symptoms being of a similar nature. High levels of disequilibrium can contribute to suffers not being able to drive a car or walk far and this can create varying levels of anxiety in some or possibly depression due to the significant level of disability.
Diagnosis
MdDS is diagnosed several ways, one being by the symptoms: in particular, the "constant rocking, swaying feeling" and the abatement of this feeling when in motion again and as a matter of exclusion. There are no definitive tests that confirm MdDS, only tests that rule out other conditions. Tests include hearing and balance, and MdDS is generally diagnosed by either a neurologist or an ear, nose, and throat specialist.
Treatment
There is no known cure for MdDS, as with most balance and gait disorders, some form of displacement exercise is thought helpful (for example walking, jogging, or bicycling but not on a treadmill or stationary bicycle). This has not been well-studied in MdDS. Medications that suppress the nerves and brain circuits involved in balance (for example, the benzodiazepine clonazepam) have been noted to help and can lower symptoms; however, it is not a cure. It is not known whether a medication that suppresses symptoms prolongs symptom duration or not. Vestibular therapy has not proved to be effective in treating MdDS.Additional research is being undertaken into the neurological nature of this syndrome through imaging studies.
Many sufferers of this syndrome have found relief by taking histamine blockers or antihistamines (Benadryl for instance). A single Benadryl gel tab at the beginning of the flight and at each 4-hour interval for longer flight.
Epidemiology
The condition is thought to be under-reported in the medical literature. A study of 27 cases conducted by Timothy C Hain in 1999 noted all but one patient to be female. The average age in this series was 49 years. This apparent gender disparity, however, may be due in part to the fact that the questionnaire which formed the basis of the study was circulated in a publication with a predominantly female reader base.Subsequent studies have produced conflicting results with regard to the gender distribution of MdDS. The trends in Hains report have recently been supported by the MdDS Balance Disorder Foundation, in a study of over 100 individuals diagnosed with MdDS. The female:male ratio was approximately 9:1; the average age of onset was 43–45 years. However, another recent study found that 44% of subjects who had experienced MdDS for 2 years or more were male, suggesting a more even distribution.
It has been shown to occur in excursions of as little as 30 minutes though it has been unclear how long it takes for symptoms to occur. The most commonly reported inciting event was a prolonged ocean cruise (~45%); however, shorter boating excursions (~22%), aircraft travel (~15%), and automobile travel (~8%) have all been described.Mal de Débarquement syndrome has been noted as far back to the times of Erasmus Darwin in 1796, and Irwin J A (1881) "The pathology of seasickness".
Cases of MdDS have been reported in children as young as eight and in both genders. Men may have a more difficult time obtaining a diagnosis due to the disparity of women reported. When sailors and soldiers returned from World War II, the syndrome was reported at a higher rate in males
Research
Repetitive transcranial magnetic stimulation
Despite MdDS causing significant disability, therapy for persistent MdDS remains virtually nonexistent. A pilot study has commenced utilizing repetitive transcranial magnetic stimulation (rTMS) this being a method of neuromodulation in which a local magnetic field is applied over the scalp to induce an electric current in the cortical structures underlying the coil. Low-frequency rTMS (e1 Hz) induces local inhibition, whereas high frequency rTMS (Q5 Hz) induces local excitation. The TMS studies have proved to help in lowering the symptoms of MdDS if the treatment is ongoing; however, it is not a cure.
Vestibulo-Ocular Reflex Research 2014
At least one clinical trial on readaptation of the vestibulo-ocular reflex undertaken by Dr Mingjia Dai from Mount Sinai Hospital in New York City produced results for a significant percentage of patients who participated in the program.Dr Dai developed an intervention that provided improvement in symptoms for 70% of the patients in the clinical trial phase. The protocol involved a physical manipulation of the patient intended to readapt the vestibulo-ocular reflex. While the program was no longer in the research phase, Dai continued to accept patients. According to Dai, success was measured as a 50% reduction of symptoms.Recent research reveals a very small percentage of MdDS cases may be related to optokinetic nystagmus (OKN).
See also
Motion sickness (seasickness, travel sickness)
Space adaptation syndrome (Space flight "zero-g" and return)
== References == |
Generalized tonic–clonic seizure | A generalized tonic–clonic seizure, or GTCS, previously known as a Grand mal seizure, is a type of generalized seizure that produces bilateral, convulsive tonic and then clonic muscle contractions. Tonic-clonic seizures are the seizure type most commonly associated with epilepsy and seizures in general and the most common seizure associated with metabolic imbalances. It is a misconception that they are the sole type of seizure, as they are the main seizure type in approximately 10% of those with epilepsy.These seizures typically initiate abruptly with either a focal or generalized onset, the former being known as focal to bilateral tonic-clonic seizure. The seizure itself includes tonic (sustained) and then clonic (repetitive short) contractions. In some seizures, the tonic phase may be preceded by brief, arrhythmic muscle jerks (myoclonus), by a clonic phase or by an absence seizure. After the GTCS, there is an extended postictal state where the person is unresponsive and commonly sleeping with loud snoring. There is usually pronounced confusion upon awakening.
Causes
The vast majority of generalized tonic-clonic seizures have a focal origin they start as a smaller seizure that occurs solely on one side of the brain and is referred to as a focal (or partial) seizure. These unilateral seizure types (formerly known as simple partial seizure or a complex partial seizure and now referred to as focal aware seizure and focal impaired awareness seizure, respectively) can then spread to both hemispheres of the brain and cause a generalized tonic-clonic seizure. This type of seizure has a specific term called "focal to a bilateral tonic-clonic seizure. Other generalized tonic-clonic seizures are idiopathic, start in large networks involving both hemispheres, and have a presumed genetic cause. Precipitating factors include chemical and neurotransmitter imbalances and a genetically or situationally determined seizure threshold, both of which have been implicated. The seizure threshold can be altered by fatigue, malnutrition, lack of sleep or rest, hypertension, stress, diabetes, the presence of strobe-flashes or simple light/dark patterns, raised estrogen levels at ovulation, fluorescent lighting, rapid motion or flight, blood sugar imbalances, anxiety, antihistamines and other factors. Tonic–clonic seizures can also be induced deliberately with electroconvulsive therapy.In the case of symptomatic focal epilepsy, the cause is often determined by MRI or other neuroimaging techniques showing that there is some degree of damage to a large number of neurons. The lesions (i.e., scar tissue) caused by the loss of these neurons can result in groups of neurons forming a seizure "focus" area with episodic abnormal firing that can cause seizures if the focus is not abolished or suppressed via anticonvulsant drugs.
Mechanism
Prodrome
Most generalized tonic–clonic seizures begin without warning and abruptly, but some epileptic patients describe a prodrome. The prodrome of a generalized tonic–clonic seizure is a sort of premonitory feeling hours before a seizure. This type of prodrome is distinct from stereotypic aura of focal seizures that become generalized seizures.
Phases
A tonic–clonic seizure comprises three phases: the tonic phase, clonic phase and postictal phase.
Tonic phaseThe tonic phase is usually the first phase. Consciousness will quickly be lost and the skeletal muscles will suddenly tense, often causing the extremities to be pulled towards the body or rigidly pushed away from it, which will cause the patient to fall if standing or sitting. There may also be upward deviation of the eyes with the mouth open. The tonic phase is usually the shortest part of the seizure, normally lasting only 10–20 seconds. The patient typically expresses brief vocalizations like a loud moan upon entering the tonic stage, due to air being forcefully expelled from the lungs. This vocalization is commonly referred to as an "ictal cry." Starting in the tonic phase, there may also be bluing of the skin from respiration impairment as well as pooling of saliva in the back of the throat. Increased blood pressure, pupillary size and heart rate (sympathetic response) may also be noted with clenching of the jaw possibly resulting in biting the tongue. The initial tonic phase may be preceded by repetitive rhythmic or arrhythmic jerks or by the absence seizure.
Clonic phaseThe clonic phase is an evolution of the tonic phase and is caused by muscle relaxations superimposed on the tonic phase muscle contractions. This phase is longer than the tonic phase with the total ictal period usually lasting no longer than 1 min. Skeletal muscles will start to contract and relax rapidly, causing convulsions. These may range from exaggerated twitches of the limbs to violent shaking or vibrating of the stiffened extremities. The patient may roll and stretch as the seizure spreads. Initially, these contractions are of a high frequency and low amplitude, which will gradually progress to decreased frequency and high amplitude. An eventual decrease in contraction amplitude just before seizure cessation is also typical.Postictal phaseThe postictal phase causes are multifactorial to include alteration of cerebral blood flow and effects on multiple neurotransmitters. These changes after a generalized tonic–clonic seizure cause a period of postictal sleep with stertorous breathing. Confusion and total amnesia upon regaining consciousness are also usually experienced and slowly wear off as the patient becomes gradually aware that a seizure occurred and remembers their identity and location. Most often, patients regain consciousness within 30 minutes. Rarely, impaired consciousness duration can last several hours after a seizure, especially with a compounding central nervous system condition or a prolonged seizure. Occasionally the patient may vomit or burst into tears from the experienced mental trauma. An additional smaller seizure can also occur several minutes after the main seizure, particularly if the patients seizure threshold has been brought unusually low by known factors or combinations of such. Examples include: severe hangovers, sleep deprivation, elevated estrogen at ovulation, prolonged physical tiredness, and drug use or abuse (including, but not limited to, stimulants, alcohol and caffeine). Rarely, the respiration is inhibited during the postictal phase, leading to sudden unexpected death in epilepsy (SUDEP). Generalized tonic–clonic seizures represent the most important risk factor for SUDEP, especially in patients with nocturnal seizures, who are living alone or do not share a bedroom.
Diagnosis
Diagnosis can be made definitively by video recordings of the seizures and Electroencephalography (EEG), which records the electrical activity of the brain. This is typically done after a seizure episode in a clinical setting with an attempt to "capture" a seizure while it happens. According to the "Harrisons Manual of Medicine," the EEG during the tonic phase will show a "progressive increase in low-voltage fast wave activity, followed by generalized high-amplitude, poly spike discharges." The clonic phase EEG will show "high amplitude activity that is typically interrupted by slow waves to create a spike-and-slow-wave pattern." Additionally, the postictal phase will show suppression of all brain activity, then slowing that gradually recovers as the patient awakens.
Management
For a person experiencing a tonic–clonic seizure, first-aid treatment includes rolling the person over into the recovery position, which can prevent asphyxiation by preventing fluid from entering the lungs. Other general actions to take as recommended by the Epilepsy Foundation include staying with a person until a seizure is over, paying attention to length of seizure as a possible indication for status epilepticus and/or indication to give rescue medication and call for emergency help, moving close objects out of the way to prevent injury. It is also not recommended to hold a person down that is having a seizure, as that can lead to injury. Nor should anything be put in a persons mouth, as these items can become choking hazards and, depending on what is put in, can potentially break the persons teeth. Long-term therapy may include the use of antiepileptic drugs, surgical therapy, diet therapy (ketogenic diet), vagus nerve stimulation, or deep brain stimulation.
Terminology
Generalized tonic–clonic seizures can have a focal onset (described above) that progresses into a generalized seizure or be a generalized seizure at the onset. The term "Grand Mal" is outdated and nonspecific, referring to generalized tonic-clonic seizures with either a focal or generalized onset.
See also
Focal seizure
Absence seizure
Epileptic seizure
Non-epileptic seizure
Tonic (physiology)
Clonus
Postictal state
Electroencephalography
References
External links
Generalized tonic–clonic seizure at Curlie |
Nonunion | Nonunion is permanent failure of healing following a broken bone unless intervention (such as surgery) is performed. A fracture with nonunion generally forms a structural resemblance to a fibrous joint, and is therefore often called a "false joint" or pseudoarthrosis (from Greek pseudo-, meaning false, and arthrosis, meaning joint). The diagnosis is generally made when there is no healing between two sets of medical imaging, such as X-ray or CT scan. This is generally after 6–8 months.Nonunion is a serious complication of a fracture and may occur when the fracture moves too much, has a poor blood supply or gets infected. Patients who smoke have a higher incidence of nonunion. The normal process of bone healing is interrupted or stalled.Since the process of bone healing is quite variable, a nonunion may go on to heal without intervention in very few cases. In general, if a nonunion is still evident at 6 months post-injury it will remain unhealed without specific treatment, usually orthopedic surgery. A non-union which does go on to heal is called a delayed union.
Signs and symptoms
A history of a broken bone is usually apparent. The patient complains of persistent pain at the fracture site and may also notice abnormal movement or clicking at the level of the fracture. An x-ray plate of the fractured bone shows a persistent radiolucent line at the fracture. Callus formation may be evident but callus does not bridge across the fracture. If there is doubt about the interpretation of the x-ray, stress x-rays, tomograms or CT scan may be used for confirmation.
Cause
The reasons for non-union are
avascular necrosis (the blood supply was interrupted by the fracture)
the two ends are not apposed (that is, they are not next to each other)
infection (particularly osteomyelitis)
the fracture is not fixed (that is, the two ends are still mobile)
soft-tissue imposition (there is muscle or ligament covering the broken ends and preventing them from touching each other)
Risk factors
Related to the person:
Age: Common in old age
Nutritional status : poor
Habits : Nicotine and alcohol consumption
Metabolic disturbance : Hyperparathyroidism
Can be found in those with NF1
Genetic predisposition
Causes related to fracture:
Related to the fracture site
Soft tissue interposition
Bone loss at the fracture
Infection
Loss of blood supply
Damage of surrounding muscles
Related to treatment
Inadequate reduction
Insufficient immobilization
Improperly applied fixation devices.
Types of Nonunion
There are typically three types of nonunion described.
Hypertrophic nonunion
In a hypertrophic nonunion, the fracture site contains adequate blood supply but the fracture ends fail to heal together. X-rays show abundant callus formation. This type of nonunion is thought to occur when the body has adequate biology, such as stem cells and blood supply, but inadequate stability, meaning the bone ends are moving too much. Typically, the treatment consists of increasing stability of the fracture site with surgical implants.
Atrophic nonunion
In an atrophic nonunion, x-rays show little to no callus formation. This is usually due to impaired bony healing, for example due to vascular causes (e.g. impaired blood supply to the bone fragments) or metabolic causes (e.g. diabetes or smoking). Failure of initial union, as when bone fragments are separated by soft tissue, may also lead to an atrophic non-union. Atrophic non-unions can be treated by stimulating blood flow and encouraging healing. This is often done surgically by removing the end layer of bone to provide raw ends for healing and the use of bone grafts.
Oligotrophic nonunion
As the name implies, an oligotrophic nonunion demonstrates some attempt by the body to heal the fracture. These are thought to arise from adequate biology but displacement at the fracture site.
Diagnosis
A diagnosis of nonunion is made when the clinician feels there will be no further bone healing without intervention. The FDA defines it as a fracture at least 9 months old that has not shown any signs of radiographic healing within the last 3 months. CT scans offer a closer look at the fracture and may also be used to evaluate how much of the fracture has healed. Blood tests can evaluate if the patient has adequate levels of nutrients such as calcium and vitamin D. Blood tests can also look for markers of infection such as ESR and CRP.
Treatment
Surgery
Currently, there are different strategies to augment the bone-regeneration process, however, there is no standardised clinical treatment guideline yet. Surgical treatment options include:
Debridement: radical surgical removal of necrotic or infected soft tissue and bone tissue is deemed essential for the healing process.
Immobilization of the fracture with internal or external fixation. Metal plates, pins, screws, and rods, that are screwed or driven into a bone, are used to stabilize the broken bone fragments.
Bone grafting. Filling of the bone defect resulting from debridement must be performed. Autologous bone graft is the "gold standard" treatment and possesses osteogenic, osteoinductive, and osteoconductive properties, although only a limited sample can be taken and there is a high risk of side effects.
Bone graft substitutes. Inorganic bone substitutes may be used to complement or replace autologous bone grafting. The advantage is that there is no morbidity on sampling and their availability is not restricted. S53P4 bioactive glass has shown good results as a promising bone graft substitute in treatment of nonunions, due to its osteostimulative, osteoconductive and antimicrobial properties.In simple cases, healing may be evident within 3 months. Gavriil Ilizarov revolutionized the treatment of recalcitrant nonunions demonstrating that the affected area of the bone could be removed, the fresh ends "docked" and the remaining bone lengthened using an external fixator device. The time course of healing after such treatment is longer than normal bone healing. Usually, there are signs of union within 3 months, but the treatment may continue for many months beyond that.
Bone stimulation
Bone stimulation may be with either electromagnetic or ultrasound waves. Ultrasound stimulation has tentative evidence of supporting better healing in long bones that have not healed after three months. Evidence; from a Cochrane review however, does not show that ultrasound decreases rates of nonunion. Another review has, however, suggested it as an alternative to surgery.
Prognosis
By definition, a nonunion will not heal if left alone. Therefore, the patients symptoms will not be improved and the function of the limb will remain impaired. It will be painful to bear weight on it and it may be deformed or unstable. The prognosis of nonunion if treated depends on many factors including the age and general health of the patient, the time since the original injury, the number of previous surgeries, smoking history, the patients ability to cooperate with the treatment. In the region of 80% of nonunions heal after the first operation. The success rate with subsequent surgeries is less.
See also
Distraction osteogenesis
References
External links
AAOS |
Bismuth | Bismuth is a chemical element with the symbol Bi and atomic number 83. It is a weakly radioactive post-transition metal and one of the pnictogens, with chemical properties resembling its lighter group 15 siblings arsenic and antimony. Elemental bismuth may occur naturally, and its sulfide and oxide forms are important commercial ores. The free element is 86% as dense as lead. It is a brittle metal with a silvery-white color when freshly produced. Surface oxidation generally gives samples of the metal a somewhat rosy cast. Further oxidation under heat can give bismuth a vividly iridescent appearance due to thin-film interference. Bismuth is both the most diamagnetic element and one of the least thermally conductive metals known.
Bismuth was long considered the element with the highest atomic mass whose nuclei do not spontaneously decay. However, in 2003 it was discovered to be extremely weakly radioactive. The metals only primordial isotope, bismuth-209, experiences alpha decay at such a minute rate that its half-life is more than a billion times the estimated age of the observable universe. For all but the most exotic of uses bismuth may be considered stable because of its tremendously long half-life.Bismuth metal has been known since ancient times. Before modern analytical methods bismuths metallurgical similarities to lead and tin often led it to be confused for those metals. The etymology of "bismuth" is uncertain. The name may come from mid-sixteenth century New Latin translations of the German words weiße Masse or Wismuth, meaning white mass, which were rendered as bisemutum or bisemutium.
Main uses
Bismuth compounds account for about half the global production of bismuth. They are used in cosmetics; pigments; and a few pharmaceuticals, notably bismuth subsalicylate, used to treat diarrhea. Bismuths unusual propensity to expand as it solidifies is responsible for some of its uses, as in the casting of printing type. Bismuth has unusually low toxicity for a heavy metal. As the toxicity of lead and the cost of its environmental remediation became more apparent during the 20th century, suitable bismuth alloys have gained popularity as replacements for lead. Presently, around a third of global bismuth production is dedicated to needs formerly met by lead.
History and etymology
Bismuth metal has been known since ancient times and it was one of the first 10 metals to have been discovered. The name bismuth dates to around 1665 and is of uncertain etymology. The name possibly comes from obsolete German Bismuth, Wismut, Wissmuth (early 16th century), perhaps related to Old High German hwiz ("white"). The New Latin bisemutium (coined by Georgius Agricola, who Latinized many German mining and technical words) is from the German Wismuth, itself perhaps from weiße Masse, meaning "white mass".The element was confused in early times with tin and lead because of its resemblance to those elements. Because bismuth has been known since ancient times, no one person is credited with its discovery. Agricola (1546) states that bismuth is a distinct metal in a family of metals including tin and lead. This was based on observation of the metals and their physical properties.Miners in the age of alchemy also gave bismuth the name tectum argenti, or "silver being made" in the sense of silver still in the process of being formed within the Earth.Bismuth was also known to the Incas and used (along with the usual copper and tin) in a special bronze alloy for knives.
Beginning with Johann Heinrich Pott in 1738, Carl Wilhelm Scheele, and Torbern Olof Bergman, the distinctness of lead and bismuth became clear, and Claude François Geoffroy demonstrated in 1753 that this metal is distinct from lead and tin.
Characteristics
Physical characteristics
Bismuth is a brittle metal with a dark, silver-pink hue, often with an iridescent oxide tarnish showing many colors from yellow to blue. The spiral, stair-stepped structure of bismuth crystals is the result of a higher growth rate around the outside edges than on the inside edges. The variations in the thickness of the oxide layer that forms on the surface of the crystal cause different wavelengths of light to interfere upon reflection, thus displaying a rainbow of colors. When burned in oxygen, bismuth burns with a blue flame and its oxide forms yellow fumes. Its toxicity is much lower than that of its neighbors in the periodic table, such as lead, antimony, and polonium.
No other metal is verified to be more naturally diamagnetic than bismuth. (Superdiamagnetism is a different physical phenomenon.) Of any metal, it has one of the lowest values of thermal conductivity (after manganese, and maybe neptunium and plutonium) and the highest Hall coefficient. It has a high electrical resistivity. When deposited in sufficiently thin layers on a substrate, bismuth is a semiconductor, despite being a post-transition metal. Elemental bismuth is denser in the liquid phase than the solid, a characteristic it shares with germanium, silicon, gallium, and water. Bismuth expands 3.32% on solidification; therefore, it was long a component of low-melting typesetting alloys, where it compensated for the contraction of the other alloying components to form almost isostatic bismuth-lead eutectic alloys.
Though virtually unseen in nature, high-purity bismuth can form distinctive, colorful hopper crystals. It is relatively nontoxic and has a low melting point just above 271 °C, so crystals may be grown using a household stove, although the resulting crystals will tend to be of lower quality than lab-grown crystals.At ambient conditions, bismuth shares the same layered structure as the metallic forms of arsenic and antimony, crystallizing in the rhombohedral lattice (Pearson symbol hR6, space group R3m No. 166) of the trigonal crystal system. When compressed at room temperature, this Bi-I structure changes first to the monoclinic Bi-II at 2.55 GPa, then to the tetragonal Bi-III at 2.7 GPa, and finally to the body-centered cubic Bi-V at 7.7 GPa. The corresponding transitions can be monitored via changes in electrical conductivity; they are rather reproducible and abrupt and are therefore used for calibration of high-pressure equipment.
Chemical characteristics
Bismuth is stable to both dry and moist air at ordinary temperatures. When red-hot, it reacts with water to make bismuth(III) oxide.
2 Bi + 3 H2O → Bi2O3 + 3 H2It reacts with fluorine to make bismuth(V) fluoride at 500 °C or bismuth(III) fluoride at lower temperatures (typically from Bi melts); with other halogens it yields only bismuth(III) halides. The trihalides are corrosive and easily react with moisture, forming oxyhalides with the formula BiOX.
4 Bi + 6 X2 → 4 BiX3 (X = F, Cl, Br, I)
4 BiX3 + 2 O2 → 4 BiOX + 4 X2Bismuth dissolves in concentrated sulfuric acid to make bismuth(III) sulfate and sulfur dioxide.
6 H2SO4 + 2 Bi → 6 H2O + Bi2(SO4)3 + 3 SO2It reacts with nitric acid to make bismuth(III) nitrate (which decomposes into nitrogen dioxide when heated).
Bi + 6 HNO3 → 3 H2O + 3 NO2 + Bi(NO3)3It also dissolves in hydrochloric acid, but only with oxygen present.
4 Bi + 3 O2 + 12 HCl → 4 BiCl3 + 6 H2OIt is used as a transmetalating agent in the synthesis of alkaline-earth metal complexes:
3 Ba + 2 BiPh3 → 3 BaPh2 + 2 Bi
Isotopes
The only primordial isotope of bismuth, bismuth-209, was traditionally regarded as the heaviest stable isotope, but it had long been suspected to be unstable on theoretical grounds. This was finally demonstrated in 2003, when researchers at the Institut dAstrophysique Spatiale in Orsay, France, measured the alpha emission half-life of 209Bi to be 2.01×1019 years (3 Bq/Mg), over a billion times longer than the current estimated age of the universe. Owing to its extraordinarily long half-life, for all presently known medical and industrial applications, bismuth can be treated as if it is stable and nonradioactive. The radioactivity is of academic interest because bismuth is one of a few elements whose radioactivity was suspected and theoretically predicted before being detected in the laboratory. Bismuth has the longest known alpha decay half-life, although tellurium-128 has a double beta decay half-life of over 2.2×1024 years. Bismuths extremely long half-life means that less than approximately one-billionth of the bismuth present at the formation of the planet Earth would have decayed into thallium since then.
Several isotopes of bismuth with short half-lives occur within the radioactive disintegration chains of actinium, radium, and thorium, and more have been synthesized experimentally. Bismuth-213 is also found on the decay chain of neptunium-237 and uranium-233.Commercially, the radioactive isotope bismuth-213 can be produced by bombarding radium with bremsstrahlung photons from a linear particle accelerator. In 1997, an antibody conjugate with bismuth-213, which has a 45-minute half-life and decays with the emission of an alpha particle, was used to treat patients with leukemia. This isotope has also been tried in cancer treatment, for example, in the targeted alpha therapy (TAT) program.
Chemical compounds
Bismuth forms trivalent and pentavalent compounds, the trivalent ones being more common. Many of its chemical properties are similar to those of arsenic and antimony, although they are less toxic than derivatives of those lighter elements.
Oxides and sulfides
At elevated temperatures, the vapors of the metal combine rapidly with oxygen, forming the yellow trioxide, Bi2O3. When molten, at temperatures above 710 °C, this oxide corrodes any metal oxide and even platinum. On reaction with a base, it forms two series of oxyanions: BiO−2, which is polymeric and forms linear chains, and BiO3−3. The anion in Li3BiO3 is a cubic octameric anion, Bi8O24−24, whereas the anion in Na3BiO3 is tetrameric.The dark red bismuth(V) oxide, Bi2O5, is unstable, liberating O2 gas upon heating. The compound NaBiO3 is a strong oxidising agent.Bismuth sulfide, Bi2S3, occurs naturally in bismuth ores. It is also produced by the combination of molten bismuth and sulfur.
Bismuth oxychloride (BiOCl, see figure at right) and bismuth oxynitrate (BiONO3) stoichiometrically appear as simple anionic salts of the bismuthyl(III) cation (BiO+) which commonly occurs in aqueous bismuth compounds. However, in the case of BiOCl, the salt crystal forms in a structure of alternating plates of Bi, O, and Cl atoms, with each oxygen coordinating with four bismuth atoms in the adjacent plane. This mineral compound is used as a pigment and cosmetic (see below).
Bismuthine and bismuthides
Unlike the lighter pnictogens nitrogen, phosphorus, and arsenic, but similar to antimony, bismuth does not form a stable hydride. Bismuth hydride, bismuthine (BiH3), is an endothermic compound that spontaneously decomposes at room temperature. It is stable only below −60 °C. Bismuthides are intermetallic compounds between bismuth and other metals.In 2014 researchers discovered that sodium bismuthide can exist as a form of matter called a “three-dimensional topological Dirac semi-metal” (3DTDS) that possess 3D Dirac fermions in bulk. It is a natural, three-dimensional counterpart to graphene with similar electron mobility and velocity. Graphene and topological insulators (such as those in 3DTDS) are both crystalline materials that are electrically insulating inside but conducting on the surface, allowing them to function as transistors and other electronic devices. While sodium bismuthide (Na3Bi) is too unstable to be used in devices without packaging, it can demonstrate potential applications of 3DTDS systems, which offer distinct efficiency and fabrication advantages over planar graphene in semiconductor and spintronics applications.
Halides
The halides of bismuth in low oxidation states have been shown to adopt unusual structures. What was originally thought to be bismuth(I) chloride, BiCl, turns out to be a complex compound consisting of Bi5+9 cations and BiCl2−5 and Bi2Cl2−8 anions. The Bi5+9 cation has a distorted tricapped trigonal prismatic molecular geometry and is also found in Bi10Hf3Cl18, which is prepared by reducing a mixture of hafnium(IV) chloride and bismuth chloride with elemental bismuth, having the structure [Bi+] [Bi5+9] [HfCl2−6]3.: 50 Other polyatomic bismuth cations are also known, such as Bi2+8, found in Bi8(AlCl4)2. Bismuth also forms a low-valence bromide with the same structure as "BiCl". There is a true monoiodide, BiI, which contains chains of Bi4I4 units. BiI decomposes upon heating to the triiodide, BiI3, and elemental bismuth. A monobromide of the same structure also exists.
In oxidation state +3, bismuth forms trihalides with all of the halogens: BiF3, BiCl3, BiBr3, and BiI3. All of these except BiF3 are hydrolyzed by water.Bismuth(III) chloride reacts with hydrogen chloride in ether solution to produce the acid HBiCl4.The oxidation state +5 is less frequently encountered. One such compound is BiF5, a powerful oxidizing and fluorinating agent. It is also a strong fluoride acceptor, reacting with xenon tetrafluoride to form the XeF+3 cation:
BiF5 + XeF4 → XeF+3BiF−6
Aqueous species
In aqueous solution, the Bi3+ ion is solvated to form the aqua ion Bi(H2O)3+8 in strongly acidic conditions. At pH > 0 polynuclear species exist, the most important of which is believed to be the octahedral complex [Bi6O4(OH)4]6+.
Occurrence and production
In the Earths crust, bismuth is about twice as abundant as gold. The most important ores of bismuth are bismuthinite and bismite. Native bismuth is known from Australia, Bolivia, and China.
The difference between mining and refining production reflects bismuths status as a byproduct of extraction of other metals such as lead, copper, tin, molybdenum and tungsten. World bismuth production from refineries is a more complete and reliable statistic.Bismuth travels in crude lead bullion (which can contain up to 10% bismuth) through several stages of refining, until it is removed by the Kroll-Betterton process which separates the impurities as slag, or the electrolytic Betts process. Bismuth will behave similarly with another of its major metals, copper. The raw bismuth metal from both processes contains still considerable amounts of other metals, foremost lead. By reacting the molten mixture with chlorine gas the metals are converted to their chlorides while bismuth remains unchanged. Impurities can also be removed by various other methods for example with fluxes and treatments yielding high-purity bismuth metal (over 99% Bi).
Price
The price for pure bismuth metal has been relatively stable through most of the 20th century, except for a spike in the 1970s. Bismuth has always been produced mainly as a byproduct of lead refining, and thus the price usually reflected the cost of recovery and the balance between production and demand.Prior to World War II, demand for bismuth was small and mainly pharmaceutical — bismuth compounds were used to treat such conditions as digestive disorders, sexually transmitted diseases and burns. Minor amounts of bismuth metal were consumed in fusible alloys for fire sprinkler systems and fuse wire. During World War II bismuth was considered a strategic material, used for solders, fusible alloys, medications and atomic research. To stabilize the market, the producers set the price at $1.25 per pound ($2.75 /kg) during the war and at $2.25 per pound ($4.96 /kg) from 1950 until 1964.In the early 1970s, the price rose rapidly as a result of increasing demand for bismuth as a metallurgical additive to aluminium, iron and steel. This was followed by a decline owing to increased world production, stabilized consumption, and the recessions of 1980 and 1981–1982. In 1984, the price began to climb as consumption increased worldwide, especially in the United States and Japan. In the early 1990s, research began on the evaluation of bismuth as a nontoxic replacement for lead in ceramic glazes, fishing sinkers, food-processing equipment, free-machining brasses for plumbing applications, lubricating greases, and shot for waterfowl hunting. Growth in these areas remained slow during the middle 1990s, in spite of the backing of lead replacement by the United States federal government, but intensified around 2005. This resulted in a rapid and continuing increase in price.
Recycling
Most bismuth is produced as a byproduct of other metal-extraction processes including the smelting of lead, and also of tungsten and copper. Its sustainability is dependent on increased recycling, which is problematic.It was once believed that bismuth could be practically recycled from the soldered joints in electronic equipment. Recent efficiencies in solder application in electronics mean there is substantially less solder deposited, and thus less to recycle. While recovering the silver from silver-bearing solder may remain economic, recovering bismuth is substantially less so.Next in recycling feasibility would be sizeable catalysts with a fair bismuth content, such as bismuth phosphomolybdate. Bismuth used in galvanizing, and as a free-machining metallurgical additive.Bismuth in uses where it is dispersed most widely include certain stomach medicines (bismuth subsalicylate), paints (bismuth vanadate), pearlescent cosmetics (bismuth oxychloride), and bismuth-containing bullets. Recycling bismuth from these uses is impractical.
Applications
Bismuth has few commercial applications, and those applications that use it generally require small quantities relative to other raw materials. In the United States, for example, 733 tonnes of bismuth were consumed in 2016, of which 70% went into chemicals (including pharmaceuticals, pigments, and cosmetics) and 11% into bismuth alloys.Some manufacturers use bismuth as a substitute in equipment for potable water systems such as valves to meet "lead-free" mandates in the U.S. (began in 2014). This is a fairly large application since it covers all residential and commercial building construction.In the early 1990s, researchers began to evaluate bismuth as a nontoxic replacement for lead in various applications.
Medicines
Bismuth is an ingredient in some pharmaceuticals, although the use of some of these substances is declining.
Bismuth subsalicylate is used as an antidiarrheal; it is the active ingredient in such "pink bismuth" preparations as Pepto-Bismol, as well as the 2004 reformulation of Kaopectate. It is also used to treat some other gastro-intestinal diseases like shigellosis and cadmium poisoning. The mechanism of action of this substance is still not well documented, although an oligodynamic effect (toxic effect of small doses of heavy metal ions on microbes) may be involved in at least some cases. Salicylic acid from hydrolysis of the compound is antimicrobial for toxogenic E. coli, an important pathogen in travelers diarrhea.
A combination of bismuth subsalicylate and bismuth subcitrate is used to treat the bacteria causing peptic ulcers.
Bibrocathol is an organic bismuth-containing compound used to treat eye infections.
Bismuth subgallate, the active ingredient in Devrom, is used as an internal deodorant to treat malodor from flatulence and feces.
Bismuth compounds (including sodium bismuth tartrate) were formerly used to treat syphilis. Arsenic combined with either bismuth or mercury was a mainstay of syphilis treatment from the 1920s until the advent of penicillin in 1943.
"Milk of bismuth" (an aqueous suspension of bismuth hydroxide and bismuth subcarbonate) was marketed as an alimentary cure-all in the early 20th century, and has been used to treat gastrointestinal disorders.
Bismuth subnitrate (Bi5O(OH)9(NO3)4) and bismuth subcarbonate (Bi2O2(CO3)) are also used in medicine.
Cosmetics and pigments
Bismuth oxychloride (BiOCl) is sometimes used in cosmetics, as a pigment in paint for eye shadows, hair sprays and nail polishes. This compound is found as the mineral bismoclite and in crystal form contains layers of atoms (see figure above) that refract light chromatically, resulting in an iridescent appearance similar to nacre of pearl. It was used as a cosmetic in ancient Egypt and in many places since. Bismuth white (also "Spanish white") can refer to either bismuth oxychloride or bismuth oxynitrate (BiONO3), when used as a white pigment. Bismuth vanadate is used as a light-stable non-reactive paint pigment (particularly for artists paints), often as a replacement for the more toxic cadmium sulfide yellow and orange-yellow pigments. The most common variety in artists paints is a lemon yellow, visually indistinguishable from its cadmium-containing alternative.
Metal and alloys
Bismuth is used in metal alloys with other metals such as iron. These alloys are used in automatic sprinkler systems for fires. It forms the largest part (50%) of Roses metal, a fusible alloy, which also contains 25–28% lead and 22–25% tin. It was also used to make bismuth bronze which was used in the Bronze Age, having been found in Inca knives at Machu Picchu.
Lead replacement
The density difference between lead (11.32 g/cm3) and bismuth (9.78 g/cm3) is small enough that for many ballistics and weighting applications, bismuth can substitute for lead. For example, it can replace lead as a dense material in fishing sinkers. It has been used as a replacement for lead in shot, bullets and less-lethal riot gun ammunition. The Netherlands, Denmark, England, Wales, the United States, and many other countries now prohibit the use of lead shot for the hunting of wetland birds, as many birds are prone to lead poisoning owing to mistaken ingestion of lead (instead of small stones and grit) to aid digestion, or even prohibit the use of lead for all hunting, such as in the Netherlands. Bismuth-tin alloy shot is one alternative that provides similar ballistic performance to lead. (Another less expensive but also more poorly performing alternative is "steel" shot, which is actually soft iron.) Bismuths lack of malleability does, however, make it unsuitable for use in expanding hunting bullets.Bismuth, as a dense element of high atomic weight, is used in bismuth-impregnated latex shields to shield from X-ray in medical examinations, such as CTs, mostly as it is considered non-toxic.The European Unions Restriction of Hazardous Substances Directive (RoHS) for reduction of lead has broadened bismuths use in electronics as a component of low-melting point solders, as a replacement for traditional tin-lead solders. Its low toxicity will be especially important for solders to be used in food processing equipment and copper water pipes, although it can also be used in other applications including those in the automobile industry, in the European Union, for example.Bismuth has been evaluated as a replacement for lead in free-machining brasses for plumbing applications, although it does not equal the performance of leaded steels.
Other metal uses and specialty alloys
Many bismuth alloys have low melting points and are found in specialty applications such as solders. Many automatic sprinklers, electric fuses, and safety devices in fire detection and suppression systems contain the eutectic In19.1-Cd5.3-Pb22.6-Sn8.3-Bi44.7 alloy that melts at 47 °C (117 °F) This is a convenient temperature since it is unlikely to be exceeded in normal living conditions. Low-melting alloys, such as Bi-Cd-Pb-Sn alloy which melts at 70 °C, are also used in automotive and aviation industries. Before deforming a thin-walled metal part, it is filled with a melt or covered with a thin layer of the alloy to reduce the chance of breaking. Then the alloy is removed by submerging the part in boiling water.Bismuth is used to make free-machining steels and free-machining aluminium alloys for precision machining properties. It has similar effect to lead and improves the chip breaking during machining. The shrinking on solidification in lead and the expansion of bismuth compensate each other and therefore lead and bismuth are often used in similar quantities. Similarly, alloys containing comparable parts of bismuth and lead exhibit a very small change (on the order 0.01%) upon melting, solidification or aging. Such alloys are used in high-precision casting, e.g. in dentistry, to create models and molds. Bismuth is also used as an alloying agent in production of malleable irons and as a thermocouple material.Bismuth is also used in aluminium-silicon cast alloys in order to refine silicon morphology. However, it indicated a poisoning effect on modification of strontium. Some bismuth alloys, such as Bi35-Pb37-Sn25, are combined with non-sticking materials such as mica, glass and enamels because they easily wet them allowing to make joints to other parts. Addition of bismuth to caesium enhances the quantum yield of caesium cathodes. Sintering of bismuth and manganese powders at 300 °C produces a permanent magnet and magnetostrictive material, which is used in ultrasonic generators and receivers working in the 10–100 kHz range and in magnetic and holographic memory devices.
Other uses as compounds
Bismuth is included in BSCCO (bismuth strontium calcium copper oxide) which is a group of similar superconducting compounds discovered in 1988 that exhibit the highest superconducting transition temperatures.
Bismuth subnitrate is a component of glazes that produces an iridescence and is used as a pigment in paint.
Bismuth telluride is a semiconductor and an excellent thermoelectric material. Bi2 |
Bismuth | Te3 diodes are used in mobile refrigerators, CPU coolers, and as detectors in infrared spectrophotometers.
Bismuth oxide, in its delta form, is a solid electrolyte for oxygen. This form normally breaks down below a high-temperature threshold, but can be electrodeposited well below this temperature in a highly alkaline solution.
Bismuth germanate is a scintillator, widely used in X-ray and gamma ray detectors.
Bismuth vanadate is an opaque yellow pigment used by some artists oil, acrylic, and watercolor paint companies, primarily as a replacement for the more toxic cadmium sulfide yellows in the greenish-yellow (lemon) to orange-toned yellow range. It performs practically identically to the cadmium pigments, such as in terms of resistance to degradation from UV exposure, opacity, tinting strength, and lack of reactivity when mixed with other pigments. The most commonly-used variety by artists paint makers is lemon in color. In addition to being a replacement for several cadmium yellows, it also serves as a non-toxic visual replacement for the older chromate pigments made with zinc, lead, and strontium. If a green pigment and barium sulfate (for increased transparency) are added it can also serve as a replacement for barium chromate, which possesses a more greenish cast than the others. In comparison with lead chromates, it does not blacken due to hydrogen sulfide in the air (a process accelerated by UV exposure) and possesses a particularly brighter color than them, especially the lemon, which is the most translucent, dull, and fastest to blacken due to the higher percentage of lead sulfate required to produce that shade. It is also used, on a limited basis due to its cost, as a vehicle paint pigment.
A catalyst for making acrylic fibers.
As an electrocatalyst in the conversion of CO2 to CO.
Ingredient in lubricating greases.
In crackling microstars (dragons eggs) in pyrotechnics, as the oxide, subcarbonate or subnitrate.
As catalyst for the fluorination of arylboronic pinacol esters through a Bi(III)/Bi(V) catalytic cycle, mimicking transition metals in electrophilic fluorination.
Toxicology and ecotoxicology
See also bismuthia, a rare dermatological condition that results from the prolonged use of bismuth.Scientific literature indicates that some of the compounds of bismuth are less toxic to humans via ingestion than other heavy metals (lead, arsenic, antimony, etc.) presumably due to the comparatively low solubility of bismuth salts. Its biological half-life for whole-body retention is reported to be 5 days but it can remain in the kidney for years in people treated with bismuth compounds.Bismuth poisoning can occur and has according to some reports been common in relatively recent times. As with lead, bismuth poisoning can result in the formation of a black deposit on the gingiva, known as a bismuth line. Poisoning may be treated with dimercaprol; however, evidence for benefit is unclear.Bismuths environmental impacts are not well known; it may be less likely to bioaccumulate than some other heavy metals, and this is an area of active research.
Bioremediation
The fungus Marasmius oreades can be used for the biological remediation of bismuth in polluted soils.
See also
Lead-bismuth eutectic
List of countries by bismuth production
Bismuth minerals
Patterns in nature
References
Bibliography
This article incorporates text from this source, which is in the public domain: Brown, R. D., Jr. "Annual Average Bismuth Price", USGS (1998)
Greenwood, N. N. & Earnshaw, A. (1997). Chemistry of the Elements (2nd ed.). Oxford: Butterworth-Heinemann. ISBN 978-0-7506-3365-9.
Krüger, Joachim; Winkler, Peter; Lüderitz, Eberhard; Lück, Manfred; Wolf, Hans Uwe (2003). "Bismuth, Bismuth Alloys, and Bismuth Compounds". Ullmanns Encyclopedia of Industrial Chemistry. Wiley-VCH, Weinheim. pp. 171–189. doi:10.1002/14356007.a04_171. ISBN 978-3527306732.
Suzuki, Hitomi (2001). Organobismuth Chemistry. Elsevier. pp. 1–20. ISBN 978-0-444-20528-5.
Wiberg, Egon; Holleman, A. F.; Wiberg, Nils (2001). Inorganic chemistry. Academic Press. ISBN 978-0-12-352651-9.
External links
Laboratory growth of large crystals of Bismuth by Jan Kihle Crystal Pulling Laboratories, Norway
Bismuth at The Periodic Table of Videos (University of Nottingham)
Bismuth breaks half-life record for alpha decay
Bismuth Crystals – Instructions & Pictures |
Developmental language disorder | Developmental language disorder (DLD) is identified when a child has problems with language development that continue into school age and beyond. The language problems have a significant impact on everyday social interactions or educational progress, and occur in the absence of autism spectrum disorder, intellectual disability or a known biomedical condition. The most obvious problems are difficulties in using words and sentences to express meanings, but for many children, understanding of language (receptive language) is also a challenge. This may not be evident unless the child is given a formal assessment.
Classification
Terminology
The term developmental language disorder (DLD) was endorsed in a consensus study involving a panel of experts (CATALISE Consortium) in 2017. The study was conducted in response to concerns that a wide range of terminology was used in this area, with the consequence that there was poor communication, lack of public recognition, and in some cases children were denied access to services. Developmental language disorder is a subset of language disorder, which is itself a subset of the broader category of speech, language and communication needs (SLCN).
The terminology for childrens language disorders has been extremely wide-ranging and confusing, with many labels that have overlapping but not necessarily identical meanings. In part this confusion reflected uncertainty about the boundaries of DLD, and the existence of different subtypes. Historically, the terms "developmental dysphasia" or "developmental aphasia" were used to describe children with the clinical picture of DLD. These terms have, however, largely been abandoned, as they suggest parallels with adult-acquired aphasia. This is misleading, as DLD is not caused by brain damage.Although the term DLD has been used for many years, it has been less common than the term specific language impairment (SLI), which has been widely adopted, especially in North America. The definition of SLI overlaps with DLD, but was rejected by the CATALISE panel because it was seen as overly restrictive in implying that the child had relatively pure problems with language in the absence of any other impairments. Children with such selective problems are relatively rare, and there is no evidence that they respond differently to intervention, or have different causal factors, from other children with language problems.In the UK education system, the term speech, language and communication needs (SLCN) is widely used, but this is far broader than DLD, and includes children with speech, language and social communication difficulties arising from a wide range of causes.The question of whether to refer to childrens language problems as a disorder was a topic of debate among the CATALISE consortium, but the conclusion was that disorder conveyed the serious nature and potential consequences of persistent language deficits. It is also parallel with other neurodevelopmental conditions and consistent with diagnostic frameworks such as the DSM-5 and ICD-11. Where there are milder or more transient difficulties, language difficulties may be a more appropriate term.
Areas of language difficulty
DLD can affect a range of areas of language and the degree of impairment in different areas of language can vary from child to child. However, although there have been attempts to define different subtypes, these have not generally resulted in robust categories. The recommendation of the CATALISE panel was that the specific areas of impairment should be assessed and documented for individual children, while recognizing that different children might have different combinations of problems. The areas which can be affected are:
Grammar – This involves the ability to combine words into grammatically correct sentences (syntax) and to combine parts of words together (morphology) such as adding grammatical endings to verbs like -ing or -ed or to add prefixes and suffixes like dis- or -ation. For instance, a child may say me jump here, instead of I jumped here. Comprehension of sentences can also be affected. For instance, there may be difficulty understanding meaning expressed by word order, and so confusion about what is blue in a sentence like the pencil on the shoe is blue, and a tendency to use general knowledge rather than linguistic cues to meaning, or problems in interpreting grammatical markers of number or tense.
Semantics – This refers to childrens ability to understand the meaning of words and how meanings are expressed by combining words together. Children with DLD often have limited vocabulary and may make heavy use of a small set of words with rather general meanings. As children with developmental language disorder get older, they may have a hard time understanding that some words have multiple meanings, for example the word "cold", which can mean a low temperature, a sickness, or being unfriendly.
Word finding – Children with word finding difficulties may know a word, but have difficulty accessing it for production – similar to the tip of the tongue phenomenon.
Pragmatics – Pragmatics refers to the ability to select the appropriate message, or interpret what others say, in relation to context. Pragmatic difficulties can give an impression of oddity, with the content of language not fitting the environmental or social context; comprehension may be over-literal; the child may chatter incessantly, be poor at turn-taking in conversation and maintaining a topic
Discourse – Discourse refers to a level of organization of language beyond the sentence. Child with limitations in this domain may have limited ability to tell a story or describe a set of events in a logical sequence
Verbal memory and learning – Problems with remembering words or sentences can affect both the learning of new vocabulary, and the understanding of long or complex sentences. Young children with DLD may say their first words later than other children. It may also take children with DLD longer to learn and remember novel words.
Phonology – Phonology is the branch of linguistics concerned with the way sounds are combined in words. Children with difficulties with phonology may fail to distinguish between certain speech sounds, such as t and k, so that cake is produced as tate. Such difficulties are not unusual as part of typical development in toddlers, but they would usually resolve by the time children are 4–5 years old. Difficulties with producing some speech sounds accurately may reduce intelligibility of speech. In addition, more subtle difficulties in recognising specific sounds in words (phonological awareness) can lead to literacy difficulties.
Relationship with speech disorders
Speech is the act of articulating sounds, and this can be impaired for all kinds of reasons – a structural problem such as cleft lip and cleft palate, a neurological problem affecting motor control of the speech apparatus dysarthria, or inability to perceive distinctions between sounds because of hearing loss. Some distortions of speech sounds, such as a lisp, are commonly seen in young children. These misarticulations should not be confused with language problems, which involve the ability to select and combine linguistic elements to express meanings, and the ability to comprehend meanings.Although speech disorders can be distinguished from language disorders, they can also co-occur. When a child fails to produce distinctions between speech sounds for no obvious reason, this is typically regarded as a language problem affecting the learning of phonological contrasts. The classification of and terminology for disorders of speech sound production is a subject of considerable debate. In practice, even for those with specialist skills, it is not always easy to distinguish between phonological disorders and other types of speech production problem.
Speech sound disorder (SSD) is any problem with speech production arising from any cause.Speech sound disorders of unknown cause that are not accompanied by other language problems are a relatively common reason for young children to be referred to speech-language therapy (speech-language pathology). These often resolve by around 4–5 years of age with specialist intervention, and so would not meet criteria for DLD. Where such problems continue beyond five years of age, they are usually accompanied by problems in broader language domains and have a poorer prognosis, so a diagnosis of DLD with SSD is then appropriate.
Relationship with other neurodevelopmental disorders
DLD often co-occurs with milder neurodevelopmental disorders of unknown origin, such as attention-deficit hyperactivity disorder, developmental dyslexia or developmental coordination disorder. These do not preclude a diagnosis of DLD, but should be noted as co-occurring conditions.
Risk factors
It is generally accepted that DLD is strongly influenced by genetic factors. The best evidence comes from the twin study method. Two twins growing up together are exposed to the same home environment, yet may differ radically in their language skills. Such different outcomes are, however, much more common in fraternal (non-identical) twins, who are genetically different. Identical twins share the same genes and tend to be much more similar in language ability. There can be some variation in the severity and persistence of DLD in identical twins, indicating that non-genetic factors affect the course of disorder, but it is unusual to find a child with DLD who has an identical twin with typical language.There was considerable excitement when a large, multigenerational family with a high rate of DLD were found to have a mutation of the FOXP2 gene just in the affected family members. However, subsequent studies have found that, though DLD runs in families, it is not usually caused by a mutation in FOXP2 or another specific gene. Current evidence suggests that there are many different genes that can influence language learning, and DLD results when a child inherits a particularly detrimental combination of risk factors, each of which may have only a small effect. Nevertheless, study of the mode of action of the FOXP2 gene has helped identify other common genetic variants involved in the same neural pathways that may play a part in causing DLD.Language disorders are associated with aspects of home environment, and it is often assumed that this is a causal link, with poor language stimulation leading to weak language skills. Twin studies, however, show that two children in the same home environment can have very different language outcomes, suggesting we should consider other explanations for the link. Children with DLD often grow up into adults who have relatively low educational attainments, and their children may share a genetic risk for language disorder.One non-genetic factor that is known to have a specific impact on language development is being a younger sibling in a large family.
Associated factors
It has long been noted that males are more affected by DLD than females, with a sex ratio of affected males-to-females around 3 or 4:1. However, the sex difference is much less striking in epidemiological samples, suggesting that similar problems may exist in females but are less likely to be detected. The reason for the sex difference is not well understood.Poor motor skills are commonly found in children with DLD. Standardized measures of motor ability confirm that children with DLD exhibit deficits in fine and gross motor skill, both simple and complex. These difficulties also extend to speech-motor ability, particularly with the control of their articulatory movements. Children with DLD have difficulty with motor sequence learning and may show deficits in other procedural motor processes as well.Brain scans do not usually reveal any obvious abnormalities in children with DLD, although quantitative comparisons have found differences in brain size or relative proportions of white or grey matter in specific regions. In some cases, unusual brain gyri are found. To date, no consistent neural signature for DLD has been found, although some studies have noted evidence for involvement of subcortical systems. Differences in the brains of children with DLD versus typically developing children are subtle and may overlap with atypical patterns seen in other neurodevelopmental disorders.
Diagnosis
DLD is defined purely in behavioural terms: there is no biological test. There are three points that need to be met for a diagnosis of DLD:
The child has language difficulties that create obstacles to communication or learning in everyday life,
The childs language problems are unlikely to resolve by five years of age, and
The problems are not associated with a known biomedical condition such as brain injury, neurodegenerative conditions, genetic conditions or chromosome disorders such as Down syndrome, sensorineural hearing loss, autism spectrum disorder, or intellectual disability.For research and epidemiological purposes, specific cutoffs on language assessments have been used to document the first criterion. Tomblin et al. proposed the EpiSLI criterion, based on five composite scores representing performance in three domains of language (vocabulary, grammar, and narration) and two modalities (comprehension and production). Children scoring in the lowest 10% on two or more composite scores are identified as having language disorder.
The second criterion, persistence of language problems, can be difficult to judge in a young child, but longitudinal studies have shown that difficulties are less likely to resolve for children who have poor language comprehension, rather than difficulties confined to expressive language. In addition, children with isolated difficulties in just one of the areas noted under subtypes tend to make better progress than those whose language is impaired in several areas.The third criterion specifies that DLD is used for children whose language disorder is not part of another biomedical condition, such as a genetic syndrome, a sensorineural hearing loss, neurological disease, autism spectrum disorder or intellectual disability – these were termed differentiating conditions by the CATALISE panel. Language disorders occurring with these conditions need to be assessed and children offered appropriate intervention, but a terminological distinction is made so that these cases would be diagnosed as language disorder associated with the main diagnosis being specified: e.g. "language disorder associated with autism spectrum disorder." The reasoning behind these diagnostic distinctions is discussed further by Bishop (2017).
Benchmarks for children with developmental language disorder
Common red flags at one year of age:
No reaction to sound
No babbling
Difficulty feeding
No imitation
Limited use of gesturesAt two years of age:
Makes minimal attempts to communicate with gestures or words
Has not spoken their first words
Difficulty following simple directions
Inconsistent response to "no"At three years of age:
Limited use of speech
Incomprehensible speech
Limited understanding of simple questions
Difficulty naming objects
Frustration related to communicationAt four years of age:
Uses only 3-word phrases
Speech is not understandable to parents
Takes a long time to understand others
Difficulty asking questions and finding words to express thoughtsAt five years of age:
Speaks only in simple sentences
Speech is not understandable to teachers
Difficulty answering questions
Difficulty with complex directions
Difficulty telling stories
Difficulty with peer interactions
Assessment
Assessment will usually include an interview with the childs caregiver, observation of the child in an unstructured setting, a hearing test, and standardized tests of language. There is a wide range of language assessments in English. Some are restricted for use by experts in speech-language pathology: speech and language therapists (SaLTs/SLTs) in the UK, speech-language pathologists (SLPs) in the US and Australia. A commonly used test battery for diagnosis of DLD is the Clinical Evaluation of Language Fundamentals (CELF).
Assessments that can be completed by a parent or teacher can be useful to identify children who may require more in-depth evaluation. The Children’s Communication Checklist (CCC–2) is a parent questionnaire suitable for assessing everyday use of language in children aged four years and above who can speak in sentences.
Informal assessments, such as language samples, are often used by speech-language therapists/pathologists to complement formal testing and give an indication of the childs language in a more naturalistic context. A language sample may be of a conversation or narrative retell. In a narrative language sample, an adult may tell the child a story using a wordless picture book (e.g. Frog Where Are You?, Mayer, 1969), then ask the child to use the pictures and tell the story back. Language samples can be transcribed using computer software such as the Systematic Analysis of Language Software, and then analyzed for a range of features: e.g., the grammatical complexity of the childs utterances, whether the child introduces characters to their story or jumps right in, whether the events follow a logical order, and whether the narrative includes a main idea or theme and supporting details.
Treatment
Treatment is usually carried out by speech and language therapists/pathologists, who use a wide range of techniques to stimulate language learning. In the past, there was a vogue for drilling children in grammatical exercises, using imitation and elicitation, but such methods fell into disuse when it became apparent that there was little generalisation to everyday situations. Contemporary approaches to enhancing development of language structure, for younger children at least, are more likely to adopt milieu methods, in which the intervention is interwoven into natural episodes of communication, and the therapist builds on the childs utterances, rather than dictating what will be talked about. Interventions for older children, may be more explicit, telling the children what areas are being targeted and giving explanations regarding the rules and structures they are learning, often with visual supports.In addition, there has been a move away from a focus solely on grammar and phonology toward interventions that develop childrens social use of language, often working in small groups that may include typically developing as well as language-impaired peers.Another way in contemporary remediation differ from the past is that parents are more likely to be directly involved, but this approach is largely used with preschool children, rather than those whose problems persist into school age.For school-aged children, teachers are increasingly involved in intervention, either in collaboration with speech and language therapists/pathologists, or as the main agents of delivery of the intervention. Evidence for the benefits of a collaborative approach is emerging, but the benefits of asking education staff to be the main deliverers of SLT intervention (the "consultative" approach) are unclear. When SLT intervention is delivered indirectly by trained SLT assistants, however, there are indications that this can be effective.In this field, randomized controlled trial methodology has not been widely used, and this makes it difficult to assess clinical efficacy with confidence. Childrens language will tend to improve over time, and without controlled studies, it can be hard to know how much of observed change is down to a specific treatment. There is, however, increasing evidence that direct 1:1 intervention with an SLT/P can be effective for improving vocabulary and expressive language. There have been few studies of interventions that target receptive language, though some positive outcomes have been reported.
How to help a child with developmental language disorder
Talk to the child often to help them learn new words
Read to them every day. Point out words you see
Point to signs in the grocery store, at school, and outside
Speak to the child in the language you know best
Listen and answer when the child talks
Get the child to ask you questions
Give the child time to answer questions
Keep them in school: children who are school-refusers have poorer language skills overall, and a higher incidence of language impairments
Outcome
Longitudinal studies indicate that problems are largely resolved by five years of age in around 40% of four-year-olds with early language delays who have no other presenting risk factors. However, for children who still have significant language difficulties at school entry, reading problems are common, even for children who receive specialist help, and educational attainments are typically poor. Poor outcomes are most common in cases where comprehension as well as expressive language is affected. There is also evidence that scores on tests of nonverbal ability of children with DLD decrease over the course of development.DLD is associated with an elevated risk of social, emotional and mental health concerns. For instance, in a UK survey, 64% of a sample of 11-year-olds with DLD scored above a clinical threshold on a questionnaire for psychiatric difficulties, and 36% were regularly bullied, compared with 12% of comparison children. In the longer-term, studies of adult outcomes of children with DLD have found elevated rates of unemployment, social isolation and psychiatric disorder among those with early comprehension difficulties. However, better outcomes are found for children who have milder difficulties and do not require special educational provision.
Prevalence
Epidemiological surveys in the US and the UK converge in estimating the prevalence of DLD in five-year-olds at around 7%. Therefore, the prevalence is about one in every 15 children. By these statistics, in a classroom of 30 students, 2 would have DLD. In research by Tomblin et al., prevalence of DLD in racial/ethnic groups was highest in Native Americans, with African Americans being the next highest, followed by Hispanic people, and then White people. No students of Asian descent presented with DLD; however, other research does indicate that DLD is present in children of Asian descent.
Research
Much research has focused on trying to identify what makes language learning difficult for some children. A major divide is between theories that attribute the difficulties to a low-level problem with auditory temporal processing, and those that propose there is a deficit in a specialised language-learning system. Other accounts emphasise deficits in specific aspects of learning and memory. It can be difficult to choose between theories because they do not always make distinctive predictions, and there is considerable heterogeneity among children with DLD. It has also been suggested that DLD may only arise when more than one underlying deficit is present.
Developmental learning disorder in adults
Relatively little research has been conducted to test the outcomes of DLD in adults. In a study comparing 17 men with DLD to siblings without DLD, researchers found that the DLD men had normal intelligence with higher performance IQ than verbal IQ. The participants still exhibited a severe and persisting language disorder, severe literacy impairments, and significant deficits in theory of mind and phonological processing. Within the DLD cohort, higher childhood intelligence and language were associated with superior cognitive and language ability at final adult outcome. In their mid-thirties, the DLD cohort had significantly worse social adaptation (with prolonged unemployment and a paucity of close friendships and love relationships) compared with both their siblings and National Child Development Study (NCDS) control cohorts, matched on childhood IQ and social class. Self-reports showed a higher rate of schizotypal features but not schizoaffective disorder. Four DLD adults had serious mental health problems (two had developed schizophrenia).
See also
Auditory processing disorder
Dyslexia
Language processing
Linguistics
Origin of speech
Pragmatic language impairment
References
Further reading
Beitchman, J. H., & Brownlie, E. B. (2014). Language Disorders in Children and Adolescents Boston: Hogrefe. ISBN 9780889373389
Paul, Rhea (2007). Language disorders from infancy through adolescence: assessment & intervention. Mosby Elsevier. ISBN 0-323-03685-6. OCLC 487807750.
External links
Helpful article by Professor Maggie Snowling: Dyslexia and developmental language disorder: same or different?
Talking Point: Check the progress of your childs language development
What Works: Database of evidence-based interventions |
Anophthalmia | Anophthalmia, (Greek: ἀνόφθαλμος, "without eye"), is the medical term for the absence of one or both eyes. Both the globe (human eye) and the ocular tissue are missing from the orbit. The absence of the eye will cause a small bony orbit, a constricted mucosal socket, short eyelids, reduced palpebral fissure and malar prominence. Genetic mutations, chromosomal abnormalities, and prenatal environment can all cause anophthalmia. Anophthalmia is an extremely rare disease and is mostly rooted in genetic abnormalities. It can also be associated with other syndromes.
Causes
SOX2
The most common genetic cause for anophthalmia is mutated SOX2 gene. Sox2 anophthalmia syndrome is caused by a mutation in the Sox2 gene that does not allow it to produce the Sox2 protein that regulates the activity of other genes by binding to certain regions of DNA. Without this Sox2 protein, the activity of genes that is important for the development of the eye is disrupted. Sox2 anophthalmia syndrome is an autosomal dominant inheritance, but the majority of patients who suffer from Sox2 anophthalmia are the first in their family history to have this mutation. In certain cases, one parent will possess the mutated gene only in their egg or sperm cell and the offspring will inherit it through that. This is called germline mosaicism. There are at least 33 mutations in the Sox2 gene that have been known to cause anophthalmia. Some of these gene mutations will cause the Sox2 protein not to be formed, while other mutations will yield a non-functional version of this protein.
RBP4
RBP4 has recently been linked to autosomal dominant form of anophthalmia. This form of anophthalmia has variable penetrance and a unique maternal inheritance effect that is rooted in pregnancy. Specifically, the disease only occurs when a mother and fetus both carry a RBP4 mutation which predisposes the fetus to vitamin A deficiency (a known environmental risk factor for anophthalmia) during pregnancy. If Vitamin A deficiency occurs during the first several months when the eye is developing, it may lead to anophthalmia. This form of anophthalmia is the first that may be intervened upon with vitamin A supplementation of retinyl esters during the first several months of pregnancy. This strategy exploits an RBP-independent pathway. Clinical research is underway. See RBP4 for more information.
Other influential genes
SOX2 and RBP4 are not the only genes that can cause anophthalmia. Other important genes include OTX2, CHX10 and RAX. Each of these genes are an important in retinal expression. Mutations in these genes can cause a failure of retinal differentiation. OTX2 is dominantly inherited. Mutation effects vary in severity, and can include microphthalmia. BMP4 is also linked to anophthalmia, as well as causing myopia and microphthalmia. It is dominantly inherited. BMP4 interacts with the Sonic hedgehog (SHH) pathway and can cause anophthalmia.
Environmental influence
Many environmental conditions have also been known to cause anophthalmia. The strongest support for environmental causes has been studies where children have had gestational-acquired infections. These infections are typically viral. A few known pathogens that can cause anophthalmia are Toxoplasma, rubella, and certain strains of the influenza virus. Other known environmental conditions that have led to anophthalmia are maternal vitamin A deficiency, exposure to X-rays during gestation, solvent abuse, and exposure to thalidomide.
Chromosome 14
An interstitial deletion of chromosome 14 has been known to occasionally be the source of anophthalmia. The deletion of this region of chromosome has also been associated with patients having a small tongue, and high arched palate, developmental and growth retardation, undescended testes with a micropenis, and hypothyroidism. The region that has been deleted is region q22.1-q22.3. This confirms that region 22 on chromosome 14 influences the development of the eye.
Classifications
There are three classifications for this condition:
Primary anophthalmia is a complete absence of eye tissue due to a failure of the part of the brain that forms the eye.
Secondary anophthalmia the eye starts to develop and for some reason stops, leaving the infant with only residual eye tissue or extremely small eyes which can only be seen under close examination.
Degenerative anophthalmia the eye started to form and, for some reason, degenerated. One reason for this occurring could be a lack of blood supply to the eye.
Prenatal diagnosis
Ultrasounds
Ultrasounds can be used to diagnose anophthalmia during gestation. Due to the resolution of the ultrasound, it is difficult to diagnose it until the second trimester. The earliest time to detect anophthalmia this way is approximately 20 weeks.
Amniocentesis
It is possible to diagnose prenatally with amniocentesis, but it may not show a correct negative result. Amniocentesis can only diagnose anophthalmia when there is a chromosomal abnormality. Chromosomal abnormalities are only a minority of cases of anophthalmia.
Postnatal diagnosis
MRI/CT
MRIs and CTs can be used to scan the brain and orbits. Radiologists use this to assess the internal structures of the globe, the optic nerve and extraocular muscles, and brain anatomy.
Examination
Physicians, specifically ophthalmologists, can examine the child and give a correct diagnosis. Some will do molecular genetics tests to see if the cause is linked with gene mutations.
Genetic testing can include chromosomal microarray analysis, single-gene testing, or multigene-panel testing. Genomic testing including exome sequencing, genome sequencing, and mitochondrial sequencing may be considered if single-gene testing or use of a multigene panel fails to confirm a molecular diagnosis.
Associations
There are a few conditions that are associated with Anophthalmia. These include:
Trisomy 13
Lenz Syndrome
Goldenhar-Gorlin Syndrome
Waardenburg syndromeAside from these associative conditions, anophthalmia in only one eye tends to be associated with complications in the other eye. These risks include a higher chance of having glaucoma or a detached retina.
Treatments
Prosthetic eye
Currently, there is not a treatment option for regaining vision by developing a new eye. There are, however, cosmetic options so the absence of the eye is not as noticeable. Typically, the child will need to go to a prosthetic specialist to have conformers fitted into the eye. Conformers are made of clear plastic and are fitted into the socket to promote socket growth and expansion. As the childs face grows and develops, the conformer will need to be changed. An expander may also be needed in anophthalmia to expand the socket that is present. The conformer is changed every few weeks the first two years of life. After that, a painted prosthetic eye can be fitted for the childs socket. The prosthetic eye can be cleaned with mild baby soap and water. Rubbing alcohol should be avoided because it may damage the prosthetic eye. Children need to be checked regularly to ensure the fit and size is appropriate.A Cochrane Review published in 2016 asked the question would the type of material used to make the prosthetic eye affect the success of the operation? Prosthetic eyes can be made from two types of material; porous or non-porous material. "If the material is porous then the artificial eye can become integrated into the body because new blood vessels can grow into the material. If the material is non‐porous, then the artificial eye remains separate from the rest of the bodys tissue." After assessing three studies, the review concluded that there wasnt enough evidence to conclude which material was better.
Cosmetic surgery
If the proper actions are not taken to expand the orbit, many physical deformities can appear. It is important that if these deformities do appear, that surgery is not done until at least the first two years of life. Many people get eye surgery, such as upper eyelid ptosis surgery and lower eyelid tightening. These surgeries can restore the function of the surrounding structures like the eyelid in order to create the best appearance possible. This is more common with people who have degenerative anophthalmia.
Epidemiology
Anophthalmia has been reported to be present in 3 out of every 100,000 births. Many instances of anophthalmia also occur with microphthalmia. A recent study in the UK indicated that anophthalmia and microphthalmia had a combined average of 1 in every 10,000 births. The annual rate of occurrence of anophthalmia/microphthalmia in the United States is about 780 children born/year. The most extensive epidemiological survey on this congenital malformation has been carried out by Dharmasena et al. and using English National Hospital Episode Statistics, they calculated the annual incidence of anophthalmia, microphthalmia and congenital malformations of orbit/lacrimal apparatus from 1999 to 2011. According to this study the incidence of congenital anophthalmia ranged from 2.4 (95% CI 1.3 to 4.0) per 100 000 infants in 1999 to 0.4 (0 to 1.3) in 2011. Parents that already have a child who suffers from anophthalmia has a 1 in 8 chance of having another child with anophthalmia. Approximately 2/3 of all cases of anophthalmia are determined to be of genetic basis. Anophthalmia is one of the leading causes of congenital blindness and accounts for 3-11% of blindness in children. Anophthalmia and microphthalmia together make up 1.7-1.8% of reconstructive surgical cases in laboratory of plastic surgery and ocular prostheses.
References
External links
MAPS Parent Support group for parents with Anophthalmic and Microphthalmic children
http://www.anophthalmia.org/ ICAN - International Childrens Anophthalmia and Microphthalmia Networkmicrophthalmia]
MACS - Microphthalmia, Anophthalmia & Coloboma Support Europe’s largest charity supporting people affected by Microphthalmia, Anophthalmia and Coloboma
www.baam.org.uk BAAM Bilateral Anophthalmia and Me
Anophthalmia and Microphthalmia Resource Guide from the National Eye Institute (NEI).
GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview
NCBI/Molecular diagnosis of anophthalmia/microphthalmia
MACS The Micro and Anophthalmic Childrens Society - Offers support and Information to families in the UK and around the world |
Cinchonism | Cinchonism is a pathological condition caused by an overdose of quinine or its natural source, cinchona bark. Quinine and its derivatives are used medically to treat malaria and lupus erythematosus. In much smaller amounts, quinine is an ingredient of tonic drinks, acting as a bittering agent. Cinchonism can occur from therapeutic doses of quinine, either from one or several large doses. Quinidine (a Class 1A anti-arrhythmic) can also cause cinchonism symptoms to develop with as little as a single dose.
Signs and symptoms
Signs and symptoms of mild cinchonism (which may occur from standard therapeutic doses of quinine) include flushed and sweaty skin, ringing of the ears (tinnitus), blurred vision, impaired hearing, confusion, reversible high-frequency hearing loss, headache, abdominal pain, rashes, drug-induced lichenoid reaction (lichenoid photosensitivity), vertigo, dizziness, nausea, vomiting and diarrhea.
Large doses of quinine may lead to severe (but reversible) symptoms of cinchonism: skin rashes, deafness, somnolence, diminished visual acuity or blindness, anaphylactic shock, and disturbances in heart rhythm or conduction, and death from cardiotoxicity (damage to the heart). Quinine may also trigger a rare form of hypersensitivity reaction in malaria patients, termed blackwater fever, that results in massive hemolysis, hemoglobinemia, hemoglobinuria, and kidney failure. Most symptoms of cinchonism (except in severe cases) are reversible and disappear once quinine is withdrawn. Attempted suicide by intake of a large dose of quinine has caused irreversible tunnel vision and very severe visual impairment.Patients treated with quinine may also suffer from low blood sugar, especially if it is administered intravenously, and hypotension (low blood pressure).Quinine, like chloroquine, inactivates enzymes in the lysosomes of cells and has an anti-inflammatory effect, hence its use in the treatment of rheumatoid arthritis. However, inactivation of these enzymes can also cause abnormal accumulation of glycogen and phospholipids in lysosomes, causing toxic myopathy. It is possible this action is the root cause of cinchonism.
References
External links
Lin, Xi; Chen, Shanping; Tee, Daniel (May 1998). "Effects of Quinine on the Excitability and Voltage-Dependent Currents of Isolated Spiral Ganglion Neurons in Culture". Journal of Neurophysiology. 79 (5): 2503–12. doi:10.1152/jn.1998.79.5.2503. PMID 9582223. |
Collagenous colitis | Collagenous colitis is an inflammatory bowel disease affecting the colon specifically with peak incidence in the 5th decade of life, affecting women more than men. Its clinical presentation involves watery diarrhea in the absence of rectal bleeding. It is often classified under the umbrella entity microscopic colitis, that it shares with a related condition, lymphocytic colitis.
Signs and symptoms
Microscopic colitis causes chronic watery diarrhea with greater than 10 bowel movements per day. Some patients report nocturnal diarrhea, abdominal pain, urgency, fecal incontinence, fatigue, dehydration and weight loss. Patients report a significantly diminished quality of life.
Causes
The cause of collagenous colitis is unknown.
Diagnosis
On colonoscopy, the mucosa of the colon typically looks normal, but biopsies of affected tissue usually show deposition of collagen in the lamina propria, which is the area of connective tissue between colonic glands. Radiological tests, such as a barium enema are also typically normal.
Treatment
First line treatment for collagenous colitis is the use of budesonide, a steroid that works locally in the colon and is highly cleared by first pass effect. Other medications that can be used are the following:
Bismuth agents, including Pepto-Bismol
5-aminosalicylic acid
Immunosuppressants, including azathioprine
InfliximabPilot-scale studies have shown some evidence of possible benefit for both Boswellia serrata extract and specific strains of probiotics in the treatment of collagenous colitis, although larger sample sizes are needed to confirm the results.
See also
Colitis
Lymphocytic colitis
Inflammatory bowel disease
Ulcerative colitis
References
== External links == |
Tarsal tunnel syndrome | Tarsal tunnel syndrome (TTS) is a compression neuropathy and painful foot condition in which the tibial nerve is compressed as it travels through the tarsal tunnel. This tunnel is found along the inner leg behind the medial malleolus (bump on the inside of the ankle). The posterior tibial artery, tibial nerve, and tendons of the tibialis posterior, flexor digitorum longus, and flexor hallucis longus muscles travel in a bundle through the tarsal tunnel. Inside the tunnel, the nerve splits into three segments. One nerve (calcaneal) continues to the heel, the other two (medial and lateral plantar nerves) continue on to the bottom of the foot. The tarsal tunnel is delineated by bone on the inside and the flexor retinaculum on the outside.
Patients with TTS typically complain of numbness in the foot radiating to the big toe and the first three toes, pain, burning, electrical sensations, and tingling over the base of the foot and the heel. Depending on the area of entrapment, other areas can be affected. If the entrapment is high, the entire foot can be affected as varying branches of the tibial nerve can become involved. Ankle pain is also present in patients who have high level entrapments. Inflammation or swelling can occur within this tunnel for a number of reasons. The flexor retinaculum has a limited ability to stretch, so increased pressure will eventually cause compression on the nerve within the tunnel. As pressure increases on the nerves, the blood flow decreases. Nerves respond with altered sensations like tingling and numbness. Fluid collects in the foot when standing and walking and this makes the condition worse. As small muscles lose their nerve supply they can create a cramping feeling.
Symptoms
Some of the symptoms are:
Pain and tingling in and around ankles and sometimes the toes
Swelling of the feet and ankle area.
Painful burning, tingling, or numb sensations in the lower legs. Pain worsens and spreads after standing for long periods; pain is worse with activity and is relieved by rest.
Electric shock sensations
Pain radiating up into the leg, behind the shin, and down into the arch, heel, and toes
Hot and cold sensations in the feet
A feeling as though the feet do not have enough padding
Pain while operating automobiles
Pain along the posterior tibial nerve path
Burning sensation on the bottom of foot that radiates upward reaching the knee
"Pins and needles"-type feeling and increased sensation on the feet
A positive Tinels signTinels sign is a tingling electric shock sensation that occurs when you tap over an affected nerve. The sensation usually travels into the foot but can also travel up the inner leg as well.
Causes
It is difficult to determine the exact cause of tarsal tunnel syndrome. It is important to attempt to determine the source of the problem. Treatment and the potential outcome of the treatment may depend on the cause. Anything that creates pressure in the tarsal tunnel can cause TTS. This would include benign tumors or cysts, bone spurs, inflammation of the tendon sheath, nerve ganglions, or swelling from a broken or sprained ankle. Varicose veins (that may or may not be visible) can also cause compression of the nerve. TTS is more common in athletes and other active people. These people put more stress on the tarsal tunnel area. Flat feet may cause an increase in pressure in the tunnel region and this can cause nerve compression. Those with lower back problems may have symptoms. Back problems with the L4, L5 and S1 regions are suspect and might suggest a "Double Crush" issue: one "crush" (nerve pinch or entrapment) in the lower back, and the second in the tunnel area. In some cases, TTS can simply be idiopathic.
Rheumatoid Arthritis has also been associated with TTS.Neurofibromatosis can also cause TTS. This is a disease that results in the formation of pigmented, cutaneous neurofibromas. These masses, in a specific case, were shown to have the ability to invade the tarsal tunnel causing pressure, therefore resulting in TTS.Diabetes makes the peripheral nerve susceptible to nerve compression, as part of the double crush hypothesis. In contrast to carpal tunnel syndrome due to one tunnel at the wrist for the median nerve, there are four tunnels in the medial ankle for tarsal tunnels syndrome. If there is a positive Tinel sign when you tap over the inside of the ankle, such that tingling is felt into the foot, then there is an 80% chance that decompressing the tarsal tunnel will relieve the symptoms of pain and numbness in a diabetic with tarsal tunnel syndrome.
Risk factors
Anything compromising the tunnel of the posterior tibial nerve proves significant in the risk of causing TTS. Neuropathy can occur in the lower limb through many modalities, some of which include obesity and inflammation around the joints. By association, this includes risk factors such as RA, compressed shoes, pregnancy, diabetes and thyroid diseases
Diagnosis
Diagnosis is based upon physical examination findings. Patients pain history and a positive Tinels sign are the first steps in evaluating the possibility of tarsal tunnel syndrome. X-ray can rule out fracture. MRI can assess for space occupying lesions or other causes of nerve compression. Ultrasound can assess for synovitis or ganglia. Nerve conduction studies alone are not, but they may be used to confirm the suspected clinical diagnosis. Common causes include trauma, varicose veins, neuropathy and space-occupying anomalies within the tarsal tunnel. Tarsal tunnel syndrome is also known to affect both athletes and individuals that stand a lot.A neurologist or a physiatrist usually administers nerve conduction tests or supervises a trained technologist. During this test, electrodes are placed at various spots along the nerves in the legs and feet. Both sensory and motor nerves are tested at different locations. Electrical impulses are sent through the nerve and the speed and intensity at which they travel is measured. If there is compression in the tunnel, this can be confirmed and pinpointed with this test. Some doctors do not feel that this test is necessarily a reliable way to rule out TTS. Some research indicates that nerve conduction tests will be normal in at least 50% of the cases.
Given the unclear role of electrodiagnostics in the diagnosis of tarsal tunnel syndrome, efforts have been made in the medical literature to determine which nerve conduction studies are most sensitive and specific for tibial mononeuropathy at the level of the tarsal tunnel. An evidence-based practice topic put forth by the professional organization, the American Association of Neuromuscular & Electrodiagnostic Medicine has determined that Level C, Class III evidence exists for the use of tibial motor nerve conduction studies, medial and lateral plantar mixed nerve conduction studies, and medial and lateral plantar sensory nerve conduction studies. The role of needle electromyography remains less defined.Tarsal tunnel syndrome (TTS) is most closely related to carpal tunnel syndrome (CTS). However, the commonality to its counterpart is much less or even rare in prevalence Studies have found that patients with rheumatoid arthritis (RA) show signs of distal limb neuropathy. The posterior tibial nerve serves victim to peripheral neuropathy and often show signs of TTS amongst RA patients. Therefore, TTS is a common discovery found in the autoimmune disorder of rheumatoid arthritis
Prevention
The exact cause of tarsal tunnel syndrome (TTS) can vary from patient to patient. However the same result is true for all patients, the compression of the posterior tibial nerve and it branches as it travels around the medial malleolus causes pain and irritation for the patient. There are many possible causes for compression of the tibial nerve therefore there are a variety of prevention strategies. One being immobilization, by placing the foot in a neutral position with a brace, pressure is relieved from the tibial nerve thus reducing patients pain. Eversion, inversion, and plantarflexion all can cause compression of the tibial nerve therefore in the neutral position the tibial nerve is less agitated. Typically this is recommended for the patient to do while sleeping. Another common problem is improper footwear, having shoes deforming the foot due to being too tight can lead to increased pressure on the tibial nerve. Having footwear that tightens the foot for extended periods of time even will lead to TTS. Therefore, by simply having properly fitted shoes TTS can be prevented.
Treatment
Treatments typically include rest, manipulation, strengthening of tibialis anterior, tibialis posterior, peroneus and short toe flexors, casting with a walker boot, corticosteroid and anesthetic injections, hot wax baths, wrapping, compression hose, and orthotics. Medications may include various anti-inflammatories such as Anaprox, or other medications such as Ultracet, Neurontin and Lyrica. Lidocaine patches are also a treatment that helps some patients.
Conservative treatment (nonsurgical)
There are multiple ways that tarsal tunnel can be treated and the pain can be reduced. The initial treatment, whether it be conservative or surgical, depends on the severity of the tarsal tunnel and how much pain the patient is in. There was a study done that treated patients diagnosed with tarsal tunnel syndrome with a conservative approach. Meaning that the program these patients were participated in consisted of physiotherapy exercises and orthopedic shoe inserts in addition to that program. There were fourteen patients that had supplementary tibial nerve mobilization exercises. They were instructed to sit on the edge of a table in a slumped position, have their ankle taken into dorsiflexion and ankle eversion then the knee was extended and flexed to obtain the optimal tibial nerve mobilization. Patients in both groups showed positive progress from both programs. The medial calcaneal, medial plantar and lateral plantar nerve areas all had a reduction in pain after successful nonoperative or conservative treatment. There is also the option of localized steroid or cortisone injection that may reduce the inflammation in the area, therefore relieving pain. Or just a simple reduction in the patients weight to reduce the pressure in the area.
Surgical treatment
If non-invasive treatment measures fail, tarsal tunnel release surgery may be recommended to decompress the area. The incision is made behind the ankle bone and then down towards but not as far as the bottom of foot. The posterior tibial nerve is identified above the ankle. It is separated from the accompanying artery and vein and then followed into the tunnel. The nerves are released. Cysts or other space-occupying problems may be corrected at this time. If there is scarring within the nerve or branches, this is relieved by internal neurolysis. Neurolysis is when the outer layer of nerve wrapping is opened and the scar tissue is removed from within nerve. Following surgery, a large bulky cotton wrapping immobilizes the ankle joint without plaster. The dressing may be removed at the one-week point and sutures at about three weeks.
Complications may include bleeding, infection, and unpredictable healing. The incision may open from swelling. There may be considerable pain and cramping. Regenerating nerve fibers may create shooting pains. Patients may have hot or cold sensations and may feel worse than before surgery. Crutches are usually recommended for the first two weeks, as well as elevation to minimize swelling. The nerve will grow at about one inch per month. One can expect to continue the healing process over the course of about one year.
Many patients report good results. Some, however, experience no improvement or a worsening of symptoms. In the Pfeiffer article (Los Angeles, 1996), fewer than 50% of the patients reported improvement, and there was a 13% complication rate.
Tarsal tunnel can greatly impact patients quality of life. Depending on the severity, the ability to walk distances people normally take for granted (such as grocery shopping) may become compromised. Proper pain management and counseling is often required.
Results of surgery can be maximized if all four of the medial ankle tunnels are released and you walk with a walker the day after surgery. Success can be improved to 80%.
Incidence
Though TTS is rare, its cause can be determined in 70% of reported cases. In the workplace TTS is considered a musculoskeletal disorder and accounts for 1.8 million cases a year, which accumulates to about $15–$20 billion a year New studies indicate an occurrence of TTS in sports placing high loads on the ankle joint (3). This can be seen in figure 1. TTS occurs more dominantly in active adults, with a higher pervasiveness among women. Active adults that experience more jumping and landing on the ankle joint are more susceptible (see figure 2). Though athletics and sport are correlations, cases are individualistically assessed because of the oddity.
Athletic activities
The athletic population tends to put themselves at greater risk of TTS due to the participation in sports that involve the lower extremities. Strenuous activities involved in athletic activities put extra strain on the ankle and therefore can lead to the compression of the tibial nerve. Activities that especially involve sprinting and jumping have a greater risk of developing TTS. This is due to the ankle being put in eversion, inversion, and plantarflexion at high velocities. Examples of sports that can lead to TTS include basketball, track, soccer, lacrosse, snowboarding, and volleyball. Participation in these sports should be done cautiously due to the high risk of developing TTS. However athletes will tend to continue to participate in these activities therefore proper stretching, especially in lower extremities, prior to participation can assist in the prevention of developing TTS.
Famous case
According to South Koreas National Intelligence Service, North Korean leader Kim Jong Un had surgery to correct TTS in his right ankle, the source of a pronounced limp. Kims disappearance from public for six weeks around the suspected surgery created worldwide speculation about the future of Kim and North Korea.
Society
As stated earlier, musculoskeletal disorders can cost up to $15–$20 billion in direct costs or $45–$55 billion in indirect expenses. This is about $135 million a day. Tests that confirm or correct TTS require expensive treatment options like X-rays, CT-scans, MRI and surgery. The three former options for TTS detect and locate, while the latter is a form of treatment to decompress tibial nerve pressure. Since surgery is the most common form of TTS treatment, high financial burden is placed upon those diagnosed with the rare syndrome.
See also
Carpal tunnel syndrome
Cuboid syndrome
References
== External links == |
Gigantism | Gigantism (Greek: γίγας, gígas, "giant", plural γίγαντες, gígantes), also known as giantism, is a condition characterized by excessive growth and height significantly above average. In humans, this condition is caused by over-production of growth hormone in childhood, resulting in people 2.4 to 2.7 m (8.0 to 9.0 ft) in height.It is a rare disorder resulting from increased levels of growth hormone before the fusion of the growth plate which usually occurs at some point soon after puberty. This increase is most often due to abnormal tumor growths on the pituitary gland. Gigantism should not be confused with acromegaly, the adult form of the disorder, characterized by somatic enlargement specifically in the extremities and face.
Cause
Gigantism is characterized by an excess of growth hormone (GH). The excess of growth hormone that brings about gigantism is virtually always caused by pituitary growths (adenomas). These adenomas are on the anterior pituitary gland. They can also cause overproduction of GHs hypothalamic precursor known as growth hormone releasing hormone (GHRH).As a result of the excessive amounts of growth hormone, children achieve heights that are well above normal ranges. The specific age of onset for gigantism varies between patients and gender, but the common age that excessive growth symptoms start to appear has been found to be around 13 years. Other health complications, such as hypertension, may occur in pediatric patients with hyper-secretion of growth hormone. Characteristics more similar to those seen in acromegaly may occur in patients that are closer in age to adolescence since they are nearing growth plate fusion.
Hormonal cause
Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are two substances that have been identified as influencing growth plate formation and bone growth and, therefore, gigantism. Their specific mechanisms are still not well understood.More broadly, GH and IGF have both been identified to be involved in most stages of growth: embryonic, prenatal, and postnatal. Moreover, the receptor gene for IGF has been shown to be particularly influential throughout various stages of development, especially prenatally. This is the same for GH receptor genes which have been known to drive overall growth throughout various pathways.Growth hormone is a precursor (upstream) of IGF-I, but each has its independent role in hormonal pathways. Yet both seem to ultimately come together to have a joint effect on growth.
Diagnostic testing
Evaluation of growth hormone hyper-secretion cannot be excluded with a single normal GH level due to diurnal variation. However, a random blood sample showing markedly elevated GH is adequate for diagnosis of GH hyper-secretion. Additionally, a high-normal GH level that fails to suppress with administration of glucose is also sufficient for a diagnosis of GH hyper-secretion.Insulin-like growth factor-1 (IGF-1) is an excellent test for evaluation of GH hyper-secretion. It does not undergo diurnal variation and will thus be consistently elevated in GH hyper-secretion and therefore patients with gigantism. A single normal IGF-1 value will reliably exclude GH hyper-secretion.
Genetic
Finding a specific genetic cause for gigantism has proven to be difficult. Gigantism is the primary example of growth hormone hyper-secretion disorders, a group of illnesses that are not yet deeply understood.Some common mutations have been associated with gigantism. Pediatric gigantism patients have shown to have duplications of genes on a specific chromosome, Xq26. Typically, these patients also experienced an onset of typical gigantism symptoms before reaching the age of 5. This indicates a possible linkage between gene duplications and the gigantism.Additionally, DNA mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are common in gigantism patients. They have been found to be present in about 29 percent of patients with gigantism. AIP is labeled as a tumor suppressor gene and a pituitary adenoma disposition gene.Mutations in AIP sequencing can have deleterious effects by inducing the development of pituitary adenomas which in turn can cause gigantism.Two specific mutations in the AIP gene have been identified as possible causes of pituitary adenomas. These mutations also have the ability to cause adenoma growth to occur early in life. This is typical in gigantism.
Additionally, a large variety of other known genetic disorders have been found to influence the development of gigantism such as multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, X-linked acrogigantism (X-LAG).Although various gene mutations have been associated with gigantism, over 50 percent of cases cannot be linked to genetic causes, showing the complex nature of the disorder.
Treatment
Many treatments for gigantism receive criticism and are not accepted as ideal. Various treatments involving surgery and drugs have been used to treat gigantism.
Pharmaceuticals
Pegvisomant is one pharmaceutical drug which has received attention for being a possible treatment route for gigantism. Reduction of the levels of IGF-I as a result of pegvisomant administration can be incredibly beneficial for the pediatric gigantism patients.After treatment with pegvisomant, high growth rates, a feature characteristic of gigantism, can be significantly decreased. Pegvisomant has been seen to be a powerful alternative to other treatments such as somatostatin analogues, a common treatment method for acromegaly, if drug treatment is paired with radiation.Finding the optimal level of pegvisomant is important so normal body growth is not negatively affected. In order to do this, titration of the medication can be used as a way to find the proper administration level.See acromegaly for additional treatment possibilities.
Terminology
The term is typically applied to those whose height is not just in the upper 1% of the population but several standard deviations above mean for persons of the same sex, age, and ethnic ancestry. The term is seldom applied to those who are simply "tall" or "above average" whose heights appear to be the healthy result of normal genetics and nutrition. Gigantism is usually caused by a tumor on the pituitary gland of the brain. It causes growth of the hands, face, and feet. In some cases the condition can be passed on genetically through a mutated gene.Other names somewhat obsolete for this pathology are hypersoma (Greek: hyper over the normal level; soma body) and somatomegaly (Greek; soma body, genitive somatos of the body; megas, gen. megalou great). In the past, while many of them were social outcasts because of their height, some (usually unintentionally) found employment in Friedrich Wilhelm Is famous Potsdam Giants regiment.
Many of those who have been identified with gigantism have had multiple health problems involving the circulatory or skeletal system, as the strain of maintaining a large, heavy body places abnormal demands on both the bones and the heart.
Society and culture
Reports of gigantism exist throughout history, with some nations and tribes taller than others. The giants of Crete are listed in various historic sources, beginning with Titan, a Greek mythological giant, and including Gigantus, after whom giants and gigantism are named. Rhodes is another island where giants were said to have lived, with the Colossus of Rhodes, a giant statue of a giant patron god Helios.
Goliath, a giant mentioned in the Bible, was a Philistine warrior who was killed by David in the war between the Israelites and the Philistines.
See also
References
Bibliography
Driesbach, Jason (2016). 4QSamuela and the Text of Samuel. BRILL. ISBN 978-90-04-32420-6.
External links
"Brief overview of overgrowth syndromes in childhood" (PDF). Archived from the original (PDF) on 22 May 2004. Retrieved 30 August 2004. (2.95 MB)
Gigantism Clinical Trials from U.S. National Institutes of Health
Gigantism information from U.S. National Library of Medicine, U.S. Department of Health and Human Services & the National Institutes of Health
Epidemiology of acromegaly from Pubmed.gov US National Library of Medicine & National Institutes of Health |
Opioid overdose | An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to respiratory depression, a lethal condition that can cause hypoxia. Other symptoms include insufficient breathing, small pupils (with the exception of pethidine, where there may be dilated pupils), and unconsciousness, however its onset can depend on the method of ingestion, the dosage and individual risk factors. Although there were over 110,000 deaths in 2017 due to opioids, individuals who survived also faced adverse complications, including permanent brain damage.Opioid overdoses are diagnosed based on symptoms and examination. Risk factors for opioid overdose include high levels of opioid dependence, use of opioids via injection, high dosed opioid usage, having a mental disorder or having a predisposition for one, and use of opioids in combination with other substances, such as alcohol, benzodiazepines, or cocaine. Dependence on prescription opioids can occur from their use to treat chronic pain in individuals. Additionally, if following a period of detoxification, which allows the tolerance level to fall, the risk of overdose upon return to use is high.Initial treatment of an overdose involves supporting the persons breathing and providing oxygen to reduce the risk of hypoxia. Naloxone is then recommended to those who cannot reverse the opioids effects through breathing. Giving naloxone via nasal administration or as an injection into a muscle has shown to be equally effective. Among those who refuse to go to hospital following reversal, the risks of a poor outcome in the short term appear to be low. Other efforts to prevent deaths from overdose include increasing access to naloxone and treatment for opioid dependence.Drug use contributes to 500,000 deaths worldwide, with opioid overdose resulting in approximately 115,000 of these deaths in 2018. This is up from 18,000 deaths in 1990. In 2018, approximately 269 million people had engaged in drug usage at least once, 58 million of which used opioids. Drug use disorders have affected around 35.6 million people worldwide in 2018. The WHO estimates that 70% of deaths due to drug use are in relation to opioids, with 30% being due to overdose. It is believed that the opioid epidemic has partly been caused due to assurances that prescription opioids were safe, by the pharmaceutical industry in the 1990s. This led to unwarranted trust and a subsequent heavy reliance on opioids. Though there are treatment interventions which can effectively reduce the risk of overdose in people with opioid dependence, less than 10% of affected individuals receive it.
Signs and symptoms
Opiate overdose symptoms and signs can be referred to as the "opioid overdose triad": decreased level of consciousness, pinpoint pupils and respiratory depression. Other symptoms include seizures and muscle spasms. Sometimes an opiate overdose can lead to such a decreased level of consciousness such that the person will not wake up.
Because of their effect on the part of the brain that regulates breathing, opioids can cause very slow or stopped breathing, during overdoses, leading to hypoxia or death if left untreated. Hypoxia is typically caused by respiratory depression. The brain uses oxygen to regulate the homeostasis of the body. In animal studies, it was found that opioids act on specific regions of the central nervous system associated with respiratory regulation, including the medulla and pons. During cerebral hypoxia, there is a lack of sufficient oxygen supply to the brain. Prolonged lack of oxygenation from respiratory depression can lead to detrimental damage to the brain and spinal cord and can leave the person unable to walk or function normally, even if treatment with naloxone is given.Alcohol also causes respiratory depression and therefore when taken with opioids can increase the risk of respiratory depression and death.In young children, opioid overdose may not be apparent right away. This is due to absorption, distribution, and metabolism differences between young children and adults, and the higher amount of opioid ingestion per kilogram of body weight.
Causes
Risk factors for opioid overdose include opioid dependence, injecting opioids, using high doses of opioids, and use together with alcohol, benzodiazepines, or cocaine. The risk is particularly high following detoxification. Dependence on prescription opioids can occur from their use to treat chronic pain. In young children an overdose is usually due to opioids that are intended for their parents, older siblings, or grandparents. In mothers who take codeine during breastfeeding, opioid overdoses have occurred in their baby. Codeine is therefore not recommended in those who are breastfeeding.
Co-ingestion
Opioid overdoses are often associated with benzodiazepines or alcohol use. Other CNS depressants, muscle relaxers, pain relievers, anti-convulsants, anxiolytics, treatment drugs of a psychoactive or epileptic variety or any other such drug with its active function meant to calm or mitigate neuronal signaling (barbiturates, etc.) can additionally cause a worsened condition with less likelihood of recovery cumulative to each added drug. This includes drugs less immediately classed to a slowing of the metabolism such as with GABAergic like GHB or glutamatergic antagonists like PCP or ketamine.
Risk factors
Metabolic disorders
Opioids are primarily metabolized in the liver, before being excreted through urine. Opioids are metabolized by phase 1 and/or phase 2 metabolism, which can lead to the activation or inhibition of these drugs. Phase 1 metabolism is the CYP pathway which consists of different cytochrome P450s – a set of enzymes that catalyze hydrolysis, reduction, and oxidation reactions – to create an active metabolite. In contrast, Phase 2 metabolism causes the opioids to undergo conjugation, with little to no interaction with the CYP pathway. The opioids undergo phase 1 and phase 2 metabolism until they are hydrophilic enough to be renally excreted.There are various factors that play a role in how an opioid is metabolized. In phase 1 metabolism, the CYP family has several polymorphisms, which can account for the difference in therapeutic responses within each individual. This diversification leads to opioids being modified at varying rates, which can cause the drug to remain in the bloodstream for either a longer or shorter period of time. Therefore, these polymorphisms control opioid tolerance and facilitate overdose.
Mental health
Evidence suggests that mental health can be a significant facilitator for opioid abuse. Given that opioids are prescribed for pain management, mental health disorders, such as depression, have been shown to increase use of opioids when treating conditions associated with chronic pain. Evidence has shown that individuals with mood and anxiety disorders have an increased likelihood of being prescribed opioids and continuing usage for lengthy periods of time, consequently increasing likelihood for dependence. As such, affected individuals have almost double the risk of using opioids for pain relief in the long-term. Additionally, mental health challenges associated with trauma, economic depression, social environments conducive to substance abuse and risk-taking behaviours have been shown to increase opioid misuse. Furthermore, mental health challenges associated with cardiovascular disease, sleep disorders, and HIV can cause opioid dependence and subsequent overdose. Notably, cyclic behaviours can be observed between mental illness and opioid abuse where individuals with mental health diagnoses engage in opioid use which further perpetuates mental health challenges and increased drug usage.
Mechanism
Opioids bind with neurological opioid receptors to provoke analgesic, sedative, and euphoric effects. Opioids function by stimulating specific G-protein coupled receptors distributed throughout the body—including the brain, skin and spinal cord. Three of the major opioid receptors include mu, kappa, delta, and nociception, each playing a role in eliciting the effects associated with opioids. An opioid overdose results from over-activation of these receptors, which can cause permanent brain damage from cerebral hypoxia or neurotoxicity.Mu receptors have an analgesic effect on the brain, and are found in various parts of the nervous system including the cerebral cortex and thalamus. They can be found in the nucleus accumbens, the pleasure centre of the brain, as well as the amygdala. Kappa receptors, in the hypothalamus, produce a similar analgesic effect. They bind with dynorphins to stimulate anti-reward effects —dysphoria— and other negative effects of withdrawal. While mu receptors are the source of addiction, kappa receptors contribute to continued abuse. They generate dysphoria in response to increasing stress levels via corticotropin-releasing factor (CRF). This increases erratic shifts in mood during withdrawal period and can prompt relapse. Delta receptors, found in the basal ganglia of the limbic system, have been shown to reduce anxiety by binding with enkephalins, although this requires further research. The most recent addition to these receptors are nociception opioid receptors. Although they have been determined to be receptors to certain ligands from opioids, their role has not yet fully understood.When opioids are ingested, the ligand binds to these constitutively active receptors to reduce neural activity. This is accomplished by inhibiting adenylyl cyclase and cyclic AMP, which are necessary for communication within the central nervous system. There is research indicating that opioids reduce pain by disrupting ion channels and vesicle fusion.Prolonged exposure to opioids can cause these receptors to become internalized, leading to increased tolerance and increased opioid use.
Prevention
Opioid overdoses can often be prevented. Clear protocols for staff at emergency departments and urgent care centers can reduce opioid prescriptions for individuals presenting in these settings who engage in drug seeking behaviors or who have a history of substance abuse. Drug seeking behaviors include but are not limited to obsessiveness or impatience when it comes to attaining medications, seeking multiple pain adjunct medications, and inconsistent physiological presentation. A prescription monitoring program may help determine if an individual is receiving a high doses of opioids or combinations of medications such as benzodiazepines and opioids that put them at high risk. Limited amount of evidence suggests opioid therapy with extended-release or long-acting formulations may increase the risk of an unintentional overdose compared to shorter-acting agents. Routinely screening using tools such as the CAGE-AID and the Drug Abuse Screening Test (DAST-10) in adults and the CRAFFT in those aged 14–18 years is recommended. Other "drug seeking" behaviors and physical indications of drug use should be used as clues to perform formal screenings.There are several medication-assisted treatments available for people with opioid use disorder or opioid dependence, who are at higher risk for opioid overdose. The selection of treatment depends on various factors, such as a persons preference, accessibility, and history of treatment. Examples of medication-assisted treatments are buprenorphine (with or without naloxone), naltrexone, and methadone. Peer support groups have tentative evidence of benefit. There is also some evidence indicating benefits in community-based overdose education and naloxone distribution programs. Buprenorphine and methadone can help decrease drug cravings. Combining pharmacologic treatments with behavioral therapy, such as support or recovery groups, can increase likelihood of overcoming addiction and reduce the risk of an opioid overdose.
Individuals diagnosed with opioid dependence should be prescribed naloxone to prevent overdose and should be directed to one of treatment options available, such as needle exchange programs and treatment centers. A naloxone prescription is also recommended when risk factors for opioid overdose are present such as history of overdose, substance use disorder, or higher doses of opioids. Brief motivational interviewing can also be performed and has been shown to improve peoples motivation to change their behavior. Despite these opportunities, the dissemination of prevention interventions in the US has been hampered by the lack of coordination and sluggish federal government response.In the United States, 49 states and the District of Columbia have expanded naloxone access at a pharmacy level via standing order, protocol order, naloxone-specific collaborative practice agreement, or pharmacist prescriptive authority.
Treatments
In people who have overdosed on opioids, basic life support and naloxone are recommended as soon as possible. Naloxone is effective at reversing the cause, rather than just the symptoms, of an opioid overdose. Compared to adults, children often need larger doses of naloxone per kilogram of body weight.Programs to provide drug users and their caregivers with naloxone are recommended. In the United States, as of 2014, more than 25,000 overdoses have been reversed. Programs training police and fire personnel in opioid overdose response using naloxone have also shown promise. Programs have been developed in cities, such as San Francisco, to increase community awareness and engagement in prevention of opioid overdose.
Epidemiology
In 2016, the World Health Organization estimates 34 million people used opioids and 19 million used opiates. Of these, about 27 million people had opioid dependence, with the majority—but a decreasing number—using illicit heroin. In 2015, 118,000 people died from opioid use disorders, causing almost one third of all drug related deaths.
United States
Of the 70,200 overdose deaths in the US in 2017, opioids were involved in 47,600 with three male deaths for each female death. This is an increase from 2016 where over 64,000 died from drug overdose, and opioids were involved in over 42,000. In 2017, the five states with the highest rates of death due to drug overdose were West Virginia (57.8 per 100,000), Ohio (46.3 per 100,000), Pennsylvania (44.3 per 100,000), Kentucky (37.2 per 100,000), and New Hampshire (37.0 per 100,000).Concerning the 2017 data in the charts below, deaths from the various drugs add up to more than 70,200 because multiple drugs are involved in many of the deaths. According to the National Safety Council, the lifetime odds of dying from an overdose in the United States is 1 in 96.
Charts of deaths involving specific opioids and classes of opioids
Awareness
The Substance Abuse and Mental Health Services Administration hosts an annual health observance known as National Prevention Week. Every third week of May, they encourage communities across the country to unite to share stories about positive mental and behavioral health and the importance of implementing prevention methods. They also sponsor recovery Month every September. Recovery Month aims to raise awareness about mental and substance use disorders and to honor individuals who recover, promoting the positive message that prevention works and that treatment is effective.International Overdose Awareness Day is on 31 August to remember those who have died from an overdose, to decrease stigma of drug-related deaths, and to promote prevention of overdose.
See also
Harm reduction
List of deaths from drug overdose and intoxication
Responsible drug use
References
External links
WHO Community Management of Opioid Overdose, 2014 |
Hyperproinsulinemia | Hyperproinsulinemia is a disease where insulin is not sufficiently processed before secretion and immature forms of insulin make up the majority of circulating insulin immunoreactivity in both fasting and glucose-stimulated conditions (insulin immunoreactivity refers to all molecules detectable by an insulin antibody, i.e. insulin, proinsulin, and proinsulin-like material). The term is composed of hyper - high, proinsulin - immature insulin molecule, and -emia - blood condition.Hyperproinsulinemia is more frequent in type 2 diabetes. It has been attributed to either a direct β-cells defect or an indirect effect of cell dysregulation under sustained elevated blood glucose (hyperglycemia).Some alleles of insulin can cause hyperproinsulinemia (see table 2: monogenic forms of type 1 diabetes, INS (insulin). For a more detailed descriptions of the insulin gene variations leading to hyperproinsulinemia see NCBIs OMIM 176730
References
== External links == |
Chronic paroxysmal hemicrania | Chronic paroxysmal hemicrania (CPH) is a severe debilitating unilateral headache usually affecting the area around the eye. It normally consists of multiple severe, yet short, headache attacks affecting only one side of the cranium. It is more commonly diagnosed in women than in men, but, unlike a migraine, has no neurological symptoms associated with it. CPH headaches are treated through the use of non-steroidal anti-inflammatory drugs, with indomethacin found to be usually effective in eliminating symptoms.
Paroxysmal hemicrania is classified by the frequency and duration of attacks experienced by patients. Episodic paroxysmal hemicrania attacks occur at least twice a year and last anywhere from seven days to a year with pain free periods of a month or longer separating them. Chronic paroxysmal hemicrania attacks occur over the course of more than a year without remission or with remissions lasting less than a month.
Signs and symptoms
Individuals with CPH suffer multiple short, severe headaches a day, often more than five, with most lasting between 5 and 30 minutes each. When compared to cluster headaches, CPH attacks are typically shorter. Each headache is centered around the eye, temple and forehead and is localized to one side of the head. While redness and watering of the eye are associated with CPH, patients typically do not experience nausea or vomiting. Although less common, CPH may also present as severe unilateral ear pain accompanied by autonomic symptoms. Autonomic symptoms may include the presence of Red Ear Syndrome.Attacks hit the patient many times a day, from 5 times a day up to 40 times a day with an average of 11 a day. Mild background pain can persist between attacks. They come in bouts that last from 7 days to 1 year separated by remission periods that can last more than 3 months in episodic patients, or less than 3 months in chronic patients. Onset is in adulthood and the disorder may last indefinitely or spontaneously go into remission. Circadian mechanisms are likely involved in paroxysmal hemicrania due to its highly cyclic nature. No particular circannual recurrence characterizes symptomatic periods, although some patients can experience a seasonal preponderance.
Causes
The causes of paroxysmal hemicrania are ultimately still unknown. Sympathetic symptoms such as miosis and ptosis might be linked with a generalized sympathetic dysfunction. Neuropathic mechanisms may be involved, since attacks can be triggered by mechanical stimulation. Perivascular neurogenic inflammatory processes can worsen symptoms or increase pain. Dilated blood vessels may contribute in stimulating trigeminal nociceptors directly, although they cannot be the origin of pain, since even suppression of vasodilation does not stop it once it’s started.Many secondary conditions have been reported to be possible causes of CPH, according to Mehta et al., most of which are arterial abrasions or tumors. These include aneurysms in the circle of Willis, middle cerebral artery infarction, parietal arteriovenous malformation, cavernous sinus and petrous ridge meningiomas, pituitary adenoma, Pancoast tumor, gangliocytoma of the sella turcica, and malignant frontal tumors. This accentuates the urgency for those diagnosed with CPH to receive an MRI head scan.
Diagnosis
CPH is a long-term disease with symptoms lasting for longer than a year, either without remission or with remissions that last less than a month. In order to be diagnosed with CPH, a patient needs to have had at least 20 attacks filling the following criteria:
Attacks of severe unilateral orbital, supraorbital, or temporal pain lasting between 2 and 30 minutes.
The headache needs to take place with one of the following:
Ipsilateral conjunctival injection and/or lacrimation
Ipsilateral nasal congestion and/or rhinorrhoea
Ipsilateral eyelid oedema
Ipsilateral forehead and facial sweating
Ipsilateral miosis and/or ptosis
Attacks need to occur more than five times a day for more than half of the time, although periods of lower frequency can occur.
The symptoms cannot be attributed to another disorder.
Attacks can be prevented completely by therapeutic doses of indomethacin.In addition, diagnosis of CPH requires that neuropathy of the supraorbital area in the temporal branch of the facial nerve be ruled out.
Comparison to cluster headaches
Though outwardly similar to cluster headaches, chronic paroxysmal hemicrania is rather different, and the two headaches are not a subset of one or the other. Key differences include:
Different gender distributions – CPH is more common in women than men, with opposite occurring with cluster headaches.
CPH attacks occur more frequently, but are shorter.
CPH affects all over the headIndividuals with CPH are far more responsive to indomethacin than individuals with cluster headaches.
CPH attacks can be provoked by neck movement.
In a study conducted by Sjaastad, heating a patients body will cause the painful side of the forehead to sweat more in CPH patients, while there will be less sweating on that side for those suffering from cluster headaches.
Treatments
A ten-patient study conducted by Pareja et al. found that all patients diagnosed with CPH were responsive to indomethacin and were able to completely control their symptoms. Doses of the drug ranged from 25 mg per day to 150 mg per day with a median dose of 75 mg per 24-hour period.
Almost all cases of CPH respond positively and effectively to indometacin, but as much as 25 percent of patients discontinued use of the drug due to adverse side effects, namely complications in the gastrointestinal tract.
According to a case study by Milanlioglu et al., 100mg of lamotrigine, an antiepileptic drug, administered twice daily alleviated all painful symptoms. No side effects were noted after two months of treatment. Dosage of lamotrigine was decreased to 50mg a day after the first two months, and no symptoms or side-effects were recorded after a three-month followup.Use of topiramate has also been found to be an effective treatment for CPH, but cluster headache medications have been found to have little effect.
Epidemiology
Although CPH is often compared to cluster headaches, it is much less prevalent, occurring in only 1–3% of those who experience cluster headaches. CPH occurs roughly in 1 in 50,000 people, while cluster headaches are comparatively more common and are found in 1 in 1000 people.
Cluster headaches occur primarily in men, while CPH is more commonly diagnosed in women. The female to male ratio of diagnosed patients can range anywhere from 1.6:1 to 2.36:1. Symptoms may begin to appear at any age, but onset usually occurs in adulthood with a mean starting age within the thirties.
History
CPH was discovered by Norwegians Ottar Sjaastad and Inge Dale in 1974. The term chronic paroxysmal hemicrania was first used in 1976 by Sjaastad to describe a condition seen in two of their patients who were experiencing repeated solitary and limited daily headache attacks on only one side of the cranium.It is possible that chronic paroxysmal hemicrania was first described by Johann Oppermann in 1747 under the term "hemicranias horologica". Oppermanns report included a 35-year-old woman who had hemicranial pain that lasted for 15 minutes and recurred regularly every hour.CPH has been included in the International Headache Societys classification system since 1988.
See also
Hemicrania continua
Rebound headaches
Tension headaches
Trigeminal neuralgia
References
== External links == |
Hypertryptophanemia | Hypertryptophanemia is a rare autosomal recessive metabolic disorder that results in a massive buildup of the amino acid tryptophan in the blood, with associated symptoms and tryptophanuria (-uria denotes "in the urine").Elevated levels of tryptophan are also seen in Hartnup disease, a disorder of amino acid transport. However, the increase of tryptophan in that disorder is negligible when compared to that of hypertryptophanemia.
Symptoms and signs
A number of abnormalities and symptoms have been observed with hypertryptophanemia.Musculoskeletal effects include: joint contractures of the elbows and interphalangeal joints of the fingers and thumbs (specifically the distal phalanges), pes planus (fallen arches), an ulnar drift affecting the fingers of both hands (an unusual, yet correctible feature where the fingers slant toward the ulnar side of the forearm), joint pain and laxity, and adduction of the thumbs (where the thumb appears drawn into the palm, related to contracture of the adductor pollicis).Behavioral, developmental and other anomalies often include: hypersexuality, perceptual hypersensitivity, emotional lability (mood swings), hyperaggressive behavior; hypertelorism (widely-set eyes), optical strabismus (misalignment) and myopia.Metabolically, hypertryptophanemia results in tryptophanuria and exhibits significantly elevated serum levels of tryptophan, exceeding 650% of maximum (normal range: 25–73 micromole/l) in some instances.A product of the bacterial biosynthesis of tryptophan is indole. The excess of tryptophan in hypertryptophanemia also results in substantial excretion of indoleic acids. These findings suggest a possible congenital defect in the metabolic pathway where tryptophan is converted to kynurenine.
Genetics
Hypertryptophanemia is believed to be inherited in an autosomal recessive manner. This means a defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
Pathophysiology
At present, no specific enzyme deficiency nor genetic mutation has been implicated as the cause of hypertryptophanemia. Several known factors regarding tryptophan metabolism and kynurenines, however, may explain the presence of behavioral abnormalities seen with the disorder.Tryptophan is an essential amino acid, and is required for protein synthesis. Aside from this crucial role, the remainder of tryptophan is primarily metabolized along the kynurenine pathway in most tissues, including those of the brain and central nervous system.As the main defect behind hypertryptophanemia is suspected to alter and disrupt the metabolic pathway from tryptophan to kynurenine, a possible correlation between hypertryptophanemia and the known effects of kynurenines on neuronal function, physiology and behavior may be of interest.One of these kynurenines, aptly named kynurenic acid, serves as a neuroprotectant through its function as an antagonist at both nicotinic and glutamate receptors (responsive to the neurotransmitters nicotine and glutamate, respectively). This action is in opposition to the agonist quinolinic acid, another kynurenine, noted for its potential as a neurotoxin. Quinolinic acid activity has been associated with neurodegenerative disorders such as Huntingtons disease, the neuroprective abilities of kynurenic acid forming a counterbalance against this process, and the related excitotoxicity and similar damaging effects on neurons.Indoleic acid excretion is another indicator of hypertryptophanemia. Indirectly related to kynurenine metabolism, indole modifies neural function and human behavior by interacting with voltage-dependent sodium channels (integral membrane proteins that form ion channels, allowing vital synaptic action potentials).
Diagnosis
Management
See also
Blue diaper syndrome
Tryptamine
Serotonin
References
== External links == |
Linear and whorled nevoid hypermelanosis | Linear and whorled nevoid hypermelanosis (also known as "Linear nevoid hyperpigmentation," "Progressive cribriform and zosteriform hyperpigmentation," "Reticulate and zosteriform hyperpigmentation," "Reticulate hyperpigmentation of Iijima and Naito and Uyeno," "Zebra-like hyperpigmentation in whorls and streaks," and "Zebra-line hyperpigmentation") is a disorder of pigmentation that develops within a few weeks of birth and progresses for one to two years before stabilizing.: 549 There is linear and whorled hyperpigmentation following the lines of Blaschko without preceding bullae or verrucous lesions.: 549 It is important to exclude other pigmentary disorders following the Blaschko lines before making a diagnosis of linear and whorled nevoid hypermelanosis. The differential diagnoses include incontinentia pigmenti, linear epidermal nevus, hypomelanosis of Ito and Goltz syndrome. Recently, a case of linear and whorled nevoid hypermelanosis was reported in a Malaysian Chinese girl.
See also
Skin lesion
List of cutaneous conditions
References
== External links == |
Cold autoimmune hemolytic anemia | Cold autoimmune hemolytic anemia caused by cold-reacting antibodies. Autoantibodies that bind to the erythrocyte membrane leading to premature erythrocyte destruction (hemolysis) characterize autoimmune hemolytic anemia.
Presentation
A common complaint among patients with cold agglutinin disease is painful fingers and toes with purplish discoloration associated with cold exposure. In chronic cold agglutinin disease, the patient is more symptomatic during the colder months.
Cold agglutinin mediated acrocyanosis differs from Raynaud phenomenon. In Raynaud phenomena, caused by vasospasm, a triphasic color change occurs, from white to blue to red, based on vasculature response. No evidence of such a response exists in cold agglutinin disease.
Other symptoms
Respiratory symptoms: May be present in patients with M pneumoniae infection.
Hemoglobinuria (the passage of dark urine that contains hemoglobin), A rare symptom that results from hemolysis, this may be reported following prolonged exposure to cold, hemoglobinuria is more commonly seen in paroxysmal cold hemoglobinuria.
Chronic fatigue, Due to anemia.
Causes
Cold agglutinins develop in more than 60% of patients with infectious mononucleosis, but hemolytic anemia is rare.
Classic chronic cold agglutinin disease is idiopathic, associated with symptoms and signs in relation to cold exposure.
Causes of the monoclonal secondary disease include the following:
B-cell neoplasms - Waldenström macroglobulinemia, lymphoma, chronic lymphoid leukemia, myeloma
Non hematologic neoplasmsCauses of polyclonal secondary cold agglutinin disease include the following:
Mycoplasma infections.
Viral infections: Infectious mononucleosis due to Epstein-Barr virus (EBV) or CMV, Mumps, varicella, rubella, adenovirus, HIV, influenza, hepatitis C.
Bacterial infections: Legionnaire disease, syphilis, listeriosis and Escherichia coli.
Parasitic infections: Malaria and trypanosomiasis.
Trisomy and translocation: Cytogenetic studies in patients with cold agglutinin disease have revealed the presence of trisomy 3 and trisomy 12. Translocation (8;22) has also been reported in association with cold agglutinin disease.
Transplantation: Cold agglutinin–mediated hemolytic anemia has been described in patients after living-donor liver transplantation treated with tacrolimus and after bone marrow transplantation with cyclosporine treatments. It is postulated that such calcineurin inhibitors, which selectively affect T-cell function and spare B-lymphocytes, may interfere with the deletion of autoreactive T-cell clones, resulting in autoimmune disease.
Systemic sclerosis: Cold agglutinin disease has been described in patients with sclerodermic features, with the degree of anemia being associated with increasing disease activity of the patients systemic sclerosis. This may suggest a close association between systemic rheumatic disease and autoimmune hematologic abnormalities.
Hyperreactive malarial splenomegaly: Hyperreactive malarial splenomegaly (HMS) is an immunopathologic complication of recurrent malarial infection. Patients with HMS develop splenomegaly, acquired clinical immunity to malaria, high serum concentrations of anti-Plasmodium antibodies, and high titers of IgM, with a complement-fixing IgM that acts as a cold agglutinin.
DPT vaccination: Diphtheria-pertussis-tetanus (DPT) vaccination has been implicated in the development of autoimmune hemolytic anemia caused by IgM autoantibody with a high thermal range. A total of 6 cases have been reported; 2 followed the initial vaccination and 4 followed the second or third vaccinations.
Other: Equestrian perniosis is a rare cause of persistent elevated titers of cold agglutinins. Also rarely, the first manifestations of cold agglutinin disease can develop when a patient is subjected to hypothermia for cardiopulmonary bypass surgery.
Pathophysiology
Cold agglutinins, or cold autoantibodies, occur naturally in nearly all individuals. These natural cold autoantibodies occur at low titers, less than 1:64 measured at 4 °C, and have no activity at higher temperatures. Pathologic cold agglutinins occur at titers over 1:1000 and react at 28-31 °C and sometimes at 37 °C.
Cold agglutinin disease usually results from the production of a specific IgM antibody directed against the I/i antigens (precursors of the ABH and Lewis blood group substances) on red blood cells (RBCs). Cold agglutinins commonly have variable heavy-chain regions encoded by VH, with a distinct idiotype identified by the 9G4 rat murine monoclonal antibody.
Diagnosis
Classification
AIHA can be classified as warm autoimmune hemolytic anemia or cold autoimmune hemolytic anemia, which includes cold agglutinin disease and paroxysmal cold hemoglobinuria. These classifications are based on the characteristics of the autoantibodies involved in the pathogenesis of the disease. Each has a different underlying cause, management, and prognosis, making classification important when treating a patient with AIHA.
Autoimmune hemolytic anemiaWarm-antibody typePrimary
Secondary (lymphoproliferative disorders, autoimmune disorders) : 259 Cold-antibody type (anemia)Primary cold agglutinin disease
Secondary cold agglutinin syndromeAssociated with malignant disease
Acute, transient, infection-associated (acute cold antibody mediated AIHA complicating Mycoplasma pneumoniae or viral infections )
Chronic (lymphoproliferative disorders) : 259 Paroxysmal cold hemoglobinuria: 259 Idiopathic
SecondaryAcute, transient (Infections other than syphilis): 259
Chronic (syphilis): 259 Mixed cold- and warm-antibody typeIdiopathic
Secondary (lymphoproliferative disorders, autoimmune disorders) Drug-induced immune hemolytic anemia : 259 Autoimmune type
Drug absorption type
Neoantigen type
Treatment
Cold agglutinin disease may be managed successfully using protective measures (clothing) alone in most cases. Special protective clothing is sometimes necessary in extreme cases. Therapy is directed at serious symptoms and the underlying disorder, if any is found.
Keep in mind that the idiopathic variety of cold agglutinin disease is generally a benign disorder with prolonged survival and spontaneous exacerbations and remissions in the course of the disease. Acute post infectious syndromes usually resolve spontaneously.
Anemia is generally mild. Only patients who have serious symptoms related to anemia or have a Raynaud type syndrome that constitutes a threat to life or quality of life require active therapy. The presence of an associated malignancy requires specific therapy.
Cold agglutinin disease is so uncommon in children that no specific recommendations for therapy are available. Intravenous immunoglobulin (IVIG) was used successfully in an infant with IgA-associated autoimmune hemolytic anemia.
Splenectomy
Splenectomy is usually ineffective for the treatment of cold agglutinin disease because the liver is the predominant site of sequestration. However, if the patient has splenomegaly, then the disease may respond to splenectomy. More importantly, a lymphoma localized to the spleen may only be found after splenectomy.
Diet and activity
Patients with cold agglutinin disease should include good sources of folic acid, such as fresh fruits and vegetables, in their diet. Activities for these individuals should be less strenuous than those for healthy people, particularly for patients with anemia. Jogging in the cold could be very hazardous because of the added windchill factor.
Consultations
A hematologist-oncologist working in collaboration with a blood banker is helpful in complicated cases of cold agglutinin disease.
Careful planning and coordination with multiple personnel are needed if patients are to undergo a procedure during which their body temperature could fall.
== References == |
Limbic encephalitis | Limbic encephalitis is a form of encephalitis, a disease characterized by inflammation of the brain. Limbic encephalitis is caused by autoimmunity: an abnormal state where the body produces antibodies against itself. Some cases are associated with cancer and some are not. Although the disease is known as "limbic" encephalitis, it is seldom limited to the limbic system and post-mortem studies usually show involvement of other parts of the brain. The disease was first described by Brierley and others in 1960 as a series of three cases. The link to cancer was first noted in 1968 and confirmed by later investigators.The majority of cases of limbic encephalitis are associated with a tumor (diagnosed or undiagnosed). In cases caused by tumor, recovery can only occur following complete removal of the tumor, which is not always possible. Limbic encephalitis is classified according to the auto-antibody that causes the disease. The most common types are:
Anti-Hu, which is associated with small-cell carcinoma of the lungs.
Anti-Ma2, associated with germ-cell tumours of the testis.
Anti-NMDAR, associated with tumors of the ovaries, commonly teratomata.Since 1999, following the publication of a case report of a 15-year-old teenager of Indian descent from South Africa who developed subacute memory loss subsequent to herpes simplex type 1 encephalitis, similar cases of non-paraneoplastic LE have been described, as has its association with auto-antibodies and response to steroid. Limbic encephalitis associated with voltage-gated potassium channel antibodies (VGKC-Abs) may frequently be non-paraneoplastic. A recent study of 15 cases of limbic encephalitis found raised VGKC-Abs associated with non-paraneoplastic disorders and remission following immunosuppressive treatment.
Classification
Limbic encephalitis is broadly grouped into two types: paraneoplastic limbic encephalitis and non-paraneoplastic limbic encephalitis.
Paraneoplastic limbic encephalitis (PNLE) is caused by cancer or tumor, and may be treated by removal of the tumor.
Non-paraneoplastic limbic encephalitis (NPLE) is not associated with cancer. More common than PNLE, it is caused by an infection, auto-immune disorder, or other condition that may never be identified.
Symptoms and signs
Symptoms develop over days or weeks. The subacute development of short-term memory deficits is considered the hallmark of this disease, but this symptom is often overlooked, because it is overshadowed by other more obvious symptoms such as headache, irritability, sleep disturbance, delusions, hallucinations, agitation, seizures and psychosis, or because the other symptoms mean the patient has to be sedated, and it is not possible to test memory in a sedated patient.
Cause
Limbic encephalitis is associated with an autoimmune reaction. In non-paraneoplastic limbic encephalitis, this is typically due to infection (commonly herpes simplex virus) or as a systemic autoimmune disorder. Limbic encephalitis associated with cancer or tumors is called paraneoplastic limbic encephalitis.
Diagnosis
The diagnosis of limbic encephalitis is extremely difficult and it is usual for the diagnosis to be delayed for weeks. The key diagnostic test (detection of specific auto-antibodies in cerebrospinal fluid) is not routinely offered by most immunology laboratories. Some of the rarer auto-antibodies (e.g., NMDAR) have no commercially available assay and can only be measured by a very small number of research laboratories worldwide, further delaying diagnosis by weeks or months. Most patients with limbic encephalitis are initially diagnosed with herpes simplex encephalitis, because the two syndromes cannot be distinguished clinically. HHV-6 (human herpes virus 6) encephalitis is also clinically indistinguishable from limbic encephalitis.There are two sets of diagnostic criteria used. The oldest are those proposed by Gultekin et al. in 2000.
A revised set of criteria were proposed by Graus and Saiz in 2005.
The main distinction between the two sets of criteria is whether or not the detection of a paraneoplastic antibody is needed for diagnosis.
Antibodies against intracellular neuronal antigens
The main antibodies within this group are those against Hu, Ma2, CV2, amphiphysin and Ri. The syndrome of anti-Ma2 encephalitis may be clinically mistaken for Whipples disease.
Antibodies against cell membrane antigens
The main antibodies within this group are those against N-methyl-D-aspartate receptors (NMDAR) and the voltage-gated potassium channel-complex (VGKC-complex). Anti-NMDAR encephalitis is strongly associated with benign tumours of the ovary (usually teratomata or dermoid cysts). Anti-VGKC-complex encephalitis is most often not associated with tumours.Patients with NMDAR encephalitis are frequently young women who present with fever, headache and fatigue. This is often misdiagnosed as influenza, but progresses to severe behavioural and personality disturbance, delusions, paranoia and hallucinations. Patients may therefore initially be admitted to a psychiatric ward for acute psychosis or schizophrenia. The disease then progresses to catatonia, seizures and loss of consciousness. The next stage is hypoventilation (inadequate breathing) requiring intubation, orofacial dyskinesia and autonomic instability (dramatic fluctuations in blood pressure, temperature and heart rate).
Investigation
Cerebrospinal fluid (CSF)
Examination of cerebrospinal fluid (CSF) shows elevated numbers of lymphocytes (but usually < 100 cells/μl); elevated CSF protein (but usually <1.5 g/L), normal glucose, elevated IgG index and oligoclonal bands. Patients with antibodies to voltage-gated potassium channels may have a completely normal CSF examination.
Neuroimaging
Brain MRI is the mainstay of initial investigation pointing to limbic lobe pathology revealing increased T2 signal involving one or both temporal lobes in most cases.Serial MRI in LE starts as an acute disease with uni- or bilateral swollen temporomesial structures that are hyperintense on fluid attenuation inversion recovery and T2-weighted sequences. Swelling and hyperintensity may persist over months to years, but in most cases progressive temporomesial atrophy develops.PET-CT is not an essential investigation but can help in suspected cases with MRI negative for early diagnosis.
Neuro-electrophysiology
EEG is mostly nonspecific slowing and epileptiform activity arising from temporal lobes.
Treatment
Limbic encephalitis is a rare condition with no randomised-controlled trials to guide treatment. Treatments that have been tried include intravenous immunoglobulin, plasmapheresis, corticosteroids, cyclophosphamide and rituximab.If an associated tumour is found, then recovery is not possible until the tumour is removed. Unfortunately, this is not always possible, especially if the tumour is malignant and advanced.
History
References
== External links == |
Botryomycosis | Botryomycosis; is a rare chronic granulomatous bacterial infection that affects the skin, and sometimes the viscera.: 255 Botryomycosis has been known to affect humans, horses, cattle, swine, dogs and cats.
Presentation
Associated conditions
There are only a handful of documented cases of botryomycosis in humans, and its pathogenesis is not completely understood. However, it is usually described in individuals with impaired immunity, or with an underlying disease such as diabetes mellitus, cystic fibrosis or HIV infection.
Causes
Staphylococcus aureus is usually the organism that causes the infection, however it can also be caused by Pseudomonas aeruginosa, Pneumocystis carinii, Proteus spp. and Actinobacillus lignieresii or other species of bacteria. The anatomic structure of its lesion is similar to that of actinomycosis and eumycetoma, and its granules resemble the sulfur granules of actinomycosis.
Diagnosis
History
The disease was originally discovered by Otto Bollinger (1843–1909) in 1870, and its name was coined by Sebastiano Rivolta (1832–1893) in 1884. The name refers to its grape-like granules (Gr. botryo = grapes) and the mistakenly implied fungal etiology (Gr. mykes = fungus). In 1919 the bacterial origin of the infection was discovered.
Notes
Concise Review of Veterinary Microbiology - Quinn and Markey 2003
External links
Essay on Pulmonary Botryomycosis |
Stannosis | Stannosis is an occupational, non-fibrotic pneumoconiosis caused by chronic exposure and inhalation of tin. Pneumoconiosis is essentially when inorganic dust is found on the lung tissue; in this case, caused by tin oxide minerals. Dust particles and fumes from tin industries, stannous oxide (SnO) and stannic oxide (SnO2), are specific to stannosis diagnoses. Hazardous occupations such as, tinning, tin-working, and smelting are where most cases of stannosis are documented. When melted tin ions are inhaled as a fume, the tin oxides deposit onto the lung nodules and immune response cells. If a worker is exposed to tin oxides over multiple events for an extended time, they are at risk of developing stannosis.
Toxicology and Physiology
Workers with acute exposures, short duration with varying dose concentrations, to tin oxides develop a mild irritation on the eyes, skin, and mucous membranes. When the inorganic metal materials are inhaled, the body activates the immune system and sends macrophages to the lungs. The macrophages try removing xenobiotic particles; however, stannous and stannic oxide interfere with the cells function. Tin deposition on lung nodules becomes apparent after X-ray imaging, although the stannosis does not appear to damage the lung tissues. Since the macrophages are laden with tin oxides but little to no fibrosis, stannosis is classified as a non-fibrotic pneumoniosis. Stannosis is an rare disease with only case-by-case appearances throughout history. Therefore, a diagnostic treatment plan has not yet been created by health officials.
Control and Prevention
Characteristics of Tin for Industrial Uses
Tin oxide metals are used for their variable valence state and positive charge deficit from their oxygen vacancy. When heated to temperatures above 2602 °C or 2875 K, tin oxides start to boil and produce fumes. For example, tin forms Sn2when heated in oxygenated environments; also called feebly acid. Tin oxide is known for being a good catalyst in solid photochemical reactions (photocatalysis) and electric production from light (photoelectrocatalysis). The energy produced form splitting water in photoelectrocatalysis is used for the creation of dehydrated dyes.Tin is found in nature as an off-white or gray crystal mineral called cassiterite. The corrosion resistant metal is harvested primarily in Malaya, Bolivia, Indonesia, Zaire, thailand, and Nigeria. Traditionally, tin was used to create containers; however, since the increase use of plastics and aluminum its no longer common. There are two allotropic forms of tin, depending on the temperature. A variety of tin alloys morphologies exist including the following metals: soft solder, fusible, pewter, bronze, Babbit, White, and phosphor bronze metal. Tin oxide metals are corrosive resistant which is important in industrial uses.
Industrial Applications of Tin oxides
Stannous oxide (SnO)
Stannous oxide (SnO) is used for manufacturing glass materials, like ceramics. The compound is insoluble in water and takes the form of a brow-black powder or blue-black crystalline solid. It is labeled as both an irritant and health hazard in the chemical safety sections of safety data sheets.
Stannic oxide (SnO2)
The primary uses for stannic oxide (SnO2) include polishing glass, marble, silver, and jewelry in addition to creating dyes for fabrics, paper, ceramic glazes, printing inks, coatings, and pigments in food polymers. Stannic oxide is also insoluble in water and dissociates in sulfuric acids and hydrochloric acid.
Case studies
De-tinning plant
In 1679, a 26 year old tin miner who worked in a smelter was found to have odd lung physiology after a radiography. He was asymptomatic despite having profuse small, metallic nodules in the lungs. At the same plant, a 55 year old man who loaded scrap tin into smelting furnaces for 15 years was assessed. His radiography confirmed that his cough and crackle was due to metallic bilateral nodules on the lungs, or stannosis. The second males biopsy revealed macrophages overwhelmed with dust deposits that affected hist connective tissue in the lungs. The case study determined that two workers in a detinning mine, who handled molten tin, developed stannosis. According to the researchers of "Stannosis: A report of 2 cases", the two workers were subject to the dustiest job of packaging tin-oxide for transportation. Tin miners are typically researched when assessing for stannosis because their exposure to tin oxides is around 70-80% in comparison to other job tasks in a plant.
Tinning milk reservoir tanks
After 17 years of painting tin hot tin powder into the inside of tanks, a 74 year old male patient developed a dry cough and progressive dyspnea. Because engineering controls and respiratory personal protective equipment were not used, the worker suffered grave lung damage. In comparison to health, non-tinning workers, the patient had significantly higher bronchoalveolar lavage fluid (BLAF) containing tin.
== References == |
Palatal myoclonus | Palatal myoclonus is a rare condition in which there are rhythmic jerky movements or a rapid spasm of the palatal (roof of the mouth) muscles. Chronic clonus is often due to lesions of the central tegmental tract (which connects the red nucleus to the ipsilateral inferior olivary nucleus).When associated with eye movements, it is known as oculopalatal myoclonus.
Signs and symptoms
Signs and symptoms of Palatal Myoclonus include:
- A rhythmic clicking sound in the ear due to the opening and closing of the Eustachian tube.- Rhythmic, jerky movements in the face, eyeballs, tongue, jaw, vocal cord or extremities (mostly hands).
Diagnosis
Classifications
physiologic, essential, epileptic, and symptomatic
Treatment
Drugs
Drugs used to treat palatal myoclonus include clonazepam, carbamazepine, baclofen, anticholinergics, tetrabenazine, valproic acid, phenytoin, lamotrigine, sumatriptan, and PIR.
A rare case of palatal myoclonus that associated with orofacial buccal dystonia has been treated with Botulinum toxin A (Dysport) injection and counseling.
Notes
http://www.tchain.com/otoneurology/disorders/central/opm.html
https://www.hindawi.com/journals/criot/2013/231505/
"NINDS Tremor Information Page". National Institute of Neurological Disorders and Stroke. July 20, 2007. Archived from the original on October 6, 2007. Retrieved 2007-10-08.
References
== External links == |
Discitis | Discitis, or diskitis, is an infection in the intervertebral disc space that affects different age groups. In adults, it can lead to severe consequences, such as sepsis or epidural abscess, but it can also spontaneously resolve, especially in children under 8 years of age. Discitis occurs post-surgically in approximately 1–2 percent of patients after spinal surgery.
Signs and symptoms
Symptoms include severe back pain, leading to lack of mobility. Some very young children may refuse to walk and arching of the back is possible. In post-operative situations, the symptoms occur within a week and result in severe low back pain or neck pain (depending on the surgical location). If untreated, the discitis may resolve on its own, causing spontaneous fusion of the intervertebral disc space, cause a chronic low grade infection, or progress to osteomyelitis and possibly even an epidural abscess. In case of concomitant inflammation of one or more vertebrae (in such cases usually involving the areas adjacent to the intervertebral disc spaces) the condition is called spondylodiscitis.
Causes
There is debate as to the cause, although hematogenous seeding of the offending organism is favored as well as direct spread. It is important to differentiate between spontaneous discitis which is usually from hematologic spread from a urinary or respiratory infection versus that from a post-operative complication which usually involves skin flora such as staph aureus.
It can be caused due to spinal tuberculosis and spread along spinal ligament to involve the adjacent anterior vertebral bodies, causing angulation of the vertebrae with subsequent kyphosis. The cause may be aseptic.
Diagnosis
Diagnosis is usually apparent on MRI although plain X-rays and CT examinations can be suggestive. The MRI will reveal air changes in the disc and possibly even external involvement involving the bone or epidural regions. A biopsy may be performed and helps with diagnosis in some cases but often an organism is not obtained. C-reactive protein levels and ESR levels will be elevated and are useful for treatment. Often, the white blood cell count will be normal and the patient will be afebrile.
Treatment
Treatment usually includes antibiotics, and reducing the mobility of the affected region, either with a back brace or a plaster cast. Without treatment, the patient may form an abscess which may need to be surgically corrected. Due to the poor vascularity of the disc, drugs required for treatment often include potent agents such as Ciprofloxacin along with Vancomycin. Occasionally, oral drugs can be used to treat the infection but it may fail and IV drugs may be required.
If the patient is an adult many surgeons and doctors now recommend moving little and often and within the pain limits of the medication. Discs respond to osmotic pressure therefore movement is beneficial to increase their blood flow and fluid dynamics. This is why disc patients are no longer told to bed rest. In children whether to bed rest or move a little is decided on an individual basis, depending on the site and severity of the discitis.
References
== External links == |
Unequal leg length | Unequal leg length (also termed leg length inequality, LLI or leg length discrepancy, LLD) is where the legs are either different lengths or appear to be different lengths because of misalignment. The condition has been estimated to affect between 40% and 70% of the population, with at least 0.1% having a difference greater than 20 mm (0.79 in).
Classification
There are two main types of leg length inequalities:
Structural differences are caused by the legs themselves being measurably different in length, usually due to differences in the length of the femur in the thigh or the tibia and fibula bones in the lower leg. This may be a birth defect or it may occur after a broken leg, serious infection, or local damage to one of the growth plates in a leg.
The other, more common, type is seen when the legs themselves are the same length, but due to neuromuscular injuries in the pelvis or upper leg, one leg or hip is held higher and tighter than the other (hypertonicity in the musculature of the pelvis or leg). These unequally tightened muscles cause the legs to seem to be different lengths, even though careful measurement would show equal lengths of the actual leg. This is called leg length alignment asymmetry (LLAA) and can be seen while lying down.
Diagnosis and workup
Unequal leg length in children is frequently first suspected by parents noticing a limp that appears to be getting worse. The standard workup in children is a thorough physical examination, including observing the child while walking and running. Also, at least in United States, standard workup in children also includes X-rays to quantify actual length of the bones of the legs.On X-rays, there is generally measurement of both the femur and the tibia, as well as both combined. Various measuring points for these have been suggested, but a functional method is to measure the distances between joint surfaces:
Femur length: The superior aspect of the femoral head and the distal portion of the medial femoral condyle.
Tibial length: The medial tibial plateau and the tibial plafondA leg length difference can result from a pelvic torsion.
Abnormal (gravity drive) pronation will drive the innominate bones forward (anteriorly). The forward rotation of the innominate will shorten the leg (See Rothbart 2006). The more pronated foot will have the more forwardly rotated innominate bone. And will be the side with the functionally short leg.
In adults, leg length discrepancy is believed to cause low back pain as a result of increased pelvic obliquity and lumbar scoliosis.
Treatment
The most common treatment for discrepancies in leg length is the use of a simple heel lift, which can be placed within the shoe. In cases where the length discrepancy is moderate, an external build up to the shoe is usually more comfortable. In severe cases, surgery can be used to make the longer leg shorter (or impede its growth), and/or make the shorter leg longer via limb lengthening.
Measurement challenges
Although prone "functional leg length" is a widely used chiropractic tool in their Activator technique, it is not a recognized anthropometric technique, since legs are usually of unequal length, and measurements in the prone position are not entirely valid estimates of standing X-ray differences. Measurements in the standing position are far more reliable. Another confounding factor is that simply moving the two legs held together and leaning them imperceptibly to one side or the other produces different results.Clinical measurement of leg length conventionally uses the distance from the anterior superior iliac spine to the medial malleolus. Projectional radiographic measurements of leg length have two main variants:
Teleroentgenogram, which projects the entirety of both legs at the same time.
Orthoroentgenogram, which takes separate images of the hip, knee and ankle.On X-rays, the length of the lower limb can be measured from the proximal end of femoral head to the center of the plafond of the distal tibia.
See also
Logan v. Zimmerman Brush Co., lawsuit over alleged job discrimination over LLI that reached the U.S. Supreme Court
References
Rothbart BA 2006. Relationship of Functional Leg-Length Discrepancy to Abnormal Pronation. Journal American Podiatric Medical Association;96(6):499-507
== External links == |
Burning feet syndrome | Burning feet syndrome, also known as Grierson-Gopalan syndrome, is a medical condition that causes severe burning and aching of the feet, hyperesthesia, and vasomotor changes of the feet that lead to excessive sweating. It can even affect the eyes, causing scotoma and amblyopia. The condition occurs more frequently in women, and usually manifests itself when a person is between twenty and forty years old.
Presentation
The burning heat is usually limited to the soles of the feet, but may extend up to the ankles or lower legs of some patients. The burning can sometimes be accompanied by feelings of pins and needles or tingling in these regions. Nighttime is when almost all people with this syndrome report the heat symptoms being the worst, with the condition getting better as morning comes. Those who have psychosomatic disorders sometimes display psychological symptoms along with the burning of feet associated with the syndrome. For most, there is no redness of the skin of their feet during the heat sensations, and almost never is there accompanying tenderness along with it.
Causes
Burning feet syndrome can be inherited, or it can be caused by pressure being put on the nerves. Links also exist between this syndrome and diseases such as hypothyroidism, diabetes mellitus, and rheumatoid arthritis; links are also believed to exist between this syndrome and Zinc deficiency. It is also linked to vitamin B (specifically pantothenic acid) deficiencies and kidney failure.
It seems to be a small fiber neuropathy.
Diagnosis
Diagnosis is mainly clinical.
Symptoms are burning sensation in soles, sometime ankles and legs in many patients. Tingling sensation and pin prick sensations are also common.
Sweating of legs and soles is seen. In some case hypertrophy of one of the legs is seen mainly in tropical region where external temperature is also higher.
Eponym
Termed Grierson-Gopalan syndrome after Coluther Gopalan and J. Grierson.
See also
Erythromelalgia
Small fiber peripheral neuropathy
Tarsal tunnel syndrome
Chemotherapy-induced acral erythema
References
== External links == |
Hereditary inclusion body myopathy | Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles.
HIBMs are a group of muscle wasting disorders that are uncommon in the general world population. One autosomal recessive form of HIBM is known as IBM2 or GNE myopathy, which is a common genetic disorder amongst people of Iranian Jewish descent. IBM2 has also been identified in other minorities throughout the world, including those of Asian, European, and South American, and Middle Eastern descent. In Japan and other East Asian countries, this disorder is known as Distal Myopathy with Rimmed Vacuoles (DMRV).
IBM2 causes progressive muscle weakness and wasting. Muscle wasting usually starts around the age of 20 – 30 years, although young onset at 17 and old onset at 52 has been recorded. It can progress to marked disability within 10 to 15 years, confining many people with IBM2 to a wheelchair. The weakness and severity can vary from person to person. In some, weakness in the legs is noticed first. In some others, the hands are weakened more rapidly than the legs. IBM2 does not seem to affect the brain, internal organs or sensation. The quadriceps are relatively spared, and remain strong until the late stages of disease, which is the reason IBM2 is often referred to as Quadriceps Sparing Myopathy (QSM).
Signs and symptoms
Some early signs of HIBMs includes:
Difficulty walking on heels, and difficulty running;
Weak index finger;
Frequent loss of balance.
On muscle biopsy, the typical finding includes inclusion bodies, rimmed vacuoles and accumulation of aberrant proteins similar to those found in senile plaques of Alzheimers disease (amyloid beta, hyperphosphorylated tau, amongst others)
Genetics
The different forms have different mutations and inheritance patterns. See the detailed descriptions for details
Mechanisms
The exact mechanisms of these diseases are not well understood. GNE/MNK a key enzyme in the sialic acid biosynthetic pathway, and loss-of-function mutations in GNE/MNK may lead to a lack of sialic acid, which in turn could affect sialoglycoproteins. GNE knockout mice show problems similar to people with IBM and in people with IBM dystroglycan has been found to lack sialic acid. However, the part of the dystroglycan that is important in muscle function does not seem to be affected. Another protein, neural cell adhesion molecule is under-sialyated in people with IBM, but as of 2016 it had no known role in muscle function.
Diagnosis
The most useful information for accurate diagnosis is the symptoms and weakness pattern. If the quadriceps are spared but the hamstrings and iliopsoas are severely affected in a person between ages of 20 - 40, it is very likely HIBM will be at the top of the differential diagnosis. The doctor may order any or all of the following tests to ascertain if a person has IBM2:
Blood test for serum Creatine Kinase (CK or CPK);
Nerve Conduction Study (NCS) / Electomyography (EMG);
Muscle Biopsy;
Magnetic Resonance Imaging (MRI) or Computer Tomography (CT) Scan to determine true sparing of quadriceps;
Blood Test or Buccal swab for genetic testing;
Classification
Types of hereditary inclusion body myopathy:
IBM2 is the most common form, and is an autosomal recessive form, caused by mutations in the GNE gene; this form mainly affects leg muscles, but with an unusual distribution that spares the quadriceps. The incidence of this form is about 10 per million per year. There are two forms: a quadriceps sparing myopathy (autosomal recessive form of inclusion body myopathy) and Nonaka type distal myopathy (distal myopathy with rimmed vacuoles). While occurring worldside it is most common in Jews of Persian origin. The GNE gene ecodes the rate-limiting, bifunctional enzyme of sialic acid biosynthesis, uridine diphosphate-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Disease occurs when both copies in the genome are non functional. The pathophysiology is still unclear. Cardiac involvement may occur.
IBM3 is a sometimes autosomal dominant and sometimes autosomal recessive form caused by mutations in MYHC2A; it is relatively mild muscle disorder.
Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD), now more commonly referred to as multisystem proteinopathy (MSP), is an autosomal dominant condition caused by mutations in VCP, HNRPA2B1 or HNRNPA1; it is a multisystem degenerative disorder that can affect muscle, bone, and/or the central nervous system.The condition now called Desmin-related myofibrillar myopathy (also called myofibrillar myopathy-1) was formerly known as inclusion body myopathy 1 (IBM1).More types of HIMBs, linked to other genes, may be identified in the future.
Treatment
Treatment is palliative, not curative (as of 2009).Treatment options for lower limb weakness such as foot drop can be through the use of Ankle Foot Orthoses (AFOs) which can be designed or selected by an Orthotist based upon clinical need of the individual. Sometimes tuning of rigid AFOs can enhance knee stability.
Prognosis
A 2009 review noted that muscle weakness usually begins after age 20 and after 20–30 years, the person usually requires a wheel chair for mobility. There was no mention of increased mortality.
Research
Because lack of sialic acid appears to be part of the pathology of IBM caused by GNE mutations, clinical trials with sialic acid supplements, and with a precursor of sialic acid, N-Acetylmannosamine, have been conducted, and as of 2016 further trials were planned.
History
Hereditary inclusion body myopathy (IBM) constitutes a unique group of neuromuscular disorders characterized by adult-onset slowly progressive distal and proximal weakness, and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. Autosomal dominant (IMB3; OMIM 605637 [1]) and autosomal recessive (IBM2; OMIM 600737 [2]) forms have been described. The autosomal recessive form, first characterized in Jews of Persian descent, is a myopathy that affects mainly leg muscles, but with an unusual distribution that spares the quadriceps, so-called quadriceps-sparing myopathy (QSM). This disorder was subsequently found in other Middle Eastern families, the gene was mapped to 9p13-p12, and in 104 affected persons from 47 Middle Eastern families the same mutation in homozygous state was found in the GNE gene. Affected individuals in families of other ethnic origins were found to be compound heterozygotes for other distinct mutations in the GNE gene. From OMIM 603824. [3]
See also
Inclusion body myositis, a more common and non-hereditary form.
Valosin-containing protein (VCP); mutations in VCP cause multisystem proteinopathy (MSP) which can present (among others) as a rare form of inclusion body myopathy.
References
External links
GeneReviews/NCBI/NIH/UW entry on Inclusion Body Myopathy 2
GeneReviews/NCBI/NIH/UW entry on Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia |
Constipation | Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement. Complications from constipation may include hemorrhoids, anal fissure or fecal impaction. The normal frequency of bowel movements in adults is between three per day and three per week. Babies often have three to four bowel movements per day while young children typically have two to three per day.Constipation has many causes. Common causes include slow movement of stool within the colon, irritable bowel syndrome, and pelvic floor disorders. Underlying associated diseases include hypothyroidism, diabetes, Parkinsons disease, celiac disease, non-celiac gluten sensitivity, colon cancer, diverticulitis, and inflammatory bowel disease. Medications associated with constipation include opioids, certain antacids, calcium channel blockers, and anticholinergics. Of those taking opioids about 90% develop constipation. Constipation is more concerning when there is weight loss or anemia, blood is present in the stool, there is a history of inflammatory bowel disease or colon cancer in a persons family, or it is of new onset in someone who is older.Treatment of constipation depends on the underlying cause and the duration that it has been present. Measures that may help include drinking enough fluids, eating more fiber, consumption of honey and exercise. If this is not effective, laxatives of the bulk forming agent, osmotic agent, stool softener, or lubricant type may be recommended. Stimulant laxatives are generally reserved for when other types are not effective. Other treatments may include biofeedback or in rare cases surgery.In the general population rates of constipation are 2–30 percent. Among elderly people living in a care home the rate of constipation is 50–75 percent. People spend, in the United States, more than US$250 million on medications for constipation a year.
Definition
Constipation is a symptom, not a disease. Most commonly, constipation is thought of as infrequent bowel movements, usually fewer than 3 stools per week. However, people may have other complaints as well including:
Straining with bowel movements
Excessive time needed to pass a bowel movement
Hard stools
Pain with bowel movements secondary to straining
Abdominal pain
Abdominal bloating.
the sensation of incomplete bowel evacuation.The Rome III Criteria are a set of symptoms that help standardize the diagnosis of constipation in various age groups. These criteria help physicians to better define constipation in a standardized manner.
Causes
The causes of constipation can be divided into congenital, primary, and secondary. The most common kind is primary and not life-threatening. It can also be divided by the age group affected such as children and adults.
Primary or functional constipation is defined by ongoing symptoms for greater than six months not due to an underlying cause such as medication side effects or an underlying medical condition. It is not associated with abdominal pain, thus distinguishing it from irritable bowel syndrome. It is the most common kind of constipation, and is often multifactorial. In adults, such primary causes include: dietary choices such as insufficient dietary fiber or fluid intake, or behavioral causes such as decreased physical activity. In the elderly, common causes have been attributed to insufficient dietary fiber intake, inadequate fluid intake, decreased physical activity, side effects of medications, hypothyroidism, and obstruction by colorectal cancer. Evidence to support these factors however is poor.Secondary causes include side effects of medications such as opiates, endocrine and metabolic disorders such as hypothyroidism, and obstruction such as from colorectal cancer or ovarian cancer. Celiac disease and non-celiac gluten sensitivity may also present with constipation. Cystocele can develop as a result of chronic constipation.
Diet
Constipation can be caused or exacerbated by a low-fiber diet, low liquid intake, or dieting. Dietary fiber helps to decrease colonic transport time, increases stool bulk but simultaneously softens stool. Therefore, diets low in fiber can lead to primary constipation.
Medications
Many medications have constipation as a side effect. Some include (but are not limited to) opioids, diuretics, antidepressants, antihistamines, antispasmodics, anticonvulsants, tricyclic antidepressants, antiarrythmics, beta-adrenoceptor antagonists, anti-diarrheals, 5-HT3 receptor antagonists such as ondansetron, and aluminum antacids. Certain calcium channel blockers such as nifedipine and verapamil can cause severe constipation due to dysfunction of motility in the rectosigmoid colon. Supplements such as calcium and iron supplements can also have constipation as a notable side effect.
Medical conditions
Metabolic and endocrine problems which may lead to constipation include: pheochromocytoma, hypercalcemia, hypothyroidism, hyperparathyroidism, porphyria, chronic kidney disease, pan-hypopituitarism, diabetes mellitus, and cystic fibrosis. Constipation is also common in individuals with muscular and myotonic dystrophy.Systemic diseases that may present with constipation include celiac disease and systemic sclerosis.Constipation has a number of structural (mechanical, morphological, anatomical) causes, namely through creating space-occupying lesions within the colon that stop the passage of stool, such as colorectal cancer, strictures, rectocoles, anal sphincter damage or malformation and post-surgical changes. Extra-intestinal masses such as other malignancies can also lead to constipation from external compression.Constipation also has neurological causes, including anismus, descending perineum syndrome, and Hirschsprungs disease. In infants, Hirschsprungs disease is the most common medical disorder associated with constipation. Anismus occurs in a small minority of persons with chronic constipation or obstructed defecation.Spinal cord lesions and neurological disorders such as Parkinsons disease and pelvic floor dysfunction can also lead to constipation.
Chagas disease may cause constipation through the destruction of the myenteric plexus.
Psychological
Voluntary withholding of the stool is a common cause of constipation. The choice to withhold can be due to factors such as fear of pain, fear of public restrooms, or laziness. When a child holds in the stool a combination of encouragement, fluids, fiber, and laxatives may be useful to overcome the problem. Early intervention with withholding is important as this can lead to anal fissures.
Congenital
A number of diseases present at birth can result in constipation in children. They are as a group uncommon with Hirschsprungs disease (HD) being the most common. There are also congenital structural anomalies that can lead to constipation, including anterior displacement of the anus, imperforate anus, strictures, and small left colon syndrome.
Pathophysiology
Diagnostic approach
The diagnosis is typically made based on a persons description of the symptoms. Bowel movements that are difficult to pass, very firm, or made up of small hard pellets (like those excreted by rabbits) qualify as constipation, even if they occur every day. Constipation is traditionally defined as three or fewer bowel movements per week. Other symptoms related to constipation can include bloating, distension, abdominal pain, headaches, a feeling of fatigue and nervous exhaustion, or a sense of incomplete emptying. Although constipation may be a diagnosis, it is typically viewed as a symptom that requires evaluation to discern a cause.
Description
Distinguish between acute (days to weeks) or chronic (months to years) onset of constipation because this information changes the differential diagnosis. This in the context of accompanied symptoms helps physicians discover the cause of constipation. People often describe their constipation as bowel movements that are difficult to pass, firm stool with lumpy or hard consistency, and excessive straining during bowel movements. Bloating, abdominal distension, and abdominal pain often accompany constipation. Chronic constipation (symptoms present at least three days per month for more than three months) associated with abdominal discomfort is often diagnosed as irritable bowel syndrome (IBS) when no obvious cause is found.Poor dietary habits, previous abdominal surgeries, and certain medical conditions can contribute to constipation. Diseases associated with constipation include hypothyroidism, certain types of cancer, and irritable bowel syndrome. Low fiber intake, inadequate amounts of fluids, poor ambulation or immobility, or medications can contribute to constipation. Once the presence of constipation is identified based on a culmination of the symptoms described above, then the cause of constipation should be figured out.
Separating non-life-threatening from serious causes may be partly based on symptoms. For example, colon cancer may be suspected if a person has a family history of colon cancer, fever, weight loss, and rectal bleeding. Other alarming signs and symptoms include family or personal history of inflammatory bowel disease, age of onset over 50, change in stool caliber, nausea, vomiting, and neurological symptoms like weakness, numbness and difficulty urinating.
Examination
A physical examination should involve at least an abdominal exam and rectal exam. Abdominal exam may reveal an abdominal mass if there is significant stool burden and may reveal abdominal discomfort. Rectal examination gives an impression of the anal sphincter tone and whether the lower rectum contains any feces or not. Rectal examination also gives information on the consistency of the stool, the presence of hemorrhoids, blood and whether any perineal irregularities are present including skin tags, fissures, anal warts. Physical examination is done manually by a physician and is used to guide which diagnostic tests to order.
Diagnostic tests
Functional constipation is common and does not warrant diagnostic testing. Imaging and laboratory tests are typically recommended for those with alarm signs or symptoms.The laboratory tests performed depends on the suspected underlying cause of the constipation. Tests may include CBC (complete blood count), thyroid function tests, serum calcium, serum potassium, etc.Abdominal X-rays are generally only performed if bowel obstruction is suspected, may reveal extensive impacted fecal matter in the colon, and may confirm or rule out other causes of similar symptoms.Colonoscopy may be performed if an abnormality in the colon like a tumor is suspected. Other tests rarely ordered include anorectal manometry, anal sphincter electromyography, and defecography.Colonic propagating pressure wave sequences (PSs) are responsible for discrete movements of the bowel contents and are vital for normal defecation. Deficiencies in PS frequency, amplitude, and extent of propagation are all implicated in severe defecatory dysfunction (SDD). Mechanisms that can normalize these aberrant motor patterns may help rectify the problem. Recently the novel therapy of sacral nerve stimulation (SNS) has been utilized for the treatment of severe constipation.
Criteria
The Rome III Criteria for functional constipation must include two or more of the following and present for the past three months, with symptoms starting for at least 6 months prior to diagnosis.
Straining during defecation for at least 25% of bowel movements
Lumpy or hard stools in at least 25% of defecations
Sensation of incomplete evacuation for at least 25% of defecations
Sensation of anorectal obstruction/blockage for at least 25% of defecations
Manual maneuvers to facilitate at least 25% of defecations
Fewer than 3 defecations per week
Loose stools are rarely present without the use of laxatives
There are insufficient criteria for irritable bowel syndrome
Prevention
Constipation is usually easier to prevent than to treat. Following the relief of constipation, maintenance with adequate exercise, fluid intake, and high-fiber diet is recommended.
Treatment
A limited number of cases require urgent medical intervention or will result in severe consequences.The treatment of constipation should focus on the underlying cause if known. The National Institute of Health and Care Excellence (NICE) break constipation in adults into two categories - chronic constipation of unknown cause and constipation due to opiates.In chronic constipation of unknown cause, the main treatment involves the increased intake of water and fiber (either dietary or as supplements). The routine use of laxatives or enemas is discouraged, as having bowel movements may come to be dependent upon their use.
Fiber supplements
Soluble fiber supplements such as psyllium are generally considered first-line treatment for chronic constipation, compared to insoluble fibers such as wheat bran. Side effects of fiber supplements include bloating, flatulence, diarrhea, and possible malabsorption of iron, calcium, and some medications. However, patients with opiate-induced constipation will likely not benefit from fiber supplements.
Laxatives
If laxatives are used, milk of magnesia or polyethylene glycol are recommended as first-line agents due to their low cost and safety. Stimulants should only be used if this is not effective. In cases of chronic constipation, polyethylene glycol appears superior to lactulose. Prokinetics may be used to improve gastrointestinal motility. A number of new agents have shown positive outcomes in chronic constipation; these include prucalopride and lubiprostone. Cisapride is widely available in third world countries, but has been withdrawn in most of the west. It has not been shown to have a benefit on constipation, while potentially causing cardiac arrhythmias and deaths.
Enemas
Enemas can be used to provide a form of mechanical stimulation. A large volume or high enema can be given to cleanse as much of the colon as possible of feces, and the solution administered commonly contains castile soap which irritates the colons lining resulting in increased urgency to defecate. However, a low enema is generally useful only for stool in the rectum, not in the intestinal tract.
Physical intervention
Constipation that resists the above measures may require physical intervention such as manual disimpaction (the physical removal of impacted stool using the hands; see fecal impaction).
Regular exercise
Regular exercise can help improve chronic constipation.
Surgical intervention
In refractory cases, procedures can be performed to help relieve constipation. Sacral nerve stimulation has been demonstrated to be effective in a minority of cases. Colectomy with ileorectal anastomosis is another intervention performed only in patients known to have a slow colonic transit time and in whom a defecation disorder has either been treated or is not present. Because this is a major operation, side effects can include considerable abdominal pain, small bowel obstruction, and post-surgical infections. Furthermore, it has a very variable rate of success and is very case dependent.
Prognosis
Complications that can arise from constipation include hemorrhoids, anal fissures, rectal prolapse, and fecal impaction. Straining to pass stool may lead to hemorrhoids. In later stages of constipation, the abdomen may become distended, hard and diffusely tender. Severe cases ("fecal impaction" or malignant constipation) may exhibit symptoms of bowel obstruction (nausea, vomiting, tender abdomen) and encopresis, where soft stool from the small intestine bypasses the mass of impacted fecal matter in the colon.
Epidemiology
Constipation is the most common chronic gastrointestinal disorder in adults. Depending on the definition employed, it occurs in 2% to 20% of the population. It is more common in women, the elderly and children. Specifically constipation with no known cause affects females more often affected than males. The reasons it occurs more frequently in the elderly is felt to be due to an increasing number of health problems as humans age and decreased physical activity.
12% of the population worldwide reports having constipation.
Chronic constipation accounts for 3% of all visits annually to pediatric outpatient clinics.
Constipation-related health care costs total $6.9 billion in the US annually.
More than four million Americans have frequent constipation, accounting for 2.5 million physician visits a year.
Around $725 million is spent on laxative products each year in America.
History
Since ancient times different societies have published medical opinions about how health care providers should respond to constipation in patients. In various times and places, doctors have made claims that constipation has all sorts of medical or social causes. Doctors in history have treated constipation in reasonable and unreasonable ways, including use of a spatula mundani.After the advent of the germ theory of disease then the idea of "auto-intoxication" entered popular Western thought in a fresh way. Enema as a scientific medical treatment and colon cleansing as alternative medical treatment became more common in medical practice.Since the 1700s in the West there has been some popular thought that people with constipation have some moral failing with gluttony or laziness.
Special populations
Children
Approximately 3% of children have constipation, with girls and boys being equally affected. With constipation accounting for approximately 5% of general pediatrician visits and 25% of pediatric gastroenterologist visits, the symptom carries a significant financial impact upon the healthcare system. While it is difficult to assess an exact age at which constipation most commonly arises, children frequently experience constipation in conjunction with life-changes. Examples include: toilet training, starting or transferring to a new school, and changes in diet. Especially in infants, changes in formula or transitioning from breast milk to formula can cause constipation. The majority of constipation cases are not tied to a medical disease, and treatment can be focused on simply relieving the symptoms.
Postpartum women
The six-week period after pregnancy is called the postpartum stage. During this time, women are at increased risk of being constipated. Multiple studies estimate the prevalence of constipation to be around 25% during the first 3 months. Constipation can cause discomfort for women, as they are still recovering from the delivery process especially if they have had a perineal tear or underwent an episiotomy. Risk factors that increase the risk of constipation in this population include:
Damage to the levator ani muscles (pelvic floor muscles) during childbirth
Forceps-assisted delivery
Lengthy second stage of labor
Delivering a large child
HemorrhoidsHemorrhoids are common in pregnancy and also may get exacerbated when constipated. Anything that can cause pain with stooling (hemorrhoids, perineal tear, episiotomy) can lead to constipation because patients may withhold from having a bowel movement so as to avoid pain.The pelvic floor muscles play an important role in helping pass a bowel movement. Injury to those muscles by some of the above risk factors (examples- delivering a large child, lengthy second stage of labor, forceps delivery) can result in constipation. Enemas may be administered during labor and these can also alter bowel movements in the days after giving birth. However, there is insufficient evidence to make conclusions about the effectiveness and safety of laxatives in this group of people.
See also
Obstructed defecation
Rectal tenesmus
References
External links
09-129b. at Merck Manual of Diagnosis and Therapy Home Edition
Constipation - Introduction (UK NHS site)
MedlinePlus Overview constipation
Constipation Guideline - the World Gastroenterology Organisation (WGO) |
Syringoma | Syringomas are benign eccrine sweat duct tumors, typically found clustered on eyelids, although they may also be found in the armpits, abdomen, chest, neck, scalp, or groin area, including genitals, in a symmetric pattern.: 663 They are skin-colored or yellowish firm, rounded bumps, 1–3 mm in diameter, and may be confused with xanthoma, milia, hidrocystoma, trichoepithelioma, and xanthelasma. They are more common in women and are most commonly found in middle-aged Asian women. While they can present at any time in life, they typically present during adolescence. They are usually not associated with any other symptoms, although can sometimes cause itchiness or irritation.
Types
The eruptive form typically presents on the anterior chest, abdomen, neck, and arms. It presents in successive crops with periods of relief in between times of active rash.
The milia-like type of syringoma is typically smaller lesions that have a milky white center that can look like milia.
The plaque type is more commonly associated with itchiness and chronic scratching that leads to epidermal thickening similar to lichen planus.
The familial form, in some cases of syringoma, exhibits a familial pattern in an autosomal-dominant pattern of inheritance. Chromosome 16q22 has been shown to be involved in the genetic links of syringoma.
Presentation
Associated syndromes
Syringomas can be found in association with other symptoms as part of a syndrome. Hailey–Hailey disease (also known as familial benign chronic pemphigus) is a blistering disease that can also include syringomas.Several systemic syndromes have also been associated with syringoma including diabetes mellitus, Down syndrome, Brooke–Spiegler syndrome, and Nicolau–Balus syndrome. Specifically, diabetes mellitus is strongly associated with clear cell syringoma consisting of nests of clear cells containing glycogen. A phosphorylase deficiency, resulting from elevated glucose levels seen in diabetes, is thought to lead to an accumulation of glycogen in the skin and within the clear cells. The incidence of syringomas has been reported in up to 40% of people with Down syndrome, and can be associated with a condition calcinosis cutis, which requires prompt medical attention. Brooke–Spiegler syndrome is a rare autosomal-dominant syndrome with cutaneous manifestations including syringomas and trichoepitheliomas. Nicolau–Balus syndrome is a rare autosomal-dominant disorder consisting of atrophoderma vermiculata and syringomas.
Pathophysiology
The pathophysiology of syringomas remains largely unknown. Familial patterns presenting in an autosomal-dominant pattern suggest a genetic link that can result in varying genetic aberrations in lesions, specifically chromosome 16q22. The most commonly accepted theory is that syringomas are benign growths that arise from the intraepidermal portion of eccrine ducts. Another theory suggests that syringomas are a reactive hyperplasia rather than a true neoplasm resulting after inflammatory processes such as eczema. A hamartomatous process possibly could explain eruptive syringomas. A hamartoma of pluripotent stem cells could precede the pathological process. Syringomas may also be under hormonal influence, explaining the female predominance.
Diagnosis
Syringomas can often be diagnosed clinically based on presentation, distribution patterns over the body, lack of associated symptoms, and family history. A definitive diagnosis requires a skin biopsy to allow the tissue to be examined under a microscope. Histologically, syringomas have a characteristic comma-shaped ("tadpole") tail of dilated, cystic eccrine ducts.
Treatment
The goal of treatment is to improve the appearance of lesions, since they are otherwise not serious and typically do not cause symptoms. Many treatment methods have been attempted, but complete removal is uncommon. No single treatment method has been shown to work consistently. Both medical and surgical treatments have been studied, each with variable success. Common destructive treatment methods include carbon dioxide lasers, dermabrasion, surgical excision, electrocoagulation, and chemical peels. Many of these methods are very time-consuming and require multiple treatment sessions. Carbon dioxide lasers are the most commonly practiced method; they can cause thermal damage, though, leading to scarring in the area. Medical therapies include topical atropine, topical retinoids, and oral tranilast.
The most common adverse effects include redness, skin discoloration, and pain. Other side effects include blistering and scarring.
See also
Acrospiroma
List of cutaneous conditions
List of cutaneous neoplasms associated with systemic syndromes
References
External links
eMedicine entry on syringomas
DermNet NZ |
Multiple epiphyseal dysplasia | Fairbanks disease or multiple epiphyseal dysplasia (MED) is a rare genetic disorder (dominant form: 1 in 10,000 births) that affects the growing ends of bones. Long bones normally elongate by expansion of cartilage in the growth plate (epiphyseal plate) near their ends. As it expands outward from the growth plate, the cartilage mineralizes and hardens to become bone (ossification). In MED, this process is defective.
Signs and symptoms
Children with autosomal dominant MED experience joint pain and fatigue after exercising. Their x-rays show small and irregular ossifications centers, most apparent in the hips and knees. There are very small capital femoral epiphyses and hypoplastic, poorly formed acetabular roofs. A waddling gait may develop. Knees have metaphyseal widening and irregularity while hands have brachydactyly (short fingers) and proximal metacarpal rounding. Flat feet are very common. The spine is normal but may have a few irregularities, such as scoliosis.By adulthood, people with MED are of short stature or in the low range of normal and have short limbs relative to their trunks. Frequently, movement becomes limited at the major joints, especially at the elbows and hips. However, loose knee and finger joints can occur. Signs of osteoarthritis usually begin in early adulthood.Children with recessive MED experience joint pain, particularly of the hips and knees, and commonly have deformities of the hands, feet, knees, or vertebral column (like scoliosis). Approximately 50% of affected children have abnormal findings at birth (such as club foot or twisted metatarsals, cleft palate, inward curving fingers due to underdeveloped bones and brachydactyly, or ear swelling caused by injury during birth). Height is in the normal range before puberty. As adults, people with recessive MED are only slightly more diminished in stature, but within the normal range. Lateral knee radiography can show multi-layered patellae.
Genetics
Multiple epiphyseal dysplasia (MED) encompasses a spectrum of skeletal disorders, most of which are inherited in an autosomal dominant form. However, there is an autosomal recessive form.Associated genes include COL9A1, COL9A2, COL9A3, COMP, and MATN3.Types include:
In the dominant form, mutations in five genes are causative: COMP (chromosome 19), COL9A1 (chromosome 6), COL9A2 (chromosome 1), COL9A3 (chromosome 20), and MATN3 (chromosome 2). However, in approximately 10%–20% of samples analyzed, a mutation cannot be identified in any of the five genes above, suggesting that mutations in other as-yet unidentified genes are involved in the pathogenesis of dominant MED.The COMP gene is mutated in 70% of the molecularly confirmed MED patients. Mutations are in the exons encoding the type III repeats (exons 8–14) and C-terminal domain (exons 15–19). The most common mutations in COL9A1 are in exons 8-10, in COL9A2 in exons 2-4, and in COL9A3 in exons 2-4. Altogether, those mutations cover 10% of the patients. The other 20% of affected people have mutations in MATN3 gene, all found within exon 2. The following testing regime has been recommended by the European Skeletal Dysplasia Network:
Level 1: COMP (exons 10–15) and MATN3 (exon 2)
Level 2: COMP (exons 8 & 9 and 16–19)
Level 3: COL9A1 (exon 8), COL9A2 and COL9A3 (exon 3)All those genes are involved in the production of the extracellular matrix (ECM). The role of COMP gene remains unclear. It is a noncollagenous protein of the ECM. Mutations in this gene can cause the pseudoachondroplasia (PSACH). It should play a role in the structural integrity of cartilage by its interaction with other extracellular matrix proteins and can be part of the interaction of the chondrocytes with the matrix and it is also a potent suppressor of apoptosis in chondrocytes. Another role is maintaining a vascular smooth muscle cells contractile under physiological or pathological stimuli.Since 2003, the European Skeletal Dysplasia Network has used an online system to diagnose cases referred to the network before mutation analysis to study the mutations causing PSACH or MED.COL9A1, COL9A2, COL9A3 are genes coding for collagen type IX, that is a component of hyaline cartilage. MATN3 protein may play a role in the formation of the extracellular filamentous networks and in the development and homeostasis of cartilage and bone.In the recessive form, the DTDST gene, also known as SLC26A2, is mutated in almost 90% of the patients, causing diastrophic dysplasia. It is a sulfate transporter, transmembrane glycoprotein implicated in several chondrodysplasias. It is important for sulfation of proteoglycans and matrix organization.
Diagnosis
Diagnosis should be based on the clinical and radiographic findings and a genetic analysis can be assessed.
Treatment
Symptomatic individuals should be seen by an orthopedist to assess the possibility of treatment (physiotherapy for muscular strengthening, cautious use of analgesic medications such as nonsteroidal anti-inflammatory drugs). Although there is no cure, surgery is sometimes used to relieve symptoms. Surgery may be necessary to treat misalignment of the hip (osteotomy of the pelvis or the collum femoris) and, in some cases, malformation (e.g., genu varum or genu valgum). In some cases, total hip replacement may be necessary. However, surgery is not always necessary or appropriate.Sports involving joint overload are to be avoided, while swimming or cycling are strongly suggested. Cycling has to be avoided in people having ligamentous laxity.
Weight control is suggested.The use of crutches, other deambulatory aids or wheelchair is useful to prevent hip pain. Pain in the hand while writing can be avoided using a pen with wide grip.
History
Multiple epiphyseal dysplasia was described separately by Seved Ribbing and Harold Arthur Thomas Fairbank in the 1930s.In 1994, Ralph Oehlmanns group mapped MED to the peri-centromeric region of chromosome 19, using genetic linkage analysis. Michael Briggs group mapped PSACH to the same area. COMP gene was firstly linked to MED and PSACH in 1995. In 1995, the group led by Knowlton did a "high-resolution genetic and physical mapping of multiple epiphyseal dysplasia and pseudoachondroplasia mutations at chromosome 19p13.1-p12."Research on COMP led to mouse models of the pathology of MED. In 2002, Svenssons group generated a COMP-null mouse to study the COMP protein in vivo. These mice showed no anatomical, histological, or even ultrastructural abnormalities and none of the clinical signs of PSACH or MED. Lack of COMP was not compensated for by any other protein in the thrombospondin family. This study confirmed that the disease is not caused by reduced expression of COMP.In 2007, Piròg-Garcias group generated another mouse model carrying a mutation previously found in a human patient. With this new model, they were able to demonstrate that reduced cell proliferation and increased apoptosis are significant pathological mechanisms involved in MED and PSACH. In 2010, this mouse model allowed a new insight into myopathy and tendinopathy, which are often associated with PSACH and MED. These patients show increased skeletal muscle stress, as indicated by the increase in myofibers with central nuclei. Myopathy in the mutant mouse results from underlying tendinopathy, because the transmission of forces is altered from the normal state. There is a higher proportion of larger diameter fibrils of collagen, but the cross-sectional area of whole mutant tendons was also significantly less than that of the wild-type tendons causing joint laxity and stiffness, easy tiring and weakness. This study is important because those diseases are often mistaken for neurological problems, since the doctor can detect a muscle weakness. This includes many painful and useless clinical neurological examination before the correct diagnosis. In this work, the researchers suggest to the pediatric doctor to perform x-rays before starting the neurological assessment, to exclude the dysplasia.COL91A mutation was discovered in 2001.
Culture
Prominent people with this condition
Danny DeVito, American actor, producer, and director
Robert Reich, former United States Secretary of Labor under President Bill Clinton from 1993 to 1997
David Wetherill, British Paralympian table tennis athlete
References
External links
GeneReview/NIH/UW entry on Multiple Epiphyseal Dysplasia, Dominant
GeneReview/NIH/UW entry on Multiple Epiphyseal Dysplasia, Recessive |
Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome | Hereditary angiopathy with nephropathy, aneurysms and muscle cramps syndrome is a rare genetic, multisystemic, COL4A1-related disorder, it is characterized by angiopathy, nephropathy, hematuria, development of kidney cysts, intracranial aneurysms (which have the potential to burst), childhood-onset muscle cramps, urinal, heart and ocular problems. Half of the people with this disorder (50%) have leukoencephalopathy, while a very small number of people with this disorder have Raynauds phenomenon.
Causes
This syndrome is caused by mutations in the COL4A1 gene, on the chromosome 13q34, this gene provides instructions for making one of the components necessary for the formation of a protein called type IV collagen, this protein is one of the main components for basement membranes throughout the body.The mutations of the gene causes the production of a protein that alters the structure of collagen type IV, because of this, the collagen molecules cant attach themselves to the basement membranes, and, without these networks, they turn unstable and thus weaken surrounding tissues, explaining the weakening of vasculature of ocular, renal, cerebral and muscular tissues.This disorder run in families following an autosomal dominant inheritance pattern
Epidemiology
Although the exact prevalence of this disorder isnt known, only six families affected by this disorder have been recorded in medical literature.
== References == |
Orbital emphysema | Orbital emphysema (/ˈɔː(r)bɪt(ə)l ˌemfɪˈsiːmə/, also known as pneumo-orbit) is a medical condition that refers to the trapping of air within the loose subcutaneous around the orbit that is generally characterized by sudden onset swelling and bruising at the impacted eye, with or without deterioration of vision, which the severity depends on the density of air trapped under the orbital soft tissue spaces.It is most commonly result from forceful sneezing, nose blowing, or coughing among patients with a history of periorbital trauma or orbital fractures that happened several hours-days in advance. Rare occasions have also been reported in relation to individuals with no traumatic past events that include: infection, esophageal rupture, postoperative complications, pulmonary barotrauma, with the same predisposing factors (sneezing, nose blowing, or coughing). A four-stage system of orbital emphysema was developed for severity classification. Clinical diagnosis can be made based on a combination of medical history, physical examination, and computed tomography. There are three kinds of orbital emphysema including palpebral emphysema, true orbital emphysema, and orbitopalpebral emphysema.Orbital emphysema on its own is a mild and self-limiting disease, and usually requires no treatment. If related visual symptoms or other acute orbital compression symptoms are present, lateral canthotomy or cantholysis, orbital decompression by needle aspiration, and bone decompression may be required to relieve orbital pressure and preserve vision.
Cause
Trauma
Blunt trauma caused by a direct blow at the orbital is the major leading cause of orbital emphysema. Any object with force and/or speed, typically a ball, fist or vehicle accidents, can result in orbital floor and/or medial wall fractures. These disruptions permit air entry into the orbital subcutaneous from the sinus, with a one-way check valve mechanism that forbids the air from exiting. Victims are often found in sport-related concussion, automobile vehicle accidents, or snowboarding accidents.
Traumatic injuries do not cause onset swelling unless there is a forceful injection of air from vigorous sneezing, nose-blowing, or coughing. These generate an acute increase in intraorbital pressure, compromising the intraorbital neurovascular structures, which subsequently trigger the development of orbital emphysema.
Postoperative complications
Orbital emphysema is a common result of certain types of surgery, in particular the ones that involve orbital medial wall. It may also occur in other oral, nasal, and maxillofacial surgical interventions, in which the occurrence is unexpected. They can weaken sinuses, bony structure, induce deep orbital tissue damages, or globe perforation that cause air leakage into the periorbital soft tissues and superiorly into the supraorbital fat. These surgical procedures may possibly introduce staphylococci, streptococci, and anaerobic bacteria via a compromised bony wall that can cause periorbital infection. The corresponding weakened or degenerated tissues cannot withstand the sudden increase in intraocular pressure and impaired ocular perfusion, driven by severe coughing or sneezing. It subsequently results in air trapped in the periorbital subcutaneous tissue and the development of orbital emphysema, which is often mistaken as allergic reactions. Without proper management can lead to cardiac life-threatening conditions such as cardiopulmonary embolism, cardiac tamponade, and respiratory distress, depending on the volume of air trapped under the facial soft tissues.
Infection
Infections can spread beyond their initial location, including lamina papyracea.
Signs and Symptoms
The signs and symptoms of orbital emphysema vary depending on the original cause, but it is preliminary associated with swelling, bruising, and tenderness around the impacted eye. It may also involve proptosis or the deterioration of vision, typically diplopia. The entrapped air may cause an acute increase in the intraocular pressure or vascular compromise that restrict ocular motility, prohibit the closure of eyelids, and the loss of sensation over the upper cheek areas.Server entrapment in the soft tissues tends to stimulate oculocardiac reflex, which is likely to generate significant vagal responses including nausea, dizziness, vomiting, bradycardia, syncope and heart block. Without treating it promptly may subsequently result in compromisation of ocular function and visual impairment.
Pathophysiology
Orbital emphysema occurs following forceful injection of air into the soft tissues of the orbit through a breach in one of the orbital walls which is typically associated with orbital fracture after blunt trauma, or less frequently with compressed air injuries, tumours and infections of the sinonasal region or complications after surgery.Orbital emphysema develops after an orbital fracture in a three-step process. After the fracture has occurred on one of the orbital walls, a sino-orbital communication is established. The communication will allow air to be forced from the sinuses into the orbit in the presence of a pressure gradient from forceful expiratory efforts, nose-blowing or even a sneeze. Orbital emphysema is typically a harmless disorder because air escapes as quickly as it enters the fracture site, and the increase in intraorbital pressure is usually transient, lasting for as long as the sneeze or nose blowing. However, when orbital soft tissues, such as fat, falls back on the sino-orbital communication, a one-way ball valve will be created, leading to the entrapment of air. When sufficient air accumulates, it will result in acute compartment syndrome and vascular compromise, causing complications including proptosis, visual impairment, central retinal artery occlusion, compressive optic neuropathy, and other severe complications caused by orbital compartment syndrome.There are three variations of orbital emphysema, namely palpebral emphysema, true orbital emphysema, and orbitopalpebral emphysema.
Palpebral emphysema
Palpebral emphysema refers to emphysema of the eyelids alone. It is a rare kind of orbital emphysema which is usually caused by fractures of the lacrimal bone. The lacrimal sac ruptures as a result of the fracture, allowing air from the nasal cavity to enter the tissues of the eyelid. Alternatively, facial subcutaneous air may simply pass into the eyelids along fascial plane to produce palpebral emphysema. As long as the orbital septum is intact, air is confined in the eyelids.
True orbital emphysema
True orbital emphysema occurs when there is air behind an intact orbital septum. This condition arises due to a fracture of more than one bony orbital walls of paranasal sinuses and tearing of adjacent sinus mucosa, and communication of a sinus with the orbit is established. This fracture usually involves the ethmoid, and sometimes involves frontal, sphenoid, and maxillary sinuses. The air usually enters the orbit when the pressure within the upper respiratory tract is increased due to expiratory efforts, nose blowing or sneezing.
Orbitopalperbal emphysema
Orbitopalpebral emphysema refers to the trapping of air inside both the soft tissues of the orbit and the eyelid. It is usually a sequelae of a true orbital emphysema. When too much air accumulates inside the orbit, the orbital septum ruptures due to high intraorbital pressure. Air may then pass freely from the orbit into the eyelids through the break in the orbital septum.
Stages
There are four stages of orbital emphysema.
Stage I
Stage I orbital emphysema can only be diagnosed with radiological films. There is only a small amount of intraorbital air, and the patient does not show any clinical signs or symptoms.
Stage II
Stage II orbital emphysema develops as the intraorbital air volume increases, causing the eyeball to displace horizontally or vertically (globe dystopia) or to protrude anteriorly (proptosis). The patient may experience diplopia as a result of the globe displacement.
Stage III
Stage III orbital emphysema develops when the limits of spontaneous decompression are exceeded. The pressure will be transmitted to orbital tissues and then to the globe, resulting in an increase in intraocular pressure which may cause visual loss when the nutrient vessels supplying the optic nerve are compressed.
Stage IV
Stage IV orbital emphysema develops when the intraorbital air mass results in an intraocular pressure of more than 60 to 70 mmHg. The significantly elevated intraocular pressure will lead to central retinal artery occlusion, which may result in permanent and irreversible damage to the retina.
Clinical Diagnosis
The diagnosis of orbital emphysema is usually made by physical examination of the eyelids, and, or by computer tomography (CT).
Physical examination
Physical examination of the eyelid can be done by the palpation for the pathognomonic cracking, crepitation, and tense tissue on the upper and lower eyelids. The findings of the examination are supported with the medical history of the patient and confirmed with orbital CT.
Computed tomography (CT)
Computed tomography is effective and sensitive in the diagnosis of orbital emphysema, as it can confirm the anatomical location and size of air, bony defects, indentation of the eyeball, and the condition of the optic nerve, as well as the presence of any extraocular muscle entrapment and herniation of preorbital fat into the sinus cavities. The location of the orbital emphysema is present near the site of the fracture. The scans are usually taken along the transverse plane. Transverse images allow the evaluation of fractures in medial and lateral orbital walls. By reformatting these transverse images or taking coronal images, the examination of orbital floor and roof is permitted. Helical scanning is preferred as it has a lower imaging time and radiation dose comparing to conventional scanning, especially when reforming transverse helical scans into coronal images. The staging of orbital emphysema can then be determined with visual acuity examination and ophthalmoscopy. A disadvantage of using a CT scan is that when detecting air after orbital trauma, the presence of a wooden foreign object can give a false positive result of orbital emphysema. The wooden object can mimic the presence of orbital emphysema. Therefore, patients’ medical history is crucial in making the correct diagnosis.
Other tests
Conventional radiography is commonly employed for imaging orbital injuries and identifying orbital fractures. It can be used to diagnose orbital emphysema because it shows the presence of air in the orbit best while the patient is standing upright. Skull films of posterior-anterior, lateral projections, and orbital rim views are recommended to show fractures in orbital rims and walls. However, CT scan is better than conventional radiography in the diagnosis of the condition, as it has a lower high false-negative rate and non-diagnostic rate.Orbital emphysema can also be diagnosed by magnetic resonance imaging (MRI). Although MRI has a low sensitivity for detecting orbital fractures, it can be used to evaluate rectus muscle pathology, optic nerve pathology, and brain pathology, as well as vascular injury.
Treatment
Orbital emphysema on its own is a mild and self-limiting disease. The majority of cases of orbital emphysema are self-resolving and do not need treatment. The underlying causes and injuries that caused orbital emphysema, on the other hand, may be serious, necessitating urgent intervention including surgery. If related visual symptoms or other acute orbital compression symptoms are present, lateral canthotomy or cantholysis, orbital decompression by needle aspiration, and bone decompression may be required to relieve orbital pressure and preserve vision. Prophylactic oral antibiotics may be needed to prevent secondary infection.
== Reference list == |
Microcystic adnexal carcinoma | Microcystic adnexal carcinoma (MAC) is a rare sweat gland cancer, which often appears as a yellow spot or bump in the skin. It usually occurs in the neck or head, although cases have been documented in other areas of the body. Most diagnosis occur past the age of 50. Although considered an invasive cancer, metastasis rarely occurs. If the tumor spreads, it can grow and invade fat, muscles, and other types of tissue. Main treatments are wide local excision or Mohs micrographic surgery, which ensures that most, if not all, cancer cells are removed surgically.
Presentation
MACs usually present as a smooth, flesh or yellow colored, slow-growing nodule or bump somewhere on the face or neck with typical development being 3–5 years. The most common location is the mouth (occurring in 74% of cases), however cases have been documented on the scalp, tongue, trunk, upper extremities, and genitals. Patients are more likely to be white, female, and middle aged or elderly, although cases have been documented in children.
Although usually presenting with no visual or physical symptoms, some patients do experience numbness, paresthesia, burning, or tingling. This may be due to the invasive nature of MACs, which can burrow deep into underlying tissues and nerves in the face. MAC is very difficult to recognize and differentiate from other conditions. Specialists may suggest a series of tests including a biopsy, an MRI, or a CT scan. The average tumor size is less than 2 cm, however cases have been documented where tumor size exceeds 7.9 cm. While death is rare among MAC patients, it can occasionally metastasize to local lymph nodes. The 10 year overall survival rate is 86.4%, however this is exceedingly close to many 10 year survival rates of populations without MACs present.
Causes
Little is known about the causes of MACs, although some evidence has shown that ultraviolet light, radiation, and genes may be causation factors. A genetic role might also be plausible, according to some studies. In several cases, patients developed a MAC after immunosuppression.
Treatment
Due to the invasive nature of MACs, most cases are treated with wide local excision in order to decrease the rate of reoccurrence. Increasingly however, Mohs micrographic surgery is being employed as it allows more specific margins to be removed, along with decreasing the size of postoperative scars and disfigurement. In rare cases, tumors can be deemed inoperable due to their size and location under vital structures of the face. Chemotherapy and radiation treatment have been used when metastasis has occurred or when an excision cannot be performed, but results have been inconclusive about their effectiveness. In some cases, radiation therapy has been shown to increase tumor size. While in other cases, it implies that it will decrease the success of the tumor regrowing. Long term follow-up is necessary, as some cases of local recurrence have been documented 30 years after the original diagnosis.
See also
Syringofibroadenoma
Skin lesion
List of cutaneous conditions
== References == |
Endometrial intraepithelial neoplasia | Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion of the uterine lining that predisposes to endometrioid endometrial adenocarcinoma. It is composed of a collection of abnormal endometrial cells, arising from the glands that line the uterus, which have a tendency over time to progress to the most common form of uterine cancer—endometrial adenocarcinoma, endometrioid type.
History
EIN lesions have been discovered by a combination of molecular, histologic, and clinical outcome studies beginning in the 1990s which provide a multifaceted characterization of this disease. They are a subset of a larger mixed group of lesions previously called "endometrial hyperplasia". The EIN diagnostic schema is intended to replace the previous "endometrial hyperplasia" classification as defined by the World Health Organization in 1994, which have been separated into benign (benign endometrial hyperplasia) and premalignant (EIN) classes in accordance with their behavior and clinical management.
EIN should not be confused with an unrelated entity, serous intraepithelial carcinoma ("serous EIC"), which is an early stage of a different tumor type known as papillary serous adenocarcinoma that also occurs in the same location within the uterus.
Clinical aspects
The average age at time of EIN diagnosis is approximately 52 years, compared to approximately 61 years for carcinoma. The timeframe and likelihood of EIN progression to cancer, however, is not constant amongst all women. Some cases of EIN are first detected as residual premalignant disease in women who already have carcinoma, whereas other EIN lesions disappear entirely and never lead to cancer. For this reason, treatment benefits and risks must be individualized for each patient under the guidance of an experienced physician.
Risk factors for development of EIN and the endometrioid type of endometrial carcinoma include exposure to estrogens without opposing progestins, obesity, diabetes, and rare hereditary conditions such as hereditary nonpolyposis colorectal cancer. Protective factors include use of combined oral contraceptive pills (low dose estrogen and progestin), and prior use of a contraceptive intrauterine device.
Biology
EIN lesions demonstrate all of the behaviors and characteristics of a premalignant, or precancerous, lesion.
Precancer Features of EIN (Table I). The cells of an EIN lesion are genetically different than normal and malignant tissues, and have a distinctive appearance under the light microscope. EIN cells are already neoplastic, demonstrating a monoclonal growth pattern and clonally distributed mutations. Progression of EIN to carcinoma, effectively a conversion from a benign neoplasm to a malignant neoplasm, is accomplished through acquisition of additional mutations and accompanied by a change in behavior characterized by the ability to invade local tissues and metastasize to regional and distant sites.
Table I: Precancer Characteristics of EIN
EIN Biomarkers. (Figure 1). There are no single biomarkers which are completely informative in recognition of EIN. The tumour suppressor gene PTEN is frequently inactivated in EIN, being abnormally turned off in approximately 2/3 of all EIN lesions. This can be seen with special tissue stains applied to histological sections known as PTEN immunohistochemistry, in which the brown PTEN protein is seen to be absent in the crowded tubular glands that make up an EIN lesion.
Diagnosis
Diagnosis of EIN lesions is of clinical importance because of the increased risk of coexisting (39% of women with EIN will be diagnosed with carcinoma within one year) or future (the long term endometrial cancer risk is 45 times greater for a woman with EIN compared to one with only a benign endometrial histology) endometrial cancer. Diagnostic terminology is that used by pathologists, physicians who diagnose human disease by examination of histologic preparations of excised tissues. Critical distinctions in EIN diagnosis are separation from benign conditions such as benign endometrial hyperplasia (a field effect in endometrial tissue caused by excessive stimulation by the hormone estrogen), and cancer.
The spectrum of disease which must be distinguished from EIN (Table II) includes benign endometrial hyperplasia and carcinoma:Table II: Disease classes that need to be distinguished from EIN.
EIN may be diagnosed by a trained pathologist by examination of tissue sections of the endometrium. All of the following diagnostic criteria must be met in a single area of one tissue fragment to make the diagnosis (Table III).
Table III: EIN diagnosis.
See also
Uterine cancer
References
External links
American Cancer Society
OncoLink an educational site from the U. of Pennsylvania
www.endometrium.org a pathology site focusing on endometrial diseasePTEN Gene
Cancer Genetics Web PTEN entry
PTEN and the Endometrium at PubMed
Entrez Gene PTEN entry |
Nasal septal hematoma | Nasal septal hematoma is a condition affecting the nasal septum. It can be associated with trauma.A septal hematoma is blood that collects in the space between the septal cartilage and the overlying perichondrium (a cross section of the cartilaginous portion of the nasal septum). A hematoma may deprive the septal cartilage of its blood supply from the overlying mucosa and can lead to permanent sequelae.The septal cartilage has no blood supply of its own and will receives all of its nutrients and oxygen from the perichondrium. An untreated septal hematoma may lead to the destruction of the septum and immediate drainage is necessary. Timely diagnosis and/or treatment of septal hematomas can cause what is called a saddle nose deformity.This condition is more common in children because the septum is thicker and the lining more flexible.
Signs and symptoms
A normal nasal septum is rigid and thin. If you have a septal hematoma, your doctor will be able to press it down with a swab as the area will be soft. A quick check in the nose will show any swelling between the nostrils.Symptoms can include:
blockage in breathing
change in nose shape
painful swelling of nasal septum
nasal congestion.On occasion, it is possible for people with a septal hematoma to experience headache, nausea, vomiting, and fainting.
Causes
The most common causes of nasal septal hematomas include:
broken nose (nasal fracture)
medication
surgery or injury to the soft tissue area.In adults, nasal septal hematoma typically occur with significant facial trauma and/or nasal fracture. However, in children, due to their thicker septum and more flexible lining, nasal septal hematoma can be caused from minor nasal trauma such as simple falls, collisions with stationary objects, or minor altercations with siblings.
Mechanism and pathophysiology
The exact mechanism for the formation of hematoma from nasal trauma is controversial, but thought to occur in nasal septal hematomas when there is force to the nasal cartilage. The force causes the perichondrial blood vessels to leak and rupture in the nasal septum. The cartilage in the septum is avascular and can be 2–4 mm thick. The septum gets its blood supply from the ethmoid and sphenopalatine arteries.The nasal septum is composed of cartilaginous, membranous, and bony components overlaid by mucoperichondrium and mucoperiosteum. Bleeding within the confines of the mucoperichnondrium leads to a septal hematoma, where as external bleeding from Kiesselbachs plexus results in epistaxis. The Kiesselbach plexus is located anterior inferior of the nasal septum, where the anastomosis of blood vessels is located.Normal nasal mucosa is pink and healthy appearing, without ulcerations, crusting, or bleeding. Some common, abnormal variations include septal deviations, spurs, and an enlarged, aerated middle turbinate. Pale or inflamed mucosa, purulence, nasal polyps, or a septal perforation are all common pathologic features that may or may not be combined with the abnormal variations listed above.
Diagnosis
The doctor will use a nasal speculum for visualization of the nasal septum, the inferior turbinate, and a portion of the middle turbinate. The view of the nasal passage may be partially obstructed by the tools used. When there is minimal obstruction, it is often possible to visualize the nasopharynx.Identifying the Nasal Septal Hematoma
If lateral bulging of the septum and fluctuance persist after the nasal administration of a vasoconstrictive agent, such as oxymetazoline, it is a strong indicator of a nasal septal hematoma. A septal hematoma is highly likely in patients who have had trauma or a sudden onset of nasal blockage that does not resolve with the removal of blood clots and the administration of a vasoconstrictive agent.Diagnosis can be made by a medical professional after performing an anterior rhinoscopy examination, by using an otoscope or a nasal speculum and overhead light source.Sometimes palpitation is used to diagnose the hematoma.
Treatment
A septal hematoma requires urgent treatment from a doctor in order to stop any further complications arising.Prompt treatment of septal hematomas can prevent complications such as ischemia of the septal cartilage, which can lead to permanent necrosis and a saddle-nose deformity. Such complication can occur rapidly, within as few as 3 days.There are two different procedures used to achieve this and will be selected upon the size of the swelling or clot. If the condition is being treated promptly and is still relatively small, then a small incision can be made to allow the blood to flow out. If the septal hematoma has been left untreated, then a doctor may need to insert a mechanism in order to fully remove the blood from the area.If left untreated, the hematoma can cause bacterial colonization that leads to infection. Within 72 hours, the infection can form a septal abscess.Treating a septal hematoma requires it to be incised and drained to prevent avascular necrosis of the septal hyaline cartilage. This will depend on diffusion of nutrients from its attached nasal mucosa.The septum can generally heal within 1 week, without any evidence of the incision. The mucosa will appear healthy and smooth.Secondary infections can be prevented by starting the patient on an antibiotic regimen immediately after the procedure and continuing the treatment while the nasal packs are in place. If an abscess is present, a specimen of the abscess can be sent for culture to ensure that the antibiotics prescribed have provided adequate coverage. Culture-directed therapy can help avert dangerous late sequalae, including the intracranial extension of a septal abscess. If the hematoma is not promptly drained, the septal cartilage may be destroyed. In such cases, a saddle-nose deformity may develop.
Prognosis
As long as the septal hematoma is treated promptly, a full recovery is common. If the condition is left untreated and develops complications such as fever, infection, or an abscess, then the nasal septal hematoma is still very treatable if seen by a doctor. If saddle nose is developed, surgery could be required.
Epidemiology
Septal hematomas are rare but can effect everyone in every age group. There is no exact number of the incidence that occur because a lot of the cases will remain undiagnosed. Although, patients that have visited an ear, nose and throat clinic for nasal septal hematomas, reported to be in between 0.8% to 1.6% of patients. 65.6% of nasal septal hematoma cases in Nigeria had unknown cause, where 30.4% were caused by trauma.Within 10 years at the University of Nigeria Teaching Hospital, there was a total of 53 patients that ranged from 5 to 65 years of age. Consisted of 37 males and 16 females. The highest age group with nasal septal hematoma was 10–18 years of age followed by 1–9 years of age.
Research
The research article went into detail about a 9-month-old going to get medical attention after an incident that happened a week prior. The child had swelling in both sides of the septum, with no history of nose bleeds. Under the general anesthesia, a nasal drain was done by a 4mm endotracheal tube. The article explained how this procedure done by medical professionals, was a new innovative way to treat the child. The research article came into conclusion that all cases of nasal septal hematoma need immediate attention to prevent from having complications and deformities. The endotracheal tube is another alternative for the nasal pack and allowed the child to be at comfort in the postoperative period.Based on a different study from patients who were treated at the University of Nigeria Teaching Hospital in Enugu Nigeria. This all occurred within a 10-year period, 53 patients were successfully treated by incision and drainage.
== References == |
Enterolith | An enterolith is a mineral concretion or calculus formed anywhere in the gastrointestinal system. Enteroliths are uncommon and usually incidental findings but, once found, they require at a minimum watchful waiting. If there is evidence of complications, they must be removed. An enterolith may form around a nidus, a small foreign object such as a seed, pebble, or piece of twine that serves as an irritant. In this respect, an enterolith forms by a process similar to the creation of a pearl. An enterolith is not to be confused with a gastrolith, which helps digestion.
In equines
Equine enteroliths are found by walking pastures or turning over manure compost piles to find small enteroliths, during necroscopy, and increasingly, during surgery for colic. Therefore, the incidence of asymptomatic enteroliths is unknown.
Equine enteroliths are typically smoothly spherical or tetrahedral, consist mostly of the mineral struvite (ammonium magnesium phosphate), and have concentric rings of mineral precipitated around a nidus.Enteroliths in horses were reported widely in the 19th century, infrequently in the early 20th century, and now increasingly. They have also been reported in zebras: five in a zoo in California and one in a zoo in Wisconsin. Struvite enteroliths are associated with elevated pH and mineral concentrations in the lumen. In California, struvite enteroliths are associated also with a high proportion of alfalfa in the feed and less access to grass pasture. This association has been attributed to the cultivation of alfalfa on serpentine soils, resulting in high concentrations of magnesium in the alfalfa.
In humans
In humans, enteroliths are rare and may be difficult to distinguish from gall stones. Their chemical composition is diverse, and rarely can a nidus be found. A differential diagnosis of an enterolith requires the enterolith, a normal gallbladder, and a diverticulum.An enterolith typically forms within a diverticulum. An enterolith formed in a Meckels diverticulum sometimes is known as a Meckels enterolith. Improper use of magnesium oxide as a long-term laxative has been reported to cause enteroliths and/or medication bezoars.Most enteroliths are not apparent and cause no complications. However, any complications that do occur are likely to be severe. Of these, bowel obstruction is most common, followed by ileus and perforation. Bowel obstruction and ileus typically occur when a large enterolith is expelled from a diverticulum into the lumen. Perforation typically occurs within the diverticulum.On plain X-rays,the visibility of the enterolith depends on its calcium content. Calcium-rich stones usually demonstrate a radiodense rim and a relatively radioluscent core. Choleic acid stones are almost always radiolucent. They sometimes can be visualized on CT scans without contrast; presence of contrast in the lumen may reveal the enterolith as a void. Most often, they are visualized using ultrasound.
Although recent surveys of enterolith composition are lacking, one early review notes struvite (as in equines), calcium phosphate, and calcium carbonate and reports choleic acid. Deoxycholic acid and cholic acid have also been reported.
Treatment
In simple cases of obstruction, where there are no complications, a variety of non-surgical and surgical techniques are used to remove the enterolith. These include crushing the enterolith and milking it back to the stomach or forward to the colon, surgical removal via an uninvolved segment of the gastrointestinal tract, and resection of the involved segment.
See also
Acid-base physiology
Bezoar
References
== External links == |
Ashermans syndrome | Ashermans syndrome (AS) is an acquired uterine condition that occurs when scar tissue (adhesions) form inside the uterus and/or the cervix. It is characterized by variable scarring inside the uterine cavity, where in many cases the front and back walls of the uterus stick to one another. AS can be the cause of menstrual disturbances, infertility, and placental abnormalities. Although the first case of intrauterine adhesion was published in 1894 by Heinrich Fritsch, it was only after 54 years that a full description of Asherman syndrome was carried out by Joseph Asherman. A number of other terms have been used to describe the condition and related conditions including: uterine/cervical atresia, traumatic uterine atrophy, sclerotic endometrium, and endometrial sclerosis.There is not any one cause of AS. Risk factors can include myomectomy, cesarean section, infections, age, genital tuberculosis, and obesity. Genetic predisposition to AS is being investigated. There are also studies that show that a severe pelvic infection, independent of surgery may cause AS. AS can develop even if the woman has not had any uterine surgeries, trauma, or pregnancies. While rare in North America and European countries, genital tuberculosis is a cause of Ashermans in other countries such as India.
History
The condition was first described in 1894 by Heinrich Fritsch (Fritsch, 1894) and further characterized by the Israeli gynecologist Joseph Asherman (1889–1968) in 1948.It is also known as Fritsch syndrome, or Fritsch-Asherman syndrome.
Signs and symptoms
It is often characterized by a decrease in flow and duration of bleeding (absence of menstrual bleeding, little menstrual bleeding, or infrequent menstrual bleeding) and infertility. Menstrual anomalies are often but not always correlated with severity: adhesions restricted to only the cervix or lower uterus may block menstruation. Pain during menstruation and ovulation is sometimes experienced and can be attributed to blockages.
It has been reported that 88% of AS cases occur after a D&C is performed on a recently pregnant uterus, following a missed or incomplete miscarriage, birth, or during an elective termination (abortion) to remove retained products of conception.
Causes
The cavity of the uterus is lined by the endometrium. This lining is composed of two layers, the functional layer (adjacent to the uterine cavity) which is shed during menstruation and an underlying basal layer (adjacent to the myometrium), which is necessary for regenerating the functional layer. Trauma to the basal layer, typically after a dilation and curettage (D&C) performed after a miscarriage, or delivery, or abortion, can lead to the development of intrauterine scars resulting in adhesions that can obliterate the cavity to varying degrees. In the extreme, the whole cavity can be scarred and occluded. Even with relatively few scars, the endometrium may fail to respond to estrogen.Ashermans syndrome affects women of all races and ages equally, suggesting no underlying genetic predisposition for its development. AS can result from other pelvic surgeries including cesarean sections, removal of fibroid tumours (myomectomy) and from other causes such as IUDs, pelvic irradiation, schistosomiasis and genital tuberculosis. Chronic endometritis from genital tuberculosis is a significant cause of severe intrauterine adhesions (IUA) in the developing world, often resulting in total obliteration of the uterine cavity which is difficult to treat.An artificial form of AS can be surgically induced by endometrial ablation in women with excessive uterine bleeding, in lieu of hysterectomy.
Diagnosis
The history of a pregnancy event followed by a D&C leading to secondary amenorrhea or hypomenorrhea is typical. Hysteroscopy is the gold standard for diagnosis. Imaging by sonohysterography or hysterosalpingography will reveal the extent of the scar formation. Ultrasound is not a reliable method of diagnosing Ashermans Syndrome. Hormone studies show normal levels consistent with reproductive function.
Classification
Various classification systems were developed to describe Ashermans syndrome (citations to be added), some taking into account the amount of functioning residual endometrium, menstrual pattern, obstetric history and other factors which are thought to play a role in determining the prognoses. With the advent of techniques which allow visualization of the uterus, classification systems were developed to take into account the location and severity of adhesions inside the uterus. This is useful as mild cases with adhesions restricted to the cervix may present with amenorrhea and infertility, showing that symptoms alone do not necessarily reflect severity. Other patients may have no adhesions but amenorrhea and infertility due to a sclerotic atrophic endometrium. The latter form has the worst prognosis.
Prevention
A 2013 review concluded that there were no studies reporting on the link between intrauterine adhesions and long-term reproductive outcome after miscarriage, while similar pregnancy outcomes were reported subsequent to surgical management (e.g. D&C), medical management or conservative management (that is, watchful waiting). There is an association between surgical intervention in the uterus and the development of intrauterine adhesions, and between intrauterine adhesions and pregnancy outcomes, but there is still no clear evidence of any method of prevention of adverse pregnancy outcomes.In theory, the recently pregnant uterus is particularly soft under the influence of hormones and hence, easily injured. D&C (including dilation and curettage, dilation and evacuation/suction curettage and manual vacuum aspiration) is a blind, invasive procedure, making it difficult to avoid endometrial trauma. Medical alternatives to D&C for evacuation of retained placenta/products of conception exist including misoprostol and mifepristone. Studies show this less invasive and cheaper method to be an efficacious, safe and an acceptable alternative to surgical management for most women. It was suggested as early as in 1993 that the incidence of IUA might be lower following medical evacuation (e.g. Misoprostol) of the uterus, thus avoiding any intrauterine instrumentation. So far, one study supports this proposal, showing that women who were treated for missed miscarriage with misoprostol did not develop IUA, while 7.7% of those undergoing D&C did. The advantage of misoprostol is that it can be used for evacuation not only following miscarriage, but also following birth for retained placenta or hemorrhaging.Alternatively, D&C could be performed under ultrasound guidance rather than as a blind procedure. This would enable the surgeon to end scraping the lining when all retained tissue has been removed, avoiding injury.Early monitoring during pregnancy to identify miscarriage can prevent the development of, or as the case may be, the recurrence of AS, as the longer the period after fetal death following D&C, the more likely adhesions may be to occur. Therefore, immediate evacuation following fetal death may prevent IUA.The use of hysteroscopic surgery instead of D&C to remove retained products of conception or placenta is another alternative that could theoretically improve future pregnancy outcomes, although it could be less effective if tissue is abundant. Also, hysteroscopy is not a widely or routinely used technique and requires expertise.There is no data to indicate that suction D&C is less likely than sharp curette to result in Ashermans. A recent article describes three cases of women who developed intrauterine adhesions following manual vacuum aspiration.Intrauterine adhesions also form after hysteroscopic surgery such as myomectomy, polypectomy or septum removal. Mechanical barriers such as Womed Leaf or hyaluronic acid gels can be used to prevent formation of IUA after such adhesiogenic procedures or after D&C.
Treatment
Fertility may sometimes be restored by removal of adhesions, depending on the severity of the initial trauma and other individual patient factors. Operative hysteroscopy is used for visual inspection of the uterine cavity during adhesion dissection (adhesiolysis). However, hysteroscopy is yet to become a routine gynaecological procedure and only 15% of US gynecologists perform office hysteroscopy. Adhesion dissection can be technically difficult and must be performed with care in order to not create new scars and further exacerbate the condition. In more severe cases, adjunctive measures such as laparoscopy are used in conjunction with hysteroscopy as a protective measure against uterine perforation. Microscissors are usually used to cut adhesions. Electrocauterization is not recommended.As IUA frequently reform after surgery, techniques have been developed to prevent recurrence of adhesions. Methods to prevent adhesion reformation include the use of mechanical barriers (Foley catheter, saline-filled balloon uterine stents, gel barriers (Seprafilm, Spraygel, autocrosslinked hyaluronic acid gel Hyalobarrier) and mechanical barrier film (Womed Leaf) to maintain opposing walls apart during healing, thereby preventing the reformation of adhesions. Antibiotic prophylaxis is necessary in the presence of mechanical barriers to reduce the risk of possible infections. A common pharmacological method for preventing reformation of adhesions is sequential hormonal therapy with estrogen followed by a progestin to stimulate endometrial growth and prevent opposing walls from fusing together. However, there have been no randomized controlled trials (RCTs) comparing post-surgical adhesion reformation with and without hormonal treatment and the ideal dosing regimen or length of estrogen therapy is not known. A recent meta analysis compared different post surgical prevention barrier strategies and concluded that there was no single clearly superior treatment. Furthermore, diagnostic severity and outcomes are assessed according to different criteria (e.g. menstrual pattern, adhesion reformation rate, conception rate, live birth rate). Clearly, more comparable studies are needed in which reproductive outcome can be analysed systematically.Follow-up tests (HSG, hysteroscopy or SHG) are necessary to ensure that adhesions have not reformed. Further surgery may be necessary to restore a normal uterine cavity. According to a recent study among 61 patients, the overall rate of adhesion recurrence was 27.9% and in severe cases this was 41.9%. Another study found that postoperative adhesions reoccur in close to 50% of severe AS and in 21.6% of moderate cases. Mild IUA, unlike moderate to severe synechiae, do not appear to reform.
Prognosis
The extent of adhesion formation is critical. Mild to moderate adhesions can usually be treated with success. Extensive obliteration of the uterine cavity or fallopian tube openings (ostia) and deep endometrial or myometrial trauma may require several surgical interventions and/or hormone therapy or even be uncorrectable. If the uterine cavity is adhesion free but the ostia remain obliterated, IVF remains an option. If the uterus has been irreparably damaged, surrogacy or adoption may be the only options.Depending on the degree of severity, AS may result in infertility, repeated miscarriages, pain from trapped blood, and future obstetric complications If left untreated, the obstruction of menstrual flow resulting from adhesions can lead to endometriosis in some cases.Patients who carry a pregnancy even after treatment of IUA may have an increased risk of having abnormal placentation including placenta accreta where the placenta invades the uterus more deeply, leading to complications in placental separation after delivery. Premature delivery, second-trimester pregnancy loss, and uterine rupture are other reported complications. They may also develop incompetent cervix where the cervix can no longer support the growing weight of the fetus, the pressure causes the placenta to rupture and the mother goes into premature labour. Cerclage is a surgical stitch which helps support the cervix if needed.Pregnancy and live birth rate has been reported to be related to the initial severity of the adhesions with 93, 78, and 57% pregnancies achieved after treatment of mild, moderate and severe adhesions, respectively and resulting in 81, 66, and 32% live birth rates, respectively. The overall pregnancy rate after adhesiolysis was 60% and the live birth rate was 38.9% according to one study.Age is another factor contributing to fertility outcomes after treatment of AS. For women under 35 years of age treated for severe adhesions, pregnancy rates were 66.6% compared to 23.5% in women older than 35.
Epidemiology
AS has a reported incidence of 25% of D&Cs performed 1–4 weeks post-partum, up to 30.9% of D&Cs performed for missed miscarriages and 6.4% of D&Cs performed for incomplete miscarriages. In another study, 40% of patients who underwent repeated D&C for retained products of conception after missed miscarriage or retained placenta developed AS.In the case of missed miscarriages, the time period between fetal demise and curettage may increase the likelihood of adhesion formation due to fibroblastic activity of the remaining tissue.The risk of AS also increases with the number of procedures: one study estimated the risk to be 16% after one D&C and 32% after three or more D&Cs. However, a single curettage often underlies the condition.
In an attempts to estimate the prevalence of AS in the general population, it was found in 1.5% of women undergoing hysterosalpingography HSG, and between 5 and 39% of women with recurrent miscarriage.After miscarriage, a review estimated the prevalence of AS to be approximately 20% (95% confidence interval: 13% to 28%).
References
External links
"The secret syndrome leaving women infertile". Daily Mirror. UK. 29 April 2010. Sophie Blake talks about being diagnosed with Ashermans syndrome.
Bruton C (10 December 2007). "The hidden threat to fertility". Times Online. Archived from the original on 27 July 2008.
Perloe M (20 July 2001) [17 August 1998]. "Ashermans Syndrome Overview". iVillage. Archived from the original on 25 December 2005.
"How Ashermans syndrome causes infertility or miscarriages". Blog: Ashermans Syndrome Watch. 19 February 2010. (awareness, education, prevention)
"What are intrauterine adhesions?". How to treat intrauterine adhesions. womedtech.com. |
Okamoto syndrome | Okamoto syndrome (OS), also known as Au–Kline syndrome (AKS), is a very rare autosomal dominant genetic condition characterised by congenital hydronephrosis, low muscle tone, heart defects, intellectual disability and characteristic facial features. Those affected often have neurological and skeletal abnormalities, as well as frequent urinary tract infections. Language and walking are usually delayed. Facial features include prominent, downturned ears, an open, downturned mouth and drooping eyelids (ptosis).The syndrome is caused by mutations in the HNRNPK gene, which codes for heterogeneous nuclear ribonucleoprotein K. This protein is involved in the process of DNA transcription and translation into proteins. A mutation in this gene impairs DNA transcription, disrupting some developmental processes. As an autosomal dominant disorder, only one faulty copy of the gene is required for the condition to occur. The syndrome is typically diagnosed based on the physical symptoms and then confirmed by genetic testing.Treatment has centred around the symptoms. Sign language and assistive language technology can aid communication. The prognosis is not yet fully known, due to the lack of patients in literature, however most of the patients have at least lived through childhood. The urinary system defects have been the most significant contributors to mortality. As of May 2019, 26 individuals worldwide were known to be affected. The syndrome was first described in 1997 by Nobuhiko Okamoto et al., and the gene responsible was first identified in 2015 by Ping-Yee Billie Au, Antonie D. Kline et al. In 2019, Okamoto proposed that Au–Kline syndrome and Okamoto syndrome were synonymous.
Signs and symptoms
Kidneys
Individuals with Okamoto syndrome are usually born with hydronephrosis, or dilation of the internal structures of the kidneys, due to narrowing (stenosis) of the passage between the kidneys and the ureters (the ureteropelvic junction), leading to a build-up of urine. There is also often vesicoureteral reflux, in which urine passes backwards from the bladder to the ureters, and frequent urinary tract infections.
Heart
Individuals with Okamoto syndrome are typically born with heart defects, which can include aortic valve stenosis, atrial or ventricular septal defect, bicuspid aortic valve or patent ductus arteriosus.
Physical features
The syndrome has a characteristic facial appearance which is similar to that of Kabuki syndrome, including prominent, downward-displaced ears that are underdeveloped, long eyelids, epicanthic folds, a short, broad nose, an open, downturned mouth and a deep groove in the midline of the tongue. Cleft palate occurs in about half of those affected. There is sometimes webbing of the neck or bulging eyes, and less commonly there is excessive hair on the forehead or other parts of the body or a unibrow. Individuals with the syndrome may also have a broad first toe and crowding of the toes, and at least two affected individuals have had polydactyly of the fifth digit (postaxial polydactyly). Some of those affected have had undescended testicles (cryptorchidism). A small minority of those affected have had congenital joint contractures such as club foot.
Neurological
Those with Okamoto syndrome typically have severe mental disability and are usually born with microcephaly. There are typically language and walking delays, and those affected have very low muscle tone and decreased reflexes. They may have neural tube defects such as lipomyelomeningocele (a form of spina bifida) or may have syringomyelia (a cyst in the spinal cord). Those with the syndrome may also have symptoms of dysautonomia (impairments in the autonomic nervous system), including gastrointestinal dysmotility, contributing to gastroesophageal reflux disease, or neurogenic bladder dysfunction, in which bladder control is limited. Dysautonomia has also led to high pain tolerance and reduced sweating in some patients. Some of those with the syndrome have been found to have an underdeveloped corpus callosum, the main band of white matter that connects the two cerebral hemispheres.
Skeletal
Okamoto syndrome patients often have skeletal problems such as scoliosis or hip dysplasia, which can lead to hip dislocation. They may be born with congenital vertebral anomalies; parts of the spine may be fused and fail to segment. There may also be extra vertebrae in the lower back. Some of those affected have been reported to have premature fusion of the skull bones (craniosynostosis), particularly those across the midline and at the front of the skull. This has led to an elongated skull shape known as scaphocephaly as well as a ridge on the forehead known as a metopic ridge.
Growth
Those affected may be born with low weight and size and may display stunted growth in childhood, although this symptom has been variable and not in every individual with Okamoto syndrome.
Hearing and eyesight
A minority of those with Okamoto syndrome have had hearing loss of both sensorineural and conductive types, and a smaller minority have had optic nerve abnormalities.
Cause
Okamoto syndrome is caused by a mutation in the HNRNPK gene, located on chromosome 9 at position q21.32. HNRNPK codes for heterogeneous nuclear ribonucleoprotein K. Ribonucleoproteins are proteins that form complexes with RNA, and they are involved in the transcription of DNA into RNA in the nucleus. They usually bind with precursor messenger RNA (pre-mRNA), which is messenger RNA that has not yet had its introns removed during splicing to be ready for translation. A mutation in one of the two copies of HNRNPK results in defects in DNA transcription, and therefore some developmental processes are disrupted or not completed.Mutations in HNRNPK that have been reported include nonsense mutations, in which the protein is truncated and usually non-functional as a result, frameshift mutations, splice-site mutations and microdeletions encompassing the gene. Rarely, missense mutations, in which one amino acid in the protein is replaced by another, have also been reported.Deletions in the region encompassing HNRNPK have been found in the cells of acute myeloid leukemia in approximately 2% of cases. Acute myeloid leukemia cells are immature white blood cells (myeloblasts) that remain in the stem-cell stage, dividing continually. Additionally, a 2015 study found that a majority of mice who had one of their HNRNPK genes artificially knocked out developed myeloid cancers, with a third developing lymphoid cancers and 4% developing hepatocellular carcinomas. The mice were also smaller, had less developed organs and had higher postnatal mortality (30%). The median lifespan of the mice that survived was less than 50% that of wild-type mice. However, blood cancers had not yet been detected in any of the Okamoto syndrome patients as of 2018.Mutations in both copies of HNRNPK are embryonic lethal in mice. Mice with both copies of the gene knocked out die before the 14th day of embryonic development.
Diagnosis
The condition has usually been diagnosed based on the physical symptoms and confirmed by genetic testing. Methods have included whole exome sequencing and comparative genomic hybridization (for microdeletions). Sanger sequencing can confirm the nature of the mutation.
Treatment
Treatment is focussed on the symptoms. Atrial or ventricular septal defects are usually treated with observation but can be surgically corrected in severe cases. Some patients have been able to use sign language or assistive language devices to facilitate communication.
Prognosis
The prognosis of the disorder is not yet fully known. A minority of patients have died in infancy due to complications from their urinary system defects, including infections in Okamotos first two patients, however most have lived through childhood and into adolescence. Motor and language skills typically improve as the patient ages. The prognosis in adulthood is not yet known, due to the lack of known patients in this age group.As an autosomal dominant condition, there is little risk of recurrence in future conceptions from unaffected parents. However, there is a slight possibility (around 1%) due to germline mosaicism, a phenomenon in which some sperm cell precursors have the mutation and others dont. Genetic counselling may be offered for this.
Epidemiology
The prevalence of the disorder is as yet unknown. As of May 2019, 26 individuals worldwide were known to be affected, with 13 of these reported in literature, mostly from 2010 to 2019.
History
Okamoto syndrome was first described in 1997 by Nobuhiko Okamoto et al. from the Department of Medical Genetics at Osaka Womens and Childrens Hospital after observing very similar symptoms and physical features in two unrelated Japanese infants. Both infants had congenital hydronephrosis due to ureteropelvic junction stenosis, low muscle tone, developmental delay and characteristic facial features including an open mouth and low-set ears.Au–Kline syndrome was first described in 2015 by Ping-Yee Billie Au, Antonie D. Kline et al. after mutations in HNRNPK were found in two individuals with similar symptoms at their respective practices in Calgary, Alberta, Canada and Baltimore, Maryland, United States. The practices were united with each other after both submitted the gene as a candidate to the online service GeneMatcher, which matched them together and allowed them to confirm the syndrome.In 2019, Okamoto proposed that Au–Kline syndrome and Okamoto syndrome were synonymous, because a mutation in the HNRNPK gene had been found in a new Okamoto syndrome patient, and the symptoms were virtually identical.
See also
CDK13-related disorder
Kabuki syndrome
References
External links
Au–Kline syndrome at the US National Institutes of Health (NIH) Genetics Home Reference |
Psychogenic amnesia | Psychogenic amnesia or dissociative amnesia is a memory disorder characterized by sudden retrograde episodic memory loss, said to occur for a period of time ranging from hours to years to decades. More recently, "dissociative amnesia" has been defined as a dissociative disorder "characterized by retrospectively reported memory gaps. These gaps involve an inability to recall personal information, usually of a traumatic or stressful nature." In a change from the DSM-IV to the DSM-5, dissociative fugue is now subsumed under dissociative amnesia.The atypical clinical syndrome of the memory disorder (as opposed to organic amnesia) is that a person with psychogenic amnesia is profoundly unable to remember personal information about themselves; there is a lack of conscious self-knowledge which affects even simple self-knowledge, such as who they are. Psychogenic amnesia is distinguished from organic amnesia in that it is supposed to result from a nonorganic cause: no structural brain damage or brain lesion should be evident but some form of psychological stress should precipitate the amnesia, however psychogenic amnesia as a memory disorder is controversial.
Definition
Psychogenic amnesia is the presence of retrograde amnesia (the inability to retrieve stored memories leading up to the onset of amnesia), and an absence of anterograde amnesia (the inability to form new long term memories). Access to episodic memory can be impeded, while the degree of impairment to short term memory, semantic memory and procedural memory is thought to vary among cases. If other memory processes are affected, they are usually much less severely affected than retrograde autobiographical memory, which is taken as the hallmark of psychogenic amnesia. However the wide variability of memory impairment among cases of psychogenic amnesia raises questions as to its true neuropsychological criteria, as despite intense study of a wide range of cases there is little consensus of which memory deficits are specific to psychogenic amnesia.Past literature has suggested psychogenic amnesia can be situation-specific or global-transient, the former referring to memory loss for a particular incident, and the latter relating to large retrograde amnesic gaps of up to many years in personal identity. The most commonly cited examples of global-transient psychogenic amnesia are fugue states, of which there is a sudden retrograde loss of autobiographical memory resulting in impairment of personal identity and usually accompanied by a period of wandering. Suspected cases of psychogenic amnesia have been heavily reported throughout the literature since 1935 where it was reported by Abeles and Schilder. There are many clinical anecdotes of psychogenic or dissociative amnesia attributed to stressors ranging from cases of child sexual abuse to soldiers returning from combat.
Cause
Neurological cause of psychogenic amnesia is controversial. Even in cases of organic amnesia, where there is lesion or structural damage to the brain, caution must still be taken in defining causation, as only damage to areas of the brain crucial to memory processing is possible to result in memory impairment. Organic causes of amnesia can be difficult to detect, and often both organic cause and psychological triggers can be entangled. Failure to find an organic cause may result in the diagnosis that the amnesia is psychological, however it is possible that some organic causes may fall below a threshold of detection, while other neurological ails are thought to be unequivocally organic (such as a migraine) even though no functional damage is evident. Possible malingering must also be taken into account. Some researchers have cautioned against psychogenic amnesia becoming a "wastebasket" diagnosis when organic amnesia is not apparent. Other researchers have hastened to defend the notion of psychogenic amnesia and its right not to be dismissed as a clinical disorder. Diagnoses of psychogenic amnesia have dropped since agreement in the field of transient global amnesia, suggesting some over diagnosis at least. Speculation also exists about psychogenic amnesia due to its similarities with pure retrograde amnesia, as both share similar retrograde loss of memory. Also, although no functional damage or brain lesions are evident in the case of pure retrograde amnesia, unlike psychogenic amnesia it is not thought that purely psychological or psychogenic triggers are relevant to pure retrograde amnesia. Psychological triggers such as emotional stress are common in everyday life, yet pure retrograde amnesia is considered very rare. Also the potential for organic damage to fall below threshold of being identified does not necessarily mean it is not present, and it is highly likely that both psychological factors and organic cause exist in pure retrograde amnesia.
Comparison with organic amnesia
Psychogenic amnesia is supposed to differ from organic amnesia in a number of ways; one being that unlike organic amnesia, psychogenic amnesia is thought to occur when no structural damage to the brain or brain lesion is evident. Psychological triggers are instead considered as preceding psychogenic amnesia, and indeed many anecdotal case studies which are cited as evidence of psychogenic amnesia hail from traumatic experiences such as World War II. As aforementioned however, an etiology of psychogenic amnesia is controversial as causation is not always clear (see above paragraph), and both elements of psychological stress and organic amnesia may be present among cases. Often, but not necessarily, a premorbid history of psychiatric illness such as depression is thought to be present in conjunction to triggers of psychological stress. Lack of psychological evidence precipitating amnesia doesnt mean there isnt any, for example trauma during childhood has even been cited as triggering amnesia later in life, but such an argument runs the risk of psychogenic amnesia becoming an umbrella term for any amnesia of which there is no apparent organic cause. Due to organic amnesia often being difficult to detect, defining between organic and psychogenic amnesia is not easy and often context of precipitating experiences are considered (for example, if there has been drug abuse) as well as the symptomology the patient presents with. Psychogenic amnesia is supposed to differ from organic amnesia qualitatively in that retrograde loss of autobiographical memory while semantic memory remains intact is said to be specific of psychogenic amnesia. Another difference that has been cited between organic and psychogenic amnesia is the temporal gradient of retrograde loss of autobiographical memory. The temporal gradient of loss in most cases of organic amnesia is said to be steepest at its most recent premorbid period, whereas for psychogenic amnesia the temporal gradient of retrograde autobiographical memory loss is said to be quite consistently flat. Although there is much literature on psychogenic amnesia as dissimilar to organic amnesia, the distinction between neurological and psychological features is often difficult to discern and remains controversial.
Diagnosis
Functional assessment of brain activity can be assessed for psychogenic amnesia using imaging techniques such as fMRI, PET and EEG, in accordance with clinical data. Some research has suggested that organic and psychogenic amnesia to some extent share the involvement of the same structures of the temporo-frontal region in the brain. It has been suggested that deficits in episodic memory may be attributable to dysfunction in the limbic system, while self-identity deficits have been suggested as attributable to functional changes related to the posterior parietal cortex. To reiterate however, care must be taken when attempting to define causation as only ad hoc reasoning about the aetiology of psychogenic amnesia is possible, which means cause and consequence can be infeasible to untangle.
Treatments
Because psychogenic amnesia is defined by its lack of physical damage to the brain, treatment by physical methods is difficult. Nonetheless, distinguishing between organic and dissociative memory loss has been described as an essential first-step in effective treatments. Treatments in the past have attempted to alleve psychogenic amnesia by treating the mind itself, as guided by theories which range from notions such as betrayal theory to account for memory loss attributed to protracted abuse by caregivers to the amnesia as a form of self-punishment in a Freudian sense, with the obliteration of personal identity as an alternative to suicide.Treatment attempts often have revolved around trying to discover what traumatic event had caused the amnesia, and drugs such as intravenously administered barbiturates (often thought of as truth serum) were popular as treatment for psychogenic amnesia during World War II; benzodiazepines may have been substituted later. Truth serum drugs were thought to work by making a painful memory more tolerable when expressed through relieving the strength of an emotion attached to a memory. Under the influence of these truth drugs the patient would more readily talk about what had occurred to them. However, information elicited from patients under the influence of drugs such as barbiturates would be a mixture of truth and fantasy, and was thus not regarded as scientific in gathering accurate evidence for past events. Often treatment was aimed at treating the patient as a whole, and probably varied in practice in different places. Hypnosis was also popular as a means for gaining information from people about their past experiences, but like truth drugs really only served to lower the threshold of suggestibility so that the patient would speak easily but not necessarily truthfully. If no motive for the amnesia was immediately apparent, deeper motives were usually sought by questioning the patient more intensely, often in conjunction with hypnosis and truth drugs. In many cases, however, patients were found to spontaneously recover from their amnesia on their own accord so no treatment was required.
In popular culture
Psychogenic amnesia is a common fictional plot device in many films, books and other media. Examples include William Shakespeares King Lear, who experienced amnesia and madness following a betrayal by his daughters; and the title character Nina in Nicolas Dalayracs 1786 opera.
In the 2009 Televisa-produced telenovela Sortilegio, the main female protagonist (Jacqueline Bracamontes) is kidnapped and her memory is wiped using drugs. In OMORI, one of the main characters (Sunny) has dissociative amnesia.
In the 2009 Breaking Bad television programs second season episode Bit by a Dead Bee, the main protagonist, Walter White, fakes a fugue state to account for his whereabouts.
See also
Effects of stress on memory
Depersonalization
Dissociative disorders
References
== External links == |
Persistent tunica vasculosa lentis | Persistent tunica vasculosa lentis is a congenital ocular anomaly. It is a form of persistent hyperplastic primary vitreous (PHPV).
It is a developmental disorder of the vitreous. It is usually unilateral and first noticed in the neonatal period. It may be associated with microphthalmos, cataracts, and increased intraocular pressure. Elongated ciliary processes are visible through the dilated pupil. A USG B-scan confirms diagnosis in the presence of a cataract.
See also
Persistent fetal vasculature
Tunica vasculosa lentis
References
http://www.djo.harvard.edu/files/1568.pdf
Wright KW, Speigel PH, Buckley EG. Pediatric Ophthalmology and Strabismus. Springer; US, New York: 2003. p. 17. |
Sotos syndrome | Sotos syndrome is a rare genetic disorder characterized by excessive physical growth during the first years of life. Excessive growth often starts in infancy and continues into the early teen years. The disorder may be accompanied by autism, mild intellectual disability, delayed motor, cognitive, and social development, hypotonia (low muscle tone), and speech impairments. Children with Sotos syndrome tend to be large at birth and are often taller, heavier, and have relatively large skulls (macrocephaly) than is normal for their age. Signs of the disorder, which vary among individuals, include a disproportionately large skull with a slightly protrusive forehead, large hands and feet, large mandible, hypertelorism (an abnormally increased distance between the eyes), and downslanting eyes. Clumsiness, an awkward gait, and unusual aggressiveness or irritability may also occur.
Although most cases of Sotos syndrome occur sporadically, familial cases have also been reported. It is similar to Weaver syndrome.
Signs and symptoms
This syndrome is characterized by overgrowth and advanced bone age. Affected individuals have dysmorphic features, with macrodolichocephaly, downslanting palpebral fissures and a pointed chin. The facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers, and have an unusually large skull and large head. Adult height is usually in the normal range, although Broc Brown has the condition and was named the worlds tallest teenager. As of late 2016, he was 78" and still growing.Individuals with Sotos syndrome often have intellectual impairment, and most also display autistic traits. Frequent behavioral impairments include attention deficit hyperactivity disorder (ADHD), phobias, obsessive compulsive disorder, tantrums, and impulsive behaviors (impulse control disorder). Problems with speech and language are also common. Affected individuals may often have stuttering, difficulty with sound production, or a monotone voice. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.Other signs include scoliosis, seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience jaundice and poor feeding. A small number of patients with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer has been associated with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If persons with this disorder have any increased cancer risk, their risk is only slightly greater than that of the general population.
Genetics
Mutations in the NSD1 gene cause Sotos syndrome. The NSD1 gene provides instructions for making a protein (histone methyltransferase) that is involved in normal growth and development. The function of this protein is unknown, however. In the Japanese population, the most common genetic change leading to Sotos syndrome deletes genetic material from the region of chromosome 5 containing the NSD1 gene. In other populations, small mutations within the NSD1 gene occur more frequently. Genetic changes involving the NSD1 gene prevent one copy of the gene from producing any functional protein. It is unclear how a reduced amount of this protein during development leads to learning disabilities, overgrowth, and the other features of Sotos syndrome.About 95 percent of Sotos syndrome cases occur by spontaneous mutation. Most of these cases result from new mutations involving the NSD1 gene. A few families have been described with more than one affected family member. These inherited cases enabled researchers to determine that Sotos syndrome has an autosomal dominant pattern of inheritance.
Diagnosis
Diagnosis is based on physical examination, looking for excessive growth among other symptoms. There are no biochemical markers for the disease.
Treatment
Treatment is symptomatic. There is no standard course of treatment for Sotos syndrome.
Prognosis
Sotos syndrome is not a life-threatening disorder and patients may have a normal life expectancy. Developmental delays may improve in the school-age years; however, coordination problems may persist into adulthood, along with any learning disabilities and/or other physical or mental issues.
Epidemiology
Incidence is approximately 1 in 14,000 births.
See also
Beckwith-Wiedemann syndrome
Perlman syndrome
Proteus syndrome
References
External links
Media related to Sotos syndrome at Wikimedia Commons
sotos at NIH/UW GeneTests |
Degloving | A degloving injury is a type of avulsion in which an extensive section of skin is completely torn off the underlying tissue, severing its blood supply. It is named by analogy to the process of removing a glove.
Effects
Typically, degloving injuries affect the extremities and limbs; in these cases, they are frequently associated with underlying fractures. Any injury which would induce degloving of the head or torso is likely to be lethal. However, controlled facial degloving is often featured in plastic surgery.
Degloving injuries invariably require major surgical interventions. Treatment options include replantation or revascularization of the degloved skins, or when these are not possible, skin grafts or skin flaps. While the preservation of the extremities and limbs is normally preferred, in some cases amputations may be advised or required. Post-operative physiotherapy is of particular importance for degloving injuries involving the hand.
Other animals
Many small mammals are able to induce degloving of their tails to escape capture; this is comparable to tail autotomy in reptiles.
References
External links
Report on degloving injuries in children |
Ectropion | Ectropion is a medical condition in which the lower eyelid turns outwards. It is one of the notable aspects of newborns exhibiting congenital Harlequin-type ichthyosis, but ectropion can occur due to any weakening of tissue of the lower eyelid. The condition can be repaired surgically. Ectropion is also found in dogs as a genetic disorder in certain breeds.
Causes
Congenital
Aging
Scarring
Mechanical
Allergic
Facial nerve palsy
Anti-cancer treatments such as erlotinib, cetuximab, and panitumumab, which block the function of EGFR (the epidermal growth factor receptor).
Diagnosis
Ectropion can usually be diagnosed with a routine eye exam and physical. The eyelids muscle tone and tightness can be assessed by pulling gently on the eyelid.
Ectropion in dogs
Ectropion in dogs usually involves the lower eyelid. Often the condition has no symptoms, but tearing and conjunctivitis may be seen. Breeds associated with ectropion include the Cocker Spaniel, the Saint Bernard, the Bloodhound, the Clumber Spaniel, and the Basset Hound. It can also result from trauma or nerve damage. Treatment (surgery) is recommended only if there is chronic conjunctivitis or if there is corneal damage. A small part of the affected lid is removed and then the lid is sewn back together.
See also
Cervical ectropion
Entropion
References
== External links == |
Degos disease | Degos disease, also known as Köhlmeier-Degos disease or malignant atrophic papulosis, is an extremely rare condition caused by blockage of arteries and veins. Individuals with this condition will develop papules. Those diagnosed with this disease may also develop complications due to impairment of internal organs. The exact underlying mechanism is still unknown, and an effective treatment is still being developed. There are fewer than 50 living patients presently known worldwide, and fewer than 200 reported in medical literature. However, many individuals may go undiagnosed due to rarity of the disease. Most individuals develop symptoms between the ages of 20–50; however, cases outside of this age range have been reported as well.
Symptoms and signs
The characteristic symptom of Degos disease is the development of papules. Initially, individuals may have skin lesions or rashes, but they will proceed to develop distinct bumps, or papules. Papules are circular in shape, have a porcelain-white center and red border. As papules age, the white centers will skin in and only the border will remain raised. Typically, papules range from 0.5 to 1 cm in width. Papules appear on the trunk and upper extremities and are not found on the individuals palms, soles, scalp, or face.Symptoms vary, depending on whether an individual has the benign variant or malignant variant of the disease. Both the benign and malignant forms have development of the characteristic papules. Individuals with the benign form will have the typical papules persisting anywhere from a few years to throughout their whole lives. In the benign form, no inner organs are affected. If an individual develops the malignant form, it means that not only are the papules present, but inner organs are involved. Most malignant cases involve problems of the gastrointestinal tract leading to small intestine lesions, abdominal pain, diarrhea, and bowel perforation. If the central nervous system is involved, symptoms can include headaches, dizziness, seizures, paralysis of cranial nerves, weakness, stroke, damage to small areas of the brain due to artery blockage (cerebral infarcts, and cerebral hemorrhage). Additional organs commonly impacted include the heart, lungs, and kidneys. Symptoms that may develop from damage to these organs include double vision (diplopia), clouding of lenses of eyes, swelling of the optic disc (papilledema), partial loss of vision, shortness of breath, chest pain, epilepsy, and thickening of pericardium.Someone with the benign form may suddenly develop symptoms of the malignant form. Symptoms can last anywhere from a few weeks to several years. Onset of symptoms typically begins to manifest between the ages of 20–50. A few cases of this condition in newborns have also been described.
Causes
The papules characteristic for this disease develop due to infarctions, or blockages in small-medium arteries and veins. The underlying cause is unknown for this disease. Though not confirmed, some cases have shown signs of inheritance between first-degree relatives. It has been suggested that the disease has a familial inheritance pattern; it is thought to be an autosomal dominant disorder. In most cases of familial inheritance, the benign variant of the disease has been present.Due to the lack of knowledge of the pathomechanism for this condition prevention strategies are not known. However, in order to prevent worsening of symptoms, consistent evaluations should be conducted by a physician.
Mechanism
Although this disease has been known for around 70 years, the pathomechanism underlying it is still unknown. Several hypotheses have been developed regarding the underlying mechanism for Degos disease. One theory suggests that inflammation of blood vessels may trigger the condition. Another theory has to do with Degos disease as a coagulopathy. Development of a thrombus and resulting reduction of blood flow is common in this condition. A reduction in blood flow throughout the body can lead to damaged endothelial cells and may perhaps lead to the formation of the characteristic papules. Another hypothesis suggests that abnormal swelling and proliferation of the vascular endothelium can lead to intestinal and central nervous system thrombosis, and ultimately lead to development of symptoms associated with Degos disease. Overall, individuals with Degos disease have abnormal blockages in their arteries and veins; however, the cause of these blockages is unknown.
Diagnosis
Clinical evaluation and identification of characteristics papules may allow a dermatologist to diagnose Degos disease. The papules have a white center and are bordered with a red ring. After lesions begin to appear, the diagnosis for Degos disease can be supported by histological findings. Most cases will show a wedge-shaped connective tissue necrosis in the deep corium. This shape is due to the blockage/occlusion of small arteries.Individuals may be diagnosed with the benign form if only the papules are present. However, an individual may be diagnosed with the malignant form if involvement of other organs like the lungs, intestine and/or central nervous system occurs. The malignant, or systematic form of this condition may suddenly develop even after having papules present for several years. In order to quickly diagnose this shift to the malignant variant of the disease, it is important for individuals to have consistent follow-up evaluations. In these evaluations, depending on which organs are suspected to be involved, the following procedures and tests may be conducted: skin inspection, brain magnetic resonance tomography, colonoscopy, chest X-ray, and/or abdominal ultrasound.
Treatment
Due to the lack of knowledge around the underlying mechanism of malignant atrophic papulosis, an effective treatment method has not been developed. Treatment for this condition is symptomatic. However, several treatment methods have been tested and are still being developed as more information regarding the condition is found. Fibrinolytic and immunosuppressive therapeutic regimens were tested and found to be mostly unsuccessful as treatment methods.After treating conditions comorbid with Degos disease, physicians have recently found improvement in symptoms with the use of eculizumab and treprostinil. Discovered by dermatopathologist, Cynthia Magro, response to eculizumab is often immediate and dramatic, but has been of limited duration and is expensive, needing to be infused every 14 days. Treprostinil use has been reported to result in clearing of gastrointestinal and central nervous system findings as well as clearing of cutaneous lesions, but reports are limited. Treprostinil may be more effective than other vasodilators because it may also increase the population of circulating endothelial cells, allowing angiogenesis.
Recent research
A 46-year-old male patient was diagnosed with the malignant, systemic form of the disease and was severely ill. The diagnosing dermatopathologist, Cynthia Magro MD, identified the presence of C5b-9 complexes in the involved vessels of the skin biopsy. For treatment of the thrombotic microangiopathy in this patient, she suggested the use of eculizumab, a humanized monoclonal antibody drug developed by Alexion Pharmaceuticals and approved by the Food and Drug Administration for treatment of Paroxysmal nocturnal hemoglobinuria. The patient experienced a dramatic improvement in his condition. Lee Shapiro MD and Aixa Toledo-Garcia MD at Albany Medical College learned of the success with the adult patient, and became the first physicians to successfully treat a pediatric Degos patient with eculizumab.Dr. Shapiro later observed the resolution of Degos skin lesions in an adult patient with an overlap syndrome involving systemic lupus, systemic sclerosis, and Degos disease who was treated with treprostinil for her pulmonary hypertension. His pediatric Degos patient was developing significant complications despite treatment with eculizumab, so Dr. Shapiros group became the first to treat a Degos patient with treprostinil. To this point, all known long-term survivors of systemic Degos disease are being treated with a combination of eculizumab and treprostinil.
History
In 1941, this disease was first described by Köhlmeier. However, it was not until 1942 that the disease was recognized as a new clinical entity by Robert Degos. Initially the condition was referred to as Degos disease or Köhlmeier-Degos disease. However, Degos himself subsequently suggested the name "papulose atrophiante maligne," translated as malignant atrophic papulosis.
References
Notes
Further reading
== External links == |
Shingles | Shingles, also known as zoster or herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. Two to four days before the rash occurs there may be tingling or local pain in the area. Otherwise, there are typically few symptoms though some people may have fever or headache, or feel tired. The rash usually heals within two to four weeks; however, some people develop ongoing nerve pain which can last for months or years, a condition called postherpetic neuralgia (PHN). In those with poor immune function the rash may occur widely. If the rash involves the eye, vision loss may occur.Shingles and chickenpox are distinct human diseases but are closely related in their life cycles. Both originate from infection of an individual with the varicella zoster virus (VZV). Chickenpox, also called varicella, results from the initial infection with the virus, typically occurring during childhood or adolescence. Once the chickenpox has resolved, the virus can remain inactive (dormant) in human nerve cells (dorsal root ganglia or cranial nerves) for years or decades, after which it may reactivate. Shingles results when the dormant varicella virus is reactivated. The virus then travels along nerve bodies to nerve endings in the skin, producing blisters. During an outbreak of shingles, exposure to the varicella virus found in shingles blisters can cause chickenpox in someone who has not yet had chickenpox; this initial infection will not trigger shingles, however. How the virus remains dormant in the body or subsequently re-activates is not well understood.Risk factors for reactivation of the dormant virus include old age, poor immune function, and having contracted chickenpox before 18 months of age. Diagnosis is typically based on the signs and symptoms presented. Varicella zoster virus is not the same as herpes simplex virus, although they belong to the same family of herpesviruses.Shingles vaccines reduce the risk of shingles by 50% to 90%, depending on the vaccine used. Vaccination also decreases rates of postherpetic neuralgia, and, if shingles occurs, its severity. If shingles develops, antiviral medications such as aciclovir can reduce the severity and duration of disease if started within 72 hours of the appearance of the rash. Evidence does not show a significant effect of antivirals or steroids on rates of postherpetic neuralgia. Paracetamol, NSAIDs, or opioids may be used to help with acute pain.It is estimated that about a third of people develop shingles at some point in their lives. While shingles is more common among older people, children may also get the disease. According to the US National Institutes of Health, the number of new cases per year ranges from 1.2 to 3.4 per 1,000 person-years among healthy individuals to 3.9 to 11.8 per 1,000 person-years among those older than 65 years of age. About half of those living to age 85 will have at least one attack, and fewer than 5% will have more than one attack. Although symptoms can be severe, risk of death is very low: 0.28 to 0.69 deaths per million.The disease has been recognized since ancient times.
Signs and symptoms
The earliest symptoms of shingles, which include headache, fever, and malaise, are nonspecific, and may result in an incorrect diagnosis. These symptoms are commonly followed by sensations of burning pain, itching, hyperesthesia (oversensitivity), or paresthesia ("pins and needles": tingling, pricking, or numbness). Pain can be mild to severe in the affected dermatome, with sensations that are often described as stinging, tingling, aching, numbing or throbbing, and can be interspersed with quick stabs of agonizing pain.Shingles in children is often painless, but people are more likely to get shingles as they age, and the disease tends to be more severe.In most cases, after one to two days – but sometimes as long as three weeks – the initial phase is followed by the appearance of the characteristic skin rash. The pain and rash most commonly occur on the torso but can appear on the face, eyes, or other parts of the body. At first, the rash appears similar to the first appearance of hives; however, unlike hives, shingles causes skin changes limited to a dermatome, normally resulting in a stripe or belt-like pattern that is limited to one side of the body and does not cross the midline. Zoster sine herpete ("zoster without herpes") describes a person who has all of the symptoms of shingles except this characteristic rash.Later the rash becomes vesicular, forming small blisters filled with a serous exudate, as the fever and general malaise continue. The painful vesicles eventually become cloudy or darkened as they fill with blood, and crust over within seven to ten days; usually the crusts fall off and the skin heals, but sometimes, after severe blistering, scarring and discolored skin remain.
Face
Shingles may have additional symptoms, depending on the dermatome involved. The trigeminal nerve is the most commonly involved nerve, of which the ophthalmic division is the most commonly involved branch. When the virus is reactivated in this nerve branch it is termed zoster ophthalmicus. The skin of the forehead, upper eyelid and orbit of the eye may be involved. Zoster ophthalmicus occurs in approximately 10% to 25% of cases. In some people, symptoms may include conjunctivitis, keratitis, uveitis, and optic nerve palsies that can sometimes cause chronic ocular inflammation, loss of vision, and debilitating pain.Shingles oticus, also known as Ramsay Hunt syndrome type II, involves the ear. It is thought to result from the virus spreading from the facial nerve to the vestibulocochlear nerve. Symptoms include hearing loss and vertigo (rotational dizziness).Shingles may occur in the mouth if the maxillary or mandibular division of the trigeminal nerve is affected, in which the rash may appear on the mucous membrane of the upper jaw (usually the palate, sometimes the gums of the upper teeth) or the lower jaw (tongue or gums of the lower teeth) respectively. Oral involvement may occur alone or in combination with a rash on the skin over the cutaneous distribution of the same trigeminal branch. As with shingles of the skin, the lesions tend to only involve one side, distinguishing it from other oral blistering conditions. In the mouth, shingles appears initially as 1–4 mm opaque blisters (vesicles), which break down quickly to leave ulcers that heal within 10–14 days. The prodromal pain (before the rash) may be confused with toothache. Sometimes this leads to unnecessary dental treatment. Post-herpetic neuralgia uncommonly is associated with shingles in the mouth. Unusual complications may occur with intra-oral shingles that are not seen elsewhere. Due to the close relationship of blood vessels to nerves, the virus can spread to involve the blood vessels and compromise the blood supply, sometimes causing ischemic necrosis. Therefore, oral involvement rarely causes complications, such as osteonecrosis, tooth loss, periodontitis (gum disease), pulp calcification, pulp necrosis, periapical lesions and tooth developmental anomalies.
Disseminated shingles
In those with poor immune function, disseminated shingles may occur (wide rash).
It is defined as more than twenty skin lesions appearing outside either the primarily affected dermatome or dermatomes directly adjacent to it. Besides the skin, other organs, such as the liver or brain, may also be affected (causing hepatitis or encephalitis, respectively), making the condition potentially lethal.: 380
Pathophysiology
The causative agent for shingles is the varicella zoster virus (VZV) – a double-stranded DNA virus related to the herpes simplex virus. Most individuals are infected with this virus as children which causes an episode of chickenpox. The immune system eventually eliminates the virus from most locations, but it remains dormant (or latent) in the ganglia adjacent to the spinal cord (called the dorsal root ganglion) or the trigeminal ganglion in the base of the skull.Shingles occurs only in people who have been previously infected with VZV; although it can occur at any age, approximately half of the cases in the United States occur in those aged 50 years or older. Shingles can recur. In contrast to the frequent recurrence of herpes simplex symptoms, repeated attacks of shingles are unusual. It is extremely rare for a person to have more than three recurrences.The disease results from virus particles in a single sensory ganglion switching from their latent phase to their active phase. Due to difficulties in studying VZV reactivation directly in humans (leading to reliance on small-animal models), its latency is less well understood than that of the herpes simplex virus. Virus-specific proteins continue to be made by the infected cells during the latent period, so true latency, as opposed to chronic, low-level, active infection, has not been proven to occur in VZV infections. Although VZV has been detected in autopsies of nervous tissue, there are no methods to find dormant virus in the ganglia of living people.
Unless the immune system is compromised, it suppresses reactivation of the virus and prevents shingles outbreaks. Why this suppression sometimes fails is poorly understood, but shingles is more likely to occur in people whose immune systems are impaired due to aging, immunosuppressive therapy, psychological stress, or other factors. Upon reactivation, the virus replicates in neuronal cell bodies, and virions are shed from the cells and carried down the axons to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The short- and long-term pain caused by shingles outbreaks originates from inflammation of affected nerves due to the widespread growth of the virus in those areas.As with chickenpox and other forms of alpha-herpesvirus infection, direct contact with an active rash can spread the virus to a person who lacks immunity to it. This newly infected individual may then develop chickenpox, but will not immediately develop shingles.The complete sequence of the viral genome was published in 1986.
Diagnosis
If the rash has appeared, identifying this disease (making a differential diagnosis) requires only a visual examination, since very few diseases produce a rash in a dermatomal pattern (sometimes called, by doctors on TV "a dermatonal map"). However, herpes simplex virus (HSV) can occasionally produce a rash in such a pattern (zosteriform herpes simplex).When the rash is absent (early or late in the disease, or in the case of zoster sine herpete), shingles can be difficult to diagnose. Apart from the rash, most symptoms can occur also in other conditions.
Laboratory tests are available to diagnose shingles. The most popular test detects VZV-specific IgM antibody in blood; this appears only during chickenpox or shingles and not while the virus is dormant. In larger laboratories, lymph collected from a blister is tested by polymerase chain reaction (PCR) for VZV DNA, or examined with an electron microscope for virus particles. Molecular biology tests based on in vitro nucleic acid amplification (PCR tests) are currently considered the most reliable. Nested PCR test has high sensitivity, but is susceptible to contamination leading to false positive results. The latest real-time PCR tests are rapid, easy to perform, and as sensitive as nested PCR, and have a lower risk of contamination. They also have more sensitivity than viral cultures.
Differential diagnosis
Shingles can be confused with herpes simplex, dermatitis herpetiformis and impetigo, and skin reactions caused by contact dermatitis, candidiasis, certain drugs and insect bites.
Prevention
Shingles can be prevented by the chickenpox vaccine if the vaccine is administered before the individual gets chickenpox. If primary infection has already occurred, there are shingles vaccines that reduce the risk of developing shingles or developing severe shingles if the disease occurs. They include a live attenuated virus vaccine, Zostavax, and an adjuvanted subunit vaccine, Shingrix.A review by Cochrane concluded that Zostavax was useful for preventing shingles for at least three years. This equates to about 50% relative risk reduction. The vaccine reduced rates of persistent, severe pain after shingles by 66% in people who contracted shingles despite vaccination. Vaccine efficacy was maintained through four years of follow up. It has been recommended that people with primary or acquired immunodeficiency should not receive the live vaccine.Two doses of Shingrix are recommended, which provide about 90% protection at 3.5 years. As of 2016, it had been studied only in people with an intact immune system. It appears to also be effective in the very old.In the UK, shingles vaccination is offered by the National Health Service (NHS) to all people in their 70s. As of 2021 Zostavax is the usual vaccine, but Shingrix vaccine is recommended if Zostavax is unsuitable, for example for those with immune system issues. Vaccination is not available to people over 80 as "it seems to be less effective in this age group". By August 2017, just under half of eligible 70–78 year olds had been vaccinated. About 3% of those eligible by age have conditions that suppress their immune system, and should not receive Zostavax. There had been 1,104 adverse reaction reports by April 2018. In the US, it is recommended that healthy adults 50 years and older receive two doses of Shingrix, two to six months apart.
Treatment
The aims of treatment are to limit the severity and duration of pain, shorten the duration of a shingles episode, and reduce complications. Symptomatic treatment is often needed for the complication of postherpetic neuralgia.
However, a study on untreated shingles shows that, once the rash has cleared, postherpetic neuralgia is very rare in people under 50 and wears off in time; in older people, the pain wore off more slowly, but even in people over 70, 85% were free from pain a year after their shingles outbreak.
Analgesics
People with mild to moderate pain can be treated with over-the-counter pain medications. Topical lotions containing calamine can be used on the rash or blisters and may be soothing. Occasionally, severe pain may require an opioid medication, such as morphine. Once the lesions have crusted over, capsaicin cream (Zostrix) can be used. Topical lidocaine and nerve blocks may also reduce pain. Administering gabapentin along with antivirals may offer relief of postherpetic neuralgia.
Antivirals
Antiviral drugs may reduce the severity and duration of shingles; however, they do not prevent postherpetic neuralgia. Of these drugs, aciclovir has been the standard treatment, but the newer drugs valaciclovir and famciclovir demonstrate similar or superior efficacy and good safety and tolerability. The drugs are used both for prevention (for example in people with HIV/AIDS) and as therapy during the acute phase. Complications in immunocompromised individuals with shingles may be reduced with intravenous aciclovir. In people who are at a high risk for repeated attacks of shingles, five daily oral doses of aciclovir are usually effective.
Steroids
Corticosteroids do not appear to decrease the risk of long-term pain. Side effects however appear to be minimal. Their use in Ramsay Hunt syndrome had not been properly studied as of 2008.
Zoster ophthalmicus
Treatment for zoster ophthalmicus is similar to standard treatment for shingles at other sites. A trial comparing acyclovir with its prodrug, valacyclovir, demonstrated similar efficacies in treating this form of the disease. The significant advantage of valacyclovir over acyclovir is its dosing of only three times/day (compared with acyclovirs five times/day dosing), which could make it more convenient for people and improve adherence with therapy.
Prognosis
The rash and pain usually subside within three to five weeks, but about one in five people develops a painful condition called postherpetic neuralgia, which is often difficult to manage. In some people, shingles can reactivate presenting as zoster sine herpete: pain radiating along the path of a single spinal nerve (a dermatomal distribution), but without an accompanying rash. This condition may involve complications that affect several levels of the nervous system and cause many cranial neuropathies, polyneuritis, myelitis, or aseptic meningitis. Other serious effects that may occur in some cases include partial facial paralysis (usually temporary), ear damage, or encephalitis. Although initial infections with VZV during pregnancy, causing chickenpox, may lead to infection of the fetus and complications in the newborn, chronic infection or reactivation in shingles are not associated with fetal infection.There is a slightly increased risk of developing cancer after a shingles episode. However, the mechanism is unclear and mortality from cancer did not appear to increase as a direct result of the presence of the virus. Instead, the increased risk may result from the immune suppression that allows the reactivation of the virus.Although shingles typically resolves within 3–5 weeks, certain complications may arise:
Secondary bacterial infection.
Motor involvement, including weakness especially in "motor herpes zoster".
Eye involvement: trigeminal nerve involvement (as seen in herpes ophthalmicus) should be treated early and aggressively as it may lead to blindness. Involvement of the tip of the nose in the zoster rash is a strong predictor of herpes ophthalmicus.
Postherpetic neuralgia, a condition of chronic pain following shingles.
Epidemiology
Varicella zoster virus (VZV) has a high level of infectivity and has a worldwide prevalence. Shingles is a re-activation of latent VZV infection: zoster can only occur in someone who has previously had chickenpox (varicella).
Shingles has no relationship to season and does not occur in epidemics. There is, however, a strong relationship with increasing age. The incidence rate of shingles ranges from 1.2 to 3.4 per 1,000 person‐years among younger healthy individuals, increasing to 3.9–11.8 per 1,000 person‐years among those older than 65 years, and incidence rates worldwide are similar.
This relationship with age has been demonstrated in many countries, and is attributed to the fact that cellular immunity declines as people grow older.
Another important risk factor is immunosuppression. Other risk factors include psychological stress. According to a study in North Carolina, "black subjects were significantly less likely to develop zoster than were white subjects." It is unclear whether the risk is different by sex. Other potential risk factors include mechanical trauma and exposure to immunotoxins.There is no strong evidence for a genetic link or a link to family history. A 2008 study showed that people with close relatives who had shingles were twice as likely to develop it themselves, but a 2010 study found no such link.Adults with latent VZV infection who are exposed intermittently to children with chickenpox receive an immune boost. This periodic boost to the immune system helps to prevent shingles in older adults. When routine chickenpox vaccination was introduced in the United States, there was concern that, because older adults would no longer receive this natural periodic boost, there would be an increase in the incidence of shingles.
Multiple studies and surveillance data, at least when viewed superficially, demonstrate no consistent trends in incidence in the U.S. since the chickenpox vaccination program began in 1995. However, upon closer inspection, the two studies that showed no increase in shingles incidence were conducted among populations where varicella vaccination was not as yet widespread in the community. A later study by Patel et al. concluded that since the introduction of the chickenpox vaccine, hospitalization costs for complications of shingles increased by more than $700 million annually for those over age 60. Another study by Yih et al. reported that as varicella vaccine coverage in children increased, the incidence of varicella decreased, and the occurrence of shingles among adults increased by 90%. The results of a further study by Yawn et al. showed a 28% increase in shingles incidence from 1996 to 2001. It is likely that incidence rate will change in the future, due to the aging of the population, changes in therapy for malignant and autoimmune diseases, and changes in chickenpox vaccination rates; a wide adoption of zoster vaccination could dramatically reduce the incidence rate.In one study, it was estimated that 26% of those who contract shingles eventually present complications. Postherpetic neuralgia arises in approximately 20% of people with shingles. A study of 1994 California data found hospitalization rates of 2.1 per 100,000 person-years, rising to 9.3 per 100,000 person-years for ages 60 and up. An earlier Connecticut study found a higher hospitalization rate; the difference may be due to the prevalence of HIV in the earlier study, or to the introduction of antivirals in California before 1994.
History
Shingles has a long recorded history, although historical accounts fail to distinguish the blistering caused by VZV and those caused by smallpox, ergotism, and erysipelas. In the late 18th century William Heberden established a way to differentiate shingles and smallpox, and in the late 19th century, shingles was differentiated from erysipelas. In 1831 Richard Bright hypothesized that the disease arose from the dorsal root ganglion, and an 1861 paper by Felix von Bärensprung confirmed this.Recognition that chickenpox and shingles were caused by the same virus came at the beginning of the 20th century. Physicians began to report that cases of shingles were often followed by chickenpox in younger people who lived with the person with shingles. The idea of an association between the two diseases gained strength when it was shown that lymph from a person with shingles could induce chickenpox in young volunteers. This was finally proved by the first isolation of the virus in cell cultures, by the Nobel laureate Thomas Huckle Weller, in 1953. Some sources also attribute the first isolation of the herpes zoster virus to Evelyn Nicol.Until the 1940s the disease was considered benign, and serious complications were thought to be very rare. However, by 1942, it was recognized that shingles was a more serious disease in adults than in children and that it increased in frequency with advancing age. Further studies during the 1950s on immunosuppressed individuals showed that the disease was not as benign as once thought, and the search for various therapeutic and preventive measures began. By the mid-1960s, several studies identified the gradual reduction in cellular immunity in old age, observing that in a cohort of 1,000 people who lived to the age of 85, approximately 500 (i.e., 50%) would have at least one attack of shingles, and 10 (i.e., 1%) would have at least two attacks.In historical shingles studies, shingles incidence generally increased with age. However, in his 1965 paper, Hope-Simpson suggested that the "peculiar age distribution of zoster may in part reflect the frequency with which the different age groups encounter cases of varicella and because of the ensuing boost to their antibody protection have their attacks of zoster postponed".
Lending support to this hypothesis that contact with children with chickenpox boosts adult cell-mediated immunity to help postpone or suppress shingles, a study by Thomas et al. reported that adults in households with children had lower rates of shingles than households without children. Also, the study by Terada et al. indicated that pediatricians reflected incidence rates from 1/2 to 1/8 that of the general population their age.
Etymology
The family name of all the herpesviruses derives from the Greek word herpēs, from herpein ("to creep"), referring to the latent, recurring infections typical of this group of viruses. Zoster comes from Greek zōstēr, meaning "belt" or "girdle", after the characteristic belt-like dermatomal rash. The common name for the disease, shingles, derives from the Latin cingulus, a variant of Latin cingulum, meaning "girdle".
Research
Until the mid-1990s, infectious complications of the central nervous system (CNS) caused by VZV reactivation were regarded as rare. The presence of rash, as well as specific neurological symptoms, were required to diagnose a CNS infection caused by VZV. Since 2000, PCR testing has become more widely used, and the number of diagnosed cases of CNS infection has increased.Classic textbook descriptions state that VZV reactivation in the CNS is restricted to immunocompromised individuals and the elderly; however, studies have found that most participants are immunocompetent, and less than 60 years old. Historically, vesicular rash was considered a characteristic finding, but studies have found that rash is only present in 45% of cases.
In addition, systemic inflammation is not as reliable an indicator as previously thought: the mean level of C-reactive protein and mean white blood cell count are within the normal range in participants with VZV meningitis.
MRI and CT scans are usually normal in cases of VZV reactivation in the CNS. CSF pleocytosis, previously thought to be a strong indicator of VZV encephalitis, was absent in half of a group of people diagnosed with VZV encephalitis by PCR.The frequency of CNS infections presented at the emergency room of a community hospital is not negligible, so a means of diagnosing cases is needed. PCR is not a foolproof method of diagnosis, but because so many other indicators have turned out to not be reliable in diagnosing VZV infections in the CNS, screening for VZV by PCR is recommended. Negative PCR does not rule out VZV involvement, but a positive PCR can be used for diagnosis, and appropriate treatment started (for example, antivirals can be prescribed rather than antibiotics).The introduction of DNA analysis techniques has shown some complications of varicella-zoster to be more common than previously thought. For example, sporadic meningoencephalitis (ME) caused by varicella-zoster was regarded as rare disease, mostly related to childhood chickenpox. However, meningoencephalitis caused by varicella-zoster is increasingly recognized as a predominant cause of ME among immunocompetent adults in non-epidemic circumstances.Diagnosis of complications of varicella-zoster, particularly in cases where the disease reactivates after years or decades of latency, is difficult. A rash (shingles) can be present or absent. Symptoms vary, and there is a significant overlap in symptoms with herpes-simplex symptoms.Although DNA analysis techniques such as polymerase chain reaction (PCR) can be used to look for DNA of herpesviruses in spinal fluid or blood, the results may be negative, even in cases where other definitive symptoms exist. Notwithstanding these limitations, the use of PCR has resulted in an advance in the state of the art in our understanding of herpesviruses, including VZV, during the 1990s and 2000s. For example, in the past, clinicians believed that encephalitis was caused by herpes simplex and that people always died or developed serious long-term function problems. People were diagnosed at autopsy or by brain biopsy. Brain biopsy is not undertaken lightly: it is reserved only for serious cases that cannot be diagnosed by less invasive methods. For this reason, knowledge of these herpes virus conditions was limited to severe cases. DNA techniques have made it possible to diagnose "mild" cases, caused by VZV or HSV, in which the symptoms include fever, headache, and altered mental status. Mortality rates in treated people are decreasing.
References
Further reading
Saguil A (November 2017). "Her |
Shingles | pes Zoster and Postherpetic Neuralgia: Prevention and Management". American Family Physician. 96 (10): 656–663. PMID 29431387.
External links
NINDS Shingles Information Page, National Institute of Neurological Disorders and Stroke |
X-linked recessive chondrodysplasia punctata | X-linked recessive chondrodysplasia punctata is a type of chondrodysplasia punctata that can involve the skin, hair, and cause short stature with skeletal abnormalities, cataracts, and deafness.: 500 This condition is also known as arylsulfatase E deficiency, CDPX1, and X-linked recessive chondrodysplasia punctata 1. The syndrome rarely affects females, but they can be carriers of the recessive allele. Although the exact number of people diagnosed with CDPX1 is unknown, it was estimated that 1 in 500,000 have CDPX1 in varying severity. This condition is not linked to a specific ethnicity. The mutation that leads to a deficiency in arylsulfatase E. (ARSE) occurs in the coding region of the gene. Absence of stippling, deposits of calcium, of bones and cartilage, shown on x-ray, does not rule out chondrodysplasia punctata or a normal chondrodysplasia punctata 1 (CDPX1) gene without mutation. Stippling of the bones and cartilage is rarely seen after childhood. Phalangeal abnormalities are important clinical features to look for once the stippling is no longer visible. Other, more severe, clinical features include respiratory abnormalities, hearing loss, cervical spine abnormalities, delayed cognitive development, ophthalmologic abnormalities, cardiac abnormalities, gastroesophageal reflux, and feeding difficulties. CDPX1 actually has a spectrum of severity; different mutations within the CDPX1 gene have different effects on the catalytic activity of the ARSE protein. The mutations vary between missense, nonsense, insertions, and deletions.
Cause
The only known cause of this condition is a mutation in the X-linked chondrodysplasia punctata 1 (CDPX1) gene. Mutations in this gene result in a deficiency of arylsulfatase E. Only 50-60% of cases have been shown to have mutations in this gene and the cause of the remaining cases is not yet known.The CDPX1 gene is located on the short arm of the X chromosome (Xp22.3) on the Crick (minus) strand. It is 33,614 bases in length.
The mature protein has a molecular weight of 68 kiloDaltons. It is glycosylated and is located in the Golgi apparatus. Its activity may be inhibited by warfarin. It seems likely that warfarin induced embryotoxicity may be due at least in part to this inhibition.Brachytelephalangic chondrodysplasia punctata (BCDP) is the non-genetic, or environmentally produced, phenocopies associated with CDPX1. Causes of BCDP can also come from genetic effects, mainly due to mutations. Keutel syndrome, deficiency of vitamin K epoxide reductase subunit 1 (VKORC1), gamma-glutamyl carboxylase (GGCX), Xp contiguous deletion syndromes, and multiple sulfatase deficiency are all genetic conditions that are associated BCDP.
Diagnosis
This condition occurs almost exclusively in males. The mutation may be spontaneous or inherited from the mother. The typical clinical features are:
flat nasal tip
short columella
maxillary hypoplasia
involvement of terminal phalanges
stippled chondrodystrophy
Biochemical confirmation
The activity of arylsulfatase E can be measured with the substrate 4-methylumbelliferyl sulfate.
Treatment
CDPX1 activity may be inhibited by warfarin because it is believed that ARSE has enzymatic activity in a vitamin K producing biochemical pathway. Vitamin K is also needed for controlling binding of calcium to bone and other tissues within the body.
See also
List of cutaneous conditions
List of radiographic findings associated with cutaneous conditions
References
== External links == |
Cutis marmorata telangiectatica congenita | Cutis marmorata telangiectatica congenita is a rare congenital vascular disorder that usually manifests in affecting the blood vessels of the skin. The condition was first recognised and described in 1922 by Cato van Lohuizen, a Dutch pediatrician whose name was later adopted in the other common name used to describe the condition – Van Lohuizen Syndrome. CMTC is also used synonymously with congenital generalized phlebectasia, nevus vascularis reticularis, congenital phlebectasia, livedo telangiectatica, congenital livedo reticularis and Van Lohuizen syndrome.It should not be confused with the more general term "cutis marmorata", which refers to livedo reticularis caused by cold.
Signs and symptoms
People with visible marks generally feel fine (physically) and can act normally, but when it is mentioned, they may become withdrawn and self-conscious. Some children may have low self-esteem due to the condition.CMTC is an uncommon, sporadic congenital vascular malformation characterized by a generalized or localized reticulated cutaneous vascular network.Cutaneous lesions described in patients with CMTC include nevus flammeus, hemangioma, nevus anemicus, café-au-lait spots, melanocytic nevus, aplasia cutis and acral cyanosis.It has a marbled bluish to deep-purple appearance. The dark skin lesions often show a palpable loss of dermal substance. The reticulated mottling frequently appears more prominent in a cold environment (physiologic cutis marmorata), but tends not to disappear with warming. Hence, the erythema may be worsened by cooling, physical activity, or crying.CMTC frequently involves the extremities, with the lower extremities involved most commonly, followed by the upper extremities, and then the trunk and face. The lower extremities often show atrophy and seldom show hypertrophy resulting in limb circumference discrepancy.When located on the trunk, the lesions of CMTC tend to show mosaic distribution in streaks with a sharp midline demarcation seen across the abdomen. The lesions are primarily localized, but can be segmental or generalized, often unilateral in appearance. Diffuse involvement of the skin is usually not observed.
Although its course is variable, the majority of lesions in mild cases fade by adolescence. Ulceration and secondary infection are complications in severe cases and can be fatal if present in the neonatal period.
Causes
Fewer than 100 cases of CMTC have been published worldwide. Petrozzi reported the first case of CMTC in the United States in 1970. CMTC is believed to be more common than suspected, as studies have shown that milder forms of the disease are not being recognized as CMTC.The pathophysiology is still unclear, with most cases occurring sporadically, although rare cases were reported in families. Studies indicated the primary involvement of capillaries, venules and veins, and possibly also that of arterioles and lymphatics.
Hypotheses that have been proposed include: environmental/external factors; peripheral neural dysfunction; failure of the development of mesodermic vessels in an early embryonic stage; autosomal dominant inheritance with incomplete penetrance and, finally, the theory of Happle.
Diagnosis
Differential diagnosis
During the first few weeks after birth, when the lesions are not very reticulated, CMTC may look very similar to vascular lesions such as port-wine stains. However, during follow-up, CMTC lesions become characteristic in their appearance. They must be differentiated from other causes of persistent reticulated vascular lesions, such as those in the following table:
Histology
Some patients have a few or no histopathologic abnormalities. Histological examination of a biopsy may show an increase in the number and size of capillaries and veins (rarely lymphatics), dilated capillaries located in the deeper dermis, and hyperplasia and swollen endothelial cells with occasional dilated veins and venous lakes.
Associated abnormalities
Associated abnormalities include the following:
Body asymmetry (extremities; macrocephaly)
Glaucoma
Cutaneous atrophy
Neurological anomalies
Vascular anomalies (nevus flammeus /Sturge-Weber/Klippel-Trénauna Adams Oliver syndrome)
Psychomotor and/or mental retardation
Chronic ulceration that can complicate long-term CMTC
Chronic urticaria.
Treatment
In general, there is no treatment available for CMTC, although associated abnormalities can be treated. In the case of limb asymmetry, when no functional problems are noted, treatment is not warranted, except for an elevation device for the shorter leg.
Laser therapy has not been successful in the treatment of CMTC, possibly due to the presence of many large and deep capillaries and dilated veins. Pulsed-dye laser and long-pulsed-dye laser have not yet been evaluated in CMTC, but neither argon laser therapy nor YAG laser therapy has been helpful.When ulcers develop secondary to the congenital disease, antibiotic treatment such as oxacillin and gentamicin administered for 10 days has been prescribed. In one study, the wound grew Escherichia coli while blood cultures were negative.
Prognosis
The prognosis is favorable in most patients with an isolated cutaneous abnormality. In the majority of cases, both the vivid red marking and the difference in circumference of the extremities regress spontaneously during the first year of life. It is theorized that this may be due to the normal maturation process, with thickening of the epidermis and dermis. Improvements for some patients can continue for up to 10 years, while in other cases, the marbled skin may persist for the patients lifetime.
One study reported an improvement in lesions in 46% of patients within 3 years. If CMTC persists into adulthood, it can result in complaints due to paresthesia, increased sensitivity to cold and pain, and the formation of ulcers.Few reports included long-term follow up of CMTC into adolescence and adulthood. While about 50% of patients seem to show definite improvement in the reticular vascular pattern, the exact incidence and cause of persistent cases are unknown.
Epidemiology
Usually observed at birth or shortly thereafter in 94% of patients, in other reports, patients did not develop skin lesions until 3 months or even 2 years after birth. Females are typically affected more often than males (64%).
Eponym
It is named for Dr. Cato van Lohuizen.
References
== External links == |
Cutaneous myxoma | A cutaneous myxoma, or superficial angiomyxoma, consists of a multilobulated myxoid mass containing stellate or spindled fibroblasts with pools of mucin forming cleft-like spaces. There is often a proliferation of blood vessels and an inflammatory infiltrate. Staining is positive for vimentin, negative for cytokeratin and desmin, and variable for CD34, Factor VIIIa, SMA, MSA and S-100.Clinically, it may present as solitary or multiple flesh-colored nodules on the face, trunk, or extremities. It may occur as part of the Carney complex, and is sometimes the first sign. Local recurrence is common.
See also
Myxoma
Skin lesion
== References == |
Amelia | Amelia may refer to:
Arts, entertainment, and media
Films
Amélia (film), a 2000 Brazilian film directed by Ana Carolina
Amelia (film), a 2009 film based on the life of Amelia Earhart
Literature
Amelia (magazine), a Swedish womens magazine
Amelia (novel), a 1751 sentimental novel by Henry Fielding
Amelia Bedelia, a series of US childrens books
Amelia Jane, a series of books by Enid Blyton
Amelia Rules!, a series of American childrens graphic novels
Music
Amelia (opera), music by Daron Hagen; libretto by Gardner McFall; story by Stephen Wadsworth
"Amelia" (song), a song by Joni Mitchell on her 1976 album Hejira
"Amelia", a song by The Mission, from the album Carved in Sand
"Amelia", a song by the Cocteau Twins on their 1984 album Treasure
"Amelia", a song by Prism on their 1977 album Prism
"Amelia", a 1972 song by Wayne Cochran and The C.C. Riders
People
Amelia (given name), including people so named
Marco Amelia (born 1982), Italian football goalkeeper
Princess Amelia (disambiguation)
Places
United States
Amelia, Louisiana, a census-designated place in St. Mary Parish, Louisiana
Amelia, Nebraska, an unincorporated community in Holt County, Nebraska
Amelia, Ohio, a village in Clermont County, Ohio
Amelia, Washington
Amelia, West Virginia
Amelia City, Florida, a town in Nassau County, Florida
Amelia County, Virginia
Amelia Courthouse, Virginia, a village in Amelia County near Richmond
Amelia Island, the southernmost of the Sea Islands, near Florida
Elsewhere
Amelia, Umbria, a town in Italy
Amelia Cove, Newfoundland and Labrador, Canada, a hamlet in the St. Barbe District, near Griguet
Ships
Amelia (ship)
HMS Amelia, ships of the Royal Navy
Other uses
Amelia (birth defect)
Amelia (typeface)
Tropical Storm Amelia (disambiguation)
Amelia (company), an internet technology company
See also
Aemilia (disambiguation)
Amélie (disambiguation) |
Urinary retention | Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladder control, mild lower abdominal pain, and a weak urine stream. Those with long-term problems are at risk of urinary tract infections.Causes include blockage of the urethra, nerve problems, certain medications, and weak bladder muscles. Blockage can be caused by benign prostatic hyperplasia (BPH), urethral strictures, bladder stones, a cystocele, constipation, or tumors. Nerve problems can occur from diabetes, trauma, spinal cord problems, stroke, or heavy metal poisoning. Medications that can cause problems include anticholinergics, antihistamines, tricyclic antidepressants, cyclobenzaprine, diazepam, nonsteroidal anti-inflammatory drugs (NSAID), amphetamines, and opioids. Diagnosis is typically based on measuring the amount of urine in the bladder after urinating.Treatment is typically with a catheter either through the urethra or lower abdomen. Other treatments may include medication to decrease the size of the prostate, urethral dilation, a urethral stent, or surgery. Males are more often affected than females. In males over the age of 40 about 6 per 1,000 are affected a year. Among males over 80 this increases 30%.
Signs and symptoms
Onset can be sudden or gradual. When the onset is sudden, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladder control, mild lower abdominal pain, and a weak urine stream. Those with long-term problems are at risk of urinary tract infections.
Causes
Bladder
Infection
Detrusor sphincter dyssynergia
Neurogenic bladder (commonly spinal cord damage, pelvic splanchic nerve damage, cauda equina syndrome, pontine micturition or storage center lesions, demyelinating diseases or Parkinsons disease)
Iatrogenic (caused by medical treatment/procedure) scarring of the bladder neck (commonly from removal of indwelling catheters or cystoscopy operations)
Damage to the bladder
Prostate
Benign prostatic hyperplasia (BPH)
Prostate cancer and other pelvic malignancies
Prostatitis
Penile urethra
Congenital urethral valves
Phimosis or pinhole meatus
Circumcision
Obstruction in the urethra, for example a stricture (usually caused either by injury or STD), a metastasis or a precipitated pseudogout crystal in the urine
Pseudodyssynergia
STD lesions (gonorrhoea causes numerous strictures, leading to a "rosary bead" appearance, whereas chlamydia usually causes a single stricture)
Emasculation
Postoperative
Risk factors include
Age: Older people may have degeneration of neural pathways involved with bladder function and it can lead to an increased risk of postoperative urinary retention. The risk of postoperative urinary retention increases up to 2.11 fold for people older than 60 years.
Medications: Anticholinergics and medications with anticholinergic properties, alpha-adrenergic agonists, opiates, nonsteroidal anti-inflammatories (NSAIDs), calcium-channel blockers and beta-adrenergic agonists, may increase the risk.
Anesthesia: General anesthetics during surgery may cause bladder atony by acting as a smooth muscle relaxant. General anesthetics can directly interfere with autonomic regulation of detrusor tone and predispose people to bladder overdistention and subsequent retention. Spinal anesthesia results in a blockade of the micturition reflex. Spinal anesthesia shows a higher risk of postoperative urinary retention compared to general anesthesia.
Benign prostatic hyperplasia: Men with benign prostatic hyperplasia are at an increased risk of acute urinary retention.
Surgery related: Operative times longer than 2 hours may lead to an increased risk of postoperative urinary retention 3-fold.
Postoperative pain.
Chronic
Chronic urinary retention that is due to bladder blockage which can either be as a result of muscle damage or neurological damage. If the retention is due to neurological damage, there is a disconnect between the brain to muscle communication, which can make it impossible to completely empty the bladder. If the retention is due to muscle damage, it is likely that the muscles are not able to contract enough to completely empty the bladder.The most common cause of chronic urinary retention is BPH. BPH is a result of the ongoing process of testosterone being converted to dihydrotestosterone which stimulates prostate growth. Over a persons lifetime, the prostate experiences constant growth due to the conversion of testosterone to dihydrotestosterone. This can cause the prostate to push on the urethra and block it, which can lead to urinary retention.
Other
Tethered spinal cord syndrome.
Psychogenic causes – psychosocial stresses, fear associated with urination, paruresis ("shy bladder syndrome") – in extreme cases, urinary retention can result.
Consumption of some psychoactive substances, mainly stimulants, such as MDMA or amphetamine.
Use of NSAIDs, or drugs with anticholinergic properties.
Stones or metastases, which can theoretically appear anywhere along the urinary tract, but vary in frequency depending on anatomy.
Muscarinic antagonists such as atropine and scopolamine.
Malfunctioning artificial urinary sphincter.
Diagnosis
Analysis of urine flow may aid in establishing the type of micturition (urination) abnormality. Common findings, determined by ultrasound of the bladder, include a slow rate of flow, intermittent flow, and a large amount of urine retained in the bladder after urination. A normal test result should be 20-25 mL/s peak flow rate. A post-void residual urine greater than 50 ml is a significant amount of urine and increases the potential for recurring urinary tract infections. In adults older than 60 years, 50-100 ml of residual urine may remain after each voiding because of the decreased contractility of the detrusor muscle. In chronic retention, ultrasound of the bladder may show massive increase in bladder capacity (normal capacity is 400-600 ml).Non-neurogenic chronic urinary retention does not have a standardized definition; however, urine volumes >300mL can be used as an informal indicator. Diagnosis of urinary retention is conducted over a period of 6 months, with 2 separate measurements of urine volume 6 months apart. Measurements should have a PVR (post-void residual) volume of >300mL.Determining the serum prostate-specific antigen (PSA) may help diagnose or rule out prostate cancer, though this is also raised in BPH and prostatitis. A TRUS biopsy of the prostate (trans-rectal ultra-sound guided) can distinguish between these prostate conditions. Serum urea and creatinine determinations may be necessary to rule out backflow kidney damage. Cystoscopy may be needed to explore the urinary passage and rule out blockages.In acute cases of urinary retention where associated symptoms in the lumbar spine are present such as pain, numbness (saddle anesthesia), parasthesias, decreased anal sphincter tone, or altered deep tendon reflexes, an MRI of the lumbar spine should be considered to further assess cauda equina syndrome.
Complications
Acute urinary retention is a medical emergency and requires prompt treatment. The pain can be excruciating when urine is not able to flow out. Moreover, one can develop severe sweating, chest pain, anxiety and high blood pressure. Other patients may develop a shock-like condition and may require admission to a hospital. Serious complications of untreated urinary retention include bladder damage and chronic kidney failure. Urinary retention is a disorder treated in a hospital, and the quicker one seeks treatment, the fewer the complications.In the longer term, obstruction of the urinary tract may cause:
Bladder stones
Atrophy of the detrusor muscle (atonic bladder is an extreme form)
Hydronephrosis (congestion of the kidneys)
Hypertrophy of the detrusor muscle (the muscle that squeezes the bladder to empty it during urination)
Diverticula (formation of pouches) in the bladder wall (which can lead to stones and infection)
Treatment
In acute urinary retention, urinary catheterization, placement of a prostatic stent, or suprapubic cystostomy relieves the retention. In the longer term, treatment depends on the cause. BPH may respond to alpha blocker and 5-alpha-reductase inhibitor therapy, or surgically with prostatectomy or transurethral resection of the prostate (TURP).Use of alpha-blockers can provide relief of urinary retention following de-catheterization for both men and women. In case, if catheter cant be negotiated, suprapubic puncture can be done with lumbar puncture needle.
Medication
Some people with BPH are treated with medications. These include tamsulosin to relax smooth muscles in the bladder neck, and finasteride and dutasteride to decrease prostate enlargement. The drugs only work for mild cases of BPH but also have mild side effects. Some of the medications decrease libido and may cause dizziness, fatigue and lightheadedness.
Catheter
Acute urinary retention is treated by placement of a urinary catheter (small thin flexible tube) into the bladder. This can be either an intermittent catheter or a Foley catheter that is placed with a small inflatable bulb that holds the catheter in place.Intermittent catheterization can be done by a health care professional or by the person themselves (clean intermittent self catheterization). Intermittent catheterization performed at the hospital is a sterile technique. Patients can be taught to use a self catheterization technique in one simple demonstration, and that reduces the rate of infection from long-term Foley catheters. Self catheterization requires doing the procedure periodically during the day, the frequency depending on fluid intake and bladder capacity. If fluid intake/outflow is around 1.5 litres per day, this would typically be performed roughly three times per day, i.e. roughly every six to eight hours during the day, more frequently when fluid intake is higher and/or bladder capacity lower.
For acute urinary retention, treatment requires urgent placement of a urinary catheter. A permanent urinary catheter may cause discomfort and pain that can last several days.
Older people with ongoing problems may require continued intermittent self catheterization (CISC). CISC has a lower infection risk compared to catheterization techniques that stay within the body. Challenges with CISC include compliance issues as some people may not be able to place the catheter themselves.
Surgery
The chronic form of urinary retention may require some type of surgical procedure. While both procedures are relatively safe, complications can occur.
In most patients with benign prostate hyperplasia (BPH), a procedure known as transurethral resection of the prostate (TURP) may be performed to relieve bladder obstruction. Surgical complications from TURP include a bladder infection, bleeding from the prostate, scar formation, inability to hold urine, and inability to have an erection. The majority of these complications are short lived, and most individuals recover fully within 6–12 months.
Sitting voiding position
A meta-analysis on the influence of voiding position on urodynamics in males with lower urinary tract symptoms showed that in the sitting position, the residual urine in the bladder was significantly reduced, the maximum urinary flow was increased, and the voiding time was decreased. For healthy males, no influence was found on these parameters, meaning that they can urinate in either position.
Epidemiology
Urinary retention is a common disorder in elderly males. The most common cause of urinary retention is BPH. This disorder starts around age 50 and symptoms may appear after 10–15 years. BPH is a progressive disorder and narrows the neck of the bladder leading to urinary retention. By the age of 70, almost 10 percent of males have some degree of BPH and 33% have it by the eighth decade of life. While BPH rarely causes sudden urinary retention, the condition can become acute in the presence of certain medications including antihypertensives, antihistamines, and antiparkinson medications, and after spinal anaesthesia or stroke.In young males, the most common cause of urinary retention is infection of the prostate (acute prostatitis). The infection is acquired during sexual intercourse and presents with low back pain, penile discharge, low grade fever and an inability to pass urine. The exact number of individuals with acute prostatitis is unknown, because many do not seek treatment. In the US, at least 1–3 percent of males under the age of 40 develop urinary difficulty as a result of acute prostatitis. Most physicians and other health care professionals are aware of these disorders. Worldwide, both BPH and acute prostatitis have been found in males of all races and ethnic backgrounds. Cancers of the urinary tract can cause urinary obstruction but the process is more gradual. Cancer of the bladder, prostate or ureters can gradually obstruct urine output. Cancers often present with blood in the urine, weight loss, lower back pain or gradual distension in the flanks.Urinary retention in females is uncommon, occurring 1 in 100,000 every year, with a female-to-male incidence rate of 1:13. It is usually transient. The causes of UR in women can be multi-factorial, and can be postoperative and postpartum. Prompt urethral catheterization usually resolves the problem.
References
== External links == |
Cochlear hydrops | Cochlear hydrops (or cochlear Menieres or cochlear endolymphatic hydrops) is a condition of the inner ear involving a pathological increase of fluid affecting the cochlea. This results in swelling that can lead to hearing loss or changes in hearing perception. It is a form of endolymphatic hydrops and related to Menieres disease. Cochlear hydrops refers to a case of inner-ear hydrops that only involves auditory symptoms and does not cause vestibular issues.
Cause and behavior
Cochlear hydrops refers to an increase in endolymphatic fluid in the inner ear. This build-up is either due to an overproduction or insufficient drainage of endolymph in the constant regulation of fluid in the inner ear. Usually, only one ear is affected. The root cause of the process is unclear and may vary from patient to patient, but can have auto-immune, viral, and/or allergic triggers, among others.The build-up of endolymph creates pressure in the scala media. This causes its diameter to increase, and the vestibular membrane to curve outwards in the direction of the vestibule. The changes to the membrane can result in changes to either the hearing perception or hearing threshold of a patient.Episodes are usually cyclical and symptoms fluctuate through time. Patients may be symptom-free between episodes, which themselves may progressively worsen, improve, or remain constant in severity or duration. For some, permanent damage occurs, and they may be left with long-term hearing loss, hearing distortion, tinnitus, and/or a feeling of fullness in the affected ear(s).A study looking at spiral ganglion cell counts compared to hair cell counts in the inner ear of patients who had Menieres disease found that they maintained more hair cells than spinal ganglion cells. Thus, it could be possible that hydrops affects auditory nerves more than hair cells. In contrast, a 2021 article by Richard Gacek posits that the hearing loss is actually caused by toxic nucleic acids that are released to the outer hair cells: "Since the outer hair cells (OHC) are freely surrounded by perilymph, their walls and nerve terminals are also bathed in this fluid. The few type-II spiral ganglion cells in contact with the OHC are unlikely to play a significant role in hearing loss because of their low numbers and the lack of a known connection to the central auditory pathway."
Symptoms
Cochlear hydrops preferentially affects the apex of the cochlea where low-frequency sounds are interpreted. Due to the fluid imbalance in this area, parts of the cochlea are stretched or under more tension than usual, which can lead to distortions of sound, changes in pitch perception, or hearing loss, all usually in the low frequencies.
Common symptoms include:
Low-frequency sensorineural hearing loss.
A feeling of fullness in the ear.
Tinnitus (ringing in the ear).
Diplacusis (the perception of sound being a different pitch in one ear).
Hyperacusis (an intolerance to loud sounds).
Depression or anxiety that the condition will worsen or progress to Menieres disease.As with Menieres disease, atypical, early, or mild cases may only present some symptoms.
Diagnosis
Diagnosis is based on symptoms and a hearing test that documents a loss in the low and mid frequencies, usually only in one ear. For patients with mild or atypical hydrops, the hearing thresholds may be normal, but they may experience a subjective, unilateral distortion of sounds in lower frequencies, such as diplacusis or that voices are sounding "robotic". Patients may also mention a feeling of pressure or fullness in the ear.To objectively test for the presence of hydrops, an electrocochleography (or ECOG) procedure can be done to detect elevated inner ear pressure. It is also possible to reveal the presence of hydrops with an MRI.If vertigo is experienced, the diagnosis progresses to Menieres disease. This occurs if the fluid increase leads to a leak or rupture of the membranes in the inner ear, causing a mixture of perilymph and endolymph.
Treatment
Treatment for cochlear hydrops is the same as for Menieres disease. Currently, no cure exists for either.If a patient has undergone sudden sensorineural hearing loss, a course of steroids is often prescribed in an attempt to recover the hearing. Steroids may be injected directly through the eardrum.Like Menieres Disease, a low salt diet is recommended as a preventative measure. A diuretic may be prescribed to help lower salt content.Betahistine is the most widely prescribed medication for the treatment of Menieres disease. The drug is thought to increase blood flow to the inner ear and to prevent the frequency and intensity of episodes. While Betahistine is considered safe, there is insufficient evidence that it is an effective treatment. It is not FDA approved in the United States, yet has still been clinically observed to benefit patients, and is considered safer and more effective than diuretics. Betahistine at high doses (such as 144 mg/day) can yield similar vertigo control as intratympanic dexamethasone.Antivirals have been proven effective for those who suspect a viral cause for their cochlear Hydrops.For some, surgery may be effective, such as an endolymphatic sac decompression. Surgery is often reserved for cases where other measures have proven ineffective and/or when vestibular issues are the main complaint, as it runs the risk of causing hearing or other nerve damage.
Prognosis
The symptoms of cochlear hydrops fluctuate, and the condition tends to stabilize or go away on its own after several years. However, because the organ of Corti undergoes stress during the hydrops episodes, long-term hearing loss, tinnitus, or hyperacusis is possible.
It is considered by some that cochlear hydrops is an early form of Menieres disease. However, while all people with Menieres disease have some form of hydrops, the majority of cochlear hydrops patients do not go on to develop Menieres disease. It takes an average of one year from the onset of symptoms for someone to develop full Menieres disease, if at all.
Relationship to Menieres Disease
The data on how often progression to Menieres disease occurs is mixed, but the majority of recent studies suggest a low likelihood.
A 1984 study from Japan looked at patients with Menieres disease and classified them into subcategories based on their first symptoms. The study found that the majority of patients with Menieres disease (104 out of 163, or 63.80%) presented vertigo with their first symptoms, and only 59 out of 163 (36.19%) of patients presented with cochlear symptoms first, such as "tinnitus or deafness." However, the study found that 59 out of 74 (79.72%) patients who started out with a cochlear hydrops diagnosis progressed to Menieres disease, and concluded that "cochlear Menieres disease frequently develops into Menieres disease."Conversely, A 2006 study from doctors at the House Ear Institute found that “conversion from cochlear hydrops to Menieres disease occurred in 33%” of diagnosed patients in a study including 46 subjects. A 2009 study from Japan found that only about 10% of their diagnosed patients with sudden low-frequency hearing loss (SLFHL) went on to develop full Menieres disease, and about 18% with recurring SLFHL developed Menieres disease. From this study, about 70% of patients who did not develop Menieres Disease maintained their hearing in the end. 30% went on to have lasting hearing difficulty, reported from a ten-year follow-up.A 2018 study from Korea found the chance of progression to Menieres disease of all participants with SLFHL to be 9.38% with an average progression time of 1.7±1.4 years, but when limited to patients with recurring symptoms "it was confirmed that about half (46.88%) of them progressed to Menieres disease." However, the study was said to have limitations as "hearing fluctuations and the possibility of transitioning to Menieres disease in the non-relapse group could not be completely ruled out."
== References == |
Dysmorphic feature | A dysmorphic feature is an abnormal difference in body structure. It can be an isolated finding in an otherwise normal individual, or it can be related to a congenital disorder, genetic syndrome or birth defect. Dysmorphology is the study of dysmorphic features, their origins and proper nomenclature. One of the key challenges in identifying and describing dysmorphic features is the use and understanding of specific terms between different individuals. Clinical geneticists and pediatricians
are usually those most closely involved with the identification and description of dysmorphic features, as most are apparent during childhood.
Dysmorphic features can vary from isolated, mild anomalies such as clinodactyly or synophrys to severe congenital anomalies, such as heart defects and holoprosencephaly. In some cases, dysmorphic features are part of a larger clinical picture, sometimes known as a sequence, syndrome or association. Recognizing the patterns of dysmorphic features is an important part of a geneticists diagnostic process, as many genetic disease present with a common collection of features. There are several commercially available databases that allow clinicians to input their observed features in a patient to generate a differential diagnosis. These databases are not infallible, as they require on the clinician to provide their own experience, particularly when the observed clinical features are general. A male child with short stature and hypertelorism could have several different disorders, as these findings are not highly specific. However a finding such as 2,3-toe syndactyly raises the index of suspicion for Smith-Lemli-Opitz Syndrome.Most open source projects that perform phenotype-driven disease or gene prioritization work with the terminology of the Human Phenotype Ontology. This controlled vocabulary can be used to describe the clinical features of a patient and is suitable for machine learning approaches. Publicly accessible databases that labs use to deposit their diagnostic findings, such as ClinVar, can be used to build knowledge graphs to explore the clinical feature space.Dysmorphic features are invariably present from birth, although some are not immediately apparent upon visual inspection. They can be divided into groups based on their origin, including malformations (abnormal development), disruptions (damage to previously normal tissue), deformations (damage caused by an outside physical force) and dysplasias (abnormal growth or organization within a tissue).
Dysmorphology
Dysmorphology is the discipline of using dysmorphic features in the diagnostic workup and delineation of syndromic disorders. In the recent years advances in computer vision have also resulted in several deep learning approaches that assist geneticists in the study of the facial gestalt.
== References == |
Experimental autoimmune encephalomyelitis | Experimental autoimmune encephalomyelitis, sometimes experimental allergic encephalomyelitis (EAE), is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodents and is widely studied as an animal model of the human CNS demyelinating diseases, including multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). EAE is also the prototype for T-cell-mediated autoimmune disease in general.EAE was motivated by observations during the convalescence from viral diseases by Thomas M. Rivers, D. H. Sprunt and G. P. Berry in 1933. Their findings upon a transfer of inflamed patient tissue to primates was published in the Journal of Experimental Medicine. An acute monophasic illness, it has been suggested that EAE is far more similar to ADEM than MS.
Types of EAE
EAE can be induced in a number of species, including mice, rats, guinea pigs, rabbits and primates.
The most commonly used antigens in rodents are spinal cord homogenate (SCH), purified myelin, myelin protein such as MBP, PLP, and MOG, or peptides of these proteins, all resulting in distinct models with different disease characteristics regarding both immunology and pathology. It may also be induced by the passive transfer of T cells specifically reactive to these myelin antigens.Depending on the antigen used and the genetic make-up of the animal, rodents can display a monophasic bout of EAE, a relapsing-remitting form, or chronic EAE. The typical susceptible rodent will debut with clinical symptoms around two weeks after immunization and present with a relapsing-remitting disease. The archetypical first clinical symptom is weakness of tail tonus that progresses to paralysis of the tail, followed by a progression up the body to affect the hind limbs and finally the forelimbs.However, similar to MS, the disease symptoms reflect the anatomical location of the inflammatory lesions, and may also include emotional lability, sensory loss, optic neuritis, difficulties with coordination and balance (ataxia), and muscle weakness and spasms. Recovery from symptoms can be complete or partial and the time varies with symptoms and disease severity. Depending on the relapse-remission intervals, rats can have up to three bouts of disease within an experimental period.
In mice
Demyelination is produced by injection of brain extracts, CNS proteins (such as myelin basic protein), or peptides from such protein emulsified in an adjuvant such as complete Freunds adjuvant. The presence of the adjuvant allows the generation of inflammatory responses to the protein/peptides. In many protocols, mice are coinjected with pertussis toxin to break down the blood-brain barrier and allow immune cells access to the CNS tissue. This immunisation leads to multiple small disseminated lesions of demyelination (as well as micro-necroses) in the brain and spinal cord and the onset of clinical symptoms.Although sharing some features, mostly demyelination, this model, first introduced in the 1930s, differs from human MS in several ways. EAE either kills animals or leaves them with permanent disabilities; animals with EAE also suffer severe nerve inflammation, and the time course of EAE is entirely different from MS, being the main antigen (MBP) in charge. Some key differences between EAE in mice, and MS in humans include:
B-cells: Some research points to anti-CD20 B-cells being the basis of the autoimmune attacks. This has been shown to be completely different in EAE and MS.
oxidative injury: Mitochondrial injury is seen in EAE and MS, but mitochondrial gene deletions have so far only been detected in MS lesions.
microglia behaviour: In contrast to experimental models of inflammatory demyelination, lesion formation in multiple sclerosis occurs on a background of pro-inflammatory microglia activation, which is seen already in the normal white matter of age-matched controls, and this may contribute to neurodegeneration in the disease.
pathological patterns: EAE is unable to reproduce MS pathological patterns III and IV.
Secondary damage
Given that some conditions as MS show cortical damage together with the WM damage, there has been interest if this can appear as a secondary damage of the WM.
Human Anti-MOG in mice
Anti-MOG associated encephalomyelitis can be passed from humans to mice, inducing MS type II demyelination (pattern II)
Immunogenetic interactions
Deficiency of TBX21 or STAT4 provides resistance against EAE, while interferon-γ-, interferon-γ-receptor-, interleukin-12 subunit α-, interleukin 12 receptor, β 2 subunit-, and interleukin 18-deficiency exacerbated disease.
In humans
Sometimes the human equivalent to EAE has been triggered in humans by accident or medical mistake. The reactions have been diverse according to the sources of the disease The researchers in the last report have termed the condition "human autoimmune encephalitis" (HAE).
The damage in the second report fulfilled all pathological diagnostic criteria of MS and can therefore be classified as MS in its own right. The lesions were classified as pattern II in the Lucchinetti system. This case of human EAE also showed Dawson fingers.Using the confluent demyelination as barrier between MS and ADEM, some other reports about EAE in humans classify its effects as ADEM but not always. In Japanese patients exposed to rabies vaccine that contained neural tissue, the clinical presentation resembled ADEM more than MS but the lesions were like acute multiple sclerosis (Uchimura and Shiraki, 1957).
Anti-TNF demyelination
Recent problems with monoclonal antibodies point to an involvement of tumor necrosis factor alpha in the multiple sclerosis onset. Specifically, a monoclonal antibody against TNF-α (adalimumab) has been reported to induce a MS-like diseaseAlso some experimental therapies for other diseases has produced MS artificially in patients. Specifically, monoclonal antibodies treating cancer like pembrolizumab and infliximab have been reported to produce MS artificially.
Specific forms of EAE
Since the discovery of the four lucchinetti patterns, new EAE models have been published, specifically mimicking the patterns I and II. DTH-EAE for pattern I (T cell and macrophage-mediated delayed-type hypersensitivity) and fMOG-EAE for pattern II (antibody-mediated focal myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalitis)Also a model for pattern III lesions has been developed in which mitochondrial metabolism is impaired, resulting in a tissue energy deficiency, a mechanism later termed "virtual hypoxia". The demyelination, characterized by loss of myelin-associated glycoprotein, has been described as "hypoxia-like". Thanks to these pattern III models some specific experimental treatments have appearedThe model for primary progressive MS is the Theilers virus model. This model presents features not available in others, like microglial activation.
Alternatives
Recently it has been found that CSF from MS patients can carry the disease to rodents, opening the door to an alternative model.
References
External links
Mult-sclerosis.org: information on EAE |
Connective tissue nevus | A connective tissue nevus may be present at birth or appear within the first few years, is elevated, soft to firm, varying from 0.5 to several centimeters in diameter, and may be grouped, linear, or irregularly distributed.: 993
See also
Skin lesion
List of cutaneous conditions
References
== External links == |
Escherichia coli | Escherichia coli (), also known as E. coli (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus Escherichia that is commonly found in the lower intestine of warm-blooded organisms. Most E. coli strains are harmless, but some serotypes (EPEC, ETEC etc.) can cause serious food poisoning in their hosts, and are occasionally responsible for food contamination incidents that prompt product recalls. The harmless strains are part of the normal microbiota of the gut, and can benefit their hosts by producing vitamin K2, and preventing colonisation of the intestine with pathogenic bacteria, having a mutualistic relationship. E. coli is expelled into the environment within faecal matter. The bacterium grows massively in fresh faecal matter under aerobic conditions for three days, but its numbers decline slowly afterwards.E. coli and other facultative anaerobes constitute about 0.1% of gut microbiota, and fecal–oral transmission is the major route through which pathogenic strains of the bacterium cause disease. Cells are able to survive outside the body for a limited amount of time, which makes them potential indicator organisms to test environmental samples for fecal contamination. A growing body of research, though, has examined environmentally persistent E. coli which can survive for many days and grow outside a host.The bacterium can be grown and cultured easily and inexpensively in a laboratory setting, and has been intensively investigated for over 60 years. E. coli is a chemoheterotroph whose chemically defined medium must include a source of carbon and energy. E. coli is the most widely studied prokaryotic model organism, and an important species in the fields of biotechnology and microbiology, where it has served as the host organism for the majority of work with recombinant DNA. Under favourable conditions, it takes as little as 20 minutes to reproduce.
Biology and biochemistry
Type and morphology
E. coli is a Gram-negative, facultative anaerobe, nonsporulating coliform bacterium. Cells are typically rod-shaped, and are about 2.0 μm long and 0.25–1.0 μm in diameter, with a cell volume of 0.6–0.7 μm3. Antibiotics can effectively treat E. coli infections outside the digestive tract and most intestinal infections but are not used to treat intestinal infections by one strain of these bacteria. The flagella which allow the bacteria to swim have a peritrichous arrangement. It also attaches and effaces to the microvilli of the intestines via an adhesion molecule known as intimin.
Metabolism
E. coli can live on a wide variety of substrates and uses mixed acid fermentation in anaerobic conditions, producing lactate, succinate, ethanol, acetate, and carbon dioxide. Since many pathways in mixed-acid fermentation produce hydrogen gas, these pathways require the levels of hydrogen to be low, as is the case when E. coli lives together with hydrogen-consuming organisms, such as methanogens or sulphate-reducing bacteria.In addition, E. colis metabolism can be rewired to solely use CO2 as the source of carbon for biomass production. In other words, this obligate heterotrophs metabolism can be altered to display autotrophic capabilities by heterologously expressing carbon fixation genes as well as formate dehydrogenase and conducting laboratory evolution experiments. This may be done by using formate to reduce electron carriers and supply the ATP required in anabolic pathways inside of these synthetic autotrophs.E. coli have three native glycolytic pathways: EMPP, EDP, and OPPP. The EMPP employs ten enzymatic steps to yield two pyruvates, two ATP, and two NADH per glucose molecule while OPPP serves as an oxidation route for NADPH synthesis. Although the EDP is the more thermodynamically favourable of the three pathways, E. coli do not use the EDP for glucose metabolism, relying mainly on the EMPP and the OPPP. The EDP mainly remains inactive except for during growth with gluconate.
Catabolite repression
When growing in the presence of a mixture of sugars, bacteria will often consume the sugars sequentially through a process known as catabolite repression. By repressing the expression of the genes involved in metabolizing the less preferred sugars, cells will usually first consume the sugar yielding the highest growth rate, followed by the sugar yielding the next highest growth rate, and so on. In doing so the cells ensure that their limited metabolic resources are being used to maximize the rate of growth. The well-used example of this with E. coli involves the growth of the bacterium on glucose and lactose, where E. coli will consume glucose before lactose. Catabolite repression has also been observed in E. coli in the presence of other non-glucose sugars, such as arabinose and xylose, sorbitol, rhamnose, and ribose. In E. coli, glucose catabolite repression is regulated by the phosphotransferase system, a multi-protein phosphorylation cascade that couples glucose uptake and metabolism.
Culture growth
Optimum growth of E. coli occurs at 37 °C (99 °F), but some laboratory strains can multiply at temperatures up to 49 °C (120 °F). E. coli grows in a variety of defined laboratory media, such as lysogeny broth, or any medium that contains glucose, ammonium phosphate monobasic, sodium chloride, magnesium sulfate, potassium phosphate dibasic, and water. Growth can be driven by aerobic or anaerobic respiration, using a large variety of redox pairs, including the oxidation of pyruvic acid, formic acid, hydrogen, and amino acids, and the reduction of substrates such as oxygen, nitrate, fumarate, dimethyl sulfoxide, and trimethylamine N-oxide. E. coli is classified as a facultative anaerobe. It uses oxygen when it is present and available. It can, however, continue to grow in the absence of oxygen using fermentation or anaerobic respiration. The ability to continue growing in the absence of oxygen is an advantage to bacteria because their survival is increased in environments where water predominates.
Cell cycle
The bacterial cell cycle is divided into three stages. The B period occurs between the completion of cell division and the beginning of DNA replication. The C period encompasses the time it takes to replicate the chromosomal DNA. The D period refers to the stage between the conclusion of DNA replication and the end of cell division. The doubling rate of E. coli is higher when more nutrients are available. However, the length of the C and D periods do not change, even when the doubling time becomes less than the sum of the C and D periods. At the fastest growth rates, replication begins before the previous round of replication has completed, resulting in multiple replication forks along the DNA and overlapping cell cycles.The number of replication forks in fast growing E. coli typically follows 2n (n = 1, 2 or 3). This only happens if replication is initiated simultaneously from all origins of replications, and is referred to as synchronous replication. However, not all cells in a culture replicate synchronously. In this case cells do not have multiples of two replication forks. Replication initiation is then referred to being asynchronous. However, asynchrony can be caused by mutations to for instance DnaA or DnaA initiator-associating protein DiaA.
Genetic adaptation
E. coli and related bacteria possess the ability to transfer DNA via bacterial conjugation or transduction, which allows genetic material to spread horizontally through an existing population. The process of transduction, which uses the bacterial virus called a bacteriophage, is where the spread of the gene encoding for the Shiga toxin from the Shigella bacteria to E. coli helped produce E. coli O157:H7, the Shiga toxin-producing strain of E. coli.
Diversity
E. coli encompasses an enormous population of bacteria that exhibit a very high degree of both genetic and phenotypic diversity. Genome sequencing of many isolates of E. coli and related bacteria shows that a taxonomic reclassification would be desirable. However, this has not been done, largely due to its medical importance, and E. coli remains one of the most diverse bacterial species: only 20% of the genes in a typical E. coli genome is shared among all strains.In fact, from the more constructive point of view, the members of genus Shigella (S. dysenteriae, S. flexneri, S. boydii, and S. sonnei) should be classified as E. coli strains, a phenomenon termed taxa in disguise. Similarly, other strains of E. coli (e.g. the K-12 strain commonly used in recombinant DNA work) are sufficiently different that they would merit reclassification.
A strain is a subgroup within the species that has unique characteristics that distinguish it from other strains. These differences are often detectable only at the molecular level; however, they may result in changes to the physiology or lifecycle of the bacterium. For example, a strain may gain pathogenic capacity, the ability to use a unique carbon source, the ability to take upon a particular ecological niche, or the ability to resist antimicrobial agents. Different strains of E. coli are often host-specific, making it possible to determine the source of fecal contamination in environmental samples. For example, knowing which E. coli strains are present in a water sample allows researchers to make assumptions about whether the contamination originated from a human, another mammal, or a bird.
Serotypes
A common subdivision system of E. coli, but not based on evolutionary relatedness, is by serotype, which is based on major surface antigens (O antigen: part of lipopolysaccharide layer; H: flagellin; K antigen: capsule), e.g. O157:H7). It is, however, common to cite only the serogroup, i.e. the O-antigen. At present, about 190 serogroups are known. The common laboratory strain has a mutation that prevents the formation of an O-antigen and is thus not typeable.
Genome plasticity and evolution
Like all lifeforms, new strains of E. coli evolve through the natural biological processes of mutation, gene duplication, and horizontal gene transfer; in particular, 18% of the genome of the laboratory strain MG1655 was horizontally acquired since the divergence from Salmonella. E. coli K-12 and E. coli B strains are the most frequently used varieties for laboratory purposes. Some strains develop traits that can be harmful to a host animal. These virulent strains typically cause a bout of diarrhea that is often self-limiting in healthy adults but is frequently lethal to children in the developing world. More virulent strains, such as O157:H7, cause serious illness or death in the elderly, the very young, or the immunocompromised.The genera Escherichia and Salmonella diverged around 102 million years ago (credibility interval: 57–176 mya), an event unrelated to the much earlier (see Synapsid) divergence of their hosts: the former being found in mammals and the latter in birds and reptiles. This was followed by a split of an Escherichia ancestor into five species (E. albertii, E. coli, E. fergusonii, E. hermannii, and E. vulneris). The last E. coli ancestor split between 20 and 30 million years ago.
The long-term evolution experiments using E. coli, begun by Richard Lenski in 1988, have allowed direct observation of genome evolution over more than 65,000 generations in the laboratory. For instance, E. coli typically do not have the ability to grow aerobically with citrate as a carbon source, which is used as a diagnostic criterion with which to differentiate E. coli from other, closely, related bacteria such as Salmonella. In this experiment, one population of E. coli unexpectedly evolved the ability to aerobically metabolize citrate, a major evolutionary shift with some hallmarks of microbial speciation.
In the microbial world, a relationship of predation can be established similar to that observed in the animal world. Considered, it has been seen that E. coli is the prey of multiple generalist predators, such as Myxococcus xanthus. In this predator-prey relationship, a parallel evolution of both species is observed through genomic and phenotypic modifications, in the case of E. coli the modifications are modified in two aspects involved in their virulence such as mucoid production (excessive production of exoplasmic acid alginate ) and the suppression of the OmpT gene, producing in future generations a better adaptation of one of the species that is counteracted by the evolution of the other, following a co-evolutionary model demonstrated by the Red Queen hypothesis.
Neotype strain
E. coli is the type species of the genus (Escherichia) and in turn Escherichia is the type genus of the family Enterobacteriaceae, where the family name does not stem from the genus Enterobacter + "i" (sic.) + "aceae", but from "enterobacterium" + "aceae" (enterobacterium being not a genus, but an alternative trivial name to enteric bacterium).The original strain described by Escherich is believed to be lost, consequently a new type strain (neotype) was chosen as a representative: the neotype strain is U5/41T, also known under the deposit names DSM 30083, ATCC 11775, and NCTC 9001, which is pathogenic to chickens and has an O1:K1:H7 serotype. However, in most studies, either O157:H7, K-12 MG1655, or K-12 W3110 were used as a representative E. coli. The genome of the type strain has only lately been sequenced.
Phylogeny of E. coli strains
Many strains belonging to this species have been isolated and characterised. In addition to serotype (vide supra), they can be classified according to their phylogeny, i.e. the inferred evolutionary history, as shown below where the species is divided into six groups. Particularly the use of whole genome sequences yields highly supported phylogenies. Based on such data, five subspecies of E. coli were distinguished.The link between phylogenetic distance ("relatedness") and pathology is small, e.g. the O157:H7 serotype strains, which form a clade ("an exclusive group")—group E below—are all enterohaemorragic strains (EHEC), but not all EHEC strains are closely related. In fact, four different species of Shigella are nested among E. coli strains (vide supra), while E. albertii and E. fergusonii are outside this group.
Indeed, all Shigella species were placed within a single subspecies of E. coli in a phylogenomic study that included the type strain, and for this reason an according reclassification is difficult.
All commonly used research strains of E. coli belong to group A and are derived mainly from Cliftons K-12 strain (λ+ F+; O16) and to a lesser degree from dHerelles Bacillus coli strain (B strain) (O7).
Genomics
The first complete DNA sequence of an E. coli genome (laboratory strain K-12 derivative MG1655) was published in 1997. It is a circular DNA molecule 4.6 million base pairs in length, containing 4288 annotated protein-coding genes (organized into 2584 operons), seven ribosomal RNA (rRNA) operons, and 86 transfer RNA (tRNA) genes. Despite having been the subject of intensive genetic analysis for about 40 years, many of these genes were previously unknown. The coding density was found to be very high, with a mean distance between genes of only 118 base pairs. The genome was observed to contain a significant number of transposable genetic elements, repeat elements, cryptic prophages, and bacteriophage remnants.More than three hundred complete genomic sequences of Escherichia and Shigella species are known. The genome sequence of the type strain of E. coli was added to this collection before 2014. Comparison of these sequences shows a remarkable amount of diversity; only about 20% of each genome represents sequences present in every one of the isolates, while around 80% of each genome can vary among isolates. Each individual genome contains between 4,000 and 5,500 genes, but the total number of different genes among all of the sequenced E. coli strains (the pangenome) exceeds 16,000. This very large variety of component genes has been interpreted to mean that two-thirds of the E. coli pangenome originated in other species and arrived through the process of horizontal gene transfer.
Gene nomenclature
Genes in E. coli are usually named in accordance with the uniform nomenclature proposed by Demerec et al. Gene names are 3-letter acronyms that derive from their function (when known) or mutant phenotype and are italicized. When multiple genes have the same acronym, the different genes are designated by a capital later that follows the acronym and is also italicized. For instance, recA is named after its role in homologous recombination plus the letter A. Functionally related genes are named recB, recC, recD etc. The proteins are named by uppercase acronyms, e.g. RecA, RecB, etc. When the genome of E. coli strain K-12 substr. MG1655 was sequenced, all known or predicted protein-coding genes were numbered (more or less) in their order on the genome and abbreviated by b numbers, such as b2819 (= recD). The "b" names were created after Fred Blattner, who led the genome sequence effort. Another numbering system was introduced with the sequence of another E. coli K-12 substrain, W3110, which was sequenced in Japan and hence uses numbers starting by JW... (Japanese W3110), e.g. JW2787 (= recD). Hence, recD = b2819 = JW2787. Note, however, that most databases have their own numbering system, e.g. the EcoGene database uses EG10826 for recD. Finally, ECK numbers are specifically used for alleles in the MG1655 strain of E. coli K-12. Complete lists of genes and their synonyms can be obtained from databases such as EcoGene or Uniprot.
Proteomics
Proteome
The genome sequence of E. coli predicts 4288 protein-coding genes, of which 38 percent initially had no attributed function. Comparison with five other sequenced microbes reveals ubiquitous as well as narrowly distributed gene families; many families of similar genes within E. coli are also evident. The largest family of paralogous proteins contains 80 ABC transporters. The genome as a whole is strikingly organized with respect to the local direction of replication; guanines, oligonucleotides possibly related to replication and recombination, and most genes are so oriented. The genome also contains insertion sequence (IS) elements, phage remnants, and many other patches of unusual composition indicating genome plasticity through horizontal transfer.Several studies have experimentally investigated the proteome of E. coli. By 2006, 1,627 (38%) of the predicted proteins (open reading frames, ORFs) had been identified experimentally. Mateus et al. 2020 detected 2,586 proteins with at least 2 peptides (60% of all proteins).
Post-translational modifications (PTMs)
Although much fewer bacterial proteins seem to have post-translational modifications (PTMs) compared to eukaryotic proteins, a substantial number of proteins are modified in E. coli. For instance, Potel et al. (2018) found 227 phosphoproteins of which 173 were phosphorylated on histidine. Interestingly, the majority of phosphorylated amino acids were serine (1,220 sites) with only 246 sites on histidine and 501 phosphorylated theronines and 162 tyrosines.
Interactome
The interactome of E. coli has been studied by affinity purification and mass spectrometry (AP/MS) and by analyzing the binary interactions among its proteins.
Protein complexes. A 2006 study purified 4,339 proteins from cultures of strain K-12 and found interacting partners for 2,667 proteins, many of which had unknown functions at the time. A 2009 study found 5,993 interactions between proteins of the same E. coli strain, though these data showed little overlap with those of the 2006 publication.Binary interactions. Rajagopala et al. (2014) have carried out systematic yeast two-hybrid screens with most E. coli proteins, and found a total of 2,234 protein-protein interactions. This study also integrated genetic interactions and protein structures and mapped 458 interactions within 227 protein complexes.
Normal microbiota
E. coli belongs to a group of bacteria informally known as coliforms that are found in the gastrointestinal tract of warm-blooded animals. E. coli normally colonizes an infants gastrointestinal tract within 40 hours of birth, arriving with food or water or from the individuals handling the child. In the bowel, E. coli adheres to the mucus of the large intestine. It is the primary facultative anaerobe of the human gastrointestinal tract. (Facultative anaerobes are organisms that can grow in either the presence or absence of oxygen.) As long as these bacteria do not acquire genetic elements encoding for virulence factors, they remain benign commensals.
Therapeutic use
Due to the low cost and speed with which it can be grown and modified in laboratory settings, E. coli is a popular expression platform for the production of recombinant proteins used in therapeutics. One advantage to using E. coli over another expression platform is that E. coli naturally does not export many proteins into the periplasm, making it easier to recover a protein of interest without cross-contamination. The E. coli K-12 strains and their derivatives (DH1, DH5α, MG1655, RV308 and W3110) are the strains most widely used by the biotechnology industry. Nonpathogenic E. coli strain Nissle 1917 (EcN), (Mutaflor) and E. coli O83:K24:H31 (Colinfant)) are used as probiotic agents in medicine, mainly for the treatment of various gastrointestinal diseases, including inflammatory bowel disease. It is thought that the EcN strain might impede the growth of opportunistic pathogens, including Salmonella and other coliform enteropathogens, through the production of microcin proteins the production of siderophores.
Role in disease
Most E. coli strains do not cause disease, naturally living in the gut, but virulent strains can cause gastroenteritis, urinary tract infections, neonatal meningitis, hemorrhagic colitis, and Crohns disease. Common signs and symptoms include severe abdominal cramps, diarrhea, hemorrhagic colitis, vomiting, and sometimes fever. In rarer cases, virulent strains are also responsible for bowel necrosis (tissue death) and perforation without progressing to hemolytic-uremic syndrome, peritonitis, mastitis, sepsis, and Gram-negative pneumonia. Very young children are more susceptible to develop severe illness, such as hemolytic uremic syndrome; however, healthy individuals of all ages are at risk to the severe consequences that may arise as a result of being infected with E. coli.Some strains of E. coli, for example O157:H7, can produce Shiga toxin (classified as a bioterrorism agent). The Shiga toxin causes inflammatory responses in target cells of the gut, leaving behind lesions which result in the bloody diarrhea that is a symptom of a Shiga toxin-producing E. coli (STEC) infection. This toxin further causes premature destruction of the red blood cells, which then clog the bodys filtering system, the kidneys, in some rare cases (usually in children and the elderly) causing hemolytic-uremic syndrome (HUS), which may lead to kidney failure and even death. Signs of hemolytic uremic syndrome include decreased frequency of urination, lethargy, and paleness of cheeks and inside the lower eyelids. In 25% of HUS patients, complications of nervous system occur, which in turn causes strokes. In addition, this strain causes the buildup of fluid (since the kidneys do not work), leading to edema around the lungs, legs, and arms. This increase in fluid buildup especially around the lungs impedes the functioning of the heart, causing an increase in blood pressure.Uropathogenic E. coli (UPEC) is one of the main causes of urinary tract infections. It is part of the normal microbiota in the gut and can be introduced in many ways. In particular for females, the direction of wiping after defecation (wiping back to front) can lead to fecal contamination of the urogenital orifices. Anal intercourse can also introduce this bacterium into the male urethra, and in switching from anal to vaginal intercourse, the male can also introduce UPEC to the female urogenital system.
Enterotoxigenic E. coli (ETEC) is the most common cause of travelers diarrhea, with as many as 840 million cases worldwide in developing countries each year. The bacteria, typically transmitted through contaminated food or drinking water, adheres to the intestinal lining, where it secretes either of two types of enterotoxins, leading to watery diarrhea. The rate and severity of infections are higher among children under the age of five, including as many as 380,000 deaths annually.In May 2011, one E. coli strain, O104:H4, was the subject of a bacterial outbreak that began in Germany. Certain strains of E. coli are a major cause of foodborne illness. The outbreak started when several people in Germany were infected with enterohemorrhagic E. coli (EHEC) bacteria, leading to hemolytic-uremic syndrome (HUS), a medical emergency that requires urgent treatment. The outbreak did not only concern Germany, but also 15 other countries, including regions in North America. On 30 June 2011, the German Bundesinstitut für Risikobewertung (BfR) (Federal Institute for Risk Assessment, a federal institute within the German Federal Ministry of Food, Agriculture and Consumer Protection) announced that seeds of fenugreek from Egypt were likely the cause of the EHEC outbreak.Some studies have demonstrated an absence of E. coli in the gut flora of subjects with the metabolic disorder Phenylketonuria. It is hypothesized that the absence of these normal bacterium impairs the production of the key vitamins B2 (riboflavin) and K2 (menaquinone) - vitamins which are implicated in many physiological roles in humans such as cellular and bone metabolism - and so contributes to the disorder.Carbapenem-resistant E. coli (carbapenemase-producing E. coli) that are resistant to the carbapenem class of antibiotics, considered the drugs of last resort for such infections. They are resistant because they produce an enzyme called a carbapenemase that disables the drug molecule.
Incubation period
The time between ingesting the STEC bacteria and feeling sick is called the "incubation period". The incubation period is usually 3–4 days after the exposure, but may be as short as 1 day or as long as 10 days. The symptoms often begin slowly with mild belly pain or non-bloody diarrhea that worsens over several days. HUS, if it occurs, develops an average 7 days after the first symptoms, when the diarrhea is improving.
Diagnosis
Diagnosis of infectious diarrhea and identification of antimicrobial resistance is performed using a stool culture with subsequent antibiotic sensitivity testing. It requires a minimum of 2 days and maximum of several weeks to culture gastrointestinal pathogens. The sensitivity (true positive) and specificity (true negative) rates for stool culture vary by pathogen, although a number of human pathogens can not be cultured. For culture-positive samples, antimicrobial resistance testing takes an additional 12–24 hours to perform.
Current point of care molecular diagnostic tests can identify E. coli and antimicrobial resistance in the identified strains much faster than culture and sensitivity testing. Microarray-based platforms can identify specific pathogenic strains of |
Escherichia coli | E. coli and E. coli-specific AMR genes in two hours or less with high sensitivity and specificity, but the size of the test panel (i.e., total pathogens and antimicrobial resistance genes) is limited. Newer metagenomics-based infectious disease diagnostic platforms are currently being developed to overcome the various limitations of culture and all currently available molecular diagnostic technologies.
Treatment
The mainstay of treatment is the assessment of dehydration and replacement of fluid and electrolytes. Administration of antibiotics has been shown to shorten the course of illness and duration of excretion of enterotoxigenic E. coli (ETEC) in adults in endemic areas and in travellers diarrhea, though the rate of resistance to commonly used antibiotics is increasing and they are generally not recommended. The antibiotic used depends upon susceptibility patterns in the particular geographical region. Currently, the antibiotics of choice are fluoroquinolones or azithromycin, with an emerging role for rifaximin. Oral rifaximin, a semisynthetic rifamycin derivative, is an effective and well-tolerated antibacterial for the management of adults with non-invasive travellers diarrhea. Rifaximin was significantly more effective than placebo and no less effective than ciprofloxacin in reducing the duration of diarrhea. While rifaximin is effective in patients with E. coli-predominant travellers diarrhea, it appears ineffective in patients infected with inflammatory or invasive enteropathogens.
Prevention
ETEC is the type of E. coli that most vaccine development efforts are focused on. Antibodies against the LT and major CFs of ETEC provide protection against LT-producing, ETEC-expressing homologous CFs. Oral inactivated vaccines consisting of toxin antigen and whole cells, i.e. the licensed recombinant cholera B subunit (rCTB)-WC cholera vaccine Dukoral, have been developed. There are currently no licensed vaccines for ETEC, though several are in various stages of development. In different trials, the rCTB-WC cholera vaccine provided high (85–100%) short-term protection. An oral ETEC vaccine candidate consisting of rCTB and formalin inactivated E. coli bacteria expressing major CFs has been shown in clinical trials to be safe, immunogenic, and effective against severe diarrhoea in American travelers but not against ETEC diarrhoea in young children in Egypt. A modified ETEC vaccine consisting of recombinant E. coli strains over-expressing the major CFs and a more LT-like hybrid toxoid called LCTBA, are undergoing clinical testing.Other proven prevention methods for E. coli transmission include handwashing and improved sanitation and drinking water, as transmission occurs through fecal contamination of food and water supplies. Additionally, thoroughly cooking meat and avoiding consumption of raw, unpasteurized beverages, such as juices and milk are other proven methods for preventing E. coli. Lastly, cross-contamination of utensils and work spaces should be avoided when preparing food.
Model organism in life science research
Because of its long history of laboratory culture and ease of manipulation, E. coli plays an important role in modern biological engineering and industrial microbiology. The work of Stanley Norman Cohen and Herbert Boyer in E. coli, using plasmids and restriction enzymes to create recombinant DNA, became a foundation of biotechnology.E. coli is a very versatile host for the production of heterologous proteins, and various protein expression systems have been developed which allow the production of recombinant proteins in E. coli. Researchers can introduce genes into the microbes using plasmids which permit high level expression of protein, and such protein may be mass-produced in industrial fermentation processes. One of the first useful applications of recombinant DNA technology was the manipulation of E. coli to produce human insulin.Many proteins previously thought difficult or impossible to be expressed in E. coli in folded form have been successfully expressed in E. coli. For example, proteins with multiple disulphide bonds may be produced in the periplasmic space or in the cytoplasm of mutants rendered sufficiently oxidizing to allow disulphide-bonds to form, while proteins requiring post-translational modification such as glycosylation for stability or function have been expressed using the N-linked glycosylation system of Campylobacter jejuni engineered into E. coli.Modified E. coli cells have been used in vaccine development, bioremediation, production of biofuels, lighting, and production of immobilised enzymes.Strain K-12 is a mutant form of E. coli that over-expresses the enzyme Alkaline Phosphatase (ALP). The mutation arises due to a defect in the gene that constantly codes for the enzyme. A gene that is producing a product without any inhibition is said to have constitutive activity. This particular mutant form is used to isolate and purify the aforementioned enzyme.Strain OP50 of Escherichia coli is used for maintenance of Caenorhabditis elegans cultures.
Strain JM109 is a mutant form of E. coli that is recA and endA deficient. The strain can be utilized for blue/white screening when the cells carry the fertility factor episome. Lack of recA decreases the possibility of unwanted restriction of the DNA of interest and lack of endA inhibit plasmid DNA decomposition. Thus, JM109 is useful for cloning and expression systems.
Model organism
E. coli is frequently used as a model organism in microbiology studies. Cultivated strains (e.g. E. coli K12) are well-adapted to the laboratory environment, and, unlike wild-type strains, have lost their ability to thrive in the intestine. Many laboratory strains lose their ability to form biofilms. These features protect wild-type strains from antibodies and other chemical attacks, but require a large expenditure of energy and material resources. E. coli is often used as a representative microorganism in the research of novel water treatment and sterilisation methods, including photocatalysis. By standard plate count methods, following sequential dilutions, and growth on agar gel plates, the concentration of viable organisms or CFUs (Colony Forming Units), in a known volume of treated water can be evaluated, allowing the comparative assessment of materials performance.In 1946, Joshua Lederberg and Edward Tatum first described the phenomenon known as bacterial conjugation using E. coli as a model bacterium, and it remains the primary model to study conjugation. E. coli was an integral part of the first experiments to understand phage genetics, and early researchers, such as Seymour Benzer, used E. coli and phage T4 to understand the topography of gene structure. Prior to Benzers research, it was not known whether the gene was a linear structure, or if it had a branching pattern.E. coli was one of the first organisms to have its genome sequenced; the complete genome of E. coli K12 was published by Science in 1997From 2002 to 2010, a team at the Hungarian Academy of Science created a strain of Escherichia coli called MDS42, which is now sold by Scarab Genomics of Madison, WI under the name of "Clean Genome E. coli", where 15% of the genome of the parental strain (E. coli K-12 MG1655) were removed to aid in molecular biology efficiency, removing IS elements, pseudogenes and phages, resulting in better maintenance of plasmid-encoded toxic genes, which are often inactivated by transposons. Biochemistry and replication machinery were not altered.
By evaluating the possible combination of nanotechnologies with landscape ecology, complex habitat landscapes can be generated with details at the nanoscale. On such synthetic ecosystems, evolutionary experiments with E. coli have been performed to study the spatial biophysics of adaptation in an island biogeography on-chip.
In other studies, non-pathogenic E. coli has been used as a model microorganism towards understanding the effects of simulated microgravity (on Earth) on the same.
Uses in biological computing
Since 1961, scientists proposed the idea of genetic circuits used for computational tasks. Collaboration between biologists and computing scientists has allowed designing digital logic gates on the metabolism of E. coli. As Lac operon is a two-stage process, genetic regulation in the bacteria is used to realize computing functions. The process is controlled at the transcription stage of DNA into messenger RNA.Studies are being performed attempting to program E. coli to solve complicated mathematics problems, such as the Hamiltonian path problem.A computer to control protein production of E. coli within yeast cells has been developed. A method has also been developed to use bacteria to behave as an LCD screen.In July 2017, separate experiments with E. coli published on Nature showed the potential of using living cells for computing tasks and storing information. A team formed with collaborators of the Biodesign Institute at Arizona State University and Harvard’s Wyss Institute for Biologically Inspired Engineering developed a biological computer inside E. coli that responded to a dozen inputs. The team called the computer "ribocomputer", as it was composed of ribonucleic acid. Meanwhile, Harvard researchers probed that is possible to store information in bacteria after successfully archiving images and movies in the DNA of living E. coli cells. In 2021, a team led by biophysicist Sangram Bagh realized a study with E. coli to solve 2 × 2 maze problems to probe the principle for distributed computing among cells.
History
In 1885, the German-Austrian pediatrician Theodor Escherich discovered this organism in the feces of healthy individuals. He called it Bacterium coli commune because it is found in the colon. Early classifications of prokaryotes placed these in a handful of genera based on their shape and motility (at that time Ernst Haeckels classification of bacteria in the kingdom Monera was in place).Bacterium coli was the type species of the now invalid genus Bacterium when it was revealed that the former type species ("Bacterium triloculare") was missing. Following a revision of Bacterium, it was reclassified as Bacillus coli by Migula in 1895 and later reclassified in the newly created genus Escherichia, named after its original discoverer, by Aldo Castellani and Albert John Chalmers.In 1996, the worlds worst to date outbreak of E. coli food poisoning occurred in Wishaw, Scotland, killing 21 people. This death toll was exceeded in 2011, when the 2011 Germany E. coli O104:H4 outbreak, linked to organic fenugreek sprouts, killed 53 people.
Uses
E. coli has several practical uses besides its use as a vector for genetic experiments and processes. For example, E. coli can be used to generate synthetic propane and recombinant human growth hormone.
See also
References
Databases and external links
EcoCyc – literature-based curation of the entire genome, and of transcriptional regulation, transporters, and metabolic pathways
Membranome database provides information about single-pass transmembrane proteins from E. coli and several other organisms
E. coli statistics
E. coli Infection | Causes & Risk Factors
Bacteriome E. coli interaction database
EcoGene (genome database and website dedicated to Escherichia coli K-12 substrain MG1655)
EcoSal Continually updated Web resource based on the classic ASM Press publication Escherichia coli and Salmonella: Cellular and Molecular Biology
ECODAB The structure of the O-antigens that form the basis of the serological classification of E. coli
Coli Genetic Stock Center Strains and genetic information on E. coli K-12
PortEco (formerly EcoliHub) – NIH-funded comprehensive data resource for E. coli K-12 and its phage, plasmids, and mobile genetic elements
EcoliWiki is the community annotation component of PortEco
RegulonDB RegulonDB is a model of the complex regulation of transcription initiation or regulatory network of the cell E. coli K-12.
Uropathogenic Escherichia coli (UPEC)
AlignACE Matrices that search for additional binding sites in the E. coli genomic sequence
E. coli on Protein Data Bank |
Toxic encephalopathy | Toxic encephalopathy is a neurologic disorder caused by exposure to neurotoxic organic solvents such as toluene, following exposure to heavy metals such as manganese, as a side effect of melarsoprol treatment for African trypanosomiasis, adverse effects to prescription drugs, or exposure to extreme concentrations of any natural toxin such as cyanotoxins found in shellfish or freshwater cyanobacteria crusts. Toxic encephalopathy can occur following acute or chronic exposure to neurotoxicants, which includes all natural toxins. Exposure to toxic substances can lead to a variety of symptoms, characterized by an altered mental status, memory loss, and visual problems. Toxic encephalopathy can be caused by various chemicals, some of which are commonly used in everyday life, or cyanotoxins which are bio-accumulated from harmful algal blooms (HABs) which have settled on the benthic layer of a waterbody. Toxic encephalopathy can permanently damage the brain and currently treatment is mainly just for the symptoms.
Signs and symptoms
"Encephalopathy" is a general term describing brain malfunctions and "toxic" asserts that the malfunction is caused by toxins on the brain. The most prominent characteristic of toxic encephalopathy is an altered mental status. Acute intoxication is a reversible symptom of exposure to many synthetic chemical neurotoxicants. Acute intoxication symptoms include lightheadedness, dizziness, headache and nausea, and regular cumulative exposure to these neurotoxicants over a number of years puts the individual at high risk for developing toxic encephalopathy. Chronic exposure to low levels of neurotoxic chemicals can also cause reversible changes in mood and affect which resolve with cessation of exposure. Acute and chronic toxic encephalopathy on the other hand, are persistent changes in neurological function that typically occur with exposure to higher concentrations and longer durations respectively. The symptoms of acute and chronic toxic encephalopathy do not resolve with cessation of exposure and can include memory loss, dementia, small personality changes/increased irritability, insidious onset of concentration difficulties, headache, lightheadedness, ataxia, involuntary movements (parkinsonism), fatigue, seizures, arm strength problems, and depression. A paper by Feldman and colleagues described neurobehavioral effects in a 57-year-old house painter with regular exposure to large amounts of solvents.Magnetic Resonance Imaging (MRI) analyses have also demonstrated increased rates of dopamine synthesis in the putamen, reduced anterior and total corpus callosum volume, demyelination in the parietal white matter, basal ganglia, and thalamus, as well as atypical activation of frontal areas of the brain due to neural compensation.The regions of interest on SPECT brain imaging include a majority of all cortical regions, and the globus pallidus in Carbon monoxide poisoning. Based on medical literature on SPECT brain imaging, signature patterns for toxic encephalopathy is a nonspecific patchy, diffuse pattern on the cortex, and sometimes is shown in subcortical regions, if exposure was severe.A thorough and standard diagnostic process is paramount with toxic encephalopathy, including a careful occupational, medication and medical history, standardized imaging and neuropsychological testing.
Causes
In addition, chemicals, such as lead, that could instigate toxic encephalopathy are sometimes found in everyday products such as prescription drugs, cleaning products, building materials, pesticides, air fresheners, and even perfumes. These harmful chemicals can be inhaled (in the case of air fresheners) or applied (in the case of perfumes). The substances diffuse into the brain rapidly, as they are lipophilic and readily transported across the blood–brain barrier. This is a result of increased membrane solubility and local blood flow, with central nervous system (CNS) solvent uptake being further increased with high levels of physical activity. When they are not detoxified immediately, the symptoms of toxic encephalopathy begin to emerge. However, in chronic situations, these effects may not become severe enough to be noticed until much later. Increased exposure time and increased concentration of the chemicals will worsen the effects of toxic encephalopathy, due to the associated structural CNS damage and direct functional impairment consequences.Subacute toxic encephalopathies are challenging to identify due to their often insidious tempo of evolution, nonspecific manifestations, relative infrequency as individual entities, and frequent lack of specific diagnostic testing. Yet they are crucial to recognize in aggregate, subacute toxic encephalopathies are a common problem that can lead to severe, irreversible harm if not diagnosed and treated efficiently. This article reviews the clinically relevant aspects of some of the more important subacute toxic encephalopathy syndromes caused by inorganic toxins, carbon monoxide (CO), anti- biotics, antineoplastic agents, and psychiatric medications.All therapeutic interventions are double-edged swords with benefits and adverse effects, and pharmacotherapy is not an exception. Shortly after the introduction of conventional antipsychotic drugs into clinical practice, relatively rare but serious complications with hyperthermia, muscle rigidity, autonomic instability, and disturbed mental status were recognized to develop in some patients treated with antipsychotics. This type of encephalopathy induced by the use of antipsychotics was referred to as neuroleptic malignant syndrome (NMS), and almost all physicians prescribing antipsychotics are nowadays aware of this adverse phenomenon. Another well-known type of encephalopathy associated with psychotropic drug therapy is serotonin toxicity (ST) or serotonin syndrome (SS), which is characterized by autonomic and neuromuscular symptoms and altered mental status. In contrast with the idiosyncratic nature of NMS, ST is a spectrum pathophysiological state assumed to derive from excess serotonergic neural transmission caused by serotonin-related psychotropic agents. In these two decades, pharmacotherapy with psychotropic drugs for patients with mental illness has been dramatically changed, and classical prototypal antipsychotics and antidepressants have been replaced with atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs), respectively. These newly developed psychotropic drugs are generally safer and more tolerable than older drugs. However, atypical antipsychotics are not free of the risk of development of NMS, and the explosive prevalence of SSRIs prescribed not only for depression but also for a number of psychiatric diagnoses such as anxiety, eating, impulse-control, and personality disorders may increase the incidence of ST. Therefore, these two pathological states still remain as major adverse effects of psychotropic drugs involving altered functioning of the central nervous system (CNS), to which all clinicians prescribing psychoactive drugs should pay attention. The popularity of SSRIs also increased the case reports of patients with discontinuation syndrome, which sometimes includes CNS symptoms like anxiety and irritability. In this chapter, the author provides a comprehensive overview of the above- mentioned adverse effects affecting the CNS function associated with psychotropic pharmacotherapy. In addition, several other pathological conditions potentially causing encephalopathic symptoms in psychiatric patients treated with psychotropic drugs, e.g., hyponatremia, valproate-induced hyperammonemia, transient splenial lesion of the corpus callosum, and so on, are also described.Fume events on aircraft have been linked to cases of toxic encephalopathy, for example in the case of JetBlue Captain Andrew Myers, who as a result of exposure needed a cane to walk, experienced tremors and struggled to speak. In the following year, the Federal Aviation Administration revoked Myers medical certificate; the workers compensation board agreed that Myers experienced brain damage as a result of the event.
Diagnosis
Rapid diagnosis is important to attempt to prevent further damage to the brain and further neurologic deficits. It is a diagnosis of exclusion, so a full work up for other possible etiologies (hepatic, uremic, infectious, oncologic) should be performed. In addition to the neurological examination, diagnostic testing could include MRI, PET or SPECT brain imaging, EEG, QEEG and most importantly, neuropsychological testing. Screening for heavy metals, as well as other toxins, should be done immediately as those are some of the most common causes and the patient can then remove themselves from the dangerous environment. In addition, a full examination of blood (CBC) and metabolites (CMP) should be done.
Treatment
Treatment is mainly for the symptoms that toxic encephalopathy causes, and vary depending on how severe the case is. Diet changes and nutritional supplements may help some patients. To reduce or halt seizures, anticonvulsants may be prescribed. Dialysis or organ replacement surgery may be needed in some severe cases.Lifelong abstinence from alcohol, a well-established neurotoxin and cause of the condition, is encouraged to prevent further loss of neurocognitive function.Management of affected individuals consists of immediate removal from exposure to the toxic substance(s), treatment of the common clinical manifestation of depression if present, and counselling for the provision of life strategies to help cope with the potentially debilitating condition.
Prognosis
Toxic encephalopathy is often irreversible. If the source of the problem is treated by removing the toxic chemical from the system, further damage can be prevented, but prolonged exposure to toxic chemicals can quickly destroy the brain. Long-term studies have demonstrated residual cognitive impairment (primarily attention and information-processing impairment resulting in dysfunction in working memory) up to 10 years following cessation of exposure. Severe cases of toxic encephalopathy can be life-threatening.
Research
Research is being done by organizations such as NINDS (National Institute of Neurological Disorders and Stroke) on what substances can cause encephalopathy, why they do this, and eventually how to protect, treat, and cure the brain from this condition.
See also
Brain damage
Chronic solvent-induced encephalopathy
Encephalopathy
Neurology
Notes
References
Lerner, David P.; Tadevosyan, Aleksey; Burns, Joseph D. (November 2020). "Toxin-Induced Subacute Encephalopathy". Neurologic Clinics. 38 (4): 799–824. doi:10.1016/j.ncl.2020.07.006. PMID 33040862. S2CID 222301922.
Bradley, Walter (2004). Neurology in Clinical Practice (4 ed.). Taylor & Francis. ISBN 9997625897.
Baker, Edward L. (May 2008). "Chronic toxic encephalopathy caused by occupational solvent exposure". Annals of Neurology. 63 (5): 545–547. doi:10.1002/ana.21394. PMID 18409195. S2CID 41546628.
Feldman, R G; Ratner, M H; Ptak, T (May 1999). "Chronic toxic encephalopathy in a painter exposed to mixed solvents". Environmental Health Perspectives. 107 (5): 417–422. doi:10.1289/ehp.99107417. PMC 1566426. PMID 10210698.
Encephalopathy Associated with Psychotropic Drug Therapy Yuji Odagaki Department of Psychiatry, Faculty of Medicine, Saitama Medical University Department of Psychiatry, Moro Hospital Japan
External links
NINDS Encephalopathy Information Page
Encephalopathy Causes, Symptoms, Diagnosis and Treatment by MedicineNet |
Delusional disorder | Delusional disorder is a mental illness in which a person has delusions, but with no accompanying prominent hallucinations, thought disorder, mood disorder, or significant flattening of affect. Delusions are a specific symptom of psychosis. Delusions can be bizarre or non-bizarre in content; non-bizarre delusions are fixed false beliefs that involve situations that could occur in real life, such as being harmed or poisoned. Apart from their delusion or delusions, people with delusional disorder may continue to socialize and function in a normal manner and their behavior does not necessarily generally seem odd. However, the preoccupation with delusional ideas can be disruptive to their overall lives.For the diagnosis to be made, auditory and visual hallucinations cannot be prominent, though olfactory or tactile hallucinations related to the content of the delusion may be present. The delusions cannot be due to the effects of a drug, medication, or general medical condition, and delusional disorder cannot be diagnosed in an individual previously properly diagnosed with schizophrenia. A person with delusional disorder may be high functioning in daily life. Recent and comprehensive meta-analyses of scientific studies point to an association between a deterioration in aspects of IQ in psychotic patients, in particular perceptual reasoning.According to German psychiatrist Emil Kraepelin, patients with delusional disorder remain coherent, sensible and reasonable. The Diagnostic and Statistical Manual of Mental Disorders (DSM) defines six subtypes of the disorder characterized as erotomanic (belief that someone is in love with one), grandiose (belief that one is the greatest, strongest, fastest, richest, or most intelligent person ever), jealous (belief that one is being cheated on), persecutory (delusions that the person or someone to whom the person is close is being malevolently treated in some way), somatic (belief that one has a disease or medical condition), and mixed, i.e., having features of more than one subtype.Delusions also occur as symptoms of many other mental disorders, especially the other psychotic disorders.
The DSM-IV and psychologists agree that personal beliefs should be evaluated with great respect to cultural and religious differences, since some cultures have widely accepted beliefs that may be considered delusional in other cultures.An earlier, now obsolete, nosological name for delusional disorder was "paranoia".
Classification
The International Classification of Diseases classifies delusional disorder as a mental and behavioural disorder.
Diagnosis of a specific type of delusional disorder can sometimes be made based on the content of the delusions, to wit, the Diagnostic and Statistical Manual of Mental Disorders (DSM) enumerates seven types:
Erotomanic type (erotomania): delusion that another person, often a prominent figure, is in love with the individual. The individual may breach the law as they try to obsessively make contact with the desired person.
Grandiose type (megalomania): delusion of inflated worth, power, knowledge, identity or believing oneself to be a famous person, claiming the actual person is an impostor or an impersonator.
Jealous type: delusion that the individuals sexual partner is unfaithful when it is untrue. The patient may follow the partner, check text messages, emails, phone calls etc. in an attempt to find "evidence" of the infidelity.
Persecutory type: This delusion is a common subtype. It includes the belief that the person (or someone to whom the person is close) is being malevolently treated in some way. The patient may believe that they have been drugged, spied upon, harmed, harassed and so on and may seek "justice" by making reports, taking action or even acting violently.
Somatic type: delusions that the person has some physical defect or general medical condition
Mixed type: delusions with characteristics of more than one of the above types but with no one theme predominating.
Unspecified type: delusions that cannot be clearly determined or characterized in any of the categories in the specific types.
Signs and symptoms
The following can indicate a delusion:
An individual expresses an idea or belief with unusual persistence or force, even when evidence suggests the contrary.
That idea appears to have an undue influence on the persons life, and the way of life is often altered to an inexplicable extent.
Despite their profound conviction, there is often a quality of secretiveness or suspicion when the person is questioned about it.
The individual tends to be humorless and oversensitive, especially about the belief.
There is a quality of centrality: no matter how unlikely it is that these strange things are happening to the person, he or she accepts them relatively unquestioningly.
An attempt to contradict the belief is likely to arouse an inappropriately strong emotional reaction, often with irritability and hostility. They will not accept any other opinions.
The belief is, at the least, unlikely, and out of keeping with the individuals social, cultural, and religious background.
The person is emotionally over-invested in the idea and it overwhelms other elements of his or her psyche.
The delusion, if acted out, often leads to behaviors which are abnormal, and out of character, although perhaps understandable in light of the delusional beliefs.
Other people who know the individual observe that the belief and behavior are uncharacteristic and alien.Additional features of delusional disorder include the following:
It is a primary disorder.
It is a stable disorder characterized by the presence of delusions to which the patient clings with extraordinary tenacity.
The illness is chronic and frequently lifelong.
The delusions are logically constructed and internally consistent.
The delusions do not interfere with general logical reasoning (although within the delusional system the logic is perverted) and there is usually no general disturbance of behavior. If disturbed behavior does occur, it is directly related to the delusional beliefs.
The individual experiences a heightened sense of self-reference. Events which, to others, are nonsignificant are of enormous significance to him or her, and the atmosphere surrounding the delusions is highly charged.However this should not be confused with gaslighting, where a person denies the truth, and causes the one being gaslit to think that they are being delusional.
Causes
The cause of delusional disorder is unknown, but genetic, biochemical, and environmental factors may play a significant role in its development. Some people with delusional disorders may have an imbalance in neurotransmitters, the chemicals that send and receive messages to the brain. There does seem to be some familial component, and immigration (generally for persecutory reasons), drug abuse, excessive stress, being married, being employed, low socioeconomic status, celibacy among men, and widowhood among women may also be risk factors. Delusional disorder is currently thought to be on the same spectrum or dimension as schizophrenia, but people with delusional disorder, in general, may have less symptomatology and functional disability.
Diagnosis
Differential diagnosis includes ruling out other causes such as drug-induced conditions, dementia, infections, metabolic disorders, and endocrine disorders. Other psychiatric disorders must then be ruled out. In delusional disorder, mood symptoms tend to be brief or absent, and unlike schizophrenia, delusions are non-bizarre and hallucinations are minimal or absent.Interviews are important tools to obtain information about the patients life situation and history to help make a diagnosis. Clinicians generally review earlier medical records to gather a full history. Clinicians also try to interview the patients immediate family, as this can be helpful in determining the presence of delusions. The mental status examination is used to assess the patients current mental condition.
A psychological questionnaire used in the diagnosis of the delusional disorder is the Peters Delusion Inventory (PDI) which focuses on identifying and understanding delusional thinking. However, this questionnaire is more likely used in research than in clinical practice.
In terms of diagnosing a non-bizarre delusion as a delusion, ample support should be provided through fact checking. In case of non-bizarre delusions, Psych Central notes, "All of these situations could be true or possible, but the person suffering from this disorder knows them not to be (e.g., through fact-checking, third-person confirmation, etc.)."
Treatment
A challenge in the treatment of delusional disorders is that most patients have limited insight, and do not acknowledge that there is a problem. Most patients are treated as out-patients, although hospitalization may be required in some cases if there is a risk of harm to self or others. Individual psychotherapy is recommended rather than group psychotherapy, as patients are often quite suspicious and sensitive. Antipsychotics are not well tested in delusional disorder, but they do not seem to work very well, and often have no effect on the core delusional belief. Antipsychotics may be more useful in managing agitation that can accompany delusional disorder. Until further evidence is found, it seems reasonable to offer treatments which have efficacy in other psychotic disorders.Psychotherapy for patients with delusional disorder can include cognitive therapy which is conducted with the use of empathy. During the process, the therapist can ask hypothetical questions in a form of therapeutic Socratic questioning. This therapy has been mostly studied in patients with the persecutory type. The combination of pharmacotherapy with cognitive therapy integrates treating the possible underlying biological problems and decreasing the symptoms with psychotherapy as well. Psychotherapy has been said to be the most useful form of treatment because of the trust formed in a patient and therapist relationship.Supportive therapy has also been shown to be helpful. Its goal is to facilitate treatment adherence and provide education about the illness and its treatment.
Furthermore, providing social skills training has been found to be helpful for many people. It can promote interpersonal competence as well as confidence and comfort when interacting with those individuals perceived as a threat.Insight-oriented therapy is rarely indicated or contraindicated; yet there are reports of successful treatment. Its goals are to develop therapeutic alliance, containment of projected feelings of hatred, powerlessness, and badness; measured interpretation as well as the development of a sense of creative doubt in the internal perception of the world. The latter requires empathy with the patients defensive position.
Epidemiology
Delusional disorders are uncommon in psychiatric practice, though this may be an underestimation due to the fact that those with the condition lack insight and thus avoid psychiatric assessment. The prevalence of this condition stands at about 24 to 30 cases per 100,000 people while 0.7 to 3.0 new cases per 100,000 people are reported every year. Delusional disorder accounts for 1–2% of admissions to inpatient mental health facilities. The incidence of first admissions for delusional disorder is lower, from 0.001 to 0.003%.Delusional disorder tends to appear in middle to late adult life, and for the most part first admissions to hospital for delusional disorder occur between age 33 and 55. It is more common in women than men, and immigrants seem to be at higher risk.
Criticism
In some situations the delusion may turn out to be true belief. For example, in delusional jealousy, where a person believes that the partner is being unfaithful (in extreme cases perhaps going so far as to follow the partner into the bathroom, believing the other to be seeing a lover even during the briefest of separations), it may actually be true that the partner is having sexual relations with another person. In this case, the delusion does not cease to be a delusion because the content later turns out to be verified as true or the partner actually chose to engage in the behavior of which they were being accused.
In other cases, the delusion may be mistakenly assumed to be false by a doctor or psychiatrist assessing the belief, just because it seems to be unlikely, bizarre or held with excessive conviction. Psychiatrists rarely have the time or resources to check the validity of a persons claims leading to some true beliefs to be erroneously classified as delusional. This is known as the Martha Mitchell effect, after the wife of the attorney general who alleged that illegal activity was taking place in the White House. At the time, her claims were thought to be signs of mental illness, and only after the Watergate scandal broke was she proved right (and hence sane).
Similar factors have led to criticisms of Jaspers definition of true delusions as being ultimately un-understandable. Critics (such as R. D. Laing) have argued that this leads to the diagnosis of delusions being based on the subjective understanding of a particular psychiatrist, who may not have access to all the information that might make a belief otherwise interpretable.
Another difficulty with the diagnosis of delusions is that almost all of these features can be found in "normal" beliefs. Many religious beliefs hold exactly the same features, yet are not universally considered delusional. For instance, if a person was holding a true belief then they will of course persist with it. This can cause the disorder to be misdiagnosed by psychiatrists. These factors have led the psychiatrist Anthony David to write that "there is no acceptable (rather than accepted) definition of a delusion."
In popular culture
In the 2010 psychological thriller Shutter Island, directed by Martin Scorsese and starring Leonardo DiCaprio, delusional disorder is portrayed along with other disorders. An Indian movie Anantaram (Thereafter) directed by Adoor Gopalakrishnan also portrays the complex nature of delusions. The plot of the French movie He Loves Me... He Loves Me Not revolves around a case of erotomania, as does the plot of the Ian McEwan novel, Enduring Love.
See also
Delusional parasitosis
Monothematic delusions
Morgellons
Paranoia
Shared delusional disorder
References
Further reading
Arnold, K.; Vakhrusheva, J. (2015). "Resist the negation reflex: Minimizing reactance in psychotherapy of delusions" (PDF). Psychosis. 8 (2): 1–10. doi:10.1080/17522439.2015.1095229. S2CID 146386637.
McDermott, Sarah (22 February 2018), "The story of a weird world I was warned never to tell", BBC News. [A related case study.]
Munro, A. (1999) Delusional Disorder: Paranoia and Related Illnesses. Cambridge: Cambridge University Press. ISBN 0-521-58180-X.
Sims, A. (1995) Symptoms in the mind: An introduction to descriptive psychopathology. Edinburgh: Elsevier Science Ltd. ISBN 0-7020-2627-1.
External links
Media related to Delusional disorders at Wikimedia Commons |
Botryoid odontogenic cyst | Botryoid odontogenic cyst is a variant of the lateral periodontal cyst. It is more often found in middle-aged and older adults, and the teeth more likely affected are mandibular (lower) canines and premolars. On radiographs, the cyst appears "grape-like". Often patients with this condition are symptomatic.
Radiographic features
The botryoid odontogenic cyst is a multi-compartmentalized variant of the lateral periodontal cyst. It is similar to the lateral periodontal cyst in all its features except that its polycystic nature is often evident through its multilocular pattern on radiographs.
Histologic features
Histologically also it resembles the lateral periodontal cyst which has a distinctive thin, nonkeratinized epithelium which is 1-5 cell layers thick and resembles the reduced enamel epithelium.
Cuboidal or columnar cells may be found composing the lining.
Focal thickened plaques of proliferating lining cells often project into the lumen areas which is commonly seen in this cyst.
Large number of rests of dental lamina are found in the connective tissue composed of glycogen rich clear cells.reference can be made to the histologic details given by shear and pindborg
References
Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001.
shafers textbook of oral pathology 5th edition |
Posterior ischemic optic neuropathy | Posterior ischemic optic neuropathy (PION) is a medical condition characterized by damage to the retrobulbar portion of the optic nerve due to inadequate blood flow (ischemia) to the optic nerve. Despite the term posterior, this form of damage to the eyes optic nerve due to poor blood flow also includes cases where the cause of inadequate blood flow to the nerve is anterior, as the condition describes a particular mechanism of visual loss as much as the location of damage in the optic nerve. In contrast, anterior ischemic optic neuropathy (AION) is distinguished from PION by the fact that AION occurs spontaneously and on one side in affected individuals with predisposing anatomic or cardiovascular risk factors.
Signs and symptoms
PION is characterized by moderate to severe painless vision loss of abrupt onset. One or both eyes may be affected and color vision is typically impaired.
Ophthalmoscopic exam
Looking inside the persons eyes at the time of onset, ophthalmoscope exam reveals no visible changes to the optic nerve head. Weeks after ischemic insult, nerve atrophy originating from the damaged posterior optic nerve progresses to involve the anterior optic nerve head. Four to eight weeks after onset, atrophy of the optic nerve head is observable upon ophthalmoscope exam.
Pupils
If both eyes are affected by PION, the pupils may look symmetrical. However, if the eyes are asymmetrically affected, i.e. one eyes optic nerve is more damaged than the other, it will produce an important sign called an afferent pupillary defect.Defective light perception in one eye causes an asymmetrical pupillary constriction reflex called the afferent pupillary defect (APD).
Arteritic PION
A-PION most commonly affects Caucasian women, with an average age of 73. At onset vision loss is unilateral, but without treatment it rapidly progresses to involve both eyes. Vision loss is usually severe, ranging from counting fingers to no light perception. Associated symptoms are jaw pain exacerbated by chewing, scalp tenderness, shoulder and hip pain, headache and fatigue.
Perioperative PION
Vision loss is usually apparent upon waking from general anesthesia. Signs observable to a bystander include long surgery duration and facial swelling. Vision loss is usually bilateral and severe, ranging from counting fingers to no light perception.
Cause
PION is a watershed infarction of the optic nerve that may cause either unilateral or, more often, bilateral blindness. PION typically occurs in two categories of people:
People who have undergone non-ocular surgery that is particularly prolonged or is associated with a significant blood loss.
People who have experienced significant bleeding from an accident or ruptured blood vessels. In these cases, the person may develop anemia (too few oxygen-delivering red blood cells in the bloodstream) and often have low blood pressure as well. This combination can produce circulatory shock, and PION has sometimes been called shock-induced optic neuropathy.The combination of anemia and low blood pressure means that the blood is carrying less oxygen to the tissues. The optic nerve can be at very high risk for damage from insufficient blood supply due to swelling (from lack of oxygen) in a confined bony space resulting in a compartment syndrome. Restricted blood flow can lead to permanent damage to the optic nerve and result in blindness (often in both eyes). For technical reasons this occurs more frequently with spinal surgeries.
Cardiovascular risk factors
Perioperative PION patients have a higher prevalence of cardiovascular risk factors than in the general population. Documented cardiovascular risks in people affected by perioperative PION include high blood pressure, diabetes mellitus, high levels of cholesterol in the blood, tobacco use, abnormal heart rhythms, stroke, and obesity. Men are also noted to be at higher risk, which is in accordance with the trend, as men are at higher risk of cardiovascular disease. These cardiovascular risks all interfere with adequate blood flow, and also may suggest a contributory role of defective vascular autoregulation.
Perioperative PION
As illustrated by the risk factors above, perioperative hypoxia is a multifactorial problem. Amidst these risk factors it may be difficult to pinpoint the optic nerves threshold for cell death, and the exact contribution of each factor.Low blood pressure and anemia are cited as perioperative complications in nearly all reports of PION, which suggests a causal relationship. However, while low blood pressure and anemia are relatively common in the perioperative setting, PION is exceedingly rare. Spine and cardiac bypass surgeries have the highest estimated incidences of PION, 0.028% and 0.018% respectively, and this is still extremely low. This evidence suggests that optic nerve injury in PION patients is caused by more than just anemia and low blood pressure.Evidence suggests that the multifactorial origin of perioperative PION involves the risks discussed above and perhaps other unknown factors. Current review articles of PION propose that vascular autoregulatory dysfunction and anatomic variation are under-investigated subjects that may contribute to patient-specific susceptibility.
Pathogenesis
PION
In both types of PION, decreased blood flow leads to the death of optic nerve cells. Ischemic injury to the optic nerve causes inflammation and swelling. Because the posterior optic nerve passes through the optic canal, a bony tunnel leading to the brain, swelling in this rigid space causes compression of the optic nerve. This compression worsens ischemia and perpetuates the cycle of injury, and swelling, and compression.
A-PION
A-PION is caused by an inflammatory disease called giant cell arteritis (GCA). GCA is an inflammatory disease of blood vessels. It is believed to be an autoimmune disease caused by inappropriate T-cell activity. When T-cells damage arteries supplying the optic nerve, a blood clot forms and stops blood flow. When blood flow stops, oxygen delivery stops and optic nerve fibers die.
Perioperative PION
The exact cause of perioperative PION is unknown. Many risk factors have been identified, all of which contribute to inadequate delivery of oxygen to optic nerve cells. Alone, none of these risk factors is enough to cause PION. However, in susceptible individuals, a combination of these risk factors produces devastating blindness. This evidence suggests that PION is a disease of multifactorial origin.Risks of perioperative PION can be divided into two categories, intraoperative ischemic pressures, and cardiovascular risk factors.
Intraoperative ischemic pressures
Many causes of decreased blood flow during surgery are systemic, i.e. they decrease blood flow throughout the body. Studies have shown that nearly all perioperative PION patients had prolonged periods of low blood pressure during the operation and postoperative anemia. The average perioperative PION patient loses 4 liters of blood during surgery, and the majority receive blood transfusions. Massive blood loss is just one cause of low blood pressure. Medications used for general anesthesia can also lower blood pressure. The average surgery duration in PION cases is 7 to 9 hours, which increases the risk of prolonged low blood pressure.Other intraoperative ischemic pressures are local, i.e. they decrease blood flow to the affected area, the optic nerve. Facial swelling, periorbital swelling, direct orbital compression, facedown position during surgery, and a tilted operating table in feet-above-head position, have all been reported to be associated with perioperative PION. All of these factors are believed to increase tissue pressure and venous pressure around the optic nerve, thereby decreasing local blood flow and oxygen delivery.Surgeries with the highest estimated incidence of PION are surgeries with a higher risk of the aforementioned conditions. In spine surgery, patients are susceptible to significant blood loss, and they are positioned face down for long periods of time, which increases venous pressure, decreases arterial perfusion pressure, and often causes facial swelling (increased tissue pressure). Spine surgery is estimated to have the highest incidence of PION, 0.028%. Long duration of feet-above-head position in prostate surgery has also been suggested to increase risk of PION.
Diagnosis
The diagnosis of PION is often difficult since the optic nerves initially appear normal. The injury occurs posterior to that portion of the nerve visible during ophthalmoscopic examination. There may be an abnormal relative pupillary response (APD) if the injury is confined to one optic nerve, but often it is bilateral and the symmetry of pupillary responses is maintained. Furthermore, MRI scanning may not be helpful. It is not uncommon for the erroneous diagnoses of malingering or cortical blindness to be made. If possible, an urgent neuro-ophthalmology consult is most likely to lead to the correct diagnosis.There is no confirmatory test for PION. PION is a diagnosis of exclusion. To prevent impending blindness, it is urgent to rule out giant cell arteritis when a patient over 50 presents with sudden vision loss.
Differential diagnosis
In the postoperative setting, without gross eye injury, visual loss requires an assessment of the whole visual system for ischemic damage. The optic nerve is not the only tissue of the visual pathway susceptible to decreased blood flow. Decreased oxygenation of the retina or brain could also impair vision.
Anterior ischemic optic neuropathy
PION is less common than Anterior Ischemic Optic Neuropathy (AION). Blood supply and surrounding anatomy make the anterior and posterior portions of the optic nerve susceptible to different ischemic pressures.The posterior optic nerve receives blood primarily from the pial branches of the ophthalmic artery. The optic canal, a boney tunnel leading to the brain, surrounds the most posterior part of this optic nerve segment.The anterior optic nerve receives blood primarily from the posterior ciliary arteries. The anterior optic nerve, a.k.a. the optic nerve head, is surrounded by the scleral canal, and is vulnerable to crowding of nerve fibers. The portion of the optic nerve head that is visible by looking into the eye with an ophthalmoscope is called the optic disc.
PION versus AION
At the onset of symptoms, ophthalmoscope examination can differentiate AION from PION. If optic nerve head involvement is observed, it is AION. PION does not produce optic atrophy that is observable via ophthalmoscope until four to eight weeks after onset. In addition, AION often shows a characteristic altitudinal defect on a Humphrey Visual Field test.
GCA
The American College of Rheumatology has defined a combination of physical symptoms and inflammatory changes to diagnose giant cell arteritis.
Prevention
Individuals with a history of high blood pressure, diabetes, and smoking are most susceptible to PION as they have a compromised system of blood vessel autoregulation. Hence, extra efforts may need to be taken for them in the form of careful or staged surgery or the controlling the anemia from blood loss (by administration of blood transfusions), and the careful maintenance of their blood pressure.
Treatment
Once visual loss has occurred, it becomes more problematic, but there are reports of recovered vision if blood transfusions and agents that raise blood pressure are administered within hours.
A-PION
If a diagnosis of GCA is suspected, treatment with steroids should begin immediately. A sample (biopsy) of the temporal artery should be obtained to confirm the diagnosis and guide future management, but should not delay initiation of treatment. Treatment does not recover lost vision, but prevents further progression and second eye involvement. High dose corticosteroids may be tapered down to low doses over approximately one year.
Perioperative
Rapid blood transfusions, to correct anemia and raise blood pressure, may improve PION outcomes. In one report of a related disease, hypotension-induced AION, 3 out of 3 patients who received rapid transfusions reported partial recovery of vision. While rapid transfusions offer some hope, the prognosis for perioperative PION remains poor. Prevention remains the best way to reduce PION.
One retrospective report proposes that incidence of PION could be reduced in high-risk cases by altering surgical management. For example, for patients undergoing spine surgery, measures could be taken to minimize intraoperative hypotension, to accelerate the process of blood replacement, and to aggressively treat facial swelling.
Epidemiology
PION most commonly affects the elderly. The mean patient age was 62 years in one series (range 18 to 90 years).The mean age varies by etiology category; patients with giant cell arteritis (GCA) are older (mean 78 years, range 50 to 82 years), while those with PION in the setting of spine surgery are younger on average.There is a higher than expected prevalence of atherosclerotic risk factors and comorbid vascular disease, especially in patients with nonarteritic (idiopathic) PION, with 87 percent of patients having at least one risk factor for, or one other manifestation of, atherosclerotic vascular disease.
While anterior ischemic optic neuropathy (AION) appears to be more common than PION after cardiac surgery, PION is relatively more common in cases of spine surgery.
References
Further reading
Luneau K, Newman NJ, Biousse V (November 2008). "Ischemic optic neuropathies". The Neurologist. 14 (6): 341–54. doi:10.1097/NRL.0b013e318177394b. PMID 19008740. S2CID 8445417.
Remigio D, Wertenbaker C (2000). "Post-operative bilateral vision loss". Survey of Ophthalmology. 44 (5): 426–32. doi:10.1016/S0039-6257(00)00107-7. PMID 10734242.
Buono LM, Foroozan R, Savino PJ, Danesh-Meyer HV, Stanescu D (June 2003). "Posterior ischemic optic neuropathy after hemodialysis". Ophthalmology. 110 (6): 1216–8. doi:10.1016/S0161-6420(03)00257-4. PMID 12799249.
== External links == |
Athletic heart syndrome | Athletic heart syndrome (AHS) is a non-pathological condition commonly seen in sports medicine in which the human heart is enlarged, and the resting heart rate is lower than normal.
The athletes heart is associated with physiological cardiac remodeling as a consequence of repetitive cardiac loading. Athletes heart is common in athletes who routinely exercise more than an hour a day, and occurs primarily in endurance athletes, though it can occasionally arise in heavy weight trainers. The condition is generally considered benign, but may occasionally hide a serious medical condition, or may even be mistaken for one.
Signs and symptoms
Athletes heart most often does not have any physical symptoms, although an indicator would be a consistently low resting heart rate. Athletes with AHS often do not realize they have the condition unless they undergo specific medical tests, because athletes heart is a normal, physiological adaptation of the body to the stresses of physical conditioning and aerobic exercise. People diagnosed with athletes heart commonly display three signs that would usually indicate a heart condition when seen in a regular person: bradycardia, cardiomegaly, and cardiac hypertrophy. Bradycardia is a slower than normal heartbeat, at around 40–60 beats per minute. Cardiomegaly is the state of an enlarged heart, and cardiac hypertrophy the thickening of the muscular wall of the heart, specifically the left ventricle, which pumps oxygenated blood to the aorta. Especially during an intensive workout, more blood and oxygen are required to the peripheral tissues of the arms and legs in highly trained athletes bodies. A larger heart results in higher cardiac output, which also allows it to beat more slowly, as more blood is pumped out with each beat.Another sign of athletes heart syndrome is an S3 gallop, which can be heard through a stethoscope. This sound can be heard as the diastolic pressure of the irregularly shaped heart creates a disordered blood flow. However, if an S4 gallop is heard, the patient should be given immediate attention. An S4 gallop is a stronger and louder sound created by the heart, if diseased in any way, and is typically a sign of a serious medical condition.
Cause
Athletes heart is a result of dynamic physical activity, such as aerobic training more than 5 hours a week rather than static training such as weightlifting. During intensive prolonged endurance or strength training, the body signals the heart to pump more blood through the body to counteract the oxygen deficit building in the skeletal muscles. Enlargement of the heart is a natural physical adaptation of the body to deal with the high pressures and large amounts of blood that can affect the heart during these periods of time. Over time, the body will increase both the chamber size of the left ventricle, and the muscle mass and wall thickness of the heart.Cardiac output, the amount of blood that leaves the heart in a given time period (i.e. liters per minute), is proportional to both the chamber sizes of the heart and the rate at which the heart beats. With a larger left ventricle, the heart rate can decrease and still maintain a level of cardiac output necessary for the body. Therefore, athletes with AHS commonly have lower resting heart rates than nonathletes.The heart becomes enlarged, or hypertrophic, due to intense cardiovascular workouts, creating an increase in stroke volume, an enlarged left ventricle (and right ventricle), and a decrease in resting heart rate along with irregular rhythms. The wall of the left ventricle increases in size by about 15–20% of its normal capacity. No decrease of the diastolic function of the left ventricle occurs. The athlete may also experience an irregular heartbeat and a resting pulse rate between 40 and 60 beats per minute (bradycardia).The level of physical activity in a person determines what physiological changes the heart makes. The two types of exercise are static (strength-training) and dynamic (endurance-training). Static exercise consists of weight lifting and is mostly anaerobic, meaning the body does not rely on oxygen for performance. It also moderately increases heart rate and stroke volume (oxygen debt). Dynamic exercises include running, swimming, skiing, rowing, and cycling, which rely on oxygen from the body. This type of exercise also increases both heart rate and stroke volume of the heart. Both static and dynamic exercises involve the thickening of the left ventricular wall due to increased cardiac output, which leads to physiologic hypertrophy of the heart. Once athletes stop training, the heart returns to its normal size.
Diagnosis
Athletes heart is usually an incidental finding during a routine screening or during tests for other medical issues. An enlarged heart can be seen at echocardiography or sometimes on a chest X-ray. Similarities at presentation between athletes heart and clinically relevant cardiac problems may prompt electrocardiography (ECG) and exercise cardiac stress tests. The ECG can detect sinus bradycardia, a resting heart rate of fewer than 60 beats per minute. This is often accompanied by sinus arrhythmia. The pulse of a person with athletes heart can sometimes be irregular while at rest, but usually returns to normal after exercise begins.Regarding differential diagnosis, left ventricular hypertrophy is usually indistinguishable from athletes heart and at ECG, but can usually be discounted in the young and fit.It is important to distinguish between athletes heart and hypertrophic cardiomyopathy (HCM), a serious cardiovascular disease characterised by thickening of the hearts walls, which produces a similar ECG pattern at rest. This genetic disorder is found in one of 500 Americans and is a leading cause of sudden cardiac death in young athletes (although only about 8% of all cases of sudden death are actually exercise-related). The following table shows some key distinguishing characteristics of the two conditions.Athletes heart should not be confused with bradycardia that occurs secondary to Relative energy deficiency in sport or Anorexia nervosa, which involve slowing of metabolic rate and sometimes shrinkage of the heart muscle and reduced heart volume.
The medical history of the patient (endurance sports) and physical examination (bradycardia, and maybe a third or fourth heart sound), can give important hints.
ECG – typical findings in resting position are, for example, sinus bradycardia, atrioventricular block (primary and secondary) and incomplete (IRBBB) or complete right bundle branch block (RBBB) – all those findings normalize during exercise.
Echocardiography – differentiation between physiological and pathological increases of the hearts size is possible, especially by estimating the mass of the wall (not over 130 g/m2) and its end diastolic diameter (not much less 60 mm) of the left ventricle.
X-ray examination of the chest may show increased heart size (mimicking other possible causes of enlargement).
Cardiac MRI - In athletes heart, there is balanced atrioventricular remodeling, reduced thickening of the heart after detraining, no late gadolinium enhancement, low to normal T1 signal, and normal extracellular volume.
Screening related conditions
Because several well-known and high-profile cases of athletes experiencing sudden unexpected death due to cardiac arrest, such as Reggie White and Marc-Vivien Foé, a growing movement is making an effort to have both professional and school-based athletes screened for cardiac and other related conditions, usually through a careful medical and health history, a good family history, a comprehensive physical examination including auscultation of heart and lung sounds and recording of vital signs such as heart rate and blood pressure, and increasingly, for better efforts at detection, such as an electrocardiogram.An electrocardiogram (ECG) is a relatively straightforward procedure to administer and interpret, compared to more invasive or sophisticated tests; it can reveal or hint at many circulatory disorders and arrhythmias. Part of the cost of an ECG may be covered by some insurance companies, though routine use of ECGs or other similar procedures such as echocardiography (ECHO) are still not considered routine in these contexts. Widespread routine ECGs for all potential athletes during initial screening and then during the yearly physical assessment could well be too expensive to implement on a wide scale, especially in the face of the potentially very large demand. In some places, a shortage of funds, portable ECG machines, or qualified personnel to administer and interpret them (medical technicians, paramedics, nurses trained in cardiac monitoring, advanced practice nurses or nurse practitioners, physician assistants, and physicians in internal or family medicine or in some area of cardiopulmonary medicine) exist.If sudden cardiac death occurs, it is usually because of pathological hypertrophic enlargement of the heart that went undetected or was incorrectly attributed to the benign "athletic" cases. Among the many alternative causes are episodes of isolated arrhythmias which degenerated into lethal VF and asystole, and various unnoticed, possibly asymptomatic cardiac congenital defects of the vessels, chambers, or valves of the heart. Other causes include carditis, endocarditis, myocarditis, and pericarditis whose symptoms were slight or ignored, or were asymptomatic.The normal treatments for episodes due to the pathological look-alikes are the same mainstays for any other episode of cardiac arrest: cardiopulmonary resuscitation, defibrillation to restore normal sinus rhythm, and if initial defibrillation fails, administration of intravenous epinephrine or amiodarone. The goal is avoidance of infarction, heart failure, and/or lethal arrhythmias (ventricular tachycardia, ventricular fibrillation, asystole, or pulseless electrical activity), so ultimately to restore normal sinus rhythm.
Management
Athletes heart is not dangerous for athletes (though if a nonathlete has symptoms of bradycardia, cardiomegaly, and cardiac hypertrophy, another illness may be present). Athletes heart is not the cause of sudden cardiac death during or shortly after a workout, which mainly occurs due to hypertrophic cardiomyopathy and arrhythmogenic cardiomyopathy (ARVC), two genetic disorders. Although a link between intensive exercise and exercise-induced arythmogenic right ventricular cardiomyopathy exists.No treatment is required for people with athletic heart syndrome; it does not pose any physical threats to the athlete, and despite some theoretical concerns that the ventricular remodeling might conceivably predispose for serious arrhythmias, no evidence has been found of any increased risk of long-term events. Athletes should see a physician and receive a clearance to be sure their symptoms are due to athletes heart and not another heart disease, such as cardiomyopathy. If the athlete is uncomfortable with having athletes heart or if a differential diagnosis is difficult, deconditioning from exercise for a period of three months allows the heart to return to its regular size. However, one long-term study of elite-trained athletes found that dilation of the left ventricle was only partially reversible after a long period of deconditioning. This deconditioning is often met with resistance to the accompanying lifestyle changes. The real risk attached to athletes heart is if athletes or nonathletes simply assume they have the condition, instead of making sure they do not have a life-threatening heart illness.
History
The athletes heart syndrome was first described in 1899 by Salomon Henschen. He compared the heart size of cross-country skiers to those who lived sedentary lives. He noticed that those who participated in competitive sports displayed symptoms of athletes heart syndrome. Henschen believed the symptoms were a normal adjustment to exercise, and felt concern was not needed. Henschen believed that the entire heart became enlarged, when in fact, only the left side becomes hypertrophic. He also believed athletes with AHS lived shorter lives than those who did not acquire the syndrome. Because his research occurred throughout the 19th century, technology was limited, and it became difficult to devise appropriate ways to measure the hearts of athletes. Few believed in Henschens theory about athletes having larger hearts than those who did not participate in sports: this theory is supported.
See also
Exercise hypertension
References
External links
Merck Manual Professional Version |
Exertional rhabdomyolysis | Exertional rhabdomyolysis (ER) is the breakdown of muscle from extreme physical exertion. It is one of many types of rhabdomyolysis that can occur, and because of this, the exact prevalence and incidence are unclear.
Cause
ER is more likely to occur when strenuous exercise is performed under high temperatures and humidity. Poor hydration levels before, during, and after strenuous bouts of exercise have also been reported to lead to ER. This condition and its signs and symptoms are not well known amongst the sport and fitness community and because of this it is believed that the incidence is greater but highly underreported.Risks that lead to ER include exercise in hot and humid conditions, improper hydration, inadequate recovery between bouts of exercise, intense physical training, and inadequate fitness levels for beginning high-intensity workouts. Eccentric contraction of muscles can result in ER more often than concentric contraction. Dehydration is one of the biggest factors that can give almost immediate feedback from the body by producing very dark-colored urine.
Mechanism
Anatomy
Exertional rhabdomyolysis results from damage to the intercellular proteins inside the sarcolemma. Myosin and actin break down in the sarcomeres when ATP is no longer available due to injury to the sarcoplasmic reticulum. Damage to the sarcolemma and sarcoplasmic reticulum from direct trauma or high force production causes a high influx of calcium into the muscle fibers increasing calcium permeability. Calcium ions build up in the mitochondria, impairing cellular respiration. The mitochondria are unable to produce enough ATP to power the cell properly. Reduction in ATP production impairs the cells ability to extract calcium from the muscle cell. The ion imbalance causes calcium-dependent enzymes to activate which break down muscle proteins even further. A high concentration of calcium activates muscle cells, causing the muscle to contract while inhibiting its ability to relax. The increase of sustained muscle contraction leads to oxygen and ATP depletion with prolonged exposure to calcium. The muscle cell membrane pump may become damaged allowing free form myoglobin to leak into the bloodstream.
Physiology
Rhabdomyolysis causes the myosin and actin to degenerate into smaller proteins that travel into the circulatory system. The body reacts by increasing intracellular swelling to the injured tissue to send repair cells to the area. This allows creatine kinase and myoglobin to be flushed from the tissue where it travels in the blood until reaching the kidneys. In addition to the proteins released, large quantities of ions such as intracellular potassium, sodium, and chloride find their way into the circulatory system. Intracellular potassium ion has deleterious effects on the hearts ability to generate action potentials leading to cardiac arrhythmias. Consequently, this can affect peripheral and central perfusion which in turn can affect all major organ systems in the body.When the protein reaches the kidneys it causes a strain on the anatomical structures reducing its effectiveness as a filter for the body. The protein acts as a dam as it forms into tight aggregates when it enters the renal tubules. In addition, the increased intracellular calcium has greater time to bind due to the blockage allowing for renal calculi to form. As a result this causes urine output to decrease allowing for the uric acid to build up inside the organ. The increased acid concentration allows the iron from the aggregate protein to be released into the surrounding renal tissue. Iron then strips away molecular bonds of the surrounding tissue which eventually will lead to kidney failure if the tissue damage is too great.
Mechanical consideration
Muscle degeneration from rhabdomyolysis destroys the myosin and actin filaments in the affected tissue. This initiates the bodys natural reaction to increasing perfusion to the area allowing for an influx of specialized cells to repair the injury. However, the swelling increases the intracellular pressure beyond normal limits. As the pressure builds in the muscle tissue, the surrounding tissue is crushed against the underlying tissue and bone. This is known as compartment syndrome which leads to greater death of the surrounding muscle tissue around the injury. As the muscle dies this will cause pain to radiate from the affected area into the compartmentalized tissue. A loss of range of motion from swelling will also be seen in the affected limb. Along with muscle strength weakness associated with the muscles involved from loss of filament interaction.
Dehydration is a common risk factor for exertional rhabdomyolysis because it causes a reduction of plasma volume during exertion. This leads to a reduction of blood flow through the vascular system which inhibits blood vessel constriction.
Diagnosis
Exertional rhabdomyolysis, the exercise-induced muscle breakdown that results in muscle pain/soreness, is commonly diagnosed using the urine myoglobin test accompanied by high levels of creatine kinase (CK). Myoglobin is the protein released into the bloodstream when skeletal muscle is broken down. The urine test simply examines whether myoglobin is present or absent. When results are positive the urine normally obtains a dark, brown color followed by serum CK level evaluation to determine the severity of muscle damage. Elevated levels of serum CK greater than 5,000 U/L that are not caused by myocardial infarction, brain injury or disease, generally indicate serious muscle damage confirming the diagnosis of ER.
Urine is often a dark "cola" color as a result of the excretion of muscle cell components.
Prevention
Military data suggest that the risk of exertional rhabdomyolysis can be lowered by engaging in prolonged lower-intensity exercise, as opposed to high-intensity exercise over a shorter time period. In all athletic programs, three features should be present: (1) emphasizing prolonged lower-intensity exercise, as opposed to repetitive max intensity exercises; (2) adequate rest periods and a high-carbohydrate diet, to replenish glycogen stores; and (3) proper hydration, to enhance renal clearance of myoglobin. Also, exercise in above-average temperature and humidity can increase risk for ER. ER can be avoided by gradually increasing intensity during new exercise regimens, properly hydrating, acclimatization, and avoidance of diuretics during times of strenuous activity.
Treatment
After ER is diagnosed, treatment is applied to 1) avoid renal dysfunction and 2) alleviate symptoms. This should be followed by recommended rehabilitation program, exercise prescription (ExRx). Treatment involves extensive hydration normally done through IV fluid replacement with administration of normal saline until CK levels reduce to a maximum of 1,000 U/L. Proper treatment will ensure hydration and normalize muscle discomfort (pain), flu-like symptoms, CK levels, and myoglobin levels for patient to begin ExRx.Although sufficient evidence is currently lacking, supplementation with a combination of sodium bicarbonate and mannitol is commonly utilized to prevent kidney failure in rhabdomyolysis patients. Sodium bicarbonate alkalizes urine to stop myoglobin from precipitating in renal tubules. Mannitol has several effects, including vasodilatation of the renal vasculature, osmotic diuresis, and free-radical scavenging.
Recovery
Before initiating any form of physical activity, the individual must demonstrate a normal level of functioning with all previous symptoms absent. Physical activity should be supervised by a health care professional in case of a recurrence. However, in some low-risk individuals, supervision by a medical professional is not required as long as the individual follows up with weekly checkups. Proper hydration prior to performing physical activity and performing exercise in cool, dry environments may reduce the chances of developing a reoccurring episode of ER. Lastly, it is imperative for urine and blood values to be monitored along with careful observation for the redevelopment of any signs or symptoms.The recovery program focuses on progressive conditioning/reconditioning the individual and improving functional mobility. However, special considerations prior to participating in the rehabilitation program include the individuals 1) extent of muscle injury, if any 2) level of fitness before the incident and 3) weight training experience. These special considerations collectively are a form of assessing the individuals capacity to perform physical activity, which is ultimately used to specify the ExRx design.
Costs
The actual cost for this condition is unknown and also dependent on the level of the condition. In some cases ER can lead to acute kidney failure and bring medical costs up due to the need for hemodialysis for recovery/treatment.
== References == |
Proteus syndrome | Proteus syndrome is a rare disorder with a genetic background that can cause tissue overgrowth involving all three embryonic lineages. Patients with Proteus syndrome tend to have an increased risk of embryonic tumor development. The clinical and radiographic symptoms of Proteus syndrome are highly variable, as are its orthopedic manifestations.Only a few more than 200 cases have been confirmed worldwide, with estimates that about 120 people are currently alive with the condition. As attenuated forms of the disease may exist, there could be many people with Proteus syndrome who remain undiagnosed. Those most readily diagnosed are also the most severely disfigured.
The syndrome is named after the Greek sea-god Proteus, who could change his shape. The condition appears to have been first described in the American medical literature by Samia Temtamy and John Rogers in 1976. American pathologist Michael Cohen described it in 1979.
Signs and symptoms
Proteus syndrome causes an overgrowth of skin, bones, muscles, fatty tissues, and blood and lymphatic vessels. Proteus syndrome is a progressive condition wherein children are usually born without any obvious deformities. Tumors of skin and bone growths appear as they age typically in early childhood. The musculoskeletal manifestations are cardinal for the diagnosis of Proteus syndrome. The severity and locations of these various asymmetrical growths vary greatly but typically the skull, one or more limbs, and soles of the feet will be affected. There is a risk of premature death in affected individuals due to deep vein thrombosis and pulmonary embolism caused by the vessel malformations that are associated with this disorder. Because of carrying excess weight and enlarged limbs, arthritis and muscle pain may also be symptoms. Further risks may occur due to the mass of extra tissue.The disorder itself does not uniformly cause learning impairments: the distribution of intelligence deficits among those with Proteus syndrome appears higher than that of the general population, although this is difficult to determine with statistical significance. In addition, the presence of visible deformity may have a negative effect on the social experiences of the affected individual, causing cognitive and social deficits.Affected individuals are at increased risk for developing certain tumors including unilateral ovarian cystadenomas, testicular tumors, meningiomas, and monomorphic adenomas of the parotid gland.Hemimegalencephaly is often found to be associated.
Orthopaedic features
The musculoskeletal manifestations of Proteus syndrome are frequent and recognizable. Patients tend to demonstrate a unique pattern of skeletal abnormalities. The orthopaedic features are usually bilateral, asymmetrical, progressive and involving all four limbs and spine. Affected patients usually have localized periarticular limb distortions, limb length discrepancy, and spine deformity. Patients with Proteus syndrome can have regular bone configuration and contours despite the bone enlargement. Patients can also exhibit deformation of the skull in the form of dolichocephaly or elongated skull and facial abnormalities. Because of the rarity of the syndrome and the variability of signs, the orthopaedic management should be individualized.
Genetics
In 2011 researchers determined the cause of Proteus syndrome. In 26 of 29 patients who met strict clinical criteria for the disorder, Lindhurst et al. identified an activating mutation in AKT1 kinase in a mosaic state gene.Previous research had suggested the condition linked to PTEN on chromosome 10, while other research pointed to chromosome 16. Prior to the findings regarding AKT1 in 2011, other researchers expressed doubt regarding the involvement of PTEN or GPC3, which codes for glypican 3 and may play a role in regulating cell division and growth regulation.
Diagnosis
Differential diagnosis
Macrodystrophia lipomatosa
Fibrolipomatous hamartoma
Neurofibromatosis type 1
Klippel–Trénaunay syndrome
Parkes Weber syndrome
Sotos syndrome
Hemangiomas
Classification
Many sources classify Proteus syndrome to be a type of nevus syndrome. The lesions appear to be distributed in a mosaic manner. It has been confirmed that the disorder is an example of genetic mosaicism.
Treatment
A team of doctors in Australia have trial tested the drug rapamycin in the treatment of a patient said to have Proteus syndrome and have found it to be an effective remedy. However, the diagnosis of Proteus syndrome in this patient has been questioned by others.The Proteus syndrome research team in the National Human Genome Research Institute at the United States National Institutes of Health have initiated a Phase 0 dose finding trial with the AKT1 inhibitor ARQ 092, which is being developed by the Arqule Corporation. In earlier tests on tissue and cell samples obtained from patients, ARQ 092 reduced phosphorylation of AKT and downstream targets of AKT in as little as two hours. The Phase 0 trial opened in November 2015. This trial is based on in vitro data showing inhibition of AKT1 in cell lines from patients with Proteus syndrome.
Notable cases
In a 1986 article in the British Medical Journal, Michael Cohen and J.A.R. Tibbles put forward the theory that Joseph Merrick (an Englishman known as the "Elephant Man") had had Proteus syndrome. However, the exact condition had by Joseph Merrick is still not known with certainty.Mandy Sellars has been diagnosed by some doctors as having this condition. Her legs and feet have grown at a disproportionate rate since birth. However, in 2013, Sellars case was profiled on British television in a special called Shrinking My 17 Stone Legs, in which it was determined that Sellars condition was not, in fact, Proteus syndrome, but rather the often-misdiagnosed PIK3CA-related overgrowth spectrum, a syndrome caused by a PIK3CA gene mutation.
See also
Epidermal nevus syndrome
Mosaic (genetics)
Overgrowth syndrome
List of radiographic findings associated with cutaneous conditions
References
External links
GeneReviews/NCBI/NIH/UW entry on PTEN Hamartoma Tumor Syndrome (PHTS) |
Geotrichosis | Geotrichosis is a mycosis caused by Geotrichum candidum.: 311
Human colonization and disease
Geotrichum candidum is also a frequent member of the human microbiome, notably associated with skin, sputum and feces where it occurs in 25-30% of specimens. The fungus can cause an infection known as geotrichosis, affecting the oral, bronchial, skin and bronchopulmonary epithelia. The inoculum may arise from endogenous or exogenous sources.In 1847 Bennett described Geotrichum candidum causing a superinfection in the tuberculous cavity. Bennett was able to differentiate infection by Geotrichum candidum from candidiasis, and diagnose the first case of geotrichosis. Other early medical case reports in 1916 and 1928 also described lung infections. Most cases affect the bronchopulmonary tree, although other sites can be involved, such as oral mucosa and vagina. Skin and gut infections are also known. Reported cases of geotrichosis have been characterized with symptoms of chronic or acute bronchitis. Exogenous geotrichosis may arise from contact with contaminated soil, fruits or dairy products.
Pulmonary geotrichosis is the most frequent form of geotrichosis. The symptoms appear to be secondary symptoms of tuberculosis. This includes symptoms such as light, thick, grey sputum, which in some cases may be blood-tinged. Patients often have a cough that produces clear or yellow sputum. Another symptom of pulmonary geotrichosis includes fine to medium rales. Patients may develop fever, rapid pulse and leukocytosis. The condition appears chronic with the presence of a little debilitation and fever. There is no chest pain and occasional wheezing can occur.
Bronchial geotrichosis does not involve the lung instead the disease persists within the bronchial. Geotrichum candidum grows in the lumen of the bronchi. The disease is characterized as an endobronchial infection. Bronchial geotrichosis is similar to the allergic reaction of aspergillosis. Symptoms include prominent chronic cough, gelatinous sputum, lack of fever and medium to coarse rales. Patients with the bronchial condition their pulse and respiration are rarely elevated. Fine mottling may be present in the middle or basilar pulmonary region. Colonization of the bronchi can be associated with Candida albicans and usually occur with patients with chronic obstructive lung disease.
Oral and vaginal geotrichosis is similar to thrush in its appearances and was often confused with this infection. The difference between oral and vaginal geotrichosis can be determined using microscope analysis. The infected area forms a white plaque and patients usually report burning sensation in the affected areas. The vaginal geotrichosis is more common in pregnant women and is often associated with vaginitis.
Gastrointestinal geotrichosis is enterocolitis associated with glutamic therapy. The symptoms usually stop once the glutamic therapy is discontinued. Establishment of the etiology of the fungi is difficult since G. candidum is found within the gut normal flora. The difference between normal gut flora form and the disease causing form is the production of toxins.
Cutaneous geotrichosis has two different types of variants which include superficial and deep infection. The superficial form the infection occurs on skin folds including submammary, inguinal, perianal and interdigital folds. The deep form develops nodules, tumours and ulcers on legs, face and hands. Geotrichosis can cause a cystic lesion appears as soft tissue on the skin.
Diagnosis
Laboratory culture
The diagnoses of geotrichosis cannot be determined without using culture or microscopic measurements. The laboratory diagnosis of geotrichosis involves collected fungi samples areas of infections without contamination. Scraping of the mouth lesions and the ulcers can provide a sample of G. candidum. Samples can also be collected from pus and mucus can be obtained from the feces. Sputum can be searched for the mucoid-like white flakes for further examination. Culturing the cylindrical barrel-shaped or elliptical fungi in considerable numbers in oral lesions is an indicator that a patient may have geotrichosis. Under the microscope the fungi appears yeast-like and septate branching hyphae that can be broken down into chains or individual arthrospores. Arthrospores appear rectangular with flat or rounded ends. Under the microscope the arthroconidia size range from 6-12μm x 3-6μm. Arthroconidia and coarse true hyphae can be observed can be observed under the microscope. Another identification method for G. candidum is selective isolation method. A selection isolation method based on the fungi tolerance to novobiocin and carbon dioxide can determine if G. candidum is the cause of illness.
Diagnostic imaging
X-rays can be used to examine the lung tissue, however it can not be used to positively diagnose geotrichosis. X-rays may show cavitation that is located the walls of the lungs tissues. The lung tissue resemble the early signs of tuberculosis. The results of an x-ray examination of pulmonary geotrichosis presents smooth, dense patchy infiltrations and some cavities. Bronchial geotrichosis shows peribronchial thickening with fine mottling may be present on middle or basilar pulmonary fields. Bronchial geotrichosis usually present itself as non-specific diffuse peribronchical infiltration.
Treatment
Geotrichosis generally has a good prognosis and patients generally have successful recovery. However, there is not a standard treatment for geotrichosis. There are several types of antimicrobial or antifungal compounds that can be used for geotrichosis treatment. Another method of treatment involves symptomatic care, bed rest, iodine therapy, aerosol nystatin and amphotericin B. Azole drugs including isoconazole and clotrimazole are used for geotrichosis treatment. Associated treatment for pulmonary geotrichosis includes the use of potassium iodide, sulfonamides or colistin. The associated asthma can be treated with desensitization and prednisolone. Amphotericin B, clotrimazole and S-fluorocytosine have become more susceptible to G. candidum. Antimycotic resistance can appear due to repeated treatment.
References
== External links == |
Acrogeria | Acrogeria (Gottrons syndrome) is a skin condition characterized by premature aging, typically in the form of unusually fragile, thin skin on the hands and feet (distal extremities). The prefix "acro" stems from the Greek akros which alludes to "extremity, tip" while the suffix "geria" comes from the Greek gerôn which means "elder".This is one of the classic congenital premature aging syndromes, occurring early in life, others being pangeria (Werners syndrome) and progeria (Hutchinson–Gilfords syndrome), and was characterized in 1940. Acrogeria was originally described by Gottron in 1941, when he noticed premature cutaneous aging localized on the hands and feet in two brothers. The problem had been present since birth.Onset is often in early childhood, it progresses over the next few years and then remains stable over time with morphology, colour and site remaining constant. A bruising tendency has been observed. Mutations in the COL3A1 gene, located at chromosome 2q31–q32, have been reported in varied phenotypes, including acrogeria and vascular rupture in Ehlers-Danlos syndrome (more especially type IV).
See also
Hutchinson–Gilford syndrome
List of cutaneous conditions
References
External links
Familial acrogeria in a brother and sister |
Giant axonal neuropathy | Giant axonal neuropathy is a rare, autosomal recessive neurological disorder that causes disorganization of neurofilaments. Neurofilaments form a structural framework that helps to define the shape and size of neurons and are essential for normal nerve function. A distinguishing feature is its association with kinky, or curly, hair; in such cases it has been called Giant axonal neuropathy with curly hair.
Genetics
Giant axonal neuropathy results from mutations in the GAN gene, which codes for the protein gigaxonin. This alters the shape of the protein, changing how it interacts with other proteins when organizing the structure of the neuron.Neurons affected by the altered protein accumulate excess neurofilaments in the axon, the long extension from the nerve cell that transmits its signal to other nerve cells and to muscles. These enlarged or giant axons cannot transmit signals properly, and eventually deteriorate, resulting in the range of neurological anomalies associated with the disorder.This disease is an autosomal recessive disorder, which means the defective gene is located on an autosome, and both parents must have 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 carriers, but are usually not affected by the disorder.
Diagnosis
Giant axonal neuropathy usually appears in infancy or early childhood, and is progressive. Early signs of the disorder often present in the peripheral nervous system, causing individuals with this disorder to have problems walking. Later, normal sensation, coordination, strength, and reflexes become affected. Hearing or vision problems may also occur. Abnormally kinky hair is characteristic of giant axonal neuropathy, appearing in almost all cases. As the disorder progresses, central nervous system becomes involved, which may cause a gradual decline in mental function, loss of control of body movement, and seizures.
Treatment
See also
Polyneuropathy in dogs and cats
References
This article may incorporate some public domain text from The U.S. National Library of Medicine
External links
Giant axonal neuropathy at NLM Genetics Home Reference
GeneReview/NIH/UW entry on Giant Axonal Neuropathy |
Sesamoiditis | Sesamoiditis is inflammation of the sesamoid bones.
Humans
Sesamoiditis occurs on the bottom of the foot, just behind the big toe. There are normally two sesamoid bones on each foot; sometimes sesamoids can be bipartite, which means they each comprise two separate pieces. The sesamoids are roughly the size of jelly beans. The sesamoid bones act as a fulcrum for the flexor tendons, the tendons which bend the big toe downward.
Symptoms include inflammation and pain.
Sometimes a sesamoid bone is fractured. This can be difficult to pick up on X-ray, so a bone scan or MRI is a better alternative.Among those who are susceptible to the malady are dancers, catchers and pitchers in baseball, soccer players, and football players.
Horses
In the horse it occurs at the horses fetlock. The sesamoid bones lie behind the bones of the fetlock, at the back of the joint, and help to keep the tendons and ligaments that run between them correctly functioning.
Usually periostitis (new bone growth) occurs along with sesamoiditis, and the suspensory ligament may also be affected. Sesamoiditis results in inflammation, pain, and eventually bone growth.
Causes
In humans, excessive forces caused by sudden bending upwards of the big toe, high heels, or a stumble can contribute to sesamoiditis. Once the sesamoid bone is injured it can be very difficult to cure, because additional pressure is put on the sesamoid bone during walking. Treatment in humans consists of anti-inflammatory medication, cortisone injections, strapping to immobilize the big toe, and orthotics with special accommodations to keep pressure off the affected bone.
In horses, sesamoiditis is generally caused by excess stress on the fetlock joint. Conformation that promotes sesamoiditis include long pasterns, or horses with long toes and low heels.
Notable cases
Josh Zeid, major league baseball pitcher
Melvin Upton, major league baseball player
JJ ODonnell, football player for Gateshead FC
References
== External links == |
Baboon syndrome | Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), more popularly known as baboon syndrome because of its resemblance to the distinctive red buttocks displayed by female baboons, is a systemic contact dermatitis characterized by well-demarcated patches of erythema distributed symmetrically on the buttocks.
The cause of the syndrome may be drug-related, i.e. induced by systemic administration of hydroxyzine penicillin, iodinated radio contrast media and others.
Symptoms and signs
The typical rash commonly appears on buttocks. This then resembles the colour of a baboons buttocks. Other areas like upper inner thigh and armpits, may be affected by the rash. The rashes are red and well-defined. The presentation is typically symmetrical and not associated with systemic symptoms.
Cause
Diagnosis
Treatment
Treatment of symmetrical drug related intertriginous and flexural exanthema involves identifying and stopping the causative agent. Topical steroids can help to reduce the redness.
Epidemiology
Baboon syndrome affects both sexes equally, and can occur at any age, but seems to be more common in childhood than in adulthood.
See also
Airbag dermatitis
List of cutaneous conditions
== References == |
Larsen syndrome | Larsen syndrome (LS) is a congenital disorder discovered in 1950 by Larsen and associates when they observed dislocation of the large joints and face anomalies in six of their patients. Patients with Larsen syndrome normally present with a variety of symptoms, including congenital anterior dislocation of the knees, dislocation of the hips and elbows, flattened facial appearance, prominent foreheads, and depressed nasal bridges. Larsen syndrome can also cause a variety of cardiovascular and orthopedic abnormalities. This rare disorder is caused by a genetic defect in the gene encoding filamin B, a cytoplasmic protein that is important in regulating the structure and activity of the cytoskeleton. The gene that influences the emergence of Larsen syndrome is found in chromosome region, 3p21.1-14.1, a region containing human type VII collagen gene. Larsen syndrome has recently been described as a mesenchyme disorder that affects the connective tissue of an individual. Autosomal dominant and recessive forms of the disorder have been reported, although most cases are autosomal dominant. Reports have found that in Western societies, Larsen syndrome can be found in one in every 100,000 births, but this is most likely an underestimate because the disorder is frequently unrecognized or misdiagnosed.
Signs and symptoms
Common symptoms
Symptoms are related to defects in connective tissue.
Congenital anterior dislocation of the knees
Dislocation of hips and shoulders
Flattened facial appearance
Prominent forehead
Depressed nasal bridge
Club foot
Cervical kyphosis
Cardiac anomalies
Cardiac defects are similar to those associated with Marfans syndrome, a disorder of the connective tissue.
Elongation of aorta
Bicuspid aortic valve
Subaortic stenosis
Mitral valve prolapse with mitral regurgitation
Atrial septal defect
Patent ductus arteriosus
Tricuspid valve prolapse
Aortic dissection and aneurysm
Aneurysm of ductus arteriosus
Other reported symptoms
These symptoms were found in rare cases of Larsen syndrome.
Cataracts
Cleft palate
Extra bones of wrist
Malocclusion
Microdontia and hypodontia
Complete agenesis of anus
Bifid uterus
Bifid tongue
Causes
Mutations in gene encoding filamin B
Filamins are cytoplasmic proteins that regulate the structure and activity of the cytoskeleton. These proteins serve as scaffolds on which intracellular signaling and protein trafficking are organized. Filamin B has been found to be expressed in human growth plate chondrocytes, which are especially important in vertebrae segmentation and skeleton morphogenesis. Genetic analysis of patients with Larsen syndrome has found the syndrome is caused by missense mutations in the gene that codes for filamin B. These mutations cause an accelerated rate of apoptosis in the epiphyseal growth plates of individuals with the mutation. The defects can cause short stature and other symptoms associated with Larsen syndrome.
Localization
Genetic analysis has found that a gene linked to Larsen syndrome, LAR1, is strongly linked to chromosome 3p markers. The locus of this gene is found in a region defined distally by D3S1581 and proximally by D3S1600. This location can be mapped to chromosome region 3p21.1-14.1. Human type VII collagen gene is found within this region in chromosome region 3p21.1. It is reasonable to believe that the joint abnormalities and cardiac anomalies associated with Larsen syndrome are related to the fact that the human type VII collagen gene is found within the same chromosome region as the LAR1 gene.
Genetics
Both autosomal dominant and recessive forms of Larsen syndrome have been reported. The former is significantly more common than the latter. Symptoms such as syndactyly, cleft palate, short stature, and cardiac defects are seen more commonly in individuals with the autosomal recessive form of the disorder. A lethal form of the disorder has been reported. It is described as being a combination of the Larsen phenotype and pulmonary hypoplasia.
Diagnosis
Ultrasound remains as one of the only effective ways of prenatally diagnosing Larsen syndrome. Prenatal diagnosis is extremely important, as it can help families prepare for the arrival of an infant with specifics necessities. Ultrasound can capture prenatal images of multiple joint dislocations, abnormal positioning of legs and knees, depressed nasal bridge, prominent forehead, and club feet. These symptoms are all associated with Larsen syndrome, so they can be used to confirm that a fetus has the disorder.
Treatment
Treatment for Larsen syndrome varies according to the symptoms of the individual. Orthopedic surgery can be performed to correct the serious joint defects associated with Larsen syndrome. Reconstructive surgery can be used to treat the facial abnormalities. Cervical kyphosis can be very dangerous to an individual because it can cause the vertebrae to disturb the spinal cord. Posterior cervical arthrodesis has been performed on patients with cervical kyphosis, and the results have been successful Propranolol has been used to treat some of the cardiac defects associated with Marfans syndrome, so the drug also has been suggested to treat cardiac defects associated with Larsen syndrome.
Prognosis
While Larsen syndrome can be lethal if untreated, the prognosis is relatively good if individuals are treated with orthopedic surgery, physical therapy, and other procedures used to treat the symptoms linked with Larsen syndrome.
See also
Boomerang dysplasia
References
External links
WebMD abstract |
Liebenberg syndrome | Liebenberg syndrome is a rare autosomal genetic disease that involves a deletion mutation upstream of the PITX1 gene, which is one thats responsible for the bodys organization, specifically in forming lower limbs. In animal studies, when this deletion was introduced to developing birds, their wing buds were noted to take on limb-like structures.The condition was first described by Dr. F. Liebenberg in 1973 while he followed multiple generations of a South African family, but it has since been noticed in other family lineages across the world.
Symptoms and signs
People who are affected by Liebenberg Syndrome suffer from three main symptoms:
Dysplasia (improper formation) of the bony components of the elbow
Abnormal shape of carpal bones
Brachydactyly, a symptom where the fingers and toes are shorter than normal.
Phenotype
People with Liebenberg Syndrome have normal overall body structure. Their morphological differences are in both of their distal humeri, elbows, hands and wrists. The elbows are enlarged with abnormally large olecranons and radial heads. Patients have relatively fixed elbow positions and are therefore unable to pronate or supinate their forearms. Their wrists are also limited in their active movements and have very prominent ulnar sides of the joints. The fingers adopt toe-like structures. Brachydactyly and camptodactyly occur; fingers are short and abnormally bent. These changes in finger shape result in small club shaped appendages. Motion is reduced in all digital joints of the hand.
Genetics
Liebenberg Syndrome follows an autosomal dominant mode of inheritance, whereby heterozygotes with this mutation express the disease phenotype.
It is caused by a heterozygous mutation to chromosome 5. It involves the inappropriate enhancement of the PITX1 gene due to genetic deletions and chromosome translocations.PITX1 is a homeobox gene which are genes that regulate proper body structure development. This PT1X gene encodes a transcription factor expressed in hind limbs. When expressed, it causes the formation of hindlimb structures.Liebenberg Syndrome is a result of one of two different genetic mutations. The first is a deletion upstream of the PITX1 gene on chromosome 5. This deletion includes the H2AFY gene, which is responsible for suppressing an upstream enhancer element known as hs1473. When H2AFY is removed, the enhancer is brought closer to PITX1 and inappropriately enhances it in forelimbs, causing them to adopt hindlimb morphology.The second mutation that can cause the phenotype for Liebenberg syndrome is a translocation of chromosome 18 and chromosome 5. Translocation mutations are ones that switch parts of non-homologous chromosomes with each other. This move introduces two enhancers from chromosome 18 to move to a position directly upstream of PITX1 on chromosome 5. The enhancers increase transcription of the PITX1 gene and cause patients to develop the same phenotype described above.
Diagnosis
Treatment
Surgery is an option to correct some of the morphological changes made by Liebenberg Syndrome. Cases exist where surgery is performed to correct radial deviations and flexion deformities in the wrist. A surgery called a carpectomy has been performed on a patient whereby a surgeon removes the proximal row of the carpal bones. This procedure removes some of the carpal bones to create a more regular wrist function than is observed in people with this condition.
References
== External links == |
Tolosa–Hunt syndrome | Tolosa–Hunt syndrome is a rare disorder characterized by severe and unilateral headaches with orbital pain, along with weakness and paralysis (ophthalmoplegia) of certain eye muscles (extraocular palsies).In 2004, the International Headache Society provided a definition of the diagnostic criteria which included granuloma.
Signs and symptoms
Symptoms are usually limited to one side of the head, and in most cases the individual affected will experience intense, sharp pain and paralysis of muscles around the eye. Symptoms may subside without medical intervention, yet recur without a noticeable pattern.In addition, affected individuals may experience paralysis of various facial nerves and drooping of the upper eyelid (ptosis). Other signs include double vision, fever, chronic fatigue, vertigo or arthralgia. Occasionally the patient may present with a feeling of protrusion of one or both eyeballs (exophthalmos).
Causes
The cause of Tolosa–Hunt syndrome is not known, but the disorder is thought to be, and often assumed to be, associated with inflammation of the areas behind the eyes (cavernous sinus and superior orbital fissure).
Diagnosis
Tolosa–Hunt syndrome is usually diagnosed via exclusion, and as such a vast amount of laboratory tests are required to rule out other causes of the patients symptoms. These tests include a complete blood count, thyroid function tests and serum protein electrophoresis. Studies of cerebrospinal fluid may also be beneficial in distinguishing between Tolosa–Hunt syndrome and conditions with similar signs and symptoms.MRI scans of the brain and orbit with and without contrast, magnetic resonance angiography or digital subtraction angiography and a CT scan of the brain and orbit with and without contrast may all be useful in detecting inflammatory changes in the cavernous sinus, superior orbital fissure and/or orbital apex. Inflammatory change of the orbit on cross sectional imaging in the absence of cranial nerve palsy is described by the more benign and general nomenclature of orbital pseudotumor.Sometimes a biopsy may need to be obtained to confirm the diagnosis, as it is useful in ruling out a neoplasm. Other diagnoses to consider include craniopharyngioma, migraine and meningioma.
Treatment
Treatment of Tolosa–Hunt syndrome includes immunosuppressives such as corticosteroids (often prednisolone) or steroid-sparing agents (such as methotrexate or azathioprine).Radiotherapy has also been proposed.
Prognosis
The prognosis of Tolosa–Hunt syndrome is usually considered good. Patients usually respond to corticosteroids, and spontaneous remission can occur, although movement of ocular muscles may remain damaged. Roughly 30–40% of patients who are treated for Tolosa–Hunt syndrome experience a relapse.
Epidemiology
Tolosa–Hunt syndrome is uncommon internationally. There is one recorded case in New South Wales, Australia. Both sexes, male and female, are affected equally, and it typically occurs around the age of 60.
References
== External links == |
Familial thoracic aortic aneurysm and aortic dissection | Familial thoracic aortic aneurysm and aortic dissection is a very rare vascular genetic disorder, its characterized by recurrent thoracic aortic aneurysms and aortic dissections within a family, these mentioned complications affect one or more aortic segments without any other disease being associated with them. People with this disorder have a higher chance of having a potentially fatal aortic rupture. This disorder is the cause of 20% of thoracic aortic aneurysmsSome families affected by this condition have shown mild versions of some symptoms that are associated with Marfan syndrome and Loeys-Dietz syndrome, these signs include tall stature, joint hypermobility, cutaneous stretch marks, and either pectus excavatum or pectus carinatum. Less common symptoms in other affected families include scoliosis, congenital heart defects, inguinal hernia, and/or livedo reticularis.
Etiology
This disorder is caused by mutations in one or more of the following genes:
FOXE3 (located on 1p33)
SMAD2 (located on 18q21.1)
LOX (located on 5q23.3-31.2)
MAT2A (located on ???)
ELN (located on chromosome 7)
HEY2 (located on 6q22.31)
TGFB3 (located on 14q24.3)
TGFBR1 (located on 9q22.33)
TGFBR2 (located on 3p24.1)
FBN1 (located on 15q21.1)
ACTA2 (located on 10q23.31
MYLK (located on 3q21.1)
SMAD3 (located on 15q22.33)
PRKG1 (located on 10q11.23-q21.1)
MFAP5 (located on 12p13.31)
TGFB2 (located on 1q41)
SMAD4 (located on 18q21.2)
MYH11 (located on 16p13.11)This disorder is inherited in an autosomal dominant manner, meaning only one copy of a mutated gene is needed in order for the disease to develop.
== References == |
Pagetoid reticulosis | Pagetoid reticulosis (also known as "acral mycoses fungoides", "localized epidermotropic reticulosis", "mycosis fungoides palmaris et plantaris", "unilesional mycosis fungoides", and "Woringer–Kolopp disease") is a cutaneous condition, an uncommon lymphoproliferative disorder, sometimes considered a form of mycosis fungoides.: 734
Symptoms and Signs
Lesions emerge as well-demarcated psoriasiform or hyperkeratotic patches and plaques, with a central clearing and an elevated border. Pagetoid reticulosis is a very slow progressive variant of mycosis fungoides and is usually localized unlike the latter.
Treatment
The most common method of treatment includes radiotherapy and/or surgical excision.
See also
Pagetoid
Cutaneous T-cell lymphoma
List of cutaneous conditions
References
== External links == |
Smokers melanosis | Smokers melanosis is seen with the naked eye as a brown to black pigmentation of the oral tissue i.e. the gums, cheeks or palate as well as in larynx. It is most often seen in the lower labial gingiva of tobacco users. Most easily it is found in Caucasians, due to their lack of a genetically caused melanin pigmentation.The brown to black colour is melanin. In skin, melanin prevents harmful UV-light from reaching deeper, sensible parts of the tissue. If UV-light penetrates deep, some of the toxic substances due to the UV-light damage to the cells, are bound to melanin in the epithelial cells and travel with the ageing cells to the skin surface, where they are expelled from the tissue surface. In this way the melanocytes and keratinocytes together protect the tissue, with melanin serving as a toxic defence and cleaning agent.
In the oral mucosa, where the ageing epithelial cells move faster to the surface compared to skin, a similar defence-mechanism seems to be present, cleaning the mucosa from different toxic chemicals penetrating the epithelium. Besides chemicals in tobacco also antimalaria-drugs cause an oral pigmentation. Smokers melanosis is like the genetic melanin pigmentations, a defence-system in action.
The microscope shows smokers melanosis to be characterized by a melanin hyperpigmentation of the lower part of the oral epithelium, similar to sun-tanned skin. The hyperpigmentation consists of melanin granules which have the shape and colour of "coffea beans". They are produced by the dendritic, octopus-like melanocytes, seen between the epithelial cells situated closest to the epithelium/connective tissue border.In tobacco-users the melanocytes are stimulated to produce melanin granules and to distribute them out to the surrounding epithelial cells for further transport to the mucosal surface, like the mechanism in melanin-pigmented skin.
Small amounts of melanin-like granules together with other electron-dense particles can also be seen within large melanosome complexes in the underlying connective tissue. If the granules derive from the epithelium, a phenomenon known as melanin incontinence, is not known. In Caucasians these granules are not expected to influence on the clinically observed degree of smokers melanosis.
Causes
Smoking or the use of nicotine-containing drugs is the cause to Smokers melanosis,. Also tar-components (benzopyrenes) are known to stimulate melanocytes to melanin production, and other unknown toxic agents in tobacco may also be the cause. These chemical agents have a polycyclic, chain-like structure. Environmental tobacco smoke from parents is causing smokers melanosis in their children Swedish snuff causes a small elevation of oral melanin pigmented individuals from 3.0% to 4.7%. Nicotine tablets have shown to stimulate to melanin pigmentation of the oral mucosa.
Treatment and prognosis
Lesions usually disappear between 3 months to 3 years for those who stop smoking. Smokers melanosis is a benign, normal physiological reaction, and does not develop into cancer. If it does not disappear, however, a biopsy can verify the diagnosis. If Smokers melanosis is destroyed by excessive smoking, as in the hard palate of reverse smokers, who smoke with the glowing part of the cigarette inside the mouth for different reasons, a pale depigmented surface is first seen, indicating the loss of the protecting melanin. Then a red inflammation sometimes occurs and cancer development may follow. In reverse smokers it is important to regularly inspect the areas with Smokers melanosis to detect any melanin destruction, in order to stop smoking in time and thus prevent a cancer to develop.
Epidemiology
A study in Sweden showed that 21.5% of smokers and 3% of nonsmokers (genetic pigmentation or unknown cause) had lesions that could be classified as an oral melanin pigmentation. A gingival melanin index in 4 degrees was established. Already with a consumption of 1-3 cigarettes a day 9.3% of all 20.333 examined showed a smokers melanosis. Pipe smokers had smokers melanosis in 16.8%. One year after the start of cigarette smoking a clinically visible smokers melanosis could be seen in 12.3% of women, and 17% among men.
In cigarette smokers who quit smoking, the number of individuals with smokers melanosis becomes slowly less frequent after 2–3 months, but can still be seen in a few former smokers three years after smoking stop.
Although clinically visible genetic melanin pigmentations in the mouth are present in several ethnic groups all over the world, more mucosal areas will be melanin-pigmentet if tobacco products are used. Smokers melanosis is found in India, Italy, Japan, Nigeria, Sweden, Turkey, USA, and several other countries.Smokers melanosis is expected to be found also in other tissue surfaces exposed to tobacco and tobacco smoke, for instance lips and in skin of the fingers holding the cigarette. Future studies will also show if the use of tobacco exaggerates the pigmentation of skin.
Gallery
See also
Melanosis coli
Peutz–Jeghers syndrome
Stomatitis nicotina
Smokeless tobacco keratosis
References
External links
YouTube the Audiopedia: What is SMOKERS MELANOSIS? What does SMOKERS MELANOSIS mean? SMOKERS MELANOSIS meaning - SMOKERS MELANOSIS definition - SMOKERS MELANOSIS explanation. |
Atrichia with papular lesions | Atrichia with papular lesions (a.k.a. "Papular atrichia") is a diffuse hair loss caused by an abnormality of the human homologue of the mouse hairless gene.: 635 : 762 It is associated with HR.
See also
Cicatricial alopecia
List of cutaneous conditions
References
== External links == |
Childhood granulomatous periorificial dermatitis | Childhood granulomatous periorificial dermatitis (CGPD), is a rare benign granulomatous skin disease of unknown cause. The disorder was first described in 1970 by Gianotti in a case series of five children. CGPD is more common in boys than girls.
Signs and symptoms
CGPD is characterized by the presence of small, raised, dome-shaped, flesh-colored or yellow-brown papules primarily distributed around the mouth, eyes, and nose. Affected children may also have papules on the ears, eyelids, cheeks, forehead, and nose. CGPD skin lesions rarely affect areas of the skin other than the face.
Cause
The cause of CGPD is unknown.
Diagnosis
The approach to diagnosing CGPD is controversial. Certain dermatologists suggest that ruling out infectious and allergic causes of similar skin eruptions and a skin biopsy demonstrating features consistent with CGPD is adequate for diagnosis. In contrast, other dermatologists advocate for performing a complete history and physical examination and obtaining laboratories and appropriate imaging to rule out cutaneous sarcoidosis. On microscopy, non-tuberculous granulomas with surrounding lymphocytes clustered around hair follicles may be seen; additionally, infiltrates of epithelioid macrophages, lymphocytes, and giant cells may also be seen.Several conditions exhibit skin findings similar to those of CGPD. These conditions include perioral dermatitis, acne vulgaris, granulomatous rosacea, contact dermatitis, folliculitis, atopic dermatitis, cheilitis, medication-induced acneiform eruptions, lupus miliaris disseminatus faciei, benign cephalic histiocytosis, granulosis rubra nasi, xanthomas, zinc deficiency, glucagonoma, cutaneous sarcoidosis, and scabies.
Treatment
Treatment recommendations for CGPD vary and may include observation without treatment, stopping the use of topical corticosteroids, and the use of topical or oral antibiotics as well as isotretinoin. Topical antibiotics such as metronidazole and erythromycin have been used for CGPD. Oral antibiotics of the tetracycline class such as minocycline, doxycycline, and tetracycline have been recommended for CGPD. Trimethoprim/sulfamethoxazole has also been used. The use of oral systemic antibiotics is limited by side effects such as nausea, vomiting, and sensitivity of the skin to sunlight. Tetracycline antibiotics are not recommended for children under the age of 8 since tetracyclines are known to deposit in teeth (thereby staining them) and impair bone growth in children.The use of calcineurin inhibitor creams such as tacrolimus or pimecrolimus on the skin is controversial and results have been mixed. Certain studies found the use of topical calcineurin inhibitors led to resolution of CGPD whereas others saw incomplete resolution or prolonged symptoms. Topical azelaic acid has been used successfully to treat CGPD. Immediate discontinuation of topical corticosteroids is recommended since corticosteroids are thought to worsen CGPD.
Prognosis
CGPD is known to be a temporary skin disease with a benign course. The skin papules typically resolve after a few months to a few years. After CGPD resolves, the skin may return to normal without scarring or may have small atrophic depressions with collagen loss, milia, or small pit-like scars.
Epidemiology
CGPD occurs most often in children of Afro-Caribbean descent before puberty though reports of this disease occurring in Asian and Caucasian children have also been described. Due to the limited number of reported cases, it remains controversial whether CGPD occurs more often in African children than in children of other races. CGPD is more common in boys than girls.
History
Gianotti et al. first described CGPD in five Italian children in 1970. In 1990, Williams et al. described a similar skin eruption in five children of Afro-Caribbean descent and coined the proposed term "facial Afro-Caribbean childhood eruption (FACE)". Subsequently, another article by Katz and Lesher first introduced the term CGPD since some reported cases were not found in children of Afro-Caribbean descent and to avoid confusion with perioral dermatitis.
See also
Perioral dermatitis
== References == |
Cylindroma | A variant of eccrine spiradenoma which can be multiple on the scalp and can coalesce to form a Turban tumour. In pathology, a cylindroma is a tumour with nests of cells that resemble a cylinder in cross section.
Types include:
Dermal eccrine cylindroma, a benign tumour of the skin
Adenoid cystic carcinoma, a malignant tumour of the salivary gland
See also
CYLD cutaneous syndrome
List of cutaneous neoplasms associated with systemic syndromes
== External links == |
Renovascular hypertension | Renovascular hypertension is a condition in which high blood pressure is caused by the kidneys hormonal response to narrowing of the arteries supplying the kidneys. When functioning properly this hormonal axis regulates blood pressure. Due to low local blood flow, the kidneys mistakenly increase blood pressure of the entire circulatory system. It is a form of secondary hypertension - a form of hypertension whose cause is identifiable.
Signs and symptoms
Symptoms of renovascular hypertension include the following:
High blood pressure (early age)
Kidney dysfunction
Narrowing of arteries elsewhere in the body
Pulmonary edema
Cause
The cause of renovascular hypertension is consistent with any narrowing/blockage of blood supply to the renal organ (renal artery stenosis). As a consequence of this action the renal organs release hormones that indicate to the body to maintain a higher amount of sodium and water, which in turn causes blood pressure to rise. Factors that may contribute are: diabetes, high cholesterol and advanced age, also of importance is that a unilateral
condition is sufficient to cause renovascular hypertension.
Pathogenesis
The pathogenesis of renovascular hypertension involves the narrowing of the arteries supplying the kidneys which causes a low perfusion pressure that is detected by the juxtaglomerular apparatus (via the macula densa cells, which act as baroreceptors; located on the afferent arteriole wall). This leads to renin secretion that causes the angiotensinogen conversion to angiotensin I. Angiotensin I then proceeds to the lung where it is converted to angiotensin II via angiotensin converting enzyme (ACE).In most people fibromuscular dysplasia or atherosclerosis is the reason for the occlusion of a renal artery which ultimately leads to this condition.
Diagnosis
The diagnosis for renovascular hypertension is done by:
Blood test (for renal function)
Urinary test (tests for microalbuminuria)
Serology (to exclude systemic lupus erythematosus )
Lipid profile
Urinalysis (to exclude presence of red blood cells)
Treatment
In terms of treatment for renovascular hypertension surgical revascularization versus medical therapy for atherosclerosis, it is not clear if one option is better than the other according to a 2014 Cochrane review; balloon angioplasty did show a small improvement in blood pressure .Surgery can include percutaneous surgical revascularization, and also nephrectomy or autotransplantation, and the individual may be given beta-adrenergic blockers. Early therapeutic intervention is important if ischemic nephropathy is to be prevented. Inpatient care is necessary for the management of hypertensive urgencies, quick intervention is required to prevent further damage to the kidneys.
Prognosis
The prognosis of individuals with renovascular hypertension is not easy to determine. Those with atherosclerotic renal artery disease have a high risk of mortality, furthermore, those who also have renal dysfunction have a higher mortality risk.
However, the majority of renovascular diseases can be improved with surgery.
See also
Fibromuscular dysplasia
Hypertensive nephropathy
Kidney failure
Renal artery stenosis
References
Further reading
Advances in Renal Hypertension Research and Treatment: 2012 Edition: ScholarlyPaper. ScholarlyEditions. 2012-12-26. ISBN 9781481636018.
Textor, Stephen C. (2009). "Current Approaches to Renovascular Hypertension". Medical Clinics of North America. 93 (3): 717–32, Table of Contents. doi:10.1016/j.mcna.2009.02.012. PMC 2752469. PMID 19427501.
Mehta, Ankit N.; Fenves, Andrew (2010). "Current opinions in renovascular hypertension". Proceedings. 23 (3): 246–9. doi:10.1080/08998280.2010.11928627. PMC 2900976. PMID 20671820.
== External links == |
Mantleoma | Mantleoma is a benign neoplasm with mantle differentiation and they tend to occur on the face, early neoplasms consist only of cords and columns of undifferentiated epithelial cells.: 675
See also
Trichodiscoma
Fibrofolliculoma
== References == |
Boutonneuse fever | Boutonneuse fever (also called, Mediterranean spotted fever, fièvre boutonneuse, Kenya tick typhus, Indian tick typhus, Marseilles fever, or Astrakhan fever) is a fever as a result of a rickettsial infection caused by the bacterium Rickettsia conorii and transmitted by the dog tick Rhipicephalus sanguineus. Boutonneuse fever can be seen in many places around the world, although it is endemic in countries surrounding the Mediterranean Sea. This disease was first described in Tunisia in 1910 by Conor and Bruch and was named boutonneuse (French for "spotty") due to its papular skin-rash characteristics.
Presentation
After an incubation period around seven days, the disease manifests abruptly with chills, high fevers, muscular and articular pains, severe headache, and photophobia. The location of the bite forms a black, ulcerous crust (tache noire). Around the fourth day of the illness, a widespread rash appears, first macular and then maculopapular, and sometimes petechial.
Diagnosis
The diagnosis is made with serologic methods, either the classic Weil–Felix test, (agglutination of Proteus OX strains), ELISA, or immunofluorescence assays in the bioptic material of the primary lesion.
The Weil–Felix test demonstrated low sensitivity (33%) in diagnosing acute rickettsial infections and low specificity, with a positive titre of 1:320 seen in 54% of healthy volunteers and 62% of non-rickettsial fever patients. Therefore, the use of the WFT should be discouraged in the diagnosis of acute rickettsial infections.
Treatment
The illness can be treated with tetracyclines (doxycycline is the preferred treatment), chloramphenicol, macrolides, or fluoroquinolones.
See also
Rocky Mountain spotted fever
References
== External links == |
List of phobias | The English suffixes -phobia, -phobic, -phobe (from Greek φόβος phobos, "fear") occur in technical usage in psychiatry to construct words that describe irrational, abnormal, unwarranted, persistent, or disabling fear as a mental disorder (e.g. agoraphobia), in chemistry to describe chemical aversions (e.g. hydrophobic), in biology to describe organisms that dislike certain conditions (e.g. acidophobia), and in medicine to describe hypersensitivity to a stimulus, usually sensory (e.g. photophobia). In common usage, they also form words that describe dislike or hatred of a particular thing or subject (e.g. homophobia). The suffix is antonymic to -phil-.
For more information on the psychiatric side, including how psychiatry groups phobias such as agoraphobia, social phobia, or simple phobia, see phobia. The following lists include words ending in -phobia, and include fears that have acquired names. In some cases, the naming of phobias has become a word game, of notable example being a 1998 humorous article published by BBC News. In some cases, a word ending in -phobia may have an antonym with the suffix -phil-, e.g. Germanophobe/Germanophile.
Many -phobia lists circulate on the Internet, with words collected from indiscriminate sources, often copying each other. Also, a number of psychiatric websites exist that at the first glance cover a huge number of phobias, but in fact use a standard text to fit any phobia and reuse it for all unusual phobias by merely changing the name. Sometimes it leads to bizarre results, such as suggestions to cure "prostitute phobia". Such practice is known as content spamming and is used to attract search engines.
An article published in 1897 in American Journal of Psychology noted "the absurd tendency to give Greek names to objects feared (which, as Arndt says, would give us such terms as klopsophobia – fear of thieves, triakaidekaphobia – fear of the number 13....)".
Psychological conditions
Specialists may prefer to avoid the suffix -phobia and use more descriptive terms such as personality disorders, anxiety disorders, and avoidant personality disorder. Terms should strictly have a Greek prefix although many are irregularly formed with Latin or even English prefixes. Many use inaccurate or imprecise prefixes, such as aerophobia (fear of air) for fear of flying.
A
B
C
D
E
F
G
H
I
K
L
M
N
O
P
R
S
T
V
W
X
Z
Cultural prejudices and discrimination
Ethnic prejudices and discrimination
The suffix -phobia is used to coin terms that denote a particular anti-ethnic or anti-demographic sentiment, such as Americanophobia, Europhobia, Francophobia, Hispanophobia, and Indophobia. Often a synonym with the prefix "anti-" already exists (e.g. Polonophobia vs. anti-Polonism). Anti-religious sentiments are expressed in terms such as Christianophobia and Islamophobia.
Medical conditions
Cultural phenomena
-phobia in the natural sciences
In the natural sciences, words with the suffix -phobia/-phobic generally describe a predisposition for avoidance and/or exclusion. For antonyms, see here
Jocular and fictional phobias
Aibohphobia – a humorous term for the fear of palindromes, which is a palindrome itself. The term is a piece of computer humor entered into the 1981 The Devils DP Dictionary.
Anatidaephobia – the fictional fear that one is being watched by a duck. The word comes from the name of the family Anatidae, and was used in Gary Larsons The Far Side.
Anoraknophobia – a portmanteau of "anorak" and "arachnophobia". It was used in the Wallace and Gromit comic book Anoraknophobia. Also the title of an album by Marillion.
Arachibutyrophobia – fear of peanut butter sticking to the roof of the mouth, from Latin arachis "peanut" and butyrum "butter". The word is used by Charles M. Schulz in a 1982 installment of his Peanuts comic strip, and by Peter ODonnell in his 1985 Modesty Blaise adventure novel Dead Mans Handle.
Charlophobia – the fictional fear of any person named Charlotte or Charlie, mentioned in the comedic book A Duck is Watching Me: Strange and Unusual Phobias (2014), by Bernie Hobbs. The phobia was created to mock name bias, a form of discrimination studied by researchers at the University of California, Berkeley and the University of Chicago.
Hippopotomonstrosesquipedaliophobia – fear of long words, from the root word sesquipedalophobia combined with monstrum and hippopotamus. This was mentioned on the first episode of Brainiac Series Five as a Tickles Teaser.
Keanuphobia – fear of Keanu Reeves, portrayed in the Dean Koontz book, False Memory, where a woman has an irrational fear of Reeves and has to see her psychiatrist, Mark Ahriman, each week, unaware that she only has the fear in the first place because Ahriman implanted it via hypnotic suggestion to amuse himself. He calls her "Keanuphobe" in his head.
Nihilophobia – fear of nothingness, from Latin nihil and "nothing, none", as described by the Doctor in the Star Trek: Voyager episode "Night". Voyagers morale officer and chef Neelix has this condition, having panic attacks while the ship was traversing a dark expanse of space known as the Void. It is also the title of a 2008 album by Neuronium.
Robophobia – irrational fear of robots and/or androids, also known as "Grimwades Syndrome". It was first used in "The Robots of Death", the fifth serial of the 14th season of the British science fiction television series Doctor Who.
Semaphobia – fear of average web developers to use Semantic Web technologies.
Venustraphobia – fear of beautiful women, according to a 1998 humorous article published by BBC News. Venustraphobia is also the title of a 2006 album by Casbah Club.
See also
List of paraphilias
Childhood phobia
Phobia
Specific phobia
References
Further reading
Aldrich, Chris (2 December 2002). The Aldrich Dictionary of Phobias and Other Word Families. Trafford Publishing. pp. 224–236. ISBN 1-55369-886-X.
External links
The Phobia List
Nursing Degree Guide |
Intracranial pressure | Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 mmHg for a supine adult. The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF.
Changes in ICP are attributed to volume changes in one or more of the constituents contained in the cranium. CSF pressure has been shown to be influenced by abrupt changes in intrathoracic pressure during coughing (which is induced by contraction of the diaphragm and abdominal wall muscles, the latter of which also increases intra-abdominal pressure), the valsalva maneuver, and communication with the vasculature (venous and arterial systems).
Intracranial hypertension (IH), also called increased ICP (IICP) or raised intracranial pressure (RICP), is elevation of the pressure in the cranium. ICP is normally 7–15 mm Hg; at 20–25 mm Hg, the upper limit of normal, treatment to reduce ICP may be needed.
Signs and symptoms of raised intracranial pressure
In general, symptoms and signs that suggest a rise in ICP include headache, vomiting without nausea, ocular palsies, altered level of consciousness, back pain, and papilledema. If papilledema is protracted, it may lead to visual disturbances, optic atrophy, and eventually blindness. The headache is classically a morning headache that may wake the person up. The brain is relatively poorly supplied by oxygen as a result of mild hypoventilation during the sleeping hours, and cerebral edema may worsen during the night due to the lying position. The headache is worse on coughing, sneezing, or bending and progressively worsens over time. There may also be personality or behavioral changes.In addition to the above, if mass effect is present with resulting displacement of brain tissue, additional signs may include pupillary dilatation, abducens palsies, and Cushings triad. Cushings triad involves an increased systolic blood pressure, a widened pulse pressure, bradycardia, and an abnormal respiratory pattern. In children, a low heart rate is especially suggestive of high ICP.Irregular respirations occur when injury to parts of the brain interfere with the respiratory drive. Biots respiration, in which breathing is rapid for a period and then absent for a period, occurs because of injury to the cerebral hemispheres or diencephalon. Hyperventilation can occur when the brain stem or tegmentum is damaged.As a rule, patients with normal blood pressure retain normal alertness with ICP of 25–40 mmHg (unless tissue shifts at the same time). Only when ICP exceeds 40–50 mmHg does CPP and cerebral perfusion decrease to a level that results in loss of consciousness. Any further elevations will lead to brain infarction and brain death.In infants and small children, the effects of ICP differ because their cranial sutures have not closed. In infants, the fontanels, or soft spots on the head where the skull bones have not yet fused, bulge when ICP gets too high. ICP correlates with intraocular pressure (IOP) but seems to lack the accuracy necessary for close management of intracranial pressure in the acute posttraumatic period.Papilledema, or the swelling of the optic disc, can be a reliable sign that ICP is elevated. Unlike other conditions that may result in the swelling of the optic disc, it is in the case of papilledema that vision may go largely unaffected.
Causes of abnormal intracranial pressure
Increased ICP
Causes of increased intracranial pressure can be classified by the mechanism in which ICP is increased:
Mass effect such as brain tumor, infarction with edema, contusions, subdural or epidural hematoma, or abscesses all tend to deform the adjacent brain.
Generalized brain swelling can occur in ischemic-anoxia states, acute liver failure, hypertensive encephalopathy, hypercarbia (hypercapnia), and Reye hepatocerebral syndrome. These conditions tend to decrease the cerebral perfusion pressure but with minimal tissue shifts.
Increase in venous pressure can be due to venous sinus thrombosis, heart failure, or obstruction of superior mediastinal or jugular veins.
Obstruction to CSF flow and/or absorption can occur in hydrocephalus (blockage in ventricles or subarachnoid space at base of brain, e.g., by Arnold–Chiari malformation), extensive meningeal disease (e.g., infection, carcinoma, granuloma, or hemorrhage), or obstruction in cerebral convexities and superior sagittal sinus (decreased absorption).
Increased CSF production can occur in meningitis, subarachnoid hemorrhage, or choroid plexus tumor.
Idiopathic or unknown cause (idiopathic intracranial hypertension, a common cause in otherwise well people especially younger women)
CraniosynostosisOne of the most damaging aspects of brain trauma and other conditions, directly correlated with poor outcome, is an elevated intracranial pressure. ICP is very likely to cause severe harm if it rises too high. Very high intracranial pressures are usually fatal if prolonged, but children can tolerate higher pressures for longer periods. An increase in pressure, most commonly due to head injury leading to intracranial hematoma or cerebral edema, can crush brain tissue, shift brain structures, contribute to hydrocephalus, cause brain herniation, and restrict blood supply to the brain. It is a cause of reflex bradycardia.
Low ICP
Spontaneous intracranial hypotension may occur as a result of an occult leak of CSF into another body cavity. More commonly, decreased ICP is the result of lumbar puncture or other medical procedures involving the brain or spinal cord. Various medical imaging technologies exist to assist in identifying the cause of decreased ICP. Often, the syndrome is self-limiting, especially if it is the result of a medical procedure.If persistent intracranial hypotension is the result of a lumbar puncture, a "blood patch" may be applied to seal the site of CSF leakage. Various medical treatments have been proposed; only the intravenous administration of caffeine and theophylline has shown to be particularly useful.
Pathophysiology
Cerebral perfusion pressure (CPP), the pressure of blood flowing to the brain, is normally fairly constant due to autoregulation, but for abnormal mean arterial pressure (MAP) or abnormal ICP the cerebral perfusion pressure is calculated by subtracting the intracranial pressure from the mean arterial pressure: CPP = MAP − ICP . One of the main dangers of increased ICP is that it can cause ischemia by decreasing CPP. Once the ICP approaches the level of the mean systemic pressure, cerebral perfusion falls. The bodys response to a fall in CPP is to raise systemic blood pressure and dilate cerebral blood vessels. This results in increased cerebral blood volume, which increases ICP, lowering CPP further and causing a vicious cycle. This results in widespread reduction in cerebral flow and perfusion, eventually leading to ischemia and brain infarction. Increased blood pressure can also make intracranial hemorrhages bleed faster, also increasing ICP.Severely raised ICP, if caused by a unilateral space-occupying lesion (e.g. a hematoma) can result in midline shift, a dangerous sequela in which the brain moves toward one side as the result of massive swelling in a cerebral hemisphere. Midline shift can compress the ventricles and lead to hydrocephalus.
Monro–Kellie hypothesis
The pressure–volume relationship between ICP, volume of CSF, blood, and brain tissue, and cerebral perfusion pressure (CPP) is known as the Monro–Kellie doctrine or hypothesis.The Monro–Kellie hypothesis states that the cranial compartment is inelastic and that the volume inside the cranium is fixed. The cranium and its constituents (blood, CSF, and brain tissue) create a state of volume equilibrium, such that any increase in volume of one of the cranial constituents must be compensated by a decrease in volume of another. *This concept only applies to adults, as the presence of fontanelles and open suture lines in infants that have not yet fused means there is potential for a change in size and intracranial volume.
The principal buffers for increased volumes include CSF and, to a lesser extent, blood volume. These buffers respond to increases in volume of the remaining intracranial constituents. For example, an increase in lesion volume (e.g., epidural hematoma) will be compensated by the downward displacement of CSF and venous blood.The Monro–Kellie hypothesis is named after Edinburgh doctors Alexander Monro and George Kellie.
Diagnosis
The most definitive way of measuring the intracranial pressure is with transducers placed within the brain. A catheter can be surgically inserted into one of the brains lateral ventricles and can be used to drain CSF (cerebrospinal fluid) in order to decrease ICPs. This type of drain is known as an external ventricular drain (EVD). This is rarely required outside brain injury and brain surgery settings.In situations when only small amounts of CSF are to be drained to reduce ICPs (e.g. in IIH), drainage of CSF via lumbar puncture can be used as a treatment. Non-invasive measurement of intracranial pressure is being studied.
Treatment
The treatment for ICP depends on the cause. In addition to management of the underlying causes, major considerations in acute treatment of increased ICP relates to the management of stroke and cerebral trauma.For long-term or chronic forms of raised ICP, especially idiopathic intracranial hypertension (IIH), a specific type of diuretic medication (acetazolamide) is used. In cases of confirmed brain neoplasm, dexamethasone is given to decrease ICP. Although the exact mechanism is unknown, current research shows that dexamethasone is capable of decreasing peritumoral water content and local tissue pressure to decrease ICP.
Ventilation
In people who have high ICP due to an acute injury, it is particularly important to ensure adequate airway, breathing, and oxygenation. Inadequate blood oxygen levels (hypoxia) or excessively high carbon dioxide levels (hypercapnia) cause cerebral blood vessels to dilate, increasing the flow of blood to the brain and causing the ICP to rise. Inadequate oxygenation also forces brain cells to produce energy using anaerobic metabolism, which produces lactic acid and lowers pH, also dilating blood vessels and exacerbating the problem. Conversely, blood vessels constrict when carbon dioxide levels are below normal, so hyperventilating a person with a ventilator or bag valve mask can temporarily reduce ICP. Hyperventilation was formerly a part of the standard treatment of traumatic brain injuries, but the induced constriction of blood vessels limits blood flow to the brain at a time when the brain may already be ischemic—hence it is no longer widely used. Furthermore, the brain adjusts to the new level of carbon dioxide after 48 to 72 hours of hyperventilation, which could cause the vessels to rapidly dilate if carbon-dioxide levels were returned to normal too quickly. Hyperventilation is still used if ICP is resistant to other methods of control, or there are signs of brain herniation, because the damage herniation can cause is so severe that it may be worthwhile to constrict blood vessels even if doing so reduces blood flow. ICP can also be lowered by raising the head of the bed, improving venous drainage. A side effect of this is that it could lower pressure of blood to the head, resulting in a reduced and possibly inadequate blood supply to the brain. Venous drainage may also be impeded by external factors such as hard collars to immobilize the neck in trauma patients, and this may also increase the ICP. Sandbags may be used to further limit neck movement.
Medication
In the hospital, the blood pressure can be increased in order to increase CPP, increase perfusion, oxygenate tissues, remove wastes, and thereby lessen swelling. Since hypertension is the bodys way of forcing blood into the brain, medical professionals do not normally interfere with it when it is found in a person with a head injury. When it is necessary to decrease cerebral blood flow, MAP can be lowered using common antihypertensive agents such as calcium channel blockers.If there is an intact blood–brain barrier, osmotherapy (mannitol or hypertonic saline) may be used to decrease ICP.It is unclear whether mannitol or hypertonic saline is superior, or if they improve outcomes.Struggling, restlessness, and seizures can increase metabolic demands and oxygen consumption, as well as increasing blood pressure. Analgesia and sedation are used to reduce agitation and metabolic needs of the brain, but these medications may cause low blood pressure and other side effects. Thus if full sedation alone is ineffective, people may be paralyzed with drugs such as atracurium. Paralysis allows the cerebral veins to drain more easily, but can mask signs of seizures, and the drugs can have other harmful effects. Paralysing drugs are only introduced if patients are fully sedated (this is essentially the same as a general anaesthetic)
Surgery
Craniotomies are holes drilled in the skull with the help of cranial drills to remove intracranial hematomas or relieve pressure from parts of the brain. As raised ICPs may be caused by the presence of a mass, removal of this via craniotomy will decrease raised ICPs.A drastic treatment for increased ICP is decompressive craniectomy, in which a part of the skull is removed and the dura mater is expanded to allow the brain to swell without crushing it or causing herniation. The section of bone removed, known as a bone flap, can be stored in the patients abdomen and resited back to complete the skull once the acute cause of raised ICPs has resolved. Alternatively a synthetic material may be used to replace the removed bone section (see cranioplasty)
See also
Brain Trauma Foundation
Copper beaten skull
Pressure reactivity index (PRx)
References
External links
Gruen P. 2002. "Monro-Kellie Model" Neurosurgery Infonet. USC Neurosurgery. Accessed January 4, 2007.
National Guideline Clearinghouse. 2005. Guidelines for the management of severe traumatic brain injury. Firstgov. Accessed January 4, 2007.
Intracranial+Pressure at the US National Library of Medicine Medical Subject Headings (MeSH) |
Primordial cyst | A primordial cyst is a developmental odontogenic cyst. It is found in an area where a tooth should have formed but is missing. Primordial cysts most commonly arise in the area of mandibular third molars. Under microscopes, the cyst looks like an odontogenic keratocyst (also called a Keratocyst odontogenic tumor) whereby the lesions displays a parakeratinized epithelium with palisading basal epithelial cells.
The term "Primordial cyst" is considered an outdated term and should be avoided. Most "primordial cysts" are actually Keratocyst odontogenic tumors (KOTs).
References
Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001. |
Acne cosmetica | The term acne cosmetica refers to acne caused by or aggravated by cosmetics.: 240 The mechanism is thought to be chemically induced plugging of the pilosebaceous orifice. This became a significant problem for dermatologists in the 1970s and 1980s, but with the improved formulations produced by cosmetic chemists in the decades since, a diagnosis of acne cosmetica has become relatively rare in dermatological practice.
The terms "non-comedogenic" and "non-acne(i)genic" appeared on moisturizers and other cosmetic compounds as manufacturers introduced re-formulations—sometimes associated with claims that the products were "oil-free" or "water-based". Although early work produced lists of comedogenic chemicals in various strengths and vehicles, it became apparent that one could not predict the actual comedogenicity of a product from its contents; rather, the finished product itself needed use-testing.The production of a low-grade folliculitis by some components of cosmetic products has led to misdiagnosis on occasion.
People may not attribute skin reactions to their cosmetics at first, but may notice worsening symptoms after using certain face makeup, sunblock or lip products.
Reactions are more likely to occur if applied cosmetics are left on and not stripped after wearing them.
See also
List of cutaneous conditions
References
== External links == |
Anterior interosseous syndrome | Anterior interosseous syndrome is a medical condition in which damage to the anterior interosseous nerve (AIN), a distal motor and sensory branch of the median nerve, classically with severe weakness of the pincer movement of the thumb and index finger, and can cause transient pain in the wrist (the terminal, sensory branch of the AIN innervates the bones of the carpal tunnel).
Most cases of AIN syndrome are now thought to be due to a transient neuritis, although compression of the AIN in the forearm is a risk, such as pressure on the forearm from immobilization after shoulder surgery. Trauma to the median nerve or around the proximal median nerve have also been reported as causes of AIN syndrome.
Although there is still controversy among upper extremity surgeons, AIN syndrome is now regarded as a neuritis (inflammation of the nerve) in most cases; this is similar to Parsonage–Turner syndrome. Although the exact etiology is unknown, there is evidence that it is caused by an immune-mediated response that can follow other illnesses, such as pneumonia or severe viral illness.
Studies are limited, and no randomized controlled trials have been performed regarding the treatment of AIN syndrome. While the natural history of AIN syndrome is not fully understood, studies following patients who have been treated without surgery show that symptoms can resolve starting as late as one year after onset. Other retrospective studies have concluded that there is no difference in outcome in surgically versus nonsurgically treated patients. The role of surgery in AIN syndrome remains controversial. Indications for considering surgery include a known space-occupying lesion that is compressing the nerve (a mass) or fascial compression, and persistent symptoms beyond 1 year of conservative treatment.
Symptoms and signs
Patients may experience poorly localised, transient pain in the wrist, i.e. where the sensory branch of the AIN is mapped in the brain. The pain is sometimes referred into the cubital fossa and elbow pain has been reported as being a primary complaint.
The characteristic severe impairment of the pincer movement of the thumb and index finger is most striking.
Clinical signs
In a pure lesion of the anterior interosseous nerve there is weakness of the long flexor muscle of the thumb (Flexor pollicis longus), the deep flexor muscles of the index and middle fingers (Flexor digitorum profundus I & II), and the pronator quadratus muscle.There is no sensory deficit since the anterior interosseous nerve has no cutaneous branch to skin, but there is a large sensory branch to the volar carpus, and transient wrist pain may be experienced.
Causes
Injuries of the forearm with compression of the nerve from swelling is the most common cause: examples include supracondylar fractures, often associated with haemorrhage into the deep musculature; injury secondary to open reduction of a forearm fracture; or dislocation of the elbow.Direct trauma from a penetrating injury such as a stab wound is a possible cause for the syndrome.Fibrous bands or Arcuate ligament~arcuate (curved) ligaments may entrap the median as well as the anterior interosseous nerve, in which case a patient may experience hand numbness as well as wrist pain.Very similar syndromes can be caused by more proximal lesions, such as brachial plexus neuritis.Anterior interosseous nerve entrapment or compression injury remains a difficult clinical diagnosis because it is mainly a motor nerve problem, and the syndrome is often mistaken for index finger and/or thumb tendon injury.
Anatomy
The anterior interosseous nerve is a branch of the median nerve, with a large sensory branch to the wrist bones, which arises just below the elbow. It passes distally, anteriorly along the interosseous membrane and innervates flexor pollicis longus, flexor digitorum profundus to index and middle finger as well as pronator quadratus, and supplies sensory feedback from the wrist bones, i.e. the carpal tunnel, not skin.
Diagnosis
Electrophysiologic testing is an essential part of the evaluation of anterior interosseous nerve syndrome. Nerve conduction studies may be normal or show pronator quadratus latency.Electromyography (EMG) is generally most useful and will reveal abnormalities in the flexor pollicis longus, flexor digitorum profundus I and II and pronator quadratus muscles.The role or MRI and ultrasound imaging in the diagnosis of Kiloh-Nevin syndrome is unclear.If asked to make the "OK" sign, patients will make a triangle sign instead. This pinch-test exposes the weakness of the flexor pollicis longus muscle and the flexor digitorum profundus I leading to weakness of the flexion of the distal phalanges of the thumb and index finger. This results in impairment of the pincer movement and the patient will have difficulty picking up a small item, such as a coin, from a flat surface.
Ericsons Test
Ericsons Test is a clinical maneuver for assessing the strength of the FDP and FPL muscles in anterior interosseous nerve syndrome, and other proximal entrapments of the median nerve.
In contrast to the "OK sign," Ericsons test isolates the action of the FDP and FPL while eliminating the contribution of the tenodesis effect and other adaptations that patients may use, usually unconsciously, to augment distal pincer strength. Failing to control for compensatory wrist tenodesis can mask an underlying proximal median nerve weakness in a patient who can otherwise make a normal OK-sign.While facing the patient in what resembles an arm wrestling stance, with elbows planted firmly on a level surface and maintained touching the thorax, the examiner uses one hand to lock the patients wrist in neutral, around which the patient curls his fingers. With the other hand, the examiner then attempts to "peel" back the tips of each individual finger against patient resistance. It is crucial that motion of the upper extremity be restricted to the distal IP joint, and that the MP and PIP joints are in full flexion and wrist neutral or slightly flexed. If the distal flexors of the index finger and thumb are weak, the patient will be unable to resist this motion, and Ericsons test is considered positive for proximal median nerve weakness.Ericsons test is frequently positive for proximal median nerve weakness (of which AIN syndrome is but one subtype) even in the context of normal imaging, EMG, and nerve conduction studies, which highlights the clinical nature of the diagnosis. Overreliance on electrical diagnostic workup unfairly excludes patients who would otherwise benefit from surgical decompression.
Treatment
Surgical decompression can give excellent results if the clinical picture and the EMG suggest a compression neuropathy.
In brachial plexus neuritis, conservative management may be more appropriate.
Spontaneous recovery has been reported, but is said to be delayed and incomplete.There may be a role for physiotherapy in some cases, and this should be directed specifically towards the pattern of pain and symptoms. Soft tissue massage, stretches and exercises to directly mobilise the nerve tissue may be used.
History
The syndrome was first described by Parsonage and Turner in 1948 and further defined as isolated lesion of the anterior interosseous nerve by Leslie Gordon Kiloh and Samuel Nevin in 1952.
References
== External links == |
Pancoast tumor | A Pancoast tumor is a tumor of the apex of the lung. It is a type of lung cancer defined primarily by its location situated at the top end of either the right or left lung. It typically spreads to nearby tissues such as the ribs and vertebrae. Most Pancoast tumors are non-small-cell lung cancers.
The growing tumor can cause compression of a brachiocephalic vein, subclavian artery, phrenic nerve, recurrent laryngeal nerve, vagus nerve, or, characteristically, compression of a sympathetic ganglion (the stellate ganglion), resulting in a range of symptoms known as Horners syndrome.
Pancoast tumors are named for Henry Pancoast, an American radiologist, who described them in 1924 and 1932.
Signs and symptoms
Aside from constitutional symptoms of cancer such as malaise, fever, weight loss and fatigue, Pancoast tumor can include a complete Horners syndrome in severe cases: miosis (constriction of the pupils), anhidrosis (lack of sweating), ptosis (drooping of the eyelid), and pseudoenophthalmos (as a result of the ptosis). In progressive cases, the brachial plexus is also affected, causing pain and weakness in the muscles of the arm and hand with a symptomatology typical of thoracic outlet syndrome. The tumor can also compress the recurrent laryngeal nerve and from this a hoarse voice and "bovine" (non-explosive) cough may occur.In superior vena cava syndrome, obstruction of the superior vena cava by a tumor (mass effect) causes facial swelling cyanosis and dilatation of the veins of the head and neck.A Pancoast tumor is an apical tumor that is typically found in conjunction with a history of smoking tobacco. The clinical signs and symptoms may be mistaken for neurovascular compromise at the level of the superior thoracic aperture. The patients smoking history, rapid onset of clinical signs and symptoms, and pleuritic pain can suggest an apical tumor. A Pancoast tumor can give rise to both Pancoast syndrome and Horners syndrome. When the brachial plexus roots are involved, it will produce Pancoast syndrome; involvement of sympathetic fibers as they exit the cord at T1 and ascend to the superior cervical ganglion will produce Horners syndrome.
Diagnosis
Diagnosis of Pancoast tumor is usually made after evaluating clinical symptoms and imaging. Chest X-ray is a good screening test even though a CT scan of the chest can provide a better resolution and extent to which internal organs are being compressed.
Treatment
The treatment of a Pancoast lung cancer may differ from that of other types of non-small-cell lung cancer. Its position and close proximity to vital structures (such as nerves and the spine) may make surgical intervention difficult. As a result, and depending on the stage of the cancer, treatment may involve radiation therapy and chemotherapy given prior to surgery (neoadjuvant treatment).
Surgery may consist of the removal of the upper lobe of a lung together with its associated structures (subclavian artery, vein, branches of the brachial plexus, ribs and vertebral bodies), as well as mediastinal lymphadenectomy. Surgical access may be via thoracotomy from the back or the front of the chest and modifications. Nonsurgical treatment may consist of radiation therapy alone or clinical trials of new combinations of treatment.
References
External links
Pancoast Tumor at eMedicine
Pulmonary sulcus tumor entry in the public domain NCI Dictionary of Cancer Terms This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms". |
Developmental coordination disorder | Developmental coordination disorder (DCD), also known as developmental motor coordination disorder, developmental dyspraxia or simply dyspraxia, is a neurodevelopmental disorder characterized by impaired coordination of physical movements as a result of brain messages not being accurately transmitted to the body. Deficits in fine or gross motor skills movements interfere with activities of daily living. It is often described as disorder in skill acquisition, where the learning and execution of coordinated motor skills is substantially below that expected given the individuals chronological age. Difficulties may present as clumsiness, slowness and inaccuracy of performance of motor skills (e.g., catching objects, using cutlery, handwriting, riding a bike, use of tools or participating in team sports or swimming). It is also often accompanied by difficulty with organisation and/or problems with attention, working memory and time management.
A diagnosis of DCD is reached only in the absence of other neurological impairments such as cerebral palsy, multiple sclerosis, or Parkinsons disease. Onset of the condition is in early childhood and is lifelong. It is thought to affect about 5% of the population.
Signs and symptoms
The World Health Organisation (WHO) recognise DCD as a condition, and have published their definition in the International Classification of Diseases. This describes DCD as:
6A04 Developmental motor coordination disorderDevelopmental motor coordination disorder is characterised by a significant delay in the acquisition of gross and fine motor skills and impairment in the execution of coordinated motor skills that manifest in clumsiness, slowness, or inaccuracy of motor performance. Coordinated motor skills are substantially below that expected given the individuals chronological age and level of intellectual functioning. Onset of coordinated motor skills difficulties occurs during the developmental period and is typically apparent from early childhood. Coordinated motor skills difficulties cause significant and persistent limitations in functioning (e.g., in activities of daily living, school work, and vocational and leisure activities). Difficulties with coordinated motor skills are not solely attributable to a Disease of the Nervous System, Disease of the Musculoskeletal System or Connective Tissue, sensory impairment, and not better explained by a Disorder of Intellectual Development.
The American Psychiatric Association (APA)s Diagnostic and Statistical Manual, DSM-5 classifies Developmental Coordination Disorder (DCD) as a discrete motor disorder under the broader heading of neurodevelopmental disorders. It is often described as a disorder in skill acquisition or motor learning, where the learning and execution of coordinated motor skills is substantially below that expected given the individuals chronological age. Various areas of development can be affected by DCD and these may persist into adulthood.In children, DCD may exhibit as delays in early development of sitting, crawling, walking; poor ability or difficulties with childhood activities such as running, jumping, hopping, catching, sports and swimming; slowness; frequent tripping and bruising; poor handwriting skills; difficulties with self care; difficulties with skills such as using cutlery or tying shoelaces; poor spatial understanding; difficulty following instructions; poor time management; and often losing objects.In adulthood, in addition to a childhood history as above, the condition may manifest as a difficulty learning new motor skills or applying skills in a different or busy environment, poor organisation and time management skills, missed deadlines and lateness for appointments (or earliness as a coping strategy), and awkward pauses before answering in conversation. There is often a history of underachievement in education or the workplace. Although skills can be acquired, such as neat handwriting, handwriting speed will then be much lower than expected. DCD has no cure. Often various coping strategies are developed, and these can be enhanced through occupational therapy, psychomotor therapy, physiotherapy, speech therapy, or psychological training.
Evidence from research and clinical practice indicates that DCD is not just a physical disorder, and there may be deficits in executive functions, behavioural organisation and emotional regulation that extend beyond the motor impairments and which are independent of diagnoses of co-morbidities. In addition to the physical or motor impairments, developmental coordination disorder is associated with problems with memory, especially working memory. This typically results in difficulty remembering instructions, difficulty organizing ones time and remembering deadlines, increased propensity to lose things or problems carrying out tasks which require remembering several steps in sequence (such as cooking). Whilst most of the general population experience these problems to some extent, they have a much more significant impact on the lives of dyspraxic people. However, many dyspraxics have excellent long-term memories, despite poor short-term memory. Many dyspraxics benefit from working in a structured environment, as repeating the same routine minimises difficulty with time-management and allows them to commit procedures to long-term memory.
People with developmental coordination disorder sometimes have difficulty moderating the amount of sensory information that their body is constantly sending them, so as a result these dyspraxics may be prone to sensory overload and panic attacks.Moderate to extreme difficulty doing physical tasks is experienced by some people with dyspraxia, and fatigue is common because so much energy is expended trying to execute physical movements correctly. Some dyspraxics have hypotonia, low muscle tone, which can also detrimentally affect balance.
Gross motor control
Whole body movement and motor coordination issues mean that major developmental targets including walking, running, climbing and jumping can be affected. The difficulties vary from person to person and can include the following:
Fine motor control
Fine-motor problems can cause difficulty with a wide variety of other tasks such as using a knife and fork, fastening buttons and shoelaces, cooking, brushing teeth, styling hair, shaving, applying cosmetics, opening jars and packets, locking and unlocking doors, and doing housework.
Difficulties with fine motor co-ordination lead to problems with handwriting,
Problems associated with this area may include:
Developmental verbal dyspraxia
Developmental verbal dyspraxia (DVD) is a type of ideational dyspraxia, causing speech and language impairments. This is the favoured term in the UK; however, it is also sometimes referred to as articulatory dyspraxia, and in the United States the usual term is childhood apraxia of speech (CAS).Key problems include:
Associated disorders and secondary consequences
People who have developmental coordination disorder may also have one or more of these co-morbid conditions:
However, a person with DCD is unlikely to have all of these conditions. The pattern of difficulty varies widely from person to person; an area of major weakness for one dyspraxic can be an area of strength or gift for another. For example, while some dyspraxics have difficulty with reading and spelling due to dyslexia, or with numeracy due to dyscalculia, others may have brilliant reading and spelling or mathematical abilities. Co-morbidity between ADHD and DCD is particularly high; the overlap between the two disorders is believed to be about 50% (approximately half of people with DCD have ADHD, and approximately half of people with ADHD have DCD).
Sensory processing disorder
Sensory processing disorder (SPD) concerns having oversensitivity or undersensitivity to physical stimuli, such as touch, light, sound, and smell. This may manifest itself as an inability to tolerate certain textures such as sandpaper or certain fabrics such as wool, oral intolerance of excessively textured food (commonly known as picky eating), being touched by another individual (in the case of touch oversensitivity) or it may require the consistent use of sunglasses outdoors since sunlight may be intense enough to cause discomfort to a dyspraxic person (in the case of light oversensitivity). An aversion to loud music and naturally loud environments (such as clubs and bars) is typical behavior of individuals with dyspraxia who have auditory oversensitivity, while only being comfortable in unusually warm or cold environments is typical of a dyspraxic with temperature oversensitivity. Undersensitivity to stimuli may also cause problems, as individuals do not receive the sensory input they need to understand where their bodies are in space. This can make it even more challenging to complete tasks. Dyspraxics who are undersensitive to pain may injure themselves without realising it. Some dyspraxics may be oversensitive to some stimuli and undersensitive to others.
Developmental Language Disorder
Developmental Language Disorder (DLD) research has found that students with developmental coordination disorder and normal language skills still experience learning difficulties despite relative strengths in language. This means that, for students with developmental coordination disorder, their working memory abilities determine their learning difficulties. Any strength in language that they have is not able to sufficiently support their learning.Students with developmental coordination disorder struggle most in visual-spatial memory. When compared to their peers without motor difficulties, students with developmental coordination disorder are seven times more likely than typically developing students to achieve very poor scores in visual-spatial memory. As a result of this working memory impairment, students with developmental coordination disorder have learning deficits as well.
Psychological and social consequences
Psychological domain: Children with DCD may struggle with lower self-efficacy and lower self-perceived competence in peer and social relations. Some demonstrate greater aggressiveness and hyperactivity.Social domain: Children may be more vulnerable to social rejection and bullying, possibly resulting in higher levels of loneliness.
Diagnosis
Assessments for developmental coordination disorder typically require a developmental history, detailing ages at which significant developmental milestones, such as crawling and walking, occurred. Motor skills screening includes activities designed to indicate developmental coordination disorder, including balancing, physical sequencing, touch sensitivity, and variations on walking activities.The American Psychiatric Association has four primary inclusive diagnostic criteria for determining if a child has developmental coordination disorder.
The criteria are as follows:
Motor coordination will be greatly reduced, although the intelligence of the child is normal for the age.
The difficulties the child experiences with motor coordination or planning interfere with the childs daily life.
The difficulties with coordination are not due to any other medical condition
If the child does also experience comorbidities such as intellectual or other developmental disability; motor coordination is still disproportionally affected.
Screening tests
Currently there is no single "gold standard" assessment test for DCD. Various screening tests may be used, including the following.
A baseline motor assessment establishes the starting point for developmental intervention programs. Comparing children to normal rates of development may help to establish areas of significant difficulty.
However, research in the British Journal of Special Education has shown that knowledge is severely limited in many who should be trained to recognise and respond to various difficulties, including developmental coordination disorder, dyslexia and deficits in attention, motor control and perception (DAMP). The earlier that difficulties are noted and timely assessments occur, the quicker intervention can begin. A teacher or GP could miss a diagnosis if they are only applying a cursory knowledge.
"Teachers will not be able to recognise or accommodate the child with learning difficulties in class if their knowledge is limited. Similarly GPs will find it difficult to detect and appropriately refer children with learning difficulties."
A diagnosis of DCD is reached only in the absence of other neurological impairments such as cerebral palsy, multiple sclerosis, or Parkinsons disease.
Classification
Developmental coordination disorder is classified in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a motor disorder, in the category of neurodevelopmental disorders.
Prevalence
The exact proportion of people with the disorder is unknown since the disorder can be difficult to detect due to a lack of specific laboratory tests, thus making diagnosis of the condition one of elimination of all other possible causes/diseases. Approximately 5–6% of children and adults are affected by this condition. and approximately 2% are severely affected.DCD is a lifelong neurological condition that is expected to be as common in males as it is in females. Currently however, the diagnosis criteria favours males which results in over 80% of males being diagnosed before the age of 16 compared to only 22% for females.
Management
There is no cure for the condition. Instead, it is managed through therapy. Physical therapy or occupational therapy can help those living with the condition.
Some people with the condition find it helpful to find alternative ways of carrying out tasks or organizing themselves, such as typing on a laptop instead of writing by hand, or using diaries and calendars to keep organized. A review completed in 2017 by Cochrane of task-oriented interventions for DCD resulted in inconsistent findings and a call for further research and randomized controlled trials.
Co-occuring conditions
DCD is know to co-occur with other Neurodevelopmental Disorders. Most commonly, Attention Deficit Hyperactivity Disorder (ADHD) co-occurs in an estimated 50% of cases, but other co-occurring conditions are Autistic Spectrum Disorder (ASD), Developmental Speech and Language Disorder and Developmental Learning Disorder.
History
Collier first described developmental coordination disorder as "congenital maladroitness". A. Jean Ayres referred to developmental coordination disorder as a disorder of sensory integration in 1972, while in 1975 Sasson Gubbay, MD, called it the "clumsy child syndrome". Developmental coordination disorder has also been called "minimal brain dysfunction", although the two latter names are no longer in use.
Other names include developmental apraxia, disorder of attention and motor perception (DAMP) dyspraxia, developmental dyspraxia, "motor learning difficulties", perceptuo-motor dysfunction, and sensorimotor dysfunction.The World Health Organization currently lists developmental coordination disorder as "Specific Developmental Disorder of Motor Function".
In popular culture
Helen Burns, a character from Charlotte Brontes Jane Eyre, is alleged to have been based on the authors dyspraxic elder sister Maria Bronte.
Ryan Sinclair, a companion of the Doctor in the BBC science fiction television programme Doctor Who, has the disorder. The character debuted in 2018.
Notable cases
People who have publicly stated they have been diagnosed with developmental coordination disorder include:
Harry Potter actor Daniel Radcliffe,
photographer David Bailey,
model Cara Delevingne,
singer Florence Welch,
UK politician Emma Lewell-Buck,
Rugby Union player Ellis Genge,
actor Will Poulter,
singer Mel B,
actor Olive Gray,
author Holly Smale,
games critic John "TotalBiscuit" Bain,
musician Toyah Willcox
English comedian Harriet Kemsley.
See also
References
Sources
Further reading
Polatajko H, Fox M, Missiuna C (1995). "An International Consensus on Children with Developmental Coordination Disorder". Canadian Journal of Occupational Therapy. 62 (1): 3–6. doi:10.1177/000841749506200101. S2CID 75856620.
Mandich A, Polatajko HJ (November 2003). "Developmental coordination disorder: mechanisms, measurement and management". Human Movement Science. 22 (4–5): 407–11. doi:10.1016/j.humov.2003.09.001. PMID 14624825.
Talukdar, A (2012). Dyspraxia/DCD pocketbook (PDF). Teachers Pocketbooks. Hampshire; UK: Management Pocketbooks. ISBN 978-1906610388. OCLC 1162296987. |
Retinal migraine | Retinal migraine is a retinal disease often accompanied by migraine headache and typically affects only one eye. It is caused by ischaemia or vascular spasm in or behind the affected eye.
The terms "retinal migraine" and "ocular migraine" are often confused with "visual migraine", which is a far-more-common symptom of vision loss, resulting from the aura phase of migraine with aura. The aura phase of migraine can occur with or without a headache. Ocular or retinal migraines happen in the eye, so only affect the vision in that eye, while visual migraines occur in the brain, so affect the vision in both eyes together. Visual migraines result from cortical spreading depression and are also commonly termed scintillating scotoma.
Symptoms
Retinal migraine is associated with transient monocular visual loss (scotoma) in one eye lasting less than one hour. During some episodes, the visual loss may occur with no headache and at other times throbbing headache on the same side of the head as the visual loss may occur, accompanied by severe light sensitivity and/or nausea. Visual loss tends to affect the entire monocular visual field of one eye, not both eyes. After each episode, normal vision returns.
It may be difficult to read and dangerous to drive a vehicle while retinal migraine symptoms are present.
Retinal migraine is a different disease than scintillating scotoma, which is a visual anomaly caused by spreading depression in the occipital cortex at the back of the brain, not in the eyes nor any component thereof. Unlike in retinal migraine, a scintillating scotoma involves repeated bouts of temporary diminished vision or blindness and affects vision from both eyes, upon which patients may see flashes of light, zigzagging patterns, blind spots, or shimmering spots or stars.
Causes
Retinal migraine is caused by the blood vessels (that leads to the eye) suddenly narrowing (constricting), reducing blood flow to the eye, which causes aura in vision.It may be triggered by:
Stress
Smoking
High blood pressure
Oral contraceptive pill
Exercise
Hay Fever
Bending over
High altitude
Dehydration
Low blood sugar
Excessive heat
Eating chocolateAfterwards, the blood vessels relax, blood flow resumes and sight returns. Usually there are no abnormalities within the eye and permanent damage to the eye is rare.
Retinal migraine tends to be more common in:
Women
People aged under 40
People with a personal or family history of migraines or other headaches
People with an underlying disease (lupus, hardening of the arteries, sickle cell disease, epilepsy, antiphospholipid syndrome, and giant cell arteritis)
Diagnosis
The medical exam should rule out any underlying causes, such as blood clot, stroke, pituitary tumor, or detached retina. A normal retina exam is consistent with retinal migraine.
Treatment
Treatment depends on identifying behavior that triggers migraine such as stress, sleep deprivation, skipped meals, food sensitivities, or specific activities. Medicines used to treat retinal migraines include aspirin, other NSAIDS, and medicines that reduce high blood pressure.
Prognosis
In general, the prognosis for retinal migraine is similar to that of migraine headache with typical aura. As the true incidence of retinal migraine is unknown, it is uncertain whether there is a higher incidence of permanent neuroretinal injury. The visual field data suggests that there is a higher incidence of end arteriolar distribution infarction and a higher incidence of permanent visual field defects in retinal migraine than in clinically manifest cerebral infarctions in migraine with aura. A 2005 study suggests that more than half of reported recurrent cases of retinal migraine subsequently experienced permanent visual loss in that eye from infarcts, but later studies suggest such loss is a relatively rare side effect.
See also
Entoptic phenomenon
Scintillating scotoma
References
== External links == |
Subungual hematoma | A subungual hematoma is a collection of blood (hematoma) underneath a toenail or fingernail. It can be extremely painful for an injury of its size, although otherwise it is not a serious medical condition.
Nature
A laceration of the nail bed causes bleeding into the constricted area underneath the hard nail plate. The blood pools under the nail, giving a reddish, brownish, blueish, or grey/blackish discoloration. The blood puts pressure to the nailbed causing pain which can be throbbing in quality and disappears when the pressure on the nail bed is relieved.Subungual hematomas typically heal without incident, though infection may occur. The pressure of the blood blister may cause separation of nail plate from the nail bed (onycholysis), but the nail should not be pulled off, as this can cause scarring of the nailbed and deformed nails. Nail discolouration may last some months.The nail plate may also become thicker and more brittle as a result of the injury (onychochauxis). The deformed nail plate will gradually grow out and be replaced by new, normal-appearing nail plate in several months time. Infrequently, the nail may become painful and require surgical drainage.
Causes
The condition is caused by a traumatic injury, such as slamming a finger in a door, or from sports activities, especially those involving sudden accelerations, such as soccer, basketball, and tennis, or going downhill, such as running or hiking rugged terrain, and ill-fitting footwear.: 52, 135 Repeatedly thrusting the toes against a shoes toe box can cause a subungual hematoma called joggers toe, runners toe, or black toenail. In a marathon, several percent of runners may be affected. Wearing footwear which fits helps prevent runners toe.If the shoe is too loose on the midfoot, the foot can slide forwards in the shoe, especially when going downhill. This may jam the toes into the end of the toebox. If the foot is sliding forwards because the shoe is too loose around the midfoot, it may be restrained by lacing the shoe carefully, or placing bulky padding between the tongue and the lacing, or by wrapping a strap in a figure-eight around the foot and ankle (image).: 86–87, 128, 142 Excessively tight or uneven fit around the midfoot may, however, cause tendon problems.: 125 Separately, if there is not enough space around the toes, the toes will also hit the toebox repeatedly. Feet become longer and wider when weight is put on them, because the arches flatten, and the toes also splay and bend.: p15, 18, 72–73 At the end of a long journey on foot, the arches flatten, the metatarsals spread, and the foot swells more than after a short one.: 52 The toes also need vertical space; a toe cap which is low enough to press on the top of the toe may also cause bruising under the nail, especially if the toe cap is stiff. If the toebox is pointed, the toes may be wedged forwards into the area with inadequate height.: 52–53, 135 Toenails which protrude unevenly may concentrate force on the toenail; properly-cut nails are therefore also important.Some susceptible runners may also have Mortons toe. In this variant of human foot anatomy, the second toe extends further out than the great toe. This can make it harder to find shoes with adequate space around the toes.
Treatment
Subungual hematomas can resolve on their own, without treatment being necessary. If they are acutely painful, they may be drained.Subungual hematomas are treated by either making a hole through the nail into the hematoma (trephining) within 48 hours of injury, draining the blood and releasing the pressure, or, less conservatively, by removing the entire nail.In hospital or medical setting, trephining is generally accomplished by using an electrocautery device or an 18-gauge needle. If neither of these is available a heated (red hot) paper clip can be used to drain the blood underneath of the nail. To do this the tip of a paper clip needs to be heated till its red hot and (the red hot) paper clip gently placed on the center of the hematoma (center of the black area underneath of the nail). A hole will appear in the nail and the blood will drain, relieving the pressure. The hole has to be covered with sterile dressing and the nail should be kept dry afterwards.Removal of the nail is typically done when the nail itself is disrupted, a large laceration requiring suturing is suspected, or a fracture of the tip of the finger occurs. Although general anesthesia is generally not required, a digital nerve block is recommended if the nail is to be removed. For trephination, the block is often more painful than the procedure.
Complication rates from both forms of treatment are low, and the nail generally recovers to a normal appearance.
See also
List of cutaneous conditions
Turf toe
References
== External links == |
Myelomalacia | Myelomalacia is a pathological term referring to the softening of the spinal cord. Possible causes of myelomalacia include cervical myelopathy, hemorrhagic infarction, or acute injury, such as that caused by intervertebral disc extrusion.In advanced stages, this disorder causes flaccid paraplegia (impairment of motor function in lower extremities), total areflexia (below normal or absence of reflexes) of the pelvic limbs and anus, loss of deep pain perception caudal (toward the coccyx, or tail) to the site of spinal cord injury, muscular atrophy (wasting away of muscle tissue), depressed mental state, and respiratory difficulty due to intercostal (muscles that run between the ribs) and diaphragmatic paralysis. Gradual cranial migration of the neurological deficits (problems relating to the nervous system), is known as ascending syndrome and is said to be a typical feature of diffuse myelomalacia. Although clinical signs of myelomalacia are observed within the onset (start) of paraplegia, sometimes they may become evident only in the post-operative period, or even days after the onset of paraplegia. Death from myelomalacia may occur as a result of respiratory paralysis when the ascending lesion (abnormal damaged tissue) reaches the motor nuclei of the phrenic nerves (nerves between the C3-C5 region of the spine) in the cervical (neck) region.
Classification
Myelomalacia affects the neurological functions in the spinal cord. Once breached, the ramification of the damage directly affects the motor functions of the body. Because the central nervous system is affected, the condition is classified under the neurological field of study.
Spinal Cord Injury
When myelomalacia occurs, the damage done to the spinal cord may range from minimal to extensive. The spinal cord and the brain work together, making them the key components of the central nervous system. Damage to this system affects specific functions of the body, primarily relating to the function of muscles. The areas most commonly injured include the cervical vertebrae (C1-C7), and the lumbar spine (L1-L5).
Symptoms
The onset of myelomalacia may be so subtle that it is overlooked. Depending on the extent of the spinal cord injury, the symptoms may vary. In some cases, the symptom may be as common as hypertension. Though every case is different, several cases reported loss of motor functions in the extremities, areflexia or sudden jerks of the limbs, loss of pain perception, or even paralysis; all of which are possible indicators of a damaged and softened spinal cord. In the most severe cases, paralysis of the respiratory system manifests in death.
Cause
The most common way the disorder occurs is from a result of hemorrhaging (bleeding within) or inadequate blood supply to the spinal cord, making it weak and susceptible to damage.Because myelomalacia involves a damaged spinal cord, it may occur in any individual. Those most at risk are the geriatric population due to weaker bone density. Once the spinal injury has occurred, one of two things may happen. Firstly, hemorrhaging within the spinal cord may cause compression, which damages the spinal cord even further. Another consequence of myelomalacia is improper circulation of blood to the area damaged, resulting in further damage to the spinal cord.
Sport Athletes
Due to extensive physical contact and activity, many athletes become victim to myelomalacia. Any accidents or injuries attained during athletic competition to the spinal cord may result in myelomalacia. Accounts of awkward landing on the ground or being hit intensively have attested to spinal cord injury.
Geriatric
With the growth in the elderly population of humans, there has been a rise to myelomalacia. Because the human body begins to deteriorate with age, and because human population is living many years longer, there has been a growth in cases of myelomalacia. As the bones in the body begin to weaken in a process known as osteopenia, the body is more vulnerable to damage. A simple fall may damage the spinal cord and myelomalacia may soon ensue.
Diagnosing
There are two tests that can provide a definite diagnosis of myelomalacia; magnetic resonance imaging (MRI), or myelography. Diffuse hyperintensity on T2-weighted imaging, and hypointensity on T1-weighted imaging of the spinal cord can be an indication of the onset or progression of myelomalacia
Treatment
There is no known treatment to reverse nerve damage due to myelomalacia. In some cases, surgery to alleviate the injury to the area may slow or stop further damage. As motor function degenerates, muscle spasticity and atrophy may occur. Medications such as NSAIDs and gabapentinoids may be prescribed to reduce swelling of the spinal cord, pain, and spasticity.Research is underway to consider the potential of stem cells for treatment of neurodegenerative diseases. There are, however, no approved stem cell therapies for myelomalacia.
See also
== References == |
Subsets and Splits
No saved queries yet
Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.